Category Archives: depression

METFORMIN REDUCES ALL CHRONIC DISEASES, INCLUDING IMPROVING THYROID FUNCTION.

this new report Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus from  McGill University; Montréal, Quebec. says nothing that is seriously clinically significant, it is merely common sense.

It does not show that metformin causes any heart or thyroid dysfunction ie change in thyroid hormone levels,  merely that it reduces TSH  in those on thyroid replacement.- indicating that  thyroid dose may be able to be tapered.    

A parallel new study from Italy  Metformin-induced thyrotropin suppression is not associated with cardiac effects  confirms there is no heart risk- quite the contrary.

People tend to fatten and slow down as they age, and these people tend to  metabolic syndrome ie obesity, cholesterolemia, hypertension, vascular disease and thus diabetes- same as patients with hypothyroidism. So type 2 diabetes, hypothyroidism (sometimes preceded by hyperthyroidism) and aging go together- usually without demonstrable direct cause and effect.

This new McGill University metformin study does not claim any cause and effect.  The link may be simply  that metformin (which is simply a carbon-hydrogen -nitrogen molecule)  improves all metabolic functions- antioxidant, nitric oxidant- including iodine/TRH/ TSH / thyroid/insulin   hormone responses. .

So as with all nutritional supplements and exercise  that improve metabolism, metformin may improve treated hypothyroidism by improving peripheral thyrooxine receptors , and thus lower need for thyroid replacement.
Metformin or the parent galega a medicinal plant extract used for many centuries reduces new diabetes and all diseases and deaths by 1/3 to 2/3.

it is among other things a prohormone regulator, improving common insulin resistance.

the definition of low TSH is arbitrary. If much below 1, it is suspicious of thyroid overactivity, excess thyroid hormones-
but rarely may reflect central ie pituitary failure to produce enough TRH/TSH and thus cause central hypothyroidism.

so TSH unless way outside the ‘normal’ range of 1 to 2 is a poor guide to health and disease, which is based on clinical  state and the thyroid hormone and antibody levels.

Most aging people develop some degrees of thyroid underactivity, which generally responds to replacement of deficient selenium, iodine and sex hormones without addition of risky thyroid hormones- for which conventional blood levels are a poor guide.

so as in all patients whatever their state and treatment, thyroid function should like all other functions be considered periodically.

ndb.


  Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus  McGill University; Montréal, Quebec.

Background: Small cross-sectional studies have suggested that metformin, a first-line oral hypoglycemic agent, may lower thyroid-stimulating hormone (TSH) levels. Our objective was to determine whether the use of metformin monotherapy, when compared with sulfonylurea monotherapy, is associated with an increased risk of low TSH levels (< 0.4 mIU/L) in patients with type 2 diabetes mellitus.

Methods: Using the Clinical Practice Research Datalink, we identified patients who began receiving metformin or sulfonylurea monotherapy between Jan. 1, 1988, and Dec. 31, 2012. We assembled 2 subcohorts of patients with treated hypothyroidism or euthyroidism, and followed them until Mar. 31, 2013. We used Cox proportional hazards models to evaluate the association of low TSH levels with metformin monotherapy, compared with sulfonylurea monotherapy, in each subcohort.

Results: A total of 5689 patients with treated hypothyroidism and 59 937 euthyroid patients were included in the subcohorts. Among patients with treated hypothyroidism, 495 events of low TSH levels were observed during follow-up (incidence rate 119.7/1000 person-years). In the euthyroid group, 322 events of low TSH levels were observed (incidence rate 4.5/1000 person-years). Compared with sulfonylurea monotherapy, metformin monotherapy was associated with a 55% increased risk of low TSH levels in patients with treated hypothyroidism (incidence rate 79.5/1000 person-years v.125.2/1000 person-years, adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09–2.20), with the highest risk in the 90–180 days after initiation (adjusted HR 2.30, 95% CI 1.00–5.29). No association was observed in euthyroid patients (adjusted HR 0.97, 95% CI 0.69–1.36).

Interpretation: In this longitudinal population-based study, metformin use was associated with an increased incidence of low TSH levels in patients with treated hypothyroidism, but not in euthyroid patients. The clinical consequences of this need further investigation.

