Tag Archives: rimonabant

SPECIALIST NATURAL MEDICINE CLINIC 2015

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

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

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

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

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

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

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

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

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

MELATONIN, LIGHT, SLEEP, SEX, DECAY; AND THE GRAVE RISKS OF DESIGNER WANNABE SUBSTITUTION.

neil.burman@gmail.com

THE ANTIOXIDANT ANTIAGING CHIEF HUMAN HORMONE MELATONIN DELAYS / LESSENS MENOPAUSE, PARKINSONS, GALLSTONES,  HYPERTENSION, HEADACHE, SEASONAL AFFECTIVE DISORDER, AGING,  ALZHEIMERS, CANCER, INSOMNIA,, OSTEOPOROSIS & GASTRO-OESOPHAGEAL REFLUX;  ONLY EXCESS LOWERS MOOD AND LIBIDO. .

Since melatonin improves sleep & serotonin level,  it not surprisingly lowers LH  luteotropic hormone and thus libido in the pharmacological doses marketed (3mg) .

Surprisingly,  there are only 8 papers on  melatonin and aging  human sexual activity  on Pubmed search..But is it a surprise that there are 186 melatonin AND sexual activity  papers on Pubmed since 1992?  including  many on  a designer melatonin agonist agomelatine– of which one of the latest  – in Prescrire a month ago- concludes: “agomelaline new drug. Adverse effects and no proven efficacy;.. Very high doses of agomelatine are oncogenic in animals. The risk in humans is not known. Dizziness, gastrointestinal and cutaneous disorders have been observed. Agomelatine is probably hepatotoxic“.

PHYSIOLOGICAL HORMONE BALANCE VERSUS SYNTHETIC DESIGNER SUBSTITUTES:
But there are lots of self-reports on Google confirming  what physiology tells us, that hormone balance is what matters.

Doctors (and hence patients) choose at their peril –  at the behest of Big Pharma, heavy marketing-  to ignore physiology – what nature teaches us about optimal function . Big pharma made a killing before WW2 with  the isolation,  patenting and mass sales of natural supplements eg hormones starting with thyroid and insulin. But these soon ran out of patent, so Big Pharma has zealously employed massive armies of researchers  and lobbyists to develop and promote synthetics cribbed from natural products ie synthetic designer drugs. The high number of $billion-a-year raincheck drugs is a tribute to their clever marketing and sleight-of-hand concealement of adverse reports – but not for the many  thousands of patients who have suffered or died as a result of eg fenfluramine, Vioxx,  Prepulsid and lately sibutramine, rimonabant, glitazone, and vaccines….

But Industry has not yet succeeded in generating a synthetic designer ie patentable form of thyroid hormone to exploit the millions with thyroid deficiency, nor a substitute for the human heart-made  hormone  digoxin, which – like the uniquely lifesaving  plant extract metformin- defy the inventiveness of Big Pharma’s  ruthless quest for  megabuck profits.

Big Pharma wants us to forget that all modern drugs for chronic use were and are  based on ancient endogenous and mineral/plant based drugs .

The chief brain antidepressant HORMONES serotonin ie its precursors (5H)tryptophan and other natural  antidepressant like St John’s wort and marine omega3;  and the chief brain anxiolytics GABA and progesterone, and harmless plant anxiolytics like valerian,  were soon supplanted by synthetic antidepressants, barbiturate-benzodiazepine and progestin designer drugs. Industry has exploited the growing dialysis market by promoting grossly costly  designer synthetic- not human- erythropoeitin analogues.

These designer drugs have been so cleverly marketed by Big Pharma – and thus politicians, governments which  Big Pharma massively funds  directly and via taxes and job promises – that for chronic use let alone acute illness they have almost wiped out the use of highly effective remedies used for millennia.  eg Lithium and metformin were ignored by the FDA for 25 years despite being the gold standard elsewhere for bipolar and type 2 diabetes respectively.  For common hypertension, rauwolfia-reserpine is  still the goldstandard bedrock treatment in a dose of  0.1mg/day or  less , combined with the also-suppressed perfect synthetic (potassium-magnesium- calcium conserving saluretic) vasodilator amiloretic amilozide in low dose. But the antihypertensive drug industry has bought so many in the antihypertensive trials and regulatory hierarchy that Europe and Britain have abandoned reserpine; and in South Africa these “experts” beholden to Big Pharma have removed these gold standard drugs from firstline therapy recommendations and even from the formulary of state clinics because they were too cheap at below a US$ a month. .

And melatonin output (average only 55mcg a day) is inverse to bloodpressure ,  it reduces both hypertension, and the anemia of renal failure, and nicotine-related vascullopathy.

The Chinese already 2500 years ago were using gender-specific sex human hormones derived from the ‘sublimation’ of youthful human urine to treat gender-specific diseases and deficiencies. But since the extraction of  sex hormones from the urine of humans in this age of viral and prion plagues (let alone the aesthetic and logistic problem of buying billions of gallons of human urine each year)  is not on, Wyeth – with the increasing monopolistic complicity of the FDA-USA government- simply substituted human hormones by xenohormones- horse estrogens (from the mass farming of tethered catheterized mares) and synthetic progestins- for both contraception,  and HRT for women. Hence the problems  for older women of the Womens’ Health Initiative which used exclusively Wyeth’s PremPro.

