title: Supplementation of atherogenic diet with B vitamins does not prevent atherosclerosis or vascular dysfunction in monkeys.
abstract: 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.
authors.affiliation: Veterans Affairs Medical Center, Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA. steven-lentz@uiowa.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Lentz
authors.forename: D J
authors.initials: DJ
authors.lastname: Piegors
authors.forename: M R
authors.initials: MR
authors.lastname: Malinow
authors.forename: D D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: 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*
chemical_list: D014665:Vasodilator Agents; D005492:Folic Acid; D002784:Cholesterol; D013917:Thrombin; D011736:Pyridoxine; D014805:Vitamin B 12