Fenofibrate

Increased plasma homocysteine levels have been associated with an increased risk of atherosclerosis. Mild folic acid deficiency is a common cause of increased homocysteine levels and the use of folic acid has been found to significant decrease circulating homocysteine concentrations.

Administration of fibrates, one of the most commonly prescribed hypolipidemic agents in Europe, has been reported to increase total plasma homocysteine levels by 17-45 percent. To date, no intervention has attempted to ameliorate the increase in homocysteine levels observed in therapy with fibrates. Therefore, some researchers front the Czech Republic investigated the hypothesis that simultaneous treatment with fenofibrate and folic acid leads to a smaller increase in plasma homocysteine levels than treatment with fenofibrate alone.

Twenty-two subjects with mixed hyperlipidemia were included in this study. Drugs known to influence homocysteine levels were discontinued at least four weeks before the start of the study (multivitamins, trimethoprim, aminophyline, metothrexate, and phenytoine), along with any hypolipidemic agent. The subjects were randomized into two groups. The control group received fenofibrate only and the folate group received fenofibrate and 10 mg of folic acid every other day for nine weeks. Homocysteine levels, serum lipid, uric acid, folic acid, and fibrinogen levels were all tested after the nine-week intervention period.

In patients treated with fenofibrate and folic acid, plasma homocysteine levels increased by 2.01 micromol/L as compared to 6.85 micromol/L for patients in the control group. The difference in the homocysteine increase between the two groups was statistically significant. Total cholesterol and triacylglycerol levels decreased after treatment by 20.4 percent and 40.2 percent, respectively. However, high-density lipoprotein cholesterol did not change significantly.

The finding that fibrates increase plasma homocysteine levels is recent. The data from this study is the first to show that folic acid supplementation in patients treated with fenofibrate significantly reduced the increase in plasma homocysteine levels. This is important since the increase in homocysteine levels post-treatment might limit the beneficial effect of fibrate therapy. One limitation of the study is the small sample size. Therefore, the results of this study need to be verified in larger groups and with other currently used fibrates.

Tomas Stulc, Vojtech Melenovsky, Barbora Grauova, Viktor Kozich, and Richard Ceska. Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy. Nutrition 17(9): 721-723 (October 2001) [Correspondence to: Tomas Stulc, MD, Third Department of Internal Medicine, Charles University, U Nemocnice 1, Praha 2, CZ 128 21, Czech Republic. E-mail: tstulc@lf1.cuni.cz.]

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