quotations and study evidence are in italics. Links are underlined.

On 14 April The South African Department of Health emailed us : ”  the Council  of Medical Schemes (CMS)  is reviewing the prescribed minimum benefit (PMB) regulations. Stakeholders are again invited to comment, this time before 11 May 2009, on the  third draft of the consultation document with input from stakeholders.” Antihypertensive medicines listed in the PMB EDL Essential Drug List are:  “Amlodipine Atenolol Enalapril Hydralazine Hydrochlorothiazide Methyldopa Sodium nitroprusside.”

Please submit as a comment to this motivation (or/and direct to CMS)  your argument for or against the evidence-based changes proposed to the EDL.

Judging from the antihypertensives, diuretics and estrogen listed, the PMB EDL  is anything but evidence-based. How can the EDL omit the prime human replacement hormones estradiol, progesterone; diotroxin; and cholecalciferol vitamin D3? when no substitutes eg ergocalciferol D2, levothyroxin  or the xenohormones  ethinylestradiol, premarin or progestins  can be proven  as good and safe.

For the long-standing evidence-based reasons set out below, the  long-used lowcost combination  co-amilozide  (amiloride + HCTZ hydrochlorothiazide) must be added to the diuretics (amiloride is on the European EDL), and reserpine to the antihypertensives list.

We all around the world are stakeholders. The argument over the best betablocker is trivial compared to the major issue that the longest- and best-proven drugs for hypertension- lowdose reserpine and co-amilozide –  are omitted. This omission will  drive up cost, but more important  (as on the RSA, and UK, and European Medicine Authority Essential Drug  Lists where reserpine is omitted) deprive patients of the best primary drugs- of huge concern considering that prevalence figures of overweight insulin- resistance hypertension and lipidemia are fast approaching 50%; with respiratory disorders (which most modern antihypertensive drugs,  except CCB calcium-channel blockers, may aggravate)  not far behind.

It is alarming that – thanks to ill-advised Guidelines  and unthinking doctors – we still see overweight older patients on atenolol plus HCTZ- with potassium level of 2.9mmol…

This week’s Medical Jnl of Australia has two commentaries on Treatment Guidelines that are very relevant to us everywhere. Where are the declarations of lack of vested interests of role-players in the South African  and UK and European Essential Drug Lists?

Ted Dace recently reviews Corporate Bias, Corporate skepticism: Turning doubt into dollars, the strategy evolved by Industry (cigarette, mineral, phenylpropanolamine, fertilizer and GM food)  to delay action against their products by casting doubt on the evidence against them.

Now, as Dace and Flavio Fuchs say, Big Pharma has strategically reversed the disinformation game by using the skepticism tactic, and Big Pharma  financial leverage  (through jobs and taxes) on Regulators and politicians, to have natural unpatentable nutriceutical supplements- even essential vitamins minerals and biologicals like fish oil and human hormones – and long out-of-patent proven old drugs- discredited by blatantly wrong data, or subjected to far more stringent evidence of benefit and lack of harm than is presently required for heavily marketed patent drugs. The latter- (provided they are owned by US pharma corporates) are allowed to be registered and marketed with only a few months trials in humans- even though very few such synthetic drugs (eg stilbestrol; practolol; thalidomide; fenphen; cerivastatin, troglitazone, psychotropes, Vioxx) survive more than a few years due to unanticipated (or blatantly  undisclosed) major adverse effects, and even though they are allowed to be registered and saturation marketed despite there being  no good evidence that they are as good as let alone better and safer than the old.

Hence the increasing disaster of unnecessary multirisk modern patent drugs:

*NSAIDS and Cox-2 inhibitors (Vioxx, Celebrex) with no advantage over sensible aspirin,  paracetamol or eg cat’s-claw-curcumin herbal blends for ordinary pain;

* statins for mild “hypercholesterolemia” when all that is needed is sensible diet-exercise and nutriceuticals;

* oral xenohormones (eg premarin, progestins, ethinylestradiol  instead of evolution-proven parenteral human sex hormone replacement;

* bisphosphonates and newer patent drugs when all that is needed to prevent osteoporosis and linked fractures is appropriate combination of vitamins B,C,D3,K; calmag, zinc, boron, manganese; and testosterone and estradiol; and

* sulphonylureas and glitazones for the epidemic of type 2 diabetes when all that is usually needed is restriction of sucrose- fructose and cooked fats, and addition of metformin or the available scores of natural insulin sensitizers.

