Category Archives: Hypertension

VITAMINs K2+D3 – VITAMIN DUO OF THE NEXT DECADE

update 16 May 2016.   to our health: neil.burman@gmail.com

HIGH TO MASSIVE DOSE VITAMIN D3 IMPORTANCE – TEN TIMES MORE THAN MAXIMUM SUNLIGHT CAN PROVIDE – IN REVERSING  COMMON VIT D DEFICIENCY/RESISTANCE FOUND IN ALL MAJOR DISEASE eg ALL  INFECTIONS, INSOMNIA, MULTIPLE SCLEROSIS MS,  Myasthenia Gravis, SLE, RA, PARKINSON’S, DEPRESSION, VASCULAR DISEASE, CANCER, VITILLIGO, PSORIASIS,  PERIPHERAL NEUROPATHIES, MENTAL ILLNESS.

  introduction:     Cape Town is the world epicenter of epidemics (of poverty – malnutrition- HIV- HAART- TB –Diabetes, asthma-COPD,  and vitamin D  and iodine deficiency). And we  are seeing neuroarthropathy with a vengeance in our township clinics, where a majority of such diabesity or/and HIV patients  admit if questioned to chronic burning cramping legs  and sore muscles/joints if not also consequent insomnia, falls and leg ulcers.

Poor ill patients  seem to  accept it- neuroarthropathy-  as a way of life since it  usually has no visible signs (for anyone to see) till late– poor circulation, ulcers, falls,  arthritis- , and  malnourished diabesity patients  have bigger worries with uncontrolled diabetes and often uncontrolled hypertension despite even insulin; and the HIV+-Tuberculosis patients  have the multiple toxic burdens of antiretroviral and antituberculous therapy.

Because the burden of these diseases as well as stress from corruption and violence  here  is amongst the highest in a major city in the world, affecting especially the poorest and most illiterate labourers, state clinics rarely have budgets to cover the necessary vitamin and mineral supplements the poor  also need on their poverty fast food diet.

Our patients  accept that in return for life extension by designer antimicrobials and antidiabetic/ antihypertensives, all they will get for pain relief  is the combination of physiotherapy, and  designer synthetic palliative drugs- paracetamol, ibrufen /diclofenac, tramadol, amitryptiline, and if lucky some ung meth sal . These factory-synthesised drugs  give little relief,  and no improvement in prognosis since they do not address the proximate causes of the neuroarthropathy,  associated depression and  work incapacity (and later strokes, arthritis, dementia, ulcers, gangrene, chronic lung/heart/ liver/ kidney/visual disease)- respective causes including stress,  infective, drug-induced, tissue glycogenation, the misguided fast-food high carbohydrate-low fat diet  obesity; and manual labour/multiple trauma  wear and tear, and nutritional deficiency including much-needed marine and saturated fats, vitamins and minerals..

The pioneer  work discussed below in Pakistan(Salahuddin ea, Basit ea), Italy (Cipriani ea) and Brazil (Coimbra ea) in using respectively Vit D3 ~700 000iu loading dose and chronically up to 1000iu /kg/day ie average 70 000iu/day, up to 120000iu per day to reverse deadly acute and chronic disease,  is comparable in its simplicity safety and low cost to :

*Semmelweis’ revolutionary discovery  Vienna in the mid 19thC  of hand disinfection to decimate childbirth sepsis deaths; and

*Pauling’s landmark lifesaving escalation of Vit C dose to a gm  per kg per day for all severe disease; and

*the parallel discovery in UK and USA of the crucial role of not just the RDA preventative microdose but also the pharmacological anti-disease benefits of 10 to 100times bigger doses of all the vitamins B complex 1 to 12.

Cipriani ea 2010 seems to be the first report on Pubmed of deliberate oral dosing with  megadose     600 000iu vit D3 ie 10 000iu/kg, albeit only in health to assess bloodlevel response and safety. Since then, as we previously noted, 2 million unit single overdose in nonagenarians in Netherlands  has been shown to do no harm – ie about 40 000iu/kg. .

And as the Australians and others report below, there is no hint of vigorous vitamin or mineral  supplements being stigmatized as performance enhancing for eg sport –  despite vitamin D3 having the distinction of being truly an anabolic ie performance-enhancing (seco)steroid .

There is no point in giving vitamin D by injection (except in those in ICU on prolonged nil per mouth) since it is so well absorbed provided given with fat eg in fishoil/coconut/DMSO oil. And obviously the higher the dose given, the more important to avoid more than a traditional multisupplement pill a day  with low calcium and vitamin A retinol; combined with a low calcium diet (ie low dairy low peanut) ; and supplementing plenty fresh green produce [providing magnesia a few hundred mgs a day, and vitamin K2 perhaps 35mcg/d].

Dr  Mike Holick Prof of Medicine at Boston University interviewed by Dr Joe Mercola Dec 2015 details  the  rationale underpinning the (eg Coimbra) massive vit D3 dose regime for severe immune disease, “as opposed to  plenty of sensible sun exposure for general good health and lower deathrate from all diseases and infections.                 Most melanoma occurs on the least sunexposed skin, with lower melanoma and all other deaths with high sun exposure. Dark days promote melatonin and thus daytime sleepiness and depression- which bright light in the morning for an hour reverses, and elevates b-endorphan, which has many times the painkilling effect of morphines ie opioids, and antidepressants. Vitamin D deficiency more than doubles the risk of all diseases; even 2000iu vit D3 a day in the 1st yr of life in Finland halved the risk of type 1 diabetes– with loss of protection if vit D dose dropped to 400iu/day. Vitamin D/ sunlight reverse leukemic cells. But maximum sunlight exposure nearer the tropics still only elevates 25OHvit D level to a maximum of about 50ng/ml- whereas increasing evidence proves that it may take more than 10 times that bloodlevel to prevent and treat deadly diseases- depending on your genetic vitamin D receptors.

 Even 1000iu/d vit D with bld level about 30ng/ml halves risk of many cancers, with doubling benefit as 25OHvit D level is doubled serially  eg by 10 000iu/d or 50 000iu/d. The kidneys however limit production of the hypercalcemic 1,25vit D, thus avoiding hypercalcemia provided calcium intake is not supplemented by calcium pills, nuts. vit A  etc. The higher the vit D level above 30ng/ml (up to >? 500ng/ml), the more  of our 2000 enzyme systems are activated  to fight all disease without hypercalcemic risks. Hunter gatherers had levels twice as high as dressed housed people today, around 50ng/ml, with increasing anticancer and antiinfection/antiautoimmune benefit from vit D up to safe levels eg 100ng/ml and higher. .”

At Thisisms.com this is multiple sclerosis  March 2016 seems to be the latest from neurologist  Dr Cicero Coimbra  via grassroots health. He stresses that to cure degenerative/ autoimmune disease eg  MS, Parkinson’s, SLE, RA, vitiligo ie to overcome genetic Vit D resistance may require vit  D titration up to 1000iu/kg/d ie up to even 40000iu/d to 200000iu/d,
And 25OHvitD blood level to 1000ng  and even 4000ng / ml for a few years to produce cure, before reducing to maintenance vit D3  eg 100iu/kg/day ie ~ 50000iu/wk.
Hypercalcemia and thus calcinosis  is avoided provided PTH level is maintained in the low normal range, not suppressed. Optimal support includes low calcium and  high water diet and  Vit B2, magnes selenium zinc phosphor  supps.

      COST IMPLICATION:

The spectrum of vitamin D3 adult dose thus extends from the

traditional prevention RDA 10iu/kg/ ie~700iu/d against rickets (infants start with 1000iu/d or 25000iu ie ½ scoop/month of standardized vit D3  100iu/mg powder)

to  vigorous 100iu/kg/day (ie 50 000iu scoop /wk ) for common disease prevention/treatment (toddlers 2000iu/d/ ½ scoop/fortnight));

 to  massive  1000iu/kg/day eg 60 000iu/dy for severe autoimmune/immunodeficiency diseases – with mandatory monitoring of levels of calcium, creatinine, 25OHvitD3 and now PTH levels;

to mega 10 000iu/kg eg 650 000iu as a loading dose for eg TB or meningitis or severe trauma—which dose may maintain  25OHvit D3 blood levels in a “sufficiency” range above ~40ng/ml for a month or two, so obviously requires appropriate maintenance dosing.

Imported vitamin D3 100cwt concentrate powder (100iu/mg) per kg from an importing pharmacist costs about R500/kg ie R0.50/100 000iu- far lower than the cost of the highrisk plant xenocalciferol vitamin D2. Thus to the State (excluding packaging and dispensing cost) , the wholesale cost of vit D3 is about R0.15 per 50 000iu per week for maintenance dose; or for 50 000iu/day R10( US $0.6)/month ie retail abt R60pm ie US$5  for megadose therapy; compared to the quoted retail US$20/month in Brazil. .

     THE NEUROPATHY OF DIABETES, DRUGS/TOXINS, POST-VIRAL,TRAUMA,  SPONDYLOSIS, DEMENTIA:

PERIPHERAL NEUROPATHY:  Already in 2006 Oh-Park ,Sheehan .ea,  Lancet. Albert Einstein College of Medicine, New York wrote about AIDS-ARV neuropathy Charcot neuroarthropathy in the era of HAART.

Young, Dancho ea Tucson, Arizona, wrote 2012,   ” Charcot arthropathy is a devastating joint condition that affects persons with neuropathy. With HIV/AIDS treatments prolonging the lives of these persons, it is likely that long-term sequelae of the disease will become more evident in the near future. Patients with this disease frequently develop peripheral neuropathy. A high index of suspicion must be raised in any patient with peripheral neuropathy of any cause and a red, hot, swollen, painful foot for Charcot neuroarthropathy to give these patients proper treatment to help prevent the devastating effects of Charcot neuropathy with its potential consequences including foot ulceration and amputation. We know only too well the same applies to diabesity, as it did in the days of heavy smoking.”
In 2013 Zubair ea in India showed that diabetics with foot ulcers had vitamin D levels 1/4 of that of matched diabetics without foot ulcers; and “factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.3), neuropathy [OR 6.9retinopathy [OR 3.3;  nephropathy [OR 3.1) and smoking [OR 4.5]. It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is a secondary effect or is a direct action of vitamin D on certain components of the immune system.”  

Tiwari, Singh, Swain  ea at Hindu Universities Uttar Pradesh,India have shown elegantly in                          

    *2012 Tiwari ea   Vascular calcification in diabetic foot and its association with calcium homeostasis.      Vascular calcification (VC), long thought to result from passive degeneration, involves a complex process of biomineralization, frequently observed in diabetes and an indicator of diabetic peripheral vascular disease.. ..In  74 patients with diabetic foot ulcer,   Vascular calcification was present in 42% of patients. Significant difference in vitamin D, HbA1C, and eGFR  levels was observed in VC +ve compared to VC -ve.  Severe vitamin D deficiency was more common in VC +ve (51%) compared to in VC -ve (18%). Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05) in patients with vitamin D < 10 ng/ml compared to others. .and        

     * Br J Nutr. 2013. Tiwari  ea  Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection.   In Diabetic Patients with and without  infection (n289), 25(OH)D (nmol/l) was significantly lower (16) v. 20ng/ml  P < 0·001) in cases than in controls. Risk of severe vitamin D deficiency (25(OH)D < 10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. ;  and the need for vitamin D supplementation in such patients for a better clinical outcome

*.in  Br J Nutr.. 2014 Tiwari ea  show Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection  . Vitamin D is a potent immunomodulator and  a common deficiency  in different population groups including patients with diabetic foot infection.   in 112 diabetic foot infection cases and 109 diabetic controls , cases had significantly higher concentrations of IL-6 (P≤ 0.001), IL-1β and TNF-α (P≤ 0.006) than controls. Risk of severe vitamin D deficiency (25(OH)D <10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1β (r -0.323; P≤ 0.001) and  IL-6 but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations.

 

This year  2016     Wukich , Sadoskas  ea. University of Pittsburgh & Georgetown USA  in Diabetes Metab Res Rev.  show that (Charcot) neuroarthropathy (CN) of the ankle and hindfoot  is challenging to treat surgically or nonsurgically. Deformities associated with ankle/hindfoot CN are often multiplanar, resulting in  malalignment; and  shortening of the limb often occurs from collapse of the distal tibia, and ankle, with  significant alterations in the biomechanics of the foot. eg predisposing the patient to lateral foot ulceration. Collapse of the talus, secondary to avascular necrosis or neuropathic fracture, further accentuates these deformities and contributes to a limb-length inequality   CONCLUSION:  Surgical reconstruction of ankle and hindfoot CN is associated with a high rate of infectious and noninfectious complications. Preoperative measures that can improve outcomes include assessment of vascular status, optimization of glycemic control, correction of vitamin D deficiency and cessation of tobacco use. 

