Tag Archives: dementia

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  .

CAPE PENINSULA HYPERTENSION & HEADACHE CENTRE

CAPE PENINSULA HYPERTENSION & HEADACHE CENTRE (50 years of experience)      at       The Natural Medicine Clinic  NMC , 1st Floor, 15 Grove Bldg, Grove  Claremont, Cape Town- between  ABSA Parkade on Grove Ave, and Warwick Sq opp Cavendish. ph 0216831465/ 071202574 or email doctor@healthspanlife.com.

As the commonest silent killer of aging people in the world, pain, obesity  and often-resultant systemic  hypertension HBP deserve the best and cheapest treatment.     Headache is rarely caused by hypertension, but unlike hypertension, is usually easily controlled if not cured.

But precisely because HBP is so common- in half of us by old age, especially at night- it is a huge moneyspinner for Big Pharma and the Disease Industry.

so the last thing the HBP Industry wants is too successful too cheap treatment. Hence they (eg the WHO,  the SA Hypertension Society and medical schools- state clinics)-  blacklist  the best baseline treatment- lowdose amilozide and lowdose reserpine, to promote sales of ever-newer unproven drugs with multiple risks. .

But 60 years of experience (5 centuries in India) confirms that Rauwolfia and its extract reserpine remain the best and sufficient treatment for most patients provided it is combined with a mild diuretic eg magnesium-potassium; or     natural herbs eg  Green tea, cranberry juice, Apple cider vinegar , Dandelion, Nettle, Fennel, buchu, horsetail;

or a magnesium-potassium conserving equivalent- the recent  proven designer ie synthetic lowdose safe diuretic amilozide eg Amiloretic 55mg 1/4 to 1/2 tab, combined with natural  lowdose reserpine 0.25mg tab 1/4 to 1/2 tab, both initially daily, eventually perhaps only 3 days a week.  . These lower HBP and associated anxiety/depression  gently but surely to avoid complications.

The NMC is open  office hours  from 9 am 6 days a week, and offers objective electronic arm and leg bloodpressure measurement and if required urine and heart testing for causes and effects of hypertension etc. If desired, appointment can be made with a hypertension-metabolic  specialist physician.

see https://healthspanlife.wordpress.com/category/reserpine/ for further details to fight dementia, stroke, heart/kidney failure, heartattack, blindness, diabetes, gangrene, etc. The last thing the Disease Industry and hospitals, medical schools  want us to do is wipe out these common diseases with safe lowcost treatment..

UPDATE: LEGISLATING REDUCED ADVERSE FOOD ADDITIVES, MANDATING ADDED MICRONUTRIENTS

  The  Mail and Guardian Health supplement (11 April 2013)  featured the dynamic South African Health Minister   Dr Aron Matsoaledi legislating lower salt -sodium chloride-  in staple processed foods  eg in cereals, butter, potato crisps,     by about half  over the next 6 years.
         This is long overdue since salt-related hypertension and often associated.  obesity are  historically  major killers not just in Afro-Americans  but in any longer-living people and especially stressed poverty-stricken  peoples as in Africa.

The linked bad nutritional -and lifestyle – choices – Salt-Stroke  – smoking- – hypertension- obesity – diabetes – heart – kidney disease – are  quoted by S.A. Stats  2010 from death certifications as rising  to 24%  of deaths after age 50 years, leading even infections at  20%  as the commonest causes  of  seniors’ death in South Africa. Nonnatural causes ie violence account for only 5%, and cancers only about 4%.

           This in a population that ( both by self- choice and by State- and supply-chain corporates)   heavily self-poisons with industry-promoted salt,  concentrated   fructose-   sucrose, ethanol , unsafe sex, and smoking –  the deadly self-abuse quintet  causing the great majority of premature deaths and  disability – diabesity- brain-heart-vascular-renal-cancer -arthritis, infections, Alzheimers(type 3 diabetes) and violence. – ie the team of  high-profit horsemen (alcohol, smoking, sugar, fructose, salt and other addictive drugs; television, sex, guns, knives, fast motoring, and ruthless medical practices)  of the global marketting corporates .
          But not a word was  said in those two salty  pages  about simultaneously legislating for  processed consumables  the other greatly needed adjustments:
REMOVING from the environment, from  consumables (water and processed food , toothpaste, sweetened  drinks and sweeteners, baby milk formulae, hygiene products, vaccines, etc,)  or at least steadily reducing, other notorious and unnecessary  toxic  marketed hazards- aluminium, aspartame + sucralose, mercury, fluoride, bromine, refined sugars, cooked fats, and pesticides, hormones, antibiotics, and estrogenics eg soya ( unless fermented) used in food, medicine,  and vaccines ; and REPLACING in processed foods commonly and increasingly deficient  micronutrients in the regional diet especially for the poor masses and children – eg minerals (magnesium, calmag phosphate, zinc, iodine, lithium,  selenium,  sulphur, boron); vitamins (especially A, B, C, D3, K2, coQ10; and other crucial  essential  antiinflammatory  antioxidant  anti-obesity insulin sensitizers eg virgin coldpressed  coconut oil and uncooked marine omega3.
      From scientific studies there is little doubt that hypertension is proportionate to sodium chloride overload, as it  is especially to deficiency of magnesium, potassium, iodine, water, and vits  B, C, D3 and K2.  But scientific evidence is still unclear as to whether it is just the excess  essential halogen mineral CHLORINE.  in NaCl that  is the dietary cause of  hypertension,  not SODIUM in NaCl- but not in other essential forms eg with carbonate.
HALOGENS  in nature are the four major  elements – fluorine, chlorine, bromine and iodine from the lightest, ie lowest atomic number,  upwards.  Fluorine as  the lightest  is one of the most reactive ie corrosive of all materials. Halogens with metals eg sodium form sea- salts. As their weight/atomic number rises, they become less reactive,   Apart from  bromine they are disinfectants.
 IODINE is certainly  the heaviest and thus least reactive halogen iodine is the  essential  mineral that in adequate intake is  major anti infection- (among the strongest antimicrobials we have)-  anticancer, healer, thyroid metabolism and thus heart regulator, and major chelator – detoxifier- against the lighter  halogens – the toxic bromine and fluorine, and excess chlorine.
 The food and drug industry needs cudgeling to stop polluting water, medicines and food with unhealthy fluorine, chlorine and bromine.
FLUORINE is still misguidedly used , promoted in drinking water , toothpaste and antibiotics ; while  for obscure reasons BROMINE.  has replaced iodine in eg bread. FLUOROSIS and BROMaiSM  are notorious poisonings – and unlike iodine and chlorine,  the fluorine and bromine have no human essential  biological benefit as even trace elements. Fluorine – like aluminium, bromine, cadmium, mercury, iron, – may be invaluable in industry, but Fluorine is not essential for mammals or humans. Its use in dentistry has with mercury amalgams long been scientifically debunked as harmful and unnecessary, and is being phased out by preventative dentists everywhere. .
         Tricyclics and other pre-1980s antidepressants had several side effects due to their nonselective interference with neurotransmitters other than the serotonin target; the fluorinated fluoxetine was selective and one of the first avoiding this problem. but the serotonin deficiency hypothesis has never been proven to be a major factor in depression.  Many current antidepressants receive this same treatment, including the selective serotonin reuptake inhibitors citalopram But antidepressants have major adverse effects, are rarely as good as talk therapy, and often do  worse than natural mood-improving nutrients eg vitamins and fish oil.
Quinolones are artificial antibiotics often fluorinated to enhance their effects,eg ciprofloxacin. But these antibiotics are notorious for terrible advese effects including crippling weakening  – rupture of tendons, and are never essential. 
 BROMINE. Africa.   is still listed as a food supplier to the baking industry in South Africa!    But Wiki writes: bromine has no proven essential function or need in humans. an unwanted side effect is ozone depletion. As a result, many organobromide compounds that were formerly in common use—such as the pesticide, methyl bromide—have been abandoned. It reacts vigorously with metals, especially in the presence of water, to give bromide salts. It bonds easily with many elements and has a strong bleaching action. Like chlorine, bromine was used as a wartime poison gas, and disinfectant / pesticide- ie a poison! so bromines were removed from medical/vet use in the 1970s. Long-term use of potassium bromide (or any bromide salt) can lead to bromism. Yet it is used in: production of brominated vegetable oil, which is used as an emulsifier in many citrus-flavored soft drinks (for example, Mountain Dew). After the introduction in the 1940s the compound was extensively used until the UK and the US limited its use in the mid 1970s and alternative emulsifiers were developed. But .Soft drinks containing brominated vegetable oil are still sold in the US (2013).  Bromine, like chlorine, is used in maintenance of swimming pools, Water purification compounds, disinfectantsinsecticides, and photographic processes. .
        Dr Joe Mercola wrote in the Huffington Post 2010: “Bromines are common endocrine disruptors. What makes it so dangerous is that it competes for the same receptors that are used to capture iodine. If you are exposed to a lot of bromine, your body will not hold on to the iodine that it needs. And iodine affects every tissue in your body — not just your thyroid.  You are already exposed to far too much chlorine and bromine. Bromine can be found in a number of places in your everyday world, including: plastics, Bakery goods and some flours often contain a “dough conditioner” called potassium bromate; •Soft drinks (including Mountain Dew, Gatorade, Sun Drop, Squirt, Fresca and other citrus-flavored sodas), in the form of brominated vegetable oils (BVOs); Medications such as Atrovent Inhaler, Atrovent Nasal Spray, Pro-Banthine (for ulcers), and anesthesia agents; Fire retardants (common one is polybromo diphenyl ethers or PBDEs) used in fabrics, carpets, upholstery, and mattresses       According to van Leeuwen, who has extensively studied the effects of sodium bromide on thyroid function:   “Although the bromide ion is widely distributed in nature, the main route of exposure in humans stems from bromide residues in food commodities as a result of the abundant use of bromide-containing pesticides, like methylbromide and ethylene dibromide, for soil fumigation in intensive horticulture and for postharvest treatment.”      One clinical consequence of overexposure to bromine is suppression of your thyroid, leading to hypothyroidism, .
         