HORMONES 2014, 13(2):252-258
Carlo Cappelli,1 Mario Rotondi,2 Ilenia Pirola,1 Barbara Agosti,3 Ana Maria Formenti,1 Pasquale De Cata,2 Massimo Salvetti,1 Luca Chiovato,2 Maurizio Castellano1

1Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia; 2Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Superiore Prevenzione e Sicurezza Lavoro Laboratory for Endocrine Disruptors, University of Pavia; 3Diabetic Unit, Spedali Civili di Brescia; Italy  http://www.ncbi.nlm.nih.gov/pubmed/24776625

Abstract

OBJECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine.
DESIGN: Heart rate, P wave duration, P wave dispersion, QTmax, QTmin and QT-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of TSH-suppression and in 31 control patients with SHT.
RESULTS: No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9±7.4 vs. 92.1±5.8 ms, p<0.001), P wave dispersion (13.1±3.4 vs. 7.1±3.5 ms, p<0.001), QTmax (399±18 vs. 388±16 ms, p=0.024), QTmin (341±14 vs. 350±17 ms, p=0.038) and QT dispersion (49.9±9.6 vs. 30.9±9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of TSH.
CONCLUSIONS: Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.

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UPDATE: LEGISLATING REDUCED ADVERSE FOOD ADDITIVES, MANDATING ADDED MICRONUTRIENTS

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

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

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

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):

MODERN SYNTHETIC PALLIATIVES- ANTIDEPRESSANTS,ANTIPSYCHOTICS, ANALGESICS, STATINS AND ANTI-INFLAMMATORIES – ARE RISKY NON-CURATIVE ESTROGENIC /FERTILITY ie METABOLIC ENDOCRINE DISRUPTORS

Accompanying his 32year old partner (with like her mother  BRCA+ breast cancer ), a   young man this week complains sorrowfully  of total erectile failure within three  days every time he resumes fluoxetine for longstanding depression.

This may suit those patients who eschew sexuality, who knowingly choose chemical castration.. But the drug doesnt fix the causes of depression, merely palliates, often no better than a placebo, sometimes worse- compared to natural multibeneficial  antidepressant supplements.

We already long  live in a sea of estrogenic endocrine disruptors decimating many species including humans,  like pesticides and PCBs, as so aptly described by Deborah Cadbury and Prof Nils Skakkebaek in classic books  eg The Feminization of Nature and The Estrogen Effect.

The commonest prescription  drugs (synthetics- antidepressants; major psychotropes;  amoxicillin,   oxidants ( betablockers eg atenolol;  nonsteroidal anti-inflammatory NSAID (which block antidepressant effects –the Paul Greengard hypothesis 2011 Rocherfeller Inst NY);  statins (cholesterol -steroid and insulin disruptors), and patent synthetic sex hormones-  are  now routine if not mandatory prescription  worldwide due to ruthless relentless marketing pressure-  disease-mongering for profit-  even in children, and worse,  in patients with cancers. The  commonest cancers- breast, prostate, uterus-  are estrogen-driven.

Such environmentally and biologically hostile designer patent drugs-for-profit   are increasingly detectable in surface wastewater globally  from human excretion, and thus drinking  water supplies .

Endocrine disruption studies of antidepressants  (eg fluoxetine Prozacs, mianserin Lantanon (its commercial analogue successor is now Remeron), Bupropion Wellbutrin Zyban;  Venlafaxine Effexor  and desimipramine)  in surface water in Canada,  USA,  Mexico, Brazil and Belgium since 2006, and longer for antipsychotics, statins  and NSAIDS, show estrogenic  ie antiandrogenic risks  for eg gender development and thus for breast/prostate cancer,   for  virility and fertility..

Doctors  mostly blithely  ignore that reproductive young females  have by evolutionary reproductive  necessity  100fold  lower androgenic:estrogenic balance (eg 3:1) than men (eg 300:1), and are also far more prone  than males both to estrogenic contraception prescription harm, and  to common  major depression and autoimmune disease like rheumatod arthritis and lupus, and thus to  the double peril of mutiple estrogenic  prescription.

Recently common NSAIDs eg ibrufen, diclofenac  and mefanemic acid have been shown to be estrogenic in fish.