Now 2016 Basit A,  Malik RA5 ea in  Universities Karachi Pakistan & Manchester UK ,  show that A single intramuscular dose of 600000IU vitamin D in  143 participants with predominantly type 2 diabetes, aged ~ 52.3years, with high Douleur Neuropathique 4 (DN4) score  by  20weeks gave significant increase in 25(OH)D (from 31.7 to 46.2±10.2ng/mL, p<0.0001) and  significant  reduction (p<0.0001)  in positive symptoms on the DN4 , and total pain score (p<0.0001, The Basit – Malik Pakistan-Manchester paper showing great efficacy of 600 000iu vit D3 load dose in peripheral neuropathy diabetics matches the huge 40% improvement benefit of similar loading and monthly vit D3 dose against severe PTB shown by Salahuddin ea in Pakistan in 2013 http://www.ncbi.nlm.nih.gov/pubmed/23331510 that we have previously analyzed in this column

ie  apart from smoking; the very low vitamin D levels common in most but especially ill people  associate   with about 5 fold  risks of uncontrolled diabetes, infections,  retinopathy , progressive leg ulcers, peripheral neuropathy  and arthritis- Charcot arthroneuropathy- -and thus  gangrene and amputation; and vigorous safe (supraphysiological) vit D boost reverses the risks. .

 

And a reminder that a 2015 study in Cape town from Coussens ea Universities in W Cape and Penn State confirm what we see daily in practice, that vitamin D deficiency is endemic  in our population

 

while as we have pointed out repeatedly, the State here continues to dispense the inferior vitamin D2 (as the fraudulently labeled “strong calciferol”, not disclosing that it is ergocalciferol  D2) despite this plant xenohormone vit D2 having been rejected by world authorities in favour of the much cheaper and effective  human D3 cholecalciferol.

 

 

       And now 2016 Cadegiani , Brasilia, Brazil another  landmark massive-vit D dose report ;  Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment.Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. This reports a patient with severe and refractory myasthenia gravis (MG) who followed a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil  (Coimbra ea) and she had her first complete remission after this type of treatment  for at least 18 months (ie at least 50 million iu) with increased vitamin D serum levels (400 to 700 ng/mL) and major fall in her AChR antibodies – but acute relapse when vit D was inadvertently stopped and her vit D level halved; with again recovery when megadose vit D was resumed  CONCLUSIONS: This case may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases

 

     The above case concurs with previous reported massive dose daily vitamin D3: Finamor , Coimbra ea , Universities of Brazil  2013 A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months ie ~7million iu  in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya “milk”) and hydration (minimum 2.5 L daily).. After treatment 25(OH)D3 levels significantly increased (from ~15 to 106-132ng/mL. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.

 

 

     neurologist Prof Dr Cicero Coimbra from Univ Sao Paulo  presents their results since 2002 in over 4000 pts ( 1000 patients each with multiple sclerosis and Parkinson’s diseases), who have been well controlled without other therapies,  provided the dose is high enough- 10 000iu/d up to about 1000iu/kg/d eg >70 000iu/d for the obese, on a low calcium ie low dairy/peanuts diet, high fluid intake and high exercise, to normalize blood calcium,  and titrate  PTH level to  the low normal range. Dr Cicero Coimbra discusses  high dose vitamin D toxicity: https://www.youtube.com/watch?v=Vxwk-YPrx7o&feature=youtu.be. PTH level should not be completely suppressed. In their clinic ( of 7 doctors)  for Autoimmune chronic diseases incl MS, RA, SLE, psoriasis, vitiligo, type 1 diabetes ,  they have treated over 4500 pts on this high quality vit D3 high fluid  low calcium diet  protocol, with only 14 cases of reversible vitamin D toxicosis (hypercalcemia) so far detected ie 0.3%. Babies of mothers thus treated in pregnancy  have high psychomotor development. (Vitamin C supplement should not be concurrently excessive to avoid oxalosis). They define success as being disease-free or non-progressive old fixed disabilities- 95% reach full cure. There vit D3 therapy  costs only ~US $20/mo, to optimize the immune system against both infections and autoimmune disease let alone cancer. Optimal dose of vit D3 replacement becomes at least 10 000iu/day for adults especially with autoimmune diseases  due to common vitamin D resistance. Ideally testing baseline blood and urine at baseline and after a few months on at least 10 000iu/d.

 

 

     In Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency:. 2010. Cipriani ,Minisola ea .University of Rome  Italy tested    48 young subjects with vitamin D deficiency with a single oral dose of 600,000 IU of cholecalciferol. The 25(OH)D level was ~15.8ng/ml at baseline and became ~77ng/ml at 3 d (P < 0.001) and ~62 ng/ml at 30 d (P < 0.001). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. CONCLUSIONS: A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.

 

       Looking at some new alarmist myth refs about vit D3 overdose :

Moderate  ie physiological increase in just vitamin D levels and intake  (from average diet and sunshine and a traditional supplement) within the average population bloodlevel range understandably has modest  benefit- reversing at least rickets-  in an  indoor living clothed population, even  1st world middleaged:  from Wisconsin Univ, Karen Hansen ea’s recent RCT – JAMA 2015- Treatment of Vitamin D Insufficiency in Postmenopausal Women confirmed this, showing little practical benefit shortterm (ie over 12mo) between placebo, and supplemented vit D3  5600iu/wk and 25000 iu a week, (~3600iu/d);  the highest dose perhaps doubling the baseline 20ng/ml  25OH vit D level. ie into the low “adequate” range average around 40ng/ml.

Be aware again that  the same university’s group published in 2014   An Evaluation of High-Dose Vitamin D 2  for Rheumatoid Arthritis Karen Hansen ea that vit D2 ~100 00iu/month  for a year actually worsens patients and lowers vit D3 levels  , so there is no longer excuse for using vitamin D2 supplement when it blocks D3 receptors and lowers blood vit D3.

The inferiority of vit D2 was confirmed in eg    Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients.  Gottschlich, Kagan U Cincinnati Ohio 201550  patients  aged 1 to 18yrs with burns  were enrolled. All participants received multivitamin supplementation ,  plus , 100 IU/kg D2, D3, or placebo daily  RESULTS: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low 25OHD  at discharge, and %deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in clinical outcomes between treatment groups, although vitamin D supplementation demonstrated clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formationThe high incidence of low serum 25OHvit D levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity. 

The perception seems to be that up to 40 000iu vit D3 a day, a bld level below abt 150-350ng/ml  is safe, ie unsafe above that. The evidence for such ceiling ie  higher dose harm in fact is lacking since as we have previously discussed here,  healthy people have taken up to 150 000iu a day for decades without evidence of harm…  provided they took adequate fluids, and did not take supplements of calcium, or also take high  vitamin A which notoriously causes acute hypercalcemic toxicity, or have rising calcium levels . .

But note that vit K2 improves absorption of vit D3 CHOLECALCIFEROL , and vit K2 and magnesia improve benefit of vit D3,while protecting against overdose effects ie calcification, stones  and confusion.  Problem in many  toxicity reports is that they used either vit D2 ergocalcif (WHICH BLOCKS THE NEEDED D3) , or used accidental massive overdose (millions of units vit D ) daily for months- or massive INJECTIONS) or combined vit D WITH CALCIUM REPLACEMENT AND/ OR EXCESSIVE VITAMIN  A  – which combinations are  dangerous;  we need magnesium (not calcium  or high vitamin A supplements).

    Vitamin D3: What’s the Latest? recent 2015 reviews from  Univ California and CommonHealth contrast the Instit Medicine IOM (Big-Pharma-sponsored)  conservative target of  vit D3 800 to max 4000iu/d with much evidence that safe optimal D3 dose may be up to 10 000 to 50 000iu/d, and up to  1 000 000iu as an acute eg antiinfection  loading dose; with risk of toxicity only if blood level exceeds 150-500ng/ml. the evidence-based IOM recommendation of optimal blood level 20-40ng/ml, up to 2000iu a day promoted by conservatives like Prof JoAnn Manson, contrasts with the more proactive view of eg Prof Michael Hollick and the Vitamin D Council promoting double that dose as supplements, safely up to 10 000iu/day.

 

   SO  I continue to take vit D3 ~70 000iu/wk ie ~10 000iu/d,  with vit K2 supp ~700mcg a wk ie 100mcg/dy and a balanced multisupplement incl. magnesia in addition to a multisupplement A-Z, and fish oil and Lugols iodine 15% 2 drops a day; with if I do get a “flu” attack during bad weather, prompt abolition by a few antibiotic doses of topup Lugols iodine 15% a few tsp (ie ~1000mgs iodine),  and vitamin D3 eg 300 000iu, and vitamin C a few tsp orally and by sniffing. .

The problem with many adverse effect reports of vit D3 overdose eg the Dominican Republic Soladek  2011 report Lowe ea below, and Prof Heaney’s response,  is that they failed to even consider the massive associated  overdose of the far more hypercalcemic vitamin A let alone calcium supp reported by most  patients. It becomes apparent that NO calcium supplement should be encouraged on a prudent diet; but instead supplements of  Vit D3, magnesia, vits K2 and C, CoQ10, and fish oil ; in addition to a balanced (A to Z) RDA-based multisupplement for seniors  like eg Solal’s,  Vital’s Multitime, Centrum etc.. with a low calcium diet if massive dose vitamin D3 is indicated as in autoimmune diseases (Coimbra ea).

Ndb

APPENDIX: RECENT REFS:
VITAMIN D ANABOLIC STEROID ABUSE IN SPORT?

the Australian Govt  Supplement Overview   has an intriguing report on vit D in sports, with no hint of vit D supplement being a steroid abuse. .http://www.ausport.gov.au/data/assets/pdf_file/0003/594174/CORP_33413_SSF_Vitamin_D_FS.pdf        Vitamin D is classified as a fat soluble vitamin which acts functionally as a steroid hormones. There are 2 different isoforms of Vitamin D: D3 (cholecalciferol) which is the important isomer formed in human   skin and D2 (ergocalciferol) which is the plant-derived ie xeno-equivalent. D2 was the first isoform to be characterised   and was first used in Vitamin D supplements and for food fortification. D3 is now considered preferable. D3 is   biologically inert until converted in the liver to 25(OH)D and to 1,25(OH)D in the kidney.  Vitamin D plays an important role in calcium and phosphorous homeostasis (bone health),but more so in  gene expression and cell growth. The recent recognition of Vitamin D receptors in most body tissues indicates a role for Vitamin D in  many aspects of health and function. Vitamin D is now known to be important for optimal muscle function.

         The principal source of circulating vitamin D comes from exposure to ultraviolet B (UVB) radiation from sunlight.   In 2010, the Institute of Medicine issued new Dietary Reference Intakes for Vitamin D, assuming no sunlight exposure: this included a Recommended Dietary Intake of 600 IU/d and an Upper Level intake of 4000 IU/d  (www.iom.edu/vitamind). BUT no evidence has ever been published to support this ceiling intake.

Whereas Vitamin D deficiency can lead to several health issues including increased risk of bone injuries, chronic musculoskeletal pain and viral respiratory tract infections. There is also emerging evidence that supplementing Vitamin D in athletes with sub-optimal Vitamin D levels may   have beneficial effects on athletic performance in particular strength, power, reaction time and balance.

         There is no universally accepted definition of vitamin D deficiency however, the following definitions based on  serum levels of 25(OH) Vitamin D are often cited:

Vitamin D deficiency: serum levels < 20 ng/ml (50 nmol/L);  Vit D insufficiency: serum levels < 30 ng/ml

Vit  D sufficiency: serum levels > 30 ng/ml    Ideal Vit D range*: 30-50ng/ml 

Toxicity: > 150ng/ml, when combined with raised serum calcium

(*Higher status may be preferred for athletes to allow a greater safety margin and to optimize performance;   some agencies working with elite athletes often set their own thresholds for desired Vitamin D concentrations)

Ie they quote no evidence for the 25OH vit D ceiling of 50ng/ml.

 

Confirmed in

  Owens DJ1, Close GL ea .  UK Universities  . 2015..A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Skeletal muscle is a direct target for  vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (~18ng/ml). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors.  Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.

