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

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

NEXT SURE TOUCH CLINIC CAPETOWN 30 April 2016     For those who (despite clinical reassurance,  and the evidence against screening for silent breast and prostate cancer as recently again published below in a British Journal) ), still want screening breast imaging,   Saturday 30 April 2016  is the next  Sure Touch imaging clinic  by our Breast  Screening  Sister  (and if required, specialist doctor)  for asymptomatic women with well breasts  who despite the futility and risks still desire  screening breast imaging.

Book  at the Natural Wellness  Clinic in Grove Bldg Claremont Cape Town (between ABSA on Grove and Cavendish). ph 021 6831465/ 021 6717415 or 0712025274  office hours to book appointments , or email doctor@healthspanlife.com, or ph Reyhana 0763910463 .  (next Thermography  clinic +- June  tba ).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Figure1

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

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

For More Information: Centers for Disease Control and Prevention

Image not available.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

update 21 Oct 2014 Dr Garry Gordon writes :

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1. Mammograms May Offer Less Benefit Than You Think:

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

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

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

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

3. False Positives are Common (and Dangerous)

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

4. Mammograms May Not Work if You Have Dense Breasts

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

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

5. There are Other Screening Options

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Benefits of mammography

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

DIET RISKS FOR BREAST CANCER:

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

It is no wonder the public is confused.

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

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

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

It is no wonder the public is confused.

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

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

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

VITAMIN INTAKE AND BREAST CANCER:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A month ago BCAction held a webinar reported by Manie Clark

updating the risks and futility of screening xray mammography.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

update 27 Sept 2015
IODINE THE QUINTESSENTIAL SUPPLEMENT

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

and

Lugols for animal thyrotoxicosis

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

and

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

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

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

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

update Dec 2014: TIME TO MANDATE LOWDOSE RESERPINE+ LOWDOSE AMILOZIDE+- AMLODIPINE(/ DIHYDRALAZINE) AS FIRST LINE THERAPY OF AVERAGE HYPERTENSION.

TIME TO COMPELL FIRST LINE POLYTHERAPY OF COMMON  HYPERTENSION WITH LOWDOSE RESERPINE+ LOWDOSE AMILOZIDE; with AMLODIPINE as 4th add-on if needed.

dedicated;  for inspiration and help,  to: Drs YK Seedat; Roy Keeton;  Norman Kaplan; Colin Dollery, Harry Seftel; Josh Barzilay; Tony Bunn; Mark Blockman;  and pharmacists  Allan Taylor and Joe Talmud.

neil.burman@gmail.com    for previous reviews see  https://healthspanlife.wordpress.com/?s=reserpine+

https://healthspanlife.files.wordpress.com/2009/04/reserpine_table.pdf

update:  16 Dec 2014 THE RISKS OF MODERN ANTIHYPERTENSIVE DRUGS:  Pubmed search for ANTIHYPERTENSIVE DERMATITIS REACTIONS brings up >156 papers from 1970 (on practolol, propranolol, atenolol, labetolol, hydralazine, ACEI); we first encountered practolol (BBlocker) problems  in the ’70s;  and captopril (ACEI) dermatitis about 1980; Dermatitis  has also been reported since 1987 with calcium channel blockers. WHY USE ACEI/ARBS and BETABLOCKERS -with their added airways and circulatory risks -EXCEPT AS LAST RESORT?   when these are now routinely combined with other synthetic designer drugs clopidogrel (a sulfonamide) , or /and non-sulfonamide warfarin, aspirin, other NSAIDs and statins; sulphonylureas, glitazones, which cause serious multiple complications including dermatitis.

The problematic Bblockers, ACEI, ARBs, aspirin, NSAIDs,  clopidogrel, warfarin  and  statins are rarely indicated; whereas  the hypersensitiviy  risk with thiazide (hydrochlorothiazide – a sulfonamide – halflife ~10hrs  ) PLUS AMILORIDE (halflife ~7.5hrs,  not a thiazide)  is rare;  and reserpine (not a sulfa, half-life ~10days)  actually suppresses allergic risk;

and natural extracts- fish oil, coconut oil,  vigorous vitamins B, C, D3, E, K2;   magnesium, zinc, selenium, boron, iodine,   garlic, curcumin, gymnema, metformin, reserpine, cayenne, MSM/DMSO, arginine, carnitine, ribose, CoQ10, proline, alphalipoic acid, acetylcysteine- do far more good without harm (than heavily marketed designer synthetics) in addressing the root causes of the common degenerative  diseases of aging rather than addressing just their symptoms, as drug companies do. .

Refs: 1. Immunopharmacol Immunotoxicol. 2013 :35:447-50 “Cutaneous antihypertensive adverse drug reactions (ADRs) have been frequently reported. Vena,  De Simone ea  University of Bari, Italy reported Eczematous reactions due to angiotensin-converting enzyme inhibitors ACEIs or angiotensin II receptor blockers ARBs  in 23 hypertensive patients patients aged 66-87 years; 19 of them were taking another drug in addition to the suspected antihypertensive medication and 15 were on polytherapy with three or more drugs to treat multiple comorbidities. The antihypertensive culprit agents were (ACE) inhibitors in 9 patients, ACEI combined to hydrochlorothiazide (HCT) in 7 subjects, ARBs  alone in 2 patients and associated with HCT in 5 cases. Eczema was generalized in 16 patients and localized in 7 cases, with predominant involvement of lower limbs. Such lesions developed after a latency of 4-30 months and were associated with moderate-to-severe itch, usually unresponsive to oral antihistamines. Histopathology  was spongiotic dermatitis with possible associated psoriasiform skin changes.”

2.  In the Textbook  Adverse Drug Reactions 2nd Ed by Anne Lee, Pharmaceutical press 2006,  the chapter Drug Skin Reactions exhaustively lists all causative drugs – only  reserpine/ rauwolfia is not mentioned since it prevents hypersensitivity:

  3. J Exp Med. 1985 Dec 1;162:1935-53. Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells. Mekori YA, Weitzman GL, Galli. Harvard & Tel Aviv Universities  “ reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response; findings strongly suggesting that whatever effects reserpine might have on immunologically nonspecific host cells, it’s effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo.

No recent review gives objective evidence-based opinion free of drug industry vested influence about optimal initial antihypertensive  drug therapy that contradict the above evidence.

13 December 2014: latest analyses of all antihypertensive trials confirm that LOWDOSE (potassium-sparing) diuretic- eg amilozide-   LOWDOSE reserpine, and if needed as 4th drug, calcium channel blocker eg amlodipine,  each  individually lower all major events including MORTALITY, ( and refractory lowers refractory pain).  Betablockers, ACEI and ARBs do not reduce mortality- and have major adverse effects. .

Thomopoulos ea (Univs Athens & Milan) J Hypertens Dec 2014   Effects of various classes of antihypertensive drugs on outcome incidence in hypertension, asks which  BP-lowering drug classes  are  effective in reducing MORTALITY?  In 55 RCTs (~200 000 individuals) all  common antihypertensive drugs lowered  BP , stroke,  and major cardiovascular events; but in 2014 use, only  a diuretic (even lowdose); and calcium antagonists  gave  significant reductions of all outcomes including mortality.

PAIN SUPPRESSED BY RESERPINE:    S Afr Med J. 1991;80:176-8.  Significant cost-saving with modification of antihypertensive therapy. Keeton & Monteagudo, Univ.Cape Town.    30 patients  on nifedipine for hypertension or chest pain were followed up for 6 months after alternative therapy- Reserpine combined with a thiazide- was instituted: blood pressure control improved and no serious side-effects were encountered. This  reduced the monthly cost by  73%. Although a self-assessment depression inventory was completed by 21 patients, our study does not fully evaluate the impact on quality of life. The likelihood of side-effects is  small–provided  the maximum daily dose of reserpine does not exceed 0.1 mg. A more considered approach is needed in the choice of antihypertensive agents.

Arch Inst Cardiol Mex. 1977 ;47:101-8. Prinzmetal’s angina Response to  treatment with reserpine. Review of physiopathological mechanisms. Guadalajara , Horwitz , Trevethan  present a case of Prinzmetal angina refractory to classic medical treatment, in which the angina attacks were suppressed with  reserpine .Coronary spasm due to alteration in the regulation of the coronary arterial tone from  autonomic nervous system illness is established, an abnormal coronary vascular reactivity is also reviewed. It is emphasized that Prinzmetal angina is an original entity, different from  coronary arteriosclerotic heart disease, which may coexist with it but which cannot be treated in the same way, because its physiopathologic mechanisms are different.

Cardiovasc Dis. 1974;1:194-201. PRINZMETAL ANGINA PECTORIS WITH NORMAL CORONARY ARTERIOGRAMS: EFFECT OF LONG-TERM RESERPINE TREATMENT.   Hernandez-Casas, Leachman ea . Baylor  St. Luke’s Houston, Texas

7 December 2014:  Medscape 2013 : the modern theory  Pathogenesis of essential hypertension HBP  is highly complex: Multiple factors modulate blood pressure (BP) for adequate tissue perfusion : Humoral (ie in the blood- hormonal, immune, nutritional), Vascular reactivity , Circulating blood volume, Vascular caliber, Blood viscosity, Cardiac output, Blood vessel elasticity, Neural – autonomic stimulation.                          Over the course of its natural history, essential HBP progresses from occasional to established HBP.  After a long invariably asymptomatic period, persistent HBP develops into complicated HBP, in which target organ damage to the aorta and small arteries, heart, kidneys, retina, and central nervous system is evident.

The progression of essential HBP begins with prehypertension in persons aged 10-30 years (by increased cardiac output) and then advances to early HBP in persons aged 20-40 years (increased peripheral resistance ), then to established HBP in persons aged 30-50 years, and finally to complicated HBP in persons aged 40-60 years.

Hence to prevent HBP becoming established and complicated by midlife, both the lifestyle/ nutritional factors, and the neural- stress and the RAAS renal-aldosterone- angiotensin systems – need to be optimized in young adulthood, in the early workplace  if not childhood ie at school: with reintroduction at  school of compulsory physical education/sport;  banning of  tobacco,  refined sugar  and retail salt sale; universal ingestion  3 times a week at least of a tsp of codliver oil  equivalent (before it becomes unobtainable;)  and a tblsp of virgin coconut oil; and if bloodpressure does not normalize, addition of at least 3 times a week 1/2 reserpine  ie 0,125mg and 1/2 amilozide ie 27.5mg , to address most of the risk factors, as detailed below a week ago. .

Kostis  ea, Univ Harvard; Rutgers,. Columbia,Texas, Am J Cardiol. 2014 Feb examined Competing cardiovascular and noncardiovascular risks and longevity in the Systolic Hypertension in the Elderly   Program SHEP with  chlorthalidone-based stepped care (n = 2,365) or placebo (n = 2,371) for 4.5 years,. all participants were advised to take active therapy thereafter. At the 22year follow-up,  gain in life expectancy free from CV death in the active treatment group was 145 days  ( p = 0.012). The gain in overall life expectancy was smaller (105 days)because of a 40-day (95% CI -87 to 161) decrease in survival from non-CV death. Compared with an age- and gender-matched cohort, participants had markedly higher overall life expectancy ( p = 0.00001) and greater chance of reaching the ages of 80 (81.3% vs 57.6%), 85 (58.1% vs 37.4%), 90 (30.5% vs 22.0%), 95 (11.9% vs 8.8%), and 100 years (3.7% vs 2.8%). In conclusion, Systolic Hypertension in the Elderly Program participants had higher overall life expectancy than actuarial controls and those randomized to active therapy had longer life expectancy free from CV death but had a small increase in the competing risk of non-CV death

The 2013 Statement by the International & American Societies of Hypertension( including all continents and South Africa) includes amiloride-HCTZide  ; and reserpine 0.1 mg/day in the array of drugs to be combined for optimal  BP control.  “Thiazide-like Diuretics: reduction of major cardiovascular CVD and  stroke events have been established. Main side effects are metabolic (hypokalemia, hyperglycemia, hyperuricemia), which  can be reduced by using low doses (eg, 12.5 mg or 25 mg of HCTZ) or by combining these diuretics with  potassium-sparing agents eg angiotensin-blockers, amiloride etc .    Note: Thiazides plus   b-blockers are also an effective combination for reducing blood pressure, BUT since both  increase blood glucose concentrations,  use with caution in patients at risk for diabetes.  Angiotensin-converting enzyme inhibitor ACEIs’ main side effect is cough (most common in women and in patients of Asian and  African background). Angioedema is an uncommon but potentially serious complication that can threaten airway function, and it occurs most frequently in  black patients.

Given the above -quoted longstanding established dangers of bblockers and ACEI; and that the  majority of older State chronic  patients around Cape Town are black and Asian women,  overweight hypertensive diabetic smokers, it is negligence on the part of State authorities that most State patients are treated with deleterious betablockers (atenolol), Angiotensin blockers and HCTZ ; instead of primarily with the longproven optimal lowdose reserpine, amilozide and amlodipine.

    30 Nov 2014  NEW  studies below  confirm  that the renin-angiotensin-aldosterone system RAAS  and the autonomic nervous systems ANS  are the two networks that primarily regulate bloodpressure.   In baseline treatment of common essential HBP, Increasing recent research points to the prime role of amiloride  –  thiazide combination  eg Moduretic, Amiloretic –  and arginine (nitric oxide stimulant) – addressing the RAAS;  – with reserpine  addressing the  ANS and anxiety.   

This combination overcomes much of the pathophysiology of  essential HBP ie raised cardiac output, and  aldosterone excess  sodium retention vascular load increase, potassium-magnesium wasting,  endothelial swelling ie stiffness  from low nitric oxide; vascular spasm;  and insulin resistance from aldosterone (and  thiazide and betablocker);  and counterbalances the harms of higher-dose thiazide (glucose intolerance-lipidemia, potassium-magnesium-wasting, hyperuricemia), but also avoids the numerous adverse effects of  spironolactone (a steroidal antihormone) and triamterene;

and the cardiorespiratory risks of betablockers, and ARBs. The evidence in fact supports use of amiloride lowdose preventatively in a highrisk prehypertensive population. just as the prohormone metformin is used preventatively in reversing weight gain to prevent diabetes, atheroma and PCOS inferti9lity..

refs: 1.  Nutr Hosp. 2014 Dec.   ALDOSTERONE: A CARDIOMETABOLIC RISK HORMONE?    Pereira Bressan  ea.University of Viçosa, Brazil..  Aldosterone is a component of the renin-angiotensin-aldosterone system, classically known for its role in sodium and water retention. Besides its renal effects, aldosterone is associated with the pathogenesis and progression of metabolic syndrome components. Diet can affect plasma aldosterone levels; high fructose and fat intake can lead to increased aldosterone levels, whereas the effect of sodium intake remains controversial. Adipose tissue, particularly visceral tissue, appears to produce a lipid-soluble factor that increases aldosterone production. Patients with metabolic syndrome have higher aldosterone levels; moreover, an increased cardiometabolic risk associated with insulin resistance could be partially mediated by the action of aldosterone via mineralocorticoid receptors. Even a subtle activation of this hormonal system may have deleterious effects on the glucose and lipid metabolism related to metabolic syndrome.

