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

It takes no rocket science to see how increasing fatness parallels increase in all common degenerative diseases, from diabetes to high blood pressure to heart, circulatory, brain, arthritic – inflammatory, depressive, memory, vision  and cancer (Barclay 2008; Hjartåker 2008 )  problems.  Major earlier studies in  eg the Netherlands, USA and UK confirmed this statistically.

 

Similarly, the century-old knowledge that diabetics are more prone to cancer has been confirmed in several countries (Czyzyk  2000), including endometrium, breast, bladder, liver, kidney,  prostate, pancreas and colon.

 

A  Hong Kong study (Yang ea 2008) registered and followed up new diabetics from 1995; showing after a mean of 4.9yrs that from the age of 35yrs on,  compared to nondiabetic controls, standardized cancer incidence in male diabetics  at 0.93% was 36% higher, and   in diabetic women at 0.62% was 27% higher – ie diabetes in  even the mildly average overweight (mean BMI 25 instead of the optimal 21-22kg/sqm)  increases cancer risk by about a third.

 

But more important, what can doctors do to reduce this increasing co-morbidity?

 

Only dictatorships – prisons, not doctors -  can compel  patients to eat, drink, exercise sensibly and not smoke. But for the disaster capitalists that now dominate the world, vice and disease pay too well. So the Disease Industry tries progressively to suppress nutritious natural preventative and curative supplements while promoting sloth,  gluttony and  nonprescription sales of the biggest killers eg sugar, tobacco,  alcohol, and noncurative designer drugs eg non-steroidal anti-inflammatories and statins.

 

STATINS increase inflammation in muscle and liver,  show   no independent  benefit in lowering C-reactive protein CRP , and  no benefit against cancer:

In the 2001 Texas Lovastatin trial  in 6600 well older people, there was no reduction in all-cause mortality, but  statin associated with 41% more cancer deaths;

in the 2002 PROSPER pravastatin  trial in 8800 well people 70-82yrs old, new cancers were 25% higher  on statin than on placebo;  

in the 2005 Oxford CTT metaanalysis  in 90 000 people, statins did not lower the incidence of cancer in  14 statin trials; but in the older –

in the 2008 Baltimore metaanalysis in  51 300 adults  from 60years up, statins associated with 6% more cancer.

 

METFORMIN STUDIES  since 1922  have shown increasing evidence that metformin not only  about halves the incidence of new diabetes and of deaths in diabetics,

it also significantly reduces CRP , reduces the risks of  osteoporosis fractures (Vestergaard 2008; Kanazawa 2008); and cancer in rodent and human cell lines, and

in the UKPDS (1998) after about 13yrs associated with about 1/3 less  all-cause and  cancer  deaths;

in the Dundee Tayside (Evans 2005) diabetic  study metformin,  associated with up to  40% less cancer in those on  the longest. and highest metformin  consumption,

in the Canadian (Bowker 2006) diabetic  study  metformin associated with half the mortality and  30%% less cancer than on other  antidiabetics. .

 

The Hong Kong 2008  study confirmed the well-known U shaped curve relationship between serum cholesterol, cancer and death,  in fact a V relationship with LDL cholesterol, with the lowest cancer  and death rate at  an LDLC of about 3.28mmol/- the risk rising linearly with LDLC below 2.8  or above 3.8mmol/L.

 

Statins lower LDL cholesterol and cardiovascular disease /mortality but not  adiposity, insulin resistance, diabetes, fractures, cancer, depression  or non-vascular  morbidity-mortality.

Metformin about halves  new diabetes, lowers obesity, insulin resistance,  lipidemia, reproductive problems, ischaemic heart disease   and in diabetics lowers both vascular and cancer events and mortality.

 

So it is insulin sensitizers (metformin or a non-prescription mix of a score of natural ones including fish oil ), not statins or nonsteroidal anti-inflammatories that must be promoted over-the-counter to combat the pandemic of overweight- reproductive- diabetes- vascular- malignant and arthritic-immune diseases that is  progressively curtailing by decades  the healthspan of the haves.

 

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com ..

  

WHY PRESCRIBE OR TAKE FORTEO- TERIPARATIDE FOR OSTEOPOROSIS?

question: how can I afford Forteo?