 

2016 Is there an optimal vitamin D status for immunity in athletes and military personnel?  He CS1, Gleeson M ea .Vitamin D is mainly obtained through sunlight ultraviolet-B (UVB) exposure of the skin, with a small amount typically coming from the diet.It is now clear that vitamin D has important roles beyond its well-known effects on calcium and bone homeostasis. Immune cells express the vitamin D receptor, including antigen presenting cells, T cells and B cells, and these cells are all capable of synthesizing the biologically active vitamin D metabolite, 1, 25 hydroxy vitamin D.There has been growing interest in the benefits of supplementing vitamin D as studies report vitamin D insufficiency (circulating 25(OH)D < 50 nmol/L) in more than half of all athletes and military personnel tested during the winter, when skin sunlight UVB is negligible. The overwhelming evidence supports avoiding vitamin D deficiency (25(OH)D< 30 nmol/L)to maintain immunity and prevent upper respiratory illness (URI) in athletes and military personnel.Recent evidence supports an optimal circulating 25(OH)D of 75 nmol/L to prevent URI and enhance innate immunity and mucosal immunity and bring about anti-inflammatory actions through the induction of regulatory T cells and the inhibition of pro-inflammatory cytokine production. We provide practical recommendations for how vitamin D sufficiency can be achieved in most individuals by safe sunlight exposure in the summer and daily 1, 000 IU vitamin D3 supplementation in the winter.

 

Sarris J1, Ng CH1. Ea, Universities  of Melbourne, & Deakin, Australia;  &  Harvard Boston; 2016  show in   Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. http://www.ncbi.nlm.nih.gov/pubmed/27113121  Adjunctive  standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several  neurochemical pathways implicated in depression. A systematic search up to 2015 for clinical trials using adjunctive nutrients for depression    RESULTS: Primarily positive results were found for studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D,.  Mixed results were found for zinc, folic acid, vitamin C, and tryptophan. . No major adverse effects were noted in the studies  adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.

Raina AH1, Bhat FA1 ea ., India.. 2016 Association of Low Levels of Vitamin D with Chronic Stable Angina: A Prospective Case-Control Study.  http://www.ncbi.nlm.nih.gov/pubmed/27114971  Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. METHODS: a prospective case-control study in  100 cases of chronic stable angina compared controls. Vitamin D deficiency was defined as <20 ng/mL, vitamin D insufficiency as 20-30 ng/mL and normal vitamin D level as 31-150 ng/mL.RESULTS: The prevalence of vitamin D deficiency among cases and controls was 75% and 10%, respectively. 13% had normal vitamin D levels (31-150 ng/mL). None had a toxic level of vitamin D. Among the controls, 10% were vitamin D-deficient, 57% had normal vitamin D levels. The mean vitamin level among cases and controls was 15.53 ng/mL and 40.95 ng/mL, respectively, statistically significant (P ≤ 0.0001). Among the cases, we found that an increasing age was inversely related to vitamin D levels (P = 0.027). Low levels may be an independent, potentially modifiable cardiovascular risk factor.

Jetty , Glueck   Kumar  ea . Jewish Hospital Cincinnati, Ohio, USA  2016  show 12mo Safety of 50,000-100,000 Units of Vitamin D3/Week in Hypercholesterolemic  Vitamin D-Deficient,   Patients with Reversible Statin Intolerance. : http://www.ncbi.nlm.nih.gov/pubmed/27114973   Such Vitamin D3 therapy (was safe and effective when given for 12 months to reverse statin intolerance in patients with vitamin D deficiency. Serum vitamin D rarely exceeded 100 ng/mL, never reached toxic levels, and there were no significant change in serum calcium or eGFR

https://riordanclinic.org/2013/10/vitamins-d3-and-k2-the-dynamic-duo/ As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.

http://www.amazon.com/MIRACULOUS-RESULTS-EXTREMELY-SUNSHINE-EXPERIMENT-ebook/dp/B005FCKN2S#reader_B005FCKN2S     is a recent book by Jeff T Bowles .

 Newsletter: Gary Null and vitamin D toxicity    2010 by John Cannell, MD http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/     “Warning: If you intend to take massive doses of vitamin D based on this newsletter, which I highly recommend you do not, read the entire newsletter. In addition, accurate determination of side effects of massive doses of vitamin D was not available in the early 1930s, nor was accurate determination of the true amount in each pill possible.    Is 2,000,000 IU/day of vitamin D toxic?   Ask Gary Null, alternative medicine guru and entrepreneur. He took his own supplement, Ultimate Power Meal, for a month and became extremely ill; one batch of Power Meal apparently contained 1,000 times more vitamin D than it should. That is, it contained 2,000,000 IU of vitamin D3 per serving instead of 2,000 IU per serving. Mr. Null became sicker and sicker as he gulped it down.

After suing his own supplier for permanent physical damage, Mr. Null then reported it took 3 months to get the extra vitamin D out of his system and that he is now alive and well. If Mr. Null took it for the full month that he claims, and if his Power Meal contained 2,000,000 IU per dose, Mr. Null consumed 60,000,000 IU in one month. Could he really be fine now with no lasting injuries?  In an attempt to answer that question, I went back to the 1930s and 40s.  Massive doses in the 1930s  The earliest references I could find to enormous doses of vitamin D were in the 1930s. In 1935, Drs. Dreyer and Reed, of the University of Illinois School of Medicine, published their observations on 700 patients treated with “massive” doses of vitamin D for up to two years.1  ….” read on..http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/ http://www.livescience.com/50765-vitamin-d-supplements-toxicity.html

Vitamin D Overdose   Dr. Liji Thomas, MD  2016  http://www.news-medical.net/health/Vitamin-D-Overdose.aspx   vitamin D toxicity can occur from high intakes of supplements containing vitamin D, but not from dietary intake. Prolonged sun exposure also does not result in vitamin D toxicity because the previtamin D3 is degraded as the skin heats up, and also because of the formation of various other non-functional forms of vitamin D from the thermally activated compound.   Long term intakes of vitamin D above the upper limit recommended causes symptoms of toxicity. However, the intakes must be higher than about 40,000 IU/day, or the serum level of 25-hydroxy above 500-600 ng/mL, and the patient is usually also taking excessive amounts of calcium as well.

Dietary Supplement–Induced Vitamin D Intoxication  Klontz KC, Acheson DW.  To the Editor 2004:    Vitamin D intoxication that is associated with the consumption of dietary supplements is reported rarely. In 2004, the Food and Drug Administration (FDA) learned of the following case. A 58-year-old woman with diabetes mellitus and rheumatoid arthritis began taking a dietary supplement called Solutions IE Ageless Formula II on January 12, 2004. Fatigue, constipation, back pain, forgetfulness, nausea, and vomiting soon developed. On March 15, 2004, she was hospitalized because her speech was slurred, and a blood glucose reading taken at home was 30 mg per deciliter. On admission, her serum levels were as follows: calcium, more than 3.75 mmol per liter; 25-hydroxyvitamin D, 460ng/ml (normal range, 9-5);; parathyroid hormone, 12 ng per liter (normal range, 10 to 65); and creatinine, 265 μmol per liter.   The patient was treated with intravenous normal saline, furosemide, and pamidronate. On March 19, 2004, while still hospitalized, she was informed by the product distributor of an error in product formulation such that 188,640 IU of vitamin D3/d  had been added to the daily serving size of six capsules instead of the intended 400 IU. IE SHE HAD TAKEN ~12.2MILLION IU OF VIT D3 IN 2 MONTHS. At discharge on March 24, the patient’s serum levels were as follows: calcium, 2.60 mmol per liter; blood urea nitrogen, 10.0 mmol per liter; and creatinine, 221 μmol per liter. The patient died from a cause unknown to us on January 8, 2005.   Laboratory analysis of the product by the FDA, obtained from one of two lots reportedly overfortified with vitamin D3, revealed 186,906 IU of vitamin D3 in each serving size of six capsules, indicating that the patient had consumed roughly 90 times the recommended safe upper limit of 2000 IU per day. Long-term daily vitamin D consumption of more than 40,000 IU (1000 μg) is needed to cause hypercalcemia in healthy persons.2     In March 2004, the product distributor announced that during the previous month it had received three complaints from customers who had been hospitalized for hypercalcemia and vitamin D toxicity

2011 Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. Lowe H1, Bilezikian JP. ea  Columbia Univ, NY.. http://press.endocrine.org/doi/10.1210/jc.2010-1999?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&   Hypercalcemia in ambulatory patients is occasionally caused by vitamin D toxicity. We report nine patients presenting to Columbia University Medical Center with hypercalcemia due to a supplement from the Dominican Republic containing massive amounts of vitamin D. All reported recently taking Soladek readily available in the Dominican Republic and in Upper Manhattan. serum calcium values before the ingestion of Soladek were not elevated  According to the manufacturer’s label, each 5-ml vial of Soladek contains vitamin D3 (600,000 IU), vitamin A (120,000 IU), and vitamin E (5 mg). Laboratory analysis by HPLC revealed that the supplement actually contained vitamin D(3) (864,000 IU) and vitamin A (predominantly retinyl palmitate 123,500 IU) per vial.IE 864000 IU VIT D /day FOR UNKNOWN DURATION. a similar case was reported earlier  http://www.thecamreport.com/2009/11/soladek-toxicity-in-a-60-year-old-woman/

Comments by Prof Robert P. Heany    Creighton University, Omaha, Nebraska  on Lowe et al:   Hypercalcemia in vitamin D intoxication JCEM   http://press.endocrine.org/e-letters/10.1210/jc.2010-1999        The report by Lowe et al. on vitamin D intoxication from an OTC supplement (1) is instructive and useful. I comment on the authors’  suggested mechanism of hypercalcemia in such cases. The authors propose that the elevated concentration of serum 25- hydroxy-vitamin D [25(OH)D] is the responsible agent, through loose binding to the vitamin D receptor. While my colleagues and I have shown that 25(OH)D can improve calcium absorption (2), I believe there is a simpler explanation for hypercalcemia in vitamin D intoxication, particularly as the reported values of 25(OH)D were not uniformly high in these nine cases. [In fact the patient with the highest serum calcium had actually the lowest value for 25(OH)D.] Instead, as Vieth suggested several years ago in a paper actually referenced by Lowe et al. (3), elevation of free circulating 1,25(OH)2D (calcitriol) is the most parsimonious explanation. This level is not commonly measured, and was not reported in the cases described by Lowe et al. Vieth has estimated the binding capacity of the D-binding protein (DBP) at approximately 4700 nmol/liter, and it is generally recognized that fewer than 5% of its binding sites are occupied at typical cholecalciferol inputs. However, in the face of huge cholecalciferol doses, as in the nine cases described here, it can easily be calculated that most or all of the binding sites on the DBP would be occupied by cholecalciferol itself as well as by 25(OH)D and 24,25(OH)2D, all of which are bound to the DBP more avidly than is calcitriol. Lowe et al. did not measure serum cholecalciferol, but it is virtually certain that its concentration would have been elevated, if for no other reason than that the capacity of the hepatic 25-hydroxylase is limited, and serum cholecalciferol concentration rises steeply for cholecalciferol inputs in excess of the saturation level of the 25-hydroxylase [which typically occurs at serum cholecalciferol levels of about 10 nmol/L and serum 25(OH)D of about 80 nmol/liter (4)].Even if all of the binding sites of the DBP were not continuously occupied by less polar metabolites, high occupancy would shift the equilibrium between the free and the bound calcitriol, so that free calcitriol concentration would likely have been substantially above normal values continuously. The authors speculate as to the origin of the elevated total calcitriol concentrations, given the down-regulation of the renal 1-á- hydroxylase in such cases. 

 

     2016.Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. Lupton JR1Michos  ea .  Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).OBJECTIVE: Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function.METHODS: We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (≥20-30 ng/mL), and optimal (≥30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression.RESULTS: In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group.CONCLUSION:  Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG

 

  1. Low-Level VitaminD Is strongly Associated with Atrial Fibrillation in Patients with Chronic Heart Failure.Belen E1, , Cetin M2ea. Atrial fibrillation (AF) freuently accompanies heart failure (HF), and causes exacerbation of symptoms and treatment failure in such patients. Vitamin D was recently suggested to be an important mediator of cardiovascular disease, including HF.OBJECTIVES: The aim of this study was to evaluate the relationship between vitamin D deficiency and AF in patients with chronic HF. METHODS: The study included 180 chronic HF patients that were divided into 2 groups based on having sinus rhythm [AF (-) group] or chronic AF [AF (+) group]. Vitamin D status was assessed via measurement of the serum 25-hydroxyvitamin D (25[OH]D) concentration.RESULTS: Mean age of the patients was 66 ± 8.7 years and 53.9% were male. There weren’t any significant differences in age, gender, body mass index, etiology or chronic HF stage between the 2 groups. The vitamin D level in the AF (+) group was significantly lower than in the AF (-) group (11.05 ng/mL vs. 20 ng/mL, p < 0.001) The left atrium to body surface area ratio (LA/BSA) was significantly higher in the AF (+) group (45.03 mm/m2 vs. 42.05 mm/m2, p < 0.01). Independent predictors (based on multiple regression) of AF were vitamin D level (OR = 0.854, 95% CI: 0.805-0.907, p < 0.001) and LA/BSA ratio (OR = 1.077, 95% CI: 1.003-1.156, p < 0.05). The optimal vitamin D cut-off value for the prediction of AF was 16.50 ng/mL, with a sensitivity of 76.0% and specificity of 65.5% (AUC = 0.75, 95% CI: 0.67-0.82).

