UPDATE: FOR MILDER PAIN, WHY USE NSAIDS (LET ALONE DICLOFENAC) OTHER THAN PARACETAMOL -ACETAMINOPHEN?

update December 08, 2014

Aspirin,  paracetamol, other NSAIDs,  and codeine  in periodic conservative analgesic use have  not been reported to cause hypoglycemia eg a few gm a day solo or in combination  in well adults-  despite  deliberate overdose of these being  notorious for causing fatal bleeding or  liver failure with hypoglycemia, or respiratory failure.

But increasingly tramadol is incriminated in dangerous hypoglycemia: Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain Fournier, Suissa, ^eaJAMA Intern Med.December      Tramadol is an increasingly widely used  weak opioid analgesic , associated with adverse events of hypoglycemia.  Analysis  in United Kingdom Clinical Practice of treatnent with tramadol or codeine for noncancer pain between 1998 and 2012  included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol  associated with  increased risk of hospitalization for hypoglycemia  in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). Conclusions  tramadol (in contrst to codeine), TRIPLED risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

update 4 March 2013  BAN DICLOFENAC?  four years on, another call comes  for the virtual banning of diclofenac, from no less than the Canadian Medical Association Journal , based on a new metanalysis of NSAID risks by University  Toronto’s McGettigan and Henry .

As this column has long pointed out, diclofenac is apparently still the only NSAID that can kill suddenly without warning.  There are many far safer alternatives eg naproxen, ibrufen; and no compelling clinical evidence or reason to use it let alone cox2 inhibitors  except false beliefs and heavy marketing.

So as this columnist concluded in 2009,  it is blatant fraud, negligence and potential indefensible homicide  to continue recommending  let alone  using diclofenac simply for profiteering.

21June 2009 It is 4 months since this column last addressed nonsteroidal anti-inflammatory drugs NSAIDs.

A new study (from USA, UK and Canada – Ray 2009) of NSAIDs  claims that in those with ischemic heart disease, the popular NSAIDS -diclofenac, ibuprofen or rofecoxib(Vioxx) – increased serious heart disease/ death by about 50-67% compared to nonusers; whereas naproxen over some 111000 patient years of use gives no significant risk or benefit.

A new study from Denmark (Fosbol 2009) this year looked at a million healthy individuals with no hospital admissions or selected therapy. Compared to no NSAID use, ibruprofen and naproxen gave no added risk of death/ myocardial infarction; diclofenac gave 67% increased risks, and the two coxibs (rofecoxib Vioxx; celecoxib Celebrex)  increased risk 100%.

So we are led to believe that naproxen or ibuprofen is the NSAID  mild-to-moderate analgesic  of choice. Naturally the American Colleges and academia – who represent the Disease Industry, not patients- recommend yet other potentially toxic drugs- like  the magical proton pump inhibitors- to counteract the adverse NSAIDS..

But is this just a myopic view beloved of big pharma, to promote their snake oils.?

Another new study from Denmark (Gislason 2009) of 110 000 patients after admission for heart failure in the 12 years 1994-2005, showed that 57% died; 9000 (8%) were rehospitalized with acute heart attack  and 40 000 (38%) were rehospitalized with heart failure. Thus heart failure in a well-nourished population has a poor prognosis. In 36 000 who had used NSAIDs compared to non-users, risk of death was doubled on  diclofenac; increased~67% on  (rofe-or cele)coxibs; and was  significantly increased 22-31% by all other NSAIDs including naproxen and ibruprofen.

It is common cause after 20 years that injected diclofenac is the only NSAID that can unpredictably cause sudden death. So it’s administration risks culpable homicide when it is totally unwarranted. No cases of sudden death from any oral NSAID   including aspirin appear on Medline, apart perhaps from the risk of hyperacute asthma (Asamoto 1999).

But what of gastrointestinal bleeding  risks of NSAIDS? a 2007 study in Japan (Yajima) scoped all orthopaedic patients who took NSAIDs for more than 4 wks: oral diclofenac increased risk of erosive gastric lesions sixfold. A new review from Seattle (Schlansky 2009) refers to Helicobacter synergism in all NSAID use.

