Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine.
BACKGROUND
An elevated total plasma homocysteine (tHcy) level is considered to be an independent risk factor for atherosclerosis. It has been reported that lipid-lowering therapy with fibric acid derivatives (fibrates) increases tHcy and total plasma cysteine (tCys) levels. The aim of this study was to determine whether therapy with folic acid, a potent tHcy-lowering agent, could modify the fenofibrate-induced elevation of plasma aminothiols.


METHODS
Patients with combined hyperlipidemia (n = 37) were randomized to receive 9 weeks of treatment with micronized fenofibrate 200 mg/day (F group) or fenofibrate 200 mg/day plus folic acid 10 mg/every other day (F+F group). tCys and tHcy levels were determined before and after the therapy with high performance liquid chromatography.


RESULTS
The tHcy level increased significantly in the F group by 51.3% and in the F+F group by 14.6% (between-group difference P =.001). Total plasma cysteine (tCys) increased similarly after both treatments (P =.72). The serum creatinine level increased in the F group by 20.7% and in F+F group only by 9.8% (P =.04). The increase of tHcy level in F group correlated with an increase of tCys and creatinine levels (r = 0.74 and 0.64, respectively). The effects on the lipid profile did not differ by treatment group.


CONCLUSIONS
Folic acid effectively reduces the fenofibrate-induced elevation of tHcy and creatinine, but it does not affect the elevation of the tCys. Folic acid has neutral effect on the lipid-lowering action of fenofibrate. Clinical efficacy of fenofibrate might be improved by folic acid coadministration.
Melenovsky
Vojtech
V
Third Department of Internal Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic. melenovsky@hotmail.com
Stulc
Tomas
T
Kozich
Viktor
V
Grauova
Barbora
B
Krijt
Jakub
J
Wichterle
Dan
D
Haas
Tomas
T
Malik
Jan
J
Hradec
Jaromir
J
Ceska
Richard
R
D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003545:Cysteine / Q000097:blood*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood
D000960:Hypolipidemic Agents; D014280:Triglycerides; D006710:Homocysteine; D014527:Uric Acid; D005492:Folic Acid; D002784:Cholesterol; D003404:Creatinine; D003545:Cysteine; D011345:Fenofibrate