Monthly Archives: December 2009

PREVENTING A SWEET DEATH WITH INSULIN SENSITIZERS -NATURE’S ENERGIZERS

neil.burman@gmail.com

The prognosis of adult-onset diabetics is far worse compared with nondiabetics.

Are doctors to be allowed to continue to kill  by omission (at the behest of drug-industry-led “authorities”) of supplements that do far better than modern designer drugs?

This month Chong and Chabner at the Mass. Gen. Hospital analyze the anticancer mechanisms of Mysterious Metformin, that “ diabetics have a higher incidenc than non-diabetics – 1.2 to 2.5- of cancers of the liver, pancreas, colon,  endometrium, breast, bladder, and non-Hodgkin’s lymphoma. Potential mechanisms to explain this greater risk include the mitogenic effects of  sugar- glucose, insulin -baseline hyperinsulinemia, exogenous insulin)-and underlying metabolic abnormalities such as increased oxidative stress, hyperglycemia, hyperlipidemia, and obesity. “ 

But cancer is the cause of death in less than 5% of people: (apart obviously from starvation, violence and infection), more than half of premature adult deaths are due to cardiovascular disease CVD- the commonest killer of older women, CVD killing 13 times as many as does breast cancer. . The common roots of CVD are those of type 2 diabetes and hypertension – excess salt sugar and fat never mind smoking and indolence.

The just- published momentous 5year Bari 2D RCT (Frye ea) bears out the farce of modern hightech invasive medicine:  with 422 collaborating research authors, it epitomizes the futility of the western medical paradigm that most patients and clinicians- under the huge vested interests  of the Disease Industry- are taught and follow- and ruling politicians happily profit from- dont bother with natural prevention, just wait till disease strikes, then depend on hightech salvage. 2368 diabetics (2/3 white males, aged about 62yrs, diabetic for about 10 years, 27% on insulin) with CVD were randomized to undergo either prompt revascularization with intensive medical therapy, or intensive medical therapy alone -either insulin-sensitization or insulin therapy. ~30% had had heart attack or cerebrovascular disease. Metformin use rose from about 50% at baseline to about 70% at the end. At 5 years, rates of survival -88% (ie 12% deaths),  freedom from major CVD events – 76.5% – and adverse/serious adverse events – did not differ significantly between the revascularization group and the medical-therapy group  or between the insulin-sensitization group and the insulin group (P mostly >0.5), although severe hypoglycemia was 50% more frequent on insulin (9%) than on metformin (6%, P=0.003). Vascularization was eventually justified in less than half of those assigned to intensive medical therapy, “

The outcome of the BARI 2D trial was thus the same as that of the COURAGE trial (Boden 2007)- in non-diabetics with CVD , no benefit of invasive over intensive medical therapy, and metformin was far safer than insulin therapy .

Chong & Chabner found a 1.4-fold higher risk for all-cause mortality for diabetic subjects. Metformin appears to lower by between 23% to 62% ie almost halve the risk of cancers  and may enhance chemotherapy – by diverse mechanisms apparently including killing of cancer stem cells- perhaps trippling the pathological complete response rate”.

And they do not even mention the crucial role of reduction of AGES in limiting cancer. Already in 1999 Beisswenger ea at New Hampshire Dartmouth Med School showed how toxic methylglyoxal levels were significantly reduced by high-dosage (1,500-2,500 mg/day) metformin compared with  low-dosage (< or = 1,000 mg/day) metformin (P = 0.001), even though the groups had similar glycemic control.

Then in 2004 Krone & Ely from New Zealand “studied glycosylated hemoglobin GHb in subjects supplementing up to 20 g ascorbic acid AA daily and found that for each 30 micromol/L increase in plasma AA, GHb was reduced by approximately 0.1. These results suggest that high AA intake can depress glycation, reduce GHb and inhibit glycation in all proteins ; with implications for aging. Moreover, AA could contribute through several other mechanisms to slowing of human aging (e.g., antioxidant properties, acceleration of pentose phosphate pathway, replacement of structural proteins).”

And the following year, a Korean University team (Do et al 2005) confirmed that “ during peritoneal dialysis (PD) with high-glucose dialysis fluid, human peritoneal mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype (EMT). In continuous ambulatory PD patients on a 12-month protocol (low-GDP solution group vs high-GDP solution group), the low-GDP group showed lower cell scores from the 1st to 12th months . Low-GDP solution showed beneficial effects such as rapid remesothelialization and less EMT in the peritoneum with time on PD.”

These studies confirm the general trend that higher glucose levels promote aging – loss of cellular control, including vascular and immune- infective, inflammatory- dysfunction; which are reduced /reversed by both lower sugar and the dozens of antioxidant insulin sensitizers like metformin, vitamins A,C,D,E & K, chromium, magnesium, exercise .

Now Cobble and Peters from University Utah ask: After metformin and Lifestyle, then what? Almost 30% of Americans have diabetes or are at risk of it by virtue of having prediabetic bloodsugar levels.