Smoking aside, mild hypertension and insidious overweight (with some degree of insulin resistance, low nitric oxide and increased reactive oxygen species contributing to lipidemia, atheroma and tissue glycation- AGES advanced glycation endproducts) are the most prevalent – and correctable-  risk co-markers for adult obesity, diabetes,  ischemic heart disease, heart -kidney failure, cancer, stroke, dementia and premature death. These risk factors are easily detected and warned about  at any consultation with a healthcare provider, even the pharmacist, nurse or naturopath. And they are  easily and cheaply reversed with safe simple  lowcost advice and prescription of  antihypertensive antifattening agents : lowdose reserpine+coamilozide, and natural supplements (vitamin-minerals, and biologicals like fish oil, arginine, carnitine, coQ10, galega/metformin, gymnema, garlic, curcumin and  pepper).

The case of hypertension: Corporate bias and the molding of prescription practices: this thoughtful critique by Flavio Fuchs from Brazil last month  sums up the massive Disease + Regulator Industry fraud in most marketing and  current  national drug recommendations – which favour modern marketed antihypertensive drugs over the old and proven combination: “Commercial strategies .. based on the results of clinical trials sponsored by drug companies. Most ..  present distortions in their planning, presentation or interpretation that favors the drugs from the sponsor, i.e. corporate bias.  Atenolol, an ineffective blood pressure agent in elderly individuals, was the comparator drug in several trials. In a re-analysis of the INSIGHT trial, deaths appeared to have been counted twice. The LIFE trial appears in the title of more than 120 reproductions of the main and flawed trial, as a massive strategy of scientific marketing. Most guidelines have incorporated the corporate bias from the original studies, and the evidence from better designed studies, such as the ALLHAT trial, have been largely ignored.  In trials published recently corporate influences have touched ethical limits. In the ADVANCE trial, elderly patients with diabetes and cardiovascular disease or risk factors, allocated to placebo, were not allowed to use diuretic and full doses of an ACE inhibitor, despite the sound evidence of benefit demonstrated in previous trials…. This reality should be modified immediately, and a greater independence of the academy from the pharmaceutical industry is necessary. “ Dr Fuchs has some 108 publications, 38 as first author, on Pubmed the past 25years.

But new studies validate (or spuriously attempt to discredit) the still- primary role of lowdose reserpine+ coamilozide in the prevention and treatment of hypertension and associated Alzheimers, diabetes, heart- kidney disease and premature mortality:

Arya ea 2009 show that reserpine ” increases longevity of the 1mm long roundworm Caenorhabditis elegans with a high quality of life, namely, enhanced and prolonged mobility (Srivastava et al 2008); and in this well established Alzheimer’s model, reserpine ameliorates Abeta toxicity, significantly delayed paralysis and increased longevity “. .

Patterson Dollery & Haslam in 1965 in London;  Rosenfeld in 1980; and the Multicenter Diuretic Cooperative Study Group in 1981, already showed that co-amilozide -hydrochlorothiazide HCTZ plus amiloride -was more potent than either alone in lowering bloodpressure, while  generally reversing the hypokalemia of essential hypertension- but without reduction in the severe hyperuricemia of HCT alone.

The Cache County Study in 2006 showed that potassium-sparing diuretic (eg co-amilozide) was the only antihypertensive drug that in the treatment of hypertension lowered the incidence of Alzheimer’s disease – by 75%.

For 30years, studies and trials with lowdose reserpine -the VA study of 1982 and the 1997 German Reserpine Study Group ( in overweight hypertensives with baseline hypokalemia  lipidemia and hyperglycemia) have shown that adding lowdose reserpine 0.05 to 0.125mg/d to thiazide (eg HCTZ, chlorthalidone or clopamide) reduces the metabolic problems inherent in essential hypertension and diuretics ( potassium -magnesium deficiency, raised uric acid- glucose cholesterol and triglyceride levels).

In 2002 Shafi ea at London University showed that in rats on an atherogenic diet, reserpine even at a high parenteral dose of 43mcg/kg/day (equivalent to > >0.25mg orally/d in average humans) reduced blood and vessel wall LDL by 1/4/ to 1/2, and aorta intima-media thickness by 3/4; HDL and triglyceride levels were unchanged. .

In 1995 Grobee & Hoes and in 1999 Cooper ea reported that non-potassium-sparing diuretics almost double the risk of sudden (arrhythmic) deaths compared to potassium-sparing drugs or addition of potassium.