But such elective  prescription of ( endocrine disruption) cancer- and infertility- promotors (antidepressants, NSAIDS, hormone contraception and HRT etc) ,  is hardly desirable or ethical  at any age, especially when patients and their parents  are not informed of the grave risks of these drugs with no proven longterm benefits (except for contraception).

new reviews  gives more insight  from a plastic surgeon into prevention, including the harms of xray mammography.

and into the gross dangerous overprescription  of diabetogenic depressing  hepato-nephro-myotoxic  statins for all.

Popular painkillers eg opioids like oxycodin, fentanyl, tramadol on the other hand are similarly also  powerful longacting hypoandrogenism–inducing drugs   promoting estrogen dominance – which further complicates the misery and depression of those in chronic pain or depression,  including from  cancer, especially in women as well as men;  who thus  require monitoring of gonadal hormone levels and, if deficient, testosterone replacement. Aloisi ea Univ Siena 2012.

ndb

Reprod Toxicol. 2012:34:80-5. In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.Müller JC, Imazaki PH, Boareto AC, Lourenço EL, Golin M, Vechi MF, Lombardi NF, Minatovicz BC, Scippo ML, Martino-Andrade AJ, Dalsenter PR.  University of Paraná,  Brazil.     .Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer.    Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
Pharmacol Biochem Behav. 2013103: 659-65..Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Lemini C, Cruz-López B, Martínez-Mota L  Universidad Nacional Autónoma de México, Mexico.Estrogen therapy may produce antidepressant-like actions, but the side effects, such as thromboembolic events, may restrict its use among women. The 17β-aminoestrogens (AEs) [prolame [17β-(3-hidroxy-1-propylamino)-1,3,5(10)-estratrien-3-ol)], butolame [17β-(3-hidroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol)], and pentolame [17β-(5-hidroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol)] induce estrogenic and anticoagulant actions, effects that could prove advantageous in an estrogen therapy; however, their antidepressant-like effects have not been described. The objective of this study was to determine the effect of these 17β-AEs (prolame, butolame and pentolame) in the forced swimming test (FST), an animal model sensitive to antidepressant drugs, and to establish the role of estrogen receptors in such actions. Ovariectomized female rats treated with prolame (10-200 μg/rat) showed a reduction in immobility and an increase in active behaviors in the FST, while this effect was not produced by butolame and pentolame (10-200 μg/rat). The antidepressant-like effect of prolame was similar to that of 17β-estradiol (E2, 5-20 μg/rat), sharing with it a biphasic profile but at higher doses. Antidepressant-like actions of prolame and E2 were not associated with changes in locomotor activity. With respect to a control group tamoxifen (15 mg/kg) by itself produced no changes in all behavioral evaluations, but canceled the antidepressant-like effect of prolame and E2. It is concluded that estrogen receptors participate in antidepressant-like effect of both estrogens in the FST. Antidepressant-like activity of different AEs is discussed considering their differences in chemical structure and the schedule used. Our results show additional central actions of prolame besides its pro-sexual, anti-coagulant, estrogenic and anxiolytic activity.
Aquat Toxicol. 2011:104::38-47. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Schultz MM, Painter MM, Bartell SE, Logue A, Furlong ET, Werner SL, Schoenfuss HL  The College of Wooster, OH   USA   Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish–a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Aquat Toxicol. 2010 ;100:354-64    .Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus.nMennigen JA, Lado WE, Zamora JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL  University of Ottawa, Ontario, Canada.    Fluoxetine (FLX) is a pharmaceutical acting as a selective serotonin reuptake inhibitor and is used to treat depression in humans. Fluoxetine and the major active metabolite norfluoxetine (NFLX) are released to aquatic systems via sewage-treatment effluents. They have been found to bioconcentrate in wild fish, raising concerns over potential endocrine disrupting effects. The objective of this study was to determine effects of waterborne FLX, including environmental concentrations, on the reproductive axis in sexually mature male goldfish. We initially cloned the goldfish serotonin transporter to investigate tissue and temporal expression of the serotonin transporter, the FLX target, in order to determine target tissues and sensitive exposure windows. Sexually mature male goldfish, which showed the highest levels of serotonin transporter expression in the neuroendocrine brain, were exposed to FLX at 0.54μg/L and 54μg/L in a 14-d exposure before receiving vehicle or sex pheromone stimulus consisting of either 4.3nM 17,20β-dihydroxy-4-pregnene-3-one (17,20P) or 3nM prostaglandin F₂(α) (PGF₂(α)). Reproductive endpoints assessed included gonadosomatic index, milt volume, and blood levels of the sex steroids testosterone and estradiol. Neuroendocrine function was investigated by measuring blood levels of luteinizing hormone, growth hormone, pituitary gene expression of luteinizing hormone, growth hormone and follicle-stimulating hormone and neuroendocrine brain expression of isotocin and vasotocin. To investigate changes at the gonadal level of the reproductive axis, testicular gene expression of the gonadotropin receptors, both the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were measured as well as expression of the growth hormone receptor. To investigate potential impacts on spermatogenesis, testicular gene expression of the spermatogenesis marker vasa was measured and histological samples of testis were analyzed qualitatively. Estrogen indices were measured by expression and activity analysis of gonadal aromatase, as well as liver expression analysis of the estrogenic marker, esr1. After 14d, basal milt volume significantly decreased at 54μg/L FLX while pheromone-stimulated milt volume decreased at 0.54μg/L and 54μg/L FLX. Fluoxetine (54μg/L) inhibited both basal and pheromone-stimulated testosterone levels. Significant concentration-dependent reductions in follicle-stimulating hormone and isotocin expression were observed with FLX in the 17,20P- and PGF₂(α)-stimulated groups, respectively. Estradiol levels and expression of esr1 concentration-dependently increased with FLX. This study demonstrates that FLX disrupts reproductive physiology of male fish at environmentally relevant concentrations, and potential mechanisms are discussed.