   Another is bromide toxicity: .Bromine — The Bully of the Halide Group:  When you ingest or absorb bromine, it displaces iodine, and this iodine deficiency leads to an increased risk for cancer of the breast, thyroid gland, ovary and prostate — cancers that we see at alarmingly high rates today. This phenomenon is significant enough to have been given its own name — the Bromide Dominance Theory.   Aside from its effects on your endocrine glands, bromine is toxic in and of itself. Bromide builds up in your central nervous system and results in many problems. It is a central nervous system depressant and can trigger a number of psychological symptoms such as acute paranoia and other psychotic symptoms.  In fact, in an audio interview, physician Jorge Flechas reported that, between 1920 and 1960, at least 20 percent of all hospital admissions for “acute paranoid schizophrenia” were a result of ingesting bromine-containing products. In addition to psychiatric problems, bromine toxicity  eg from the old BromoSelzer can manifest as the following: Skin rashes and severe acne; Loss of appetite and abdominal pain; Fatigue; Metallic taste; Cardiac arrhythmias. . These effervescent granules, developed by the Emerson Drug Company of Baltimore, were used to treat heartburn, upset stomach, indigestion, headaches and hangovers. Bromides were withdrawn from the American market in 1975 due to their toxicity.  Bromo-Selzer still  on the market  no longer contains bromide.                                                                                                                   
       
          Bromines in Your Bread Box: Potassium Bromate:  The ban on bromines have not prevented them from sneaking into your foods and personal care products.  You probably are not aware of this, but nearly every time you eat bread in a restaurant or consume a hamburger or hotdog bun you are consuming bromide, as it is commonly used in flours.  The use of potassium bromate as an additive to commercial breads and baked goods has been a huge contributor to bromide overload in Western cultures.  Bromated flour is “enriched” with potassium bromate. Commercial baking companies claim it makes the dough more elastic and better able to stand up to bread hooks. However , successful companies manage to use only unbromated flour without any of these so-called “structural problems.”  Potassium bromate is also found in some toothpastes and mouthwashes, where it’s added as an antiseptic and astringent. It has been found to cause bleeding and inflammation of gums in people using these products. Mountain Dew, one of the worst beverages you can drink, uses brominated vegetable oil as an emulsifier. Not only that, it contains high fructose corn syrup, sodium benzoate, more than 55 mg of caffeine per 12 ounce can, and Yellow Dye #5 (tartrazine, which has been banned in Norway, Austria and Germany.)  A weapon of mass destruction — in a can.   .Even drinking water can be a source of bromide. When drinking water containing bromide is exposed to ozone, bromate ions are formed, which are powerful oxidans.
   Sodium bromate can also be found in personal care products such as permanent waves, hair dyes, and textile dyes. Benzalkonium is used as a preservative in some cosmetics.    Finally, bromine and chlorine were the most common toxic elements reportedly found in automobiles, according to  David Brownstein, MD (March 2007). They showed up in the seats, armrests, door trim, shift knobs and other areas of the car.  The United States is quite behind in putting an end to the egregious practice of allowing bromine chemicals in your foods. In 1990, the United Kingdom banned bromate in bread. In 1994, Canada did the same. Brazil recently outlawed bromide in flour products.    Iodine Levels and Cancer Risk:  Iodine levels have significantly dropped due to bromine exposure; declining consumption of iodized salt, eggs, fish, and sea vegetables; and soil depletion. In the U.S. population, there was a 50 percent reduction in urinary iodine excretion between 1970 and 1990. What’s this doing to our country’s health?   The Japanese consume 89 times more iodine than Americans due to their daily consumption of sea vegetables, and they have reduced rates of many chronic diseases, including the lowest rates of cancer in the world.
            The RDA for iodine in the U.S. is a meager  0.15 mg/day, which pales in comparison with the average daily intake of 13.8 mg/day for the Japanese.  There is a large body of evidence suggesting that low cancer rates in Japan are a result of their substantially higher iodine levels. Iodine has documented antioxidant and anti-proliferative properties.   A strong case can be made that your iodine RDA should be closer to what the Japanese consume daily, if breast cancer rates are any indication. Low iodine can lead to fibrocystic breast disease in women (density, lumps and bumps), hyperplasia, and atypical mammary tissue. Such fibrocystic changes in breast tissue have been shown to reverse in the presence of iodine supplementation after 3-4 months.   If youwant to be tested  for iodine deficiency, the urine iodine challenge test is the best way to assess your iodine level.
              Bromine and Your Thyroid   Adding to the negative health effects of bromine, the damage to your thyroid health deserves special mention. bromine exposure depletes your body’s iodine by competing with iodine receptors. Iodine is crucial for thyroid function. Without iodine, your thyroid gland would be completely unable to produce thyroid hormone. Even the names of the different forms of thyroid hormone reflect the number of iodine molecules attached — T4 has four attached iodine molecules, and T3 (the most biologically active form of the hormone) has three–showing what an important part iodine plays in thyroid biochemistry.   Hypothyroidism is far more prevalent than once thought in the U.S. The latest estimates are that 13 million Americans have hypothyroidism, but the actual numbers are probably higher. Some experts claim that 10 to 40 %  of Americans have suboptimal thyroid function.   Many of these folks may actually have nothing wrong with their thyroid gland at all — they may just be suffering from iodine deficiency.
        Seven Tips for Avoiding Bromine and Optimizing Iodine   Trying to avoid bromine is like trying to avoid air pollution — all you can do is minimize your exposure. That said, here are a few things you can do to minimize your risk:
       1. Eat organic as often as possible. Wash all produce thoroughly. This will minimize your pesticide exposure. 2. Avoid eating or drinking from (or storing food and water in) plastic containers. Use glass and safe ceramic vessels.
        3. Look for organic whole-grain breads and flour. Grind you own grain, if possible. Look for the “no bromine” or “bromine-free” label on commercial baked goods. 4. Avoid sodas. Drink natural, filtered water instead.          .
         5. If you own a hot tub, look into an ozone purification system. Such systems make it possible to keep the water clean with minimal chemical treatments. 6. Look for personal care products that are as chemical-free as possible. Remember — anything going on you, goes in you,                                                                                          
        . 7. When in a car or a building, open windows as often as possible, preferably on opposing sides of the space for cross ventilation. Utilize fans to circulate the air. Chemical pollutants are much higher inside buildings (and cars) than outside.
           Avoid Unfermented Soy Another major contributor to thyroid dysfunction that I did not discuss above is unfermented soy. Soy isoflavones – estrogenics- can wreak havoc on your thyroid. Kaayla Daniel’s groundbreaking book, The Whole Soy Story: The Dark Side of America’s Favorite Health Food is a powerful exposé that reveals the truth about the soy myths that have infiltrated our culture. So if you want to keep your thyroid healthy, you’ll definitely want to avoid bromines, and unfermented soy products of all kinds, including soy milk.”
               These changes  – removing fluoride, bromine, aluminum, mercury, lead, unfermented soy-  from consumables, and cutting added iron and chlorine – may possibly add fractional cost to production?  but will hugely improve educability and health, productivity and employability, and reduce premature disability and death  far more than just  hypertension- vascular risks;  and greatly reduce acute and chronic illness and infections, hospitalization and need for risky modern  chronic prescription medication..  And since iodine deficiency is widely endemic ,  increasing population iodine intake up to 12mg a day  like Japanese get,  – not 0.15 mg/ d – will  hugely reduce premature aging,  common goiter and hypothyroidism, infections, vascular disease  and cancer
But of course Corporates, Governments and the Disease , Drug and Hospital Industries  dont want disease ,  jobs and profits to be decimated by natural supplements avoiding most common diseases- the Fraud of Modern Medicine since Only Disease Pays.

