Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.
The aim of this study was to observe the effect of folate and antioxidants alone on homocysteine levels and oxidative stress markers, and to evaluate whether their co-administration promotes their effects. One hundred patients with hyperhomocysteinemia were randomized into four equal groups, which were then treated with folate, antioxidants or
folate plus antioxidants for 2 months; group IV was a control group. Serum homocysteine, folate and oxidative stress markers were measured before the study, at the end of folate and/or antioxidants administration and 3 months later. Folate caused a significant decrease in homocysteine concentration. Antioxidants did not influence homocysteine concentration, but they improved the antioxidative defense (plasma antioxidant capacity and intraerythrocyte
glutathione were increased) and partially prevented lipid peroxidation (malondialdehyde level was slightly decreased). Supplementation with folate had a similar effect on intracellular glutathione and plasma malondialdehyde. Simultaneous administration of folate and antioxidants did not show any additive effect with the exception of a slower decrease of folate concentration after its supplementation had been discontinued. Folate may be considered as an effective antioxidant in patients with hyperhomocysteinemia; this can be a result of decreased production of free radicals due to a reduced level of homocysteine. Its antioxidative effect cannot be promoted by co-administration of antioxidants.