And industry attempts to keep a stranglehold on the  vast diabetes market by continually synthetising new depot forms of human insulin; and  synthetic alternatives to the gold standard and  only plant-derived antidiabetic prohormone (metformin, in use for well over 50 years, the only drug ever that has been tested in a 20year randomized controlled trial, and proven to be the only prescription drug that reduces all major diseases and thus deaths by almost 50% -) by continually bombarding the market with largely unnecessary synthetic designer drugs to discourage use of metformin, diet and lifestyle change. These include  new sulphonylureas, acarbose, glitazones and now gliptins, none of which have undergone longterm trials, and which uniformly prove (unlike established old drugs) to have major adverse effects even at registered doses.

Like amphetamines, orlistat  and rimonabant have had to be progressively restricted- sibutramine is the latest to be cancelled last week in Europe. due to adverse effects that the suppliers finally failed to prevent becoming common knowledge. Is it surprising that the USA FDA – which runs  on the massive funding of and input from Big Pharma-  has still not suspended sibutramine use there?

And surprise surprise- Wikipedia dismisses metformin for weight loss with one reference, although there are scores of trials including major 3-5year  prevention trials on three continents that show that metformin use in the overweight  (even BEFORE diabetes occurs) produces both significant fat loss and approximate halving (30 to 80% reduction) in new diabetes and new cancer.

And  wiki  confirms that while the human hormones leptin,  amylin and gliptins-incretins- work in synergy with all other hormones, micronutients to potently regulate optimal sugar and fat and energy metabolism, none of them have been marketed as the natural forms- that is the last thing that Big Pharma – the FDA- Uncle Sam wants when with some effort they can already market designer adaptations to produce more golden  $billion raincheques.

This despite the fact that Turek’s 2010 USA transcontinental trial showed recently in rodents that   combination injection of the natural hormones amylin and leptin “decreased food intake (by 26%) and reduced body weight (by 15%) and epididymal fat (by 78%)”. 15% of 100kg body mass is 15kg weight loss.  A year before, Ravussin ea published the 6 month trial in obese humans of the designer derivatives of leptin and amylin  confirming that the patented combination  indeed lowered body weight by 12.7%.But the common adverse effect of the injection was nausea.

This farcical commercial merry-go-round – which puts patients at grave risk- is  despite the fact that there are dozens of safe proven natural ie unpatentable antidiabetic insulin sensitizers/ obesity-reversing supplements freely available, from garlic and fenugreek to galega officinalis, gymnema, coleus, calcium, chromium, zinc and vitamin D3.

MELATONIN DOSE:
Hypnotics  including melatonin promote sleep, not sex. Hence sex works best after sleep  rest ie well after midnight,  early morning. But unlike melatonin, designer synthetic hypnotics have dangerous side-effects and addiction problems, without any longterm benefits.

Clearly for anyone not in an institution or at risk of cancer,  melatonin dose should be kept as low as is prudent to optimize sleep – not sedate.

This dose may be as low as 0.05mg/night- hence dose should be titrated upwards from a pinch to the average optimal of 0.25mg/night, but as high as is well tolerated without hangover/daytime drowsiness.

So for the hyperanxious-anxiety-panic disorders, melatonin may well best be taken  in the morning at low dose, and early evening to unwind.
That low dose reverses impotence in rats is not surprising- 10 to 100mcg/kg as used in rodents equates to between 1-10mcg/kg in humans ie  0.05 to 1mg in adults.

Studies show that the right dose for sleep in humans is about 0.1 to 0.3mg – not the 3mg caps/pills that are unthinkingly marketed, prescribed and swallowed by unwise patients.

Melatonin in excess can worsen depression and cognition; and even be arousing.
but since it generally improves sleep and growth and reproduction and energy balance  and immunity and bloodpressure and cancer control and anorexia – fragility reversal,
it should equally clearly be supplemented at night
in physiological dose ie 0.05 – 1mg- combined with especially vitamin D3, and during the day or for an hour before sleep with bright (sunshine or artificial light) exposure, which dramatically improves Parkinsons disease..

LEVELS OF MELATONIN AND LIGHT:
The recent Bronowski Institute study shows how bright fluorescent light (does a TV or computer screen count? – surely?)  should be encouraged for an hour before bedtime since it markedly reduces Parkinsons; but in older people should then be followed by a melatonin supplement  dose  for all the antiaging reasons. As
Rabbi Michoel Gourarie writes in Personal Growth, turning on a light in the dark- even the one small candle of ancient times- can do as much to cheer up one or a host of people.

So especially in institutions sleep should be preceded by bright light for an hour before lights out.
The most most important  aspect for us all is
sequential light (both via stimulation and via vitamin D – soltriol -from sunlight) ; and  then darkness for sleep’s melatonin  value in insomnia & fatigue and especially against autism, ADHD, cancer, hypertension, diabetes (insulin sensitizer ), & especially for retarding menopause ie infertility.

The recent trials data increases greatly the potential of melatonin against premature aging ie against cancer as well as against gonadopause  that was already widely promoted 15 yrs ago by Regelson, Colman  and Pierpaoli – In 1995 Pierpaoli in The Melatonin Miracle summed up how melatonin given to aging mice maintained youthful size gonads, significantly higher sex hormones, and extended their healthspan and lifespan by 30% ie to a century in human terms.