Pharmacol Biochem Behav. 2008 ;88:332-40.Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats.Martínez-Mota L, Cruz-Martínez JJ, Márquez-Baltazar S, Fernández-Guasti A  Instituto Nacional de Psiquiatría  Mexico City In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17beta-estradiol (E2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E2 (5, 10, 20 and 40 microg/rat) or the combination of E2 [at sub-threshold (5 microg/rat) and optimal (10 microg/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E2 at the supra-physiological doses of 10 and 20 microg/rat produced antidepressant-like effects. E2 at 5 microg/rat (that re-established the levels of this hormone to physiological levels) and at 10 microg/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST.

Chemosphere. 2006:;65:1836-45.. Effects of the antidepressant mianserin in zebrafish: molecular markers of endocrine disruption.van der Ven K, Keil D, Moens LN, Hummelen PV, van Remortel P, Maras M, De Coen W. University of Antwerp,  Belgium.    Due to their environmental occurrence and intrinsic biological activity, human pharmaceuticals have received increasing attention from environmental and health agencies. Of particular, ecotoxicological concern are drugs that affect nervous- and endocrine-systems. Zebrafish genome-wide oligo arrays are used to collect mechanistic information on mianserin-induced changes in gene expression in zebrafish. Gene expression analysis in brain and gonad tissue clearly demonstrated the estrogenic activity of mianserin and its potency to disrupt normal endocrine (estrogenic) signaling, based on induction of molecular biomarkers of estrogenicity (e.g., vitellogenin1 and zona pellucida proteins). The possible mechanism underlying this estrogenic activity of mianserin is disturbance of the Hypothalamo-Pituitary-Gonadal (HPG) axis by direct interference of mianserin with the serotonergic and adrenergic systems in the brain of zebrafish. Taking into account the importance of the HPG-axis, and considering the concept of ‘critical window of exposure’, our results reveal the importance for more elaborate testing of endocrine disruptive effects of aquatic antidepressants at different lifestages and during longer exposure periods (e.g., life cycle studies). Although there is a low concordance between the gene expression results in this study and previous cDNA microarray hybridizations, the global mechanistic expression patterns are similar in both platforms. This argues in favor of pathway-driven analysis of gene expression results compared to gene-per-gene analysis.

 

J Hazard Mater. 2013 Jun 15;254-255:242-51. .Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish.  Ji K, Liu X, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Seoul National University,  Korea.This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

University of Algarve, Portugal  .buprofen (IBU) is one of the most sold over-the-counter non-steroidal anti-inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels’ gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels’ reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short-term reactive oxygen species (ROS)-generator.

