THE MOST IMPORTANT RCT IN HALF A CENTURY ON APPROPRIATE USE OF HRT IN WOMEN: Conjugated Oral Versus Transdermal Estrogen Replacement

Nabhan ea at Indiana University have just published perhaps the most important randomized controlled trial RCT in half a century on physiological benefits and pitfalls of Estrogen replacement ERT in women.

Pubmed search under menopause or HRT trials yields reports only from 1975, simply because that is when Medline was established.

But in fact William Masters  ea in 1953 in St Louis published the first traceable- and most important ever-  sex hormone SHRT  RCT,  giving balanced testosterone plus estradiol (in a ratio that they found was optimally 20:1) or placebo parenterally for 13 months apparently blind to already institutionalized old women at a mean age of 73years;  showing that while 1/3 were not unsurprisingly too far gone to benefit, 2/3 of them recovered sufficiently over 6 weeks that the nursing care on the ward could be halved for the next year of followup- without any significant reported adverse effects, and with uniform atrophy of the endometrium at 6months on curettage. This trial may not have been double blind, but Masters and Grody detailed  the randomization to hormone or control injection.

Albeit using perhaps half  the dose of hormones as far longer- acting esters (than Masters used),  Gelfand  in Montreal (1987-2004) confirmed the long-term safety and benefits of combined depot injection. As Gelfand wrote in 1999,  “The objectives for the management of a menopausal patient are ( I ) to increase longevity, (2) to prevent age-related deterioration, (3) to maintain a quality of life, (4) to prevent induced risks, and (5) to maintain a physiologic hormone balance.”   We  should  regard longevity as the lowest  priority,  Gelfand’s other four objectives are equally paramount- and the bedrock of medicine especially endocrinology is to mintain physiological balance. Why should   women be treated otherwise?

As this column has regularly described, most women  find that the  dose of about 0.5 to 1 mg testosterone and 25  to 50mcg of estradiol daily as a pro rata +- fortnightly tiny subcutaneous  depot (self) injection) via a 25g needle is optimal, providing reasonably physiological mean  blood levels, and once dose titration has found the right recipe,  some (like most men) prefer it to the bother of patches or creams.

And many groups world wide  have  for decades done so with  human E+T hormone combination long term as implants, albeit in a much lower ratio. Now this combination has become the physiological gold standard as creams and patches, which allows the patient more promptly and safely to determine her optimal dose and route of each sex hormone. Three monthly depot injection of Nebido testosterone undecanoate has become the gold standard in men, as it  will in due course in women at 5%  to 10% of the male dose.

For over 30 years scientific studies have broadcast the many adverse effects of oral CEE with progestins, especially on the risk of breast cancer long term. But, led by drug companies and their well-paid researchers and lobbyists promoting patented equine and other designer hormones so as to suppress the sale of cheap human sex hormones, women and gynecologists duped themselves into following Wyeth’s saturation marketing and, especially in the English-speaking countries, continued to use mostly oral conjugated equine estrogen and synthetic progestins.

Barbara Seamen, who died last year, was a prophet of sex hormone benefits and risks as Margaret Sanger was of proven safe barrier contraception. But  the climate against advocacy for women was still so hostile in USA  that even in 1978 Barbara and her psychiatrist husband Gideon Seamen published their book Women and the Crisis in Sex Hormones in UK (as Sanger had had to do with her book My Fight for Birth Control in 1934). A decade before the Seamens’ book,  Dr Robert Wilson’s hysterical  Feminine Forever had been  published in 1966 in USA – marketing  premarin CEE 1.25mg a day – leading up to the flood of endometrial cancer by the mid-1970s, and increasing breast cancer (Henderson ea 1980)..

But many doctors and patients were convinced about the dangers of progestin when the first badly analyzed results of the WHI- with oral OCEE premarin + MPA provera- were published in 2002; although the CEE- only arm of the WHI was allowed to continue another 2 years until it too was wrongly stopped because of overestimated accruing adverse events in all-age EXCEPT when started well under 60yrs.

But the hardest skeptics had to concede that oral CEE at the then-standard dose of 0.625mg/d (equivalent to estradiol 1mg/d) in women post hysterectomy reduces all common major aging events (fractures, breast & colon cancer, cardiovascular, memory problems and all-cause mortality) when started appropriately soon after menopause and used for up to 9 years- with the only adverse effects being increase in adiposity, urinary incontinence, venous thromboses and gallstones. .

The Womens’ Health Initiative WHI 2007 showed plainly that OHT started (as is conventional practice) soon after menopause ie near age 50yrs with OCEE alone (ie after hysterectomy) or with CEE+MPA,  for up to 8 years,  reduced all-cause mortality by 30%; BUT whereas CEE alone in this young cohort reduced both (breast cancer and CVD and fracture) events AND (breast cancer and CVD and fracture ) mortality by about 30% , CEE+MPA increased CHD and stroke events by 49%.

Thus in the young WHI cohort, given that all-cause mortality also fell by 30%, CEE +MPA must have reduced breast cancer mortality by even more to offset increased mortality from CVD in the young CEE+MPA cohort. . This improvement in survival after breast cancer with “appropriate” early and long term OHT has been long recognized.

Earlier studies eg the open prospective StaTur ( Soriano-Gullen ea 2005) in France  in girls with Turner Syndrome had already suggested  ” that growth hormone and estrogen (from about age 12yrs)   attain optimal adult height; and the use of percutaneous vs. oral estrogens was associated with greater height (_2.1 cm; 95% confidence interval, 1.00–3.25).”

Now the 12month Indiana trial highlights the physiological benefit for teenagers of human transdermal TD E2 (HERT 25 then 37.5mcg/day) versus  +- 20 times the estradiol equivalent dose as conjugated equine oral xenoestrogen (0.3mg then 0.46mg CEE/day) in obese short  prepubertal girls age +- 14 (range 11-17) yrs with Turner Syndrome TS (half 45XO karyotype; mean height 1.427m , weight 49.6kg, BMI 25.3kg/sqm).   At a CEE dose per kg body weight similar to that used in PMW postmenopausal women (mean weight +- 73kg, BMI 28.5kg in the WHI), the TDHRT dose had far superior effect over oral hormone therapy OCEE in promoting  better height,  bone density, and uterine and breast growth catch-up .

According to CDC tables 2000, the average height of USA 14yr old girls was 1.6m and BMI  19.3kg/sqm; but girls at 1.45m height had  mean BMI 17.7kg/sqm; thus the TS girls in the Indiana study at baseline  were 17cm shorter than average normal 46XX girls, but (like postmenopausal women) 43% over average weight for height. They report that there was no difference between the estrogen routes in change in body composition.

Although the Indiana study for economic reasons  omits blood sex hormone levels, the results highlight some stark facts about unopposed parenteral HERT versus OCEE in women without functioning ovaries:

* lowdose TD ERT had far more effect than OCEE in promoting progressive height and bone density accrual; but

*TD ERT is far more potent than the perceived “equivalent” dose of OCEE in promoting both myometrium, and glandular proliferation (breast and and endometrial) .