2. Semin Nephrol Sept  2014 . . Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels.    Judd EK1, Calhoun DA2, Warnock DG2. University of Alabama.    Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. In the absence of demonstrable renal, vascular and common endocrine causes, pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Dogma attributes increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects. However, emerging research,  has identified and defines the function of amiloride-sensitive sodium channels eNaC and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. It thus highlights the cardinal role of amilozide in hypertension therapy.

3. Pflugers Arch. 2014 Nov:  Salt controls endothelial and vascular phenotype.Kusche-Vihrog ,  Brand ea. University of Muenster,  Germany. High salt (NaCl) intake promotes  development of vascular diseases independent of  rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. We focus on  endothelial Na+ channel (EnNaC)-controlled nanomechanical properties, since high Na+ leads to an EnNaC-induced Na+-influx and subsequent stiffening of endothelial cells. Mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of arginine, direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function.

4. J Clin Hypertens (Greenwich). 2014 Jan  Epithelial sodium channel eNaC inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.   Bhagatwala , Dong  ea, Regents University, Augusta, GA.. Overactivity of epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In a nonplacebo-controlled clinical trial , the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.
5. J Hum Hypertens. 2013 Nov Diastolic blood pressure reduction ontributes more to the regression of left ventricular hypertrophy: a meta-analysis of randomized controlled trials.  Zhang  Huang ea Sun Yat-sen University, ChinaLeft ventricular hypertrophy (LVH) is an independent cardiovascular risk factor; however, the key strategy necessary for LVH regression in hypertensive patients is not clear. A meta-analysis was conducted to study the effect of blood pressure reduction on LVH regression. A total of 17 randomized controlled trials comprising 2196 hypertensive patients (mean age, 56.3 years; 64.1% were men) were identified. The most significant decrease in LVH was seen in patients with a mean age over 60 years in the DBPM10 group. The renin-angiotensin system inhibitor was found to be the most effective antihypertensive drug for LVH regression. This meta-analysis result indicates that proper DBP reduction plays an important role in the regression of echocardiographic LVH in hypertensive patients.

6. Hypertension. 2012 .Double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension. Stears, Brown ea University of Cambridge.    Hypertension guidelines advise limiting dose of thiazide diuretics and avoiding combination with β-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. . For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001).  There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or β(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.

7.   Am J Physiol Endocrinol Metab. 2008  Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.  Gunawardana , Piston ea .Vanderbilt University, Nashville, TN. Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we  demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

8.  Circulation. 1995 Comparison of five antihypertensives and placebo on nutritional-hygienic therapy in  Treatment of Mild Hypertension Study (TOMHS). Liebson, Stamler ea . St Luke’s Medical Center, Chicago, in a double-blind, placebo-RCT  of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five  antihypertensive agents: (1) thiazide (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin), (4) calcium antagonist (amlodipine ), or (5) ACEI (enalapril).  Changes in BP averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that continued for 48 months.  chlorthalidone  caused the greatest decrease in LVM at each follow-up visit (average decrease, 34 g),  (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). 

9.  Arch Intern Med. 1981  Multiclinic comparison of amiloride, hydrochlorothiazide, and hydrochlorothiazide plus amiloride in essential hypertension. Multicenter Diuretic Cooperative Study Group.   [No authors listed}  A randomized, double-blind, multicenter study comparing amiloride hydrochloride, amiloride hydrochloride plus HCTZ, and HCTZwas conducted in 179 patients with mild to moderate essential hypertension (diastolic pressure, 95 to 115 mm Hg). After 12 weeks of treatment, significant reductions in pressure were observed for all three treatment groups. Systolic pressure reduction was greatest for amiloride plus hydrochlorothiazide. Baseline vs 12-week average supine pressures were 153/101 vs 139/93ie -14/8 mm Hg for amiloride, 160/100 vs 137/90 ie -23/10mm Hg for amiloride plus HCTZ, and 154/101 vs 134/89 ie -20/12mm Hg for HCTZ. Baseline vs treatment mean serum potassium levels were 4.24 vs 4.47 mEq/L for amiloride, 4.24 vs 3.86 mEq/L for the combination, and 4.15 vs 3.56 mEq/L for HCTZ. The changes in serum potassium level from the baseline for amiloride plus HCTZ were significantly different from those for HCTZ throughout the study (except for week 6). All drugs were well tolerated, and no drug-related toxic reaction was detected. This study demonstrates the efficacy of amiloride and amiloride plus HCTZ as diuretic antihypertensive potassium-conserving agents.

27 Nov 2014 THE IMPORTANCE OF NORMALIZING RESISTANT HYPERTENSION : THE ALLHAT TRIAL Furberg ea  December  2002 was the biggest  trial that compared a thiazide with other standard antihypertensive drugs in highrisk patients, and confirmed thiazide’s  superiority over amlodipine, lisinopril, and especially doxazosin. This was confirmed in the smaller shorter CONVINCE multinational trial Black ea a few months later, which showed that as single therapy, verapamil was inferior to a thiazide or atenolol.

The latest report of the landmark  5 year USA ALLHAT trial by Munter ea  now reports  on apparent   Treatment-resistant hypertension aTRH  and the incidence of cardiovascular disease and end-stage renal disease: “These results demonstrate that aTRH increases the risk for cardiovascular disease by almost 50%, doubled end-stage renal disease, and increased all-cause mortality- heart and peripheral circulatory failure  – by 30%. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14684 (ALLHAT) participants to determine association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined  Apparent treatment-resistant hypertension aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002.

24 Nov 2014  NOTE  how Big Pharma has lied in corrupting the Wikipedia section (in italics below)  on reserpine so as to try to further sideline this excellent natural drug: the adverse  highlights below  in red are based on ancient data from when Reserpine  was used decades ago in the West in 5 to 50 times higher doses than have been used without adverse effects in trials the past  20 years, and for centuries in India as the parent Rauwolfia:

Reserpine:because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.Nonsense. This ignores the numerous side-effects of betablockers, ACEI, ARBs and CCBs other than amlodipine.  The reserpine-induced depression is considered by some researchers to be a myth, while others claim that teas made out of the plant roots containing ie lowdose reserpine has a calming, sedative action that can actually be considered antidepressant.[4] Notably, reserpine was the first compound shown to be an effective antidepressant in a randomized placebo-controlled trial.[5]      It may take the body days to weeks to replenish the depleted VMAT, so reserpine’s effects are long-lasting- a major advantage if patients take drugs irregularly. Tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine.[8]

This depletion of dopamine can lead with reserpine overdose to drug-induced parkinsonism. THIS IS ONLY IN EXCESSIVE RESERPINE DOSE.  Reserpine has been discontinued in the UK for some years due to its numerous interactions and side effects. nonsense it was discontinued to protect Big Pharma newer antihypertensive drugs eg  Cardura, metoprolol, lisinopril; ARBs, Exforge etc .

“THE Reserpine-THIAZIDE  COMBINATION (WITH OR WITHOUT OTHER OLD DRUGS EG POTASSIUM-SPARERS AND HYDRALAZINE)  is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality:

“The Hypertension Detection and Follow-up Program,[14] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,[15] , the Systolic Hypertension in the Elderly Program, and now the Chinese reserpine trial 2011- which outstanding results  the Wiki article  doesnt bother to  mention. .

Reserpine is rarely used in the management of hypertension today. NONSENSE – that is merely the explicit wish and intent of Big Pharma.  Reserpine is listed as an option by the JNC 7.[17] Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.[18]   The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25 mg – IN FACT 0.0625 t0 0,125MG/dAt doses of less than 0.2 mg/day, reserpine has few side effects, the most common of which is nasal congestion- SO WE NEVER PERSIST WITH  above 0.125mg/d

ONLY IN GROSS OVERDOSE:”There has been much concern about  Reserpine causing: depression leading to suicide; nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration , stomach cramps,diarrhea.. . hypotension, bradycardia; Congested nose,erectile dysfunction drowsiness, dizziness,.. nightmares. Parkinsonism … General weakness, fatigue … may worsen asthma ; hyperprolactinemia… dangerous decline in blood pressure at doses needed for treatment. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. . The above litany conveniently omits that these problems were reported in uncontrolled studies using reserpine doses averaging 0.5+ mg per day.[22][23] they do not occur at effective  low antihypertensive reserpine dose combined with lowdose diuretic. “

Nine years ago we reviewed in the BMJ  why reserpine plus thiazide is  The best-proven two-drug hypertension regime in primary care,

update 20 Nov 2014  the Sept  2014 influential French review Prescrire Int reviews the available evidence Treating essential hypertension- As in 2004, the first choice is usually a thiazide diuretic TZD  .. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/90-100  mmHg. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. systematic  meta-analyses of  tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose TZDs and angiotensin-converting enzyme (ACEI) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevent  about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Systematic reviews conclude that neither calcium-channel blockers CCBs, ACEI nor beta-blockers BBs are more effective than thiazide diuretics TZDs  in reducing mortality or the incidence of stroke. The efficacy of the TZD chlorthalidone is supported by the highest-level evidence, three comparative clinical trials versus placebo, an ACEI, or a CCB, in more than 50 000 patients. In one of these trials, chlorthalidone was superior to the ACEI lisinoprilin preventing stroke; and  to the CCB amlodipine in preventing heart failure. The effect of hydrochlorothiazide HCTZ , combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, BBs, or a CCBHCTZ appeared more effective than the BB atenolol in reducing the incidence of coronary events.  Indapamide another TZD is less convincing that it is more effective than chlortalidone or HCTZ. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As in 2004, in 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be a thiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACEI: captopril, lisinopril or ramipril.

But TZDiuretic halflife is at best 15hrs (HCTZ); and for smoother hypertension control they need to be gentle and not major diuresis-inducing,  so that they do not disturb sleep or daytime function. and TZDs dont damp down compensatory heart speedup and arrhythmia, or lipidemia-hyperglycemia- which reserpine does. and lowdose reserpine doesnt cause the cough or breathlessness that ACEI, ARBs or BBs may.

This review needs to be read with Shamon & Perez‘  2009 University of British Columbia Canadian Cochrane report : the first systematic review of reserpine for essential hypertension  “Many antihypertensive agents exist today for primary hypertension (systolic blood pressure >/=140 mmHg and/or diastolic blood pressure >/=90 mmHg).  Reserpine was  a second-line therapy in some of those trials.   Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with hypertension.  MAIN RESULTS: Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction on reserpine compared to placebo (WMD –8mm, 95% CI -14.05, -1.78).   None of the included trials reported withdrawals due to adverse effects.   AUTHORS’ CONCLUSIONS: Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. But this analysis is outdated because it has long been common cause that  the best firstline treatment of hypertension is the balanced combination of reserpine with a potassium-sparing diuretic.

Lowdose Reserpine is the sole anxiolytic antidepressant antipsychotic antiserotoninergic antihypertensive drug that lasts, acts  for weeks  rather than days (amlodipine) or  hours (the TDZs, ACEI, ARBs)- and has no adverse effects; so it doesnt matter when it is taken;  when stopped, it takes weeks for it to completely wear off. And severe stress anxiety insomnia is so often a major component of severe essential hypertension. “Reserpine is an ancient tranquilizer, derived from a plant used in India for centuries. It has a powerful tranquilizing action, has been used to treat hypertension, and was found to be an antidepressant (Davies and Shepherd, 1955)”

Hence combining lowdose eg 0.125mg/d or less reserpine – even 3 days a week ie 0.05mg/d-  with amilozide 13-27mg/d as a morning or midday  dose  is ideal- especially when nighttime systolic hypertensionNSBP  is the strongest predictor of CVEs cardiovascular events, as shown in a new international study in Europe, Brazil, and Japan by Universities of USA, UK and Europe:  Roush, Zamalloa ea The ABC-H Investigators ; Journal of Hypertension (Oct 2014)   Prognostic impact from clinic, daytime, and night-time systolic blood pressure NSBP in nine cohorts of 13 844 patients with hypertension;     To determine which SBP measure best predicts cardiovascular events (CVEs- coronary artery disease CAD and stroke) independently, systematic review was conducted for all patients with hypertension,>1+ years follow-up..   Nine cohorts (n = 13 844) were from Europe, Brazil, and Japan. Results: Overall, NSBP’s dispersion exceeded DaySBP’s dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for ClinicSBP and DSBP ( P = 0.004)  Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP:  In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely. This trial confirms the 2012 Hosomi ea Japanese trial showing that to minimize (repeat) stroke from night BP variance, Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.

Weiss’s Herbal Medicine  2001 pp 151-157 reviews why lowdose reserpine/rauwolfia is the prime baseline antihypertensive, via the central especially  autonomic nervous system as a major anxiolytic.

There is no evidence in chronic treatment of common essential hypertension to justify loop diuretics eg furosemide , as is common practice locally. .

update 12 Oct 2014     For the past decade we have advocated  for uncomplicated patients the gold-standard evidence-based combination of reserpine  0.0625 to 0.125 mg with  1/4  Amilozide (ie hydrochlorothiazide  HCTZ 12,5mg and amiloride 1.25mg) ie HAR daily as the most cost-efficient baseline treatment of hypertension.    Sometimes patients require the lower doses 1/4 tab each reserpine and Amiloretic 55mg) only 3 times a week for good control once on some cod liver oil, coconut oil and multivite-multimineral  to reverse arteriosclerosis, insulin resistance, reactive oxygen species,  and promote nitric oxide.

For more resistant cases we add  dihydralazine 25 mg/d or amlodipine 5 to 10mg as add-ons if required  – if necessary both-  occasionally for optimal HBP control around 120  to 130 systolic (the new international  Guideline target). With this regime of up to five drugs all more than 40 years in use, for hypertension we rarely find need to add the more costly / troublesome old eg methyldopa, or betablockers, spironolactone,   or new eg ACEI or ARBs ,  with   their  cardio-respiratory risks that are so rare with the  multi-low dose reserpine- amilozide- amlodipine- dihydralizane  combination.

There are now 250 000 antihypertensive drug studies on Pubmed since 1947.

