title: Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers.
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 micromol/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 (< or = 16 micromol/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.
authors.affiliation: Department of Hematology, Leyenburg Hospital, The Hague, The Netherlands. m.denheijer@aig.azn.nl
authors.forename: M
authors.initials: M
authors.lastname: den Heijer
authors.forename: I A
authors.initials: IA
authors.lastname: Brouwer
authors.forename: G M
authors.initials: GM
authors.lastname: Bos
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: N M
authors.initials: NM
authors.lastname: van der Put
authors.forename: A P
authors.initials: AP
authors.lastname: Spaans
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: C M
authors.initials: CM
authors.lastname: Thomas
authors.forename: H L
authors.initials: HL
authors.lastname: Haak
authors.forename: P W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: W B
authors.initials: WB
authors.lastname: Gerrits
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D012016:Reference Values; D013924:Thrombophlebitis / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics
chemical_list: D004338:Drug Combinations; D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D011736:Pyridoxine; D006879:Hydroxocobalamin