title: Folic Acid does not limit endothelial dysfunction induced by ischemia and reperfusion: a human study.
abstract: Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7+/-1.0%; after IR, 1.5+/-1.3%, P<0.01). A similar effect was observed in the folic acid group (before IR, 6.3+/-1.1%; after IR, 2.1+/-1.0%, P=ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.
authors.affiliation: Department of Internal, Cardiovascular, and Geriatric Medicine, Azienda Ospedaliera Universitaria Senese, University of Siena, Italy and Department of Medicine, Mount Sinai and University Health Network Hospitals, University of Toronto, Ontario, Canada.
authors.forename: Saverio
authors.initials: S
authors.lastname: Dragoni
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Stolfo
authors.forename: Silvia
authors.initials: S
authors.lastname: Sicuro
authors.forename: Sandro
authors.initials: S
authors.lastname: Forconi
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005492:Folic Acid / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D017534:Radial Artery / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D006397:Hematinics; D005492:Folic Acid