Carnitine What it is Unlike most vitamins and vitamin-like substances, carnitine was identified and synthesised long before the discovery of its nutritional role. Its presence in meat extracts was demonstrated in 1905 and it was correctly identified as ß-hydroxy-a -butyrobetaine and given the common name carnitine. Fifty years later it was found to be an important dietary requirement of certain insects. Earlier this nutritional effect had been ascribed to vitamin BT which was found in 1952 to be carnitine. Early research literature also calls carnitine vitamin B11. Carnitine occurs in all biological systems but there is still considerable debate whether or not it should be classified as a vitamin because it only appears to be an essential dietary component for a few animal species. It is probably equally vital for all animals but most species, including horses, synthesise it in adequate amounts. It seems to function particularly in fatty acid metabolism in the liver. It is an unusual type of vitamin material because, of the two stereo-isomers which have been separated, only the laevorotatory form is biologically active. The active form of most other vitamin substances is the d-form with the notable exception of ascorbic acid. What it does The early research work showed that it was an essential dietary factor for all species of the insect family Tenebrionidae. Larvae fail to survive or grow in the absence of carnitine. There is no evidence to date that it is essential for any other insect families. So far a few micro-organisms have been found which also require an external supply. Whether supplied by the diet or from endogenous synthesis, carnitine is essential in the metabolism and movement of fatty acids within and between cells. It has been found that it forms an enzyme, carnitine acetyltransferase, which is part of the mechanism for releasing CoA and acetyl-CoA. The effect of carnitine on fatty acid metabolism seems to be limited to fatty acids with chain lengths greater than C8. It seems to have a particular affinity for palmitic acid and one current hypothesis is that its function is to carry these long chain molecules across the mitochondrial membranes. This may not be its only role since it has recently been shown that palmitylcarnitine stimulates fat synthesis in livers so another vitamin role of carnitine may be the regulation of lipogenesis. Carnitine acetyltransferase is found uniformly distributed within the brain where it seems to have a more important role than choline acetyltransferase. It is also interesting to note that a similar relationship exists between the amino acid lysine and carnitine as occurs between tryptophan and niacin. In each case the amino acid can be converted into the vitamin. If insufficient is available No deficiency problems in vertebrates have yet been found under practical conditions. There is a suggestion that young foals on a low plane of nutrition may grow more rapidly when carnitine has been supplied directly or indirectly. Therefore, rather than deficiency effects, it appears that there may be beneficial effects from increasing dietary inputs. These may be partially due to the inhibitory effects of carnitine on thyroxine. If too much is given Large amounts of carnitine (up to 1 g per kg liveweight per day) have been given without apparent untoward effect. It is only excreted slowly from animals and excess carnitine can take as long as 3 months to be eliminated. Biosynthesis The production of carnitine appears to occur mainly in the liver. The starting point is trimethyl-lysine which is produced by methylating lysine and the usual source of the methyl groups is methionine. The reaction takes place in stages. One of the first steps is the production of an aldehyde using PALP as a cofactor. This is oxidised to a butyrate by an NAD-linked dehydrogenase. The final stage is hydroxylation by a ketoglutarate-ferrous ascorbate compound. Thus, the endogenous production of carnitine requires two amino acids, lysine and methionine, and three vitamins, niacin, vitamin B6 and ascorbic acid. Animals deprived of lysine show fatty accumulations in the liver which can be dispersed by an exogenous supply of carnitine, which demonstrates the dependence of carnitine production on the presence of adequate lysine. How it is measured The biological assay of carnitine is interesting because it depends on the specific requirement of the yellow mealworm Tenebrio molitor. It can also be determined chemically by conversion to crotonobetaine and measurement by spectrophotometer. The most accurate method appears to be an enzymatic method based on the release of CoA from acetyl-CoA in the presence of limiting amounts of carnitine. Assessment of status It is very widely distributed in animals and plants, though animal tissue is by far the richer source. Since it occurs in all parts of the animal it is not possible to make any accurate assessment of total status from an assay of plasma or tissue content. Relationships with other ingredients Dependence on lysine, methionine, vitamin B6, niacin and ascorbic acid has already been mentioned. Since it also appears to have roles in phosphatide production and in nervous activity, it is closely allied to choline. Requirements and allowances Horses do not have a dietary requirement for carnitine even though it has a vital function. In species of micro-organisms and insects where it is needed, 5-10 mg per kg diet/substrate seems to be required for maximum production/survival. Growth rates of foals may be improved when 25-40 mg carnitine are added per kg feed. It also appears to be required by human athletes and performance horses. Excessive accumulation of acetyl-CoA with depletion of the intra- mitochondrial pool of free coenzyme A could seriously impair aerobic oxidation of carbohydrate during sustained athletic exercise. Carnitine assists in both fat and carbohydrate oxidation and acts as a buffer in the mitochondrial acetyl-CoA : CoA ratio. Performance horses may be given 10 g carnitine per day or feeds containing 1 g/kg. Livestock conditions suggesting further needs Horses on a low-lysine diet may develop a fatty liver condition which could be dispersed by a dietary input of carnitine. Similarly, poor growth in young foals on low-lysine feeds might be improved by a supply of carnitine. A horse not performing at its maximum potential might show a response to supplements of carnitine.