Eur J Appl Physiol (1992) 65:13-17 European oum., Applied Physiology and Occupational Physiology © Springer-Verlag1992 Effect of carnitine loading on long-chain fatty acid oxidation, maximal exercise capacity, and nitrogen balance O. J. Heinonen 1, J. Takala 2, and M. H. Kvist 1 1Paavo Nurmi Center, Sports Medical Research Unit and Department of Physiology,Universityof Turku, Kiinamyllynkatu 10, SF-20520 Turku, Finland 2 Critical Care Research Program, Department of Intensive Care, Kuopio UniversityHospital, Kuopio, Finland Accepted January 3, 1992 Summary. Carnitine has a potential effect on exercise capacity due to its role in the transport of long-chain fatty acids into the mitochondria for p-oxidation, the export of acyl-coenzyme A compounds from mito- chondria and the activation of branched-chain amino acid oxidation in the muscle. We studied the effect of carnitine supplementation on palmitate oxidation, maxi- mal exercise capacity and nitrogen balance in rats. Daily carnitine supplementation (500 mg. kg-1 body mass for 6 weeks) was given to 30 rats, 15 of which were on an otherwise carnitine-free diet (group I) and 15 pair-fed with a conventional pellet diet (group II). A control group (group III, n = 6) was fed ad libitum the pellet diet. Palmitate oxidation was measured by collecting 14CO2 after an intraperitoneal injection of [1-14C]palmi- tate and exercise capacity by swimming to exhaustion. After carnitine supplementation carnitine concentra- tions in serum were supranormal [group I, total 150.8 (SD 48.5), free 78.9 (SD 18.4); group II, total 170.9 (SD 27.9), free 115.8 (SD 24.6) gmol. 1- l] and liver carnitine concentrations were normal in both groups [group I, to- tal 1.6 (SD 0.3), free 1.2 (SD 0.2); group II, total 1.3 (SD 0.3), free 0.9 (SD 0.2) gmol.g-1 dry mass]. In mus- cle carnitine concentrations were normal in group I [to- tal 3.8 (SD 1.2), free 3.2 (SD 1.0) gmol.g -1 dry mass] and increased in group II [total 6.6 (SD 0.5), free 4.9 (SD 0.9) gmol.g-i dry mass]. Despite the difference in muscle carnitine concentrations there were no differ- ences among the groups in cumulative palmitate oxida- tion after 3 h [group I, 39.7 (SD 11.6)%; group II, 29.6 (SD 14.0)%; group III, 36.5 (SD 10.8)% of injected ac- tivity] or swimming time to exhaustion [group I, 9.7 (SD 2.9); group II, 8.4 (SD 3.6); group III, 7.1 (SD 2.8) h]. A borderline increase in nitrogen balance was observed in group II. We concluded that increasing carnitine tis- sue concentrations by carnitine supplementation had no effect on palmitate oxidation and maximal exercise ca- pacity in the rats studied. Offprint requests to: O. J. Heinonen Key words: L-Carnitine supplementation - Fatty acid metabolism - Muscle metabolism - Nitrogen balance - Prolonged submaximal exercise Introduction It has been shown that carnitine may play a central role in exercise capacity during prolonged exercise because it transports activated long-chain fatty acids from the cy- tosol into the mitochondria for/3-oxidation (Fritz 1963). Prolonged low intensity exercise has been characterized by increased utilization of fatty acids, which eventually have become the major energy source for muscles (Felig and Wahren 1975). Without carnitine, it has been found that long-chain fatty acids cannot penetrate the mito- chondrial membrane for energy production, but accu- mulate in the cytoplasm, interfering with other meta- bolic functions (Stumpf et al. 1985). Acyl-coenzyme A (CoA) compounds have been shown to accumulate in the mitochondria during ischaemia and apparently also during exercise (Siliprandi 1986), and this accumulation has been potentially harmful (Stumpf et al. 1985). Car- nitine has been seen to export these acyl-CoA com- pounds out of mitochondria (Chalmers et al. 1984; Stumpf et al. 1985) and thereby to stimulate the flux of substrates along the citric acid cycle (HOlsmann et al. 1964). Exclusion of dietary carnitine for 6 weeks has been found to reduce tissue carnitine concentrations by 50% but to have no effect on palmitate oxidation and maxi- mal exercise capacity in rats (Heinonen and Takala, sub- mitted for publication). Severe carnitine deficiency has impaired muscle function, fatty acid oxidation, and caused myopathy. Since it has been shown that these changes can be normalized by carnitine supplementation (Engel and Angelini 1973) and since muscle carnitine concentration and the capacity of fatty acid oxidation in vitro have been seen to be interrelated (Cederblad et al. 1976), carnitine supplementation may have potential major effects on muscle metabolism. Carnitine has also