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Orthomolecular Medicine News Service, November 13, 2008

Why treat nutritional deficiency with drugs?

by Andrew W. Saul (OMNS, November 13, 2008) A recent study suggested that statins might be used to avoid the effects of nutritional deficiency. Writing in the New England Journal of Medicine, the Jupiter group described a study of statin drugs in people with high C-reactive protein and low cholesterol. (1) High C-reactive protein levels are associated with inflammation and heart disease/stroke. The authors concluded that, in apparently healthy persons with elevated C-reactive protein levels, rosuvastatin (Crestor) significantly reduced the incidence of major cardiovascular events. Their much-publicized claim, that this statin lowers the risk of heart attack by approximately one half, is technically correct though highly misleading. The reported annual incidence of coronary events was 37 people in 10,000 (controls) and 17 people in 10,000 (treated). Similar results were reported for risk of stroke. When expressed as a proportion, a 46% improvement (17/37) sounds large. However, an improvement of 20 events (37-17) in 10,000 people known to be at risk is less impressive. Such an improvement means that 500 people (10,000/20) with this increased risk would need to take the tablet daily for a year, to prevent one person suffering an event. The paper does not explicitly report deaths. One reason for this may be that if a person on statins suffered a heart attack, that person was about three times more likely to die than a control who was not on statins. The cost of rosuvastatin per person is approximately $1000 per year. So, treating enough people to prevent one heart attack costs $500,000 per year. Since about 70% of the heart attacks were not fatal, prevention of a single death from heart attack would cost even more, approximately $1,700,000. Giving the benefit of the doubt, we may allow for a similar reduction in stroke and say that "only" $250,000 is needed to protect one person from a stroke or heart attack. It is hardly surprising that Astra Zeneca's share price increased by $1.3 billion dollars on release of this paper and the corresponding media hype. (2) The media suggested millions of healthy people could cut their risk of heart disease by taking statins. (3) They also claimed that statins could cut the risk of heart attack for "everyone". (4) This is inaccurate and incorrect. The study did not include normal healthy people, only a sample of a relatively small number of people, suffering from inflammation (increased C-reactive protein) - a known cause of heart disease and stroke. Out of 89,890 people considered for inclusion, 17,802 people (19.8%) met the specific criteria of poor health for the study. Widespread prescription of statins to healthy people is not supported by these findings. The fact that statins produce a modest improvement is unsurprising, since they are known to lower inflammation, as do many nutritional supplements. As Bill Sardi has pointed out, Crestor lowered C-reactive protein by 37%, but vitamin E lowers it by 32%, (5) and vitamin C by 25.3%. (6,7) These effects are similar to those of statins and would be expected to provide comparable benefits, without side effects and at a lower cost. Crestor and other statin drugs have serious side effects. The incidence of established side-effects, such as rhabdomyolysis (0.3 per 10,000 per year), myopathy (1.1 per 10,000) and peripheral neuropathy (1.2 per 10,000 per year) seems low, (8) but may be underestimated as it takes time to establish long-term side-effects. (The depletion of coenzyme Q10 by statins is a particular concern.) The figures imply that for every ten people who avoid a cardiovascular event, at least one previously healthy person will suffer a non-trivial side effect of the statin drug. The doctors reported a statistically significant increase (270) in diabetes in the statin group compared to the placebo group (216). Over the course of the study, this corresponds to an increased risk of approximately 61 in 10,000 people. So, the number of people on statins reported to become diabetic was greater than the number that avoided a heart attack! These people might have shorter lives and be at greater risk of heart disease in the long term. Notably, the Jupiter study was stopped early, which the authors admit prevents assessment of how side-effects might outweigh reported benefits in the longer term. The study was to last 3-5 years and the criteria for stopping were not included in the original published design. (9) The paper claims that when the study was stopped "these [diabetic] events were not adjudicated by the end-point committee". The committee either knew about the diabetes in which case it was considered, or it did not and the committee was not doing its job properly. The Jupiter name stands for Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; the reader might think this "justification" sounds more like a marketing plan than a scientific endeavor. The researchers did not address the underlying cause of the inflammation and increased C-reactive protein: they simply treated the condition with drugs. In many cases, raised C-reactive protein is a result of nutritional deficiency. (10) It is worth mentioning that several nutritional supplements inhibit inflammation and lower C-reactive protein, without causing known side effects. Deficiency in vitamins A, (11) B6, C, E, A, folate, carotenoids and lycopene, (12) and selenium (for example) is associated with raised C-reactive protein. (13,14,15) We suggest that the $250,000 cost of preventing a single cardiovascular event with rosuvastatin might be better spent funding a study of such inexpensive alternatives the deficiency of which may be the cause of the problem. The people at risk could be encouraged to supplement their diet and restore their health without using these expensive drugs to conceal their underlying sickness. Stick with the supplements! References: (1) Ridker P.M. Danielson E. Fonseca F.A.H. Genest J. Gotto A.M. Kastelein J.J.P. Koenig W. Libby P. Lorenzatti A.J. MacFadyen J.G. Nordestgaard B.G. Shepherd J. Willerson J.T. Glynn R.J. for the JUPITER Study Group (2008) Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein, NEJM, 359(21), 2195-2207.



