Folate Co-Administration
Improves the Effectiveness of Fenofibrate to Decrease the
Lipoprotein Oxidation and Endothelial Dysfunction Surrogates
O. MAYER JR., J. ŠIMON, L. HOLUBEC1,
R. PIKNER, L. TREFIL2
Second Department of Internal Medicine, Faculty of Medicine,
Charles University, 1Department of Immunodiagnostics,
2Department of Clinical Biochemistry and Hematology,
University Hospital, Plzeň, Czech Republic
Received date September 6, 2005
Accepted date November 22, 2005
On-line available December 12, 2005
Summary
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.
Key words
Fenofibrate • Homocysteine • Folate • Lipoprotein oxidation •
Endothelial dysfunction
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