Monthly Archives: June 2008







          While urologists,  andrologists and internists  demand blood hormone  levels to diagnose male hypogonadism ,  adrenal, thyroid  or other endocrine dysfunction ,  many gynecologists still apparently  give postmenopausal HRT without ever measuring levels.

           Do baseline and achieved sex hormone levels matter ?

           Older authorities(mostly male or trained by men) did not believe so; hence we still see women presenting  on  eg implants or Premarin up to 2,5mg/day for years, with Estrogen  levels of well above 3nmol/L ->10 times what is necessary and safe),  or SHBG levels well over 200nmol/L; some of them grossly bloated and dysfunctional if not with mushrooming breast cancers or  the obesity metabolic syndrome.


      The textbook HORMONE REPLACEMENT THERAPY HRT (A Wayne  Meikle ed: Humana Press, USA  1999: p266) says  in Men’s Sex Hormone Replacement SHR: “the  general principle of SHR  is to normalize the (TT) level”.  “The safe course is to duplicate normal physiology as much as possible:  HRT  should allow self-administration, be convenient, affordable, minimal discomfort, with predictable responses. TT-cypionate  or TT-enanthate  100mg/week maintains physiological levels between 16-32 ie mean 24nmol/L.   Mixtures of short-and-long-acting TT  (eg Sustanon) are  thus  not recommended”.


At p412 Davis & Burger, for TT Replacement  in women, say:  “replace TT levels to at least the UPPER level of  normal physiological range for young ovulating women”.

     Meikle’s  authoritative  Textbook thus stresses the importance of  duplicating  normal human  physiology .  This  requires  using human systemic (ie not oral) hormones which can  and  must  be measured before and periodically on SHR –

 ie  using only systemic TT in men, systemic TT + E2 + Progesterone in women.


The 2000 Management of the Menopause Millenium Review (Studd JW ea, London) strongly promotes measuring hormone levels and balance in both sexes: ”calcium loss decreases with serum E2> 72pmol/L; vasomotor symptoms at >126-252pmol/L; and lipids changes at  250pmol/L- whereas breast cancer BRCA cells responds  to  E2>36pmol/L”  but does not say how these interact with TT levels;  so it is  important to monitor the serum E2, to keep it in the therapeutic window above about 100 but below 250pmol/L ie mean about 200pmol/l;  many women do not feel better on solo ERT – so few persist  on it; Studd ea  thus recommend “E2 patch rather than orally, for less hypertension, gallstones, DVT & hepatic protein formation.”      “it  is mandatory to measure BMI and % body fat;   the single best screen for Insulin resistance is a  fasting glucose/insulin(G:I) ratio below 4,5.

       “Depression is the commonest functional disorder of aging men, in whom aging sexhormone changes – PEDAM(Partial Endocrine  Deficiency of Aging  Men)-  include falling androgens, rise in SHBG, arteriosclerosis  & CVD,  and decrease in brain hormones & wellbeing – with especially decrease in melotonin & sleep, muscle strength, RBC, cognition, bone,  immunocompetence,  &  erection.”


       The Johannesburg gynecologist editor of Wyeth’s Menopause Update August 2001 certainly advocates frequent E2 measurements to titrate the frequency and dose of E2 implants, “aiming for a blood level of 0.35-0.45nmol/L: side effects occur when the dose exceeds the patient’s needs”.  Kopenhager in the same issue promotes “lowdose ERT – 1mg/day oral E2 causing less side-effects like headache, swelling or mastalgia, without increase in body mass”; but he overlooks the fact that 0.05ug of E2/day systemically will often suffice, that body weight says nothing about the steady gain in fatmass and loss in muscle  mass with aging and unopposed estrogen.   Prof  Frank Guidozzi from Johannesburg in the same issue makes the  point about TT replacement even for men – 250mg ester/ fortnight intramuscularly ie  a mean 12mg TT/day, or 5mg/day by patch, or 120mg undecanoate/day orally..