 The latest  and definitive study  published on reserpine for HBP in Clin Drug Investig. 2011;31:769-77 is   Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China a  massive  3 year (4500 patient-years) study  by  Wu Y, Li L. ea of   Peking University Health Science Center, China   .  A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide  HCTZ 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and  reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although used in China for more than 30 years, there have been few comprehensive evaluations of this treatment.          METHODS  open-label surveillance study in Shanghai in local primary healthcare settings. Subjects  with  essential hypertension, aged ≥35 years at the time of enrolment. Patients with secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional HCTZ was added. Blood pressure (BP) was measured every 3 months.    RESULTS: A total of 1529 patients (65%  female; mean age 65.7 years) entered the study with mean BP 149/89. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipids, uric acid and potassium improved.                                                               CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

The mean  15/10  BP lowering  from a mean baseline BP of 149/89 after 3 years of the four-drug Chinese combination  in China   compares  starkly with the mean ~51/30 mm Hg lowering (from untreated HBP of 200/120 down to ~149/90)  over 4 months reported  below  by Alan Taylor in his 1989 thesis study in local rural Africans with similar doses of reserpine, HCTZ and dihydralazine- Taylor’s study achieving in rural Blacks  in 4 months the starting BP of the Chinese some 25 years later.  But  the long Chinese study speaks to to the tolerance of the HTDR combination.

The China reserpine study  of 1500 pts, 4500 pt years, strongly complements the ~13 trials  of reserpine   between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials)  in 7500 patients for 1 to 3 years;   showing that low dose reserpine (and lowdose  thiazide ) together are  as good as or better than all more modern drugs- especially when augmented by amiloride.

(As Prof YK Seedat reported  here  in 2000), the China   paper reports zero noteworthy dihydralazine  risks at 12.5mg/d :     J Hum Hypertens. 2000 ;14:739-47. Hypertension in developing nations in sub-Saharan Africa. Seedat YK. University of Natal,  South Africa.  There is a rapid development of  ‘second wave epidemic’ of cardiovascular disease that is now flowing through developing countries and the former socialist republics. It is now evident from WHO data that coronary heart disease and cerebrovascular disease are increasing so rapidly that they will rank No. 1 and No. 5 respectively as causes of global burden by the year 2020. In spite of the current low prevalence of hypertensive subjects in some countries, the total number of hypertensive subjects in the developing world is high, and a cost-analysis of possible antihypertensive drug treatment indicates that developing countries cannot afford the same treatment as developed countries. Control of hypertension in the USA is only 20% (blood pressure <140/90 mm Hg). In Africa only 5-10% have a blood pressure control of hypertension of <140/90 mm Hg. There are varying responses to antihypertensive therapy in black hypertensive patients. Black patients respond well to thiazide diuretics, calcium channel blockers vasodilators like alpha-blockers, hydralazine, reserpine and poorly to beta-blockers, angiotensin-converting enzyme inhibitors and All receptor antagonists unless they are combined with a diuretic.  There are social, economic, cultural factors which impair control of hypertension in developing countries. Hypertension control is ideally suited to the initial component on an integrated CVD control programme which has to be implemented.  The existing health care infrastructure needs to be orientated to meet the emerging challenge of CVD, while empowering the community through health education.

Interestingly, a new  metaanalysis of HCTZ trials  by Musini ea Cochrane Database Syst Rev. 2014 May   Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. shows that BP lowering  over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews. 

2009:     ABSTRACT: When modern antihypertensive drugs cost far more than the old and tried, and have around 40% risk of adverse effects (Girerd 2002 Paris),  and give inferior risk reduction, it is unethical for routine hypertension patients initially to  be  prescribed modern drugs singly or in combination in uncomplicated cases before trying the gold standard old risk-free lowdose reserpine-amilozide combination.

2009 has been a landmark year of published studies on first-line  hypertension treatment.

IT IS COMMON CAUSE THAT:

i. hypertension  (with or without overweight- excessive waist girth) is today the commonest presenting, simply detectable, monitorable and controllable chronic lifestyle degenerative disease;

ii. the bedrock prevention and therapy  of essential hypertension is  public- patient  education – exercise, stopping smoking,  and minimizing salt (since 1904) , sugar, alcohol and cooked fat intake so as to reduce overweight;

iii. genetics and the above risk factors aside, three  of the primary “endogenous”  and easily correctable causes of essential hypertension are water deficiency; marine omega3 (EPA eicosapentanoic and DHA docosahexanoic acid) deficiency; and insulin resistance if not frank adiposity/overweight and diabetes.

So adequate water intake, and fish oil, and metformin/galega to tolerance, (in appropriate adipose/overweight  cases) are cornerstones of antihypertensive therapy along with diet and lifestyle changes before any antihypertensive drugs are added.

Recently there have been contentious suggestion  (eg Law and Ward UK 2009)  that target bloodpressure should be that of youth- 120/70 down to 100/60 – as long as it does not fall so low that the patient gets dizzy on standing up. But the non-contentious gold standard remains  that no one should be left with bloodpressure above at most 140/90 sitting.

ANTIHYPERTENSIVE DRUGS: There are over 34 000 RCTs, reviews and metaanalyses  (since 1965) on Pubmed on these drugs.

Controlling   hypertension asymptomatically  before it causes damage and symptoms is the heart of successful prevention.

It is now claimed  that hypertension risk starts as low as >120/70, that we should be targeting this level if tolerated.

This can only be done gently and slowly, if possible by optimising diet , lifestyle and natural supplements.

But prevention in asymptomatic patients must especially be at most a once-a-day regime, and avoid causing symptoms, and still give stable cover even if taken erratically. Only reserpine provides gentle cover lasting weeks, thus avoiding wide BP variation due to erratic dosing.

Apart from the notorious adverse effects of the older antihypertensives like guanethidine, methyldopa and atenolol, search of Pubmed under  ‘ARBs, ACEI Cough;’ and under metaanalysis ‘antihypertensive cough’  with the established drugs, reveals 10 abstracts since the mid 1990s.

The nub of the matter is, the lowest-cost multiple-combination therapy (lowdose reserpine -amiloride – hydrochlorothiazide) gives the best bloodpressure and risk reduction with zero adverse effects – especially when combined with probably the best pluripotential drug of all,  fish oil..   A new Cochrane metaanalysis from Univ Brit Columbia confirms that lowdose thiazide gives the best reduction of all antihypertensives in both all-morbidity and mortality outcomes -RR 0.89 (CI 0.82-0.97, p=0.0067 = highly significant) . And that metaanalysis didn’t deign to mention reserpine in the abstract.

There are at least a dozen trials each of reserpine and thiazide  showing that they are the best,  ideally in lowdose combination .   As always, one fixed-dose combination pill (eg Brinerdin, Rautrax Imp) may work for many. But it is both cheaper, more efficient and scientific to prescribe the components separately so that reserpine and amilozide can  each be titrated individually to tolerance, starting with eg reserpine (0.25mg tab ) 1/4/day and amilozide (55mg tab) 1/4 a day (costing locally retail  perhaps US$0.5/month, $6/year) …

In some patients eventually this dose 3 days a week is all that is needed. With sensible advice about omitting sugar and smoking, and minimal alcohol, salt and cooked fats, and adding a multinutrient including magnesium, vitamins and the many favourable biologicals (including appropriate physiological sexhormone replacement), few patients need more than 1/2 a tab each of reserpine and amilozide for optimal BP and metabolic-vascular risk control. In the rare still- resistant cases, amlodipine is the next safest effective antihypertensive  drug to add, starting with 2.5mg/d. But of course in those with insulin resistance (ie most cases), metformin is the most appropriate pluripotential drug.

Yet no trial has shown  lower cost, and better superiority and safety  of any modern-drug  or combination over the triple-combination  lowdose amilothiazide (thiazide since 1956, amiloride since 1967)  with  lowdose reserpine (from the ages-old rauwolfia – extracted  as reserpine since 1949). Since the German Reserpine trials, and results of ALLHAT and SHEP showing that reserpine as add-on gave  by far the best clinical outcomes, no head-on trials against modern drugs dare be done by drug companies or the clinicians they employ.

Over a year ago this column   reviewed that fifty year old treatments of overweight -hypertension – diabetes are still best, echoing an SAMJ analysis 24 years ago of New antihypertensive drugs–blessing or costly nemesis? .

In 1989 pharmacist Alan Taylor published his MPharm thesis (Rhodes University)  on Cost Effective Antihypertensive Therapy at A Day Hospital. – showing in a prospective randomized controlled trial for 4 months that stepped outpatient care (starting with a mean untreated BP of about 200/120) achieved the target BP ( then <165/95) in 73% compared to 11.5% on individualized treatment, and with a cost saving of 36%, with somewhat lower incidence of side effects. Hydrochlorothiazide HCT 12.5 to 25mg/d was the first step;  methyldopa 250-500mg/d or reserpine  0.1mg/d  as the 2nd; hydralazine 10-50mg/d  low dose as the 3rd, alternatively atenolol  100mg as the 3rd or 4th step. Individualized treatment reduced bloodpressure by a mean  32.6/19 whereas stepped-care did so by 51.6/29.5mm Hg.. The HCT-Reserpine- Hydralazine-atenolol regime was the most frequently prescribed (in 61.6%),

Obviously today methyldopa, hydralazine  and atenolol have become last-ditch add-ons, with amlodipine being the 1st- choice 4th drug to add to reserpine and amilozide. ,

and  in 2007 Rayner, Blockman ea from the Hypertension Clinic    at Groote Schuur Hospital found that at two community  health clinics  in Cape Town, only 40% of patients achieved a bloodpressure below 140/90, on a mean of 2.4 drugs per patient   – clinics where reserpine and amilozide were unwisely  removed from the available drug list years ago, for no plausible reason, leaving hydrochlorothiazide, atenolol, hydralazine and amlodipine as the choices- with invariably poor results in poor patients attending such free clinics.

MODERN DRUGS?  But why should patients be subjected to the multiple and indisputable major risks of modern antihypertensive drugs compared to the gold standard lowdose reserpine and low dose amilozide?

eg

ABs angiontensin blockers – ACEI agiotensin converting enyme inhibitors and ARBs angiotensin receptor blockers like enalapril, candesarten  – pervasive cough, rashes, but far worse, lifethreatening angiodema, asphyxiation, skin sloughing; and now well-recognized acute or slowly progressive loss of kidney function- which doesnt always reverse on stopping the drug (Onuigbu ea  2008, 2009); Suissa ea  2006 at McGill University published the first major longterm – > 10year- followup (1982-1997)  of hypertensive diabetes patients, showing that compared to thiazide, only  ACEI increased the risk of endstage kidney failure 4.2 fold.

betablockers like atenolol, metoprolol – too slow heart rate, cold extremities, more depression, impotence,  asthma, glucose intolerance/ diabetes, heart failure, deaths;

and even calcium channel blockers -the gold standard of which is amlodiopine- have a formidable list of potential adverse effects (that lowdose reserpine and amilozide lack), of which some may be major nuisance if not dangerous eg (from the Sandoz product sheet): Often: dizziness; palpitations; muscle-, stomach– or headache; dyspepsia; nausea – in 1 in 100 users; Sometimes: blood disorders, gynecomastia, impotence, depression, insomnia, tachycardia – in 1 in 1,000 users;  erratic behavior, hepatitis, jaundice – in 1 in 10,000 users; Very rarely: hyperglycemia, tremor, Stevens-Johnson syndrome – in 1 in 100,000 users. ”

From the trials and experience, lowdose amlodipine is certainly the modern drug of choice to add if counselling plus ceiling doses of reserpine and amilozide, plus fish oil plus  metformin for underlying adiposity/insulin resistance,  do not adequately control hypertension and other risk factors.

Why use modern drugs with their major potential hazards  except for special circumstances last ditch?; when lowdose reserpine plus lowdose amilozide titrated to best effect rarely need a 4th drug added for good BP control;  and practically – unlike methyldopa, guanethidine and more modern drugs-  never causes persisting symptoms.

THIAZIDE ADVERSE EFFECT possible in even very low dose: anaphylaxis: Goetschalckx ea in 2007 could find exactly 49 case reports of allergic thiazide-induced pulmonary oedema in the literature after 50 years of use ie millions of patient-years. Thiazides are obviously sulphonamides, but fortunately serious- anaphylactic- reactions like lupus vascullitis and shock – are extremely rare. Wikipedia does not even mention these under thiazides, and no abstracts on Pubmed even guess at their rare  incidence. 50 cases in at least 10million patient years is an incidence of below 5 per million.

RESERPINE:   In 2007 Jos Barzilay ea documented Getting to goal blood pressure: why reserpine deserves a second look.

We last year examined closely the trials on thiazides and reserpine 1, 23.

and we published on line the only ever tabulation of all accessible trials  of thiazides and reserpine, showing in the ~12 thiazide trials between 1985 (the UK MRC trial)  and 2003 (the CONVINCE trial) that  in 115000 patients for a mean of 4 years,  thiazide is as good as or better than all more modern drugs;

and that reserpine in ~13 trials between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials)  in 7500 patients for 1 to 3 years is as good as or better than all more modern drugs. Of course  the 2003 ALLHAT  and CONVINCE papers were by far the biggest trials validating thiazide as the gold standard in 50 000 patients for  3 and 5 years respectively;

and the VA trials of 1977, 1982 and  and 1990 in 1479 patients showing reserpine as equal or superior to betablockers,  and the German trials of 1997  in 400 patients (Griebenow, Pittrow ea 1997) validating reserpine as equivalent to thiazide or a CCB, and the combination of thiazide and reserpine superior to an ACEI.

Now in 2009:

Shamon ea’s Cochrane review last month confirms that reserpine  alone is at least equivalent  in antihypertensive effect to any  modern first line antihypertensive alone ;

Wald and Law’s metanalysis of single or combination antihypertensives confirms that  “The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.”

Wright ea’s Cochrane review confirms that

“thiazides reduce all-cause mortality by 11%;   Low-dose thiazides (8 RCTs) reduced CHD  by 28%;

Beta-blockers and CCB reduced stroke by 17% and 42%, but not CHD  or mortality .        ACE inhibitors reduced mortality 17%; stroke  35%.

No RCTs were found for ARBs or alpha-blockers.”

However, that abstract does not enumerate the major adverse effects of betablockers and ABs.

Wright ea’s   ALLHAT reanalysis confirms that thiazide was superior to the ACEI, CCB, betablocker and especially the alphablocker doxazocin. neither alpha-blockers, ACEI nor CCBs  surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF. new-onset DM associated with thiazides does not increase CVD outcomes.”

