Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Antioxidants and statins – A different perspective
- Eric S Freedland (8 December 2001)
-
Will they stop?
- B C Rao (9 December 2001)
-
other pathway / vitamin K / psychiatric effects
- Mark Metzelaar (9 December 2001)
-
It will be appreciated if a possible mechanism of adverse effect is suggested
- S K Maulik (10 December 2001)
-
Re: Will they stop?
- Mark Metzelaar (10 December 2001)
-
Speaking of HMG CoA reductase inhibitors...
- Kenneth M Jacobie (11 December 2001)
-
Why should we waste money?
- Seralathan (12 December 2001)
|
|
|||
|
Eric S Freedland, Medical Director, Zone Perfect Fresh Food Delivery 5 Bessom Street, No. 318, Marblehead, MA 01945
Send response to journal:
|
Last month there were several electronic responses to Kmietowicz’s report hailing statins as the new aspirin.1 I concur with many of the responses, especially Rosch’s contention that “There is abundant evidence that the beneficial lowering activities of statins are not due to any lipid lowering activities but rather unassociated anti-inflammatory effects.” I also share the concerns of many who point out that we still do not understand completely how statins work, they do indeed have side- effects, and all statins lower CoQ10. Now we are warned to avoid antioxidants in these patients because they may interfere with the statin’s ability to raise HDL.2 While raising HDL may be desirable, before we advocate using statins and avoiding antioxidants, shouldn’t we consider the possibility that the statins may somehow consume or compete with a protective anti-oxidant or anti-inflammatory function of the antioxidants in question (vitamin E, vitamin C, and Beta carotene)? The fact is we simply do not know what are the long-term effects of statin agents. I share Ravnskov’s fear that statins and fibrates have proven carcinogenic in rodents at levels close to those prescribed to humans,3 and changing guidelines are placing millions more on these agents, possibly for life. Given the potential for risk do we really want to blindly forge on with statins and avoid antioxidants? Rather than simply targeting lab numbers, we need more data and understanding tempered with a focus on treatment and prevention of the underlying causes of disease. The vascular endothelium is the primary site of dysfunction in cardiovascular disease. Statin agents have an independent effect on improving endothelial function in part by increasing the bioavailability of NO.4, 5 6 Antioxidants such as vitamin E can be depleted by concomitant use of statin agents,7 and their combined use has been shown to enhance endothelium-dependent, flow-mediated dilation and endothelium- independent nitroglycerin-induced dilation. This underscores the importance of adequate availability of vitamin E for patients receiving statins. Brown and Hu describe a substantial body of evidence linking intake of antioxidant vitamins, particularly vitamin E, with reduced coronary disease, and emerging evidence suggests their role in modulating endothelial function.8 Interestingly, omega 3 fatty acids (especially fish oil), and statins share similar actions: both enhance endothelial nitric oxide synthesis, inhibit the production of pro-inflammatory cytokines, lower cholesterol levels, prevent atherosclerosis and are of benefit in coronary heart disease, stroke and osteoporosis.7 Omega 3s also have anti- arrhythmic properties, and the available evidence suggests a role in secondary prevention of CHD. Their established role in primary prevention will need to await future clinical trials but there is substantial evidence to support it.9 Before advocating the liberal use of statins (and avoiding antioxidants), perhaps we ought to consider lifestyle interventions, especially dietary strategies. Potential conflict of interest: My company delivery daily to the client's doorstep, 3 gourmet meals and two snacks prepared according to sound, science-based nutritional principles. We also advocate omega 3s. 1. Kmietowicz Z. Statins are the new aspirin, Oxford researchers say. BMJ 2001; 323:1145-. 2. Gottlieb S. Antioxidant vitamins make lipid lowering drugs less effective. BMJ 2001; 323:1323a-. 3. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. Jama 1996; 275:55-60. 4. Plana JC, Jones PH. The use of statins in acute coronary syndromes: the mechanisms behind the outcomes. Curr Atheroscler Rep 2001; 3:355-64. 5. Dobrucki LW, Kalinowski L, Dobrucki IT, Malinski T. Statin-stimulated nitric oxide release from endothelium. Med Sci Monit 2001; 7:622-7. 6. Mueck AO, Seeger H, Wallwiener D. Further evidence for direct vascular actions of statins: effect on endothelial nitric oxide synthase and adhesion molecules. Exp Clin Endocrinol Diabetes 2001; 109:181-3. 7. Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F. Additional benefit of vitamin E supplementation to Simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol 1998; 32:711-716. 8. Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr 2001; 73:673-86. 9. Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med 2001; 161:2185-92. |
|||
|
|
|||
|
B C Rao, General Practitioner Clinic and Apoorva Diagnostic Centre, CMH Road,Indiranagar,Bangalore 560008.India.
