Supplementation of atherogenic diet with B vitamins does not prevent atherosclerosis or vascular dysfunction in monkeys.
BACKGROUND
Hyperhomocysteinemia is associated with increased risk of atherosclerotic and thrombotic vascular disease. In many patients, hyperhomocysteinemia can be treated or prevented by dietary supplementation with B vitamins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven.


RESULTS
Using an atherogenic diet that produces both hyperhomocysteinemia 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 atherosclerotic lesions in monkeys. After 17 months, plasma total homocysteine increased from 3.6+/-0.3 to 11.8+/-1.7 micromol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogenic diet supplemented with B vitamins (3.8+/-0.3 micromol/L). Serum cholesterol increased from 122+/-7 to 550+/-59 mg/dL in the unsupplemented group (P<0.001) and from 118+/-5 to 492+/-55 mg/dL in the supplemented 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 failed to prevent intimal thickening in the carotid or iliac arteries.


CONCLUSIONS
These findings demonstrate that supplementation with B vitamins prevents hyperhomocysteinemia but is not sufficient to prevent the development of vascular dysfunction or atherosclerotic lesions in monkeys with marked hypercholesterolemia, even in the absence of preexisting atherosclerosis.
Lentz
S R
SR
Veterans Affairs Medical Center, Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA. steven-lentz@uiowa.edu
Piegors
D J
DJ
Malinow
M R
MR
Heistad
D D
DD
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D001777:Blood Coagulation / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005492:Folic Acid / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000503:physiopathology; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D010314:Partial Thromboplastin Time; D011736:Pyridoxine / Q000008:administration & dosage*; D013917:Thrombin / Q000494:pharmacology; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014805:Vitamin B 12 / Q000008:administration & dosage*
D014665:Vasodilator Agents; D005492:Folic Acid; D002784:Cholesterol; D013917:Thrombin; D011736:Pyridoxine; D014805:Vitamin B 12