Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate were studied in four healthy male adults. Glucose and amino acids were infused alone for 3 h, then continued for another 5.5 h together with a lipid emulsion containing only long-chain triglycerides or a 50:50% (wt/wt) mixture of medium-chain and long-chain triglycerides. During the fat-free infusion, the concentration of free carnitine rose, whereas the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 h reduced free carnitine to lower values (32.4 +/- 4.7 mumols/l) than long-chain triglycerides infusion (44.4 +/- 2.7 mumol/l). By contrast, the plasma concentrations of short-chain acylcarnitine (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/l; P less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/l; P less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. This suggests that intravenous medium-chain triglycerides are not metabolized independently of carnitine. Carnitine may play an important role in removing acyl and acetyl groups from mitochondria and in restoring the intramitochondrial CoA level. Fat substrates are converted into compounds that might be utilized by tissues that do not normally oxidize fatty acids, creating an interorgan energy cycle.