ADVERSE METABOLIC EFFECTS OF CHLORTHALIDONE, SPIRONOLACTONE AND ALL MODERN ANTIHYPERTENSIVES – BUT NOT LOWDOSE RESERPINE+CO-AMILORETIC.

A new paper from University Texas  states “chlorthalidone, the first-line drug therapy for hypertension”. They then show that it “causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.”

But there is no evidence exept in the manufacturers’   mind to claim that chlorthalidone is the first-line drug therapy for hypertension. Chlorthalidone is simply another thiazide- which all share the same problems. But hydrochlorothiazide has no effect on the autonomic nervous system.. Nor does amiloride in  sensible real life use.

However, the gold standard of initial therapy for most cases of hypertension remains the triple combination (at US$6/year) of lowdose co-amilothiazide (amiloretic) eg 6.5 to 13mg/day (or 3 times a week) plus lowdose reserpine 1/4 to 1/2 a day (or 3 x a week) – which combination -especially with fish oil and multinutrient (vits A-K, zinc, magnesium,  arginine,  carnitine, CoQ10 etc) for multisystem benefits- has no adverse effects while reversing essential hypertension and other cardiovascular risks in all but the most advanced cases.

This avoids the major disadvantage of gynecomastia from spironolactone – which even at 50 mg/d caused gynecomastia in 6.9% , ie there is still potent antiandrogenic effect at low dose, which is bad for both genders in a world already heavily polluted by xenoestrogenics.

BEWARE OF POLYPHARMACY WITH DESIGNER DRUGS

Q:  surely polypharmacy is bad?

A: yes- if we use long-term-unproven multiple designer drugs to treat each symptom, instead of evidence-based remedies that address underlying causes. .  Statins and antihypertensives lower cholesterol, vascular disease and bloodpressure, but  despite mulltiple adverse effects they dont address the causes.

We have to beware double standards. We cannot criticise FDA – AMA devotees for polypharmacy when as holistic physicians we advocate it.

15 years ago I tired of taking and promoting futile risky drugs for each disease;

so soon I was taking 30 pills of different evidence-based supplements a day.

Now I take and advise the gamut of perhaps 70 as one drink of a polysupplement blend twice a day- the only exception remains fish oil capsules, and perhaps some hormone creams and tabs including for  eg resistant hypertension, arrhythmia etc  if indicated.

So  we  are still promoting polypharmacy, albeit now rational and evidence-based, not a toxic mix of designer patents .

We – physicians,  homeopaths,  nutritionalists, cooks – distinguish good natural polypharmacy ie well-mixed diet from bad prescription polypharmacy with multiple unproven designer drugs. what is worse than a diet high in cornstarch, sugar,  cooked fats, artificial sweeteners and colourants – that are all endorsed by the FDA?!

But for serious and chronic illnesses, polypharmacy is essential eg for tuberculosis, AIDS and other bad infections;  cancer;   rheumatoid arthritis, vascular disease, osteoporosis – if necessary using holistic appropriate combination of rational designer drugs like ARVs, antihypertensives, cytotoxics, antibiotics with appropriate natural combination of eg vitamins, minerals and biologicals eg  hormones, fish oil, human biologicals like coQ10/arginine/cysteine/arginine/glucosamine, and herbs..

DEATH YET AGAIN IN THE TEMPEST, THE TIME OF CHOLERA. CRY THE BELOVED COUNTRIES STRICKEN BY PLAGUES AS IN PHARAOH’S TIME: WHO NOW WILL TRY THE TYRANTS?

It is 2 months since we lamented  World Toilet Day.

This week 27 January we lament the annual International Holocaust Memorial Day, for crimes against humanity everywhere. .

Ironically  Scriptures tell us this  sabbath’s Torah portion  is about the 10 plagues that were inflicted on the innocent people of Egypt because their tyrannical Pharaoh 3400 years ago  stubbornly refused to release the enslaved people of Moses, at least allow them some rest and respite from beatings and infanticide and daily hard labour..

So what has changed in the past 2 months, 3400 years?

Profiteering tyrants never learn, repent from their cruel greed-  except sometimes in Shakespearean parable, the brilliant  RSC stage production of The Tempest now showing in Cape Town, where the freed spirit  Arial in turn entrances the  Christian European despots  – (who keep piously crossing themselves,  led by the inimitable SirTony Sher as the  wizard Prospero tormenting his black slave Caliban,  John Kani)  to repent and reform.

Mugabe the megalomaniac cunning despot –  venerated  and aped for  long by the infantile Mbeki and now Motlante,  Zuma and the big powers-  has lost much of his country’s citizens (to starvation, to plagues, to his thugs’ genocidal  violence and plundering  for 25years,  or to  flight by stealth -unlike the Israelites’  legendary divine escape from Mitzraim into the Sinai wilderness  for 40years). This the Roman Catholic teacher Mugabe, with a BA in Administration, and Masters degrees in Science and Law from London University, apparently the most  broadly academically qualified leader in the world – but no hypocrite, no theological pretensions. He proudly models himself on Hitler but in addition as His Excellency the Honourable, and on immoral “practicing” Christian leaders like Bush and Blair …  .

There were reportedly 13.3 million Zimbabwean citizens 18 months ago, with 31births per 1000 and 21 deaths per 1000 population. Now there are said to be some 4million work-seeking Zimbabwean refugees in South Africa; and with deaths there now  rumoured  to exceed 5000 a day – almost 2 million a year- that till-recently thriving country is rapidly being depopulated.

Now in Zimbabwe, apart from the few thriving  on US dollars and imported commodities,  those who remain –  the children and  the old–  are dying like flies from  plagues ancient and modern for want of clean water, safe sanitation and starvation. And still divine retribution or a UN  peacekeeping commando force has not removed Mugabe and his vampires armed by China and now South Africa -nobody is prepared to spend a cent rescuing Zimbabwe simply because it is Africa, and  the power-holders in the rest of the World don’t care. .. while Mugabe continues to blame Britain for his country’s woes. There are no more functioning hospitals because there are no supplies, no power, no water, and no staff – those who cannot flee are too busy trying to find food and water for survival.Those in power drive their Rolls funded with South African government donations  to live in palatial suites in South African hotels.

And in turn, for want of clean water  and sanitation, and jobs, education, housing and security  that President Mandela  promised South Africa in 1994, and Mbeki and Zuma in  1999 and again in 2004, increasing masses  of South Africans are now dying from the ancient plagues of cholera,   typhoid and  TB,  fear, ignorance, violence from lack of law enforcement officers and teachers and jobs, exposure,  from lack of water, electricity,  jobs, housing, starvation; and the new plague of AIDS.

The ANC leaders since 1998-  the President Economist Mbeki and President  resistance general Jacob  Zuma,  the medical doctors Nkososama Zuma & Tshabalala- Msimang, the lawyer Professor Asmal, the economist Trevor Manuel –  in 1998/9 directed Parliament to spend the country’s riches on R64billion of hightech arms we do not need and cannot use – most skilled people have fled the country, and there are no armed invaders in sight –  then to  give away to buddies South Africa’s oil reserve, iron, airliners, forestry and game reserves, then on farces like Sarafina and hundreds of corrupt MPs in Travelgate – while denying the masses with AIDs lifesaving antiretrovirals till forced to give in a year ago.

And still the RSA government goes on giving multimillion dollar handouts to Mugabe’s horde (while Mugabe and his puerile wife and retinue go on shopping sprees with Government funds)  and burning (with terminal environmental pollution) our irreplaceable coal  that is needed  for oil, gas, and thence plastics and medicines.

Yet to this day Mbeki, Motlante, Zuma continue to treat the electorally defeated Mugabe obsequously as head of state, do nothing to have him and his murderous gang arrested by an international peace force within days and restore basic services, supplies  and order there.

Why not? Because as before, what Mugabe  gets away with, other despots in turn can. It is not 2 years ago that Mbeki said “please Mr Mugabe, do the right thing. Where thou leadest, we must follow.” And still the de facto South African President Jacob Zuma does nothing to arrange a rescue occupying force to restore sanity in Zimbabwe – as Israel had to send in  this  month  to stop daily bombardment  of it’s people from cowardly terrorists using  Palestinian civilians as shields in mosques and schools in Gaza. .

Now the upcoming election  in South Africa celebrates SADEC’S Cesspool Day of Progressive Illiteracy Violence and Plagues, that the ANC under Zuma-Zuma-Manuel- Mbeki in their divine arrogance and cruel indifference to suffering  continue to inflict on Zimbabwe and South Africa, almost 50million people. Not benign self-serving patriarchal enslavement that has existed since time immemorial, just progressive deprivation and hopelessness.