UPDATE: SOME REMARKABLE LIQUID HEALTH SUPPLEMENTS – NOT STATINS BUT SULFUR-DMSO, LUGOL’S IODINE, FISH OIL and COCONUT OIL.

update 6 May 2014  see new insights at    DMSO – The Persecuted Drug by Dr. Stanley Jacob 27 Feb 2011

update 3  November 2013   IODINE DOSE AND DOSING:     the traditional approach is that of eg the Linus Pauling Institute at Oregon State University   and Wikipedia advocating the recommended daily allowance of 150 mcg  0.15mg a day for adults;  and the safe upper limit at ten times that intake;  but quoting  up to eg 7mg  a day  for treating fibrocystic breast disease; but  a single dose of ~100mg KI for nuclear exposure..
             But comprehensive discussion on maximum  iodine dosing by the Weston Price Foundation (2009) quotes  to much research, eg by MDs Dr Guy Abraham,  David Brownstein,  Broda Barnes ea – using for therapy  of disease  6.25mg up to 50mg/day, but historically up to 10gm a day (if this wasnt confusing mg with gm!).
             Dr Sarah Myhill in Wales UK  and Joe Mercola in USA put widely differing opinions and evidence  in perspective in 2013.
             The maximum available pharmaceutical grade 15% Lugols iodine contains about 100mg/ml ie ~10mg a drop, ie  a drop a week orally provides ~1.4mg ie 1400mcg a day- 10times the maximum recommended maintenance daily allowance RDA, although that is conservatively what healthy Japanese are estimated to ingest  in their traditional natural diet ..
          So the conservative  practical approach is to use 2% (Lugol’s) iodine ie containing 20mg/ml or 2mg per drop, about 1.3mg iodine/drop. While allergy to natural  iodine has apparently never been  reported, the prudent  might start with a test dab on the skin for using it as a paint. For oral use,  a test dose orally might be eg a teaspoon (4ml containing about 25 mcg iodine) of a mixture of 1 drop 2% Lugol’s in a glass of  water.
          Abraham and Brownstein 2005 reported Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine. This affirms the principle that no essential micronutrient  should be taken in isolation but ideally as part of good natural diet (now hard to achieve on the now traditional fast food genetically modified urban mass diet)- or with a balanced multisupplement including more realistic vigorous doses of vitamins C and D, and magnesium, selenum, boron, etc ..

UPDATE 18 JUNE 2013  Ji Sayer reviews    Evidence-Based Medicinal Properties of Coconut Oil

16 March 2013  THE THREE  OILS  SYMPHONY –  FISH OIL, COCONUT OIL, DMSO,- and EXPOSURE OF THE DEADLY OMEGA6 HOAX OF THE 20TH CENTURY:

this  “Three  Oils Symphony ” lacks references on virgin coconut oil. A comprehensive on-line synthesis  referenced to 1995 is by Dr Ray Peat.

Wikipedia puts in perspective the up-to-date  100% safe and multibeneficial virgin ie unprocessed cold-pressed  coconut oil versus the risks of  hydrogenated coconut or palm oils let alone omega6 oils. .
Fot those who have concerns about the safety, toxicology  of DMSO, the detailed randomized controlled trial of 1967-8 is exhaustively reported by Dr Richard Brobyn , confirming no serious adverse effects topically or systemicaly up to 90 days.
THE DEADLY HOAX OF OMEGA6  SUPPLEMENTS AND THE CHOLESTEROL HYPOTHESIS: A NIH team in Bethesda has just published a remarkable review in BMJ of the  Sydney Heart Study 1966-1973  with a review of recovered data, confirming that substitution of omega6  linoleic acid as safflower oil and margarine in modern marketed staple diet  was a monumental deadly marketing hoax for the past 50 years, since it almost doubled deaths in those men studied  from age 30-59 years. Wikipedia notes this deadly delusion  that safflower (oleic/ linoleic) oil is health protective. The same applies to oleic acid– high in olives, many nuts eg sunflower oil,  and animal fats especially when cooked- as Wiki summarises, excess omega6 increases the risk of breast cancer, and by Stephen Cunnane’s hypothesis, aggravates inflammation eg arthritis, cardiovascular and malignant, by worsening marine omega3 deficiency. .  This may not apply to some exceptional groups- Reverse epidemiology –  but is supported by hard science as weighed up carefully by Chris Masterjohn and his thoughtful dissection of Dr Daniel Steinberg’s  The Cholesterol Wars 
      These studies highlight one of the biggest marketing  Deadly Drug Hoaxes of the 20th Century, that lowering LDL cholesterol with  cholesterol-busters- statins –  is  necessary and beneficial for most people, for primary prevention 0f cardiovascular disease with average 1st world  population “mild to moderate” hypercholesterolemia.  When these synthetics-  statins -produce numerous serious adverse effects.  This contrasts with the legion benefits and zero adverse drug effects when natural anti-disease (anti-oxidant/ antithrombotic,  insulin-sensitizing  nitric- oxide promoting)   supplements- coconut oil, fish oil, DMSO, metformin, CoQ10, arginine, carnitine,  minerals and vitamins etc  – are combined in appropriate titrated doses.  .
IS FISH OIL BETTER THAN COCONUT OIL? PROBABLY EQUALLY IMPORTANT:

COMPARATIVE BENEFITS OF FISH OIL AND COCONUT OIL

Can anyone  find any published research that supports Peskin and Rowen 2011 book condemning fish oil supplement.,     and Dr Rowen’s article on Why Fish Oil makes you age faster?

