We are very sad to share the news that Dr Neil Burman passed away on the 2nd June after a short illness. A loving father, grandfather, husband and doctor, he will be dearly missed by all.
We will leave this blog as an archive and memorial to him.
We are very sad to share the news that Dr Neil Burman passed away on the 2nd June after a short illness. A loving father, grandfather, husband and doctor, he will be dearly missed by all.
We will leave this blog as an archive and memorial to him.
update 22 Mar 2019 at the equinox.. firstname.lastname@example.org
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.
and Naik, Hegde ea ea recently reported Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis
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 showing “No 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/
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
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)
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.
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.
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).
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.
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.
update 16 May 2016. to our health: email@example.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.
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:
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 6.9; retinopathy [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 600 000 IU vitamin D in 143 participants with predominantly type 2 diabetes, aged ~ 52.3years, with high Douleur Neuropathique 4 (DN4) score by 20 weeks gave significant increase in 25(OH)D (from 31.7 to 46.2±10.2 ng/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.
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 2015: 50 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 formation. The 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).
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).
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.
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.
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-Ã¡- 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
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.
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 .
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. Knapen, Vermeer 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 Concerns: If 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.
update 10 Dec 2016 remember that quotations from experts are in italics:
Note noteworthy timeous new reviews: in the latest 7 dec BMJ :
advising on low sugar low starch to treat obesity diabetes,
of the extensive comment on bad new USA guidelines by Nina Teicholtz of 2015 ,
together with reviews of Gary Taubes new book Dec 2016 on The Case against Sugar http://articles.mercola.com/sites/articles/archive/2016/12/11/gary-taubes-the-case-against-sugar.aspx , being a bigger disaster than even smoking and other drugs..
These help to back up Tim Noakes, Zoe Harcomb, Richard Feinman, Peter Wise and at least two dozen other scientific teams around the world, and Integrative medicine, against the fastfood-pharma – hightech medicine – hospital industry trying to discredit Banting diet and needed proven supplements for deficiencies – of natural vits D+C+ iodine +magnes + multisupps , cannabinoids, fishoil + BID HRT (eg melatonin, cholecalciferol, progesterone etc), and other natural supps, and homeopathy,-
so as to keep people profitably sick by the sugary lowfat diet and smoking, vaccines , and patent Big Pharma-raincheck prescription antimicrobials, statins, fosamaxes and ranelates, antithrombotics, designer hormone substitutes,screening mammo and chemotherapy, bariatrics , nsaids, ACEIs and ARBs, antidementia, patented antidiabetics, analgesics, opiates,calcium, aluminium, mercury, and psycho-pharmaceuticals- none of which address the CAUSES of disease as do coaching on better diet, lifestyle and integrative medicine. …
Even more remarkable is the total ignoral of the 25 + scientific RCTs done http://smashthefat.com/science/ and published since 2000 that validate very low carbs high fat Banting (calorie distribution: 8.5% carbs, 62% fat, 30% protein) as much better than the current USA – RSA low fat (54% carbs, 29% fat, 17% protein) generous PUFA and carbs diet. See update review of the experts below at https://healthspanlife.wordpress.com/2015/08/29/adopting-low-carbs-high-fat-healthy-diet-for-most/
Harcombe and Noakes have now published Mistake or mischief: The universities of Stellenbosch/Cape Town low-carbohydrate diet review: debunking the Naude, Volmink ea critique. http://www.samj.org.za/index.php/samj/article/view/11605/7753 A major error of the US/UCT analysis was that it missed the point, did not even consider the very low carbs high fat (+- 8.5% vs 62% fat) intake of the ketogenic Banting regime. The Naude review classified low carbs as diet cals below 45% carbs, high fat as diet cals above 35% from fat. So they did not analyse at all the ketogenic +-8% very low carbs, 60%+ ie very high fat Banting diet.
The latest is Prof Richard David Feinman’s series of papers from the prestigious SUNY State Univ. NY https://feinmantheother.com/ . on the benefits of Warburg ketogenic ie low carbs diet for cancer, never mind obesity diabetes, and epilepsy ( which goes back to 1931 on Pubmed) , the latest eg Nel ea 2014 Jefferson Med College USA https://www.ncbi.nlm.nih.gov/pubmed/24675110and perhaps Autism Spectrum Disorder https ://www.ncbi.nlm.nih.govpubmed/27841033
. Now Prof Peter Wise emeritus oncologist from ImperiaL College London has thrown a cat among the pigeons http://www.bmj.com/content/355/bmj.i5792, in his November 2016 BMJ critique of Cancer drugs, survival, and ethics, pointing out how ‘Despite considerable investment and innovation, chemotherapy drugs have had little effect on survival in adults with metastatic cancer’. A meta-analysis 2004 explored the contribution of cytotoxic chemotherapy to five year survival in 250 000 adults with solid cancers from Australian and US trials.3-important effect was shown on five year survival only in testicular cancer (40%), Hodgkin’s disease (37%), cancer of the cervix (12%), lymphoma (10.5%), and ovarian cancer (8.8%). In the remaining patients—including those with the commonest tumours of the lung, prostate, colorectum, and breast—drug therapy increased five year survival by less than 2.5%—an overall survival benefit of 1 to 3 months., as in Europe. Drug treatment can therefore only partly explain the 20% improvement in five year survival mentioned above. The approval of drugs with such small survival benefits raises ethical questions, including whether recipients are aware of the drugs’ limited benefits, whether the high cost:benefit ratios are justified, and whether trials are providing the right information. In search of ethics : Many irregularities and competing interests—in pharma, in trials, in government approval, and in the clinical use of cancer drugs—impact ethically on the care and costs of patients with cancer. . Spending a six figure sum to prolong life by a few weeks or months is already unaffordable, and inappropriate for many of the 20% of the (Western) population who will almost inevitably die from solid tumour metastases. Ethical cancer care demands more prompt and radical treatment of localised and regional disease, together with highly skilled, earlier, supportive care are the important yet underfinanced priorities in cancer control. Finally, aggressively targeting the less than ethical actions of stakeholders in the heavily veiled medical-industrial complex may be the only way forward: current market driven rather than health driven priorities and practices do not benefit cancer patients.”
