Fenofibrate-induced hyperhomocysteinemia may be prevented by folate co-administration

Several prospective studies reported that fibrates might increase blood total homocysteine (tHcy) concentrations. Because of this adverse effect, elevated tHcy could potentially compromise the cardiovascular benefit resulting from lipid-lowering by fibrates. In our study we aimed to find out whether the folate co-administration would modify the fibrate-induced elevation of tHcy.

Twenty-four volunteers (m 17, f 7; mean age 54.9 years) with total cholesterol > or =6 mmol/L and triglycerides less than 5 mmol/L, with normal blood pressure, normal blood glucose and without any pharmacotherapy and/or clinical vascular or metabolic disease, were included in an open, randomised, prospective, crossover study. We measured lipids, tHcy, folate, vitamin B12 and renal function markers after diet, after a 6-month administration of 200 mg of fenofibrate (3 months in monotherapy followed by 3 months in combination with 10 mg of folate) and further on after an identical period of fluvastatin administration (3 months of 40 mg followed by 3 months of 80 mg).

Fenofibrate in monotherapy, beside the expected lipid-lowering effect, increased tHcy from 10.0 to 14.2 microM/L ( p<0.001). Co-administration of folate decreased tHcy to 10.6 microM/L. In contrast, fluvastatin did not significantly influence the tHcy concentrations.

Co-administration of folate to fenofibrate therapy has the potential to reverse the fibrate-induced elevation of tHcy.