Each potassium-sparing agent has it’s  promoter, but amiloride does not have the feminizing effects of spironolactone, and is the only one that also conserves essential magnesium. Spironolactone deserves  it’s place on the EDL, but so does amiloride.

And finally, metanalysis (Burman 2004) of  the ~ dozen trials each of  non-potassium-sparing diuretic (in at least 116 000 patients) or reserpine (in at least 7400 patients) spread over 20 years , against other antihypertensive drug, shows that reserpine alone or (co-)thiazide alone is as good as or better than any well-tried modern drug eg ACEI,  ARB(angiotensin-converting enzyme inhibitor or ARB angiotensin receptor blocker), betablocker or CCB calcium channel blocker alone.

The two German Reserpine Study Group trials (Pittrow ea 1997) showed in 400 overweight hypertensives that the combination of reserpine 0.1mg plus a thiazide -clopamide 5mg/d – was considerably better than an ACEI  or CCB  alone (about 60% had hypertension normalized versus elalapril 29% or nitrendapine 45%); And without the cough/ angioedema, arrhythmia or rash problems of ACEI, ARBS or CCBs. . .

Big Pharma Disinformation: Fernandes ea 2009 found that in rats, “low doses” of reserpine preferentially induce deficits in tasks involved with emotional contexts. But the dose they used was anything but low dose for humans: they used 0.1-0.5mg/day reserpine / kg in rats- but given the recognised ~10 times faster metabolism of rodents,  this dose converts in humans to ~0.01- 0.05 mg/kg ie for an average 75kg adult 0.75 to 1.375mg/day. The lowdose regime long recognised for humans is around 0.025 to 0.075mg/day. So they were using a dose about 12 to 30 times higher- which we stopped using decades ago.

And a followup 2009 analysis Shafi ea from the landmark Systolic Hypertension In the Elderly SHEP trial  showed the folly of continuing to use diuretic dose of thiazide to treat  essential hypertension- especially when combined with atenolol which compounds metabolic and respiratory adversity. Chlorthalidone even 12.5 mg or less a day almost doubled the risk of diabetes in the first year, and >25mg/d combined with atenolol trebled the risk; whereas combination with a potassium supplement neutralized the risk of diabetes – potassium depletion being the mediator of thiazide-induced diabetes..

Sica in 2006 analysed the consensus that in terms of diuretic and antihypertensive efficacy, chlorthalidone is more than twice as potent at hydrochlorothiazide HCTZ ie chlorthalidone 25mg = >50mg HCT. Yet we know from patient observation that even 7mg/d coamilozide combined with reserpine 50mcg/d  is effective antihypertensive.  Adversity from highdose chlorthalidone clopamide or HCT (which should not be used for uncomplicated hypertension)  is irrelevant to the modern optimal management of hypertension..

A little alcohol is healthy- but most people use much more (as well as cigarettes)  at their peril, and society does nothing except bury the corpses and fork out insurance.. So  it is classic fraud, cynical hypocrisy for Regulators and Big Pharma to quote overdosed drugs as reason not to use eg low dose reserpine or low dose co-amilozide.

CONCLUSION: It is not co-amilozide let alone reserpine that deserves the second look proposed by Barzilay ea 2007; – these  are the long-established sine-qua-non first, second and third-line drugs for treatment of all grades of essential hypertension, as world hypertension experts eg Profs Marvin Moser, Norman Kaplan,  MK Mani, YK Seedat, Roy Keeton and Harry Seftel have long advised. As Professor Fuchs implies, it is the regulators and gatekeepers in all countries – the Governments/Medicines Control Councils, the Hypertension Societies and the Medical Aid Schemes, that must produce – if necessary by order of  a Court of Law – evidence to justify the omission from national essential drug lists of lowdose coamilozide with lowdose reserpine as the first pharmacological tier for all grades of essential hypertension. This proven regime (currently costing retail prepacked in RSA about US$6/year), together with enforced advice about low salt-lowfat- low sugar /alcohol diet, natural essential  supplements, active exercise and no smoking, is all that most hypertensive patients need.



  1. As an author who was cited and commented, I am naturally glad with. The point, however, is the issue under discussion. How could any regulatory drug agency worldwide does not recommend diuretics as part of the pharmaceutical armamentarium to control high blood pressure? Is this because the corporate bias is influencing the judgment of the experts? The association of hydrochlorothiazide and amiloride is surely among the more efficacious agents to start the treatment of hypertension, please see the MRC trial with elderly patients and the INSIGHT trial.

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