This observation obviously cannot simply be extrapolated from sex-hormone-naive girls to PMW; but it reinforces that

*in PMW,  human estrogen  (rather than breast-cancer-promoting OCEE) should be given parenterally in small enough dose  to replicate low average monthly physiological (free) estrogen levels in young women, and

*should never be given without ensuring that physiological androgen (and progesterone) levels as (in healthy young women) are available (naturally or by parenteral androgen replacement ART and parenteral progesterone replacement PRT) to offset the proliferative effect of even lowdose estrogen on both breast and uterus, let alone on dissolution of muscle collagen as witnessed by the doubling of postmenopausal stress incontinence on OET.

The Karolinska institute showed in 2007 that lowdose testosterone patch reversed the increase in breast proliferation caused by OE+P; and in 2008 that endogenous free TT levels have antiproliferative effect on breast tissue, perhaps mediated via the progesterone receptor; this confirms the observations of Masters, Greenblatt, Schleyer-Saunders, Gelfand, Gambrell, Vliet, Buster, Clarkson, Whitehead, Studd, Burger, Davis, Dimitrikakis Zhou and Bondi, and Davies’  Cape Town group, that the preservation of youthful female testosterone balance protects both breast and womb of primates from the proliferative effect of estrogen and progestin.

And in 2006 the Karolinska also reported in a retrospective observational study that previous HT (mostly OHT)  use was associated with a 70% increase in meningioma.

Last year l’hermite, Genazzani ea reviewed the sixty-year -known benefits of parenteral over  oral estrogen and progestins.

Shufelt and Braunstein last month  sum up the accumulating safety data on female  testosterone replacement TRT the past sixty years: that “replacement of serum plasma testosterone levels to or slightly above the reference range for young women does not increase the risk of hepatotoxicity, endometrial hyperplasia, behavioral, cardiovascular, cancer or haematolological adversity. Models of superphysiologic testosterone levels, such as polycystic ovarian disease, have not shown an increased risk of breast cancer. As with all hormone therapy, testosterone therapy should be individualized to optimize benefits without risks”.

ie   all SHT-  ERT,  TRT and PRT-  should be parenteral and titrated to physiological SH balance so as to give maximal well-being without causing significant proliferation in acne, hirsutism, adiposity, breast or uterus.

Hence it is unwise  to give  even TD estrogen unopposed even  after hysterectomy.

Even unopposed progesterone- as is now so popular as “natural” over-the-counter cream- has proliferative effects on the uterus and breast, so should not be used post menopause  without monitoring these organs and ensuring adequate blood levels of balancing androgen. While  progesterone itself  has many physiological benefits, both natural progesterone  and synthetic progestins  may activate dormant breast cancer (Horwitz 2008),  accelerate aging hearing loss (Sellars 1971; Dubno 2008; Horner 2008; Price 2009); and overall,  RCTs do not show that they reduce fracture risk.  And of course liberal use of progesterone will suppress what endogenous estrogen and testosterone remains  post menopause, as oral and depot synthetic hormones do in contraceptive use.

As always in human physiology, it is unpredictable to what extent progesterone may convert to testosterone and estradiol. Despite Dr John Lee’s enthusiastic advocacy (backed by no RCTs), the absence  of proven benefit of progesterone on bone density and fracture risk long term discredits progesterone as a significant source of estrogen and testosterone- but does not negate it’s indisputable role in longterm balanced HRT as an immunomodulating neuropsychoprotective.

The comprehensive recent review of HRT by Santiago Palacios points out that progesterone has a different function profile from all synthetics, being anti-aldosteronergic ie not fluid-retaining, and weakly anti-androgenic. He  stresses the target of ultralowdose estrogen to maximize the benefit:risk ratio, with consensus that appropriate HT started soon after menopause almost halve both CHD and fracture risk.

The KEEPS RCT now well under way (Harman, Naftolin ea – with roughly similar CEE  and TDERT dose to the Indiana trial, and vaginal progesterone) will no doubt again confirm the better safety profile of TD ERT over premarin, with no risk from the cyclical  progesterone- but that trial is only to run for 5 years ie to finish in 2012, so it will not negate Henderson’s strong 30year-old data that  oral CEE +- progestin taken for  more than about a dozen years  increases the incidence of breast cancer, although it lowers  mortality. So far KEEPS is running smoothly without concerns arising (Mitch Harman personal communication).

Prescribing appropriate OHT extends healthspan and lifespan. But should it ever be preferred if it increases the risk of thrombosis, and  from the 2nd decade of use breast cancer?  whereas this risk is minimized with addition of appropriate testosterone, especially if  all SHRT is parenteral.

In contrast to Victorian times when only a minority of women survived to menopause, the average age of menopause is now around woman’s  midlife, and there is never contra-indication to the healthspan-lengthening benefits of  balanced SHRT for the second half-century of life.

CONCLUSION:

The Indiana study in hormone-deficient teens is a signpost that both young and old need the youthful balance of physiological levels estradiol, testosterone and progesterone – for far more than reproduction, sexuality and femininity- but, crucially, at physiological parenteral dose that will not expose her to breast cancer activation, ie avoiding oral HT.

Crucial as  all three prime hormones  are in the young, sexuality and femininity   are sadly not essential for reproduction-  but once experienced, cherished  while the heart and eyelashes  still flutter… For obvious reasons well known to sexually active adults, like PMW at all ages, girls with Turner’s syndrome should also be  entitled to the benefits of appropriate triple hormone replacement from mid-teens so they too can experience appropriate mature adult sensuality and bonding.

The estrogen-progestin treatment of Turner’s Syndrome and PMW   is also a paradigm of the increasingly common problem of flattened sexuality in young women-  from birth-control  xeno-hormones;  cortisone and psychotrope use; AIDs and ARV use; metabolic syndrome and diabetes; and after pelvic cancer therapy or sterilization. All these women should be considered for appropriate  parenteral sex hormone therapy  (if necessary with all three hormones) based on both their clinical picture and full hormone profile.

ndb

Fighting the 8th AGE: the mandatory panacea metformin and other natural supplements.

Exciting new anti-aging evidence has been published this year:

The Bard  spelled out the 7 ages of man. Now we know we have to deal with more AGEs – Advanced Glycation End Products- , and more evidence to prolong the healthy ages of man.

GLYCATION: some of us are fudge addicts. Fortunately with the natural supplements available, we can have  a little of our cake and safely eat it.

But as Wiki details,  such  lethal exogenous glycations and (AGEs) Advanced Glycation Endproducts “are typically formed when sugars are cooked with proteins or fats (eg fudge, baked puddings, sweet crackling/baked beans !). Temperatures over 120°C (~248°F) greatly accelerate the reactions, but so do  lower temperatures with longer cooking times. These compounds are digested with about 30% efficiency. Browning reactions (usually Maillard type reactions – like fudge, crackling!) are evidence of pre-formed glycations. Indeed, sugar is often added to products such as french fries and baked goods to enhance browning. Glycation may also contribute to the formation of acrylamide, a potential carcinogen, during cooking. Until recently, it was thought that exogenous glycations and AGEs were negligible contributors to inflammation and disease states, but recent work has shown that they are important.”

