Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial

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  • Rima Obeid, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland
  • ,
  • Susanne H Kirsch, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany
  • Sarah Dilmann, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany
  • Cosima Klein, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany
  • Rudolf Eckert, Marien Hospital Geriatric Centre, St. Wendel, Germany
  • Jürgen Geisel, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany
  • Wolfgang Herrmann, Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Germany

PURPOSE: 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.

Original languageEnglish
JournalEuropean Journal of Nutrition
Volume55
Issue3
Pages (from-to)1021–1028
Number of pages8
ISSN1436-6207
DOIs
Publication statusPublished - 2016

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