Category Archives: anti-aging

VITAMINs D3 + K2+ UPDATE – PRIMA VITAMIN DUO OF THE NEXT DECADE

update 22 Mar 2019 at the equinox.. neil.burman@gmail.com

ONGOING WILFUL MISCONCEPTION, DENIAL OF HIGHDOSE VITAMIN D3  LOADING DOSE, NOT VIT D2:  the 2017  trial https://www.atsjournals.org/doi/full/10.1164/rccm.201705-0936OC  from Harvard, Mongolia and London centres by Ganmaa, Willette, Jolliffe  ea High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial in 390 pts, in fact was only apparently for 8 weeks, using ‘biweekly’ vit D3 140 000iu doses; their comment that the 8week serum ?25OHvit D was elevated from 6 to only 60ng/ml suggests that they were given a moderate dose of only 560 000iu over 8 weeks, without the crucial up front 640 000iu loading dose repeated after a month  as in Salhuddin’s trial in Pakistan . so it is unsurprising that the Mongolian trial, unlike the Pakistan trial, showed no benefit after only 8 weeks. Biweekly is ambiguous, either fortnightly or every two weeks, but the mediocre response suggests 140 000iu Vit D  every 2 weeks ie 70 000iu/wk, with a bld level of 60ng/ml comparable to what we see on 50 000iu/wk as standard minimal supplement dose in adults. I  take 100 000iu vit D3/wk,  running my bld level at around 100 to 120ng/ml, with normal calcium and PTH levels.

As studies have shown exhaustively below,   unlike highdose vit C which has dramatic lifesaving benefit, oral vitamin D3  supplement works slowly over months unless, like antibiotics and vit C,  given as a upfront loading dose of vit D3  around 10 000iu/kg. no toxicity has ever been reported from even eg 2million iu as oral  loading dose, as happened in a nursing home in Netherlands to 2 nonagenarians.

Lately we have been eeing patients with poor blood 25OHlevel and PTH response on vit D3 50 000iu/wk. But in each case it turns out that this is due to fraud. Where D3 has been the gold standard for more than a decade, doctors and pharmacists are mostly still ignorant of the benefit of vigorous dose, and especialy that using the human, mammal  ie lanolin-derived  hormone Vitamin D3 cholecalciferol is crucial, not the plant xenohormone  vit D2 ergocalciferol, which is only perhaps 1/16th of the benefit of vit D3. giving  D2 actually lowers 25OHvitD3 level and  25OHvitD2 blocks vit D3 receptors, and thus a may actually worsen eg Rheumatoid arthritis.  This error is perpetuated by the local supplier here, Aspen, fraudulently supplying vit D2 50 000iu tabs  called “strong Calciferol” without indicating that it is D2, not D3. Most doctors, pharmacists and dispensing nurses are not taught this vast difference; but the fraud is perpetuated by the local Medical Schools and thus State Clinics  dispensing the same fraudulent D2 Strong Calciferol instead of  the needed vit D3- also without indicating on pillbags and scripts that it is D2 not D3.                        The original Lennon-Aspen Strong Calciferol data sheet from 1974 updated  2004  still on line http://home.intekom.com/pharm/lennon/calcifer.html    does not indicate that it is vit D2 not D3.

J Clin Endocrinol Metab. 2014 May 14:jc20141069. Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3. Swanson CM1, Barrett-Connor E, , Cauley JAOrwoll ES ea ; For the Osteoporotic Fractures in Men (MrOS) Study Research Group, from USA and Belgium. “In a cohort of older men, 25(OH)D2 is associated with lower levels of 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol levels. The  study  measured vitamin D2 and D3 levels and examined their associations with each other and with total vitamin D. a cross-sectional analysis of 679 randomly selected participants. 25-Hydroxyvitamin D2 [25(OH)D2], 25(OH)D3, 1,25-dihydroxyvitamin D2 [1,25(OH)2D2], and 1,25(OH)2D3 were measured using liquid chromatography-tandem mass spectrometry. Results: 25(OH)D2 and 1,25(OH)2D2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D2 levels did not correlate with higher total 25(OH)D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D2 was not positively associated with total 1,25(OH)2D levels (r = -0.11; P = .13), and median 1,25(OH)2D level was not higher in those with detectable vs undetectable 25(OH)D2. Higher 25(OH)D2 was associated with lower 25(OH)D3 (r = -0.35; P < .001) and 1,25(OH)2D3 (r = -0.32; P < .001), with median levels of both D3 metabolites 18-35% higher when D2 metabolites were undetectable..”
    This study thus corroborates two  trials by Karen Hansens group:
An Evaluation of High-Dose Vitamin D 2  for Rheumatoid Arthritis Karen Hansen ea that vit D2 ~100 00iu/month  for a year actually worsens patients and lowers vit D3 levels”  , so there is no longer excuse for using vitamin D2 supplement when it blocks D3 receptors and lowers blood vit D3. whereas trials of vit D3 in RA for long enough show significant nenefit.

and Naik, Hegde ea  ea recently reported   Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis

Journal of Clinical and Diagnostic Research: JCDR 2017, 11 (4): BC18-BC22   ‘VDD was seen in PTB patients, which worsened in majority of the study population after treatment; hence it would be advisable to recommend Vit D supplementation in PTB patients for a better outcome. Vitamin D (Vit D) modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. Vit D Deficiency (VDD) is been implicated as a cause in diabetes, immune dysfunction and Tuberculosis (TB). Impaired metabolism of Vit D and an adverse outcome is associated with Pulmonary Tuberculosis (PTB). Directly Observed Treatment Short Course (DOTS) consist of drugs like rifampicin and isoniazid, which respectively cause accelerated loss of Vit D due to increased clearance and impairment of 25-hydroxylation causing diminished Vit D action.  Forty four newly diagnosed PTB patients of both the sexes in the age group of 18 to 60 years before starting DOTS were recruited to participate in this non- randomized controlled trial with their voluntary consent. RESULTS: Mean Vit D levels of the study population aged 43±13 years was 20.7 ng/ml  at the time of diagnosis. After completion of six months of therapy mean Vit D reduced to 17.5 ng/ml (p-value=0.041). On individual observations, 70% of the participants showed a decrease in Vit D levels from their baseline, whereas 30% showed an increase. Comparison between the two groups indicated the possible role of younger age in the improved status.’
UPDATE: VITAMIN D3 IN PREVENTION AND THERAPY January 2018 neil.burman@gmail.com
introduction:     Cape Town is the world epicenter of epidemics (of poverty – malnutrition- HIV- HAART- TB –Diabetes, asthma-COPD,  and vitamin D  and iodine deficiency). And we  are seeing neuroarthropathy with a vengeance in our township clinics, where a majority of such diabesity or/and HIV patients  admit if questioned to chronic burning cramping legs  and sore muscles/joints if not also consequent insomnia, falls and leg ulcers.

The media have lately labelled  calcium plus vitamin D supplements as useless because of the recent review December 2017 by a Chinese team Zhao ea  showingNo significant associations  were found in trials between supplements of calcium, vitamin D or their combination and incidence of  fractures. eg  https://www.medscape.com/viewarticle/890687/

  But the trials Zhao ea  reviewed https://www.ncbi.nlm.nih.gov/pubmed/29279934 that were long enough ie at least a year (to meaningfully improve bone and muscle strength and coordination- not just 4 or 6 months)  used vitamin D dose of between 400iu and  1000iu/d or at most 100 000iu/month,  or 500 000iu once. Thus none used significantly high vit D doses to provide a vigorous ~>7000iu/d or >100iu/kg/d ie ~>50 000iu/wk as is now recognized as achieving an average 50+ng/ml 25OHvit D level.

 The gold standard, the biggest longest costliest  trial ever, the  Womens Health Initiative, in many thousands of American women mean age ~63yrs for an average of 7years, ie about 55000 patient- years of vitamin D+ calcium  supplement , independent of HRT  reduced fractures by an astounding 35% with vit D3 only 400iu/d ie a paltry  1 million iu vit D3 – but crucially spread daily over 7 years, not a bolus annually or one-off dose. https://link.springer.com/article/10.1007/s00198-012-2224-2

 

     As our previous reviews  below have shown, vitamin D3 orally  in adults  up to 2million iu as single dose, or up to 150 000iu daily for decades,  has  produced no adversity. Only ill- advised  longterm vitamin D injection, or rarely, combination of highdose vit D with higher dose calcium supplement or overdose of vitamin A, has produced hypercalcemic  toxicity.
Recent reviews by Cochrane , and German groups have confirmed that eg
Even in the population range of natural ie food and solar ie skin vit D intake and thus bloodlevels averaging <10 to >40 ng/ml, better vitamin D levels give surprisingly significant 12% lower all-cause mortality. Even just face and hands sun exposure gives significant vit D benefit.  NO OTHER NUTRITIONAL SUPPLEMENT GLOBALLY LOWERS ALLCAUSE MORTALITY LIKE THIS.

    Since natural ie avoidable  all-cause medical  mortality from middle age  is overwhelmingly from vascular and cancer causes (apart from frailty fractures and infections in the old), the 12% LOWER mortality at higher epidemiological  vit D3 intake and levels confirms that higher vit D3 also significantly reduces vascular and cancer disease; as shown in lower premature degenerative disease rates closer to equatorial than at darker latitudes.

   But supplements with vit D2, or alphacalcidiol or calcitriol, gives no benefit in lower mortality, may worsen risks – as does avoidance  of sun exposure.

    The  crucial benefit of supra physiological  ie megavit D3 supplement eg >1000 iu/kg/d is born out by its proven curative benefit the past 15 years in multiple sclerosis, vitilligo, psoriasis, myasthenia gravis ( Coimbra Protocol 2016  https://www.coimbraprotocol.com/general-information)

 

 and now in high loading dose eg 10 000iu/kg  in severe tuberculosis (Salhuddin ea, Pakistan 2013)- as sunlight was for advancing TB in sanatoria a century ago eg Trial By TB Holme CJ, Proc RCPEdinburgh 1997.27.1-53..
IMPORTANCE IN HIGHRISK COUNTRIES AND CITIES: like so many other places, in Africa we have rife  poverty, pollution (especially lead, mercury, aluminium, fluoride, bromide;   smoking, alcohol,  antibiotics, estrogenics, pesticides, aspartame, ROS reactive oxygen species and insulin resistance, and unnatural harmful nonfoods eg sugar, margarine and plant cookingoils);
and malnutrition with especially diet deficiencies of clean water, fish oil(Epa+ Dha), coQ10,   iodine, magnesium, selenium, triglyceride eg animal fat and coconut oils; and vitamins especially D, C, Bco, K2;
Increasingly nonphysical lifestyle and pervasive stress and disturbed unnatural sleep;
And in the aging women , depletion of especially anticancer neuroprotective progesterone,
and in men, depletion of testosterone.
And thus not just epidemics but endemic  infections ( HIV, TB, hepatitis, HPV, other STDs); as well as chronic degenerative saccharine diseases  – obesity, diabetes, reno-cardio- cerebro-vascular, fatty liver, arthritis, as well as cancers, and aging diseases- osteoporosis and fractures, frailty, failing vision and memory etc,  worse in the aging population.  And worse since world population in our lifetime since WW2 has tripled to near 7.5billion people,  and birthrate continues to mushroom especially in the most water-and -literacy-scarce eg Africa and Arabia.

So since people globally in all social classes are increasingly  stressed sedentary  urban dwellers and indoor workers, with the deteriorating global food chain, combating the tidal wave of common communicable ie infectious,  and noncommunicable ie DEGENERATIVE (obesity-diabetes-vascular ,malignant, arthritic, fracturing, dementing)  diseases ,  all – especially those with longer life expectation-  increasingly require  supplementation for both detox, and vigorous supplementation of the micronutrients listed.

While a few  common deficiencies like coq10, vit K2, lutein /zeoxanthine, glucosamine-chondroitin and  marine oil are scarce costly essentials, at least the majority of the major  deficient essentials- (animal  and coconut oils, trigycerides, vitamins D3, C and Bco, magnesium, lugols iodine, selenium,   (and iron in children and younger women) are easily and cheaply supplemented.

 COST:   Vitamin D3 as Pharmacopoeia /USP standard powder is freely available wholesale through an importing pharmacist by the kg powder – @ 100 000iu/gm at about R600 ie US$50/kg =~ US$0.025 per 50 000iu per week… a flat 1ml measuring scoop hold just 1/2gm of such powder ie ~50 000iu vit D3. Tablets/capsules have to be assembled and are thus costly by comparison.

new references:
JAMA. 2017 Dec 26;318:2466-2482.Systematic Review and Meta-analysis.. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults:

The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies reached mixed conclusions regarding the association. Randomized trials from July, 2012, to July, 2017 were analyzed. Results:A total of 33  trials involving 51 145 participants fulfilled inclusion criteria. There was no significant association of calcium or vitamin D or the combination with risk of hip or nonvertebral or total fractures compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; vitamin D: RR, 1.21 [ CI, 0.99 to 1.47]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [CI 0.85 to 1.39]. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.   These findings do not support the routine use of these supplements in community-dwelling older people.

J Nutr. 2017;147:1325-1333.  Vitamin D Supplementation Trials Aimed at Reducing Mortality Have Much Higher Power When Focusing on People with Low Serum 25-Hydroxyvitamin D Concentrations. Brenner H Schöttker B ea  Univ.Heidelberg  Germany https://www.ncbi.nlm.nih.gov/pubmed/?term=Vitamin+D+Supplementation+Trials+Aimed+at+Reducing+Mortality+Have+Much+Higher+Power+When+Focusing+on+People+with+Low+Serum Background: Evidence of an inverse association between serum vitamin D and mortality from epidemiological studies has prompted efforts to reduce mortality by vitamin D supplementation. Objective: We aimed to assess the expected impact of the 2 different approaches on effect sizes and power of intervention studies.Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured in 9579 participants aged 50-75 y in the German Epidemiologische Studie  (ESTHER) study who were followed for mortality for a median of 12.4 y. .Results: An inverse association between serum 25(OH)D and mortality was observed only for participants with vitamin D insufficiency or deficiency and was strongest for the latter. Accordingly, the expected effects were much stronger and the expected power was much higher for interventions that targeted these groups than for untargeted interventions. For example, a targeted intervention study with 10,000 older adults (age 50-75 y) with serum 25(OH)D <50 nmol/L that increases serum 25(OH)D concentrations by 20 nmol/L in the intervention group (n = 5000) would be expected to yield a 26% reduction of all-cause mortality that could be detected with 89% power within 5 y of follow-up compared with a 10% mortality reduction and 20% power in an untargeted intervention study of the same size.Conclusions: Vitamin D supplementation trials aimed at reducing mortality in older adults have much higher power when focused on those with low serum 25(OH)D concentrations.

Cochrane Database Syst Rev. 2014(1):CD007470. Vitamin D supplementation for prevention of mortality in 95,286 adults in 56 RCTs. Bjelakovic,Gluud ea University of Nis, Serbia,https://www.ncbi.nlm.nih.gov/pubmed/24414552 The present systematic review updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of mortality     Vitamin D3 statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02;   44,492 participants; 4 trials). Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17 (95% CI 1.02 to 1.34); P 0.02;  42,876 participants; 4 trials). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02;; 710 participants; 3 trials).                      AUTHORS’ CONCLUSIONS:  Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased hypercalcaemia.

Osteoporos Int. 2013 Feb;24(2):567-80. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Prentice ea , USA.   https://link.springer.com/article/10.1007/s00198-012-2224-2     The Women’s Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.   RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98).

Endocr Pract. 2014;20:341-51. Large, single-dose up to 600 000iu oral vitamin D2 or D3 supplementation  in adult populations: a systematic review. Kearns MD1, Alvarez JA1, Tangpricha V2.Emory University, Atlanta, Georgia. Endocr Pract. 2014 Apr;20(4):341-51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128480/A

Daily vitamin D supplementation is often inadequate in treating vitamin D deficiency due to poor compliance. A single, large dose of vitamin D given at timed intervals may be an alternative strategy.   METHODS: We conducted a systematic literature review to investigate the efficacy of a single large bolus dose to treat vitamin D deficiency. We identified 2,243 articles in PubMed using the terms “high dose vitamin D,” “single dose vitamin D,” “bolus vitamin D,” or “annual dose vitamin D.”  Manuscripts were also excluded if the study: (1) did not use oral cholecalciferol or ergocalciferol, (2) used vitamin D analogs, (3) enrolled participants under age 18 years, (4) administered doses <100,000 international units (IU) (2.5 mg), or (5) administered >1 dose per year. References of eligible manuscripts and the Cochrane databases were also searched.     Large, single doses of vitamin D consistently increased serum/plasma 25-hydroxyvitamin D (25[OH]D) concentrations in several vitamin D-sufficient and -deficient populations. Vitamin D3 doses ≥300,000 IU provided optimal changes in serum/plasma 25(OH)D and parathyroid hormone (PTH) concentrations. Vitamin D supplementation also impacted bone health and extraskeletal endpoints.   CONCLUSION:  single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months. Lower doses, however, may be sufficient in certain populations. Vitamin D doses >500,000 IU should be used judiciously in order to minimize adverse events.

Am J Case Rep. 2016;17:51-4. Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment.  Cadegiani F. Endocrinology Unit, Corpometria, Brasilia, Brazil.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734680/  Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. CASE REPORT: This is a case report of a patient with severe refractory myasthenia gravis (MG) who followed  massive-dose treatment (80,000 to 120,000 IU/day) promoted by a (Coimbra) medical center in Brazil (but still not proven), and she had her first complete remission after this type of treatment with increased vitamin D serum levels (400 to 700 ng/mL). CONCLUSIONS: This case report may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases.

https://www.vitamindwiki.com/Vitamin+D+and+Sun+conference+%E2%80%93+Germany+June+2017         JOINT INTERNATIONAL SYMPOSIA “VITAMIN D IN PREVENTION AND THERAPY” AND “BIOLOGIC EFFECTS OF LIGHT”  June, 2017, Schlossberg Hotel, Homburg/Saar, Germany 
 Click here to download all of the talks and posters from VitaminDWiki    AVOIDANCE OF SUN EXPOSURE AS A RISK FACTOR FOR MAJOR CAUSES OF DEATH  Pelle G. Lindqvist. Clintec, Karolinska Institut Sweden  From an evolutionary perspective, there must be an evolutionary selection advantage in having adequately pigmented skin for the regional ultraviolet (UV) radiation. One possible mechanism might be differences in life expectancy; however, there is no such evidence. Based on the large prospective Melanoma in Southern Sweden (MISS) cohort (n=29,518), we assessed differences in life expectancy by sun exposure adjusted for age, income, education, marital status, smoking and comorbidity. Low sun exposure habits were found to be a major risk factor for all-cause mortality. This was caused by an increased risk of death due to cardiovascular disease (CVD) and non-cancer/non-CVD. Therefore, due to the increased life span among those with highest sun exposure, this exposure naturally results in an increased prevalence of cancer death. In addition, sun exposure increases the incidence, but is related to better prognosis of skin cancer. The findings indicate that there is a need for modification of guidelines regarding sun exposure.

    THE IMPACT OF DOSE, BODY SURFACE AND OTHER FACTORS ON UVB-INDUCED VITAMIN D SYNTHESIS: A SYSTEMATIC REVIEW AND META-ANALYSIS  Nadine Jager1 Jorg Reichrath ea Saarland University, Homburg, Germany;    Background: Vitamin D deficiency is a worldwide health problem. Under most living conditions in Europe and North America, up to 90% of the body’s requirements of vitamin D have to be fulfilled by the ultraviolet B (UVB)-induced cutaneous synthesis of this prohormone. As a consequence, it is of high scientific interest to determine the impact of various factors on UVB-induced cutaneous vitamin D production, measured as serum 25(OH)D3 concentration. Aim: It was the aim of this systematic review and metaanalysis to investigate our present scientific knowledge on this topic. Additionally, the half-life of 25(OH)D3 was estimated.  Materials and Methods: A systematic literature search was conducted using MEDLINE and cross-referenced studies to investigate the impact of exposure to artificial UV- sources on vitamin D status. Relevant parameters included 25(OH)D3 serum level before and after exposure, UV source and dose (in standard erythema dose (SED)) and time of exposure. Summary mean differences and 95% confidence intervals were derived from random-effects meta-analysis to account for possible heterogeneity across studies. Results and   Conclusion: We found 15 papers published in the past 7 years. In summary, our study indicates that single doses between 0.75 and 3 SED result in the highest increase in serum 25(OH)D3 per dose unit (SED). Exposure with higher single doses of UVB resulted in less pronounced increases in serum 25(OH)D3 per dose unit. It can be concluded that UVB exposure with single doses between 0.75 and 3 SED are desirable in respect to cutaneous vitamin D synthesis. Interestingly, the increase in 25(OH)D3 serum concentration was not proportional to the amount of exposed body surface. Partial exposure of the body surface resulted in relatively higher increase of 25(OH)D3 serum concentration per SED (AH-25(OH)D/SED/% body surface) as compared to exposure of the whole body. For instance, exposure of face and hands resulted to an 8-fold higher increase in AH-25(OH)D/SED/% body surface as compared to whole body irradiation. Moreover, our results confirm the relevance of the baseline 25(OH)D3 level. The lower the baseline, the higher was the 25(OH)D3 increase after irradiation. In the studies included in this systematic review, the half-life of 25(OH)D3 can be estimated to be about two months.

     CAN WE ADAPT THE “COIMBRA-PROTOCOL” (HIGH DOSAGE VITAMIN D CURE OF MS) TO THE TREATMENT OF CANCER AS WELL?  Spitz &  Thoennissen.  Wiesbaden, Germany; Introduction: Vitamin D is known to play an important role in the development and progress of cancer. In certain types of cancer, the figures of Vitamin D sensitivity go up to as much as 70 to 80%. The reason why the remaining patients do not profit from a sufficient Vitamin D level with regard to cancer is not known. Thesis: Due to a kind of vitamin D resistance, some patients are not able to overcome the cancer development in their body. In 2016, Carlberg and Haq suggested that the need for vitamin D supplementation depends on the vitamin D status in relation to the personal vitamin D response index of an individual rather than on the vitamin D status alone (1). In addition, Cicero G. Coimbra and his co-workers were able to produce a remission in patients with autoimmune diseases (above all multiple sclerosis (MS) but also vitiligo and psoriasis patients) by applying individual vitamin D doses up to 100,000 IU per day in a large number of cases (2). Putting this information together, it seems justifiable to make a similar approach in cancer patients. Conclusion: Individual high doses of Vitamin D should be tested as adjuvant therapy with regard to their efficacy not only in autoimmune disease but also in case of cancer.

update 16 May 2016.   to our health:   neil.burman@gmail.com                   HIGH TO MASSIVE DOSE VITAMIN D3 IMPORTANCE – TEN TIMES MORE THAN MAXIMUM SUNLIGHT CAN PROVIDE – IN REVERSING  COMMON VIT D DEFICIENCY/RESISTANCE FOUND IN ALL MAJOR DISEASE eg ALL  INFECTIONS, INSOMNIA, MULTIPLE SCLEROSIS MS,  Myasthenia Gravis, SLE, RA, PARKINSON’S, DEPRESSION, VASCULAR DISEASE, CANCER, VITILLIGO, PSORIASIS,  PERIPHERAL NEUROPATHIES, MENTAL ILLNESS.

Poor ill patients  seem to  accept  neuroarthropathy-  as a way of life since it  usually has no visible signs (for anyone to see) till late– poor circulation, ulcers, falls,  arthritis- , and  malnourished diabesity patients  have bigger worries with uncontrolled diabetes and often uncontrolled hypertension despite even insulin; and the HIV+-Tuberculosis patients  have the multiple toxic burdens of antiretroviral and antituberculous therapy.

Because the burden of these diseases as well as stress from corruption and violence  here  is amongst the highest in a major city in the world, affecting especially the poorest and most illiterate labourers, state clinics rarely have budgets to cover the necessary vitamin and mineral supplements the poor  also need on their poverty fast food diet.

Our patients  accept that in return for life extension by designer antimicrobials and antidiabetic/ antihypertensives, all they will get for pain relief  is the combination of physiotherapy, and  designer synthetic palliative drugs- paracetamol, ibrufen /diclofenac, tramadol, amitryptiline, and if lucky some ung meth sal . These factory-synthesised drugs  give little relief,  and no improvement in prognosis since they do not address the proximate causes of the neuroarthropathy,  associated depression and  work incapacity (and later strokes, arthritis, dementia, ulcers, gangrene, chronic lung/heart/ liver/ kidney/visual disease)- respective causes including stress,  infective, drug-induced, tissue glycogenation, the misguided fast-food high carbohydrate-low fat diet  obesity; and manual labour/multiple trauma  wear and tear, and nutritional deficiency including much-needed marine and saturated fats, vitamins and minerals..

The pioneer  work discussed below in Pakistan(Salahuddin ea, Basit ea), Italy (Cipriani ea) and Brazil (Coimbra ea) in using respectively Vit D3 ~700 000iu loading dose and chronically up to 1000iu /kg/day ie average 70 000iu/day, up to 120000iu per day to reverse deadly acute and chronic disease,  is comparable in its simplicity safety and low cost to :

*Semmelweis’ revolutionary discovery  Vienna in the mid 19thC  of hand disinfection to decimate childbirth sepsis deaths; and

*Pauling’s landmark lifesaving escalation of Vit C dose to a gm  per kg per day for all severe disease; and

*the parallel discovery in UK and USA of the crucial role of not just the RDA preventative microdose but also the pharmacological anti-disease benefits of 10 to 100times bigger doses of all the vitamins B complex 1 to 12.

Cipriani ea 2010 seems to be the first report on Pubmed of deliberate oral dosing with  megadose     600 000iu vit D3 ie 10 000iu/kg, albeit only in health to assess bloodlevel response and safety. Since then, as we previously noted, 2 million unit single overdose in nonagenarians in Netherlands  has been shown to do no harm – ie about 40 000iu/kg. .

And as the Australians and others report below, there is no hint of vigorous vitamin or mineral  supplements being stigmatized as performance enhancing for eg sport –  despite vitamin D3 having the distinction of being truly an anabolic ie performance-enhancing (seco)steroid .

There is no point in giving vitamin D by injection (except in those in ICU on prolonged nil per mouth) since it is so well absorbed provided given with fat eg in fishoil/coconut/DMSO oil. And obviously the higher the dose given, the more important to avoid more than a traditional multisupplement pill a day  with low calcium and vitamin A retinol; combined with a low calcium diet (ie low dairy low peanut) ; and supplementing plenty fresh green produce [providing magnesia a few hundred mgs a day, and vitamin K2 perhaps 35mcg/d].

Dr  Mike Holick Prof of Medicine at Boston University interviewed by Dr Joe Mercola Dec 2015 details  the  rationale underpinning the (eg Coimbra) massive vit D3 dose regime for severe immune disease, “as opposed to  plenty of sensible sun exposure for general good health and lower deathrate from all diseases and infections.                 Most melanoma occurs on the least sunexposed skin, with lower melanoma and all other deaths with high sun exposure. Dark days promote melatonin and thus daytime sleepiness and depression- which bright light in the morning for an hour reverses, and elevates b-endorphan, which has many times the painkilling effect of morphines ie opioids, and antidepressants. Vitamin D deficiency more than doubles the risk of all diseases; even 2000iu vit D3 a day in the 1st yr of life in Finland halved the risk of type 1 diabetes– with loss of protection if vit D dose dropped to 400iu/day. Vitamin D/ sunlight reverse leukemic cells. But maximum sunlight exposure nearer the tropics still only elevates 25OHvit D level to a maximum of about 50ng/ml- whereas increasing evidence proves that it may take more than 10 times that bloodlevel to prevent and treat deadly diseases- depending on your genetic vitamin D receptors.

 Even 1000iu/d vit D with bld level about 30ng/ml halves risk of many cancers, with doubling benefit as 25OHvit D level is doubled serially  eg by 10 000iu/d or 50 000iu/d. The kidneys however limit production of the hypercalcemic 1,25vit D, thus avoiding hypercalcemia provided calcium intake is not supplemented by calcium pills, nuts. vit A  etc. The higher the vit D level above 30ng/ml (up to >? 500ng/ml), the more  of our 2000 enzyme systems are activated  to fight all disease without hypercalcemic risks. Hunter gatherers had levels twice as high as dressed housed people today, around 50ng/ml, with increasing anticancer and antiinfection/antiautoimmune benefit from vit D up to safe levels eg 100ng/ml and higher. .”

At Thisisms.com this is multiple sclerosis  March 2016 seems to be the latest from neurologist  Dr Cicero Coimbra  via grassroots health. He stresses that to cure degenerative/ autoimmune disease eg  MS, Parkinson’s, SLE, RA, vitiligo ie to overcome genetic Vit D resistance may require vit  D titration up to 1000iu/kg/d ie up to even 40000iu/d to 200000iu/d,
And 25OHvitD blood level to 1000ng  and even 4000ng / ml for a few years to produce cure, before reducing to maintenance vit D3  eg 100iu/kg/day ie ~ 50000iu/wk.
Hypercalcemia and thus calcinosis  is avoided provided PTH level is maintained in the low normal range, not suppressed. Optimal support includes low calcium and  high water diet and  Vit B2, magnes selenium zinc phosphor  supps.

      COST IMPLICATION:

The spectrum of vitamin D3 adult dose thus extends from the

traditional prevention RDA 10iu/kg/ ie~700iu/d against rickets (infants start with 1000iu/d or 25000iu ie ½ scoop/month of standardized vit D3  100iu/mg powder)

to  vigorous 100iu/kg/day (ie 50 000iu scoop /wk ) for common disease prevention/treatment (toddlers 2000iu/d/ ½ scoop/fortnight));

 to  massive  1000iu/kg/day eg 60 000iu/dy for severe autoimmune/immunodeficiency diseases – with mandatory monitoring of levels of calcium, creatinine, 25OHvitD3 and now PTH levels;

to mega 10 000iu/kg eg 650 000iu as a loading dose for eg TB or meningitis or severe trauma—which dose may maintain  25OHvit D3 blood levels in a “sufficiency” range above ~40ng/ml for a month or two, so obviously requires appropriate maintenance dosing.

Imported vitamin D3 100cwt concentrate powder (100iu/mg) per kg from an importing pharmacist costs about R500/kg ie R0.50/100 000iu- far lower than the cost of the highrisk plant xenocalciferol vitamin D2. Thus to the State (excluding packaging and dispensing cost) , the wholesale cost of vit D3 is about R0.15 per 50 000iu per week for maintenance dose; or for 50 000iu/day R10( US $0.6)/month ie retail abt R60pm ie US$5  for megadose therapy; compared to the quoted retail US$20/month in Brazil. .

     THE NEUROPATHY OF DIABETES, DRUGS/TOXINS, POST-VIRAL,TRAUMA,  SPONDYLOSIS, DEMENTIA:

PERIPHERAL NEUROPATHY:  Already in 2006 Oh-Park ,Sheehan .ea,  Lancet. Albert Einstein College of Medicine, New York wrote about AIDS-ARV neuropathy Charcot neuroarthropathy in the era of HAART.

Young, Dancho ea Tucson, Arizona, wrote 2012,   ” Charcot arthropathy is a devastating joint condition that affects persons with neuropathy. With HIV/AIDS treatments prolonging the lives of these persons, it is likely that long-term sequelae of the disease will become more evident in the near future. Patients with this disease frequently develop peripheral neuropathy. A high index of suspicion must be raised in any patient with peripheral neuropathy of any cause and a red, hot, swollen, painful foot for Charcot neuroarthropathy to give these patients proper treatment to help prevent the devastating effects of Charcot neuropathy with its potential consequences including foot ulceration and amputation. We know only too well the same applies to diabesity, as it did in the days of heavy smoking.”
In 2013 Zubair ea in India showed that diabetics with foot ulcers had vitamin D levels 1/4 of that of matched diabetics without foot ulcers; and “factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.3), neuropathy [OR 6.9retinopathy [OR 3.3;  nephropathy [OR 3.1) and smoking [OR 4.5]. It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is a secondary effect or is a direct action of vitamin D on certain components of the immune system.”  

Tiwari, Singh, Swain  ea at Hindu Universities Uttar Pradesh,India have shown elegantly in                          

    *2012 Tiwari ea   Vascular calcification in diabetic foot and its association with calcium homeostasis.      Vascular calcification (VC), long thought to result from passive degeneration, involves a complex process of biomineralization, frequently observed in diabetes and an indicator of diabetic peripheral vascular disease.. ..In  74 patients with diabetic foot ulcer,   Vascular calcification was present in 42% of patients. Significant difference in vitamin D, HbA1C, and eGFR  levels was observed in VC +ve compared to VC -ve.  Severe vitamin D deficiency was more common in VC +ve (51%) compared to in VC -ve (18%). Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05) in patients with vitamin D < 10 ng/ml compared to others. .and        

     * Br J Nutr. 2013. Tiwari  ea  Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection.   In Diabetic Patients with and without  infection (n289), 25(OH)D (nmol/l) was significantly lower (16) v. 20ng/ml  P < 0·001) in cases than in controls. Risk of severe vitamin D deficiency (25(OH)D < 10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. ;  and the need for vitamin D supplementation in such patients for a better clinical outcome

*.in  Br J Nutr.. 2014 Tiwari ea  show Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection  . Vitamin D is a potent immunomodulator and  a common deficiency  in different population groups including patients with diabetic foot infection.   in 112 diabetic foot infection cases and 109 diabetic controls , cases had significantly higher concentrations of IL-6 (P≤ 0.001), IL-1β and TNF-α (P≤ 0.006) than controls. Risk of severe vitamin D deficiency (25(OH)D <10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1β (r -0.323; P≤ 0.001) and  IL-6 but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations.

 

This year  2016     Wukich , Sadoskas  ea. University of Pittsburgh & Georgetown USA  in Diabetes Metab Res Rev.  show that (Charcot) neuroarthropathy (CN) of the ankle and hindfoot  is challenging to treat surgically or nonsurgically. Deformities associated with ankle/hindfoot CN are often multiplanar, resulting in  malalignment; and  shortening of the limb often occurs from collapse of the distal tibia, and ankle, with  significant alterations in the biomechanics of the foot. eg predisposing the patient to lateral foot ulceration. Collapse of the talus, secondary to avascular necrosis or neuropathic fracture, further accentuates these deformities and contributes to a limb-length inequality   CONCLUSION:  Surgical reconstruction of ankle and hindfoot CN is associated with a high rate of infectious and noninfectious complications. Preoperative measures that can improve outcomes include assessment of vascular status, optimization of glycemic control, correction of vitamin D deficiency and cessation of tobacco use. 

Now 2016 Basit A,  Malik RA5 ea in  Universities Karachi Pakistan & Manchester UK ,  show that A single intramuscular dose of 600000IU vitamin D in  143 participants with predominantly type 2 diabetes, aged ~ 52.3years, with high Douleur Neuropathique 4 (DN4) score  by  20weeks gave significant increase in 25(OH)D (from 31.7 to 46.2±10.2ng/mL, p<0.0001) and  significant  reduction (p<0.0001)  in positive symptoms on the DN4 , and total pain score (p<0.0001, The Basit – Malik Pakistan-Manchester paper showing great efficacy of 600 000iu vit D3 load dose in peripheral neuropathy diabetics matches the huge 40% improvement benefit of similar loading and monthly vit D3 dose against severe PTB shown by Salahuddin ea in Pakistan in 2013 http://www.ncbi.nlm.nih.gov/pubmed/23331510 that we have previously analyzed in this column

ie  apart from smoking; the very low vitamin D levels common in most but especially ill people  associate   with about 5 fold  risks of uncontrolled diabetes, infections,  retinopathy , progressive leg ulcers, peripheral neuropathy  and arthritis- Charcot arthroneuropathy- -and thus  gangrene and amputation; and vigorous safe (supraphysiological) vit D boost reverses the risks. .

 

And a reminder that a 2015 study in Cape town from Coussens ea Universities in W Cape and Penn State confirm what we see daily in practice, that vitamin D deficiency is endemic  in our population

 

while as we have pointed out repeatedly, the State here continues to dispense the inferior vitamin D2 (as the fraudulently labeled “strong calciferol”, not disclosing that it is ergocalciferol  D2) despite this plant xenohormone vit D2 having been rejected by world authorities in favour of the much cheaper and effective  human D3 cholecalciferol.

 

 

       And now 2016 Cadegiani , Brasilia, Brazil another  landmark massive-vit D dose report ;  Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment.Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. This reports a patient with severe and refractory myasthenia gravis (MG) who followed a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil  (Coimbra ea) and she had her first complete remission after this type of treatment  for at least 18 months (ie at least 50 million iu) with increased vitamin D serum levels (400 to 700 ng/mL) and major fall in her AChR antibodies – but acute relapse when vit D was inadvertently stopped and her vit D level halved; with again recovery when megadose vit D was resumed  CONCLUSIONS: This case may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases

 

     The above case concurs with previous reported massive dose daily vitamin D3: Finamor , Coimbra ea , Universities of Brazil  2013 A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months ie ~7million iu  in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya “milk”) and hydration (minimum 2.5 L daily).. After treatment 25(OH)D3 levels significantly increased (from ~15 to 106-132ng/mL. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.

 

 

     neurologist Prof Dr Cicero Coimbra from Univ Sao Paulo  presents their results since 2002 in over 4000 pts ( 1000 patients each with multiple sclerosis and Parkinson’s diseases), who have been well controlled without other therapies,  provided the dose is high enough- 10 000iu/d up to about 1000iu/kg/d eg >70 000iu/d for the obese, on a low calcium ie low dairy/peanuts diet, high fluid intake and high exercise, to normalize blood calcium,  and titrate  PTH level to  the low normal range. Dr Cicero Coimbra discusses  high dose vitamin D toxicity: https://www.youtube.com/watch?v=Vxwk-YPrx7o&feature=youtu.be. PTH level should not be completely suppressed. In their clinic ( of 7 doctors)  for Autoimmune chronic diseases incl MS, RA, SLE, psoriasis, vitiligo, type 1 diabetes ,  they have treated over 4500 pts on this high quality vit D3 high fluid  low calcium diet  protocol, with only 14 cases of reversible vitamin D toxicosis (hypercalcemia) so far detected ie 0.3%. Babies of mothers thus treated in pregnancy  have high psychomotor development. (Vitamin C supplement should not be concurrently excessive to avoid oxalosis). They define success as being disease-free or non-progressive old fixed disabilities- 95% reach full cure. There vit D3 therapy  costs only ~US $20/mo, to optimize the immune system against both infections and autoimmune disease let alone cancer. Optimal dose of vit D3 replacement becomes at least 10 000iu/day for adults especially with autoimmune diseases  due to common vitamin D resistance. Ideally testing baseline blood and urine at baseline and after a few months on at least 10 000iu/d.

 

 

     In Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency:. 2010. Cipriani ,Minisola ea .University of Rome  Italy tested    48 young subjects with vitamin D deficiency with a single oral dose of 600,000 IU of cholecalciferol. The 25(OH)D level was ~15.8ng/ml at baseline and became ~77ng/ml at 3 d (P < 0.001) and ~62 ng/ml at 30 d (P < 0.001). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. CONCLUSIONS: A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.

 

       Looking at some new alarmist myth refs about vit D3 overdose :

Moderate  ie physiological increase in just vitamin D levels and intake  (from average diet and sunshine and a traditional supplement) within the average population bloodlevel range understandably has modest  benefit- reversing at least rickets-  in an  indoor living clothed population, even  1st world middleaged:  from Wisconsin Univ, Karen Hansen ea’s recent RCT – JAMA 2015- Treatment of Vitamin D Insufficiency in Postmenopausal Women confirmed this, showing little practical benefit shortterm (ie over 12mo) between placebo, and supplemented vit D3  5600iu/wk and 25000 iu a week, (~3600iu/d);  the highest dose perhaps doubling the baseline 20ng/ml  25OH vit D level. ie into the low “adequate” range average around 40ng/ml.

Be aware again that  the same university’s group published in 2014   An Evaluation of High-Dose Vitamin D 2  for Rheumatoid Arthritis Karen Hansen ea that vit D2 ~100 00iu/month  for a year actually worsens patients and lowers vit D3 levels  , so there is no longer excuse for using vitamin D2 supplement when it blocks D3 receptors and lowers blood vit D3.

The inferiority of vit D2 was confirmed in eg    Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients.  Gottschlich, Kagan U Cincinnati Ohio 201550  patients  aged 1 to 18yrs with burns  were enrolled. All participants received multivitamin supplementation ,  plus , 100 IU/kg D2, D3, or placebo daily  RESULTS: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low 25OHD  at discharge, and %deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in clinical outcomes between treatment groups, although vitamin D supplementation demonstrated clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formationThe high incidence of low serum 25OHvit D levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity. 

The perception seems to be that up to 40 000iu vit D3 a day, a bld level below abt 150-350ng/ml  is safe, ie unsafe above that. The evidence for such ceiling ie  higher dose harm in fact is lacking since as we have previously discussed here,  healthy people have taken up to 150 000iu a day for decades without evidence of harm…  provided they took adequate fluids, and did not take supplements of calcium, or also take high  vitamin A which notoriously causes acute hypercalcemic toxicity, or have rising calcium levels . .

But note that vit K2 improves absorption of vit D3 CHOLECALCIFEROL , and vit K2 and magnesia improve benefit of vit D3,while protecting against overdose effects ie calcification, stones  and confusion.  Problem in many  toxicity reports is that they used either vit D2 ergocalcif (WHICH BLOCKS THE NEEDED D3) , or used accidental massive overdose (millions of units vit D ) daily for months- or massive INJECTIONS) or combined vit D WITH CALCIUM REPLACEMENT AND/ OR EXCESSIVE VITAMIN  A  – which combinations are  dangerous;  we need magnesium (not calcium  or high vitamin A supplements).

    Vitamin D3: What’s the Latest? recent 2015 reviews from  Univ California and CommonHealth contrast the Instit Medicine IOM (Big-Pharma-sponsored)  conservative target of  vit D3 800 to max 4000iu/d with much evidence that safe optimal D3 dose may be up to 10 000 to 50 000iu/d, and up to  1 000 000iu as an acute eg antiinfection  loading dose; with risk of toxicity only if blood level exceeds 150-500ng/ml. the evidence-based IOM recommendation of optimal blood level 20-40ng/ml, up to 2000iu a day promoted by conservatives like Prof JoAnn Manson, contrasts with the more proactive view of eg Prof Michael Hollick and the Vitamin D Council promoting double that dose as supplements, safely up to 10 000iu/day.

 

   SO  I continue to take vit D3 ~70 000iu/wk ie ~10 000iu/d,  with vit K2 supp ~700mcg a wk ie 100mcg/dy and a balanced multisupplement incl. magnesia in addition to a multisupplement A-Z, and fish oil and Lugols iodine 15% 2 drops a day; with if I do get a “flu” attack during bad weather, prompt abolition by a few antibiotic doses of topup Lugols iodine 15% a few tsp (ie ~1000mgs iodine),  and vitamin D3 eg 300 000iu, and vitamin C a few tsp orally and by sniffing. .

The problem with many adverse effect reports of vit D3 overdose eg the Dominican Republic Soladek  2011 report Lowe ea below, and Prof Heaney’s response,  is that they failed to even consider the massive associated  overdose of the far more hypercalcemic vitamin A let alone calcium supp reported by most  patients. It becomes apparent that NO calcium supplement should be encouraged on a prudent diet; but instead supplements of  Vit D3, magnesia, vits K2 and C, CoQ10, and fish oil ; in addition to a balanced (A to Z) RDA-based multisupplement for seniors  like eg Solal’s,  Vital’s Multitime, Centrum etc.. with a low calcium diet if massive dose vitamin D3 is indicated as in autoimmune diseases (Coimbra ea).

Ndb

APPENDIX: RECENT REFS:
VITAMIN D ANABOLIC STEROID ABUSE IN SPORT?

the Australian Govt  Supplement Overview   has an intriguing report on vit D in sports, with no hint of vit D supplement being a steroid abuse. .http://www.ausport.gov.au/data/assets/pdf_file/0003/594174/CORP_33413_SSF_Vitamin_D_FS.pdf        Vitamin D is classified as a fat soluble vitamin which acts functionally as a steroid hormones. There are 2 different isoforms of Vitamin D: D3 (cholecalciferol) which is the important isomer formed in human   skin and D2 (ergocalciferol) which is the plant-derived ie xeno-equivalent. D2 was the first isoform to be characterised   and was first used in Vitamin D supplements and for food fortification. D3 is now considered preferable. D3 is   biologically inert until converted in the liver to 25(OH)D and to 1,25(OH)D in the kidney.  Vitamin D plays an important role in calcium and phosphorous homeostasis (bone health),but more so in  gene expression and cell growth. The recent recognition of Vitamin D receptors in most body tissues indicates a role for Vitamin D in  many aspects of health and function. Vitamin D is now known to be important for optimal muscle function.

         The principal source of circulating vitamin D comes from exposure to ultraviolet B (UVB) radiation from sunlight.   In 2010, the Institute of Medicine issued new Dietary Reference Intakes for Vitamin D, assuming no sunlight exposure: this included a Recommended Dietary Intake of 600 IU/d and an Upper Level intake of 4000 IU/d  (www.iom.edu/vitamind). BUT no evidence has ever been published to support this ceiling intake.

Whereas Vitamin D deficiency can lead to several health issues including increased risk of bone injuries, chronic musculoskeletal pain and viral respiratory tract infections. There is also emerging evidence that supplementing Vitamin D in athletes with sub-optimal Vitamin D levels may   have beneficial effects on athletic performance in particular strength, power, reaction time and balance.

         There is no universally accepted definition of vitamin D deficiency however, the following definitions based on  serum levels of 25(OH) Vitamin D are often cited:

Vitamin D deficiency: serum levels < 20 ng/ml (50 nmol/L);  Vit D insufficiency: serum levels < 30 ng/ml

Vit  D sufficiency: serum levels > 30 ng/ml    Ideal Vit D range*: 30-50ng/ml 

Toxicity: > 150ng/ml, when combined with raised serum calcium

(*Higher status may be preferred for athletes to allow a greater safety margin and to optimize performance;   some agencies working with elite athletes often set their own thresholds for desired Vitamin D concentrations)

Ie they quote no evidence for the 25OH vit D ceiling of 50ng/ml.

 

Confirmed in

  Owens DJ1, Close GL ea .  UK Universities  . 2015..A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Skeletal muscle is a direct target for  vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (~18ng/ml). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors.  Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.

 

2016 Is there an optimal vitamin D status for immunity in athletes and military personnel?  He CS1, Gleeson M ea .Vitamin D is mainly obtained through sunlight ultraviolet-B (UVB) exposure of the skin, with a small amount typically coming from the diet.It is now clear that vitamin D has important roles beyond its well-known effects on calcium and bone homeostasis. Immune cells express the vitamin D receptor, including antigen presenting cells, T cells and B cells, and these cells are all capable of synthesizing the biologically active vitamin D metabolite, 1, 25 hydroxy vitamin D.There has been growing interest in the benefits of supplementing vitamin D as studies report vitamin D insufficiency (circulating 25(OH)D < 50 nmol/L) in more than half of all athletes and military personnel tested during the winter, when skin sunlight UVB is negligible. The overwhelming evidence supports avoiding vitamin D deficiency (25(OH)D< 30 nmol/L)to maintain immunity and prevent upper respiratory illness (URI) in athletes and military personnel.Recent evidence supports an optimal circulating 25(OH)D of 75 nmol/L to prevent URI and enhance innate immunity and mucosal immunity and bring about anti-inflammatory actions through the induction of regulatory T cells and the inhibition of pro-inflammatory cytokine production. We provide practical recommendations for how vitamin D sufficiency can be achieved in most individuals by safe sunlight exposure in the summer and daily 1, 000 IU vitamin D3 supplementation in the winter.

 

Sarris J1, Ng CH1. Ea, Universities  of Melbourne, & Deakin, Australia;  &  Harvard Boston; 2016  show in   Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. http://www.ncbi.nlm.nih.gov/pubmed/27113121  Adjunctive  standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several  neurochemical pathways implicated in depression. A systematic search up to 2015 for clinical trials using adjunctive nutrients for depression    RESULTS: Primarily positive results were found for studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D,.  Mixed results were found for zinc, folic acid, vitamin C, and tryptophan. . No major adverse effects were noted in the studies  adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.