But are they correct in assuming inevitable  progressive nature of type 2 diabetes to insulin dependence let alone cancer and reno/vascular disease? When major trials on the  American and Eurasian continents have shown that preventative metformin can reduce the onset of new diabetes by up to 70%. And that doesn’t begin to utilize the scores of other weight- and insulin-resistance-reducing natural agents available, apart from drastically reducing sugar, salt, alcohol and fat intake, and enforcing – conditioning- regular exercise at places of education, work and retirement.

The minority of countries that (claim to) respect human rights cannot enforce ‘desired” religious or sexual practices, or deny appropriate education, security, contraceptives, basic shelter and nutrition health services for all, as South Africa like Zimbabwe even under ‘majority’ rule  still continue to deny to millions after hundreds of years while obscenely enriching loyal comrades.

Equally, can society – which  pays for illness and disability- continue to allow increasing abandonment of exercise even at schools, and neglect to enforce drastic food-chain reduction of salt, sugars and cooked fats, and neglect to compel prescription of the numerous adiposity-reducing insulin sensitizers- fish oil and especially metformin-  balanced with calcium-magnesium ascorbate and vitamins B3+6+9+12- C- D- K – to lessen the lethal pandemic of overweight-related diseases?  Many societies already drastically restrict smoking and penalize drunken driving. At least some  states have sensibly banned sugar-fortified cooldrinks at schools – a logical move strongly opposed by the sugar barons. But because it boosts jobs and taxes,  ruthless ‘authorities’  have been quick to obey the infinitely corrupt American Government  and promote swine flu vaccination  and Tamiflu even though  these were never proven to be safe let alone effective or necessary.

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LISTING THE SCORES OF NATURAL WEIGHT-REDUCING INSULIN SENSITIZERS:

 neil.burman@gmail.com

 one of the great frauds of the corporate Prescription Drug Innovators- backed by their tools the FDA and the other Drug regulators, academics and political lobbyists they fund – is to omit to mention the natural nutrients that invariably do better than the patented prescription drugs they want mimicked.

Or they  hide behind the FDA smokescreen that natural products cannot be recommended until they have undergone far more rigorous trials than was required of modern designer drugs- which moderns rarely stand the test of time – efficacy, necessity and safety- with chronic use.

A classical example is the entries that one is led to on search for Insulin Sensitizers: eg – apart from metformin- many sites list only designer drugs eg the dangerous pioglitazone (Actos) or rosiglitazone (Avandia)- eg in Self-management of Diabetes  , and New Drugs for Type 2 Diabetes  and US Patent 6153632 – Method and composition for the treatment of diabetes ‘

 Wikipedia search leads to anti-diabetic drugs, where only biguanides and glitazones are listed under insulin sensitizers . – but there is a detailed listing and discussion of the dozens of alternatives natural insulin sensitizers.

FOODS THAT HURT: agents which slow metabolism, block insulin/ sensitivity or promote fat gain -adiposity: –

cooked fats; excess ie refined sugars eg sucrose (table sugar), glucose, fructose (eg fruit juice, cornstarch); NaCl; yam, cassava, celery-seed, rosemary ; betablockers, most antidepressants and major anxiolytics; cortisone; alcohol; HGH; synthetic sex hormones, aspartame; cholesterol-lowering drugs (statins lower testosterone, impair muscle, mood and liver- but no chronic trials show that they reduce insulin resistance or newdiabetes); most administered antidiabetic drugs (eg sulphonylureas, insulin/insulin mimetics eg gliptins) except metformin (& perhaps glimepiride). Sulphonylureas (relative to metformin) increase mortality by 43% & CVD mortality by 70% (DARTS 2006).

FOODS THAT HEAL: Combine fibre with the abundant metabolic stimulants that reduce insulin resistance, adiposity, appetite, calorie absorption, cell damage & lipidemia-

The VITAMINS – A, B2, B3, B5, B6, B7, B8, B9, B12, C, D, E, K;

The MINERALS – Ca, Mg, K, Zn, Cr, Se, Va, Zn;

The BIOLOGICALS fish oil, MCT, ribose; CoQ10; alpha-lipoic acid; arginine; 5HTP, carnitine; carnosine; n-acetyl cysteine, testosterone, estradiol; melatonin; inositol; GABA; taurine; thyroid;

the drug metformin derived from the plant galega biguanide ;and at least 66 other plants incl. aloe; sutherlandia; barley; basil; cinnamon, garlic, onion, cabbage, cucumber, spinach, nettle, white sweet potato,  gymnema, coleus, indigofera, fenugreek, curcumin, ginseng, olive leaf, dandelion, bilberry, kidneybean, stevia, psyllum, milk thistle, – see Pubmed on individual nutrients, and Hyperglycemic and Hypoglycemic Herbs .

Few of the above are commonly perceived staple foods; but they are easily combined – at modest dose and cost – in a twice daily food supplement regime. Since they combat all disease, there is hardly longer justification for using even the prescription drug metformin, let alone other (futile, risky) heavily marketed drugs- except that with rising demand, unless one grows one’s own foodstuffs, natural herbs and refined micronutrients especially in multiblends become far more expensive than prescription metformin. .