 

Aquat Toxicol. 2011 ;105:264-9..Non-steroidal anti-inflammatory drug (NSAID) ibuprofen distresses antioxidant defense system in mussel Mytilus galloprovincialis gills.Gonzalez-Rey M, Bebianno M   University of Algarve,  Portugal.Active pharmaceutical ingredients (APIs) are presently considered an emergent class of environmental contaminants. Ibuprofen (IBU) is one of the most applied non-steroidal anti-inflammatory drugs (NSAIDs) in the world. Several authors report the occurrence of IBU in influents and effluents of waste water treatment plants (WWTPs), surface, river and public tap water in numerous countries. However, very little is known about the risks and chronic effects of IBU exposure in non-target organisms. This approach undertakes the assessment of several oxidative stress biomarkers responses through the analysis of antioxidant enzymes activities (superoxide dismutase – SOD, catalase – CAT, glutathione S-transferase – GST, glutathione reductase – GR) and lipid peroxidation (LPO) levels in sentinel species mussel Mytilus galloprovincialis gills exposed for 2 weeks to an environmental realistic concentration of IBU. Results clearly show the significant induction and positive correlation between SOD activity and LPO in exposed gills, concomitant to an antioxidant defense depletion of CAT, GR and GST compared to controls. The integration of all biomarkers in mussels’ gills separates non- and exposed groups supporting the breakdown of the redox defense system and IBU’s pro-oxidant action. Further studies are needed to test possible endocrine disruption effects in mussels’ reproduction fitness as IBU is involved on prostaglandins biosynthesis inhibition.

BMC Med. 2013; 11:57..  The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. CUNY School of Public Health  York, .Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.   METHODS:A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using ‘(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)’ restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.RESULTS:Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).    CONCLUSIONS:  Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.

 