Raina AH1, Bhat FA1 ea ., India.. 2016 Association of Low Levels of Vitamin D with Chronic Stable Angina: A Prospective Case-Control Study.  http://www.ncbi.nlm.nih.gov/pubmed/27114971  Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. METHODS: a prospective case-control study in  100 cases of chronic stable angina compared controls. Vitamin D deficiency was defined as <20 ng/mL, vitamin D insufficiency as 20-30 ng/mL and normal vitamin D level as 31-150 ng/mL.RESULTS: The prevalence of vitamin D deficiency among cases and controls was 75% and 10%, respectively. 13% had normal vitamin D levels (31-150 ng/mL). None had a toxic level of vitamin D. Among the controls, 10% were vitamin D-deficient, 57% had normal vitamin D levels. The mean vitamin level among cases and controls was 15.53 ng/mL and 40.95 ng/mL, respectively, statistically significant (P ≤ 0.0001). Among the cases, we found that an increasing age was inversely related to vitamin D levels (P = 0.027). Low levels may be an independent, potentially modifiable cardiovascular risk factor.

Jetty , Glueck   Kumar  ea . Jewish Hospital Cincinnati, Ohio, USA  2016  show 12mo Safety of 50,000-100,000 Units of Vitamin D3/Week in Hypercholesterolemic  Vitamin D-Deficient,   Patients with Reversible Statin Intolerance. : http://www.ncbi.nlm.nih.gov/pubmed/27114973   Such Vitamin D3 therapy (was safe and effective when given for 12 months to reverse statin intolerance in patients with vitamin D deficiency. Serum vitamin D rarely exceeded 100 ng/mL, never reached toxic levels, and there were no significant change in serum calcium or eGFR

https://riordanclinic.org/2013/10/vitamins-d3-and-k2-the-dynamic-duo/ As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.

http://www.amazon.com/MIRACULOUS-RESULTS-EXTREMELY-SUNSHINE-EXPERIMENT-ebook/dp/B005FCKN2S#reader_B005FCKN2S     is a recent book by Jeff T Bowles .

 Newsletter: Gary Null and vitamin D toxicity    2010 by John Cannell, MD http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/     “Warning: If you intend to take massive doses of vitamin D based on this newsletter, which I highly recommend you do not, read the entire newsletter. In addition, accurate determination of side effects of massive doses of vitamin D was not available in the early 1930s, nor was accurate determination of the true amount in each pill possible.    Is 2,000,000 IU/day of vitamin D toxic?   Ask Gary Null, alternative medicine guru and entrepreneur. He took his own supplement, Ultimate Power Meal, for a month and became extremely ill; one batch of Power Meal apparently contained 1,000 times more vitamin D than it should. That is, it contained 2,000,000 IU of vitamin D3 per serving instead of 2,000 IU per serving. Mr. Null became sicker and sicker as he gulped it down.

After suing his own supplier for permanent physical damage, Mr. Null then reported it took 3 months to get the extra vitamin D out of his system and that he is now alive and well. If Mr. Null took it for the full month that he claims, and if his Power Meal contained 2,000,000 IU per dose, Mr. Null consumed 60,000,000 IU in one month. Could he really be fine now with no lasting injuries?  In an attempt to answer that question, I went back to the 1930s and 40s.  Massive doses in the 1930s  The earliest references I could find to enormous doses of vitamin D were in the 1930s. In 1935, Drs. Dreyer and Reed, of the University of Illinois School of Medicine, published their observations on 700 patients treated with “massive” doses of vitamin D for up to two years.1  ….” read on..http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/ http://www.livescience.com/50765-vitamin-d-supplements-toxicity.html

Vitamin D Overdose   Dr. Liji Thomas, MD  2016  http://www.news-medical.net/health/Vitamin-D-Overdose.aspx   vitamin D toxicity can occur from high intakes of supplements containing vitamin D, but not from dietary intake. Prolonged sun exposure also does not result in vitamin D toxicity because the previtamin D3 is degraded as the skin heats up, and also because of the formation of various other non-functional forms of vitamin D from the thermally activated compound.   Long term intakes of vitamin D above the upper limit recommended causes symptoms of toxicity. However, the intakes must be higher than about 40,000 IU/day, or the serum level of 25-hydroxy above 500-600 ng/mL, and the patient is usually also taking excessive amounts of calcium as well.

Dietary Supplement–Induced Vitamin D Intoxication  Klontz KC, Acheson DW.  To the Editor 2004:    Vitamin D intoxication that is associated with the consumption of dietary supplements is reported rarely. In 2004, the Food and Drug Administration (FDA) learned of the following case. A 58-year-old woman with diabetes mellitus and rheumatoid arthritis began taking a dietary supplement called Solutions IE Ageless Formula II on January 12, 2004. Fatigue, constipation, back pain, forgetfulness, nausea, and vomiting soon developed. On March 15, 2004, she was hospitalized because her speech was slurred, and a blood glucose reading taken at home was 30 mg per deciliter. On admission, her serum levels were as follows: calcium, more than 3.75 mmol per liter; 25-hydroxyvitamin D, 460ng/ml (normal range, 9-5);; parathyroid hormone, 12 ng per liter (normal range, 10 to 65); and creatinine, 265 μmol per liter.   The patient was treated with intravenous normal saline, furosemide, and pamidronate. On March 19, 2004, while still hospitalized, she was informed by the product distributor of an error in product formulation such that 188,640 IU of vitamin D3/d  had been added to the daily serving size of six capsules instead of the intended 400 IU. IE SHE HAD TAKEN ~12.2MILLION IU OF VIT D3 IN 2 MONTHS. At discharge on March 24, the patient’s serum levels were as follows: calcium, 2.60 mmol per liter; blood urea nitrogen, 10.0 mmol per liter; and creatinine, 221 μmol per liter. The patient died from a cause unknown to us on January 8, 2005.   Laboratory analysis of the product by the FDA, obtained from one of two lots reportedly overfortified with vitamin D3, revealed 186,906 IU of vitamin D3 in each serving size of six capsules, indicating that the patient had consumed roughly 90 times the recommended safe upper limit of 2000 IU per day. Long-term daily vitamin D consumption of more than 40,000 IU (1000 μg) is needed to cause hypercalcemia in healthy persons.2     In March 2004, the product distributor announced that during the previous month it had received three complaints from customers who had been hospitalized for hypercalcemia and vitamin D toxicity

2011 Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. Lowe H1, Bilezikian JP. ea  Columbia Univ, NY.. http://press.endocrine.org/doi/10.1210/jc.2010-1999?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&   Hypercalcemia in ambulatory patients is occasionally caused by vitamin D toxicity. We report nine patients presenting to Columbia University Medical Center with hypercalcemia due to a supplement from the Dominican Republic containing massive amounts of vitamin D. All reported recently taking Soladek readily available in the Dominican Republic and in Upper Manhattan. serum calcium values before the ingestion of Soladek were not elevated  According to the manufacturer’s label, each 5-ml vial of Soladek contains vitamin D3 (600,000 IU), vitamin A (120,000 IU), and vitamin E (5 mg). Laboratory analysis by HPLC revealed that the supplement actually contained vitamin D(3) (864,000 IU) and vitamin A (predominantly retinyl palmitate 123,500 IU) per vial.IE 864000 IU VIT D /day FOR UNKNOWN DURATION. a similar case was reported earlier  http://www.thecamreport.com/2009/11/soladek-toxicity-in-a-60-year-old-woman/

Comments by Prof Robert P. Heany    Creighton University, Omaha, Nebraska  on Lowe et al:   Hypercalcemia in vitamin D intoxication JCEM   http://press.endocrine.org/e-letters/10.1210/jc.2010-1999        The report by Lowe et al. on vitamin D intoxication from an OTC supplement (1) is instructive and useful. I comment on the authors’  suggested mechanism of hypercalcemia in such cases. The authors propose that the elevated concentration of serum 25- hydroxy-vitamin D [25(OH)D] is the responsible agent, through loose binding to the vitamin D receptor. While my colleagues and I have shown that 25(OH)D can improve calcium absorption (2), I believe there is a simpler explanation for hypercalcemia in vitamin D intoxication, particularly as the reported values of 25(OH)D were not uniformly high in these nine cases. [In fact the patient with the highest serum calcium had actually the lowest value for 25(OH)D.] Instead, as Vieth suggested several years ago in a paper actually referenced by Lowe et al. (3), elevation of free circulating 1,25(OH)2D (calcitriol) is the most parsimonious explanation. This level is not commonly measured, and was not reported in the cases described by Lowe et al. Vieth has estimated the binding capacity of the D-binding protein (DBP) at approximately 4700 nmol/liter, and it is generally recognized that fewer than 5% of its binding sites are occupied at typical cholecalciferol inputs. However, in the face of huge cholecalciferol doses, as in the nine cases described here, it can easily be calculated that most or all of the binding sites on the DBP would be occupied by cholecalciferol itself as well as by 25(OH)D and 24,25(OH)2D, all of which are bound to the DBP more avidly than is calcitriol. Lowe et al. did not measure serum cholecalciferol, but it is virtually certain that its concentration would have been elevated, if for no other reason than that the capacity of the hepatic 25-hydroxylase is limited, and serum cholecalciferol concentration rises steeply for cholecalciferol inputs in excess of the saturation level of the 25-hydroxylase [which typically occurs at serum cholecalciferol levels of about 10 nmol/L and serum 25(OH)D of about 80 nmol/liter (4)].Even if all of the binding sites of the DBP were not continuously occupied by less polar metabolites, high occupancy would shift the equilibrium between the free and the bound calcitriol, so that free calcitriol concentration would likely have been substantially above normal values continuously. The authors speculate as to the origin of the elevated total calcitriol concentrations, given the down-regulation of the renal 1-á- hydroxylase in such cases. 

 

     2016.Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. Lupton JR1Michos  ea .  Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).OBJECTIVE: Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function.METHODS: We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (≥20-30 ng/mL), and optimal (≥30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression.RESULTS: In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group.CONCLUSION:  Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG

 

  1. Low-Level VitaminD Is strongly Associated with Atrial Fibrillation in Patients with Chronic Heart Failure.Belen E1, , Cetin M2ea. Atrial fibrillation (AF) freuently accompanies heart failure (HF), and causes exacerbation of symptoms and treatment failure in such patients. Vitamin D was recently suggested to be an important mediator of cardiovascular disease, including HF.OBJECTIVES: The aim of this study was to evaluate the relationship between vitamin D deficiency and AF in patients with chronic HF. METHODS: The study included 180 chronic HF patients that were divided into 2 groups based on having sinus rhythm [AF (-) group] or chronic AF [AF (+) group]. Vitamin D status was assessed via measurement of the serum 25-hydroxyvitamin D (25[OH]D) concentration.RESULTS: Mean age of the patients was 66 ± 8.7 years and 53.9% were male. There weren’t any significant differences in age, gender, body mass index, etiology or chronic HF stage between the 2 groups. The vitamin D level in the AF (+) group was significantly lower than in the AF (-) group (11.05 ng/mL vs. 20 ng/mL, p < 0.001) The left atrium to body surface area ratio (LA/BSA) was significantly higher in the AF (+) group (45.03 mm/m2 vs. 42.05 mm/m2, p < 0.01). Independent predictors (based on multiple regression) of AF were vitamin D level (OR = 0.854, 95% CI: 0.805-0.907, p < 0.001) and LA/BSA ratio (OR = 1.077, 95% CI: 1.003-1.156, p < 0.05). The optimal vitamin D cut-off value for the prediction of AF was 16.50 ng/mL, with a sensitivity of 76.0% and specificity of 65.5% (AUC = 0.75, 95% CI: 0.67-0.82).

 

Vitam Horm. 2016;100:255-71. doi: 10.1016/bs.vh.2015.10.001. Epub 2015 Nov 30. Molecular Approaches for Optimizing Vitamin D Supplementation.   Carlberg C1.Vitamin D can be synthesized endogenously within UV-B exposed human skin. However, avoidance of sufficient sun exposure via predominant indoor activities, textile coverage, dark skin at higher latitude, and seasonal variations makes the intake of vitamin D fortified food or direct vitamin D supplementation necessary. Vitamin D has via its biologically most active metabolite 1α,25-dihydroxyvitamin D and the transcription factor vitamin D receptor a direct effect on the epigenome and transcriptome of many human tissues and cell types. Different interpretation of results from observational studies with vitamin D led to some dispute in the field on the desired optimal vitamin D level and the recommended daily supplementation. This chapter will provide background on the epigenome- and transcriptome-wide functions of vitamin D and will outline how this insight may be used for determining of the optimal vitamin D status of human individuals. These reflections will lead to the concept of a personal vitamin D index that may be a better guideline for an optimized vitamin D supplementation than population-based recommendations.

 

  1. Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis.Zhao, , Huang J3. The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015.METHODS: We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration.: Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007).CONCLUSIONS:   Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥30ng/ml  was associated with a 60% lower risk of bladder cancer incidence.

the Ides of March 2016:  Where have we been the past 5 years in ignoring the crucial role of K2 supplement  with vit D3? against cancer, fractures, infections, vascular disease and diabetes , 

      like the crucial role of Lugols iodine + selenium, and magnesium (not calcium), coQ10, and animal, marine and coconut ie saturated fat oil- supplement  for all chronic disease prevention?

     Considering that our western processed food staple diet, and the diet of the poor majority everywhere,  is increasingly deficient especially in these nutrients,  with by profit-motivated industrial design  disease-promoting cholesterol-depletion, refined sugars, transfats, antibiotics, hormones,  and noxious at-any-dose elements from fluorine and aluminium upwards.

 

I see I was  promoting K2 in my emails 4 years ago,  and since 2009, on my Healthspanlife blog  ie in  my lectures  and thus in my healthspanlife blends .

     But  I indeed don’t seem to have published a review of K2 on my blog- till now!
– and there are so many refs out there since the first K2 mention on Pubmed in 1946,
and its first Pubmed  human supplement mention in 2002  Improvement with maternal supplement of vitamin K2  of vitamin K status of breastfeeding infants  (MK40).  Nishiguchi T, Terao T ea.   Semin Thromb Hemost. 2002 : 28533-8.

Unlike the Big Pharma-Disease-Industry- controlled denialists of conservative safe  natural phamacological vitamin therapy  like the   Linus Pauling Institute   and   Wikipedia                 https://en.wikipedia.org/wiki/Vitamin_K2,

the vitamin  K2 Polish scientist Dr Katarzyna Maresz PhD     2015 writes (see abstract below)  Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health.  Maresz K1. International Science and Health Foundation Krakow, Poland    Inadequate calcium intake can lead to decreased bone mineral density, thus  increase the risk of bone fractures. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. … The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.
      While vit D3  cholecalciferol soltriol  was the multiprevention megavitamin   of the past decade, and CoQ10 the decade before that, catching up with the protean benefits of increasingly diet- deficient vitamins published (350 000 Pubmed citations) the past century, and of vitamin K since 1936, and K2 since 1946,
vit K2 is the most publicized ie advancing megavit of the current decade:
Adequate intake ie ~45 to ~150mcg/d is crucial with magnesium, boron etc to balance vigorous  vit D3 supplement,
for both bone, immune/cancer, and cardiovascular health.
Thus even just ~55mcg/d K2 supplement HALVES the risk of cardiovascular disease – very important in overweight/stressed/ aging people. 

BUT The authorities quoted have assessed safety and optimal longterm effective doses of vitamin K3 and vitamin D3 IN ISOLATION  for major prevention. However, we know that optimal nutrition is balanced nutrition, not one or two nutrient is superdose with an average fastfood mediocre diet. 

This finally convinces me to add vit K2 ~ 35 to 100mcg/day ie 200 to 700mcg/wk  to my own  vit D3 supplements. at a trivial bulk wholesale cost of  ~10mg/d 1% K2 ie ~R0.1/day or R14 – ( US$1)   bag  per 40 weeks of vit D3 @ 50 000iu vit D3 twice a month.

Like  Mercola 2010  http://articles.mercola.com/sites/articles/archive/2010/08/26/this-could-be-even-bigger-than-the-vitamin-d-discovery.aspx,             Byron Richards already in 2010 wrote a major review promoting K2 multipurpose: http://www.wellnessresources.com/health/articles/vitamin_k2_bones_cardiovascular_health_blood_sugar_control_cancer_prev/

As a recent BBC review   details,    “Vitamin K1 has a relatively short half-life and is rapidly cleared from the blood  by the liver within eight hours. In comparison vitamin K2 has a longer half-life of up to 72 hours, meaning it remains biologically active in the body for longer.   Vitamin K2 is also absorbed better by the body, and is linked to cardiovascular health. It directs calcium to the bones, and prevents it from being deposited where it shouldn’t be, for example arteries and organs, where it can cause harm.

The Kansas Riordan Clinic  promotes the Superhuman Duo  of D3+K:   they point out that ” Because an accurate LD50 for vit D in humans has never been determined (thank God!) most researchers use the LD50 for dogs as an estimate for humans, using a hypothetical human subject weighing  50kg, 110 pounds: in order to reach the LD50 dose, that subject would need to consume over 3,500 of the 50,000 IU D3 caps in a 24 hour period (146 capsules an hour,  total  175million iu) in order to have a 50% chance of dying. By conscientiously using vitamin K2 in conjunction with D3, this issue of “metastatic calcium” is thoroughly avoided.  Finally, like vitamin D3, strong evidence demonstrates vitamin K’s amazing ability to reduce cancer risk. For example, men taking vitamin K2 mk7 (a naturally occurring long acting form of K2) at 45 mcg a day can statistically reduce their risk of prostate cancer by 60%! That is just one of many cancer risks that are reduced significantly by regular K2 ingestion.      As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.

            For the safety of vigorous dose of vitamin D3, the masses of D3  evidence we assembled by August 2015   is that 2million units as a single oral dose does no harm to nonagenarians, nor has over 100 000iu a day for 28 years ie over a billion  iu  in middle-aged women.  

 In 2015,    Like *Joe Leech                                          and             *Hogne Vik   ,                                                    *Angela Pifer nutritionist notes the essensiality of balancing vit D3 with K2  “Vitamin D3 should never be taken alone. Always take a combination Vitamin D3/ Vitamin K2 liquid emulsion, at night for best absorption. This is because vitamin D3 improves calcium absorption across the GI tract and vitamin K2 is the cofactor needed to transfer calcium into your bones, and not your arteries.   (Eur J Clin Nutr. 2016 Feb 24. doi: 10.1038/ejcn.2016.3. Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules.   KnapenVermeer  ea . Maastricht University, Netherlands.   In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt  fortified with vitamin K2 (as menaquinone-7, MK-7) and vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7, For 42 days in healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules.  RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found.   CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.)

Some recent of the other 5000 K2 refs on Pubmed, apart from the abundant reviews by Garry Gordon, Joe Mercola, Mike Howard, Jeff Dach, Townsend letter, ea  , are

Integr Med (Encinitas). 2015;14; 34-9.  Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health.  Maresz K1. International Science and Health Foundation Krakow, Poland    Inadequate calcium intake can lead to decreased bone mineral density, thus  increase the risk of bone fractures. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. An adequate intake of vitamin K2 has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K2, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. An increased intake of vitamin K2 could be a means of lowering calcium-associated health risks.    “  Calcium ConcernsIf at least 32 mcg/d of vitamin K2 is present in the diet, then the risks for blood-vessel calcification and heart problems are significantly lowered, the elasticity of the vessel wall is increased. Moreover, the beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women has been seen in clinical trials. If less vitamin K2 is present in the diet, then cardiovascular problems may arise. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. A study on 564 postmenopausal women also revealed that intake of vitamin K2 was associated with decreased coronary calcification, whereas intake of vitamin K1 was not.  ”  A recent, double-blind, randomized clinical trial investigated the effects of supplemental MK-7, MenaQ7 (NattoPharma ASA, Hovik, Norway) for a 3-year period in a group of 244 postmenopausal Dutch women. The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.It showed a significant improvement in cardiovascular health as measured by ultrasound and pulse-wave velocity, which are recognized as standard measurements for cardiovascular health. In that trial, carotid artery distensibility was significantly improved for a 3-year period as compared with that of a placebo group. Also, pulse-wave velocity showed a statistically significantly decrease after 3 years for the vitamin K2 (MK-7) group, but not for the placebo group, demonstrating an increase in the elasticity and reduction in age-related arterial stiffening.” 

*     Nutrients. 2015 Oct ;7;8905-15.  Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).Vossen, Kroon ea  Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months.  We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
*            
Ugeskr Laeger. 2015 Aug;177:V12140700. Vitamin K2 influences several diseases]. Hey H1, Brasen CL. Lillebælt, Kabbeltoft, In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients witr can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.
*           Oman Med J. 2014;29;172-7. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review.  El Asmar, Arbid  ea, American University of Beirut, Lebanon. Vascular calcification, a cause of cardiovascular morbidity and mortality, is an actively regulated process involving vitamin K dependent proteins (VKDPs) among others. Vitamin K is an essential micronutrient, present in plants and animal fermented products that plays an important role as a cofactor for the post-translational γ-carboxylation of glutamic acid residues in a number of proteins. These VKDPs require carboxylation to become biologically active, and they have been identified as having an active role in vascular cell migration, angiogenesis and vascular calcification. calcification.
*             Dermatoendocrinol. 2015 Jan;6e968490. Vitamin K: an old vitamin in a new perspective.   Gröber U, Reichrath J, Holick MF, Kisters Essen, Germany.&  Boston, MA USA. The topic of “Vitamin K” is currently booming on the health products market. Current research increasingly indicates that the antihaemorrhagic vitamin has a considerable benefit in the prevention and treatment of bone and vascular disease. Vitamin K1 (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-7, menaquinone-7). Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically reduced. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, inhibit vessel wall calcification, support endothelial integrity, facilitate bone mineralization, are involved in tissue renewal and cell growth control, and have numerous other effects.

2016 CHOOSING BREAST SCREENING, BAD DIET/LIFESTYLE ARE OBSESSIVE-COMPULSIVE DISORDERS. SCREENING MAMMOGRAPHY ASSAULT UPDATE : FLOOD OF PROGRESS AGAINST BREAST CANCER/ DISEASE.

neil.burman@gmail.com  Cape Town.                   read this  in concert with:               combating rising-occurrence-of-breast-cancer-in-younger-women;  and

 

UPDATE 22 APRIL 2016:     BREAST SCREENING OF WELL WOMEN BY SOUTH AFRICAN  MEDICAL SCHEMES a reminder:

DIAGNOSTIC  xray mammography is an invasive  DIAGNOSTIC  procedure FOR A BREAST LUMP/BLEEDING  that irradiates and crushes  the breasts; and is therefore universally recommended by independent experts and trials  ONLY  for women ( with a breast lump) where cancer needs to  be excluded; and provided as a free service by the state every 10 years, and by medial schemes as a prescribed medical benefit PMB  on demand.

                         BREAST SCREENING IMAGING  IN THE WELL:  as this column   has repeatedly pointed out from international experts’ and local experience, because of the long-known RISKS of xray mammography- which risks balance if not exceed the BENEFITS- the RSA Council for Medical Schemes has just publicized  again   that screening mammography for the above reasons is not a PMB . “ 4. Screening: Current evidence regarding Screening Mammography to reduce mortality of breast cancer is conflicting. Screening xray mammogram is therefore not  prescribed minimum benefit (PMB) level of care. Clinical breast examination is considered PMB level of care. “http://www.medicalschemes.com/files/Circulars/Circular24Of2016.pdf
.
          To capture the images (PICTURES)  of findings on clinical breast exam (which remains the worldwide gold standard as to whether xray mammogram is needed), the Natural Wellness Clinic follows  the SA Cancer Association and many authorities worldwide for the past 5 years in offering no-xray no-crushing simple mechanical breast  Sure Touch imaging as part of the clinical exam for those who desire the extra reassurancehttp://www.cansa.org.za/get-screened-early-detection/.

     See the new reviews below of the efficiency of ultrasound (China 2015) over  xray mammography;
and  of Sure Touch  by Prof Cary Kaufman(Univ Washington)  ea at  the 2014 San Antonio Breast Cancer Symposium, which confirms what we tabulated 2 years ago from 11 comparative trials, that in 6 comparative trials, Sure Touch was equal to or better  (sensitivity vs specificity vs accuracy) overall than xray mammography, ultrasound or  clinical exam; clinical exam plus one if not two of the nonxray screenings  greatly improve risk assessment before deciding whether mammography- or lump excision- is warranted. .
UPDATES:
October is breast cancer awareness month. For that, the Radiological Association of RSA recently published on line a lengthy promo for screening mammography http://www.grocotts.co.za/content/newsletter-nycu-october-breast-cancer-awareness-month-22-09-2015  that ignores the tsunami of expert evidence showing that xray mammography actually does more harm than good, and overall doesnt save lives. and at the same time criticizes Sure Touch and thermography as prescreening, while ignoring that they are done by highly trained practitioners eg nurses and radiographers, and have many evidence-based studies supporting their use.
      As this column has pointed out for years, and radiologists and oncologists remain silent about, the USA Government National Cancer Institute and the  UK NHS cancer website continue to point out objectively that the benefits and harms of well-breast screening mammography are finely balanced- without even mentioning the gigantic cost of screening in resources, patient discomfort, and major emotional drain; when in such older western women, below 4% die of breast cancer. Contrary to the blind for-profit  mantra for annual breast-crushing -and irradiating xray mammography from the Radiology Associations, the Cancer Association of South Africa recently continues to promote  SureTouch – non-invasive device for safe breast screening
      In the prestigious Jnl of the Royal Society of Medicine 2015,
in the July issue  two  major international  groups –  Autier ea from France and London and Tabar ea from Sweden, Cambridge, London, Atlanta and Tapei – fiercely contest the spin, the validity of Swedish studies the past decades  that claimed benefit from screening mammography.
 and
     in the September issue of the same leading UK journal, two breast screening experts- from Denmark and London-  again point out the dangers of and lack of benefit from routine xray screening mammography:
         In support of   the comprehensive review of Xray  Mammography screening is harmful and should be abandoned , by Prof Peter C Gøtzsch  Nordic Cochrane Centre, Rigshospitalet, Denmark,

     Prof Michael Baum  University College London, London responded:   “Catch it early, save a life and save a breast’: this misleading mantra of mammography:     The one thing every layperson and politician knows with confidence with regard to breast cancer is that you’ve got to ‘catch it early,’ preferably before you can even feel it.    It may come as a shock to some readers, but I disagree and there’s such a thing as ‘catching it too early’. Like Peter Gøtzsche in the current edition of the JRSM,1 the global breast cancer screening programme has to be considered a ‘failed experiment.’ I also agree that the screening service as now provided should be closed down. I would go on to suggest that all the human and technological resources released by the closure of the National Health Service Breast Screening Service (NHSBSP), be redeployed into more fruitful areas for enhancing women’s health. That aside we have much to learn from the fact that the experiment, set up in good faith, has indeed failed to live up to our expectations. The mantra, ‘Catch it early, save a life and save a breast’, turns out to be a false promise. Screening may have a borderline effect on reducing cause-specific mortality but does not save lives as judged by the outcome measure of all-cause mortality.2 As far as saving breasts is concerned, the opposite is the truth. Populations of women attending for screening have a greater chance of a mastectomy than any control group.2

         The hypothesis being tested in the experiment originated in the last half of the 20th century and was based on the assumption of the log linear kinetics of cancer development with distant dissemination being determined by the size (a poor surrogate for ‘age’) of the cancer. This was considered so self-evident as to have been translated into an ideological expression of faith. Yet, the experiment failed. The national breast screening programmes around the world have provided us with a natural experiment of the greatest historical importance, first, because it failed to deliver and, second, because of the recognition that mammography in asymptomatic women leads to the over-diagnosis of ‘pseudo-cancers’.3

        Cancer was defined by its microscopic appearance about 200 years ago. The 19th century saw the birth of scientific oncology with the discovery and use of the modern microscope. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer.4 As earlier generations had correlated the autopsy findings observed with the unaided eye with the clinical course of cancer 100 years earlier,5 so Virchow correlated the microscopic pathology of the disease. However, the material he was studying came from the autopsy of patients dying from cancer.

       In the mid-19th century, pathological correlations were performed either on cadavers or on living subjects presenting with locally advanced or metastatic disease that almost always were pre-determined to die in the absence of effective therapy. Since then without pause for thought, the microscopic identification of cancer according to these classic criteria has been associated with the assumed prognosis of a fatal disease if left untreated. There is a syllogism at the heart of the diagnosis of cancer and therefore runs like this; people frequently die from malignant disease, under the microscope this malignant disease has many histological features we will call ‘cancer,’ ergo anything that looks like ‘cancer’ under the microscope, will kill you. I would therefore like to restate the argument, that some of these earliest stages of ‘cancer’ if left unperturbed, would not progress to a disease with lethal potential. These pathological entities might have microscopic similarity to true cancers, but these appearances alone are insufficient to predict a life-threatening disease. If we stand back and take a broader look at nature this shouldn’t be surprising.

      Conventional mathematical models of cancer growth are linear or logarithmic, in other words completely predictable at the outset; predicting transition from in-situ phases to early invasive and from early invasive to late invasive over time. Most natural biological mechanisms are non-linear or better described according to chaos theory. The beauty of the tree in full leaf and the symmetry of a sprig of broccoli, reflect their fractal geometry that looks remarkably similar to the appearance of the mammary ducts and lobules under the microscope.6 The rate of growth and the development of the lung along with the fingers and toes in the fetus cannot be described in linear terms. Prolonged latency followed by catastrophe should not be all that surprising.7 We accept the case for prostate cancer, as we know that most elderly men will die with prostate cancer in situ and not  die of prostate cancer. In fact, the UK national PSA screening trial (ProtecT) is predicated on that fact with two a priori outcome measures defined, deaths from prostate cancer versus the number of cancers over-detected and treated unnecessarily.8

      Further support for this contention comes from other sources. For example, there has been an epidemic of bilateral mastectomies in the USA following the uncontrolled proliferation of MRI scans in the routine work-up of women presenting with a single focus of early breast cancer.9,10 The MRI scan is guilty of unveiling not only latent foci of pseudo-cancers outside the index quadrant but also latent foci harboured in the contra-lateral breast. This is heartbreaking when one considers all the work over three decades and all the patient volunteers in trials of breast conservation.11,12 We now know with the utmost confidence that breast-conserving surgery is a safe alternative to more radical surgery, yet that hard won knowledge is brutally ignored when the surgeon is induced to treat the MRI image rather than the patient. Next, it is worth noting that contrary to all common sense predictions, the increased rate of detection of duct carcinoma in situ has led to an increase in the mastectomy rate for the screened population.2,3 Up to 45% of screen detected cases of duct carcinoma in situ end up having mastectomy because of the multi-centricity of the disease.13 Yet, the paradox is that clinically detected multi-centric invasive breast cancer is relatively uncommon.14         In conclusion, therefore, we can state, with a great deal of conviction, that a large proportion (in the order of 50%3) of screen detected (pre-clinical) foci of breast cancer is not programmed to progress if left unperturbed. This observation is of seismic importance and could set the agenda for breast cancer research for the next decade. If we choose to ignore these observations, because they fail to support our ideological belief system, then we will have missed an opportunity of a lifetime and that would be unforgivable.

The superiority of even ultrasound screening over xray mammography has been shown in women with dense breasts (like most today in our obese society) in  Br J Cancer. 2015 ; 112: 998–1004. A multi-centre randomised trial comparing ultrasound vs mammography for screening breast cancer in high-risk Chinese women Shen ea,  Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials.   Methods: At 14  centres across China during 2008–2010, 13 339 high-risk women aged 30–65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrolment and 1-year follow-up.   Results:  Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group (P=0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P=0.04) with a better diagnostic accuracy (0.999 vs 0.766, P=0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P=0.51) and positive predictive value (72.7 vs 70.0% P=0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively.

      update:         28 July 2015 Mammography’s $4-Billion Problem   Millions of women receive false-positive results annually, and 20,000 are overtreated.  by Shannon Firth             WASHINGTON — For too many women, breast cancer screening does more harm than good, a researcher said here.     Thermography is a non-invasive imaging procedure which uses a heat-sensitive camera to capture an image of the human body. Since we are pretty much symmetrical beings, seeing one breast significantly warmer than the other would be a red flag, suggesting the presence of a heat-generating lesion. The lesion could be an abscess, or increased blood vessels feeding an early tumor, or simply a recent hematoma from injury. In any case, no radiation is used to obtain the image, there is no compression of the breast, and the study can be repeated frequently with no risk of inducing neoplastic transformation. Studies show that thermography can diagnose significant inflammatory disease up to several years before a mammogram shows calcification. Insurance does not pay for this test. Thermography does not diagnose cancer. Nor does mammography. At least thermography is helpful and does no harm. And if a mass is palpated, then excisional biopsy is indicated no matter what the tests show. Common sense needs to prevail.

July 06, 2015  Mammograms Again Found to Have No Impact on Mortality   JAMA Intern Med.  .  Breast Cancer Screening, Incidence, and Mortality Across US Counties   Harding, Pompei; Burmistrov, Welch, Abebe, Wilson,     Harvard University, Cambridge, Massachusetts   Importance  Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate.   Objective  To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size.  Design, Setting, and Participants  An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53 207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015.   Exposures  Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years.   Main Outcomes and Measures  Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population.Results  Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P  = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12).   Conclusions and Relevance  When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis.

            Unlike irradiation and crushing by mammography, Sure Touch  physical (pressure transducer) scanning on its own combined with usual clinical exam  is similar to ultrasound in scope and feel, but better –  in comparative trials is  like if not better than mammography  in sensitivity and specificity, but without the significant harms of crushing and  xray irradiating mammography. ( Only tissue biopsy can confirm or exclude  potentially threatening cancer (or pick up-  over-diagnose- pre-cancers -many of which are best left unknown in eg breast, prostate, colon, will never cause cancer disease in lifetime).
 As Prof Peter Gotzsche says, WELL people with a silent ie tiny internal  cancer – whether in situ eg DCIS, or localized,  DO NOT HAVE DISEASE; ie such silent lumps vanishingly rarely   cause illhealth.
see latest warnings at    Too Much Medicine   Alexandra Barrett Univ Sydney, Australia:    Overdiagnosis in mammography screening: a 45 year journey from shadowy idea to acknowledged reality: note the  graph about overdiagnosis, that as with screening for silent prostate cancer, the rate of advanced cancer hasnt increased with invasive screening, DESPITE the ~40% futile  increase in (early) breast cancer diagnosis by crushing, biopsy , irradiation and surgery. Not saving lives , but perhaps earlier death by screening terrorizing, , burning, cutting and poisoning. .

Figure1

2 March 2015: this update says it al about the futility and risks of breast cancer mammography screening:

Breast Cancer Screening: Benefits and Harms:  Jill Jin, MD, MPH

For More Information: Centers for Disease Control and Prevention

Image not available.

Breast cancer is the second most common cancer among women in the United States.

BENEFITS OF SCREENING    Screening for breast cancer means looking for signs of breast cancer in all women, even if they have no symptoms. The goal of screening is to catch cancers early. Early-stage cancers are easier to treat than later-stage cancers, and the chance of survival is higher. Routine screening for breast cancer lowers one’s risk of dying of breast cancer.

Screening for breast cancer is done by mammography. A mammogram is a special series of x-rays taken of the breast. A doctor looks for any abnormal signs or patterns on the mammogram that might be breast cancer. These signs usually show up on the mammogram before any lump can be felt in the breast. If there is anything unusual on the mammogram, more tests have to be done. These tests can include another mammogram, an ultrasound, or a biopsy. Studies have shown that women who have routine mammograms have 10% to 25% less chance of dying of breast cancer than women who do not have mammograms.

CURRENT US SCREENING GUIDELINESIn the United States, the US Preventive Services Task Force recommends that women aged 50 to 74 years get a screening mammogram every 2 years. For women younger than 50 years, some women may choose to be screened, but not all women need to be. This depends on several factors, as discussed below.
      POSSIBLE HARMS OF SCREENING Mammograms are not perfect tests. Some cancers are missed by a mammogram. On the other hand, sometimes mammograms find things that look like cancer but turn out not to be cancer. This is called a false-positive result. False-positive mammogram results lead to more testing, which is time consuming and can cause unnecessary anxiety. On average, among all 50-year-old women who start breast cancer screening, more than half will have a false-positive mammogram result over the next 10 years

Another possible harm of screening is overdiagnosis. This means finding something on a mammogram that is breast cancer or has a chance of becoming breast cancer, but is such a low-risk type of tumor that it would never have caused any health problems if left alone. Instead, because it was found on mammogram, standard cancer treatment, such as surgery and radiation therapy, is recommended. In cases of overdiagnosis, these treatments are unnecessary and costly and can have both physical and psychological side effects. It is difficult to know exactly how often overdiagnosis happens, but some studies estimate that 1 in 5 breast cancers found on mammograms are overdiagnosed and lead to unnecessary treatment.

   BALANCING BENEFITS AND HARMS  The pros and cons of breast cancer screening are different for every woman. Age is an important factor. Even though the general recommendation is to start screening at 50 years of age, for women at higher risk (such as those who have breast cancer in their family), it may be a good idea to start screening at a younger age. Each woman also has different personal values, especially toward the idea of unnecessary medical tests and treatments.      

Why I’m Opting out of MammographyChristie AschwandenJAMA Intern Med.    at  a routine appointment a few days after my 40th birthday, my gynecologist gave me a prescription for a mammogram. There was no discussion, no explanation. Just a slip of paper, handed to me without a word as I left the examination room. When I asked the doctor what she’d just given me, she told me it was an order for a mammogram. I could call the number to schedule an appointment.    “Wait—why should I get a mammogram?” I asked.                                                    “Because it could save your life.” Her voice conveyed a note of impatience…  read on..

 24 Jan 2015        early diagnosis ( by screening the well), and treatment of pre-cancer of eg breast and prostate is increasingly discredited as dangerous, especially for women at ~10years younger prime-of life ( and much higher risk than men)  due to menopause. .

           so just how safe can it be- for cancer spread, and misdiagnosis- when needle biopsy is done on a silent 7mm incidentally palpated lump, and the surgeon sticks a needle in (blind)  and stirs up the lump before biopsy.  What does stage 1A at the excision 2 months later mean then?
            BACKGROUND .  we have oft reported below that the mammoth ATLAS trial showed that  after diagnosis of preclinical “cancer” at around 50years (by screening mammography, biopsy, mostly mastectomy or DHRT, then annual screening mammo on tamoxifen for 5 to 10 years),  15  years after diagnosis, of the hundreds of women who had by then died +-70-yrs old of diverse causes, only 14% had had clinical cancer recurrence but 45% had silent breast cancer present at autopsy.
       This is the same cancer  rate found in random adults killed in accidents. SO WHAT  MAMMOGRAPHY SCREENING OF WELL BREASTS ACHIEVED EXCEPT COUNTLESS IRRADIATION, SURGERIES AND THUS STRESS?
        Now the IBIS-1 trial shows that   Between 1992 and 2001, 7154 eligible women aged 35 to 70 years were randomized to 5 years of tamoxifen 20 mg/day or placebo. All women were deemed to be at increased risk for breast cancer based on predefined family history or benign breast disease criteria. In this  20-year follow-up report, the cumulative incidence of breast cancer (defined as invasive breast cancer or DCIS) was reduced ~47% from   12.3% with placebo to 7.8% with tamoxifen  (P < .001). Reductions were seen in the risk for developing ER-positive breast cancer (HR, 0.66) and DCIS (HR, 0.65) but not ER-negative breast cancer (HR, 1.05). BUT There was no significant difference in breast cancer–specific or overall mortality. –and  in IBIS1, tamoxifen increased uterine cancer rate from 20 on placebo to 29 on tamoxifen, of whom 5 women in the tamoxifen group died from endometrial cancer compared with none in the placebo group (P = .06).
and in the Asian-  Taiwan population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes. in  22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004,     15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group.  Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08–1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a 31% significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19–1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes.

And Tamoxifen prevention lessens future breast cancer, but both tamoxifen and the enormous burden of mass screening do not save lives, create vast numbers of patients. so early diagnosis and treatment  of preclinical breast cancer- overdiagnosis- does not save lives, in fact seriously increases non-breastcancer  mortality including by increasing diabetes, melanoma, deepvein thrombosis, uterine carcinoma, depression-stress-related vascular disease, etc..
22 January 2015

Commentary: Prof Peter  Gøtzsche  Nordic Cochrane, Denmark. Int. J. Epidemiol. Jan 2015: SCREENING- A SEDUCTIVE PARADIGM THAT HAS GENERALLY FAILED US: Screening healthy people has face value and great public and political appeal. It looks so simple, and yet screening is fraught with difficulties. These start already with the terminology, and common slogans like, ‘Catch the disease early, before it has produced any symptoms!’ are misleading on two counts.

First, disease means lack of ease, which is not what we understand by being healthy; but people who work with screening tend to forget that they deal with healthy people. For example, women being invited to mammography screening are often called patients in scientific articles.            The second error is the assumption that the disease is caught early. That is rarely the case, and breast cancer is again a good example. If we assume that the growth rate for a particular cancer is constant, then the women have harboured the cancer for 21 years on average before it is large enough to be detected by mammography screening.1 Finding precursors to cancer is of course an entirely different matter.

A third problem with screening is that it always causes harm. Sometimes it also leads to benefits, and sometimes the benefits are sufficiently large to outweigh the harms. The main focus in screening trials should therefore be to quantify the harms, but this has rarely been the case, if ever. Screening trials focus on disease-specific mortality, which may seem natural, but it is the wrong outcome. Screening leads to overdiagnosis, and interventions that are beneficial for real patients can be lethal for healthy overdiagnosed people. Radiotherapy of overdiagnosed women may kill at least as many as those who are spared dying from breast cancer by attending breast screening.2

Total mortality should therefore be the primary outcome in screening trials of mortality, and Saquib et al. report a systematic review in this issue of the journal that aimed at clarifying whether screening lowers total mortality for diseases that carry a high disease-specific mortality.3 They focused on cancer, cardiovascular diseases, type 2 diabetes and chronic obstructive pulmonary disease. They did not find any screening trials for hypertension or chronic obstructive pulmonary disease. Disease-specific mortality was reduced with ultrasound for abdominal aortic aneurysm in men, mammography for breast cancer and faecal occult blood test and flexible sigmoidoscopy for colorectal cancer, but the risk ratio point estimates for all-cause mortality were all very close to 1.00 (range 0.98–1.03).

Screening proponents often say that disease-specific mortality is the right outcome, arguing that in order to show an effect on total mortality, trials would become unrealistically large. I believe this argument is invalid, for both scientific and ethical reasons. We do randomized trials in order to avoid bias, and our primary outcome should therefore not be a biased one. Drug interventions are usually more common in a screened group, and they tend to increase mortality for a variety of non-disease related reasons.4

From an ethical perspective, it is problematic to screen the whole population in a certain age group without knowing whether this makes people live longer, while knowing almost certainly that it makes people less happy. It took 50 years after the first randomized trial of mammography started before we knew what the psychological consequences are of the many false-positive findings.5 A specially designed questionnaire was developed using focus groups and women who had attended screening were followed up for 3 years. Even after so long a time, those who had experienced a false-positive diagnosis had an anxiety level (and other psychological problems) that fell between that for women with breast cancer and women who had always been told they did not have cancer. This study showed for the first time that the psychological harms of breast screening are substantial and long-lasting, and they affect a huge number of healthy women, as the cumulative risk of a false-positive result after 10 mammograms ranges from about 20% to 60%.6 Added to this comes the psychological harm inflicted on all the overdiagnosed women who do not know that they are overdiagnosed but think that they suffer from a fatal disease. It is therefore pretty clear that any utility analysis that takes the psychological harms of breast screening into account will come out negative, as was recently reported by the Swiss Medical Board.7

It is worth noting that when screening does not work, it might be because beneficial effects are outweighed by harmful ones. Diabetes drugs, for example, are approved on the basis of their glucose-lowering effect without knowing what they do to patients. And the only large trial of tolbutamide ever performed was stopped prematurely because the drug increased cardiovascular mortality.4 Rosiglitazone was once the most-sold diabetes drug in the world, but it was taken off the market in Europe in 2010 as it causes myocardial infarction and cardiovascular death; and pioglitazone has been linked to heart failure and bladder cancer.4

Screening is popular, but we need to be much more careful in the future when we contemplate approaching healthy people with our screening tests, and should demand much stronger evidence than when we treat patients.”

Stanford University Saquib ea.Int J Epidemiol. 2015 Jan.  Screening for disease doesnt  save lives in asymptomatic adults? Systematic review of meta-analyses and randomized trials. Several popular screening tests, such as mammography and prostate-specific antigen, have met with wide controversy and/or have lost their endorsement recently. We systematically evaluated evidence from randomized controlled trials (RCTs) as to whether screening decreases mortality from diseases where death is a common outcome.We selected 19 diseases (39 tests) out of 50 diseases/disorders for which USPSTF provides screening evaluation. Screening is recommended for 6 diseases (12 tests) out of the 19. Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for NO DISEASES FOR ALL-CAUSE  mortality estimates .  Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively.  CONCLUSIONS:Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent.
 Thus the  $trillion  screening mammo war   by the Disease Industry  on healthy breasts to create and find as much silent precancer as possible to profiteer burn and cut hots up. Its about ethics- that women are made anxious about the necessity (usually none)  for screening  and the harms understated:  Germany  (like Switzerland,  Scandinavia, Canada and USA)  also has grave doubts.
Mammo skeptics make new bid to stop U.K. breast screening trial   Frances Rylands-Monk, AuntMinnieEurope.com staff writer
with some good Forum comments that follow:

September 16, 2014 A U.K. clinical trial examining whether mammography screening should be offered to a broader range of women must be halted due to ethical and medical concerns, according to a letter published in BMJ by a group of longtime opponents to breast screening. But not everyone agrees, and the controversy looks set to continue.    In a strongly worded letter published (BMJ) on 16 September,  a group led by Dr. Susan Bewley raised concerns about the U.K. age-extension trial, which is examining whether the age range for screening should be extended to both younger and older women. They challenge the design of the trial as well as the qualifications of its chief investigator, calling the study an “out of control trial with ineffective oversight.”“Our concerns relate to the science and ethics of this trial. Women should always be told the full facts — here they are unwittingly participating in a research trial without fully realizing that the harm/benefit ratio is uncertain,” Bewley said. “There is no overall mortality benefit from breast screening at any age if you look at the Nordic Cochrane review — only a reduction in breast cancer mortality.”

update 9 November 2014  WOMEN WITH HIGHEST BLOOD VITAMIN D  HAVE 90% LOWER RISK OF BREAST CANCER : PLoS One. 2013; 8(1): e49312.  Evidence from a Chinese Population Based Case-Control Study and Meta-Analysis of the Observational Studies   Peizhan Chen,Hui Wang ea; Chinese Academy of Sciences,  Shanghai,  China
NATIONAL CANCER INSTITUTE:   Table 3. Estimated Benefits and Harms of Mammography Screening for 10,000 Women Who Undergo Annual Screening Mammography Over a 10-Year Period:
Age, y No. of Breast Cancer Deaths Averted With Mammography Screening Over Next 15 y No. (95% CI) With ≥1 False-Positive Result During the 10 yc  No. (95% CI) With ≥1 False Positive Resulting in a Biopsy During the 10 yc  No. of Breast Cancers or DCIS Diagnosed During the 10 y That Would Never Become Clinically Important (Overdiagnosis)d 
40 1–16 6,130 (5,940–6,310) 700 (610–780) ?–104e
50 3–32 6,130 (5,800–6,470) 940 (740–1,150) 30–137
60 5–49 4,970 (4,780–5,150) 980 (840–1,130) 64–194

         Invisible Risks, Emotional Choices — Mammography and Medical Decision Making   Lisa Rosenbaum, M.D. cardiologist & journalist    N Engl J Med  October 16, 2014:       in 1993, frightened New York City parents agitated for asbestos removal from schools. As often occurs, public fear trumped expert risk assessment; the parents’ demands were met, the victory was celebrated, but then the celebration crashed. It turned out that removing the asbestos would mean closing the schools for weeks, disrupting parents’ lives. “As the costs of the removal came on-screen,” writes behavioral economist Cass Sunstein, “parents thought much more like experts, and the risks of asbestos seemed tolerable: Statistically small, and on balance worth incurring.”1

It is partly because our perceptions of risk are so influenced by our changeable emotions that we turn to experts to perform cost–benefit analyses. From environmental regulations to nuclear energy, such expert assessments inform policies meant to improve public health and welfare. We would not ask airline passengers to create standards for aviation safety or car owners to optimize fuel-emission standards, and in medicine, too, we still depend on expert-generated guidelines. Increasingly, however, in this era of patient-centered care and shared decision making, those guidelines emphasize the role that patient preference should play in the weighing of risk and benefit for any given evidence-based recommendation. This approach, with virtue on its side, is driven by the aspiration that we can, with the proper tools, empower patients to think like experts. But can we?