 

Vitam Horm. 2016;100:255-71. doi: 10.1016/bs.vh.2015.10.001. Epub 2015 Nov 30. Molecular Approaches for Optimizing Vitamin D Supplementation.   Carlberg C1.Vitamin D can be synthesized endogenously within UV-B exposed human skin. However, avoidance of sufficient sun exposure via predominant indoor activities, textile coverage, dark skin at higher latitude, and seasonal variations makes the intake of vitamin D fortified food or direct vitamin D supplementation necessary. Vitamin D has via its biologically most active metabolite 1α,25-dihydroxyvitamin D and the transcription factor vitamin D receptor a direct effect on the epigenome and transcriptome of many human tissues and cell types. Different interpretation of results from observational studies with vitamin D led to some dispute in the field on the desired optimal vitamin D level and the recommended daily supplementation. This chapter will provide background on the epigenome- and transcriptome-wide functions of vitamin D and will outline how this insight may be used for determining of the optimal vitamin D status of human individuals. These reflections will lead to the concept of a personal vitamin D index that may be a better guideline for an optimized vitamin D supplementation than population-based recommendations.

 

  1. Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis.Zhao, , Huang J3. The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015.METHODS: We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration.: Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007).CONCLUSIONS:   Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥30ng/ml  was associated with a 60% lower risk of bladder cancer incidence.

the Ides of March 2016:  Where have we been the past 5 years in ignoring the crucial role of K2 supplement  with vit D3? against cancer, fractures, infections, vascular disease and diabetes , 

      like the crucial role of Lugols iodine + selenium, and magnesium (not calcium), coQ10, and animal, marine and coconut ie saturated fat oil- supplement  for all chronic disease prevention?

     Considering that our western processed food staple diet, and the diet of the poor majority everywhere,  is increasingly deficient especially in these nutrients,  with by profit-motivated industrial design  disease-promoting cholesterol-depletion, refined sugars, transfats, antibiotics, hormones,  and noxious at-any-dose elements from fluorine and aluminium upwards.

 

I see I was  promoting K2 in my emails 4 years ago,  and since 2009, on my Healthspanlife blog  ie in  my lectures  and thus in my healthspanlife blends .

     But  I indeed don’t seem to have published a review of K2 on my blog- till now!
– and there are so many refs out there since the first K2 mention on Pubmed in 1946,
and its first Pubmed  human supplement mention in 2002  Improvement with maternal supplement of vitamin K2  of vitamin K status of breastfeeding infants  (MK40).  Nishiguchi T, Terao T ea.   Semin Thromb Hemost. 2002 : 28533-8.

Unlike the Big Pharma-Disease-Industry- controlled denialists of conservative safe  natural phamacological vitamin therapy  like the   Linus Pauling Institute   and   Wikipedia                 https://en.wikipedia.org/wiki/Vitamin_K2,

the vitamin  K2 Polish scientist Dr Katarzyna Maresz PhD     2015 writes (see abstract below)  Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health.  Maresz K1. International Science and Health Foundation Krakow, Poland    Inadequate calcium intake can lead to decreased bone mineral density, thus  increase the risk of bone fractures. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. … The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.
      While vit D3  cholecalciferol soltriol  was the multiprevention megavitamin   of the past decade, and CoQ10 the decade before that, catching up with the protean benefits of increasingly diet- deficient vitamins published (350 000 Pubmed citations) the past century, and of vitamin K since 1936, and K2 since 1946,
vit K2 is the most publicized ie advancing megavit of the current decade:
Adequate intake ie ~45 to ~150mcg/d is crucial with magnesium, boron etc to balance vigorous  vit D3 supplement,
for both bone, immune/cancer, and cardiovascular health.
Thus even just ~55mcg/d K2 supplement HALVES the risk of cardiovascular disease – very important in overweight/stressed/ aging people. 

BUT The authorities quoted have assessed safety and optimal longterm effective doses of vitamin K3 and vitamin D3 IN ISOLATION  for major prevention. However, we know that optimal nutrition is balanced nutrition, not one or two nutrient is superdose with an average fastfood mediocre diet. 

This finally convinces me to add vit K2 ~ 35 to 100mcg/day ie 200 to 700mcg/wk  to my own  vit D3 supplements. at a trivial bulk wholesale cost of  ~10mg/d 1% K2 ie ~R0.1/day or R14 – ( US$1)   bag  per 40 weeks of vit D3 @ 50 000iu vit D3 twice a month.

Like  Mercola 2010  http://articles.mercola.com/sites/articles/archive/2010/08/26/this-could-be-even-bigger-than-the-vitamin-d-discovery.aspx,             Byron Richards already in 2010 wrote a major review promoting K2 multipurpose: http://www.wellnessresources.com/health/articles/vitamin_k2_bones_cardiovascular_health_blood_sugar_control_cancer_prev/

As a recent BBC review   details,    “Vitamin K1 has a relatively short half-life and is rapidly cleared from the blood  by the liver within eight hours. In comparison vitamin K2 has a longer half-life of up to 72 hours, meaning it remains biologically active in the body for longer.   Vitamin K2 is also absorbed better by the body, and is linked to cardiovascular health. It directs calcium to the bones, and prevents it from being deposited where it shouldn’t be, for example arteries and organs, where it can cause harm.

The Kansas Riordan Clinic  promotes the Superhuman Duo  of D3+K:   they point out that ” Because an accurate LD50 for vit D in humans has never been determined (thank God!) most researchers use the LD50 for dogs as an estimate for humans, using a hypothetical human subject weighing  50kg, 110 pounds: in order to reach the LD50 dose, that subject would need to consume over 3,500 of the 50,000 IU D3 caps in a 24 hour period (146 capsules an hour,  total  175million iu) in order to have a 50% chance of dying. By conscientiously using vitamin K2 in conjunction with D3, this issue of “metastatic calcium” is thoroughly avoided.  Finally, like vitamin D3, strong evidence demonstrates vitamin K’s amazing ability to reduce cancer risk. For example, men taking vitamin K2 mk7 (a naturally occurring long acting form of K2) at 45 mcg a day can statistically reduce their risk of prostate cancer by 60%! That is just one of many cancer risks that are reduced significantly by regular K2 ingestion.      As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.

            For the safety of vigorous dose of vitamin D3, the masses of D3  evidence we assembled by August 2015   is that 2million units as a single oral dose does no harm to nonagenarians, nor has over 100 000iu a day for 28 years ie over a billion  iu  in middle-aged women.  

 In 2015,    Like *Joe Leech                                          and             *Hogne Vik   ,                                                    *Angela Pifer nutritionist notes the essensiality of balancing vit D3 with K2  “Vitamin D3 should never be taken alone. Always take a combination Vitamin D3/ Vitamin K2 liquid emulsion, at night for best absorption. This is because vitamin D3 improves calcium absorption across the GI tract and vitamin K2 is the cofactor needed to transfer calcium into your bones, and not your arteries.   (Eur J Clin Nutr. 2016 Feb 24. doi: 10.1038/ejcn.2016.3. Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules.   KnapenVermeer  ea . Maastricht University, Netherlands.   In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt  fortified with vitamin K2 (as menaquinone-7, MK-7) and vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7, For 42 days in healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules.  RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found.   CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.)

Some recent of the other 5000 K2 refs on Pubmed, apart from the abundant reviews by Garry Gordon, Joe Mercola, Mike Howard, Jeff Dach, Townsend letter, ea  , are

Integr Med (Encinitas). 2015;14; 34-9.  Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health.  Maresz K1. International Science and Health Foundation Krakow, Poland    Inadequate calcium intake can lead to decreased bone mineral density, thus  increase the risk of bone fractures. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. An adequate intake of vitamin K2 has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K2, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. An increased intake of vitamin K2 could be a means of lowering calcium-associated health risks.    “  Calcium ConcernsIf at least 32 mcg/d of vitamin K2 is present in the diet, then the risks for blood-vessel calcification and heart problems are significantly lowered, the elasticity of the vessel wall is increased. Moreover, the beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women has been seen in clinical trials. If less vitamin K2 is present in the diet, then cardiovascular problems may arise. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. A study on 564 postmenopausal women also revealed that intake of vitamin K2 was associated with decreased coronary calcification, whereas intake of vitamin K1 was not.  ”  A recent, double-blind, randomized clinical trial investigated the effects of supplemental MK-7, MenaQ7 (NattoPharma ASA, Hovik, Norway) for a 3-year period in a group of 244 postmenopausal Dutch women. The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.It showed a significant improvement in cardiovascular health as measured by ultrasound and pulse-wave velocity, which are recognized as standard measurements for cardiovascular health. In that trial, carotid artery distensibility was significantly improved for a 3-year period as compared with that of a placebo group. Also, pulse-wave velocity showed a statistically significantly decrease after 3 years for the vitamin K2 (MK-7) group, but not for the placebo group, demonstrating an increase in the elasticity and reduction in age-related arterial stiffening.” 

*     Nutrients. 2015 Oct ;7;8905-15.  Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).Vossen, Kroon ea  Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months.  We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
*            
Ugeskr Laeger. 2015 Aug;177:V12140700. Vitamin K2 influences several diseases]. Hey H1, Brasen CL. Lillebælt, Kabbeltoft, In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients witr can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.
*           Oman Med J. 2014;29;172-7. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review.  El Asmar, Arbid  ea, American University of Beirut, Lebanon. Vascular calcification, a cause of cardiovascular morbidity and mortality, is an actively regulated process involving vitamin K dependent proteins (VKDPs) among others. Vitamin K is an essential micronutrient, present in plants and animal fermented products that plays an important role as a cofactor for the post-translational γ-carboxylation of glutamic acid residues in a number of proteins. These VKDPs require carboxylation to become biologically active, and they have been identified as having an active role in vascular cell migration, angiogenesis and vascular calcification. calcification.
*             Dermatoendocrinol. 2015 Jan;6e968490. Vitamin K: an old vitamin in a new perspective.   Gröber U, Reichrath J, Holick MF, Kisters Essen, Germany.&  Boston, MA USA. The topic of “Vitamin K” is currently booming on the health products market. Current research increasingly indicates that the antihaemorrhagic vitamin has a considerable benefit in the prevention and treatment of bone and vascular disease. Vitamin K1 (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-7, menaquinone-7). Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically reduced. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, inhibit vessel wall calcification, support endothelial integrity, facilitate bone mineralization, are involved in tissue renewal and cell growth control, and have numerous other effects.

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.

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..

THE 2014 VIRUS SEASON DAWNS: URGENT UPDATE: AVOIDING THE SEMMELWEIS REFLEX; natural antibiotics- Vitamins C & D3 – avoiding vitamin denialism.

update 22/3/2014the March equinox:Vaccines and antivirals for preventing   and  treating  influenza in healthy adults have  very modest benefit.  as  the seasonal flu epidemic wanes in the northern hemisphere and approaches in the south, Authorities eg the US CDC  continue relentlessly to promote mass flu vaccination. The South African Authority NICD recommends vaccination for anyone at high risk ie the elderly, infants or the sick, and carers. It also recommends antivirals eg Tamiflu for infection- but the BMJ recently publishes  Study claiming Tamiflu saved lives was based on “flawed” analysis. a 2012 BMJ  report by the samemedical journalist   Zosia Kmietowicz   notes Cochrane group rejects Roche’s offer of “advisory board” to discuss analysis of oseltamivir data. The 2011 Cochrane question remains unresolved:  Does Oseltamivir Tamiflu  Really Reduce Complications of Influenza?

But current Cochrane review of controlled trial publications to 2013 confirms  Vaccination of pregnant women is recommended internationally, while healthy adults are targeted in North America. The overall efficacy of inactivated vaccines in preventing confirmed influenza has a NNV of 71 (95% CI 64 to 80). . Live aerosol vaccines have an overall effectiveness corresponding to a NNV 46 (95% CI 29 to 115). Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms CONCLUSIONS: Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women.  This review includes 90 studies, 24 of which (26.7%) were funded totally or partially by industry. Out of the 48 RCTs, 17 were industry-funded (35.4%).