          As Fritz Schumaker said, there is a need for the right amount of  all things, from water to air.  A bit too little or a bit too much food, insulin or cortisone will be seen and felt fairly soon; whereas with thyroid, vitamin D and the sex steroids it may take months to years before it becomes apparent – when it may be too late, with broken marriage, spirits, heart or bones, or cancer.  Optimal doses, blood levels and balance  are apparent throughout nature and  for all hormones – with balance between the hormones – between the strengthening androgens and the fattening estrogenics – being the most important to balance the bloodpressure and lipids, thrombosis and bruising, fat-mass and lean-mass,  concrete and intuitive skills,  hypo-and hyper-immunity,  apathy and drive.  


            Well-published clinical studies for 80 years since hormone measurements began (McLeod  & Banting; Albright; Dubois, Masters, Bulbring, Hayward, Stoll, Mackay,  Wang, Henderson, Greenblatt, Speroff, Vermeulen, Roitt & Delves, Nieschlag & Behre, Motohashi,  Studd, Whitehead, Maartens et al)  have  shown the importance of  titrating doses and measuring  bloodlevels of the superhormone family – estrogens and androgens, cortisone, insulin and thyroid –  in men and women,  on every system, the mind and body.



Sue Davis et al from Monash University  have been eloquent advocates of normalizing female TT levels above the 1.5nmol/L level;  this has been done by eg  Schleyer-Saunders in London, Gelfand and Gambrell in Augusta,  Morrie Gelfand et al at McGill Quebec, and Davey’s group  in Cape Town for over 30 years. There seems to be wide consensus that E2 level should be between 0.1-0.25nmol/L – but bearing in mind that breast cancer increases in proportion to the estrogen dose, and that plasma E2 reflects the (free)  plasma estrogens and androgens only in the presence of normal SHBG and in the absence  of any other estrogenics.


The Healthy TT level in Young Men

      Most seem to take it for granted that, at any adult age, a plasma TT anywhere above the bottom of the population range (eg 10nmol/L) is normal and adequate. Pfizer claims  in it’s Viagra trials that only impotent men with TT below about 8nmol/L were excluded,  since  those with TT level less  than about 2sd or 20% below the lower range of “normal” were not classified as hypogonadal.


Yet this level is 1/4 of the vigorous youthful 35-40nmol/L which we sometimes find in dynamic men even  in their mid-fifties.  Aversa A ea in  Italy (in Clin Endoc 2000:53:517-22) show how Androgens and Erection correlate, that  older  impotent men have  TT  around 13-19, mean 16nmol/L  ie half the level of young men;  those with vascular impotence having 25% higher E2 & SHBG, and  40% lower free TT (only about 45pmol/L,  versus 75pmol/L) than in  the psychogenic group; thus fTT correlates with penile elasticity;  (cf  male TT “normal range” at all age  9-35 ie mean 22nmol/L- whereas eg Greek  recruits at  army intake: mean TT level about 32nmol/L-Mantzoros et al).

        Salmimies’ paper  (1982) already 20 years ago illustrated that there is no sharp cutoff point for impotence, for response to TT:  “15 diverse hypogonadic men received im TTEnanthate (25 to 250 mg TT) or placebo injections 2 weekly, each dose for 4 weeks. All patients with pre treatment plasma TT values below 2 ng/ml(ie <7nmol/L) reported impaired sexual function. In four patients with TT between 2 and 4.5 ng/ml who reported impairment, TTE 50 to 250mg successfully improved rated sexual behaviour. Four matched men with TT level in the same 2 – 4.5ng/ml range reported high erectile function that did not change with TT E inj. These data indicate that male sexual behaviour is impaired at an individual plasma TT below between 2.0 and 4.5 ng/ml        ie : the range of erectile loss or response is at least between 7 and 16nmol/L on their assay.

But did they, does anyone,  give enough TT, achieve adequate blood levels for long enough in non-responders?