He provoked counterattack from vested interests: Twenty UK medical oncologists retort in BMJ: http://www.bmj.com/content/355/bmj.i6487.As UK health professionals specialising in the drug treatment of cancer, we think that Wise’s analysis strays into the territory of unbalanced opinion.
So we come back to addressing the causes of disease for both prevention and treatment, by integrative ie combining natural and hightech means.
updated 29 Aug 15
Six months later after the first World fat>carbs HFLC groundbreaking congress in Cape Town, Pubmed and Google search show no obvious new information on this life-and-death topic that the February Cape Town International Banting Congress highlighted. .
but the publication of Real Food Revolution II Raising Superheroes now provides much new evidence and impetus.
While carnivores ( mammals and pterodactyls-birds) from ~300million years ago survived the extinction of the carnivorous big dinosaurs sixty million years ago, so have current carnivorous primates- tarsiers– and us carnivorous humans nurtured from conception on animal protein and animal fats:
Top anthropologist Prof Gail Kennedy (of UCLA and much work at Olduvai Gorge) in her classic 2005 Journal of Human Evolution article “From the ape’s dilemma to the weanling’s dilemma: early weaning and its evolutionary context“ summed up >2million years of evolution of exclusive human breastmilk ie animal-protein-and-fat>carbs -based infant feeding: ” Although humans have a longer period of infant dependency than other hominoids, human infants, in natural fertility societies, are weaned far earlier than any of the great apes: chimps and orangutans wean, on average, at about 5 and 7.7 years, respectively, while humans wean, on average, at about 2.5 years. Assuming that living great apes demonstrate the ancestral weaning pattern, modern humans display a derived pattern that requires explanation, particularly since earlier weaning may result in significant hazards for a child. Clearly, if selection had favored the survival of the child, humans would wean later like other hominoids; selection, then, favored some trait other than the child’s survival. It is argued here that our unique pattern of prolonged, early brain growth and the neurological basis for human intellectual ability cannot be sustained much beyond one year by a human mother’s milk alone, and thus early weaning by one year, when accompanied by supplementation with more nutritious adult foods, is vital to the ontogeny of our larger brain, despite the associated dangers. Therefore, the child’s intellectual development, rather than its survival, is the primary focus of selection. Consumption of more nutritious foods derived from animal protein increased by ca. 2.6M yrs ago when a group of early hominins displayed two important behavioral shifts relative to ancestral forms: the recognition that a carcass represented a new and valuable food sourced potentially larger than the usual hunted prey; and the use of stone tools to improve access to that food source. The shift in the hominin ‘‘prey image’’ to the carcass and the use of tools for butchery increased the amount of protein and calories available, irrespective of the local landscape. However, this shift brought hominins into competition with carnivores, increasing mortality among young adults and necessitating a number of social responses, such as alloparenting. The increased acquisition of meat ca. 2.6 M yrs ago had significant effects on the later course of human evolution and may have initiated the origin of the genus Homo.”
The thesis of Raising Superheroes by Kennedy’s summation of human brain dietary evolution from babies nurtured on animal meat and fat is supported by serious studies: a 2010 critique in The Keto Diet for Health; in the textbook Guts and Brains ,2007 ed paleoarcheologist Wil Roebroeks at Univ Leiden .; and University Michigan anthropologist John Speth’s Springer Verlag 2010 The Paleoanthropology and Archaeology of Big-Game Hunting – Protein, Fat, or Politics?
Many sensible voices including locally like Kath Megaw encourage breastfeeding till at least a year in South Africa. Certainly http://www.nhs.uk/conditions/pregnancy-and-baby/pages/solid-foods-weaning.aspx doesnt say anything different from what sense and the authorities quoted below say- breast milk and then mushy whole food.
NICUS the Nutrition Info Centre of University Stellenbosch recommendations on line for 6-12mo infants certainly advocate increasing meats, fish, vegs, fruits & pulses. But the SA Guidelines on weaning 2012 Introducing solid foods from Stellenbosch University Dietetics says plainly “Complementary food is semi-solid porridges & milk that are given from six to eight months, then vegetables or fruit and then progressing to a mixed diet in mashed form small portions of solid food given until 12 months, when family foods are integrated”. ie NICUS advocates while weaning off breast, get baby (hooked) only on cereals for 2 months. where is the evidence to justify solely cereals as started diet? There is no good science published to justify this belief, marketeering; and no parallel in the non-primate infant world. .
NICUS say further: “Both early (< 4 months) and late (> 7 months) introduction of gluten should be avoided. Gluten should be gradually introduced while the infant is still being breastfed as this may reduce the risk of celiac disease, type 1 diabetes mellitus and wheat allergy.
“More than 14% of energy from proteins in the eight- to 24-month period may cause an early adiposity rebound and the development of overweight in young children. A dietary fat intake of 30-45% of total energy is recommended. The American Heart Association (AHA) has a limit of 40% fat of total energy with an emphasis on a more liberal intake of unsaturated fat and a focus onensuring adequate intakes of omega-3 fatty acids in infants and children.
In fact scientific evidence has never supported the obsession against eating (animal) saturated fat, triglycerides; nor human need for promoting the plant protein gluten. As we were and are taught in basic biology, only water, essential aminoacids- protein, essential fatty acids- fats- and the trace ~two dozen vitamins and minerals are, as eg all textbooks say, essential nutrients required for normal human body function that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health (e.g., niacin, choline), and thus must be obtained from a dietary source. . So its marketing hype that gluten is any more of an essential macronutrient than sugar, carbohydrates .
Wiki succinctly lists essential ie indispensable macronutrients (like the trace ~two dozen micronutrient vitamins and minerals) as: Essential fatty acids (EFAs) and essential amino acid EAA nutrients
The Wiki entry on gluten has a major paragraph on the common problem of gluten intolerance (especially wheat) , but no claim that it is an essential nutrient- for the simple reason that the gluten-containing cereals eg wheat and related grains, (including barley and rye) are like carbs not essential foodstuffs, and commonly cause distant health problems.