 In conclusion: what the Drug industry would dearly have us ignore is The Unitarian Hypothesis for the aetiology of diabetes mellitus. Morrison ea 2006 note that “over the years, insulin insufficiency will develop in most cases of even type 2 diabetes, with insulin therapy eventually required in order to achieve normoglycaemia. The Unitarian Hypothesis presents an overall cascade of biochemical and physiological interactions, a logic which embraces the points of entry of a variety of insults, all of which can lead to the clinical picture of hyperglycaemia and its attendant adverse outcomes.

The hypothesis buttresses the belief that nature – the genetic predisposition which directs potential antibody development; and nurture – the environmental influences such as stress, exercise, nutritional status (over- or under-), infective and toxic attack, can aggravate or initiate aspects of the cascade of reactions leading to hyperglycaemia. The causative agents functioning internally within the cascade are imputed to be free radicals, oxidizing molecular species and antibodies and the corollary to this overview concept would be that a situation that minimizes the genesis and accumulation of these three agents would minimize the development of diabetes mellitus.        

Currently the debate is rife about the use of free radical scavengers and antioxidants in the treatment and prevention of diabetes mellitus. The verdict is still out on this approach. Our research on rootcrops such as yams and cassava, staple foods in tropical countries, indicates the presence of cyanoglycosides such as linamarin, which on digestion yields cyanide radicals. These radicals are pancreatotoxic especially in the undernourished state. Dog models however, have shown that free radical scavengers such as riboflavin, Vitamin B2, is protective against this toxic damage. Further, scientific investigations have clearly demonstrated the role of antibody attack and have been able to ward off the appearance of type 1 diabetes mellitus in susceptible individuals, by the early use of immunosuppressive therapy such as cyclosporin.

Thus the Unitarian Hypothesis demonstrates how all types of clinical syndromes being described in diabetes mellitus are not necessarily variants of a specific illness but rather manifestations of a central process of membrane damage→antibody response→insulin inadequacy (quantitatively or qualitatively); and the future intervention in containing this disease may well lie in focusing on preservation of the integrity of the body’s cell membranes.”

SEX HORMONE BALANCE FORMULA

2009/12/23 Chris Hatlestad <docgenki@yahoo.com> writes:
I came across an older response to a testosterone question on the FACT website where you responded with a formula for the T:E2 ratio or A:E ratio.  I have been following the FAI or free androgen ratio which is s-T*0.0347/SHBG with normal 0.7-1.0 and find most everyone low.  However, I like the A:E ratio concept.
What is the 30 that you multiply to the s-T?.  Also, I am typically measuring total estrogens which is E2+E3.  What about using this number and including DHEA-s in the equation for a true A:E ratio.
Also, do you do any hormone implants and if so, how do you calculate or guestimate dosing, men or women?  Sourcing for the implants beyond College Pharm?
Thanks
Chris Hatlestad, MD
Integrative Medicine & Family Medicine, Center for Environmental Medicine
10748 NE Halsey Street  Portland, OR 97220
503-261-0966 (office) 503-252-2691 (fax)
docgenki@yahoo.com
www.cemmed.com

hi Chris,
thanks.
in the SI unit scale (which USA proposed switching to, then reneged on!), basal SHBG averages about 20-30 nmol/L.  So I correct the A:E ratio back to  a basal normative SHBG of 30… SHBG  binds  1000 times more to TT than  it does to estrogen… hence the higher the SHBG, the lower the free androgen ie FAI relative to estrogen. The FAI alone ignores estrogen.  Its like ignoring T3 level in assessing thyroid function- one need the whole axis eg T3 xT4/TSH. .

on the one hand I prefer to use E1+E2+E3.
On the other, we can no longer get S- E1 measured here, there is too little demand .  and remember that empirically, it is said that E2 is about ?7 times as potent as E1 and 80 times as potent as E3.
similarly, all the other androgens would have to be brought into the calculation at their disparate   androgenic potencies.  So for cumulative functional effect one would  have a complex formula factoring in the potencies.

Hence, KISS- keep it simple –  s-T x 30/ (E2 x measured SHBG).
DHEA is of course one parent hormone, and one never knows how far it is going to convert to androgens vs estrogens. So I measure it if affordable- but like Wiebke Arlt,  find it useful to replace only in the old.  at least with 7keto DHEA one knows that it cannot be bioconverted back to TT or estrogen- it is simply a weak androgen.
My late inspiration, breast surgeon Dr Roald Maartens here used a formula of 12 hormones for managing (pre)cancer hormone-related diseases. But  not even experts  like Leon Speroff,  Bill Creaseman or David Dent could help him validate and spread his program. I tried to get his thesis validated and published posthumously, but his family jealously decided to let it die with him rather than risk someone else stealing his glory… such is science.

I have an English  copy of his unpublished MS, but I cant find anyone who can understand the dense math. His brilliant son helped him with the computer formulae and the program that one of his acolytes still uses blindly, but as I say they blocked my offer to help spread his concept.