“Although most   research work has been done with reference to diabetes, these results are important for all, as exogenous AGEs are implicated in the initiation of retinal dysfunction, cardiovascular diseases, type II diabetes, cancer and many other age-related chronic diseases. Food manufacturers have added AGEs to foods, especially in the last 50 years, as flavor enhancers and colorants to improve appearance. Foods with significant browning, caramelization, or with directly added preformed AGEs can be exceptionally high in these proinflammatory and disease initiating compounds. A long list of foods with very high exogenous AGEs includes:  donuts, barbecued meats, cake, and dark colored soda pop”

This explanation of one of the root causes of the multisystem degenerative diseases of aging dispels the myths that the fast food chain and what the  Drug Industry promotes are healthy, that we need a patent drug per disease eg statin for lipidemia, antihypertensives for hypertension, anti thrombotics for thromboses,  anti-inflammatories  for pain, etc.

GALEGA METFORMIN: THE LONGEST-USED ANTIGLYCATION MEDICINAL:  The longest randomized controlled drug trial RCT ever, the UKPDS (Holman 2008) in type 2 diabetes DM2 showed that long term metformin double-blind for up to 20 years (mean 13.6yrs) (and up to 30years open use), lowers all-cause morbidity and mortality by about 1/3.  Other anti-diabetic drugs eg Sulphonylureas by contrast do little but lower hyperglycemia – without reducing mortality, but adding major risk of hypoglycemia – increasing the risk of dementia long term..

According to Schnider and Kohn from Ohio in 1980 (via Pubmed) , the concept of advanced  glycation/glycosylation in human aging and diabetes was  already well described, so the clinical concept is over 35 years old — but metformin has been under intensive research since 1922 ie for over 85years, and in human use (as the parent herb galega officinalis) for thousands of years – although the first mention on Pubmed of metformin as a blocker of glycation end products was in 1995. .

A new Dutch study (Kooy 2009) in humans has confirmed that metformin (850-2550mg/d) in the medium-term (a mean of 4.3yrs) added to insulin in DM2 lowers macrovascular endpoints by 39% p.02, weight by a mean of 3kg, and insulin requirement by 20iu/d.

A Buenos Aires study (Schurman 2009) notes that “AGEs  are implicated in the complications of diabetes and aging, affecting several tissues: in bone cells in culture, metformin treatment of osteoblastic cells prevented these AGE-induced alterations.”

There can be no doubt that,  given that the lethality of advanced obesity and  DM2 is as bad as smoking, it is crucial to reverse early ie prevent from developing all the mechanisms of obesity- diabetic damage including from hyperglycema itself; wasting from intracellular energy deficit due to insulin resistance; oxidation, nitric oxide deficiency; and above all else, AGEs from sugars fusing with fats or protein – especially fructose.  “It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel. Glycation is the first step in evolution of these molecules through a complex series of very slow reactions in the body known as Amadori reactions, Schiff base reactions, and Maillard reactions; all lead to AGEs.  Some AGEs are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as: type I and II diabetes mellitus (beta cell damage), cardiovascular diseases (endothelium, fibrinogen, and collagen are damaged), Alzheimer’s disease Vitek ea 1994 (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy (myelin is attacked), and other sensory losses -deafness ( demyelination) and blindness (mostly  microvascular damage in the retina).”

“This range of diseases is the result of the very basic level at which glycations interfere with molecular and cellular functioning throughout the body. Glycated substances are eliminated from the body slowly, since the renal clearance factor is only about 30% ie half-life about double the average cell life. As a consequence, long-lived cells (such as nerves, brain cells), long-lasting proteins (such as eye crystalline and collagen), HBA1c and DNA may accumulate substantial damage over time. Metabolically-active cells such as the glomeruli in the kidneys, retina cells in the eyes, and beta cells (insulin-producing) in the pancreas are also at high risk of damage. The endothelial cells of the blood vessels are damaged directly by glycations, implicated in atherosclerosis. Atherosclerotic plaque tends to accumulate at areas of high blood flow (such as the entrance to the coronary arteries) due to  increased presentation of sugar molecules, glycations and AGEs at these points. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurysms; causing strokes if in the brain.”.

As Desai & Wu from University  Saskatchewan  sum up  2007,” AGEs are unavoidable byproducts of various metabolic pathways formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, leading to aging – vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer’s disease. In recent years, compounds that prevent the formation of AGEs or degrade the existing AGEs have been recognized or patented including 1. galega-metformin -guanidine; 2. pioglitazone (patented), 3 angiotensin blockers , 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, etc.. “

CROSS-LINKAGE AND AGING: Ward Dean 2009 spells out “the Crosslinkage Theory of Aging: AGEs and Crosslinkages – New Respect for Crosslinkage Theory.  Dr Johan Bjorksten in 1941 first proposed The Cross-linkage Theory of Aging   that aging was caused by inter- and intramolecular crosslinks in proteins, nucleic acids, and other vital macromolecules that caused them to gradually stiffen and lose their function”.

OTHER ANTI-AGEs BLOCKERS: Cataract formation is associated with low vitamin C (Tessier 1998); while Quian ea in 2000 showed that both vits C & E lowered AEGs in diabetic rats. Other natural AGEs blockers include taurine; L-Carnosine, L-Arginine, DMAE dimethylaminoethanol ;   PABA (para aminobenzoic acid); Thiamine HCl ; Alpha R Lipoic acid; Pyridoxal 5’ phosphate;  and to inhibit Amadori products: EDTA,  vits B1,B6, C & E , coQ10, Green Tea, Hawthorn, Grape Seed, Milk Thistle, Ginger Root, Ginkgo, bioflavinoids (Morimitsu 1995 ); curcumin ; and melatonin (Sailaja 2000);  to which one can add for antiaging:  huperzine A and DMAE.

Many companies are racing to market new ie patentable synthetic anti-AGEs agents like peptides ; benfotiamine and pyridoxamine . But as with some 1000 available natural insulin sensitizers, there are plenty of natural anti-AGEs supplements, starting with : galega officinalis (50% guanidine with negligible content of galegine) and it’s extracts aminoguanidine, galegine and dimethylguanidine-metformin. Already in 1999 Tanaka ea showed in rats that metformin treatment may be effective in the prevention of diabetic complications through not only lowering plasma glucose, but also directly inhibiting AGEs formation.   Sowers 2002 theorizes that the reason that statins “do not reverse endothelium-dependent and -independent vascular dysfunction in DM2 (in contrast to in non-diabetics) is precisely because of AGEs.  But Jinnouchi 2006 shows that atorvastatin also reduces AGES.

These studies affirm that  METFORMIN is the Gold Standard (Bailey ea 2007: Merck Sante), arguably both the safest and the most pluripotential therapeutic agent ever discovered, being an age-old medicinal plant extract (Werner and Bell 1922).

So we do not need patent designer inhibitors (of AEGs  or reactive oxygen species or insulin resistance or lipidemia or inflammation or appetite-weight gain) – there are dozens available from nature, with galega- metformin the longest and  broadest potential proven and used, that when simply and safely titrated slowly upwards to good tolerance, at least halves the incidence of new diabetes and thus adds at least a decade to health and longevity.

THE GODDESS PANACEA: A panacea is defined as a “cure all”, to “retard the aging process”, and to increase the “quality of life”. Today a balanced diet and lifestyle is far from a guarantee of healthspan.  Despite  denial by  the food and drug industry (aka the FDA, the Disease Industry  who want to suppress the old so as to sell  their   new  designer patents) metformin fulfills all the criteria for a panacea in a stressed fattening population, from promoting copulation, conception and pregnancy to healthy  old age.