But (as in the case of  the murderous Kissinger Kindergarten – Cheney, the Bushes, Rumsfeld and Wolfowitz, and their British allies  that  increasingly disrupted and impoverished  the world since the comic Reagan  reign), who will try for treason the ’elected’ (by fraud and lies) outgoing  tyrants in America, in the ANC,  the  arch-leaders of the  former Apartheid regime, and now Mugabe’s Gang?

Orwell in 1949 projected such anarchic governments to 1984 – by when the Kissinger-Rumsfeld gang was already hard at work on their Shock Doctrine,. As a result, the rate of western degeneration has accelerated:  Margaret  Attwood  in turn published the prophetic The Handmaid’s Tale(1984)  of enslavement in a future rabidly religious impoverished USA- and the endgame she in turn predicted in 2004 in her brilliant book  Oryx and Crake, is now happening to us, America and it’s dependents Israel and Britain bogged down in insoluble wars of Western imperialist  making against Islam while the world  faces environmental distater in our lifetime and plunged  into the worst economic recession ever – of America’s making 1 2 3 ..So much for Milton Friedman and Kissinger’s blueprint so assiduously carried out by the Cheyney-Bush disciples since Reagan’s time. Eerily, Kissinger again visited the Kremlin last year, more than 60 years after his first contacts with the Soviets.

Nothing was learnt from Victorian folly,  Rhodes’ Boer War and Matabele massacre, and Milner’s Kindergarten, which entrenched economic oppression and deprivation  of the poor  in Southern Africa for another century till this day.

Now, after six thousands years of in turn Pharanoic, pagan Roman, Arab Muslim and Christian- European enslavement,1 the poor continue to be enslaved throughout the world  by the legendary tyranical greed of a few hundred families. Once again, Marquez’ Time of Cholera for want of compassionate love.

part 2: WIKIPEDIA ERRORS IN SEX HORMONE ARTICLES

DOZENS OF MISTAKES IN WIKI MEDICAL ARTICLES:

SEX HORMONES:

In Endocrinology we learnt decades ago to use only human hormones in humans for endocrine ie hormone replacement, because of the problems of xenobiotics- animal (and plant) hormones eg:

1. risk of infection/ prion transmission;

2. risk of antibodies neutralizing their benefit;

3. they work on human hormone receptors- foreign hormones like equilins (and designer progestins) certainly bind to the respective sex hormone receptors, but they have some unwanted effects, and also block the intended human hormones from acting there.

4. the predominant hormone in premarin is estrone E1.  This hormone usually dominates by default post menopause- when women with low estradiol and often androgens suffer the multisystem degenerative aging diseases of hormone decline including breast cancers. Also, it is progestin and estrone dominance, not E2, which are most commonly associated with breast cancer.

5. For the above reasons, all hormone deficiencies that are treated by endocrinologists use only human hormones in physiological doses to produces blood levels in the healthy young range. Why are postmenopausal women denied the same right?

The Wiki Equilin entry says at present:

“Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin, the most commonly used form of estrogen for hormone replacement therapy in the United States of America. Estrone is the major estrogen in Premarin (about 50%) and equilin is present as about 25% of the total. “Estrone sulfate is usually the major form of estrogen in women.”. Equilin is not normally present in women” .

But under estrone wiki contradicts itself, it says “Estrone is the least abundant of the three hormones” in healthy young women ie less than estrone and estradiol. So it confirms the truth, that estrone is certainly not “the major form of estrogen in women”- at least not during the ~40years of menstruation. During the reproductive years, the blood estradiol averages about 20% higher than estrone.

XENOHORMONES: Why does wiki not even have an entry for xenohormone under xeno-, under premarin or under hormone replacement therapy? It states incorrectly under Estrogens that “nonsteroidal estrogens include synthetic estrogens known as xenoestrogens” – yet under Estinyl wiki states that estinyl was the first orally active synthetic steroidal estrogen. Wiki does say “ xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it”. Obviously equilins ie premarin are xenobiotic hormones in humans. But under Estrogens it does say “In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens.” And “The “first orally effective estrogen”, Emmenin, derived from the late-pregnancy urine of Canadian women, was introduced in 1930 by Collip and Ayerst Laboratories.”   Actually  Chinese physicians introduced them 2600years ago.

But at least Emmenin is human hormones. Equilins are xenohormones ie potent foreign hormones not found in humans. It is unclear why women should be treated with premarin – ie horse excreta. In Western medicine, humans are generally advised NOT to drink urine or extracts of urine.   Where does the FDA keep it’s brains and ethics about women? – does it consider them mares?

So why (except for Wyeth’s and the FDA’s economic benefit, and women’s detriment) does the FDA allow premarin, when it is mostly equilins and estrone, with negligible estradiol? At least oral estradiol – even in micronised oral microdose- is the most physiological human hormone.

Conventional Premarin  by mouth to control menopause symptoms produces combined estrogen levels  and effects  >10 times higher than those of healthy young women, which is surely why it is associated with both early promotion of subclinical breast cancer so that there is a spike of cancer in the first 2 years (such cancers have surely been present, growing slowly for at least a decade); and gradual increase in new breast cancers presenting after  about 12 years on premarin – all of which are apparently triggered initially by progestin/ progesterone (Horwitz 2008). . By definition, horse waste premarin is NOT a hormone replacement in humans- it would indeed be HRT for mares.

English is an explicit language. In humans, “Hormone” refers to dozens of different messenger chemicals- Wiki lists at least 60- which include testosterone, progesterone and the estrogens estrone, estradiol and estriol- but progestins and the many equilins are not listed.

Common daily misuse should not change the meaning of words.

So  HORMONE REPLACEMENT HRT in humans refers to physiological replacement of any available  missing hormone  by the same human hormone to the usual healthy functional level eg insulin by insulin to normal insulin and glucose levels, thyroid by thyroid, or cortisone by cortisone etc . Using a different hormone would be substitution. One cannot in practice replace a human heart  or kidney by anything but a human heart or kidney, nor human red blood cells by anything but compatible human red blood cells . One cannot effectively and safely replace insulin, growth hormone or most other hormones (including testosterone, estradiol and progesterone) by mouth- which is why percutaneous insulin has been available for >80years, and percutaneous sex hormones for >60years  (see eg Sex Endocrinology Handbook for the Profession: Schering Corporation, New Jersey  first edition 1944). And a human kidney transplant – not dialysis- is replacement of physiological kidney function.

We do not  use or need  the longterm risks of costly  synthetics eg bisphosphonates  to prevent and treat osteoporosis when the natural supplements- appropriate HRT, fish oil, minerals and vitamins safely abolish osteoporotic bone fractures – which bisphosphonates cannot do since they address only one of many  fracture risk factors . There is no evidence whatsoever to justify the wiki marketing hype that “bisphosphonates are the main pharmacological measures for treatment”, nor that  “newer drugs such as teriparatide and strontium ranelate” are anywhere as effective and safe in osteoporosis. In addition, none of these marketed drugs give the ~50% reduction in all premature aging disease and mortality that the full collation of natural supplements do.

HORMONE THERAPY HT refers to use of (usually megadoses ie) supraphysiological doses for treatment of some pathology eg highdose cortisone for allergy, asthma; premarin or estinyl for treatment of a bleeding problem or prostate cancer; or estinyl for contraception- suppression of normal physiology; or high-dose testosterone HT for the androgen resistance syndrome or female breast cancer, highdose thyroid for thyroid resistance syndrome.  Thus kidney dialysis uses synthetics, artificial therapy to purify the blood until a working transplant replaces the dead kidneys.

Thus metformin and the dozens of similar insulin sensitizers are prohormones for hormone therapy of metabolic syndrome and type 2 diabetes because they reduce insulin resistance, allowing insulin to work effectively at  normal insulin levels rather than the futile raised insulin levels found in insulin resistance or after sulphonylureas.

It is at least  thirty years since it was first observed that xenoestrogens and xenoprogesterones – especially by mouth- are not compatible with older women in that they cause common and serious adverse effects both short term and long term, whereas physiological doses  and blood levels of  appropriate balanced human hormones adjusted to tolerance do nothing but good.

