Pharmacokinetic and metabolic interrelationships among branched-chain keto and amino acids in humans.

Equimolar loads (0.55 mmol/kg) of alpha-ketoisocaproic acid (KICA) or alpha-keto-beta-methyl-n-valeric acid (KMVA), leucine, or isoleucine were given to healthy human subjects. Branched-chain keto acid (BCKA) and amino acid (BCAA) blood levels increased severalfold within minutes for greater than 3 hours. Time course and magnitude of the increments were different for each substance. Keto acids augmented the concentrations of their corresponding amino acids, and amino acids those of the respective keto acids. Each individual keto or amino acid affected all other constituents of the BCKA-BCAA pool. KICA and leucine greatly diminished KMVA, isoleucine, alpha-ketoisovaleric acid, and valine concentrations in blood. Leucine and isoleucine increased significantly more in response to leucine or isoleucine than to administration of equimolar loads of KICA or KMVA. The data suggest that an inappropriate increase in KICA or leucine in BCKA- or BCAA-containing supplements may stimulate the catabolism of BCKAs and BCAAs. Furthermore, if keto acid-containing supplements are given to increase low leucine, isoleucine, or valine concentrations, the dose must be significantly higher than for amino acid-containing supplements.