Supplementation of atherogenic diet with B vitamins does not prevent atherosclerosis or vascular dysfunction in monkeys

Background--Hyperhomocysteinemia is associated with increased risk of ather osclerotic and thrombotic vascular disease. In many patients, hyperhomocyst einemia can be treated or prevented by dietary supplementation with B vitam ins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven. Methods and Results--Using an atherogenic diet that produces both hyperhomo cysteinemia and hypercholesterolemia, we tested the hypothesis that dietary supplementation with B vitamins (folic acid, vitamin B-12, and vitamin B-6 ) would prevent hyperhomocysteinemia, vascular dysfunction, and atheroscler otic lesions in monkeys. After 17 months, plasma total homocysteine increas ed from 3.6 +/-0.3 to 11.8 +/-1.7 mu mol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogen ic diet supplemented with B vitamins (3.8<plus/minus>0.3 mu mol/L). Serum c holesterol increased from 122 +/-7 to 550 +/- 59 mg/dL in the unsupplemente d group (P<0.001) and from 118<plus/minus>5 to 492 +/- 55 mg/dL in the supp lemented group (P<0.001). Responses to endothelium-dependent vasodilators, both in resistance vessels in vivo and in the carotid artery ex vivo, were impaired to a similar extent in groups that did and did not receive vitamin supplements, Anticoagulant responses to the infusion of thrombin were also impaired to a similar extent in both groups. Vitamin supplementation faile d to prevent intimal thickening in the carotid or iliac arteries. Conclusions--These findings demonstrate that supplementation with B vitamin s prevents hyperhomocysteinemia but is not sufficient to prevent the develo pment of vascular dysfunction or atherosclerotic lesions in monkeys with ma rked hypercholesterolemia, even in the absence of preexisting atheroscleros is.