An old study from Germany (Hammes 1996)  shows again a potential trap of testing one substance in isolation and in rodents – in this case, EPA + DHA (as Maxepa) about 130mg/day for 6 months if anything harmed the retina in diabetic rats. Does this have any bearing on the global benefits of natural EPA+DHA and brod supplements  in  humans?

By contrast, El-seweidy ea in Egypt in 2002  showed also in diabetic rats that “combined treatment with galega (aminoguanidine) and omega3  markedly reduced all the adverse blood markers and nearly restored the atrophy of islets of Langerhans and the peripheral lymphocytic infiltration compared to untreated diabetic rats and those treated only with guanidine.”

The cardinal principle of nutrition and medicine is synergy- that we do not or should not eat single foods in isolation, nor expect disease to respond to a single extract/medicine;   nutrients and nutriceuticals complement each other. This is obviously contrary to the imperative of the Disease Industry to sell a profiteering rainmaker snake-oil per disease..

GALEGA/METFORMIN AS MANDATORY PREVENTION AND THERAPY: The common lethal poisons that humans consume – sugar, salt, alcohol, aspirin, paracetamol, ibrufen and cigarettes – are freely sold over the counter.

Metformin must thus similarly be released for over the counter sale as the only proven panacea (aside perhaps from fish oil) and the only drug ever in RCT for 20year AND  proven to be without any major adverse effect – including for halving deaths in diabetes, and (in four major trials on four different continents) halving the incidence of new diabetes in the overweight, and reversing progressive weight gain. And it can be simply and cheaply manufactured from basic chemicals in 5 minutes.

It  must thus be made mandatory prescription to tolerance for prevention obesity and diabetes in the overweight (ie those whose BMI persists despite attempted correction above about 25kg/sqm),  let alone in all diabetics.

JUGGLING THE BEST SEX HORMONE HRT REGIME FOR WOMEN.

An update review by Barry Wren from an Australian Menopause Clinic again debunks the myth that appropriate HRT in postmenopausal women PMW increases the risk of breast cancer, cardiovascular  disease CVD and thrombosis. It  stresses that “benefits of HRT include  less:  symptoms of menopause;  osteoporotic fractures,  ischaemia and cardiovascular-related death, forgetfulness, dementia and colorectal cancer; and  improved well-being, quality of life,  vagina, sexual enjoyment and bladder capacity,  with increased longevity. Oral  OHT doubles the risk of thromboembolism”. But on it’s own  in the young women in the Womens’ Health Initiative, oral equine estrogen (premarin)  reduced all major risks even new breast cancers and death from breast cancer.

As we hear regularly in women who have unwisely followed hysterical advice to stop HT,  stopping appropriate HT leads to fairly rapid loss of many of the above benefits. It has been  obvious for a century  that permanent appropriate Human Hormone Replacement HRT of any of the dozens of our hormones that run out   is  (like a complete supplement of all the vitamins, minerals and the biologicals other than HRT)  prudent if not essential.

But we have to understand the reasons, risks and different regimes available. Nobody may prescribe or administer any sex HT Hormone Therapy without the necessary up-to-date training and experience, ensuring that the patient is having the necessary periodic examinations to ensure both safety and that the SHRT is appropriate. So patients must not self-treat with over-the-counter  supplements.

But only doctors and pharmacists who have costly current dispensing licenses may dispense and compound any hormone creams. And oral HT including phyto/plant hormones are  under suspicion of promoting cancer long term, let alone hepatic first pass effects like thrombosis and gallstones, and fluid retention oedema and hypertension (Genazzani ea 2008) .

INJECTION: tiny safe self-injection of combined hormone subcutaneously  (like insulin) is easy every one to three weeks, as most men use for HRT.  Monthly injection of depot preparations that last about three weeks  is not advised for anyone, especially not women with a womb as they are liable to have break-through periods. But unlike men, many women prefer to use hormone creams daily. The Depot hormone injections have climbed in price – what is now available averages about R75 per month. BUT (unless she gets the injection from her doctor regularly & proportionately every 1 to 3 weeks), women have to lay out about R1000 for self-injection (since  pharmacists will not likely  split a multi-vial or a set of three vials).

Provided that they ensure that they are appropriately trained in such therapy, all doctors are licensed to give periodic chronic injections – which should always be exclusively by tiny subcutaneous injection to avoid the notorious ie potentially crippling complications of intramuscular injections. But if nothing else is required, doctors are entitled to charge about R100 fee for the responsibility of an injection visit. Like insulin, patients easily learn to give it themselves- for men about 160mg depot-testosterone every 2wks (as opposed to 1gm testosterone undecanoate Nebido every 3 months- or about 1/10th of the male dose for women deficient in testosterone).

Synthetic ie xenohormones – those not normally produced by humans- eg progestins, ethinylestradiol-  may be invaluable (although by no means essential)  for birth control; but should not be used for PMW, especially not orally.

USING CREAMS: it is indeed best for women to (initially) juggle the balance of the three hormones  (all of which are made to the highest standard in South Africa)  until you have determined what ratio and quantity suits you best.

For the slim small older woman who needs both hot flash control and energizing, memory, ache relief:  the first priority is to control hot flashes, skin & hair without arousing breast and womb discomfort:

so try the 0.25% Bies(trogen) (E2 + E3- usually 1:4 ratio)  initially 1/2 ml scoop 1 – 2 x/day with the progesterone 3% cream initially just ¼ to 1/3 ml scoop a day ie 4 to 1 or 3:1 . This is ideally rubbed into the face as makeup- or if you like, dilute them in simple aqueous cream. Increase the combined dose to double if necessary to get control of the flashes – but the higher the Biest dose, the higher the risk of waking the breasts and womb, or getting thrombosis and ankle swelling.

And (unless your androgen level is still high) use just enough Testosterone cream 0.5% eg 1/2 to 1 scoop once (or twice) a day – below the waist ie vaginally or between the thighs or on the soft sole of the foot – to energize, improve alertness, libido, muscle and bone strength. Supplementing estrogen and progesterone alone may suppress necessary androgen.

In the bigger plump younger woman, who desires memory, energy, fat loss and libido rather than hot flash and skin improvement, using testosterone below the waist and progesterone on the face in the above gradually increasing doses often suffices, without the fattening and breast-womb arousing risks of extra estrogen. Such women often make enough estrogen from testosterone and in their excess fat stores.

But once the average women is well past 60yrs, low-dose estrogen often becomes advisable anyway for balance.

Old women benefit from and tolerate perhaps 1/6th to 1/10th the doses of appropriate balanced  human sex hormones of younger women.

THE THREE PRIME HUMAN SEX HORMONES: there are no risks from any appropriate HRT, only risks from avoiding it. Progesterone alone lacks some of the benefits of testosterone and estrogen eg on muscle- bone and hearing. Of the three hormone types, only androgen protects and improves muscle mass and strength. Testosterone excess (hairy face, acne, anger, clitoris growth, husky voice) is easily avoided with sensible balanced dose adjustment. Progesterone and testosterone have major benefits that estrogen may lack eg on hyperimmunity and inner hostility- issues that may not concern the gyne surgeon.