I gave up using profitable implants 20 years ago since they may be beneficial and acceptable for many patients, but have a double digit failure/complication rate; are costly; are dependent on how tightly they are compacted ie have widely varying release time- E2 perhaps 6 to 24 months, TT perhaps 3-4 months.

When I first met the woman (whom I married 4 years later), the local Emeritus Professor of Gyne had given her 300mg E2 and 150mg TT in 3 successive implant sessions in 5 months, turning her from chronic fatigue into a bloated over-estrogenized wreck. He never could explain why he defied physiology (as was taught by eg Hans Selye over 60 years ago),  instead of giving her- as is normal with implants – at least twice as much TT as E2. (He is still bravely working in the local University menopause Clinic at over 80 years of age).   Her s-E2 level was over 3000 pmol/L while her s-T was only about 6nmol/L. Since it is major hastle trying to dissect out implants, I simply balanced the excess E2 with depotestosterone injection every fortnight till her s-E2 dropped below normal after 2 years, since when (now aged 63 years) she has been happily on fortnightly sc  20mg:1mg  TT:E2 depot injection a la William Masters & Grody’s 1953 formula. . If we had someone to make progesterone implants here, I would have used combined progesterone estradiol and testosterone implants, as Mannie Schleyer-Saunders in London did for decades with excellent results. You have brave compounding pharmacists there who do so,  so go for it with triple implants or triple subcutaneous depot-sexhormone  self-injection!

go see if you can get Leon Speroff there interested again in Maartens’ formula?   I am delighted to see that Dr Speroff  is still publishing prolifically, now validating depot hormones subcutaneously as I have been advocating at international congresses the past 6 years, and on this column.
Seasons Greetings- take care!

ndb  in sunny Cape Town

MAGNIFICENT METFORMIN

neil.burman@gmail.com

only 5 weeks since our last review,

twelve  new papers further confirm the supremacy  of the galega plant extract  metformin as the most important chronic preventative drug ever, alongside other natural nutrient supplements eg – fish oil, vitamin C, the human hormones  vitamin  D, sex hormones, thyroid:

PCOS:

1. Aled Rees’ team at Wales’ Cardiff  University  show in a randomized controlled double-blind RCT that obese  women with PCOS (hirsutism and failing periods) even at a mean of 30 (18-35) years have evidence of insulin resistance and early vascular disease; which at their weight around 96.5kg and BMI 35kg/sqm, with waist around 108cm and hips around 120cm, is reversed by metformin: 1500mg/day compared to placebo for 12 weeks  reduced weight by 2kg, body fat by 2.5%, waist by 5cm, bloodpressure by 7% and improves circulation; with 18% fall in insulin resistance (HOMA-IR) , 15% fall in free androgen index, and 21% fall in the testosterone: estradiol ratio.

2.A Tehran University Iran (Ashrafinia) RCT (although not big enough to be statistically significant)  shows that metformin is 81% better than ovarian diathermy in treatment of PCOS inferrtility.

3. and the  German University Erlangen open study –Effect of Metformin Treatment for 2 Years without Caloric Restriction on Endocrine and Metabolic Parameters in Women with Polycystic Ovary Syndrome-(Oppelt)  similarly showed that  even without calorie restriction,   while “no significant changes in body mass index or HOMA-IR were observed,  on metformin  a significant decrease in hirsutism, in fasting and 2-h insulin levels was observed,  with a significant increase in sex hormone-binding globulin (SHBG) levels, while total testosterone (TT) levels and the free androgen index decreased significantly; with significant improvement in lipids.”

These bear out what this column has previously  reported about the superiority of metformin over surgery or other (designer synthetic) hormone therapy  from the work of eg Charles Glueck and  Louis Ibanez for PCOS metabolic syndrome and infertility. .

Diabetes :
4. A retrospective Massachussets study (Brownstein) shows again that  in recent diabetics, the relative risk for heart attack with rosglitazone Avandia  was  120% higher  compared to metformin or  pioglitazone Actos;
5. and a retrospective UK study (Tzoulaki) that pioglitazone was associated with reduced all cause mortality compared with metformin.
But these are retrospective studies, not controlled prospective trial.  they do not mention  the cardinal fact that  pioglitazone does the opposite of metformin, it increases body weight,  heart failure and fracture rate;  and that after a decade of intensive pioglitazone  promotion and trials, there is no evidence from hundreds of direct randomized controlled trials in at least 26 000 patients  that pioglitazone reduces all-cause mortality and chronic diseases  including cancers by a third, as metformin did in the longest RCT ever, the 20year UKPDS, and in many other studies.  No modern designer drug does what metformin does .
6.A systematic review in children by University Sydney shows that   metformin for about 6 months lowers insulin resistance and overweight.
and in new rodent studies:
7. from Russia, (Anisimov ea)  metformin significantly reduces cancer risk, increasing lifespan by 8% and breast cancer latency by 13%, halving breast cancer transplantability and with melatonin reducing Ehrlich tumour growth by 40%  ; 8. from North Carolina (Quaile) that the minimum toxic dose of metformin in the diet was equivalent (by the usual average 10:1 conversion for faster rodent metabolism) to between 60 and 120mg / kg/day ie about 4-8gm /d  for about 5 years in humans;

9. and from Poland (Labuzek) that metformin shows beneficial effects in experimental models of neuroinflammatory diseases like Alzheimers.