Chemosphere. 2009 ;77 :1285-91.Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in Canadian sewage and surface water samples.  Lee HB, Peart TE, Svoboda ML, Backus S. Aquatic Ecosystem Protection Research Branch, Environment Canada      Rosuvastatin (RST) and atorvastatin (ATO) are prescription drugs and members in the statin family used for the treatment of elevated cholesterol levels. A method using solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of ATO, RST and its metabolite rosuvastatin lactone (RSTL) in sewage and surface water samples has been developed. In the influent and effluent samples collected from 11 sewage treatment plants located in Ontario, Canada, ATO, RST, and RSTL were detected in all samples with median concentrations of 166 ng L(-1) (influent) and 77 ng L(-1) (effluent) for ATO, 448 ng L(-1) (influent) and 324 ng L(-1) (effluent) for RST, as well as 158 ng L(-1) (influent) and 41 ng L(-1) (effluent) for RSTL. Due to the inter-conversion between RST and RSTL, the total concentration of RST and RSTL in a sewage sample should be reported. The median removal rate by wastewater treatment was 66% for ATO and 22% for RST and RSTL combined. These statins were quite persistent in sewage. After a storage period of 21 and 62 days, there was only a slight decrease in ATO concentration and no change in the total RST concentrations. These three compounds were also detected in a number of surface water samples at low ng L(-1) concentrations. This is the first reported occurrence and fate of RST and RSTL in the Canadian aquatic environment.
Ecotoxicol Environ Saf. 2011;74:1216-25. Chronic exposure to diclofenac on two freshwater cladocerans and Japanese medaka.Lee J, Ji K, Lim Kho Y, Kim P, Choi  Seoul National University,  Korea.
Consequences of long-term exposure to diclofenac up to 3 months were evaluated using freshwater crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). Marked decrease of reproduction was observed at 25 mg/L for D. magna, and at 50 mg/L for M. macrocopa. Three-month exposure of fish to 0.001-10 mg/L of diclofenac resulted in significant decreasing trend in hatching success and delay in hatch. The hatching of the eggs produced from the fish exposed to 10 mg/L was completely interfered, while fertility of the parent generation was not affected. Gonadosomatic index (GSI) of female fish was also affected at 10 mg/L. Predicted no effect concentration of diclofenac was estimated at 0.1 mg/L, which is a few orders of magnitude greater than those observed in ambient water. Therefore direct impact of diclofenac exposure is not expected. However its bioaccumulation potential through food web should warrant further evaluation.\
J Toxicol Environ Health A. 2009;72(10):633-41. Life-cycle exposure of fathead minnows to a mixture of six common pharmaceuticals and triclosan.Parrott JL, Bennie DT Water Science and Technology Directorate, Environment Canada,Fathead minnows were exposed for a life cycle to environmentally relevant concentrations of a mixture of six common pharmaceuticals and one personal care product (nominal concentrations: 1,000, 300, 100, 30, or 10 ng/L). Mean measured concentrations of each chemical in the highest fish exposure aquaria were: naproxen 793 ng/L, gemfibrozil 662 ng/L, diclofenac 331 ng/L, ibuprophen 217 ng/L, triclosan 115 ng/L, salicylic acid 67 ng/L, and acetaminophen (chemical analysis inconclusive, nominal 1000 ng/L). Fish exposed for a life cycle even to the highest concentrations of the six pharmaceuticals and personal care product (PPCP) mixture showed no significant changes in growth and development compared to control. Length, weights, condition factors, liver weights, and gonad weights of PPCP-exposed fish were similar to water and solvent controls (0.000005% ethanol v/v). There were no marked effects of PPCP mixture exposure on external sex characteristics of the fish or on egg production. The only parameter that appeared to be affected was percent larval deformities in F1, which showed a significant increase in the 100- and 300-ng/L (nominal) PPCP mixture. Larvae from control fish had 4.7% (water controls) and 3.4% (solvent controls) deformities, compared to 9.3% in the 100-ng/L (nominal) PPCP mixture and 9.2% deformities in the 300-ng/L (nominal) PPCP mixture. Chronic exposure to environmentally relevant concentrations of seven PPCP most often detected in Canadian municipal wastewater effluents (MWWE) did not appear to affect fathead minnow survival, growth, or egg production, although it produced quantitative increases in deformities in the F1 generation.
Hum Reprod. 1993 Aug;8(8):1168-72.Autonomic nervous modulation and effects of a prostaglandin synthase inhibitor on human cervical secretion.Jonsson B, Hammarström  Karolinska Hospital, Stockholm, Sweden.Modulation of cervical secretion at ovulation time was studied in 10 women with regular menstruations. In an in-vivo model with repeated collection of mucus samples during three 90-min periods, the amounts of mucus in a control cycle and in three experimental cycles were compared. Drugs interacting with the autonomic nervous system and a prostaglandin synthase inhibitor were administered at time of ovulation. The cholinomimetic drug carbacholine significantly increased cervical secretion, while the anticholinergic drug butylscopolamine markedly inhibited this secretion. A long-lasting decrease in secretion was seen after administration of the prostaglandin synthase inhibitor diclofenac. Beside regulation of cervical secretion by the ovarian hormones, these results suggest an autonomic nervous modulation of cervical secretion, and in addition an impact on cervical by a prostaglandin synthase inhibitor. The effects on fertility regulation in the female are discussed.
Water Res. 2010 Jan;44(2):555-66.   Oxidative transformation of micropollutants during municipal wastewater treatment: comparison of kinetic aspects of selective (chlorine, chlorine dioxide, ferrate VI, and ozone) and non-selective oxidants (hydroxyl radical).Lee Y, von Gunten U. Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland.  Chemical oxidation processes have been widely applied to water treatment and may serve as a tool to minimize the release of micropollutants (e.g. pharmaceuticals and endocrine disruptors) from municipal wastewater effluents into the aquatic environment. The potential of several oxidants for the transformation of selected micropollutants such as atenolol, carbamazepine, 17 alpha-ethinylestradiol (EE2), ibuprofen, and sulfamethoxazole was assessed and compared. The oxidants include chlorine, chlorine dioxide, ferrate(VI), and ozone as selective oxidants versus hydroxyl radicals as non-selective oxidant. Second-order rate constants (k) for the reaction of each oxidant show that the selective oxidants react only with some electron-rich organic moieties (ERMs), such as phenols, anilines, olefins, and deprotonated-amines. In contrast, hydroxyl radicals show a nearly diffusion-controlled reactivity with almost all organic moieties (k>or=10(9)M(-1) s(-1)). Due to a competition for oxidants between a target micropollutant and wastewater matrix (i.e. effluent organic matter, EfOM), a higher reaction rate with a target micropollutant does not necessarily translate into more efficient transformation. For example, transformation efficiencies of EE2, a phenolic micropollutant, in a selected wastewater effluent at pH 8 varied only within a factor of 7 among the selective oxidants, even though the corresponding k for the reaction of each selective oxidant with EE2 varied over four orders of magnitude. In addition, for the selective oxidants, the competition disappears rapidly after the ERMs present in EfOM are consumed. In contrast, for hydroxyl radicals, the competition remains practically the same during the entire oxidation. Therefore, for a given oxidant dose, the selective oxidants were more efficient than hydroxyl radicals for transforming ERMs-containing micropollutants, while hydroxyl radicals are capable of transforming micropollutants even without ERMs. Besides EfOM, ammonia, nitrite, and bromide were found to affect the micropollutant transformation efficiency during chlorine or ozone treatment.
Toxicol Appl Pharmacol. 2007 Dec 1;225:142-53. .Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, Hecker M, Murphy MB, Yu RM, Lam PK, Wu RS, Giesy JP.Michigan State University,       The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11beta2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11beta2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The beta-agonist salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

