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Letter to the Editor: Antioxidant supplements and simvastatin-niacin therapy

Netke S, Ivanov V, Roomi W, Niedzwiecki A, Rath M.

Arteriosclerosis, Thrombosis, and Vascular Biology 2001 Dec; 21(12):2099-2100

Comments on “Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy in Patients with Coronary Artery Disease and Low HDL”

To the Editor:

This paper(1) attracted our attention firstly because of the wide implications of the paper and secondly because of the related editorial comments(2) that sort of urged the physicians to “stop prescribing antioxidant vitamins to prevent and treat heart disease”.

In these studies subjects with CAD were divided into 4 treatment groups namely (1) placebo group, (2) antioxidant group, (3) simvastatin-niacin group (S-N) and (4) simvastatin-niacin plus antioxidant group (S-N+A). P values for between groups comparisons of changes from the individual values at the start of the till end of the study period (12 months) for several parameters (Table 2) indicate that there were no significant differences between S-N group and S-N+A group in respect of plasma cholesterol, plasma tri-glycerides, VLDL-C, IDL –C, LDL -C, HDL-C, HDL3-C, ApoA-I, Apo A-II, Apo-B. However the changes in HDL2- C values differed significantly between these two groups.

The intakes of simvastatin in these groups at the start of the studies ranged between 10 to 20 mg. During the course of the studies intakes were raised to 20 to 40mg for the subjects whose LDL-cholesterol levels were not lowered to less than 90mg/dl. Similarly the intakes of niacin were increased from 2g per day to 3 to 4 g per day for the subjects in whom the rise in HDL-cholesterol level was less than 10mg/dl. Evidently some subjects failed to respond to the pre-determined treatment requiring modification of the treatment and thus creating sub-groups that got higher levels of medications. Such sub-groups should have been treated separately and separate comparisons of the sub-groups receiving higher level of medications should have been made. Then again number of subjects in each group that required such interventions with increased dosage of simvastatin and niacin would in itself become relevant and essential parameter for interpreting the treatment effects. These aspects have not been considered in interpreting the data. These aspects are particularly important in evaluating the quantum of rise in HDL2-C, as it is quite possible that higher levels of HDL2 in S-N GROUP were related to higher intakes of niacin. Neglect of these several factors has possibly leaded to unwarranted conclusions.

Authors state “HDL-C and HDL3-C and apo A-1 responses were modestly blunted in S-N+A group”. This is not borne out by P values given in Table 2. None of these values are significantly different.

In face of these facts the title of the paper “Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy..” is highly misleading.

Antioxidants, such as vitamin C, have been shown to increase HDL levels and lower total cholesterol in several other studies3-5. It is worthwhile noting here that the recent studies in natural approaches to health have already challenged the traditional cholesterol theory of heart disease6. Use of antioxidants has still been shown to directly improve atherosclerotic conditions7. Several million people are in urgent need of right type of medication for atherosclerotic conditions. With some statin withdrawn from the market and some others attracting adverse comments, it is likely that we may have to depend more and more on antioxidants either alone or in combination with lower doses of few selected statins. It is therefore imperative that we should have incontrovertible evidence against the use of antioxidants before we stop using them.

Shrirang Netke
Vadim Ivanov
Waheed Roomi
Aleksandra Niedzwiecki
Matthias Rath


1.Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary Artery disease and low HDL. Arterioscler Thromb Vasc Biol. 2001; 21:1320-1326.

2.Kuller LH. A time to stop prescribing antioxidant vitamins to prevent and treat heart disease. Arterioscler Thromb Vasc Biol. 2001; 21:1253.

3.Cerna O, Ramacsay L. Ginter E. Plasma lipids, lipoproteins and atherogenic index in men and women administered vitamin C. Cor Vasa.1992; 34:246-54.

4. Gatto LM, Hallen GK, Brown AJ, Samman S. Ascorbic acid induces a favorable lipoprotein profile in women. J Am Coll Nutr. 1996; 15:154-8.

5. Kruwoska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P. HDLl-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr.2000;72:1095-100.

6. Rath M, Pauling L. A unified theory of human cardiovascular disease leading the way to abolition of this disease as a cause of human mortality. J Ortho Med. 1992; 7:5-16.

7. Rath M, Niedzwiecki A. Nutritional supplement program halts progression of early coronary atherosclerosis documented by ultrafast computed tomography. J Appl Nutr.1996;48:67-78.



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