Costanzo ea’s Italian study confirms that CCBs reduce the risk of stroke by 14% compared to ACEI; reduce allcause mortality by a trivial 4%; increase heart failure by 17% compared with ‘active’ treatment;

Hoffman ea’s review from New York confirms that, in autopsies of Alzheimer cases, those on antihypertensives had far less plaques that those without hypertension.

Sozen ea confirms that “ABs- Drugs with blocking effects on the renin-angiotensin-aldosterone system –  do not improve endothelial dysfunction long-term in hypertensive patients”.

Mackenzie ea’s Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension shows that central Pulse Pressure was only reduced significantly by perindopril, lercanidipine, and bendrofluazide, whereas atenolol had no effect. Lercanidipine reduced the augmentation index, whereas atenolol increased it. Aortic pulse wave velocity was not changed by any of the drugs. In summary, despite similar reductions in peripheral systolic and PPs with the 4 classes of drug, changes in central pressure and augmentation index varied. Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension, the choice of therapy may be influenced by these findings in the future.”

Landmark’s Norwegian abstract confirms that thiazides (and betablockers)  increase insulin resistance and blood glucose risk (let alone lipidemia), but simply – selectively- as usual ignores that neither lowdose amilozide nor reserpine do this.

Nothing illustrates better why the triple combination of amilozide and reserpine is the best.

It has previously been pointed out that in the long term Cache County study, potassium-sparing diuretic was the only antihypertensive that lowered- in fact by 75% – the incidence of new Alzheimers disease;  and amilozide-like combinations are more effective than either component alone in safely and effectively lowering hypertension. – Patterson Dollery & Haslam in 1968; Rosenfeld in 1980; and the Multicenter Diuretic Cooperative Study Group in 1981.

CONCLUSION:  Reserpine has indisputable central and peripheral benefits in lowering central pressure via peripheral vasodilation, and via mild lowering of anxiety, cardiac rate and cardiac output; while thiazide and amiloride both lower both excessive body salt and water, while thiazide vasodilates and conserves calcium,  and amiloride  reverses the  potassium -magnesium depletion  seen in hypertension and with thiazide. .

Since the lowdose combination of reserpine and amilozide is superior to all other first-line drugs alone or in combination, and retail costs about   US$1 a month in South Africa, (with negligible adverse effects compared to all other antihypertensive drugs), this combination is the mandatory  firstline therapy for all  hypertensive patients, with rare exceptions. This regime  starts with amilozide 13.75mg (1/4 tab) and reserpine 0.0625mg (1/4tab) /d- and many patients can eventually be controlled with these doses just 3 days a week; with other antihypertensives added only if hypertension is not controlled with these increased to the ceiling tolerated eg of amilozide 27.5mg/d and reserpine 0.125 mg/d (maximum reserpine 0.25 mg 5/week ie 0.18mg/d if tolerated).

Since roleplayers are there to serve patients, not the Drug and Disease Industry, all roleplayers ( National Hypertension societies, provincial and national health and medical school authorities, medical schemes and all health practitioners)  have no choice but to obey the gold-evidence-based medicine set out herein, and reinstate reserpine and amilozide as mandatory 1st-line therapy of essential hypertension, with motivation  for alternatives to be provided in the  exceptional cases.

Unlike the USA and the East  where reserpine is still in national recommendations,  Authorities, regulators, suppliers and prescribers  in South Africa, Australia, the UK and Europe can no longer continue to defraud the public and deny patients this best treatment, since the two tablets (cheap amilozide and reserpine) are freely and universally available for  at most the retail South African prices quoted (less in bulk buy).

There is no shortage of reserpine, HCT or amiloride;  and the evidence for them over all modern antihypertensives  is binding under  rules of evidence and therefore medical ethics. The current evidence discussed shows that this  old lowdose combination is superior to all modern drugs and modern marketted combinations in both reduction of all-cause endpoints, adverse effects, and cost.

As Henry Black said recently, triple antihypertensive therapy is simply Back to the Past – and it can be both very low cost and risk-free..

And if proof is wanted, we must agree on a simple long term multicentre trial of the lowdose reserpine-amiloretic regime versus modern marketed combinations.- as in  ALLHAT but comparing combinations..But who is to pay for yet another trial to prove what is already so well proven?

35 years after Illich’s Medical Nemesis, it is very sad to have to be fighting overwhelming profiteering vested interests for what is now by far the commonest and most easily correctable major common degenerative disease – mild to moderate hypertension.

SPECIALIST NATURAL MEDICINE CLINIC 2015

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

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

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

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

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

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

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

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

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

METFORMIN REDUCES ALL CHRONIC DISEASES, INCLUDING IMPROVING THYROID FUNCTION.

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

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

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

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

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

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

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

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

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

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

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

ndb.


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

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

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

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

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

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

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

Abstract

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

THE STATIN- FOR- ALL -SENIORS HOAX: FOR WHOM TOLLS THE BELL? FOR WHOM ARE STATINS EXCEPT RARE HIGH-RISK PATIENTS’ SEVERE HYPERCHOLESTEROLEMIA, AND PROFITEERING? FURTHER DISCREDITED FOR PRIMARY PREVENTION:

neil.burman@gmail.com

19 Sept 2014 update:     ABSTRACT:  readers  of this column recently commend its statin commentary, last updated in June, about the controversy of statins  in primary prevention of cardiovascular disease CVD. This update now  reviews crucial major recent evidence that the marketing hype  of “statin deficiency” in the average aging population is a  dangerous fabrication (eg Vytorin) of the $billion Disease and Drug corporate industry  – especially when statins inhibit omega3  and CoQ10 which like other human micronutrient protectors- magnesium, iodine, arginine, carnitine, ribose, vitamins , B, D3, C & K2,   and human  sex hormones – are increasingly deficient  or imbalanced in an aging western population and urban convenience food  diet.

     The prizewinning immunologist   Dr Duncan Adams from Univ Otago   in the elite QJM 2011 pithily demolishes The Great Cholesterol ie Statin Myth, commends the statin trials metanalysis of  Ray ea from Cambridge 2010 that showed no benefits of statins in mild to moderate cholesterolemia. .     More evidence says  dont use  natural supplements along  with statins to reduce statin risks and enhance statin benefits, but better to avoid the risks  from statins, smoking and excessive alcohol eg ROS reactive oxygen species , in an aging slothful  fattening population:  with improved exercise, more water, a Banting-type low-carbs high-fat and -greens – fermented (ie high in vit K2)  diet, a multivite-multimineral plus vigorous well-tolerated supplements of CoQ10,vits D3 and C, fish oil,  magnesium, sulphur, coconut oil, and appropriate metformin and human sex hormone replacement.
     Rather than  Big Pharma’s promotion of  Statinopause, statin deficiency ,  we need to address the multiple age-and diet-related deficiencies (and some excesses)  that lead to the preventible degenerative diseases of aging- and which are worsened by the Food Factory chain  promotion that has dictated the (Gary Taubes’  Diet Delusion  and Nina Teicholtz’ The Big Fat Surprise) expose  of processed grain-fed nutrient-depleted (but fructose-loaded) foods, high carbs low animal fat/cholesterol diet for forty years. This has   compounded the deficiency of -fat-soluble micronutrients   like vitamins D3, CoQ10, A,  E & K2,  lecithin and marine omga3 – EPA and DHA; and naturally compounded pollution  by environmental-  radioactivity, electromagnetic and radiofields-,   and air, foodchain and drug pollution the past 50 years years by plastics, CO2 and volatile emissions, mercury, aluminium, fluoride, lead, bromide;   micromineral depleted salt, fatally potent endocrine disruptors, antibiotics, xenohormones, pesticides  and numerous other synthetic drugs launched on the public until they are recognized to kill humans.        
                                                                                    

  Margaret McCartney  general practitioner, Glasgow writes : We lack the tools to help patients decide about statins BMJ 2014; 349 doi:     The National Institute for Health and Care Excellence (NICE) recently approved atorvastatin for people in England and Wales who have a 10% risk of a cardiovascular event within 10 years; it had previously been a 20% risk.1 GPs are advised to treat such people—which includes everyone older than 85—and to continually review everyone else in case they pass the 10% threshold.

          This decision on funding statins is based primarily on cost effectiveness to the NHS.2 The press release from NICE mentioned the potential benefit to the population (namely, it “could help prevent up to 28 000 heart attacks and 16 000 strokes each year”3) but not the absolute benefit to the individual.

But life is more complicated than that: people make choices for multiple reasons. Many patients stop taking statins after starting them4; others, faced with the choice of taking a drug with a small chance of benefit, would rather not do so; and some people will want to take them no matter how low their risk may already be.

We lack the tools to accurately predict individual risk at such low thresholds—leading to overtreatment and, to a lesser extent, non-identification of risk.5 The general practice cake is finite; cutting a bigger slice for healthy people at lower risk means a smaller slice for people who have symptoms and are unwell. The chance of a longer life is offered to people who are willing to take tablets consistently, but we know that these compliant patients are already more likely to live longer, even when taking a placebo.6 7 This policy, which benefits people who are already the healthiest, has the potential to widen health inequalities.

       Who is keeping an overview of where NICE is taking us? The conflicts of interest among the members on its drafting panels are buried in minutes rather than in the guidance itself, and we still lack public access to most of the trial data that NICE uses.8 But we are told to press ahead regardless when, most bewildering of all, we don’t have a decent shared decision aid—designed and tested for the five million more people advised to take statins—about the benefits and harms of statinisation and the management of cardiovascular risk.

      “Should I take statins?” is a question asked of GPs every day. We urgently need better tools to allow guidance to guide, rather than dictate new targets. Our lack of resources to deal with such a common question simply isn’t acceptable.

Background:
2013 Italian  Statin HMGA   study Pasin ea shows that statins- cholesterol-busters- do not help patients with sepsis.
A 2010   review Yue ea of all published studies in  3,022 postmenopausal women (mean age, >62.7 y), showed  that statin use doesnt prevent fractures or increases bone density.

why should synthetic designer metabolic poisons – statins-  be expected to help peripheral  conditions like fracture risk and menopause?  when statins promote diabetes – insulin resistance, and  block healthy  metabolism throughout the body, in brains, muscles, kidneys, skin- but especially  lowering liver manufacture of cholesterol that is one of our top lifegivers  for our needed reproductive and adrenal steroids- including our two prime anabolic steroids( vitamin D3 and androgen). And statins increase the risk of highly malignant Merkel Cell skin carcinoma by 25%, as well as dermatitis eg Ma .  ..

We have known for  ~forty  years that while anticholesterol drugs  are  valuable for  rare people with severe hypercholesterolemia HCH risk of  vascular disease, statins’  longterm adverse effects are numerous, and there has never been evidence to justify their routine mass  use  for mild to moderate HCH- ie CVS risk below ~15 to 20% in 10 years-   despite the Cholesterol-statin industry investing multimillions in their promotional trials and in their lobbyists.

The Sheffield Cholesterol  and Multiple Risk Table by Jackson ea 25 years ago in the Lancet  was impressive  as a guide to  life extension by taking a statin permanently. When used for secondary prevention of coronary heart disease CHD , treatment with an inhibitor of hydroxymethylglutaryl-coenzyme-A reductase HMGA results in worthwhile benefit that clearly exceeds any risk in patients whose risk of coronary death is 1.5% or more per year ie >15% per 10 years. This evidence can be extrapolated logically to primary prevention of coronary disease provided that treatment is targeted at those with similar or higher risk. The table highlights the predominant effect of age on coronary risk; a person who is free of vascular disease and younger than 52 years is unlikely to have the specified degree of risk. Even in older people (60-70 years) several risk factors are generally required to attain this degree of risk. Some people are candidates for lipid- lowering drug treatment with serum cholesterol as low as 5.5 mmol/L, whereas others with cholesterol as high as 9.0 mmol/L are not. Although cholesterol lowering is a powerful method for preventing coronary events in people at high risk, cholesterol measurement by itself is not a good way to identify those with high risk. At that stage I had already been advised for 20 years , and declined on the evidence,  to take an anticholesterol drug , since in my early 50s despite my cholesterol of 6-7, my normal weight, HDLC, Hcy, Lpa,  bloodpressure, blood glucose, lifestyle and diet  put me at low risk
.Now the updated Sheffield 2011 Table  is  by  Jackson et al  in the prestigious QJM. At my age and low risk factors (no FH of CHD despite familial risks  (diabetes, atrial fib and mild lipidemia), my  Sheffield score of about 10 barely  puts me into the statin benefit range of 5 months gained. My coronaries and carotids are clear of plaque at last imaging, on all the natural supplements mentioned in this review, but not statin or any other designer hypolipidemic drug. If my patients have already been started elsewhere on a statin, I suggest they try just 5mg/day to minimize risks. . .
ADVERSE EFFECTS:  by design, they are antimetabolic;  oxidant ie increase ROS reactive oxidant species;  reduce CoQ10 by 39%.  Although these adverse effects are dose dependent and may be rare, they are cumulatively serious against muscle, liver, kidneys, memory, mood,  pancreas,  skin, sexual function; they cause diabetes, neuropathy and perhaps worsen cancer.  Thus they are like cancer chemotherapy, only for severely ill patients ie those with severe familial hypercholesterolemia..
     As  Beyond Health summarizes last year,      “Cholesterol does not cause heart disease. The French  Paradox- they have the highest average cholesterol in Europe, around 250mg(6mmol/L), but the lowest incidence of heart disease and half the heart attacks we have here in the U.S. In Crete, the home of the healthy Mediterranean diet, a 10-year study failed to find a single heart attack despite average cholesterol levels well over 200 (5 mmol). There are as many heart attacks in people with cholesterol levels over 300 (7.5mmol) as those whose levels are under 200 . Half of all heart attacks occur in people with normal cholesterol levels.   Cognitive problems affect about 15 percent of statin users, including episodes of temporary amnesia called transient global amnesia (TGA). Statins have an adverse effect on tau, a protein made by brain cells that helps maintain their structure. Abnormal tau proteins are linked with neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.  Statins  cause progressive cognitive decline, ranging from mild to severe, and anxiety, depression, inability to deal with stress, and violent behavior. Statin-takers are more likely to develop peripheral neuropathy, and to experience tremors and vertigo.  Other health issues linked with statins include cancer, suppressed immunity, cataracts and optic nerve problems, liver damage, impotence and loss of libido, hypersensitivity reactions that can lead to the autoimmune disease lupus, birth defects if taken by pregnant women, skin rashes and dryness, hair loss, gastrointestinal problems, insomnia, and pancreatitis. “
LESSONS FROM FAMILIAL HYPERCHOLESTEROLEMIA:
Wiki says In FH, Initial studies showed increased activity of HMGA but more showed that this did not explain the very abnormal cholesterol levels in FH patients. The binding of LDL to its receptor, and effects of impaired binding on metabolism  proved to be the underlying mechanism for FH.  Heterozygous FH is a common genetic disorder inherited   in 1:500 people in many “European”   populations – the Afrikaner, French Canadians, Lebanese Christians, and Finns have high rates of specific mutations that make FH particularly common in these groups. Homozygous FH is much rarer, occurring in 1 in a million births. Heterozygous FH is normally treated with lipid lowering agentsstatins, bile acid sequestrants.. . Homozygous FH often does not respond to medical therapy and may requires radical  other treatments.
 