(Bi)Estrogen excess-  especially if used  alone-  does the reverse (of testosterone): promotes endometriosis and breast activation; excess actually weakens muscle eg bladder leak by melting collagen; it fattens; has little benefit directly on depression (although it does reduce dryness and pain); may promote thrombosis since unlike testosterone it does not diminish clotting; and may promote anxiety, hostility- this is why progesterone cream is often the best for monthly PMS and for perimenopausal anxiety (against the raging hostility from estrogen swings).

Above all else, remember that estrogen stimulates both breasts and womb- so estrogen must always be balanced by enough progesterone and(/or) testosterone. And if the hormones are allowed to run out by widening the gap between injections beyond two weeks, or between cream doses by more than two days, vaginal bleeding likely will occur.

The initial outlay cost of the three different hormone creams is up to R500 retail- you find out for yourself how long each tub lasts; as opposed to having an experienced pharmacy eg the manufacturing AntiAging pharmacy in Gauteng  compound ie mix what you want in one or two tubs that will last a few months. Try your local pharmacy – but finding one with experience is difficult.

PREVENTION? OR WAITING FOR DISEASE FROM NEGLECT TO CRIPPLE YOU? Many  gynecologists (like urologists) are primarily surgeons concerned with reproduction, menstrual, pelvic and cancer problems, and treat the menopause years often with fattening hormone pills (HT- which have more risks) and surgery..  They do not have to deal with the much wider irreversible medical problems of old age (obesity-diabetic, insulin resistance, lipidemia, vascular, immune, fracturing, arthritic, visual and hearing loss,  depression, and dementias – and no least, common sudden premature death)# – which are largely AVOIDABLE with appropriate natural supplements from the beginning, including balanced non-oral human sex hormones. As a BBC news report this month  says, memory (ie cellular) deterioration  begins on average  before age thirty.

It is not the gynecologist, but patients  and Family/ general practitioners GPs and specialist physicians including endocrinologists and geriatricians who have to deal long term and medically (not surgically)  with these easily preventable crippling killer diseases..  Surgery cannot address the basic pathogenic cause of chronic degenerative disease.

The discomfort and fattening of the 5-10 MENOPAUSE years is a concern for all doctors – and the earlier the menopause (whether natural or surgical), the more important it is to start appropriate simple balanced non-oral HRT and other effective medical prevention of fattening and diabetes eg other insulin sensitizers like metformin. Avoiding the late postmenopausal  silent killer degenerative diseases of aging (# above) is crucial  essential duty of doctors – but mostly of patients themselves,  since- obstetrics and trauma  aside-  most doctors earn more by disease than by prevention..

ndb

THE CANADIAN CAUTIONARY ABOUT PROMOTING UNSUSTAINABLE FISH OIL INTAKE.

A  sober analysis from four Canadian Universities in this St Patrick’s Day issue of the CMAJ warns against zealous promotion of fish intake in the face of dwindling global fish resources.

There can be little doubt that, in adequately nourished western communities, fish oil- the EPA-DHA omega3- is the single most important essential multisystemic “micronutrient” from conception to grave, for both intellectual, mood, reproductive, immunity and healthspan optimization.

Just as it was once, but no longer is, the staple diet of the Western hemisphere billion people (the Americas and Europe), fish is the staple diet of Asia and the subcontinent, as it was in Africa till the fish, and most people, got wiped out by external  and despotic African greed.

The overwhelming bulk of world fish production is sucked up by the eastern hemisphere. Except for the tiny affluent minority, fresh fish – especially those rich in oil- is unaffordable to most humans other than those still able to catch fish for personal consumption at sea- or riverside. . However, the Canadian analysis overlooks harsh facts that need to be confronted at WHO level, if the “haves” give a tinkers’ damn about the poor:

Most fish is distributed processed to be low in oil ie canned if not powdered as fish meal. Since the benefit of fish oil is destroyed by traditional (plant oil) deep frying or high-heat baking, or lost in grilling, little fish now consumed globally has significant fish oil content- oily fish eaten as sushi or eg raw herring.

Fish oil on the other hand is the inevitable “waste product” of factories, the spilloff of canneries and fishmeal production. Virtually no canned fish available locally has much more than 1% fish oil left – worse, the fish oil is often replaced by saline or, worse, plant omega6. And who eats the residual juice/ oil in the can?

Yes, it will take 40 tons of fish oil a day to supply just 1gm of fish oil (about 250mg EPA-DHA) a day for every South African – and local harvests of the oil-rich pelagic fish- if not already too contaminated with heavy metals, dioxin etc- have plummeted apparently by 90% due to massive overfishing for the Asian market, aggravated no doubt by pollution and global warming and poaching .

But worse, the lunatic money-mad Western-led industrial complex -that has for 50 years (despite the availability of nuclear, solar and battery power) refused to budge from oil-driven vehicles and power supplies- has made huge inroads into competing with the food chain for scarce marine omega3 oil, even for krill and algae sources. And the majority of humans cannot compete for fish oil with the prices that the haves – car owners, airlines, shippers, industry- will pay for oil-based energy.

So the problem is not that the 6 billion poor in the world each need a few gms of fish oil a week- say 20 million tons a week.

But according to Google search eg on Wikipedia , global world consumption of industrial oil by 2007 was up to 80 million tons a week,

whereas world fish production was about 1.4million tons/ week of which only 1/4 is oil fish- ~350 000 tons /week

and world fish oil production was probably at peak a million tons a year in 2005 ie 20 000 tons a week .

So the nightmare problem that the Canadian analysis avoids is that the Eastern hemisphere (like the western affluent) will pay any price for their staple fish; and the world population needs 15 times as much fish oil for consumption as was peak world fish oil output; and the terrorist world industrial complex (G20) wants to go on using 100million tons of industrial oil a week- for energy as well as plastics-

and prey for industrial oil on the tiny world marine fish oil reserves - which produce about 0.025% of the weekly world oil output…

when world fish oil production is falling, now down to 0.1% of ideal global fish oil intake for all humans.

It is mindboggling to imagine to what extent average learning and behavioural skills have fallen accross childhood and adulthood – in both affluent and poor communities -as a result of declining (fish) brainfood intake. The dramatic benefit of modest (3gm/day) fishoil supplementation in English and Australian children against the epidemic attention deficit disorder, and against vascular disease, mixed dementias and crippling degenerative arthritis in the aging populations, illustrates the desperate need to include fish oil for all in the basic staple diet. It is too late when academic and job failure, mood disorder, physical disability and dementia are entrenched, let alone the working prematurely dead from preventable vascular disease. .

And still there is no process in sight to mass- manufacture – at prices affordable to the masses- the crucial neeeded human EPA- DHA from plant oil or from fossil oil or from basics like water and air and sugar.

The prospect of EPA-DHA production from genetically modified algae/plants/ micro-organisms offers yet more horror prospects of (Montsano) irreversible contamination of the environment, as has happened with basics like grains.

ndb

TOWARDS MANAGED AGING part 3

The first two chapters have covered musculskeletal, cancer and cardiovascular diseases and HRT.

THE COMMON PATHOPHYSIOLOGIES:  So apart from genetic programming, there are at least six possible pathophysiologies common to the preventable aging co-morbidities of apoptosis (our predestined cell death- only cancer cells are immortal) , fattening-diabetes-cancer; osteoporosis-fractures, and CVD-stroke.