     Andy  Guay’s 2001 abstract  illustrates the same point, there is a (?semilog) linear response ; (as  is  seen eg in Gilbert Forbes’  1980’s elegant demonstration of the semilog linear response between total TT dose and lean body mass over years). In Guay’s 44 patients (apparently 50-70yrs old) studied in detail, altho 14.9pg/ml is in the lowest quintile of the “normal” fTT range, there was 100% response to Viagra. Drop the fTT 30% and the response fell 25%; drop the fTT 45% from 14.9 to 8.1 and the response drops 84%; drop the fTT 50% to 7.4 and the response drops by 91%.

      This predictable dose response curve correlates with the finding in wasting AIDS, (Rabkins’ and Wagner’s,  Bhasin’s, and Grinspoon’s groups), that some sick men with AIDS wasting do not become anabolic at 100mg TTenanthate/ week but, improve only when the dose is increased to 150 or even 200mg/week imi- ie to a mean TT level of 30 – 40nmol/L. Bhasin’s group in LA was the first to report, in 1995, that in HEALTHY men, modestly superphysiological doses of TT cypionate or enanthate  (eg 200mg/week) (which no more than double normal  TT blood levels to around 60nmol/L,  still below the danger level of 80nmol)  improve muscle mass and strength by 10-20%; and correspondingly in frail elderly – without adverse effect.

      Thus it is  obvious that there is no arbitrary TT bloodlevel cutoff point above which Viagra is justified de novo before trial of TT replacement. Since there are no absolute contraindications to physiological systemic human TT replacement [except untreated (prostate or breast) cancer]; and since there are no risks of such measured replacement except with untreated frank heart-failure, jaundice or untreated cancer, the phosphodiesterase inhibitors  PDI (with risk of sudden death) are never justified (at a local cost of about >US$130/month) until weekly subcutaneous gluteal selfinjection of depot TT has been tried for a few months at a cost of about US$3 to $5/month.


Our own search  a few years ago (Burman, Bornman ea)  traced over 73  published reports of studies which give TT levels in groups of  “normal” men  the past 40 years; of which about 64 reports measured TT levels in men below 39 years of age. Four  were longitudinal studies in such young men, amongst about 38 longitudinal and cross-sectional studies.  Bearing in mind Klee and Vermeulen’s recent conclusions (2000-2001) that laboratory method (RIA) has changed little the past 40 years and that all reliable measures (TT, fTT, bioavailable TT etc) correlate fairly well,  our plots confirm that  mean male TT level falls about 0.7% per year (range 0.2% to 2%pa) between youth and old age ie about 40% over 50years;  but that in healthy lean  young men under 39years, the mean TT level has remained about 24nmol/L(+-16%) for 40 years; in the 22 studies between 1958 & 1985, the range was 16-35nmol/L-mean 25; in the 42 studies since 1987, the range was 14-40nmol/L-mean 27nm; – Bornman’s Pretoria series(in young men admitted for voluntary sterilization) understandably  yielding the lowest testosterone means…

          But these figures belie that  while TT falls modestly, the TT/(E2XSHBG) product  falls drastically since both E2 and SHBG rise with aging, especially with disease: eg values may change  from  youthful (TT) 25X(SHBG norm) 20/(E2: 0.1X measured SHBG:20) = 250;  to  an aging man’s     15X20/(0.15X30)   = 66; ie the TT/E2 product has fallen by 75%.


Chapter 2 follows soon.



   As it often does, the BBC health news item (CALL TO  RETHINK CHILDHOOD BMI TESTING  (Sunday, 29 June 2008) misses the point.

         While anyone can see if someone is carrying excess fat by inspection of the unclad waist and ideally waist girth measurement, BMI is invaluable as an objective measure of weight-for-height – but how can weight or BMI ever  be a measure of fitness?
         Weight-for- height reflects the aggregate of lean mass and fat mass.
Except in body builders, athletes, the lean mass is as much a factor of hormone balance (anabolics- androgens, vitamin D, growth hormone) and water balance as it is of exercise.
Fat mass is far more a reflection of calorie intake than of calorie expenditure – physical excercise.