Many medical decisions involve considerable uncertainty and complex tradeoffs, but none seem to highlight the tension between emotions and risk assessment more than mammography screening. Although the U.S. Preventive Services Task Force (USPSTF) recommended in 2009 that women under 50 years of age not undergo routine mammography screening, and that those between 50 and 75 years of age be screened less frequently, screening rates have apparently held steady or perhaps even increased. There are many possible reasons for this trend: physicians’ habits, conflicting guidelines, medicolegal concerns, radiologists’ preference for the status quo, and the mandating of screening coverage for women of all ages in the Affordable Care Act. But I suspect that the trends also reflect the powerful role that emotions play in both reinforcing women’s commitment to screening and the challenge of communicating the potential harms of mammography.

Consider a discussion with a 45-year-old woman with no family history of breast cancer about the most likely harm of screening: a false positive result. Maybe you say, “For someone like you, there is around a 50% chance that if you have regular screening over the next 10 years, you will have a false positive result. That could lead to repeat testing, potentially including a biopsy, and lots of worry and anxiety.”2 But though doctors striving to reduce unnecessary testing tend to emphasize the psychological stress involved, this possibility does not seem to loom large for women facing this decision.

Perhaps these results reflect the likelihood that, when facing tough tradeoffs, we anticipate and try to avoid regret, rather than anxiety. Despite the demonstrable harms on the population level, cancer screening rarely begets regret for the individual. As Ransohoff and colleagues have written about the persistence of prostate-cancer screening, “the screening process is one without negative feedback. A negative test provides reassurance. A positive one is accompanied by gratitude that disease was caught early. And a false positive test, regardless of the distress it may cause, is nevertheless followed by relief that no cancer was ultimately found.”5 So women who have had false positive mammograms may spend the rest of their lives worrying that they are at heightened risk for breast cancer. But they are not left with regret about having had the test in the first place.

What about the risk of overdiagnosis — being diagnosed with and treated for a tumor that would never have become clinically significant? The potential toxic effects of treatments, ranging from chemotherapy and radiation to lumpectomy and mastectomy, make overdiagnosis the greatest potential harm of mammography screening. Though overdiagnosis has been notoriously difficult to quantify, a recent analysis of data on mammography screening over the past 30 years suggests that of all breast cancers diagnosed, 22 to 31% are overdiagnosed.6 Nevertheless, there are few risks of this magnitude that are more “off-screen” than overdiagnosis.

The first challenge in conveying this risk to women is that many are simply unaware that overdiagnosis occurs. One survey showed that only 7% of women believed that there could be tumors that grow so slowly that an affected woman would need no treatment; another study showed that women found the concept confusing even after a brief educational intervention. After being educated, women thought the information should be considered in decision making, but most believed it would not affect their own intent to be screened.3,7

This disconnect between awareness and intent speaks to the fundamental challenge of conveying the potential harms of mammography screening. That is: we do not think risk; we feel it. As research on risk perception has shown, we are often guided by intuition and affect.8 For example, when our general impressions of a technology are positive, we tend to assume that its benefits are high and its risks are low. We estimate our personal risks of disease not on the basis of algorithms and risk calculators, but rather according to how similar we are, in ways we can observe, to people we know who have the disease. And when we fear something, we are far more sensitive to the mere possibility of its occurrence than its actual probability.

That may be why overdiagnosis does not resonate emotionally. We do not see women walking around with “an overdiagnosis.” Instead, we see breast-cancer survivors. We do not hear people complaining about having endured radiation, chemotherapy, and a lumpectomy. What we hear instead is, “Thank goodness I had a mammogram and caught it early.” Our relatives do not eye us critically when we get a mammogram that reveals a nascent tumor. But people shake their heads and say, “I wish she had taken better care of herself,” when we are diagnosed after not having been screened. Thus, we can be educated about overdiagnosis. We can refine our estimates about its likelihood and incorporate them into our recommendations, as the USPSTF did in 2009. But it is hard to summon fear of a risk that remains invisible.

So how do we balance the goal of engaging women in decision making with the reality that emotions play a powerful role in shaping our understanding of benefit and risk? Some experts emphasize the need to address sources of misperception that inform beliefs far outside clinical encounters. Researchers at Dartmouth, for example, have described the misleading nature of various screening-advocacy campaigns. One advertisement by the Komen Foundation, for instance, features a photo of a beautiful young woman, with a caption reading, “The 5-year survival rate for breast cancer when caught early is 98%. When it’s not? 23%.”9 Though 5-year survival rates, because of lead-time bias and overdiagnosis, do not actually tell you whether the test saves lives, the visceral appeal of “catching something early” easily eclipses the difficult mental calculations one must undertake to figure out why early detection does not necessarily mean living longer.

The problem is that once impressions have formed, whatever their source, educational efforts to address misperceptions often fail and can even backfire. In a recent randomized trial evaluating approaches to vaccine education, for example, researchers found that, among parents least likely to vaccinate their children, exposure to information emphasizing that there is no link between vaccines and autism mitigated misperceptions but nevertheless further reduced their intention to vaccinate.10 Indeed, the fact that sound scientific information that challenges beliefs can simply intensify those beliefs has been recognized by cognitive psychologists for decades. What was more disappointing in this study was that more creative attempts to engage parents emotionally, such as using images or narratives of children dying of measles, not only failed to increase vaccination intent but also cemented some parents’ conviction that there is a link between vaccines and autism.

If there is tension between belief and sound medical information regarding vaccines, for which the benefits so clearly outweigh the risks, the tension is only heightened for decisions with more complex tradeoffs. The vaccine study thus raises two key challenges for the profession.

The first is empirical. As the locus of decision making shifts toward the patient, this study reminds us how little we know about how beliefs inform interpretation of medical evidence — or about how to negotiate those beliefs in pursuit of better health. Closing this empirical gap is daunting. Not only does each person have his or her own belief system, but the particular beliefs that are relevant for a decision regarding, say, elective percutaneous coronary intervention or palliative chemotherapy may be quite different from those relevant to childhood vaccination or mammography screening. Moreover, even though it is more practical and financially feasible to conduct a study that looks at how interventions affect knowledge and intent, what we really need are long-term studies of how new approaches to sharing information affect downstream behaviors and outcomes.

Which brings us to the second challenge, more ethical than empirical: How do we balance the need to honor preferences and values with the imperative to translate our evidence base into better population health? Our current default, particularly since medical recommendations are increasingly debated publicly, is to emphasize that decisions are “personal.” After the 2009 guidelines were published, the Obama administration and many physician leaders were all over the news reminding us of the importance of personal preferences. But even as more data accrue, including a recent review suggesting that the harms of mammography are greater than we once thought and the benefits fewer,11 the message we hear is not “Let’s do fewer mammograms.” Rather, it is “Let’s honor patients’ preferences.”

Though we certainly need to be sensitive to patients’ values, it is often hard to distinguish values from an emotional understanding of risk. Consider the decision to initiate statin therapy for primary prevention of cardiovascular disease. One patient, an avid tennis player, may recognize the potential for improved cardiovascular health but feel that the prospect of myalgias simply outweighs any potential benefit. That is a preference. Another patient hates drug companies and therefore believes that statins must lack cardiovascular benefit and be highly likely to cause myalgias and liver disease. That is an emotional understanding of risk. Both patients arrive at the same choice, but should we really celebrate them as equally informed decisions?

The tangled nature of emotions and values is particularly relevant to mammography screening, as evidenced in qualitative research done since the 2009 guidelines were released. One study explored the beliefs and attitudes of an ethnically diverse sample of women in their 40s. Though many were unaware of the guidelines, the researchers found that educating them about the new recommendations strengthened rather than diminished their commitment to screening. Women also expressed fears that the guidelines were an attempt by insurers to save money and keep them from getting the care they needed. Many women, expressing their abiding conviction that mammograms save lives, said they would have “no use” for a decision aid and viewed the weighing of benefits and harms as “irrelevant.” In fact, many said they wanted to be screened more than once a year and beginning before the age of 40 years. Finally, many believed that it was unjust that laywomen had been left out of the guideline-development process and the weighing of potential benefits and harms that it entailed.12

Such responses echo a broader debate among leading scholars of risk perception about whom we should rely on to evaluate risk. Some, such as Sunstein,1 recognizing our general difficulties in thinking about probabilities, argue that this task ought to be left to experts who can create policies to maximize public welfare. But the psychologist Paul Slovic has argued that the very concept of risk is subjective. Whereas experts tend to conceive of risk as “synonymous with expected annual mortality,” Slovic reminds us that riskiness means more to people than mortality rates.13

Undoubtedly, the recognition of the affective nature of risk perception is critical to the physician’s role in helping patients live longer, higher-quality lives. But even if we can, in some general way, address misleading statistics that drive inflated perceptions of the benefits of mammography, what do we do about the 38-year-old woman who insists on annual screening because she just lost her best friend to breast cancer? Or the 43-year-old with fibrocystic breasts who last year had a false positive mammogram and is now convinced her risk is even higher? Is there some hierarchy of emotional reasoning dictating that certain causes of heightened fears are more acceptable than others? Or because we know it is often impossible to tease out sources of belief, much less rank them, is a better approach the more paternalistic one: definitive guidelines on which physicians base their recommendations, with less emphasis on the role that patient preference ought to play?

One of the hallmarks of heuristic reasoning, as emphasized by Daniel Kahneman,14 is that faced with a hard question, we answer an easier one instead. In some sense, then, as a profession, we have fallen into a collective heuristic trap. Rather than confront these thorny ethical questions head on, we have answered an easier question: Should we respect patients’ values and preferences? The right answer will always be yes. The much harder question is how to balance that respect with our professional responsibility to use our expertise to translate clinical science into better population health.

Defaulting to patient preference in the face of uncertainty has become the moral high ground. But it is as much our job to figure out how to best help our patients lead healthier lives as it is to honor their preferences. No matter how well we can define the tradeoffs of a medical decision, the threshold at which we decide that benefits outweigh harms is as subjective as individual patients’ perceptions of those tradeoffs. But this recognition does not stop us from making rigorous attempts to quantify the tradeoffs, any more than it should stop us from trying to better understand how our patients’ feelings and beliefs inform their understanding of those numbers, consequent behaviors, and health outcomes. As Slovic has emphasized, experts’ efforts to communicate risk will fail in the absence of a structured two-way process. “Each side, expert and public, has something valid to contribute,” he notes. “Each side must respect the insights and intelligence of the other.”13                                   

update 21 Oct 2014 Dr Garry Gordon writes :

  “Hello ,  What are you doing to detox your patients on a daily basis? We live in a crazy world where  nutritional supplements with little or no clear risks to consumers are seized/ restricted, but Authorities drag feet  on stopping the use of a proven toxin like BP-A found as a coating inside of most canned goods.  Please understand that Randy Jirtle at Duke has shown that BP-A made healthy brown Agouti mice become obese, yellow and diabetic!  That effect led to an epigenetic change, which will persist for generations and was shown to be an epigenetic change in methylation.Plan to protect yourself with lots of methylation support. I take my Beyond B12 sublingual product that provides Methyl Folate and Methyl B12. Please know virtually everyone tests positive for BP-A in urine much of the time, as we have great difficulty in avoiding this poison in our daily living. Yet authorities  ignores the dangers although they finally are doing something to protect babies a little.How can anyone practice effective medicine today and ignore the toxin burden we all carry. Remember when I got out of training in 1958 normal sperm count was 140 million; today few have 40 million. I detox daily with my “Power Drink” and PEMF and I definitely show real benefits even at age 79.“BPA has been linked to possible health problems of the brain, breast and prostate. In 2008, the environmental group Natural Resources Defense Council asked the FDA to ban use of the chemical because of what it termed “serious adverse health effects.”In 2011, the American Medical Association deemed BPA an “endocrine-disrupting agent” and urged that “BPA-containing products with the potential for human exposure be clearly identified.” The FDA said it continues to evaluate the safety of BPA-containing products.”http://online.wsj.com/article/SB10001424127887323740804578600113164806902.html?mod=djemHL_t

Wassertheil-Smoller S ea .   Albert Einstein College of Medicine, NY, write in Breast Cancer Res Treat. 2013 Oct;141(3):495-505.  Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women’s health initiative..  “Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk.   a prospective cohort study  of 7,728 women aged 50-79 at enrollment in the women’s health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis, showed :” At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60-0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.

Tying up Garry Gordon’s two themes above  is obviously the fact that , as in eg the USA ARED (Centrum) trial, the Lemon-Rollo McMaster supermouse trials and the Scottish Highlands,  and China supplement trials, multisupplements are longterm (especially with vigorous levels of vitamins C and D and magnesium) both antioxidant, insulin sensitizing, methylating, Nitric-oxide promoting and (heavy metal) detoxicants- ie promote healthspan and suppress degenerative diseases and infection. . .

 UPDATE 18 OCT 2014: more arguments against screening mammography from UK and Canada:Curr Oncol. Oct 2014; 21(5): 210–214.  Reflections on screening mammography and the early detection of breast cancer.  A Countercurrents Seriesa    S.A. Narod, MD  *Women’s College Research Institute, Women’s College Hospital, Toronto, ON.A little learning is a dangerous thing.— Alexander Pope, An Essay on CriticismIn the stormy aftermath of the recent publication of results from the 25-year Canadian National Breast Screening Study (nbss)1, various opinions questioning the validity of the study’s results have been expressed27. I was a latecomer to the study. In 2005, I was charged with oversight of the final record linkage and the statistical analysis and interpretation of the final data set. Dr. Anthony Miller has been my mentor since 1987. Our first joint paper, on screening for cervical cancer, was published in 19918. I chose not to respond to individual criticisms, but instead to collect my thoughts and to try to explain why the study authors saw no benefit from screening.Most of the criticism from the radiology community focuses on issues of study design (which they claim was inadequate) and on the quality of the mammography (which they also claim was inadequate). Cancer survivors bolster those criticisms with testimonials and appeals to common sense. Supporters of the study are drawn from the public health community, and they tend to focus on overdiagnosis and health economics.The report at issue is not the first emerging from the nbss. Earlier reports9,10 were criticized for not having allowed adequate follow-up time. But the 25-year results resemble the early results, and the authors are no longer criticized for premature disclosure. None of the first-generation critics have acknowledged the consistency; instead, they look elsewhere and point out other weaknesses. They claim that high-risk women were assigned to the mammography arm in violation of the principle of randomization. In his bestseller The Emperor of All Maladies, Siddhartha Mukherjee says, as a matter of fact, that high-risk women were assigned surreptitiously to the mammography arm, which explains the lack of observed benefit11.The most recent nbss report1 tallied the breast cancers that occurred in each of the two study arms after the screening period ended (that is, between years 6 and 25), counting 2584 cancers in the screening arm and 2609 cancers in the control arm. If the screening arm had been enriched for women at “high risk,” that enrichment must have been performed in a peculiar fashion, using only risk factors that have a transient effect. Perhaps Dr. Mukherjee would care to explain what those factors were. It follows that the excess of cancers seen in the screening period (years 1–5: 666 vs. 524) was a result of early diagnosis and not from stacking the deck.In any case, compelling evidence against the criticism of assignment of high-risk women to the screening arm is provided in the most recent analysis1, and that criticism is no longer raised (although no one has retracted or apologized). Instead, critics now insist that many women with palpable lesions were sent directly to the screening arm by duplicitous research assistants. There is no reason to believe that such actions (which would involve a national conspiracy of dozens of coordinators who spoke two official languages) were taken, but even if they had been, the study and its conclusions would not necessarily be invalidated. Even if all the women with prevalent cancers had been shunted to the screening arm, the situation could still be remedied by ignoring all cancers found at the first screening round (prevalent cancers) and focusing instead on the incident cancers. Such a strategy is not uncommon in screening studies. In the nbss, no woman had the opportunity to “cross the floor” from one study arm to the other after initial assignment. Therefore, if we exclude all prevalent cases from the analysis and focus on women with no cancer at study entry, we can re-evaluate the benefit of mammography thereafter. The hazard ratio for death from breast cancers detected in screening rounds 2–5 was 0.90 (95% confidence interval: 0.69 to 1.16;p = 0.40).But what about crossover? It is claimed that a certain proportion of the women in the control arm—perhaps as high as 20%—opted for screening off-study, in particular after the screening period was over. That crossover will, some say, eclipse a benefit of screening that might otherwise have ensued. That is, the benefit of mammography (which might well have been substantial) was nullified by a subcohort of independently-minded women who went for mammography at the end of the 5 years. That speculation is fanciful, but if true, should be welcomed, because it can now be said to a patient who, at age 40, requests a mammogram, that there is no hurry; she can come back in 5 years for a mammogram and achieve the same net benefit. And when she comes back at age 45, she can be reprieved again until age 50.Crossover is a form of contamination that results in misclassification of the exposed and unexposed groups. In a trial, it will tend to bias the result toward the null. The best way to avoid misclassification is to randomize the patients after they agree to participate—as the nbss did. In contrast, in the Swedish two-county trial (discussed in more detail a little later in this article), the subjects were randomized by intention-to-treat—that is, by whether they received or did not receive an invitation to mammography1215. Of the 78,085 women in Sweden who were offered screening, 69,645 accepted and 8440 declined. In effect, then, 8440 women in the Swedish study were de facto misclassified (versus an undisclosed number of hypothetical crossers-over in the Canadian study). The proponents of the Swedish study do not see that misclassification as a shortcoming, but instead use it to buoy their argument in favour of screening. They say that if everybody invited for screening came for screening, then the protective effect would have been more profound. In the Swedish study, all women in the control group were offered a screening test after the screening period ended (a reasonable thing to do); but those authors were not criticized for “contaminating” their study.

The second issue raised concerns the quality of the mammography. After all, the nbss tests were completed 30 years ago using 30-year-old technology. I still wonder how things might have been done differently. Mammography screening identified 212 women with breast cancer who would otherwise have been missed. They had cancers that were, on average, 1.4 cm in size, with 67% being node-negative. The survival of those women was very good. At the end of the study period, 170 women with a nonpalpable mammography-detected breast cancer were alive or had died of other causes. How many of those lives did screening save? Fifty? Twenty-five? Ten? Unfortunately, all we can say is that the number was too few to be noticed. If a significant number of those 170 lives had, in fact, been saved, surely the difference between study arms would have been noticeable. Breast cancer deaths numbered 180 in the mammography group and 171 in the control group. Perhaps some of the survivors believe that their lives were saved. They might perhaps have written a letter to the editor of their local newspaper extolling the virtues of mammography. But 42 women with a nonpalpable mammography-detected cancer died (none of whom has written a letter to the editor).

I am also among the authors of several publications on the benefits of screening by magnetic resonance imaging (mri) in high-risk women1618. Those studies were greeted as successes, given that they demonstrated how, with the use of mri, breast cancers could be downstaged. Those studies were accepted by the radiology community as being supportive of screening. Whether mri reduces mortality has not yet been shown. I cannot predict whether  mri screening will be effective in reducing mortality 10 years down the line, but I fully expect that if a mortality benefit fails to materialize, the studies will be criticized for using 30-year-old equipment and a poor study design.

Much of the criticism of the nbss has come from Drs. Daniel Kopans and László Tabár, and fellow travellers such as Siddhartha Mukherjee and Patrick Borgen27,11. They use the Swedish two-county trial as evidence of a good study that supports the use of mammography and quote a 30% reduction in mortality. Naturally, they do not criticize their canonical study, but it is time to take a closer look.

In the nbss, women were randomized on an individual basis after they had attended the study centre. The result was two groups of equal size and 100% compliance with the first screen. In Sweden, the two counties were divided into 19 geographic strata that were then divided into either 2 blocks (Östergötland) or 3 blocks (Kopparberg). The resulting 45 blocks were randomized, and women in more than half the blocks were sent a letter of invitation to screening. Of the 59% of women who received an invitation, 89% came for the first screen and 83% came for the second screen14.

The Canadian women were offered 5 mammograms 1 year apart. The Swedish women were offered mammograms every 2 years (ages 40–49) or every 3 years (ages 50–74) for up to 8 years. They underwent fewer screens (Table i). The cancers detected by mammography in Canada were similar in size to those detected in Sweden (Table i), but the size of the cancers occurring in the control group were very different. Those comparisons suggest that physical examinations or breast cancer awareness (or both) were important contributors to the size of cancers detected in Canada. A diminution of cancer mortality would not be expected to be associated with a 0.2 cm mean difference in tumour size, but might be expected with a net reduction of 0.7 cm in size19. Of the cancers detected in the screening arm of the Canadian trial, 68% were palpable. That fact has been a source of criticism. But a physical examination was not conducted as part of the screening protocol in Sweden, and the comparable number of palpable tumours was not given. Therefore, given the much longer mean time between screening visits in Sweden, and the high proportion of women in the screening arm that were never screened, I estimate that between 70% and 80% of the cancers in the mammography arm in Sweden would have been palpable and could have been detected by physical examination—had it been done. The fact that the relevant number is not given is a critical lapse. Suppose, for the sake of argument, that 100% of the cancers detected in the screening arm in Sweden were in fact palpable (not a gross exaggeration). What then would be the point of mammographic screening? And if that number (the palpable fraction) is not available, how can the results be judged? Neither the Swedish nor the Canadian trial can exclude the possibility that the benefit from invitation to mammography might have been restricted to women with palpable cancers.

A comparison of key parameters in the Canadian National Breast Screening Study (nbss) and the Swedish two-county trial

The Canadian study reports the number of cancers detected in the follow-up period after the end of the screening period and the number of subsequent deaths from breast cancer. From year 6 to year 25, 2584 incident cancers occurred in the screening group, resulting in 298 deaths (11.5%), and 2609 incident cancers occurred in the control group, resulting in 321 deaths (12.3%). Those data are important because they confirm that, in the absence of screening, the cancer incidence and mortality are equal in the study groups. Where are the comparable numbers for the Swedish study? Again, they are not given. But in looking at the extraordinary Figure 1 from the most recent report of the Swedish study12, the mortality curves are seen to continue to separate at 25 to 29 years after the initiation of screening, and long since screening had stopped.

Tabár and colleagues ask readers to believe that the benefits of mammography are everlasting (or at least for 20 years beyond the end of screening). They make that claim despite having no surety about whether the deaths from breast cancer in years 25–29 were the result of cancers diagnosed during the screening period or diagnosed after screening had stopped. They claim that most of the deaths from breast cancers diagnosed in the control arm occurred more than 10 years after diagnosis. Thus, the reader is asked to accept that a mean of 2.3 mammograms obtained in year 1–7 are more likely than a baseline imbalance in breast cancer risk to lead to a reduction in breast cancer mortality of 30% in years 25–29!

The incidence and mortality rates corresponding to cancers that were diagnosed after the screening trial was stopped are unavailable. Seeing the survival curves corresponding to cases detected in the screened and unscreened cohorts would be interesting. In the nbss, most cancer deaths occurred, as expected, within 10 years from diagnosis1. When the nbss was challenged as to having achieved an even balance in the study groups, the authors provided the relevant data. The Swedish authors should do the same. Patrick Borgen has stated that the  nbss is the “worst clinical trial ever done”5—an extraordinary statement. Either he has devoted his life to poring over medical tracts with the zeal of a Talmudic scholar, or he is speaking nonsense. But refuting his claim is easy: it takes merely the time required to read the Swedish papers.

Once the facts are accepted (that screening mammography fails to do what it was intended to do, and that overdiagnosis is real and substantial), then the most interesting questions can begin to be addressed. Did the nbss  fail because mammography is not a sufficiently sensitive imaging technique? Or has the screening community been working under false premises?

Consider sensitivity. Proponents of mammography say that the technique is currently better than it was in the 1980s, largely because it is more sensitive. (Specificity is also important, but is not at issue here.) They argue that “the more sensitive, the better.” The earlier a cancer can be identified and managed, the better. The smaller, the better. But those contentions generate an interesting paradox. Consider a woman with a small early-stage breast cancer. The recommendation is that this woman be followed with annual bilateral mammography for 5 or more years to identify recurrences and contralateral cancers20. That recommendation is based on the knowledge that the risk of contralateral cancer is between 0.5% and 0.8% annually21 and that a diagnosis of contralateral cancer is associated with an increase in mortality from breast cancer22. (It has not been shown that screening for contralateral cancer reduces mortality.) But mri is a much more sensitive screening tool than mammography, and by using mri in that setting, a small contralateral breast cancer can be identified in 4% of women with newly-diagnosed breast cancer23. And yet routine mri of the contralateral breast is not recommended, because it has not been shown to improve survival. Instead, the recommendation for follow-up with annual mammography continues. The paradox is this: If 8 years’ worth of incident breast cancers can be identified in one shot, why bother to pick them up in dribs and drabs? The mri-detected occult lesions are understood not to be clinically meaningful because they do not adversely affect mortality (overdiagnosis); however, if a similar lesion were to be found as a primary cancer in the ipsilateral breast, the radiologists insist that it is clinically meaningful. Once the paradigm that an increase in sensitivity increases overdiagnosis is accepted (that is, not all lesions are clinically meaningful), then it is the responsibility of clinicians to try to determine the ideal level of sensitivity.

The nbss has been berated for working with 30-year-old machinery, but I think that the greater problem is that clinicians are still working under 30-year-old assumptions. How much is really known about the relationship between size and survival? How confident is our community about early detection? It is universally accepted that tumour size and survival are inversely related for women diagnosed with palpable breast cancer24. That understanding is the rationale for early detection by mammography or other means. But it does not logically follow that a decrease in tumour size will necessarily lead to a decrease in mortality.

Consider two analogous situations. First, among women with breast cancer who experience a local recurrence, the strongest predictor of death is a short time from diagnosis to local recurrence25. However, that finding does not imply that a further shortening of the time from diagnosis to recurrence through intensive imaging would worsen survival. Second, studies of children with neuroblastoma noted that the children diagnosed in the first year of life experienced much better survival than those diagnosed thereafter26. That observation encouraged physicians to consider that screening for neuroblastoma by measuring urinary metabolites would increase the proportion of children diagnosed in the first year and thereby reduce mortality. The resulting clinical trial unfortunately found no benefit27. Neuroblastoma with a favorable prognosis is detectable by screening, but those cases are associated with a very high rate of spontaneous regression or maturation of the neuroblastoma into benign ganglioneuroma. Very few cases of neuroblastoma detected by screening have unfavourable biologic features such as N-Myc amplification28.

The relationship between breast cancer size and survival is not fixed, and the slope of the curve that defines the relationship varies according to the stage and pathologic features of the breast cancer24. The strongest relationship is seen with large cancers and node-positive cancers29. The relationship is attenuated among women with triple-negative cancers, with her2 (human epidermal growth factor receptor 2)–positive cancers, and with BRCA1-positive cancers19,30. Size does not predict mortality well for women with nonpalpable cancers29. Is it possible that there are additional categories wherein the size–survival relationship does not hold, and that eventually every woman with breast cancer will be able to be assigned to one of those categories? If more specific categorization were to be possible, then there would be no expectation of benefit from early detection—through mammography or any other means. In statistical terms, the question is “Are there variables n1, n2, n3, … nx, such that, after adjusting for n1, n2, n3, … nx in a follow-up study, size is no longer predictive of survival?” For example, in a study of 5423 women with cancers of less than 2.0 cm, tumour size was not predictive of survival after adjustment for grade, hormone receptor status, and her2 expression30. Those data suggest that, as the mean size of breast cancers in a population diminishes, further reductions in size can achieve only marginally less benefit. The lesson of mammography should be used to rethink the fundamentals of breast cancer and its natural history so that planning can commence for the experiments and clinical studies that will lead to better outcomes in the future.

 

Curr Oncol. Oct 2014; 21(5): 215–216.  re: Reflections on screening mammography and the early detection of breast cancer   Baum, MD ChM* *Professor Emeritus of Surgery &  Medical Humanities, University College, London, U.K.

I welcome this opportunity to comment on the piece by Dr. Steven Narod in this issue of Current Oncology. His commentary systematically responds to, and rebuts, the near-hysterical reactions to the recent publication of the 25-year follow-up results of the Canadian National Breast Cancer Screening Study1. I admire his restraint in the face of criticisms that go way beyond the boundaries of polite scientific disputation.

Much of the criticism the authors of the trial have faced goes so far as to accuse them of being guilty of scientific misconduct and fraud. Those charges are libellous, but I’m sure that Narod et al. are wise enough not to resolve their differences in a court of law, but simply to open their books to scientific scrutiny, in a way that fair-minded clinicians can judge who are the real culprits. Narod has achieved precisely that end in his timely and measured response. My only criticism is minor … in that he doesn’t go far enough. For example, it could easily be pointed out that the results of the National Breast Cancer Screening Study sit comfortably within the confidence intervals of a Cochrane Collaboration overview of the screening trials, with no hint of heterogeneity2. If anything, the trial in that overview that is closest to being an outlier is the Swedish two-county trial, whose authors are the shrillest of all the critics3.

The debate is so polarized that, leaving aside possible conflicts of interest, the only assumption that can be made is that the clash is one of ideology rather than scientific discourse. In other words, the true believers in the screening dogma will never be persuaded of the error of their ways by data alone, and so when facts don’t fit their prejudice, they resort to ad hominem attacks.

I was one of those who established the first screening centre in London and South East England in 1988, but as an open-minded clinical scientist, I allowed the emerging new data to change my mind. With all due modesty, that is what is called an expression of scientific integrity. Of course, as Narod points out, the prolonged and futile debate merely inhibits real progress on the subject. The importance of breast screening programs lies not in their success, but in their failure. As Huxley put it, “The tragedy of science is the slaying of a beautiful hypothesis by an ugly fact.”

The national breast screening programs around the world have provided us with a natural experiment of the greatest historical importance, not because of their success in reducing breast cancer mortality, but because of the observations that have emerged concerning overdiagnosis of the disease4,5. About two hundred years ago, cancer was defined by its microscopic appearance. With the discovery and use of the modern microscope, the nineteenth century saw the birth of scientific oncology. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer6. As earlier generations had correlated autopsy findings observed with the unaided eye with the clinical course of cancer one hundred years earlier7, so Virchow correlated the microscopic pathology of the disease. However, the material he was studying came from the autopsies of patients dying from cancer. In the mid-nineteenth century, pathology correlations were performed either on cadavers or on living subjects presenting with locally advanced or metastatic disease who were almost always predetermined to die in the absence of effective therapy. Since then, and without pause for thought, the microscopic identification of cancer according to those classical criteria has been associated with the assumed prognosis of fatal disease in the absence of treatment.

A syllogism at the heart of the diagnosis of cancer therefore runs like this: People frequently die from malignant disease. Under the microscope, this malignant disease has many histologic features that we will call “cancer.” Ergo, anything that looks like “cancer” under the microscope will kill you. The screening debacle therefore suggests that some of the earliest stages of “cancer,” if left unperturbed, will not progress to a disease with lethal potential. Those pathologic entities might have microscopic similarity to true cancers, but their appearances alone are insufficient to predict a life-threatening disease.

Conventional mathematical models of cancer growth are linear or logarithmic—in other words, completely predictable at the outset. They predict transition from in situ phases to early invasive, and from early invasive to late invasive over time. Most natural biologic mechanisms are nonlinear or are better described by chaos theory8. Prolonged latency followed by catastrophe should not be all that surprising. We accept the case for prostate cancer, because we know that most elderly men will die with prostate cancer in situ and not of prostate cancer. In fact, the United Kingdom’s national prostate-specific antigen screening trial (protect) is predicated on that fact, with two a priori outcome measures defined: deaths from prostate cancer, and the number of cancers over-detected and treated unnecessarily9.

Next, it is worth noting that, contrary to all common-sense predictions, the increased detection rate of ductal carcinoma in situ has led to an increase in the mastectomy rate for the screened population4,5. Up to 45% of women with a screen-detected case of ductal carcinoma in situ end up undergoing mastectomy because of the multicentricity of the disease10. And yet the paradox is that clinically detected multicentric invasive breast cancer is relatively uncommon11. Surely that is proof enough that at least half the foci of ductal carcinoma in situ will regress if left alone; of course, determining which half remains the problem.

In conclusion, then, it can be stated with a great deal of conviction that a large proportion (on the order of 50%) of screen-detected (preclinical) foci of breast cancer are not programmed to progress if left unperturbed. That observation is of seismic importance and could set the agenda for breast cancer research into the next decade. The choice to ignore those observations, either because they do not support personal prejudice or because of some sleazy political agenda, will result in our community missing an opportunity of a life-time—and that would be unforgivable.

Narod is to be congratulated for his systematic and robust rebuttal of the unjustified attempts to destroy the credibility of the Canadian trial by a small group of vociferous critics who provide a background noise so loud that it nearly drowns out the true signal of the 25-year experiment of population screening for breast cancer.

“There’s non so blind as those that will not see.”— Jonathan Swift, Polite Conversation

Curr Oncol. Oct 2014; 21: 205–207. Screening mammography: the turning of the tide?  W.D. Foulkes, MBBS PhD McGill University, Montreal, Quebec     This issue of Current Oncology features a Counter-currents article by Dr. Steven Narod, “Reflections on screening mammography and the early detection of breast cancer”1, that is accompanied by a commentary from Professor Michael Baum2 supporting Narod’s thesis. Indeed, in Baum’s view, Narod’s only error was not to push home the point that the Canadian National Breast Cancer Screening Study (nbss) is not an outlier among mammography screening studies. He commends Narod for a measured response to the widespread criticism that followed publication of the 25-year follow-up results of the by now notorious nbss.

It seems as if almost everyone has an opinion on screening mammography. Everyone is entitled to an opinion, of course; but discussions about mammographic screening tend to take on a special, almost unique, quality—which perhaps speaks to the investments (financial, psychological, and career) made by many of the protagonists, which Professor Baum fleetingly mentions as potential conflicts of interest in his editorial. Baum prefers to see the ongoing debate—if that is what it is—as a clash of ideologies. But what are these ideologies that are so opposed?

Essentially, Baum’s argument is that the proponents of screening are not really scientists, in the sense that they do not accept refutation of data by data. He could be right, but I think the more parsimonious and psychologically more plausible explanation is that the aforementioned investments are simply too great: the stakes are too high. That the stakes are high is, in my view, very clear. Breast cancer is a common disease, and if population-based screening mammography is shown to have failed and is therefore no longer offered, billions of dollars would be saved every year in the United States alone3.

Narod contrasts the results of two large trials of mammography (one carried out in Sweden, the two-county study) with the nbss data. Having read these carefully laid out arguments, I think that most disinterested, but informed, readers will accept that many of the legion of criticisms that have been placed at the door of the nbss simply do not hold up to scrutiny. But mud sticks, and so many observers who do not like the results of the nbss point again and again to the same “flaws.”

One of Narod’s most telling points is that the survival curves for the two arms of the Swedish trial continue to remain separate up to 29 years after the trial was started. That observation is not consistent with any known effect of mammographic screening. It is much more likely that the populations were simply different to start with.

Further discussion of the pros and cons of these two trials is now fairly pointless. There are not much new data to be had, and I can’t see Drs. Kopans and Tabár, on reading Narod’s article, deciding that perhaps the benefits of mammography have, after all, been overestimated. Without new data, we can’t resolve this critical issue. So perhaps we need to stop the current process and actually do some new research to gather the required data.

A recent Perspective article in the New England Journal of Medicine4 noted the presence of a deep chasm separating women’s views of the likely benefit of mammographic screening and the actual data available. The nongovernmental Swiss Medical Board subsequently determined that women could not make informed decisions about screening without access to more nuanced information. Moreover, the Board felt that the benefits of mammographic screening were likely to be so small that no new screening programs should be introduced and existing programs should be allowed to run down. Their decision caused the expected uproar, but it is interesting to note that the results of a reader poll after a Clinical Decisions article 2 years earlier in the New England Journal of Medicine5 showed that a clear majority did not think that screening mammography should be started at age 40. Those results are contrary to the recommendation of many breast cancer organizations. But on the basis of these newer findings, it seems to me that the tide has turned, insofar as there are now enough interested parties prepared to question the benefits of mammography.

One of the points that Narod makes bears some discussion: He sees the problem not in terms of 30-year-old mammography machines in nbss study, but in 30-year-old thinking about the biology of breast cancer on the part of those who support screening. Logically, it can be seen that, as breast cancers enlarge, the number of cancer cells within them increases, which can provide opportunities for more malignant clones to emerge. Earlier detection will thus prevent those emerging clones from worsening outcomes. This quasi-Halstedian view, that a breast cancer makes a stately progression through biologically distinct and distinguishable stages and that the grade worsens as the tumour enlarges (assumptions that are at the heart of the original explanation of how mammography “works”6), are no longer part of mainstream thinking about breast cancer biology. Even ductal carcinoma in situ seems to possess many of the molecular changes found in invasive breast cancers, albeit at lower frequencies7,8. It seems as if the “die is cast” fairly early in the life of a breast cancer9. Intrinsic subtypes hold true as cancers grow and metastasize10, and the sojourn time varies from subtype to subtype11. Some breast cancers regress12. Others grow very rapidly13. These are not ideal biologic circumstances for the success of an “across the board” screening program. That conclusion is even borne out by a careful examination of the two-county study data14. The one group for whom screening mammography would be hoped to work—women between 40 and 49 years of age with a grade iii breast cancer (a group likely to contribute disproportionately to the observed mortality from breast cancer)—does not seem to achieve any mortality savings (see Figure 20 in Tabár et al.14). Survival at 16 years from randomization was identical in the invited and screened groups (relative risk: 0.95; 95% confidence interval: 0.55 to 1.64). One wonders if, in fact, the shoe is on the other foot. What has been learned about interpreting screening data from the current understanding of the natural history of breast cancer?

On the other side of the ledger, overdiagnosis has emerged in the past several years as a major issue in breast cancer screening. Quantifying the benefits and harms of mammography make for sobering reading by disinterested parties. If one starts with a sample of 1000 U.S. women 50 years of age, and if those women are screened annually for a decade, fewer than 4 women will avoid a breast cancer death; 3–14 women will suffer the consequences of over-diagnosis; and many hundreds will have at least 1 false alarm15. Work by Welch and Frankel suggests that women would think differently about mammographic screening for breast cancer if they were made aware of those figures at time of invitation for screening. Using best estimates, only 1 woman in 4 who develop a screen-detected breast cancer will avoid a breast cancer death16. The other 3 will do just as well, or just as poorly, without screening—or, of more concern, will have been diagnosed with a cancer that was not destined to ever present clinically. In the observational Norwegian study, only one third of the reduction in deaths from breast cancer could be attributed to mammographic screening per se17. Most women with a screen-detected breast cancer are therefore either diagnosed early (but with no effect on outcome) or are overdiagnosed.

We have been here before. Maureen Roberts, director of the Edinburgh breast screening project, died of breast cancer in 1989. While hopeful that mammographic screening would benefit women, she concluded from an analysis of the Edinburgh trial results that it did not. Before she died, she wrote “Breast screening: time for a rethink?” for the British Medical Journal18, concluding, “I feel sad to be writing this; sad because naturally after so many years I am sorry that breast screening may not be of benefit. I am also sad to seem to be critical of the many dear and valued colleagues I’ve worked with over the years, particularly those who have made such a magnificent contribution to the care and welfare of women with breast cancer. But they will recognise that I am telling the truth.”

It is time to work toward a trial of screening mammography that will incorporate variable thresholds, molecular markers, genetic testing, and psychological and physical measures of the effect of overdiagnosis. One of the two authors of the New England Journal of Medicine Perspective article discussed earlier, an ethics representative on the Swiss Medical Board, has argued that there is a moral requirement for a randomized controlled trial of mammography19 based on Welch’s idea of differing detection thresholds. I believe that women will be interested in such a study. But because almost every major U.S. medical organization focusing on breast cancer prevention, diagnosis, or treatment has stated that women should begin undergoing mammography annually from the age of 40 years, will any agency have the courage to fund it?

 
October 07, 2014  Dr. Joe Mercola DC  does a nice review of recent critiques  in   Why So Many Mixed Messages on Mammogram Benefits?
Earlier this year, one of the largest and longest studies of mammography to date — involving 90,000 women followed for 25 years — found that mammograms have no impact on breast cancer mortality. The Canadian Breast Screening Trial ll Miller ea 
Over the course of the study, the death rate from breast cancer was virtually identical between those who received an annual mammogram and those who did not, while 22 percent of screen-detected invasive breast cancers were over-diagnosed, leading to unnecessary treatment. The researchers concluded “the data suggest that the value of mammography screening should be reassessed.”2
A Cochrane Collaboration review also found no evidence that mammography screening has an effect on overall mortality, which, taken together, seriously calls into question whether mammography screening really benefits women.3
Public health agencies, however, have been slow to update their recommendations. The American Cancer Society recommends annual mammograms for average-risk women starting at the age of 40, while the US Preventive Services Task Force recommends mammograms every other year starting at age 50
The conflicting recommendations send women mixed messages on whether screening is helpful or harmful, yet, earlier this year the Swiss Medical Board made a clear-cut recommendation: no more systematic mammography.  
Why Did the Swiss Medical Board Do Away with Routine Mammograms? 
After a year of reviewing the available evidence and its implications, the Swiss Medical Board, an independent health technology assessment initiative, noted they became “increasingly concerned” about what they were finding. The “evidence” simply did not back up the global consensus of other experts in the field suggesting that mammograms were safe and capable of saving lives.
        On the contrary, mammography appeared to be preventing only one death for every 1,000 women screened, while causing harm to many more. Their thorough review left them no choice but to recommend that no new systematic mammography screening programs be introduced, and that a time limit should be placed on existing programs.  
In their report, made public in February 2014,4 the Swiss Medical Board also advised that the quality of mammography screening should be evaluated and women should be informed, in a “clear and balanced” way, about the benefits and harms of screening.  
Unfortunately, many women are still unaware that the science backing the health benefits of mammograms is sorely lacking. Instead of being told the truth, women are guilt-tripped into thinking that skipping their yearly mammogram is the height of medical irresponsibility. It can be hard to stand your ground against such tactics.  
      When it comes to cancer prevention, however, many doctors are just as confused and manipulated as the average person on the street because of the relentless industry and media propaganda that downplays or ignores research that dramatically contradicts their profit-based agenda.
Five Facts About Mammograms That Every Woman Should Know
Before your next (or first) mammogram, you may be interested to know the following:

1. Mammograms May Offer Less Benefit Than You Think:

In one survey, most women said they believed mammography reduced the risk of breast cancer deaths by at least half and prevented at least 80 deaths per 1,000 women screened.5 In reality, mammography may, at best, offer a relative risk reduction of 20 percent and prevent in absolute terms only onebreast-cancer death per 10,000 women.

2. Mammography May Increase the Risk of Breast Cancer in Women with a BRCA 1/2 Mutation:

Results published in the British Medical Journal (BMJ) show that women carrying a specific gene mutation called BRCA1/2 (which is linked to breast cancer) are particularly vulnerable to radiation-induced cancer.6

Women carrying this mutation who were exposed to diagnostic radiation (which includes mammograms) before the age of 30 were twice as likely to develop breast cancer, compared to those who did not have the mutated gene. They also found that the radiation-induced cancer was dose-responsive, meaning the greater the dose, the higher the risk of cancer developing.

3. False Positives are Common (and Dangerous)

In the US, the risk of having a false-positive test over 10 mammograms is a concerning 58 percent to 77 percent!78 When a woman is told she may have breast cancer, it causes considerable anxiety and psychological distress. Meanwhile, you will be subjected to more testing, such as biopsy or surgery, which carry their own set of risks, unnecessarily.

4. Mammograms May Not Work if You Have Dense Breasts

Up to 50 percent of women have dense breast tissue, which makes mammograms very difficult to decipher. Dense breast tissue and cancer both appear white on an X-ray, making it nearly impossible for a radiologist to detect cancer in these women. It’s like trying to find a snowflake in a blizzard.

Breast density laws have been passed in California, Connecticut, New York, Virginia, and Texas, making it mandatory for radiologists to inform their patients who have dense breast tissue that mammograms are basically useless for them. A law is now being considered at a federal level as well.

5. There are Other Screening Options

There are other screening options, each with their own strengths and weaknesses, and you have a right to utilize those options.  Remember, only a biopsy can confirm cancer.  Screening tools only aid in the process of showing concern.  

Your Waist Size Is Linked to Your Breast Cancer Risk It’s important to remember that getting a mammogram, if you choose to, is not the same as prevention. In order to truly avoid breast cancer, you need to focus your attention on actual prevention and not just early detection, and one way to do this is by maintaining a healthy weight, and, particularly, a healthy waist size.

Researchers analyzed data from 93,000 mostly overweight post-menopausal women. This included data such as their general health, cancer status, and skirt size (which was used as a gauge of waist size). The latter – skirt size – was strongly linked to breast cancer risk.9 As TIME reported:10

An increase in skirt size was the single most predictive measure of breast cancer risk, the study concluded. When women went up a single skirt size over a 10-year span between their mid-20s and mid-60s, they were shown to have a 33% greater risk of developing breast cancer after menopause. Buying two skirt sizes up during that same period was linked to a 77% increased risk.”

Clothing sizes can be quite ambiguous, of course, with a size 8 in one brand equal to another’s size 10. Yet, the premise that increasing waist size might increase cancer risk is sound. Breast cancer is the most common cancer in women, and obese women are thought to be up to 60 percent more likely to develop cancer than those of normal weight.

The reason for this increased risk is because many breast cancers are fueled by estrogen, a hormone produced in your fat tissue. So the more body fat you have, the more estrogen you’re likely to produce. However, excess fat around your mid-section may be particularly dangerous.

Why Your Waist-to-Hip Ratio Matters     If you have a high waist-to-hip ratio, i.e. you carry more fat around your waist than on your hips, you may be at an increased risk for certain chronic conditions. Certain body compositions do tend to increase your risk of chronic disease, and carrying extra inches around your midsection has been repeatedly shown to increase cardiovascular health risks. Your waist size is also a powerful indicator of insulin sensitivity, as studies clearly show that measuring your waist size is one of the most powerful ways to predict your risk for diabetes, and this could also play a role in cancer as well.

To calculate your waist-to-hip ratio, measure the circumference of your hips at the widest part, across your buttocks, and your waist at the smallest circumference of your natural waist, just above your belly button. Then divide your waist measurement by your hip measurement to get the ratio. (The University of Maryland offers an online waist-to-hip ratio calculator11 you can use.) To determine your waist-to-hip ratio, get a tape measure and record your waist and hip circumference. Then divide your waist circumference by your hip circumference. For a more thorough demonstration, please review the video below.

Waist to Hip Ratio Men Women
Ideal 0.8 0.7
Low Risk <0.95 <0.8
Moderate Risk 0.96-0.99 >0.81 – 0.84
High Risk >1.0 >0.85

  The Sugar Connection  Obesity, including abdominal obesity, is driving up rates of breast cancer in many developed countries. And what is driving up rates of obesity? Many factors, actually, but sugar certainly plays a primary role. There is no shortage of research linking excessive sugar consumption with obesity, and the intake of sugar-sweetened beverages appears to have a particularly strong link. It was more than five years ago when UCLA researchers found that adults who drank at least one sugar-sweetened beverage a day are 27 percent more likely to be overweight or obese.12 Even those who only drank soda occasionally had a 15 percent greater risk.

This is far more than simply an issue of consuming “empty calories,” as sugary drinks, soda, and even fresh-squeezed fruit juice contain fructose, which has been identified as one of the primary culprits in the meteoric rise of obesity and related health problems—in large part due to its ability to turn on your “fat switch.” Alarmingly, research presented at the American Heart Association’s Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions suggested sugary beverages are to blame for about 183,000 deaths worldwide each year, including 133,000 diabetes deaths, 44,000 heart disease deaths, and 6,000 cancer deaths.