But the alarming disinformation is in that RSA article Introducing solid foods table 1 and the NICUS table Nutrient requirements @ 6 to 12 mo. Their recommended figures are: “total fat RDA 30gm/d ie ~270kcals and protein 13.5gm ie 54kcals on a total average RDA calorie intake of 710kcals”. That leaves the majority ie the balance of the energy intake- 385kcals to be made up by carbohydrates – ie 385/4 = ~ 95gm carbs. That gives their recommended (non-protein) carbs:fat energy ratio as 385:270 ie >1.4– which they imply can come also from plant oils. This RDA contrasts with the long-known (see below) (white and black) mothers’ s breast milk carbs:(animal) fat energy ratio of almost half (of what NICUS recommends 1.4:1): 30:38 kcals/gm ie ratio~0.8.
And even more dangerously, that Univ Stellenbosch table gives the RDA of vitamin D as 5mg/d ie 40 000iu/d. Neither that gross overdose, nor 5mcg/d = 400iu/d, are near the modern proven necessity of perhaps 1000 iu/d in swaddled urban babies – the vast majority of whom in Africa are black and therefore make even less vit D3.
rice milk: as http://everythingbirthblog.com/2012/01/rice-milk-why-it-says-not-to-give-it-to-children-under-five/ rice / and Noakes’ team says, Rice/ricemilk – like the vast profitable fast food industry in baby purees and formulae- is ( like the killer Food mega-industry carbs and plantoil-based food pyramid of the past 40 years of Ancel Keyes ea ) a marketing (Gerber’s) legend, but not a necessity or good for babies- it lacks fat and protein; and may be contaminated with eg arsenic!
As the Real Food Revolution book II Raising Superheroes says, promoting natural real food is not about banning carbs or promoting high protein intake – thats impossible and unnecessary on mixed real food- but eating more fresh unprocessed energy, as mostly animal incl fish fat more than natural ie plant carbs, as in breast milk; with rarely if ever processed foods including synthetic transfats and refined carbs like sugars, “white” flours and starches, and the derived alcohols.
17 May 2015 ADAPTING AND ADOPTING BANTING FOR BABIES a la Canadian-WHO recommendations and age-old good practice. canada-guidelines-advise-meat-as-baby-first-food/ Health Canada clarifies stance on meat for babies
Prof Tim Noakes’ team asks for all to sign petitions supporting his argument. We can doubt he needs it since he knows better than most how strong the evidence is.
When us Seniors’ generation was born around WW2, as in ancient times we were from > 6 months age gradually weaned off breast onto and brought up on real fresh food- butter, cream, home-grown veggies, fresh fish and pasture-fed meat /hens (and thus eggs and whole cows’ milk); with a tsp of codliver oil a day as the quintessential brainfood for those of us not brought up on oily ie pelagic sea fish..
Food was produced (like us humans) – especially by us mostly poor – without antibiotics, GMO, pesticides; and packaged, dressed without plastic, let alone massive electromagnetic exposure (microwave, TV, computers, cellphones and then WiFi). Like most on the planet, we had no cars or TV, so we also got plenty of sunshine- vits cholecalciferol D3, and ascorbic acid C (from abundant organic sun-drenched fresh fruit) – and exercise walking/ cycling to transport/ school/ sport or outdoor work as herders, farm/ building labourers etc if not the minority of us in shops/ factories/ office. Basic education and care – literacy-numeracy and hygiene – was provided mostly by state schools competing widely with mission schools, staffed from dedicated teachers’ /nurses/theological training colleges with intensive community experience; and (if mostly from the bible) literate parents from church/ libraries and radio.
But in our >50 years in medicine, all those aeons-old social foundations have increasingly been wiped out , especially in Africa by the ever-more corrupt advertising (especially on TV) and Fast Food- GMO- Disease Industry in partnership with corrupt oligarchy government that closed teachers’ and nurses training colleges; and rural /farm depopulation with mass migration driven by government-led poverty to city ghettoes. .. .
Already by 1970, teaching hospitals- following USA -devised corrupt industry factory-farm-food marketeering (not science and nutritional evidence-based) – started (by the non-medical Ancel Keys) nagging us via our medical school cholesterol clinics to start cutting cholesterol ie meat- dairy- fat intake in exchange for increasing intake of factory mass-produced refined and then genetically modified and insecticide-laden carbohydrates (sugar, maize, soya) and unproven synthetic hydrogenated seed-oils; and cholesterol-busting drugs like clofibrate, the statins, and aspartame – none of which were ever scientifically validated, and have been increasingly incriminated like sugar, fructose and smoking the past 30 years as major health pollutants. .
The scientific evidence has never the past 50 years shown benefits even matching harms from the profit-driven junk marketing of cholesterol-busting drugs and diets – artificial low-animal -fat cholesterol high carbs diets , and synthetic omega6 hydrogenated plant oils like “margarines” and Cremora, and sunflower cooking oils – for any common disease let alone average lipidemias. But the American public was bludgeoned into obeyance/obeisance and then silence, and have suffered increasing obesity and disease ever since – to the joy of the profiteering Fast Food and Disease Industry and their lobbyists in and outside governments. Now the SA Dieticians’ Association attack Noakes (and thus pre-1960s healthy normal world practice, and still Canadian guideline) diet promotion of more animal fat calories than carbs calories for weaning infants;
but the milk comparison the Dieticians quote in their attack- like the figures in the breastmilk Wiki review – shows remarkable conformity between UK mothers’ breast milk and eg Bantu mothers (1950)- milk has about 26% more calories/100gm from animal fat ie +- 38cals than from milk carbs +- 30cals, with protein ~1.1g%.. Obviously, LCHF promoters do not preach no-carbs diets since there is no such real food free of carbs.
The message has always been to take more fat calories than carbs calories, especially not refined empty calories like sugar and commercial fructose-laden drinks and GMO maize. Laymen have difficulty grasping that these refined simple sugars are slow cumulative poisons like longterm smoking, aspartame (Canderel) , oral synthetic sexhormones, fluoride, aluminium, mercury, lead, excess iron, etc. And obviously with poverty and dependency increasing in RSA due to almost worst- in-the -world State schooling since 1994, infant mortality from joblessness and thus stress, violence , malnutrition are increasingly rife in the Born-Frees ie those born in the new South Africa since 1990.
