Effects of acute hypercarnitinemia during increased fatty substrate oxidation in man

Abstract

To test whether carnitine availability is rate-limiting for fat oxidation under conditions of augmented oxidative use of fatty substrates, two series of studies were performed. In study no. 1, l-carnitine (1 g + 0.5 g/h intravenously [IV]) or saline was given to eight volunteers during a 4-hour infusion of a 10% triglyceride emulsion, thereby increasing plasma free-carnitine levels from 38 ± 4 to 415 ± 55 μmol/L. Fat infusion increased plasma triglyceride levels (80%) and lipid oxidation (30%), and decreased (28%) carbohydrate oxidation (as measured by indirect calorimetry); hypercarnitinemia had no influence on these responses. In study no. 2 in 12 healthy subjects a bolus of l-carnitine (3 g) or saline was administered 40 minutes before aerobic exercise (bicycling for 40 minutes at 60 W), followed by 2 minutes of anaerobic exercise (250 W) and 50 minutes of recovery. Oxygen consumption (Vo 2), increased to 18.3 ± 0.7 mL · min −1 · kg −1 during aerobic exercise, reached a maximum of 46.0 ± 0.8 mL · min −1 · kg −1 during the anaerobic bout, and returned to baseline within a few minutes, with no difference between control and carnitine. At virtually identical mean energy expenditure rates (196 ± 7 v 197 ± 7 J · min −1 · kg −1, saline v carnitine), after carnitine administration the entire exercise protocol was sustained by a lower mean carbohydrate oxidation rate (42.1 ± 3.6 v 36.5 ± 2.3 μmol · min −1 · kg −1, P < .03) and a higher mean lipid oxidation rate (6.7 ± 1.0 v 8.3 ± 0.7 μmol · min −1 · kg −1, P < .05). Since oxidation rates were similar in the basal state and during steady-state aerobic exercise, this difference was concentrated in the recovery phase. The exercise-induced increment in heart rate during the entire study period tended to be smaller with carnitine than with saline (mean difference, 4.2 beats/min, P < .05); again, this difference was greater during recovery from anaerobic exercise. The exercise-induced changes in blood glucose, free fatty acids (FFA), lactate, pyruvate, glycerol, citrate, and β-hydroxybutyrate concentrations were similar with saline and carnitine. During recovery from exercise, carnitine, but not saline, induced a sharp increase in plasma short-chain carnitine concentrations, together with a significantly lower lactate to pyruvate ratio ( P < .02). We conclude that carnitine (1) is not rate-limiting for β-oxidation in the resting state, during lipid loading, or during aerobic exercise; and (2) hypercarnitinemia slightly favors lipid oxidation over carbohydrate oxidation, particularly during recovery from intense exercise, and is associated with a faster recovery of heart rate.