WHAT IS THE NEED FOR NSAIDS? The Wikipedia entry on NSAIDs  sums it up: it has almost four times as much text on the numerous  adverse effects of NSAIDs as on their uses- in fact the  article does not discuss the advantages of NSAIDS as analgesics; in fact it states plainly  that alone  just  “their gastrointestinal effects  are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States”.

All designer drugs are dangerous in overdose. Without overdose, paracetamol has no risk – and the Wikipedia entry thereon is balanced and highly favourable even for infants. We know well that paracetamol- a fatal liver toxin in overdose- should not be marketed without a built-in simple liver (and antineuritic) protective of  eg (carbo-or N-acetyl-)cysteine, alphalipoic acid and vitamin BCo.  But the Disease – Big Pharma Industry is not interested in prevention- Only Disease Pays. And Regulators, lobbyists and legislators  protect their source of work and income- the Drug Industry.

Fish oil (EPA+DHA) is probably  the most beneficial NSAID supplement we have (- perhaps ahead of other front-runners like vitamins C, D, magnesium and CoQ10-) halving all sudden deaths, and reducing by at least a third all major chronic degenerative diseases from CVD to diabetes, arthritis, learning, depression, behaviour disorders. Industry wont pay for head-on comparative trials. But the trial evidence suggests that fish oil and oral EDTA have better risk-benefit than aspirin and other antiplatelet agents, NSAIDs and warfarin.

We know that for moderate trauma and small – medium (even knee) joint pain/  contusions, self-massage with any natural NSAID like arnica or wintergreen is all that is needed, combined if necessary orally with up to 3 to 4gm paracetamol /day +- if needed a little codeine.   Prior 2002 found no significant difference in pain relief between paracetamol and naproxen in tension headache.

For more serious pain,  short of strong opioids, there is in fact no overall trial evidence that weak opioids or NSAIDs are better than eg hypnotherapy, or acupuncture,  or judicious paracetamol; to which latter if necessary a little codeine can be added as step-up analgesia. The latter  agents have none of the deadly risk of NSAIDs. Amadio 1984 showed that of Peripherally Acting Analgesics: ” paracetamol at up to 4 g per day compares favorably in analgesic potency to aspirin and other NSAIDs, and  should be considered the treatment of choice for mild-to-moderate pain”.  Skovlund 1991 showed no significant difference between naproxen and paracetamol in postpartum uterine spasms.

Six RCTs – five in mostly European peoples and one in Hong Kong- found paracetamol equal to diclofenac (Voltaren) – March 1994 in arthritis; Brevik 1999 and Kubitzek 2003 in dental surgery; Hoogewijs 2000 and Woo 2006 after trauma; and Munishankar 2008 after Caesarian section.  In a Cochrane analysis 2003, Towheed showed that in the one placebo-controlled RCT in osteoarthritis, paracetamol was clearly superior to placebo with a similar safety profile. And the general principle of therapy applies, that if required, combination of analgesics from different groups is better than single drug therapy. But given the many potentially fatal risks of the NSAIDs – compared to paracetamol, opioids and if indicated  aspirin –  there is no compelling reason to add NSAIDs  for pain.

We know that it is negligent to initially sentence people with  spontaneous mild-moderate head/neck/backache or tendonitis at the shoulder, elbow, knee etc to bedrest, NSAIDS, opioids or referral for xrays, scans or surgery. 95% will settle rapidly with reassurance, posture instruction and simple topicals and paracetamol analgesia. Otherwise most pain will disappear with firm reassurance with brief simple laying on of hands eg massage and traction with gentle rotational manipulation and instruction in auto-reinforcement –  pressure point eg earlobe pressure, or acupuncture, or hypnosis. And most of the remainder resolve quickly with  simple targeted injection with a little local anaesthetic plus depot steroid.

And we know that with judicious use, topical corticosteroid injection – never mind judicious brief systemic steroid (corticosteroid, calciferol, testosterone) has little or no risk and far greater target and multisystemic benefit than NSAIDs; and for chronic conditions, like fish oil at least address the underlying pathogenic mechanisms/causes- whereas NSAIDs and paracetamol ignore these.

Is drug-speeded resolution of inflammation essential and beneficial except for the drug vendor? A careful RCT by Bradley ea from Indiana University in 1992 observed that “joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee osteoarthritis”.

