Tag Archives: reserpine

update Dec 2014: TIME TO MANDATE LOWDOSE RESERPINE+ LOWDOSE AMILOZIDE+- AMLODIPINE(/ DIHYDRALAZINE) AS FIRST LINE THERAPY OF AVERAGE HYPERTENSION.

TIME TO COMPELL FIRST LINE POLYTHERAPY OF COMMON  HYPERTENSION WITH LOWDOSE RESERPINE+ LOWDOSE AMILOZIDE; with AMLODIPINE as 4th add-on if needed.

dedicated;  for inspiration and help,  to: Drs YK Seedat; Roy Keeton;  Norman Kaplan; Colin Dollery, Harry Seftel; Josh Barzilay; Tony Bunn; Mark Blockman;  and pharmacists  Allan Taylor and Joe Talmud.

neil.burman@gmail.com    for previous reviews see  https://healthspanlife.wordpress.com/?s=reserpine+

https://healthspanlife.files.wordpress.com/2009/04/reserpine_table.pdf

update:  16 Dec 2014 THE RISKS OF MODERN ANTIHYPERTENSIVE DRUGS:  Pubmed search for ANTIHYPERTENSIVE DERMATITIS REACTIONS brings up >156 papers from 1970 (on practolol, propranolol, atenolol, labetolol, hydralazine, ACEI); we first encountered practolol (BBlocker) problems  in the ’70s;  and captopril (ACEI) dermatitis about 1980; Dermatitis  has also been reported since 1987 with calcium channel blockers. WHY USE ACEI/ARBS and BETABLOCKERS -with their added airways and circulatory risks -EXCEPT AS LAST RESORT?   when these are now routinely combined with other synthetic designer drugs clopidogrel (a sulfonamide) , or /and non-sulfonamide warfarin, aspirin, other NSAIDs and statins; sulphonylureas, glitazones, which cause serious multiple complications including dermatitis.

The problematic Bblockers, ACEI, ARBs, aspirin, NSAIDs,  clopidogrel, warfarin  and  statins are rarely indicated; whereas  the hypersensitiviy  risk with thiazide (hydrochlorothiazide – a sulfonamide – halflife ~10hrs  ) PLUS AMILORIDE (halflife ~7.5hrs,  not a thiazide)  is rare;  and reserpine (not a sulfa, half-life ~10days)  actually suppresses allergic risk;

and natural extracts- fish oil, coconut oil,  vigorous vitamins B, C, D3, E, K2;   magnesium, zinc, selenium, boron, iodine,   garlic, curcumin, gymnema, metformin, reserpine, cayenne, MSM/DMSO, arginine, carnitine, ribose, CoQ10, proline, alphalipoic acid, acetylcysteine- do far more good without harm (than heavily marketed designer synthetics) in addressing the root causes of the common degenerative  diseases of aging rather than addressing just their symptoms, as drug companies do. .

Refs: 1. Immunopharmacol Immunotoxicol. 2013 :35:447-50 “Cutaneous antihypertensive adverse drug reactions (ADRs) have been frequently reported. Vena,  De Simone ea  University of Bari, Italy reported Eczematous reactions due to angiotensin-converting enzyme inhibitors ACEIs or angiotensin II receptor blockers ARBs  in 23 hypertensive patients patients aged 66-87 years; 19 of them were taking another drug in addition to the suspected antihypertensive medication and 15 were on polytherapy with three or more drugs to treat multiple comorbidities. The antihypertensive culprit agents were (ACE) inhibitors in 9 patients, ACEI combined to hydrochlorothiazide (HCT) in 7 subjects, ARBs  alone in 2 patients and associated with HCT in 5 cases. Eczema was generalized in 16 patients and localized in 7 cases, with predominant involvement of lower limbs. Such lesions developed after a latency of 4-30 months and were associated with moderate-to-severe itch, usually unresponsive to oral antihistamines. Histopathology  was spongiotic dermatitis with possible associated psoriasiform skin changes.”

2.  In the Textbook  Adverse Drug Reactions 2nd Ed by Anne Lee, Pharmaceutical press 2006,  the chapter Drug Skin Reactions exhaustively lists all causative drugs – only  reserpine/ rauwolfia is not mentioned since it prevents hypersensitivity:

  3. J Exp Med. 1985 Dec 1;162:1935-53. Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells. Mekori YA, Weitzman GL, Galli. Harvard & Tel Aviv Universities  “ reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response; findings strongly suggesting that whatever effects reserpine might have on immunologically nonspecific host cells, it’s effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo.

No recent review gives objective evidence-based opinion free of drug industry vested influence about optimal initial antihypertensive  drug therapy that contradict the above evidence.

13 December 2014: latest analyses of all antihypertensive trials confirm that LOWDOSE (potassium-sparing) diuretic- eg amilozide-   LOWDOSE reserpine, and if needed as 4th drug, calcium channel blocker eg amlodipine,  each  individually lower all major events including MORTALITY, ( and refractory lowers refractory pain).  Betablockers, ACEI and ARBs do not reduce mortality- and have major adverse effects. .

Thomopoulos ea (Univs Athens & Milan) J Hypertens Dec 2014   Effects of various classes of antihypertensive drugs on outcome incidence in hypertension, asks which  BP-lowering drug classes  are  effective in reducing MORTALITY?  In 55 RCTs (~200 000 individuals) all  common antihypertensive drugs lowered  BP , stroke,  and major cardiovascular events; but in 2014 use, only  a diuretic (even lowdose); and calcium antagonists  gave  significant reductions of all outcomes including mortality.

PAIN SUPPRESSED BY RESERPINE:    S Afr Med J. 1991;80:176-8.  Significant cost-saving with modification of antihypertensive therapy. Keeton & Monteagudo, Univ.Cape Town.    30 patients  on nifedipine for hypertension or chest pain were followed up for 6 months after alternative therapy- Reserpine combined with a thiazide- was instituted: blood pressure control improved and no serious side-effects were encountered. This  reduced the monthly cost by  73%. Although a self-assessment depression inventory was completed by 21 patients, our study does not fully evaluate the impact on quality of life. The likelihood of side-effects is  small–provided  the maximum daily dose of reserpine does not exceed 0.1 mg. A more considered approach is needed in the choice of antihypertensive agents.

Arch Inst Cardiol Mex. 1977 ;47:101-8. Prinzmetal’s angina Response to  treatment with reserpine. Review of physiopathological mechanisms. Guadalajara , Horwitz , Trevethan  present a case of Prinzmetal angina refractory to classic medical treatment, in which the angina attacks were suppressed with  reserpine .Coronary spasm due to alteration in the regulation of the coronary arterial tone from  autonomic nervous system illness is established, an abnormal coronary vascular reactivity is also reviewed. It is emphasized that Prinzmetal angina is an original entity, different from  coronary arteriosclerotic heart disease, which may coexist with it but which cannot be treated in the same way, because its physiopathologic mechanisms are different.

Cardiovasc Dis. 1974;1:194-201. PRINZMETAL ANGINA PECTORIS WITH NORMAL CORONARY ARTERIOGRAMS: EFFECT OF LONG-TERM RESERPINE TREATMENT.   Hernandez-Casas, Leachman ea . Baylor  St. Luke’s Houston, Texas

7 December 2014:  Medscape 2013 : the modern theory  Pathogenesis of essential hypertension HBP  is highly complex: Multiple factors modulate blood pressure (BP) for adequate tissue perfusion : Humoral (ie in the blood- hormonal, immune, nutritional), Vascular reactivity , Circulating blood volume, Vascular caliber, Blood viscosity, Cardiac output, Blood vessel elasticity, Neural – autonomic stimulation.                          Over the course of its natural history, essential HBP progresses from occasional to established HBP.  After a long invariably asymptomatic period, persistent HBP develops into complicated HBP, in which target organ damage to the aorta and small arteries, heart, kidneys, retina, and central nervous system is evident.

The progression of essential HBP begins with prehypertension in persons aged 10-30 years (by increased cardiac output) and then advances to early HBP in persons aged 20-40 years (increased peripheral resistance ), then to established HBP in persons aged 30-50 years, and finally to complicated HBP in persons aged 40-60 years.

Hence to prevent HBP becoming established and complicated by midlife, both the lifestyle/ nutritional factors, and the neural- stress and the RAAS renal-aldosterone- angiotensin systems – need to be optimized in young adulthood, in the early workplace  if not childhood ie at school: with reintroduction at  school of compulsory physical education/sport;  banning of  tobacco,  refined sugar  and retail salt sale; universal ingestion  3 times a week at least of a tsp of codliver oil  equivalent (before it becomes unobtainable;)  and a tblsp of virgin coconut oil; and if bloodpressure does not normalize, addition of at least 3 times a week 1/2 reserpine  ie 0,125mg and 1/2 amilozide ie 27.5mg , to address most of the risk factors, as detailed below a week ago. .

Kostis  ea, Univ Harvard; Rutgers,. Columbia,Texas, Am J Cardiol. 2014 Feb examined Competing cardiovascular and noncardiovascular risks and longevity in the Systolic Hypertension in the Elderly   Program SHEP with  chlorthalidone-based stepped care (n = 2,365) or placebo (n = 2,371) for 4.5 years,. all participants were advised to take active therapy thereafter. At the 22year follow-up,  gain in life expectancy free from CV death in the active treatment group was 145 days  ( p = 0.012). The gain in overall life expectancy was smaller (105 days)because of a 40-day (95% CI -87 to 161) decrease in survival from non-CV death. Compared with an age- and gender-matched cohort, participants had markedly higher overall life expectancy ( p = 0.00001) and greater chance of reaching the ages of 80 (81.3% vs 57.6%), 85 (58.1% vs 37.4%), 90 (30.5% vs 22.0%), 95 (11.9% vs 8.8%), and 100 years (3.7% vs 2.8%). In conclusion, Systolic Hypertension in the Elderly Program participants had higher overall life expectancy than actuarial controls and those randomized to active therapy had longer life expectancy free from CV death but had a small increase in the competing risk of non-CV death

The 2013 Statement by the International & American Societies of Hypertension( including all continents and South Africa) includes amiloride-HCTZide  ; and reserpine 0.1 mg/day in the array of drugs to be combined for optimal  BP control.  “Thiazide-like Diuretics: reduction of major cardiovascular CVD and  stroke events have been established. Main side effects are metabolic (hypokalemia, hyperglycemia, hyperuricemia), which  can be reduced by using low doses (eg, 12.5 mg or 25 mg of HCTZ) or by combining these diuretics with  potassium-sparing agents eg angiotensin-blockers, amiloride etc .    Note: Thiazides plus   b-blockers are also an effective combination for reducing blood pressure, BUT since both  increase blood glucose concentrations,  use with caution in patients at risk for diabetes.  Angiotensin-converting enzyme inhibitor ACEIs’ main side effect is cough (most common in women and in patients of Asian and  African background). Angioedema is an uncommon but potentially serious complication that can threaten airway function, and it occurs most frequently in  black patients.

