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

Objectives. 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. Methods. Twenty-four volunteers (m17, f7; mean age 54.9 years) with total cholesterol greater than or equal to6 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). Results. Fenofibrate in monotherapy, beside the expected lipid-lowering effect, increased tHcy from 10.0 to 14.2 mumol/l (p<0.001). Co-administration of folate decreased tHcy to 10.6 mumol/l. In contrast, fluvastatin did not significantly influence the tHcy concentrations. Conclusion. Co-administration of folate to fenofibrate therapy has the potential to reverse the fibrate-induced elevation of tHcy.