About 77 percent of food items in US grocery stores contain added sugar. So it’s no wonder that, while the American Heart Association recommends a daily sugar limit of six teaspoons for women and nine for men, the average American consumes more like 22. If health agencies really wanted to make a dent in breast cancer, they would focus on sharing the truth about sugar (and grains), and their role in obesity and cancer. Unfortunately, breast cancer is big business, and mammography is one of its primary profit centers. This is why the industry is fighting tooth and nail to keep it, even if it means ignoring (or downplaying) the truth.

Avoiding Sugar and Other Top Breast Cancer Prevention Tips   I believe the vast majority of all cancers, including breast cancer, could be prevented by strictly applying basic, commonsense healthy lifestyle strategies, such as the ones below. No available screening method, whether mammography or otherwise, is going to lower your risk of breast cancer… but the tips that follow will:

    • Avoid sugar, especially fructose, and processed foods. All forms of sugar are detrimental to your health in general and tend to promote cancer. Refined fructose, however, is clearly one of the most harmful and should be avoided as much as possible. This automatically means avoiding processed foods, as most are loaded with fructose.
    • Optimize your vitamin D levelsVitamin D influences virtually every cell in your body and is one of nature’s most potent cancer fighters. Vitamin D is actually able to enter cancer cells and trigger apoptosis (programmed cell death). If you have cancer, your vitamin D level should probably be between 70 and 100 ng/ml. Vitamin D works synergistically with every cancer treatment I’m aware of, with no adverse effects. Ideally, your levels should reach this point by exposure to the sun or a tanning bed, with oral vitamin D used as a last resort and balanced by other nutrients like vitamin K2 and magnesium.
    • Limit your protein. Newer research has emphasized the importance of the mTOR pathways. When these are active cancer growth is accelerated. One way to quiet this pathway is by limiting your protein to one gram of protein per kilogram of lean body mass, or roughly a bit less than half a gram of protein per every pound of lean body weight. For most people, this ranges between 40 and 70 grams of protein a day, which is typically about 2/3 to half of what they are currently eating. You can eat 25% more if you are exercising or pregnant.
    • Avoid unfermented soy productsUnfermented soy is high in plant estrogens, or phytoestrogens, also known as isoflavones. In some studies, soy appears to work in concert with human estrogen to increase breast cell proliferation, which increases the chances for mutations and drives the phenotype associated with cancer.
    • Improve your insulin and leptin receptor sensitivity. The best way to do this is by avoiding sugar and grains and restricting carbs to mostly fiber vegetables. Also make sure you are exercising, especially with Peak Fitness.
    • Exercise regularly. One of the primary reasons exercise works to lower your cancer risk is because it drives your insulin levels down, and controlling your insulin levels is one of the most powerful ways to reduce your cancer risks. It’s also been suggested that apoptosis (programmed cell death) is triggered by exercise, causing cancer cells to die in the way nature intended. Studies have also found that the number of tumors decrease along with body fat, which may be an additional factor. This is because exercise helps lower your estrogen levels, which explains why exercise appears to be particularly potent against breast cancer.

In addition to exercise, try to limit your sitting time to three hours a day while taking 10,000 daily steps during your non-exercise hours.

  • Maintain a healthy body weight. This will come naturally when you begin eating right and exercising. It’s important to lose excess body fat because fat produces estrogen, creating a vicious self-perpetuating cycle.
  • Drink a pint to a quart of organic green vegetable juice daily. This is a simple way to get more cancer-fighting nutrients into your diet. Please review my juicing instructions for more detailed information.
  • Get plenty of high-quality, animal-based omega-3 fats, such as krill oil. Omega-3 deficiency is a common underlying factor for cancer.
  • Curcumin. This is the main active ingredient in turmeric and in high concentrations can be very useful adjunct in the treatment of cancer. It actually has the most evidence-based literature supporting its use against cancer of any nutrient, including vitamin D.13 For example, it has demonstrated major therapeutic potential in preventing breast cancer metastasis.14 It’s important to know that curcumin is generally not absorbed that well, so I’ve provided several absorption tips here. Newer preparations have also started to emerge, offering better absorption. For best results, you’ll want to use a sustained-release preparation.
  • Avoid drinking alcohol, or at least limit your alcoholic drinks to one per day.
  • Avoid electromagnetic fields as much as possible. Even electric blankets may increase your cancer risk.
  • Avoid synthetic hormone replacement therapy, especially if you have risk factors for breast cancer. Many forms of breast cancer are estrogen-fueled, and according to a study published in the Journal of the National Cancer Institute, breast cancer rates for women dropped in tandem with decreased use of hormone replacement therapy. (There are similar risks for younger women who use oral contraceptives. Birth control pills, which are also comprised of synthetic hormones, have been linked to cervical and breast cancers.) If you are experiencing excessive menopausal symptoms, you may want to consider bioidentical hormone replacement therapy instead, which uses hormones that are molecularly identical to the ones your body produces and do not wreak havoc on your system. This is a much safer alternative.
  • Avoid BPA, phthalates, and other xenoestrogens. These are estrogen-like compounds that have been linked to increased breast cancer risk.
  • Make sure you’re not iodine deficient, as there’s compelling evidence linking iodine deficiency with certain forms of cancer. Dr. David Brownstein, author of the book Iodine: Why You Need It, Why You Can’t Live Without It, is a proponent of iodine for breast cancer. It actually has potent anticancer properties and has been shown to cause cell death in breast and thyroid cancer cells. For more information, I recommend reading Dr. Brownstein’s book. I have been researching iodine for some time ever since I interviewed Dr. Brownstein, as I do believe that the bulk of what he states is spot on. However, I am not at all convinced that his dosage recommendations are correct. I believe they are far too high.
  • Avoid charring your meats. Charcoal or flame-broiled meat is linked with increased breast cancer risk. Acrylamide—a carcinogen created when starchy foods are baked, roasted, or fried—has been found to increase cancer risk as well.
 
 27 Sept 2014   Three  thoughtful  new reviews, from Universities in Australia (Robin Bell),  Kuwait (Yusuf Luqmani) and Cape Town (Tim Noakes),  highlight the deadly ethical  problem of the myth-based zealous profiteering  Disease Industry promotion in the well of cancer screening,  and the high carbs low fat-low cholesterol  diet, and “statin deficiency” – iatrogenic  “OBSESSIVE-COMPULSIVE DISORDERS ” that profiteers cultivate in the guileless.
       It is not coincidence that the Food and Disease Industry insist that the dangerous high carbs low fat diet they have promoted for the past 40 years, and mass cancer screening for the past >20years , are correct- for the simple perverse reason that such lies pay ie Only Disease Pays. This brings us via  Lupton’s question of Ethics vs Science  in the fraught  narrow parenting domain,  to our everywhere dilemma:  Can Health Science , Human,  Animal and plant  Rights Survive the Onslaught of ruthless commerce and politics?

           Breast screening: an obsessive compulsive disorder.  in Cancer Causes Control. 2014 Jul 11.  Prof Yunus Luqmani  a British oncology biochemist,  Kuwait University writes   “Mammographic screening was  founded on the premises that “it  saves lives”, early is better than late,’  which prevails  in several countries but  controversial since its inception. Findings and interpretation of clinical trials data vary considerably, with disagreement on the outcome and value of such  procedure, not just about the benefits but about the potential harms of mass screening. Many are being screened for the benefit of the few. Even this might be acceptable  but  for concern for many  women with screen detected cancers that will potentially not cause them harm, and who are very likely receiving unnecessary treatment. Many  call for complete cessation of indiscriminate screening if not re-assessment of  age  and periodicity . Of great concern is that screening is being vigorously advocated by many healthcare workers, the media, and lay persons alike without proper awareness or appreciation of the consequences. Although some National leaflets  now present a truer picture, there is   distinct lack of transparency to allow women to distinguish perception from reality and to make informed choices. How many would elect to be screened if they knew that for every one woman who is notionally saved by early detection, anywhere from 2 to 10 otherwise healthy women are being turned into breast cancer patients?  

          Screening mammography – early detection or over-diagnosis     Climacteric. 2014 Sep 16:1-7. Epidemiologist  Prof Robin Bell  Monash University,  Australia examines  benefits and harms of organized screening mammography. Most  recent reduction in breast cancer-specific mortality is explained by use of adjuvant therapy rather than screening mammography. Impact of screening mammography in countries where women present with early disease and have access to adjuvant treatment is modest. There is a wide range of estimates for the magnitude of over-diagnosis. All-cause mortality (rather than breast cancer-specific mortality) should be used when assessing impact of screening as otherwise the harm of cancer treatment in those  over-diagnosed will be missed. Conclusions The benefits and harms of screening mammography are finely balanced. The impact of screening mammography is at best neutral but may result in overall harm. Women should be informed of the issue of over-diagnosis. It is time to review whether organized mammographic screening programs should continue.  
        AND ON DIET:             It is common cause that humans consume their energy requirements from what they can get- and since animal protein is the most costly,  and excess harmful, this means from carbs or fat, of which natural  animal/ dairy/ nut  fat is the most satisfying. So while keeping energy output and adequate animal protein intake  stable, needed energy intake comes from balance of fat and carbs.
       A  major bone of contention locally is the merits of the Banting diet –  in his words,  ‘four meals per day, consisting of meat, greens, fruits, and dry wine’- before the age of mass refined and chemically-and genetically-polluted food and maize-fed livestock.
        Cereals-carbohydrates in his time 160 years ago were thus largely replaced by fresh meat fats and fresh produce. Considering he was born in 1796, his life of  82 years was   almost double the then average lifespan despite his having been severely obese until he found his optimal diet advised by Dr William Harvey based on Professor Claude Bernard’s work on diabetes.
        But Banting was a businessman  of the pre-automobile  era:  unlike labourers, you walked, or you saddled up- without tarmac, coaches were slow. With modern understanding of the importance of avoiding the sedentary lifestyle and overload of both alcohol, salt, refined carbohydrates, protein, and synthetic ie transfats (margarine) , the Banting diet has adapted in modern times  to be optimal for many people for both energizing and keeping slim and well – with its accent on minimal refined/ processed carbs including concentrated cereals,  pure starches, cooked fatty pastries, and commercial fruit juice;
        with high natural fat 50+% as the  ideal brain-muscle-metabolic energy source- from unprocessed meat,  fish, eggs, cream, coconut, butter, cheese;  and modest mixed nuts; matched with copious  greens and other lowstarch rainbow vegetables.
     The futility of low fat (ie high carbs) diet was borne out in the biggest and costliest   -$billion – trial ever- the Women’s Health Initiative  WHI, published in 2006 (Rossouw ea)  and for cancer,  this week (Thomson ea)“Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years,  who participated in the WHI Dietary Modification Trial;  randomly assigned to  intervention [40%]) or comparison group  [60%]) in a free-living setting,  enrollment between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.  Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.    “Dietary advice to reduce fat for cancer and cardiovascular disease, stroke or coronary heart disease   prevention after menopause  was not supported in the  WHI.   The diet had no effects on incidence of CHD , stroke ,  or CVD. In fact  Women with higher baseline fat intake (quartile) had breast cancer risk only  HR-0.76; 0.62, 0.92 during intervention). Thus the highest  fat intake lowered breast cancer risk by 24%There were no intervention effects   ie no benefits of low fat diet on invasive breast 1.08  or colorectal cancer, other cancers, cancer-specific or overall mortality.
 
        and  the WHI (Shikany ea 2006 and 2011further showed direct association of  higher Dietary carbs (glycemic load GL  glycemic index)   and risk of breast cancer and cardiovascular disease risk factors .There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94-2.13; P = 0.07).   GL inversely associated with high-density lipoprotein HDL  cholesterol (P for trend = 0.004) and positively with triglycerides,  total cholesterol (P = 0.018) and low-density lipoprotein cholesterol.
            Professor Tim Noakes  Cape Town keeps on pointing out the lack of science in the perverse western (Ancell Keys)   paradigm of high carbs low fat processed diet (as in the WHI) , with  futile overreliance on  synthetic drugs eg statins,  and appliances, surgery  to reverse the consequent epidemic degenerative diseases- and keep the medical disease industry profitable. .

This brings us to the cutting edge of modernity: Can  Ethics Survive the Onslaught of Science ? (Prof Michael Lupton, Bond University, Australia  2013)?  Can health science  survive the onslaught of perverse incentives, profiteering- the Semmelweis Reflex that denies what is cheap, natural and best?
24 Sept 2014  update after the Angela Jolie hype: This month’s JAMA say it all: the less breast  surgery the better:
Use of and Mortality After Bilateral Mastectomy Compared With Other Surgical Treatments for Breast Cancer in California, 1998-2011. Kurian &  Gomez    Stanford Univ.  JAMA. 2014;312:902-914.                Bilateral mastectomy is increasingly used to treat unilateral breast cancer. Because it may have medical and psychosocial complications, a better understanding of its use and outcomes is essential to optimizing cancer care. Conclusions and Relevance  Use of bilateral mastectomy increased significantly throughout California from 1998 through 2011 and with median follow-up of 89 months  was not associated with lower mortality than that achieved with breast-conserving surgery plus radiation. Unilateral mastectomy was associated with higher mortality than were the other 2 surgical options.
Contralateral Prophylactic Mastectomy   Is It a Reasonable Option?         Editorial|Sept 3, 2014     Lisa Newman, Univ Michigan,   JAMA. 2014;312:895-897 The professional oncology community has worked diligently to generate data that facilitate surgical planning and the decision-making process for patients with newly diagnosed breast cancer. Several lines of evidence support the importance of prioritizing treatment of the known cancer over and above consideration of a risk-reducing mastectomy for the unaffected breast (contralateral prophylactic mastectomy [CPM]). For example, the equivalent overall survival for breast-conserving surgery (BCS) and mastectomy makes CPM an unnecessary option for women who are eligible for lumpectomy and desire breast preservation. Incidence of metachronous contralateral breast cancer (ie, contralateral cancer detected several months after initial breast cancer diagnosis) is relatively low, at 0.25% to 1% per year,1,2 and these cancers are usually detected at early, highly curable stages. Synchronous occult contralateral breast cancer is uncommon, as documented by studies revealing incidental cancer in only 1% to 3% of CPM specimens.3,4 Survival is comparable for patients with unilateral vs metachronous bilateral breast cancer5,6 and typically is associated with the stage of first cancer, consistent with the concept that the initially presenting tumor has a lead-time advantage in establishing distant organ micrometastases.
The corollary is obvious:    Less Informed Women With High Anxiety Are More Likely to Choose Bilateral Mastectomy for Breast Cancer  San Francisco Cancer Symposium  PracticeUpdate Editorial Team, 2014 Sept   Women with higher anxiety levels and less knowledge about breast cancer recurrence and survival are more likely to choose bilateral mastectomy ,    Katharine Yao, MD, of  University of Chicago  stated, “There is so much information about breast cancer that it’s easy for patients to get overwhelmed. As doctors, we have to be aware of each patient’s knowledge level and the concerns and worries he or she has. We need to do a better job of educating patients that the risk of developing contralateral breast cancer is actually low and that breast cancer can come back in other parts of the body no matter what type of surgery they have.”    Overall, 59% of patients chose lumpectomy, 32% unilateral mastectomy, and 9% CPM. Eighty-three (58%) considered CPM, and 12 (21%) of this latter group chose CPM contralateral prophylactic mastectomy.
 
11 August 2014  The current SA Menopause Society newsletter says:

Benefits of mammography

“the benefits of screening mammography are modest at best” (Elmore & Harris BMJ 2014;348:g3824). This is the conclusion after the latest research to come out of Norway where the introduction of screening has been gradually introduced over the last 2 decades (Weedon-Fekjaer et al BMJ 2014;348:g3701).The Norwegian authorities invited women between 50 and 70 years old to attend for screening every second year and looked at before and after death rates from breast cancer. They found RELATIVE risk reduction of 28% in those invited compared with those not invited to be screened. Without knowing the ACTUAL risk reduction or the harms of screening this sounds like a “good deal”. However it is an observational study not a randomised trial and therefore susceptible to various biases.For women to make up their own minds about screening, actual figures of benefits and harms need to be given because without accuracy perceived dangers and benefits are very far from reality. For example in the US or UK asking women about their estimates of breast cancer deaths – taking 1000 women aged 50 and following them for 20 years – gave the following results:

Of 1000, number
alive after 20 years
Deaths from
breast cancer
Deaths from
other causes
Women’s estimates
without screening
801 160 39
with screening 881 80 39
In reality
without screening
956 5 39
with screening 956-7 4 39-40

Women believe that breast cancer is a far greater threat than it really is. They also believe that screening halves such risk.

If actual death reductions from breast cancer are taken into account, screening benefits are modest at best and if all cause deaths are taken into account the benefits all but disappear.

20 July 2014 Two new papers from Scandinavia highlight the harms of screening mammography.:

Clin Adv Hematol Oncol. 2014 June;12:407-11    Screening mammography:   do the benefits always outweigh the harms?  Brodersen J, Jørgensen KJ, Brawley OW.

APMIS. 2014 May 26. doi: 10.1111/apm.12278.
Overdiagnosis: How cancer screening can turn indolent pathology into illness.    Brodersen J1, Schwartz LM, Woloshin S. The shift from illness to disease has had a profound impact on modern medicine – particularly in the realm of cancer screening. In screening, it is not patients with illness who seek help from the healthcare system; it is asymptomatic healthy individuals who are invited into the healthcare system to be examined for pathology. The underlying assumption of screening is that abnormalities and pathology always progress. If this were true, it would always make sense to look for disease even when people feel well. The million (or more accurately multi-billion) dollar question is whether the fundamental assumption that disease invariably leads to illness is valid. This is the question that the present paper will try to explore and answer.
The current Wiki article on Cancer Screening    firmly denies benefit for screening for silent prostate cancer;  and for xray screening mammography it  firmly questions  the benefit in lives saved versus the harms of screening.  The balance for screening mammogram is summed up by Wiki : “The phenomenon of finding pre-invasive malignancy or nonmalignant benign disease is commonplace in all forms of cancer screening, including pap smears for cervical cancer, fecal occult blood testing for colon cancer, and prostate-specific antigen testing for prostate cancer. All of these tests have the potential to detect asymptomatic cancers, and all of them have a high rate of false positives and lead to invasive procedures that are unlikely to benefit the patient.”
                Reality  remains that, in average  lean  well adults ie without obvious risks , the only screening justified is regular noninvasive SELF- EXAMINATION of breast, skin, testes, electronic bloodpressure; and professional optometric, dental,  skin and bloodpressure screening and, if suspicious, urine multistix exam.  By contrast, regular xray (chest or  mammogram- cumulative radiation risk) and pelvic  internal exams are highly invasive, thus indicated only for symptomatic or familial-risk cases. .
PEER (perverse) PRESSURE, Beliefs, perceptions, indoctrination –  by peer bodies, Corporates like Hospitals and Big Pharma, Regulators,  Accredition Bodies and dangled incentives – which obviously have commercial group vested self-interests  –  die hard:                                     Prev Med. 2014 Jul 16.Miller JW1,  Goff BA ea .  CDC & Washington State University, USA,   studied Physicians’ Beliefs about Effectiveness of Cancer Screening Tests: National Survey of Family Physicians, General Internists, and Obstetrician-Gynecologists(excluding breast radiologists, pathologists,  and oncologist/surgeons). RESULTS: of   1574 respondents-   62% response rate- the majority agreed with the effectiveness of: mammography aged 50-69 years, Pap tests  aged 21-65 years, and colonoscopy for aged ≥50 years.  Physicians typically listed their respective specialty organizations as a top influence for screening  recommendations.  CONCLUSIONS: There were several substantial inconsistencies between physician beliefs in the effectiveness of cancer screening tests and the actual evidence of these tests’ effectiveness which can lead both to underuse and overuse of cancer screening tests.
This outcome obviously damns professional bodies in respect at least of the evidence discouraging  screening mammography of well breasts.
   Its as Soren Kierkegaard wrote 150 years ago about religious conviction- the difficulty of following ethical theistic belief against the majority tide of convenience and venality;
  and Steven Jay Gould’s Non-Overlapping Magisteria of Science and Religion- for some (but not all), the difficulty of reconciling apparent scientific medical evidence (is it ever immutable? ) with belief, dogma- whether from mythical (is it always?)  religious belief, or simply vested interest.
       As we were taught 50 years ago, if new medical discoveries stand the test of time – they often dont-  it takes a generation for  the majority to accept, apply them. Almost two generations of women have now been martyred by repetitive screening xray mammography. Must it take yet another generation before such barbaric screening is abandoned? As Winwood Reade  and AC Grayling philosophized, countless millions have suffered genocide, holocaust in the post-Greko-Roman “enlightened”  two  millennia for vested interests in the guise of religious let alone medical dogma  .
14 July 2014:  BASTILLE DAY CLARION CALL FOR TRUTH TO PROTECT WOMEN:      Screening mammography & Bambi  This column reported these issues a few months ago (see Dr Gerd Gigerenzer PhD  below in May, and April 16, 2014  from the Swiss Medical Board: Abolishing Mammography Screening Programs? ), but they are worth repeating from Groote Schuur Hospital.  A professor of Obstets and Gyne there writes in the current South African Menopause Matters  news email (“an  editorial opinion that does not necessarily represent the views of  SAMS”) :
(the answer to his question: Whatever happened to Evidence-Based medicine? is quite simple: if  it doesnt pay, then evade, deny and mock the evidence, or better, shoot the messenger who dares blow the whistle on  inconvenient truth. )

The Professor writes: “Screening mammography is an emotive subject. Correctly so, because if it did clearly have more benefits than harms then it should be advocated, promoted and sold as an intervention in every woman’s interest.

      Regrettably screening mammography does not clearly have more benefits than harms and given that it is an unpleasant and costly process it should not be promoted. Both the protagonists and the antagonists claim ample facts supporting their arguments while finding fault with the others’ data. One of the latest trial outcomes from Canada (Miller et al BMJ 2014;348:g366) reports on a large group of women (nearly 90 000) who were randomised to mammography annually for 5 years or annual physical breast examination. This took place in the 1980s and the women were in their 50s and were followed up for 25 years.

Diagnoses of breast cancer and deaths from the disease were collected from national databases, as were all-cause mortality figures. The researchers showed that during the 5 years of mammography (or not) more women were diagnosed with breast cancer in the mammography arm (and treated) but the deaths were not significantly different in the two groups. Similarly over the entire study period there were more cancers diagnosed in the mammography arm but the number of deaths were similar, with the conclusion that mammography was not superior to annual examinations and resulted in overdiagnoses.

This is essentially a negative outcome if “deaths avoided” or “lives saved” are taken as the end points. Maybe modern screening techniques work better but also maybe better treatments have reduced mortality rates. The most recent Cochrane Review suggests that if 1000 women aged 50 were screened for 10 years then 4 women would die from breast cancer. Without screening 5 would die.

If the group’s deaths from any cancer are counted then the results are 21 per 1000 with or without mammography. So does mammography screening save lives? The supposed benefit?

If the harms are tallied for the same 1000 women then 100 in the mammography arm would have a false positive-evaluation and 5 would have an unnecessary partial or complete breast removal (Gøtzche et al Cochrane Reviews 2013;6:CD001877). The financial and convenience costs are not commented on.

Yet screening mammography is treated like a religion. Any suggestion to curtail its promotion is seen as “unfair to women” or not doing “the right thing”. A bit like Bambi bashing. How can something so obviously right be challenged?

Nowhere are the facts more disguised than in breast cancer screening pamphlets (Gigerenzer BMJ 2014;348:g2636). The data are presented without numbers ”Most doctors feel that early detection tests for breast cancer save thousands of lives each year” or as relative risk reduction with the difference between 4 and 5 deaths per 1000 being a “20% reduction in deaths”. A final fallacy of the leaflets is extrapolating ahead where 1 life saved over a decade means 2.5 lives over 25 years which is not supported by the data.

No wonder 98% of women in France, Germany and the Netherlands overestimate the benefit of screening by a factor of 10, 100 or more, or do not know. They get much of their information from leaflets – put out by people whose likelihoods depend on screening – which are blatantly misleading. Advertising of medicines is not allowed to make claims that cannot be backed up by evidence, so why can screening pamphlets?

These semi-facts promote beliefs that screening prevents or reduces the risk of breast cancer and saves many lives through the early detection of aggressive tumours. These beliefs are not valid according to an independent Swiss group reporting in a lead article in NEJM (Biller-Andorno & Jüni 2014;370:1965-7) which states that public health programmes that do not produce more benefits than harms are hard to justify ethically – like mammography screening.

Their report caused an uproar because it challenges a tightly held myth – like the existence of Bambi.    What has happened to evidence-based medicine?

Menopause Matters is a monthly review of matters menopausal that have recently appeared in the journals. It is produced for the South African Menopause Society by Athol Kent and the summaries concentrate on clinical issues although some underlying patho-physiology will be included to ensure a scientific basis for the work. It does not necessarily reflect the views of SAMS or its managementf
15 June 2014 this month:  SMALL BENEFITS, SUBSTANTIAL HARMS WITH MAMMOGRAPHY SCREENING  is a trenchant review by Prof Cornelia Baines breast clinician from Canada on why xray screening mammography does well breasts and women far more harm than good.                Prof Stephen  Duffy statistician at UCL argues the reverse.

DIET RISKS FOR BREAST CANCER:

already 30 years ago Seely and Horrobinin Diet and breast cancer: possible connection with sugar consumption hypothesized: younger and older women (possibly pre- and post-menopausal women) differ with respect to such correlations. In older women a strong correlation was found between breast cancer mortality and sugar consumption (correlation coefficient = 0.9).. In younger women the correlation with diet is weak. A possible connecting link between sugar consumption and breast cancer is insulin. This is an absolute requirement for the proliferation of normal mammary tissue and experimental mammary tumours may regress in its absence. Insulin secretion occurs in response to blood glucose level and could be excessive if the regulatory mechanism is overtaxed by large sugar intake. The same mechanism might account for the increased risk of mammary cancer in diabetics.
  A  major Nurses’ Health decades-long Study  review from Harvard shows no relationship between fat intake and breast cancer.
By contrast, studies from  Mexican  2004,  Canada 2005, Italy 2006 , and New York  2009 confirm direct association between sugar intake and breast cancer. . Only a study from Denmark 2005  shows no relationship.
Hence the HighFat LowCarbs (William Banting 1863) diet is now established by the rigorous scientific references of the past 150 years  assembled by science writer Gary Taubes in The Diet Delusion ,  and advised to all  for prevention and management of obesity and all other common major diseases including breast and all cancers.
      As investigative journalists write recently, like Taubes and rational scientists the past 50years,  the major cause of all common chronic degenerative disease including cancer and immunoincompetence is not fat but refined carbs – the root cause of the SACCHARINE DISEASES  that Cleave, Campbell, Burkitt reported occurring in pastoral tribes converting to the western commercialized diet of sugar, refined cereals and rice .                   They note that in the Mouse Cancer Study in cancer-prone mice, 2011,  which claimed that high (fat)cholesterol intake promotes breast cancer, the control mice  (not major carnivores but omnivores) were fed a balanced natural chow with 4.5% fat, 23% protein, and 50% carbohydrate, whereas the test mice were fed a totally synthetic chow meant to represent a western human  cholesterolemic  diet: 20% fat, 17% protein, and 48% carbohydrate. So in fact the high risk factor for cancer and all disease was not the higher fat intake (20%  as dairy fat) vs 4.5%- from fish meal and soy/cereals) but the 48% carbs (2/3  sucrose, 15% (malto)dextrins -which absorb as rapidly as glucose) intake and 19% casein (a major health problem)   in the test chow. They failed to include a control group on what is natural mouse diet ie free of refined carbs and milk :  “RSPCA 2014:   Wild mice – opportunistic omnivores- will eat a wide variety of seeds, grains, and other plant material as well as invertebrates, small vertebrates and carrion”. Thus plenty of natural seed/grain fats and mixed protein and plant carbs,  zero sugar or refined carbs- ie the Banting diet. ..
A new 18year observational  followup  study from Swedenlast year in 62000 people assessed total energy intake – carbohydrate  from median 61 to 39% , protein 11 to 19% , and  fat 27 to 42% . LCHP scores were positively related to intake of animal protein, but negatively related to plant protein. For carbohydrate and fat, associations were consistent in sucrose and whole grain and saturated and unsaturated fat, respectively. Across the range of macronutrients, there was no clear significant trend for particular cancers. This is not surprising as the intake of carbs range d from 40 to 60% and fat from 27 to 42%. Thus no cohort was on a highfat low carbs ketogenic diet as Banting, Noakes  et al find successful. . the lowest % carbs group at best had similar fat % intake ie there was no low-carbs cohort taking below 30% carbs..There is a vast difference in calorie intake  between their “optimal’  LCHP 42:40 fat:carbs ie 1:1  , versus the  true ketogenic HifatLowcarbs diet of eg 50:<30 fat:carbs ie >1.66:1.
       Allowing up to 20% protein in total energy intake, fat may need to  be  close to 50% energy and carbs below 30%, thus ensuring ketogenesis to shed excess fat and avoid depositing more glycogen and adiposity ; so eg for a 2000kcal/day  diet, thats  up to 100gms protein 400kcal mostly from flesh and nuts; carbs below 150gms 600kcal (in nuts and  rainbow vegs) , and fat up to 1000 kcal ie 110gms from cream (not milk), nuts, avo, eggs, butter, cheese and fatty flesh. .

It is no wonder the public is confused.

The truth of more than four decades worth of research is now very clear: the potential benefit of mammography screening is small and the harms are substantial at all ages, but especially so for women in their 40s.

The bottom line is that mammography screening, implemented to reduce breast cancer deaths due to earlier detection of breast cancer, has been eclipsed by therapy and increased awareness.

– See more at: http://umanitoba.ca/outreach/evidencenetwork/archives/4490#sthash.rf9YcMYp.dpuf

It is no wonder the public is confused.

The truth of more than four decades worth of research is now very clear: the potential benefit of mammography screening is small and the harms are substantial at all ages, but especially so for women in their 40s.

The bottom line is that mammography screening, implemented to reduce breast cancer deaths due to earlier detection of breast cancer, has been eclipsed by therapy and increased awareness.

– See more at: http://umanitoba.ca/outreach/evidencenetwork/archives/4490#sthash.rf9YcMYp.dp

VITAMIN INTAKE AND BREAST CANCER:

VITAMIN C  each 100mg/day increment reduces allcause mortality by 27%, and breast cancer mortality by 22%:   a metaanalysis by the Karolinska- Harris ea   last month found 10 trials of vitamin C use and intake  in breast cancer, included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72-0.91) for total mortality and 0.85 (95% CI 0.74-0.99) for breast cancer-specific mortality. The summary RR for a 100mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59-0.89) for total mortality and 0.78 (95% CI 0.64-0.94) for breast cancer-specific mortality- ie 25% lower mortality for every 100mg higher daily vit C intake..

VITAMIN D AND BREAST CANCER:
20 years  ago Newmark from Sloan Kettering NY wrote :  High dietary fat increases mammary epithelial cell proliferation, particularly the “hormonally driven” hyperproliferation during breast growth and development in young animals. Increased dietary calcium (and probably vitamin D) lessens the increase of proliferation induced by high fat. These data, although limited, suggest that the maximum effect of diet (high fat increase, as well as calcium and vitamin D modulation) on eventual breast cancer may be during puberty, and adolescence, when the mammary gland is actively growing and developing. (3) An inverse epidemiological correlation exists between sunlight availability as a source of vitamin D and the risk of breast cancer in the U.S. and Canada. (4) Current vitamin D and calcium dietary intake in the U.S. is far below the RDA in all female age groups, particularly for the elderly. (5) Reduction of breast cancer risk, and simultaneously osteoporosis, might be achieved by increasing dietary intake of calcium and vitamin D to RDA levels. This may be particularly applicable to females during puberty and adolescence.
      20 years later we now still find:Vitamin D and Cancer: The promise not yet fulfilled(California) ; and is there a link (France)?

BUT The Vitamin D Council    sums up the study evidence eg in a major Brit J Cancer metaanalysis last month of 30 prospective studies in 32000 BRCA  patients, and a Chinese study a year ago,   show  that  those with highest  vitamin D levels have 50-90% lower risk of  breast cancer risk, and mortality, and the chance of breast cancer spreading.  so far all they can recommend is that  vitamin D dose should for a robust adult not exceed        10 000iu/day, or pro rata at longer intervals eg 150 000iu a fortnight.  Compared to those with the lowest quartile of plasma 25(OH)D level, women with highest quartile 25(OH)D level showed a significant decreased breast cancer risk (Q4 vs.Q1: OR = 0.10, 95% CI = 0.06–0.15) and every 1 ng/ml increment of plasma 25(OH)D level led to a 16% lower odds of breast cancer.

         It is likely that- given the limits on vitamin C intake due to diarrhoea, and cost, and bloating-  increments in vit D3 intake above the current mediocre 400iu/d norm- up to the generally well-tolerated 10 000iu/day, with supplement of vitamin K2-  will give even better benefit against breast cancer than vitamin C.     
                                                                                                                               
20 May 2014 BREASTS TO KILL: KILLER BRAS
          For the past 4 years, Sure Touch examiners  have observed that many women who wear underwired bras have a string of pearl – fibrous lumps- where the bra wire cuts into them inferiorly; and sometimes radially under the ‘ spokes’ of the bra cups.  We have not yet detected a cancer in such symmetrical  lumpiness, which we find diminishes with change to a soft bra and healing massage with Lugols iodine, coconut oil and DMSO.
          This bra risk   was postulated  in  the book  Dressed To Kill: The Link Between Breast Cancer and Bras(1995, 2005), (NaturalNews).     
Dr Joe Mercola muses: ” Would you believe that two of the nation’s most prominent cancer organizations are completely disinterested in a common wardrobe practice that studies suggest could be a leading cause of breast cancer in women? Wearing bras, says the book  ,appears to be a common trigger of this harrowing disease, yet the American Cancer Society (ACS) and the Susan G. Komen Foundation continue to deny any link between the two.
            ” Authors Sydney Ross Singer and Soma Grismaijer, husband and wife medical anthropologists, have conducted extensive research into the link between bras and breast cancer. They are convinced that the lymphatic constriction imposed by wearing bras prevents women’s bodies from effectively clearing out toxins and other waste, leading to an accumulation of these cancer-causing substances. Bras can also cut off circulatory flow within the body, leading to other health problems.
              “[B]ecause lymphatic vessels are very thin, they are extremely sensitive to pressure and are easily compressed,” the Singers are quoted as saying, noting that the perpetual use of bras over the course of several decades can eventually lead to cancer. “Less oxygen and fewer nutrients are delivered to the cells, while waste products are not flushed away.”
             These are powerful claims, and science seems to back them. Based on an analysis comparing women who wear bras to those who don’t, breast cancer risk was found to be significantly higher among women in the former group. At the same time, women who do not wear bras have about the same risk of developing breast cancer as the average man does, which is not very high.
               Beginning in 1991, the Singers initiated a 30-month “Bra and Breast Cancer” study that evaluated roughly 4,000 women from five major U.S. cities. All the women were Caucasian and came from mostly middle-income homes, ranging in age from 30 to 79. About half of them had previously been diagnosed with breast cancer.After determining the bra-wearing habits of all the women, the Singers determined that wearing a bra increases a woman’s risk of developing breast cancer by double. Shockingly, wearing a bra to sleep at night is even worse, with three out of four, or 75 percent, of women who engage in this practice regularly developing the condition.
                 “Women who want to avoid breast cancer should wear a bra for the shortest period of time possible — certainly for less than 12 hours daily,” said Sydney Singer, as quoted by HealingCancerNaturally.com.     One would think that such information would be pertinent to Komen and other cancer organizations, which are purportedly raising money to find a cure. But the Singers and others have never been able to get their attention, with both Komen and the ACS denying any link between bras and breast cancer.So the Singers are calling on women everywhere to not only boycott supporting these organizations, but also to send over their bras whenever they are asked for money. Awareness about the potential dangers of wearing bras should at least be acknowledged by these groups that claim to support cancer awareness, and yet the response of ACS and Komen on the issue has been less than acceptable.
           “Because of this unscientific stonewalling of this information,” Singer wrote, “over the past 20 years 2,000,000 women in the US alone have gotten breast cancer who may have prevented it by simply loosening their bra and wearing it less time each day.”
             To learn more about Dressed To Kill, visit:
http://www.killerculture.com.
19  May 2014 update:  Dr Gerd Gigerenzer PhD, professor at a number of top USA and German institutions and expert in uncertainty, heuristic problem-solving, writes: This One Graphic Will Change the Way You Look at Breast Cancer Screening:The most trenchant reasoning against screening xray mammography this year is in  Time Magazine 1 May 2014;  which he argues definitely applies to screening mammography: he details four tricks used by zealous proponents of screening mammography to infamously  persuade gullible women why ““If you haven’t had a mammogram, you need more than your breasts examined.”  These tricks are as follows, but are debunked  by the absolute facts in his Fact Box below. He says:

“First, look at the benefit. Out of every thousand women aged 50 and older, five without screening died from breast cancer, compared to four in the screening group. This is an absolute reduction of 1 in 1,000. In fact, it might even be an optimistic estimate because the Canadian follow-up study of women for 25 years after these trials found no reduction at all. But the exact number is not my point here. What I want to explain is how women are being misled.

Trick #1: State that screening reduces breast cancer mortality by 20% or more, because it sounds more impressive than explaining that the absolute risk reduction is 1 in 1,000.   This trick has been used for years in pamphlets. You might think, well, it’s not much, but at least one life is saved. But even that is not true. The number of deaths from all cancers, breast cancer included, is the same in both groups, as seen in line two of the fact box.            And that leads us to                                                                                                                             trick #2: Don’t mention that mammography screening doesn’t reduce the chance of dying from cancer. Talk only about the reduction in dying from breast cancer.      Often, and particularly if a person had multiple cancers, the exact cause of death is unclear. For this reason, total cancer mortality is the more reliable information when you look at it in terms of the larger goal: saving lives. In plain words, there is no evidence to date that routine mammography screening saves lives.             Now let’s look at the harms.

Trick #3: Don’t tell women about unnecessary surgery, biopsies and other harms from overtreatment. If you are asked, play these down.            The first way a mammogram can harm women is if it comes back with a false positive, leading to invasive and unnecessary biopsies. This isn’t the rare fluke most people seem to think it is. This happens to about a hundred out of every thousand women who participated in screening. Legions of women have suffered from this procedure and the related anxieties. After false alarms, many worried for months, developing sleeping problems and affecting relationships with family and friends.

Second, not all breast cancers are life-threatening. Women who have a nonprogressive or slowly growing form that they would never have noticed during their lifetime often undergo lumpectomy, mastectomy, toxic chemotherapy or other interventions that have no benefit for them and that are often accompanied with damaging side-effects. This happened to about five women out of a thousand who participated in screening.

The final trick #4    Tell women about increased survival. For instance, “If you participate in screening and breast cancer is detected, your survival rate is 98%.” Don’t mention mortality.

1 May 2014 update:  Dr Iona Heath FRCP, past president of the New Zealand Royal College of GPs ,  says in March that  Breast cancer mammography screening causes more harm than good.  Dr Kurt Kroenke from Univ Indiana two weeks ago  wrote That most screening test results will be normal or negative is commonplace, but the reality that abnormal results are frequently false-positive is not always well appreciated, nor is it fully conveyed to patients. How does a patient feel after a false-positive test result? Tosteson and colleagues1 concluded from their longitudinal study that “false-positive mammograms are associated with a measurable, small, and transient effect on personal anxiety.” However, a closer look at all the outcomes assessed in this well-done study reveal some adverse consequences that, although not serious, may nonetheless be meaningful.
          Given the harms of  screening, the Spanish consortium sum it up nicely last February:  Optimal (mammography)  screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group.   This last group  is in reality tiny.                                                                                                                                                                    
        As this ongoing Woman’s Care column  stresses, very few well women at any age justify screening mammography, or any screening beyond thorough annual review and bloodpressure  and breast exam check. Only if the annual checkup, with  the examining clinician’s concern about clinical breast feel, or the woman’s  breast symptoms (which in fact rarely originate in the breast and are mostly easily resolved) raise suspicions, may some sort of  no-xray breast imaging be justified- soft SureTouch or ultrasound, or no-touch thermography .  No woman without an obvious  growing solitary breast lump or nipple bleeding/ discharge warrants the harms of initial xray screening mammogram.
                                                                                                                                                                        Unlike Bone Density  Screening available on request,  Sure Touch Breast screening is not charged for since it is part of a proper professional clinical consultation- which can be booked for any regular workday. It is the expert clinical consultation, and any necessary advised evidence-based   natural breast supplements and other changes for prevention, that are billed- obviously at viable market rates, but reduced on justified request based on usual means test.
Breast imaging on its own, without expert clinical assessment and advice , is hazardous because it may cause unwarranted concern and lead to the fearsome  and costly invasive cascade; and because breast imaging without thorough risk factor assessment including expert clinical exam may miss disease that justifies further steps if not immediate resolution.
                                                                                                                                                                HOW TO AVOID UNSETTLING, HARMING WOMEN?  As applies to unjustified mass prostate screening of well men, two new relevant publications below this month highlight the widening gap around MASS BREAST MAMMOGRAPHY SCREENING, between realist  holists- independent  Swiss reviewers  looking at the welfare of women and the real cost-benefits  of  breast screening till now – versus the burn & cut-at-any-cost  screening-industry Dutch career  radiologists’ and cancer experts’vested-interest view looking solely at breast cancer deaths 2004-5, like most for-profit breast -career specialists   targeting every last well breast from 40years upwards.
The latest Cochrane metanalysis  2013 “found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death.”
                                                                                                                                                                       Boston San Francisco- Illinois and Spanish- Catalonia–  universities’  reviewers recently make a less in-your-face case  against universal mass mammography screening,  rather selective screening frequency based on individualized risk factors and  potential harms.. But they dont refer to equally effective non-xray imaging techniques; or the fact that no imaging techniques except tissue histology can confirm or exclude cancer. .
                                                                                                                                                                against: DO NO HARM:  April 16, 2014 / NEJM  Perspective   from the Swiss Medical Board: Abolishing Mammography Screening Programs?          Nikola Biller-Andorno, and Peter Jüni, http://www.nejm.org/doi/full/10.1056/NEJMp1401875?query=TOCIn January 2013, the Health Ministers of the Swiss Cantons, the Swiss Medical Association, and the Swiss Academy of Medical Sciences mandated the Swiss Medical Board (a medical ethicist,  a clinical epidemiologist, a clinical pharmacologist, an oncologic surgeon, a nurse scientist, a lawyer, and a health economist), an independent health technology assessment initiative,  to prepare a review of mammography screening.We were aware of the controversies that have surrounded mammography screening for the past 10 to 15 years. When we reviewed the available evidence and contemplated its implications in detail, however, we became increasingly concerned.
          First, we noticed that the ongoing debate was based on a series of reanalyses of the same, predominantly outdated trials. The first trial started 50 years ago in New York City and the last  in 1991 in the United Kingdom.1 None of these trials were initiated in the era of modern breast-cancer treatment, which has dramatically improved the prognosis of women with breast cancer. Could the modest benefit of mammography screening in terms of breast-cancer mortality that was shown in trials initiated between 1963 and 1991 still be detected in a trial conducted today?
                                                                                                                                                                      
             Second, we were struck by how nonobvious it was that the benefits of mammography screening outweighed the harms. The relative risk reduction of approximately 20% in breast-cancer mortality associated with mammography that is currently described by most expert panels2 came at the price of a considerable diagnostic cascade, with repeat mammography, subsequent biopsies, and overdiagnosis of breast cancers — cancers that would never have become clinically apparent. The recently published extended follow-up of the Canadian National Breast Screening Study is likely to provide reliable estimates of the extent of overdiagnosis. After 25 years of follow-up, it found that 106 of 484 screen-detected cancers (21.9%) were overdiagnosed.3 This means that 106 of the 44,925 healthy women in the screening group were diagnosed with and treated for breast cancer unnecessarily, which resulted in needless surgical interventions, radiotherapy, chemotherapy, or some combination of these therapies.
      In addition, a Cochrane review of 10 trials involving more than 600,000 women showed no evidence of mammography screening benefit  on overall mortality.1 In the best case, the small reduction in breast-cancer deaths was attenuated by deaths from other causes. In the worst case, the reduction was canceled out by deaths caused by coexisting conditions or by the harms of screening and associated overtreatment. Did the available evidence, taken together, indicate that mammography screening indeed benefits women?
                                                                                                                                                                        
      Third, we were disconcerted by the discrepancy between women’s perceptions of the benefits of mammography screening and the benefits to be expected in reality. The figure  Women’s Perceptions of the Effects of Mammography Screening on Breast-Cancer Mortality as Compared with the Actual Effects. shows the numbers of 50-year-old women in the United States expected to be alive, to die from breast cancer, or to die from other causes if they are invited to undergo regular mammography every 2 years over a 10-year period, as compared with women who do not undergo mammography. The numbers in Panel A are derived from a survey about U.S. women’s perceptions,4 in which 717 of 1003 women (71.5%) said they believed that mammography reduced the risk of breast-cancer deaths by at least half, and 723 women (72.1%) thought that at least 80 deaths would be prevented per 1000 women who were invited for screening. The numbers in Panel B reflect the most likely scenarios according to available trials1-3: a relative risk reduction of 20% and prevention of 1 breast-cancer death. The data for Switzerland, reported in the same study, show similarly overly optimistic expectations. How can women make an informed decision if they overestimate the benefit of mammography so grossly?
                                                                                                                                                                        
      The Swiss Medical Board’s report was made public on February 2, 2014 . It acknowledged that systematic mammography screening might prevent about one death attributed to breast cancer for every 1000 women screened, even though there was no evidence to suggest that overall mortality was affected. At the same time, it emphasized the harm — in particular, false positive test results and the risk of overdiagnosis. For every breast-cancer death prevented in U.S. women over a 10-year course of annual screening beginning at 50 years of age, 490 to 670 women are likely to have a false positive mammogram with repeat examination; 70 to 100, an unnecessary biopsy; and 3 to 14, an overdiagnosed breast cancer that would never have become clinically apparent.5 The board therefore recommended that no new systematic mammography screening programs be introduced and that a time limit be placed on existing programs. In addition, it stipulated that the quality of all forms of mammography screening should be evaluated and that clear and balanced information should be provided to women regarding the benefits and harms of screening.
The report caused uproar and was emphatically rejected by a number of Swiss cancer experts and organizations, some of which called the conclusions “unethical.” One of the main arguments used against it was that it contradicted the global consensus of leading experts in the field — a criticism that made us appreciate our unprejudiced perspective resulting from our lack of exposure to past consensus-building efforts by specialists in breast-cancer screening. Another argument was that the report unsettled women, but we wonder how to avoid unsettling women, given the available evidence.
The Swiss Medical Board is nongovernmental, and its recommendations are not legally binding. Therefore, it is unclear whether the report will have any effect on the policies in our country. Although Switzerland is a small country, there are notable differences among regions, with the French- and Italian-speaking cantons being much more in favor of screening programs than the German-speaking cantons — a finding suggesting that cultural factors need to be taken into account. Eleven of the 26 Swiss cantons have systematic mammography screening programs for women 50 years of age or older; two of these programs were introduced only last year. One German-speaking canton, Uri, is reconsidering its decision to start a mammography screening program in light of the board’s recommendations. Participation in existing programs ranges from 30 to 60% — variation that can be partially explained by the coexistence of opportunistic screening offered by physicians in private practice. At least three quarters of all Swiss women 50 years of age or older have had a mammogram at least once in their life. Health insurers are required to cover mammography as part of systematic screening programs or within the framework of diagnostic workups of potential breast disease.
                                                                                                                                                                              

     It is easy to promote mammography screening if the majority of women believe that it prevents or reduces the risk of getting breast cancer and saves many lives through early detection of aggressive tumors.4 We would be in favor of mammography screening if these beliefs were valid. Unfortunately, they are not, and we believe that women need to be told so. From an ethical perspective, a public health program that does not clearly produce more benefits than harms is hard to justify. Providing clear, unbiased information, promoting appropriate care, and preventing overdiagnosis and overtreatment would be a better choice.

from the  Universities of Zurich &  Bern,  Switzerland; and   Harvard Medical School, Boston . Dr. Biller-Andorno is a member of the expert panel of the Swiss Medical Board; Dr. Jüni was a member of the panel until August 30, 2013

                                                                                                                                                                      FOR-SCREENING– FOR CAREER/PROFIT :  do the maximum: 
Breast. 2014 Apr 5.  Breast cancer screening halves the risk of breast cancer death: A case-referent study. Paap E, Verbeek AL,Broeders MJ ea.  Netherlands Breast Screening Centres.   Large-scale epidemiologic studies have consistently demonstrated the effectiveness of mammographic screening programs, however the benefits are still subject to debate. We estimated the effect of the Dutch screening program on breast cancer mortality. In a large multi-region case-referent study, we identified all breast cancer deaths in 2004 and 2005 in women aged 50-75 who had been invited for screening (cases). Cases were individually matched to referents from the population invited to screening. A total of 1233 cases and 2090 referents were included in this study. We found a 58% reduction in breast cancer mortality in screened versus unscreened women (adjusted OR = 0.42, 95% CI 0.33-0.53). Screening, i.e. early detection and treatment, has resulted in a substantial reduction in breast cancer mortality, indicating that the Dutch breast cancer screening program is highly effective.
                                                                                                                                                                 update  23 March 2014: Caroline Huang at the  Ethox Centre at Oxford writes in   Screening mammography: benefits, harms, and evidence-based guidelines in the US and UK:   The Ethox Centre is a multidisciplinary bioethics research centre in the University of Oxford’s Nuffield Department of Population Health.“Authors Bleyer and Welch claim there has been only an 8% reduction in late-stage breast cancer diagnoses (an absolute reduction of 8 cases per 100,000 women), and while mortality has decreased, it appears that most of the benefit has come from better treatment rather than better screening. (For cancer screening to be considered effective, the US National Cancer Institute says that cancer deaths and late-stage cancer diagnoses should decrease, while early-stage cancer diagnoses should increase.[2])
Contrast these findings to another mammography study published the same week in The Lancet, conducted by an independent panel in the UK as a meta-analysis of 11 randomized trials.[3] The panel estimated overdiagnosis of early-stage breast cancers in the UK to be between 11 and 19%. Crucially, though, there appeared to be a 20% mortality benefit from screening alone.What might account for these significantly different estimations of breast cancer screening effectiveness? The most obvious factor is the frequency and age at which average-risk women are offered mammography. In the UK, women ages 50-70 are offered screening every three years through the NHS Breast Cancer Screening Programme. In the US, women ages 40-70 are typically offered screening every one or two years.      
                      Though a 2009 US Preventive Services Task Force (USPSTF) report recommended that average-risk women should receive screening from ages 50-74 every two years,[4] this recommendation has been not been adopted by professional organizations such as the American Cancer Society, the American College of Radiologists, and the National Cancer Institute. In fact, a study published in November in Preventive Medicine showed that there has been no difference in mammograms provided across any age groups in the US since the 2009 USPSTF report was published.[5]These two studies (and many others preceding them) raise plenty of practical questions about diagnostic thresholds, benefits of population screening, limitations of current radiology technologies, and understanding of which cancers do and do not become invasive. But I want to raise a broader question: should there be an ethical imperative compelling different US professional groups that address the same disease or disorder to adopt a common set of evidence-based guidelines?                                                                                                                                                       
          And if there isn’t, then what is the value of having a group like the USPSTF to issue recommendations that may ultimately be ignored by its target audiences?A few reasons for adopting a common set of evidence-based guidelines might be reducing patient and provider confusion, enhancing low-cost access to care, and potentially redistributing funds to further the reach of proven services or improve research. While the National Breast Cancer Screening Programme requires only the NHS to adopt and implement new recommendations, the more fragmented US system means that screening is not organized by a single body and thus involves competing recommendations that could confuse patients trying to make informed choices and providers trying to assist them in doing so. Additionally, because US insurers are increasingly moving towards funding only evidence-based services, having a common set of guidelines would help ensure that providers’ recommended services are covered under patients’ insurance rather than falling into a category of services with questionable benefit that might not be covered. This is perhaps not the optimal ethical consideration to have to make, but it is a necessary component of realistic preventive care. Finally, at the health system level, providing mammograms only to women ages 50-74 might mean that resources currently allocated to mammograms for women ages 40-49 could be put towards more mammograms for women ages 50-74 or other related preventive health services or research.Despite these reasons, however, it would be equally problematic to remove clinical groups’ ability to disagree with recommendations that they believe result from poor statistics or faulty logic. It also does not seem like there is intrinsic opposition to adopting recommendations produced by independent panels or other clinical groups.   
                                                                                                                                                                        The same Preventive Medicine study discussed above references two cases in which recommendations resulted in immediate changes to screening patterns: (1) the National Cancer Institute and American Cancer Society’s 1997 recommendation that mammography be expanded to women ages 40-49 resulted in increased screening, and (2) the USPSTF’s 2008 recommendation against prostate cancer screening in men ages 75 and older resulted in fewer early-stage prostate cancer diagnoses. So the USPSTF has not always been unsuccessful in having its recommendations taken seriously, even in a case where less screening is recommended, and at least one breast cancer screening recommendation has previously had a quick adoption in practice.These cases – as well as the USPSTF 2002 recommendation that originally suggested offering mammography to women ages 40-49 once every 1-2 years, which is reflected in current clinician groups’ guidelines – suggest that the USPSTF’s target audiences aren’t willfully ignoring meta-analyses of available data. Rather, clinicians, advocacy groups, and patients have questioned the methodology behind the 2009 USPSTF recommendation, in a similar fashion to the critiques being raised over the NEJM study.                                                                                
                                                                                                                                                                        
               For example, the American College of Radiology suggested that Bleyer and Welch failed to properly account for an increasing incidence of invasive late-stage breast cancers unrelated to screening uptake.[6] In light of this information, we might reframe the second question to ‘How do we ensure that groups like the USPSTF incorporate the right kind of data into their analyses and recommendations?’ That answer might have to do with rethinking how consultation with relevant clinical and patient advocacy groups is carried out, as well as examining a broader range of data sources. To circle back to the contrast between the NEJM and Lancet findings, it is important to think about how and why the UK’s National Breast Cancer Screening Programme seems to have lower rates of overdiagnosis and greater mortality benefit from screening relative to the US screening system.                                                                                                                                                                                                                                                                             At the very least, these kinds of contradictory non-US outcomes should prompt a re-evaluation of which kinds of evidence we have chosen to evaluate.We might also point to the discourse around prostate-specific antigen (PSA) testing – which has been linked to overdiagnosis of early-stage, non-invasive prostate cancer – as one model for where breast cancer screening recommendations may go. Importantly, while clinical organizations have not reached consensus in whether PSA testing should be recommended as a yearly exam for men over 50,[7] they do agree that a careful discussion of PSA testing’s potential harms and benefits is always appropriate.Indeed, the authors of both the Lancet and NEJM articles conclude with similar thoughts: physicians must initiate conversations about the pros and cons of mammography so that patients can make informed choices. That assertion seems uncontroversial enough to be accepted by the various professional groups involved – so perhaps any common set of guidelines we should expect groups to adopt should relate to the communication of evidence rather than potentially controversial or insufficient evidence itself.”
                                                                                                                                                                      15/3/ 2014 update: Great Mammography Debate :  Dr. Patrick Borgen, Chairman of Surgery at Maimonides Medical Center in Brooklyn, New York, talks about the role of screening mammography, a topic bracketed by strong opinions. It has been a particular focus of discussion at the 31st Annual Miami Breast Cancer Conference, held March 6 through March 9, 2014, in Miami, Florida.