Send response to journal:
|
This news item couldnot have come at a more appropriate time. Indian doctors, including cardiologists have a strange fascination for prescribing vitamins. The prescription market for vitamin E which is coprescribed with statins is huge. I sincerely hope this news will reduce this wasteful habit and save some money for our poor patients. |
|||
|
|
|||
|
Mark Metzelaar, self-employed independent research
Send response to journal:
|
L.S., Niacin was used by some Psychiatrists around 1947 to stop hallucinations in some schizophrenics. Niacin makes a flush that relieves histamine and therefore can stop some allergies, swallowing (p.e. brain parts in psychiatric disorders) and inflammation reactions. Another very important compound is the natural vitamin K 1 or 2 (not the hazardous synthetical changed form; K3). This micro-nutriënt in doses of 45mg a day almost stops ignitions that led to parkinson, hart-attacks, joint inflammation. This is supposed to work this way in intercepting cytokinin, interleukin 6, an ignition precursor. http://www.lef.org (search for vitmin K) Maybe its more important to stop the inflamatory reactions without lowering cholesterol? Lower cholesterol could give lower life energy, higher suicides-rate and depressions in some people. In my opinion vitamin K is much more important than statins. Of course, for people in high risk groups: The combination vitamin K with statins and niacin would probably be perfect and an almost 100% cure? For the niacin: a flush almost every day garantees that inflamatory reactions on histamin are stopped. Lower doses might not have these advantages, or less. Same for some so called 'psychiatric patients' (whatever that could be, according to some never full proved psychiatric philosophies) where cerebral allergies are involved like neurogenic inflammation (cytokinin and others), disturbed NO-metabolism, histamin nerve cells (normaly around 3%), homocystein levels, etc. Till now, psychiatry does nothing with all the scientific data since 1947 to treat those people by relieving those allergies or sensitivities (psychiatry doesn't diagnose individuals for this at all). |
|||
|
|
|||
|
S K Maulik, ADDITIONAL PROFESSOR ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, 110029, INDIA
Send response to journal:
|
The observation made in the study is interesting. But considering the number patients include in the study, it will be inappropriate to draw any definite conclusion about the observations. It would have been more attractive, if ay mechanism of such an adverse effect of the antioxidant vitamins on statins was also investigated. |
|||
|
|
|||
|
Mark Metzelaar, self-employed indepedent research
Send response to journal:
|
Niacin is a vitamin too; namely B3. CoQ10 a micro nutriënt out of the 'vitamin-corner' and has more than some proof of effectiveness against heart-attacks. Same for taurin; an amino-acid micro-nutriënt. Yes: for vitamine E the research is conflicting.
|
|||
|
|
|||
|
Kenneth M Jacobie, Licensed Massage Therapist Latham NY 12110
Send response to journal:
|
An unflinching determination to take the whole evidence into account is the only method of preservation against the fluctuating extremes of fashionable opinion. Alfred North Whitehead (1861-1947) Cholesterol is a 27-carbon steroid that is an essential component of the cell membrane, the immediate precursor to steroid hormones, the substrate for bile acids required for the absorption of fats and fat soluble vitamin from the intestine and required for the assembly of very low density lipoprotein (VLDL) in the liver. As such one has to believe that this must be a compound that the body keeps under tight regulation. Yet hypercholesterolemia, hyperlipidemia and thromboembolic disorders are very common? What drug companies hope is that doctors never ask themselves: What is the normal chemical mechanism for cholesterol regulation in man? This answer is found only in the study of nutrition. Remember disease is considered to be a harmful deviation from the normal structural or functional state of an organism. A diseased organism commonly exhibits signs or symptoms indicative of its abnormal state. Thus, the normal condition of an organism must be understood in order to recognize the hallmarks of disease. Most of the individuals that will read this have not been educated in contemporary nutritional biochemistry. If they had they would understand that Vitamin E, is an essential fat-soluble vitamin, which encompasses eight naturally occurring compounds in two classes, not ONE! The first class, tocopherols, have four members designated alpha, beta, gamma and delta. The two major forms, .alpha.