The first 7.5year case followup  of melatonin benefits in delaying menopause came from Poland 2 years ago; but already in 2005 an Italian team  Bellipanni ea showed in a 6month study that melatonin 3mg/day “abrogates hormonal, menopause-related neurovegetative disturbances and restores menstrual cyclicity and fertility in perimenopausal or menopausal women. At present we assert that the six-month treatment with MEL produced a remarkable and highly significant improvement of thyroid function, positive changes of gonadotropins towards more juvenile levels, and abrogation of menopause-related depression.”

Previously  in 1992, Sandyk ea in New York proposed that There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification.” .  And in 1984 Aleem ea had shown “Suppression of basal luteinizing hormone concentrations by melatonin in postmenopausal women.” ie that supplemental melatonin can suppress rising LH – although the primary cause of menopause is gonadal aging-  exhaustion,- which in  both men and women leads to the compensatory rise in LH if the pineal and pituitary glands are themselves still capable of responding to feedback. The primary cause of  hot flashes is due largely  to falling estrogen level, with  all other menopause symptoms being caused by gonadal hormone exhaustion.  But Bellipanni’s 2005 study showed that melatonin supplement  could produce better gonadal and thyroid hormone output.

So all  aging folk should  take the combined hormones vitamin D3 about 5000iu/day,  and  melatonin,  building slowly to perhaps   1 –  3mg  at night, from age 30yrs if not earlier;  but with cancer, under medical supervision, building to vit D3 10 00 to 50 000iu/day ( monitoring the serum calcium) and melatonin  to perhaps  40mg/d – plus a titrated dose of the anticancer prohormone metfornin. .

RESTRAINING UNNECESSARY RISING COSTS OF COMMON DRUG THERAPY AND CONFLICTS OF INTEREST:

The review published yesterday by Discovery Health  “Medicine expenditure up by 26% in private healthcare industry” based on the Mediscor Medicines Review resonates with this week’s editorial from JAMA on Resolving Unreported Conflicts of Interest. Apart from anticancer therapy (which affects relatively few patients but is very costly), by far the two top drug costs to the private  health system in RSA  are antihypertensive and hypolipidemic drugs.

But why are these two groups of drugs 1/6th of  local private medicines expenditure?

The reason is quite plainly vested interests- between prescribers, drug developers and retailers, for  well-known reasons:
1.  Modern western medicine  rarely attempts to address the pathogenesis  of disease – it takes too much effort by prescribers and patients to try to change diet and  lifestyle. And  the only “modern” drug that addresses the main causes of the common degenerative diseases – overweight, (pre) diabetes type 2, lipidemia, atheroma, thrombosis,  hypertension, cancer, arthritis, dementia – is the antioxidant, insulin-sensitising, energising,  nitric-oxide-promoter, antilipidemic, antithrombogenic, antihypertensive, anti-infertility, anti-PCOS,  appetite-and-weight-suppressive,  anticancer, and diabetes-preventing   plant-derived metformin. This is the only prescription drug  ever – with zero serious persisting adverse effects in appropriate dose –    that has been  shown (including in the only 20year randomized controlled trial ever) to actually reduce all  major morbidity and all-cause mortality by over one-third.

2. Only new ie under-patent drugs are $billion dollar –a-year rainchecks in a $trillion dollar industry where only disease pays (not prevention- which keeps patients out of hospitals & specialist centres  and off new drug) .

So the Disease Industry has correctly pinpointed overweight and hypertension as the two leading risk factors to bombard consumers with new drugs;

but  has created the  gigantic marketing ploy  that these common lifestyle-diet problems  need designer drugs: that
average mild to moderate hypertension must be treated by combinations of angiotensin-and adrenergic, and calcium-blockers – which  do not reduce all-cause morbidity and mortality.;
and  even average lipid levels  by statins and now even the futile  ezetimibe –which do not reduce all-cause morbidity and mortality;
and overweight-obesity  by patented drugs like Orlistat and Rimonabant –which do not reduce all-cause morbidity and mortality  ,
and type 2 diabetes by new sulphonylureas, glitazones and even more toxic and expensive injectables  like gliptins- –which do not reduce all-cause morbidity and mortality .

But  simple analysis of the hundreds of better-quality  published studies and trials (not those ghost-written in glossy journals  for drug companies to promote their products) shows that:

For average mild-to-moderate hypertension, no modern drugs (with many serious  adverse effects)   surpass for benefit  the triple and zero-side-effect  combination of lowdose reserpine plus lowdose coamiloretic- in RSA costing retail about R45 per 4 months ie about $2/month;

For average-risk overweight adults with or without lipidemia and diabetes, nothing surpasses the global benefits- major reduction in all-cause mortality and mortality- of  metformin started in low dose eg 250mg/day and increased  slowly to tolerance.
Obviously primary prevention  for everyone includes a few grams a day of the essentials that  deplete at all ages with longevity, the degrading food chain,  pollution and stress – the natural ~50  replacement supplements of  vitamins and minerals and the human biologicals EPA+DHA, CoQ10, arginince, carnitine, n-acetyl cysteine, alphalipoic acid, taurine, carnosine, MSM, chondroglucosamine, lutein, bioflavinoid,  choline, inositol, 5HTP, GABA, melatonin, plus key plant supplements eg ginkgo, milk thistle, galega, gymnema, coleus etc;

all of which can be simply taken as a powder blend in water twice a day with a teasp of cod liver oil or a fish oil capsule;
at a global retail cost of as little as R100/$12 a month ( plus  in older people, appropriate physiological  human sex hormones).