The Diet Association fails to ask simply: where are the references for promoting protein-and fat-rich food for weanlings? They are listed abundantly in the social and medical literature of the past century, especially the current literature we seniors in health science practice have read weekly the past 50 years from the 1960s; and conveniently now analyzed in depth by medical journalist Nina Teicholz and her numerous experts of the past 50 years she interviewed, in chapters 5 and 6 of The Big Fat Surprise 2014 (Scribe Pubs, Australia & UK);
following in the footsteps of contrarian ie high-carbo-sceptic investigative nutritionists like the archetypal insulin-resistant William Banting 1869 (ironically a distant kinsman of Fred Banting the Nobel-winning discoverer of insulin 50 years later) and his physician Dr William Harvey; Vilhjalmur Stefansson from 1923; Arthur Pennington 1949; Robert Atkins since 1963, Gerald Reaven from 1965 (Syndrome X); WPU Jackson & George Campbell in Cape Town from 1968, Denis Burkitt and Tom Cleave in Africa from 1970, James le Fanu since 1984 (the Rise and Fall of Modern Medicine 2001); Gary Taubes since 2001 (Good Calories Bad Calories 2007); Rooseboom ea 2006 (The Dutch Winter Famine of 1944-45); and Sam Feltham Slimology 2014, the 25 RCTs so far from many universities reported between 2000 and 2014 that Feltham et al detail eg ( in his book Slimology) by numerous contrarian academic clinician experts; all these authorities show that for health and reversing obesity in adults, the LCHF diet is uniformly more successful than the HCLF diet.
Increasing adverse experience with antibiotics, multiple vaccines, factory foods eg formula milk powders, GMO crops, tap water, doctored dairy milk, aspartame, pesticides like DDT and Roundup glyphosphate, crops grown in heavily polluted but nutrient-exhausted soil, and grain/antibiotic/hormone grown foods partly explains why we should avoid as far as possible exposing (future and current) pregnant women and infants to antibiotics, sugar, concentrated fructose, commercial dairy and processed refined cereal products, and aluminium-mercury-tainted vaccines, as far as possible.
In conclusion: it is sad that ADSA the Association for Dietetics in SA, attacks evidence-based Banting proponents personally instead of rebutting in academic scientific robust debate – the scientific media- the best scientific references and policies as thoroughly assessed and promoted by real-world experts below. Clearly, ADSA cannot quote any good science to support its contrary destructive commerce-based policy (of the past ~40 years ) about diet providing the majority of energy as sugars and hydrogenated omega6 – (it and the local medical schools havent done so) instead of low carbs high animal-fat natural food- so now it hides behind the sub judice rule.
Gwyneth Paltrow 2013 has provoked the wrath of the dietetic establishment by saying that she avoids feeding her children bread, rice and pasta, because she believes that these carbohydrate foods aren’t good for them. Paltrow was writing in her new low-carb, gluten-free cookbook, It’s All Good, which is out in April, and whose recipes are said by her publisher to “form the basis of the diet Gwyneth goes back to when she’s been overindulging, when she needs to rebuild, or lose weight.” Dieticians who subscribe uncritically to government nutritional guidelines have been wheeled out to testify to how ‘vital’ carbohydrate is in the diet, and warn in the bleakest terms of the dangers of restricting it. “Paltrow is putting her children, aged eight and six, “at risk of nutrient deficiencies”, warns one. Her children “won’t be able to think straight as their brain won’t be functioning”, says another. In the same Daily Mail piece, it is even observed that Paltrow’s children are thin – shock horror! – as if this was automatically cause for concern. So accustomed are we to the sight of overweight children, thin ones are beginning to look unusual …… read on
Dr Sheila Innis’ recent review Impact of maternal diet on human milk composition and neurological development of infants Am J Clin Nutr. 2014;99:734S-41S. http://www.ncbi.nlm.nih.gov/pubmed/24500153 from Univ British Columbia, Vancouver, Canada concludes unequivocally what vast evidence shows: that animal fat especially Omega3 marine DHA & EPA are crucial for neurodevelopment and all membranes – such natural saturated animal fats make up some 20% of adult brain. Maternal nutrition has little or no effect on many nutrients in human milk; for others, human milk may not be designed as a primary nutritional source for the infant; and for a few, maternal nutrition can lead to substantial variations in human milk quality. Human milk fatty acids are among the nutrients that show extreme sensitivity to maternal nutrition and are implicated in neurological development. Extensive development occurs in the infant brain, with growth from ∼ 350 g at birth to 925 g at 1 y, with this growth including extensive dendritic and axonal arborization. Transfer of n-6 (omega-6) and n-3 (omega-3) fatty acids from the maternal diet into human milk occurs with little interconversion of 18:2n-6 to 20:4n-6 or 18:3n-3 to docosahexaenoic acid (DHA) and little evidence of mammary gland regulation to maintain individual fatty acids constant with varying maternal fatty acid nutrition. DHA has gained attention because of its high concentrations and roles in the brain and retina. Studies addressing DHA intakes by lactating women or human milk amounts of DHA at levels above those typical in the United States and Canada on infant outcomes are inconsistent. However, separating effects of the fatty acid supply in gestation or in the weaning diet from effects on neurodevelopment solely due to human milk fatty acids is complex, particularly when neurodevelopment is assessed after the period of exclusive human milk feeding
. The Canada guidelines The Canadian statement 2013 reads unequivocally: POSITION STATEMENT Weaning from the breast: Barbara Grueger; Canadian Paediatric Society , Community Paediatrics Committee Paed Child Health 2013: updates the similar previous Canadian Paediatric Society position statement 2004. ” – “North American parents have traditionally introduced rice cereal as a first food. There seems to be a movement away from this practice in the general mama community, especially white rice cereal. Baby-led weaning is a method of foods introduction wherein the baby is offered whole foods. The baby has complete control with this method. For example, you steam a whole artichoke, place it on baby’s tray and allow him to decide what to do with it. Infant cereal, pureed meats and fish are recommended as first foods by the American Academy of Pediatric AAP, Canadian Paediatric Society (CPS), Dieticians of Canada, Breastfeeding Committee for Canada, Public Health Agency of Canada, and Health Canada. CPS also identifies poultry, cooked egg yolk and well-cooked legumes (beans, lentils, chick peas) to be good sources of iron and suitable for first foods”.) Exclusive breastfeeding provides optimal nutrition for infants until they are six months old. After six months, infants require complementary foods to meet their nutritional needs. This is when weaning begins. Weaning is the gradual process of introducing complementary foods to an infant’s diet while continuing to breastfeed. The timing and process of weaning need to be individualized by mother and child. Weaning might be abrupt or gradual, take weeks or several months, be child-led or mother-led. Physicians need to guide and support mothers through the weaning process. “Breast milk is the optimal source of nutrition in infancy. Breastfeeding protects infants from a wide array of infectious and noninfectious