10 In June an international team   (Jiralerspong ea Texas/ Germany) showed in an observational study that Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a 3fold higher pCR pathological complete response rate (24%) than do diabetics not receiving metformin (8%) . In response,  Garcia & Tisman from California point out yet another mechanism for this improvement,  that metformin induces malabsorption deficiency of both folate and especially metabolically active holotranscobalamin; which is  potentiated by neoadjuvant chemotherapy induced lowering of holotranscobalamin., despite apparently normal measured  total B12 levels.

This reminds us of  three  truisms:
diabetics are more prone to cancer and neuropathy and homomocysteinemia, these  need to be more concientously screened for;
diabetics are even more in need of all micronutrient supplements as antioxidants, insulin sensitizers, anti- glycation agents, nitric oxide providers, neurotropics;
and where cancer occurs, the golden rule is that no supplements  (other than metformin) should be given until conventional (radio/chemo/surgical) therapy  of the cancer has been commenced or refused. Folate and B12 should not be withheld simply because they may antagonize one link in the carcinogenic chain- there are dozens of dietary adaptations and micronutrients that are major anticancer adjuvants. without putting the patient at greater risk from vascular and osteoporotic disease than ever she was from cancer.
So that is at least 2 new studies a week confirming metformin’s supremacy.
Hence the obligation grows to prescribe as anchor support metformin to comfortable safe tolerance for life not just in all diabetics but also in all overweight people- starting if necessary in childhood-  who cannot maintain both optimal BMI, blood sugar and lipids off it.  And for protection against cancer and Alzheimers and vascular disease, to all perhaps over 50years.

But of course, global  metformin / galega use  along with other supplements  (from vitamins- minerals to all the other useful natural biologicals and insulin sensitizers- – from arginine to zeaxanthine including appropriate sex hormone replacement SHRT)-  will do away with perhaps 90% of the grounds for modern prescription drugs and non-post-trauma surgery/procedures, and much infertility and obstetric problems.  Painful shrinkage for the massive and toxic new -drug / disease/ hospital/hightech industry and the millions of workers it employs as lobbyists and marketeers. Hence redoubling of the effort by the Disease Industry and most governments  to suppress such natural prevention at all costs, by buying over politicians, medical regulators and powerful medical associations and patient groups..

14 Nov 2009   METFORMIN THE MASTER DRUG: FIGHTING NEMESIS- ADVANCED GLYCATION ENDPRODUCTS, AGES.

It’s just a month since this column reviewed the only “drug” that is (like fish oil)  a universal panacea: A STUDY OF THE CENTURY: METFORMIN PREVENTION OF THE TIMEBOMB  DIABETES.

Now a  new study from Univ. N Carolina (Cantrell ea) shows that metformin is not just major benefit against prostate and  breast cancer but also against endometrial (womb) cancer.

de la Monte and Wands (2005-2008)  from Brown University RI crystallize what has been obvious the past decade, that Alzheimers disease- they call it type 3 diabetes mellitus-  is not an inevitable part of aging but  is as much a product of insulin resistance – the  overweight  (fast food- couch potato- stress) pandemic- as are all the other interrelated  common diseases that constitute premature aging;   and therefore even more reason for everyone  to take galega/ metformin or other insulin sensitizers preventatively from as young as possible.

And a new novel study from Colorado University (Nadeau ea) again demonstrates that even juvenile type 1 insulin dependent diabetics have insulin resistance and need metformin and all the other anti-AGES agents  as well.

The McMaster University (Lemon Boreham and Rollo) landmark Supermouse Trial   5 years ago used a a novel model of our current self-induced obesity pandemic- a transgenic  mouse-  to show  that unlimited access to ‘balanced’ chow grows, learns, sickens and kills  far earlier than normal mice – which even in a lab environment neither overeat nor get lazy nor fatten. .   But 10fold increase in all the scores of evidence-based conditioned essential micronutrients (that deplete as we age) greatly increased the supermice’s learning, healthspan and lifespan. Such supplements include many powerful  natural insulin sensitizers.

Emory Univ Atlanta (Narayan and Williamson 2009) claim in a new review that “trials show that lifestyle intervention reduces diabetes incidence by over 50% and is more efficacious than metformin. But neither experience nor realistic long term  trials show this.