Given the above -quoted longstanding established dangers of bblockers and ACEI; and that the  majority of older State chronic  patients around Cape Town are black and Asian women,  overweight hypertensive diabetic smokers, it is negligence on the part of State authorities that most State patients are treated with deleterious betablockers (atenolol), Angiotensin blockers and HCTZ ; instead of primarily with the longproven optimal lowdose reserpine, amilozide and amlodipine.

    30 Nov 2014  NEW  studies below  confirm  that the renin-angiotensin-aldosterone system RAAS  and the autonomic nervous systems ANS  are the two networks that primarily regulate bloodpressure.   In baseline treatment of common essential HBP, Increasing recent research points to the prime role of amiloride  –  thiazide combination  eg Moduretic, Amiloretic –  and arginine (nitric oxide stimulant) – addressing the RAAS;  – with reserpine  addressing the  ANS and anxiety.   

This combination overcomes much of the pathophysiology of  essential HBP ie raised cardiac output, and  aldosterone excess  sodium retention vascular load increase, potassium-magnesium wasting,  endothelial swelling ie stiffness  from low nitric oxide; vascular spasm;  and insulin resistance from aldosterone (and  thiazide and betablocker);  and counterbalances the harms of higher-dose thiazide (glucose intolerance-lipidemia, potassium-magnesium-wasting, hyperuricemia), but also avoids the numerous adverse effects of  spironolactone (a steroidal antihormone) and triamterene;

and the cardiorespiratory risks of betablockers, and ARBs. The evidence in fact supports use of amiloride lowdose preventatively in a highrisk prehypertensive population. just as the prohormone metformin is used preventatively in reversing weight gain to prevent diabetes, atheroma and PCOS inferti9lity..

refs: 1.  Nutr Hosp. 2014 Dec.   ALDOSTERONE: A CARDIOMETABOLIC RISK HORMONE?    Pereira Bressan  ea.University of Viçosa, Brazil..  Aldosterone is a component of the renin-angiotensin-aldosterone system, classically known for its role in sodium and water retention. Besides its renal effects, aldosterone is associated with the pathogenesis and progression of metabolic syndrome components. Diet can affect plasma aldosterone levels; high fructose and fat intake can lead to increased aldosterone levels, whereas the effect of sodium intake remains controversial. Adipose tissue, particularly visceral tissue, appears to produce a lipid-soluble factor that increases aldosterone production. Patients with metabolic syndrome have higher aldosterone levels; moreover, an increased cardiometabolic risk associated with insulin resistance could be partially mediated by the action of aldosterone via mineralocorticoid receptors. Even a subtle activation of this hormonal system may have deleterious effects on the glucose and lipid metabolism related to metabolic syndrome.

2. Semin Nephrol Sept  2014 . . Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels.    Judd EK1, Calhoun DA2, Warnock DG2. University of Alabama.    Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. In the absence of demonstrable renal, vascular and common endocrine causes, pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Dogma attributes increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects. However, emerging research,  has identified and defines the function of amiloride-sensitive sodium channels eNaC and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. It thus highlights the cardinal role of amilozide in hypertension therapy.

3. Pflugers Arch. 2014 Nov:  Salt controls endothelial and vascular phenotype.Kusche-Vihrog ,  Brand ea. University of Muenster,  Germany. High salt (NaCl) intake promotes  development of vascular diseases independent of  rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. We focus on  endothelial Na+ channel (EnNaC)-controlled nanomechanical properties, since high Na+ leads to an EnNaC-induced Na+-influx and subsequent stiffening of endothelial cells. Mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of arginine, direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function.

4. J Clin Hypertens (Greenwich). 2014 Jan  Epithelial sodium channel eNaC inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.   Bhagatwala , Dong  ea, Regents University, Augusta, GA.. Overactivity of epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In a nonplacebo-controlled clinical trial , the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.
5. J Hum Hypertens. 2013 Nov Diastolic blood pressure reduction ontributes more to the regression of left ventricular hypertrophy: a meta-analysis of randomized controlled trials.  Zhang  Huang ea Sun Yat-sen University, ChinaLeft ventricular hypertrophy (LVH) is an independent cardiovascular risk factor; however, the key strategy necessary for LVH regression in hypertensive patients is not clear. A meta-analysis was conducted to study the effect of blood pressure reduction on LVH regression. A total of 17 randomized controlled trials comprising 2196 hypertensive patients (mean age, 56.3 years; 64.1% were men) were identified. The most significant decrease in LVH was seen in patients with a mean age over 60 years in the DBPM10 group. The renin-angiotensin system inhibitor was found to be the most effective antihypertensive drug for LVH regression. This meta-analysis result indicates that proper DBP reduction plays an important role in the regression of echocardiographic LVH in hypertensive patients.

6. Hypertension. 2012 .Double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension. Stears, Brown ea University of Cambridge.    Hypertension guidelines advise limiting dose of thiazide diuretics and avoiding combination with β-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. . For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001).  There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or β(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.

7.   Am J Physiol Endocrinol Metab. 2008  Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.  Gunawardana , Piston ea .Vanderbilt University, Nashville, TN. Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we  demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

8.  Circulation. 1995 Comparison of five antihypertensives and placebo on nutritional-hygienic therapy in  Treatment of Mild Hypertension Study (TOMHS). Liebson, Stamler ea . St Luke’s Medical Center, Chicago, in a double-blind, placebo-RCT  of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five  antihypertensive agents: (1) thiazide (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin), (4) calcium antagonist (amlodipine ), or (5) ACEI (enalapril).  Changes in BP averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that continued for 48 months.  chlorthalidone  caused the greatest decrease in LVM at each follow-up visit (average decrease, 34 g),  (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). 

9.  Arch Intern Med. 1981  Multiclinic comparison of amiloride, hydrochlorothiazide, and hydrochlorothiazide plus amiloride in essential hypertension. Multicenter Diuretic Cooperative Study Group.   [No authors listed}  A randomized, double-blind, multicenter study comparing amiloride hydrochloride, amiloride hydrochloride plus HCTZ, and HCTZwas conducted in 179 patients with mild to moderate essential hypertension (diastolic pressure, 95 to 115 mm Hg). After 12 weeks of treatment, significant reductions in pressure were observed for all three treatment groups. Systolic pressure reduction was greatest for amiloride plus hydrochlorothiazide. Baseline vs 12-week average supine pressures were 153/101 vs 139/93ie -14/8 mm Hg for amiloride, 160/100 vs 137/90 ie -23/10mm Hg for amiloride plus HCTZ, and 154/101 vs 134/89 ie -20/12mm Hg for HCTZ. Baseline vs treatment mean serum potassium levels were 4.24 vs 4.47 mEq/L for amiloride, 4.24 vs 3.86 mEq/L for the combination, and 4.15 vs 3.56 mEq/L for HCTZ. The changes in serum potassium level from the baseline for amiloride plus HCTZ were significantly different from those for HCTZ throughout the study (except for week 6). All drugs were well tolerated, and no drug-related toxic reaction was detected. This study demonstrates the efficacy of amiloride and amiloride plus HCTZ as diuretic antihypertensive potassium-conserving agents.

27 Nov 2014 THE IMPORTANCE OF NORMALIZING RESISTANT HYPERTENSION : THE ALLHAT TRIAL Furberg ea  December  2002 was the biggest  trial that compared a thiazide with other standard antihypertensive drugs in highrisk patients, and confirmed thiazide’s  superiority over amlodipine, lisinopril, and especially doxazosin. This was confirmed in the smaller shorter CONVINCE multinational trial Black ea a few months later, which showed that as single therapy, verapamil was inferior to a thiazide or atenolol.

The latest report of the landmark  5 year USA ALLHAT trial by Munter ea  now reports  on apparent   Treatment-resistant hypertension aTRH  and the incidence of cardiovascular disease and end-stage renal disease: “These results demonstrate that aTRH increases the risk for cardiovascular disease by almost 50%, doubled end-stage renal disease, and increased all-cause mortality- heart and peripheral circulatory failure  – by 30%. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14684 (ALLHAT) participants to determine association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined  Apparent treatment-resistant hypertension aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002.

24 Nov 2014  NOTE  how Big Pharma has lied in corrupting the Wikipedia section (in italics below)  on reserpine so as to try to further sideline this excellent natural drug: the adverse  highlights below  in red are based on ancient data from when Reserpine  was used decades ago in the West in 5 to 50 times higher doses than have been used without adverse effects in trials the past  20 years, and for centuries in India as the parent Rauwolfia:

Reserpine:because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.Nonsense. This ignores the numerous side-effects of betablockers, ACEI, ARBs and CCBs other than amlodipine.  The reserpine-induced depression is considered by some researchers to be a myth, while others claim that teas made out of the plant roots containing ie lowdose reserpine has a calming, sedative action that can actually be considered antidepressant.[4] Notably, reserpine was the first compound shown to be an effective antidepressant in a randomized placebo-controlled trial.[5]      It may take the body days to weeks to replenish the depleted VMAT, so reserpine’s effects are long-lasting- a major advantage if patients take drugs irregularly. Tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine.[8]

This depletion of dopamine can lead with reserpine overdose to drug-induced parkinsonism. THIS IS ONLY IN EXCESSIVE RESERPINE DOSE.  Reserpine has been discontinued in the UK for some years due to its numerous interactions and side effects. nonsense it was discontinued to protect Big Pharma newer antihypertensive drugs eg  Cardura, metoprolol, lisinopril; ARBs, Exforge etc .

“THE Reserpine-THIAZIDE  COMBINATION (WITH OR WITHOUT OTHER OLD DRUGS EG POTASSIUM-SPARERS AND HYDRALAZINE)  is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality:

“The Hypertension Detection and Follow-up Program,[14] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,[15] , the Systolic Hypertension in the Elderly Program, and now the Chinese reserpine trial 2011- which outstanding results  the Wiki article  doesnt bother to  mention. .