diseases. With few exceptions, healthy term infants require only breast milk (with vitamin D supplementation)  to meet all their nutritional requirements until they are about six months old. The Canadian Paediatric Society, Dietitians of Canada, Health Canada and the WHO recommend exclusive breastfeeding for the first six months of life and continued breastfeeding with complementary foods for up to two years and beyond (no upper limit has been defined). Iron from meat has the best bioavailability and can be readily absorbed from the gastrointestinal tract. After six months of age, when breastmilk alone cannot provide enough, additional protein sources (such as meat, fish, egg yolk, tofu, lentils and cheese) are needed. Roughage should also be introduced to the diet, although it is not clear when adding fibre becomes necessary. There is no conclusive evidence that delaying the introduction of eggs, fish and nuts (including peanuts) beyond four to six months of age helps to avoid food allergies. As a greater variety of solids and liquids are introduced to a baby’s diet, weaning will progress. “A review of the literature using MEDLINE (1966 to 2012), the Cochrane database and relevant websites, WHO, the Canadian Paediatric Society, Health Canada and the American Academy of Pediatrics, concluded: Given the limited nature of evidence on weaning, the recommendations in this statement are based largely on expert opinion and consensus. “Generally, infants were breastfed longer in ancient times than in Western societies today. Mothers in Zulu societies have traditionally breastfed their infants until 12 to 18 months, at which point a new pregnancy would be anticipated. Ancient Hebrews completed weaning at about three years. Around the world it is not uncommon for children to be completely weaned at two to four years of age. Anthropological studies have described final weaning at the following points: when the infant reaches four times his birth weight; when the infant’s age is six times the length of gestation (ie, 4.5 years); or when the first molar erupts. “The early introduction of mixed feedings began in early 19th-century Western society. Prominent contemporary physicians such as American Pediatric Society founders Drs. Luther Emmett Holt and Job Lewis Smith recommended that weaning begin at around nine to 12 months of age or when the canine teeth appeared. Smith recommended against weaning during the summer months because of the risk of “weanling diarrhea”. As weaning was recommended earlier and earlier, infant mortality increased. Introduction of weaning foods was an important cause of infant mortality in the 19th century. In the early 20th century, mothers were encouraged by the medical community to raise their children scientifically or “by the book”. In the 1920s, the United States government published Infant Care, referred to at the time as the “good book” and read by women from all socioeconomic groups. It recommended cod liver oil, orange juice and artificial feeding. “In 2008, according to the Public Health Agency of Canada, 87% of children were breastfed for some period of time while only 16.4% were exclusively breastfed for six months. Still, this figure represents a steady increase in breastfeeding rates over the previous five years. Breastfeeding duration varies depending on maternal age. Only 11% of infants of mothers aged 25 to 29 years continue to breastfeed exclusively for six months, compared with 20% of infants of mothers 35 years or older. The most common reason mothers give for weaning is a perceived insufficiency in milk supply. Women who breastfeed for longer than three months most often cite return to work as their reason for weaning. Canadian breastfeeding practices may continue to improve because many mothers receiving employment insurance can delay their return to work for 12 months postpartum. Nutritional and developmental issues : At around four to six months of age, most infants are developmentally ready to handle puréed foods. They are developing the oral motor coordination necessary to accept different food textures. However, they are at risk for choking on chunky food pieces such as nuts, whole grapes and hot dog wheels that require advanced oral motor coordination not achieved before three years of age. “Sucking and chewing are complex behaviours with reflex and learned components. The learned component is conditioned by oral stimulation. If a stimulus is not applied while neural development is occurring, an infant may become a poor eater. There is a relationship between prolonged sucking without solids and poor eating. While it is ideal for infants to be exclusively breastfed for six months, it is also true that after a certain age, human milk alone cannot supply all of an infant’s nutritional requirements. Individual circumstances may make it appropriate for some infants to start complementary feedings as early as four months of age. “Age-appropriate intake of calories and micronutrients is important for growth, motor and mental development. Delaying the introduction of nutritional solid foods much beyond six months of age puts an infant at risk for iron deficiency anemia and other micronutrient deficiencies. Picciano et al followed older weaning infants (12 to 18 months of age) by collecting data on dietary intake and growth. Many of the study children were ingesting less than the recommended levels of fat (less than 30% of total calories), iron and zinc. Grains, whole milk, dairy products and meats were identified as important sources of iron, vitamin E and zinc. By four to six months of age, iron stores from birth are diminishing, necessitating the introduction of iron-containing foods at six months of age for all infants. Iron supplementation after the first weeks of life or at four months of age for the exclusively breastfed infant has been recommended by some groups. When there is a delay in introduction of iron fortified foods, oral iron supplementation needs to be considered. The process of weaning While the best method for transitioning from fully breastfeeding to complete nutritional independence is not known, the process should meet the needs of both baby and mother. Physicians may refer mothers to the La Leche League’s website and the Canadian Paediatric Society’s Caring for Kids website (see Resources for parents, below). Weaning can be either natural (infant-led) or planned (mother-led). Gradual weaning (infant-led weaning) occurs as the infant begins to accept increasing amounts and types of complementary food while still breastfeeding on demand. With gradual weaning, the complete wean usually occurs between two and four years of age. In Western cultures, there remains a relative intolerance to this type of weaning and many mothers who breastfeed their older baby or child become “closet nursers”. Closet nursing takes place privately, at home. This relative secrecy tends to compound erroneous beliefs about appropriate breastfeeding duration.
http://www.thestar.com/news/canada/2012/09/24/hold_the_pablum_’give_that_baby_some_meat’_new_canadian_guidelines_advise.html : Megan Ogilvie Health Reporter, 2012 Forget squash and sweet potatoes; steak is now recommended for baby’s first solid food. In a major departure, new Canadian guidelines say parents should be offering their six-month-old infants meat, fish, poultry or meat alternatives two or three times a day.. these iron-rich foods should be the first that babies consume when being introduced to solids. The recommendations, part of a joint statement quietly released last week by Health Canada, are sure to give some parents pause. Previously, it was recommended that babies start out eating infant cereals, followed by fruits and vegetables, as they transition to solid foods.