Answer: why on earth prescribe or use  a synthetic like Forteo? with all it’s risks eg  see http://www.umm.edu/altmed/drugs/teriparatide-121950.htm; and   http://www.drugs.com/forteo.html :
“What is the most important information I should know about Forteo?
This medication has been found to cause an increased risk of bone cancer in animal studies. It is not known if this risk is also increased in humans treated with Forteo. Talk with your doctor about your individual risk.Forteo can cause side effects that may impair your thinking or reactions. “

So  Insurance is right not to pay for it- all it benefits is the manufacturer, prescriber and dispenser. There do not seem to be any published followup data for Forteo beyond 3 years- not surprising since it involves daily injection at gigantic cost, and was only invented in 2002.  Look at the lesson of bisphosphonates- increasing reports of bone (jaw, long bone) collapse since 1995.

Remember- the chief risk factor  for fractures with osteoporosis is not low bone density but falls- inco-ordination and muscle frailty. So rather use permanently the basket of  safe lowcost natural dozen anabolic supplements  (including vitamins, minerals, proline and appropriate HRT) that protect ALL aging  systems, detailed in previous papers under  http://healthspanlife.wordpress.com/category/osteoporosis/

POLL AMONG WOMEN AND HEALTH PROFESSIONALS ON APPROPRIATE HRT

Let’s hear from women  and doctors on

WHY NOT USE PERMANENTLY BENEFICIAL  POSTMENOPAUSAL HORMONE REPLACEMENT  HRT THAT AVOIDS PERIODS AND BREAST TENDERNESS? (see the preceding paper hereunder).

naturally, for perspective in the poll analysis,  women taking part in this poll should supply their age, profession, and age since menopause.  

Health workers should indicate their profession, age bracket and gender.

   to vote, click on comments

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com ..

WHY NOT USE BENEFICIAL POSTMENOPAUSAL HORMONE REPLACEMENT HRT THAT AVOIDS PERIODS AND BREAST TENDERNESS?

The new paper  this week from the WISDOM trial (stopped prematurely  in Oct 2002 as a result of the  precipitous closure of the main premarin-provera prempro arm of the Women’s Health Initiative WHI) concludes that  Combined HT  (ie oral prempro) started many years after the menopause can improve health related quality of life. 

 

 This  trial  in UK, Australia and NZ  was identical to the 2002  (USA) cohort of the WHI – women mean age  about 63.5yrs with uterus,  treated with the xenohormones  prempro  or placebo, BMI mean about 28.3 kg -    except that in the WHI the age range was    50-79yrs ( 45% 60-69yrs; 21.5% were 70yrs plus) versus in WISDOM. age  50 to 69yrs  (74% 60yrs +).

 

As opposed to physiological doses of parenteral human  estrogen-progesterone HRT, apart from the obvious known risks of oral xenohormones – increased fluid retention, gallstones, breast cancer, adiposity, hepatic first pass inflammatory effect -   one striking practical  question arising from these trials is, why would  postmenopausal women- let alone women a mean of about 15 years postmenopausal – want to take hormone therapy causing breast discomfort and menstruation, and known for 30 years to promote latent breast cancer? Surely only men could  so trivialize the needs of women?

 

    In WISDOM, 32% discontinued for this reason (menstruation); and such OHT gave  no relief from tiredness, depression, headache, irritability or migraine, but greatly increased arrhythmia; leukorrhoea,   and breast tenderness (13% who discontinued). These figures were matched in the WHI after a mean of 5.2 yrs, when 40% of women reportedly had to see a gynecologist due to  problem vaginal bleeding on prempro  vs 6% on placebo.

 

The benefits of  OHT for up to 10 years (Nurses study; WHI; Oulu trial (Heikkinen ea 2006) and especially permanent conservative balanced  HRT (testosterone and thus estrogen for men, for women  testosterone-estrogen-progesterone replacement) till past 90years has been overwhelmingly  proven in long term clinics world wide (eg Greenblatt; Schleyer-Saunders; Gelfand; Whitehead & Studd; Burger & Davis; Vliet; Shippen;  Nieschlag & Behre; Carruthers, Kauffman) – all of whom have observed reduction in premature degenerative diseases in their attending patients .

 

       It is common cause that  even appropriate OHT- started soon after menopause- reduces all-cause major illness and mortality by one-third, even after breast cancer. By avoiding OHT, one  may reduce the incidence of breast cancer; but only about 4% of women die of breast cancer – it rarely cripples; more than half of such  women thus suffer and die prematurely from other hormone-deficiency diseases like vascular, dementing  and  osteoporotic problems, which are halved by  appropriate HRT. 

