VITAMIN SUPPLEMENTATION REDUCES BLOOD HOMOCYSTEINE LEVELS - A CONTROLLED TRIAL IN PATIENTS WITH VENOUS THROMBOSIS AND HEALTHY-VOLUNTEERS

Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombos is and is inversely related to plasma folate and vitamin B12 levels. W e assessed the effects of vitamin supplementation on plasma homocystei ne levels in 89 patients with a history of recurrent venous thrombosis and 227 healthy volunteers. Patients and hyperhomocysteinemic (homocy steine level >16 mu mol/L) volunteers were randomized to placebo or hi gh-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg hy droxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers without hyperhomocysteinemia was also randomized into three additional regime ns 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'-pho sphate levels. Supplementation with high-dose multivitamin preparation s normalized plasma homocysteine levels (less than or equal to 16 mu m ol/L) in 26 of 30 individuals compared with 7 of 30 in the placebo gro up. Also in normohomocysteinemic subjects, multivitamin supplementatio n strongly reduced homocysteine levels (median reduction, 30%; range, -22% to 55%). In this subgroup the effect of folic acid alone was simi lar 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 lo wering (median reduction, 10%; range, -21% to 41%). Our study shows th at combined vitamin supplementation reduces homocysteine levels effect ively in patients with venous thrombosis and in healthy volunteers, ei ther with or without hyperhomocysteinemia. Even supplementation with 0 .5 mg of folic acid led to a substantial reduction of blood homocystei ne levels.