Effects of phenytoin on plasma high-density lipoprotein cholesterol levels in men with low levels of high-density lipoprotein cholesterol.

A low level of high-density lipoprotein cholesterol (HDL-C) is an important and common risk factor for coronary heart disease. Cross-sectional studies and uncontrolled clinical trials have suggested that phenytoin can significantly raise HDL-C levels. This study was undertaken to determine whether phenytoin can raise HDL-C levels in men with low levels of HDL-C. Ninety-two men currently receiving outpatient care at a Veterans Affairs medical center and with baseline HDL-C levels < or = 1.16 mmol/L (45 mg/dL) were recruited to participate in this randomized, placebo-controlled, double-blind clinical trial. Participants received a placebo or 100 mg, 200 mg, or 300 mg of phenytoin once daily for 14 weeks. Lipid levels were measured at baseline and at 6, 10, and 14 weeks. After 14 weeks of treatment, the 200-mg and 300-mg phenytoin groups together achieved a significant 10% increase in HDL-C levels compared with placebo after adjusting for differences in baseline HDL-C levels, age, and body mass index. Other lipid levels did not significantly change in the phenytoin groups compared with placebo. Average compliance was 98% or greater for each of the treatment groups. Eighteen participants dropped out of the study with similar numbers from each treatment group. Side effects were mild and mostly transient. Low doses of phenytoin are well tolerated and can effectively increase HDL-C levels in men with low levels of HDL-C.