Compared to treatment with drugs alone, the combination of antioxidant vitamin supplements and cholesterol-lowering drugs resulted in a smaller increase in high-density lipoprotein cholesterol (HDL), the so-called “good” cholesterol that reduces the risk of coronary artery disease (CAD). The adverse effect on HDL appeared specific for the HDL(2) component, which is responsible for most of the risk-reducing benefits of HDL.
“It looks like antioxidant supplements in general – and certainly the vitamins that have been evaluated in a number clinical studies involving thousands of patients – have no value on their own, and when combined with lipid drug therapy, it looks like the vitamins actually interfere with the lipid therapy’s ability to raise HDL cholesterol,” says B. Greg Brown, M.D., professor of medicine at the University of Washington, Seattle and one of the study authors.
“The antioxidant vitamins interfere with the lipid therapy-induced rise in the very best part of HDL cholesterol – HDL(2), the large, buoyant cholesterol particle, which is the most protective component of HDL,” he says.
In an editorial accompanying the paper, University of Pittsburgh epidemiologist Lewis H. Kuller, M.D., Dr.P.H., says the results of the Seattle study and other negative investigations make a compelling case against recommending antioxidant vitamin supplements to prevent or treat CAD.
“It will be important that physicians advise their patients that the use of antioxidants could be hazardous, especially in combination with lipid-lowering drugs,” he says.
He adds that “the next chapter in the antioxidant saga” will be written by results of several ongoing clinical trials.
Factors involved in the development of CAD include metabolic activities that result in oxidation of low-density lipoprotein cholesterol (LDL, or “bad” cholesterol), analogous to rusting inside a metal pipe. A large number of population studies have suggested that people who consume diets rich in antioxidant vitamins have a reduced risk of CAD. However, several large clinical studies of vitamin E, beta carotene, and other natural antioxidants have failed to show a beneficial effect on CAD risk or disease progression.
Researchers led by Marian C. Cheung, Ph.D., speculated that low levels of HDL might reflect reduced antioxidant protection against LDL oxidation and CAD. They tested the hypothesis in a one-year study involving 153 patients who had CAD and low HDL levels (average 32 milligrams per deciliter). They ranged in age from 33 to 74.
The patients were randomly assigned to one of four treatment groups: drug therapy with simvastatin (marketed as Zocor) and niacin; a four-antioxidant vitamin supplement cocktail; drug therapy plus the antioxidant supplements; or a placebo. Simvastatin and niacin are standard treatments to lower total cholesterol and LDL, while increasing HDL. The cocktail included vitamin supplements E and C, beta carotene, and selenium.
After a year of treatment, researchers found that the combination of simvastatin and niacin increased HDL by an average of 25 percent, compared to 18 percent when the antioxidant vitamin supplements were added to the mix. Additionally, the average HDL(2) level increased by 42 percent with drug therapy alone, whereas HDL(2) levels were unchanged in patients who received simvastatin, niacin and the antioxidant cocktail. The antioxidant supplements alone and placebo had no effect on HDL or other cholesterol levels.
“This unexpected adverse interaction between antioxidants and lipid therapy may have important implications for the management of CAD,” concludes Cheung.
Other study co-authors are Xue-Qiao Zhao, Alan Chait, and John J. Albers. The American Heart Association does not recommend using antioxidant vitamin supplements. The association recommends that Americans eat a variety of foods daily from all of the basic food groups:
six or more servings of breads, cereals, pasta and starchy vegetables;
five servings of fruits and vegetables; two to four servings of skim milk, low-fat dairy products; and
up to six cooked ounces of lean meat, fish, or poultry.
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