Serum-cholesterol-lowering effect of metronidazole and possible mechanisms of action

In five patients with Crohn's disease long-term therapy with metronidazole (400 mg b.i.d.) was followed by a significant reduction of total serum cholesterol from 179 mg/dl to 156 mg/dl, 134 mg/dl, and 143 mg/dl, after 2-4 months, 6 months, and 9-12 months, respectively. Lipoprotein analysis before and after 3 weeks of administration of metronidazole (400 mg/day) to five normolipemic volunteers revealed that LDL-cholesterol was reduced by 21% (P less than 0.05), whereas HDL-cholesterol remained unchanged. Biliary secretion of cholesterol and bile acids were reduced by 13% and 20% (P less than 0.05), respectively, which might suggest a decreased sterol synthesis. The amount and percentage of intestinal cholesterol absorption were decreased by 33% and 22% (P less than 0.05). Thus, a possible decrease in sterol synthesis and a reduction of cholesterol absorption might be responsible for the serum-cholesterol-lowering effect of metronidazole. However, caution should be taken when considering metronidazole for long-term treatment of patients with hypercholesterolemia due to possible side effects.