title: Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial.
abstract: OBJECTIVE
  Unmetabolized folic acid (UMFA) is common in serum of elderly individuals receiving folic acid (FA)-fortified foods or supplements. We studied the effect of supplementing FA or B-complex on serum concentrations of (6S)-5-methyltetrahydropteroylglutamate [(6S)-5-CH3-H4Pte] and UMFA in elderly people and explored factors associated with detectable UMFA post-supplementation.
  
  
  METHODS
  This is a randomized single-blind non-controlled trial on 58 elderly people using daily 400 µg FA (n = 31) or 400 µg FA, 10 µg cyanocob(III)alamin and 8 mg pyridoxine (n = 27) for a median of 23 days. Main outcome includes changes in concentrations of serum (6S)-5-CH3-H4Pte and UMFA.
  
  
  RESULTS
  Total homocysteine declined by a median of 1.6 (p = 0.074) in the FA and 1.3 µmol/L (p = 0.009) in the B-complex arms (p = 0.66 between the arms). Serum (6S)-5-CH3-H4Pte significantly (p < 0.001 vs. baseline) increased by a median of 9.2 and 6.5 nmol/L in the FA and B-complex groups, respectively (p = 0.152 between the groups). Compared to FA, B-complex reduced cystathionine and caused lower post-intervention serum UMFA, percentage of UMFA to (6S)-5-CH3-H4Pte and prevalence of UMFA ≥ 0.21 nmol/L. Higher serum cystathionine and whole-blood folate predicted higher post-intervention serum UMFA.
  
  
  CONCLUSIONS
  FA caused higher UMFA as compared to B-complex. Pyridoxine appears to improve folate recycling. Data on serum UMFA should be interpreted in relation to other vitamins involved in folate metabolism. Serum UMFA is suggested to play a sensory role through which the cell recognizes FA available for metabolism via dihydrofolate reductase.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany. rima.obeid@uniklinikum-saarland.de.|Aarhus Institute of Advanced Studies, University of Aarhus, Høegh-Guldbergs Gade 6B, Building 1632, 8000, Århus C, Denmark. rima.obeid@uniklinikum-saarland.de.
authors.forename: Rima
authors.initials: R
authors.lastname: Obeid
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Kirsch
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dilmann
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
authors.forename: Cosima
authors.initials: C
authors.lastname: Klein
authors.affiliation: Marien Hospital Geriatric Centre, 66606, St. Wendel, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Eckert
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herrmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003540:Cystathionine / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D008297:Male; D018401:Sample Size; D016037:Single-Blind Method; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood*
chemical_list: D015415:Biomarkers; D014803:Vitamin B Complex; D003540:Cystathionine; D005492:Folic Acid
keywords: Elderly; Serum folate; Supplementation; Unmetabolized folic acid; Vitamin B12; Vitamin B6