title: Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?
abstract: BACKGROUND
  In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12-related metabolic abnormalities.
  
  
  OBJECTIVE
  We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function.
  
  
  METHODS
  In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum.
  
  
  RESULTS
  In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food.
  
  
  CONCLUSIONS
  In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population.
authors.affiliation: Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. jamesmills@nih.gov
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Tonia C
authors.initials: TC
authors.lastname: Carter
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: James F
authors.initials: JF
authors.lastname: Troendle
authors.forename: Eileen R
authors.initials: ER
authors.lastname: Gibney
authors.forename: Barry
authors.initials: B
authors.lastname: Shane
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005492:Folic Acid / Q000097:blood*; D005527:Food, Fortified; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000378:metabolism*; D055815:Young Adult
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005293:Ferritins; D005492:Folic Acid; D014805:Vitamin B 12