While oral premarin alone in historical American doses  (and oral estradiol in Europe),  in appropriate use in young postmenopausal women (eg in the WHI), reduced all deaths and all major degenerative diseases by a third, these still increase the risk of thrombosis, gallstones and hypertension. And oral progestins block many of the benefits of estrogen and human progesterone, and promote breast cancer.

At present, apart from foodstuffs and plant extracts,  it seems that only one solitary animal ie non-human extract is indispensable for human therapy: chondroitin. Trials show that it is best combined with glucosamine (from cornstarch). Recent RCT for long enough shows that this combination not just reverses cartilage loss but (in not too advanced cases with bone grating on bone) actually restores cartilage so that normal function returns to previously crippled knees needing replacement. But unlike the xenoestrogens in premarin and EE, chondroitin is a natural  essential glycoprotein in all species including humans. We simply do not any longer harvest chondroitin or growth hormone from human corpses- only blood and organs for transplantation from highly selected donors, with exhaustive permission. (we also need extra free fatty acids- fish EPA and DHA- but technically these are not made by fish, they are made by marine algae).

Thus premarin and EE are unique in being the only xenohormones, xenobiotics from other species, that humans- women (rarely men)- are advised by doctors to take for “replacement”- when there has never been any evidence that they are as  effective and safe longterm as pure human estrogen  whether orally or parenterally.

It is difficult to find on Google a definition of esterified estrogen EE versus conjugated equine estrogen CEE. But the landmark 2004 article from Washington State and Leiden Universities gives the game away. It shows that Conjugated equine estrogen CEE (ie premarin) contain estrone sulfate approximately 53% and equilin sulfate about 25% (and dozens of other steroids in the remaining 22%). Esterified estrogen EE contains approximately 80% estrone sulfate and approximately 11% equilin sulfate; and in that trial, at equivalent medium to high doses, the CEE gave over double the risk of deep vein thrombosis VT; whereas (compared to controls), EE use did not increase VT.. .And under Estrogen, wiki states (without a reference) “In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated equine estrogens.”

So it is unarguably clear from both 50 years of observation and trials that postmenopausal women are put in jeopardy whether they are denied appropriate  sex hormone replacement SHRT for almost the second half of their lives , or given the false comfort of “convenience” oral therapy especially with xenohormones such as premarin and progestin, or bisphosphonates. Men are not exposed to such bias at the behest of a giant USA manufacturer like Wyeth, and the USA government – the FDA – or the scientifically unverified change of mind of a leading gynaecologist like William Masters between 1953 and 1957). .

Men (and women) with biochemically and clinically proven (relative) hypoandrogenism are given the best endocrine  replacement ie testosterone through the skin. As with oral HT in women, androgens by mouth have been shown for decades to be either hazardous or ineffective, whereas testosterone through the skin to physiological  balanced youthful sex hormone  blood levels does nothing but good in men and women.

Wiki does not even have articles on androgen deficiency in men and women, merely mentioning the deficiency among many causes of sexual dysfunction. . But it is crucial to note that, irrespective of sexual complaints (which many patients are too inhibited to raise), relative androgen deficiency (in relation to available estrogenics) is common in most older people with chronic diseases, and worth trial of replacement.

Physiological correction of testosterone deficiency (from levels below the average of healthy robust sexually active young adults) into the upper range of healthy young adults often gives major improvement not just in sexual function, but also in reversing overweight- metabolic syndrome- obesity; depression; mood and mental problems; chronic fatigue and pain; osteoporosis and frailty; hypertension and cardiovascular disease; cancer, autoimmune diseases and infectivity; and anaemia.

The benefits of parenteral human  SHRT (as opposed to oral xenoHT) – including reduction in the mortality from cancer, cardiovascular, osteoporotic, autoimmune, mental and  mood diseases, and total mortality even on HRT after breast cancer- are set out in detail in a major 2008 review “Could transdermal estradiol + progesterone be a safer postmenopausal HRT” by a leading International Menopause Society team under Professor Andreas Genazzani.

By contrast, a 13year review of 67700 postmenopausal US women by the American cancer Society released 2 days ago showed an incidence of breast cancer of only 0.26% per year. The adjusted rate on estrogen+progestin (largely premarin + provera there) was increased by about 80% compared to non-users, mostly in the first 2 years as in the Womens’ Health Initiative. On premarin alone, in  average ie overweight to obese women , premarin alone associated with 50% more cancer only after >10years – as in Henderson’s study of 1982.

As discussed above after 60years of use of appropriate balanced non-oral human hormone replacement (estradiol, prodesterone, testosterone), the evidence is that if anything breast cancer and deaths from all causes are reduced.

So why use oral HT especially premarin and progestin for shortterm convenience,  when non-oral appropriate  (triple) HRT  gives minimal risk but major lifetime benefits?

And two centers (Harvard, and North Carolina) review fresh data that restoring low testosterone level to average level  with depot tesosterone injection in symptomatic men with androgen deficiency provides mulltisystemic benefits without increasing any risks including that of prostate cancer.

In conclusion, it is obvious that for researching health matters, the public is advised to use first the websites of international expert associations eg ISSAM- the International Society for Aging Males; IMS- the International Menopause Society; and Medline- Pubmed;

rather than those which are prone to commercial or academic local bias (by drug/ equipment companies and other local vested/ financial interests) like universities, patient support associations, the FDA/NIH, other National Health Services, private practice and craft groups, wikipedi or lay associations/ reports and advice.

Wikipedia health articles should be depended on only if they are certified by international consensus bodies like ISSAM and IMS, or if material facts are referenced to a verifiable expert source. Neither trials, reviews nor metanalyses are necessarily reliable evidence.

This review is not criticism of Wikipedia for providing an excellent open forum, it just highlights the potential biases in a forum which is not subject to oversight by an international panel of specialists in that field who do not individually  have vested interests or limited experience. And who doesn’t? The two criteria are in a sense mutually exclusive, since  the greater one’s  age and experience, the more biased, closed-minded, entrenched one may become.

Detailed referenced reviews the past year on each of these topics are published below.

ndburman mrcp(uk) gonadopause physician.

WIKIPEDIA IS INVALUABLE, BUT BEWARE IMPORTANT BIAS IN IT’S CHRONIC DISEASE ARTICLES PART 1:

Wikipedia is now the top and invaluable reference source for the public.

Wikipedia entries are commendably frequently updated; but this does not mean that the entries are both up to date, objective and unbiased, since they are constantly being altered by conflicting outside editors.

We suggest amendments in  Wiki  health entries where appropriate as follows.

It will obviously have most effect if the recommendations to Wiki are based on consensus by the relevant international leaders- eg the International Society for Aging Males ISSAM, the International Menopause Society IMS, the International Pediatric Association, and so on; NOT by drug companies and their product promoters including individual disease associations (which by definition do not take a holistic multisystemic  view) or private and academic national groups whom/which drug companies sponsor/influence- including the problem of ghost writing! Many entries on Wiki appear to suffer from this problem of vested interests.

INTRODUCTION: EBM:

The Wiki article on EBM  Evidence-based_management ie  Evidence-Based Medicine hits the nail on the head. Medical diagnosis and treatment need to be evidence- based- but as the heretical pioneers Shaughnessy and Slawson stress, this must be POEM- patient-orientated evidence that matters. However, for the Drug Industry and their state arm  the USA FDA, the chronic major degenerative diseases are the biggest money-spinners since they arguably need lifelong drugs. Hence the Disease Industry  has invented epidemics of chronic diseases that were regarded as inevitable or self-induced until drug companies came up with designer drugs for each new  disease to medicalize – eg  epidemics of erectile dysfunction, mild to moderate hyperlipidemia, anxiety, mild-to-moderate depression, mild PMS and menopause syndromes, smoking, alcoholism,  and so on. Then  they and the FDA  generated trials and procedures  testing these patients with new “diseases”, and convinced the public that despite clinically insignificant benefits in trials often lasting well under a year, tested against only placebo,  the drugs could be registered  for chronic use even though there were long- proven natural remedies that did as well or better. They (their well-paid researchers, statisticians and often professional spin writers) then produce and pay for publication of  drug  trial reports claimed to be favourable, even though the evidence is weak or in fact adverse. . And the FDA is at least consistent- it still allows American chronic drugs to be thus launched with  only short trials, without head-to-head comparison against proven remedies – but blocks dubious foreign drugs like rimonabant..