         So regular measurement of height, weight and waist girth is crucial at all ages  for monitoring both fat mass – the major marker of the risk of the obesity diseases from early puberty, infertility and type 2 diabetes to cardiovascular disease, cancer and weightbearing osteoarthritis – and lean mass. Low lean mass for height (the LMI- lean mass index) reflects reflects low  protein-exercise levels and thus risk of future frailty- fractures.

         Hence the increasing problem of fatness frailty in those who are pampered by abundance of food, transport and physical leisure – especially in postmenopausal women, especially those on oral estrogen-progestin hormone therapy- apparent “normal” BMI but increasing girth and fat mass while lean- muscle- mass declines inexorably. These are the patients we see in practice every day,  in whom weight and BMI is especially misused, in whom doctors dismiss a weight gain of say 1/2kg a year while this may mask a fat gain of 2.5kg a year while 2kg of lean mass a year is being lost.

       These are the patients in which doctors (who should know better)  negligently continue to ignore that the older patient often has  excess estrogenic:androgen balance if not frank androgen deficiency syndrome; and/or  negligently deny the patient metformin prescription until she has frank diabetes and obesity!

          There are thus two distinctly separate imperatives at all ages but especially in young schoolchildren, when habits are being set:  monitoring of fat mass- which must be regulated by prescription of  metformin supplement  (or equivalent natural weight-insulin resistance reducers) to tolerance long term if all else fails so as to halve the inexorable progession to overweight, metabolic syndrome and diabetes;  and enforcement of minimum exercise standards to promote both physical and mental health.

FROM LIFESPAN TO HEALTHSPAN: Dr Tory Hagen at Linus Pauling Institute

Congratulations to Dr Tory Hagen on being appointed to the Jamieson Chair in Healthpan Research at the Linus Pauling Institute at Oregon State University 
     and to venture capitallist   Burgess Jamieson for having the vision to fund such research to extend healthspan.
Dr Hagen’s work has shown that lipoic acid and carnitine can improve memory, mobility and overall function in aging.
He has aready attracted over  US$7million other research funds- amongst over US$70 million being spent on the new Linus Pauling Science Centre and related research.


So NICE and the National Obesity Forum have  approved rimonabant Acomplia for use by NHS patients.  UK. 24  June 2008. See article.
Why has the USA not approved it? because  “On June 13, 2007, FDA’s Advisory Committee  concluded that the French manufacturer Sanofi-Aventis failed to demonstrate the safety of rimonaban tand voted against recommending the anti-obesity treatment for approval”  “The risk benefit ratio on the usage of Rimonabant is not yet established, so better alternates can be chosen.”
See reference.

why has EU and the UK National Obesity Forum  NOF given the nod to rimonabant but not the proven metformin?  One need only look at the sponsors listed on the NOF website to guess- drug companies who all market anti-obesity wannabe drugs: Sanofi-Aventis, Abbott, Roche, Canderel.

 It is the same with hypertension and lipidemia drugs: the most effective – metformin,  nicotinic acid, and lowdose reserpine plus amiloretic- are not profitable, so despite their total safety and great efficacy in appropriate dose,  big manufacturers will not pay for trials and marketing to promote them, so regulators and eg lipidemia / hypertension societies ignore if not delist them, as  has happened to reserpine  in UK, Europe and South Africa.

Why are  Merck- Bristol-Myers Squibb not sponsors of NOF  since they market the original Glucophage metformin?
Perhaps it is because this 85year old plant extract (developed in Scotland)  is too successful, but out of patent: it is the only drug that has ever been tested in a double-blind randomized controlled trial RCT for 20 years, which in new overweight type 2 diabetics reduced all common major degenerative diseases and all-cause premature deaths by almost 40% (which no other patented drug does) without a single serious aderse effect- in fact it greatly reduces deaths from common lactic acidosis which is common in seriously ill older patients  Similarly in three large RCTs in overweight non-diabetics (in USA, China and India), it halved the incidence of new diabetes. It’s primary purpose is to reduce appetite and  insulin resistance and thus improving energy uptake into brain and muscle -and thus improve mood and exercise capacity, and reduce hypertension, lipidemia, cancer, vascular disease, arthritis and fat stores including in the liver.