               Commentary  The mammography debate is one of the facets of the Miami Breast Cancer Conference this year.   It seems as though the field of breast cancer has always been controversial, going back half a century, and breast cancer is a disease that, more than most others, is very polarizing. This disease engenders great passion—and great debate, which has been ongoing about the role of screening mammography.

            A few weeks ago, The New York Times covered an article that was published in the British Medical Journal 1 about the Canadian National Breast Screening Study. On the surface, this study failed to show any benefit from mammography. That was the story that the writer, Gina Kolata, picked up and ran with. Ms. Kolata had written about her own experience with breast cancer a number of years ago; her breast cancer had not been picked up on a mammogram, and so she is somewhat biased.

               In short, the Canadian study evaluated mammograms from more than 90,000 women who had very primitive mammograms between 1980 and 1984, and that is really the first problem with this study: the technology and the equipment then was incredibly limited, such that the mammograms only showed 30% of breast cancers; whereas, today, mammography detects 70% to 80% of breast cancers. Thus, taking results generated by technology from 34 years ago and making a conclusion about them in today’s world is a stretch.

One of the fundamental flaws of the Canadian study, besides the dated technology on which the conclusions were based, was that it was not randomized. Nurses, and, in some provinces in Canada, doctors, did a clinical breast exam, and, if they felt a mass or a lump, they preferentially put the patient into the mammography arm. That is what I would have done in their place; if I felt a lump, I would not be willing to send someone home.

By the end of the study, there were more than 100 extra breast cancers in the mammography arm and more breast cancers that had spread to lymph nodes in the mammography arm. And, in fact, the chance of dying of breast cancer was higher in the mammography arm.

All of the authorities with whom I have ever spoken or read who have reviewed this study dismiss it as very flawed. A number of the doctors who were involved with the study resigned their positions in protest. Despite all of that, The New York Times ran an article headlined, “Vast Study Casts Doubts on Value of Mammograms” (February 11, 2014).

Well, it is a vastly flawed study, and, in fact, there are six other, much larger and much better controlled studies, all of which showed a reduction in breast cancer mortality from 20% up to 40% in women who have mammograms—and that is certainly what we observe clinically.

We felt that it was important to really highlight this at the Miami Breast Cancer Conference this year. My guess is that our audience already knows this; but, what we would like to give them is the science about why the Canadian study was flawed so that they can talk to their patients and talk to their colleagues who may not be in the breast cancer field. That is really what I think our mission is for part of this year’s conference.

We think that this is dangerous information. We think that women will unnecessarily lose their lives to breast cancer if they forego mammography, which this study frankly says one should. I have a busy practice in Brooklyn, New York, and, at least once or twice a week, I see someone, without any question, whose life was saved by a mammogram.

I think that we all agree we need something better than mammography. We all agree that mammography can lead to over-diagnosis of breast cancers, and over-diagnosis happens, of course, when we screen for diseases in other areas of the body. We all accept this limitation.

But, for a major media outlet to take a single study that was deeply flawed and not even mention the existence of other studies, even as a point–counterpoint, I think was a bit outrageous!

12 March 2014 this publication on the Huffington Post website  today under screening mammography is as appropriate as when it was published in 2010:

The NBCAM has assured women that “early (mammography) detection results in a cure nearly 100 percent of the time.” More specifically, the NBCAM is directed to claims for reducing the incidence and mortality of breast cancer through early detection by annual mammography starting at age 40. Moreover, mammograms can miss cancers in premenopausal women due to the density of their breasts, and also fail to detect cancers smaller than half an inch.

Still denied by the ACS is clear evidence that premenopausal mammography poses significant risks of breast cancer. The routine practice of taking two films annually for each breast results in approximately 0.5 rad (radiation absorbed dose) exposure. This is about 500 times the dose from a single chest X-ray and is broadly focused on the entire chest rather than narrowly on the breast. This is also 25 times higher than is allowed by the Environmental Protection Agency for whole-body radiation from local nuclear industries (0.02 rad). Moreover, the breast is the most sensitive organ to ionizing radiation.

As warned by the prestigious National Academy of Sciences in 1972 but still ignored by the ACS, the premenopausal breast is highly sensitive to the risks of cancer from mammography, as each rad exposure increases the risks of breast cancer by 1 percent. This results in a cumulative 10 percent increased risk for each breast following a decade of routine screening. This can also accounts for the 19-percent increased incidence of breast cancer since 1975. Not surprisingly, the prestigious U.S. Preventive Task Force, supported by the National Breast Cancer Coalition, warned last year against routine premenopausal mammography. Also, not surprisingly, routine premenopausal mammography is practiced by no nation other than the U.S.

Risks of premenopausal mammography are some four-fold greater for the 2 percent of women who are carriers of the A-T gene (ataxia telangiectasia) and are highly sensitive to the carcinogenic effects of radiation. By some estimates, this accounts for up to 20 percent of all breast cancers diagnosed annually. Compounding these problems, missed cancers are common in premenopausal women due to the density of their breasts.

That most breast cancers are first recognized by women was admitted by the ACS in 1985. “We must keep in mind that at least 90 percent of the women who develop breast cancer discover the tumors themselves.” Furthermore, an analysis of several 1993 studies showed that women who regularly performed breast self-examination (BSE) detected their cancers much earlier than women failing to examine themselves. The effectiveness of BSE, however, depends on training by skilled professionals, enhanced by an annual clinical breast examination. Nevertheless, in spite of such evidence, the ACS dismisses BSE, and claims that “no studies have clearly shown [its] benefit.”

As reported in our 1999 publication in the International Journal of Health Services, an article in a leading Massachusetts newspaper featured a photograph of two women in their twenties. The article promised that early detection by mammography results in a cure “nearly 100 percent of the time.” Questioned by journalist Kate Dempsey, an ACS communications director responded: “The ad isn’t based on a study. When you make an advertisement, you just say what you can to get women in the door. You exaggerate a point — Mammography today is a lucrative [and] highly competitive business.”

If all 20 million U.S. premenopausal women submitted to annual mammograms, the minimal annual costs would be $2.5 billion. Such costs would be increased some fourfold if the industry, supported by radiologists, succeeds in its efforts to replace film machines, costing about $100,000, with high-tech digital machines, costing over $400,000, even in the absence of any evidence for their improved effectiveness.

With this background, it is hardly surprising that the National Breast Cancer Awareness Month neglects to inform women how they can reduce their risks of breast cancer. In fact, we know a great deal about its avoidable causes which remain ignored by the ACS. These include:

    • Prolonged use of the Pill, and estrogen replacement therapy.
    • Prolonged consumption of milk from cows injected with a genetically engineered growth hormone to increase milk production. This milk is contaminated with high levels of a natural growth factor, which increases risks of breast cancer by up to seven-fold.
    • High consumption of meat, as it is contaminated with potent natural or synthetic estrogens. These are routinely implanted in cattle before entry into feedlots, about 100 days prior to slaughter, to increase muscle mass and profits for the meat industry.
    • Prolonged exposure to a wide range of hormonal ingredients in conventional cosmetics and personal care products.
  • Living near hazardous waste sites, petrochemical plants, power lines, and nuclear plants.

The enthusiastic and continuing support of premenopausal mammography by the ACS is hardly surprising in view of its major conflicts of interest that still remain unrecognized. Five radiologists have served as ACS presidents. In its every move, the ACS promotes the interests of the major manufacturers of mammogram machines and films, including Siemens, DuPont, General Electric, Eastman Kodak and Piker. The mammography industry also conducts research for the ACS, serves on its advisory boards, and donates considerable funds. DuPont is also a substantial backer of the ACS Breast Health Awareness Program. It sponsors television shows touting mammography; produces advertising, promotional materials and literature for hospitals and doctor; and lobbies Congress for legislation promoting the availability of mammography. The ACS has been and remains strongly linked with the mammography industry, while ignoring or criticizing the value of breast self-examination, even following training by a qualified nurse or clinician.

The ACS conflicts of interest extend well beyond the mammography industry. The ACS has received contributions in excess of $100,000 from a wide range of “Excalibur (industry) Donors,” who manufacture carcinogenic products. These include petrochemical companies (DuPont, BP and Pennzoil), Big Pharma (AstraZenceca, Bristol Myers Squibb, GlaxoSmithKline, Merck & Company and Novartis), and cosmetic companies (Christian Dior, Avon, Revlon and Elizabeth Arden).

Samuel S. Epstein, M.D. is professor emeritus of Environmental and Occupational Medicine at the University of Illinois at Chicago School of Public Health; Chairman of the Cancer Prevention Coalition; and a former President of the Rachel Carson Trust. His awards include the 1998 Right Livelihood Award and the 2005 Albert Schweitzer Golden Grand Medal for International Contributions to Cancer Prevention. Dr. Epstein has authored 270 scientific articles and 20 books on cancer prevention, including the groundbreaking “The Politics of Cancer” (1979), and most recently “Toxic Beauty” (2009, Benbella Books: http://www.benbellabooks.com) about carcinogens, besides other toxic ingredients, in cosmetics and personal care products. Email: epstein@uic.edu. Web: http://www.preventcancer.com.

update 6 March 2014    Switzerland debates dismantling its breast cancer screening programme   BMJ 2014;348:g1625   “A row has erupted in Switzerland after the Swiss Medical Board  recommended that the country’s mammography screening programme for breast cancer be suspended because it leads to too many unnecessary interventions.
              In a report made public on 2 February, the board said that while systematic mammography screening for breast cancer saved 1-2 women’s lives for every 1000 screened, it led to unnecessary investigations and treatment for around 100 women in every 1000.1 “The desirable effect is offset by the undesirable effects,” said the report, which was based on study data from 1963 to 1991   comparing 1000 women who were screened with 1000 women who were not. The report also concluded that screening was not cost effective.…”

update 1 Mar 2014 Supporting informed decision making when clinical evidence and conventional wisdom, clash.   The nub of the screening mammography war – and all hard-sell marketing hype-  is elegantly analyzed by a USA multiUniversity Communications team in Against conventional wisdom: when the public, the media, and medical practice collide.      Jakob Jensen ea argue that “the screening mammography  controversy was driven by the systematic removal of uncertainty from science communication. To increase comprehension and adherence, health information communicators remove caveats, limitations, and hedging so science appears simple and more certain. This streamlining process is, in many instances, initiated by researchers as they engage in dissemination of their findings, and  is facilitated by public relations professionals, journalists, public health practitioners, and others whose tasks involve using the results from research for specific purposes.   Uncertainty is removed from public communication because many communicators believe that it is difficult for people to process and/or that it is something the audience wants to avoid. Uncertainty management theory posits that people can find meaning and value in uncertainty.                  CONCLUSIONS: Science is routinely simplified as it is prepared for public consumption.     In line with the model of information overload, this practice may increase short-term adherence to recommendations at the expense  of long-term message consistency and trust in science”. 

          The Mammography Saves Lives  screening campaign  was and is to recruit all older women to regular screening; it  was progressively oversold   by removing, ignoring the science uncertainty. “Science is routinely simplified as it is prepared for public consumption. In line with the model of information overload, this practice may increase short-term adherence to recommendations at the expense of long-term message consistency and trust in science”.


We see the same collusion between corporate marketeers and government regulators in so many high-profit industries:
  on Pubmed,  screening mammography features for 50 years, and continued to expand exponentially without hindrance until enough epidemiologists – led by the Cochrane Group- collectively  rang enough alarm bells the past decade. The zealous huge-profit USA  radiology-oncology industry simply shouted down the negative result of the massive Canadian Screening Mammography trial outcome   30 years ago in 90 000 women, and continue to do so with the 25year results now reported. The huge Breast Industry retaliates by threatening whistle blowers.

*at the same time around 50years ago, as many of us were starting medical studies, Keys and Stamler  et al in USA did bad epidemiological studies that subverted the facts of  healthy indigenous diets around Europe, Africa and Asia, and the healthy traditional English-speaking (USA and the British Empire) working population’s mainly fresh meat/fish  fat and farm produce diet,
      to claim that the reverse be promoted-  factory-produced low fat low cholesterol high carbohydrate (cereals, potato, white flour and white rice) –  and worse, quadrupling of fructose and sucrose intake, with increasing obesity;   and then noxious statins- for-all for the resultant carbs-inducedlipidemia “epidemic”;  and the  dangerous hypoglycemic drugs for mushrooming type 2 diabetes, and NSAIDs for arthritis; and numerous wannabe antiobesity drugs; and finally the new industry of bariatric surgery!.
        see the classic expose books: John Gofman’s  Preventing Breast Cancer 1996; James le Fanu ‘s  The Rise and Fall of Modern Medicine 1999 ; Gary Taubes’ The Diet Delusion (2007);  Ben Goldacre’s Bad Pharma 2012 and Peter Gotzsche’s Mammography Screening: Truth, Lies and Controversy 2013

*and as a result,  the past 30years,- against all rational food  science and biology – Montsanto’s Government- approved  rape  of healthy food agriculture by genetically modified crops laced with toxic environmentally persistent glyphosate C3H8NO5P- Roundup.

It is no irony that one of the leading medical scientists of the 20th century Dr John Gofman took part in  the Manhattan  nuclear Project, was a pioneer of VLDL lipidology, and then an activist for protecting women against the accumulating harm of mammography – “there is no safe dose of radiation”.

 at Exam. Resulting Risk of Mammogram-Induced Breast Cancer. 1998
Any age in 1 exam: 1 chance in about 1,100.
30-34 range. 5 exams: 5 chances/1100, or 1 chance in 220.
Any age in 1 exam: 1 chance in about 1,900.
35-49 range. 10 exams: 10 chances/1900, or 1 chance in 190.
Any age in 1 exam: 1 chance in about 2,000.
50-64 range. 15 exams: 15 chances/2,000, or 1 chance in 133.

Dr Emily Transue MD eloquently describes her personal disillusionment with screening mammography.

                                                                                                                                                                                     update 23 Feb 2014     Like Wikipedia on breast screening, Karen Kaplan in the L.A.Times this week challenges mammography radiologists: stop lying to patients about the benefits of screening mammography. As Dr David Katz in the Huffington Post muses, can we unmuddle mammography?                                                                            The USA National Cancer Association promotion conspicuously avoids mentioning the equal balance between benefits and risks of screening mammography, 
and Dr Charles Wright in the Toronto Globe and Mail  says   “It’s time for a new approach to mammograms  
     The New York Times review this week turns the report of the Canadian trial to focus on the importance of breast self-examination; their other review  agrees that  Vast Study Casts Doubts on Value of Mammograms.
It is damning that Cochrane studies   (which date from about 1994) -for mammography published only since year 2000 – have consistently found that screening mammography imaging has no material longterm survival benefit for women with apparently normal breasts, with numerous potential harms.
      The question remains, should people  without suspicious cancer  symptoms or bad family history  have any invasive screening (of breast and prostate) beyond regular appropriate physical examination? when all of us should follow  sensible lifestyle, diet and appropriate supplements to minimize both acute and chronic diseases, and thus die well in old age.
                If women without apparent high risk  will not be satisfied by clinical reassurance, prescreening  image recording without compression irradiation will depend on what is locally available.
The USA National Cancer Institute at the NIH , while dutifully promoting regular screening mammography, negates their promotion by listing  precisely  7 lines,  one benefit : Early detection of breast cancer with screening mammography means that treatment can be started earlier in the course of the disease, possibly before it has spread. Results from randomized clinical trials and other studies show that screening mammography may  reduce the number of deaths from breast cancer among women ages 40 to 70, especially for those over age 50..
            But it lists 46 lines of potential harms:”What are some of the potential harms of screening mammograms?      
1. “Finding cancer early doesnt  reduce a woman’s chance of dying from breast cancer or any cause. Even though mammograms can detect malignant tumors that cannot be felt, treating a small tumor does not always mean that the woman will not die from the cancer. A fast-growing or aggressive cancer may have already spread to other parts of the body before it is detected.                                                              
2. Fear: “Women with such detected  early tumors live a longer period of time fearing that they likely have a fatal disease… screening mammograms dont help prolong the life of a woman who is suffering from other, more life-threatening health conditions. Depression anxiety let alone suicide are increased .
3. “False-negative results occur when mammograms appear normal even though breast cancer is present. Overall, screening mammos miss about 20% of breast cancers that are present at the time of screening.. from  high breast density i.e., glandular tissue and connective tissue, together known as fibroglandular tissue) and fatty tissue.  Because fibroglandular tissue and tumors have similar density, tumors can be harder to detect in women with denser breasts more often among younger women than among older women because younger women are more likely to have dense breasts. As a woman ages, her breasts usually become more fatty, and false-negative results become less likely. False-negative results can lead to delays in treatment and a false sense of security for affected women.                              
4. “False-positive results occur when radiologists decide mammograms are abnormal but no cancer is actually present. All abnormal mammograms should be followed up with additional testing (diagnostic mammograms, ultrasound, and/or biopsy) to determine whether cancer is present… more common for younger women, women who have had previous breast biopsies, women with a family history of breast cancer, and women who are taking estrogen (for example, menopausal hormone therapy).        False-positive mammogram results can lead to anxiety and other forms of psychological distress in affected women. The additional testing required to rule out cancer can also be costly and time consuming and can cause physical discomfort. .                                                                                                            
5. “Overdiagnosis and overtreatment. Screening mammograms can find cancers and cases of ductal carcinoma in situ (DCIS, noninvasive tumor  cells that may become cancerous build up in the lining of breast ducts) that need to be treated. However, they can also find cancers and cases of DCIS that will never cause symptoms or threaten a woman’s life, leading to “overdiagnosis” of breast cancer. Treatment of these latter cancers and cases of DCIS is not needed leads to “overtreatment.” Overtreatment exposes women unnecessarily to the adverse effects associated with cancer therapy.      Because doctors often cannot distinguish cancers and cases of DCIS that need to be treated from those that do not, they overtreat .                                                                                                                              
6. “Radiation exposure. Mammograms require very small doses of radiation. The risk of harm from this radiation exposure is extremely low, but repeated x-rays have the potential to cause cancer. 

They fail to list other adverse effects:                                                                                       7. Pain and bruising of crush mammography- sometimes prolonged;                     8. spreading early and likely dormant cancer.                                                                   9. Increased incidence of breast cancer and thus more irradiation, mastectomy and all-cause mortality, and                                                                                                              10. complications of surgery, radiotherapy and chemotherapy.                                                 ………………………..

           the Rapid Responses to the 25year  Breast cancer incidence and mortality of the Canadian National Breast Screening Study show again the Great Divide between objective  epidemiological evidence,  and vested-interest belief by those whose careers and incomes depend on zealous pursuit of early (pre)cancers.
              Prof Michael Baum as a former UK Screening Mammography leader again trenchantly quotes reality to protect women from terrorism by screening mammography and mastectomy, in particular urging the same policy of watchful waiting to see the natural course of early  cancer-   that has saved so many men from harmful diagnostic and therapeutic invasion of asymptomatic prostate cancer.
                  We must stress that, if the patient refuses or is denied conventional oncotherapy, Watchful Waiting should always be supported including by all possible improvements in multibeneficial diet, lifestyle and supplements, and avoidance of cancer-promoting estrogenics .
…………………………………….
     Women who choose not to have mammography and oncotherapy for highly suspicious lumps or even advancing cancers, or have been classified by cancer clinics  as too advanced for oncotherapy- told they have very short life expectancy- illustrate the lesson of watchful waiting with active intervention. We  see surprising regression in breast lumps, breast cancer and quality life extension in those who refuse to accept the oncologists’  death predictions  and who apply strong faith and  some of the many evidence-based changes and preventative natural supplement remedies we have  collated,    before or  even after the gamut /  gauntlet  of crush mammography, biopsy, surgery and radio-chemotherapy.
                                                                                                                                                           update 21 Feb 2014 The Oncologist publishes epidemiologist Archie Bleyer’s   “Were Our Estimates of Overdiagnosis With Mammography Screening in the United States Based on Faulty Science”?   rebuttal of radiologist Prof Daniel Kopans’  denial of the overdiagnosis of breast cancer.
        The point Bleyer again makes is that women have the choice provided they are fully informed of the pros and cons, and the options to screening mammography  and biopsy.
                 16 Feb 2014 update:   a slew of new papers reinforces the futility and hazards of mammography screening for early breast cancer- and the divide between the vested interests of mammographers/ oncologists – those who make their living from finding every possible cancer-  and the welfare of women:
                    Natural News today reviews criticisms of mammography from USA.
   in  NEJM 13 Feb , 2014,       Lisa Rosenbaum MD , Univ Pensylvania:  sums up the dilemma of real but unprofitable evidence vs profiteering, culture  and feeling  : Misfearing” — Culture, Identity, and Our Perceptions of Health Risks  Despite knowing that heart disease kills more women each year than all cancers combined, most women fear breast cancer far more — and their health-related behavior reflects this difference. If our sense of risk is less about fact than about feeling, how do we adjust it?
                
BMJ Feb 11,  2014: 25year  Breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial   Anthony  Miller, Cornelia  Baines, Steven  Nar ea,  compared breast cancer incidence and mortality up to 25 years later  in 89 835 volunteer women aged 40-59 randomly assigned to mammography (five annual mammography screens) or control (no mammography) in 15 screening centres in six Canadian provinces, 1980-85 . .  Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community.  Main outcome measure Deaths from breast cancer.  Results During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). in those aged 40-49 and 50-59 . During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis.   Conclusion Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.
                        Editorial Too much mammography  11 February 2014   BMJ 2014;348:g1403 http://dx.doi.org/10.1136/bmj.g1403  Mette Kalager,Hans-Olov Adami, Michael Bretthauer, Norway.                                     Long term follow-up does not support screening women under 60.   Before being widely implemented, mammography screening was tested in randomised controlled trials in the 1960s to 80s. Meta-analyses of these trials showed a relative reduction in deaths from breast cancer of between 15% and 25% among women aged 50 to 69.1 2 3 Only the Canadian National Breast Screening Study showed no reduction in breast cancer mortality.1 2 3 This large randomised controlled trial compared physical breast examination with combined physical breast examination and annual mammography in women aged 40 to 59.1 2 3    In a linked paper (doi:10.1136/bmj.g366), Miller and colleagues present the results for up to 25 years of follow-up in the Canadian study.4 No difference in breast cancer mortality was observed between the mammography and control arms, whereas a significant excess incidence of invasive breast cancer was observed in the mammography arm, resulting in 22% overdiagnosis. This means that 22% of screen detected invasive cancers would not have reduced a woman’s life expectancy if left undetected. The major strengths of this study include its randomised design, intense intervention with five annual mammography screenings, high compliance, and complete, long term follow-up. The lack of mortality benefit is also biologically plausible because the mean tumour size was 19 mm in the screening group and 21 mm in the control group. This 2 mm difference—which might be even smaller if overdiagnosed cancers could be excluded from the screening group—represents a minimal proportion of the entire clinical course for breast tumours.  But the trial also has some potential limitations. No quantitative data are available on the degree of contamination in the control arm or possible confounding by screening mammography after the trial. It seems unlikely, however, that such potential limitations would conceal a clinically important benefit. The rate of overdiagnosis did not include ductal carcinoma in situ, and the trial provides no data for women older than 60.

               The Canadian study, launched in 1980, is the only trial to enroll participants in the modern era of routine adjuvant systemic treatment for breast cancer, and the women were educated in physical breast examination as advocated today.4 These important features may make this study more informative for a modern setting, compared with other randomised trials. The results of the study are strikingly similar—for both lack of efficacy and extent of overdiagnosis—to recent studies evaluating today’s screening programmes.5 6 7 The real amount of overdiagnosis in current screening programmes might be even higher than that reported in the Canadian study,4 because ductal carcinoma in situ, which accounts for one in four breast cancers detected in screening programmes,8 was not included in the analyses.

                Other studies also indicate that improved treatment rather than screening is the reason for the decline in breast cancer mortality during the past four or five years.5 7 Even though different studies arrive at different reductions in breast cancer mortality (from 10% to 25%), these benefits translate to only marginal differences in absolute effects. Much larger variation is seen in the estimates of overdiagnosis.6 In studies based on statistical modelling, overdiagnosis was less than 5%.6 By contrast, most observational studies report higher estimates of overdiagnosis, ranging from 22% to 54%,6 depending on denominator used.9 When the number of breast cancers detected at screening is used as the denominator (as in the Canadian study), the amount of overdiagnosis observed in the previous randomised controlled trials is strikingly similar (22-24%).4 10

How do the data on mammography screening compare with data on prostate cancer screening by prostate specific antigen, which is currently not encouraged in the United Kingdom and other countries owing to its small effect on mortality and large risk of overdiagnosis (www.screening.nhs.uk/prostatecancer)? The figure on bmj.com shows that the absolute harms (overdiagnosis) and benefits (mortality reduction) are not very different between the screening types. The 20 year risk of breast cancer for a 50 year old woman is 6.1% with screening (including 22% overdiagnosis 4),11 and 5.0% without screening; and the corresponding numbers for prostate cancer in a 50 year old man are 3.9% with screening (including 45% overdiagnosis 12) and 2.7% without screening.11 The 20 year risk of death from cancer for a 55 year old woman is 1.5% with screening (assuming a 20% reduction in mortality2)11 and 1.9% without screening; and the corresponding numbers for prostate cancer in a 55 year old man are 1.0% with (assuming a 20% reduction in mortality12) and 1.3% without screening.11

           Nevertheless, the UK National Screening Committee does recommend mammography screening for breast cancer but not prostate specific antigen screening for prostate cancer, stating that the “aim is to only implement programs that do more good than harm and that the informed choice is a guided principle of screening” (www.screening.nhs.uk/screening). Because the scientific rationale to recommend screening or not does not differ noticeably between breast and prostate cancer, political pressure and beliefs might have a role.

             We agree with Miller and colleagues that “the rationale for screening by mammography be urgently reassessed by policy makers.” As time goes by we do indeed need more efficient mechanisms to reconsider priorities and recommendations for mammography screening and other medical interventions. This is not an easy task, because governments, research funders, scientists, and medical practitioners may have vested interests in continuing activities that are well established.

                RESPONSES:  12 February 2014  BMJ 2014;348:g366 :                     1. rebuttal by USA  radiologists : Daniel B. Kopans, Professor of Radiology Harvard Medical School. Having been one of the experts called on in 1990 to review the quality of their mammograms I can personally attest to the fact that the quality was poor (1). To save money they used second hand mammography machines. The images were compromised by scatter since they did not employ grids for much of the trial. They failed to fully position the breasts in the machines so that cancers were missed because the technologists were not taught proper positioning, and their radiologists had no specific training in mammographic interpretation.   

The CNBSS’s own reference physicist wrote:“..in my work as reference physicist to the NBSS, [I] identified many concerns regarding the quality of mammography carried out in some of the NBSS screening centers. That quality [in the NBSS] was far below state of the art, even for that time (early 1980’s). ” (2)

In this latest paper (3) the authors gloss over the fact that only 32% of the cancers were detected by mammography alone. This extremely low number is consistent with the poor quality of the mammography. At least two thirds of the cancers should be detected by mammography alone (4). In their accompanying editorial (5) Kalager and Adami admit that ” The lack of mortality benefit is also biologically plausible because the mean tumour size was 19 mm in the screening group and 21 mm in the control group….a 2 mm difference.” Poor quality mammography does not find breast cancers at a smaller size and earlier stage and would not be expected to reduce deaths.

The documented poor quality of the CNBSS mammography is sufficient to explain their results and all of the above disqualifies the CNBSS as a scientific study of mammography screening, but it was even worse than that. In order to be valid, randomized, controlled trials (RCT) require that assignment of the women to the screening group or the unscreened control group is totally random. A fundamental rule for an RCT is that nothing can be known about the participants until they have been randomly assigned so that there is no risk of compromising the random allocation. Furthermore, a system needs to be employed so that the assignment is truly random and cannot be compromised. The CNBSS violated these fundamental rules (6). Every woman first had a clinical breast examination by a trained nurse (or doctor) so that they knew the women who had breast lumps, many of which were cancers, and they knew the women who had large lymph nodes in their axillae indicating advanced cancer. Before assigning the women to be in the group offered screening or the control women they knew who had large incurable cancers. This was a major violation, but it went beyond that. Instead of a random system of assigning the women they used open lists. The study coordinators who were supposed to randomly assign the volunteers, probably with good, but misguided, intentions, could simply skip a line to be certain that the women with lumps and even advanced cancers got assigned to the screening arm to be sure they would get a mammogram. It is indisputable that this happened since there was a statistically significant excess of women with advanced breast cancers who were assigned to the screening arm compared to those assigned to the control arm (7). This guaranteed that there would be more early deaths among the screened women than the control women and this is what occurred in the NBSS. Shifting women from the control arm to the screening arm would increase the cancers in the screening arm and reduce the cancers in the control arm which would also account for what they claim is “overdiagnosis”.                                                                                                                                          The analysis of the results from the CNBSS have been suspect from the beginning. The principle investigator ignored the allocation failure in his trial and blamed the early excess of cancer deaths among screened women on his, completely unsupportable, theory that cancer cells were being squeezed into the blood leading to early deaths. This had no scientific basis and was just another example of irresponsibility in the analysis of the data from this compromised trial and he finally retracted the nonsense after making front page headlines (6).

      The compromise of the CNBSS trial is indisputable. The 5 year survival from breast cancer among women ages 40-49 in Canada in the 1980’s was only 75%, yet the control women in the CNBSS, who were supposed to represent the Canadian population at the time, had a greater than 90% five year survival. This could only happen if cancers were shifted from the control arm to the screening arm. The CNBSS is an excellent example of how to corrupt a randomized, controlled trial. Coupling the fundamental compromise of the allocation process with the documented poor quality of the mammography should, long ago, have disqualified the CNBSS as a legitimate trial of screening mammography. Anyone who suggests that it was properly done and its results are valid and should be used to reduce access to screening either does not understand the fundamentals, or has other motives for using its corrupted results.

        2.  confirmation:   http://www.bmj.com/content/348/bmj.g366?tab=responses  Per-Henrik Zahl, MD & statistician Norwegian Institute of Public Health.   In this 30-year old study, the authors report no mortality reduction when screening with mammography and 22% overdiagnosis (1). The sensitivity of the mammography technique has improved tremendously in the last three decades. Ten years ago we got digital mammography and recently we have got tomosynthesis (2). The detection rate at mammography in the Canadian study was about 3 per 1000 in the second and later screening rounds (3). In digital mammography, the corresponding detection rate is 6 per 1000 screened woman and in tomosynthesis, the detection rate is 8 per 1000 (2). It could even have been higher if the pathologists had time to perform more biopsies (personal communications). In tomosynthesis a large number of stellate lesions appear, many more than in traditional mammography, and they are probably representing a reservoir of overdiagnosed breast cancers. In the last 15 years, the rate of interval cancer has been constant and is at the same level as in Canada 30 years ago (4). Thus, the level of overdiagnosis is far much bigger today than in Canada 30 years ago.

             update 6 Feb 2014 This column has noted  that in the 2012 report of the the giant ATLAS (and aTTom) trials in 37  countries the past decade (discussed in detail below), despite the claimed 80% cure rate of early silent  breast cancer (diagnosed by mammography screening at around 55yrs),   by 15 years after repeated screening mammography- surgery-radiotherapy,  tamoxifen for 5 or 10 years and annual screening mammography followup,   of the women who had died by age 70yrs and had autopsy,   some 43% had (silent) recurrence of breast cancer- although this had been detected in far fewer living women. The 15 year ATLAS results overall were depressing- in those originally early silent estrogen-receptor positive breast cancers, although only about 20% had clinical recurrence by a mean age of 70yrs, of the 22% who had died by then,  almost half ie 43% had recurrence of breast cancer at autopsy.
How successful was tamoxifen versus placebo?
Why was  the Atlas trial  felt not to justify a no-tamoxifen control group?
               Sir Richard Peto’s earlier Oxford review (Horm Res 1989;32:165) Effects of Adjuvant Tamoxifen and of Cytotoxic Therapy on Mortality in Early Breast Cancer. An Overview of 61 Randomised Trials Among 28,896 Women  sought information worldwide on mortality according to assigned treatment in all randomised trials that began before 1985 of adjuvant tamoxifen or cytotoxic therapy for early breast cancer (with or without regional lymph node involvement). Coverage was reasonably complete for most countries. In 28 trials of tamoxifen nearly 4,000 of 16,513 women had died,  reductions in mortality due to treatment  were significant when tamoxifen was compared with no tamoxifen (p < 0.0001), any chemotherapy with no chemotherapy (p=0.003), and polychemotherapy with single-agent chemotherapy (p=0.001). In tamoxifen trials, there was a clear reduction in mortality only among women aged 50 or older, for whom assignment to tamoxifen reduced the annual odds of death during the first 5 years by about one fifth. In chemotherapy trials there was a clear reduction only among women under 50, for whom assignment to polychemotherapy reduced the annual odds of death during the first 5 years by about one quarter. Direct comparisons showed that combination chemotherapy was significantly more effective than single-agent therapy. Because it involved several thousand women, this overview was able to demonstrate particularly clearly that both tamoxifen and cytotoxic therapy can reduce five-year mortality.
         A decade later  the 1998 Tamoxifen for early breast cancer: overview of the randomised trials:  Oxford Early Breast Cancer Trialists’ Collaborative GroupCorresponding Author (The Lancet, 1998: 351,: 1451 – 1467) confirmed Peto’s review:  In 1995, information was sought on each woman in any randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen before recurrence on 37 000 women in 55 such trials, comprising about 87% of the worldwide evidence. Compared with the previous such overview, this approximately doubles the amount of evidence from trials of about 5 years of tamoxifen and, taking all trials together, on events occurring more than 5 years after randomisation.
                Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor protein (ER) measured in their primary tumour. Among them, the overall effects of tamoxifen appeared to be small, and subsequent analyses of recurrence and total mortality are restricted to the remaining women (18 000 with ER-positive tumours, plus nearly 12 000 more with untested tumours, of which an estimated 8000 would have been ER-positive). For trials of 1 year, 2 years, and about 5 years of adjuvant tamoxifen, the proportional recurrence reductions produced among these 30 000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and 47% (SD 3), respectively, with a highly significant trend towards greater effect with longer treatment (χ21=52·0, 2p<0·00001). The corresponding proportional mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively, and again the test for trend was significant (χ21= 8·8, 2p=0·003). The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years. The proportional mortality reductions were similar for women with node-positive and node-negative disease, but the absolute mortality reductions were greater in node-positive women. In the trials of about 5 years of adjuvant tamoxifen the absolute improvements in 10-year survival were 10·9% (SD 2·5) for node-positive (61·4% vs 50·5% survival, 2p<0·00001) and 5·6% (SD 1·3) for node-negative (78·9% vs 73·3% survival, 2p<0·00001). These benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose (which was generally 20 mg), and of whether chemotherapy had been given to both groups. In terms of other outcomes among all women studied (ie, including those with “ER-poor” tumours), the proportional reductions in contralateral breast cancer were 13% (SD 13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of 5 years of tamoxifen (although the number of cases was small and these ratios were not significantly different from each other). The absolute decrease in contralateral breast cancer was about twice as large as the absolute increase in the incidence of endometrial cancer. Tamoxifen had no apparent effect on the incidence of colorectal cancer or, after exclusion of deaths from breast or endometrial cancer, on any of the other main categories of cause of death (total nearly 2000 such deaths; overall relative risk 0·99 [SD 0·05]).
            So, for corroboration we need the autopsy results of the women in the earlier tamoxifen vs placebo studies; and the 20 year results of the Atlas study. The ATLAS study reports clearly that silent breast cancer was more than twice as high in autopsied cases as in screening mammography during life. The conundrum remains whether  early cancer detection by regular repeated screening mammography, and early treatment by biopsy, surgery, radiotherapy and tamoxifen, is more beneficial or more harmful to women long term?
24 Jan 2014   Overdiagnosis    Overtreatment of Breast Cancer   .Am Soc Clin Oncol Educ Book. 2012;32:e40-e45. doi:  Alvarado M, Ozanne E, Esserman L. meetinglibrary.asco.org/sites/meetinglibrary.asco.org/files/Educational Book/PDF Files/2012/zds00112000e40.pdf  Dept Surgery Univ Calif San Francisco. write:   “Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses.                                                                                                                                
        Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions.”                                                                                                                                                                                             5 January 2014:   Quantifying the Benefits and Harms of Screening Mammography.  H Gilbert Welch & Honor Passow  , Dartmouth Geisel school of medicine, NewHampshire  write:  JAMA Intern Med. 2013 Dec 30.                   Like all early detection strategies, screening mammography involves trade-offs. If women are to truly participate in the decision of whether or not to be screened, they need quantification of its benefits and harms. Providing such information is challenging, however, given the uncertainty-and underlying professional disagreement-about the data. In this article, we attempt to bound this uncertainty by providing a range of estimates-optimistic and pessimistic-on the absolute frequency of 3 outcomes important to the mammography decision: breast cancer deaths avoided, false alarms, and overdiagnosis. Among 1000 US women aged 50 years who are screened annually for a decade,                                                                        0.3 to 3.2  ie ~0.17%  will avoid a breast cancer death                                                490 to 670  ie ~58% will have at least 1 false alarm recall, and                               3 to 14 ie         0.85%  will be overdiagnosed and treated needlessly.                                            We hope that these ranges help women to make a decision: either to feel comfortable about their decision to pursue screening or to feel equally comfortable about their decision not to pursue screening. For the remainder, we hope it helps start a conversation about where additional precision is most needed
                                                                                                                                                                     A recent review of a new book by journalist Rolf Hefti- The Mammogram Myth–  consolidating the controversy for and against screening mammography is reviewed by Cape Ray. The book relies heavily on Dr John Gofman (1919-2007), a distinguished medical scientist,  a key member of the Manhattan Project that developed the first atomic bomb used on Nagasaki. In 1996 Gofman published a book entitled Preventing Breast Cancer: The Story of a Major, Proven, Preventable Cause of This Disease, in which he made the astonishing claim that 75% of all breast cancers were caused by women being exposed to ionising radiation from X-rays. As highlighted in a review in JAMA, Gofman’s claim — based on an extensive literature review and certain critical assumptions — was at variance with every other authority, including the National Academy of Sciences and the National Council on Radiation Protection.  Martin Yaffe of Toronto has recently shown that the risk of radiation-induced breast cancer from mammographic screening is not negligible, but this risk is small when compared to the expected reduction in mortality achieved through screening.
                                                                                                                                                                   So the dilemma for health professionals, and for  the target of the zealous Cancer Screening Industry-  healthy women in their prime-of-life middle years- remains:  why have xray mammography screening when the independent evidence from expert epidemiologists is that screening mammograpy  to find preclinical ie precancer does not in fact  meaningfully save lives, entend health or reduce breast surgery and cancer therapy, it actually increases all these risks compared to waiting till cancer presents clinically.                                                                                                                                             Zahl Jorgensen and Gotzsche  in their latest review show that Overestimated lead times in cancer screening has led to substantial underestimation of overdiagnosis.
and Gotzsche’s new book is an expose  of  Deadly Medicines and Organised Crime.  
                                                                                                                          20 July 2013   HUMAN PROGESTERONE  BREASTCANCER RISK  REVISITED: Its 3 years since this column last reviewed progesterone, in the context of osteoporosis,  bone building.   While the first Pubmed report on progesterone implants  is apparently sixty years ago (probably in veterinary reproductive use), Drs John Lee and Kathy Dalton promoted use of solo human progesterone P4 for (post)menopausal protection,  also  against cancer including breast cancer; which l’Hermite 2013 from France, and eg David Sturdee from UK, have recently favourably  summarized in respect of balanced transdermal estrogen and oral micronized progesterone P4. The evidence for P4 as  almost global protection as HRT   has largely been confirmed provided progesterone is used in moderation – ideally transdermally/ transvaginally  like estrogen (Genazzani ea);  some believe in the basal physiological bloodlevel of about 1 to 2 nmol/L,  in balance with basal levels of human estrogen and androgens.                                                                                                                                Vanadin Seiffert-Klauss ea in Munich have recently (2012) confirmed that “women in the (~10year) menopause transition lose trabecular bone at a rapid rate despite intermittently high and usually normal estrogen levels –  especially the lean women (BMI<20kg), and those with family fracture history”.  And in their PEKNO study, “Decreasing rates of ovulation, hormonal changes, and increasing bone loss pre-date menopause by several years.;  in addition to estradiol, progesterone may play a significant role in the interrelationship between the ovaries and the skeleton in women.  differentiation of human osteoblasts from perimenopausal women has been shown to be dose-dependent on progesterone at physiological concentrations.  Higher progesterone levels, as seen in the luteal phase of ovulatory cycles, may be associated with more bone formation and with slightly less bone resorption than anovulatory cycles in which progesterone levels are low (< 5.8 ng/ml)”.                 These data led to the initiation  in perimenopausal women of a large, prospective, 2-year observational PEKNO study – from which interim data indicate that a decrease in ovulation correlated with an increase in the loss of bone mineral density (BMD). A meta-analysis in women *with normal ovulation estimated a BMD increase of 0.5% per year, vs *with ovulatory disturbances (anovulation or short luteal phase) a BMD decrease of 0.7% per year in young women ; but * in postmenopausal women a 1.3% increase per year in BMD when receiving hormone replacement therapy with unopposed estrogens, and a further 0.4% increase in BMD in women receiving estrogens plus progestogens. The role of progesterone in bone metabolism in perimenopausal women who are estrogen-replete requires further study.”  
                                   Thus they show that postmenopausally, addition of progestin may boost BMD by 31% more than ERT alone. But currently some experts eg Kuhl and Schneider and David Zava   feel that evidence warrants caution, that oral human progesterone P4  may have a  role in breast cancer promotion;  although it has protective benefit against estrogen dominance in most circumstances eg against endometrial cancer. As this column has previously reviewed, longterm experience of experts like Greenblatt & Gambrell, Gelfand,  Lee Vliet  in N America;   Schleyer-Saunders, Whitehead & Studd (London) , Burger & Davis (Australia) ; and Davies ea (Cape Town) showed no increase but reduction in all postmenopausal morbidity including cancer with  non-oral eg implants of BIDHRT (estradiol balanced  with human antiestrogen eg testosterone and/or progesterone).
                                                                                                                                                              Now Stephenson ea  at the Tyler Women’s Wellness Center, Texas publish a 3  year study showing multiple benefits and no adverse effects of balanced   compounded bioidentical transdermal hormone therapy BIDHRT on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures in peri- and postmenopausal women. Conventional  nonhuman hormone therapy HT eg CEE and medroxyprogesterone results in increased thrombotic events, and an increased risk of breast cancer and dementia  in large prospective clinical trials including the HERS and the Women’s Health Initiative studies.  Physiologic human sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile, yet long-term studies of this treatment model are lacking.  In a  prospective, approved closed-label study, 75  women who met strict inclusion/exclusion criteria were enrolled; following baseline hormone evaluation,  women received compounded transdermal bioidentical hormone therapy of BiEst (80%Estriol/20%Estradiol), and/or Progesterone to meet established physiologic reference ranges for the luteal phase.          Subjects receiving  BIDHRT in doses targeted to physiologic reference ranges administered in a daily dose showed significant favorable changes in  menopausal symptoms, cardiovascular biomarkers, inflammatory factors, immune signaling factors, and health outcomes, despite very high life stress, and home and work strain in study subjects. There were no associated adverse events. This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in populations with high perceived stress and a history of stressful life events prior to, or during the menopausal transition.
                                                                                                                                                              This Texas   study supports the 2009 metanalysis by Holtorf:The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?   Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone.  Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. 
                                                                                                                                                                          And of course the recent 4year Kronos KEEPS study by Harman ea 2012 confirms that in early postmenopausal woemen, parenteral physiological-dose  estradiol has subtle benefits over oral premarin, with or without  parenteral progesterone, with no significant adverse effect..                                                                                                                                                                                                                                                                                                                                                                                                                  17 June 2013  SHOULD WE EVER TELL A PATIENT WITH A BREAST LUMP THAT IT’S CANCER?  or THAT IT MAYBE PRECANCER?  This was and is a  major dilemma in medicine. One of the big  lessons arising out of the high technology in living memory ie the past >century-our grandparents’ time-  is that before modern laboratory, imaging and surgical diagnostics, all we could do was wait and see, the trial of observation and therapy, prayer, meditation. Now we have gone to the other extreme in the aging,  bullying them to have risky invasive screening on the crass assumption that screening and early radical – invasive ie potentially  harmful-  treatment of silent ie precancer saves lives- when the evidence has become progressively clearer that unselective invasive screening of asymptomatic prostates and breasts simply creates worried well,  overdiagnoses silent disease which may never cause illness or death ,  and may hasten misery; whereas combining natural preventative remedies may benefit all systems  including regress cancer.
                                                                                                                                                             Silent hypertension and unrealised overweight/ metabolic syndrome  are radically different from cancer. With simple measurement  of asymptomatic arterial hypertension, visceral obesity and eg glycosuria, the earlier that risk factors are defined and addressed, and the earlier the adiposity/glycosuria/ hypertension corrected with lifestyle, abolishing smoking and boozing,  and diet improvements, supplements and if necessary the safest prescription drugs-  initially fish oil,  lowdose amiloretic and reserpine, metformin, and the basket of vitamins and minerals especially magnesium, zinc,  vits C and D3 –  the sooner is the progressive  risk  reversed to the heart, brain, mind, vision, lungs, digestive and excretory system, joints and legs, let alone to fertility, carcinogenesis and other immunoendocrine  functions                                                                                                                                                           So instead of driving well aging women witless with disease-mongering-  forced regular invasive xray screening mammography-  we should  instead respect the power of the mind over disease, and use simple careful history, and physiological  biometrics including behaviometrics to persuade and condition those at risk to take sensible precautions including if necessary supplements, exercise and corrective diet/psycho/hypnotherapy. The lesson of screening breasts and prostates for silent cancer  the past 20 years is that so many cases of silent dormant cancer regress spontaneously if left well alone, especially if they are left undiagnosed and instead just the score of common risk factors for  all common diseases addressed as this column keeps exploring. So when asymptomatic changes and lumps in breasts are detected by noninvasive means eg clinical or Sure Touch or thermal exam, there is no need to alarm the woman by labelling her a patient with breast disease – it is more than healing for her to show her that within a month, these changes can be reversed with  all the appropriate natural  steps as described in Combatting Breast Cancer , including the Magic Oils. If there were indeed (pre)malignant changes present, they too regress as normally happens in so many – so  leave well alone. As reviewed below,  up to  45% of apparently well adults who are killed  have silent cancers;    and in the giant ATLAS and aTTom trials in 37  countries the past decade (discussed in detail below), despite the claimed 80% cure rate of early silent  breast cancer (diagnosed at around 55yrs)  by 5 and 15 years after repeated screening mammography- surgery- and radiochemotherapy,  and annual screening mammography followup,   of the women who had died by age 70yrs and had autopsy, the similar 43% had (silent) recurrence of breast cancer. So  like men,  asymptomatic women should be discouraged from invasive screening; but the higher their risk score, the more readily they should be offered simple noninvasive breast screening, and thereby encouraged to optimize diet, habits, lifestyle, body build-fitness,  including with the battery of multibenefit preventative supplements . Like millions of partisans have sung in bitter wars and holocausts, Hirsh  Glik’s “Never Say that You Are Trodding the Final Path“- remains the hope-givimg mantra that all patients and caregivers  must hold to – the power of positive thought and action  if not prayer. Both mistakes and miracles happen.                                                                                                                                                                                                                                                                                 upate June 14 2013: a new review from Oxford University  Breast cancer mortality trends in England (1979-2009) and the assessment of the effectiveness of mammography screening concludes: In the Oxford region,  For all ages combined, mortality rates peaked for both underlying cause and mentions in 1985 and then started to decline, prior to the introduction of the NHSBSP in 1988.  There was no evidence that declines in mortality rates were consistently greater in women in age groups and cohorts that had been screened at all, or screened several times, than in other (unscreened) women, in the same time periods. Conclusions Mortality statistics do not show an effect of mammographic screening on population-based breast cancer mortality in England.update June 10 2013  a  review published today  by Coldman and Phillips on   Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program   in Canada over 40years showed that ” the extent  of overdiagnosis of invasive cancer  was modest and primarily occurred among women  over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated  for all age groups.”                                                                                                                                                                                                                                                                                                                   update 9 June 2013:    THE HARMFUL COERSIVE PRESSURE APPLIED ON WOMEN,  AND ON THEIR BREASTS, WITH SCREENING  XRAY  MAMMOGRAPHY:      Womens’ wishes must be respected when they  prefer no-xray no-squeeze prescreening, choose not to have xray mammography. Breast discomfort and breast trauma from xray mammography -breast sandwiching –   vary greatly between women and especially in young more hormonally-driven  breasts.. The pressure is manyfold:  not just in crushing the breasts, but in PTSD- post-traumatic stress disorder: Oxana Palesh & Cheryl Koopman report this month Breast cancer: PTSD—prevalent and persistent:  Receiving a diagnosis of breast cancer is likely to have aconsiderable impact on the psychological wellbeing of the patient. In a recent observational study, Vin-Raviv et al.1 reported that 23% of 1,139 women with newly diagnosed localized breast cancer experienced post-traumatic stress disorder (PTSD) symptoms. This is not to deny that many women experience post-traumatic character growth, as a recent Greek study discusses.   Posttraumatic stress disorder and posttraumatic growth in breast cancer patients.  But Elklit and Blum and O’Connor ea in Denmark a year earlier highlight  PTSD   as being highly relevant in oncology settings after early breast cancer.. This awareness has been reviewed on Pubmed from before 1997. A recent report says the physical crushing force applied in such breast compression  – snackwiching –  is briefly up to about  130 Newtons, ie 13 kg or  25 pounds force.    This compares to the gentle 1.5 to 2kg force applied briefly when having a mechanical tactile Sure Touch surface breast anatomical mapping, or professional clinical breast exam; or zero force with a no-touch infrared thermomammogram. Hence some  women report breast pain, bruising and discomfort for weeks after a compression xray mammogram. And because oncologists insist on followup regular xray mammography after cancer therapy with breast-conserving surgery & radiochemotherapy, women increasingly ignore breast lumps let alone any screening breast exams at all. It is common cause that stress, anxiety  increase cortisol, insulin  and thus estrogenic stimulation, and thus cancer risk to  breasts.  It is still unknown how much the longterm risk of breast problems and cancer is increased from rupturing breast cells (let alone spreading cancer cells) with repeated successive compression xray mammography and the cumulative xray dose used – especially when perhaps 1 in 10 women screened is recalled  by radiologists for more compression views, to find (by biopsy of perhaps 10 to 20 women per 1000) the 2 to 4 clinically undetected tiny breast (pre)cancers in each 1000 women so screened preventatively… And it is obvious that with denser more active breasts in young women- monthly high-turnover glandular cells (especially in those on cyclic synthetic estrogen-progestin contraception) –  both breast fragility and sensitivity are higher the earlier that xray mammography is commenced as radiologists insist.