Hence in our lifetime we have seen the rise and spectacular  fall – fatal for many patients- of many trumpeted medicines – of  stilbestrol, anabolic steroids, practolol, thalidomide, ticrynafen, barbiturates, antidepressants, fenformin, Vioxx, benzbromarone, troglitazone, cerivastatin, antiarrhythmics, phenfen, and antiplatelet drugs. And the Bush Administration recently forced through legislation immunizing the drug industry against claims for  damages from failed drugs! Mostly me-too drugs whose sole need and purpose was to create profit for industry for a few years before complications force their disappearance. This indeed is the FDA – Drug Industry’s  60  year commercial War Against Humanity (Elaine Feuer)  and compassion, Al Gore’s The Assault on Reason, Naomi Klein’s Disaster Capitalism, Ivan Illich’s Medical Nemesis.

The FDA-Disease Industry (and medical schemes)  then calls this sham  process  EBM, and denies the same recognition to long proven  optimal remedies  eg parenteral human HRT because there is no need, and no sponsor, to do long-term trials on natural remedies long-proven in clinical practice studies. The only “designer” drug – metformin- which is in fact a simple tagged plant extract-  that has ever been subjected to a 20 year trial  was effectively kept  off the USA market until the  trial was nearing completion in the mid-1990s – ie metformin in the UKPDS, which proved to be the only designer drug ever that almost  halves both all mortality and all chronic major degenerative diseases including type 2 diabetes. And still the FDA demanded a 10-000 patient one-year trial  – COSMIC- to prove the safety of metformin- after all, it was a Scottish invention and long-proven European drug, thus not to be trusted because it was not invented in USA. As if the Americans were not of recent European origin.

Similarly, the FDA (and the British)  embargoed/derided  lithium- the gold standard drug against bipolar disease- until 1970, forcing Mogens Schou to do an unethical double-blind withdrawal trial on stabilized patients to prove it’s efficacy – 100% of whom relapsed within 6 months on placebo, and restabilized back on Lithium. .

Hence all drug study and trial reports, especially for  registered drugs – however prestigious the journal and origin- have to be examined carefully to see if they were done without bias/spin to paint the new drug in a rosy light. The Womens’ Health Initiative most certainly was not unbiased despite the close to $1billion cost – it scandalously failed to test Wyeth’s two xenohormones against the gold standard, human estradiol and progesterone. Similarly, the statins for mild-to-moderate hypercholesterolemia  have never been tested head to head against the only drugs that reduce all-cause morbidity and mortality by 1/3 to 1/2- metformin, fish oil, appropriate balanced human hormone replacement, and a blend of effective safe doses of all the beneficial minerals, vitamins and biologicals including some herbs.

Similarly, the Viagra trials were fraudulent- they excluded men with frank hypogonadism (since Viagra will not work without testosterone priming). But Pfizer  and the FDA also colluded to refuse to disclose, publish the testosterone levels of men enrolled in the Viagra trials- when it has been known since the early 1980s that there is a dose-response correlation between erectile function up to a plateau above a serum testosterone of about 4.5ng/ml 16nmol/L -.1982 Salmimies ea. It turns out from other Viagra trials that the serum testosterone of trialists was around 13.5nmol/L.. So most of the men using Viagra/Cialis  did not/do not  need 2 Viagra tabs a week costing hundreds of dollars a month (as the NHS was conned into providing), but a conservative shot of depot testosterone perhaps 160mg every fortnight at a cost of below $5/month- with far more multisystem benefit, and none of the deadly risks (sudden death or stroke or blindness) of Viagra.

The Wiki article on erectile dysfunction dismisses testosterone deficiency as being a rarer cause of erectile dysfunction, but fails to mention the obvious, that partial androgen deficiency ie a serum testosterone below the mid-range -ie average- often responds to adequate depot injection trial of testosterone to elevate the blood level into the mid range of healthy young men (not just the range of elderly men, as is so often done).

Such is the power of fraudulent drug company deceit in collaboration with Regulators.

It is hollow hypocrisy that the UK has now introduced a regulator of alternative practitioners- but neither the USA, UK nor  other governments  have ordered their Medicines Regulators  to drastically restrict many of the scheduled drugs discussed below (and a few risky complementaries like black cohosh and kava) when there are far safer proven  alternatives. Manufacturers and Regulators themselves are certainly not going to do this- not when their  raison d’etre is well-paid screening and registering as many new drugs as possible, not policing old drugs.

PART 1: THERAPY OF COMMON MULTISYSTEMIC DEGENERATIVE DISEASES OF AGING:

1.1 Hypercholesterolemia and statins

1.2 Osteoporosis and Bisphosphonates

1.3 Hypertension and antihypertensives

1.4 Diabetes type 2, Obesity, metformin and other weight-reducing drugs.

1.5 Pain, arthritis and NSAIDs.

1.6 Fish Oil

1.7 MULTIPLE DESIGNER DRUG INTERACTIONS

PART 2: SEX HORMONES see next publication.

1.1 Under hypercholesterolemia wiki says “statins are the most commonly used and effective forms of medication for the treatment of high cholesterol”. But the wiki entries on statins, cardiovascular disease and hypercholesterolemia, and Pubmed, give no evidence to justify statins’ heavily marketed primary use in mild-to-moderate hypercholesterolemia and diabetes, no reference that shows they are as good and safe as the old proven combination of natural evidence-based remedies – vitamins, minerals and biologicals (including appropriate eg non-prescription fish oil, carnitine, CoQ10, arginine, ribose, carnosine,  galega officinalis- metformin, and appropriate sex hormone replacement).

It is metformin and appropriate HRT, not statins, that reduces both cardiovascular and all-cause deaths by at least a third, and meformin that halves the incidence of new diabetes when used preventatively in the adipose with insulin resistance etc. It is metformin, not statins, that merit marketing over the counter:  in sensible use imetformin is totally safe, unlike unregulated poisons like cigarettes, alcohol and  sugar.

None of the vast statin trials show that statins do any good other than lowering CVD risk by a third. So it is a blatant dangerous lie to state as Wiki does that “statins are the most effective medication for treatment of high cholesterol”- this claim certainly does not apply to the universal common mild to moderate hypercholesterolemia MMHC. Familial or secondary severe hypercholesterolemia justifying statins is generally rare; and  the indolent overweight/ diabetics with MMHC have enough problems with diabetic cardiovascular disease, neuromyopathy,  and osteoporosis without the added risk (fatigue; myalgia; hepatorenal; depressive; sexual; skin; respiratory impairment; and cancer associated with severe hypolipidemia) of statins, when metformin and the other antioxidant insulin-sensitizing supplements like appropriate HRT are safe and far more effective across the board – and do not deplete and antagonize  crucial and very expensive CoQ10 as statins do..

1.2 Under bisphosphonates, wiki says “In osteoporosis, alendronate and risedronate are the most popular first-line drugs. If these are ineffective or the patient develops digestive tract problems, intravenous pamidronate may be used. Alternatively, strontium ranelate or teriparatide are used for refractory disease, and the SERM raloxifene is occasionally administered in postmenopausal women instead of bisphosphonates”.

But popular does not mean most effective or safe. Wiki quotes no sources to prove that bisphosphonates- now with a notoriously long list of complications – or the designer drugs mentioned are anywhere near as good and safe for osteoporosis and all diseases of aging as the baker’s dozen of appropriate human HRT, vitamins and minerals. The popularity of bisphosphonates, premarin, statins and SERMs is obviously based simply on heavy marketing.

1.3 ANTIHYPERTENSIVES: the Wiki entries for hypertension, antihypertensives and reserpine are in total conflict – for the obvious main reason that the main entries are written by those sponsored by new-drug companies. On the other hand, Wiki says correctly under Reserpine: “it is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality… In some countries reserpine is still available as part of combination drugs for the treatment of hypertension, in most cases they contain also a diuretic.”  see Pubmed  for at least a dozen such landmark studies.  It was confirmed as recently as the SHEP(1995) and ALLHAT (2007) trials that combinations containing reserpine are the best for resistant hypertension. And numerous trials up to the 1990s showed that lowdose reserpine plus a lowdose diuretic is as good as any more modern drug for mild-to-moderate hypertension. And trials show that lowdose thiazide diuretic plus a potassium-sparing diuretic eg amiloretic is better than a thiazide alone, and such combination was the only drug regime  associated with halving of dementia in the Cache County study.