Now a  followup report from the landmark Diabetes Prevention Program DPP in the USA ( first reported in 2002) in  middleaged overweight laizzez- faire volunteers (not patients) gives the longest ever controlled observation study (the DPPOS) – a mean of 8.5 years- of the benefits of strenuous lifestyle+ diet (LSD) alone for 8.5yrs, or with metformin  for 8.5yrs plus  strenuous LSD added for 5.7yrs,   or just adding LSD  for 5.7yrs  to the initial placebo laizze faire group.
The outcomes are impressive:
The original placebo group (on average attempted diet + exercise) had a diabetes incidence in the first 2.8years of 11.0 (9.8-12.3)% ie per 100 patient years (ie an enormous 5.5% a year, or perhaps 55% over 10 years); with LSD for the next 5.7 yrs their incident  diabetes halved to 5.6 (4.8-6.5)% ie perhaps 1% a year- a reduction of about 82% .
The original LSD group after 2.8yrs had had a new diabetes rate of 4.8%; continuing this regime for 3 times as long saw their new diabetes rate climb to 5.9%;
but the just metformin group– who had new diabetes rate of 7.8% – with added LSD for 5.7yrs saw their new diabetes rate fall further to 4.9% (compared to 11% on placebo and routine counseling) – and unlike the LSD-alone group, they maintained their original weight loss, in fact those over 60years maintained a further 2kg weight loss. Compared to the original placebo group diabetes incidence of 55% over 10years, metformin plus sustained exercise lowered new diabetes to about 8,9% over 10years ie 84% reduction in risk.

Thus this unique 10year study confirms that adding even lowdose metformin to LSD more than halves the incidence rate compared to  the average laizzez- faire patient on feeble diet-exercise alone, and maintains better fatloss than either mild or strenuous LSD alone. We know from clinical experience that titrating metformin to tolerance can maintain weight loss of 8% -provided it is not combined with psychotropes that hugely increase weight gain..

Thus there is every reason to always add metformin cautiously from the beginning to diet-exercise counseling in every overweight patient battling to lose fat and regain fitness, to abolish the lethal risks of metabolic syndrome and its diverse consequences- diabetes, cancer, cardiovascular disease, arthritis, dementia  etc.

It is common knowledge that less than 10% of patients maintain significant weight loss on any diet and exercise regime- it goes against human nature. The DPPOS confirms that preventative metformin to tolerance plus sensible diet and exercis is  the only regime that maintains weight loss and thus improves all health- drastically lowers all-cause premature disease and mortality.

No heavily marketed  designer “appetite/weight suppressant” drugs remotely achieves all the benefits of metformin, a unique  anti-glycation antioxidant,  appetite and weight suppressant, and anti-cancer, -stroke, -vascular , -infection, -arthritis , -infertility, and -dementing- disease natural nutrient. Hence as previously described, Big Pharma and the Disease Industry do all they can to suppress it’s preventative use (including having Regulators threaten us) , since no modern designer drug can compete. A short-term study (3 months) like the new University California Davis trial (Banazewska ea) (of statin versus metformin in PCOS) says nothing about the longterm benefits that matter to patients– not the Drug Industry whose concern is shorterm profit at all cost.

ARE SYNTHETIC HORMONES THAT WERE DESIGNED FOR CONTRACEPTION IN HEALTHY YOUNG WOMEN SUITABLE FOR POSTMENOPAUSAL PREVENTION?

It is at least 70years  since modern science suggested hormone contraception with prolactin or progesterone or estrogen; and since estrogen therapy of menopause was first described (by Prof Joe Meigs himself) on Pubmed – with presentation of endometrial cancer after 8 years on estrogenics .

In general, after 50 years of hormone contraception since we were students, with more than a hundred million women now on low-dose hormone contraception, such synthetics – a progestin with or without ethinylestradiol EE2 – are considered pretty safe in current low dose compared to unplanned pregnancy or physical contraceptive methods, provided contra-indications are respected; with almost 50% reduction in future endometrial and ovarian cancer; and no change in mortality from breast cancer.

But in A Short History of Oral Contraception (2006), Prof Wolfgang Oelkers notes that Ethinylestradiol EE2 was only discovered in 1938 and the first highly active progestin in 1954, leading to the registration of the first oral contraceptive OC pill in USA in 1961-  and within 10years the occurrence of malignant hypertension on such OC pill, with acute and often irreversible renal failure due to the EE2 activating both the renin-angiotensin syndrome and thrombosis. (I had the misfortune to have to put on chronic dialysis a beautiful young university student who presented on such OC pill in 1974 with thrombotic thrombocytopenic purpura with irreversible renal failure, while I was working at the Leeds General Infirmary under the dialysis pioneer Dr Frank M Parsons).

Oelkers notes that even ultralow dose combinations of EE2 and 3rd-generation progestins can still cause thrombosis; and The thromboembolic risk associated with the recently introduced transdermal combined  contraceptive Evra®does not seem to be any better than modern oral contraceptives, since it also uses EE. This, unlike natural oestradiol, seems to affect hepatic protein synthesis  independent of its route of application.    In postmenopausal hormone replacement therapy, the transdermal route of oestradiol application seems to be devoid of a prothrombotic risk.  Development of a transdermal combined hormonal contraceptive with oestradiol instead of EE would provide a great next  chapter in this endocrine story.