(2) Mail Online (2008) Crestor news helps AstraZeneca market value leap by more than £1.3bn, 9:25 PM, 10th Nov.



(3) Smith R. (2008) Millions could cut heart attack risk by taking statins, study finds, telegraph.co.uk, 7:55AM GMT, 10 Nov.



(4) Hope J. (2008) The new statin drug that cuts the risk of heart attacks and strokes for EVERYONE, Daily Mail, 11th Nov.



(5) Devaraj S. Tang R. Adams-Huet B. Harris A. Seenivasan T. de Lemos J.A. Jialal I. (2007) Effect of high-dose alpha-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease, Am J Clin Nutr, 86(5), 1392-1398.



(6) Block G. Jensen C.D. Dalvi T.B. Norkus E.P. Hudes M. Crawford P.B. Holland N. Fung E.B. Schumacher L. Harmatz P. (2008) Vitamin C treatment reduces elevated C-reactive protein, Free Radic Biol Med, Oct 10. [Epub]



(7) Sardi B. (2008) The Headline You Should Be Reading: Statin Drugs Don't Save Lives And May Increase Your Risk For Diabetes, Knowledge of Health Report, Nov 11.



(8) Law M. Rudnicka A.R. Statin Safety: A Systematic Review, The American Journal of Cardiology, 97(8), Suppl 1, S52-S60.



(9) Ridker P.M. JUPITER Study Group (2003) Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial, Circulation, 108(19), 2292-2297.



(10) Ford E.S. Liu S. Mannino D.M. Giles W.H. Smith S.J. (2003) C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults, European Journal of Clinical Nutrition, 57, 1157-1163.



(11) Root M.M. Hu J. Stephenson L.S. Parker R.S. Campbell T.C. (1999) Determinants of plasma retinol concentrations of middle-aged women in rural China. Nutrition 15, 101-107.



(12) Boosalis M.G. Snowdon D.A. Tully C.L. Gross M.D. (1996): Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study, Nutrition, 12, 475-478.



(13) Friso S. Jacques P.F. Wilson P.W. Rosenberg I.H. Selhub J.(2001) Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels, Circulation, 103(23), 2788-2791.



(14) Devaraja S. Jialal I. (2000) Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients, Free Radical Biology and Medicine, 29(8), 790-792.



(15) Upritchard J.E. Sutherland W.H. Mann J.I. (2000): Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes, Diabetes Care, 23, 733-738. Nutritional Medicine is Orthomolecular Medicine Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource. Editorial Review Board: Damien Downing, M.D.

Harold D. Foster, Ph.D.

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James A. Jackson, PhD

Bo H. Jonsson, MD, Ph.D

Thomas Levy, M.D., J.D.

Erik Paterson, M.D.

Gert E. Shuitemaker, Ph.D. Andrew W. Saul, Ph.D., Editor and contact person. Email: omns@orthomolecular.org

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