It has been established for decades, and we see in hypertension practice every day, that the best results, with zero adverse effects, are with low dose of reserpine eg starting with ½ a reserpine tablet (ie 0.125mg/day) and half an amiloretic tablet (ie 27.5mg/day); usually reducing to ¼ of each tablet daily after a week. In many cases the dose can be reduced to 3 times a week because amiloretic has a gentle action over 24hours, but reserpine over weeks- so (unlike with modern drugs) forgetting the occasional dose does not matter. It’s cardioprotective, bone-protective and antianxiety benefits persist, with neutral effect or benefit on the metabolic and allergic and oedema  problems that abound with modern regimes.

But under Antihypertensives and Hypertension, this optimal regime is barely mentioned to be condemned – because it is old-fashioned, and the most effective therapy for mild to moderate hypertension. But it costs as little as $0.50 a month in eg South Africa, 1/300th of the price of an inferior designer combination like Prexum Plus. So it was removed from state codes in eg UK, Europe and South Africa precisely because it is too cheap and too good, it drastically reduces revenues from modern drugs. This despite the fact that this optimal combination has not been tested as first-line therapy against any modern drug- trials up to the 1990s showed that it was too good, so no drug company dare allow head-to-head trials again. And Regulators and involved politicians simply ignore these hard facts since their massive incomes depend on promoting modern, not old, drugs.

1.4 Antidiabetic and anti-obesity drugs: Wiki correctly says “Metformin is usually the first-line medication used for treatment of type-2 diabetes.” In practice, it is always the first line drug in a new type 2 diabetic since such patients invariably have excessive visceral girth and body fat if not rising BMI (above about 23kg/sqm except in a gymnast/athlete). But Wiki then perpetuates a disinformation myth: “Initial metformin dosing is 500 mg twice daily but can be increased up to 1000 mg twice daily”. This is nonsense, the reason why so many patients drop out of metformin trials and treatment, since perhaps half of us ( especially smaller people) are genetically slow metabolizers of metformin. . Metformin must simply be started at very low dose eg ¼ tablet (125mg/day), and adjusted upwards every day or two to tolerance- avoiding more than reduction in appetite and loosening of stools… with this simple approach, whether for diabetes control or, far more important, for obesity-diabetes and polycystic ovary syndrome prevention , the average tolerated dose is about 2.5 to 3gm a day in split dose (except with the new sustained release tablet). .

Wiki then says “metformin is also available in combination with other oral diabetic medications.”- but this is also dangerous marketing hype, such fixed combinations are to be avoided at all costs  since combination of metformin with any other antidiabetic drug both brings the disastrous risk of hypoglycemia, and neutralizes some of the benefits of  optimal dose metformin combined with optimised diet and lifestyle.  This is the heart of the reason not to delay metformin till diabetes- neurovascular- pancreatic disease is established, by when sometimes irreparable damage – glycation – is common, with irreversible eg kidney, nerve, eye or heart damage.

Wiki correctly states that the French drug  rimonabant was soon abandoned, and never released in the USA. And under Obesity Wiki indicates the adverse effects and lack of longterm safety-efficacy data that confirm why orlistat and sibutramine have no place in overweight-obesity-diabetes prevention and treatment when metformin is by far the best proven. .

1.5 NSAIDS NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: The Wiki entry is pretty good except that it ignores the obvious – not only are these drugs poor analgesics, little better than the old paracetamol Tylenol, but they also have major risks- not just gastrointestinal bleeding but also heart and kidney failure, dermatoses and sudden death. Wiki discreetly omits to mention that there are many cheap proven old supplement NSAIDs  that in combination do better without risk (eg MSM methylsulphonomethane; vitamins (B3, B5, C, D); curcumin; cat’s claw, boswelia, bromelain, arnica, fish oil) than the problems of aspirin and the other myriad patent NSAIDS; and that, trauma aside, NSAIDS do nothing for the cause ie the underlying disease.

And there is no evidence whatsoever to support the for-profit rationale for promoting use of the NSAIDS- that they (even ibuprofen) are any better or safer short-term or long-term than judicious appropriate use of paracetamol+-codeine, or natural supplements eg judicious appropriate steroids- whether corticosteroid, secosteroid (vitamin D3) or sex steroid SHRT eg estrogen and testosterone. Detailed referenced reviews the past year on each of these topics are published below.

1.6 FISH OIL: Coyly, the only NSAID that Wiki lists under “other” is omega 3 – which actually reduces all major degenerative diseases and mortality by 20 to 50%…

But Wiki certainly gives full credit to the myriad health  benefits- and lack of adverse effects- of fish oil -EPA+DHA – in appropriate dose.

1.7 MULTIPLE DESIGNER DRUG INTERACTIONS: The older we are, the more likely we are to suffer from multiple chronic diseases, the more likely we are to be recommended different drugs for each disease- especially if we shop around consulting a doctor per disease. In particular, the use of multiple designer and synthetic drugs that interfere with normal metabolism is high risk- and becomes higher in older people who are prone to combined degenerative diseases like osteoporosis, muscle frailty, vascular disease, diabetes, anxiety, depression, arthritis and infections.

Eg there are on Pubmed since 1992 at least 6 reports on serious bisphosphonate – induced dermatoses, and 9 on statin dermatoses. . Statins are notorious for causing insidious myositis- especially with antibiotics; and there are reports of myositis-arthitis with bisphosphonates.   Statins can cause interstitial pneumonitis, fatigue and  weakness; bisphosphonates can contribute to lung problems via reflux, antihypertensive drugs via bronchial irritation. NSAIDs cause gastritis, oedema, hypertension, heart failure. the modern antidiabetics and antihypertensives  can aggravate heart failure. Yet doctors who advise against any HRT and other medicinal supplements frequently prescribe statin, bisphosphonate, NSAIDs, modern antidiabetics, antihypertensives  and periodic antibiotics together. This is criminal, since these drugs are mostly  unnecessary in either mild-to-moderate lipidemia, or osteoporosis, or arthritis, or hypertension, or  type 2 diabetes.

In conclusion, especially as specialists  (except for the old-fashioned increasingly rare general practitioner and the specialist in general internal medicine) tend to be increasingly specialized in one niche organ system or area of medicine ( but not in comprehensive and preventative care) , it is obvious that for serious illness, the patient is advised to study personally the latest illness advances  remedies and problems. But for researching health matters, the public is advised to use the websites of international multidisciplinary expert associations eg ISSAM- the International Society for Aging Males; IMS- the International Menopause Society; and  Medline- Pubmed;

rather than those which are prone to commercial or academic  bias (by local vested/ financial  eg drug/ equipment company/institutional interests) like Wikipedi,   universities, patient support associations,  the FDA/NIH, other National Health Services,  private practice  and craft groups,  or patient’s or lay associations’ reports and advice; especially the mass media which are especially open to marketing hype and sensationalism, and which with publication deadlines and bias to sensationalism, bad or lurid  news,  seldom succeed in tracking down objective unbiased expert opinions.Like Only Disease Pays, Only Bad News Pays.

And once disinformation is published, the media  (unlike Wikipedia) rarely bother to give equal time to  or opportunity for correction of misinformation- eg withdrawing bad information from websites. Which is not to say that old ideas should be deleted from the internet- they should just give the date of last update, and indicate if they are outdated.
Wikipedia health articles should be depended on only if they are certified by international multidisciplinary consensus bodies (of specialists and family practitioners)  like ISSAM and IMS.; or if material facts are referenced to a verifiable expert source. For the reasons stated, neither trials, reviews, metanalyses or “expert opinions” – even on Pubmed- are necessarily reliable evidence.

Detailed reviews of all these topics have been published the past year below on this column.

HRT MISINFORMATION CORRECTED BY INTERNATIONAL AUTHORITIES.

The new study from the Women’s Health Initiative WHI -Ness 2009 : Influence of Estrogen Plus Testosterone Supplementation on Breast Cancer misreports/ conceals the truth:  contrary to it’s title, and  claim that “we found a modest,  albeit non-significant, elevation in breast cancer risk associated with Estrogen + TESTOSTERONE use”, it  did not study the human hormones estrogen and  testosterone at all.  CEE is what it says- a mixture of sexhormones common to most mammals plus the xenohormone equilins that are not found in humans.

The  risky “convenience factor” of oral hormones aside, has it ever been shown that the combination of human and equine estrogens  is as good or safe as the endogenous balanced human estrogens?  Was it  purely “convenience” for women that changed pioneer gynecologist and sexologist William Masters (who died just 8years ago) from being an ardent  advocate of balanced parenteral testosterone-estradiol replacement in the first RCT of HRT (Masters & Grody 1953) to a marketeer (apparently without any trials to back up his conversion) of Wyeth’s convenience premarin pill by 1957?