The question  is, where is the logic of commercial marketed HT that forces the postmenopausal endometrium and ductal breasts to go on proliferating cyclically? One would have thought  that doctors and women learnt their lesson by 1980  with the increase in endometrial and breast cancer on long term unopposed oral estrogen therapy – mostly premarin in USA. Physiological testosterone replacement in men does not do this to the prostate, nor to the breasts or other organs in women. .

The published trials show that unopposed transdermal estradiol gave much lower rates of endometrial bleeding than OET- but seldom none at all.. 

And recently Horwitz and Sartorius  showed that even progesterone combined with estradiol  can be the trigger of latent breast cancer. .

 

Yet Medline reports  plainly that William Masters and  peers had firmly recorded by the time they reported the first randomized controlled HRT trial in 1953 that parenteral (intramuscular)  testosterone TT- estradiol E2 abolished endometrial and breast problems in even older, institutionalized  women (about 20 years post menopausal)- with nothing but benefits for the majority  of the women (remarkably only one-third failed to improve). They determined by trial and error that the optimal ratio was 20:1  TT:E2 – and they persevered for a mean of 13 months with a dose of TT 20mg plus 1mg E2 esters  twice a week (ie averaging about 2.8mg TT and 0.4mg E2 a day) .

       We have followed their regime for about a decade, but using a physiological approach with only 20mg TT ester and 1mg E2 ester subcutaneously every +-  fortnight  ie about 1mg TT and 0.05mg E2 a day. W rarely have to vary this ratio or dose in young women, whereas elderly women tolerate far less, complaining of breast and pelvic  tenderness  on the youthful dose. So for those who eschew the tiny injections and can afford cream, we use a combination of about 0.125% estrogen (80% E3, 20% E2) with 1% testosterone and 0.75% progesterone for young women, and about 1/8th that strength for the elderly. We

 let women  titrate the dose to symptom and bone  improvement without unwanted symptoms. With such combination in conservative balanced doses, we find that women have no more periods, and their endometrium and breasts  remain quiescent  on followup ultrasound and mammography respectively. .

 

 Recently the Karolinska Institute (Zang et al)  has  confirmed that combining testosterone with estradiol reduced the proliferative effect of estrogen on the endometrium- but they ignored Masters’ and Grody’s papers of 1953, the Karlinska trial used vigorous doses of oral HT in a too-low ratio of TT 10: E2 1.

 

And a separate paper  (Hofling et al) from the Karolinska  also confirms the findings of Zhou and Dimitrikakis, and Thomas Clarkson’s team at Wake Forrest,  that testosterone suppresses breast proliferation in humans, rats and monkeys.

        It is common cause that the healthy young woman has an average serum TT:E2 ratio of about 4:1 (mean sTT about 1.5-2nmol/L, mean sE2 about 0.4-0.5nmol/L)- compared to in healthy lean young  men , sTT about 25-30nmol/L, sE2 about 0.1nmol/L ie >270:1- men being relatively resistant to testosterone. .

 

     .Exogenous unopposed estrogen promotes adiposity, thrombosis, arrhythmia, autoimmunity, inflammation  cellular proliferation, and profound vaginal collagen loss (hence doubling that rate of stress urinary incontinence) -  but  has no demonstrated benefit ie anabolic effect on mood or muscle (except the uterus) – ie the opposite effects of TT.

So  it defies logic why normally mildly testosterone-dominant young women are sentenced by most doctors- at the dictate of drug companies marketing their profitable horsepills -   to have their necessary androgen levels (both ovarian and adrenal) either naturally depleted by age and surgery, or worse, further suppressed by HT (without balancing TT), as in the case of the combined OC pill, depotprogestin injections, or postmenopausal estrogenic herbs, or estrogen +- progestin therapy- especially in 20 times higher doses widely prescribed  OHT  than are necessary parenterally. . .

        Appropriate patenteral HRT (esters of TT:E2 20mg:E2 1mg, or just TT 200mg for men) fortnightly by tiny subcutaneous self-injection need cost no more than R40 or US$5/month .  In the absense of lowdose progesterone in the injection, adding lowdose progesterone cream quadruples the cost.

IS THE BBC ONE MINUTE HEALTH NEWS BAD FOR HEALTH? RECOMMENDING ASPIRIN RATHER THAN FISH OIL?