Thus at any age it is the best drug for treating overweight and obesity, polycystic ovary syndrome PCOS, pregnancy overweight and pregnancy diabetes, type 2 diabetes, lipidemia, vascular disease and thrombosis risk. No other drug reduces obesity safely and sustainably by 20kg over 2 years as we have seen, and by 8% over 4 years as Glueck et al have reported, and halves all-cause mortality over 5 years in type 2 diabetes as it does in Canada.

Since some patients metabolize metformin very slowly and therefore do not tolerate average daily doses (500- >3500mg/day),  metformin should simply be started at no more than about 125mg/day eg  a quarter fragment of a small metformin tablet, and increased gradually to tolerance over weeks- which dose averages about 2500mg/day. Most trials eg the DPP in USA lost 25% of trialists at the outset because they ignored this obvious rule, starting foolishly  at eg 500 and even 1000mg/day.  As with any other chronic drug, the patient must be warned of signs of intolerance (which they should report promptly) -nausea,  bloating, diarrhoea- on which they must promptly halve if not stop the drug till these symptoms settle then rebuild the dose to a  well-tolerated level.

Thus nobody in their right mind would recommend or take any drug except metformin for increasing overweight or obesity let alone diabetes (even for  the resistant overweight type 1 diabetic). Why use a drug like rimonabant with serious risk of hypertension, anxiety and depression when it is never required?

This is not to say that metformin is essential, since there are a thousand natura insulin-resistance  and appetite- reducing  natural nutritional microsupplements, out of which one can simply safely and cheaply combine  a few dozen in one’s diet twice a day- fish oil, and most others in a powder blend. Naturally these are not patentable, hence they are against the interests of the big drug companies.

Perhaps the biggest fraud of all is to ignore prescription of metformin as an adjuvant to diet and lifestyle until the patient has sustained enormous damage in developing obesity and type 2 diabetes- with long experience that vascular, renal, lipidemia, eye and nervous system disease from this metabolic progression may occur well before obesity or diabetes become obvious. Why otherwise do we continue to see fat elderly patients worsening on glitazones,  statins, sulphonylureas,  and even  highdose insulin? when all they need is optimal titration with metformin and the legion natural alternatives vailable.


    Should older osteoarthritic patients- who mostly have high risk of all the common major degenerative diseases of aging and premature mortality- be fobbed off with non-steroidal anti-inflammatory drug – NSAIDs?


    This University of London study  on  confirms what has long been obvious- that it is foolish if not negligence to poison the body by noncurative-and potentially fatal – shotgun therapy eg oral  anti-inflammatories,  or intramuscular diclofenac, when self- inunction can do better.
              However, the report is surely an unnecessary punt for ibuprufen cream, and seriously misleading if not dangerous  on major scores including long term cost  for the older population
          1.  There is no need to use synthetic designer NSAIDs-  which inherently have  higher risk of eg sensitiziation;
       when either  selfmassage of the relevant sore point with any anti-inflammatory , even teatree oil or ung meth sal,
        or  appropriate targeted injection of the relevant tendon, ligament or joint with a few ml of local anaesthetic +- depot corticosteroid, may be more effective,  often speedily curative  and totally safe.

And     2.  the BBC report says  “the most common cause of  pain in the knee is osteoarthritis – a condition caused by abnormal wearing of the cartilage… an estimated third of over 50s suffer from knee pain…  in half of those the problem is classed as severe.” 