              Hence Regulators in most countries have reduced recommendations for routine screening mammography to starting at age >50yrs and stopping by 70-75years (ie 10-12 times on average through midlife); whereas Radiology Associations ignore the risks and still advise screening annually from age 40 years,  for life  –   ie at least THREE times as many times from age 40years. So women are doubly exposed to harmful pressure both in being bullied that they need screening xray mammography – the lie that  ” screening mammography saves lives”  when the benefit of this is unproven, and in being forced to undergo breast crushing repeatedly. A woman who recently attended for Sure Touch in Port Elizabeth   objected to having her breasts snackwiched again by compression mammography. The flippant analogy is eerie when one considers how such women are expected to attend annually to have their breasts both flattened and irradiated – and more so with cumulative frying after therapeutic radiotherapy. No wonder some end up with a hard breast. . So while the young at heart may   love nudging breasts-,  and massage  heals, (and Bissell and Fletcher at the Berkley lab show that gentle nudging with about 50 gm pressure knocks errant breast ductal cells back into healthy behaviour) –   crushing force and coersion do women harm, not good; in contrast to men where forceful digital massage may (also with putative risk) relieve the infected painful prostate.. .

And Gøtzsche   and Jørgensen in  .Cochrane Database Syst Rev. have Jun 4 published update stats against Screening for breast cancer with mammographyfrom  PubMed and the WHO ‘s International Clinical Trials Registry  (to November 2012).  Eight eligible trials  included 600,000 women  in the age range 39 to 74 years. Three trials with adequate randomisation did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90); four trials with suboptimal randomisation showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly from differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).  Surgeries – Lumpectomies and mastectomies (RR 1.20-1.31, 95% CI 1.08 to 1.42) were significantly more in the screened groups . The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy.              AUTHORS’ CONCLUSIONS: If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening through 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 10%  will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.        To help ensure that the women are fully informed before they decide whether or not to attend screening, we have an evidence-based lay  leaflet http://www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening”.                                                                                                              

update 26 May 2013  Apart from the strident promotion of preventative mastectomy by a film star,  reports the past week prompt review of :  why and whether  aggressive breast cancer may have doubled  in young women 25-39years old; and  it’s prevention by natural steps.

update 22 May 2013:   WHY DO SO MANY  WOMEN HAVE  RELAPSE OF BREAST CANCER BY 25 YEARS AFTER  DIAGNOSIS AND APPARENTLY CURATIVE TREATMENT OF EARLY SILENT BREAST CANCER?:three landmark new papers shine more light on why 43% of women who died by 15 years after aggressive treatment of  initial silent preclinical breast cancer had relapse/recurrence  of breast cancer at autopsy  – the  depressing result of the monumental 180 000 women-year  ATLAS trial:

Lisa Willis, Karen Page, Trevor Graham, Tomás Alarcón, Malcolm  Alison    & Ian  Tomlinson  from Universities of London, Oxford, Cambridge, and Barcelona  this month dissect  “What Can Be Learnt about Disease Progression in Breast Cancer Dormancy from Relapse Data?   why Breast cancer patients have an anomalously high rate of relapse up to 25 years  after apparently curative surgery removed the primary tumour. Disease progression during the intervening years between resection and relapse is poorly understood. There is evidence that the disease persists as dangerous, tiny metastases that remain at a growth restricted, clinically undetectable size until a transforming event restarts growth. This suggests a natural question and  a surprising answer: why are interesting trends in long-term relapse data not more commonly observed?”       But they are observed: another recent  15 year followup study, from Denmark (Grantzau ea), furthermore shows that DXRT after early breast cancer almost doubles the risk of radiotherapy-associated second cancer to 1:200 of women so treated..

       Thus at least dangerous dormant micrometastases, and the enormous cumulative  radiation exposure from both screening mammography over decades, and DXRT itself, will explain much of the 43% recurrence rate of breast cancer by 15 years (at autopsy in those who had died by then, at a  mean of only 70 years) seen in the ATLAS trial.

  These reports raise yet further doubts about the wisdom  of  regular mass xrayscreening of well breasts from age 50 years let alone 40years, and worse-  zealous major surgery and DXRT for preclinical disease, and then even worse, ongoing xray mammographic surveillance into old age.

      They point in the opposite direction:  that xray screening of well breasts should be avoided;  DXRT avoided in localized early breast cancer; and surveillance for breast cancer limited to the many available non-xray methods;

     and that women must be encouraged instead to maintain prevention with combination of safe natural (and multisystem-protecting)  means as discussed repeatedly in this column – lifestyle, diet, exercise, and massage and oral use of safe natural preventative supplements. Anticancer antiangiogenesis factors from our diet  are legion, include  cannabis, mushrooms, resveratrol, green tea, black rasberry  and Royal jelly. One would not recommend soya against breast cancr because of its phytoestrogen potential.

               Xradiation has been known for decades eg 1978 1990 to be both an angiogenic and an antiangiogenic factor in tumour growth angiogenesis (Judah Folkman 1971) . so it is  obviously a double-edged sword that should certainly not be used in the witchhunt for silent and usually irrelevant precancer in well breasts.

                   So we have the ludicrous situation reported today in JAMA  that despite all the evidence for 20 years now to stop or at least halve  mass xray screening and thus (over)treatment of silent early breast cancer, Physicians, Patients Not Following Advice From USPSTF on Mammography Screening: In 2009, the US Preventive Services Task Force (USPSTF) recommended against routine screening mammography for women under 50 years and advised biennial rather than annual screening for women aged over 49yrs. But women and physicians ignored these recommendations.  A new study from Harvard  found that in 2005 to 2011, the percentage of women aged 40 to 49 years reporting that they had undergone mammography screening in the previous year was the same, about 47%. As for women aged 50 to 74 years, the percentage reporting mammography screening in the previous 12 months for each year analyzed also remained essentially the same, in the upper 50% range.”

        Update 21 April 2013FIFTEEN YEAR FOLLOWUP STUDIES OF BREAST CANCER AND ALLCAUSE  MORTALITY FROM MENOPAUSE ONWARDS:                                                                           Overall, long-term studies do not favour invasive breast screening or adjuvant therapy of early breast cancer,  but actually argue  against  early diagnosis and treatment of both silent breast and prostate  cancer.  Rather, the focus must be on safe natural prevention to reduce the occurrence of all common degenerative diseases of aging.

       It is instructive to juxtapose  the diverse 15 year followup studies in 14 countries (Nordic Cochrane- Gotzsche, Jorgensen ea) of women routinely xray- mammography screened or not, with the 15 year ATLAS study (that ended in 2010)  reviewed below in 36 countries,  of women zealously xray- screened for early breast cancer, prompt  biopsies and surgical/  radiotherapy treatment- the majority mastectomy-  and then randomized to tamoxifen for up to  10 years. and it is reported by the ATLAS authors that there was a major breach of protocol – The protocol stated that 20 000 patients would need to be randomised in ATLAS and the other trials of tamoxifen duration to detect reliably an absolute difference of 2–3% in mortality. Entry to ATLAS was halted in 2005 (with 12 894 patients, including 6846 with ER-positive disease) because the MA.17 trial  showed benefit from continued endocrine treatment after 5 years of tamoxifen..   Yet the MA17 trial was with a different drug- letrozole;  and bizarely, the trial conclusion was that “the results from the analyses based on the Cox model with time-dependent covariates  were similar for letrozole and placebo.”  ie that letrozole was no better than placebo.. Thus, like the Womens’ Health Initiative misguided early termination,  it is unclear why MA17 was used as reason to terminate the ATLAS trial.
             The 15 year ATLAS results overall were depressing- in those originally early silent estrogen-receptor positive breast cancers, although only about 20% had clinical recurrence by a mean age of 70yrs, of the 22% who had died by then,  almost half ie 43% had recurrence of breast cancer at autopsy.              Many new such trials are under way.
The aTTom trial  the UK arm of the ATLAS trial similarly “followed women with early breast cancer after initial treatment  for about 15 years:  it  randomly assigned 6934 women (39% ER-positive, 61% ER-untested) at the completion of 4 or more years of tamoxifen therapy to either 5 additional years of tamoxifen or cessation of tamoxifen therapy. With a median follow-up of 4.2 years, there was a slight, non-significant advantage for the 10-year tamoxifen arm (RR, 0.94; 95% CI, 0.81–1.09; P = .4). Thus, the optimal duration of therapy is not known, but it is at least 5 years”. For undisclosed reasons this trial has apparently  never been published in full although it was first reported in 2008- this raises the usual question by eg Booth and Tannock 2008  of bias against negative results, whether there was suppression by sponsors…  And the aTTom trial design was heavily criticised at the outset in 1996.
                The meta-analysis published the past week by Heidi Nelson ea for the USPSTF  confirms the ATLAS study, showed that tamoxifen/ raloxifen for 5 years reduced absolute mortality from breast cancer by about 0.16% per year. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms.
         It then becomes apparent  that  having early breast cancer detected – without the adverse risk factors of xray mammography of repeated breast crushing, radiation,  biopsies and overtreatement,                             but with better application of safe preventative measures including vitamin D3, melatonin, metformin, iodine, DMSO, coconut oil,  fish oil, sutherlandia, I3C/DIM, vitamins and minerals                  – while women will live healthy longer,  few women  (perhaps <5% of all deaths) will die of breast cancer.  The common risk factors (for all common premature disease and deaths) are  m   anaged with the same basket of safe natural effective preventatives including supplements like appropriate balanced hormone replacement -that this column addresses.                                                                                                                                                                                                                                                    
Dr.  Northrup says“[Gilbert Welch] pointed to a study [from] way back, of women who died in car accidents in their 40s. They sectioned their breast tissues and found that 40 percent of them – this is normal healthy women dying in car accidents – had evidence of ductal carcinoma in situ that was never going to go anywhere. This is the big dilemma,” .   Welch and Black 1997 reported Among seven autopsy series of women not known to have had breast cancer during life, the median prevalence of invasive breast cancer was 1.3% (range, 0% to 1.8%) and the median prevalence of DCIS was 8.9% (range, 0% to 14.7%). Prevalences were higher among women likely to have been screened (that is, women 40 to 70 years of age).

     Erbas ea at Univ Melbourne studied all sources for the prevalence of ductal carcinoma in situ. “The reported prevalence of undiagnosed DCIS in autopsy studies, of approximately 9%, has been used to suggest a larger reservoir of DCIS may exist in the population”.

      Update 18 April 2013:  a  new study from  Italy   graphically illustrates the lower sensitivity of xray screening – U/S ie  ultrasound picked up ‘significantly’ more tiny asymptomatic breast cancers  missed in 22,131  women with negative mammography.  “The overall U/S detection was 0.185%, but 0.55% with previous cancer vs 0.145% in women without cancer history (p = 0.0004),  0.22% in dense breasts (p = 0.17) vs .156% in fatty breasts. The U/S- generated invasive assessment was 0.19%  The benign to malignant open surgical biopsy ratio was  thus 0.17.”  This is likely more overdiagnosis unless the women simply apply the preventative measures recommended below.

             But while no screening method can diagnose cancer (only invasive biopsy can), and none can guarantee there arnt cancer cells busy germinating especially if stirred up by severe anxiety,  radiation, crushing, biopsy etc, Sure Touch mapping is more accurate than even U/S for  reassuring while reducing referral rate for U/S.

UPDATE 14 APRIL 2013: Because of the evidence the past score years set out below  that xray screening actually does more harm than good, integrative  medical clinics world wide do not promote xray screening mammography. But such clinics including in Cape Town generally offer regular safe and lower-cost  anatomical eg Sure Touch mechanical tactile if not ultrasound or MRI, and physiological no-touch eg thermography ie bloodflow studies,  –  for those who need peace of mind. Some women choose to alternate Sure Touch and thermomammography.

     While only 1 in 200 women have the familial gene risk,  the majority of older women have  the common multiple risk factors eg longevity, estrogenic and heavy metal pollution, stress, overweight density, smoking, alcohol; and  there are many simple remedies described in these  columns that can reverse most of the risk factors – not just of even genetic breast cancer and increasing overweight,  but of all the major diseases of aging.

The problem remains the stubbornness of third party payers including governments to listen to both the evidence and to womens’ wishes, and pay for such safe, cheaper and arguably more accurate prscreening than crush xray mammography, if any is desired or desirable .

Dr Johnnie Ham MD MSc MBA Californian ObGyn discusses why xray screening mammography and aggressive medical assault on  well breasts- the witchhunt for the pot of hidden gold,  silent preclinical breast cancer –  is a giant  con by the  for-profit high-tech medical goliath  industry   terrorizing and mutilating  naive women.

Governments -WHO  silence on harms of screening mammography : What is tragicomedy is that worldwide, government Regulators seem to be standing silently firm, not saying a word about the harm likely exceeding the medical benefit- the screening and cancer  industry is far too profitable in jobs, taxes and votes. Search on the internet for Government warnings on harms of screening mammography does not yield a word of warning. Regulators and Medical Schemes piously promote quality screening, but say nothing about the harms versus benefits. The FDA still promotes annual screening mammography  on line without a word about the risks and harms of mammography; others like the UK NHS promote it every 2 to 3 years.    Yet the US Senate is actually considering a Republican Act to promote more xray breast imaging.

UPDATE 12 April 2013  The Wiki entry on breast cancer prognosis says now: “One result of media hype- breast cancer’s high visibility -(compared to other cancers in eg men, and other common major diseases) is that statistics may be misinterpreted, such as the claim that breast cancer will be diagnosed in one in eight women during their lives—a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95.[132] This obscures reality that about ten more women will die from heart disease or stroke than from breast cancer.[133]The emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own.[134] Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and pre-cancers, even while overlooking serious cancers. According to Prof Gilbert Welch of  Dartmouth Institute, research on screening mammography has taken the “brain-dead approach that says the best test is the one that finds the most cancers” rather than the one that finds dangerous cancers.[134]

The latest  report  Lancet 2011) on the Relevance of breast cancer hormone receptors and other factors to efficacy of Tamoxifen protection after breast cancer looked at 20 trials (n=21,457) in early breast cancer . In oestrogen receptor (ER)-positive disease, about 5 years of tamoxifen halved recurrence rates throughout the first 10 years but  no further gain or loss after year 10; risk was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years. Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality.

       This is not surprising as tamoxifen like  all synthetic  sex hormones  /blockers has  a long list of adverse effects on bone, brain, cardiovascular, bladder, mood, immunity, body weight and metabolism,  womb etc.

But the Oxford UK-led (Davies ea)  landmark monumental  ATLAS trial (2012)  from 1996 -2010 in 36 countries and 180 000 women-years (mean presentation  age mid 50s, ER+ breast cancer about 1 cm size,   2/3 had mastectomy – which is now known to increase mortality) showed that after 6846 women taking tamoxifen  for up to 10 years, at about 15 years from diagnosis, tamoxifen in absolute terms  was only marginal benefit- marginally reduced the risk for breast cancer recurrence, compared with stopping tamoxifen (617 vs 711; P = .002), reduced breast cancer mortality  relatively by 8% (331 vs 397 deaths; P = .01) but that’s only about 1% in absolute terms, and reduced overall mortality by 10% (639 vs 722 deaths; P = .01). Over all, approximately 1/5 clinically relapsed,  1/7 deaths were from breast  cancer; but of those who died, webfigures 4a and 4b of  the supplementary appendix   of the main ATLAS  report showed that at autopsy almost half  (43%) indeed had recurrent breast cancer. This gives the lie to early screening and treatment-  15 years later, even with tamoxifen for  10 years, early xray mammography detection and conventional surgical-radio-chemotherapy treatment does not cure much more than half of women with preclinical ER+  breast cancer that screening detects.The risk for recurrence by year 15 was 21.4% in the continuers group and 25.1% in the control group. ie only 3.7% absolute reduction. In addition, breast cancer mortality by year 15 was significantly reduced by nearly 3%; it was 12.2% in the continuers group and 15.0% in the control group. ie only 2.8% absolute reduction. Thus even in these women with early breast cancer, the cure rate even with tamoxifen was poor- slight reduction in the 25% recurrence  and 15% breast cancer mortality rates. But almost  half of the women who died had recurrence.  Once again, the actual results published 4 months ago in the final Lancet report were much less impressive than the media release published 5 days later. Of these >6000 women allocated after initial surgery/ radio/chemotherapy to the tamoxifen or placebo  trial, 85% did not die of breast cancer. But the cure rate was at best still only about 75%, and only  half of those who died -by a mean of age 70 years – of any  causes were free of breast cancer.

11 April 2013  the SA Menopause Society Menopause Matters today  also features The Great Mammography Debate- concluding “The point being that the treatments of breast cancer are not benign and need to be drawn into the calculations when assessing the harms of screening mammography. If these treatments are carried out on a significant number of people who are not in danger of being harmed by their breast cancer in the first place (those over-diagnosed) then the scales of benefit versus harm from routine mammography may well tip in favour of harm. If so it may be unwise or even unethical to recommend screening by mammography.”

9 April 2013  Robert Stern at University of Arizona writes that “xray mammography alone is not a very good screening modality and has strikingly variable false positive, false negative, specificity, and efficacy rates, depending on what you read and who you believe.

   Worldwide, the days of simple repetitive yearly/ biannual mammograms for every living woman over some arbitrary age may be over soon.. breast cancer screening is about to evolve into a personalized, patient-centered program. It means you can’t just  order a mammogram when a  flag pops up saying it’s time.  It means understanding fairly complex risk stratification, the indications for these new technologies, and the clinical context for various imaging strategies”, mostly still based on irradiation;  as detailed in the American Medical Journal by Drukteinis ea at the Florida Mofitt Cancer Centre ..

8 April 2013: UPDATE:  see  vitamin D3 and Breast Cancer.

JAMA publishes on line from University Basel  Switzerland,   Shaw and Elger’s viewpoint on Evidence-Based Persuasionoften  an ethical imperative to  forcefully guide a hesitant patient into what seems to be the best decision, using arguments from Removal of Bias to Recommending Options and occasionally even Creating New Biases.      The eternal problem remains, what is truly right? Is mass flu vaccine right? Is screening xray  mammography truly lifesaving? especially if one quotes impressive but misleading relative risk reduction rather than in fact the crucial trivial absolute reduction?  Is Directive Counselling however well-meant exercising undue influence? They conclude that it  is an essential part of modern medical practice, without which it may be impossible to respect patients’ autonomy. Such necessary persuasion needs to meet 6 criteria.

A month ago BCAction held a webinar reported by Manie Clark

updating the risks and futility of screening xray mammography.

24 Mar 2013. THE COVERUP OF HARMS AND FUTILITY OF XRAY BREAST SCREENING CONTINUES IN USA Many opinions from around the world in recent NEJMs say it all about screening mammography:  most are subjective, emotive. There is no impartial objective evidence to support the gold standard xray mammography at all (except arguably  in cases of obvious cancer- when biopsy, and MRI scan is better and safer).   When there are acceptable prescreenings that do no harm and when combined,  give good sensitivity and specificity eg any two of  mechanical tactile imaging, thermomammography, breast ultrasound and (if affordable) MRI.
         Karla Kerlikowske ea  co-author already four peer-reviewed Pubmed-listed studies on xray  mammography this year..  the latest on screening well women from the  Breast Cancer Surveillance Consortium asks: Screening Outcomes in Older US Women Undergoing Multiple Mammograms in Community Practice: Does Interval, Age, or Comorbidity Score Affect Tumor Characteristics or False Positive Rates?Uncertainty exists about appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risks from 1999 to  2006 on 140000  women aged 66 to 89 years at study entry undergoing mammo     . About 7% had  breast cancer,  in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims.  Cumulative probability of a false-positive mammo result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48% of annual screeners aged 66 to 74 years had a false-positive result compared with 29% of biennial screeners. These women  who undergo biennial screening mammo had similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.
But their abstract abysmally fails to ask and answer the obviously far more important question:  – did screening mammo  give any  significantly lower mortality, surgery   or  radiotherapy at 15 or 20year followup compared to a matched  randomly selected cohort not screened over the same period, or compared to women who were screened only once at the outset??
   All independent studies show that women regularly screened by xray mammogram  do no better and sustain far more harms, in fact may die sooner than those not screened. Why did they not say this in their abstract, that xray mammo screening is unethical abusive harmful exploitation of women?
    The BCSC website registers over 8million screening mammograms done there 1996-2009 – 24% of women had 5 or more xray screens- ` yet similarly  fails to mention the crucial harms and mortality data in screened versus unscreened women.  The reason is obvious:  admitting the truth, that xray screening mammo is not only futile but harmful, would kill what must now be a $10billion a year   industry in USA for xray manufacturers, radiologists, breast surgeons, hospitals, medical schemes, oncologists and Big Pharma in the Find a Hidden  Breast Cancer Conspiracy against older women. . Indeed, the endgame would be that lawyers will swarm to call on women to sue the Breast Cancer Industry for wrongful assault.
23 Mar 2013Dr Enza Ferreri is a London-based  Italian journalist philosopher of science, christian human and animal  rights activist, including saving  Britain from an Islamist President Charles Windsor.. She yesterday wrote a devastating critique of screening xray mammography, its profiteering  oversell by  Scandinavian and English-speaking governments’ propaganda that omit  to explain all the risks and lack of benefits. “On one side you have the stories about women whose ” life  was saved” by breast screening, on the other  women whose life was made hell by discovery of a possibly benign DCIS, and those who endure a nightmare of false positives believing that she has breast cancer when she hasn’t. “
22 Mar 2013 Even this month’s  European Radiology Congress, and the South African Menopause Society  SAMS newsletter Menopause Matters, and the Annals of Family Medicine a new Copenhagen study- now question  screening xray mammography, including cumulative radiation damage to heart and lungs; and chronic psychological trauma from false positive reports.
False-positive findings on screening mammography causes long-term psychosocial harm: 3 years after a false-positive finding, women experience psychosocial consequences that range between those experienced by women  with a normal mammogram and those with a diagnosis of breast cancer. Not even a “positive” breast biopsy is a guarantee that it is cancer that needs treatment -apparently 4% of breast biopsies may be misread. so 2nd opinions are advised.
     the  SAMS author says: ”   the fundamental question  is “Does screening for cancer improve length or quality of life?”  The latest arguments from the UK ask if screening saves lives, if you take all causes of death into account (Baum BMJ 2013;346:f385).  Firstly, the author accepts that screening saves lives. If 10 000 women are screened for a decade then 4 deaths will be avoided. As treatments improve as they are doing all the time, then deaths avoided become lower, maybe 2 per 10 000 in the near future and thus screening becomes less valuable… current data about survival need to be used when making calculations about prolonging life.
     Secondly, overdiagnosis is important because if some women who do not have life-threatening disease are treated, they may die from the treatment. Mastectomy, radiation, chemo- or endocrine therapy are not trivial treatments. Surgery carries anaesthetic and sepsis possibilities, especially in obese patients.   Radiation is not without its risks, raising the incidence of ischaemic heart disease 27%  and of lung cancer 78%. These risks would be worth taking if there were no cases of overdiagnosis – but there are – somewhere between 10% and 50% -so any lives saved may be cancelled out by deaths caused.     So with all-cause mortality no longer showing benefit, it devolves to other factors such as the positive peace of mind screening provides or the negative over-investigation of false positives to sway decisions for or against screening. No wonder the editor of the BMJ (26th January 2013) asks “At what stage must we seriously consider whether this screening is a good use of £96m of  NHS budget?”  So how should we advise our patients? The statistics show the “lives saved” argument is neutralized. The cost of screening, time involved and morbidity from false positive tests are all non-fatal harms so these have to be weighed against  peace of mind of a negative result and these calculations are in the mind of the beholder.     The parallels with prostate specific antigen screening are uncanny and PSA testing is rapidly falling into disfavour or even disrepute. It seems those with vested interests are those promoting mammography screening. The moral position of doctors is becoming increasingly complex – can it be correct to say mammography screening in low-risk women is “the right thing to do”?
16 Mar 2013   Recently Bateman in Cape Town suggests  “PinkDrive intervention ‘over-rated’ : Breast health professionals are questioning the life-saving impact of the high profile non-profit breast cancer organisation PinkDrive.
      The Pink Drive website opens with some  fallacies eg  that:                                         xray mammo 23kg breast compression causes no pain or damage – wrong; that     It is a tool to diagnose breast cancer“-      wrong-only  histology does; and that diagnostic breast irradiation is no risk after age 40years ;  wrong- this column has quoted authoritative opinion and research eg Lemay,  Sherbrooke Univ 2011  to the contrary, the linear no-threshold model, although Mina Bissell’s  Berkley Lab 2011 research paper perhaps contradicts this – the jury is still out . .
          It is significant that of the seven Platinum Pink Drive sponsors, two are private Hospital chains with  major vested interest in the Breast Cancer Surgery and Reconstruction  Industry.
Contrary to the Pink Drive website stating  that mammograms diagnose breast cancer, a major new  study from Japan on xray mammography of almost 120000 women found histological cancer in 0.22% of those  who underwent mammography alone, 0.37% of those who underwent ultrasonography alone, and 0.5% of the 974 participants who underwent both mammography and ultrasonography. Recall rate due to mammographic abnormalities was 4.9% for women screened only with mammography and 2.6% for those screened with both modalities. The cancer detection rate was 0.22% for women screened only with mammography  and 0.31% for those screened with both modalities. Their conclusion that It is possible to reduce the recall rate in screening mammography by combining mammography and ultrasonography for breast screening is precisely the point, that  hazardous xray mammography screening with its immediate and  longterm risks is not needed when any two of the three well-tested lowcost zero-risk portable facilities are available eg Sure Touch Mechanical Tactile imaging, thermomammgraphy, and ultrasound, and two  combined give high sensitivity and specificity.
Neither of the above new abstracts raised the issue of overdiagnosis or longterm hazards.. In fact the NCI Nat Cancer Institute Journal itself published a study this month  from San Fran  University California showing that  in 140 000  women from 66years upward screened  between 1999 and 2006, Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48%  of annual screeners aged 66 to 74 years had a false-positive result compared with 29%  of biennial screeners. Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity. Thus  even cancer comes and go. Reducing xray screening  in USA   to every second year reduced the frequency of false positive recall – overdiagnosis – from almost half – 48% – by above one third, without increase in advanced cancer.
A Comparative Table shows the many methods, procedures  for objective breast imaging (mammography) available.  Of the established procedures  it lacks only comparison with the gold standard- the oldest ie  manual clinical examination-  and with forty year old Infrared Thermography. As this column has stressed previously, mammography is not a patented word for xray breast imaging, it is simply a generic description of breast (mammo-) and image (-gram) . Any image of the breast is thus a mammo-gram, and the process is mammo-graphy.
SCREENING METHODS COMPARATIVE TABLE:                   this table shows the relative merits of some different methods of breast imaging. Mechanical Tactile Sure Touch Imaging leads the field  for combined sensitivity and specificity, portability, all-age utility without problems of breast density interference, cost, risks and reproducible mapping. Like a photograph, a  plaster or other cast of the bust would thus also be a mammogram image- and unlike plastic surgeons,  dermatologists and thermographers, other health professionals and patients alike too often forget to record a photograph to compare changes in the skin and breast serially. .
NEJM 28 Feb from Harvard, Adler and Colbert’s  “Mammography Screening Poll Results”  is a sobering commentary  on the health professionals’ wrong perceptions about routine X-ray mammography screening of all well breasts from midlife. What do readers say about the indisputable overwhelming independent evidence against routine X-ray screening mammography?
One has to question  the rationality of most NEJM readers – surprisingly few in total – who responded to the poll after Bleyer and Welch’s  , Mette Kalager’s  , Baum, Jorgensen and Gotzsche’s publications last year, that the majority of NEJM readers polled still  promote X-ray screening despite the hard evidence, the absence of benefit from screening irradiation of well breasts- significant reduction in mortality in such women – in the face of multiple hazards of such screening.
The risks, the  list of hazards – in five broad categories – is so great that as pointed out below last month, not even the NCI National Cancer Institute itself any longer clearly  promotes routine  X-ray mammography screening. As Colbert and Adler and the 2nd Canadian mammography trial 20 yrs ago noted (Miller and Baines) , the evidence for presymptomatic screening X-ray mammo is no better than clinical digital exam. Early diagnosis of silent  breast precancer by xray screening and biopsy does not save lives, it is a vast waste of money except for the career Breast Industry, that has been characterized as  terrorizing and damaging gullible submissive women (Winifred Cutler, Athena Inst).

There are certainly many safe natural ways we  reviewed recently of  reversing the  risks of breast  proliferation and cancer, thus justifying periodic safe low cost breast screening  – mammo-imaging – by independent  eg digital, mechanical tactile  ” Sure Touch ” , ultrasound and/ or thermo- means.26 Feb 2013. There is a flood of new progress against breast disease , breast cancer and  xray screening mammography: Contrary to  the for-profit Breast industry,  like all independent authorities including the Cancer Association of South Africa CANSA , the National Cancer Institute of America in 2013 no longer recommends routine xray mammography   screening-          it rates  the EVIDENCE on X-ray screening mammography          as FAIR evidence for its sole and arguable benefit –  Decrease in total and breast cancer mortality –        -*Consistency of studies is only Fair. External Validity: Good.  Internal Validity: Variable,.           But as GOOD evidence for the FIVE major  HARMS of  xray  screening    -* both  consistency, internal & external validity -are good –

  • Discomfort if not cellular rupture and bruising from violent 23 kg 50 lb crushing,
  • Overdiagnosis and Resulting Treatment – including mastectomy or radiochemotherapy- of Insignificant Cancers:
  • False-Positives with Additional Testing and Anxiety.
  • False-Negatives with False senseof Security and Potential Delay in Cancer Diagnosis.
  • Radiation-Induced Breast Cancer.

Winifred Cutler’s Athena Institute  team warns again that screening X-ray mammography on well women is dangerous , inflicts terror,  it does not reduce but may worsen the occurrence of invasive breast cancer. The  Berkeley  Institute’s  Dr Venugopalan  under profs Mina Bissell and Daniel Fletcher  show that simply gentle massage  helps – Compressing Breast Cancer Cells Can Stop Out-of-Control Growth Shelley Hwang ea show that in California simple lumpectomy for early breast cancer reduced deaths (up to 2009) by 28% compared to mastectomy. Belinski & Boyages at the  Westmead Centre in Australia show again that common very low vitamin D levels more than double the risk of breast cancer let alone colon and all other cancers. A  Harvard team (Liu ea) has just shown that the carnage of legalized poisoning (smoking  – lungcancer, vascular;  alcohol -liver disease, violence;  adulteration with refined sugar/fructose – diabetes, vascular disease, cancer)  aside,  breast cancer far outstrips the other common cancers (colon, prostate cancer) in  preventible  life years lost. Willaims ea show again the major benefit of metformin against lethal breast cancer. Amadou ea in France confirm again the strong  link between abdominal obesity and breast cancer from childhood throughout life. This again highlights the criminal stupidity of delaying metformin use till obesity let alone infertility or diabetes are established. Metformin can safely be introduced at any stage of life provided it is started at very low dose eg below 250mg/day and cautiously titrated to the maximum well-tolerated dose to avoid nausea and diarrhoea- and temporarily halved or stopped in case of intercurrent gastrointestinal upset. . Grani et al from Rome, Italy    and many others remind us that both thyroid and breast malfunction are common by middle age and need to be sought and managed together.    We know that in most aging populations, deleterious deficiency of especially  magnesium, iodine, selenium, sulphur, and  vits B, C, D and K , and melatonin and sex hormones is very common along with crippling multitoxic carcinogenic overload. So it is logical to use multisupplements, and massage anti- inflammatory anti-cancer antioxidant  chelating antiestrogenic deep – penetrating iodine, coconut oil and DMSO – into the breasts as multidisease prevention and part of treatment. Oz ea in Turkey show that DMSO is  more effective against breast cancer than thalidomide.  But more importantly, DMSO enhances transport of any anticancer  agents into cancer cells. Already in 2008 Frederick ea showed that Lugol’s Iodine is an important antiestrogen adjuvant against breast cancer. Hence we advise  the harmless combination of natural multisystem micronutrients- especially  fish oil, coconut oil, DMSO,   vitamin C, D, K, melatonin, metformin, selenium, Lugol’s iodine and appropriate progesterone/ testosterone/ DHEA  – as nutrient supplements against all chronic aging diseases especially in women at risk of breast cancer.  . At Univ  Newcastle on Tyne,   Dr Dorota Overbeck-Zubrzycka’s  landmark  PhD  thesis just published on    FOXP3 regulates metastatic spread of breast cancer via control of expression of CXCR4 chemokine receptor promises new gene therapy in future. and her parallel study with Harvey,  A. Griffiths & C. Griffith,  Randomised control trial of Breast Tactile Imaging as an assessment tool for diagnosis of breast lumps in 2009/10 is now being published in full in a leading UK journal, validating this ( Sure Touch) bedside and outpatient clinic procedure as an established no-risk screening procedure, objective breast mapping  record for anxious women as shown in USA, Indian and Chinese studies. Thus increasingly Authorities are accepting that screening X-ray mammography harms far outweigh trivial if any improvement in survival. But screening – by eg regular clinical exam and mechanical tactile mapping –  for early signs of breast degeneration allows gentle safe self – treatment of all multisystem diseases that reverses both the breast degeneration and multisystem risk factors.

4 Feb 2013 UPDATE: BREAST SCREENING: Time lag to benefit after screening for common internal problems:   routine high-tech mass screening is inappropriate insurance.
a lot of the prestigious British Medical Journal last issue of 23 January 2013 is dedicated to the Breast Screening controversy; with a number of critics questioning the November 2012 Government  (Marmot) whitewash of the gigantically costly- and risky- NHS  screening mammography program. Professor Michael Baum of London University in particular has argued against this process for the past decade, after being the lead UK breast surgeon to set up this program in the 1990s and realizing it’s folly and risks.

Editorial: Breast cancer screening: what does the future hold?

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f87  Cite this as: BMJ 2013;346:f8Cliona C Kirwan, National Institute for Health Research clinician scientist in surgical oncology          :  “Overdiagnosis remains a problem; quantifying its effects and minimising its impact are priorities.
The role of national breast screening programs and the quality and transparency of information given to participating women are increasingly the subject of heated debate. In the past 12 months alone, the BMJ, the Lancet, and the New England Journal of Medicine have published 24 articles debating the value of breast cancer screening. After calls for an impartial review of the value of breast screening in the United Kingdom, the findings of an independent panel of experts, led by Professor Marmot, were published in November 2012.1Currently in the UK, women aged 50-70 years are invited for screening every three years; 2.3 million women were invited during 2010-11. The rate of uptake currently stands at 73.4%, having steadily increased in the past decade.2The primary aim of screening is to reduce mortality from breast cancer. Reduced breast cancer related mortality is balanced against the cost of screening in terms of physical and psychological harm to women and the financial impact on health services.Much recent debate has concerned overdiagnosis—that is, diagnosis of a condition that would never cause symptoms or death during a patient’s lifetime. Although over-investigation can cause harm (pain and anxiety from mammography and biopsies), this is usually …”

Personal View     Harms from breast cancer screening outweigh benefits if death caused by treatment is included : Prof Michael Baum

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f385 (Published 23 January 2013)      Cite this as: BMJ 2013;346:f385

13 Jan  2013   As this column has long noted, routine high-tech mass screening is inappropriate insurance/prevention. Contrary to the gospel of the American Radiology, Breast and endoscopy costly screening industry,  and Curves International,  no human  survives   for  > 10 000 years to benefit from routine hightech screening  to avoid premature disease and death ie ‘save a life’ . . There is still grave doubt about the risk:benefit of routine prostate screening in the well.
A new January 2013 BMJ paper by a California University team Lee et al    looks at  ‘noninvasive’ cancer  screening of  breast (xray mammography) and colon (testing stool for occult blood)   in Europe and USA. It found that  at least 1000 patients must be screened for at least 10 years – ie >10 000 patient-years of screening- before screening for either cancer could be claimed to save  a life. The corollary is that such screening of the well has a very low  chance – below 1:10 000 in any year, ie  0.01%  –  of finding a silent killer cancer that will save/  extend a life.

Thus they advise against screening people with an expected lifespan of below about 10 years.   But who would undergo such bothersome risky screening even over 10  years for a proposed benefit  (in death risk reduction)  of 0.1% a decade ? They found the reasons against routine screening of those not at high risk ( ie no suspicious personal symptoms or familial history) are as usual   those of the ensuing anxiety, the  procedures – radiation and colonoscopy and biopsies – and overdiagnosis. The worst is of course the cumulative risk of breast irradiation, and perforation death from colonoscopy:        “For cancer screening,  about one in 10 patients who are screened (with xray mammography , or with fecal occult blood testing) will have a false positive result,  leading to recall worry and likely biopsy/  colonoscopy.  Serious complications (such as perforation, major bleeding, and death) occur in 3.1 colonoscopies per 1000 screened.  One in 100 routinely mammography-screened  women will be  biopsied, and one in 1000 will be subject to overdiagnosis (that is, diagnosed with a breast cancer that was unlikely to have been clinically evident during their lifetime) and possibly unnecessary treatment.”