Perhaps our expert ornithologists and sea researchers can find good support for their argument in birds and marine life- why do warmwater fish have so little marine oil?

there is still zero support  against good fishoil supplement for cooler climate populations on literature search.

a 2012  Univ Virginia  analysis  concluded that “With the possible exceptions of Vitamin D and omega-3 fatty acids there is no data to support the widespread use of dietary supplements in Westernized populations; indeed, many of these supplements may be harmful.”

But see the exhaustive favourable fish oil evaluation up to Jan 2012 at the Linus Pauling Univ oregon website .

and  recent new  papers  promote fish oil supplement- but mostly for people in the colder northern hemisphere or airconditioned cities, offices, factories, homes. .

Just two recent 2007/2009 papers express some doubt about the potential risk of fish oil triggering atrial fibrillation. But I have had worsening familial atrial fib for 23 years , and a tsp a day of cod liver oil helps control it.

I cant find any reference supporting their  argument that  pure modest-dose  fish oil supplement- as all authorities recommend. – is dangerous except Peskin’ and Rowens’.

BUT their argument may be valid for people who live in warm climates. South African cities are certainly not warm for much of the year; and the more industrious work in airconditioning when it is warm. Their argument  against fish oil supplement might certainly be valid for those who live in the tropics  outside cities   ie latin America, North and Central Africa, the middle east, northern India-Pakistan, accross subtropical asia and the near-equatorial  pacific.islands., who thrive on coconuts.

Peskin’s theory that low-freezing point  fish oil is essential only for denizens of the cold  deep may well apply also to human and animal inhabitants of the semi-arctic/antarctic land masses or living at cool high altitude like Mexico city.

It rings a bell with the opposite: coconut oil (melting point 24-26C) being staple food and so heathgiving for those living in hot (coconut palm) climates –  it thins in  more than temperate climates (20 to 40C) , hence may have a different protective lubricant/rheological effect to the vital antifreeze benefit of fish oil in  human and animal/marine dwellers living at -20 to <20C.  .

Thus it seems rational that I, we  now balance my 1tsp codliver oil a day with 1 desertsp  coconut oil twice a day, and advise  accordingly – the best of both oils. . .

for seriously ill pts I recommend up to 2gm fish oil concentrate 2x/day, with up to 60gm coconut oil twice a day, if tolerated. .

Rowen and Peskin’s  published references (other than vegetarian tribes that eat virtually no seafood) for their  contrary  viewpoint are in their 2011 book,

Does their theory  apply to more affluent people who live and work mostly in controlled temperatures (the mid twenties)  in 1stworld countries?  ..

So if you live in a hot city with warmed houses and offices, combining the two oils makes sense for you too.      Arctic  and antarctic circle outdoor dwellers certainly need their marine oil.

while Rowen supports Peskin’s  antifishoil argument,  analysis may justify both oils depending on the climate the population lives in eg fish oil in the icy latitudes, coconut oil in the triopics- and both in balance in the temperate zones.

In fact the Peskin-Rowen theory supports our policy to recommend both fish oil and coconut oil combined:

go back to the Peskin-Rowen book – even just their joint summation at the end: They stress that those who eat no seafood  and live long are 5 tribes  of humans:      vegetarian  Adventists- SDAs – who destress, and walk/exercise a lot and  also do not smoke, altho they may live in all climates in USA- where presumably they are mostly caucasians ; but  SDAs have total racial/tribal diversity . The other longevity claims  in closed tribal communities are heavily doubted. More recent researchers have concluded that  the older people get, the more they tend to exaggerate, confabulate  their age because it brings them eg more attention- eg the tribes Rowen/Peskin list – the Hunzas of Pakistan, Okinawans of Japan, Vilcambans of Equador, Abhascans of the caucasus, not to mention our own oldest old whether in tribal villages or in our cities. . That would explain why they live at such diverse altitudes and latitudes. And isolated tribal people are mostly poor,  dont have mechanized transport, and have to work outdoors till they drop,; and as % of their communities, the young leave to find work or get massacred/ conscripted, kidnapped, banished/ sold  as slaves   in wars against invaders, so their aging seniors are all that are left in those areas.

Peskin/Rowen ignore that by proven Darwinian evolution,  land-ambulant mammals evolved : from micro-organisms to eg mammalian coelocanths only about 400 000 years ago, in deep ocean waters, and hence are very oily.        But mammalian evolution dates back about 160million yrs;   and our endothermy– ability to thermoregulate  arguably dates from the dinosaurs and thus birds  about 300million years ago.

Perhaps human endothermic adaptation evolved when the first homo sapiens evolved at the tips of Africa and migrated from Africa around the globe some 10 000 to 100 000 years ago ( ie before and after the last Ice Age that started 40 000yrs ago and ended about 20 000yrs ago);  thus spreading from temperate  sunny  climates to cold semi-arctic lands of Europe, Asia, Iceland, Greenland  and Canada, and extremely hot equatorial/desert regions.

Hence we adapted from obligatory hot climate survival at up to 50C – the coconut eaters- to icy conditions down to -40C – who survived on  antifreeze fish oils as a staple. Fish oils freeze apparently between  18C    and -50C (DHA

update: 4 Feb 2013          HALOGEN AND HEAVY METAL IMBALANCE:
As radiologist  Dr Jeff Dach stresses now, Drs Abrahams and Brownstein and many others  have repeatedly reported the overwhelming evidence that          Iodine Treats Breast Cancer.  Whether this is taken orally, topically or most rationally both ways- by mouth and by deep massage driven in by DMSO- is  a matter of conviction and zeal.
Conversely areas with chronic iodine defciency– like Africa – have a high rate of goitre,  hypothyroidism through to obesity, vascular disease, growth impairment and cretinism- mental slowness and retardation. And perhaps not incidentally also have much higher rates of  endemic infections, fibrocystic breast disease, hypertension,heart and kidney diseases,  and cancer.
But while iodine supplementation in salt was a good idea elsewhere, salt overload is a major contributor to hypertension in black Africans,  so iodized salt is not the answer; and the fast food cult with salting and biltong – dried fish and meat – and cheap local cigarette smoking and alcohol – has worsened the hypertension problem.
It is increasingly recognized that it is the chloride rather than the sodium in salt that is the culprit in salt-related hypertension.  So we have  overload of three prevalent toxic halogens aggravating iodine deficiency here-  chloride in diet and as chlorine;  bromine that has crazily replaced iodine in bread; and fluorine added to drinking water where it is  not already toxically overloaded in fluorosis areas.
So far from just for thyroid deficiency,  iodine – plus selenium plus magnesium plus sulfur-  replenishment has become crucial both as  major anabolics, to reverse deadly   iodine deficiency,  and as  displacer-chelator (along with the century-old Nobel-prize winning EDTA)  of   deadly bromine, fluorine , lead, mercury, cadmium, iron and aluminium overload   (Guy Abraham) – all common in criminally polluted South Africa  where industrial warfare has ravaged the subcontinent since the late 19th century. .
Who cares about selenium supplements and balance? It is harrowing to see a recent study from Univ Pretoria that “A total of 896 maize grain samples were obtained from all the maize silos throughout South Africa (231 silos) and analysed for selenium (Se) content.  Of the samples analysed, 94% contained below 50 μg selenium/kg DM and can thus be classified as deficient from an animal and human nutritional point of view. Maize grain in South Africa is therefore a poor source of Se for animals and humans.”  Yet absorbable selenium deficiency is a critical factor in the risk of AIDS, let alone cancers and other infections.  The  art of selenium balance is to use organic selenium supplement, but unlike iodine therapy with multimiligram doses,  ,  no more than  400mcg/day selenium  to avoid selenosis.
These respective  elemental  overloads and deficiencies are incalculably big  problems in the prevalence of cancer, thyroid, osteoporosis,  dental, liver,  heart-renal-stroke and mental disease in South Africa, from violence (mad as hatters- endemic intoxication by smoking, alcohol,  cannabis, mandrax, meth  etc) and immune deficiency (endemic AIDS, TB, hepatitis, herpes) to steadily falling  school  attendance and academic results.
This in turn is catastrophically  aggravating the worsening poverty, unemployability, malnutrition and thus grant dependency  of the masses, and the worsening crisis in  the shortage of qualified and competent  administrators, politicians, scientists, lecturers, nurses  etc..
DMSO, Lugol’s iodine and coconut oil thus join fish- codliver oil -all with melting points around our comfortable habitat  temperature –  as a group of vital cheap antioxidant especially brain micronutrients for South Africa. And it is brains, intellect that  we all need above all else from conception to grave.