Wiki reports that The Ortho Evra contraceptive patch and the Evra contraceptive patch are both intended to gradually release into the systemic circulation approximately 20 µg/day of ethinyl estradiol and 150 µg/day of norelgestromin. Since such hormones bypass hepatic metabolism, no wonder the doses delivered still have thrombotic risks. 

Does that make such massively profitable contraceptive hormones that were designed in fierce competition for fertility (and ovarian) suppression in healthy young women both safe and effective for the ageing no-longer-healthy fattening (post)menopausal women? Parenteral physiological balanced HRT does not cause the fattening and muscle loss that OHT does.

Now young Janey asks an important question: “I am 56 yrs old and very happy with Yaz (ethinyl estradiol EE2 plus drospirenone). I do menstruate while on the placebo. I would like to find a doctor who will let me stay on Yaz, which I like a lot, or if absolutely necessary try the Testosterone, Bi-estrogen, Progesterone combo. I worry about weight gain that occurs in almost all cases of oral HRT. I need the bone protection and hair, skin and vagina health benefits that have been wonderful on Yaz. “

CANCER RISK OF ORAL XENOHORMONE THERAPY:

In July this column last visited ovarian cancer as a relatively rare disease but with high (70%) mortality due to its late presentation, hence feared more  than other womens’ cancers eg breast, endometrial or cervix.

So it is worth revisiting the major Danish observational study spanning 10 years published last July ; which documented almost a million women for   8 years. The crude primary ovarian cancer OvCa incidence rate in never-users (5 million women-years) was only 0.04%, vs 0.052% in current  HT users (1.4million women-years) ie overall, hormone therapy HT increased the risk by 1.3, or 30%. That study concluded: “Combined therapy with norethisterone was associated with an increased risk of epithelial ovarian cancer (RR, 1.55; 95% CI, 1.36-1.76), which was not significantly different from the RRs associated with medroxyprogesterone, levo- norgestrel, or cyproterone acetate CPA”.

The only regime in that series which was not statistically significantly associated with increase in OvCa was in the 23 women who developed OvCa on solo transdermal E2TD ie hormone replacement HRT (out of a total of 64000 women-years on E2TD), where OvCa relative risk increased by 13% but the 95% confidence interval spanned unity (0.74 – 1.71) ie not significant . By contrast, oral estrogen HT for some 287 000women years increased OvCa risk significantly by 34%; and any progestin added to estrogen ie in some 847 000 women years increased OvCa risk above no HT by 47% to 68%.

This neutral effect on OvCa only of unopposed E2TD is most reassuring for women. All the synthetic progestins they compared – including the antiandrogen CPA- were associated with significantly more OvCa (let alone BRCA).

The nub of the matter is that gynecological cancers generally do not apparently proliferate without the influence of female cyclical hormone levels- FSH, LH, estrogen – and especially oral estrogens and progestins. In the main study of cancer with Turner syndrome, in 3425 women in UK followed for some 17years ie 58000 patient-years, breast cancer was 70% less common than average women, while the only gynecolological cancers that appeared to increase were endometrial cancer 8fold at age 15-44years, and gonadoblastoma of the ovary by 8% by age 25years- and gonadoblastoma is over 90% associated with the ‘male’ chromosome Y . These statistics are reassuring considering that most such women were treated with oral estrogen therapy, and that uterine cancer is avoidable if estrogen therapy is appropriately opposed with some progestin, with periodic withdrawal bleeding allowed.

Unbalanced anabolics eg vitamins or sex hormones merely promote dormant malignant cells already present, they do not cause cancer de novo; and adult cancers take an average of 20 years to present clinically.

There is no report on Pubmed of testicular cancer developing on testosterone TT replacement let alone abuse; nor of increased ovarian or breast or uterine or colonic cancer in long term female testosterone users – if anything long term testosterone replacement in women appears to diminish breast proliferation in rodents, monkeys and humans, as this column has regularly reviewed..

It is common cause from clinical menopause practice and trials that pharmacological ie unphysiological oral estrogen – progestin therapy – while improving bone density- increases body fat and if anything decreases lean ie muscle mass and collagen -hence the increasing postmenopausal fatness frailty and urinary incontinence of elderly women on oral HT.

DROSPIRENONE

The new combinations with  drospirenone for contraception ( Yaz/Yasmin- drospirenone DSP -ethinylestradiol EE2 in fertile women), and post menopause (Angeliq – DSP -estradiol E2) certainly seems to reduce fluid retention and thus weight and hypertension problems, and to have anti-androgenic benefits when required. There is apparently no published longterm data on DSP to judge it’s influence on cancer and mortality.

This column has regularly detailed reasons for postmenopausal women PMW to avoid oral transhepatic sexhormone therapy with the high doses of oral estrogen needed to control menopause symptoms, and the multiple adverse effects of transhepatic xenohormones like EE2, premarin and progestins. But 50 years of experience including the under 60’s cohort of the WHI, and the Oulu trial (Heikkinen ea ) certainly showed overwhelming benefit of oral estradiol/conjugated estrogen-progestin combination when started appropriately in well young PMW for up to 10 years. It has been well known for three decades that continuing such OHT well beyond 10 years gradually increases the incidence of BRCA above non-users.

