title: Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype.
abstract: BACKGROUND
  Riboflavin (vitamin B(2)) is the precursor for FAD, the cofactor for methylenetetrahydrofolate reductase (MTHFR). MTHFR catalyzes the formation of 5-methyltetrahydrofolate, which acts as a methyl donor for homocysteine remethylation. Individuals with the MTHFR 677C-->T mutation have increased plasma total homocysteine (tHcy) concentrations, particularly in association with low folate status. It has been proposed that riboflavin may act together with folate to lower plasma tHcy, particularly in individuals with the thermolabile MTHFR T variant.
  
  
  METHODS
  We measured B-vitamin status and plasma tHcy in 126 healthy individuals 20-63 years of age (42 CC, 42 CT, and 42 TT MTHFR genotypes) at baseline and after three interventions (4 months): placebo plus natural diet; daily 400 microg folic acid supplement plus natural diet; and increased dietary folate to 400 microg/day.
  
  
  RESULTS
  At baseline and after nutritional intervention, lower riboflavin status was associated with increased plasma tHcy concentrations. Plasma tHcy was 2.6 micromol/L higher in the lowest plasma riboflavin quartile compared with the highest (P <0.02) and was 4.2 micromol/L higher in the highest erythrocyte glutathione reductase activation coefficient (EGRAC) quartile compared with the lowest (P <0.001). This effect was not restricted to those with the T allele. Folic acid given as a 400 microg/day supplement appeared to exacerbate a tendency toward riboflavin deficiency, as suggested by an increase in the proportion of individuals with EGRAC > or =1.4 from 52% to 65% after supplementation (P <0.05).
  
  
  CONCLUSIONS
  Folate and riboflavin interact to lower plasma tHcy, possibly by maximizing the catalytic activity of MTHFR. The effect may be unrelated to MTHFR genotype.
authors.affiliation: Cardiovascular Sciences Research Group, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, Wales CF14 4XN, United Kingdom. moatsj@cardiff.ac.uk
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Moat
authors.forename: Pauline A L
authors.initials: PA
authors.lastname: Ashfield-Watt
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Powers
authors.forename: Robert G
authors.initials: RG
authors.lastname: Newcombe
authors.forename: Ian F W
authors.initials: IF
authors.lastname: McDowell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000503:physiopathology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005838:Genotype; D005980:Glutathione Reductase / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D012044:Regression Analysis; D012256:Riboflavin / Q000097:blood*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D005980:Glutathione Reductase; D012256:Riboflavin