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?…

TOURISM HEALTH: SAFARI HEALTHSPANLIFE HEALING CAPE TOWN HOLIDAY 2013.

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

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

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

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

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

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

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

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

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

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

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

THE GROWING RISKS OF CHEMO-FOG; THE ETHICAL DILEMMA OF INFORMED CONSENT. WHAT SHOULD BE OBLIGATORY SCREENING?

neil.burman@gmail.com.      for debate.

ETHICAL CONSIDERATIONS: given the increasing evidence of cognitive and mood effects of cancer and fear on patients with extracranial cancer, let alone after chemo-and radio-therapy, it becomes a major ethical issue as to whether the patient alone should be the decision-maker in the fearmongering-driven decision about whether  to have xray-screening mammography  or prostate  or colon cancer screening in the absence of symptoms and familial high risk.

Similarly, given the epidemic nature of HIV-AIDs and  overweight-prediabetes-Hypertension in Africa, and the giant public cost of illness and deaths  from these diseases, should screening and treatment  for these be voluntary or compulsory?

Equally, are patients diagnosed with cancer, hypertension or HIV-AIDs  competent to make decisions alone for themselves about cancer or other  therapy? Can the patient alone decide about active interventions, versus withdrawal from all therapy – giving up and accepting death – when there are so many options that may help and even cure despite advanced cancer, AIDs and diabetes-hypertension. Surely the patient’s most responsible relative needs to be involved.

  We frequently see such patients plunge into therapy, or withdraw from therapy to die. Current cancer reviews from America, Italy and Portugal  explore this need for truly informed consent. and adequate support for cancer, AIDs and hypertension. 

The need is as great in  AIDs- HIV infection- in our local state AIDs  clinics,   patients have to bring along a buddy, someone – partner, family or friend – from their neighbourhood- who can be relied upon to support the patient through thick and thin, ensure compliance with both complicated drug therapy and all aspects of nutrition and function in consultation with the medical and social backup team.

BACKGROUND:

The analogy of Cancer  with AIDs and overweight-prediabetes-hypertension  is strong. With HIV-AIDs there is oftem  inital  anxiety and depression in anticipation of the screening test, especially in someone who has symptoms; and then if the test is positive. more guilt, anger, fear and despair needing support till the patient adjusts to living with HIV and the necessary prevention and precautions;  until the cycle repeats itself when deterioration necessitates active therapy for active AIDs ARVs (antiretroviral therapy) and if necessary antituberculous therapy. . Both AIDs and ARVs can seriously affect both mood, cognition and thus behaviour. The latest Pubmed  reviews are  from Spain and USA.

 In survivors of brain cancer as well as cancer outside the nervous system, the effects of radiotherapy on the brain’s longterm mental, sensory, cognitive  and motor  function and hormone output, are well known, even in the absence of nervous system malignancies or direct nervous system therapeutic irradiation. The same applies to the deadly longterm consequences of untreated overweeight-prediabetes-hypertension and HIV-AIDs.

Cramond 1968 is the earliest reference found on Pubmed search  (for cognitive impairment and cancer),  an omnibus pair of articles that reviewed all of organic psychosis – cognitive, mood and behaviour effects on the brain of organic disease;  but in the second article   he  quoted only a case of intracranial cancer.  He did not refer to brain effects of extracranial cancer or chemo-radiotherapy.

The first report of brain impairment after combined radio-chemotherapy appears on Pubmed in 1978.  

” Affective and cognitive effects of chemotherapy in cancer patients”   was  first linked in 1980  by  Silberfarb PM, Philibert D, and Levine PM         

 and Chemo brain in  a 2005 review  of  cognitive impairment in patients before any treatment. 