So why are synthetic  NSAIDs and especially the Coxibs  still used? Why do academics and Regulators still allow, promote  them for  routine use, other than to profit Big Pharma, and cause perhaps a quarter million deaths a year globally?

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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  .

CHRONIC ILLNESS- MANAGED ANTIAGING & GENERAL PRACTICE CLINIC SOUTH AFRICA

update 6 April 2015

In Claremont  Cape Town

A  Specialist Family Internist Clinic offers consultations by appointment especially for managing (and ideally preventing)  the major chronic degenerative diseases of aging  and  maintaining physical, mental (and why not sexual?) vigour to a ripe and healthy old age; as well as preventing and managing acute disease at all ages.

The clinic (a specialist physician and a nutritionalist)  offers all-system evaluation and if available, natural  (as well as essential prescription orthrodox) prevention/treatment including metabolic – weight-endocrine-diabetes; heart-lung -kidney; hypertension; neurological-pain; joint & muscle; abdominal, immune system ie infection, cancer and auto-immune  support;  genito-urinary, & sexual problems;

and appropriate screening – ECG, non-xray ( no-touch thermography- eg thermomammogram;   SureTouch tactile) mammograms, non-xray (ie  ultrasound) BMD ie  bone fracture risk measurement, body composition, and appropriate hormone profiling/replacement.

Phone during office hours for appointment: for Claremont office  ph 021-6717415  or 6831465 (or 083-6299160) – at Grove Medical Bldg 1st floor no 15 (opp ABSA Bank Parkade c/o Grove Ave Pearce Rd)  , or neil.burman@gmail.com ;  or consultation by telephone/Skype or email .

by appointment only:        OFFICE HOURS: by appt: ph office:  9am-5pm weekdays, 9am-1pm Saturdays.  AFTER  HOURS up to 9pm any day generally at office: –  email doctor   neil.burman@gmail.com  or ph 6am to 9pm  0836299160. EMERGENCIES  cannot be dealt with- acute emergencies and trauma, bleeding cases  must go to any  Emergency Unit .

Billing according to means ie specialist professional rates:  eg as a preferred provider for Discovery Health-  consultation procedure  0190; for needy patients, what the medical scheme pays  Detailed medical report and advice protocol provided at R300. Even Hospital Plans have to pay for outpatient consultation for scores of PMBs ie Prescribed Medical benefit conditions like Menopause.

 Needy patients desiring brief consultation can be seen by arrangement at GP rate.    Bone density scan  (covered by some medical schemes)  procedure 3612..  Non-xray mammograms are not yet covered by medical schemes codes: R650 for SureTouch including clinical consultation, R800 for thermomammogram.

MAGNIFICENT METFORMIN

neil.burman@gmail.com

only 5 weeks since our last review,

twelve  new papers further confirm the supremacy  of the galega plant extract  metformin as the most important chronic preventative drug ever, alongside other natural nutrient supplements eg – fish oil, vitamin C, the human hormones  vitamin  D, sex hormones, thyroid:

PCOS:

1. Aled Rees’ team at Wales’ Cardiff  University  show in a randomized controlled double-blind RCT that obese  women with PCOS (hirsutism and failing periods) even at a mean of 30 (18-35) years have evidence of insulin resistance and early vascular disease; which at their weight around 96.5kg and BMI 35kg/sqm, with waist around 108cm and hips around 120cm, is reversed by metformin: 1500mg/day compared to placebo for 12 weeks  reduced weight by 2kg, body fat by 2.5%, waist by 5cm, bloodpressure by 7% and improves circulation; with 18% fall in insulin resistance (HOMA-IR) , 15% fall in free androgen index, and 21% fall in the testosterone: estradiol ratio.

2.A Tehran University Iran (Ashrafinia) RCT (although not big enough to be statistically significant)  shows that metformin is 81% better than ovarian diathermy in treatment of PCOS inferrtility.

3. and the  German University Erlangen open study –Effect of Metformin Treatment for 2 Years without Caloric Restriction on Endocrine and Metabolic Parameters in Women with Polycystic Ovary Syndrome-(Oppelt)  similarly showed that  even without calorie restriction,   while “no significant changes in body mass index or HOMA-IR were observed,  on metformin  a significant decrease in hirsutism, in fasting and 2-h insulin levels was observed,  with a significant increase in sex hormone-binding globulin (SHBG) levels, while total testosterone (TT) levels and the free androgen index decreased significantly; with significant improvement in lipids.”