Healthy Pregnancy, Baby & Child by Sarah TheHealthyHomeEconomist One of most misguided and damaging pieces of advice coming from the vast majority of pediatricians, dieticians, and other “experts” is to give rice cereal as a baby first food around the age of 4-6 months. This advice is extremely harmful to the long term health of the child, contributing greatly to the epidemic of fat toddlers and the exploding problem of childhood obesity. Rice cereal is never a healthy baby first food. Not only is it an extremely high glycemic food when eaten alone (spikes the blood sugar) but it also contains ample amounts of double sugar (disaccharide) molecules, which are extremely hard for such an immature digestive system to digest. The small intestine of a baby mostly produces only one carbohydrate enzyme, lactase, for digestion of the lactose in milk. It produces little to no amylase, the enzyme needed for grain digestion until around age one.Now, at least one governmental body is waking up to the harmful notion of cereal grains as the “ideal” baby first food. Health Canada in collaboration with the Canadian Pediatric Society, Dietitians of Canada and Breastfeeding Committee for Canada has issued new guidelines for transitioning a baby to solid food and two of the first weaning foods recommended. Meat and eggs! While these guidelines are certain to rile vegetarian and vegan groups, the fact is that meat and eggs are indeed perfect weaning foods for a baby. Not only are these animal foods extremely easy to digest compared with cereal grains, but they also supply iron right at the time when a baby’s iron stores from birth start to run low. The inclusion of meat in these baby first food guidelines is in line with the wisdom of Ancestral Cultures which frequently utilized animal foods for weaning. A traditional first food in African cultures is actually raw liver which the mother would pre-chew in small amounts and then feed to her child. The guidelines specifically note the role that ancient wisdom played in the decision to no longer recommend cereal grains and instead suggest meat: “While meat and fish are traditional first foods for some Aboriginal groups, the common practice in North America has been to introduce infant cereal, vegetables, and fruit as first complementary foods.” Soft boiled egg yolks are also an ideal choice as a baby first food as they supply ample iron as well as choline and arachidonic acid which are both critical for optimal development of the baby’s brain which grows as its most rapid rate the first year of life. Unfortunately, while the suggestion of meat and eggs is a good one, the joint statement from Health Canada also inexplicably includes tofu and legumes which are both a terrible choice as a baby first food. The starch in legumes would cause the same digestive problems as rice cereal and the endocrine disrupting isoflavones in tofu would be a disaster for baby’s delicate and developing hormonal system. But, let’s give credit where credit is due. At least meat and eggs are appropriately included on the baby first food list. Good on you Health Canada! Perhaps your neighbor country to the South will wake up and get a clue about how to properly feed babies based on your lead. I’m not holding my breath. Sarah, The Healthy Home Economist
Int J Obes (Lond). 2005;29 Suppl 2:S8-13. How much protein is safe? Agostoni C1, Riva E. ea University of Milan, Italy Since breastfeeding and human milk seem to prevent, while high dietary proteins in the first 2 yr of life seem to promote later overweight, questions have been raised on the safe levels of proteins in the early years. How much protein (as a percentage of total calorie intake) is safe RESULTS: We should move from the figure of 7-8% in the 4-month exclusively breastfed infants up to the maximum acceptable levels of 14% in 12-24-month-old infants. When protein supply represents less than 6% and energy is limited, fully breastfed infants are likely to enter a status of negative nutrient balance. Over the limit of 14% energy from proteins in the 6-24 months period, some mechanisms may begin to operate, leading young children towards an early adiposity rebound and overweight development, beyond any genetic predisposition. Preliminary data seem to indicate a causal role for whole cow’s milk proteins. CONCLUSION: We suggest maintaining breastfeeding as long as possible, and, in case human milk is insufficient, to introduce infant formulas, appropriate for age, up to 18-24 months, in order to keep protein intakes in the safe range of 8-12% within a diet adequate in energy and balanced as far as macronutrients.
Health Canada clarifies stance on meat for babies By Global News with files from Jennifer Tryon Health September 25, 2012 Health Canada is clearing the air about what kind of solid foods babies should be introduced to. The clarification comes after some media outlets reported Tuesday that the agency changed its list of recommended first foods for Canadian babies to include meat and meat alternatives – like eggs, tofu and legumes – to help meet nutritional needs. For the record, Health Canada has not recently modified these guidelines. Since 2004, the agency has recommended iron-rich foods, such as meat and iron-fortified cereal, as a baby’s first solid foods, because iron is crucial to brain development. Most baby cereals now contain iron. There is no scientific evidence suggesting meat is harder on a baby’s digestive system, but parents are reminded to puree the meat with water or breast milk, so it’s easier for the child to swallow. Registered dietitian Cora Rosenbloom also tells Global National‘s Jennifer Tryon that there’s no reason to withhold eggs. “There’s really no evidence to say that food allergies are going to be more common if eggs are introduced earlier.” Link to Health Canada’s current recommendations. Follow Jennifer on Twitter: @JenTryon
note that quotations are in italics.
update 14 Sept 2016 firstname.lastname@example.org having just received a sorrowful posting from Diana below, I now discover that there are a number of similar complaints that I had missed and not posted; so I have now posted them under comments. This condition is such a nightmare for sufferers that I post them as you submitted them, with your name and email if thats how you sent them. I can delete your contacts if you like, but the more you sufferers communicate and exchange ideas the better for sufferers.
Sufferers must surely have tried some nonirritating local anaesthetic cream, or eg virgin coconut oil, or simply massage for relief.
given the risk of even low strength estrogen cream being well absorbed from mucous membranes more than from skin, and thus (altho beneficial for brains, bones, skin, heart etc) potentially adverse for endometrium, breast, and many other target organs, we leave the vascular engorger estrogen as the last resort- first try anything but topical sex hormonesl then if still desperate, sparingly up to 3% progesterone cream; testosterone cream is also healing, but virilizing ie not to be used if arousal, clitoromegally, breast proliferation is not wanted.
Since my 2009 review, there are some 15 new abstracts in English on Pubmed from USA, Canada, Europe, Israel and Japanese groups. There dont seem to have been any major breakthroughs in management of this rare and distressing disorder. Antiepileptics may be promising- like cannabinoid oil , and the ketogenic diet are, in epilepsy.
Since the brain responds so well to more natural dietary fats (eg animal triglycerides, MCT- coconut oil, fish oil ie EPA, DHA) and withdrawal of excitogenic glucose loading that most people indulge in, and so many patients today are overweight with estrogenizing glucose insulin resistance, in general I encourage patients to think of epilepsy let alone memory loss (including Alzheimers) and mood disorders as brain diabetes, glucose toxicity with deprivation of good needed dietary fats; and thus to try Banting diet rather than the populist fast food industry-promoted disasterous high carbs low fat low cholesterol fad of the past 50 years. This simple dietary advice is at worst harmless distraction, and generally beneficial for the unhappy women with multifactorial PGAD,
Given their ubiquitous benefits in so many disorders, harmless trial is warranted with: vigorous vitamin D3 replacement to the commonly optimal level around 100ng/ml (which may require the average safe 10 000 iu vit D3.day, but perhaps 10 times that with unpredictable vitamin D resistance) seems worth considering for this rare but extremely distressing disorder ie PGAD;
lowdose naltrexone LDN;
hypnotherapy has been reported helpful, but potentially hazardous.
If not obviously due to psychiatric, or tumour eg Tarlov cysts, or pelvic venous problems, PGAD may be likened to variant true epilepsy or the only somewhat less common PNES syndrome – psychogenic non-epileptic seizure syndrome – that like PGAD has been increasingly recognized only this millennium, and which is overall even more of a dis-ease and psychiatric problem that true epileptic diseases, .
abstracted English refs published since 2009 review:
J Sex Med. 2014 Jan;11(1):136-9. A periclitoral mass as a cause of persistent genital arousal disorder. Bedell S1, Goldstein AT, Burrows L.New York University describe a woman who developed PGAD in association with a periclitoral mass, a potential physical cause of the disorder that has not been previously described in the medical literature.A postmenopausal woman presented with 6 months of persistent, unrelenting genital arousal and clitoral pain that was unrelated to sexual stimuli. Careful examination revealed a tender, firm, mobile, left-sided mass that appeared to compress the dorsal nerve of the clitoris.Complete excision of the mass resulted in full resolution of her symptoms over several weeks. Localized causes of persistent genital arousal, though rare, should be included in the differential diagnosis PGAD as detection and treatment can lead to a complete recovery.
J Sex Med. 2013 Jun;10(6):1549-58. Cognitive and emotional determinants characterizing women with persistent genital arousal disorder. Carvalho J1, Veríssimo A, Nobre PJ. Porto, Porto, Portugal. email@example.com The aim of this study was to characterize the cognitive and emotional style of women reporting PGAD. More precisely, the content of sexual beliefs, thoughts, and emotions during sexual intercourse was explored.Forty-three women presenting PGAD and 42 controls responded to a web survey. This study was cross-cultural in nature and women worldwide (over 18 years old) were asked to participate. After controlling for sociodemographic characteristics and psychopathology, findings showed that women reporting PGAD symptoms presented significantly more dysfunctional sexual beliefs (e.g., sexual conservatism, sexual desire as a sin), as well as more negative thoughts (e.g., thoughts of sexual abuse and of lack of partner’s affection) and dysfunctional affective states (more negative and less positive affect) during sexual activity than non-PGAD women. Notwithstanding the impact of neurophysiological determinants in the etiology of this syndrome, results support the psychological conceptualization of PGAD and highlight the role of cognitive-behavioral therapy (CBT) for PGAD symptomatology. More specifically, cognitive and behavioral strategies would be aimed at targeting maladaptive sexual beliefs and thoughts, as well as regulating negative affective states resulting from a dysfunctional cognitive style regarding sexuality. In all, CBT in association with a medical/pharmacological approach, could be clinically relevant in the management of PGAD.\
J Sex Med. 2013 Feb;10(2):439-501 Persistent genital arousal disorder: characterization, etiology, and management. Facelle TM1, Sadeghi-Nejad H, Goldmeier D.New Jersey Medical School-Surgery-Urology, Newark, NJ 07103, USA.. Since its first description in 2001, many potential etiologies and management strategies have been suggested. To review the literature on PGAD, identify possible causes of the disorder, and provide approaches to the assessment and treatment of the disorder based on the authors’ experience and recent literature.PubMed searches through July 2012 were conducted to identify articles relevant to persistent sexual arousal syndrome and PGAD. PGAD is characterized by persistent sensations of genital arousal in the absence of sexual stimulation or emotion, which are considered unwanted and cause the patient at least moderate distress. The proposed etiologies of PGAD are plentiful and may involve a range of psychologic, pharmacologic, neurologic, and vascular causes. PGAD has been associated with other conditions including overactive bladder and restless leg syndrome. Assessment should include a through history and physical exam and tailored radiologic studies. Treatment should be aimed at reversible causes, whether physiologic or pharmacologic. All patients should be considered for cognitive therapy including mindfullness meditation and acceptance therapy.
Restless Legs (Ekbom’s) Syndrome, common with iron deficiency, diabetes, kidney failure etc, is bad enough. But combination with restless genitals is an awful prospect. Normally it is men who famously have restless genitals that cannot be sated…
Sandra Leiblum first described persistent genital arousal disorder in women in 2001, and since then has reported on some 171 cases in New Jersey.
restless leg syndrome and/or an overactive bladder, urethral hypersensitivity; involuntary genital arousal with unprovoked orgasms, onset often during early menopause, as well as the 5 diagnostic criteria of persistent genital arousal disorder (PGAD) – :
Leiblum discriminates such disorder from Female Sexual Arousal Disorder on the basis that “FSAD women displayed the greatest problems in desire, arousal, lubrication, orgasm, and pain while women with PGAD reported somewhat more desire than the control group but did not meet the cutoff score for sexual dysfunction.
It is strange that no other gyne or sexual health clinics in the world have so far reported clusters of such patients as have these two clinics in New Jersey and Den Hage .
Leiblum ea could elicit only perhaps 1 such case (ie 1%) at a sexual health clinic in London UK. From an Internet survey she reported in 2007 that in the 50% of cases who had all 5 diagnostic criteria, “ they were significantly more likely to be depressed (55% vs. 38% who did not have all 5) and to report panic attacks (31.6% vs. 14.6%). They were more anxious and more likely to monitor their physical sensations. Both groups reported high rates of childhood and adult sexual abuse, although the PGA women reported a higher prevalence of sexual victimization. They were significantly more likely to endorse negative feelings about their genital sensations and also more likely to complain of chronic fatigue syndrome than women without the condition (10% vs. 0%). There were no significant relationships with pharmacologic agents and symptoms. It is hypothesized that for a subset of women, psychological factors, namely anxiety, reinforce exacerbate and maintain PGAD.”
But they have anything but nymphomania (origin 1775: Oxford English dictionary), although they may be so mislabeled ie pseudo-nymhomania (Fenichel 1933). Kinsey’s 1948 book on Female Sexual Responsiveness did not even mention, index nymphomania. Kuperman 1961 in his chapter on Sex Hormones unknowingly implies the difference between nymphomania and pseudonymphomania: “nymphomania may occasionally be treated successfully and paradoxically with androgens.. these patients who respond to androgens by a decrease in desire for frequent stimulation are probably those who have been unable to achieve satisfying orgasm, which androgen provides.. in other such patients, progesterone suppositories as an antiandrogen agent may diminish unwanted desire and erotic tendencies. ”
Stuckey ea describe a single case who was cured by coil embolization of pelvic varicose veins- a more realistic therapy than embolization of the clitoris to infarct it, or amputation as was practiced by eminent UK physicians in Victorian times.. .
Women with RGS/PGAS do not have either a central arousal disorder or craving for love/attention, but vascular- neuropathic clitoral engorgement; which topical progesterone or anaesthetic eg lignocaine cream may relieve by treating the endpoint, not the cause.
If varices are the strong associate, perhaps it is worth considering the pathophysiology of varices, which are apparently often associated with sensory neuropathy, presumably through swelling pressure on nerves – local varicose oedema. Vercellini ea note that pelvic varices are one common cause of pelvic pain in women.
Increased pressure and thrombosis aside, varicose veins are strongly associated with female gender, ie with testosterone:estrogen level about 1/200th of that in middle-aged men, and loss of collagen (ie ascorbic acid) in smooth muscle and extracellular matrix.
Higher female estrogen is associated with stronger bones, and oedema, stress incontinence and vascular relaxation; but it notoriously contributes nothing to muscle growth and strength except in the unique uterus itself – only estrogen grows the uterus. Only androgen grows body muscle mass and strength. From early menopause, testosterone falls gradually; but especially with fattening, estradiol falls gradually but fat-derived estrone increases, reversing the premenopausal estradiol>estrone dominance. Hence across midlife women mostly shrink their skeletons and lean mass but expand their fat mass steadily- ie couch potatoes develop increasing fatness frailty.
Hence (compression stockings for varicose legs aside), especially in women, apart from raising the legs, the foot of the bed at night, we commonly see varicose vein discomfort and distension in the legs and anus (piles) relieved by a few grams of bioflavinoid – ascorbic acid blend a day. A topical cream may augment this.
And as regards neuropathy of the legs, apart from GABA plus 5HTP for nonspecific relief, we often see significant improvement with a vigorous blend of nerve nutrients including vitamins BCo, zinc and alphalipoic acid.
It may add to understanding of this awful problem if other sufferers contribute their experience. Anonymity will obviously be preserved if their comments are published.
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.
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 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.
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.
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.
12 February 2015 Why I’m Opting out of Mammography JAMA 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. .
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.”
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.”
|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
“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
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 expressed2–7. 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 mammography12–15. 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 women16–18. 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 Borgen2–7,11. 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?
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!7, 8 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|
|Moderate Risk||0.96-0.99||>0.81 – 0.84|
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:
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.
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?
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:
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.
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:
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: firstname.lastname@example.org. 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”.
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.
*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.
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 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.
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.. .
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.
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..
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 2013: FIFTEEN 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.
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. This obscures reality that about ten more women will die from heart disease or stroke than from breast cancer.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. 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.
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.
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.
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 Persuasion, often 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.
updating the risks and futility of screening xray mammography.
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 –
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.
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f385 (Published 23 January 2013) Cite this as: BMJ 2013;346:f385
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. 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. They thus state that universal screening may not be reasonable. 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.“
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…
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 .
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);
..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 is needed in microgram mcg amounts for the thyroid, milligram mg amounts for breast and other tissues, and therapeutically as anticancer in gram amounts.- 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 perspective, the 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.
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 .. …
and IODINE, A CRITICAL NUTRIENT 2014 http://drlwilson.com/Articles/IODINE.htm
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.
re adding enough selenium, chromium, vit C, Magnesium, Vitamin B2/3
Until 2007, in the United States, Lugol’s solution was unregulated and available over the counter as a general reagent, an antiseptic, a preservative, 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. 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. The LD50 for Iodine is 14,000 mg/kg [Rat] and 22,000 mg/kg [Mouse].
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 which classifies Iodine as having low toxicity. Potassium Iodide is not considered hazardous.[15
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
see lugols_dosage_chart. . But for obvious reasons stick to 2% till you know you tolerate and need much stronger drops.