What ranking to give them depends on the individual and tribe.

*catabolism by (relative) gonadopause ie sexhormone deficiency without a balancing fall in catabolic cortisol levels- especially when gonadopause is brought on early by sterilization, hysterectomy, infection, cancer therapy, other chronic disease, or high stress and pollution;

*nitric oxide depletion;

*lifelong and progressive deficiency of the score other human biologicals- especially the marine essential fatty acids (EPA eicosapentanoic acid and DHA docosahexanoic acid- so essential from conception to death for both cell maintenance and immunity;

*increased reactive oxygen species ROS due to falling endogenous and dietary antioxidants;

*common aging-related deficiency of  minerals eg magnesium, calcium, zinc, chromium, lithium, selenium, manganese, boron,  (iron); vitamins; and human biologicals eg chondroglucosamine, CoQ10, carnitine, ribose, arginine, carnosine, Nacetylcysteine (and the sex hormones);

*insulin resistance – prediabetes, metabolic syndrome, PCOS, diabetes; and

*accumulating overload of: multiple metals eg cadmium, iron, aluminium, mercury, lead, arsenic, asbestos, copper (even zinc and iron); radiation; and estrogenics eg pesticides, plastics and sexhormone tablets, and from smoking, food and environmental pollution, that can simultaneously promote cancer, neuro-/vascular and osteoporosis problems.

There is a huge basket of natural supplements- fish oil, cal-mag zinc, boron, lithium, the vitamins A (bcarotene) to K, and the human biologicals (eg proline, CoQ10, arginine, ribose, carnitine and appropriate hormone balance with eg testosterone-estradiol -progesterone, growth hormone), and galega and other herb extract. These are trophic in improving anabolism ie immune protection, tissue regrowth, antioxidation, optimal NO levels, and preventing sugar tissue damage- advanced glycation end products AGES, atheroma and arteriosclerosis as well as collagen and mineral loss from diverse muscle and bone – ie preventing many of the risk factors for both fractures (frailty, weak bones and muscles – skeletal and smooth ie gastrointestinal and heart ) and vascular and immune and malignant disease .

Given the common pathogenic factors of all the common major aging diseases, one should simply add the natural supplements- arginine glutamine and proline, vitamins, minerals, glucosamine-chondroitin, and the other natural insulin sensitizers eg N acetyl cysteine, ribose, carnitine, CoQ10 and galega officinalis, to combat all aging diseases; and when hypogonadism becomes likely- with chronic illness, or from middle age- add appropriate parenteral balanced physiological-dose testosterone-estradiol- progesterone to restore the average levels of healthy slim youthful adults.

Detox: While some of these above supplements may be chelators – removers of heavy metals- in their own right, the high prevalence of metal overload may justify routine addition to supplements (within recognized tolerance and safe limits) of extra harmless non-prescription chelators like, vitamin C, thiamine, magnesium, selenium, zinc, garlic, lipoic acid, malic acid, and bromelain, and the aminoacids eg calcium EDTA, carnitine, cysteine.

CONCLUSION:

with plenty of research to prove it, it is never too early, and never too late, to  do easily what’s necessary to avoid most of the risks for the linked aging diseases that disable and kill prematurely – frailty, obesity-diabetes, circulatory (heart, stroke), arthritic, fracturing, blinding, deafening, dementing and early death.

What’s necessary is simply

*sensible diet and lifestyle including exercise and recreation;

*lifelong appropriate vigorous nutritional supplements including appropriate hormone replacement; and

*avoidance of smoking and overweight, sugar and cooked fats, and if possible avoidance of any modern man-invented drugs (or foodstuffs eg aspartamate, cornstarch) for chronic use including hormone therapy- especially man-designed hormones, and drugs invented to replace natural drugs eg to reduce cholesterol, obesity, fractures, pain, anxiety, depression, hypertension, memory loss etc.

Usually both natural supplements and other complementary therapies, and old proven “drugs” (like metformin for overweight/ infertility/ diabetes, or lowdose reserpine + lowdose co-amilothiazide as baseline therapy for all hypertension) are both safer and better- if not as fast- as modern marketed therapies.

(for detailed scientific links and refs, see the technical version of 13 Sept 2008)

TOWARDS MANAGED AGING part 2.

The previous chapter covered the commonest problems of aging: cancer, fractures and arthritis.

CARDIOVASCULAR-STROKE CVD AND DEMENTING DISEASE:

It has been recognized for decades that the age-old antioxidants, and the three antihomocysteine vitamins (B6 B9 B12), and nitric oxide promoters eg nitroglycerin NG, are major benefit against chronic CVD and it’s symptoms if not during acute myocardial infarction and stroke. NG remains the mainstay of treatment for angina. Nitric oxide is a key vasodilator, neurotransmitter and immune modulator; it’s therapeutic level is boosted by nitroglycerine; metformin (Kanazawa 2008); human sex hormones and arginine.

As with oxygen, vitamins, minerals, biologicals, foods, alcohol and all therapeutics, balance – the right amount- is everything. But vigorous timely combination of the dozens of natural biologicals that decline with age – the essentials eg fish oil, CoQ10, arginine, carnitine and ribose, and sex hormones, combined with often-diet-deficient minerals and vitamins – virtually avoid disability/ death from and surgery for heart disease (Sinatra and Roberts: Reversing Heart Disease 2007) .

Short of replacement, one cannot fix the worn-out heart, kidney, hip, spine, joints or mind once these are broken – as happens in virtually all aging adults. Half of older people die suddenly- and half of heart attacks and strokes kill suddenly or cripple permanently. Fortunately very few are crippled or killed by the commonest cancers (breast, prostate womb), so the common cancers are the least worry of aging. Of the perhaps 1 in 10 adults who develop breast or prostate cancer, with sensible management, less than perhaps 1 in 20 dies from the cancer.

But nothing can reverse sudden death, or worse, more than the mildest memory loss from dementing diseases (unless these are not due to Alzheimers’ or widespread vascular damage). And without (rare) mental or surgical transformation, very few people manage to reverse obesity back to health. So it is negligence, suicide to wait till obesity, vascular, cancer, fracturing or dementing diseases develop, when these can mostly be prevented.

OBESITY AND DIABETES PREVENTION/ TREATMENT: Overweight is the commonest avoidable cause of the diseases of aging – obesity, aging, vascular, musculoskeletal, dementing and malignant diseases.

Metformin (Werner & Bell 1922) – dimethylguanidine – is the only ‘synthetic’ drug (a tagged antihyperglycemic extract of the galega officinalis plant) that has been proven to be a panacea against virtually all major diseases, a heavy-metal chelating, anti-infection clot-avoiding anticancer antihypertensive antioxidant insulin sensitizer (without increasing C peptide) that also reduces lipidemia; and bone resorption (and thus unblocks obesity-related delayed adolescent growth) via promotion of nitric oxide. It is the only designer drug ever that has been proven in a 20 year randomized controlled trial RCT (mean 13.6yrs- the UKPDS, Holman ea 1998) to reduce all major adverse events including cancer and all-cause mortality by 36% in diabetics; and reduce new diabetes by about 50% (30 – 70%) in major prevention trials in the overweight over a mean of about 3 years in the USA, India and Chinese Diabetes Prevention Programs; and produces and sustains about 8% weight loss in the overweight for at least 4years – without a singe major adverse effect.