These bear out what this column has previously  reported about the superiority of metformin over surgery or other (designer synthetic) hormone therapy  from the work of eg Charles Glueck and  Louis Ibanez for PCOS metabolic syndrome and infertility. .

Diabetes :

4. A retrospective Massachussets study (Brownstein) shows again that  in recent diabetics, the relative risk for heart attack with rosglitazone Avandia  was  120% higher  compared to metformin or  pioglitazone Actos;

5. and a retrospective UK study (Tzoulaki) that pioglitazone was associated with reduced all cause mortality compared with metformin.

But these are retrospective studies, not controlled prospective trial.  they do not mention  the cardinal fact that  pioglitazone does the opposite of metformin, it increases body weight,  heart failure and fracture rate;  and that after a decade of intensive pioglitazone  promotion and trials, there is no evidence from hundreds of direct randomized controlled trials in at least 26 000 patients  that pioglitazone reduces all-cause mortality and chronic diseases  including cancers by a third, as metformin did in the longest RCT ever, the 20year UKPDS, and in many other studies.  No modern designer drug does what metformin does .

6.A systematic review in children by University Sydney shows that   metformin for about 6 months lowers insulin resistance and overweight.

and in new rodent studies:

7. from Russia, (Anisimov ea)  metformin significantly reduces cancer risk, increasing lifespan by 8% and breast cancer latency by 13%, halving breast cancer transplantability and with melatonin reducing Ehrlich tumour growth by 40%  ; 8. from North Carolina (Quaile) that the minimum toxic dose of metformin in the diet was equivalent (by the usual average 10:1 conversion for faster rodent metabolism) to between 60 and 120mg / kg/day ie about 4-8gm /d  for about 5 years in humans;

9. and from Poland (Labuzek) that metformin shows beneficial effects in experimental models of neuroinflammatory diseases like Alzheimers.

10 In June an international team   (Jiralerspong ea Texas/ Germany) showed in an observational study that Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a 3fold higher pCR pathological complete response rate (24%) than do diabetics not receiving metformin (8%) . In response,  Garcia & Tisman from California point out yet another mechanism for this improvement,  that metformin induces malabsorption deficiency of both folate and especially metabolically active holotranscobalamin; which is  potentiated by neoadjuvant chemotherapy induced lowering of holotranscobalamin., despite apparently normal measured  total B12 levels.

This reminds us of  three  truisms:

diabetics are more prone to cancer and neuropathy and homomocysteinemia, these  need to be more concientously screened for;

diabetics are even more in need of all micronutrient supplements as antioxidants, insulin sensitizers, anti- glycation agents, nitric oxide providers, neurotropics;

and where cancer occurs, the golden rule is that no supplements  (other than metformin) should be given until conventional (radio/chemo/surgical) therapy  of the cancer has been commenced or refused. Folate and B12 should not be withheld simply because they may antagonize one link in the carcinogenic chain- there are dozens of dietary adaptations and micronutrients that are major anticancer adjuvants. without putting the patient at greater risk from vascular and osteoporotic disease than ever she was from cancer.

So that is at least 2 new studies a week confirming metformin’s supremacy.

Hence the obligation grows to prescribe as anchor support metformin to comfortable safe tolerance for life not just in all diabetics but also in all overweight people- starting if necessary in childhood-  who cannot maintain both optimal BMI, blood sugar and lipids off it.  And for protection against cancer and Alzheimers and vascular disease, to all perhaps over 50years.

But of course, global  metformin / galega use  along with other supplements  (from vitamins- minerals to all the other useful natural biologicals and insulin sensitizers- – from arginine to zeaxanthine including appropriate sex hormone replacement SHRT)-  will do away with perhaps 90% of the grounds for modern prescription drugs and non-post-trauma surgery/procedures, and much infertility and obstetric problems.  Painful shrinkage for the massive and toxic new -drug / disease/ hospital/hightech industry and the millions of workers it employs as lobbyists and marketeers. Hence redoubling of the effort by the Disease Industry and most governments  to suppress such natural prevention at all costs, by buying over politicians, medical regulators and powerful medical associations and patient groups..