Reserpine is rarely used in the management of hypertension today. NONSENSE – that is merely the explicit wish and intent of Big Pharma.  Reserpine is listed as an option by the JNC 7.[17] Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.[18]   The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25 mg – IN FACT 0.0625 t0 0,125MG/dAt doses of less than 0.2 mg/day, reserpine has few side effects, the most common of which is nasal congestion- SO WE NEVER PERSIST WITH  above 0.125mg/d

ONLY IN GROSS OVERDOSE:”There has been much concern about  Reserpine causing: depression leading to suicide; nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration , stomach cramps,diarrhea.. . hypotension, bradycardia; Congested nose,erectile dysfunction drowsiness, dizziness,.. nightmares. Parkinsonism … General weakness, fatigue … may worsen asthma ; hyperprolactinemia… dangerous decline in blood pressure at doses needed for treatment. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. . The above litany conveniently omits that these problems were reported in uncontrolled studies using reserpine doses averaging 0.5+ mg per day.[22][23] they do not occur at effective  low antihypertensive reserpine dose combined with lowdose diuretic. “

Nine years ago we reviewed in the BMJ  why reserpine plus thiazide is  The best-proven two-drug hypertension regime in primary care,

update 20 Nov 2014  the Sept  2014 influential French review Prescrire Int reviews the available evidence Treating essential hypertension- As in 2004, the first choice is usually a thiazide diuretic TZD  .. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/90-100  mmHg. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. systematic  meta-analyses of  tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose TZDs and angiotensin-converting enzyme (ACEI) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevent  about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Systematic reviews conclude that neither calcium-channel blockers CCBs, ACEI nor beta-blockers BBs are more effective than thiazide diuretics TZDs  in reducing mortality or the incidence of stroke. The efficacy of the TZD chlorthalidone is supported by the highest-level evidence, three comparative clinical trials versus placebo, an ACEI, or a CCB, in more than 50 000 patients. In one of these trials, chlorthalidone was superior to the ACEI lisinoprilin preventing stroke; and  to the CCB amlodipine in preventing heart failure. The effect of hydrochlorothiazide HCTZ , combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, BBs, or a CCBHCTZ appeared more effective than the BB atenolol in reducing the incidence of coronary events.  Indapamide another TZD is less convincing that it is more effective than chlortalidone or HCTZ. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As in 2004, in 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be a thiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACEI: captopril, lisinopril or ramipril.

But TZDiuretic halflife is at best 15hrs (HCTZ); and for smoother hypertension control they need to be gentle and not major diuresis-inducing,  so that they do not disturb sleep or daytime function. and TZDs dont damp down compensatory heart speedup and arrhythmia, or lipidemia-hyperglycemia- which reserpine does. and lowdose reserpine doesnt cause the cough or breathlessness that ACEI, ARBs or BBs may.

This review needs to be read with Shamon & Perez‘  2009 University of British Columbia Canadian Cochrane report : the first systematic review of reserpine for essential hypertension  “Many antihypertensive agents exist today for primary hypertension (systolic blood pressure >/=140 mmHg and/or diastolic blood pressure >/=90 mmHg).  Reserpine was  a second-line therapy in some of those trials.   Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with hypertension.  MAIN RESULTS: Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction on reserpine compared to placebo (WMD –8mm, 95% CI -14.05, -1.78).   None of the included trials reported withdrawals due to adverse effects.   AUTHORS’ CONCLUSIONS: Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. But this analysis is outdated because it has long been common cause that  the best firstline treatment of hypertension is the balanced combination of reserpine with a potassium-sparing diuretic.

Lowdose Reserpine is the sole anxiolytic antidepressant antipsychotic antiserotoninergic antihypertensive drug that lasts, acts  for weeks  rather than days (amlodipine) or  hours (the TDZs, ACEI, ARBs)- and has no adverse effects; so it doesnt matter when it is taken;  when stopped, it takes weeks for it to completely wear off. And severe stress anxiety insomnia is so often a major component of severe essential hypertension. “Reserpine is an ancient tranquilizer, derived from a plant used in India for centuries. It has a powerful tranquilizing action, has been used to treat hypertension, and was found to be an antidepressant (Davies and Shepherd, 1955)”

Hence combining lowdose eg 0.125mg/d or less reserpine – even 3 days a week ie 0.05mg/d-  with amilozide 13-27mg/d as a morning or midday  dose  is ideal- especially when nighttime systolic hypertensionNSBP  is the strongest predictor of CVEs cardiovascular events, as shown in a new international study in Europe, Brazil, and Japan by Universities of USA, UK and Europe:  Roush, Zamalloa ea The ABC-H Investigators ; Journal of Hypertension (Oct 2014)   Prognostic impact from clinic, daytime, and night-time systolic blood pressure NSBP in nine cohorts of 13 844 patients with hypertension;     To determine which SBP measure best predicts cardiovascular events (CVEs- coronary artery disease CAD and stroke) independently, systematic review was conducted for all patients with hypertension,>1+ years follow-up..   Nine cohorts (n = 13 844) were from Europe, Brazil, and Japan. Results: Overall, NSBP’s dispersion exceeded DaySBP’s dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for ClinicSBP and DSBP ( P = 0.004)  Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP:  In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely. This trial confirms the 2012 Hosomi ea Japanese trial showing that to minimize (repeat) stroke from night BP variance, Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.

Weiss’s Herbal Medicine  2001 pp 151-157 reviews why lowdose reserpine/rauwolfia is the prime baseline antihypertensive, via the central especially  autonomic nervous system as a major anxiolytic.

There is no evidence in chronic treatment of common essential hypertension to justify loop diuretics eg furosemide , as is common practice locally. .

update 12 Oct 2014     For the past decade we have advocated  for uncomplicated patients the gold-standard evidence-based combination of reserpine  0.0625 to 0.125 mg with  1/4  Amilozide (ie hydrochlorothiazide  HCTZ 12,5mg and amiloride 1.25mg) ie HAR daily as the most cost-efficient baseline treatment of hypertension.    Sometimes patients require the lower doses 1/4 tab each reserpine and Amiloretic 55mg) only 3 times a week for good control once on some cod liver oil, coconut oil and multivite-multimineral  to reverse arteriosclerosis, insulin resistance, reactive oxygen species,  and promote nitric oxide.

For more resistant cases we add  dihydralazine 25 mg/d or amlodipine 5 to 10mg as add-ons if required  – if necessary both-  occasionally for optimal HBP control around 120  to 130 systolic (the new international  Guideline target). With this regime of up to five drugs all more than 40 years in use, for hypertension we rarely find need to add the more costly / troublesome old eg methyldopa, or betablockers, spironolactone,   or new eg ACEI or ARBs ,  with   their  cardio-respiratory risks that are so rare with the  multi-low dose reserpine- amilozide- amlodipine- dihydralizane  combination.

There are now 250 000 antihypertensive drug studies on Pubmed since 1947.

 The latest  and definitive study  published on reserpine for HBP in Clin Drug Investig. 2011;31:769-77 is   Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China a  massive  3 year (4500 patient-years) study  by  Wu Y, Li L. ea of   Peking University Health Science Center, China   .  A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide  HCTZ 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and  reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although used in China for more than 30 years, there have been few comprehensive evaluations of this treatment.          METHODS  open-label surveillance study in Shanghai in local primary healthcare settings. Subjects  with  essential hypertension, aged ≥35 years at the time of enrolment. Patients with secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional HCTZ was added. Blood pressure (BP) was measured every 3 months.    RESULTS: A total of 1529 patients (65%  female; mean age 65.7 years) entered the study with mean BP 149/89. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipids, uric acid and potassium improved.                                                               CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

The mean  15/10  BP lowering  from a mean baseline BP of 149/89 after 3 years of the four-drug Chinese combination  in China   compares  starkly with the mean ~51/30 mm Hg lowering (from untreated HBP of 200/120 down to ~149/90)  over 4 months reported  below  by Alan Taylor in his 1989 thesis study in local rural Africans with similar doses of reserpine, HCTZ and dihydralazine- Taylor’s study achieving in rural Blacks  in 4 months the starting BP of the Chinese some 25 years later.  But  the long Chinese study speaks to to the tolerance of the HTDR combination.

The China reserpine study  of 1500 pts, 4500 pt years, strongly complements the ~13 trials  of reserpine   between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials)  in 7500 patients for 1 to 3 years;   showing that low dose reserpine (and lowdose  thiazide ) together are  as good as or better than all more modern drugs- especially when augmented by amiloride.

(As Prof YK Seedat reported  here  in 2000), the China   paper reports zero noteworthy dihydralazine  risks at 12.5mg/d :     J Hum Hypertens. 2000 ;14:739-47. Hypertension in developing nations in sub-Saharan Africa. Seedat YK. University of Natal,  South Africa.  There is a rapid development of  ‘second wave epidemic’ of cardiovascular disease that is now flowing through developing countries and the former socialist republics. It is now evident from WHO data that coronary heart disease and cerebrovascular disease are increasing so rapidly that they will rank No. 1 and No. 5 respectively as causes of global burden by the year 2020. In spite of the current low prevalence of hypertensive subjects in some countries, the total number of hypertensive subjects in the developing world is high, and a cost-analysis of possible antihypertensive drug treatment indicates that developing countries cannot afford the same treatment as developed countries. Control of hypertension in the USA is only 20% (blood pressure <140/90 mm Hg). In Africa only 5-10% have a blood pressure control of hypertension of <140/90 mm Hg. There are varying responses to antihypertensive therapy in black hypertensive patients. Black patients respond well to thiazide diuretics, calcium channel blockers vasodilators like alpha-blockers, hydralazine, reserpine and poorly to beta-blockers, angiotensin-converting enzyme inhibitors and All receptor antagonists unless they are combined with a diuretic.  There are social, economic, cultural factors which impair control of hypertension in developing countries. Hypertension control is ideally suited to the initial component on an integrated CVD control programme which has to be implemented.  The existing health care infrastructure needs to be orientated to meet the emerging challenge of CVD, while empowering the community through health education.

Interestingly, a new  metaanalysis of HCTZ trials  by Musini ea Cochrane Database Syst Rev. 2014 May   Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. shows that BP lowering  over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews. 

2009:     ABSTRACT: When modern antihypertensive drugs cost far more than the old and tried, and have around 40% risk of adverse effects (Girerd 2002 Paris),  and give inferior risk reduction, it is unethical for routine hypertension patients initially to  be  prescribed modern drugs singly or in combination in uncomplicated cases before trying the gold standard old risk-free lowdose reserpine-amilozide combination.

2009 has been a landmark year of published studies on first-line  hypertension treatment.

IT IS COMMON CAUSE THAT:

i. hypertension  (with or without overweight- excessive waist girth) is today the commonest presenting, simply detectable, monitorable and controllable chronic lifestyle degenerative disease;

ii. the bedrock prevention and therapy  of essential hypertension is  public- patient  education – exercise, stopping smoking,  and minimizing salt (since 1904) , sugar, alcohol and cooked fat intake so as to reduce overweight;

iii. genetics and the above risk factors aside, three  of the primary “endogenous”  and easily correctable causes of essential hypertension are water deficiency; marine omega3 (EPA eicosapentanoic and DHA docosahexanoic acid) deficiency; and insulin resistance if not frank adiposity/overweight and diabetes.

So adequate water intake, and fish oil, and metformin/galega to tolerance, (in appropriate adipose/overweight  cases) are cornerstones of antihypertensive therapy along with diet and lifestyle changes before any antihypertensive drugs are added.

Recently there have been contentious suggestion  (eg Law and Ward UK 2009)  that target bloodpressure should be that of youth- 120/70 down to 100/60 – as long as it does not fall so low that the patient gets dizzy on standing up. But the non-contentious gold standard remains  that no one should be left with bloodpressure above at most 140/90 sitting.