The same arguments apply strongly against routine screening of men for prostate cancer, or smokers for lung cancer,  in the absence of symptoms. . It should be noted that even the Wikipedia Mammography review now strongly highlights the arguments against mass screening mammography. The introduction sums it up bluntly: “task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.[3][4] The Cochrane Collaboration (2011) concluded that mammograms reduce mortality from breast cancer by an absolute amount of 0.05% or a relative amount of 15%, but also result in unnecessary surgery and anxiety, resulting in their view that it is not clear whether mammography screening does more good or harm.[5] They thus state that universal screening may not be reasonable.[6]     Mammography has a false-negative (missed cancer) rate of at least 10 percent. This is partly due to dense tissues obscuring the cancer and the fact that the appearance of cancer on mammograms has a large overlap with the appearance of normal tissues. A meta-analysis review of programs in countries with organized screening found 52% over-diagnosis.[6]

It can be argued that noninvasive screeing that finds suspicious premalignant signs can then motivate prevention by natural means- lifestyle diet and appropriate supplements. But since these preventative steps (including blood-pressure and waist/breast  girth measurements and monthly self-exam for breast changes)    hugely  reduce the risks of all serious  acute and  chronic diseases, accidents and premature disability and death, routine mass screening for common ‘silent’  internal cancers eg breast, prostate  colon lung womb and ovary , is irrelevant, risky and huge waste of resources for no benefit. Not applying sensible diet,  lifestyle, blood-pressure checks   and supplements is like failing to maintain  your car, house, computers and electrical appliances etc , until  these  crucial assets  break  down. The evidence against hightech screening of the well of course does not  stop the anxious well  from worrying. As a heavy cigarette-smoking prof  of lung medicine  said 30 years ago, if an anxious patient demands a scope despite reassurance that the risk:benefit doesnt justify it, it is wise to do it.  Or someone else will. At least in the context of the younger adult who will thereby be more motivated to apply prevention, non-xray non-invasive screening by eg Sure Touch breast mapping- from onset of menopause, or younger  in eg diabetics   and others more prone to cancer eg in AIDS,  – and ultrasound quantitative bone-density risk measurement  from toddlers upwards , in exercising ie sportspeople,  and in any serious chronic disease especially with hormone overtones  eg thyroid,  diabetes, COPD/ asthma, cancer, arthritis, paralysis, AIDS,TB, cardiacs, renal, liver disease –  are relatively low cost  and safe compared to the traditional  xray screening procedures. The brilliant new French movie The Intouchables is all about choices  of lifestyle and the risks entailed.  Thats what screening, and voluntary prevention, are about.  No  adult  should be pressurized – by vested interests –  into having hightech eg xray (breast, bone)  or more invasive (eg scope, biopsy) screening without understandable explanation of the possible  although  infrequent immediate and distant risks,  and remote if any  benefits. Only the frequent  incidental unexpected screening discovery of hypertension,  increased breast lumpiness/density,  and low bone density, and initiation of simple lifestyle diet changes  and safe supplement  therapy- the below- listed scores of supplements against all common degenerative diseases  (and if needed the best primary antihypertensive  – lowdose reserpine and co-amilozide – costs perhaps  $1  a month to control  most; and simple (breasts, arthritis, wound   or elsewhere)  antiinflammatory  self massage if indicated with Lugol’s iodine, and analgesic antioxidant coconut oil and DMSO),  gives huge early and permanent preventative  pain and inflammatory benefits without risks.  There are also  promising studies on Pubmed between 1989 and 2011 of the benefits of DMSO in management of prostate problems in rats, and humans for transrectal procedures  and intravenously as cancer adjuvant palliation. DMSO-MSM is cheaply and safely available . It comes back to basics that are anathema to politicians,  Government, profiteers, Big Business Pharma and the Disease Industry.  Motivating and enforcing better lifestyle and natural diet (minimizing sugar , aspartame, alcohol, processed food especially cornstarch) , and healthgiving realistic doses of supplements – vits (all –  especially B, C,  D3 and K), minerals  (especially Mg, Zn, I2, Se, P, Bo,) and biological (plant  and sealife – not land animal) extracts,  (including fish oil, metformin, bioidentical human hormones, tryptophan, MSM, DMSO, chondroglucosamine,  coconut oil, cinnamon, pepper, curcumin, arginine, carnitine, carnosine, ribose, coQ10, proline, rauwolfia) – reduces the occurrence of serious disease drastically with decades of health extension. This vastly reduces  profit to the Disease Hospital-Drug  and processed food- alcohol – tobacco industry in delayed disease till very old age, and thus loss of  skilled workers’  jobs – that need to be taken up  elsewhere. That’s called reinvention, recycling…

THE NEGLIGENCE- MORTALITY AND MORBIDITY- OF WITHHOLDING APPROPRIATE HEALTHSPAN-EXTENDING PHYSIOLOGICAL HUMAN HRT FROM AGING MEN AND WOMEN

update 10 Dec 2015  a reader in Germany  responds:  “ Excellent! I wonder when lawyers will start suing for withholding hormone replacement. 
I think you have made a very strong point by stating that government, medicine and industry are more interested in disease than health.”
      HRT UPDATE 8 Dec 2015: THE NEGLIGENCE- MORTALITY AND MORBIDITY- OF WITHHOLDING APPROPRIATE PHYSIOLOGICAL HEALTHSPAN-EXTENDING HUMAN HRT FROM AGING MEN AND WOMEN :

its been a long time since this column last reviewed HRT for women (the KEEPS Trial) and for men, other than in the contexts of prevalent cancer phobiamongering.  Both our experience in practice, and longterm observational studies, are increasingly affirmative. Why should we be surprised?

Global pollution and overheating, antibiotic, alcohol and sugar abuse, and shortage of drinkable/arable water and therefore food are the dominant “natural” threats of the next decade let alone century. As a 2013 German-Chinese study says, Water-sustainability requires > 60% of arable land for soil water replenishment.
But thanks to worsening indoor living, sloth and food production policies, deficiency of antiinfection- anticancer antioxidant growth-promoting (not just rickets-and – goiter-preventing) microdose anabolic vitamin D3 and iodine have taken the lead , for the half of mankind who do not go hungry, in the essential needed mineral-vitamin microsupplements in life-and- lifequality-limiting micronutrient deficiencies for young and old. These micronutrient deficiencies are so easily and cheaply remedied for a few $ per person per year- but there is no incentive for high-tech profit-based government, medicine and industry to promote these since Only Disease Pays.

Now the recent October interview with leading Canadian andrologist Dr Alvaro Morales Testosterone Deficiency Focus of New Canadian Guidelines echoes what we have learned  the past 50 years over our career lifetimes about appropriate parenteral natural physiological HRT being as important for deficient aging men- testosterone replacement. This matches need for appropriate parenteral natural physiological HRT for postmenopausal women- for whom progesterone cream often suffices as the safe baseline, adding parenteral testosterone and parenteral estrogen only as selectively indicated.ie in both genders to conservatively restore physiological balanced baseline bloodlevels of healthy young adults. .
Its now 13 years since the USA hysterical banning (2002 then 2003) of all HRT after the badly designed and bad analyses and premature stopping of the Womens’ Health Initiative; which illogically tested unphysiological and long-discredited patent oral xeno- ie non-human hormones (premarin and medroxyprogestin) in mostly elderly women long past the Change- the midlife menopause and menopause symptom decade (ie late forties to late fifties).

Many of us in the International Menopause Society objected to this dangerous hysteria from 2002 onwards, but the Americans involved in the WHI refused to concede for a decade that they were wrong, since such admission would have opened them to culpable negligence claims.. . .

in 2013 co-editors Dr Nick Panay(UK) and Dr Ana Fenton (NZ) asked in the leading journal Climacteric about the Womens’ Health Initiative:WHI: have our worst fears come true? . This was based on ongoing analyses of studies eg by Drs Sarrell, Katz ea at Yale University that showed The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years who were denied HRT.

Ongoing studies over 60 years (Schleyer-Saunders, Lee, Dalton, Greenblatt, Gelfand, Gambrell, Schneider, Davey, Shapiro, Cheifitz, Burger & Davis, Nieschlag & Behre, Notelowitz, Lunenfeld, Utian, Harman, Bhasin, Zitzman, Hader, Saad ea) have clearly confirmed what was apparent from experience in the 1940s, and Masters and Grody’s initial landmark HRT studies in the1950s in both sexes, that appropriate human parenteral balanced HRT (testosterone/ progesterone, plus estrogen for women) retard all risks of aging degenerative diseases in sex-hormone deficient aging people; and also extend both healthspan and longevity ie are antiaging.

           Now we have come full circle with longterm followup of stable physiological parenteral testosterone replacement- patches, fortnightly depotTT – or quarterly Nebido TUndecanoate – in 100 000s of men globally to a mean testosterone level around 18nmol/L (let alone to appropriate testosterone  replacement in women):

ongoing followup from a European observer personal communication last week is borne out by already published studies below: “there is no evidence from various registries of increased incidence and/or severity of prostate cancer with testosterone treatment.

      Increasing signals are that adequate testosterone treatment is protective, for the prostate as well as the immune, cardiovascular, nervous, musculoskeletal and cognitive-mood systems. One registry follows both hypogonadal men who refused testosterone treatment, and those on replacement. In 8 years follow-up of 296 elective hypogonadal men , 26% had major cardio-/vascular medical endpoints (21 deaths -19 = 6% cardiovascular, 30 =10% strokes, and 26 = 9% myocardial infarction, in total 77 events) . The elective Nebido testosterone replacement group (360 men) reported NO cardio/vascular endpoints ie no medical deaths, strokes, or heart attacks.(1 traffic accident death, 1 postsurgical complication death), q.e.d. p<0.0000…

REFS- in italics :
BOTH SEXES:
Clin Interv Aging. 2014 Jul 23;9:1175-86.. Off-label use of hormones as an antiaging strategy: a review. Samaras N1ea Geneva University Switzerland. Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. http://www.ncbi.nlm.nih.gov/pubmed/25092967

     WOMEN: The latest of many are the Danish studies of up to 16 yearsfollowup ;        2008 http://eurheartj.oxfordjournals.org/content/29/21/2660.abstract

and
2012 http://www.ncbi.nlm.nih.gov/pubmed/?term=BMJ+%28Schierbeck+et+al+2012%3B345%3Ae6409,

the USA KEEPS RCT of lower-dose premarin vs estradiol patch +- parenteral progesterone in perimenopausal women by Harman, Naftolin ea http://www.keepstudy.org/publications/index.cfm,

and again
Clin Endocrinol (Oxf). 2014 Oct;81(4):621-8. doi: 10.1111/cen.12459. Epub 2014 May 5. Transdermal testosterone improves verbal learning and memory in postmenopausal women not on oestrogen therapy. Davis ea . Monash University, Australia. Randomized, placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300 mcg/day, or identical placebo, for 26 weeks. 92 postmenopausal women aged 55-65 years, on no systemic sex hormone therapy. Eighty-nine women, median age 60 years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1•57; 95%CI 0•13, 3•01) P = 0•03 At 26 weeks, the median total testosterone was 1•7 nm (interquartile range (IQR) 1•1, 2•4) in the testosterone group and 0•4 nm (IQR 0•3, 0•5) in the placebo group. The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials.
Testosterone in women-the clinical significance. Davis & Wahlin-Jacobsen .Lancet Diabetes Endocrinol. 2015 (12):980-92. http://www.ncbi.nlm.nih.gov/pubmed/26358173.      Testosterone is as much an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes. Adverse cardiovascular effects have not been seen in studies of transdermal testosterone therapy in women. http://www.ncbi.nlm.nih.gov/pubmed/24716847

    MEN:
BJU Int. 2014;114:125-30. Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer. Balbontin, Morgentaler ea With a median of 31-months follow-up, long-acting testosterone injections in men mean 62yrs with prostate cancer treated with brachytherapy produced significant clinical benefits. There were no cases of rising serum PSA, prostate cancer progression or recurrence.
J Urol. 2015;193:80-6. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. Haider A1, Zitzmann M Yassin ea Germany In 3 parallel, prospective, ongoing, cumulative registry studies 1,023 hypogonadal men received testosterone therapy since 1996. Patients were treated when total testosterone was 12.1 nmol/l or less (350 ng/dl) with symptoms of hypogonadism. Maximum followup 17 years (1996 to 2013), median followup was 5 years. Mean baseline patient age was 58 years and 41 years. Patients received testosterone undecanoate injections in 12-week intervals. Prostate monitoring/ biopsies were performed according to EAU guidelines. RESULTS: A total of 11 patients were diagnosed with prostate cancer in the 2 urology settings at proportions of 2.3% and 1.5%, respectively. The incidence per 10,000 patient-years was 54.4 and 30.7 , respectively, ie mean 0.42% pa – well below that in the general population. No prostate cancer was reported by the andrology center. CONCLUSIONS:Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer. If guidelines for testosterone therapy are properly applied, testosterone treatment is safe in hypogonadal men. http://www.ncbi.nlm.nih.gov/pubmed/?term=Incidence+of+Prostate+Cancer+in+Hypogonadal+Men+Receiving+Testosterone+Therapy%3A+Observations
Eur Heart J. 2015 Oct 21;36(40):2706-15. Normalization of testosterone level is associated with halved incidence of myocardial infarction and mortality in men. Sharma R1, ea University of Kansas retrospectively examined 83 010 male veterans with documented low TT levels http://www.ncbi.nlm.nih.gov/pubmed/26248567
Prostate Cancer Prostatic Dis. 2015 Dec;18(4):382-7. Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading.Pichon ea, France http://www.ncbi.nlm.nih.gov/pubmed/?term=Preoperative+low+serum+testosterone+is+associated+with+high-grade+prostate+cancer+and+an+increased+Gleason+score+upgrading+A+Pichon1%2C5%2C
Horm Mol Biol Clin Investig. 2015 Jun;22(3):101-9. Obesity and hypogonadism are associated with an increased risk of predominant Gleason 4 pattern on radical prostatectomy specimen. Neuzillet , ea France http://www.ncbi.nlm.nih.gov/pubmed/26047422
BJU Int. 2013;111:880-90. Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment. Raynaud ea france http://www.ncbi.nlm.nih.gov/pubmed/23294726
Exp Clin Endocrinol Diabetes. 2015 Nov;123(10):608-13. The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance.Krysiak ea Poland . No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone. http://www.ncbi.nlm.nih.gov/pubmed/26600057
Swiss Med Wkly. 2015 Nov 24;145:w14216. Hypotestosteronaemia in the aging male: should we treat it? Christe N1, Meier CA1.Switzerland http://www.ncbi.nlm.nih.gov/pubmed/26599486 The term male hypogonadism is defined as the failure to maintain physiological concentrations of testosterone, a physiological quantity of sperm or the combination of both. Aetiologically, androgen deficiency can originate from the testes (primary hypogonadism) or from the hypothalamic-pituitary regulation of the testicular function (secondary hypogonadism). The causes of hypogonadism are very diverse .. But how about the aging male? It is known that there is a highly variable age-related decline in testosterone levels; whether this represents a variation of normality or has a true disease value requiring therapy has been disputed over more than a decade. The key questions surrounding this debate concern not only the age-dependent threshold for serum testosterone but, more importantly, the risks and benefits of testosterone replacement therapy in the aging male. randomised controlled trials of testosterone administration in aging males with a size of at least 100 patients and a follow-up of at least 6 months, identified eight studies. These studies mostly tried to evaluate the effect of testosterone on bone density, muscle strength and body composition, rather than clinically meaningful endpoints. Moreover, these trials have provided evidence for relevant cardiovascular adverse events in elderly men. This supports the need for further studies to define the treatment threshold for testosterone levels in the aging male, as well as with regard to the long-term risks and relevant benefits of testosterone therapy in this population. Until we have more solid data in aging males, testing for testosterone deficiency and testosterone replacement should remain reserved for patients with predisposing conditions, symptoms and signs of bona fide hypogonadism.
Rev Endocr Metab Disord. 2015 Nov 21. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease.Traish AM1, Zitzmann M2.Boston & Germany Univ. Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributing to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. http://www.ncbi.nlm.nih.gov/pubmed/26590935
Cancer Causes Control. 2015 Nov 20. Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial. Schenk JM1, EA USA & Australian Univ. examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial. In this 3 yr nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free.. We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA. http://www.ncbi.nlm.nih.gov/pubmed/26589415
by contrast,

seer.cancer.gov/statfacts/html/prost.htm reports:
In recent years, the number of prostate cancer deaths IN USA was 21.4 per 100,000 men per year ie 0.021%pa . c/f apparently no prostate cancer deaths in the TRT studies. These rates are age-adjusted and based on 2008-2012 cases and deaths. Lifetime Risk of Developing Cancer: Approximately 14.0 percent of men will be diagnosed with prostate cancer at some point during their lifetime, based on 2010-2012 data

LUGOL’S IODINE THE QUINTESSENTIAL SUPPLEMENT: against all diseases including cancer; & infections from fungi & protozoa to TB & HIV:

update 7 November 2015: comments & feedback please.
Orthoiodosupplementation in a Primary Care Practice Jorge D. Flechas, M.D. its undated but the latest ref is 2004..
but informative 2014 iodine update video by Dr Jorge Flechas:
some points: “why women have so many more thyroid problems eg estrogen blocks iodine; whereas ovary hot nodules may cause thyrotoxicosis from secreting T2.  Iodine alerts the brain, so dont take at night! give no more than ~12mg/d ie 2 drops 15% in pregnancy, it stimulates the baby!
“Iodine ie I2 diffuses into cells whereas iodide need to be transported in; babies lack the symporter Iodide transporter, so babies need iodine not iodide.
ie thyroid, ovary and WBCs can make thyroxine- but preferably  they mop up low iodine intake. Thyroid supplements doesnt provide enough iodine for needs elsewhere .
” Millions of women in Japan and Korea on their marine diet used to normally ingest ~13.5mg iodine a day, producing very low neonate problem rates in pregnancy and with IQ far higher than average.
“in the west, Iodine has been taken out of bread and milk, and salt intake cut – associated with increased rate of ADD in USA 500% and more cancer thyroid, breast, ovaries, endomet, cretinism, goitre .. – as iodine intake and output in USA has been halved by admin policy…
the kidneys excrete excess ingested iodine, so avoiding overdose from high iodine intake.

“ie if sufficiency, a 50mg iodine load will excrete >90% . so the spot test for low iodine excretion, and 24 hr high iodine excretion, reflect defective sodium symporter problem. This corrects with ongoing iodine supplement. 80% of vegans in USA are iodine deficient due to skipping seaweed for iodine! Asians eat seaweed in everything.. the body can hold 1.5gms iodine; 50mg in the thyroid, 20% in the skin, 30% in muscles…
– if depleted of iodine, we cant sweat or use our muscles (fibromyalgia), brains, or control the breasts or ovaries.. .. just add ATP cofactor ie incl vits B2 & B3 to iodine…
“Bread & esp cooldrink’ iodine (eg Mountain Dew) has been replaced by bromine, which causes schizoid behaviour… .. Iodine reverses the immortality of cancer cells.
” 3000mg/d ester C , and highdose iodine, and B2+B3 , reverse the iodine symporter block, & abolish the fibromyalgia in 80% of sufferers. .

This Flechas review is encouraging for repletion with Lugol’s 50 to 100mg iodine /day ie 6 to 12 drops 15%; after perhaps a precautionary skin test dose for allergy.
especially for protecting breasts, cancer, diabetics, obesity, heart disease, immune, memory and stroke problems.. .

It does seem that as with vits C and D3, iodine has a minimal RDA as far as basic prevention goes ie ~0.15mg – 1mg/d for avoiding cretinism (cf scurvy with >10mg/d vit C, or frank rickets with 400iu/d vit D3) ; and at the other end of the spectrum ie treating severe disease, grams a day of iodine and vit C, and vit D3 >50 000iu ie >1mg/day..

Then longterm maintenance with eg ~12 mg iodine a day ie 2drops/d 15% Lugols,  cf 1 to 3 gm a day vit C, vit D3 ~7000iu ~ 0.2mg/day… .

perhaps the corollary may be that , (as with vit D3 eg 2million ie ~ 50mg), a massive accidental load dose eg 2gms iodine- 20ml 15% Lugols- (which apparently bypasses the detox reaction at lower ie buildup dose, and incidentally provides 1gm potassium) may be both harmless and will reload for who knows how many years- presumably provided one takes a good magnesium and selenium ie realfood Banting diet .

To test tolerance, and try to reverse my familial irreversible atrial fibrillation, I have built up my Lugols’ dose  so far  to 15% 1 to 2 tsp a day ie 4 to 8ml, ~800mg combined (I + I2) iodine with 400mg potassium K  a day;
whereas a load dose vit D3 eg 0.6 to a million units (6-10gms of standard max strength 100 cwt powder – with a good magnesium and vit K2 diet as in realfood Banting) will replete safely and harmlessly for less than a year.
Its a pity the simple IODINE urine test is- unlike the skin patch test duration- so tediously long and costly (and both can occasionally mislead),
whereas the blood  vit D calcium-creat levels are quick to take but costly  tests.. .

But in those who can afford them , the tests are essential to validate the clinical results we get with iodine and vit D3 .

update 27 Sept 2015
IODINE THE QUINTESSENTIAL SUPPLEMENT

see prev Healthspanlife.wordpress.com ie May 2014 update.

quotes from authorities are in italics: please feed back on errors and experience

Massive iodine deficiency is  as universal worldwide (compared to 50 years ago) as are
*deficiencies of:                                                                                                ..vitamin C (except those who live on fresh fruit and veg);
..vitamin D (except those who work outdoors in sunny climes);
..magnesium; and
..natural saturated fats in all except keen carnivores;
..and increasing deficiency of other vitamins in the food chain, forced on the public by government-sponsored industries and “health authorities” for 50 years now;
*and unnecessary dangerous food-chain toxins ( refined carbohydrates; calcium/bromine/ fluorine/salt, aluminium, mercury supplements, synthetics eg transfats, pesticides eg glyphos Roundup, GMO foodstuffs, antibiotics ; and steroids). .

But with seafood almost wiped out by greed and pollution, and increasing global nuclear pollution, and failure by food producers to supplement   iodine never mind vit D and magnesium in the depleted food chain,

iodine repletion with vigorous Lugols iodine (with its consort selenium) is even more of a priority than concomitant vitamin D (with its consort vit K2) and magnesium supplementation, and vitamin C, plus a broad balanced other score A to Z multisupplement ..

So the dangerous scaremongering myths need to be debunked about the “dangers” of iodine at over a mg a day – when the safe general therapeutic dose is not just ~12mg/d but up to 100mg/d for longterm prevention, and over a gm/d for major diseases; ie >10 000 x the RDA. The US recommended adult dose of iodine for nuclear exposure is about 120mg, without any mention of remotest risk of toxicity.

This 1000 x order of magnitude with iodine is like
*the almost 10 000x margin between minimalistic vitamin C 10mg/d dose (RDA now 60mg/d) to avoid scurvy, up to >3v-7gm a day to treat infections, and >30 gm/day (intravenously, or buffered orally) to treat cancer;

*and vitamin D3 (RDA now up to ~800iu/d) up to 250 x more eg from 200iu /d to prevent rickets vs 50 000iu/d to treat some serious diseases, vs 2million iu single doses and 150 000iu/d for decades that have no documentable toxic effects in adults.
Infants obviously need proportionate dosing of all, not left to depend on mother’s milk when she has received no more than the usual prenatal supp folate and iron.. . .

The heaviest essential metal iodine is perhaps the most rare essential mineral – Wiki: “Iodine is rare in the Solar System and Earth’s crust (47th/60th in abundance):”- hence iodine deficiency is universal – especially now it has become fashionable in our lifetime to stop adding iodine to foodstuffs; and instead food manufacturers pump in toxic halides like bromine and fluoride (like dangerous mercury and aluminium in vaccines, aluminium in antacids) that (unlike chlorine,  iodine and refined sugars) have no essential biological need and benefit , only risks;

and recognition that commercial pure white runny salt NaCl – overdosing chlorine- is adverse because of worsening hypertension with aging and fast foods, instead of encouraging seasalt. .
The myths have been debunked that
*(unlike our essential blood chlorine in moderation), either fluorine or bromine are essential trace element halogens, any more than commercial cane sugar or fructose are biologically essential in our diet;

*and the Wolff-Chaikoff Effect myths (that iodine is toxic at much more than a mg a day) debunked by Abraham & Brownstein’s  review of scientific evidence the past century  including  Wartofsky, et al   1970  that we overdose with iodine at only 20 x the RDA (0.15mg/d) ie over a mg/ day,

*and the myth that only potass KI /sodium NaI iodides should be supplemented. The most proven iodine is in Lugols iodide providing the balance between  KI and free I2.

*Another commercially driven myth is that blood thyroid hormone levels are adequate to diagnose biologically significant iodine sufficiency, and commercial thyroxine to treat patients– the commercial hormones dont address, may worsen the serious iodine deficiency throughout the body that contributes hugely to acute and chronic, common and rare diseases

Studies of traditional Japanese after WW2 showed that their far better cancer-, cardiovascular,- thyroid health (before they emigrated to America, or took up Western diet) was attributable especially to the kelp ie iodine intake in their then-safe seafood diet, giving them an average iodine intake of about 12 mg/day- at least 100 times the current American imposed RDA of 0.15mg/d. But who can trust kelp, seafood from the poisoned oceans and rivers any more?

I recently took for a day each approx 20drops Lugols 2% pd in water ie iodine ~9mg a day; then 15% 4 drops ie 30mg/d …then up to , then 10drops ~70mg/d to test for detox reaction. I carry on with ~50mg/d,  as  many patients take it . I suppose my lack of detox reaction is not surprising since I have been detoxing for years on about 6 gm a day of a 50 -supp -multiblend( half vit C).- but no more than a mg/d of potass iodide. I  find physical and mental stamina better, no longer have  angina from stress or walking fast- which I could not do a fortnight before due to angina and fatigue. . .

One shudders to think of the billions of people – especially kids- who are dull, not achieving their full potential for lack of iodine, either because health professionals dont think we need more, or because patients are dismissed as euthyroid based on the usual thyroid lab hormone tests (which ignore iodine deficiency/excess in the majority who dont fall clearly in the over-or underactive blood hormone range).

Conventional western medicine apparently no longer considers or measures iodine deficiency, forgetting that iodine is the primary essential deficient mineral (along with magnesium, selenium, sulphur, phosphate; and iron in kids and reproductive women) for all systems in the body, not just for thyroid hormone levels- which dont reflect iodine security anywhere outside thyroid hormone production by the thyroid. .

IODINE OVERDOSE?
Iodine is needed in microgram mcg amounts for the thyroid, milligram mg amounts for breast and other tissues, and therapeutically as anticancer in gram amounts.[2]- Dr. David Miller
The theoretical iodine lethal LD50 for humans ie 1/10th of rodent dose is about 2 gm / kg, eg 6gm for a newborn baby, 140gm for an adult… a bottle of 20ml 2% Lugols in water contains 400mg, a 100ml bottle of 15% in water contains 15gm iodine(ie a 20ml bottle 3g) ie a harmless dose except corrosive if swallowed neat,.

Hence retailers if at all dispense Lugols 2%; we dont lightly prescribe/dispense 15% Lugols except for topical massage. And for cancer and we stick to 20ml dropper bottles.
not even Dischem and Clicks at Cavendish stock Lugols- only 2% iodine tinct IN ALCOHOL ie strictly for burning scratches… so no retailer should sell 100ml of any Lugols prep, only 20ml 2% Lugols, as is enforced in USA. It is indeed apparently regulated in the same way here., ‘tho’ the SA Medicines formulary doesnt mention that (recommends it only preop for eg thyroid storm), nor the multidisease benefits of Lugols including on the brain, wounds, infections, cardiac, vascular, cancer lungs etc;

nor the usual DETOXIFICATION REACTIONS as heavy metals are mobilized, for which (like eg metformin) the Lugol’s dose must be started low and titrated to tolerance with lots of fluids including magnesium, seasalt, selenium , vits B. eg Brief symptoms from heavy metal detox include “headaches, agitation, palpitations, nervousness, the jitters or irritated thyroid symptoms; pimples; skin rashes; fatigue, muscle aches, fever, diarrhea, worsen sinus/asthma, and brain fog. “. http://nourishingplot.com/2014/08/30/detoxing-fluoride-bromine-and-chlorine-naturally/ , http://www.iodine-resource.com/lugols-iodine.html ,   http://www.tiredthyroid.com/blog/2013/07/15/iodine-protocol-asthma-hives-sulfite-sensitivities/ and http://drsircus.com/medicine/iodine/iodine-and-detoxification. If these heavy metal detox reactions occur, stop the Lugols a few days, increase the detox remedies, then resume Lugols at a lower dose that you dont react to.
Threads   indicate that detox problems go away once iodine dose exceeds 50mg/d- especially if taken with a multisupp incl vit C, magnes , BCo, & selenium; and plenty of seasalt in water. (the only one of these not in a multisupplement AntiAging blend is salt).

In perspectivethe thyroid holds 50 milligrams of iodine, the breasts hold 200 milligrams, the skin holds 400 milligrams of iodine, and the whole body holds 2,000 milligrams, and possibly much more. Iodine is found and used in every hormonal receptor in the body. in 1911, 900 milligrams 0.9gm/day!) were considered usual and safe dosage. At 6 grams 6,000 milligrams/day!), iodine has been used to cure syphilis, skin lesions, and chronic lung disease. Iodine makes us smarter, helps with mental functioning. Low iodine is associated with low IQ’s with a difference of up to 13.5 points in children; but iodine deficiency is also associated with mental functioning in adults, because iodine not only chelates lead, but, according to Dr. Jorge Flechas, iodine prevents lead from lodging in the body in the first place. Low thyroid function decreases brain circulation, which slows intellectual function. low thyroid function is associated with cognitive impairment, memory loss, depression, slowness of mind, anxiety, suicidal tendencies, and a variety of psychiatric disorders. Bleichrod’s meta-analysis of 17 studies showed iodine sufficiency increases IQ by 13.5 points in children. Iodine prevents heart disease. Iodine is needed with the use of cordless phones, cell phones and now smart meters to prevent hypothyroidism. Iodine decreases insulin needs in diabetics.

IODINE ALLERGY? The risk of iodine allergy is quite low – Drs. Abraham and Brownstein were only able to identify 3 of 4,000 people who had a negative response to the iodine. People do not become allergic to iodine per se, but people react to the displacement of bound heavy metals; and can become allergic to protein-bound iodine as is found in shellfish or to the binding agents, excipients, fillers, preservatives and/or synthetics (rather than the bioavailable form of iodine itself) commonly found in tablets, capsules, and even liquids. Actually, iodine can help eliminate food allergies according to Dr. Derry.
But dont take Lugols at the same time as vit C, which neutralizes the antimicrobial effects of Lugols. so take them at opposite ends of the day.

and because iodine attacks only pathogens and abnormal cells, not our good probiotic biome or healthy cells, it has none of the risks of pesticides , antibiotics, antivirals, radiotherapy, chemotherapy etc.

RESEARCH ON LUGOL’S IODINE?
despite Dr Jean Lugol having published his landmark 1829 work on his iodine complex  ie ~185 years ago, there is predictably little research on it published on Pubmed, for the obvious reason that Big Pharma and the Disease Industry and governments wont fund research on such a cheap cure, which would greatly increase survival, but in the short term reduce illness and thus need for health industry workers, hospital beds, pharmacies and new drugs.
There are apparently only three clinically relevant LUGOL’s papers listed on Pubmed ie in the past 50 years:-

from India 2012 Consul ea – confirming that painting the cervix with Lugols (the Schiller test ) and vinegar is as effective as Pap smear for screening; thus combined, the two simple cancer diagnostic paints make up for Lugols iodine for cervix cancer being only about 85% sensitive and specific ie not as reliable alone as a costly lab Pap smear…
Greece 2007 Theodoropoulou ea  confirming that preoperative Lugol’s iodine 80mg/d for 15 days in euthyroid people was accompanied by increased intrathyroid total iodine but no changes in intrathyroid hormone HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.
and
Italy 1986 Marani ea  –Iodine is therapeutic in various pathologies where immunity plays a dominant role, eg it facilitates cure in tuberculosis, lepromatous, syphilitic and mycotic incl sporotrichosis lesions . This effect does not depend on iodine’s action on the micro-organism responsible, but on host immune boosting. . Iodine may also be used in Panniculitis, in erythema nodosum, in nodular vasculitis, erythema multiforme etc. . To establish relationship between dietary iodine and immune response, 607 infants in an area of endemic goitre were studied: 215 were given Lugol solution (2 drops- presumably 20mg? a week for about 8 months ; and 392 not. Immune response was assessed by the skin test tetanus toxoid (in the U.S. 80% of paediatric cases aged 2-10 years old were positive). A significant difference was noted in the average diameter of the infiltrations after the tetanus toxoid skin test in the two groups considered (P less than 0.001). The results indicate that an adequate iodine intake is necessary for normal retarded immune response – a fact that the disease industry and Big Pharma blatantly ignore. . . (Iodine does not have the adverse effect of antibiotics on our gut biome, or causing antibiotic-resistant pathogens)

But there are dozens of scientific Lugol’s studies not referenced by Pubmed:

The End of Antibiotics and the Rise of Iodine as an Effective Alternative 2008 Mark Sircus

Iodine and viral infection?
David Derry, MD, PhD Thyroid Science 2009 Iodine: the Forgotten Weapon Against Influenza Viruses

Mamo & Naissides International Journal of Infectious Diseases (2005) from Australia show Iodine Could be effective in the treatment of human immunodeficiency virus and AIDS-associated opportunistic infections. as it is in rodents and cats .

Inactivation of human immunodeficiency virus by iodine-releasing products Harbison & Hammer Boston, Massachusetts 1989  showed that “povidine-iodine completely inactivated HIV at concentrations of greater than or equal to 0.5% ie is highly effective at killing HIV.
Betadine is simply “a stable complex of povidone and elemental iodine, contains 9.0% to 12.0% available iodine ie 90-120mg/ml .. Free iodine slowly liberated from the povidone-iodine PVPI solution kills microbe (but not healthy mammalian) cells through iodination of lipids and oxidation of cytoplasmic and membrane compounds, thus exhibits a broad range of microbicidal activity against bacteria fungi protozoa and viruses. Slow release of iodine from the PVPI complex in solution minimizes iodine toxicity towards mammal cells.” This compares exactly with a similar iodine complex  15% Lugols which contains about 10% ie 100mg iodine /ml water .. at far lower cost than but identical safety and efficacy to the patented Betadine – a modern designer marketable patented crib of Lugol’s .. …

see also
http://jeffreydachmd.com/wp-content/uploads/2014/03/The-Guide-to-Supplementing-with-Iodine-Stephanie-Burst-ND.pd

and

Lugols for animal thyrotoxicosis

and IODINE, A CRITICAL NUTRIENT 2014 http://drlwilson.com/Articles/IODINE.htm

and

Iodine: Its Role In Health and Disease: New Exciting Concepts Michael B. Schachter, M.D. 2007:   Guy Abraham MD, former professor of obsts gyne & endocrinology at UCLA School of Medicine, has written papers about iodine that drastically changed my thinking about its role in health and the prevention and treatment of disease. I had been impressed by Dr. Abraham’s previous work, which showed that vitamin B6 and magnesium could be very helpful to women with premenstrual syndrome (PMS) and was eager to learn what he had to say about iodine. Through a series of articles termed “The Iodine Project,” Dr. Abraham proposed that the optimal daily dose of iodine for a WELL person is approximately 12.5 mg, which is 100 times the RDA of 0.125 mg, ie that the current prevailing medical opinion that more than 2 mg a day of iodine is toxic is wrong. He traces the source of this major blunder to a scientific experiment on rats that was published in 1948 by Drs. Wolff and Chaikoff, which erroneously concluded that iodine inhibits the thyroid gland at doses of about 20 times the recommended daily allowance (RDA) for iodine. This conclusion was later generalized to humans and can be found in medical textbooks, including endocrinology and nutrition textbooks. Guy Abraham wrote in 2005: In hypertension, iodine sufficiency resulted in normalization of blood pressure without medications; as reported by other physicians using this program. Best results were achieved when orthoiodosupplementation was combined with a complete nutritional program emphasizing magnesium instead of calcium. Obesity increases the requirement for iodine and up to 100 mg elemental iodine/day may be required to achieve and maintain sufficiency. Increased demand for iodine occurs with excessive amounts of goitrogens from the diet and lifestyle. eg, smoking increases serum thiocyanate levels, interfering with the sodium/iodide supporter function. Low thyroid iodine is associated with thyroid hyperplasia and cancer. Could thyroid hormones cause the same iodine depletion in breast tissue? The prevalence of breast cancer is higher in women on thyroid hormones. Medical iodophobia resulted in removal of iodate from bread 20 years ago, replacing it with the goitrogen bromate- which associated with increased obesity, diabetes, and hypertension, thyroid and breast cancer. Recent reports show association between low iodine intake in women during pregnancy and attention deficit and hyperactivity disorder (ADHD) in their offspring. The most plausible explanation is a decreased sensitivity of the nuclear thyroid hormone receptor to thyroid hormones. We previously reported evidence for improved receptor response to thyroid hormones following iodosupplementation. Therefore, iodine is not only necessary for the synthesis of thyroid hormones but also for their effect on target cells. This effect is probably due to iodination of the thyroid hormone receptor. The essential element iodine, which is the inorganic, non-radioactive forms, deserves more attention from researchers and clinicians. It maybe the missing link in patients currently resistant to conventional hormonal therapy.
and see
http://www.earthclinic.com/remedies/lugols-iodine-supplements2.html
re adding enough selenium, chromium, vit C, Magnesium, Vitamin B2/3
and

Until 2007, in the United States, Lugol’s solution was unregulated and available over the counter as a general reagent, an antiseptic, a preservative,[11] or as a medicament for human or veterinary application .

However, effective August 1, 2007, the DEA now regulates Lugol’s solution (and, in fact, all iodine solutions containing greater than 2.2% iodine) as a List I precursor because it may potentially be used in the illicit production of methamphetamine.[12] However, transactions of up to one fluid ounce (30 ml) of Lugol’s solution are exempt from this regulation. When buying Lugol’s Solution on places like Amazon, most sellers fail to indicate the DEA tracking requirement. On the other hand Lugol’s Iodine solution is available over the counter in Canada and Mexico.
Toxicity Because it contains free iodine, Lugol’s solution at 2% or 5% concentration without dilution is irritating and destructive to mucosa, such as the lining of the esophagus and stomach.
Doses of 10 mL of 5% solution have been reported to cause gastric lesions when used in endoscopy.[13] The LD50 for Iodine is 14,000 mg/kg [Rat] and 22,000 mg/kg [Mouse].[14]
Most guidelines accept that anything with an LD50 >2 g/kg (-5 g/kg in some countries) can be classed as having a low acute toxicity[citation needed] which classifies Iodine as having low toxicity. Potassium Iodide is not considered hazardous.[15
http://jeffreydachmd.com/breast-cancer-prevention-with-iodine/

Iodine Dosages
Treatment of Influenza and other Diseases iodine-dosages 2009 “After testing over 500 patients, I found that 94.7% of my patients are deficient in inorganic iodine. Dr. David Brownstein In this chapter I will present different views and practices from present as well as from the long past when iodine was vastly more popular as a medicine than it is today. For whatever irrational reason, doctors and patients fear iodine thus en mass do not use to its fullest potential.
Humans tolerate large doses of iodine but the ultra high doses that were used many decades ago are not required to get the most out of iodine therapy. Just a little goes a long way, as the governmental iodized salt programs showed but this dosage level was only effective for Goiter and its avoidance. It actually takes very little iodine to prevent this disease but no one ever said that was the only purpose and need for iodine in the body. Today people are more deficient then ever before because our need for iodine has increased in direct proportion to our toxic burdens especially of other competing halogens. Read on at http://drsircus.com/medicine/iodine/iodine-dosages
Pps
see lugols_dosage_chart.  . But for obvious reasons stick to 2% till you know you tolerate and need much stronger drops.

UPDATE: COLORECTAL CANCER SCREENING IN LOWRISK PATIENTS- NO BENEFIT ON ALL-CAUSE MORTALITY. IS IT ANYTHING BUT A HUGE EXPENSE- AND RISK?

neil.burman@gmail.com

21 Dec 2014 Update: No response has been received from or published by  Annika  Steffens ea  of Australian universities in the past 2 months on the allcause mortality difference by CRC screening in their massive colorectal  cancer CRC screening study in an older population. .

But a number of autopsy studies the past 40 years throw more light on how infrequent CRC actually is elsewhere , Australia apparently having one of the highest rates at 0.125% pa.

As regards apparently undiagnosed cancer found at autopsy: colon cancer is very infrequent, and its import drops with age; and is no more common in sudden death potential organ donors than in others. In Japan over 20 years, the incidence of unsuspected colon cancer in 3600  routine autopsies  was only 0.03%pa. In Singapore in 1000 random autopsies on the other hand, incidental CRC was found in 10 ie a prevalence of 1%. In the Connecticut Cancer registry over 50 years, one cancer trebled the risk of a second cancer- especially  high risk of cancers of lung, larynx, mouth, pharynx; breast;colon, uterus,  ovary, cervix; suggesting a common etiology involving  smoking & HPV? , ie an intriguing link  between female genital tract, breast, airway  and colon but not prostate.. However studies since at least 2005  including from RSA 2007, do indicate a link between HPV and prostate cancer, the latest from Crete University 2014.

So smoking, alcohol and  STDs- especially HPV- are a deadly triad in   male-dominated  permissive countries like South Africa – but  likely worse in strict Islamic countries that keep citizens (subjugated women even more than men) overdressed ie minimize sunshine and thus lifegiving vitamin D3 levels.  .

refs: A  new study   from France asks:  Are suicide rates higher in the cancer population? An investigation using forensic autopsy data.  Med Hypotheses. 2014  de la Grandmaison,  Charlier ea Versailles Saint-Quentin University,    note previous population-based studies have identified increased suicide rates among cancer patients.  In total, 232 cases were included in both the suicide and the control groups.  Cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03).  the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding.

Crit Rev Oncol Hematol. 2012 Cancer prevalence and mortality in centenarians: a systematic review. Pavlidis ,  Audisio  ea  Univ of Ioannina,Greece.   Data analysis demonstrates how cancer incidence and cause of death present a threefold decrease after age 90 and reach 0-4% above age 100. In addition, the number of metastatic sites are remarkably less and incidental malignant tumours or multiple primary cancers are more frequent, indicating that cancer in centenarians carries a more indolent behaviour. Cancer in the very elderly is relatively uncommon as a disease and as a cause of death. It is characterized by a slow growth and a modest life-threatening potential.

Arch Pathol Lab Med. 2009 Unexpected neoplasia in autopsies: potential implications for donor tissue  safety. Sens, Cooley ea University of North Dakota.-Medical examiner cases are increasingly used as tissue donor referral sources to meet ever-growing need for transplant tissues. Assumption is often made that traumatic and sudden deaths have minimal risk of unsuspected neoplasia.-A retrospective, 5-year review of 412 autopsies from a regional, primarily forensic, autopsy service to determine the incidence of unsuspected neoplasia, potential donor referral suitability. Unsuspected neoplasia rate at autopsy was 7% (29 of 412 patients); cancer was the cause of death in 41% (12 of 29 patients) of these individuals. In patients with a history of cancer, the discordance of cancer diagnosis was 44% (4 of 9 patients [11 patients with known cancer, 2 who refused medical evaluation were excluded from the study]). Nearly 60% (17 of 29 patients) of the unsuspected cancer cases had no apparent reason for deferral of tissue procurement before the autopsy examination.

Ueyama,Tsuneyoshi ea  Kyushu University, Japan.  During the past 20 yr, 17 colorectal carcinomas (0.47%) were incidentally detected among 3,638 autopsied patients without clinically evident colorectal carcinoma, including 2,232 males and 1,406 females, more than 40 yr old. Among the 15 male and two female index subjects, six (0.33%) were detected in the first and 11 (0.60%) in the second decade.

Cancer. 1988 Mar 1;61(5):1059-64.  Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore.   Lee YS1 Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. It was observed further that incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase.

Natl Cancer Inst Monogr. 1985  Summary: multiple primary cancers in Connecticut, 1935-82.  Curtis,  Fraumeni ea   The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.

J Am Geriatr Soc. 1979   Cancer in the aged: an autopsy study of 940 cancer patients.    Ishii, Hosoda ea  In an autopsy study of 940 elderly cancer patients, 1,030 cancers were identified. The prevalence rate for overall cancer declined after age 85 in men and after age 75 in women. The chief sites of major cancers were the stomach, lung, esophagus, liver, and pancreas, in that order. Incidental cancers (chiefly of the prostate, thyroid, and colon) were found more often in patients over 80 years old. For multiple primary cancers, the prevalence rate was relatively constant until the age of 70, when it rose to a peak in the 80–84 age group before declining to the original level

4 Nov 2014  update: a new POSTAL study Colorectal cancer CRC  screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study. by Steffen ea, from Australian universities shows the usual ~50% reduction BY SCREENING  in colorectal cancer occurrence, in a population mean age 60yrs followed for a mean of 3.78yrs in 741 000 screened pts , mean 60yrs at screening, mean BMI 27kg ie a high-risk population . .   But it glaringly omits  mentioning the most important data:     what was the allcause mortality reduction if any in the screened versus the unscreened cohorts after 3.78years? By this strange data omission, it must be assumed that the study showed no such benefit?.

All that the study confirmed is that it detected about 1000 new colon cancers in about 200 000 older people followed for almost 4 years ie an annual incidence of ~ 1 in 400 000 or 0.125% per year . This rate is similar to  the 0.12% cases pa ie per year  of early breast or  prostate cancer   claimed  in USA SEER data;  but the Australian CRC cancer rate reported is strangely almost three times the overall USA CRC incidence rate of about 0.04%pa found in USA men and women combined, similar to the lung cancer incidence reported there. . If the Australian data presented is correct, there must be something colotoxic (Perhaps their high beer and barbeque  intake?)  in the Australian diet compared to the European and USA population, since the great majority of all such citizens are of European “Caucasian”  origin?

This compares to South Africa where the latest stats for the whole population (NRC/CANSA 2007)   (assuming only maybe <1/4 of the population are 45yrs and up) are : prostate or breast 0.05%pa, lung or  CRC 0.01%pa, and cervix (much younger- due to abuse and STD) 0.05%pa. That study reported the lifetime risk of CRC in RSA as 1:115 in men, 1:199 in women, compared to , prostate 1:26 and breast 1:35, cervix 1:42,  uterus 1:176,  lung men 1:91  women  1:250.

There remains  no good evidence of lives saved ie reduction in all-cause mortality by such hugely costly population cancer screening for these commonest cancers. All that it achieves is the knowledge of previously silent cancer,  which would mostly have been buried unknown with the patient dying of other common causes- ie creating the worried well who have become “cancer survivors”.

we await response from the authors  on this primary issue .

Do any   studies show that there is   meaningful survival benefit from  costly mass screening for internal disease  of adults not at high risk, except for hypertension?  Mass CRC screening of people not at increased risk ( from family history, bowel symptoms or disease) is like breast and prostate screening, no apparent benefit on the most crucial issue, all-cause mortality.

19 Sept 2014   .    is there anything to update? CONCLUSION: not really. Conservatism urges avoidance of screening anyway in those with short lifespan from other major disease, or age eg above 75years- UNLESS there is good evidence of meaningful life extension. As we concluded in 2011, is such screening worth perhaps  1 month life extension in old age?

So far there is still no good evidence to support regular mass population screening in apparently well adults without risks for any degenerative disease  EXCEPT for hypertension;  glaucoma;   malignant melanoma; and  women at risk of cervix cancer ie sexually active at a younger age.

Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancerDinh T,  Levin TR  ea 1Archimedes Inc, San Francisco  present a model rationale for FOBT screening from age 50yrs, with a single elective colonoscopy at 66yrs if FOBT remains negative – at a cost of US$10000 per putative QALY gained. .   Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy.   METHODS:  We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials.  RESULTS:   A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT.    .  CONCLUSIONS:  In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.  Clin Gastroenterol Hepatol. 2013 Sep;:1158-66.

16 Sept 2014: PREVENT INSTEAD OF SCREEN: Dr  Ng  from DANA FABER CANCER INST, BOSTON MASS asks in .  Vitamin D for Prevention and Treatment of Colorectal Cancer: What is the Evidence?   Vitamin D insufficiency is highly prevalent in the U.S, particularly among colorectal cancer (CRC) patients- – studies suggest that higher vitamin D levels are associated with lower risk of incident CRC as well as improved survival in patients with established CRC. There remains a great need to improve prognosis for patients with CRC, and investigating vitamin D as a potential therapeutic modality is an attractive option in regards to safety and cost, particularly in this era of expensive and often toxic anti-neoplastic agents.  Curr Colorectal Cancer Rep. 2014 Sep 1;10:339-345

But as we know well from many studies, conventional “high” doses of vitamins C (eg  hundreds of  mgs/d)  and D (a few hundred to a few thousand iu/d)  have only modest benefit for prevention and against existing disease-  it requires about 10-15fold higher vit D3 ie 80-100iu/kg/day, and 100 to 500 more vit C ie a few to a few score gms vit C a day to have major impact. These must not be in isolation, as they may be limited by conditioned deficiency of other micronutrients especially vits K2. . We know well from eg the ATBC trial of vits A and E that too much and too late may be harmful, especially if these are not in natural balanced forms of all the vits A and E groups.