Why are so many doctors  unable to  state scientific fact, acknowledge – especially  in the title and abstract-  that WHI, and Ness’s paper, actually studied  xenohormones, not physiological doses of human hormones? Xenohormone  is quite simply a  hormone that is foreign (xeno-) to humans.  Ness ea actually found   that only full-strength oral Estratest -methyltestosterone MTT  1.25mg + conjugated equine estrogens- CEE 0.625mg/d) (not half-strength, nor any other types of T+E) was significantly associated with (almost double) breast cancer , and then only in the first year.  And it does not report the influence  in those women of CEE+MTT (compared to no HRT, or CEE alone) on breast cancer mortality or all-cause mortality; nor the influence on all other major chronic degenerative diseases.

The statement  in their  abstract  is  misleading that ” women using E+T have a significantly increased risk of invasive breast cancer.”  They found this increase ONLY with CEE 0.625mg/d plus MTT 1.25mg/d in the first year in those elderly women, not with any other type or route of appropriate  E+T.

As with other early reports from the WHI, it is  misleading to generalize their results (when Estratest was always an inappropriate combination of xenohormones -by an inappropriate route)  to other populations, other types and doses and routes of HRT).  But of course they dare not say so, that would be lambasting the FDA for negligently allowing ongoing use of MTT – this toxic anabolic xenosteroid has long been declared  obsolete for obvious reasons, banned in eg Germany since 1988 and South Africa more recently.

MTT methyltestosterone – ie xenotestosterone- is no more “testosterone” than, say,  ethinylestradiol  – xenoestradiol-  is estradiol, or medroxyprogesterone – xenoprogesterone- is human progesterone, or GABApentin is human GABA.  Except for patent protection, there is no evidence that the synthetic designer  ie xenoderivative (which is  not metabolized safely to the natural respective human hormone) of the natural estradiol,  progesterone, testosterone or GABA is either as good or as safe as the original. Drug companies studiously avoid any comparative trials that could test this. This disadvantage does not apply to esters like depot injection  testosterone cypionate/ undecanoate  or estradiol valerate, which are gradually broken down at a predictable rate  to deliver the natural testosterone or estradiol, which- at physiological blood levels and balance- have all the advantages of the endogenous human hormones in youth.

An editorial from Norway in the August 2008 Lancet similarly wrongly  blames breast cancer on “hormone replacement therapy”, claiming that the fall in breast cancer incidence is likely due to decreased HT use since  publication of the WHI,  and thus proclaiming that any HRT should be used only for menopausal symptoms for the shortest time possible. This is again negligently false, since the WHI showed that when used appropriately in young postmenopausal women PMW, estrogen – CEE even at a massive dose equivalent to 2mg estradiol a day- alone lowered the incidence of new breast cancer, and all other major common diseases and deaths,  by a third. And even the lowdose combination of estrogen + progestin for up to 9 years  eliminated all major chronic diseases in such women  (the Oulu study Heikkinen 2006). The use of such potent non-human hormones in elderly women in the WHI was most inappropriate since such hormones have been known for decades to have significant risks compared to physiological parenteral human hormones- eg Women & the Crisis in Sex Hormones, Harvester Press UK  Seaman 1978.

The findings in the WHI validate appropriate oral HT, but it has been abundantly clear since the design paper of the WHI in 1998 that these results with xenohormones  cannot be extrapolated to other women, other types of hormones given by other routes.

The above journal reports also casually ignore the numerous proven long term benefits (which far exceed trivial dose-adjustable risks) of appropriate parenteral human HRT, whatever the appropriate physiological combination of estrogen, progesterone and testosterone that we have used for the past >50 years (eg Masters and Grody 1953; Greenblatt, Gambrell; Gelfand; Studd; Davis & Burger et al) let alone insulin, thyroid, cortisol etc . These benefits of parenteral human  sex HRT (as opposed to oral xenoHT) – including reduction in the mortality from breast cancer and total mortality even on HRT after breast cancer- are set out in detail in a major 2008 review “Could transdermal estradiol + progesterone be a safer postmenopausal HRT” by a leading  International Menopause Society team under Professor Andreas Genazzani.

As they sum up, the answer ( from 60 years of modern use,  2600 years of therapeutic use and  a million years of successful evolution of homo sapiens on these balanced human hormones )  is:  yes.

And the major benefits- reduction in all chronic degenerative aging diseases -including breast cancer- with appropriate parenteral human HRT including testosterone replacement has been shown in numerous appropriate studies (not studies with xenohormones) for over 50 years in both men and women, as set out in numerous reviews hereunder.

HealthSpan Life! Update: FUTILITY OF DELAYED INTENSIVE GLUCOSE CONTROL FOR COMPLICATIONS OF TYPE 2 DIABETES

This new USA study is hardly breaking news, we have known it for at least a generation :

it shows again that delayed  intense blood   Glucose Control introduced in longstanding chronic diabetic patients with sulphonylureas , glitazones or insulin has no benefit on Vascular Complications in Veterans with Type 2 Diabetes ie adverse  degenerative outcomes.

However, it is unclear why this trial did not use metformin to it’s full potential. The dose specified in Methods (Abraira 2002)  was to titrate dose to a maximum of 2gm/day, whereas the average tolerated dose is almost 3gm/day (ie some people metabolize faster and safely tolerate more)  provided the dose is slowly titrated up from no more than 125mg/day till the highest tolerated dose is found.

And the trial  further diminished  the crucial benefit of metformin by an  unfounded  assumption  that metformin works only in the obese- so in this trial  patients were excluded from metformin with BMI <27kg.

So  that BMI threshold included in the  metformin trial  only  men with body fat above about 22% or body fat > 20kg; or women above 34% or body fat > 20kg (extrapolated from eg Knapik ea 1982 in US military personnel) ; whereas it is well established that risk rises progressively from BMI above about 22.5kg or body fat much above about 15kg. Thats why  the now-recognized definition of overweight is BMI>25kg. Only top bodybuiders, superathletes will have BMI up to perhaps 27kg/sqm  with fat mass down to 5% ie lean mass index of 25.6kg/sqm (see textbooks on bodymass and fitness of Gilbert Forbes; Tony Lohman).  The average  urban non-athlete non-labourer is already carrying increasing excess (and metabolically disadvantageous) body fat the higher BMI exceeds ~23kg/sqm- with in men lean mass index  LMI   about  19kg/sqm, in  women LMI often below 17kg/sqm.

It  again bears out the devastating futility, the criminal negligence  of not reversing overweight early,  delaying metformin, fish oil, nicotinamide  and other insulin sensitizing antioxidant nitric oxide boosters  (including appropriate non-oral HRT)   till obesity let alone established hypertension, lipidemia, cardio/vascular-renal disease, cancer  or diabetes develops.

The four major  metformin diabetes prevention trials (in different continents) repeatedly discussed in this column  show how well even a modest dose of metformin – 750mg to 2000mg  a day –  can reduce incidence of  new diabetes type 2 by 30 to 90%- so metformin titrated to tolerance plus early & permanent fish oil and other insulin sensitizing antioxidant nitric oxide boosters  (including appropriate non-oral HRT) can almost abolish type 2 diabetes if started early enough and maintained.

ANOTHER FAILED TRIAL: THE JUPITER CRESTORstatin TRIAL STOPPED TOO EARLY TO SHOW LONG-TERM RISK/BENEFIT especially FOR PRIMARY PREVENTION?

Yesterday we commented with concern on some non-disclosure in the recent JUPITER (Crestor- rosuvastatin) trial report as follows: (the figures have been corrected since the JUPITER report gave some stats as percentage but others as incidence per year):

JUPITER NON-DISCLOSURE:  in the huge  statin  JUPITER trial of Crestor 20mg/d, over the mean of 1.9yrs in 17803 patients mean age 66yrs BMI 28.3kg/sqm, 48% with metabolic syndrome, starting with LDLC below 180mg 3.4mmol/L :

mean LDLC  was reduced from about 2.8 to 1.4mmol/L;

there was 50% reduction in defined total cardiovascular endpoints ie stroke,  AMI, hospitalization for revascularization or angina, or death from stroke or myocardial infarction.Thus incident deaths by heart failure or arrhythmia or pulmonary embolism, or death from bleeding on anticoagulants, were not reported as primary events or under CVD deaths!

40% reduction in cancer deaths,

but only 20% reduction in all-cause mortality-

and (in fine print), 25% increase in incident diabetes p0.01.