However, as we have repeatedly discussed, why should Kitty subject herself to the longterm risks of eg breast cancer from such oral use of any designer hormones like orohepatic estrogens and progestins? when evidence is that physiological human HRT with non-oral, or oral micronized (see Dr Lee Vliet’s books) sexhormones, has no risks, only benefits – especially when human E2+- estriol E3 are balanced by progesterone P4 and testosterone TT as by creams, or implants, or tiny subcutaneous self-injection, all easily available by prescription in US.

And when oral EE2 ethinylestradiol for contraception is associated with low but real thrombosis and biliary risks; and when it is enormously potent compared to human estradiol; and when it’s successor competitor diethylstilbestrol DES is still causing horrendous problems in women and their children and grandchildren after it was recklessly prescribed from the 1940s to the 1970 without there ever being evidence of benefit let alone safety.

Lowdose EE2 has certainly proved it’s relative safety when used as birth control in young healthy non-overweight women. But just as oral prempro has proved that it causes problems and little benefit when started after the age of 60years in overweight women ie those already with atheromatous disease, why take potent synthetic oral EE2 post menopause? Using a potent synthetic is neither prudent, physiological nor replacement.

Recently a Brazilian trial confirms equal benefit of “nonoral HRT (nasal spray- estradiol -micronized vaginal progesterone) ; or oral HT (low-dose estradiol-drospirenone ) for 2 years on metabolic, vascular and body fat risks in early postmenopause; but once again that Triglycerides and von Willebrand factor levels decreased significantly only with nonoral treatment”– ie the nonoral- parenteral- route is better protection against atheroma and thrombogenesis.

DSP combined with oral E2 is certainly theoretically advantageous HT for those PMW with hypertension and fluid retention. But since no longterm trials or studies of DSP use are available yet, it is too early to judge if DSP+E2 is as safe as physiological HRT with appropriate combination of E2/ estriol E3/ P4/ TT.

But as we have repeatedly pointed out, the evidence from both evolution, and 60 years of experience, and trials, is that physiological parenteral human hormones ie not by the orohepatic route have distinct safety and physiological benefits, as comprehensively detailed by l’Hermite, Genazzani ea on behalf of the International Menopause Society recently , as well as all the data this column has previously reviewed on the importance of balance non-oral testosterone as part of the HRT regime.

So the answer for Janey is: be a volunteer guinea-pig if you like, but dont use Yaz (ie EE2)  but rather use  the natural  E2 -containing Angeliq – in low dose. Since all other synthetic progestins increase ovarian cancer in women, rather use natural progesterone parenterally until Schering publishes a controlled trial showing that drospirenone does not increase ovarian cancer when fed to reproductive age female rodents (let alone women) for the human equivalent of a decade or more. There are no human studies reporting drospirenone use for a decade or more.

But  preferably enroll yourself in a longterm randomized comparative trial of the new (eg Angeliq)  versus the old. – balanced appropriate estradiol-estriol-progesterone-testosterone, whether as a cream or depot injection-  titrated to what suits you.  Why risk the new but long-term unproven when the evidence for the old (as long as human evolution with balanced non-oral human estrogen +P4+TT) is so strong.

And while you may find out the best for you  by your trial and error without longterm adverse effect, none of us may  learn better by your self-experimentation?

MAMMOGRAPHY INCREASES RISK OF BREAST CANCER

neil.burman@gmail.com

Wednesday, 2 December , 2009 by:  S. L. Baker features writer:

“Mammograms cause breast cancer, groundbreaking new research declares , especially in those at high risk with familial (breast/ovarian/ prostate/ uterine/- colonic) cancer.”

A 50% increase in risk is relatively small compared to doubling or five-fold increase in risk as eg smoking may cause. But for cancer that affect perhaps one in ten women, even 20% increase in risk is significant.

But remember that while even appropriate HRT reduces deaths from breast cancer by a third- as with prostate cancer, it seems to reduce the incidence of highly malignant cancer, merely bringing to attention earlier the less serious ones.

So patients starting any HRT should be screened first and then periodically so that the HRT cannot be blamed for having caused the cancer. The recent APHRODITE  trial of testosterone patch in women with androgen deficiency (which this column commented on in August)  only lasted 2 years, which shows the fallibility of screening mammography annually  in missing sleeping  small cancers until they are accelerated by anabolics.

As this column has repeatedly reviewed, all evidence from rodents to primates to humans is that appropriate balanced  physiological testosterone replacement reduces breast proliferation, and thus in the long term reduces the occurrence and risk of breast cancer.

It is common cause that cancers take an average of 20 years from their origin to become clinically evident.

Ultrasound is not as sensitive as xray mammography in detecting cancer.

So until accurate thermal scanning is proven to be anywhere near as specific and sensitive as mammography, the latter remains the best diagnostic tool we have available. For women who already have a suspicious breast lump/pain/discharge, diagnostic mammography remains the gold standard, with ultrasound and MRI as backup aids.