14 Nov 2009   METFORMIN THE MASTER DRUG: FIGHTING NEMESIS- ADVANCED GLYCATION ENDPRODUCTS, AGES.

It’s just a month since this column reviewed the only “drug” that is (like fish oil)  a universal panacea: A STUDY OF THE CENTURY: METFORMIN PREVENTION OF THE TIMEBOMB  DIABETES.

Now a  new study from Univ. N Carolina (Cantrell ea) shows that metformin is not just major benefit against prostate and  breast cancer but also against endometrial (womb) cancer.

de la Monte and Wands (2005-2008)  from Brown University RI crystallize what has been obvious the past decade, that Alzheimers disease- they call it type 3 diabetes mellitus-  is not an inevitable part of aging but  is as much a product of insulin resistance – the  overweight  (fast food- couch potato- stress) pandemic- as are all the other interrelated  common diseases that constitute premature aging;   and therefore even more reason for everyone  to take galega/ metformin or other insulin sensitizers preventatively from as young as possible.

And a new novel study from Colorado University (Nadeau ea) again demonstrates that even juvenile type 1 insulin dependent diabetics have insulin resistance and need metformin and all the other anti-AGES agents  as well.

The McMaster University (Lemon Boreham and Rollo) landmark Supermouse Trial   5 years ago used a a novel model of our current self-induced obesity pandemic- a transgenic  mouse-  to show  that unlimited access to ‘balanced’ chow grows, learns, sickens and kills  far earlier than normal mice – which even in a lab environment neither overeat nor get lazy nor fatten. .   But 10fold increase in all the scores of evidence-based conditioned essential micronutrients (that deplete as we age) greatly increased the supermice’s learning, healthspan and lifespan. Such supplements include many powerful  natural insulin sensitizers.

Emory Univ Atlanta (Narayan and Williamson 2009) claim in a new review that “trials show that lifestyle intervention reduces diabetes incidence by over 50% and is more efficacious than metformin. But neither experience nor realistic long term  trials show this.

Now a  followup report from the landmark Diabetes Prevention Program DPP in the USA ( first reported in 2002) in  middleaged overweight laizzez- faire volunteers (not patients) gives the longest ever controlled observation study (the DPPOS) – a mean of 8.5 years- of the benefits of strenuous lifestyle+ diet (LSD) alone for 8.5yrs, or with metformin  for 8.5yrs plus  strenuous LSD added for 5.7yrs,   or just adding LSD  for 5.7yrs  to the initial placebo laizze faire group.

The outcomes are impressive:

The original placebo group (on average attempted diet + exercise) had a diabetes incidence in the first 2.8years of 11.0 (9.8-12.3)% ie per 100 patient years (ie an enormous 5.5% a year, or perhaps 55% over 10 years); with LSD for the next 5.7 yrs their incident  diabetes halved to 5.6 (4.8-6.5)% ie perhaps 1% a year- a reduction of about 82% .

The original LSD group after 2.8yrs had had a new diabetes rate of 4.8%; continuing this regime for 3 times as long saw their new diabetes rate climb to 5.9%;

but the just metformin group– who had new diabetes rate of 7.8% – with added LSD for 5.7yrs saw their new diabetes rate fall further to 4.9% (compared to 11% on placebo and routine counseling) – and unlike the LSD-alone group, they maintained their original weight loss, in fact those over 60years maintained a further 2kg weight loss. Compared to the original placebo group diabetes incidence of 55% over 10years, metformin plus sustained exercise lowered new diabetes to about 8,9% over 10years ie 84% reduction in risk.

Thus this unique 10year study confirms that adding even lowdose metformin to LSD more than halves the incidence rate compared to  the average laizzez- faire patient on feeble diet-exercise alone, and maintains better fatloss than either mild or strenuous LSD alone. We know from clinical experience that titrating metformin to tolerance can maintain weight loss of 8% -provided it is not combined with psychotropes that hugely increase weight gain..

Thus there is every reason to always add metformin cautiously from the beginning to diet-exercise counseling in every overweight patient battling to lose fat and regain fitness, to abolish the lethal risks of metabolic syndrome and its diverse consequences- diabetes, cancer, cardiovascular disease, arthritis, dementia  etc.