A current German review  Methodological quality of systematic reviews on influenza vaccination.   Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high  but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001).  this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05).

20/1/2014   Protecting us from the new year northern hemisphere viruses:   natural antibiotics- Vitamins C & D: avoiding vitamin denialism as cause of more deaths.

Abstract: The Semmelweis  Reflex is about rejecting, deriding important new scientific discoveries or any serious sincere statement/action.    I didnt  fully appreciate the importance of that  age-old human  (mostly male) evil – mocking, martyrdom  and murder by denialism-  until I started this review of the current flu season threat and the role of supplements, and researched  pioneer medical martyrs Drs Ignaz Semmelweis, Jack Drummond  and Linus Pauling  as  paradigms of the scourge of modern vested-interest denialism and falsehoods, in medicine as much as politics, religion etc..

In fact,  just as it is negligence to deny (as Semmelweis’s persecutors did) gloving up or  properly washing  hands between examining patients , or ensure that every adult has bloodpressure checked occasionally, it is clearly bad practice  not to ensure that everyone – especially the young and old,  takes a multinutrient plus extra vigorous dose vitamins D3 and C, plus some protective herbs- garlic, cinnamon, ginger, origanum; and fish oil and/or coconut oil if not both; and drastically cut down sweetness intake- especially fructose, sucrose  and aspartame that now pervade all mass- produced food and drinks..

update 21 January 2014 : URGENT: THE 2014 FLU EPIDEMIC:     “High H1N1 prevalence and mortality rates a concern:    Type A (H1N1) influenza, the  commonest flu virus in Canada this year, has a higher  than anticipated mortality rate  causing some to wonder if it’s virulence has increased.             The worrisome factor  “is the reported mortality rate,” says  McGill University. As of Jan. 13, there were twenty confirmed deaths in Canada   attributed to H1N1. “There are more deaths than what we expect for the regular H1N1 influenza, The strain this year could be more virulent . 96% of this year’s lab -confirmed influenza is H1N1. The virus is unusual in that it appears to affect younger people more than other strains of seasonal influenza. People  20 to 65 are being hit harder than usual, comprising 52% of flu cases.                                  However, if you look at Europe,  it’s still H3N2. Its an example of how   you never know what the flu is going to do.”           Alberta confirmed a death  on Jan. 8, due to the virus H5N1, an avian virus. The  deceased woman had recently returned from China. The mortality rate is higher with H5N1 than H1N1, “but fortunately, it’s not an easy virus to transmit”. So far, it seems that there are no cases of H5N1 transmission from human-to-human. It seems   like the cases of H5N1 are few and far between and related to contact with birds in  China.     Patrick Janukavicius, Montréal, Quebec.  In the same period, at least 20 children have reportedly died of the same strain in USA.

update 12 Jan 2014  THE ANTIFLU VACCINE DECEPTION: this review by Doc Joe Mercola     stresses the disease-mongering myths,  futility and risks in real life of flu vaccination  and antiflu drugs eg Tamiflu ; and the overwhelming importance of natural immune boosters like Vit D3 & C, zinc, selenium,  herbs, and hygienic prevention.

1 Jan 2014  CURRENT INFLUENZA STATUSThe  22 December  solstice is the sun at its southern nadir seen from planet Earth, the onset respectively of real winter in the Northern hemisphere, and real summer in South Africa. Last year   the Gregorian New Year heralded a fierce flu season in the northern hemisphere, and as usual feathered- and jet-propelled  air travel brought the corresponding surge at the bottom of Africa.

And ominously, the Plagues & Pandemics   (Howard Phillips 2012) of temperate climates  that did so much historically  to mould global demography not least  the past 360 years in South Africa ( –STDS- pox, bubonic, polio, cholera, influenza, and now  tuberculosis, Mad Cow disease, and   HIV-AIDS). and especially antibiotic-resistant germs – are all on the increase despite (or because of) the increasingly futile $trillion armamentarium of 20th century designer vaccines and other antimicrobials.. 

Pneumonia is a welcome   friend of the old, often rapidly relieving prolonged degenerative incapacity;  such ending mostly by virus respiratory infection  the gateway for the  final bacterial infection.  

Unlike the  selflimited coronavirus common cold, breath-and hand-borne type A  influenza, although usually mild in the well,  is the commonest trigger in the frail.  Many  of us in our (grand)parents’ time lost relatives in the 1918/1919 “Spanish”  H1N1  flu pandemic. But that was a unique  global catastrophe because it killed mostly  armies  of healthy men, and then  young working adults, apparently from cytokine storm, with 30 % of the workforce out for up to3 weeks if not  20% mortality.  This is harrowingly described in the recently published   Letters ( to his Mother) of Dr Arthur Conan Doyle, who lost – apart from his first wife to TB- more young relatives to the  flu  than to warfare.

The recent spring  months here – apart from seasonal allergies -have seen declining viral respiratory illness in Cape Town, with the  upper respiratory accent often shifted down to more gastritis-enteritis .

But New Year 2014   UK and northern North America forecast  and are having a  wet if not white New Year.  ‘Flu rates are reported already high  and rising  in USA and Canadamostly influenza A H1N1(swine-avian flu-the main 1918/19 killer); including already 6 deaths in USA and 3 in Canada.

but not in Europe, where  the influenza (A > B) prevalence is still low and slightly more H3N2 than H1N1;  in UK there has rather been been increase in RSV respiratory syncytial virus bronchitis in infants. .  .

In fact by 28 December the exploding H1N1 deathtoll had hit 13 in Texas alone; especially in youths; with increasing Tamiflu resistance reported eg in Missisippi.. On 24 Dec the USA CDC mailed an emergency Advisory Notice to Clinicians: Early Reports of pH1N1-Associated Illnesses for the 2013-14 Influenza Season: From November through December 2013, CDC has received a number of reports of severe respiratory illness among young and middle-aged adults, many of whom were infected with influenza A pH1N1 pdm09 virus. Multiple pH1N1-associated hospitalizations, including many requiring intensive care unit (ICU) admission, and some fatalities have been reported.  While it is not possible to predict which influenza viruses will predominate during the entire 2013-14 influenza season, pH1N1 has been the predominant circulating virus so far. For the 2013-14 season, if pH1N1 virus continues to circulate widely, illness that disproportionately affects young and middle-aged adults may occur. 

Our  regional  South African Communicable Diseases Institute says H1N1 was documented here from April to September. But of 2566 pts with severe respiratory illness for January to October 2013 enrolled and tested at the five sentinel sites, only 6% were positive for influenza – mostly virus -H1N1. A pneumonia case in Cape Town was found to be due to Leigionnaire’s.

Now from China 147 human cases of avian influenza H7N9 have been confirmed including 48 deaths. – especially from poultry contact. No vaccine is currently available for avian influenza (H7N9) virus.

SAPA–AFP, 10 December 2013:  Resistant flu virus keeps contagiousness.  A mutant form of the H7N9 flu virus that is resistant to frontline drugs is just as contagious as its non-resistant counterpart, according to a study, published inthe journal Nature Communications.  The virus has claimed dozens of  lives since its outbreak in February. H7N9 is believed to have spread to humans from poultry, where it circulates naturally. The World Health Organisation (WHO) said on its website that “so far”, no evidence has emerged of  “sustained” transmission of H7N9 among people.

And H7N1 and H7N7 has broken out in ostriches in South Africa,

So never mind the  common cold  coronaviruses and many other prevalent infections, increased caution is due against all common diseases at this season- both the USA H1N1 swine flu circulating the past few years,  and now the Chinese H7N9 flu. . And the MERS-Co Virus Middle-East SARS-type outbreak has not gone away… 9 new cases reported the past week or two  from the KSA alone .the-deadly-middle-east-coronavirus-outbreak/

A  current NEJM  has a new report of a trial of quadrivalent Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children by vaccine manufacturers GSK. The vaccine reduced severity by perhaps 70%- but at a cost of 1.5% serious adverse events, 50% more than the control group (hepatitis A vaccine only).                                                                                    The question remains- why risk  flu vaccine’s ~1.5% serious adverse events when a single high dose of vitamin D3  300 000iu  even just annually, and regular vitamin C with a multivite  including zinc and selenium (at trivial cost ) largely cover one  against a multitude of infections including AIDS and TB, and all degenerative health   problems?

PRECAUTIONS:

Is it coincidence, or divine evolution, that we have had available at low cost  for about 60 year (never mind zinc,  selenium, iron, iodine, vitamins A and vitamin E) two safe natural major antimicrobials in vigorous safe dose   –  vitamins  C and D3?  Medico-Pharma Big Business and governments have been heavily discrediting and ruthlessly suppressing these  for their own profiteering vested interest  even as plagues of HIV, TB,  influenza rage, and Big Business determinedly profits hugely from killer  smoking and alcohol sales despite increasing  marketing restriction?   South Africa- a major producer of alcohol and tobacco-smoke, and fossil-fuel-burning power stations, factories and motorvehicles – continues to lead the world with  the highest road and respiratory death rates  despite zealous attempts to reduce their lethal  use.

Apart from optimal hygiene including  avoiding livestock  and poultry contact, smoking, alcoholism and pollution including  swimming and sick buildings- air-conditioning-           what can we take  to minimize avoidable influenza  ie immune depletion risk? apart from enough  sunshine, exercise, rest, sleep, walking barefoot, not carrying a cellphone,   and good mixed fresh organic diet? The clinical benefit of influenza vaccines is anything but proven, and the adverse risks appreciable.

Big Business and thus governments  and the media  profit from illness, so they keep publishing articles promoting Big Business: new antibiotics, vaccines  and other synthetic drugs that do not prevent or cure but if anything perpetuate chronic degenerative obesity-diabetes-vascular-respiratory,- digestive-arthritic-cancer diseases; – and  GMO-genetically modified preserved  food  and bottled drinks stuffed with slow poisons like refined cornstarch – fructose; salt; sucrose and cereals, soya,  Roundup, antibiotics, preservatives, estrogenics,  aspartame,  and especially boiled and baked omega6 and sugars;  instead of marine omega3 and MCT- medium chain triglyceride virgin coconut oil, and unrefined cereals eg oats, wholewheat bread etc..  

Big Business and it’s cash-cow  Disease Industry decries  the natural healthgiving lowsugar Asian/ Mediterranean  diet-organically pastured and grown livestock meat and dairy products, lightly cooked if not raw (oily)  fish,  fruit and nuts, coloured veggies,  and plenty of  oils in their natural plant form. These were  the norm till food processing became Big Business in our lifetime post WW2, and the developed world was bluffed by Organized Medicine, the Food Barons and Big Pharma  with the masterly fiction of Ancel Keyes, into jettisoning the natural longevity “sea and farm” diet of the east eg Japan, and West eg Mediterranean (fresh produce & cholesterol-rich dairyproducts, meat and fish)  for the Diet Deception (Gary Taubes, Tim Noakes) and Bad Pharma ( James le Fanu, Ben Goldacre) of Ancel Keyes‘  low-fat high-refined cereals, margarine; and  the cholesterol -busting and psychotropes/ painkillers /antidementia/antivascular/ antidiabetic disease Designer Drugs-for-all  myths.

It spends multimillions promoting alcohol,  smoking and ever-newer designer prescription drugs and vaccine, and  disinformation on old well-proven cheap drugs like  reserpine, amilozide, metformin,  natural physiological  human hormone replacement,  natural antioxidants and anti-inflammatories ,  and decrying  ineffective but deliberately lowdose and isolated or imbalanced  vitamins and minerals .

The ATBC vits A+E trial  (isolated highdose vits A and E) was  one such  farce in very high risk smokers in an icy climate. . Others have been the recent Norwegian trial using only up to 1000iu vit D supplement a day,

and the current Annals Int Medicine editorial  review of three new articles condemning multisupplements: , on which Mike Howard publishes a scathing critique

*a commercial multisupplement in the TACT  post-heart attack trial – but the composition of the multisupplement  included only deficiency-disease prevention microdoses of micronutrients including 100iu vitamin D3/d and equally negligible vitamin K-  not pharmacological doses of key vitamins eg vits B, C, D & K2 that are well proven to greatly reduce infections and chronic degenerative diseases ;

* the  Physicians’ Health Study  randomized elderly professional men  to placebo or combinations of vitamin C (500 mg synthetic ascorbic acid), vitamin E (400 IU of synthetic alpha-tocopherol), beta-carotene (50 mg Lurotin), and a multivitamin (Centrum Silver – this included  anti-deficiency disease low dose of all common vits and minerals BUT   only 400iu Vit D3),   .