 Has the BBC Health Bite 23/08/08  done it again?   -  perhaps putting vulnerable people at risk  – by recommending aspirin  from middle age for primary prevention based on  a local retrospective  observational study in only 12000 people;

 

when  the latest  (2006, 2006)  metaanalyses of the six major aspirin  primary prevention trials  in over 90 000 subjects  showed  no significant benefit on all cause mortality, or stroke,  or cardiovascular mortality;  and  BBC  fails to mention the real aspirin problems –  that 28% may be aspirin resistant, or the legion problems that can be caused by even low dose aspirin, which offset it’s trivial cost. .

 

This contrasts with the latest metaanalysis of fish oil prevention, from Tufts in Boston 2006   which concludes that “consumption of  n–3 FAs from fish and fish-oil supplements reduces all-cause mortality, cardiac and sudden death, and stroke”- without any noteworthy linked adverse events… not to mention major benefit on behaviour, learning/ memory, arthritis, depression, eyes, skin, and  reduction in obesity-diabetes- insulin resistance.

         And recommending aspirin without including the dozens of multibenefit evidence-based  preventative supplements – many of which can mitigate the risks of aspirin- is surely more risky – especially in a high- alcohol-intake nation?

    The low  benefit:risk ratio of aspirin applies also to warfarin. 

Thrombolytics, heparin and then  warfarin may be indispensible after highrisk thromboses, but it has yet to be proven that  for chronic prevention those high-risk therapies which require regular laboratory monitoring are as safe let alone as good as fish oil and oral EDTA.

 Warfarin has far more risks (than aspirin) -apart from bleeding there is - as a result of vitamin K antagonism –  vascular calcinosis, osteoporosis and malignancy.

       So in view of the risks, and the scant benefits, of longterm aspirin and warfarin, if any trial is needed it is one to disprove the obvious,  that combining fish oil with EDTA gives far higher benefit :isk long term than warfarin and/or aspirin.

See the HRT  and supplement papers  above and  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com ..

FOR DEBATE: ESTRIOL E3 AS PART OF OPTIMAL HRT

The FDA in January issued a circular   warning about false claims for estriol and other BioIdentical Hormone Therapy, citing a citizen petition by Wyeth. 
The FDA has been criticised for “banning” estriol, but it sets the record straight on it’s website.

  However, FDA concedes that it has never received any aderse effect reports about estriol – merely the gripes from the Drug Industry about competition..
In the recent scientific literature  ie Medline, there are no serious adverse events or side-effects reported in the 8 trials of Estriol listed. Nor any case reports of SAEs related to estriol use.

Olivia A.M. Franks, ND and Jonathan V. Wright, MD,  Life Extension Scientific Advisory Board Member   Magazine August 2008 review :  Estriol: Its Weakness is Its Strength
Estriol, an estrogen that has virtually been ignored by the mainstream medical community, is one of the three principal estrogens produced by the body. Estriol was originally thought to have little significance due to its weak estrogenic activity when compared with estrone and estradiol. Nonetheless, research has found that its weakness may very well be its strength…  read on

FOR OPTIMAL AGING IN MEN AND WOMEN: APPROPRIATE NATURAL SUPPLEMENTS INCLUDE HUMAN HRT:

 ie  

melatonin -  essential unless you get plenty of sleep and sunlight;

 

insulin sensitizers including Vitamin D,  fish oil  if the slightest overfat,

even before diabetes develops;     

          plus  balanced

*thyroid+cortisone+estrogen +progesterone+teststerone

if their measured levels are not optimal. *these  require medical supervision.

 

 

Remember that the aging ie postmenopausal woman

who still cares about her  looks

should use estrogen-progesterone  cream on the face,  but

for best (ie cheapest) absorption- and optimal mood, bone and pelvic floor protection

use the testosterone  cream  internally.

(or for lowest cost- use   progesterone cream  on  the face.

plus  testosterone + estradiol by tiny injection ~ fortnightly),

.

In both genders,

like balanced estrogen plus  testosterone,

solo progesterone  protects the

skin, hair, heart, breasts, mood, brain, thyroid,  bladder, immunity  and circulation,

but not   strength, bones or hearing –

 

only the  right  balance of estrogen  and testosterone  does so.

 

Remember- there is no upper age limit on appropriate supplements –

the key to health is -  we don’t stop eating because we age!