UPDATE 2 Feb 2013.    Dr Cynthia Koelker MD is a modern family practitioner in Ohio who muses on DMSO as effective non-prescription pain relief.                            A recent NaturalNews.com review  notes “Miracle cure’ controversy and why people should use DMSO for cancer, inflammation and more;  There is evidence that DMSO can cause cancerous cells to become benign.          DMSO can pass through human skin like water and enter cells. It can also stop or slow the development of cancers, such as breast, skin, bladder, colon, and ovarian cancer. Some people use it for cancer prevention. DMSO is used to help patients in withdraw from conventional cancer treatment and is promoted as an immune system booster.
Cancer centers use DMSO to protect healthy cells from chemotherapy and to decrease side effects from the deadly drugs. The DMSO Potentiation Therapy uses DMSO to allow chemotherapy to target cancer cells. This allows doctors to use extremely small doses of chemo, which lowers profits for the drug companies. No doubt the use of DMSO with conventional treatment, or better yet with other natural cures, is blocked because of the effect on drug profits.

A California research group in 2010  noted that Intractable and untreatable pain from cancer remains a challenge,  major impact on patients’ quality of life and survival. A significant number of patients receiving analgesic therapy with opioids report persisting pain of a higher intensity than the pain in those who were not on this class of drugs. DMSO is a naturally derived, inexpensive, non-toxic solvent and pharmaceutical agent that has been demonstrated to have numerous health enhancing and therapeutic benefits. In the present article, we provide the scientific evidence and substantiate possible application of DMSO as a well-tolerated excitatory modulator in the management of cancer pain. 

A 2009  North Carolina University study by   Satia JA,  White E ea. of supplement users over 10 years ie 770000 patient years showed surprising benefits in    cancer reductions with use of MSM   as well as fish oil, melatonin, St Johns Wort (all against colon cancer);   and chondroglucosamine (lung  and colon cancer) .    But  Garlic use associated with 1/3 increase in colon cancer.
 
Hence it is apparent that DMSO-MSM  – like coconut oil- is a major natural healer and potentiates many drug treatments  including against cancer and pain; and thus it follows that far lower doses of other medications may be needed if DMSO is used.

UPDATE:  27 January 2013  Stefanie Seneff ea at MIT point  out that   perverse modern industry has subverted agriculture and nutrition in                                         1. creating sulfur deficiency in crops (and thus in humans) through oversupplementing phosphate  at the expense of sulfur;                                                 2. driving down optimal cholesterol levels (ie cholesterol sulfate) through combined  obsssive futile cholesterol restriction and cholesterol-busters eg statins;  and                                                                                                                                              3.  the overload of fructose in processed food.   So increasingly both fast -processed -food eaters and the poor are sulfur deficient since they dont eat much food sulfur  –“eggs, onions, garlic, and leafy dark green vegetables like kale and broccoli, Meats, nuts, and seafood; Methionine, an essential amino acid, that we are unable to synthesize, is found mainly in egg whites and fish. A diet high in grains like bread and cereal is likely to be deficient in sulfur. This deficiency is worsened by acid rain and soft water- and worsens the epidemic metabolic syndrome, diabetes , vascular disease, Alzheimers,  and cancer.”   She reviews why these diseases are much lower in those living in volcanic  mountainous areas  eg Iceland, South America where sulphur abounds in food, and  along with enough ascorbic acid (also seriously deficient in processed foods)  is the backbone of vital cholesterol sulfate and its daughter sterols  (vit D3 sulfate, the corticosteroid and  sex-  and heart – ouabain- hormones). 

She points out the crucial role of iron sulfate in energizing cell metabolism by insulin and glucose, depositing needed cholesterol in cell membanes and promoting myoglobin  and brain strength instead of adverse tissue, hemoglobin and especially brain glycation  AGES – advanced glycation endproducts.

Is it surprising that (not just the rare  patients with serious hypercholesterolemia eg familial, nephrotic, cirrhotic  who needs statins)  but the progressive   deliberate successful poisonng of  the entire UK-USA population  with  statins by Big Pharma aided by the FDA and most Govt Regulators,  to drive down healthy average cholesterol levels to hypocholesterolemia,  is  notorious for causing brain fog, depression, fatigue, dermatitis, muscle pain/dissolution (rhabdomyolysis)  and liver-kidney- heart  dysfunction , while doing nothing to combat  insulin resistance, obesity and diabetes?

When –  instead of statins and other designer drugs  – to combat wasting diseases like infections eg AIDS and TB, cancer, diabetes (muscle wasting as fat accumulates), osteoporosis, atheroma,  heart/liver/kidney  failure and  neuro/muscular disease eg neuropathy, stroke, Alzheimers and muscular dystrophy-  what the population  needs is especially detox of heavy metal and eg estrogenic plastic overload;  more vitamin B, C , D3, K,  coQ10, arginine, carnitine, zinc, chromium  and magnesium, melatonin and GABA,  marine omega3,  sulphur in diet or as methionine/cysteine/DMSO/ MSM/glutathione;  and for serious lipidemia and resistant obesity at any age, metformin -dimethyl guanidine.

It is speculative  as to when nutrigenomics – ie costly genetic testing – is going to prove widely useful in real live clinical practice to provide useful diet guidance for our common lifestyle and  aging diseases.

Already in 1995 Shen and Murphy at Wisconsin University showed that while amyloid proten fibril deposits are a neurotoxic  cornerstone of Alzheimers’ disease in mice and man,  pure DMSO  totally prevents the formation of  amyloid betasheets at least in testtubes.

In 1999 Cherry ea  in Australia and 2004  House ea in Staffordshire confirmed the adverse effects of  aluminium and ferric deposits in Alzheimers;  and the potential benefits of heavy metal chelators like EDTA with enough magnesium  and calcium..  .

and by 2009 Gupta ea  in India showed also on the workbench that garlic extract – ie sulfur- both prevents amyloid sheet fibrillation and dissolves it.

So there are different safe  nutritional ways of  slowing if not dissolving amyloid plaques as well as atheroma plaques  in Alzheimeirs with combinations of  minerals, vitamins and other antioxidants/  chelators including sulfur foods like  DMSO, MSM and garlic.

