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European Journal of Nutrition

, Volume 55, Issue 3, pp 1021–1028 | Cite as

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

  • Rima ObeidEmail author
  • Susanne H. Kirsch
  • Sarah Dilmann
  • Cosima Klein
  • Rudolf Eckert
  • Jürgen Geisel
  • Wolfgang Herrmann
Original Contribution

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.

Keywords

Unmetabolized folic acid Elderly Supplementation Vitamin B6 Vitamin B12 Serum folate 

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

Notes

Acknowledgments

The study was registered: Clinical Trials NCT01105351.

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

394_2015_916_MOESM1_ESM.doc (30 kb)
Supplementary material 1 (DOC 30 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Rima Obeid
    • 1
    • 2
    Email author
  • Susanne H. Kirsch
    • 1
  • Sarah Dilmann
    • 1
  • Cosima Klein
    • 1
  • Rudolf Eckert
    • 3
  • Jürgen Geisel
    • 1
  • Wolfgang Herrmann
    • 1
  1. 1.Department of Clinical Chemistry and Laboratory MedicineUniversity Hospital of the SaarlandHomburgGermany
  2. 2.Aarhus Institute of Advanced StudiesUniversity of AarhusÅrhus CDenmark
  3. 3.Marien Hospital Geriatric CentreSt. WendelGermany

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