We  may need less food, but we need more natural micronutrient supplements including human hormones to make up for their  increasing (relative) deficiency  in our food chain and our own  metabolic reserves, as well as to  counter  increasing pollution and the demands of increasing  longevity.. 

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com ..

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 …www.fda.gov/ohrms/dockets/ac/07/slides/2007-4306s1-09-FDA-Bruno.ppt   Worries about Rimonabant?. In the Pipeline: 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.

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com

                     

A UNIFYING HYPOTHESIS: THE END OF MUSCULOSKELETAL (OSTEOPOROSIS- ARTHRITIS) CRIPPLEDOM

  “Musculoskeletal disability is the most prevalent of the major health problems of our aging population.  Rheumatoid arthritis and osteoarthritis, compared with other chronic diseases, appear to make the greatest contribution to subsequent disability among the elderly.  Disease outcomes evolve over years, even decades” (ARAMIS -the national chronic disease data bank Arthritis, Rheumatism, and Aging Medical Information  System from  diverse U.S. / Canadian  locations, managed by  Stanford University Department of Medicine, California, 2003 ):

 Thus (major trauma aside)  it is a huge relief that  in aging adults, both osteoporosis spinal/limb collapse, and rheumatoid and  osteo-arthritis   can now be reversed in most cases by early  amd probably permanent  prevention and treatment with relatively lowcost and safe combination of   multiple  proven drugs, most of them natural and nutritional supplements. 

It is obvious from observation in daily practice that the nonspecific musculoarthritic stiffening of older people -including polymyalgia rheumatica-  is usually easily reversed by early replacement with antioxidants including fish oil  and  appropriate steroid   hormone replacement  HRT  according to bloodlevels – vitamin D3 and testosterone in both sexes,   plus estradiol-progesterone  in deficient women, +- lowdose prednisone.

Obviously, collapsing spine and hips incur increasing immobility  osteoarthritis and frailty;

increasing arthrits incurs increasing immobility  osteoporosis; and frailty;

and increasing vascular disease (including rheumatoid/ lupus arthritis) with worse microcirculation  incurs increasing ostoporosis, frailty  otheoarthritis, and tissue, cartilage, bone and disc ischemia.  .

But, just as gouty tophi melt away with alkalis, allopurinol and probenecid, it is gratifying to see how osteoarthritic nodules and pain gradually regress and functionality return over months,  with restoration of  youthful bone density and  articular cartilage on modest dose of anabolic glucosamine plus chondroitin, combined as always with  the safe natural anti-inflammatories and antiosteoporotic agents - the vitamins  nicotinamide, pantothenate,  pyridoxine, folic acid and B12, C, D, K; the minerals calcium magnesium boron zinc and manganese; and the biologicals  fish oil, proline, .MSM, cat’s claw, boswelia, bromelain, curcumin,  and appropriate anabolic  HRT including testosterone for both genders. 

Since daily practice is clear proof, it does not need sophisticated randomized controlled trials to prove the obvious, that

provided prevention is started before spine, bones and joints are seriously damaged,

*osteoporosis is  easily safely and cheaply preventible and curable;

*chondroglucosamine restores lost articular cartilage, as two controlled  trials (Belgium; Czech)  have shown .

And it does not take wild imagination that combining  early and permanently the above  anabolic bone-muscle- cartilage-restorative and anti-inflammatory supplements with remittive substances for inflammatory arthritis will permanently prevent disability.

So it is gratifying to find trials of both
* the benefit of chondroglucosamine on synovial retention in both humans and rats with inflammatory arthritis;  and
* The full  4 year   BeSt  (Dutch)  trial report of last month, that starting with methotrexte plus inflximab instead of methotrexte prednisone + sulfasalazine  makes negligible difference  to 4year outcome -  without the farcical costs  and potentially deadly adverse effects of infliximab. 
It is instructive that the BeSt paper did not give P  or confidence intervals in the abstract- and  the full paper confirmed  that the differences are not statistically significant.

 

The  BeSt paper confirms that-: starting with methotrexate in all cases,  adding one drug at a time for unresponsiveness gave much poorer result than combined therapy from the start. The  endresult after 4 years was much better if infliximab , OR prednisone + sulfasalazine, was started ab initio;. 