* The third study- on lowdose (traditional anti-deficiency disease) Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer was simply a literature review of 26 best-quality  published trials of microdoses – not pharmacological safe macrodoses.

ie these  three trials published in this  Annals Internal Medicine issue to please Big Pharma advertisors to discredit supplements shared the usual problem of now well-known futile lowdose supplement doses  at least of vitamins D3 and K, if not also vitamin C in the multigram dose scientifically promoted by the Drs  Stone- Klenner-Pauling followers.

Sir Jack Cecil  Drummond (1891-1952) was one of the world’s pioneer 20th century  biochemists and nutritionists in UK,  from  1916- 1952 discovering or defining  and promoting  under his world-famous biochemist professors Rosenheim, Halliburton and Funk the role especially  of vits A, B, C  and E. Thanks to his and Churchill’s forceful vision and foresight, he oversaw  food supply and diet  and thus keeping Britons healthy through and after WW2. He was  so successful in promoting healthy cheap and unpatentable micronutrients and natural fresh food  (in the face of the mushrooming megaprofit  processed food  and designer drug industry) that it  speculatively led to his and his family’s  1952 assassination by competing interests  in France The Vitamin Murders, Fergusson 2007. .

        MURDER BY DENIALISM: It is incontrovertible   common cause that irrational and often jealous medical denialism costs endless lives:
* Scurvy prevention:  Dr James Lind (who did the first ever recorded clinical trial) showed by 1750 that sailors’ scurvy on long sea voyages  was preventable; but  despite his pioneer discovery, the British navy cost the lives of thousands more seamen from scurvy when the Admirals  neglected for 50years until the Napoleonic Wars to supply the fresh produce-  eg limes – that rapidly cured and prevented the lethal scourge.

This despite the fact that another UK navy surgeon Dr John Woodall had already over 130 years earlier- by 1617 – published in UK  The Surgeon’s Mate stating We have in our owne country here many excellent remedies generally knowne,- Scurvy-grasse, Horse-Reddish roots, Nasturtia Aquatica, Wormwood, Sorrell, and many other good meanes… to the cure of those at home…and Sea-men returned from farre who by the only natural disposition of the fresh aire and amendment of diet, nature herselfe in effect doth the Cure (of scurvy- for which antiscorbutic citrus had been known since antiquity) without other helps. the Lemmons, Limes, Tamarinds, Oranges, and other choice of good helps in the Indies… do farre exceed any that can be carried tither from England.

* Childbed fever prevention:  in 1865  Dr Ignaz Semmelweis (1818 -’65) an AustroHungarian Roman Catholic ob-gyne in Vienna, was locked up, and beaten to death  within weeks, because he showed – to the outrage of his peers- that handwashing with chlorinated lime eradicated the epidmic puerperal fever (three times that in the midwives’ ward)  in  the  doctors’ labour wards; 70years before Thir Reich terrorists took charge, his senior colleagues reacted violently to his progressive promotion of (what was already more advanced British and  French) hygiene and science, and his urging them to wash their hands after examining corpses before examining women in labour..  .  Tragically for Semmelweis and new mothers in the Hapsburg empire then,  Pasteur (b 1822) and Lister (b 1827) ‘s germ antiseptic discoveries  were already being implemented further west, but  had not yet been publicized.

    *metformin after centuries of use as an antidiabetic herb galega officinalis,  and its extraction as an antidiabetic in 1922, came into increasing use globally from the 1950s as the best treatment for type 2 diabetes, but the USA- to protect their own new patent antidiabetic  drugs – ruthlessly suppressed  its use there (like that of the natural salt lithium for manic depression)  for 40years till the mid-1990s.

     *AIDS and ART denialism: until  5 years  ago in South Africa   the  overwhelming-majority “people’s”  government  (with the country’s vast resources),  and its successive  “health”  ministers,   cost the lives of an estimated 300 000  AIDS victims through sufferers  – indigent state dependents-  being denied  antiretroviral ART  drugs, (never mind still till now denied quality education and civil  security,  and thus    adequate basic nutrition, and meaningful housing,  jobs and thus hope.)  Genocidal AIDS denialism about which the still-ruling (since 1994) leadership cadre did nothing until under  intense  international pressure and repeated Constitutional Court orders, combined with political rival factioneering in the ruling party,   they  ousted the denialist president and his denialist Disease Minister in 2008.

DENIALISM TARGETS IN NUTRITION: 

VIGOROUS VITAMIN C ASCORBIC ACID  PHARMACOTHERAPY : Much effort and Big Pharma money  has been  spent to denigrate the irrefutable science-based work   (between their advocacy years shown) of Drs Irvine Stone (1934-1984), Fred Klenner(1948-74) and Linus Pauling (1970-1991) of  antibiotic dose >50 to 1000 mg/kg/d pure vitamin C (not the antiscurvy  10mg/d)  – as a universally needed essential in primates. We primats,  like guineapigs and a few birds and fish species,  are among the few  that do not make their own since we  lost the needed gene and thus enzyme in our evolution..

It took about 150 years after Lind’s publication for the antiscorbutic factor to be named as vitamin C by Dr Jack Drummond, another 10 years for it to be assayed and its structure proven- but despite the pioneering clinical work of Dr Fred Klenner in the 1950s proving the lifesaving benefit of tens of grams a day intravenously, it took another 20 years before Dr Linus Pauling  took up Dr Irvine Stone’s conviction and put highdose vitamin C  on the world Nobel prize map; just on Pubmed,  vitamin C has >51 000 citations  since 1921, and intravenously in 763 entries  since 1946, with  Dr Fred  Klenner reporting  it intravenously  asmajor antibiotic in the Southern Medical journal from 1948..

The 2009 book  Injectable Vitamin C and the Treatment of Viral and Other Diseases collection  of  medical journal papers from the 1930s to 2006 details the exhaustive scientific evidence proving the uniform benefit of even 1gm a day vit C both as an antimicrobial antiinflammatory antioxidant  and immunomodulator against major crippling / lethal diseases from polio to tuberculosis, pneumonia, hepatitis, rabies, encephalitis, neuritis, poisoning, cancer, and pancreatitis;                                                                                   

          and the persistent resistance of the FDA and other multinational Regulators to recognize (so as to protect their domestic patent drug manufacturers- Big Pharma and their politician and civil service lobbyists )- such uniquely safe and effective natural drug therapy.         The final chapters of that 2009 book pose the crucial questions of overwhelming vested interest by the organized medical – hospital –pharmaceutical mega-industry and governments in not eradicating preventable disease, the Big Pharma banning of natural effective remedies-  The Origin of the 42-Year Stonewall of Vitamin C, and Medical Resistance to Innovation,

The  University of Oregon,  the  Riordan-Gonzalez group and more recently Hemila and Chaker‘ and Ullah et al’ s 2012 reviews have  published much  validating what Drs Goodall, Lind, Drummond, Stone, Klenner, Pauling and Cameron started.

VIGOROUS   VITAMIN D3 CHOLECALCIFEROLPHARMACOTHERAPY  costing wholesale ~ <US$0.5/month for ~200 000iu /month  in South Africa)  reduces serious infection by perhaps 90% ie 9fold: . eg 80iu/kg/d – 500iu/d (15000u/month) for an infant, 50 000iu/wk or 200 000iu/mo for an adult; who if obese, may need two  to three times the average dose, to achieve the (?) optimal 25OH vit D level of around 70ng/ml for health, higher for any acute or chronic chronic illness.

The modern prophets of vitamin D3 have been the three pre-WW2 doyens :

Prof Chris E Nordin (MB ChB 1950) working in bone physiology for 60 years now; 84 papers on vitamin D on Pubmed 

Prof Walter Stumpf (1927-2012; MD 1952) the recently deceased  professor at North Carolina University, neuropsychiatrist and radiobiologist  in his 60year medical career with over 500 publications (76 on Vit D on Pubmed) including early discovering that vitamin D targets all systems and diseases; professor-walter-e-stumpf-ahead-of-his-time/ and https://healthspanlife.wordpress.com/tag/stumpf-dr-walter/

paralled by Prof Robert Heaney (MD 1951) at Creighton University, osteoporosis and nutrition authority with 119 vitamin D papers on Pubmed since 1982, over 400 publications to date;

succeeded by Prof Mike Holick (PhD 1971, MD 1976) with 391 publications on vitamin D since 1970 on Pubmed, who has done more than most to show that the maximum daily body production of vitamin D3 with plenty of sunlight is enough to prevent rickets and reduce all disease, but nowhere near the pharmacologically therapeutic 80iu/kg/d needed to maintain a vigorous all-disease protective bloodlevel of 60-100ng/ml.

and Dr John Cannell (MD 1976, registered psychiatrist from 1993, nutritionalist), a  legendary whistleblower .   who successively campaigned against  #cigarette smoking; and  uncovered:   # the cigarette-smoking  (Black Lung) compensationitis fraud of miners’ pneumoconiosis;          #the fictitious inflated “above national average” school results (Lake Woebegone)  that all states were inventing and  reporting (as is still happening – mass government deception- in South Africa) ;  then the  
# recovered memory therapy (RMT) scandal – a form of psychotherapy in which patients recovered memories of abuse that they had no previous memory of. Such therapy resulted in false memory syndrome (FMS) of events that never occurred as well as an epidemic of multiple personality disorder (MPD), a rare disorder historically conceived of as being a hysterical disorder.  Unfortunately, many MPD patients believed the psychiatrist conducting the RMT and went home to falsely accuse their parents and others of horrendous acts that never occurred. Cannell teamed up with two Harvard professors to write a peer reviewed paper on RMT, debunking the witch-hunt;                                                                               then since the 1990s researching and promoting  # vitamin D deficiency as major cause of much psychopathology including autism, and vigorous vitamin D therapy to correct multiple diseases, through the Vitamin D Council. He has (co)authored some 13 papers, and published a book. .

Now a major longterm German Cancer Research screening program has just publishd   the 2002-2013 ESTHER study (Perna ea) of 10 000 citizens followed with serial 25OH vit D  levels; to assess the association of apparently unsupplemented vit D levels with fatal and nonfatal CVD in the same study population.  Follow-up data, including survival status, up to over 9  years. Comparing subjects with 25(OH)D levels below 12ng/ml and above 20ng/ml resulted in the lower vitamin D level cohort showing a higher hazard ratio of 1.27 (95% confidence interval = 1.05-1.54) for total CVD and 1.62 (1.07-2.48) for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, we observed an increased cardiovascular risk at 25(OH)D levels below 30ng/ml. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD. Our results support evidence that low 25(OH)D levels are associated with moderately increased risk of CVD, BUT  the observed association is much stronger for fatal than for nonfatal events.

But the benefit of sunlight in healing tuberculosis has been used for well over a century; while the Google antibiotic benefit of calciferol on Pubmed goes back at least to 1950.

In a prospective 16 mo trial in press from Australia, vit D3 even just 60 000iu/month (ie 2000iu/day) halved antibiotic use in seniors.  (Tran, Neale  ea 2014) Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial.

Since the toxic dose of vitamin D long term  reportedly may be as high as 600 000iu/day or a blood level well >150ng/l , imagine how much better the antimicrobial benefit of vitamin D3 at 80 to 100iu/kg/day or pro rata – even higher eg 10 000+iu/day for obese people who sequester more vit D in fat. .

