title: Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease.
abstract: OBJECTIVE
  To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation.
  
  
  RESULTS
  The PACIFIC study was a double-blind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2.0 mg daily, folic acid 0.2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2.0 mg folic acid reduced homo-cysteine by 1.8 micromol x 1(-1) [95% confidence interval (CI) 1.3-2.3] and 0.2 mg reduced homocysteine by 1.2 micromol x 1(-1) [95% CI 0.8-1.7). The higher dose reduced homocysteine significantly more than the lower dose (P=001).
  
  
  CONCLUSIONS
  Both doses of folic acid reduced homocysteine, but the effects of the 2.0 mg dose were about one third greater than the 0.2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.forename: Stephen
authors.initials: S
authors.lastname: MacMahon
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
authors.forename: David
authors.initials: D
authors.lastname: Wilcken
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001315:Australia; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006397:Hematinics / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011725:Pyridines / Q000627:therapeutic use; D013841:Thiazepines / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D006397:Hematinics; D011725:Pyridines; D013841:Thiazepines; D006710:Homocysteine; C106266:omapatrilat; D005492:Folic Acid