Fenofibrate-induced hyperhomocysteinemia may be prevented by folate co-administration.
OBJECTIVE
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 (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).


RESULTS
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.


CONCLUSIONS
Co-administration of folate to fenofibrate therapy has the potential to reverse the fibrate-induced elevation of tHcy.
Mayer
Otto
O
Dept. of Internal Medicine, Charles University, Medical Faculty, 13 E. Benese St., 320 00 Pilsen, Czech Republic. mayerjr@lfp.cuni.cz
Simon
Jaroslav
J
Holubec
Lubos
L
Pikner
Richard
R
Subrt
Ivan
I
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D018592:Cross-Over Studies; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects*; D000077340:Fluvastatin; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006397:Hematinics / Q000494:pharmacology* / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced* / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D006397:Hematinics; D000960:Hypolipidemic Agents; D007211:Indoles; D006710:Homocysteine; D000077340:Fluvastatin; D005492:Folic Acid; D011345:Fenofibrate