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Eur J Nutr. 2016 Apr;55(3):1021-8. doi: 10.1007/s00394-015-0916-z. Epub 2015 May 6.

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

Author information

1
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany. rima.obeid@uniklinikum-saarland.de.
2
Aarhus Institute of Advanced Studies, University of Aarhus, Høegh-Guldbergs Gade 6B, Building 1632, 8000, Århus C, Denmark. rima.obeid@uniklinikum-saarland.de.
3
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany.
4
Marien Hospital Geriatric Centre, 66606, St. Wendel, Germany.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01105351.

KEYWORDS:

Elderly; Serum folate; Supplementation; Unmetabolized folic acid; Vitamin B12; Vitamin B6

PMID:
25943647
DOI:
10.1007/s00394-015-0916-z
[Indexed for MEDLINE]

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