It is common knowledge that less than 10% of patients maintain significant weight loss on any diet and exercise regime- it goes against human nature. The DPPOS confirms that preventative metformin to tolerance plus sensible diet and exercis is  the only regime that maintains weight loss and thus improves all health- drastically lowers all-cause premature disease and mortality.

No heavily marketed  designer “appetite/weight suppressant” drugs remotely achieves all the benefits of metformin, a unique  anti-glycation antioxidant,  appetite and weight suppressant, and anti-cancer, -stroke, -vascular , -infection, -arthritis , -infertility, and -dementing- disease natural nutrient. Hence as previously described, Big Pharma and the Disease Industry do all they can to suppress it’s preventative use (including having Regulators threaten us) , since no modern designer drug can compete. A short-term study (3 months) like the new University California Davis trial (Banazewska ea) (of statin versus metformin in PCOS) says nothing about the longterm benefits that matter to patients– not the Drug Industry whose concern is shorterm profit at all cost.

THE CRUCIAL IMPORTANCE OF NON-ORAL ROUTE and LOWER DOSE OF SEX HORMONE REPLACEMENT SHRT in the majority-the overweight, diabetic, cardiac, thrombosis, transplant, dementia and cancer risks.

Obviously our   skin (unless injured or diseased) – arguably our  major organ of heat control, sweating, vitamin D activation  and sexual enticement- serves as a major impenetrable barrier to  absorption or leakage. Unlike amoebae- which live or die by their exterior- we feed and excrete via our digestive tract, using our skin mainly for attraction-  or repulsion!.

It is common cause that, with intravenous injection ivi as the fastest alternative route (to swallowing), absorption is hardly better (than the skin) across aged dry vagina; better across moist ie mucous membranes eg of the eyes, nose, mouth and vagina/rectum; better by deep inhalation or subcutaneous s.c. placement (injection or pellet); and best  by intramuscular injection imi – which is now rarely achieved with  a standard 3/4 inch needle into the upper outer buttock in a fattening population . Such injections are mostly delivered s.c.

Which route is preferable depends obviously on the speed of action required eg high blood peak for an urgently needed antibiotic, analgesic, anaesthetic, antiasthma, acute insulin or resuscitation; as opposed to slow smooth delivery for maintenance eg hormone, antidepressant or analgesic delivery.

For depot injections, why use anything bigger than a 25g 10mm long needle?  so that safe subcutaneous   s.c.i.  is ensured,  guaranteeing  avoidance of the many minor and major risks of intramuscular   imi.

eg Meyer ea at Cornell Univ NY 1990 reported  that subcutaneous administration of the gonadotropin releasing hormone agonist leuprolide took half the time to first response with double the amount absorbed compared to the same dose by the transdermal TD route.

Minto, Handelsman ea in 1997 showed that injection of an oil-based depot sex hormone into the fattier gluteal (ie upper outer buttock) region (as compared to the lean deltoid ie upper arm true imi) gave significantly slower smoother less peaked absorption and action of the hormone.

And obviously total delivery to the body is going to be less absorbed  through the tightly layered  skin than if 100% delivered under the skin by injection/implant. Fatty – steroidal- gonadal hormones are particularly altered by digestion and transhepatic absorption. But so will transdermal absorption fall with aging, drying of the skin.

Hence in postmenopausal women PMW  the average dose equivalence for similar symptom- hot flash- relief has been found to be estradiol 1mg or CEE 0.625mg orally, but about 0.05mg E2  a day by modern TD designer patch (containing 4mg E2, changed twice a week)  or cream;  ie an effective oral: TD dose ratio of about 20:1. But  oral estrogen eg 1mg E2 raises the E1 estrone (the hormone most associated with breast cancer) blood level  5-fold more than the E2 level, and increases urine estrogen excretion about 100fold; whereas the E2 patch 0.05mg/day raises serum E2 to a satisfactory ~120pmol/L  but with  little  increase in E1 level  or urine estrogen excretion. Thus TD but not oral ET restores the youthful healthy balance of blood E2>E1 aout 1.2 :1.