Pine Tree Source v Fossil Fuel Source of MSM and DMSO:  Mike Pritchard-Jones in 2008 detailed the great but  academic debate .

But already by 1957, MacDonald ea at UCLA affiirmed the primary role of calcium and sulfur  in bone healing after fracture in rats. Yet the first Pubmed entry on sulfur deficiency disease in human nutrition – from a casava diet- is from Nigeria in 1968. and the latest from India  in 2012 from their  staple cereal-legume diet

A 2012 study Julien ea from Quebec and Greece shows important benefit of DMSO  against excessive tau phosphoprotein deposits in Alzheimers Disease.

Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins.

Like GABA,   Melatonin is a prime ubiquitous brain hormone that  (like the sex steroids ) also  declines  from age 30years, that profoundly maintains memory by preventing both hyperphosphorylation of tau protein and amyloid beta protein, in melatonin doses reported from 3 to 9mg/night.. theories about its therapeutic role go back 25 years on Pubmed.. so melatonin is conveniently combined with the supplement GABA before bedtime, while GABA is the ideal daytime anxiolytic for these distressed patients.

23 January 2013

For some time many of us have been taking and recommending the multisystem benefits of evidence-based natural micronutrients  – fish oil, coconut oil, vitamins, minerals,  and biologicals like HRT and  metformin –dimethyl guandine HCl – all  natural  supplements.

Now we have added medicinal natural DMSO liquid, the universal miscible solvent, never mind its crystallized sister form DMSO2-MSM.

DMSO   gives early and permanent preventative  benefits without risks in many musculoskeletal, cardiac and  neurological conditions. It is the only remedy registered in USA for chronic interstitial cystitis, and solely for that rare condition.  But it  is reported major benefit against trauma, thermal and radiation burns and scars, all infections, sinusitis-otitis, goitre, and pain including headache, gingivitis, dry socket; infertility from tubal blockage; dermatitis; burns, asthma; arteritis, arthritis, lumpy mastitis, diabetic and viral (eg shingles and herpes simplex) and other neuritis, and ischemic/varicose and diabetic ulcers and swollen varicose legs.

DMSO thus understandably has good synergy with the similarly anti-inflammatory antioxidants like tumeric,  fish and coconut oils; and metformin which also like DMSO and MSM crosses membranes well including into the brain.

We are seeing good pain and swelling relief with massage with combined DMSO + coconut oil+ zinc + Lugol’s iodine 15% including on scars and painful/lumpy breasts, head, neck, back, abdomen, joints, sprains, skin (pre)cancer etc. As usual one has to beware of too hastily overdoing movement after effective pain relief.

Ongoing experience suggests that sore or lumpy breasts including new painful lumps months after excision and radiotherapy be massaged  daily orinitially twice daily:  first with coconut oil, then Lugol’s (15%) iodine, then medicinal grade(98%) DMSO to improve deep penetration of the iodine to promote healthy tissue regrowth from deep. It is encouraging how tender  lumps disappear within days , including on repeat breast mapping with mechanical tactile Sure Touch scanning.

Adverse effects: apart from possible smell and taste (which some of us don’t experience), pure DMSO may cause redness and burning, as may strong iodine; this is avoided either by diluting the DMSO in a bit of water; or better by applying coconut oil first, then the iodine then last the DMSO.

One must be careful starting  with DMSO. Extracted from woodpulp, it is volatile, warms on mixing with eg the oils, or undiluted on the tongue. But there is no evidence of toxicity apart from the smell – which my metabolism apparently does not produce even on a tsp of 99% medicinal DMSO twice a day.. Megadoses of up to a gram per kg have reportedly  been used in severe conditions. Fair-skinned people are more sensitive to it so doses should be lower, starting with massage of sore/superficial lesions and/or just ¼ tsp by mouth. Any taste of it is obviously easily masked by mixing it with the essential oils (fish oil, coconut oil) and supplement powders listed, and whatever else is desired eg yoghurt, fruit squash or just water.

There are promising studies on Pubmed between 1989 and 2011 of the benefits of DMSO in management of prostate problems in rats, and humans for transrectal procedures , and intravenously as cancer adjuvant palliation. DMSO-MSM is cheaply and safely available

CHEMISTRY and further references::

DMSO2  MSoM  METHYLSULPHONYLMETHANE  C2H6O2S or (CH3)2 SO2  dimethylsulfone crystals melt @ 109C and boils @ > 238C. its Molar mass is 94,.  Density 1.45

DMSO MSiM METHYLSULPHINYLMETHANE C2H6SO Dimethylsulfoxide Me2SO crystals melt @ 19C , and boils @  189C      Its Molar mass is  78.  Density. 1.1

So the two dimethylsulfa sisters cost the same and  have the same benefits against pain, chronic cystitis, arthritis, brain trauma, radiation and cancer http://www.dmso.org/ .   But only the melted ie liquid form at household temperature is the strong penetrating solvent. It’s not clear whether oral DMSO gives better blood levels than DMSO2 –MSM, since only the DMSO is melted at body temperature whereas DMSO2 is not..

The purist argument against DMSO/DMSO2 as sulphur supplement is that sulphur is not an essential element. But this is obviously  fallacious since our chief components are the elements CHOPNS carbon hydrogen oxygen phosphate nitrogen sulphur- we cannot survive without ingesting these. Only plants and microbes can apparently photosynthesize living tissue  from CHOPNS by breathing  air and absorbing water.

MSO2 ie MSM has also been shown in humans to readily   cross the blood-brain barrier. In the rat DMSO carries diazoxide into the ischemic brain to mitigate hypoperfusion, and protects the brain against scute traumatic brain injury

Comprehensive updated review of DMSO to January 2013 from the USA Natural Medicine Database supplied by the Drug Information Centre of Groote Schuur Hospital UCT   echoes Steinberg’s review (Albert Einstein Med Centre in Philadelphi)  aAnn N Y Acad Sci. 1967;141:532-50 The employment of dimethyl sulfoxide as an antiinflammatory agent and steroid-transporter in diversified clinical diseases. that 90% DMSO massage in some 500 cases, gave overall good outcome in 80% with no serious or sustained adverse effects reported.

In particular, no evidence can be found overall in the accessible literature supporting one old report that a DMSO product was withdrawn in Japan because of cataract concerns.. A 2011 review of transdermal joint DMSO use from Arizona University found no evidence of human eye toxicity in their series or in the reported literature.

Studies on DMSO have been ongoing at University Oregon for >45years:

Ann N Y Acad Sci. 1967;141:214-20.The effect of DMSO e on the induction of breast cancer in the rat.  Fletcher WS, Dennis DL at Univ Oregon showed that in the rat, breast cancer induced by nitrobenzene was progressively reduced by 18months by DMSO 50ppm (ie 0.5%) in their water from after and even better from before the cancer was provoked. In humans this equates roughly to taking 10gm DMSO in 2L fluid a day..