 BUT infliximab gave 13% neurological adverse events AEs vs 2% with preds; and more infectious deaths and more non-melanoma skin cancers with infliximab.
 In the end after 4 yrs, the overall risk:benefit in the respective groups favoured initial 

*initial mtx  + preds + SSA- 4yr totals of 4gm preds (174 pt yrs)  (and  with last resort where required) infliximab 39pt yrs;  over  
*initial mtx +  infliximab  -4yr totals  181pt yrs infliximab  and (as last resort)  0.6gm preds 28pt yrs preds .

Since preds costs about 3c/mg & the total high dose preds  averaged 1gm/yr , thats

 Prednisone about R30/yr; 

 Chloroquine about R750/patient year;

  Methotrexate perhaps R500/patient year;
  SSA around R 6000 /patient year. 

  infliximab about  R100 000/ patient year
so keeping infliximab as last resort rather than first makes major sense to both cost and survival.

   
David Gotlieb of the SA Arthritis group still recommends as primary therapy
“methotrexate -   hydroxychloroquine
 methotrexate -    Sulphasalazine
 Sulphasalazine – hydroxychloroquine
  methotrexate -    hydroxychloroquine – sulphasalazine.
 plus for Articular RA, my usual regimen is to start at 7.5mg per day and maintain this dose until the DMARDS take effect. This is usually at approximately 2 months. Ithen start a slow reduction – to 5mg per day for a further month to 2 months, and then 2.5mg per day. Further reduction then depends on progress. If possible, the dose is then reduced to 2.5mg alternate day, an subsequently to 2.5mg every third day.    Only then do I consider stopping the drug.
If at any step reduction, the patient becomes stiff or swollen, I maintain the previous level a further month before attempting a reduction again.
If a small maintenance dose is still required – it is almost invariably at 2.5 mg per day or less.”

The UK and USA guidelines do not recommend  early anti-TNF tumour necrosis  drugs like infliximab.   

Indomethacid has been reported to accelerate articular loss, whereas other anti-inflammatories do not slow the loss; while in one  2005 USA trial, doxycycline merely slowed the progression of OA joint narrowing by 30%.   

 

CONCLUSION:  all cases of arthitis  (and suspected fracture) should be seen early – within days- by a medical doctor; and osteoporosis risk also assessed; if only by ultrasound; 

if symptoms do not settle rapidly on symptomatic therapy (eg for gout, sexually transmitted disease)  and appropriate antimicrobials for possible micro-organism causes, and apprpriate HRT,

then appropriate baseline xrays and blood tests should be done, (including hormones, and  to exclude tuberculosis, STDs) ,

and appropriate anti-inflammatories and anabolics should be started:

modest initial symptom-controlling prednisone+chloroquine+ methotrexate -  R100pm.

+appropriate HRT(testosterone for all, + estradiol for women)  about               R40pm;

add       4gm cod liver oil /day                                                                    R20pm;  

+ modest natural  anti-arthritic antiosteoporotic agents  about                     R200pm

 

since the above supplements are also  protection against major vascular

depression, memory &  anti-infective problems,       a    total R360pm $50pm   provides wide multisystem protection. 

See the HRT  and supplement papers  below, and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to info@healthspanlife.com

THE HYSTERICAL BANNING OF APPROPRIATE HRT SEXHORMONE REPLACEMENT AFTER AGE 60YRS

question: What are the reasons given for forbidding HRT after age 60yrs.   S.

 

ANSWER:     Hysteria on the part of   self-proclaimed experts  who supported  the misguided plan of the Wyeth  premarin-provera Womens’s Health Initiative  WHI 13 years ago, then misinterpreted  and swallowed the patently wrong  results when they were examined in 2002-4 together with the largely meaningless Million Women Study MWS- both of which the International Menopause Society has consistently refuted.   http://www.imsociety.org/pdf_files/ims_recommendations/ims_updated_recommendations_on_postmenopausal_hormone_therapy_27_02_07.pdf?SESSID=qe5239k4hiqd662fqf0h1og6a2 

 

  In 2003 no less than the chairman of the German Commission on the Safety of Medicines Professor Bruno Muller-Oerlinghausen, reportedly described HRT as a “national and international tragedy after evidence emerged that it had caused thousands of deaths. More women have probably died from the … hormone therapy than damaged children were born in the wake of the thalidomide scandal.”   http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=214066. This was pure hysteria, there was no such evidence.

 

The N American Menopause Society (NAMS) has repeatedly since 2002   been urged  to  recant from the WHI -  and MWS-generated hysteria (Utian 2007), and has now done so at  http://www.menopause.org/PSHT08.pdf.