Conversely, in  girls with delayed puberty and growth,   physiological effect appears to be even higher with TD estradiol  E2  than oral conjugated oral estrogen CEE Premarin. In a recent trial undeveloped girls with Turner’s syndrome were randomly assigned to receive initially  CEE 0.3mg/d orally, or TD E2 0.025mg/d patch (17β-estradiol, Vivelle TD) for one year – doses chosen based on published E2  equivalence  about 20:1. After 12 months the girls on TD ERT had better improvement in uterine, height, breast, and bone density growth than oral HT CEE. Hence they too (like postmenopausal  PMW) needed far lower total dose estrogen exposure parenterally than orally. PMW certainly rarely if ever want bigger breasts or womb, so even lower transdermal microdoses are ideal for them.

Nachtigal ea 2009 show that oral but not TDE2 accelerate platelet reactivity ie thrombosis risk in some PMW.

Villa ea 2008 show that low dose 1mg/d micronized E2  lowers insulin resistance, whereas higher dose 2mg/d increases it.

Verhoeven ea 2006 showed that oral micronized E2, but not TD  E2 treatment, significantly reduced arginine compared with placebo – and good arginine levels are crucial in maintenance of immunity; insulin sensitivity;   growth hormone output; wound repair; fertility; and adequate nitric oxide levels for optimal muscle, heart and circulation..

And Shifren ea 2008 showed that compared with oral CEE, TD E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters – more adverse hepatic first-pass effects of oral HT as regards both cancer and cardiovascular disease. .

Thus, given that the higher the rate of breast and uterus proliferation the greater the risks in later life, sex hormone therapy and replacement in women (let alone men) should always be parenteral- the lowest dose to achieve the desired goal- be it feminization in Turner’s Syndrome; contraception; or postgonadopausal HRT in men or women.

The ill-informed reaction to the poorly planned Womens’  Health Initiative led to a massive fall in all HRT use.

MEMORY PROTECTION:

Yet abundant studies reviewed in this column the past two years show the incalculable benefits of appropriate balanced (E+P+T) in PMW.  No-where is this better shown than in neuroprotection especially against Alzheimer’s disease AD, in which- in eg  the Womens’ Health Initiative–  introduction  of oral xenohormones well after age 60years worsened the risk of AD, but  CEE  started soon after menopause greatly reduced AD risk.

University   Beijing has shown that women who have taken lowdose oral E2 0.5-1mg plus progesterone 0.5-2mg for 4 to 33yrs have  significantly less hippocampal atrophy;   similarly at Univ S California,  studies in AD-prone mice show that early oophorectomy worsens the AD pathology and behaviour changes, but this deterioration is better blocked by E2 + progesterone combined than by E2 alone.

Testosterone replacement is probably brain-protective in men;  it remains to be seen whether it adds  memory protection in women when combined with E+P. A  2006 British study of estrogen treatment in male to female transsexuals showed few and inconsistent changes in memory and cognition.

But a new Spanish study does show that when female-to-male transsexuals are treated with testosterone for 6 months, they show significant improvement in visual but not verbal memory.  And a new Swedish study shows that “The most positive effects of estrogen plus progestogen therapy concerning memory and urinary tract and vaginal complaints were found in women with the highest and/or moderate testosterone levels (P < 0.05).”

A  recent UK  MRC study shows the critical importance of optimal thyroid function in memory, since excess of either thyrotropin or thyroid hormone can be adverse.

And it has long been known that the more hypoglycemic episodes diabetics experience, the worse long-term memory.

Thus balance of  all three major sex hormones- estrogen, testosterone and progesterone, as well as insulin and the thyroid axis,  is  crucial in cognitive performance especially in women.

HORMONE CREAMS: for those who prefer creams to  pills, implants or injections, a major advantage is that  women  can start low with all three main sex hormones as appropriate, and titrate them individually upwards to tolerance or designated ceilings. Once optimal intake and levels of each have been attained, they can then if wished be combined, compounded.

CONCLUSION:

As this column discussed two weeks ago: mid- twentieth-century women now potentially live to double the age of those born in the early Victorian era; but increasing numbers undergo premature menopause and especially relative androgen deficiency due to  elective sterilization, hysterectomy, survival from cancer and radiotherapy, or increasing cancer risk from smoking, alcohol, suppressed menstruation due to birth control hormones, cortisone use eg for autoimmune diseases and transplantation, nuclear fallout or the feminization of nature .

