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
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
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
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
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
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
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
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.
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;
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.