JC de la Torre  in  1975 wrote “DMSO  has been tested in various experimental injuries of the central nervous system CNS in relation to other therapies. It appears  a useful drug in acute extradural mass-forming lesions, middle cerebral artery occlusion, respiratory anoxia, and spinal cord injuries, in rhesus and squirrel monkeys, dogs, and rats. The data from these studies suggest that in the experimental models, DMSO is clearly superior to no treatment, and appears to be more generally effective than other comparable treatments. No satisfactory answer has yet been found to explain the beneficial effects of DMSO…..”

and 2009  JC de la Torre and  SW Jacobs  Oregon University , ea  described  Pharmacology of DMSO in cardiac and CNS damage: “The pharmacological effects of DMSO administration include some desirable properties that may be useful in the treatment of medical disorders resulting in tissue injury and compromised organ systems. These properties include the reported effects of DMSO on impaired blood flow, suppression of cytotoxicity from excess glutamate release that may result in lethal NMDA-AMPA activation, restriction of cytotoxic Na(+) and Ca(2+) entry into damaged cells, blocking tissue factor (TF) from contributing to thrombosis, reduction of intracranial pressure, tissue edema, and inflammatory reactions, and inhibition of vascular smooth muscle cell migration and proliferation that can lead to atherosclerosis of the coronary, peripheral, and cerebral circulation. Review of the basic and clinical literature on the biological actions of DMSO in cardiac and CNS damage or dysfunction indicates that this agent, alone or in combination with other synergistic molecules, has been reported to neutralize or attenuate pathological complications that harmed or can further harm these two organ systems. The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease. “

Rheology is obviously crucial for health. . The lower the melting point and the higher the viscosity the healthier. Coconut oil (melts at 24C) and DMSO(19C) a universal solvent miscible in both water and oil have similar melting point well below the temperature of the healthy human (+-37C), while fish oil http://www.high-fortune.com/En-index-SW04.asp. melts at similar temperature (20C, freezes at 10C.)  Since the brain is about 20% omega3 ie fish oil, it perhaps explains why both coconut oil and DMSO with similar melting point and rheology –good flow- to omega3 have such profound benefit crossing the bloodbrain barrier and fighting vascular and inflammatory degenerative disease eg Alzheimers, as well as against cancer, which while supported by vascular growth factor VGF depend on hypoxia and thus acidosis..

PLoS One. 2012;7:e33361. doi: 10.1371/journal.pone.0033361. .Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.Lim EJ, Hong DY, Yang YM. Ea Konkuk University, Seoul, South Korea. Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which MSM inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers.

Invest Radiol. 2008:43::298-305..Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature.Cyran CC, Brasch RC ea. University of California San Francisco:  To evaluate the potential of quantitative assays of vascular characteristics based on dynamic contrast-enhanced magnetic resonance imaging (MRI) using a macromolecular contrast medium (MMCM) to search for and measure effects of dimethyl sulfoxide (DMSO) on cancer vasculature. treated control (n = 8) and DMSO-treated (n = 7) human breast cancer xenografts (MDA-MB-435) in rats were imaged dynamically by MMCM-enhanced MRI before and after a 1-week, 3-dose treatment course. CONCLUSION: Reductions in cancer microvascular leakiness induced by a 7-day course of DMSO could be detected and measured by dynamic MMCM-enhanced MRI and were confirmed by microscopic measurements of the leaked macromolecular agents in the same cancers. Results support the robustness of an MMCM-enhanced MRI approach to the characterization of cancers and providing first evidence for an in vivo effect of DMSO on cancer blood vessels.

Neoplasma 2004;51:460-4.Acetaminophen (paracetamol) and DMSO modulate growth and gemcitabine cytotoxicity in FM3A breast cancer cells in vitro.Bilir A, Guneri AD, Altinoz MA. McGill University, Quebec, Canada. Addition of antioxidants to chemotherapy is an unresolved problem in oncology. It is still an issue of debate, whether antioxidants may reduce rough cellular toxicity and thereby the systemic side effects of the chemotherapy, without sacrificing the anti-tumor efficacy.  Tumor-sensitivity towards gemcitabine a  new anti-cancer agent can be increased with anti-inflammatory agents.  Acetaminophen  and DMSO are two unique anti-inflammatory and anti- oxidant agents with unrelated structures,  both able to block RR and COX, simultaneously. we monitored efficacy of acetaminophen and DMSO to modulate growth and gemcitabine sensitivity in breast tumor cells, Peculiarly, acetaminophen alone stimulated S-phase, which was not accompanied with enhanced plating, rather resulting in 40.3% growth inhibition at the 96 hour. DMSO alone significantly diminished both the plating and S-phase, which resulted in 71.7% growth inhibition at the 96 hour. Gemcitabine drastically reduced S-phase and plating until 72 hours, yet at 96 hours it lost its efficacy to suppress the S-phase with concomitant 2-fold rise in cell numbers in comparison to 72 hour time point. Both DMSO and acetaminophen brought S-phase to around zero percent in combination with gemcitabine until 48 hours, yet they both reduced early cytotoxicity of gemcitabine at the same time interval. However, at the 96 hour, they both strongly augmented gemcitabine efficacy to block S-phase and prevented the rise in plating.

Oncol Nurs Forum. 1991;18:683-5.Case report: topical DMSO for mitomycin-C-induced skin ulceration.Alberts DS, Dorr RT  Arizona Cancer Center. Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors’ experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice.

WHO SAYS LARGE DOSES OF NATURAL MARINE OIL ARENT MAJOR HEALTH BENEFIT?

who says Large doses of fish oil don’t prevent heart attack or stroke?

update 8 August 2013 the  OregonUniversity Linus Pauling Institute website still promotes the numerous benefits of fishoil.

update 2 August 2013    the Topol- Rowen- Peskin rejection of need for  fish oil EPA+DHA was  not supported by the recently NEJM-published  R&P 5 year trial in Italy, which compared  modified ie patented ethylester marine essential fatty acids with olive oil.

This R&P  trial was thus not a trial of fish oil (concentrate or otherwise), nor placebo-controlled, since olive oil is hardly a placebo- in the 13.4year Spanish EPIC trial  published last year , olive oil dramatically reduced all-cause mortality by 1/4 and CVD mortality by 44%. The full 2013 NEJM R&P paper is inexcusably silent in omitting this cardinal fact that it was no ways placebo-controlled- placebo means an inert comparator.

Thus  it can only be concluded from the Italian R&P trial that addition of patented processed EthylEster EFAs for only 5 years  gives no more benefit than the already major protection of olive oil and  mediterranean lifestyle alone. Contrary to Topol-Rowen-Peskin, this  R&P trial says nothing about the longterm benefits of vigorous fish oil intake in a high-risk population eg in USA/ other populations (especially smokers)  not  on a mediterranean/ Asian  high-fish intake.

the 2010 Nordic study ( Dyerberg  ea  Copenhagen University- who first reported in 1978 the association between marine omega3 PUFA and health in Eskimos) http://www.nordicnaturals.com/images/pdfs/tgstudy.pdf details the better bio-availability of natural ie triglyceride- bound fish oil- EPA+DHA compared to that in processed ethylester low-triglyceride omega3 products-   as used in the R&P and GISSI trials of patented commercial designer products. .

2 June 2013 Its some 4 years since this healthsite started promoting marine oil for optimal development and health.

    what say you to the latest hype about the  predictable negative result of the Italian N-3  Cardiovascular Risk and Prevention trial  R&P from the NEJM? ie that omega3 oil was no better than olive oil.
the major problem is that the R&P trial didnt use  natural clean FISH OIL, nor    in primary prevention.
Nowhere does it say it used fish oil- it says N-3 ie omega3, and in patients with multiple vascular disease. Nor does the original 2010 R&P plannng paper  state that in fact  it used  a patent formula of  chemically changed ethyl esters in tertiary  prevention,

like the GISSI trial used apparently patent branded altered  Om3  after heart attacks – it wasnt  natural clean fish oil..
the GISSI abstracts 1999 and 2008 also dont mention fish oil.
 So  it wasnt natural   fish oil  like I use and promote- clean codliver oil or clean om3  concentrate from clean factories in northern Europe and now even from Cape Town..  The R&P abstract paper cleverly doesnt mention  the brand Omega3  name- but Pfizer funded the trial…
Its the “top” journals  likely up to their  old tricks, publishing probable infomercials paid for in this case by Pfizer and mates,  without making that clear.
I cant see if these Italian trials used Lovza/Omacor or whatever  Big Pharma  chemically altered snakeoils.
But looking at the extensive debate already around Dr Topol’s condemnation of real fishoil  supplement,   many commentators  fell into the same trap- they didnt notice that  R&P didnt use fish oil, but about 850mg/day  ethyl esters of omega3.

