3-Hydroxypropionic acid and methylcitric acid are not reliable indicators of marginal biotin deficiency in humans

J Nutr. 2004 Feb;134(2):317-20. doi: 10.1093/jn/134.2.317.


In two studies comprising 10 and 11 subjects, respectively, marginal biotin deficiency was induced experimentally by an egg-white diet in healthy men and women. The following urinary organic acids were assessed for their usefulness in detecting marginal biotin status: 1) 3-hydroxypropionic acid and methylcitric acid, organic acids that reflect decreased activity of the biotin-dependent enzyme propionyl-CoA carboxylase and 2) methylcrotonylglycine and isovalerylglycine, organic acids that reflect decreased activity of methylcrotonyl-CoA carboxylase. Mean 3-hydroxypropionic acid excretion rates remained normal during biotin depletion in both studies. By the end of the depletion period, 3-hydroxypropionic acid excretion identified only 5 of 21 marginally deficient subjects. Mean methylcitric acid excretion increased (P < 0.0001) in the first study but not in the second. Mean methylcrotonylglycine excretion increased in each study (P < 0.004 and P < 0.05, respectively); methylcrotonylglycine excretion identified 13 of 21 marginally deficient subjects. Mean isovalerylglycine excretion increased only in the first study (P = 0.006) and identified only 6 of 21 deficient subjects. We conclude that none of these organic acids is as sensitive an indicator of marginal biotin deficiency as 3-hydroxyisovaleric acid, which reflects decreased methylcrotonyl-CoA carboxylase.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biotin / administration & dosage
  • Biotin / deficiency*
  • Biotin / urine
  • Carbon-Carbon Ligases / metabolism
  • Carbon-Carbon Ligases / urine
  • Citrates* / metabolism
  • Diet
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Lactic Acid / analogs & derivatives*
  • Lactic Acid / metabolism
  • Male
  • Reference Values


  • Citrates
  • Lactic Acid
  • Biotin
  • hydracrylic acid
  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase