The effect of low-dose phenytoin on high-density lipoprotein cholesterol

We examined whether low doses of phenytoin, which should be associated with few dose-related side effects, may increase the levels of high-density lipoprotein (HDL) cholesterol. Of 35 healthy adult men who consented to participate, 31 completed the study. They took no medications and consumed no alcohol during the study. We used a three-arm, parallel, prospective, randomized, double-blind research design. Subjects took a single-blind placebo capsule once daily at bedtime for 2 weeks and then were randomly assigned to receive identical-appearing capsules containing 30 mg or 100 mg of phenytoin or placebo, once daily at bedtime for 4 weeks. The HDL cholesterol and HDL subfractions were determined from 12-hour fasting blood samples obtained at the beginning and end of the single-blind period and at the end of the third and fourth weeks of the double-blind period. Mean differences between baseline and posttreatment HDL cholesterol levels with placebo, 30 mg phenytoin, and 100 mg phenytoin were 0.010 mmol/L (0.4 mg/dl), 0.005 mmol/L (0.2 mg/dl), and 0.096 mmol/L (3.7 mg/dl), respectively (p = 0.2947); baseline and posttreatment HDL2 and HDL3 levels were not different among the groups. Total cholesterol levels were significantly higher in subjects taking phenytoin 100 mg than in those taking phenytoin 30 mg or placebo. The results suggest that phenytoin in dosages of up to 100 mg daily for 4 weeks has no substantial effect on HDL cholesterol or HDL subfractions.