The  gynecologist- led SA Menopause society SAMS  followed the  Wyeth lead of the N American Menopause Society NAMS, rather than  evidence and the International Menopause Society.

 

 Despite Dr Utian’s review last year, and the now balanced  IMS and NAMS position, the SAMS website still damagingly  (17 August 2008) declaims publically: “The guiding principle should be to take the smallest possible dose for the shortest time necessary. After the first five years, women – with guidance from their doctors – should try and come off  hormone therapy and see how they cope without hormones.” http://www.samenopausesociety.co.za/.  

 

As IMS and Dr Utian point out, all  reason, observational and scientific evidence reject such  limited approach which  focuses largely  on symptoms, instead of the far more important long term prevention of degeneration of mood, mind, skin, hair, bones, muscles, heart, circulation etc,  which  prevention  appropriate physiological supplements provide for the second half of lifespan after menopause/ “andropause” – which can defer disability, add decades to health. . 

 

 The WHI tested only Wyeth’s oral HT -  the xenohormones  premarin and provera – in mostly overweight  elderly women, it did not test physiological parenteral balanced human  hormones as we have evolved on for millennia, as used in men and in all other branches of endocrinology, and has been used appropriately and safely worldwide for over fifty year. . The WHI cost almost a billion US$  (for both the HT – in 15400 women for a mean of almost 6 years- and diet and calcium trial arms),  likely the costliest  trial that will ever be done. The HT  caused a few  older  women problems,  but the hysteria  (in USA, UK & Europe) resulted in perhaps millions of women since then suffering   from stopping or avoiding HRT. But  like all wars, it produced some  invaluable results.

 

We stopped using oral HRT pills  where possible here in the early ’90s because we saw such bad results overall in overweight stressed women.

Despite  the warnings about high risk:benefit problems,   Wyeth – like Robert Wilson’s Feminine Forever- 1966-   persuaded the NIH & the American Menopause Society, the  FDA and  most American doctors and women-  that postmenopausal women need & will benefit from premarin-provera forever, or just premarin after hysterectomy. . This was despite the massive evidence against commercial HT pills in the Seamans’ book Women and the Crisis in Sex Hormones (UK 1978).

 

But when the WHI  trial after about 7 years  was misreported to show that  (at age 50-79yrs), the only benefits  OVERALL were reduction in the (5 to 10year) menopause SYMPTOMS, and  reduction in fracture and colon cancer   BUT  apparent increase in vascular disease dementia and breast cancer, the WHI  panicked and stopped both trials (premarin-provera, and premarin alone) – and worse, roundly condemned all  post menopausalsex hormone replacement .

 

It has taken  the International Menopause Society 6 years to get them to understand what was obvious from the original planning paper of 1998, and the first trial result of 2002 with their poor statistics, that the results apply ONLY to  those  commercial  oral pills they used, and to the older women they inappropriately put on horsepills despite them being overweight, smoking, hypertensive etc- ie at high risk.

 

When the WHI belatedly published results by  age breakdown (first in 2004), it confirmed what we always knew – that horsepills STARTED FROM MENOPAUSE are ok for symptom control for up to 10 years , they reduce all deaths and most degenerative disease by almost 40%  (except for insidious increase in obesity, DVT, urinary incontinence, and gallstones.- and this in an age when, as the BBC reports  14 Aug 2008,* Obesity ‘equal to terror threat’  The threat to the nation and the NHS from rising obesity is as grave as that posed by terrorism, a government adviser says”. ). 

 

This low risk:benefit advantage  was well shown in both WHI and the 10 year Oulu Finland trial (Heikkinen 2006) when even women on lowdose  ie 1mg/d estradiol  +- 2.5mg  progestin did brilliantly.

 But we have known for decades that the oral combination gradually promotes breast cancer, which increases after 12-15yrs (Henderson ea 1980).

 

So all  HRT after  age 60yrs was wrongly condemned  by “Authorities” , when it has been known for decades that in lower dose started from menopause even appropriate oral HT  long term does far more good than harm . The major risks are when it – ie megadose estrogen-progestin = hormone therapy -is started  in the overweight or well after age 60yrs, when it is more likely to trigger already threatening  thrombosis, cancer or dementia – as has been well shown with tibolone started at a mean of 68yrs (Cummings ea LIFT trial NEJM August 2008).

