title: High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease.
abstract: OBJECTIVE
  We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans.
  
  
  BACKGROUND
  Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known.
  
  
  METHODS
  Fourteen patients with ischemic heart disease, age 62 +/- 12 years (mean +/- SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as "normal" versus "abnormal" on the basis of MBF response to adenosine 140 microg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis.
  
  
  RESULTS
  Folate was associated with a reduction in mean arterial pressure (100 +/- 12 mm Hg vs. 96 +/- 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 +/- 0.59 ml/min/g vs. 2.16 +/- 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 +/- 0.59 vs. ml/min/g 1.41 +/- 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 +/- 0.61 ml/min/g vs. 2.12 +/- 0.69 ml/min/g, placebo vs. folate, p = NS).
  
  
  CONCLUSIONS
  The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.
authors.affiliation: Department of Medicine (Cardiac Unit), Massachusetts General Hospital, Boston, Massachusetts 02114, USA. atawakol@partners.org
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.forename: Raymond Q
authors.initials: RQ
authors.lastname: Migrino
authors.forename: Kusai S
authors.initials: KS
authors.lastname: Aziz
authors.forename: Justyna
authors.initials: J
authors.lastname: Waitkowska
authors.forename: Gotfred
authors.initials: G
authors.lastname: Holmvang
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Alpert
authors.forename: James E
authors.initials: JE
authors.lastname: Muller
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: Henry
authors.initials: H
authors.lastname: Gewirtz
mesh_terms: D000241:Adenosine; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D005492:Folic Acid; D000241:Adenosine