So while there is some- but relatively little-  competition between generics, the major saving in both cost, risks and prevention is between therapeutic equivalents eg lowdose coamilozide+reserpine, metformin, and other safe effective  supplements – which are all that are needed for prevention and most treatment of all the major degenerative diseases of aging including osteoporosis  (which agents  Industry and their funded lobbyists- researchers, academics, regulators  try persistently to denigrate if not actively suppress)-  vs other newer- and heavily marketed  classes of antihypertensives, appetite ,  lipidemia and osteoarthritis-osteoporosis  suppressants.

This issue of promoting evidence-based best  therapeutic equivalents is indeed blowing against the wind, the tsunami of $billion dollar adspend by Big Business to promote their designer labels. But all countries- while  run by ruthless politician big business looking after their own interests – do pay some lip service to restraining the normative  monopolistic and price-fixing racketeering that screws the man in the street- both in gross overpricing, and in massive tax evasion by big business, and in rigging of elections and tenders .

Our own Medical Schemes Council is in the process of open consultations about the revised necessary and approved drug lists for all diseases in the medical schemes industry. Hence urgent vigorous debate is urgently required – in all countries- before vested interests further strangle citizens’ choice of and access to both cheap old drugs to eg reverse the dropping of reserpine by bureaucrats in UK, Europe and state clinics here, and reverse the rising tide of suppression of the best prevention and treatment there is- the base of all modern medicines – minerals, vitamins and the numerous proven safe human and plant biologicals.

The trend by the FDA and EU and Big Business in RSA must be reversed, before they (in the interests of their own pockets filled with paybacks by Big Pharma) put all supplements totally on prescription by health professionals- the very people whose livelihood (including their shares in Big Pharma, med schemes and hospitals) depends on new quick-fix designer drugs which cure and prevent no chronic degenerative disease ie on avoiding effective doses and combinations of proven supplements.

As it is, the medical schemes in RSA are now compelled to pay for the services of witchdoctors (who admittedly probably kill far fewer people than do modern prescriptions and surgery for non-urgent conditions) yet these schemes- while insuring for profit people who persist in suicidal and homicidal smoking and alcohol and sexual behaviour-  flatly refuse to pay for the best prevention  there is – the supplements mentioned- because  they are neither promoted by Big Pharma nor on prescription.

Numerous references are available under many keywords on this website below.

ndb

META-ANALYSIS: METFORMIN – THE ONLY DRUG WHICH SAFELY AND LIFESAVINGLY LOWERS CRP, OVERWEIGHT AND RELATED INFLAMMATION.

Medline was started in 1966  but has been expanded to record journal papers back to 1950. There are already 768 RCT metformin references  listed on Medline since 1969; and 323 on metformin double blind RCTs (compare lithium- since the first in 1968,  respectively 611 and 335 reports).  Obviously many of these  RCTs refer to it simply as background or previous or exclusion therapy or  alternatives.  In the 50 latest  of the 323,   metformin was distinctly involved in 42% as one of the trial  arms; in the 50  earliest, 52% involved diabetes as one of the primary trial arms.

Thus  there are perhaps 150 published double blind RCTs of metformin  itself, (which after lithium- (used from about 1850)  must  thus be  the longest   (over 40years)  and still  regularly  used and tested single chronic “drugs”. Reserpine (isolated in 1952 from a centuries-old medicinal plant) dating from the first report in 1966 is still like metformin and lithium the gold standard in it’s field of hypertension,  but with only 74 and 47 reports respectively reflecting the concerted collusion of drug regulators and the drug industry to try to suppress it by no longer using it as a gold standard for comparison. All three are uniquely safe and effective in their fields provided doses are appropriately tailored. Since  these old drugs  have  been in clinical use already for > 50years,   there may be more  RCTs than those listed.

Paracetamol has been in use almost the longest of any synthetic drug (from 1886), but ( unlike metformin, lithium and reserpine ) is  contraindicated   for long term chronic daily prevention.

But the centuries-old appetite-overweight–diabetes-reducing plant galega officinalis finally yielded up it’s unique antihyperglycemic guanide secret when  dimethylguanidine- metformin was isolated 86 years ago in Dublin, Ireland  by Werner and Best,  the same year that insulin was isolated  in Canada under the leadership of another visionary Celtic British Isles physiologist,  John Macleod from Aberdeen.

If Banting and Macleod deserved the 1923 Nobel prize for insulin for DM1,  more so did Werner and Bell for isolating metformin for DM2 when almost 95% of diabetics are now type 2.  But hindsight is great.  DM2 was only recognized a decade after insulin and metformin’s extraction  (Himsworth, the Lancet 1936),  like gout a relatively rare disease of lazy overindulgence  for obvious reasons   until the fast foods and prosperity – expanding waistlines from  the 1950.  So there was no impetus to develop metformin commercially in it’s first 30 years,  in obvious contrast to the need for insulin for  the scourge of wasting juvenile diabetes mellitus type 1 DM1 in millions of young sufferers already in the 1920s.

