title: Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering.
abstract: Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/- 2.7%, p = 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteine-lowering, but does not modulate markers of inflammation.
authors.affiliation: Queen Elizabeth II Health Sciences Centre, Division of Cardiology, 6896-1796 Summer St, Halifax, NS, Canada. ltitle@dal.ca
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Title
authors.forename: Ehud
authors.initials: E
authors.lastname: Ur
authors.forename: Karen
authors.initials: K
authors.lastname: Giddens
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McQueen
authors.forename: Bassam A
authors.initials: BA
authors.lastname: Nassar
mesh_terms: D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D006710:Homocysteine; D002097:C-Reactive Protein; D005492:Folic Acid; D005996:Nitroglycerin