-tocopherol and .gamma. -tocopherol, differ structurally only by a methyl group substitution at the 5-position. The second class, tocotrienols, are molecules related to the tocopherols and also consist of four members designated alpha, beta, gamma and delta. The tocotrienol structure differs from the tocopherols by possessing three double bonds in their side chain rather than being saturated. In the early 80's studies of cereal grains revealed that barley was particularly effective in lowering lipid levels in animal models. Qureshi et al., Atherosclerosis, 51: 75-87, (1984). The ability of barley extracts to lower lipids in vivo prompted the purification and identification of the chemical constituents responsible for cholesterol suppressive activity. Alpha-Tocotrienol was recovered from barley extracts using state-of- the-art methods and was designated as the biologically active component based on subsequent in vitro and in vivo evaluation. Qureshi et al., J. Biol. Chem., 261: 10544-10550, (1986). A U.S. patent was issued to The Wisconsin Alumni Research Foundation specifically claiming the use of alpha-tocotrienol for the lowering of lipids, U.S. Pat. No. 4,603,142, to Qureshi et al. (1986). The richest sources of tocotrienols are cereals (such as barley, oats, rice, wheat and rye) and vegetable oils such as palm oil and rice bran oil. Tocotrienols have been shown(and are patented by Bristol-Myers Squibb Company US 5217992) to suppress HMG CoA reductase resulting in the inhibition of cholesterol biosynthesis and a subsequent drop in LDL cholesterol, apolipoprotein B, thromboxane B.sub.2, platelet factor 4 and glucose levels. (Wright, et al, A Symposium On Drugs Affecting Lipid Metabolism, Houston, Tex. (November 1989)). In J. Biol. Chem261: 10544- 10550, (1986), Qureshi, et al. indicated that the hypocholesterolemic effects of alpha-tocotrienol is brought about by the suppression of HMGR as measured by hepatic HMGR activity. (Qureshi, et al, J. Biol. Chem, 261: 10544-10550, (1986)). Wright et al, supra, showed that tocotrienol-rich fraction (TRF) fed to hypercholesterolemic swine resulted in a dramatic decrease in serum total cholesterol and LDL-cholesterol levels. Qureshi, et al, showed that gamma and delta-tocotrienols suppress HMGR activity. (Qureshi, et al, Suppression of Cholesterolgenesis in Hypercholesterolemic Humans by Tocotrienols of Barley and Palm Oils, presented at the Antioxidant and Degenerative Diseases Conference, Berkeley, Calif., (January, 1990)). U.S. Pat. No. 4,603,142 to Qureshi et al., (1986) discloses the use of alpha-tocotrienol for the lowering of lipids. It was later discovered that Gamma-tocotrienol and delta-tocotrienol are responsible for nearly all of the biological activity and the alpha- tocotrienol possesses minimal biological activity towards suppression of HMG-CoA reductase The tocotrienols are structurally related to the tocopherols and differ only by possessing unsaturation in the isoprenoid side chain. Like the tocopherols, the tocotrienols have antioxidative activity, (Yamaoka, et al, Yukagaku, 34: 120-122 (1985)). Active oxygen species are known to play pivotal roles in the genesis of atherosclerotic plaques, thrombotic episodes, ischemic damage, cancer, aging, dementia, and inflammatory conditions. (Sies, H., Oxidative Stress; Academic Press, New York, (1985); Santrucek, M., Krepelka, J., Drugs of the Future, 13: 973-996 (1988)). Of particular interests are the potential protective effects of antioxidants on lipoproteins, since oxidized LDL is thought to be atherogenic. (Buckley, M., Goa, K. L., Price, A. H., Brogden, R. N., Drugs. 37: 761-800 (1989); Gwynne, J. T., Schwartz, C. J., Am. J. Cardiology, 62: 1B-77B (1988)). It is not at all surprising that statins are being considered the next wonder drug... If one looks closely Statin drugs, they have every property of vitamin E, especially after you take the tocotrienol faction into consideration. Is the chemical industry stealing from nature, and not admitting it due to conflicts of interest? Please consider that Lipitor is the one of the best selling drugs in the world... As far as the NEJM Vol. 345:1583-1592 is concerned. It's this simple: There is sadly too much money in helping drug companies make money than helping people not get diseased. Perhaps when doctors study nutritional biochemistry and not just clinical pharmacology the medical system would truly be healthcare, not disease care and 'profit as usual' for the drug industry. As long as doctors continue to be "drug brokers" there will be continued erosion in the public's trust. Especially in those people who know how to spot publication bias. |
|||
|
|
|||
|
Seralathan , assistant surgeon Coimbatore
Send response to journal:
|
In this part of India,when a patient comes back from the specialist,he insisists his G.P. to prescribe some vitamins and naturally the G.P.prefers a combination of vitamins with anti-oxidants .According to your latest information this trend will not only adds the monthly expenditure towards medical bill,but also harms the patint .So developing countries should be informed to avoid anti-oxidants with statins. |
|||