ANTIHYPERTENSIVE DRUGS: There are over 34 000 RCTs, reviews and metaanalyses  (since 1965) on Pubmed on these drugs.

Controlling   hypertension asymptomatically  before it causes damage and symptoms is the heart of successful prevention.

It is now claimed  that hypertension risk starts as low as >120/70, that we should be targeting this level if tolerated.

This can only be done gently and slowly, if possible by optimising diet , lifestyle and natural supplements.

But prevention in asymptomatic patients must especially be at most a once-a-day regime, and avoid causing symptoms, and still give stable cover even if taken erratically. Only reserpine provides gentle cover lasting weeks, thus avoiding wide BP variation due to erratic dosing.

Apart from the notorious adverse effects of the older antihypertensives like guanethidine, methyldopa and atenolol, search of Pubmed under  ‘ARBs, ACEI Cough;’ and under metaanalysis ‘antihypertensive cough’  with the established drugs, reveals 10 abstracts since the mid 1990s.

The nub of the matter is, the lowest-cost multiple-combination therapy (lowdose reserpine -amiloride – hydrochlorothiazide) gives the best bloodpressure and risk reduction with zero adverse effects – especially when combined with probably the best pluripotential drug of all,  fish oil..   A new Cochrane metaanalysis from Univ Brit Columbia confirms that lowdose thiazide gives the best reduction of all antihypertensives in both all-morbidity and mortality outcomes -RR 0.89 (CI 0.82-0.97, p=0.0067 = highly significant) . And that metaanalysis didn’t deign to mention reserpine in the abstract.

There are at least a dozen trials each of reserpine and thiazide  showing that they are the best,  ideally in lowdose combination .   As always, one fixed-dose combination pill (eg Brinerdin, Rautrax Imp) may work for many. But it is both cheaper, more efficient and scientific to prescribe the components separately so that reserpine and amilozide can  each be titrated individually to tolerance, starting with eg reserpine (0.25mg tab ) 1/4/day and amilozide (55mg tab) 1/4 a day (costing locally retail  perhaps US$0.5/month, $6/year) …

In some patients eventually this dose 3 days a week is all that is needed. With sensible advice about omitting sugar and smoking, and minimal alcohol, salt and cooked fats, and adding a multinutrient including magnesium, vitamins and the many favourable biologicals (including appropriate physiological sexhormone replacement), few patients need more than 1/2 a tab each of reserpine and amilozide for optimal BP and metabolic-vascular risk control. In the rare still- resistant cases, amlodipine is the next safest effective antihypertensive  drug to add, starting with 2.5mg/d. But of course in those with insulin resistance (ie most cases), metformin is the most appropriate pluripotential drug.

Yet no trial has shown  lower cost, and better superiority and safety  of any modern-drug  or combination over the triple-combination  lowdose amilothiazide (thiazide since 1956, amiloride since 1967)  with  lowdose reserpine (from the ages-old rauwolfia – extracted  as reserpine since 1949). Since the German Reserpine trials, and results of ALLHAT and SHEP showing that reserpine as add-on gave  by far the best clinical outcomes, no head-on trials against modern drugs dare be done by drug companies or the clinicians they employ.

Over a year ago this column   reviewed that fifty year old treatments of overweight -hypertension – diabetes are still best, echoing an SAMJ analysis 24 years ago of New antihypertensive drugs–blessing or costly nemesis? .

In 1989 pharmacist Alan Taylor published his MPharm thesis (Rhodes University)  on Cost Effective Antihypertensive Therapy at A Day Hospital. – showing in a prospective randomized controlled trial for 4 months that stepped outpatient care (starting with a mean untreated BP of about 200/120) achieved the target BP ( then <165/95) in 73% compared to 11.5% on individualized treatment, and with a cost saving of 36%, with somewhat lower incidence of side effects. Hydrochlorothiazide HCT 12.5 to 25mg/d was the first step;  methyldopa 250-500mg/d or reserpine  0.1mg/d  as the 2nd; hydralazine 10-50mg/d  low dose as the 3rd, alternatively atenolol  100mg as the 3rd or 4th step. Individualized treatment reduced bloodpressure by a mean  32.6/19 whereas stepped-care did so by 51.6/29.5mm Hg.. The HCT-Reserpine- Hydralazine-atenolol regime was the most frequently prescribed (in 61.6%),

Obviously today methyldopa, hydralazine  and atenolol have become last-ditch add-ons, with amlodipine being the 1st- choice 4th drug to add to reserpine and amilozide. ,

and  in 2007 Rayner, Blockman ea from the Hypertension Clinic    at Groote Schuur Hospital found that at two community  health clinics  in Cape Town, only 40% of patients achieved a bloodpressure below 140/90, on a mean of 2.4 drugs per patient   – clinics where reserpine and amilozide were unwisely  removed from the available drug list years ago, for no plausible reason, leaving hydrochlorothiazide, atenolol, hydralazine and amlodipine as the choices- with invariably poor results in poor patients attending such free clinics.

MODERN DRUGS?  But why should patients be subjected to the multiple and indisputable major risks of modern antihypertensive drugs compared to the gold standard lowdose reserpine and low dose amilozide?

eg

ABs angiontensin blockers – ACEI agiotensin converting enyme inhibitors and ARBs angiotensin receptor blockers like enalapril, candesarten  – pervasive cough, rashes, but far worse, lifethreatening angiodema, asphyxiation, skin sloughing; and now well-recognized acute or slowly progressive loss of kidney function- which doesnt always reverse on stopping the drug (Onuigbu ea  2008, 2009); Suissa ea  2006 at McGill University published the first major longterm – > 10year- followup (1982-1997)  of hypertensive diabetes patients, showing that compared to thiazide, only  ACEI increased the risk of endstage kidney failure 4.2 fold.

betablockers like atenolol, metoprolol – too slow heart rate, cold extremities, more depression, impotence,  asthma, glucose intolerance/ diabetes, heart failure, deaths;

and even calcium channel blockers -the gold standard of which is amlodiopine- have a formidable list of potential adverse effects (that lowdose reserpine and amilozide lack), of which some may be major nuisance if not dangerous eg (from the Sandoz product sheet): Often: dizziness; palpitations; muscle-, stomach– or headache; dyspepsia; nausea – in 1 in 100 users; Sometimes: blood disorders, gynecomastia, impotence, depression, insomnia, tachycardia – in 1 in 1,000 users;  erratic behavior, hepatitis, jaundice – in 1 in 10,000 users; Very rarely: hyperglycemia, tremor, Stevens-Johnson syndrome – in 1 in 100,000 users. ”

From the trials and experience, lowdose amlodipine is certainly the modern drug of choice to add if counselling plus ceiling doses of reserpine and amilozide, plus fish oil plus  metformin for underlying adiposity/insulin resistance,  do not adequately control hypertension and other risk factors.

Why use modern drugs with their major potential hazards  except for special circumstances last ditch?; when lowdose reserpine plus lowdose amilozide titrated to best effect rarely need a 4th drug added for good BP control;  and practically – unlike methyldopa, guanethidine and more modern drugs-  never causes persisting symptoms.

THIAZIDE ADVERSE EFFECT possible in even very low dose: anaphylaxis: Goetschalckx ea in 2007 could find exactly 49 case reports of allergic thiazide-induced pulmonary oedema in the literature after 50 years of use ie millions of patient-years. Thiazides are obviously sulphonamides, but fortunately serious- anaphylactic- reactions like lupus vascullitis and shock – are extremely rare. Wikipedia does not even mention these under thiazides, and no abstracts on Pubmed even guess at their rare  incidence. 50 cases in at least 10million patient years is an incidence of below 5 per million.

RESERPINE:   In 2007 Jos Barzilay ea documented Getting to goal blood pressure: why reserpine deserves a second look.

We last year examined closely the trials on thiazides and reserpine 1, 23.

and we published on line the only ever tabulation of all accessible trials  of thiazides and reserpine, showing in the ~12 thiazide trials between 1985 (the UK MRC trial)  and 2003 (the CONVINCE trial) that  in 115000 patients for a mean of 4 years,  thiazide is as good as or better than all more modern drugs;

and that reserpine in ~13 trials between 1977 (the Veterans’ Admin trial) and 1997(the German reserpine research group trials)  in 7500 patients for 1 to 3 years is as good as or better than all more modern drugs. Of course  the 2003 ALLHAT  and CONVINCE papers were by far the biggest trials validating thiazide as the gold standard in 50 000 patients for  3 and 5 years respectively;

and the VA trials of 1977, 1982 and  and 1990 in 1479 patients showing reserpine as equal or superior to betablockers,  and the German trials of 1997  in 400 patients (Griebenow, Pittrow ea 1997) validating reserpine as equivalent to thiazide or a CCB, and the combination of thiazide and reserpine superior to an ACEI.

Now in 2009:

Shamon ea’s Cochrane review last month confirms that reserpine  alone is at least equivalent  in antihypertensive effect to any  modern first line antihypertensive alone ;

Wald and Law’s metanalysis of single or combination antihypertensives confirms that  “The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.”

Wright ea’s Cochrane review confirms that

“thiazides reduce all-cause mortality by 11%;   Low-dose thiazides (8 RCTs) reduced CHD  by 28%;

Beta-blockers and CCB reduced stroke by 17% and 42%, but not CHD  or mortality .        ACE inhibitors reduced mortality 17%; stroke  35%.

No RCTs were found for ARBs or alpha-blockers.”

However, that abstract does not enumerate the major adverse effects of betablockers and ABs.

Wright ea’s   ALLHAT reanalysis confirms that thiazide was superior to the ACEI, CCB, betablocker and especially the alphablocker doxazocin. neither alpha-blockers, ACEI nor CCBs  surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF. new-onset DM associated with thiazides does not increase CVD outcomes.”

Costanzo ea’s Italian study confirms that CCBs reduce the risk of stroke by 14% compared to ACEI; reduce allcause mortality by a trivial 4%; increase heart failure by 17% compared with ‘active’ treatment;

Hoffman ea’s review from New York confirms that, in autopsies of Alzheimer cases, those on antihypertensives had far less plaques that those without hypertension.

Sozen ea confirms that “ABs- Drugs with blocking effects on the renin-angiotensin-aldosterone system –  do not improve endothelial dysfunction long-term in hypertensive patients”.

Mackenzie ea’s Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension shows that central Pulse Pressure was only reduced significantly by perindopril, lercanidipine, and bendrofluazide, whereas atenolol had no effect. Lercanidipine reduced the augmentation index, whereas atenolol increased it. Aortic pulse wave velocity was not changed by any of the drugs. In summary, despite similar reductions in peripheral systolic and PPs with the 4 classes of drug, changes in central pressure and augmentation index varied. Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension, the choice of therapy may be influenced by these findings in the future.”

Landmark’s Norwegian abstract confirms that thiazides (and betablockers)  increase insulin resistance and blood glucose risk (let alone lipidemia), but simply – selectively- as usual ignores that neither lowdose amilozide nor reserpine do this.