         The common causes of pain in the knees in the older  are many; but assuming that the clinical condition  indeed points to knee  “osteoarthritis”- a heterogenous multifactorial basket – (and not eg simple external ligament strain or bursitis-   it  is proven that while a chondro-glucosamine CGS combination has little analgesic effect, such a biological  oral combination  actually restores lost cartilage by millimeters over months to years, so that many people sentenced (usually by surgeons)  to eg bilateral knee replacement for destructive painful OA knees may recover completely without surgery  and are  walking normally within months and a decade later.


      Let alone analgesics masking if not   if not allowing more cartilage damage, it is dubious –indeed impossible-  that diffusely painful  overloaded osteoarthritic knees will  respond enough during the pain phase to just topical  analgesic anti-inflammatory massage therapy.


  And 3. The BBC report gives no details of the patients and the duration of the reported  trial. This topical cream approach was debunked by a metanlysis in the BMJ in 2004;


          4. older osteoarthritic patients are at high risk of all the chronic degenerative diseases of aging- hip, spinal  disc, hypertensive, atheromatous etc.
      So oral chondroglucosamine is simply combined with a combination of  natural safe effective  lowcost oral analgesic  anti-inflammatory antioxidant  weight-reducing  and anabolic  supplements (eg  fish oil 4gm/day  plus cat’s claw, MSM, bromelain, boswelia, curcumin, proline, GABA  and some vitamins and minerals), for progressive reversal of both pain, inflammation and the causative overweight and cartilage loss.

      The analgesic but risky  NSAIDs can be weaned off in due course while  the CGS continues as longterm protection.


More important still, the aging and overweight homo erectus is especially prone to pain and disability from degeneration and prolapse of the 23 intervertebral fibrocartillage discs  so well shown on

         In 2003 van Blitterswijk ea at the Netherlands Cancer Institute reported a man with a  lumbar disc prolapse (on MRI scan  with longstanding  lumbar pain,  which healed completely over 2 years on CGS.  They review the cartilagenous nature of the intervertebral discs with their hygroscopic sponge nuclei composed of proteoglycans including CGS, 

 and  fed by capillaries  from the periphery.

They noted that GCS is anti-inflammatory and anti-catabolic.  They concluded: “oral CGS can pass the gastrointestinal tract and can indeed reach articular cartilage, probably also intervertebral discs, where it may have at  least a chondroprotective effect  and, quite possibly, a regenerative effect. Contrary to NSAIDs, no significant adverse  clinical, hematological, hemostatic or other side effects were found in any  clinical study using CGS supplementation.

Contrary to degenerated cartilage, these dietary supplements had  no apparent effects on normal cartilage metabolism This may suggest a tropism of these agents for cartilage in the reactive  state, characterized by enhanced proteoglycan turnover.

GS/CS does not contribute to insulin resistance in  diabetics, probably because the pharmacokinetics and tissue distribution of GS/CS and glucose are different“. 


       In 2006  Grunhagen ea at Oxford University again noted that the avascular disc cells need the low concentration of blood oxygen and glucose that reaches them from the periphery.
         In 2007 Ulrich ea at UCSF showed that repeated disc injury (during healing) causes persistent inflammation, probably enhancing disc degeneration.


        But it is not just multiple joints that  warrant the protective benefit of long term CGS:
In 1979  Nakazawa ea in a German journal reported that CS for over 5 years lowered mortality and thrombosis in the elderly.
In 1985 Corsa ea in Italy showed significant improvement in peripheral vascular disease and lipidemia with high-dose glycosaminoglycan.
In 1997 McCarty in San Diego proposed that  GS may like heparan protection against atherogenesis. 
In 1998 Nowak ea in  Poland  showed that GS levels are raised in ischemic diabetics,and fall with exercise or other control of hyperglycemia.
In 2001 Talpur ea in Washington DC showed that CGS in rats had no adverse effects in IGR rats, and lowered systolic BP.
In 2002 Coccheri ea in Italy and in 2005 Lauver ea in Michigan  showed that glycosaminoglycan healed varicose ulcers and peripheral arterial and coronary ischemia, lowers fibrinogen and is lipolytic.
In 2005 Duan ea  in USA  showed that GS significantly reverses atherosclerosis, and
in 2006 Tannock ea in US that GS reduces longterm arteriosclerosis although it promotes it short term. .
 n 2007 in USA, Champattanachai ea  showed that  rise in endogenous NacetylGS is  an endogenous stress-activated response that improves cell survival;