Dr Robert F  Cathcart wrote 30 to 20 years ago in  Med Hypotheses. 1981 Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy   The amount of oral ascorbic acid tolerated by a patient without producing diarrhea increase somewhat proportionately to the stress or toxicity of his disease. Bowel tolerance doses of ascorbic acid ameliorate the acute symptoms of many diseases. Lesser doses often have little effect on acute symptoms but assist the body in handling the stress of disease and may reduce the morbidity of the disease. However, if doses of ascorbate are not provided to satisfy this potential draw on the nutrient, first local tissues involved in the disease, then the blood, and then the body in general becomes deplete of ascorbate (Anascorbinemia and Acute Induced Scurvy). The patient is thereby put at risk for complications of metabolic processes known to be dependent upon ascorbate.                     1984 Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS). evidence is that massive doses of ascorbate (50-200 grams per 24 hours) suppress the symptoms of the disease and can markedly reduce secondary infections. In combination with usual treatments for the secondary infections, large doses of ascorbate will often produce a clinical remission which shows every evidence of being prolonged if treatment is continued. .. despite continuing laboratory evidence of helper T-cell suppression. There may be a complete or partial destruction of the helper T-cells during an initial infection that does not necessitate a continuing toxicity from some source to maintain a permanent or prolonged helper T-cell suppression. However, it is possible ascorbate may prevent that destruction if used adequately during that prodrome period. Emphasis is put on the recognition and treatment of the frequent intestinal parasites. Food and chemical sensitivities occur frequently in the AID syndrome and may aggravate symptoms considered to be part of the AID syndrome. A topical C-paste has been found very effective in the treatment of herpes simplex and, to a lesser extent, in the treatment of some Kaposi’s lesions.  Increasingly, clinical research on other methods of treating AIDS is being “contaminated” by patients taking ascorbate.                                                     1991 A unique function for Vitamin C is as reducing substance,  electron donor. When vitamin C donates its two high-energy electrons to scavenge free radicals, much of the resulting dehydroascorbate is re-reduced to vitamin C and therefore used repeatedly. Conventional wisdom is correct in that only small amounts of vitamin C are necessary for this function because of its repeated use. The point missed is that the limiting part in nonenzymatic free radical scavenging is the rate at which extra high-energy electrons are provided through NADH to re-reduce the vitamin C and other free radical scavengers. When ill, free radicals are formed at a rate faster than the high-energy electrons are made available. Doses of vitamin C as large as 1-10 g per 24 h do only limited good. However, when ascorbate is used in massive amounts, such as 30-200+ g per 24 h, these amounts directly provide the electrons necessary to quench the free radicals of almost any inflammation, and reduces NAD(P)H and therefore  provide the high-energy electrons necessary to reduce the molecular oxygen used in the respiratory burst of phagocytes. In these functions, the ascorbate part is mostly wasted but the necessary high-energy electrons are provided in large amounts.

A recent review from Atlanta Kearns ea found 30 papers which aggregate to show that annual vitamin   D3 dose (not D2) of  optimally 300 000 to 500 000iu (wholesale cost ~R5 in South Africa)  for deficient adults is best for avoiding poor patient compliance with minimal risk and major benefit.

THE INFERIORITY OF VITAMIN D2 SUPPLEMENT: It should be noted that the long-used Lennon’s Strong Calciferol datasheet  (1974 updated 2004) does not indicate that this 50 000iu tablet labelled ‘calciferol’  is in fact vitamin D2 (ergocalciferol), not the fourfold more potent cholecalciferol D3 formed by sunlight in the skin. This is disclosed only on the Lennons website.. and in the South African Medicines Formulary.  So ‘Strong Calciferol’ in South Africa (actually  the D2 not D3 form of calciferol) is convenient but seriously deceptive mislabeling-  much weaker than the ideal vitamin D3, and therefore its effect unpredictable compared to D3- in fact Dierkes ea Norway show that  giving D2 may actually lower 25OH vit D level in the blood..   Sadly, despite this being reported to the local manufacturers and authorities, no correction of the clinically serious misperception created by the Strong Calciferol label and insert has been issued  to health practitioners by the Medicines Control Council and the manufacturer Aspen-Lennons. 

A recent 8yr study in Cape Town blacks   Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in South Africa Martineau, Nhamoyebonde ,Wilkinson ea   confirmed that vitamin D deficiency (serum 25(OH)D <20 mg/L) is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Cape Town as it is Europe. Vitamin D deficiency was present in 62.7% of 370 participants and was associated (OR ~5.4)  with active TB in both HIV-uninfected  and HIV-infected -(P < 0.001) people. Vitamin D status varied according to season:  25(OH)D concentration was double in summer-January- March compared to winter (23 vs 12ng/l; P < 0.001). Reciprocal seasonal variation in TB notifications was observed:lowest in autumn  and highest in spring October through December (4,2 vs. 5; P < 0.001). Vitamin D deficiency is highly prevalent among black Africans in Cape Town and is associated with susceptibility to active TB both in the presence and absence of HIV infection.

Antimicrobial implications of vitamin D is detailed by Youssef,  Peiris ea (USA  Dermato-Endocrinol  2011)   against all microorganisms – viruses, fungi, bacteria, protozoa  (except perhaps leishmaniasis)  as both profound prevention and therapy; in many cases without commercially invented marketed antimicrobials to which there is growing and deadly  microbial resistance, let alone toxicity.. There is evidence that seasonal vitamin D deficiency  status contributed greatly to the 1918/19 flu-pneumonia pandemic (Grant & Giovannucci 2009).

and finally, a month ago JAMA published from Marianna  Baum,  Richard Marlink ea the universities of Miami, Harvard and Florida  Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic  Antiretroviral-Naive HIV-Infected Adults in Botswana A Randomized Clinical Trial,  that Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive.  2 year supplementation with either daily vitamins BCo,  C and E, selenium alone, or B,C,E with selenium vs placebo: study  conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART between  2005 and July 2009.  Results  participants receiving the combined supplement of vitamins plus selenium vs placebo had half the  risk of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46); and secondary events of combined outcomes for disease progression  or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56); . There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated  unlikely  related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.Conclusions and Relevance  In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing vitamins BCo,C,E and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

THE PARADOX OF THE GLUCOSE- ASCORBIC ACID- CHOLESTEROL- STEROID CASCADE:              Is it coincidence, or  evolution, that the basic animal fast-energy circulating anabolic substrates are glucose, fatty acids and aminoacids?   from which basic glucose C6H12O6 ( from ingested  fructose C6H12O6 and sucrose C12H22O11, or fats or protein)  the liver manufactures the basic cardinal steroid  cholesterol C27H46O.     Then from cholesterol we metabolize by adding or splitting off carbon molecules  the crucial anabolic and regulating  human hormones-                                                                                                                    1. ouabain C29H44O12  the  adrenal hormone  made also  in the hypothalamus and heart ; adrenal),                                                                                                                                           2.  active calciferol C27H44O the strengthening and reproductive secosteroid;                                                                                                                                   3 the prime sex/ reproductive steroids  pregnenolone C21H32o2,  and thence progesterone C21H30O2,  testosterone C19H28O2, DHEA C19H24O2. and thence estradiol C18H24O2. and                                                       4 the prime adrenal mineralo/glucocorticoid steroids  cortisol C21H30O5, aldosterone C21H28O5.

But we primates and a few other species lost the ability to synthetise on demand in quantities of grams a day the crucial vitamin C ascorbic acid C6H8O6 that is key to all the above.                                                                                            And vested interests in the Disease Industry want us to believe the biological nonsense  heresy  that we must ingest minimal unprocessed foods- cholesterol, fats (especially dairy, marine oil Omega3 and medium-chain triglyceride- coconut oil)   and abundant vitamins C and D3, but eat abundant processed foods-  refined plant Omega6,  refined carbs- fructose,  sucrose, fruit juice,  cooldrinks, cereals, confections- which overload causes insulin resistance and thus lipidemia,  obesity- metabolic syndrome -diabetes, cancer and cardiovascular disease.

The Semmelweis reflexA current Wiki essay sums up the current genocidal problems of deliberate deceptions/denialism in Diet, Vitamins and causality  – for ruthless profit and possibly cynical eugenics: “The Semmelweis  effect is a metaphor for the reflex-like tendency to reject new evidence or new knowledge because it contradicts established norms, beliefs or paradigms.The term originated from the saga of Dr Ignaz Semmelweis, who discovered that childbed fever mortality rates reduced ten-fold when doctors washed their hands with a chlorine solution before examining  patients. His hand-washing suggestions were rejected by his contemporaries, often for non-medical reasons. For instance, some doctors refused to believe that a gentleman’s hands could transmit disease (see Contemporary reaction to Ignaz Semmelweis).   In his book The Game of Life, Timothy Leary provided the following polemical definition of the Semmelweis reflex: “Mob behavior found among primates and larval hominids on undeveloped planets, in which a discovery of important scientific fact is punished”. The expression has found way into philosophy and religious studies as “unmitigated Humean skepticism concerning causality“.[2]”

Idealism, ethics may evolve; but the  problem of  human bigotry, self-interest and subjective ie personal bias do not diminish, they spread.  It is classic that Semmelweis  (1818-1865) the observant innovative  Catholic medical scientist of his time (before microbes and antiseptics   were known) was fatuously condemned  not just by his jealous  competing Vienna colleagues,  but even by his progressive and reformist  Copenhagen  contemporary obgyn Prof Carl Levy (1808-1865)- who outlived him by only 4 months;

ironically at the same time that their Copenhagen contemporary Dr Soren Kierkegaard (1813-1855) was increasingly  isolating himself on the lonely ethical journey  against the convenience lazzez- faire  tide, writing for ethical life and religion against the hypocrisy  of the Church and becoming the father of both reformist theology and psychology. But unlike Semmelweis who was way ahead of the bioscience  and humanity of his time, Kierkegaard stuck to and isolated himself in   promoting the incompatible ie  blind-faith-based   religion – the dilemma of Abraham’s conviction (or delusion)  to sacrifice his son-  and ethical morality;

and closely followed by    Rudolph Steiner (1861-1925) another more  profound European  thinker who bridged  science, spirituality, progressive education, architecture, agriculture, natural medicine, nutrition,    and   social  reform;

contrary to the rationalists of the 19th Century “Age of Enlightenment” and since, like   British historian-philosopher -ethicist  Winwood Reade (1838 – 1875)  who published the enduring secularist’s bible The Martyrdom of Man (1872), of which  Churchill wrote  25 years later  “he was right but wrong to say it” on the book’s critique of the wrongs of war and religion, of mankind’s selfishness, corruption  and destructiveness (by the greedy aggressive acquisitive minority)  against the  weak masses and the environment) that carries on worse in the 21st century than even the 20th century;                                                                                                                                          and    150 years later bioscientist and philosopher Stephen Jay Gould (1941-2002) rationalized sadly   the non-overlapping Magisteria of Science and Faith, objective “provable” science – which in fact is seldom immutably constant as is mathematics-  and purely faith-based  “unprovable” religious belief.

It was only a year ago that Richard Conniff published his column on   Strange Behaviours, The Medical Martyrs. And the medical  hero martyrs in this review-  Semmelweis,  Margaret Sanger, Drummond  and Pauling –  never made it onto his list.

But then nor did  the modern medical  freedom fighters  Steve Biko,  Agostinho Neto,  Che Guevera. Jonas Savimbi, Neil Aggett, and the living spouse of Steve Biko, Dr Mamphele Ramphele….

Women of the Century apart (like Margaret Sanger, Marie Curie, Eleanor Roosevelt, Golda Meir, Indira Gandhi,  Helen Keller, Benazir BhuttoMother Theresa, Aung San Suu Kyi -many of whom have been martyred),                 it is a philosophical debate whether among the men  the medical martyr  Semmelweis (1818-1865) ranks with  his  19thC contemporaries-   Lincoln (1809-1865), Kierkegaard(1813-1855), Pasteur (1822-95), Lister (1827-1912)  ;  and his successors (and 20th C  leading achievers): Koch(1843-1910), Edison(1847-1931), Steiner (1861-1925), Gandhi(1869-1948),  Weizmann(1874-1952), Churchill (1874-1965), Einstein (1875-1955), Jung (1875-1961), FD Roosevelt(1882-1945), JK Galbraith(1908-2006), Martin Luther King (1929-68), Pauling and Mandela   as arguably giant enduring male leaders -innovators-  teachers and achievers  of the past two centuries.

Unlike eg Socrates, Hippocrates  and Jesus of Nazareth, one of the  five greatest polymath medical and ethical sages of all time Rabbi Dr Moses Maimonides (RamBam)  avoided martyrdom by burying himself in practicing selfless medical service for sultan and peasants alike, and jurisprudence   for his GreekoRoman based  Islamic-Sephardic   times and philosophy, like his guru predecessor Avicenna and his contemporary savant Averroes. .

CONCLUSION:   Today it can  be argued that the denial of effective phamacotherapeutic doses of especially  vitamins C and D3, let alone supportive doses of balancing vits (A, B1,3,5,6,9 & 12, E and K2); the often-crucially  deficient minerals (eg magnesium, sulphur, phosphate, iodine, zinc and selenium), and biologicals like human transdermal balanced HRT, coenzyme Q10, alphalipoic acid, milk thistle, cinnamon, fish oil, chondroglucosamine, DMSO, coconut oil,  is a repetition of denialism of the germ theory,  and of optimal physiological human micronutrition as well as macronutrition. .

      – especially when patients are poor and thus malnourished, and plagued by diarrhoea and stress, TB, lipidemic vascular disease and cancer; and when antiretroviral ART- although life-saving- is even more diabetogenic and neurotoxic  than untreated AIDs.