 

So all hormone-deficient people benefit from permanent physiological  replacement- ie HRT- as with eg thyroid or adrenal failure, started the earlier the better.

But sex hormones for both men and women are best taken parenterally [ie not by mouth- when they are absorbed via the liver (hepatic 1st pass) , digested & broken down]. So with tablets, 10 times more is needed for symptom control, while the risks rise for hepatitis-gallstones, hypertension, thrombosis & breast cancer.

 

So like men, women should take permanent appropriate human HRT based on their blood levels and response- but ideally parenterally, (not orally = HT) - 

 estradiol around 0.025 to .07mg/d (compared to oral  dose around 0.5 to 1mg/d)

 - testosterone  0.3 to 1mg/d (compare the old  oral methyltestosterone 1.25mg/d, or for  men  oral testosterone  undecanoate 120mg/d vs about 8mg/d by  eg fortnightly or injection)

 - progesterone 1 to 5mg/d (oral 200mg/d)

by subcutaneous  injection fortnightly- very cheap;  or expensively by creams, implants, patches, sprays, suppositories .

 

Lowdose micronized human hormones are also effective and safe (Dr Lee Vliet), but only micronized estradiol is  available here.Major clinics around the world have used such  balanced parenteral or oral replacement for over 50 years, and seen nothing but good results- some women of over 90yrs just keep coming for eg their implants every 6 months (Gambrell 2004 personal communication). All the common degenerative diseases are reduced eg Alzheimers perhaps by 90% (Cache County Study).

Even supplements, including HRT,  can never abolish death and disease permanently!  only defer and minimize disease. That’s why patients have to be screened first,  and then periodically thereafter, so already active disease eg cancer can be promptly dealt with.

 

Part of the problem with oral HT is that the synthetic progestins – while protecting the uterus- have some bad effects like blocking estrogen benefit on the heart, brain and bone. The natural human progesterone on the other hand does only good (apart from lack of benefit on bone, and association with failing hearing).

 

The major problem with HRT is that  (in men and women), doctors and patients mostly take a shortterm view- just treat symptoms & sexual complaints. They negligently refuse to recognized that all supplements are essential for the second half of life, and act accordingly. This is the danger of focussing on symptoms instead of the whole patient’s needs. Its like ignoring a  knock in  the engine/bearings; or  smoking, or ignoring  increasing obesity till the patient dies or first gets diabetes, heart attack,  stroke, cancer, dementia, fracture – when it is often too late to restore health. This is criminal negligence.

 

On the other hand, calcium supplement  alone has slight benefit on bone, but increases coronary calcification disease.

 

In the WHI, Calcium plus lowdose vit D 400iu  lowered hip fracture  by 30%, but increased kidney stones by 17%. it is better and safer to take  a complete supplement which includes calmag boron zinc manganese proline and the vitamins B,C,D & K.  Adding the other trace elements plus bcarotene + vit E plus the biologicals gives major protection against not just fractures but also all major common disease. So ideally (in addition to thyroid, cortisol, insulin resistance & sex hormones),   the vit D level should be measured, and if low the supplement increased to 1000 to 7000iu./day or 50 000iu/week.

 

Why not phyto(plant) -estrogen or drug substitutes for HRT? on the one hand, the only proven supplements that reverse osteoporosis and restore   are HRT plus the basket of other supplements;  and the only supplements proven to improve menopause symptoms are appropriate HRT, or  the supplement GABA (the main brain neurotransmitter).,

But kava and black cohosh have been restricted/ banned because they may rarely be associated with fatal  hepatitis.

 

Soy and other phytoestrogens may reduce menopause symptoms, but have not been shown to be safe longterm, and there is concern that they may increase breast/ prostate cancer. And no modern designer drugs- statins, prozacs, tibolone, raloxifen, biphosponates, tranquilizers, nonsteroidal anti-inflammatories, the viagras  – despite all their  costs, risks and  heavy marketing-produced multibillion $$  sales  – have shown anywhere near the global benefits of the natural supplements discussed above.-  (unlike the natural supplements), none of the modern wannabe substitutes  reduce all-cause mortality and morbidity as do supplements including appropriate HRT.  

See the HRT  and supplement papers  above and below , and the recommended condition-specific supplement product information.. For specialist  internist consultation on appropriate supplements including HRT for individual circumstances, email your concise health details to doctor@healthspanlife.com

 

see also