14 Sept 2014   A colleague is surprised that  at 72yrs I have never had a screening scope.

so I recheck the evidence after 3 years, since my 2011 review. Even The USA National Cancer Institute review of colon cancer screening  (updated to 24 July 2014) agrees  that Based on solid evidence, there is little evidence that screening for colorectal cancer (CRC) reduces all-cause mortality, possibly because of an observed increase in other causes of death, although in some studies it may reduce CRC mortality;   and there is always serious risk of harms. Overall, the NCI concludes that  On initial (prevalence) examinations, from 1% to 5% of unselected persons screened  with stool gFOBT guaiac faecal occult blood test (collected over 3 days, repeated up to yearly )   have positive test results ie 30 per 1000 recalled; of whom on imaging  2% to 10% have cancer and approximately 20% to 30% have adenomas,[26,27] depending on how the test is done.That translates to colon cancer detected in  about 3% of 6%  = 0.18% of the target population screened  – of whom 74% occur between 55 and 84 yrs. .

As a recent Spanish team review last year says, No strategy, whether alone or combined, has proven definitively more effective than the rest:   Economic evaluation of colorectal cancer (CRC) screening   Cruzado J1Carballo F. ea  1Colorectal Cancer Prevention Program for  Instituto Murciano de Investigación Biosanitaria,  Murcia, Spain Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and (then) studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed.. Best Pract Res Clin Gastroenterol. 2013 ;27:867-80.  

BUT:  Is aging per se a real risk factor for suffering colon cancer? No good evidence yet.  all cancers do increase with aging. But there is still no hard evidence of meaningful life extension from colon, breast or prostate  screening for silent risks in those without other cancer risk factors.

The NCI found four completed  trials of FOBT faecal occult blood testing since 2004 – in Minneapolis(46500), Denmark (31000), Sweden(68000) and UK(151000) – ie 300 000 older lowrisk adults- these   find no benefit in terms of increased length of life. The longest, –  30 year followup in Minneapolis – looks at the longterm mortality benefit of CRC screening– and as with breast and prostate screening for silent cancer in those without significant risk factors.   So organized mass population screening eg every 1  or 10 years from age 50 years does not save lives in the elderly at low risk ie no colon symptoms- at an enormous cost in the scores  of well people  – about 1.2 per 1000- needed to screen, with about 3% of these found positive needing imaging- at major risk of unforseen problems-  to find one cancer, shorten the lead time, save a life from silent cancer. We all die from something eventually. 99.82% of the population screened did not develop colon cancer.

In firstworld people the risk of colon cancer is generally below that of breast and prostate cancer respectively: Wiki sums it up-                                                                    Based on rates from 2007-2009, 5% of US men and women born today will be diagnosed with colorectal cancer during their lifetime.[95] The median age at diagnosis for cancer of the colon and rectum in the US was 69 years of age. Approximately 0.1% were diagnosed under age 20; 1.1% between 20 – 34; 4.0% between 35 – 44; 13.4% between 45 – 54; 20.4% between 55 a-64; 24.0% between 65 – 74;  25.0% between 75- 84; and 12.0% 85+ years. Rates are higher among males (54 per 100,000 c.f. 40 per 100,000 for females). about 20% of such cancer patients have a familial genetic risk.

so faecal screening would be the mass screening method of choice, with about 25% recall rate for costly colon imaging to find the 1.2  cases per 1000 in the target population. But that is supposed to uncover silent colon cancer 2 years earlier, allowing expected drastic reduction in the 75% mortality of clinically presenting colon cancer. So why do no trials of  colon cancer screening show reduction in all-cause mortality? Perhaps its because the lethal colon cancers occur  and present clinically younger in those with lethal genetic risks eg Lynch syndrome, or predisposing colon inflammation eg ulcerative colitis, Crohn’s; or those with multiple polyposis  who are more likely to bleed early.

But we know that real chronic colonic  disease is par excellence a western Saccharine Disease ie of our urban fastfood high sugars,  low fibre diet, inadequate water intake,  and slothful low sunshine ie couch potato  low vitamin D  constipated  lifestyle; with often smoking and alcoholism. . Naturally the Wiki review, written to favour regular screening to find profitable more  silent cancers (like breast and prostate screening) , does not mention this. .

Shaukat A1, Church TR ea  (in N Engl J Med. 2013;369:1106-14  Long-term mortality after screening for colorectal cancer    Minneapolis VA Health Care System USA).  In randomized trials, fecal occult-blood testing FOBT  reduces mortality from colorectal cancer. However, duration of the benefit is unknown, as are the effects specific to age.  METHODS:  In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008.  RESULTS:  Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths 2% were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction).     CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy.

For mass Sigmoidoscopy screening,   Five sigmoidoscopy screening RCTs have reported incidence and mortality results.- Norway 2 trials;  and  United Kingdom; Italy; and the U.SA, in 166,000 participants in the screened groups and 250,000 controls. Follow-up ranged from only 6 to 13 years.   There was an overall 28% relative reduction in CRC mortality (RR, 0.72; 95% CI, 0.65–0.80), an 18% relative reduction in CRC incidence (RR, 0.82; 95% CI, 0.73–0.91), and a 33% relative reduction in the incidence of left-sided CRC (RR, 0.67; 95% CI, 0.59–0.76). There was no effect on all-cause mortality.

For mass colonoscopy screening, no trials have been completed to give any evidence of longterm mortality benefit.

One group proposes a screening program based on  periodic stool FIT faecal immunological test , with a single colonoscopy at 66yrs.  Dinh , Levin ea Archimedes Inc, San Francisco,( Clin Gastroenterol Hepatol. 2013 ;11:1158-66   Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancer)  In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.

UPDATE  20 Oct  2011 A chiropracter asks: what is the recommendation regarding screening colonoscopy, mammography, prostate for cancers? would MD’s and DO’s get one and if so in what circumstance?

My answer:

The only link between breast, prostate, bowel, ovary and womb cancers is that these organs (unlike cervix cancer) are genetically linked through common sex hormone influences; and (apart from the breasts) coincidentally abut ..

Prostate cancer associates with higher estrogen and DHT levels. As for usually estrogen-dependent breasts and  breast cancer screening in low-risk breasts discussed previously, the overwhelming evidence favours no screening at all without symptoms  or risk factors. Unlike for breast cancer,  treatment for prostate cancer (as for  colon cancer) seems to make no difference except when there is obstruction or bleeding. For asymptomatic PRCA the rule remains: watchful waiting. Like women and breast cancer, many men have undiagnosed ie asymptomatic prostate cancer at autopsy for other causes of death.

Colon cancer is different.   it is less common in women with estrogen replacement.

But unlike prostate and breast cancer where invasive screening of all lowrisk patients likely causes more harm  (including despondency) than good,  it is hard to find good colon cancer studies of asymptomatic lowrisk people that show no benefit of screening colon imaging. Studies of colon cancer imaging are inevitably by practitioners who have  a major commercial vested interest in such imaging.

But how many studies have been done comparing colon screening with no screening in patients who truly have none of the risk factors –  – heredity, meat diet, smoking, overweight, bleeding,  inflammatory bowel disease, polyps, diabetes?

Few articles are against such colon screening ie rationalize or philosophize against it .

A 2011 Medscape review from a New Jersey University team concludes cautiously: “In particular, education and intervention efforts for colon imaging should be focused on patients that have risk factors eg diabetes, obesity, or are former/current smokers. This population represents a sub-group of patients who are having CRC screening at a rate lower than the average-risk population. Significant reductions in CRC incidence and mortality might be possible by providing targeted screening interventions to increased-risk individuals and by educating physicians on the importance of recommending screening to these patients even in the face of multiple competing demands”. ie it  encourages  colon screening in  increased risk individuals. 

Search of Pubmed for “incidental colon cancer at autopsy” reveals only three  studies, >20 years ago,  two in the orient.

Ueyama ea, Kyushu University, Japan in Am J Gastroenterol.1991    Colorectal carcinomas incidentally detected in 3,638 autopsied cases and inpatients  during the past 20 yr.   17 colorectal carcinomas (0.47%) were incidentally detected among autopsied patients without clinically evident colorectal carcinoma, including 2,232 males and 1,406 females more than 40 yr old. Among the 15 male and two female index subjects, six (0.33%) were detected in the first and 11 (0.60%) in the second decade. During their survival periods, fecal occult blood studies were performed in 14 cases and positive in 12 (86%); however, two of them had gastric ulcers which were responsible for the occult blood. During the recent 11 yr, six cases (0.48%) of colorectal carcinoma (four of them males; two, females) also were detected among 1,249 inpatients who were examined by barium enema and/or colonoscopy, including 816 males and 433 females, 40 yr old, or more, in the Department of Radiology. Fecal occult blood was detected in four cases (67%) before colonic investigation. Compared with 708 surgically resected carcinomas, the incidental lesions from both sources were smaller, consisted of higher percentages of Dukes’ A type, and arose predominantly from the sigmoid colon and, rarely, from the rectum. These results indicate that the prevalence of colorectal carcinoma and its predominance in the sigmoid colon have not only apparently but actually increased in Japan, apart from improved diagnostic capabilities, and that false-negative rates with occult blood tests were surprisingly low in these autopsied cases and inpatients.

 Lee YS in Cancer 1988 studied Incidental carcinoma of the colorectum at autopsy in Singapore. . . Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. Incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase. The current underdiagnosis of ascending colon carcinomas has to be taken into consideration when any future increase in right-sided cancers of the large bowel is observed. 

Suen ea Cancer. 1974 studied Cancer and old age – autopsy study of 3,535 patients over 65 years old, in New York from 1960 to 1970 ie a decade earlier than the above oriental studies; they showed that men had cancer nearly twice as frequently as women (40% vs. 24%); and more incidental ie less aggressive neoplasms as age advanced. The most frequent cancers were those of the prostate (12% of men), gyne (7.5% of women- breast 3%) , kidney 3.5%, and colon 5.6%.. 70% of the cancers were already diagnosed in life ie 30% were incidental findings. Cancer tended to metastasize less frequently in the elderly.  The most common sites of latent asymptomatic cancer reported by Berg et al The prevalence of latent cancers in cancer patients. Arch. Pathol 1971. in their study of 5636 cancer patients with ages ranging from the teens to over 80,were prostate, thyroid, colon, and kidney. They further emphasized that cancer of the colon and kidney were the ones most easily missed clinically. In our study, the most frequent sites of incidental cancer, among the common cancers, were prostate (incidental 67%), kidney (51%), colon (31.5%), and breast 16.6%.

And  researchers from the Universities of California, North Carolina and Harvard –  Walter ea show in 2005  Screening for colorectal, breast, and cervical cancer in the elderly: Am J Medicine  that “characteristics of individual patients that go beyond age should be the driving factors in screening decisions… in one study -Selby ea A case-control study of screening sigmoidoscopy and mortality from colorectal cancer . N Engl J Med . 1992; .”For colorectal cancer screening, fecal occult blood testing has the strongest evidence of benefit in elderly patients, while flexible sigmoidoscopy reduces mortality from colorectal cancer by 59% .Flexible sigmoidoscopy has fewer complications than colonoscopy, with perforations occurring in less than 0.1 of 1000 examinations; .” But they did not report data on benefit of colorectal screening of lowrisk adults in terms of actual overall life extension ie reduction in all-cause mortality- which benefit has not been shown in rigorous analysis of xray screening mammography or screening blood and digital exams of lowrisk men for prostate cancer. .

Lack of significant life extension by breast and colon screening was shown by Rich and Black from Vermont USA in Clin Pract. 2000 When should we stop screening? Given a starting age of 50 years, screening throughout life has a maximum potential life expectancy benefit of 43 days for breast cancer and 28 days for colon cancer.

These 1 month extensions in life expectancy do not justify screening the entire population of older persons- surely only those of us with significant risk factors need be screened.

CONCLUSION: from the above references from autopsy series, the prevalence  of   incidental ie asymptomatic colon cancer at routine autopsy  in older deaths varies between about 0.5% and 3% in oriental and New York patients. So since I dont have any symptoms or risk factors listed, after 50 years in medicine I havent had colon or prostate imaging for a potential 4 week gain in life expectancy. I will do so promptly if I get colon symptoms.

I tell my older lowrisk patients the dubious potential benefit of cancer screening, and the serious risks, from overdiagnosis- polyps and lowgrade cancers that might never present in lifetime, to perforation ; while explaining to them that well-patient  breast, prostate  and colon cancer screening is hugely profitable universal policy.

For non-emergency consultations and especially costly and invasive procedures, doctors and patients need reminding that it’s the patient’s choice, not the doctors’..

This brings us to one of the ethical dilemmas of medicine: when our experience, and careful sifting of the hard evidence, conflicts with conventional wisdom- which is often based on belief and vested interests- evidence slanted hy bias- surely we practitioners have both a right to express our evidence-based personal conviction, and a duty to do so. Thus we surely have a duty  to give the patient the hard evidence both for and against- be it about the power of prayer and belief, about contraception and abortion, for and against statins for mild-moderate lipidemia, or in the low-risk patient, screening mammography, prostate or colon screening.

 

 

SPECIALIST NATURAL MEDICINE CLINIC 2015

SPECIALIST NON-XRAY PAIN, BONE, BREAST, BRAIN,  HEART, CHEST, GENITOURINARY, HORMONE RISK SCREENING  @ NATURAL MEDICINE CLINIC

for appointments for consultations,   or non-xray procedures by registered practitioners :  Sure Touch breast prescreening on  Saturday mornings next on  7 February 2015  by Sister Zeneath Ismail – cash R650 (then R450 if followup scan desired within 3 months);   -QUS  ultrasound quantitative bone density  cash R450 -tariff item 3612-  anytime;  Unlike radiologists’  and thermography reports (which describe only  the imaging finding), the rates quoted include relevant breast or bone consultation and management planning  by specialist nurse & physician.

IF BOOKED TOGETHER, (not necessarily the same morning) then combined breast and bone screening is R1000.

OTHER SERIOUS health problems ARE DEALT WITH BY CONSULTATION DURING THE WEEK (OR ON A DIFFERENT SATURDAY MORN) : heart- ECG,  fatigue, HRT, sexual health, hypertension, depression, memory/dementia, lung & lungfunction, anaemia-haematology; kidney/bladder/pelvic, hormone-endocrine, depression, osteoporosis, sleep, diabetes, thyroid, adrenal; cramp; skin,  infection including STDs & HIV/AIDs, stroke, epilepsy-neurology, dizziness, heartburn/digestive/liver,  neuropathy,  sexual health, menopause, HRT, genitourinary; immune problems, or arthritis relief;

Thermography no-touch infrared screening  for suspicious  cancer /inflammatory  changes:  by Radiographer Melinda-next 23 March 2015.   R900 breasts; R1100  head and  upper;  or lower body & pelvis;  R1300 whole body.

Bookings/queries contact Evelyn/ Reyhana / Val at  the Natural Medicine Clinic, 1st Floor no 15, Grove Medical Bldg, opp ABSA (parking ABSA Parkade )  near Warwick/Cavendish  Square Claremont Cape Town RSA, ph +27216831465 or a/h +2783 4385248 or reyhanadaya@yahoo.com  .

For the disabled – by arrangement  drive  up the ramp  to the Clinic door on the Grove Bldg 1st floor  parking deck.

Under CMS Council for Med Schemes Reg 10(6), open Medical schemes eg hospital plans  have to pay from their own funds (not members’ savings) for appropriate outpatient consultation (tariff item 0191) for  PMBs ie major conditions eg  cancer,   depression, neck/spinal problems, serious heart, lung, other disease., etc. Breast and osteoporosis concerns are generally part of menopause consultations N95.9   (if not already eg breast cancer code C50) and thus are often billable  med scheme benefits. The menopause billable item only applies if you are 45yrs upwards, unless you have had total hysterectomy.

On patients’ requests, appropriate invoice can be prepared and submitted to your scheme for refund of your due benefits. Some schemes eg hospital plans  falsely deny due benefits until reported to their regulator  CMS. For medical plans where the billable tariff benefit rate is higher than the breast screening fee paid, the med plan rate 0191  will be charged eg R790 by the contracted  specialist,  and refundable by Discovery to the member. some basic schemes eg Keycare, Bonitas require preauthorization, or referral by their contracted GP  .

CAPE PENINSULA HYPERTENSION & HEADACHE CENTRE

CAPE PENINSULA HYPERTENSION & HEADACHE CENTRE (50 years of experience)      at       The Natural Medicine Clinic  NMC , 1st Floor, 15 Grove Bldg, Grove  Claremont, Cape Town- between  ABSA Parkade on Grove Ave, and Warwick Sq opp Cavendish. ph 0216831465/ 071202574 or email doctor@healthspanlife.com.

As the commonest silent killer of aging people in the world, pain, obesity  and often-resultant systemic  hypertension HBP deserve the best and cheapest treatment.     Headache is rarely caused by hypertension, but unlike hypertension, is usually easily controlled if not cured.

But precisely because HBP is so common- in half of us by old age, especially at night- it is a huge moneyspinner for Big Pharma and the Disease Industry.

so the last thing the HBP Industry wants is too successful too cheap treatment. Hence they (eg the WHO,  the SA Hypertension Society and medical schools- state clinics)-  blacklist  the best baseline treatment- lowdose amilozide and lowdose reserpine, to promote sales of ever-newer unproven drugs with multiple risks. .

But 60 years of experience (5 centuries in India) confirms that Rauwolfia and its extract reserpine remain the best and sufficient treatment for most patients provided it is combined with a mild diuretic eg magnesium-potassium; or     natural herbs eg  Green tea, cranberry juice, Apple cider vinegar , Dandelion, Nettle, Fennel, buchu, horsetail;

or a magnesium-potassium conserving equivalent- the recent  proven designer ie synthetic lowdose safe diuretic amilozide eg Amiloretic 55mg 1/4 to 1/2 tab, combined with natural  lowdose reserpine 0.25mg tab 1/4 to 1/2 tab, both initially daily, eventually perhaps only 3 days a week.  . These lower HBP and associated anxiety/depression  gently but surely to avoid complications.

The NMC is open  office hours  from 9 am 6 days a week, and offers objective electronic arm and leg bloodpressure measurement and if required urine and heart testing for causes and effects of hypertension etc. If desired, appointment can be made with a hypertension-metabolic  specialist physician.

see https://healthspanlife.wordpress.com/category/reserpine/ for further details to fight dementia, stroke, heart/kidney failure, heartattack, blindness, diabetes, gangrene, etc. The last thing the Disease Industry and hospitals, medical schools  want us to do is wipe out these common diseases with safe lowcost treatment..

The Nonscience Witch Hunt Against HRT for Deficiency Syndromes Must End: An A4M Position Paper on Physician-Prescribed HRT

Our Oct 2014 cover
The Nonscience Witch Hunt Against Hormone Replacement Therapies for Deficiency Syndromes Must End
An A4M Position Paper on Physician-Prescribed HRT

Introduction  “Unless we put medical freedom into the Constitution, the time will come when medicine will organize into an undercover dictatorship to restrict the art of healing to one class of Men and deny equal privileges to others; the Constitution of the Republic should make a Special privilege for medical freedoms as well as religious freedom.”~Benjamin Rush (1745–1813), physician, writer, educator,
humanitarian, and Founding Father of the US

Since the inception of the anti-aging medical movement in 1991, various establishment parties have ruthlessly leveraged their positions of power in academic, political, and regulatory arenas for the purpose of attempting to limit the use of hormone replacement therapies (HRT) in adults with documented clinical deficiencies. For over 15 years, a prolonged and calculated campaign of deceit, fraud, and suppression has threatened physician licensures and liberties to treat and prescribe life-improving therapies, leading potentially to the direct compromise of patients’ health and longevity. Dozens of physicians have been sanctioned and punished with loss of license and academic standing. This pernicious abuse of position and power is particularly prevalent with regard to recent challenges made against human growth hormone (HGH), testosterone (TRT), and DHEA replacement therapies that are trumpeted by the mainstream media. Biased reporters frequently – and inappropriately – demonize legitimate physicians and clinical compounding pharmacies that are reluctantly positioned on the frontline of a decades-old agenda to limit freedom of choice and information, and the physicians’ most essential responsibility to select the best course of therapy and medication for their patients.

This conflict is being played out of late in the arena of anti-aging medicine, a clinical specialty that has flourished in its 22 year long history, garnering the support of more than 100,000 physicians and scientists worldwide who practice or research life-enhancing, life-extending interventions today. Prof. Dr. Imre Zs.-Nagy, of the University of Debrecen Medical and Health Science Center (Hungary), and founder of the Archives of Gerontology and Geriatrics (published by Elsevier), observes: “In my role as a basic and clinical scientist, I have had an opportunity to witness more than four decades of advances and declines in the arena of preventive medical care … there has been little else as dramatic, important, beneficial, and significant as the anti-aging medical movement.”1
   
Continual vigilance is necessary to countermand those whose financial and professional successes depend on repeated, calculated attempts to discredit the science and substance of anti-aging medicine.
   
Remarks Tanjung Subrata, MD, of Udayana University School of Medicine (Indonesia):
Anyone who does not believe in evil is not paying attention to the recent affairs of the past twenty years. We are living in a time of unprecedented tribulation and changes at-large – and in health care, in particular. All that is necessary for evil to prevail is for men of good will to do nothing. In this modern age of zero tolerance for alternatives to establishment medicine, and the willingness of our governmental officials to resort to police state tactics to suppress innovative schools of thought, progress in medicine halts and dies.2

A4M Position
The American Academy of Anti-Aging Medicine (A4M), its numerous worldwide affiliated scientific and medical societies, and befriended organizations support the judicious application of modern and advanced medical technologies to address the changes in chemical, hormonal, physical, and nutritional needs that occur with aging. Such repletion includes the restoration of hormones to an optimal physiological state when deficiency is determined by objective assessment.
   
Hormone replacement therapy (HRT) is an essential and extensively documented protocol for clinical intervention in the disorders of aging. HRT maintains an unblemished safety and efficacy profile that has been documented by 20 years of clinical application. Yet, a perfect storm of misguided media, combined with biased parties whose livelihoods hinge on disparaging the anti-aging medical movement, has grossly compromised access to HRT, placing the lives of hundreds of thousands of patients worldwide in potential jeopardy.
   
Experienced anti-aging physicians have been prescribing HRT for more than 20 years. PubMed contains more than 20,000 peer-reviewed studies of HRT, of which a preponderance document the life-enhancing and/or life extending benefits of HRT in aging adults. See Appendix A “Literature Review,” which presents a selection of such studies that represent the objective evidence that supports the A4M position.

The Anti-Aging Medical Movement
The goal of anti-aging medicine is not to merely prolong the total years of an individual’s life, but to ensure that those years are enjoyed in a productive and vital fashion. As established in 1991 by the physicians of the American Academy of Anti-Aging Medicine (A4M), the field of anti-aging medicine developed as a direct extension to the science of elite sports medicine of the 1980s. Just as sports medicine aims to keep the athlete’s body functioning at its optimum level, anti-aging medicine seeks to keep the human physiology performing at its peak. In other words, the similar principle, of extending and maximizing the healthy human lifespan, is at the core of both anti-aging medicine and sports medicine.

The Official Definition of Anti-Aging Medicine
The clinical specialty of anti-aging medicine thus is defined as follows:      Anti-aging medicine is a clinical specialty is founded on the application of advanced scientific and medical technologies for the early detection, prevention, treatment, and reversal of age-related dysfunction, disorders, and diseases. It is a health-care model promoting innovative science and research to prolong the healthy lifespan in humans. As such, anti-aging medicine is based on principles of sound and responsible medical care that are consistent with those applied in other preventive health specialties. The phrase “anti-aging,” as such, relates to the application of advanced biomedical technologies focused on the early detection, prevention, and treatment of aging- related disease.

Anti-aging medicine utilizes diagnostic protocols that are supported by scientific evidence to arrive at an objective assessment upon which effective treatment is assigned. Physicians who dispense anti-aging medical care are concerned with the restoration of optimal functioning of the human body’s systems, organs, tissues, and cells. Attempting to rebrand what they cannot deny, those in positions of power in academic, political, and regulatory arenas are inventing new catchphrases including longevity medicine, successful aging, healthy aging, and the like, in an effort to dilute and absorb the A4M’s original definition of anti-aging medicine. To implement this campaign, we suspect that these individuals have pejoratively solicited major media outlets to denigrate the A4M, its officers, and its members.
   
Anti-aging medicine is, in essence, a euphemism for early detection and advanced preventative medicine. It is a health-care model that emphasizes personalized, patient-focused, high-quality metabolic-specific medical care.

Critics with A Dark Agenda (Political Elites)
Scientifically based and well documented in leading medical journals, anti-aging medicine is among the fastest-growing medical specialties throughout the world. As an innovative model for advanced preventive health care that cannot be denied, anti-aging medicine has been disparaged by individuals with their own political and financial agendas in attempts to restore monopolistic control over the field of aging intervention. Critics of the science of anti-aging medicine most commonly hail from academia: as such, these naysayers many times have little or no medical training in aging intervention and may be nonclinicians.
   
Perhaps the most inconceivable reality is that at the very highest levels of academia, government, and science, truth and objective scientific method are not at all sacred to the political elites. We in clinical medicine via our training, discipline, and conditioning naively believe and act in the public interest, for the good of our patients’ health, and by professional standards of medical ethics. The (elite) medical establishment operates contrary to this position, reports investigative reporter Tim Bolen (www.bolenreport.com), who for 30 years has amassed data and evidence exposing a calculated effort to deride innovative medical therapeutics. Bolen observes:  Without a doubt, a stealthy control group – a cabal, if you will, in status-quo medicine exists. Approved by Big Pharma, parts of academia, and segments of the government, this group exerts its control in many different ways. I have uncovered information showing anonymous, and not-so-anonymous, funding of groups, loosely describing themselves as “Quackbusters or Skeptics” whose only purpose is to attack cutting-edge health care offerings. Those groups, in turn, train, and fund sub-groups. Data suggests that the “Quackbusters or Skeptics” donated over $1 Million US to Wikipedia to purchase control over pages with medical content. More, the Skeptic training camps teach their recruits how to operate together to control that same Wikipedia and Search Engines. Further, these covert groups drive media on issues particularly pertaining to alternative health care, in an effort to limit coverage of innovative discoveries and to vilify therapies that are not part of AMA/FDA/Big Pharma establishment medicine health care.

There are TWO main “skeptic” organizations – the James Randi Educational Foundation (JREF) and the Center For Inquiry (CFI). Both are well funded from secret sources.

JREF reported, in 2010, a total income of $999,971.00 and a Total Asset claim of $1,736,101.

The Center For Inquiry, Inc (CFI), based in Amherst, New York shows on their Form 990 that they took in $5,242,304 in Total 2009 Income, and they had, that year, Total Assets of $3,017,144. Their Schedule B ANONYMOUS contributions totaled $2,318,652.

More, CFI claimed that they received, in 2009, in addition to their anonymous contributions, a so-called “Management Fee Income” of $2,458,156. What do you suppose they managed? And who paid them to manage it? Maybe they manage Wikipedia health care articles? How about Search Engine Optimization (SEO) bringing skeptic, including Stephen Barrett’s (Quackwatch), articles to the first page of Google?

Much more – This cabal minimizes and delays innovative medical advancements by lodging anonymous complaints to state licensing boards against cutting-edge practitioners. Their insidious campaign also controls grant monies and research funding, somewhat silencing the voices of innovative medicine in favor of mainstream views. By leveraging control of the media in direct jeopardy of journalistic integrity, this control group seeks to suppress all in medicine that is not fully controlled by the establishment. To permit this level of manipulation and disinformation is wrong and ethically corrupt. The fate of a valuable avenue of medical innovation for the public interest – anti-aging medicine – stands at-risk.3

A JAMA commentary purported to address the legality of human growth hormone (HGH, GH) treatment by physicians for growth–hormone deficient (GHD) patients.4 It is the view of A4M that the commentary contained a number of incorrect, misplaced references and studies, and multiple basic scientific errors, in an apparent attempt to damage the anti-aging medical profession and the physicians practicing solid, evidence-based medical health care focused on improving and maintaining patients’ quality of life. It is A4M’s further opinion that the authors selected self-serving studies, in which they failed to qualify the conclusions in an effort to bolster what A4M believes is a disinformation campaign. It is A4M’s opinion, for example, that they incorrectly intermingled Internet sales of homeopathic pseudo-“GH” sprays, amino acids, and sports nutritional over-the-counter products in order to inflate their incorrect claims suggesting an illegal diversion of HGH by physicians and pharmacies, implying a black market in FDA-approved prescription injectable HGH for hormone replacement treatments by anti-aging physicians where none exists.

Misrepresentation in Competitive Sports
As an unfortunate consequence of media confusion and outright deception aiming to deliberately misrepresent anti-aging medical care, the reality of the clinical practice of hormone replacement therapy has become muddled. A recent Sports Illustrated article states: “In the sports world, the term ‘anti-aging’ has often come to signify therapy that uses hormones – usually testosterone and HGH – and … DHEA.”5 This erroneous definition grossly misrepresents the legal and ethical physiological use of hormones and supplements as being synonymous with the inappropriate use of hormones for sports enhancement. The A4M is squarely opposed to this myopic interpretation of “anti-aging” and urges reference to the official definition of anti-aging medicine as presented above.

Page 1, 2, 3, 4, Appendix/Notes

All Artificial Sweeteners Raise Your Risk of Diabetes by Altering Your Gut Microbiome

why we must avoid all artificial sweeteners – if you must sweeten, use only the natural ie herbal intense sweeteners  stevia;  xylitol or  lo han go. available from Natural Medicine Clinic, 15 Grove Bldg, Grove Ave, Claremont Cape Town ph +27216831465)

By Dr. Mercola Oct 1st 2014: Artificial Sweeteners Raise Your Risk of Diabetes by Altering Your Gut Microbiome

Both artificial sweeteners and certain gut microbes have previously been linked to obesity, and according to the latest research, artificial sweeteners may raise your risk of diabetes by disrupting your intestinal microflora. According to the authors of the widely publicized study:1
“[W]e demonstrate that consumption of commonly used non-caloric artificial sweeteners formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota.
The researchers found that artificial sweeteners alter certain metabolic pathways associated with metabolic disease, and that it can induce gut dysbiosis and glucose intolerance in otherwise healthy people.
Glucose intolerance is a condition in which your body loses its ability to cope with high amounts of sugar, and it’s a well-known precursor to type 2 diabetes. It also plays a role in obesity, because the excess sugar in your blood ends up being stored in your fat cells.
The fact that artificial sweeteners may exacerbate metabolic disorders like diabetes is a severe blow to diabetics who dutifully follow recommendations to switch to diet foods and beverages in order to control their diabetes.
The fact that artificial sweeteners are NOT a dieter’s nor a diabetic’s best friend has been known by researchers for some time. The problem is that it hasn’t received the necessary traction in the media—until now.2, 3
“Collectively, our results link non-caloric artificial sweeteners (NAS) consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage,” the researchers note.
Artificial Sweeteners Can Cause Glucose Intolerance by Altering Your Microbiome
The researchers initially started out testing the artificial sweeteners saccharin, aspartame, and sucralose in mice, and were “surprised” when the mice developed glucose intolerance.
As noted by New York University microbiologist Martin Blaser,4 no one had previously considered that artificial sweeteners might exacerbate metabolic disease by way of the microbiome.
Of the three non-caloric sweeteners tested, saccharin had the most pronounced effect on glucose levels. This led to a human trial, in which data from 400 people enrolled in a nutritional study were assessed.
Those who consumed high amounts of artificial sweeteners were found to have higher levels of HbA1C—a measure of blood sugar—compared to non-users or occasional users of artificial sweeteners.
Seven volunteers who did not use artificial sweeteners were then recruited, and asked to consume the equivalent of 10-12 single-dose packets of artificial sweeteners daily for one week.
Four of the seven people developed “significant disturbances in their blood glucose,” according to the researchers. Some became pre-diabetic within just a few days!
The reason for this dramatic shift was traced back to alterations in gut bacteria. Some bacteria were killed off, while others started proliferating. As noted in the featured NPR article:5
“It could be that for some people who responded negatively to the artificial sweetener, the bacteria that got crowded out were helping to keep glucose in check.”
This mirrors previous research,6 which has found that bacterial populations in the gut of diabetics differ from non-diabetics.
Another 2008 study demonstrated that sucralose can alter the microbiome in rats by reducing colonies of beneficial gut bacteria, and research published in Clinical and Experimental Rheumatology7 in 2012 revealed a potential link between aspartame and irritable bowel syndrome (IBS). Imbalanced gut flora has also been linked to obesity.
Compelling Results Suggest We Should Reconsider Widespread Use of Artificial Sweeteners
In sharp contrast to many other studies, this one was actually able to clearly show causality, meaning there’s a direct cause and effect relationship between consuming artificial sweeteners and developing elevated blood sugar levels. As reported by The Scientist:8
“Four weeks of treatment with gut bacteria-depleting antibiotics reversed the glucose intolerance in mice that continued to receive saccharin. This led the team to examine whether the microbiomes of the mice were somehow altering glucose metabolism.
Transplantation of feces from non-antibiotic-treated mice that consumed saccharin- or glucose-containing water into germ-free mice within six days induced the same blood-sugar elevations in animals that were never themselves exposed to the sweeteners.
‘This is the elegant and home run experiment that shows causality in mice,’ said [pathologist Cathryn] Nagler.
Using shotgun metagenomic sequencing on the fecal samples, the researchers showed that mice given saccharin or those that received a fecal transplant from saccharin-fed mice had a different microbiome composition compared to mice given sugar or no sweeteners.”
Cathryn Nagler, who wrote an accompanying commentary9 in the journal Nature, said the findings were “very compelling,” noting that “the study suggests… we should step back and reassess our extensive use of artificial sweeteners.”
Aspartame Raises Insulin Levels as Much as Sugar
Other studies have also linked artificial sweeteners to metabolic alterations that promote type 2 diabetes—contrary to conventional thinking and health recommendations.
For example, one 2012 study10 found that chronic lifetime exposure to aspartame, commencing in utero, produced changes in blood glucose parameters in mice. Not only was aspartame found to decrease insulin sensitivity compared to controls, it also wrought havoc on brain function…
Another study published in 2007 in the journal Diabetes Care11 found similar results. Here, the researchers investigated the effect of different macronutrient compositions on plasma glucose and insulin levels during an acute bout of exercise in men with type 2 diabetes.
They hypothesized that using fructose or aspartame would have a lower impact on insulin release and glucose response than a sucrose-sweetened meal. Those of you who have been reading my articles featuring experts on sugar and fructose like Dr. Richard Johnson and Dr. Robert Lustig will immediately recognize this as a fatally flawed hypothesis. And indeed, that is what they discovered. According to the authors:
“Contrary to all expectation, the aspartame breakfast induced a similar rise in glucose and insulin levels at baseline than the sucrose meal, even if the aspartame meal had the same taste, and was 22 percent lower in calories and 10 percent lower in carbohydrates, with an inferior glycemic index… Considering the lack of evidence on the aspartame utilization in patients with type 2 diabetes, we consider that these clinical observations, in an exercise setting, raise important concerns regarding the safety of aspartame as suggested by international guidelines.”
Obesity Continues to Rise
According to a recent JAMA study,12, 13 the obesity rate among American adults has continuously climbed over the last decade. Between 1999 and 2012, the average age-adjusted waist circumference increased from 95.5 centimeters (37 19⁄32 inches) to 98.5 centimeters (38 25⁄32 inches). Abdominal fat also rose from 46.4 percent in 1999-2000 to 54.2 percent in 2011-2012. The United Kingdom is facing a similar health crisis. According to September 17 article in Mail Online:14
“Obesity is a ‘slow-motion car crash’ which is threatening to bankrupt the NHS, according to its chief executive. Simon Stevens said the problem is now more deadly than smoking and causing millions to suffer life-long illness and disability. He also revealed that – absurdly – the NHS is spending far more on drastic weight loss surgery than trying to prevent the problem in the first place. A quarter of adults and a fifth of children are now considered obese and the rates have almost doubled in 20 years…
Next month, Mr. Stevens will publish a set of plans to tackle the problem which will see the NHS and private firms urged to do more to help staff lose weight. Doctors and nurses will be encouraged to be healthy role models for patients and hospitals told to ban junk food from canteens. NHS trusts and private companies will also be urged to help staff lose weight by holding slimming classes, running clubs or just providing bike racks at work. Mr. Stevens, who took up post last April, said: ‘Obesity is the new smoking, and it represents a slow-motion car crash in terms of avoidable illness and rising health care costs…” [Emphasis mine]
Artificial Sweeteners Can Severely Hinder Weight Management Efforts
Those who switch to artificial sweeteners are typically carrying extra pounds and/or are diabetic, or prone to these conditions. Unfortunately, this may be the absolute worst diet change you could implement if you’re overweight or diabetic. Research has repeatedly shown that artificially sweetened no- or low-calorie drinks and other “diet” foods tend to stimulate your appetite, increase cravings for carbs, stimulate fat storage and weight gain, and promote insulin resistance and diabetes.
There are a number of different reasons for this. First of all, artificial sweeteners basically trick your body into thinking that it’s going to receive sugar (calories), but when the sugar doesn’t arrive, your body signals that it needs more, which results in carb cravings. This connection between sweet taste and increased hunger can be found in the medical literature going back at least two decades (see list of selected studies below). But artificial sweeteners also produce a variety of metabolic dysfunctions that promote weight gain—and now we can add gut dysbiosis and altered microbiome to that list!
In 2011, the UT Health Science Center in San Antonio publicized the results of two important studies, saying:15
“In the constant battle to lose inches or at least stay the same, we reach for the diet soda. Two studies presented [June 25, 2011] at the American Diabetes Association’s Scientific Sessions suggest this might be self-defeating behavior. Epidemiologists from the School of Medicine at The University of Texas Health Science Center San Antonio reported data showing that diet soft drink consumption is associated with increased waist circumference in humans, and a second study that found aspartame raised fasting glucose (blood sugar) in diabetes-prone mice…
‘Data from this and other prospective studies suggest that the promotion of diet sodas and artificial sweeteners as healthy alternatives may be ill-advised,’ said Helen P. Hazuda, Ph.D., professor and chief of the Division of Clinical Epidemiology in the School of Medicine. ‘They may be free of calories but not of consequences.’” [Emphasis mine]
Sampling of Studies Refuting ‘Diet’ Claims
Here’s a sampling of some of the studies published through the years, clearly refuting the beverage industry’s claims that diet soda helps with weight management. The 2010 review in the Yale Journal of Biology and Medicine16 is of particular relevance here, as it offers a great historical summary of artificial sweeteners in general, and the epidemiological and experimental evidence showing that artificial sweeteners tends to promote weight gain. It also illustrates that as usage of artificial sweeteners has risen, so has obesity rates—despite all these “diet friendly” products.

Source: Yale Journal of Biology and Medicine June 8 2010: v83(2)
Preventive Medicine 1986 Mar;15(2):195-20217
This study examined nearly 78,700 women aged 50-69 for one year. Artificial sweetener usage increased with relative weight, and users were significantly more likely to gain weight, compared to those who did not use artificial sweeteners—regardless of their initial weight. According to the researchers, the results “were not explicable by differences in food consumption patterns. The data do not support the hypothesis that long-term artificial sweetener use either helps weight loss or prevents weight gain.”
Physiology and Behavior, 198818
In this study, they determined that intense (no- or low-calorie) sweeteners can produce significant changes in appetite. Of the three sweeteners tested, aspartame produced the most pronounced effects.
Physiology and Behavior, 199019
Here, they found that aspartame had a time-dependent effect on appetite, “producing a transient decrease followed by a sustained increase in hunger ratings.”
Journal of the American Dietetic Association, 199120
In a study of artificial sweeteners performed on college students, there was no evidence that artificial sweetener use was associated with a decrease in their overall sugar intake either.
International Journal of Obesity and Metabolic Disorders, 200421
This Purdue University study found that rats fed artificially sweetened liquids ate more high-calorie food than rats fed high-caloric sweetened liquids. The researchers believe the experience of drinking artificially sweetened liquids disrupted the animals’ natural ability to compensate for the calories in the food.
San Antonio Heart Study, 200522
Data gathered from the 25-year long San Antonio Heart Study also showed that drinking diet soft drinks increased the likelihood of serious weight gain – far more so than regular soda23 On average, for each diet soft drink the participants drank per day, they were 65 percent more likely to become overweight during the next seven to eight years, and 41 percent more likely to become obese.
Journal of Biology and Medicine, 201024
This study delves into the neurobiology of sugar cravings and summarizes the epidemiological and experimental evidence concerning the effect of artificial sweeteners on weight.

According to the authors: “[F]indings suggest that the calorie contained in natural sweeteners may trigger a response to keep the overall energy consumption constant. …Increasing evidence suggests that artificial sweeteners do not activate the food reward pathways in the same fashion as natural sweeteners… [A]rtificial sweeteners, precisely because they are sweet, encourage sugar craving and sugar dependence.”
Yale Journal of Biology and Medicine, 201025
This review offers a summary of epidemiological and experimental evidence concerning the effects of artificial sweeteners on weight, and explains those effects in light of the neurobiology of food reward. It also shows the correlation between increased usage of artificial sweeteners in food and drinks, and the corresponding rise in obesity.
Appetite, 201226
Here, researchers showed that saccharin and aspartame both cause greater weight gain than sugar, even when the total caloric intake remains similar.
Trends in Endocrinology & Metabolism, 201327
This report highlights the fact that diet soda drinkers suffer the same exact health problems as those who opt for regular soda, such as excessive weight gain, type 2 diabetes, cardiovascular disease, and stroke.28, 29 The researchers speculate that frequent consumption of artificial sweeteners may induce metabolic derangements.
Nature, 201430
This study was able to clearly show causality, revealing there’s a direct cause and effect relationship between consuming artificial sweeteners and developing elevated blood sugar levels.

People who consumed high amounts of artificial sweeteners were found to have higher levels of HbA1C—a long-term measure of blood sugar—compared to non-users or occasional users of artificial sweeteners.

Seven volunteers who did not use artificial sweeteners were then recruited, and asked to consume the equivalent of 10-12 single-dose packets of artificial sweeteners daily for one week.

Four of the seven people developed “significant disturbances in their blood glucose,” according to the researchers. Some became pre-diabetic within just a few days.

The reason for this dramatic shift was traced back to alterations in gut bacteria. Some bacteria were killed off, while others started proliferating.
Are There ANY Safe and Healthy Alternatives to Sugar?
One of the best strategies to kick the sugar habit is to implement intermittent fasting, and to make sure you’re eating enough healthy fats. Once your body has the proper fuel, your sweet cravings will radically diminish. If you need a sweetener you could use stevia or Luo Han, both of which are safe natural sweeteners. For a comprehensive review of the best and worst sweeteners, please see my previous article, “The 4 Best, and 3 Worst Sweeteners to Have in Your Kitchen.” Just remember, if you struggle with high blood pressure, high cholesterol, diabetes, or extra weight, then you have insulin sensitivity issues and would benefit from avoiding ALL sweeteners.
If you’re having trouble weaning yourself off soda, try Turbo Tapping. Turbo Tapping is a clever use of the Emotional Freedom Technique (EFT), specifically designed to resolve many aspects of an addiction in a concentrated period of time. Last but not least, if you experience side effects from aspartame or any other artificial sweetener, please report it to your National or Regional Health Dept without delay. It’s easy to make a report — just go to your National  Consumer Complaint Coordinator page, find the phone number for your state, and make a call reporting your reaction.

METFORMIN REDUCES ALL CHRONIC DISEASES, INCLUDING IMPROVING THYROID FUNCTION.

this new report Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus from  McGill University; Montréal, Quebec. says nothing that is seriously clinically significant, it is merely common sense.

It does not show that metformin causes any heart or thyroid dysfunction ie change in thyroid hormone levels,  merely that it reduces TSH  in those on thyroid replacement.- indicating that  thyroid dose may be able to be tapered.    

A parallel new study from Italy  Metformin-induced thyrotropin suppression is not associated with cardiac effects  confirms there is no heart risk- quite the contrary.

People tend to fatten and slow down as they age, and these people tend to  metabolic syndrome ie obesity, cholesterolemia, hypertension, vascular disease and thus diabetes- same as patients with hypothyroidism. So type 2 diabetes, hypothyroidism (sometimes preceded by hyperthyroidism) and aging go together- usually without demonstrable direct cause and effect.

This new McGill University metformin study does not claim any cause and effect.  The link may be simply  that metformin (which is simply a carbon-hydrogen -nitrogen molecule)  improves all metabolic functions- antioxidant, nitric oxidant- including iodine/TRH/ TSH / thyroid/insulin   hormone responses. .

So as with all nutritional supplements and exercise  that improve metabolism, metformin may improve treated hypothyroidism by improving peripheral thyrooxine receptors , and thus lower need for thyroid replacement.
Metformin or the parent galega a medicinal plant extract used for many centuries reduces new diabetes and all diseases and deaths by 1/3 to 2/3.

it is among other things a prohormone regulator, improving common insulin resistance.

the definition of low TSH is arbitrary. If much below 1, it is suspicious of thyroid overactivity, excess thyroid hormones-
but rarely may reflect central ie pituitary failure to produce enough TRH/TSH and thus cause central hypothyroidism.

so TSH unless way outside the ‘normal’ range of 1 to 2 is a poor guide to health and disease, which is based on clinical  state and the thyroid hormone and antibody levels.

Most aging people develop some degrees of thyroid underactivity, which generally responds to replacement of deficient selenium, iodine and sex hormones without addition of risky thyroid hormones- for which conventional blood levels are a poor guide.

so as in all patients whatever their state and treatment, thyroid function should like all other functions be considered periodically.

ndb.


  Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus  McGill University; Montréal, Quebec.

Background: Small cross-sectional studies have suggested that metformin, a first-line oral hypoglycemic agent, may lower thyroid-stimulating hormone (TSH) levels. Our objective was to determine whether the use of metformin monotherapy, when compared with sulfonylurea monotherapy, is associated with an increased risk of low TSH levels (< 0.4 mIU/L) in patients with type 2 diabetes mellitus.

Methods: Using the Clinical Practice Research Datalink, we identified patients who began receiving metformin or sulfonylurea monotherapy between Jan. 1, 1988, and Dec. 31, 2012. We assembled 2 subcohorts of patients with treated hypothyroidism or euthyroidism, and followed them until Mar. 31, 2013. We used Cox proportional hazards models to evaluate the association of low TSH levels with metformin monotherapy, compared with sulfonylurea monotherapy, in each subcohort.

Results: A total of 5689 patients with treated hypothyroidism and 59 937 euthyroid patients were included in the subcohorts. Among patients with treated hypothyroidism, 495 events of low TSH levels were observed during follow-up (incidence rate 119.7/1000 person-years). In the euthyroid group, 322 events of low TSH levels were observed (incidence rate 4.5/1000 person-years). Compared with sulfonylurea monotherapy, metformin monotherapy was associated with a 55% increased risk of low TSH levels in patients with treated hypothyroidism (incidence rate 79.5/1000 person-years v.125.2/1000 person-years, adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09–2.20), with the highest risk in the 90–180 days after initiation (adjusted HR 2.30, 95% CI 1.00–5.29). No association was observed in euthyroid patients (adjusted HR 0.97, 95% CI 0.69–1.36).

Interpretation: In this longitudinal population-based study, metformin use was associated with an increased incidence of low TSH levels in patients with treated hypothyroidism, but not in euthyroid patients. The clinical consequences of this need further investigation.

HORMONES 2014, 13(2):252-258
Carlo Cappelli,1 Mario Rotondi,2 Ilenia Pirola,1 Barbara Agosti,3 Ana Maria Formenti,1 Pasquale De Cata,2 Massimo Salvetti,1 Luca Chiovato,2 Maurizio Castellano1

1Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia; 2Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Superiore Prevenzione e Sicurezza Lavoro Laboratory for Endocrine Disruptors, University of Pavia; 3Diabetic Unit, Spedali Civili di Brescia; Italy  http://www.ncbi.nlm.nih.gov/pubmed/24776625

Abstract

OBJECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine.
DESIGN: Heart rate, P wave duration, P wave dispersion, QTmax, QTmin and QT-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of TSH-suppression and in 31 control patients with SHT.
RESULTS: No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9±7.4 vs. 92.1±5.8 ms, p<0.001), P wave dispersion (13.1±3.4 vs. 7.1±3.5 ms, p<0.001), QTmax (399±18 vs. 388±16 ms, p=0.024), QTmin (341±14 vs. 350±17 ms, p=0.038) and QT dispersion (49.9±9.6 vs. 30.9±9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of TSH.
CONCLUSIONS: Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.