Nothing illustrates better why the triple combination of amilozide and reserpine is the best.

It has previously been pointed out that in the long term Cache County study, potassium-sparing diuretic was the only antihypertensive that lowered- in fact by 75% – the incidence of new Alzheimers disease;  and amilozide-like combinations are more effective than either component alone in safely and effectively lowering hypertension. – Patterson Dollery & Haslam in 1968; Rosenfeld in 1980; and the Multicenter Diuretic Cooperative Study Group in 1981.

CONCLUSION:  Reserpine has indisputable central and peripheral benefits in lowering central pressure via peripheral vasodilation, and via mild lowering of anxiety, cardiac rate and cardiac output; while thiazide and amiloride both lower both excessive body salt and water, while thiazide vasodilates and conserves calcium,  and amiloride  reverses the  potassium -magnesium depletion  seen in hypertension and with thiazide. .

Since the lowdose combination of reserpine and amilozide is superior to all other first-line drugs alone or in combination, and retail costs about   US$1 a month in South Africa, (with negligible adverse effects compared to all other antihypertensive drugs), this combination is the mandatory  firstline therapy for all  hypertensive patients, with rare exceptions. This regime  starts with amilozide 13.75mg (1/4 tab) and reserpine 0.0625mg (1/4tab) /d- and many patients can eventually be controlled with these doses just 3 days a week; with other antihypertensives added only if hypertension is not controlled with these increased to the ceiling tolerated eg of amilozide 27.5mg/d and reserpine 0.125 mg/d (maximum reserpine 0.25 mg 5/week ie 0.18mg/d if tolerated).

Since roleplayers are there to serve patients, not the Drug and Disease Industry, all roleplayers ( National Hypertension societies, provincial and national health and medical school authorities, medical schemes and all health practitioners)  have no choice but to obey the gold-evidence-based medicine set out herein, and reinstate reserpine and amilozide as mandatory 1st-line therapy of essential hypertension, with motivation  for alternatives to be provided in the  exceptional cases.

Unlike the USA and the East  where reserpine is still in national recommendations,  Authorities, regulators, suppliers and prescribers  in South Africa, Australia, the UK and Europe can no longer continue to defraud the public and deny patients this best treatment, since the two tablets (cheap amilozide and reserpine) are freely and universally available for  at most the retail South African prices quoted (less in bulk buy).

There is no shortage of reserpine, HCT or amiloride;  and the evidence for them over all modern antihypertensives  is binding under  rules of evidence and therefore medical ethics. The current evidence discussed shows that this  old lowdose combination is superior to all modern drugs and modern marketted combinations in both reduction of all-cause endpoints, adverse effects, and cost.

As Henry Black said recently, triple antihypertensive therapy is simply Back to the Past – and it can be both very low cost and risk-free..

And if proof is wanted, we must agree on a simple long term multicentre trial of the lowdose reserpine-amiloretic regime versus modern marketed combinations.- as in  ALLHAT but comparing combinations..But who is to pay for yet another trial to prove what is already so well proven?

35 years after Illich’s Medical Nemesis, it is very sad to have to be fighting overwhelming profiteering vested interests for what is now by far the commonest and most easily correctable major common degenerative disease – mild to moderate hypertension.

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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  .

TOURISM HEALTH: SAFARI HEALTHSPANLIFE HEALING CAPE TOWN HOLIDAY 2013.

Health- slante, l’chaim!, hayah, sawubona! – in any country or language  is a blessing, a gift- not a right. It is insurance that has to be planned and enforced. Leaving it to fate, illness and hoping for a cure is often too late, sometimes crippling if not often  fatal. With comprehensive natural supplements, we can and should all die peacefully at an  active fit advanced  age  90years +  –   not old, incapacitated and demented. We owe this prevention to both ourselves, our  kids and our aging seniors.

So sensible lifestyle aside, promoting health  includes simple low-cost  (no-xray/no-laboratory) periodic screening:  for all,  from childhood:  of weight,  girth, eyes, teeth, bloodpressure, brainfunction- memory; and ultrasound bones – at any pharmacy/ optometrist, school or clinic;                         and  for women:  checking the breasts and pelvis for risk of  cancer.

The HealthSpanLife  South African Natural Medicine Clinic SANMC next to Cavendish Mall on the slopes of Table Mountain in beautiful Cape Town – one of the favourite world tourist  and heritage centres-  is a specialist clinic  staffed by experienced  registered professional practitioners- a medical internist specialist  (also UK registered);  a homeopath;  and a Muslim nursing sister.

It provides  one-stop holistic screening and diagnostics, and – uniquely-  evidence-based  natural remedies- nutritional support for all symptoms and chronic conditions-  also  for menopause-andropause-genitourinary- breast-sexual dysfunction- obesity-pain/headache –chiropractic  and detox ,

as well as if needed  appropriate modern specialized  testing and prescription medicines for all chronic major conditions including bio-identical hormone replacement for both genders (including implants);

and integrated referrals nearby (and in Gauteng)  as patients desire eg for autism, acupuncture, aromatherapy, physiotherapy, aquarobics,  advanced scopes, delicate restorative micro (eg hands, toes)-as well as major (eg bariatric, spinal,eye-, ear- neuro-)  surgery, infertility, xray/other scans, cancer, hyperbaric oxygen, spiritual intervention, psychiatric-hypno- therapy, and eg genetic profiling and counselling,   dialysis and transplantation, and stem cell therapy. …

Gentle Non-xray  ultrasound bone-density measurement (recommended by Cape Town , UK, and USA universities),  and tactile mechanical breast mapping (recommended by CANSA, UK, USA, Indian and Chinese studies) are available at SANMC (and in Gauteng) by appointment, and are covered by some medical aid plans;  whereas menopause consultations are covered by all open plans.

As typified by a new review last month,    World opinion is to use xray  mammography and  xray bone density imaging  only as last resort and only  in the elderly – or in staging those with breast cancer- because of the major problems and risks of xray imaging..   As world experts Profs Cornelia Baines epidemiologist in Canada, Mike Baum breast surgeon  in London and Peter Gotzsche epidemiologist  in Denmark  say,  there never has been any independent scientific evidence to support hazardous routine mass mammography crush xray screening of well women, let alone any repeated mass xray screening for decades, or the dangerous fictitious marketing hype of the American radiology-Breast Surgeons and Curves International nonsense  that xray mammo screening saves lives ..

While health tariffs must rise with inflation,  where med aid doesn’t cover, New Year 15% discount applies through January on cash-paid clinic services and in-house products. . .

For out-of-town/ overseas  visitors, accommodation and travel locally and throughout Africa and beyond can be arranged by outside experts around  clinic appointments. .  http://www.capetown.gov.za/en/visiting/Pages/default.aspx

For appointments visit  the SANMC at 1st floor no.  15 Grove Medical Bldg on Pearce St  cnr Grove Ave (parking opposite at ABSA on Grove);    or  phone +2721-6831465/  -6717415; or fax  +27865657215; or email the manageress, doctors or Sister at   sales@healthspanlife.co.za  to discuss needs,  timing and preliminary costing. For details, references  and rationale for screening and prevention,  see https://healthspanlife.wordpress.com/?s=screening.

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 HOURSby 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.

SIMPLE SAFE LOWCOST RISK MEASUREMENT AND CORRECTION: THE SOCIOECONOMIC IMPACT OF OSTEOPOROSIS

  neil.burman@gmail.com

Already just since April 2010, Pubmed (the on-line catalogue of peer-reviewed medical journal papers)  reveals four reviews – from USA, Mexico, Ireland and Cambridge UK-  on the huge socioeconomic impact of neglect  of long-available safe cheap measurement  and prevention of osteoporosis in aging populations. Especially that osteoporosis is underdiagnosed, and hence the need for improved use of diagnosis screening and preventatives.

And another study  from France reviews the deadly potential cutaneous (let alone gastrointestinal and other) risks of bisphosphonate and strontium drugs  prescribed for osteoporosis . Their  risk of serious adverse effects  may be <1:10 000 – but no study has ever been done comparing such $billion raincheck designer drugs with simple balanced lowcost safe combination of the score of natural supplements (some 7 vitamins, about 8 minerals and 5 human biologicals- costing as little as about US$10 a month) that are proven to prevent and heal osteoporosis let alone have major benefit on most major chronic diseases. .

The analogy is so simple- one does not treat :

anything but major pain with opioids or risky non-steroidal drugs  (or a sore throat with antibiotics) when simple safe modest-dose non-addictive analgesics and local therapy suffice; or

overweight,  or type 2 diabetes , or common mild to moderate hypercholesterolemia with any designer drug but metformin until control (with diet, lifestyle, supplements including metformin and appropriate other hormone adjustments)  is no longer good enough; or

 mild to moderate  hypertension requiring drug therapy with anything but perfectly safe lowdose reserpine plus lowdose amilozide – which suffice in almost 90% of mild to moderate cases- when more modern designer drugs (eg betablockers, angiotensin-converting – enzyme inhibitors and even the older methyldopa and calcium channel blockers) and newer drugs  both have infrequent but serious adverse effects, and are   less effective (they do not have the long duration and safety record of reserpine plus amilozide that makes it so effective even with erratic use) .

The socioeconomic model that measures the impact of a therapy only on one disease eg osteoporosis obviously also by intent supports the global profiteering and job-creation interests of Big Pharma and their well-rewarded allies – Government, Regulators, Universities, Research, Corporations and private practice. For these big-money industries, the use of a safe shotgun of unpatented and nonprescription supplements that more than halves the incidence, premature disability and mortality of both fractures AND all the common major aging degenerative diseases is anathema, since it reduces the Aging Diseases Industry from a $trillion goldmine in the aging who still vote, travel and earn, to a $billion expense when it matters far less- in the very old.

Hence Big Pharma is fighting a global war to abolish free choice of foodstuffs and supplements, conspire with governments to dictate what sources of foodstuffs must be eaten, and put all micronutrient supplement under doctors’ prescription! and above all else, suppress comparisons of designer prescription drugs with the gold standard old drugs and highly effective safe combinations of supplements.

This column has regularly published the growing irrefutable proof that high technology appliances and drugs are simply not needed to measure, prevent and treat common fragility fracture risk or any of the associated linked common chronic degenerative aging diseases.

And Guglielmi ea from Italian and Singapore Universities recently published another landmark review  confirming the voluminous evidence,  recent reviews from UK, that quantitative ultrasound QUS scan has replaced Dual Xray DXA bone mass density BMD  scan as the goldstandard fracture risk measurement test in common practice . Portable lowcost and therefore far more widely available QUS avoids the irradiation risk of costly centralized DXA, and the increasing overreading of bone density and hence risk score with aging due to accumulating calcification over the lower spine and hips.

It is of course intuitively and logically obvious that QUS devices that fix the target bone at a standardized site between the QUS heads as with eg the heelbone in eg the Norland CUBA footbox will eliminate most performer technique variation with a manually moved contact as in eg the Sunlight Beammed system.