Werner and Bell need to be honoured   as isolating by far  the most important chronic drug of our time  for the epidemic chronic degenerative diseases of aging in the increasingly overweight since the 1950s, (and especially with AIDs and ARVs  increasing metabolic syndrome). It is a  prohormone that in the overweight improves the  function of the vital hormone insulin,  if started preventively before diabetes and obesity develop, largely preventing  obesity and  metabolic syndrome MBS, and thus  more than  halves the incidence and mortality of diabetes and it’s fellow scourges: vascular disease, cancer, infection, arthritis etc.  It has also been shown to be a prohormone in lowering TSH without affecting thyroid hormone levels, thus further reducing the tendency to obesity- related high SHBG in women with PCOS. Metformin, like lithium and reserpine,  is thus  bad news indeed for the Disease and Undertaking industries, to be blocked and replaced by new designer drugs  at any cost.

Insulin by contrast cannot be swallowed, and works well  and extends life long term only in DM1.  The longest (20year – mean 13.6yrs – from 1978 to 1998) drug trial ever – on metformin and sulphonylureas,  the UKPDS,  has just had  the 10year follow-on  published.But  Chakrabarti and Fearnley in UK already in 1965 described the fibrinolytic effect of metformin in coronary artery disease- and  the USA chose to obstruct  obstruct metformin  till 1995.

So while DM1 was conquered in Canada, it was  in the British Isles that DM2 was first delineated (Himsworth 1936), and metformin isolated(1922)  and  established for coronary artery disease (1965) and  and uniquely validated  for DM2 and lipidemia and all-cause mortality  protection (1978-2008 – Holman ea).

But  the trials confirming metformin’s unique role in improving function and outcomes in PCOS and infertility(Glueck ea), and in reversing peripubertal obesity- growth delay- DM2 (Freemark ea) ,  and the delineation of PCOS (Stein & Levinthal, Chicago 1935)  were mostly done in USA;

and the landmark Diabetes Prevention Program  DPP trials in  primary prevention in the overweight,  showing that metformin  can more than halve  the incidence of new diabetes,  were carried out the past  decade  in China (Wenying ea 2001), USA (Knowler ea 2002)  and  India (Ramachandran 2006)  if built up slowly from low dose (eg 125mg/day up to tolerance – a mean of about 2.7gm/d in caucasoids.

METANALYSIS of metformin effect on CRP C reactive protein: if one counts just abstracts and full papers on metformin and CRP reported on Medline and the internet, a study this month from Univ College London is at least the 14th prospective study. These  studies-  from   USA(4), UK(2),  Saudi ArabiaFinland,   GreeceBosniaItalyBrazil, Mexico and   Israel, looked at metformin’s effect on inflammation – CRP,   between 2002-  and now -the paper by Chu,  Reaven ea at Univ Calif San Diego;   in +- 4000 subjects (20 to 3234); 6 studies with diabetes mellitus DM2; 5 studies with PCOS polycystic ovary syndrome, and 3 in metabolic syndrome MBS. These papers – including 4 RCTs-  exclude those which looked futilely at burnt-out – advanced- resistant DM2 ie in those who refused to comply and reduce obesity.

This metanalysis confirms that metformin in effective dose (they tested between 850-2000mg/day for 1 to 12 months)- not even   titrated to tolerance –  reduces  inflammation (reactive oxygen species,  VLDL ,  raised white cell count, fibrinogen and CReactive Protein CRP); which partly explains why it is the only drug ever discovered which lowers both appetite, overweight, abdominal girth, hypertension,  leptin, insulin resistance; hot flashes (due to everyday insulin resistance); cancer,  hepatitis, fatty liver, blindness,  kidney failure, neuropathy, gout, infectivity, CVD, stroke, arrhythmia, heart-attack, heart failure, dementia; and halves both CVD and non-CVD mortality and new diabetes;  while promoting nitric oxide, HDL, fertility, successful pregnancy, normal infants and childhood growth.

It is the only drug ever tested in an RCT lasting 20years; and the only drug that in numerous RCTs has never shown a serious unpredictable adverse effect let alone related fatality.

But ignoring overweight, hypertension and PCOS, waiting till obesity let alone diabetes mellitus DM2 develops before starting metformin is negligence, since DM2  already increases risk of the many complications and death fourfold; and waiting till DM2 is severe before reversing weight gain with metformin, now   requiring hypoglycemic drugs, is a criminal, terrible risk of heart, brain, kidney, limb and eye failure and premature death.

Titrated from low starter dose to tolerance – ideally with blood metformin level monitoring like many other chronic drugs – with sensible diet and without hypoglycemic drugs- metformin has no serious adverse effects ie risks. Tendency to diarrhoea and raised homocysteine can easily be prevented by  both sensible dose titration and some supplement of calcium carbonate, folic acid B12 and B6- which should anyway be taken regularly as part of multisupplement for prevention of the whole group of interrelated chronic major degenerative diseases of aging .