                  and Fulop ea  propose the molecular basis for this;

and finally in 2008 Jones ea in USA conclude that “GS signalling represents a unique endogenously recruitable mechanism of cardioprotection“.


     Then there is the major body of evidence to support nutriceutical supplements not just for minimising  atheroma and osteoarthritis but also against overweight, (pre) diabetes, hypertension, osteoporosis, lipidemia, osteoporosis, cancer and dementia- with nitric oxide donor, antihomocysteine, antioxidant, insulin sensitizer  and anabolic supplements.


       So rather than dismissing the painful arthritic patient with some NSAID cream, the BBC report should have focussed on the golden opportunity- opportunistic screening-  that every consultation presents – to assess quickly the aging risks- simply a history questionnaire, BMI and waist measurement, arm  and ankle bloodpressure (ankle-brachial gradient)- and counselling  the patient both about the cardinal role of sensible exercise diet and lifestyle, and about taking the evidence-based lowcost combination of fish oil and a blend of up to threescore vitamins, minerals and biologicals  including CGS (and where appropriate- in most older people- appropriate non-oral balanced human hormone replacement HRT)..


 refs available on Pubmed.






Hats off to the NEJM in  bucking the trend, publishing free online a Sounding Board against releasing a (Merck) statin for over-the-counter purchase – see article


Dr Tinetti highlights the  accumulating insidious long term risks of statins- the latest being  haemorrhagic stroke and lung damage; and as Jacobson’s Mayo Clinic proceedings review the same month says, al least 5% ie 1:20 patients REPORT muscle pain and fatigue, if not also depression, impotence, liver-kidney problems etc. see Mayo Clinic.


As Mary Tinetti says, and has been stressed for over a decade by eg the Sheffield group, there has never been evidence that statins give safe overall benefit- major reduction in cardiovascular risk – UNLESS  the patient already has serious lipidemia with existing ischaemic disease ie 10year risk exceeding about 2% per year.


The simple reason is that in practice, statins do nothing for the underlying CAUSE of  common atheroma-  lipidemia –  which is the metabolic syndrome  X  (MBSx ) of overweight- insulin resistance – type 2 diabetes,  from excess calorie and fat intake,  from stress (cortisol) and from lack of  physical exercise (which statins aggravate).


Except in rare cases of severe hypercholesterolemia (genetic  or irreversible liver/renal disease), cholesterol per se is not a significant risk factor since it is a vital substrate for our metabolism. Statins thus do absolutely nothing for  the mountain of non-cardiovascular morbidity and mortality, from infections, overweight, arthritis and depression to cancer.


The agents which the vast majority of  us need- those becoming overweight ie heading into MBSx – are not wannabe synthetics like statins but  those that lower  excessive clotting and insulin resistance,  reverse fat gain  and hepatic steatosis, and thus ENERGISE muscles ie exercise – the 80-year old metformin or it’s parent herb galega,, minerals,  vitamins, fish oil, fibre, fenugreek,  cinnamon, garlic; ginger, gymnema; ribose, coleus, CoQ10, carnitine, acetylcysteine, and where appropriate with (relative) deficiency), physiological systemic human sex-hormone replacement (depot testosterone, estradiol). 


Any healthcare provider who fails to enforce such simple holistic low-cost primary prevention early (which halves all-cause disease and deaths, adds decades to health and thus vastly reduces the cost and disability-dependence burden)   should be disciplined for negligence. Disease  certainly pays the Disease industry,  shareholders, Governments , Academia and Regulators – but not the individual- for whom Only Prevention Pays.