       But search of Pubmed and Google  for STATIN mortality reduction IN FAMILIAL HYPERCHOLESTEROLEMIA gives few reports showing  that statins meaningfully reduce mortality  and add  QALYs quality life years.
                        A current comprehensive  Medscape review August 2014 Familial Hypercholesterolemia Medication  does not specify any  % reduction in mortality on statins or any other drugs, despite lowering LDLc levels 50-60%.
and  Familial Hypercholesterolemia.  Youngblom E, Knowles JW. Editors.  GeneReviews® Univ. Washington 2014 Jan  says Familial hypercholesterolemia (FH) is characterized by severely elevated LDL cholesterol (LDL-C) levels that cause atherosclerotic plaque deposition in arteries and a markedly increased risk of coronary artery disease at an early age. In FH, the more common CVD is coronary heart disease (CHD), which may manifest as angina and myocardial infarction; stroke occurs more rarely. Heterozygous FH is relatively common (prevalence 1:200-500). Persons with untreated FH are at an approximately 20-fold increased risk for CHD. Untreated men are at a 50% risk for a fatal or non-fatal coronary event by age 50 years; untreated women are at a 30% risk by age 60 years. In contrast, homozygous FH (HoFH)  is much rarer (prevalence 1:160,000 to 1:1,000,000). Most individuals with HoFH experience severe CHD by their mid-20s. The rate of either death or coronary bypass surgery by the teenage years is high.
Indeed,  Fred Raal, Dave Marais ea from their clinics’  long term results at   Wits and UCT showed Reduction in Mortality in Subjects With Homozygous Familial Hypercholesterolemia Associated With Advances in Lipid-Lowering TherapyCirculation 2011 but the ~60% reduction in mortality in the statin era in this rare group (187 such subjects, mostly Afrikaners, very few smokers) was even so statistically barely significant. When the patients lost to follow-up in the statin-naive group were included in the analysis and censored on the date that statin therapy became available, the hazard ratio for the end point of death remained barely significant at 0.38 (95% CI 0.15–0.94; P 0.04), and the hazard ratio for the end point of MACE was not significant 0.54 (95% CI 0.25–1.18; P=0.12)
However, a  new JAMA study   from the Netherlands paints a gloomy picture- following almost 277  kids from age ~14 years for  Ten-Year Follow-up After Initiation of Statin Therapy in Children With Familial Hypercholesterolemia, after 10 years twice as many of those on statins were smoking  compared to their “normal” sibs, but worse, the FH sibs on statins, despite 20% lower cholesterol,  had the same increase in carotid artery thickening as their sibs without FH.
 
Nordestgaard, Tybjærg-Hansen ea for the European Atherosclerosis Society Eur Heart J. 2013 say . Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population:  to prevent coronary heart disease: consensus. .  Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, LDLC targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counseling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD.                                                                                                                                                            
THE FAILURE OF EZETIMIBE, VYTORIN:
But ezetimibe as an addon to statin eg in  Vytorin has been thoroughly discredited.  As Forbes.com said last year,   Pharma & Healthcare 2013   The Fate Of New Cholesterol Drugs Depends On IMPROVE-IT   “.But  Improve-It was not completed as planned in 2013. The new American  guidelines delivered a strong statement questioning the increasingly controversial theory that LDL lowering by itself is beneficial. “We found that non-statin therapies really didn’t provide an acceptable risk reduction benefit compared to their potential for adverse effects in the routine prevention of heart attack and stroke,”  IMPROVE-IT is the large, seemingly endless outcomes trial studying Vytorin, which has been a blockbuster drug for Merck. But the drug’s reputation, and its sales, have diminished in recent years because of a raging controversy over the lack of any evidence for clinical benefit. Vytorin lowers LDL cholesterol but no one knows if it improves outcomes. The IMPROVE-IT trial is supposed to resolve this controversy next year, but it will do so only as the patent on the drug nears expiration.     There’s a really good analogy to help understand the way IMPROVE-IT could impact the fate of the PCSK9 inhibitors. Just recently supporters of Amarin’s fish oil pill Vascepa thought the drug would coast to approval for a broad new indication. Their optimism was based largely on an agreement with the FDA that did not require a large outcome study before approval. But over the past few years several large outcome trials– not entirely dissimilar to IMPROVE-IT– failed to demonstrate clinical benefit for drugs that, like Vascepa, lowered triglycerides. The FDA tore up its earlier agreement with Amarin. In all likelihood Vascepa will not gain the new indication it seeks until an ongoing outcome study is successfully completed. The other Merck CVS drug trial of Tredaptive, a combination of simvastatin and niacin B3 vitamin, failed to show the new drug was better than a statin alone.

However, the Improve-It trial already failed when it showed no significant target benefits of more intensive LDLC lowering by it’s planned   2.5  years finish ie  2010 ; so numbers  (10 000 to 18000)  and time were increased to 18000 subjects, to finish now.. The latest is that results will be released  17 November…

what do other  STATIN  trials show? A Canticle for Statins?

COMPARISON OF THE 2011 CAMBRIDGE METANALYSIS AND  2013 COCHRANE STATIN METANALYSES:

 Ray et al from Cambridge Univ UK in Arch Intern Med. 2010:  a   meta-analysis of 11 randomized controlled trials (Jupiter, Allhat, Ascot, Mega, AfCaps, WOSCOPS, ASPEN, CARDS, Prevend-it, PROSPER, HYRIM) involving 65,229 participants  ie ~244,000 person-years , mean age 62yrs,  systolic BP 141, LDLC 3.45, mean duration 3.7yrs (Jupiter only 2.2yrs), 19% diabetics,   found no  benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.
and 3  years later Taylor ea (London Univ Cochrane Database Syst Rev. 2013)  concluded  in   their abstract: Statins for the primary prevention of cardiovascular disease THAT  Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. In Eighteen randomised control trials   in  56,934 participants , mean age 57yrs, cholesterol baseline 6.17mol/l, LDLC 4.1;  duration 1 to 5.3years ie mean about 3.15 years ( they did not report mean bloodpressure). . Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced 14%  by statins (OR 0.86, 95% CI 0.79 to 0.94).  as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81) There was no evidence of any serious harm caused by statin prescription .                         

BUT
t
heir full published paper tables   showed that statin use – in a mean time of only 3 years-   ” increased Diabetes 18% from 2.4% on placebo to 2.9% on statin; with  more fatal strokes,  liver, renal, arthritis adversity. and all-cause mortality from 5-1 to 4.4%; NUMBER NEEDED TO TREAT NNT 96. THE ABSTRACT DOES NOT GIVE THESE GLUM NUMBERS, that statins benefit  only 1 in a hundred.  BUT the dull paper states  Only the JUPITER trial showed strong  evidence of a reduction in total mortality.
As this column has previously pointed out, the Jupiter Trial was clearly flawed when we first reviewed it, and further debunked by diverse major groups by 2011/2 .
so while  the Cochrane study patients were 5 years younger but had baseline LDLC 19% higher,  than in the Cambridge analysis,   ie by age and LDLC, the Cochrane analysis could still not show meaningful reduction in mortality other than in the disputed Jupiter study.. But the Cochrane trials had only 1/8th of the diabetics in the Cambridge analysis.
 
     The 2013 Cochrane statin review’s   evidence for using statins for primary prevention in higher-risk persons without CVD  admits it’s antimortality benefit   is based solely on the weight of the seriously flawed Jupiter trial. But while the Taylor Cochrane analysis used only 8 of the trials (skipping PROSPER, ASCOT and ALLHAT)  analysed in the Ray Cambridge analysis, the Cochrane analysis added another 10 trials. Despite covering 7 more trials than the Cambridge 2010 analysis, the Cochrane analysis included 25% fewer patients than the Cambridge analysis,

     So  what the innocuous abstract of the London  UK  Cochrane review   failed to say is that, in their full paper (available on application)  weighted by the biased Jupiter trial,   to lower mortality by 14% in about 3.5years, to avoid one death,   96 well people need to take fairly vigorous dose statin for 1 to 5.4 years – or 1 patient for a few hundred years–   with serious risks of diabetes (up 18%), liver, kidney, myopathies, peripheral neuropathy, intracerebral hemorrhage (ICH), and other diseases of the central nervous system (eg  cognitive impairment, depression, sleep disorders, nightmare, and headache- . mood (suicide risk increased 2.5 fold – Davison & Kaplan 2014 Canada );

and (unlike the anticancer benefits of metformin and vitamin D3) no benefits in reducing cancers rates. Such bad risk: benefit ratio confirms what  has always been known, that there is no place for mass long-term consumption of statin whether in a mythical Polypill (Wald and Law 2003–   with adverse Bblocker, ACEI and aspirin,) or even more farfetched added to our diet staples- water, bread etc..

It is common cause that diabetes increases major  risks 4 fold; so advocating  96 well people to take a statin to lower  mortality  by 1 case in 3.5 years ie 330 patient-years while >3% develop diabetes, stroke, depression, myositis, hepatorenal  and other major complications,  is  negligence,  when patients do so much better on metformin plus other natural proven life-extending  supplements like fish oil, coconut oil, vitamins esp vit D3 & K2,  minerals etc. 

As Pubpeer said on 27  July 2014, its a crisis of  trust in what top journals (in this case the Cochrane Review) publish. For TRUST read distrust…

This is in contrast to metformin prevention in similar overweight well people,  which lowers all risks by at least a third, with no adverse effects  provided dose is started low and titrated to tolerance ie ~250 to 2500mg a day. THE BMJ STATIN FUROR JUNE 2014:
Just last month, the long-awaited independent review of the BMJ June 2014 STATIN publication (of articles denouncing the value of statins for mass primary prevention ) confirmed  that the BMJ editors under  Dr Fiona Godlee were correct in  standing by the June papers  that there is no mortality benefit from statin treatment in people at less than a 20% 10-year risk of cardiovascular disease, as Canada implements.,
The panel, chaired by Dr Heath with  six internationally renowned experts, concluded the journal had handled the two articles appropriately and that its processes were timely and reasonable. 

Now  three new 2014  studies put more wolves  among the Big Pharma profiteering disease-mongering sheep:
one from India describing many promising new competitors to displace statins;  one from Oxford University warning yet again of the adverse effects of anticholesterols, this time by CETP inhibitors; and one from New York University mocking the wannabe Statinopause, statin deficiency:

      George,  Elangovan  ea in India  J Cardiovasc Pharmacol Ther. 2014 Jul  Look  into the Crystal Ball -Upcoming Drugs for Dyslipidemia: say: . Although statins are effective anti-dyslipidemic drugs, their use is fraught with issues such as failure of adequate lipid control in 30% of cases and intolerance in select patients. The limited potential of alternatives such as fibrates, bile acid sequestrants and niacin has spurred search for novel drug molecules with better efficacy and safety, eg  promising cholesteryl ester transfer protein CETP inhibitors such as evacetrapib and anacetrapib; (MTP) inhibitors eg lomitapide; Apo CIII inhibitors eg  mipomersen;  PCSK9 inhibitors eg evolocumab, alirocumab; farnesoid X receptor modulation; and Lp-PLA2 inhibition. While it may not be an easy proposition to dismantle statins from their current position as a cholesterol reducing agent and as a drug to reduce coronary and cerebro-vascular atherosclerosis, our improved understanding of the disease and appropriate harnessing of resources using sound and robust technology could make rapid in-roads in our pursuit of the ideal anti-dyslipidemic drug.

BUT
Miller NE. University of Oxford, UK   in F1000Res.2014 Jun   warns  Time to think again about .  CETP inhibitors and cardiovascular disease:   Inhibition of cholesteryl ester transfer protein (CETP) lowers plasma LDLC concentration and raises HDLC, suggesting it might prevent CVD. From the outset, however, the concept has been controversial owing to uncertainty about its effects on HDL function and reverse cholesterol transport (RCT). Although there has long been good evidence in rabbits  that CETP inhibition reduces atherosclerosis , the first information on CETP as a CVD risk factor in a prospectively followed cohort was not published until after the first Phase 3 trial of a CETP inhibitor had begun. The worrying finding that in humans CVD incidence was related inversely to plasma CETP has since been reproduced in each of five further prospective cohort studies. Similar results were obtained in subjects on or off statin therapy, for first and second CVD events, and for mortality as well as CVD morbidity. Additionally, two recent studies have found alleles of the CETP gene to be associated with an increased risk of myocardial infarction. Meanwhile, CETP gene transfer in mice was found to increase RCT from peripheral macrophages in vivo, and human plasma with high CETP activity was shown to have a greater capacity to remove cholesterol from cultured cells than plasma with low activity. This mounting evidence  in humans and mice for a protective function of CETP has been given remarkably little attention, and indeed was not mentioned in several recent reviews.  It appears to show that CETP inhibition does not test the HDL hypothesis as originally hoped, and raises a pressing ethical issue regarding two Phase 3 trials of inhibitors, involving more than forty thousand subjects, which are currently in progress. As the weight of evidence now clearly supports an adverse effect of CETP inhibition on CVD, an urgent review is needed to determine if these trials should be discontinued.
and
Han, Weinberger, SutinNew York University. J Gen Intern Med. 2014 Aug. warn:  Statinopause.        Statins are the cornerstone of lipid-lowering therapy for CVD prevention. The  American College of Cardiology (ACC) and American Heart Association (AHA) 2013 guidelines represent a fundamental shift in how statins will be prescribed; recommending  statins for nearly all older patients up to age 75 years, including healthy adults with low normal lipid levels and no atherosclerotic cardiovascular disease (ASCVD) risk factors other than age. Under the 2013 guidelines, age becomes a main determinant for initiating statin therapy for primary prevention among older adults. Specifically, according to the new guidelines, white males aged 63-75, white females aged 71-75, African American males aged 66-75, and African American females aged 70-75 with optimal risk factors would be recommended for statin treatment for primary prevention. Based on the new guidelines, one could term these older adults as having “statin deficiency,” a condition warranting statin treatment. We call this putative condition of age-related statin deficiency “statinopause.” After careful examination of the trial evidence, we find very little support for the new recommendations for primary prevention. The lack of evidence underscores the need for clinical trials to determine the risks and benefits of statin therapy for primary prevention among older adults.                                                                                                                                                           
HALF OF PATIENTS DISCONTINUE STATINS WITHIN A YEAR IN REAL LIFE:     Already in 2009    Goldenberg N1, Glueck C: wrote  in real life practice, about half of patients who are prescribed statins discontinue the medication by the end of the year. from the  Cholesterol and Metabolism Center,  Jewish Hospital, Cincinnati, Ohio, USAin  Vasc Health Risk Manag. .    Efficacy, effectiveness and real life goal attainment of statins in managing  CVS  risk. Statins became available in 1987 for the treatment of hypercholesterolemia .   Multiple, well-designed, placebo-controlled, double-blind studies revealed that each 1% reduction in serum cholesterol level was associated with about 1% reduction in risk of CVS events. Low-density lipoprotein (LDLC) cholesterol reduction to less than 78 mg/dL may be associated with reduction of atheroma burden. Patients with high levels of high specificity C-reactive protein and having LDLC less than 3.4 mmol/L (130 mg/dL) in primary prevention settings benefited from aggressive LDLC reduction with rosuvastatin over a 2-year period.  Medication adherence is lower in younger patients, women, and absence of known CHD. Personal features of the prescribing physician and dispensing pharmacies also affect patients’ compliance. More studies are needed to evaluate if “compliance packets” would benefit patients in a real life situation.
STATINS DEPLETE  Co10, OMEGA3 AND OTHER ESSENTIALS:.
     Coenzyme q10 therapy 2014  .Garrido-Maraver J1,  Sánchez-Alcázar ea . at Seville Universities say coenzyme Q10 (CoQ10) have  key role in mitochondrial bioenergetics; antioxidant; obligatory cofactor for uncoupling proteins and a modulator of the mitochondrial transition pore; expression of genes ; human cell signaling, metabolism and transport. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 causes no serious adverse effects in humans.  Oral a CoQ10 is a frequent  antioxidant used in many diseases that may provide a significant symptomatic benefit.