Since it is eliminated exclusively by the kidneys, the absolute contraindications to metformin are temporary and obvious on simple observation – oligoanuria and/or acidosis (unexplained rapid breathing/ hyperventilation); and it should be stopped for a few days around xray contrast media injections..   As with any other drug, it should be briefly reduced to low dose (and if no rapid improvement, stopped) and the doctor consulted if new symptoms eg nausea, bloating, abdominal pain, faintness, confusion, unstable urinary output, rapid breathing  or diarrhoea develop; and the dose re-titrated more cautiously to tolerance.

Strangely, a Statement by the American Heart Association and the NHLBI on Diagnosis and Therapy of the Metabolic Syndrome as recently as 2005  negligently failed to mention metformin as the only agent that safely and effectively lowers all inflammatory markers and risks – despite three crucial  abstracts/papers already Medline-listed by 2003.

But given the universal availability of Medline, clinicians  are bound first by their primary duty  to practice evidence-based medicine that matters to patients. They cannot hide behind the ignorance, regulations, omissions and smokescreens of Big Pharma, regulators- bureaucrats;  and especially  academics who are heavily influenced by  conflicts of  vested interests.

$Billions are  spent futilely  by Big Pharma  to invent and dishonestly register and  market risky raincheck  designer chronic  drugs that attempt without success to give  the crucial healthspan-prolonging multisystemic benefits of metformin (and fish oil, and appropriate vigorous supplements- vitamins, minerals and human biologicals like CoQ10 and  non-oral sexhormone replacement), – including sulphonylureas, glitazones, gliptins, statins, fibrates, oral xenohormones, appetite suppressants NSAIDS and antithrombotics, ACEIs and ARBs.

Statins for example – which now gross perhaps $20billion a year in sales-  have just  been shown in a UK  1991-2006 analysis (compared to controls) to increase   myopathy/myalgia by 10fold at 3 months, 20fold by 6 months and 27-fold at 1 year; with 10year incidence of about 0.7%.  This compares with the 10year risk of hospitalized  rhabdomyolysis in USA patients on modern statins of  0,044%.

But a 2007 analysis from Boston of the 23 large statin RCTs in 300 000 patient years  showed inverse relation between LDL lowering and cancer – and in the  recent Hong Kong study (Yang, Chan ea 2008), the cancer and death  rates rose progressively when LDLC levels fell   below a mean of 3.28mmol/L, while in the 2008 Baltimore statin meta-analysis in people from 60yrs upwards, cancer increased by 6% on statin.

Few of these   wannabe new drugs are subjected to even 2 years of RCT, let alone the 20year RCT of metformin, before being launched on the innocent casualties, the public,  by Big Pharma’s  for-profit-at-any-cost War against Humanity.

Everything in life is potentially dangerous in excess, from food to love to oxygen to water; but common sense- experience- soon teaches safe doses. There is a criminal, hypocritical   regulatory obsession  that insists that metformin must be reserved only for PCOS and DM2 but is too dangerous to prescribe to prevent increasing overweight and disease – when it is the most-proven and safest modern drug for prevention of overweight and obesity that fuels the chronic major degenerative diseases.

A recent innovative study from  the Hatter CVD Institute at University College London shows that metformin almost halves myocardial infarction size in both normal and diabetic rats. So why is it’s use so restricted, when cigarettes, the statins and NSAIDs- with multiple serious adverse effects- are allowed over-the-counter?

Metformin seems to be the only drug which addresses all organ systems that appear to be involved in the primary pathophysiology of DM2 -metabolic defects in liver and in peripheral target tissues, such as fat and muscle and pancreatic β cells.

One need look no further than the overwhelming profit motive   that drives  the $trillion disease  industry to prefer diseases that pay to effective prevention which would more than halve the need for common drugs and acute care,   that avoids banning  the sale of eg cigarettes  and   sugar, and avoids mandatory immediate long jail term and confiscation both  of driver’s license and vehicle  and gun license for drunken driving especially with a weapon.

This paradox is especially obvious in the most violent warmongering “civilized” country in the world this decade under the Bush Gang- the USA – that confiscates even houses of those who grow proven medicinal cannabis for personal use, when cannabis has been long proven to have perhaps one thousandth of the toxicity of sugar or  cigaretes,  and a fraction of the risks of alcohol overuse .

This is the self-styled 1st-world  country that leads the world – especially   it’s parent Europe-  in trying to suppress  natural proven nutritional supplements – eg the (pro)hormones  metformin and non-oral human estrogen, testosterone and progesterone, which  work against  the causes  and mortality of common degenerative disease.

They do  this so as to favour their own costly but risky and inferior  chronic designer drugs and acute disease industry that rarely help  resolve the chronic major aging diseases. .  As usual, they promote diseases  that pay,  while preaching the opposite.

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

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

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

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

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

INTRODUCTION: EBM:

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

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

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

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

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

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

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

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

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

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

1.1 Hypercholesterolemia and statins

1.2 Osteoporosis and Bisphosphonates

1.3 Hypertension and antihypertensives

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

1.5 Pain, arthritis and NSAIDs.

1.6 Fish Oil

1.7 MULTIPLE DESIGNER DRUG INTERACTIONS

PART 2: SEX HORMONES see next publication.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SLIMMING DRUGS CANCELLED.