Even transdermal administration is  better than nothing, perhaps  better  (for the frail and noncompliant eg oldies) than oral or injection eg of vitamins D3 & C and progesterone , metformin, (in addition to the usual magnesium chloride, vits A, BCo & E)  may be beneficial whether by patch or cream for both healing, infection, calming,  heart, circulation, infection, arthritis, osteoporosis,   and neuritis, applied under coconut oil,  codliver oil and DMSO as further analgesic, anti-inflammatory,  memory and absorption enhancers.

REFERENCES:     New reviews bear out the major benefits of micronutrient supplements selenium,  zinc, silver, vits A, B, C, D, E;  and DMSO, sutherlandia and aloe  against HIV-AIDs. and co-infection;

Micronutrient supplementation for children with HIV infection. Irlam JH,  Rollins NC ea . Cochrane Database Syst Rev. 2013 Oct 11;10:CD010666.

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.Baum MK,  Marlink R ea .JAMA. 2013 Nov 27;310(20):2154-63. .

Preliminary trial of aloe vera gruel on HIV infection.Olatunya OS,  Oyelami OA. ea, J Altern Complement Med. 2012 Sep;18(9):850-3. doi: 10.1089/acm.2010.0735.

In vitro effects of Sutherlandia frutescens water extracts on cell numbers, morphology, cell cycle progression and cell death in a tumorigenic and a non-tumorigenic epithelial breast cell line.Stander A,  Joubert AM. ea, J Ethnopharmacol. 2009 Jul 6;124(1):45-60

Sulfur in human nutrition and applications in medicine.Parcell S.Altern Med Rev. 2002 ;7(1):22-44.

Coconut (Cocos nucifera L.: Arecaceae): in health promotion and disease prevention.DebMandal M, Mandal S.Asian Pac J Trop Med. 2011 Mar;4(3):241-7

below  are some of the  most recent  94 studies  of vitamin D and human infectionin   published just  in 2013:

New insights on the role of vitamin D in the progression of renal damage: Kidney Blood Press Res. 2013;37:667-78. . Lucisano S, Santoro D.ea  Many studies indicate relationship between hypovitaminosis D and survival, vascular calcification, bone mineral metabolism, immune, cardiovascular and endocrine. Vitamin D analogs reduces proteinuria, in particular through suppression of the renin-angiotensin-aldosterone system (RAAS) and exerts anti-inflammatory and immunomodulatory effects. In particular vitamin D deficiency contribute to an inappropriately activated RAAS, as a mechanism for progression of chronic kidney disease (CKD) and/or cardiovascular disease. Human and experimental models of CKD showed that vitamin D may interact with B and T lymphocytes and influence the phenotype and function of the antigen presenting cells and dendritic cells, promoting properties that favor the induction of tolerogenic T regulators rather than T effectory. Interstitial fibrosis may be prevented through vitamin D supplementation. .

Should vitamin D supplementation be a regular part of asthma care? Gordon BR.Otolaryngol Clin North Am. 2014 Feb;47:97-108. .Vitamin D (vitD3) deficiency occurs frequently and has profound effects on health, especially asthma.

Vitamin D in asthma and future perspectives.Huang H,  Zarogoulidis K. ea Drug Des Devel Ther. 2013 Sep 23;7:1003-13.

 vitamin D deficiency associated with development of Acinetobacter baumannii infections in critically ill patients?; Türkoğlu M, Aygencel G et al.; Journal of Critical Care 28 (5), 735-40 (Oct 2013)

Association between vitamin D and hepatitis C virus infection: a meta-analysis. Villar LM, Romero-Gomez M. ea World J Gastroenterol. 2013 Sep 21;19(35):5917-24.

Association between prehospital vitamin D status and hospital-acquired bloodstream infections. Quraishi SA, Christopher KB. Ea, Am J Clin Nutr. 2013 Oct;98(4):952-9.

Human parvovirus B19 associated dilated cardiomyopathy. Jain P, Jain A, Khan DN, Kumar M. BMJ Case Rep. 2013 Aug 5;2013.

The role of vitamin D supplementation in the risk of developing pneumonia: three independent case-control studies. Remmelts HH,  van de Garde EM ea  .Thorax. 2013 Nov;68(11):990-6.

Correlation between serum vitamin D level and severity of community acquired pneumonia in young children   Ren J, Sun B, Miao P, Feng X. Zhongguo Dang Dai Er Ke Za Zhi. 2013 Jul;15(7):519-21. Chinese. http://www.ncbi.nlm.nih.gov/pubmed/23866270

Role of vitamins D, E and C in immunity and inflammation. Shaik-Dasthagirisaheb YB, Pandolfi F. J ea Biol Regul [Correlation between serum vitamin D level and severity of community acquired pneumonia in young children].Homeost Agents. 2013 Apr-Jun;27(2):291-5.

Pre-hospital vitamin D concentration, mortality, and bloodstream infection in a hospitalized patient population.Lange N, Christopher KB ea. Am J Med. 2013 Jul;126(7):640.e19-27.

Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic. Pinzone MR, Nunnari G. eA Eur Rev Med Pharmacol Sci. 2013 May;17(9):1218-32.

Vitamin D deficiency and sudden unexpected death in infancy and childhood: a cohort study.Cohen MC, Offiah A, Sprigg A, Al-Adnani M. Pediatr Dev Pathol. 2013 Jul-Aug;16(4):292-300.

Serum 25-hydroxyvitamin D3 and the risk of pneumonia in an ageing general population.Aregbesola A, Tuomainen TP. ea J Epidemiol Community Health. 2013 ;67:533-6.

Treatment of pulmonary tuberculosis.Nunn A, Phillips PP, Abubakar I.Curr Opin Pulm Med. 2013 ;19(3):273-9.

Role of vitamin D in children with respiratory tract infection.Esposito S, Baggi E, Bianchini S, Marchisio P, Principi N. Int J Immunopathol Pharmacol. 2013 J26(1):1-13.

Tuberculosis incidence correlates with sunshine: an ecological 28-year time series study.Koh GC, Dedicoat M. PLoS One. 2013;8:e57752.

Improving outcomes in patients with psoriasis.Tidman MJ. Practitioner. 2013 ;257:27-30, 3.

vitamin C refs & infection:

Authors’ perspective: What is the optimum intake of vitamin C in humansFrei B, Birlouez-Aragon I, Lykkesfeldt J.  Crit Rev Food Sci Nutr. 2012;52(9):815-29.

Micronutrients at the interface between inflammation and infectionascorbic acid and calciferol. Parts 1 & 2: .Ströhle A, Wolters M, Hahn A. Inflamm Allergy Drug Targets. 2011 ;10:54-74- FULL TEXT IS ON LINE. .

Vitamin C for preventing and treating tetanus Cochrane Database Syst Rev. 2008 Apr 16;(2):

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?…

HealthSpan Life! Update: STEVIA- A HEALTHFUL MEDICINAL SWEETENER AT LAST, unlike rebaudioside

update 28 June 2013  Four years is a long time  for an update.
and Dr Joe Mercola again prompts it in an analysis of aspartame and sucralose hazards, versus the benefits of stevia.
      Search of Pubmed and Google shows not one scientific report of adverse effect of the natural foodstuff stevia , only its beneficial effect on reversing insulin resistance, hyperglycemia, weight gain and hypertension.
In fact a recent trial from an Indian University shows that  it has potent antibreast cancer activity, as one would expect of an insulin sensitizer.
Wikipedia now reports last week:  “Two 2010 review studies found no health concerns with stevia or its sweetening extracts.[54][55] In addition, a 2009 review study found that stevioside and related compounds have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions; and  pancreas, renal and hepatic protection, “.
By contrast, the patented  pure isolate rebaudioside A is reportedly much sweeter than stevia, but has no reported benefit on bloodpressure or blood sugar.
       Four years on, there are still no reports on chronic safety studies in humans or rodents. Why is this?
January 2009  Dr Joe Mercola reminds us  that while the FDA has recently banned natural stevia as unsafe, it has now approved Pepsi and Coke to use the patented stevia extract rebaudioside A in cooldrinks. More USA spin, Disaster Capitalism, it’s 50year old War against Patients  – like the Iraqi  war and The  Pakistan  Deception – to favour it’s own industry rather than  peoples’ health and wellbeing.
This despite the fact that the first human clinical  studies of this single chemical  have been published in only 2008-  and show no benefit on blood sugar or bloodpressure reduction, nor adverse effect.
On the other hand, the results of trials on Pubmed.com  with stevia are impressive:
Chan, Hsieh  ea Taipei published in 2000 and 2003  that  1 and 2 year RCTs in mild hypertension that 750mg stevia a day produced significant reduction in hypertension, with significant reduction in heart damage compared to placebo. There ws no change in weight or blood chemistry.
Ferri ea Brazil 2006 showed that stevia up to 1.5gm/day for 6 months produced no significant fall in mild hypertension.
Gregersen ea Denmark in 2004 showed in type 2 diabetics that 1gm stevia compared to maize starch reduced 4hour glucose response by 18%, and insulin/glucose response by 40%.

No adverse effects have been reported on Pubmed from stevia.
Wiki says steviol glycosides are about half stevioside and half rebaudioside A . . So, as usual, it may be that the whole plant extract is better than the isolated rebaudioside A  that has been approved for commercial use in USA- althought the evidence from trials and centuries of use favours  natural stevia, which in Chinese in moderate but not Brazilians in double dose reduces mild hypertension; and in Danes appears to be a good insulin senstitizing antidiabetic.
Thus the evidence is strong that stevia extract taken as sweetener powder  – (but not the patented rebaudioside A) – will be useful adjunctive protection against glucose-insulin resistance, diabetes and hypertension. Few of us are likely to use 1 to 2gms of stevia a day as a sweetener , but the principle of prevention is to combine the widest range of nutrients in the diet, including the hundreds of natural insulin sensitizers eg  stevia, vitamins, minerals, and human and plant biologicals.
(I now use up to about stevia 150mg/day in hot drinks instead of my usual +- 25gms/d  of sucrose – 1 tsp per cup – so a sweeter tooth that likes  say 3tsp sugar per cup might use 500mg stevia a day).
HealthSpan Life! provides 30% stevia drops in 30ml designer mini bottles suitable for handbag or pocket to provide about 1tsp of sugar sweetness from 3-4 minidrops ie about 200 tsp of sugar sweetness per bottle  – which from the above evidence will aid reduction in obesity, metabolic syndrome, diabetes-hypetension-lipidemia, and thus in cancer- renal-vascular-dementia risk, opposite to that of sugar (and perhaps aspartamate).

NON-INVASIVE OUTPATIENT PREVENTION AND SCREENING

 November 2012 was a red- letter fire-cracker month for women:

Following on their recent turn-around at last  in belatedly beginning to question the risk-benefit of universal invasive  X-ray screening mammography,  even the SA Menopause Society has just sent out a News By Fax affirming what we have known  for 20 yrs – that women need not / should not stop HRT at any age, but take balanced physiological non-oral hormones . This is because (unlike oral synthetic / designer non-human hormones)  balanced human hormones by evolutionary design  reduce all risks including of cancer. Synthetics never do.

And a 3rd book has been published this year that screening X-ray mammography does not save lives.

The only universal compulsory routine  screening tests of well prudent adults that have been proven to save lives and at-risk but still symptom free i.e. hearts, eyes, kidneys, legs and brains are periodic bloodpressure testing, and periodic glaucoma screening; since such common aging problems are mostly easily reversed by simple safe low-cost old treatment (unlike risky costly modern drugs);.

It is human madness and scandalous political corruption that periodic simple battery- operated bloodpressure screening (and recording along with pulse, height and waist girth – all major markers of adult risk) has not been made compulsory from starting prep school  and work. 

All prudent thinking well active middle-aged  adults  – those without common  risk factors, who can thus now expect to live on average to their 80s – must  ask themselves whether they will truly benefit from  internal cancer screening – there is no good evidence to justify it;  and then, if they still want screening, whether they want it uncomfortably invasive or not.

 CANCER SCREENING
Just like unjustified colon  screening of the whole population at low risk ( functionally – stool occult -blood test), if desired the low-risk breast can be screened functionally – without high-pressure irradiation – by thermography;
and anatomically  (like the colon by detailed external scanning) the breast also in fine detail non-invasively by gentle mechanical tactile – Sure Touch – mapping, instead of damaging crushing irradiation X-ray (like potentially risky internal colonoscopy).

The Natural Medicine Clinic offers state of the art bloodpressure and non-invasive breast, bone, prostate, colon, heart, lung, brain and hormone screening, and Pap smears. Phone for appointment with a specialist.