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.