Synthetic patent designer drugs dont do what the natural  food/supplement/human biophysiologic product  does.

   Ethyl esters eg ethinylestradiol, and xenohormones eg Premarin,  are  dangerously different from  estradiol.  Look at the controversy, the danger in using  altered natural products eg:
slowrelease niacin instead of natural niacin.
or  neurontin/lyrica or benzos  instead of natural  GABA to bind to the GABA receptors.                                                                                  or  anabolic steroids eg methyltestost instead of testosterone.         or methylprogesterone Provera instead of progesterone.                 or margarine instead of butter !.                                                             or  methanol  –   dangerously different from  ethanol;                        or synthetic substitutes for natural digoxin…      

or the Women’s Health Initiative- which through gross misrepresentation stopped many women from using beneficial physiological human HRT for 10 years, despite the bad design of the WHI that used  long-proven risky xenohormones (premarin, provera) at dangerous older age, while in the first 6 years it enormously benefitted women in the first decade after menopause.. .

It’s  dis-ingenouos of Messrs Rowen,  Topol  and Peskin  not to state this, that the R&P TRIAL  DIDNT USE FISH OIL..
Dr Rowen and Mr Peskin are heavily promoting their own PEO Parent Essential Oil  Brand of Omega6 plant oils. The evidence is that such combination is excellent benefit- but I see no science, no reason not to balance it with clean fish oil since this is now so deficient in general diet.
But surely Prof Topol is doing patients a huge disservice in backing the R&P trial in dumping fish oil  -when that trial didnt use fish oil, and makes no conclusion about fish ol?

I await the full  copy of the R&P study – which the NEJM mysteriously doesnt  make available on line as they usually do with any seriously important  new  study.. .

No-one doubts that good plant oils , good mixed diet have benefit.
there is no doubt that a few gms of fish oil a day have huge  benefit.
Its the balance that matters- and the avoidance of  smoking, sloth, adiposity, refined sugars and cooked animal fats that matters.
so I see no reason to change from taking/ recommending   daily  a tsp (or 4)   of codliver oil (ie about 800 – 3000mg EPA+DHA) ,
and olives/ mixed nut/plant/olive oils on salads/pasta etc ,
     and a tsp of DMSO, and  2 tsp coconut oil/day.
   A recent Australian paper analyses usefully the growing problem of dwindling resources and  the inestimable health importance   of marine  oil – but does not mention viable  marine  om3   synthesis. Like a cure for HIV-AIDS,  the latter  is an elusive  improbability.  .  There is still no objective independent eg  Cochrane review of  prescription omega-3-acid ethyl esters (P-OM3), despite Omacor being on the market for over 20 years .  Why is this?
      Wikipedia specifically notes that  Lovaza/Omacor  has not been shown to lower the rates of all cause mortality and cardiovascular mortality, or the combination of mortality and non-fatal cardiovascular events.[3]It is .. fishoil that has been  chemically altered”…  and the USA FDA still hasnt licensed such derivatives for anything but severe hypertriglyceridemia.   And the US Supreme Court banned patenting of any natural marine oil extract.  Whereas in stark contrast, unpatentable  natural marine omega3  EPA+ DHA–   clean  marine  oil- lowers all  major morbidity  from conception,  and all-cause mortality.

what say you?…

UPDATE: WHAT’S THE PROBLEM WITH BONE DENSOMETRY AT ALL AGES AND SEXES??

neil.burman@gmail.com

WHAT’S THE PROBLEM WITH BONE DENSOMETRY?

Answer: none provided it is safely and economically measured and safely and economically corrected at all ages from small children to dotage. It is so cheap and easy to halve  the fracture risk and rate in all, and thus save vast suffering, costs and especially deaths.

A spinal surgeon laments as we all do  the poor correlation between dual xray bone density analysis DXA and fracture risk.
The simple answer is that bone density is not the top risk factor for fractures,

The chief risk for fractures in the aging is falls and fragility ie global health balance  including agility-co-ordination, balance, and strength- muscle mass.

As this column has previously detailed, DXA is valuable for looking at risk areas in the hip or a vertebra;
but just as screening X-ray mammography overdiagnoses clinically relevant breast cancer,   trunkal DXA measurement  increasingly overreads bone density  as we age because of false densification- vascular calcification overlying hips and spine, and progressive collapse wedging of vertebrae.

That’s why,  as  this column has previously referenced,  QUS -quantified ultrasound – done mostly at the heelbone, has become the international gold standard for monitoring global fracture risk, since that bone measured in its long axis  is generally free of overlying vascular calcification and collapse wedging. It is recommended by  international bodies, many leading universities from Cape Town to Cambridge to Scotland, Japan and USA. .

There is generally  good  correlation between true DXA measurement at hip and spine, and heel QUS measurement.
And QUS lacks the cumulative radiation risks of DXA.
That’s why QUS bone density  is increasingly recommended from childhood, for monitoring and thus simple prevention of frailty   – thus avoiding  the mushrooming  fracture and frailty risk in later life

http://www.ncbi.nlm.nih.gov/pubmed/22878531 Osteoporos Int. 2012 Aug  Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria.Chan ea  Garvan Institute of Medical Research,Sydney,  Australia.

http://www.ncbi.nlm.nih.gov/pubmed/22037972 Osteoporos Int. 2012 Jan:143-53.Quantitative ultrasound of  heel and fracture risk. Moayyeri ea .University Cambridge  UK. Metanalysis: 21 studies with 55,164 women and 13,742 men were included  with a total follow-up of 279,124 person-years. All QUS parameters were associated with risk of different fracture:  1 SD decrease in BMD associated with almost doubling of  hip fracture risk.  (RR by BUA  1.69, SOS was 1.96). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Different validated devices predicted fracture risks with similar performance; with  similar performance in men and women. This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women.

Oct 30, 2010.

FRAILTY FRACTURES- OSTEOPOROSIS- ARE ALSO COMMON- AND EASILY PREVENTED-  IN AGING MEN

The just-published Champ study of osteoporosis in men over 70yrs in Australia shows the high risk for older men as well: 25% had vertebral fractures, but only 77% of the men with fractures had even osteopenia let alone osteoporosis on DXA screening. and this does not factor in the overreading by DXA at the spine and hip owing to the high prevalence of both calcinosis and vertebral collapse. And abysmally few of the men were taking realistic preventatives.

The study bears out:

that frailty,  usually from aging  – is the chief risk factor for non-violent fractures;

and  the low sensitivity of especially  DXA screening, never mind the folly of waiting for fractures or dementia or worse before doing safe lowcost (QUS bone risk) screening as one incentive to starting multipreventative supplements.

As the GIOS Project in Spain yet again confirms, simple  diagnosis and safe  treatment of those at risk of non-violent fractures is scandalously neglected.

And it does not require costly risky high technology – xray screening  bisphosphonates or strontium ranelate..

Like doctors, men are far more resistant than even women to heeding warning to start screening and supplements early enough.

The  CHAMP  study again highlights the importance of asymptomatic middleaged men never mind women having periodic no-xray ultrasound quantitative bone strength scans  routinely as the gold standard so as to prompt them to take the appropriate blend of the fewscore supplements effective against both frailty fractures as well as the associated lipid- diabetes- vascular -respiratory- dementia- cancer diseases.