No other designer ie invented drug for chronic prevention can claim such multisystemic benefits and lack of adverse effects in sensible tolerable dose Unlike metformin, no new drugs are subjected to rigorous trials of even five years before they are launched on the unsuspecting public. So it is left to chance whether patients die or are crippled by new drugs before there is such outrage that they are cancelled. And the American Government has made it impossible to sue their profiteering devious drug companies for such negligence! . SEX

HORMONE REPLACEMENT SHRT: Estrogen is a known immunostimulator ie it easily awakens (auto)immune reactions and malignant growth; whereas progesterone and testosterone are known immunomodulators ie balance immune responses. In cell cultures, estrogen too may have dimorphic ie opposing effects on nitric oxide (Walsh 2003; Shih 2006; Richette 2007).

But in postmenopausal women transdermal or oral estrogen replacement ERT with or without cyclic synthetic progestins for 6 – months increases NO levels (Serin 2001; Kesim 2005). But progesterone followed by estrogen promotes activation of dormant breast cancer cells – so in both men and women these must always be at physiological bloodlevels with balancing testosterone levels, all at the lowest necessary doses.

Testosterone on the other hand is the well-known crucial stimulator of nitric oxide synthetase (Shabsingh 2004), like vitamin D and metformin an immune balancer fighting infection and cancer, muscle and bone frailty, thrombosis and depression.

So for youthful health (not least lifelong healthy necessary sexuality), most aging men (as often as do women) need physiological ie non-oral testosterone replacement to replace their youthful testosterone and estrogen levels; and women need non-oral replacement of estrogen and testosterone to restore balance. And both need some progesterone as well for optimal health.

It is unfair that aging men are given only safe parenteral testosterone ie spared the risks of testosterone tablets (which were banned some time ago), but aging and more vulnerable women are told it’s OK to take sex hormone therapy – tablets- by mouth. It has been well known for decades that (unlike balanced non-oral hormones) this is risky – especially using xenohormones – hormones foreign to humans: premarin from mares’ urine, and progestin ie synthetics.

TOWARDS MANAGED ANTIAGING: part one.

TOWARDS MANAGED ANTIAGING:

INTRODUCTION: As a specialist in managed anti-aging, preventative medicine, I am asked by a gynecologist – the ultimate “midwife” of fertility, childbirth and everyone’s successful midlife:

what are the underlying mechanisms common to the increasing disabling problems of aging- fatness frailty, arthritis and fractures, the circulatory, memory, vision, hearing and cancer afflictions, and premature death? when humans are capable of living healthily to well over 100years?

It goes without saying that we humans are our own worst enemies and the greatest (and cruelest) threat to healthy survival of life. But aside from bad choices, bad governments, bad Corporations, bad Regulators – smoking, alcoholism, cooked fat, and sugar (including sugary drinks), poor exercise and recreation, diet-lifestyle, and environmental and medicine pollution – read Rachel Carson’s Silent Spring, Deborah Cadbury’s The Feminization of Nature, and Margaret Attwood’s : Oryx and Crake – in specific diseases these mechanisms include many deficiencies, and reversible pollutants.

SPECIFIC (BUT LINKED) DISEASES:

CANCER: this is the most feared although the least common or disabling of the major diseases of aging. Provided early symptoms and risks are not ignored, it rarely kills, it causes well below 5% of aging adult deaths- slightly more in reckless men than women. Genetics (family history), and pollution of the food chain and the environment, and medicines, play a part.

But the common and avoidable cancers are easy to generalize. The commonest cancers – those of the second half of life – are the gender and sex-hormone-related cancers: breast, prostate, colon, womb and ovary. These generally take decades to reach clinical significance – many eg of breast or prostate never do, they are simply found incidentally at autopsy.

Causes involve all the overlapping mechanisms including genetic, alcohol, smoking, stress, lack of exercise, excess calories, dietary (sugar, high-temperature cooking especially fat), progressive fall in micronutrient essentials like vitamins & minerals, increasing environment and food toxins; and above all, random mutations and the progressive imbalances of aging. The worst is that most of us now outlive our youthful balance of exercise and rest, our necessary good lean mass and low fat mass; and especially balance of hormones.

We need lifelong our abundance  of the energizing anabolics ie builders- apart from balanced food and minerals, they include the androgens, vitamin D, thyroid (T3 and T4), melatonin, growth hormone, which fall with aging and which we omit, forget to check and replace.

We don’t need or want those that increase with age – the fattening catabolics cortisone, estrogens, insulin and leptin that so often rise too high with aging, fattening, and inappropriate estrogen/insulin-boosting therapies. Virtually all aging humans eventually require some hormone replacement HRT, earlier rather than later- but it’s never too late to start. This means physiological correction in children or adults of hormone deficiency, not use in high dose as hormone therapy HT of eg inflammation or reproductive problems.

It is common cause that in both long-term historical follow-up clinics the past 50 years (Byrd & Burch; Schleyer-Saunders; Gelfand; Greenblatt Gambrell et al; the Nurses Study); and in the trials- the Women’s Health Initiative (2002, 2004) and the Finland Oulu trial (Heikkinen 2006), women randomized to appropriate conservative dose oral estrogen-progestin from menopause and followed for up to 10 or more years had virtually one-third reduction in all common major diseases- including breast, womb and colon cancer, arthritis, fractures, heart attack, stroke, dementias, and in cancer- and all-cause deaths.

Men followed for a decade and more from initiation of appropriate HRT- parenteral (ie via the skin to the bloodstream – not enteral- via the bowel & liver) testosterone supplement have similar striking reduction in prostate cancer -and all-cause deaths (Behre & Nieschlag Germany; Carruthers London; Kaufman USA) .

There is still no proof (except in people with strong history of the sex-hormone-related cancers or with suggestive symptoms), that routine screening (ie pelvic exam, blood tests or mammography) makes any difference to the low risk of death from breast or prostate cancer. There is strong evidence that appropriate balanced sex hormone replacement long term – with appropriate screening- reduces the death rate from such and all  cancers.

OSTEOPOROSIS FRACTURES AND ARTHRITIS: Ignoring the fractures and osteoarthritis incurred as a result of a major accident, or stroke-induced fall, or visa versa; and ignoring disuse osteoporosis after stroke/ paralysis, alcoholism or cortisone therapy: what factors contribute simultaneously to aging arthritis, osteoporosis and stroke-cardiovascular disease CVD?

Quite simply, failure to maintain lifelong – provide- the full basket of balanced bone, muscle and circulation-supporting supplements –magnesium, calcium, zinc, boron, manganese; vitamins especially B6-9-12, C, D3, E & K, and the human biologicals – chondroglucosamine, proline, carnitine, creatine, arginine, CoQ10 etc, which run out in most people after midlife…

Kanawasa ea (Japan Oct 2008) “suggests that metformin can induce the differentiation and mineralization of bone cells”, and that that this drug is beneficial for not only preventing overweight, cholesterol problems, thrombosis, diabetes, hypertension and cancer, but also fractures by promoting both bone and muscle strength.. It is common cause that diabetes is associated with weaker bones and more fractures (Yamamoto 2006) let alone arthritis. .