        Statin treatment and new-onset diabetes: a review of proposed mechanisms. Brault ,  Daskalopoulou ea .2014  at McGill and Harvard say   New-onset diabetes has been observed  involving statin therapy. To explain this association, three major mechanisms have been proposed . First, certain statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling.

     Michel de Lorgeril ea .Universite Joseph Fourier, Grenoble France  BMC Med.2013 ask: do statins inhibit omega-3?. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions. .Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins – after the implementation of the New Clinical Trial Regulation in 2007 – are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3; and contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins  inhibit n-3.

ie statins undo the proven benefits of omega3 and CoQ10. .

VITAMIN D AND CHD:

 Charles Glueck ea at the same Cincinnati Jewish Hospital. in  Med Hypotheses. 2011 describe HOW Vit D repletion reverses statin intolerance in 91% of statin-intolerant patients. Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.   Myositis-myalgia is the most common cause of statin intolerance, leading to cessation of statin use, with consequent failure to lower LDL cholesterol to target levels for primary and secondary prevention of cardiovascular disease (CVD). Despite published and new empirical evidence, the medical establishment has refused to accept it, requiring placebo-controlled, double-blind studies, none having been reported to date.

Glueck’s promotion of vitamin D as antidote or alternative to statin is borne out by at least 5 papers on Pubmed since 2003 (Kajinami), Yavuz 2009 ea ) –  some of which show that vit D level may rise significantly on statin.
       Now a  major review from Universities of Newcastle UK and Harvard by Kunadian, Manson ea   Am Heart J. 2014 of  Vitamin D deficiency and coronary artery disease: concludes: Coronary artery disease being the leading cause of death in developed countries, older patients are at particularly high risk of poor outcomes following acute coronary syndrome,  and impaired nutrition, including low vitamin D levels, may play a role.  Longitudinal studies have demonstrated increased cardiovascular mortality and morbidity associated with vitamin D deficiency. Low vitamin D levels have been linked to inflammation, higher coronary artery calcium scores, impaired endothelial function and increased vascular stiffness. Most available trials have tested only low doses of supplementation in relatively low-risk populations.


Specific Critiques of the Jupiter study and Contrasting results from other studies: :
 Wiki quotes Dr. Michel de Lorgeril, et al  In 2010,  published “a critical reappraisal” of the JUPITER Trial in the Archives of Internal Medicine,  what they saw as flaws in the trial, pointing out that the cardiovascular mortality rate and the case-fatality rate for myocardial infarction were much lower than they expected; they also questioned whether the study had been biased and perhaps manipulated because it was sponsored by a pharmaceutical company with a strong commercial interest in the outcome. They concluded that, “The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.  In addition, some prior and some subsequent studies have contrasted with the JUPITER trial results.       Five  other major university papers in prestige journals  also criticized the Jupiter study in 2011/12: Samson ea Florida State, Serebruany Johns Hoplins; Ridker Harvard, and  Morrissey ea Cedars-Mt Sinai;  while Lopez and Wright from Spain and Canada published an exhaustive debunking of the Jupiter claims of significantly reduced mortality.
            as we have long questioned about mass use of statins, Jay Cohen MD 2014 Aug 4th asks in  the MedicationSense E-Newsletter again: what is The Truth About Crestor: Is Crestor Dangerous And, if so, Why?  Crestor is the newest statin and the strongest statin yet. Statins are highly touted drugs for reducing cholesterol. Studies clearly show that statins improve cholesterol numbers (by lowering LDL and raising HDL) and may reduce C-reactive protein. Statins impede atherosclerosis, reduce heart attacks and strokes, and cardiac death. Thus, the statins Lipitor and Zocor are not only the #1 and #2 top-selling drugs in America, but also household names.  Other statins include Pravachol, Mevacor, and Lescol–and now ultra-potent Crestor. Until 2001, there was another statin: Baycol. It was then the newest statin and a potent statin–until it was withdrawn because of dozens of deaths. Is Crestor another Lipitor or another Baycol? Although Crestor has been on the market only a year, it has already been linked to numerous cases of severe muscle breakdown, kidney toxicity, and deaths. Public Citizen recently petitioned the FDA to ban Crestor...
 

       Conclusion: these references reviewed confirm that  is no justification for the myth of routine use of statins for primary prevention in the average population, especially in view of their risks, especially  increase in diabetes, and the availability of safe and far more globally healthgiving natural antiaging antioxidant energizing  insulin-sensitizing supplements that do a far better job of reversing both CVD and all other major diseases. .

update  16 June 2014 as this column has argued since 2008 (and this author for 40 years in refusing to take them for lack of proof)-  given their numerous serious and nuisance harms-  there never has been good enough evidence to justify synthetic designer cholesterol-busters for primary prevention with mild-to-moderate cholesterolemia ie without the presence of cardiovascular disease;

in contrast to   harmless multipurpose (antiatheroma antidiabetic antithrombotic antihypertensive anticancer all-disease prevention) micronutrient supplements like fish oil, coconut oil, DMSO, metformin,  vitamins esp C D & K2, minerals esp magnesium, chromium, zinc, iodine; , human nonoral HRT, CoQ10, arginine, carnitine, carnosine ; numerous mixed medicinal herbs; etc.

In the Statin-use debate creates furor at BMJ    CMAJ  on June 16, 2014,   Carolyn Brown argues  “Statins are beneficial for people with proven coronary artery disease, but a recent BMJ article questioned their use as a prophylactic measure.            “Are statins going to have a big impact on coronary artery disease or are they going to be one of the big mistakes that the medical profession has made?” That’s the question asked by Dr. James Wright, a Canadian who co-authored an analysis of the evidence on statins that appeared in the British Medical Journal (BMJ) in October 2013. 

      ” It seems like a straightforward question, but that article has led to a furor in the United Kingdom, with a well-known researcher calling for its retraction and the BMJ editor-in-chief Fiona Godlee defending the journal’s publishing process on radio and television. At issue is the clinical uncertainty about the preventive use of statins. “We’re fairly certain that benefits outweigh the harms in people with proven coronary artery disease (CAD). That’s based on a highly statistically significant but modest reduction in total mortality,” says Wright, who is managing director and chair of the Therapeutics Initiative (TI) at the University of British Columbia. But he says most prescriptions for statins are aimed at preventing CAD.

               “The evidence for this is not as rigorous and serious adverse effects have been documented. The UK’s National Institute for Health and Care Excellence (NICE) recently proposed extending preventive use of statins from patients who have a 20% chance of developing CAD in the next 10 years (its current guideline) to those with a 10% risk. This has led to a debate over the accuracy of risk calculators, unnecessary prescribing in seniors (since age is a major risk factor) and adverse effects. Canada’s guidelines recommend statin therapy in patients with risk below 20% only if their levels of cholesterol or other indicators exceed certain thresholds. Wright believes the statin issue has become heated because “so many people are taking them. They have been in the news so much and there [is] so much money being spent on them.” “Publication of our article has reignited the debate,” says Dr. Kamran Abbasi, international editor of the BMJ, who spoke on behalf of Godlee. “There are people who disagree vehemently on this issue. They can’t reach any sort of consensus on it at the moment.” The BMJ article re-analyzed data from the Cholesterol Treatment Trialists (CTT) Collaboration meta-analysis and cited adverse effects rates from various studies.

             ” Sir Rory Collins, a researcher at Oxford University and head of the CTT group, corresponded directly and met with Godlee in December 2013 about the article, calling for a retraction. He has also stated his view in media interviews. As a result of Collins’ complaint, the article was corrected, as the authors agreed that they had erred in reporting rates of side effects from the observational study. Wright says, “The issue around side effects is just that there is some harm.” The analysis had cited a rate of statin-related adverse effects of 18%; in fact, the original study found 17.4% of patients had a “statin-related event” but only approximately 9% discontinued statin therapy as a result. The correction affirmed that the CTT study failed to show that statins reduced the overall mortality risk in patients with a less than 20% risk of CAD over 10 years. Godlee also published an editorial explaining the journal’s decisions on how to handle the controversy and appointed an independent panel to rule on whether a retraction is warranted. Collins says he has submitted detailed material to this panel and maintains that there remain “extensive problems” with the analysis paper, beyond what the correction addressed. Charlotte Haug, vice-chair of the Committee on Publication Ethics (COPE).

update 2010   A new review, this time from a top team in France, further demolishes the deceptive  Jupiter trial promoting rosuvastatin Crestor, confirming that it was fatally flawed:

Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER Crestor controversy: a critical reappraisal.

Michael de Lorgeril ea conclude: ” The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.”

This concurs with the fraud of modern medicine increasingly pursued by combined Drug Industry and Government Regulator conspiracy, including www.lef.org/…/Media-Attempts-to-Misrepresent-Scientific-Findings.htm

and

Justice Dept declares war on doctors.

and why use a drug that can cause cancer , and tendinopathy, and  thrombocytopenia? Pubmed  shows at least 7 causally linked case reports since 1992 and 2008 , including one  now for rosuvastatin.

and Univ California San Diego alone reports 300 cases of statin-related myopathy.

contrast this with the trial report last week from a hypertension unit in Israel where a simple combination of vits C & E, coQ10 and selenium for 6 months – with no risks- lowered arterial stiffening, hypertension, lipidemia and glucose.

so why use statins except in severe familial lipidemia?

Feb 4th 2010 

 Early last year this column pointed out that the JUPITER trial was another nail in the coffin of primary use of statins.

Now a University California    Davis team concur further   in “Another look at the results of the JUPITER trial…  that many of the participants did not receive care consistent with current standards. Thus, the benefit of statin therapy would have been more difficult to demonstrate if standard therapeutic recommendations had been followed. In conclusion, these considerations cast doubt on the contention that statin therapy should be initiated in apparently healthy individuals on the basisof elevated high-sensitivity C-reactive protein levels.

UPDATE: SOME REMARKABLE LIQUID HEALTH SUPPLEMENTS – NOT STATINS BUT SULFUR-DMSO, LUGOL’S IODINE, FISH OIL and COCONUT OIL.

update 6 May 2014  see new insights at    DMSO – The Persecuted Drug by Dr. Stanley Jacob 27 Feb 2011

update 3  November 2013   IODINE DOSE AND DOSING:     the traditional approach is that of eg the Linus Pauling Institute at Oregon State University   and Wikipedia advocating the recommended daily allowance of 150 mcg  0.15mg a day for adults;  and the safe upper limit at ten times that intake;  but quoting  up to eg 7mg  a day  for treating fibrocystic breast disease; but  a single dose of ~100mg KI for nuclear exposure..
             But comprehensive discussion on maximum  iodine dosing by the Weston Price Foundation (2009) quotes  to much research, eg by MDs Dr Guy Abraham,  David Brownstein,  Broda Barnes ea – using for therapy  of disease  6.25mg up to 50mg/day, but historically up to 10gm a day (if this wasnt confusing mg with gm!).
             Dr Sarah Myhill in Wales UK  and Joe Mercola in USA put widely differing opinions and evidence  in perspective in 2013.
             The maximum available pharmaceutical grade 15% Lugols iodine contains about 100mg/ml ie ~10mg a drop, ie  a drop a week orally provides ~1.4mg ie 1400mcg a day- 10times the maximum recommended maintenance daily allowance RDA, although that is conservatively what healthy Japanese are estimated to ingest  in their traditional natural diet ..
          So the conservative  practical approach is to use 2% (Lugol’s) iodine ie containing 20mg/ml or 2mg per drop, about 1.3mg iodine/drop. While allergy to natural  iodine has apparently never been  reported, the prudent  might start with a test dab on the skin for using it as a paint. For oral use,  a test dose orally might be eg a teaspoon (4ml containing about 25 mcg iodine) of a mixture of 1 drop 2% Lugol’s in a glass of  water.
          Abraham and Brownstein 2005 reported Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine. This affirms the principle that no essential micronutrient  should be taken in isolation but ideally as part of good natural diet (now hard to achieve on the now traditional fast food genetically modified urban mass diet)- or with a balanced multisupplement including more realistic vigorous doses of vitamins C and D, and magnesium, selenum, boron, etc ..

UPDATE 18 JUNE 2013  Ji Sayer reviews    Evidence-Based Medicinal Properties of Coconut Oil

16 March 2013  THE THREE  OILS  SYMPHONY –  FISH OIL, COCONUT OIL, DMSO,- and EXPOSURE OF THE DEADLY OMEGA6 HOAX OF THE 20TH CENTURY:

this  “Three  Oils Symphony ” lacks references on virgin coconut oil. A comprehensive on-line synthesis  referenced to 1995 is by Dr Ray Peat.