 If any prescription drug warrants release to over-the-counter status it is METFORMIN, given that no serious adverse effect has EVER occurred  with sensible use   and instruction (ie self dose titration to tolerance) in  trials of either PRIMARY prevention of diabetes and overweight, or even SECONDARY therapy eg  in polycystic ovary syndrome – infertility- pregnancy, or the 20 year  UKPDS  United Kingdom trial  in type 2 diabetics.


The same cannot be said for eg sugar, alcohol or smoking  tobacco, which  – since they are the greatest  marketed insidious killers universally on sale – should be heavily scheduled regulated drugs if not (in the case of smoking tobacco) banned.


Eight major new studies (below)  published this year confirm that old is best, and give the lie to costly marketing-hype trials trying to promote newer anti-hypertensive ( beta-, calcium channel- and angiotensin blockers), anticholesterol (statin), antidiabetic and antithrombotic blockbuster drugs. 

So the Veterans, MRC, TOMHS, SHEP, ALLHAT, German Reserpine, Cache County, USA, UK, Indian, Chinese and now Turkish, POISE, Australian and the Eniwa antidiabetes, antihypertension and cardiovascular studies. show that one can achieve unsurpassed prevention and treatment of a range of conditions –

overweight or already diabetic, hypertension, stroke, heart-failure, thrombosis, arrhythmia, lipidemia, diabetes, dementia and all-cause premature death –

using low-dose diuretic – ideally co-amiloretic 7 to 13.5mg/d, (or a buchu-dandelion-calmag-potassium equivalent) plus low-dose reserpine 0.05 to 0.1mg (or the herbal parent rauwolfia extract), plus metformin (or the herbal parent galega with other highly effective insulin sensitizer / appetitie regulators), including fish oil 3 – 4gm/day.

Trials for 30 years have shown that only the plant extract metformin reduces all deaths in type 2 diabetes

–         In the 20year UKPDS (Holman ea) only metformin lowered all major diseases and deaths by 36%;

–         In a Canadian Medicaid Program (Johnson ea), metformin halved deaths in diabetics over 5 years.

Now Servier’s ten-thousand patient ACCORD trial (in North America) confirms that, in contrast to the parallel  but less aggressive ten thousand patient ADVANCE trial in the rest of the world, RELATIVE TO METFORMIN, multiple drugs to lower HBA1c intensively below 6.5% increase deaths by 22% by the 2nd yr, from heart attack, hypoglycemia etc. 

The higher death rate in ACCORD was associated, inter alia, with much higher use (than in ADVANCE) of insulin; glitazone; incretins; sulphonylurea; statin – none of which prevented a mean of 3kg weight gain. (There was no such weight gain in ADVANCE).

Since humans first became aware of the dangers of human indolence and overeating, observation has shown an inexorable link between increasing overweight and morbidity and premature mortality.

Drug companies (and their paid armies of researchers and lay / academic lobbyists) will not or cannot accept the obvious, that lipidemia and hyperglycemia are not the prime causes of disease that need to be suppressed, but are simply manifestations of disturbed metabolism due to excess calorie (and often salt) intake, leading to insulin resistance.

So they keep churning out new data promoting new antihypertensives, statins and hypoglycaemic agents – which massive studies like TOMHS, SHEP, ALLHAT, UKPDS, PROactive and now ACCORD and the Australian antihypertensive metanalysis debunk.

“Authorities” (which as in South Africa, UK and the EU, downplay metformin or lowdose reserpine / rauwolfia and lowdose diuretics) are mostly (it seems) paid panderers to Big Pharma’s (the drug industry’s) zeal to sell newer blockbusters at any cost. They thereby deny the overweight public the best anti-lipidemia, weight-limiting and antihypertensive agents available.

For the Disease Industry, only disease pays – cheap effective prevention does not.

References / Abstracts: Continue reading