 By 2007 chemo fog was no longer regarded as an illusion in a major New York Times review

There are increasing numbers of long-lived survivors of cancer treatment -especially in middle-aged ie prime-time women after breast cancer. .

Now teams from Amsterdam and Oxford universities 2011,  and Harvard 2010,   show cognitive impairment is common long term in survivors treated even only with cancer chemotherapy for non- nervous system cancers. . This is associated with predictable white and grey matter damage from cytotoxic drugs- such poisons naturally damage healthy as well as killer cells.

 This was and is  the deadly fallacy of the profiteering screening xray mammography industry marketeering that “xray mammography saves lives” highlighted previously in this column, that lowdose irradiation and chemotherapy would not damage healthy tissues. .

Obviously this  cognitive impairment long term with cancer, and iatrogenic after chemo/radiotherapy,  must also be weighed up by the patient who faces multiple choices of therapies for cancer – especially as conventional allopathic cancer therapy does not cure even 10% of all cancers.

Most patients who die old – with or without a history of cancer- have some usually undiagnosed ie dormant cancer somewhere in their body.

This applies also to those considering having invasive screening tests for clinically asymptomatic cancers of eg the breast and prostate, for which the wished-for longterm benefits of preclinical diagnosis and treatment have been disproven, indeed discredited by the risks.. As a result, even the value of colon screening for all is being increasingly questioned in the asymptomatic without family history of colon disease.

This doubt about screening obviously falls away in patients who have strong risk (from previous cancer or family history) of the Big Five sexhormone-linked cancers – breast, prostate, colon, endometrium and ovary.

 Obviously accumulating life stresses, familial anxiety-depression and dementia,  aging-related vascular disease, smoking, alcohol, virus infection, multiple hormone and other imbalances (dietary and minerals; vitamin- and other biologicals) will compound the problem of cancer-therapy-associated mood, cognitive and behavioural  impairment. These need anticipation ie simple holistic prevention with safe natural supplements from as young as possible, to prevent both cancer and the other common comorbid degenerative diseases of aging.

The authoritative Life Extension Foundation lists many useful and often evidence-based brain-protective supplements.

www.cancer-prevention.net  is a comprehensive review of different strategies, although it strangely discredits itself because it is incomprehensibly undated, anonymous and unreferenced. .

 But each putative individual supplement can be simply referenced for it’s evdence base  on Google and Pubmed.

CONCLUSION: Like untreated asymptomatic hypertension, diabetes,  menopause and AIDs, cancer screening let alone cancer itself is often associated with  organic brain problems-  depression, cognitive and perhaps behavioural.  These require  evaluation and consideration at all time, especially in regards to invasive screening and management- or avoidance of these. Is eager consent to invasive screening or invasive therapy- or refusal thereof – truly informed ethical consent, understanding of benefits and risks?

 The similarity  between hypertension, HIV-AIDs and cancer is that both avoidance of risk factors, lifestyle and supplements can make a major difference.

The difference is that many cancers can be left well alone, the immune system optimized by optimal diet-lifestyle and supplements, with permanent remission or progression often unaffected by conventional allopathic cancer therapy. In asymptomatic eg lung, prostate and breast cancer, and eg asymptomatic chronic leukemia,  screening of those not  symptomatic, not at high risk is thus fultile. Treatment can wait till cancer if ever presents clinically, while all practice sensible prevention.

 In HIV carriers and asymptomatic overweight-prediabetes-hypertension in  Africa at least,  only a tiny proporttion will not progress to terminal AIDs or malignant diabetes-hypertension, so regular monitoring is necessary to decide when to start ARVs and metformin plus antihypertensives to prolong life and health for decades. It can be strongly arguesd that compulsory periodic HIV and waistgirth and bloodpressure screening are both lifesaving and in the public interest since early diagnosis and mandatory intervention can be life-and health-saving.

Helen Zille, the Leader of the Opposition here, has the last word this morning, on the paradigm shift in thinking needed  in ‘Tackling the new AIDs denialism’.

Is recklessly spreading AIDs by unprotected sex- as African male culture apparently still promotes despite the outrage the promiscuous  then deputy-president Jacob Zuma himself provoked a decade ago in his rape trial- any different from reckless promotion of harmful screening xray mammography, or the legislative ignoral of the need for regular mandatory screening for hypertension and HIV?