Metabolic functions of L-carnitine and its effects as feed additive in horses. A review.

L-carnitine, a betaine derivative of beta-hydroxybutyrate, is found in virtually all cells of higher animals and also in some microorganisms and plants. In animals it is synthesized almost exclusively in the liver. Two essential amino acids, i.e., lysine and methionine serve as primary substrates for its biosynthesis. Also required for its synthesis are sufficient amounts of vitamin B6, nicotinic acids, vitamin C and folate. The first discovered ergogenic function of L-carnitine is the transfer of activated long-chain fatty acids across the inner mitochondrial membrane into the mitochondrial matrix. For this transfer acyl-CoA esters are transesterified to form acylcarnitine esters. Thus, in carnitine deficiency fat oxidation and energy production from fatty acids are markedly impaired. Skeletal muscles constitute the main reservoir of carnitine in the body and have a carnitine concentration at least 200 times higher than blood plasma. Uptake of carnitine by skeletal muscles takes place by an active transport mechanism which transports L-carnitine into muscles probably in the form of an exchange process with gamma-butyrobetain. In young animals including foals, the capacity for biosynthesis of carnitine is not yet fully developed and apparently cannot meet the requirements of sucking animals. Sucking animals depend therefore on an extra supply of carnitine which is usually provided with milk. Additionally, young animals including foals possess a lower concentration of carnitine in blood plasma than adult animals. Besides its role as carrier of activated acyl groups, L-carnitine functions as a buffer for acetyl groups which may be present in excess in different tissues during ketosis and hypoxic muscular activity. Other functions of L-carnitine are protection of membrane structures, stabilizing of a physiologic CoA-SH/acetyl-CoA ratio and reduction of lactate production. Animal's derived feeds are rich in L-carnitine whereas plants contain usually very little or no carnitine. Carnitine is absorbed from the small intestine by active and passive transport mechanisms. From the increase in renal excretion of L-carnitine after oral supplementations of 10 g/d to horses it has been concluded that the efficiency of absorption of L-carnitine is rather low (about 5 to 10% of the supplied dose). A further decrease in fractional carnitine absorption was observed when the oral dose of carnitine was increased. L-carnitine is virtually not degraded in the body and renal excretion of carnitine is comparatively small under normal conditions. The concentration of L-carnitine in blood plasma of horses varies markedly between animals and between different days. In addition, circadian changes in carnitine concentration in plasma have been reported. Peak concentrations were found during late afternoon, being up to 30% higher than those in the morning. In breeding mares the carnitine concentration in blood plasma declines with onset of lactation. In resting skeletal muscles about 90% of the total carnitine content is present as free carnitine with the remaining part being available as carnitine esters. With increasing exercise intensity a continuing greater proportion of free carnitine (up to 80%) is converted into carnitine esters, mainly into acetylcarnitine. This shift from free to acetylcarnitine is readily reversed within about 30 min after termination of exercise. It appears that acute exercise does not have a marked effect on the content of total carnitine in skeletal muscle whereas training seems to elevate its total concentration in the middle gluteal muscle of 3 to 6 year old horses and to reduce variation of its concentration compared to age-matched untrained horses. Oral supplementations of 5 to 50 g of L-carnitine per day to horses elevated the carnitine concentration in blood plasma to about twice its basal concentration. No clear relationship existed, however, between the orally administered dose of carnitine and the increase of L-carni