These figures show implausibly higher reductions than other  primary statin prevention trials:  eg Mills’ concurrently published metanalysis   Canadian Universities’  Study showed reduction of only 7% in all-cause mortality, 23% reduction in heart attack, but only 11% reduction in major cardiovascular events –   for perhaps obvious reasons eg:

1. JUPITER  was allowed to run less than half the usual major statin trial time; and

2. possibly  stricter exclusions for cardiovascular events; and

3. inexplicable exclusions of major causes, cases of CVD events and deaths..  which deaths were lumped under non-CVD …

So if in JUPITER cancer deaths fell by 40%  and  major vascular events by 50%, the much shorter mean duration of the trial, and the major exclusions, explain why CVD events showed such great reduction, despite  only 20%. reduction in total deaths.   It is puzzling that not even the original full paper nor the editorial reveals the number of deaths from cardiovascular causes, nor the non-CVD non-cancer causes– but the small reduction in total mortality suggests that (unless there was some other undisclosed non- CVD- non-cancer cause of mortality), the fall in CVD mortality must have been far lower than 20%. All previous major trial reports- of statins,  HRT,  metformin etc- have tabulated both total CVD deaths and  all the causes of death- why not in JUPITER?

It is common cause that statins, which materially interfere with liver function, will materially interfere with anticoagulation and thus make antioagulation stabilization more hazardous. .

 

Yesterday the lead author Dr Ridker kindly replied immediately to these queries as follows:

Dear Dr Burman,

Within JUPITER, the definition of “cardiovascular deaths” was extremely strict, essentially requiring hospitalization and records. Thus, many “true cardiovascular” deaths (and any that would have occurred out of hospital) are unfortunately classified as “non-cardiovascular”. Thus, to avoid confusion, we reported all cause mortality. For what it is worth, for deaths adjudicated as clearly cardiovascular, the same approximate 20 percent hazard reduction is seen that was seen for death overall. Most of the deaths avoided are thus truly cardiovascular, not cancers.

Paul Ridker

 

If we look more closely at the results published in the JUPITER trial, the results now look even more disturbing:

In a mean of only 1.9years, there were understandably only 35 deaths from cancer on Crestor versus 58 off it – a reduction of 40%, but placebo cancer incidence of only about 0.34%pa. Average expected lifetime mortality from cancer at this age would be about 4.5%, but in this cohort in whom there were no signs of cancer at the start, negligible cancer mortality would be expected in only 1.9years as the common cancers have far longer genesis time.

So, deducting the cancer deaths from all deaths (198 on Crestor vs 247), there were 163 non-cancer deaths on Crestor vs 189 off it – a reduction of only 14%.But JUPITER wont say what cause each of the “non- cancer” deaths was certified. .

The previous major trials of statins ran for a mean of 5 years, and showed either no change or some worrying trend to more cancers and more non-natural deaths on statins.

By comparison, the Jupiter trial for a mean of only 1.9years seems to be the only medium-term (let alone long term) trial of rosuvastatin vs placebo – another trial of Crestor vs placebo of more than a year is not apparent on Pubmed abstracts..

Rosuvastatin has been reported  on Pubmed only since A new statin: a new standard. Olsson AG.Am J Manag Care. 2001.

So there is apparently no medium-term (with a mean approaching 4 to 5 yrs) placebo-controlled trial of rosuvastain, nor long-term experience, let alone longterm trials,  on which to judge it’s risk: benefit ratio. But the frequent occurrence of adverse effects of other statins have been documented for decades.

If as Dr Ridker says, the definition of “cardiovascular deaths” was extremely strict, thus many “true cardiovascular” deaths (and any that would have occurred out of hospital) are unfortunately classified as “non-cardiovascular”.. For what it is worth, for deaths adjudicated as clearly cardiovascular, the same approximate 20 percent hazard reduction is seen that was seen for death overall, then one must deduce that many of the non-cancer (and even cancer) deaths may in fact have been vascular. In the absence of the results for suicidal, accidental and other non-cancer deaths, it may be suspected that many of the non-cancer deaths – eg outside the core trial hospitals- were in fact cardiovascular, although classified as other because of the strict CVD death criteria. So the Crestor-related reduction in CVD deaths may well have been far less than 20%, despite  the reduction in other events..

Since JUPITER also does not disclose the changes in girth or weight in the two trial arms, or what added other systemic therapy these patients required on the trial, the fact that there was also 25% increase in incident diabetes also suggests that apart from lipidemia, Crestor if anything worsened rather than improved metabolic syndrome.  there was likely even higher conversion rate to metabolic risk factors eg  ie rise in body fat and waist girth on Crestor.

But since (like the Women’s Health Initiative) the JUPITER trial was stopped prematurely despite there being no major reduction in all-cause or CVD mortality or demonstrated increased risk, and no disclosure of what the non-cancer deaths were from, no conclusion can be reached about the risk-benefit ratio of Crestor for LONG TERM prevention– which is what primary prevention (where compliance is notoriously low) is about- ESPECIALLY with very low baseline LDLC BUT also raised CRP. .At best we see that reduction  in number of deaths deaths was matched by similar number of new diabetes cases.

We know that like Crestor in JUPITER, metformin in polycystic ovary syndrome also halves CRP.  But as we have reported  previously below, unlike Crestor or any statin,  metformin in appropriate titrated dose has an excellent safety record,  almost  halves morbidity and mortality in diabetics, and about halves new diabetes in preventative studies as well as reversing weight gain.

This  unjustified positive  media spin for Crestor (but ignoring metformin) is particularly worrying since Crestor has been in use only since 2001 ie for about 7years; and since the drug was tested also on many South Africans and is marketed in RSA apparently for primary prevention. Remember that it is not a decade since  cerivastatin Baycol  crashed  due to drug-related deaths – after  the same time in use as Crestor has been .Yet Astra-Zeneca reports Crestor sales of about $3.5billion for the past year, their third-biggest raincheck on gross  annual sales of close to $30billion.

Investors may be, but a lot of thinking people will not be impressed with JUPITER eg in Scientific American, Pharma Blog, Canadianmedicine ,

BY JUPITER, HOW LOW SHOULD BLOOD CHOLESTEROL BE DRIVEN BY DRUGS?

  Q.   Some cardiologists including in JUPITER argue for drastic lowering of LDL cholesterol.

A. This narrow cardiology argument focusing  solely on  statin for vascular disease  is counterproductive and counter-intuitive. because it ignores basic metabolism, physiology. It is correct for patients with severe lipidemia,  or perhaps advanced vascular disease with refractory mild-to-moderate hypercholesterolemia MMHC .

and the new Canadian Universities’  Study metanalysis   of statins in preventing primary cardiological disease– finds reduction of only 7% in all-cause mortality, 23% reduction in heart attack, but only 11% reduction in major cardiovascular events .

One cannot ignore that if you lower the vascular risk by 11% with statin (as the Canadian analysis shows, and you lower all-cause mortality by only 7% or 20% (JUPITER) , so  you are not addressing the other major common chronic degenerative diseases which statins don’t address, or actually worsen – fatigue-myositis-hepatorenal impairment, lung impairment, cancer, osteoporosis,  obesity, diabetes, impotence (let alone depression) which occur frequently in real life (not trials) on statin.

Statin-for-all enthusiasts do not address the fact that , against a sensible background of improved diet and lifestyle factors, statins do nothing for the core pathogenesis of mild-to-moderate hypercholesterolemia MMHC (and  of most of the  non-vascular diseases above-listed) – ie insulin resistance and overweight.

A simple head-to-head trial would prove the obvious, that metformin plus a balanced appropriate supplement of all the vitamins, minerals, and biologicals- especially fish oil, magnesium & chromium, vits B,C,D,E,K, arginine, carnitine, coQ10, etc. Acute lab tests  do show some insulin-sensitizing benefit of statin, but no clinical trial of any duration in practice has apparently ever shown that statin (as opposed to metformin) reduces excess body fat, insulin resistance, existing or incident diabetes, or incident cancer as metformin does.

But Pubmed lists not a single comparative randomized controlled trial  of statin VERSUS metformin. No statin manufacturer would be crazy enough to mount such a trial! So no researchers can afford to do so. And the statin industry generates huge revenues for Regulators and IRS, so they wont argue for sanity.

and the new Israeli study shows poor compliance with Statin.

and a new 24yr population study of men by Universities Laval & Montreal confirms that, “compared with those who remained well, incident diabetes without cardiovascular disease had a relative mortality risk RR of 3, and those with cardiovascular disease an RR of 4)”.

