Plasma concentration of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans

Background Blood based indicators of biotin status in humans were shown to be useful tools in several clinical situations including pregnancy We previously validated the activity of the biotin dependent enzyme propionyl coenzyme A carboxylase (PCC) in lymphocytes as a sensitive and specific blood based indicator of marginal degrees of biotin deficiency However the measurement of PCC activity in population studies presents substantial ana lytic challenges 3 Hydroxyisovaleryl carnitine (3HIA carnitine) in creases in response to the decreased activity of the biotin dependent enzyme methylcrotonyl coenzyme A carboxylase and might reflect biotin status Objective We sought to determine whether the plasma concentration of 3HIA carnitine increases significantly in marginal biotin deficiency Design We experimentally induced marginal asymptomatic biotin deficiency in 10 healthy adults (8 women) by having the subjects consume undenatured egg white for 28 d biotin status was then repleted Plasma concentrations of 3HIA carnitine were measured on days 0 14 28 35 and 50 by liquid chromatography mass spectroscopy Results The mean plasma 3HIA carnitine concentration increased with depletion (P < 0 0001) and decreased with repletion (P < 0 0001) Plasma 3HIA carnitine concentrations were greater than the upper limit of normal concentrations in 7 of 10 subjects by day 14 and in 9 of 10 subjects by day 28 and decreased to within normal limits in 9 of 10 subjects by day 50 Conclusions These studies provide evidence that 3HIA carnitine is an early and sensitive indicator of marginal biotin deficiency The ease of sample collection small sample volume requirement and stability of 3HIA carnitine during storage suggest that plasma 3HIA carnitine concentration is likely to be a useful indicator of marginal biotin deficiency for larger population studies Am J Clin Nutr 2010 92 1399-405