Evidence-based  reviews hereunder   have  warned since April ie for 6 months of the obvious  fraud of  modern touted designer appetite-weight suppressants (which among other adverse effects often cause depression if not suicide)
.
The Sanofi-Aventis drug  rimonabant was turned down in USA in Feb 2006,  June 2007 and again April 2008, based on lack of efficacy and safety.
 
The question remains: why prescribe new designer drugs  especially for overweight and type 2 diabetes with diet-resistant overweight, without a long trial record of both safety and efficacy,
when metformin and it’s parent herb galega officinalis  titrated simply to tolerance has been the proven gold standard for centuries,  losing on average 6% of weight (up to 20kg in 2yrs) and halving the incidence of new diabetes, while  in diabetics it almost halves the death rate and most major chronic degenerative  diseases of aging.
 
Based on the clear published evidence  (of risk, and lack of long term benefit from rimonabant, and abundant evidence of the superiority of metformin)  on which rimonabant was never  licenced in USA ,  patients who were prescribed rimonabant in 2008 have a prima facie case for damages against both European Regulators, the NHS  and doctors there who prescribed it.
 
and this month, for similar reasons, the Merck clone taranabant crashes out. 
 

The for-profit Disease Industry and the  researchers and Regulators they pay will  never stop trying to promote the profitable new over the proven  cheap old. So it’s up to consumers- the public- to seek out the evidence for themselves.

 Fenfluramine / Phen-Fen/ Ponderax crashed a decade ago after lethal complications  .

Orlistat (foul faecal problems) and  sibutramine(hypertension, nausea/vomiting, palpitation, and sweating) have major potential adverse effects, and do not do as well as metformin for longterm reduction in all-cause mortality and major adverse outcomes.

now   Anti-obesity drug use suspended 23 Oct 2008 
The European Medicines Agency  is recommending doctors do not prescribe the anti-obesity drug rimonabant, also known as Acomplia – it says the risk of serious psychiatric problems and even suicide are too high.

 

Why accept  risky mediocre  new drugs  (sibutramine, orlistat) or risky bariatric surgery (40% complications in first 6 months) when only metformin simply adjusted to tolerance  has been shown for decades to reduce all-cause mortality by at least 1/3 to 1/2, and even reduce cancer incidence.

 Tesofensine  seems similar to sibutramine in it’s potential to increase bloodpressure, dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia. But the longest trial so far seems to be only  24 weeks.

 

Most importantly, it is medical negligence to wait for frank obesity,  instead of early prescribing metformin to tolerance  to prevent progression from mild overweight  to obesity, diabetes, vascular disease, depression and cancer.

THE HEAVYWEIGHT OLYMPICS: METFORMIN WINS GOLD. RIMONABANT-Acomplia DISQUALIFIES ITSELF.

The latest Rimonabant  reports  from USA and UK confirm that there is no place for it for overweight : Rimonabant  produces the same average weight loss as metformin (about 6kg/yr, 0.5kg/month more than placebo) but no study yet shows  that it has the safe benefits of metformin adjusted to tolerated dose (average 2gm/day in Caucasians): halving of new diabetes rates, halving of all deaths and almost halving major common degenerative diseases of aging.
Contrary to the lying blatant adverts promoting it below (still on the internet)  in this  latest  (SERENADE)  trial, serious diverse events  were up to 10fold  more frequent with rimonabant versus placebo: dropout 19.6 vs 10.7%; discontinuation 9.4 vs 2.1%; adverse psychiatric psychiatric event 5.1 vs 0%;  dizziness (10.9% vs. 2.1%), nausea (8.7% vs. 3.6%), anxiety (5.8% vs. 3.6%), depressed mood (5.8% vs. 0.7%), asthenia 3.6 vs 0.7% and paresthesia (2.9% vs.1.4%).    This contrasts with the 80year old plant extract metformin which – in dose simply adjusted to tolerance- has never been shown in dozens of trial for up to 20 years to have any serious adverse effects.  
 
 So like acarbose, there is no long term evidence that rimonabant is any competition for metformin for either obesity weight loss or type 2 diabetes.
The FDA has for these good reasons  (and no doubt also the fact that it is not a USA- but Italian- developed drug), . declined to licence rimonabant in USA.   In UK ie Europe , where it was not surprisingly  first registered and  – without evidence of longterm safety and benefit as has been so well established for metformin –  is most heavily ie indefensibly used instead of metformin, there have been already 5 associated deaths and 720 adverse reaction reports.  After the endless problems with amphetamines, fenfluramine, glitazones and gliptins, prescribers should be prosecuted for believing implausible advertisements for a new drug instead of staying with the proven metformin. It is firmly established that prescribers and dispensers  (not snakeoil marketeers or bureaucratic regulators) are responsible for their choice and issuing of  appropriate prescription drugs. Thats what doctors and pharmacists undergo arduous training and  onerous registration for.  .
Rimonabant’s  intended mechanism- blockade of cannabinoid receptors- naturally gives it the opposite action to cannabis- ie it causes depression  and dizziness in about 10%;  nausea, anxiety;   and  is  potentially epileptogenic,  and theoretically predisposes to other neurodegenerative diseases as well as hypertension, heart disease, stroke, pain  and cancer.
 Thus rimonabant  perhaps lessens  obesity longterm  , arthritis  and diabetes   (there is as yet no evidence for this) but  shows no prospect of benefit on all-cause morbidity and mortality. 
It’s like statins for mild-moderate hypercholesterolemia, acarbose  for obesity/diabetes, or  kava/black cohosh for menopause symptoms: why prescribe drugs that can cause acute hepatitis or worse when there are safer and more effective longterm preventatives?
 