Southampton University UK has also just published a study showing good correlation between peripheral QUS measurement and direct bone density measurement of excised fractured femoral heads from elderly hip replacement patients. .  .

And a Madrid team has just published a survey showing good correlation in children between 5 and 12 years between QUS measurements  and calcium-vitamin D intake.

CONCLUSION:  Safe and lowcost QUS can and thus should be used for bone risk measurement at all ages and locations – including schools and even the bedside;  in contrast to DXA which must not be used in those who are pregnant or not  at least post reproductive if not post-middle-aged.

Even in    the chronically frail or mentally dependent, periodic QUS screening is as crucial as eg bloodpressure screening since eg hypertensive , elderly, dementing or stroke patients share so many risk factors, and are thus are even more prone to osteoporosis- and incidental osteoporotic fracture easily converts the walking wounded  from needing supervised care to being totally wheelchair- or- bed- dependent.

ABANDONED DOCTRINE OF TRUTH IN MEDICINE: POSTMENOPAUSAL HRT:USE HUMAN TRANSDERMALS. WHY RISK TABLETS? BIG PHARMA WINNING THE DISINFORMATION WAR.

 5 June 2010. neil.burman@gmail.com 

Part 1: Transdermal better than oral estrogen for replacement: the importance of appropriate HRT.

part 2: Information warfare, Big Pharma, Appropriate HRT and the Doctrine of Deception.

PART 1: TRANSDERMAL BETTER THAN ORAL ESTROGEN: THE IMPORTANCE OF APPROPRIATE HUMAN HRT OVER PATENTED MEDICINES :

The  health bite today from the BBC  correctly highlights one of the many critical reasons why appropriate routine Hormone Replacement HRT should be taken permanently  by any route  – but preferably transdermally, not as tablets.  In the appropriate low human dose HRT reduces the natural risk of stroke- and of the far more common chronic major diseases that cripple and kill – ie heart disease, cancer, fractures, dementia..

  But the Menopause Societies (South African, British  and  International) ie BMS , SAMS ,   IMS , and  the BMJ must promptly issue strong statements to the media condemning the BBC again for its typical misleading  elementary misreporting- in this instance  as regards progestins..  

 Transdermal and oral hormone replacement therapy and the risk of stroke: The source report –  this week’s BMJ –   describes HRT use in UK over about 6.7years among postmenopausal stroke victims mean age 70years (50 to 79) compared to matched controls without strokes. But the inexcusable error in the BBC report is that it twice mentions progesterone as being quoted in the BMJ study- which is nonsense.  The  BMJ report never mentions progesterone,  it repeatedly says progestogen -ie synthetics progestins since these were and are deliberately and wrongly routinely prescribed (instead of progesterone) for HRT due to manufacturer-led market disinformation.

  Progesterone is the original natural progestogen- but no major drug company promotes it, so it has been rarely used except by thinking women who prefer to use prime ie human – bioequivalent- hormones!  

In the adjusted risk statistics, lowdose transdermal estradiol TD replacement  0.025 to 0.05mg a day lowered stroke risk by 19%; whereas the average gynecologist’s  arbitrary  patent pharmacological oral  dose (20 to 40fold higher than the TD dose)  of  about 0.625 conjugated estrogens CE equivalent to 1 to 2 mg estradiol OET ) a day increased stroke risk by 35% . Thus, in contrast to lowdose estradiol  TD which reduced the natural stroke rate, OET  and highdose  estrogen TD  increased the stroke rate by 50% – 90%.  

COMPARISON WITH USA WOMENS’ HEALTH INITIATIVE WHI:  the WHI  showed that on premarin 0.625mg/d the absolute  risk of stroke in USA women age 50 to 79years was about 0.3% ie 3 cases per 1000 women per year -but about 45% higher in depressed women on antidepressants. And  depression is even  more common after midlife, especially without HRT. This cohort from the volunteer WHI trial  was a mean of 63years at enrolment ie 7years younger than the British real-life cohort; and since the risk of stroke approximately doubles with every 10 years of aging, the basic risk in the British study women may have been about 5 cases per 1000 per year or 33 per 1000patients over the duration of the British stroke and HRT study. ie annually 4 cases per 1000 on lowdose estrogen TD versus 6 cases per 1000 on OET 

Despite vast evidence  that physiological replacement doses of the human hormone progesterone (the original progestogen in humans) has endless benefits for older adults, doctors, government clinics and committees overwhelminglly still are lead by the marketing hype of drug companies (and the regulators  lobbyists and governments they fund) to use  drugs designed for profit  eg xenohormone progestens that they wish  were and falsely claim are as good as the original one that our bodies produce.

Truthful information  on HRT for women is widely and easily available from even Wiki    and the real authorities like the British and International Menopause Societies, and any university department of gynecology. .   Thus today’s BBC report reflects the BBC’s willful  neglect  of the most basic check of its facts before publishing health bites. In this case, it misleads women that  conventional combined oral HRT (in fact containing the synthetic progestin that most drug companies and doctors encourage women to take) is beneficial in somewhat lowering the risk of stroke  (never mind womb cancer) – whereas such synthetic progestins. progestogens   especially in oral HRT have numerous sinister other adverse effects  eg breast cancer and heart disease,  compared to the numerous proven benefits of  lowdose human progesterone. .

KEEPS: THE DEFINITIVE HEAD-TO-HEAD TRIAL OF APPROPRIATE HRT: ORAL vs NON-ORAL ERT WITH OR WITHOUT PROGESTERONE.: The small but definitive 5year KEEPS double blind randomized controlled trial RCT is now more than half way through and due to report in 2012, comparing the alternative regimes in women in the early menopause (10years younger and less overweight than in WHI) . “ KEEPS is a multicenter trial that will evaluate the effectiveness of 0.45mg of conjugated equine estrogens CEE Wyeth Premarin, a weekly estradiol TD Climara patch delivering 0.05mg estradiol a day -( both in combination with cyclic oral, micronized progesterone (Prometrium Solvay) 200mg for 12 days each month), and placebo”.

Recent information from KEEPS is that it is proceeding smoothly, with no significant differences so far between the three arms- no increase in serious adverse events has yet been seen by the Independent Monitoring Committee in the still unblinded results.  

 Wyeth (now Pfizer since 2009) is not crossfunding KEEPS, although they may be hoping that  their premarin in lower dose will prove to be as safe as or better than estrogen TD in the medium term.. But given the ~70year experience with oral HT mainly premarin 0.625mg/d promoting breast cancer increase (although not mortality) after >12-15years of use , it is remotely unlikely that even ¼ of the long-standard premarin oral dose will prove anywhere as safe and effective as parenteral balanced human hormones for permanent protection in aging women.  One hopes it is, to vindicate the insistence of so many doctors on still prescribing OHT for  even just the first 10 years of menopause,  despite so much damning evidence to the contrary (see this entire website of reviews).

SO WHY PRESCRIBE, RECOMMEND HRT PILLS FOR POSTMENOPAUSAL WOMEN? when hard evidence is that non-oral  balanced human HRT (appropriate estrogen, progesterone and testosterone) is far superior in both benefits and zero risks for women? Whereas it is common cause that conventional oral HT ie about 0.625mg CE or equivalent started at menopause increases the  early risk of dangerous deep vein thrombosis DVT; and  begins to increase the risk of breast cancer to above that of untreated women after a cumulative dose of about 2 – 3 gms oral estrogen – after 10 – 15years ie by prime post retirement midlife in the midsixties. It is only some compensation that other cancers, fractures, ischaemic heart disease, dementia and (breast cancer- and all-cause) mortality, are reduced by appropriate m0dest doses of such OET combined with appropriate progestin; but such regime increases the risk of DVT, gallstones and fatness frailty- increasing body fat with increasing muscle wasting due to collagen loss which also promotes increase in the natural tendency to fractures and urinary incontinence by the midsixties.

Promoters of oral estrogen, bisphosphonates, SERMS,  and strontium cleverly ignore the hard fact that by far the greater risk for aging fractures is not bone density but muskuloskeletal ie failing bone and muscle strength and global co-ordination – which bisphosphonates do nothing to promote, while estrogen and strontium nad SERMS  may promote bone strength but not crucial muscle strength, and SERMS double the laready very high rate of stress urunary incontinence. .

  American major authorities do anything to promote their own commercial interests.  so they have long given their drug regulator the FDA – which is unashamedly paid for by big pharma- unbridled licence to make nonsensical claims and draconian laws. And because drug companies fund the FDA and the lobbyists and legislators in USA to promote their  products, (in a $trillion disease industry – some 8% of American GDP) they have the vast profits to in turn influence medicines regulators and legislators throughout the world to follow their profitable lead.

So  only the FDA and regulators  decide what foods are good for people, what supplements (of microfood stuffs) people may take, and licence designer synthetics for human prescription after trials of only a few months in a few hundred subjects – but insist  that old proven nutritional remedies may not even be claimed to have any health, preventative and therapeutic benefits unless they have undergone massively costly controlled trials that Big Pharma will never fund.

 Their hypocritical deadly nonsense is then to use draconian measures to stop suppliers from making any health claims for even supplements that are well known to be gold standards for prevention and treatment eg fish oil and the scores of other highly effective and safe biologicals- minerals, vitamins, human (eg glucosamine, chondroitin, n-acetylcysteine, coQ10, arginine, carnitine, carnosine), and plant products- that are (co)-hormones, antioxidants, true anabolics, nitric oxide promotors, anti-inflammatories, antidepressants, memory and vision promotors, neurotropics, insulin sensitizers, antiatheroma, hypolipidemic , antimicrobial etc. .  

In fact they now proclaim that citizens may not even buy supplements, foodstuffs  or even legally prescribed compounded hormone creams made from legal components (as are all other prescriptions made by manufacturing pharmacists practicing alone or in Big Pharma), unless the FDA has proclaimed them safe, because “they have not been proven safe”.

 This despite the facts that most  enduringly successful prescription drugs  (eg reserpine, metformin, digoxin, the synthetic progestins) are derived from/ based on successful evolution of and human experience  with the parent supplement eg vitamin, mineral and other biologicals  (eg non-oral progesterone, estradiol, testosterone)  over thousands of years,   and millions of patient years experience  in the past >100years of scientific discovery. 

The Disease Industry- FDA-Big Pharma – organized medicine international network- proclaims that no claims may be made for the benefits of supplements (the vehicles, parents  of most prescription drugs in use) unless they have been tested in rigorous trials to the same standards as designer drugs are recently tested.  

Yet the FDA and regulators allow the marketing of generics- chemical identicals but often far from identical pharmacology and therapeutic action- without clinical trials. Where is the logic for the vendetta against supplement creams  like individually compounded bioidentical hormones that produce measurable physiological levels and appropriate relief?

