Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy.
BACKGROUND
Homocysteine is associated with an increased risk of atherosclerosis. The administration of fibrates has been reported to significantly increase plasma homocysteine levels, a potentially adverse effect of fibrates. We investigated the hypothesis that concomitant treatment with fenofibrate and folic acid leads to a smaller increase in plasma total homocysteine levels than treatment with fenofibrate alone.


METHODS
A randomized, open-label study compared the effect of micronized fenofibrate (200 mg daily) alone versus fenofibrate plus folic acid (10 mg every other day) on plasma homocysteine levels. Twenty-two patients with mixed hyperlipidemia participated. The 9-wk treatment period was preceded by a 4-wk wash-out period without hypolipidemic drugs.


RESULTS
In patients treated with fenofibrate only, plasma homocysteine levels increased by 6.85 +/- 5.23 micromol/L (from 12.27 +/- 3.15 to 19.13 +/- 7.20 micromol/L); in patients treated with fenofibrate and folic acid, plasma homocysteine levels increased by 2.01 +/- 2.88 micromol/L (from 10.14 +/- 2.32 to 12.15 +/- 3.08 micromol/L). The difference in the homocysteine increase between the two groups was statistically significant at P = 0.014.


CONCLUSIONS
Folic acid supplementation in patients treated with fenofibrate significantly reduced the increase in plasma homocysteine levels. More studies are needed to clarify whether amelioration of this side effect increases the clinical benefit of fibrates.
Stulc
T
T
Third Department of Internal Medicine, Charles University, Prague, Czech Republic. tstulc@lf1.cuni.cz
Melenovský
V
V
Grauová
B
B
Kozich
V
V
Ceska
R
R
D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000008:administration & dosage / Q000009:adverse effects*; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D010865:Pilot Projects; D012307:Risk Factors
D000960:Hypolipidemic Agents; D006710:Homocysteine; D005492:Folic Acid; D011345:Fenofibrate