JUPITER NON-DISCLOSURE:  in the huge  statin  JUPITER trial, over the mean of 1.9yrs in 17803 patients mean age 66yrs BMI 28.3kg/sqm, 48% with metabolic syndrome, starting with LDLC below 180mg 3.4mmol/L, on rosuvastatin Crestor 10mg dly vs placebo, mean LDLC  was reduced from about 2.8 to 1.4mmol/L; there was 50% reduction in cardiovascular endpoints, 40% reduction in cancer deaths, but only 20% reduction in all-cause mortality- and (in fine print), 25% increase in incident diabetes p0.01.  So if cancer deaths fell by 40%  and  major vascular events by 50%, why did all-cause-mortality fall by only 20%.?  It is puzzling that not even the original full paper nor the editorial reveals the number of deaths from cardiovascular causes, nor the non-CVD non-cancer causes– but the small reduction in total mortality suggests that (unless there was some other undisclosed non-CVD- non-cancer cause of mortality), the fall in CVD mortality must have been far lower than 20%. All previous major trial reports- of statins,  HRT,  metformin etc- have tabulated both total CVD deaths and  all the causes of death- why not in JUPITER? see follow-up commentary 7 January.

In primary trials with metformin prevention (which were  much longer  than JUPITER) , incident diabetes was decreased by 30 to 90% without even dose titration to optimally tolerated dose (~2.5gm/d). And the mean 50%  reduction  in new diabetes concurs with the Saskatchewan reduction in all mortality  of 50% over 5yrs in diabetics (Johnstone 2002-6), and the  36% reduction in all mortality in diabetics in the mean 13.6year UKPDS, as detailed in previous reviews below.. and the  >6year 40% reduction in all- cause  mortality with appropriate estrogen therapy  in the Womens’ Health Initiative.

So it is metformin, not statin, which should be available over-the-counter, and mandatory first line prevention and therapy for growing overweight,  for essential hypertension and MMHC (ie any facet of the metabolic syndrome)  and thus against all the common metabolic diseases of aging, as well as being bedrock treatment for all type 2 diabetics. .  It is criminally dangerous to argue otherwise.

For recent refs   see

CANCER WITH DELIBERATE HYPOCHOLESTEROLEMIA: TIME TO STOP DRASTIC CHOLESTEROL LOWERING. September 2, 2008

PUT INSULIN SENSITIZERS eg METFORMIN/ GALEGA (NOT STATIN OR ASPIRIN) IN THE DIET TO LOWER ALL COMMON DEGENERATIVE DISEASES INCLUDING CANCER. August 30, 2008

new from HealthSpan Life: Poll: OBLIGATORY METFORMIN (or equivalents) FOR OVERWEIGHT? December 31, 2008

and Cardiologists Drs Sinatra and Roberts’  books on Reversing Heart Disease, and Metabolic Cardiology.

New Year’s DEATH KNELL FOR BISPHOSPHONATES FOR OSTEOPOROSIS; and mercury amalgams for teeth.

This column commented on New Year’s day  on the latest adverse reports on bisphosphonate – early silent histological bone changes, and oesophageal cancer.

And a new review has just appeared from the American Dental Association showing that osteonecrosis of the jaw occurs in 4% of alendronate Fosamax users even with shortterm use.

Medscape reports this week that two papers on bisphosphonate adverse reports from 2008 are among the 10 most read news items by general internists the past year. That’s good news, because at least Internists (by one of whom this column is largely written) are taking note.

We hope that patients, family practitioners, dentists, gynecologists, lawyers, regulators, medical schemes and orthopaedic surgeons also read these reports.

2008 has become the death knell  year for bisphosphonates for osteoporosis:

search of Pubmed under “bisphosphonate adverse effects case reports” lists dozens of reports –

*osteonecrosis of both the jaw and long bones leading to bone collapse;

*malignancy with high mortality;

* lethal oesophageal inflammatory lesions (even with intravenous bisphosphonate) ,

*cardiac arrhythmia;

*severe musculoskeletal pain including synovitis (eg carpal tunnel syndrome), arthritis;

*cutaneous vasculitis, toxiderma;

*hearing loss;

*many eye pathologies eg nodular scleritis, uveitis.

 

This column has repeatedly pointed out that

# there is never compelling indication in osteoporosis for a bisphosphonate since

# excellent improvement in bone density with abolition of osteoporosis fracture risk is always provided by the ±baker’s dozen of long-proven natural supplements;

# this safe economic combination provides significant all-system protection permanently, whereas bisphosphonates were designed to and do target only osteoporosis, and

# bisphosphonates have had to be progressively limited in duration of use – now down to 2 years.

 

So it’s like oral sex hormone therapy OHT:

# Why use oral HT (for “convenience”) , when avoiding the oro-hepatic route reduces the needed dose for clinical effect by 90 to 95%, and thus avoids both shortterm risks of OHT- thromboses, gallstones, unmasking of  undetectible cancers-

and longterm gradual increase in breast cancer with accumulating dose much beyond 10 years;

equally,

# why use bisphosphonate at all?

when there are more effective- natural – supplements that also give multisystem protection lifelong.

 

So, while waiting for ponderous Regulators (despite the screams of bisphosphonate manufacturers) to ban bisphosphonate for osteoporosis,

It has become clearly negligent for anyone to promote, approve, prescribe or supply bisphosphonate for osteoporosis.

 

The evidence set out in this column till today is now so incontrovertible that

# it becomes necessary to advise patients already on bisphosphonates for osteoporosis that bisphosphonate is far from the best prevention/ treatment, and they should change over to the ~baker’s dozen of proven natural supplements.

# no judge can uphold the defenses of those who are sued when patients present with one of the numerous complications of bisphosphonates;

and

# those registered “authorities”  (medical practitioners, pharmacists, medical schemes and other providers/ gatekeepers) who continue to prescribe/ dispense/ advocate/ pay for / allow bisphosphonate for osteoporosis should be reported to their respective Regulator be prosecuted,  and convicted  of scandalous negligence for ignoring the tidal wave of reports of complications, the past 5 years.

Ignorance of recent problems, failure to check Pubmed  for warnings is no excuse when we are all bound to operate according to the best evidence – not regulatory / academia /concensus  decisions which are often based on opinion and group interests rather than the evidence – and when it takes 2 minutes to do an update Pubmed search on the risk-benefit of any drug.

 Nobody can longer be tolerated to prescribe, advise, dispence or gate-keep/ regulate medicines who does  not have constant access to and use Pubmed.

It is criminal to argue as defence that these complications were “negligible, not seen in double blind randomized controlled trials” – which never last long term ie well beyond 10 years –

and that the nutritional supplements – all of which are part of human biology- have to be proven in trials to be better than eg the bisphosphonates-

and that authorities had decided  that eg the bisphosphonates were safe enough. .

To vindicate the bisphosphonates for primary use in osteoporosis is and always has been simple. It was and  is up to the drug industry to produce the trial results of head-to-head comparison against the basket of proven supplements for long enough- 5 to 10 years- as was done for metformin in the hallmark 20year UKPDS (1998), when the supplements together, but not bisphosphonates, have been shown to reduce all-cause chronic degenerative disease and mortality by about half. .Manufacturers ducked that obligatory necessity, as the Regulators (ie Governments) constantly allow them  to do with new drugs for chronic disease..

But it would now be unethical to enroll patients in such a tria – of bisphosphonates for osteoporosis-  without first showing them and independent assessors  the safety and risk data on the respective arms of such a trial- and thus unethical to do such a trial since nobody would give informed consent on the evidence already available. 

The analogy is, ironically, mercury  amalgams- falsely disguised under the term “silver” fillings since they are up to 75% mercury, (not silver)  -which are at last, after decades of heeldragging, being banned (as they were banned in Scandanavia last year) because of the indisputable decades-known systemic toxicity of mercury, which the FDA finally had to concede in a USA  recent court prosecution of the FDA. If that applies for ” pregnant women,  unborn babies and children”, then surely read all humans.

     Imagine having to take a government to court to force it to follow long-available strong scientific evidence- but thats what also happened in South Africa recently over mandatory treatment for AIDS – and the “responsible” ministers  -a medical doctor, and the president  (a British MA in Economics) no less- repeatedly ignored court orders, until they were belatedly removed.

Now we must if necessary go the same legal route over bisphosphonates for osteoporosis if regulators will not take swift heed and stop their use as primary therapy for osteoporosis. Human rights demand no less.