NEXT POSTING: CARDIOVASCULAR FACTORS:

THE MULTI – TRILLION-DOLLAR WAR AND IT’S COST TO HEALTH

This was written a year ago but overlooked in drafts.

When they started this unwinnable Iraq (and Afghanistan) war, were  the Bush  gang unaware of the bottomless pit  of economic and environmental  and moral ruin  – let alone imminent extinction- their greed was  leading the West into?

Not according to sober people like Noam Chomsky, Margaret Attwood, Deborah Cadbury, Levy and Scott-Clark, Al Gore.

And now President Obama is expected by the world to put Humpty together again, like FD Rooseveld did 70 years ago when the world’s resources were still largely untapped..  But this time round, Humpty has been vaporized,  America and Britain are bankrupt.

In times of great injustice,  the people of Britain rose up against tyrannical kings; America against British tyranny;  and most recently  South Africa against white tyranny.

But sadly, prosperous  NATO  peoples of the Northern Hemisphere – whose family heads were raised in the times of Rooseveld and Churchill-  have again lost their survival  let alone moral will:  despite progressive warnings in the media the past 35 years, they have gladly followed devious immoral political leaders into progressive warring (as the “English” world  worshipfully followed Hitler and Mussolini in the 1930s).  And re-elected the  ruthless Bush and Blair gangs despite their obvious lies. And have still failed to put these gangsters (and their well-paid puppets like Gaddafi, Musharaf, Mugabe, Mbeki and Zuma) on trial for engineering the global and regional collapse.

So global health and  life expectancy – indeed, human fertility and prospects of survival- plummet – from violence, starvation, dysnutrition, pollution, depression,  stress and thus more stress-induced diseases.

Next time you are at a Mall bookshop, browse through if not buy Joseph Stiglitz & Linda Blimes’  prophetic  book The Three Trillion Dollar War

It details why greedy leaders ancient and modern go to war – for the massive personal  profit, at the expense of others.

The three trillion dollar cost- by 2006 -  of the Bush gang’s War on Terrorism (the cost calculated by leading economists) is just the cost to Americans,
excluding many times that cost for the rest of the world affected by the permanent state of war and resultant rampant inflation, further global warming and burn-up of commodities.

Never mind the hundreds of thousands killed or maimed in the Iraq and Afghanistan-Pakistan conflict (future cost for Americans alone projected to exceed $20 trillion) , and incalculable damage to health in the region, the ripples hugely aggravate poverty, mental ill-health and starvation in the rest of the world, as aggression and counter-aggression consume resources and  rack up the stakes between all hawkish leaders like Bush, Blair, Putin, Mugabe, Zuma at al. .

As Stiglitz & Blimes  say, one can speculate how such untold war costs could have been spent on peaceful developments everywhere, no matter that USA families – who then earned an average of $70 000 a year – can afford it, while the majority of earthlings- as in South Africa – survive or die on less than a dollar a day, often below $1000 per extended family per year.

But who cares about lives and health lost, the mushrooming of the most  basic food costs when war is untold billion-dollar contracts to politicians’  cronies including medical suppliers, as even South Africa experiences..

NEW PANDEMIC RESISTANT INFLUENZA

The devastating outbreak of cholera in Southern Africa is due to politically  (mal)engineered breakdown  of elementary services  for which the taxpayer and householders pay. The same could be argued for the countless deaths from HIV and now multiple-resistant TB in South Africa – systematic deliberate economic sabotage by Governments (and the Big Business that keeps them in power)  rooted in corruption, self-interest and disdain for the poor majority and even their voters.

But the early release articles published in JAMA this  2 March under an editorial from Harvard University are stark reminder of ongoing perils not just from “new” infections like AIDs (and of course from politicians and snake-oil salesmen)  but also from mutating influenza viruses.

Now it is the H1N1 strain that goes on re-circling the world.                                                 And  virtually all isolates (cases) have been resistant to known antiviral drugs.

The implication is terrifying – resistant strains have apparently spread even without exposure to antimicrobials.

According to the latest findings as summed up by the Harvard team, “

“an axiom of good infectious disease practice [is that] inappropriate use of anti-infectives invariably results in resistance.”³ But if drug-resistant strains can out-compete susceptible ones in the absence of anti-infective pressure, it follows that for this organism and this agent, the most basic “truth” about anti-infective resistance may be wrong……. For now, the best tools to mitigate influenza infection are tried-and-true—vaccination, social distancing, hand washing, and common sense.”

But now that it has come out that mercury may have been withdrawn from vaccines but often  replaced by aluminium, and with the changing patterns of virus types, some remain skeptical about the cost:benefit of vaccines.

There is much evidence  that everyone should be taking supplements of fish oil, minerals and vitamins regularly lifelong, including 3gms vitamin C a day (the Irvine Stone-Pauling hypothesis) or less to individual bowel tolerance..

But for those at higher risk of infections, especially children and the frail/elderly,  apart from the  items listed by the Harvard team above, everyone needs to up their self-defenses at least seasonally  against all diseases including infection,               with supplements- especially probiotic; a multinutrient; and especially:

vitamin C powder both as nasal snuff,  and orally to tolerance (which rises during stress eg infection) short of diarrhoea- which may be 10 or 50gms a day depending on an individual’s diarrhoea threshold;

beta-carotene about 10 000iu/d;             vitamin D about 5000iu/d;

zinc about 20mg/day; selenium; and especially - IF IRON DEFICIENT- IRON ;

and appropriate sex hormone replacement - powerful immune modulators.

herbs like aloe; shiitake (mushroom),  sutherlandia, and many Chinese herbs;

and for the overweight or those already with metabolic syndrome or diabetes- extra insulin sensitizers like the herb galega officinalis or it’s derivative metformin (an anti-infective biguanide)  to tolerance short of diarrhoea. .

THE MYTH OF STATINS: THEY HAVE NO CLEAR NON- CARDIOVASCULAR CVD BENEFITS

A new study from Israel (Shalev, Chodick 2009) claims a 45% reduction in all-cause mortality with statin “even in primary prevention” – “the primary prevention cohort initially had no evidence of CHD or CVD” – thus like the JUPITER study postulating significant reduction also in non-CVD mortality..

But their  table shows that at baseline in  their “primary prevention” cohort,  58% had hypertension, 25% diabetes, a staggering 18% morbid obesity. . If these comorbidities – hypertension, diabetes, obesity- are not integral part and parcel of the spectrum of insulin resistance-metabolic-vascular (the lethal seeding of subintimal plaque) disease, then what are they?

Patients with such conditions can hardly be classified as “primary prevention” – and statins are notoriously known for doing nothing to reverse insulin resistance and weight gain, let alone diabetes and cancer- so they cannot influence the NON-CVD morbidity and mortality that affects the majority of us overweight elderly survivors from around WW2.

Paul Ridker conceded this in the Jupiter trial , admitting that probably a high percentage of deaths were indeed from CVD, not from non-CVD causes.

Only metformin does safely and effectively reduce non-CVD morbidity as much as it does CVD, and should have been used as baseline  in all trialists – there are no absolute contraindications long term.

So far there is no evidence that statins significantly lower any non-CVD disease/ mortality.

Obviously in secondary prevention after major CVD events, the great majority of deaths will be from CVD- so statins can indeed modestly lower allcause mortality- but  without any significant reduction in non-CVD mortality.