Wikipedia puts in perspective the up-to-date  100% safe and multibeneficial virgin ie unprocessed cold-pressed  coconut oil versus the risks of  hydrogenated coconut or palm oils let alone omega6 oils. .
Fot those who have concerns about the safety, toxicology  of DMSO, the detailed randomized controlled trial of 1967-8 is exhaustively reported by Dr Richard Brobyn , confirming no serious adverse effects topically or systemicaly up to 90 days.
THE DEADLY HOAX OF OMEGA6  SUPPLEMENTS AND THE CHOLESTEROL HYPOTHESIS: A NIH team in Bethesda has just published a remarkable review in BMJ of the  Sydney Heart Study 1966-1973  with a review of recovered data, confirming that substitution of omega6  linoleic acid as safflower oil and margarine in modern marketed staple diet  was a monumental deadly marketing hoax for the past 50 years, since it almost doubled deaths in those men studied  from age 30-59 years. Wikipedia notes this deadly delusion  that safflower (oleic/ linoleic) oil is health protective. The same applies to oleic acid– high in olives, many nuts eg sunflower oil,  and animal fats especially when cooked- as Wiki summarises, excess omega6 increases the risk of breast cancer, and by Stephen Cunnane’s hypothesis, aggravates inflammation eg arthritis, cardiovascular and malignant, by worsening marine omega3 deficiency. .  This may not apply to some exceptional groups- Reverse epidemiology –  but is supported by hard science as weighed up carefully by Chris Masterjohn and his thoughtful dissection of Dr Daniel Steinberg’s  The Cholesterol Wars 
      These studies highlight one of the biggest marketing  Deadly Drug Hoaxes of the 20th Century, that lowering LDL cholesterol with  cholesterol-busters- statins –  is  necessary and beneficial for most people, for primary prevention 0f cardiovascular disease with average 1st world  population “mild to moderate” hypercholesterolemia.  When these synthetics-  statins -produce numerous serious adverse effects.  This contrasts with the legion benefits and zero adverse drug effects when natural anti-disease (anti-oxidant/ antithrombotic,  insulin-sensitizing  nitric- oxide promoting)   supplements- coconut oil, fish oil, DMSO, metformin, CoQ10, arginine, carnitine,  minerals and vitamins etc  – are combined in appropriate titrated doses.  .
IS FISH OIL BETTER THAN COCONUT OIL? PROBABLY EQUALLY IMPORTANT:

COMPARATIVE BENEFITS OF FISH OIL AND COCONUT OIL

Can anyone  find any published research that supports Peskin and Rowen 2011 book condemning fish oil supplement.,     and Dr Rowen’s article on Why Fish Oil makes you age faster?

Perhaps our expert ornithologists and sea researchers can find good support for their argument in birds and marine life- why do warmwater fish have so little marine oil?

there is still zero support  against good fishoil supplement for cooler climate populations on literature search.

a 2012  Univ Virginia  analysis  concluded that “With the possible exceptions of Vitamin D and omega-3 fatty acids there is no data to support the widespread use of dietary supplements in Westernized populations; indeed, many of these supplements may be harmful.”

But see the exhaustive favourable fish oil evaluation up to Jan 2012 at the Linus Pauling Univ oregon website .

and  recent new  papers  promote fish oil supplement- but mostly for people in the colder northern hemisphere or airconditioned cities, offices, factories, homes. .

Just two recent 2007/2009 papers express some doubt about the potential risk of fish oil triggering atrial fibrillation. But I have had worsening familial atrial fib for 23 years , and a tsp a day of cod liver oil helps control it.

I cant find any reference supporting their  argument that  pure modest-dose  fish oil supplement- as all authorities recommend. – is dangerous except Peskin’ and Rowens’.

BUT their argument may be valid for people who live in warm climates. South African cities are certainly not warm for much of the year; and the more industrious work in airconditioning when it is warm. Their argument  against fish oil supplement might certainly be valid for those who live in the tropics  outside cities   ie latin America, North and Central Africa, the middle east, northern India-Pakistan, accross subtropical asia and the near-equatorial  pacific.islands., who thrive on coconuts.

Peskin’s theory that low-freezing point  fish oil is essential only for denizens of the cold  deep may well apply also to human and animal inhabitants of the semi-arctic/antarctic land masses or living at cool high altitude like Mexico city.

It rings a bell with the opposite: coconut oil (melting point 24-26C) being staple food and so heathgiving for those living in hot (coconut palm) climates –  it thins in  more than temperate climates (20 to 40C) , hence may have a different protective lubricant/rheological effect to the vital antifreeze benefit of fish oil in  human and animal/marine dwellers living at -20 to <20C.  .

Thus it seems rational that I, we  now balance my 1tsp codliver oil a day with 1 desertsp  coconut oil twice a day, and advise  accordingly – the best of both oils. . .

for seriously ill pts I recommend up to 2gm fish oil concentrate 2x/day, with up to 60gm coconut oil twice a day, if tolerated. .

Rowen and Peskin’s  published references (other than vegetarian tribes that eat virtually no seafood) for their  contrary  viewpoint are in their 2011 book,

Does their theory  apply to more affluent people who live and work mostly in controlled temperatures (the mid twenties)  in 1stworld countries?  ..

So if you live in a hot city with warmed houses and offices, combining the two oils makes sense for you too.      Arctic  and antarctic circle outdoor dwellers certainly need their marine oil.

while Rowen supports Peskin’s  antifishoil argument,  analysis may justify both oils depending on the climate the population lives in eg fish oil in the icy latitudes, coconut oil in the triopics- and both in balance in the temperate zones.

In fact the Peskin-Rowen theory supports our policy to recommend both fish oil and coconut oil combined:

go back to the Peskin-Rowen book – even just their joint summation at the end: They stress that those who eat no seafood  and live long are 5 tribes  of humans:      vegetarian  Adventists- SDAs – who destress, and walk/exercise a lot and  also do not smoke, altho they may live in all climates in USA- where presumably they are mostly caucasians ; but  SDAs have total racial/tribal diversity . The other longevity claims  in closed tribal communities are heavily doubted. More recent researchers have concluded that  the older people get, the more they tend to exaggerate, confabulate  their age because it brings them eg more attention- eg the tribes Rowen/Peskin list – the Hunzas of Pakistan, Okinawans of Japan, Vilcambans of Equador, Abhascans of the caucasus, not to mention our own oldest old whether in tribal villages or in our cities. . That would explain why they live at such diverse altitudes and latitudes. And isolated tribal people are mostly poor,  dont have mechanized transport, and have to work outdoors till they drop,; and as % of their communities, the young leave to find work or get massacred/ conscripted, kidnapped, banished/ sold  as slaves   in wars against invaders, so their aging seniors are all that are left in those areas.

Peskin/Rowen ignore that by proven Darwinian evolution,  land-ambulant mammals evolved : from micro-organisms to eg mammalian coelocanths only about 400 000 years ago, in deep ocean waters, and hence are very oily.        But mammalian evolution dates back about 160million yrs;   and our endothermy– ability to thermoregulate  arguably dates from the dinosaurs and thus birds  about 300million years ago.

Perhaps human endothermic adaptation evolved when the first homo sapiens evolved at the tips of Africa and migrated from Africa around the globe some 10 000 to 100 000 years ago ( ie before and after the last Ice Age that started 40 000yrs ago and ended about 20 000yrs ago);  thus spreading from temperate  sunny  climates to cold semi-arctic lands of Europe, Asia, Iceland, Greenland  and Canada, and extremely hot equatorial/desert regions.

Hence we adapted from obligatory hot climate survival at up to 50C – the coconut eaters- to icy conditions down to -40C – who survived on  antifreeze fish oils as a staple. Fish oils freeze apparently between  18C    and -50C (DHA

update: 4 Feb 2013          HALOGEN AND HEAVY METAL IMBALANCE:
As radiologist  Dr Jeff Dach stresses now, Drs Abrahams and Brownstein and many others  have repeatedly reported the overwhelming evidence that          Iodine Treats Breast Cancer.  Whether this is taken orally, topically or most rationally both ways- by mouth and by deep massage driven in by DMSO- is  a matter of conviction and zeal.
Conversely areas with chronic iodine defciency– like Africa – have a high rate of goitre,  hypothyroidism through to obesity, vascular disease, growth impairment and cretinism- mental slowness and retardation. And perhaps not incidentally also have much higher rates of  endemic infections, fibrocystic breast disease, hypertension,heart and kidney diseases,  and cancer.
But while iodine supplementation in salt was a good idea elsewhere, salt overload is a major contributor to hypertension in black Africans,  so iodized salt is not the answer; and the fast food cult with salting and biltong – dried fish and meat – and cheap local cigarette smoking and alcohol – has worsened the hypertension problem.
It is increasingly recognized that it is the chloride rather than the sodium in salt that is the culprit in salt-related hypertension.  So we have  overload of three prevalent toxic halogens aggravating iodine deficiency here-  chloride in diet and as chlorine;  bromine that has crazily replaced iodine in bread; and fluorine added to drinking water where it is  not already toxically overloaded in fluorosis areas.
So far from just for thyroid deficiency,  iodine – plus selenium plus magnesium plus sulfur-  replenishment has become crucial both as  major anabolics, to reverse deadly   iodine deficiency,  and as  displacer-chelator (along with the century-old Nobel-prize winning EDTA)  of   deadly bromine, fluorine , lead, mercury, cadmium, iron and aluminium overload   (Guy Abraham) – all common in criminally polluted South Africa  where industrial warfare has ravaged the subcontinent since the late 19th century. .
Who cares about selenium supplements and balance? It is harrowing to see a recent study from Univ Pretoria that “A total of 896 maize grain samples were obtained from all the maize silos throughout South Africa (231 silos) and analysed for selenium (Se) content.  Of the samples analysed, 94% contained below 50 μg selenium/kg DM and can thus be classified as deficient from an animal and human nutritional point of view. Maize grain in South Africa is therefore a poor source of Se for animals and humans.”  Yet absorbable selenium deficiency is a critical factor in the risk of AIDS, let alone cancers and other infections.  The  art of selenium balance is to use organic selenium supplement, but unlike iodine therapy with multimiligram doses,  ,  no more than  400mcg/day selenium  to avoid selenosis.
These respective  elemental  overloads and deficiencies are incalculably big  problems in the prevalence of cancer, thyroid, osteoporosis,  dental, liver,  heart-renal-stroke and mental disease in South Africa, from violence (mad as hatters- endemic intoxication by smoking, alcohol,  cannabis, mandrax, meth  etc) and immune deficiency (endemic AIDS, TB, hepatitis, herpes) to steadily falling  school  attendance and academic results.
This in turn is catastrophically  aggravating the worsening poverty, unemployability, malnutrition and thus grant dependency  of the masses, and the worsening crisis in  the shortage of qualified and competent  administrators, politicians, scientists, lecturers, nurses  etc..
DMSO, Lugol’s iodine and coconut oil thus join fish- codliver oil -all with melting points around our comfortable habitat  temperature –  as a group of vital cheap antioxidant especially brain micronutrients for South Africa. And it is brains, intellect that  we all need above all else from conception to grave.

UPDATE 2 Feb 2013.    Dr Cynthia Koelker MD is a modern family practitioner in Ohio who muses on DMSO as effective non-prescription pain relief.                            A recent NaturalNews.com review  notes “Miracle cure’ controversy and why people should use DMSO for cancer, inflammation and more;  There is evidence that DMSO can cause cancerous cells to become benign.          DMSO can pass through human skin like water and enter cells. It can also stop or slow the development of cancers, such as breast, skin, bladder, colon, and ovarian cancer. Some people use it for cancer prevention. DMSO is used to help patients in withdraw from conventional cancer treatment and is promoted as an immune system booster.
Cancer centers use DMSO to protect healthy cells from chemotherapy and to decrease side effects from the deadly drugs. The DMSO Potentiation Therapy uses DMSO to allow chemotherapy to target cancer cells. This allows doctors to use extremely small doses of chemo, which lowers profits for the drug companies. No doubt the use of DMSO with conventional treatment, or better yet with other natural cures, is blocked because of the effect on drug profits.

A California research group in 2010  noted that Intractable and untreatable pain from cancer remains a challenge,  major impact on patients’ quality of life and survival. A significant number of patients receiving analgesic therapy with opioids report persisting pain of a higher intensity than the pain in those who were not on this class of drugs. DMSO is a naturally derived, inexpensive, non-toxic solvent and pharmaceutical agent that has been demonstrated to have numerous health enhancing and therapeutic benefits. In the present article, we provide the scientific evidence and substantiate possible application of DMSO as a well-tolerated excitatory modulator in the management of cancer pain. 

A 2009  North Carolina University study by   Satia JA,  White E ea. of supplement users over 10 years ie 770000 patient years showed surprising benefits in    cancer reductions with use of MSM   as well as fish oil, melatonin, St Johns Wort (all against colon cancer);   and chondroglucosamine (lung  and colon cancer) .    But  Garlic use associated with 1/3 increase in colon cancer.
 
Hence it is apparent that DMSO-MSM  – like coconut oil- is a major natural healer and potentiates many drug treatments  including against cancer and pain; and thus it follows that far lower doses of other medications may be needed if DMSO is used.

UPDATE:  27 January 2013  Stefanie Seneff ea at MIT point  out that   perverse modern industry has subverted agriculture and nutrition in                                         1. creating sulfur deficiency in crops (and thus in humans) through oversupplementing phosphate  at the expense of sulfur;                                                 2. driving down optimal cholesterol levels (ie cholesterol sulfate) through combined  obsssive futile cholesterol restriction and cholesterol-busters eg statins;  and                                                                                                                                              3.  the overload of fructose in processed food.   So increasingly both fast -processed -food eaters and the poor are sulfur deficient since they dont eat much food sulfur  –“eggs, onions, garlic, and leafy dark green vegetables like kale and broccoli, Meats, nuts, and seafood; Methionine, an essential amino acid, that we are unable to synthesize, is found mainly in egg whites and fish. A diet high in grains like bread and cereal is likely to be deficient in sulfur. This deficiency is worsened by acid rain and soft water- and worsens the epidemic metabolic syndrome, diabetes , vascular disease, Alzheimers,  and cancer.”   She reviews why these diseases are much lower in those living in volcanic  mountainous areas  eg Iceland, South America where sulphur abounds in food, and  along with enough ascorbic acid (also seriously deficient in processed foods)  is the backbone of vital cholesterol sulfate and its daughter sterols  (vit D3 sulfate, the corticosteroid and  sex-  and heart – ouabain- hormones). 

