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

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European Journal of Nutrition Aims and scope Submit manuscript

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.

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Abbreviations

BHMT:

Betaine hydroxymethyl transferase

DHFR:

Dihydrofolate reductase

GFR:

Glomerular filtration rate

FA:

Folic acid

holoTC:

Holotranscobalamin

MCV:

Mean corpuscular volume

SAM:

S-adenosylmethionine

(6S)-5-CH3-H4Pte:

(6S)-5-methyltetrahydropteroylglutamate

(6S)-5-HCO-H4Pte:

(6S)-5-formyltetrahydropteroylglutamate

(6S)-H4Pte:

(6S)-5,6,7,8-tetrahydropteroylglutamate

SHMT:

Serine hydroxymethyl transferase

(6R)-5,10-CH+-H4Pte:

(6R)-5,10-methenyltetrahydropteroylglutamate

tHcy:

Total homocysteine

UMFA:

Unmetabolized folic acid

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Acknowledgments

The study was registered: Clinical Trials NCT01105351.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Clinical Chemistry and Laboratory Medicine, University Hospital of the Saarland, Building 57, 66421, Homburg, Saar, Germany

    Rima Obeid, Susanne H. Kirsch, Sarah Dilmann, Cosima Klein, Jürgen Geisel & Wolfgang Herrmann

  2. Aarhus Institute of Advanced Studies, University of Aarhus, Høegh-Guldbergs Gade 6B, Building 1632, 8000, Århus C, Denmark

    Rima Obeid

  3. Marien Hospital Geriatric Centre, 66606, St. Wendel, Germany

    Rudolf Eckert

Authors
  1. Rima Obeid
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  2. Susanne H. Kirsch
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  3. Sarah Dilmann
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  4. Cosima Klein
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  5. Rudolf Eckert
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  6. Jürgen Geisel
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  7. Wolfgang Herrmann
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Correspondence to Rima Obeid.

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Obeid, R., Kirsch, S.H., Dilmann, S. et al. Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial. Eur J Nutr 55, 1021–1028 (2016). https://doi.org/10.1007/s00394-015-0916-z

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  • DOI: https://doi.org/10.1007/s00394-015-0916-z

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