refs:
“June 4, 2008 ” Acomplia linked to deaths in the U.K.;  While the FDA has been slammed by some drugmakers for its too-conservative approach to drug approval, it may have made the right move with Acomplia. But recent findings by the U.K.’s drug regulator show Sanofi’s weight-loss drug has been linked to five deaths and 720 adverse reactions since the company launched it in Britain two years ago.” http://bcbsma.medscape.com/viewarticle/575640
July 2007 http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON2031809 The European Medicines Agency has recommended that Acomplia (rimonabant), a medicine for the treatment of obesity, must not be used by patients with major depression or those being treated with antidepressants, because of the risk of psychiatric side effects.Questions and answers    How many people have been treated with Acomplia?
Acomplia was granted marketing authorisation in the EU in June 2006.  Currently, rimonabant has been launched in 19 countries, including 13 European countries.  Up to the end of May 2007, it is estimated that about 240,000 patients have been treated with Acomplia worldwide.  Approximately 41,000 patients have been treated with Acomplia in the United Kingdom.
How many people treated with Acomplia might develop psychiatric side effects?
The evidence suggests that one in ten people who take Acomplia may develop psychiatric side effects.  The commonest psychiatric side effects are low mood and depression.  Anxiety, irritability, nervousness and sleep disorders may also occur commonly.  Approximately one patient in every hundred may experience suicidal thoughts.Up to the end of June 2007, the MHRA had received a total of 318 cases, from UK sources, of adverse drug reactions which were suspected to have been caused by Acomplia.  The total number of adverse reactions reported in these cases was 921 because some reports described more than one adverse reaction.  Three hundred and sixty-four (364) psychiatric reactions have been reported.  Amongst these, there have been 48 reports of depression, 16 reports of suicidal thoughts and one report of self-injury.
 
Nonclinical Overview: CNS Toxicity with Rimonabant        CNS Toxicity. Rimonabant blockade of CB1 receptors appears to influence the anti-convulsant tone of ECS; Rimonabant induced http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4306s1-09-FDA-Bruno.ppt
 
Continuing on the theme of unexpected toxicity landmines, I wanted to take a look at a highly anticipated obesity drug from Sanofi. Rimonabant is a small
pipeline.corante.com/archives/2004/07/20/worries_about_rimonabant.php – 55k –
 

From Wikipedia, the free encyclopedia 19/8/2008

Rimonabant (also known as SR141716, Acomplia,  is an anorectic anti-obesity drug. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite.

Side effects Shortly after market introduction, press reports and independent studies suggest that side effects occur stronger and more commonly than shown by the manufacturer in their clinical studies. Reports of severe depression are frequent. This is deemed to result from the drug being active in the central nervous system, an area of human physiology so complex that the effects of a drug are extremely difficult to predict or anticipate.[5]

Because the drug has the opposite effects of cannabinoid receptor agonists such as tetrahydrocannabinol (THC, one of the substances found in marijuana), which is neuroprotective against excitotoxicity,[6] it can be theorized that Rimonabant promotes the development of neurodegenerative diseases of the central nervous system such as Multiple sclerosis, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Huntington’s disease in persons who are susceptible.[7] The reported development of previously clinically silent multiple sclerosis in one patient taking Rimonabant suggests that any patients with an underlying neurological condition should not take Rimonabant, given the neuroprotective role of the endocannabinoid system in many experimental paradigms of neurological disease.

In June 2007[8]  the US FDA  voted not to recommend the drug’s approval because of concerns over suicidality, depression and other related side effects associated with use of the drug.

The risk benefit ratio on the usage of Rimonabant is not yet established. 

 

 

Rimonabant and the FDA    By Richard N. Fogoros, M.D., http://heartdisease.about.com/b/2008/04/02/rimonabant-and-the-fda.htm April 2, 2008

Rimonabant, the long-awaited weight-loss and smoking-cessation drug that is available in most Western countries except the U.S., took another blow this week at the American College of Cardiology Scientific Sessions in Chicago, where the results of the STRADIVARIUS trial were presented. In this trial, obese patients randomized to receive rimonabant lost significantly more weight and more inches from their waists than patients on placebo, and in addition they had significantly improved HDL, triglyceride, and CRP levels. But unfortunately, the volume of their atherosclerotic plaques (the primary endpoint of the study) was not significantly improved over the placebo group. Furthermore, patients on rimonabant had a significantly higher incidence of psychiatric effects, mainly depression and suicidal ideation. This study may prove to be the final nail in the coffin for rimonabant in the U.S. American doctors and patients who have been anxious for the approval of rimonabant, and who may wonder why the FDA would refrain from approving a drug that significantly improves weight loss, smoking cessation, and lipid and inflammation profiles, should read this article on rimonabant and the FDA.

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