She points out the crucial role of iron sulfate in energizing cell metabolism by insulin and glucose, depositing needed cholesterol in cell membanes and promoting myoglobin  and brain strength instead of adverse tissue, hemoglobin and especially brain glycation  AGES – advanced glycation endproducts.

Is it surprising that (not just the rare  patients with serious hypercholesterolemia eg familial, nephrotic, cirrhotic  who needs statins)  but the progressive   deliberate successful poisonng of  the entire UK-USA population  with  statins by Big Pharma aided by the FDA and most Govt Regulators,  to drive down healthy average cholesterol levels to hypocholesterolemia,  is  notorious for causing brain fog, depression, fatigue, dermatitis, muscle pain/dissolution (rhabdomyolysis)  and liver-kidney- heart  dysfunction , while doing nothing to combat  insulin resistance, obesity and diabetes?

When –  instead of statins and other designer drugs  – to combat wasting diseases like infections eg AIDS and TB, cancer, diabetes (muscle wasting as fat accumulates), osteoporosis, atheroma,  heart/liver/kidney  failure and  neuro/muscular disease eg neuropathy, stroke, Alzheimers and muscular dystrophy-  what the population  needs is especially detox of heavy metal and eg estrogenic plastic overload;  more vitamin B, C , D3, K,  coQ10, arginine, carnitine, zinc, chromium  and magnesium, melatonin and GABA,  marine omega3,  sulphur in diet or as methionine/cysteine/DMSO/ MSM/glutathione;  and for serious lipidemia and resistant obesity at any age, metformin -dimethyl guanidine.

It is speculative  as to when nutrigenomics – ie costly genetic testing – is going to prove widely useful in real live clinical practice to provide useful diet guidance for our common lifestyle and  aging diseases.

Already in 1995 Shen and Murphy at Wisconsin University showed that while amyloid proten fibril deposits are a neurotoxic  cornerstone of Alzheimers’ disease in mice and man,  pure DMSO  totally prevents the formation of  amyloid betasheets at least in testtubes.

In 1999 Cherry ea  in Australia and 2004  House ea in Staffordshire confirmed the adverse effects of  aluminium and ferric deposits in Alzheimers;  and the potential benefits of heavy metal chelators like EDTA with enough magnesium  and calcium..  .

and by 2009 Gupta ea  in India showed also on the workbench that garlic extract – ie sulfur- both prevents amyloid sheet fibrillation and dissolves it.

So there are different safe  nutritional ways of  slowing if not dissolving amyloid plaques as well as atheroma plaques  in Alzheimeirs with combinations of  minerals, vitamins and other antioxidants/  chelators including sulfur foods like  DMSO, MSM and garlic.

Pine Tree Source v Fossil Fuel Source of MSM and DMSO:  Mike Pritchard-Jones in 2008 detailed the great but  academic debate .

But already by 1957, MacDonald ea at UCLA affiirmed the primary role of calcium and sulfur  in bone healing after fracture in rats. Yet the first Pubmed entry on sulfur deficiency disease in human nutrition – from a casava diet- is from Nigeria in 1968. and the latest from India  in 2012 from their  staple cereal-legume diet

A 2012 study Julien ea from Quebec and Greece shows important benefit of DMSO  against excessive tau phosphoprotein deposits in Alzheimers Disease.

Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins.

Like GABA,   Melatonin is a prime ubiquitous brain hormone that  (like the sex steroids ) also  declines  from age 30years, that profoundly maintains memory by preventing both hyperphosphorylation of tau protein and amyloid beta protein, in melatonin doses reported from 3 to 9mg/night.. theories about its therapeutic role go back 25 years on Pubmed.. so melatonin is conveniently combined with the supplement GABA before bedtime, while GABA is the ideal daytime anxiolytic for these distressed patients.

23 January 2013

For some time many of us have been taking and recommending the multisystem benefits of evidence-based natural micronutrients  – fish oil, coconut oil, vitamins, minerals,  and biologicals like HRT and  metformin –dimethyl guandine HCl – all  natural  supplements.

Now we have added medicinal natural DMSO liquid, the universal miscible solvent, never mind its crystallized sister form DMSO2-MSM.

DMSO   gives early and permanent preventative  benefits without risks in many musculoskeletal, cardiac and  neurological conditions. It is the only remedy registered in USA for chronic interstitial cystitis, and solely for that rare condition.  But it  is reported major benefit against trauma, thermal and radiation burns and scars, all infections, sinusitis-otitis, goitre, and pain including headache, gingivitis, dry socket; infertility from tubal blockage; dermatitis; burns, asthma; arteritis, arthritis, lumpy mastitis, diabetic and viral (eg shingles and herpes simplex) and other neuritis, and ischemic/varicose and diabetic ulcers and swollen varicose legs.

DMSO thus understandably has good synergy with the similarly anti-inflammatory antioxidants like tumeric,  fish and coconut oils; and metformin which also like DMSO and MSM crosses membranes well including into the brain.

We are seeing good pain and swelling relief with massage with combined DMSO + coconut oil+ zinc + Lugol’s iodine 15% including on scars and painful/lumpy breasts, head, neck, back, abdomen, joints, sprains, skin (pre)cancer etc. As usual one has to beware of too hastily overdoing movement after effective pain relief.

Ongoing experience suggests that sore or lumpy breasts including new painful lumps months after excision and radiotherapy be massaged  daily orinitially twice daily:  first with coconut oil, then Lugol’s (15%) iodine, then medicinal grade(98%) DMSO to improve deep penetration of the iodine to promote healthy tissue regrowth from deep. It is encouraging how tender  lumps disappear within days , including on repeat breast mapping with mechanical tactile Sure Touch scanning.

Adverse effects: apart from possible smell and taste (which some of us don’t experience), pure DMSO may cause redness and burning, as may strong iodine; this is avoided either by diluting the DMSO in a bit of water; or better by applying coconut oil first, then the iodine then last the DMSO.

One must be careful starting  with DMSO. Extracted from woodpulp, it is volatile, warms on mixing with eg the oils, or undiluted on the tongue. But there is no evidence of toxicity apart from the smell – which my metabolism apparently does not produce even on a tsp of 99% medicinal DMSO twice a day.. Megadoses of up to a gram per kg have reportedly  been used in severe conditions. Fair-skinned people are more sensitive to it so doses should be lower, starting with massage of sore/superficial lesions and/or just ¼ tsp by mouth. Any taste of it is obviously easily masked by mixing it with the essential oils (fish oil, coconut oil) and supplement powders listed, and whatever else is desired eg yoghurt, fruit squash or just water.

There are 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

CHEMISTRY and further references::

DMSO2  MSoM  METHYLSULPHONYLMETHANE  C2H6O2S or (CH3)2 SO2  dimethylsulfone crystals melt @ 109C and boils @ > 238C. its Molar mass is 94,.  Density 1.45

DMSO MSiM METHYLSULPHINYLMETHANE C2H6SO Dimethylsulfoxide Me2SO crystals melt @ 19C , and boils @  189C      Its Molar mass is  78.  Density. 1.1

So the two dimethylsulfa sisters cost the same and  have the same benefits against pain, chronic cystitis, arthritis, brain trauma, radiation and cancer http://www.dmso.org/ .   But only the melted ie liquid form at household temperature is the strong penetrating solvent. It’s not clear whether oral DMSO gives better blood levels than DMSO2 –MSM, since only the DMSO is melted at body temperature whereas DMSO2 is not..

The purist argument against DMSO/DMSO2 as sulphur supplement is that sulphur is not an essential element. But this is obviously  fallacious since our chief components are the elements CHOPNS carbon hydrogen oxygen phosphate nitrogen sulphur- we cannot survive without ingesting these. Only plants and microbes can apparently photosynthesize living tissue  from CHOPNS by breathing  air and absorbing water.

MSO2 ie MSM has also been shown in humans to readily   cross the blood-brain barrier. In the rat DMSO carries diazoxide into the ischemic brain to mitigate hypoperfusion, and protects the brain against scute traumatic brain injury

Comprehensive updated review of DMSO to January 2013 from the USA Natural Medicine Database supplied by the Drug Information Centre of Groote Schuur Hospital UCT   echoes Steinberg’s review (Albert Einstein Med Centre in Philadelphi)  aAnn N Y Acad Sci. 1967;141:532-50 The employment of dimethyl sulfoxide as an antiinflammatory agent and steroid-transporter in diversified clinical diseases. that 90% DMSO massage in some 500 cases, gave overall good outcome in 80% with no serious or sustained adverse effects reported.

In particular, no evidence can be found overall in the accessible literature supporting one old report that a DMSO product was withdrawn in Japan because of cataract concerns.. A 2011 review of transdermal joint DMSO use from Arizona University found no evidence of human eye toxicity in their series or in the reported literature.

Studies on DMSO have been ongoing at University Oregon for >45years:

Ann N Y Acad Sci. 1967;141:214-20.The effect of DMSO e on the induction of breast cancer in the rat.  Fletcher WS, Dennis DL at Univ Oregon showed that in the rat, breast cancer induced by nitrobenzene was progressively reduced by 18months by DMSO 50ppm (ie 0.5%) in their water from after and even better from before the cancer was provoked. In humans this equates roughly to taking 10gm DMSO in 2L fluid a day..

JC de la Torre  in  1975 wrote “DMSO  has been tested in various experimental injuries of the central nervous system CNS in relation to other therapies. It appears  a useful drug in acute extradural mass-forming lesions, middle cerebral artery occlusion, respiratory anoxia, and spinal cord injuries, in rhesus and squirrel monkeys, dogs, and rats. The data from these studies suggest that in the experimental models, DMSO is clearly superior to no treatment, and appears to be more generally effective than other comparable treatments. No satisfactory answer has yet been found to explain the beneficial effects of DMSO…..”

and 2009  JC de la Torre and  SW Jacobs  Oregon University , ea  described  Pharmacology of DMSO in cardiac and CNS damage: “The pharmacological effects of DMSO administration include some desirable properties that may be useful in the treatment of medical disorders resulting in tissue injury and compromised organ systems. These properties include the reported effects of DMSO on impaired blood flow, suppression of cytotoxicity from excess glutamate release that may result in lethal NMDA-AMPA activation, restriction of cytotoxic Na(+) and Ca(2+) entry into damaged cells, blocking tissue factor (TF) from contributing to thrombosis, reduction of intracranial pressure, tissue edema, and inflammatory reactions, and inhibition of vascular smooth muscle cell migration and proliferation that can lead to atherosclerosis of the coronary, peripheral, and cerebral circulation. Review of the basic and clinical literature on the biological actions of DMSO in cardiac and CNS damage or dysfunction indicates that this agent, alone or in combination with other synergistic molecules, has been reported to neutralize or attenuate pathological complications that harmed or can further harm these two organ systems. The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease. “

Rheology is obviously crucial for health. . The lower the melting point and the higher the viscosity the healthier. Coconut oil (melts at 24C) and DMSO(19C) a universal solvent miscible in both water and oil have similar melting point well below the temperature of the healthy human (+-37C), while fish oil http://www.high-fortune.com/En-index-SW04.asp. melts at similar temperature (20C, freezes at 10C.)  Since the brain is about 20% omega3 ie fish oil, it perhaps explains why both coconut oil and DMSO with similar melting point and rheology –good flow- to omega3 have such profound benefit crossing the bloodbrain barrier and fighting vascular and inflammatory degenerative disease eg Alzheimers, as well as against cancer, which while supported by vascular growth factor VGF depend on hypoxia and thus acidosis..

PLoS One. 2012;7:e33361. doi: 10.1371/journal.pone.0033361. .Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.Lim EJ, Hong DY, Yang YM. Ea Konkuk University, Seoul, South Korea. Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which MSM inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers.

Invest Radiol. 2008:43::298-305..Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature.Cyran CC, Brasch RC ea. University of California San Francisco:  To evaluate the potential of quantitative assays of vascular characteristics based on dynamic contrast-enhanced magnetic resonance imaging (MRI) using a macromolecular contrast medium (MMCM) to search for and measure effects of dimethyl sulfoxide (DMSO) on cancer vasculature. treated control (n = 8) and DMSO-treated (n = 7) human breast cancer xenografts (MDA-MB-435) in rats were imaged dynamically by MMCM-enhanced MRI before and after a 1-week, 3-dose treatment course. CONCLUSION: Reductions in cancer microvascular leakiness induced by a 7-day course of DMSO could be detected and measured by dynamic MMCM-enhanced MRI and were confirmed by microscopic measurements of the leaked macromolecular agents in the same cancers. Results support the robustness of an MMCM-enhanced MRI approach to the characterization of cancers and providing first evidence for an in vivo effect of DMSO on cancer blood vessels.

Neoplasma 2004;51:460-4.Acetaminophen (paracetamol) and DMSO modulate growth and gemcitabine cytotoxicity in FM3A breast cancer cells in vitro.Bilir A, Guneri AD, Altinoz MA. McGill University, Quebec, Canada. Addition of antioxidants to chemotherapy is an unresolved problem in oncology. It is still an issue of debate, whether antioxidants may reduce rough cellular toxicity and thereby the systemic side effects of the chemotherapy, without sacrificing the anti-tumor efficacy.  Tumor-sensitivity towards gemcitabine a  new anti-cancer agent can be increased with anti-inflammatory agents.  Acetaminophen  and DMSO are two unique anti-inflammatory and anti- oxidant agents with unrelated structures,  both able to block RR and COX, simultaneously. we monitored efficacy of acetaminophen and DMSO to modulate growth and gemcitabine sensitivity in breast tumor cells, Peculiarly, acetaminophen alone stimulated S-phase, which was not accompanied with enhanced plating, rather resulting in 40.3% growth inhibition at the 96 hour. DMSO alone significantly diminished both the plating and S-phase, which resulted in 71.7% growth inhibition at the 96 hour. Gemcitabine drastically reduced S-phase and plating until 72 hours, yet at 96 hours it lost its efficacy to suppress the S-phase with concomitant 2-fold rise in cell numbers in comparison to 72 hour time point. Both DMSO and acetaminophen brought S-phase to around zero percent in combination with gemcitabine until 48 hours, yet they both reduced early cytotoxicity of gemcitabine at the same time interval. However, at the 96 hour, they both strongly augmented gemcitabine efficacy to block S-phase and prevented the rise in plating.

Oncol Nurs Forum. 1991;18:683-5.Case report: topical DMSO for mitomycin-C-induced skin ulceration.Alberts DS, Dorr RT  Arizona Cancer Center. Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors’ experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice.