Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation

PLoS One. 2013;8(2):e56194. doi: 10.1371/journal.pone.0056194. Epub 2013 Feb 14.

Abstract

Background: Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate.

Aim: Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation.

Study design and methods: Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined.

Results: Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks.

Conclusion: Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dietary Supplements* / analysis
  • Folic Acid / administration & dosage
  • Folic Acid / blood
  • Folic Acid / metabolism*
  • Folic Acid / urine*
  • Glutamates / blood
  • Glutamates / metabolism
  • Glutamates / urine
  • Homocysteine / blood
  • Homocysteine / urine
  • Humans
  • Male
  • Urinalysis
  • Vitamin B 12 / blood
  • Vitamin B 12 / urine
  • Vitamin B 6 / blood
  • Vitamin B 6 / urine
  • Young Adult

Substances

  • Glutamates
  • Homocysteine
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12

Grants and funding

This work was supported financially by the “Kompetenznetz Adipositas” (“Competence Network for Adiposity”) funded by the Federal Ministry of Education and Research (FKZ: 01GI1126). Further support by the Commission of the European Communities, within the 7th Framework Programme, NUTRIMENTHE, FP7- 212652 and by the Munich Center of Health Sciences (McHealth) is gratefully acknowledged. This manuscript does not necessarily reflect the views of the Commission and in no way anticipates the future policy in this area. BK is a recipient of the Freedom to Discover Award of the Bristol-Myers Squibb Foundation, New York, NY, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.