 This despite the fact that millions of patients have been and continue to be  damaged (iatrogenesis that results in vast numbers of hospital admissions and deaths annually) the past 50 years by drugs promoted by the FDA at the pushing of Big Pharma, based on far too short poor and often fraudulent reports which the drug industry ruthlessly manipulates.

  This led to the disasterous use of stilbestrol in pregnancy from the 1940s to the 1970s;         to the disasterous registration and extensive liberal prescription – in many cases even promotion over-the-counter- of practolol, thalidomide,  chloromycetin and other antibiotics;     potentially fatal unnecessary patent anti-inflammatories  up to the Cox2   inhibitors (eg Vioxx, celebrex) as painkillers;  barbiturates benzos and antidepressants;   lately sulphonylureas and glitazones as firstline drugs for type 2 diabetes instead of the gold standard metformin; new antihypertensive drugs as firstline therapy instead of the goldstandard lowdose amiloretic plus reserpine; appetite-weight suppressants instead of metformin;  bisphosphonates for osteoporosis instead of the goldstandard combined dozen vigorous vitamins minerals and sex hormones that halve all major diseases; and statins for uncomplicated mild to moderate cholesterolemia  instead of goldstandard combined minerals vitamins  metformin and HRT.

  And the simple fact that drug companies  will no longer risk funding head to head trial of one of their profitable drugs against gold standard old drugs or supplements of proven great all-disease medicinal value; since prevention does not pay- only disease pays.

The cost of protectionism for the lucrative Big Pharma industry – for the sake of trade and taxes – is vast  as witnessed by governments sponsoring eg statin , H1N1 flu vaccines , modern antidepressants, bisphosphonates and nonsteroidal anti-inflammatories, and when each of these products of unproven benefit in mass use nets the manufacturers  obscene multibillion dollar profits- in the case of vaccines, with 100%  indemnity guaranteed them at taxpayers’ ie the consumers’  expense!

The lesson from the new UK  study of oral versus estrogen TD is that appropriate ie balanced physiological-dose  human sex hormones are the logical 1st-choice prevention and treatment for postmenopausal women (and their peer mates) – not the multirisk wannabe synthetic substitutes that  Big Pharma keep hammering on the public- new psychotropes, NSAIDs, Cox2 antagonists, statins, bisphosphonates which lack the multisystem benefits of physiological balance of evolution-evolved natural micronutrients ie nutriceuticals.

Part : 2. DOCTRINE OF CENSORSHIP and DECEIPT;   vs DOCTRINE OF TRUTH/… see next review above this.

UPDATE: THE FRAUD OF BIG PHARMA MODERN CHRONIC DRUGS

neil.burman@gmail.comUPDATE: see 14 June 2010. The Statin Scam Unravels. 

 

Update: 6 May  2010: this week’s recall of Johnson and Johnson’s Tylenol, Motrin, Zyrtec, and Benadryl due to negligent contamination , in particular of Tylenol for children, leapfrogs America’s household favourite Johnson and Johnson J&J to 2nd place (with at least 6 bad drugs) in the fraudsters mafia roll of dishonour behind the unreachable leaders Pfizer with about a dozen notorious fraud drugs. What is another $81million fine to J&J  that had sales of >$63billion in each of the last two years with profit of above 20%, and that despite the recall still maintained this turnover in quarterly sales for the 1st quarted this year? 

The major thing is that despite J & J’s gross negligence endangering the lives of children, the FDA has taken no other action against them. They terrorize  with armed marshalls  for trivia and shut down small firms making safe health supplements and physicians using them, but the Big Pharma mafia are the darlings of the FDA and Government since they pay such vast amounts in fees and taxes to Govt and lobbyists- politicians and academicians- trialists – that they are untouchable in every country.. 

14 April 2010: So we  can throw away the fraudulent  Pfizer’s fraudulent Neurontin gabapentin  we have been taking? when there never was  evidence that it is as good and safe as it’s parent (our chief brain neurotransmitter aminoacid )  GABA; while it’s younger twin sister  Lyrica – pregabalin– designed  for extension of patent benefits –  is worse  … just like we can throw away the chronic nonsteroidal anti-inflammatories eg Voltaren diclofenac , Vioxx and Celebrex  that are  such heart risks, poor painkillers,   and do  nothing for the underlying destructive chronic disease process. Drugs for massive profit for the beloved Big Pharma Industry that  politicians go to endless lengths to protect.- even Obama and George Brown as witnessed by the multibillion dollar swine flu scam, even now  in 2010 with Obama’s Pharmacare bill. 

 And now Harvard  University shows that even Neurontin and lamotrigine  increase the risk of suicide by42% and 81% respectively. So the long list of fraudulently overmarketed  or hazardous -improperly registered  or prescribed drugs  without adequate trials or obligatory definite  indications-  grows. 

And then there is the Disease Industry hypermarketing technique of Diseasemongering-  promoting previously ignored or unrecognized variable human traits like anxiety, insomnia, lowgrade depression, mild  hypercholesterolemia, female low sexual desire, erectile dysfunction, postural or stress backache- to diseases requiring permanent designer drug therapy eg benzos, viagras, prozacs, statins, NSAIDS nonsteroidal anti0inflammatories;  or “corrective surgery” for all. 

Pfizer,  Bayer, GSK  and  Roche  with the 100% support of their respective government regulators and politicians   continue to vie for top place as the biggest fraudsters of all time – competing with  the food, tobacco, booze, media, vehicle, financial, lawyer, minerals, fuel  and politics  industries..   

Why is this? Because the public – taxpayers and the poorer consumers- are at their most vulnerable, pawns if not cannonfodder and guineapigs  when it comes to trust in government regulators and the giant consumer product  industries – manufacturers and big distributors-  that Govts  regulate – especially the disease and drug industries.  

  And government regulators are controlled by elected politicians   who ( apart from a few altruistic successful honest folk who stand out and are nominated for  or called to office -but not Ralph Nader) –  as  mostly  lawyers or failed businessmen/ workers or carreer trade unionists,   rarely seek higher office  except to further their own financial interests and power lust.   

Winston Churchill and Frank Rooseveldt vie with Margaret Sanger, Mahatma Ghandi  and Nelson Mandela  for honour as the leading persistent (western)  fighter for justice, human rights of the 20th century if not all time, since they were skillful – brave  but above all tough enough (unlike many heroic martyrs) to survive to see it through. 

Hence there is enormous incentive for collusion between politician/ government officials who control the taxes and spending thereof,  and the big businesses that control the big money that escapes the tax officials – including Big Pharma. In South Africa there is no incentive whatsoever for the MCC Medicines Control Council Regulator to work efficiently as all income it generates is absorbed by the Fiscus/Dept Health, which blatantly refuse to produces annual financials for the MCC – effectively a parastatal supposedly under an independent CEO and Board. 

 Below is a list of costly modern disaster or dubious largely chronic drugs and their manufacturers that earn  the profound distrust of consumers: (where there are a proliferation of me-too analogues in a group eg benzos, statins, NSAIDS, bisphosphonates, only the original one or two are listed since they led/lead the pack): 

PFIZER -Wyeth -Searle – Upjohn:  Neurontin; Geodon,  Bextra,  Zyvox,  Lyrica; Lipitor;  Celebrex; PremPro; aspartame; Rezulin;  Viagra; and Ativan=lorazepam/ Xanor=alprazolam – two  of the most addictive   chronic  “anxiolytic” benzos – again, in Wiki and MIMS their  indications are far fewer than the pages of problems they  cause us since the 1970s , papering over and masking symptoms by numbing the mind (as with alcohol and smoking) instead of patients addressing the underlying cause of their anxieties with psychotherapy including learning self-hypnosis control.   

Collectively, Pfizer (the conglomerate of rash clones it has swallowed) has as many modern disaster/fraud  drugs as the next two combined of its  major league fraud competitors: 

Johnson & Johnson – Risperdal  ;   prepulsid;  Tylenol, Motrin, Zyrtec, and Benadryl 

Bayer – Trasyol; Yaz/min Baycol, Paxil, Flonase, Cipro; 

Astra-Zenca – I.C.I. – Seroquel, Nexium ; Crestor,Tenormin, Losec; and thalidomide.. 

Roche  – Xenical, Roaccutane, Tamiflu; Valium. . 

Glaxo-Smith-Kline  GSK -swineflu vaccine; Avandia, Paroxetine. 

Sanofi-Aventis (Hoechst-Rhone-Poulenc)  – Actonel  ; benzbromarone;  swine flu vaccine; Cosaldon -Trental [Cosaldon R was an excellent peripheral vasodilator oxypentifylline plus vitamin E; then Hoechst subtly started downplaying Cosaldon R as it’s patent expired, and introduced the slightly phonetically changed  and far more costly ‘new’   drug Trental pentoxyfylline.. Hoechst would naturally not explain (except obviously on grounds of profiteering from the new patent substitute)  why they substituted an inferior “new”  drug for the better  older version which included the safe dose of vitamin E.] 

 Merck – Vioxx; Zocor,   Fosamax; gardasil. 

Eli  Lilly – Prozac, Zyprexa; memantine ; and DES-diethylstilbestrol, perhaps the most infamous of all commercialized drugs in causing problems even in grandchildren of those so recklessly exposed to it without evidence of benefit. (Eli Lilly was the last company to stop manufacturing it – in 1997! despite evidence of it’s disasterous effects published in 1953, and of cancer from 1971 . ) 

Novartis -Ciba Geigy- Voltaren, swineflu vaccine. 

Abbott labsMeridia=Reductil   

Biogenesis labs – Acomplia; rimonabant  

Bristol-Myers Squibb -Pravastatin;   Plavix, warfarin; And the sustained  cover-up of the COSMIC  metformin  obligatory postmarketing trial  done at the insistence of the FDA on a huge 9000 subjects for 1 year in about 1996/7.   This trial was eventually submitted for publication only in 2004 and thus published in 2005- but for the previous year  BMS and their licensor  the original patent-holder  Merck  denied any knowledge of such a trial although the summary was presented and published a year earlier at a US diabetes congress by the authors, and we supplied the COSMIC abstract- written by BMS researchers who did the COSMIC trial- to BMS and Merck… .        why would BMS and Merck  delay publication of this trial  for so many years, and blatantly deny knowledge of it after the first report of the trial result at a USA diabetes congress ? 

The answer can only be the predicted- because it confirmed in the biggest metformn trial cohort ever- 8000 patient-years- that metformin in diabetics gave zero significant adverse drug effects, with the all-cause deathrate in fact 9% lower than in those on other conventional antidiabetic therapies; and  four major diabetes prevention  trials of metformin in four continents confirmed that it at least halves the incidence of new diabetes- with zero significant adverse effects; and in the intervening years between this trial and it’s result publication, both BMS and Merck developed and launched their respective combinations of metformin and a sulphonylurea (M + SU) . This despite the fact that it was clear since at least the 1970s that the addition of sulphonylurea to  metformin is a desperate last resort since it is fraught with risk of hypoglycemia and reversal of the reduction in fatness produced  by metformin alone.           