They thus spend the second half of their lives post menopause, with increasing premature mortality and morbidity from diseases of hormone deficiency:   fattening and diabetes; heart and circulatory disease; muscle and bone frailty; arthritis; infections,  incontinence;  and worst of all, depression,  cancer  or loss of memory; and not least, loss of vital  sexuality. These are all largely avoidable by appropriate early and permanent non-oral balanced HRT and a blend of the other three-score other natural  supplements.

As Prof  Robert Greenblatt from Augusta  wrote in The Menopause Syndrome (Medcom Press)  in 1974, ” the menopause is a physiological endocrine hormone deficiency state. It is good practice to offset endocrine deficiency states by hormone replacement therapy to restore hormone balance”- whether in a teenager or a grandmother.

And Prof Emanuel  Schleyer-Saunders from London stressed in the same colloquium that even 35 years ago, half of all hospital beds were occupied by diseases of old age- obesity-diabetic-vascular, mental and malignant- which (as Masters and Grody had shown 20years earlier) are delayable by decades provided balanced parenteral permanent HRT is started early in menopause- which starts insidiously in the mid-forties if not earlier.

Whereas Masters and Grody in St Louis, and Gelfand in Quebec,  established this by long term injections of testosterone TT and estradiol E2  esters (which for decades have been available as a 20:1 mixture lasting 2 to 3 weeks), Schleyer-Saunders and then Whitehead and Studd  in London,  and Gambrell in Augusta, maintained this long term by pellet implants every few months.  Schleyer-Saunders showed with pellets that continuous balancing TT reduced the incidence of breakthrough bleeding from 20% on E2   alone , and 12% on E2 + progesterone P, to 8% on E2 + TT,  but only 5% on all three ie E2 + P + TT – with reduction in cancers. He generally used a dose of 25mg of each hormone, but (at a time when  women were far slimmer) 50mg E2 implant  in women post oophorectomy.

Yet MacLennan ea from the International Menopause Society now report that in Australia, as a result of the hysteria generated by the wrong Womens’ Health Initiative and Million Women Study reports (in which most women used oral xenoHT), only 12% of postmenopausal use hormone replacement.

Convenience should be the last factor considered. Unless balanced  lowdose mcronized estradiol, testosterone and progesterone are used orally  – since micronized particles largely  bypass  transhepatic absorption- there is no longer excuse for the risks of oral CEE,  progestins and similar hormone therapy with hepatic first pass adverse effects.  “Convenience” is no defense  against charge of negligence  when the patient develops major complications from oral sex hormones. So the patient who insists on oral hormones should sign an informed consent form that she has been warned,  but accepts the risks of the oral (as opposed to the physiological parenteral) regime.

All  women (and men) – especially with chronic or serious acute ill health – should thus be ensured  permanent  youthful sex hormone levels with appropriate physiological HRT that avoids both hepatic first pass metabolism and hormone excess/ imbalance. Traditional American industrial hormone therapy ( dominant the past 50 years due to the connivance of the FDA with it’s supporting drug industry) with oral xenohormones eg CEE, progestins and anabolic steroids cannot provide the physiological replacement required, that is ensured with titrated human hormones  in every other branch of endocrinology for the past generation.

It remains an indictment of American medicine and legislators that their Disease and Drug  Industry- the FDA and mainstream physicians-   put their  commercial interests ahead of  womens’ welfare   in making postmenopausal women the exception to the rule of  evidence-based medicine especially endocrinology. The most vulnerable group (after children)- the older women – are thus as always the main innocent victims of the FDA-led  Disease Industry’s  War on Humanity, the Black Mass of organized commercial Big-Pharma “medicine”- of which 13  USA firms in  about 2006 had half the world’s gross “medicines” turnover of ~ $600billion. Based especially  on womens’ ills and vulnerability- particularly cosmetics and cosmetic surgery, screening mammography and hysterectomy-  the Beauty/Disease Industry is thus truly a multi-$trilliondollar moneyspinner, disaster capitalism targeting women.

TOWARDS MANAGED AGING part 3

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

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

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

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

*nitric oxide depletion;

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

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

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

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

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

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

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

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

CONCLUSION:

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

What’s necessary is simply

*sensible diet and lifestyle including exercise and recreation;

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

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

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

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

TOWARDS MANAGED AGING part 2.

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

CARDIOVASCULAR-STROKE CVD AND DEMENTING DISEASE:

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

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

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

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

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

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

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

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

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

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

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

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