© 1998 American Heart Association, Inc.
Original Contributions |
Vitamin Supplementation Reduces Blood Homocysteine Levels
A Controlled Trial in Patients With Venous Thrombosis and Healthy Volunteers
From the Departments of Hematology (M. den H., I.A.B., H.L.H., P.W.W., W.B.J.G.) and Clinical Chemistry (A.P.S.), Leyenburg Hospital, The Hague; the Department of Hematology, Daniel den Hoed Clinic, Rotterdam (G.M.J.B.); the Department of Pediatrics, Laboratory of Pediatrics and Neurology (H.J.B., N.M.J. van der P.), and the Department of Obstetrics and Gynecology, Laboratory of Endocrinology and Reproduction (C.M.G.T.), University Hospital Nijmegen, Nijmegen; and Departments of Clinical Epidemiology and Hematology (F.R.R.), University Hospital Leiden, Leiden, the Netherlands.
Correspondence to Martin den Heijer, MD, PhD, Department of General Internal Medicine, University Hospital, Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail m.denheijer{at}aig.azn.nl
Abstract—Hyperhomocysteinemia is a
risk factor for atherosclerosis and thrombosis and is
inversely related to plasma folate and vitamin B12 levels. We assessed
the effects of vitamin supplementation on plasma homocysteine levels in
89 patients with a history of recurrent venous thrombosis and 227
healthy volunteers. Patients and hyperhomocysteinemic (homocysteine
level >16 µmol/L) volunteers were randomized to placebo or
high-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg
hydroxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers
without hyperhomocysteinemia was also randomized into three additional
regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg
hydroxycobalamin. Before and after the intervention period, blood
samples were taken for measurements of homocysteine, folate, cobalamin,
and pyridoxal-5'-phosphate levels. Supplementation with high-dose
multivitamin preparations normalized plasma homocysteine levels
(
16 µmol/L) in 26 of 30 individuals compared with 7 of 30 in
the placebo group. Also in normohomocysteinemic subjects, multivitamin
supplementation strongly reduced homocysteine levels (median reduction,
30%; range, -22% to 55%). In this subgroup the effect of folic acid
alone was similar to that of multivitamin: median reduction, 26%;
range, -2% to 52% for 5 mg folic acid and 25%; range, -54% to
40% for 0.5 mg folic acid. Cobalamin supplementation had only a slight
effect on homocysteine lowering (median reduction, 10%; range, -21%
to 41%). Our study shows that combined vitamin supplementation reduces
homocysteine levels effectively in patients with venous thrombosis and
in healthy volunteers, either with or without hyperhomocysteinemia.
Even supplementation with 0.5 mg of folic acid led to a substantial
reduction of blood homocysteine levels.
Key Words: homocysteine • vitamin supplementation • venous thrombosis • folate • MTHFR
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