A new  retrospective study just published from the UK patient database confirms the  folly known all along  of combination of SU with metformin in that  that over a mean of 4 years on therapy, the metformin+SU therapy reduced all-cause mortality by 23% compared to SU alone; while metformin alone compared to SU alone reduced mortality 1/3 more ie  by 30% – with trivial risk of hypoglycemia. This was similar to the outcome in the 20year UKPDS RCT, where metformin reduced all-cause mortality by 36% over a mean of 13 years, making it the safest and most effective  drug ever patented for  chronic degenerative  disease. . 

And note the cynical folly of the many manufacturers of the grossly overpromoted and overprescribed  bisphosphonates and statins  – which  have numerous serious adverse effects and  should be last-ditch therapy in metastatic bone cancer and in rare  serious hyperlipidemia, not for osteoporosis, not for mild to moderate lipidemia and certainly not over-the-counter as profiteers crave. 

ENDURINGLY BENEFICIAL MODERN CHRONIC DRUGS: 

The above drugs contrast with vey  few modern chronic designer drugs that are still the leaders in their fields, whether as original or generic – although none of them has been shown to address all-cause mortality and pathogenesis. 

Pfizer’s Norvasc=amlodipine  is a rare modern designer exception – dating from the late 1980s,  it’s patent has only just run out-  proving it’s enduring worth for longterm hypertension therapy as the premier 4th-line drug to add when reserpine 0.125mg plus amiloretic 1/2 (ie HCT 25mg + amiloride 2.5mg)  daily are inadequate for optimal control; with very low risk of serious adverse effects. 

BMS’  Captopril & Merck‘s  Renitec – angiotensin converting enzyme inhibitors ACEI –  date from the mid-late ’70s, and while they were and are the first of the invaluable ACEI inhibitors, 5th line antihypertensive drugs for common use, they have formidable potential for lifethreatening adverse effects- but they are on essential drug lists. In the past dozen years big pharma has attempted to substitute angiotensin 11 receptor blockers ARBs, for the aging ACEI,   but a recent metanalysis shows that neither group of drugs significantly lowers fatal or nonfatal cardiovascular events- and they all (unlike reserpine + coamiloretic + amlodipine) have risk of life-threatening  adverse effects. 

DRUGS FROM THE GOLDEN AGE: 

Virtually all other current  designer drugs of enduring and safe worth for chronic longterm use originated from the golden era of innovative and enduring designer drugs mostly around WW2 up to the 1960s: 

The modern  birth control OC pill taken chronically  by millions of women for up to decades for either contraception or symptom control, certainly dates enduringly and endearingly  from the post war Golden Era  as     Estinyl (Schering 1930s)  , with  or alternatively just a  progestin. Modern preparations are relatively so safe that they are the preferred contaceptives for millions of young women.  But we have just seen two young women unwisely started on Bayer-Schering’s Yaz/Yasmin develop in one case hypertension and major weight gain, the other hives- so such innovations are not necessarily better than established brands of OC . 

MSD’s 40year old Sinemet still the firstline gold standard for Parkinsons; Moduretic- amiloretic/ amilozide- still the first drug and permanent baseline  (in low dose eg half tab3 x a week or 1/4 – 1/2 a day) for hypertension; Epilim valproic acid for epilepsy; Tryptanol; 

Sanofi-Aventis Hoecht’s Lasix furosemide still the leading diuretic for  chronic severe heart failure, cirrhosis, nephrosis. 

Merck’s 80yr old metformin- the only laboratory – originated drug (a teak of the galega plant’s biguanide) that reduces all-cause mortality – by no less than 36%, without a single serious adverse effect or mortality if sensibly used; 

Bayer’s Adalat; Aspirin (1899) ; prednisone; 

Novartis-Ciba-GeigyImipramine-Tofranil the first successful commercialise and still enduring major antidepressant. 

Roche’s                            Rivotril; 

Abbott-Knoll                Isoptin; 

GSK’s  Zyloprim;   Imuran;  Panado- still the lead patent mild-moderate painkiller, safe at prescribed dose. 

Pfizer -GDSearle’s  Aldactone; Sulfasalazine; and the 100year old phenytoin -Dilantin, still a longterm lifesaving antiepileptic despite occasional major adverse effects. 

Boot’s  Brufen-  the NSAID nonsteroidal anti-inflammatory drug on Essential Drug Lists,  altho there is no evidence that this group of drugs is essenntial since they do not alter the course of the underlying chronic inflammatory disease or reduce longterm mortality and morbidity, are little if at all better than Panado+- codeine as painkillers, and have formidable risks. http://en.wikipedia.org/wiki/Ibuprofen#History  

Astra-Zenca-ICIs   Inderal was the first of the major new cardiovascular protectant beta-blockers which  are essential drugs., altho all have formidable potential adversity ; as with ACEI, no special optimal favourite has yet emerged;  they have some special chronic indicatiions, including heart conditions and special cases of hypertension. . 

THE BIG PHARMA RAINCHECK  MONEYSPINNERS: 

The US drug industry is reputedly worth >$100billion a year and the biggest industry to >$200billion; and globally some $643 billion, of which the United States produces almost half.  The gross industrial output in USA was apparently about $26 thousand billion in 2008 ie the drug inductry alone approaches 8% of total gross manufacturing output there.   

 It is surely no co-incidence that virtually all  the above  common fraud-drug  pharmacy companies are among the dozen top money-spinners listed on 2009 financials.. But perhaps the biggest racketeering of modern times has yet to be quantified, perhaps  $100 billion  of wasted money on last year’s swine flu  “pandemic” that never happened, in futile mass screening lab tests and vaccines and Tamiflu – giving massive profits  (some companies claimed >$6billion) with total indemnity against litigation to Roche, GSK, Novartis,  Baxter,  Sanofi et al.. The USA-dominated WHO hastily changed the core definition of pandemic early in the North American outbreak so it could declare the nonsensical pandemic to suit the pockets of the profiteering American-European conglomerate and the political lobbyists they employ in Government and beaurocracy… 

 So do we wonder why we can’t trust Big Pharma prescription drugs and doctors’ judgment? Read the stats of a 5years study of the relevant risks,  of  deaths from prescription drugs in USA ( versus natural supplements)  exceeding  over 106 000 to 1.   Thats why Big Pharma and it’s “regulators” like the US Govt FDA, the UK MCC, European medicines Authority EMA, and organized doctors, are so desperate to stop the public buying the supplements people choose- when early and permanent use of balanced natural supplements at least halve serious disease and thus medical consultations, prescription drug use and hospitalization. For profit, only disease (not prevention) pays. 

Of the  103  drugs that achieved  $billion sales  in 2006,: considering the chronic  disease drugs, only valproate and J & J’s contraceptive dates back to the 1980s; Wyeth’s Premarin-Prempro dates back to 1995; and  (omiting duplicate entries) only 33 were oral drugs for chronic major common degenerative (as opposed to infective or malignant or autoimmune )  diseases.  And of the ~33 , only  10 (in descending order of sales value on that list)  even vaguesly justified their  ranking and sales- amlodipine, venlafaxine, bupropion, metoprolol, Viagra ,carvedilol, valproate, ramipril, paroxitine and premarin- 

Reuter’s forecast of the 10  >$5billion raincheques for 2010  include in descending rank for common chronic diseases only the tablets Lipitor, Plavix, Diovan and Crestor- none of which are  proven essential drugs for common average disease use. They are there solely because of heavy marketing by Big Pharma, despite their mediocre results and major potential risks, with far better results given by long-proven natural supplements or by lowdose reserpine-amiloretic combination, then amlodipine . 

Finally, landmark  drugs that were not invented by, or were laregly ignored by,  suppressed by drug companies as medicinals: 

EDTA ethilenediaminetetraacetate was invented 80 years ago but never patented by Big Pharma as a medicine. Yet as an oral nutritional supplement in modest dose it is perfectly safe, and removes toxic lead, mercury, iron and many other heavy metals  (now routinely polluting the environment -food and water- chain)  from the body,  as well as uric acid– being effective preventative against gout, and an antiatheroma agent. It is apparently not a scheduled medicine in either USA, UK or South Africa, being a routine ie harmless – beneficial- food  additive preservative. 

Yet despite the vast evidence favouring fish oil, metformin and EDTA as perfectly safe and effective chronic  anticoagulation, the Disease Industry persists in promoting rat poison- warfarin, dicoumarol– as the common chronic anticoagulant, despite its’ proven risks of promoting hemorrhage, fractures – already known since at least 1998vascular calcinosis already known since 1998 and most recently published last month; and even cancer .   

Metformin is unique, the widest multidisease panacea ever extracted (from a traditional antidiabetic plant)  and patented. Like EDTA it was eventually identified in 1922 by university researchers Werner and Bell in Ireland – but only patented  and produced for routine diabetic use since the 1950s- and deliberately obstructed for use in the USA for another 40 years by the FDA and Big Pharma, which were busy as bees designing and mass marketing far less safe and effective USA sulphonylureas although these were already discredited by the  UGDP  almost 50 years ago, when metformin was ‘rediscovered’ and came into its own. 

Reserpine  also a plant (rauwolfia) extract  remains (with coamiloretic, amilozide)  both in low dose the first-line drug treatment of all classes of hypertension– which since the prevalence of this disease now approachines 50 % in aging adults, makes these drugs amongst the most prevalent essential drugs needed. As even wiki says,  from many major studies over decades, “Reserpine is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality” – in at least a score conclusive trials of the individual components reserpine, thiazide and amiloride, the triple combination is by far the best firstline therapy, at a cost in South africa of about  $US1 a month.. . But Big Pharma and its profiteer lobbyists continue to suppress the combination fraudulently based on decades-old overdosage data. 

By contrast well over 100 natural micronutrient substances – cinnamon, garlic, ginger, codeine, reserpine, digoxin, huperzine A, galega-metformin and many other plant extracts; vitamins especially B,C,D  in higher dose; , minerals especially calmag,  zinc, chromium, boron, iodine, iron  and even lithium; and human biologicals that deplete with aging like glucochondroitin, CoQ10, acetylcysteine, arginine, cartnitine , GABA, 5HTP  and almost 20  other hormones  replaced chronically – provide almost every chronic major degenerative  disease with the best prevention and treatment, without the almost invariable  risks of  the modern designer chronic drugs discussed above. 

 Since alcohol and tobacco, salt and sugar are still freely sold over the counter OTC  without any restrictions except some  to children , the commonest causes of chronic degenerative disease in more than slightest daily usage, it is obviously lowdose vitamin K,  vitamin C and D, lithium, magnesium, reserpine, metformin- galega  and EDTA that should be mandatorily supplemented in the food chain for the fattening aging 1st-world populations, and allowed OTC purchase;  while indications are severely limited  for prescription of sulphonylureas, statins, bisphosphonates and the dozens of other disaster or dubious  designer drugs listed above.