Carnitine (earlier known as vitamin Bt) is a quaternary amine, beta-hydroxy-gamma-trimethylaminobutyrate. It is a very hygroscopic compound and is found in biological samples both as free carnitine and as the ester of a wide variety of acyl compounds. Of the two types of carnitine, L-and D-carnitine, only L-carnitine is biologically active. This has been shown in a number of species (Grandjean et al., 1993). Carnitine is synthesized in the liver and kidneys. The synthesis depends on two precursors, L-lysine and methionine, as well as ascorbic acid, nicotinamide, vitamin B6 and iron (Borum, 1991). Deficiency in any cofactor will cause L-carnitine deficiency. In rats, total acid-soluble carnitine and free carnitine in plasma and tissues were reduced in a vitamin B6 deficiency but increased when vitamin B6 was provided in a repletion diet (Cho and LeKlem, 1990; Ha et al., 1994). It has been suggested that early features of scurvy (fatigue and weakness) may be attributed to carnitine deficiency. Vitamin C is a cofactor for two alpha-ketoglutarate-requiring dioxygenase reactions (epsilon-N-trimethyllysine hydroxylase and gamma-butyrobetaine hydroxylase) in the pathway of carnitine biosynthesis. Carnitine concentrations are variably low in some tissues of vitamin C-deficient guinea pigs (Rebouche, 1991). Choline has also been shown to affect carnitine homeostasis in humans and guinea pigs (Daily and Sachan, 1995). Choline supplementation resulted in decreased urinary excretion of carnitine in young adult women; choline resulted in the conservation of carnitine in guinea pigs. In adult women Hongu and Sachan (2003) concluded that the choline-induced decrease in serum and urinary carnitine is buffered by carnitine preloading. These supplements shift tissue partitioning of carnitine that favors fat mobilization, incomplete oxidation of fatty acids and disposal of their carbons in urine.
Carnitine appears to be absorbed across the gut by an active process dependent on Na+ as well as by a passive diffusion that may be important for the absorption of large doses of the factor. The uptake of carnitine from the intestinal lumen into the mucosa is rapid, and about one-half of the carnitine taken up is acetylated in that tissue. Absorption of carnitine in dietary supplements (0.5 to 4 g per day) is 15 to 25% (Rebouche, 2006). Tissues such as cardiac muscle and skeletal muscle require carnitine for normal fuel metabolism but cannot synthesize carnitine and are totally dependent on the transport of carnitine from other tissues. Free carnitine is excreted in urine, with the principal excretory product being trimethylamine oxide (Mitchell, 1978). Carnitine is highly conserved by the human kidney, which reabsorbs more than 90% of filtered carnitine, thus, playing an important role in the regulation of carnitine concentration in blood. For the dog, 95% to 98% of the carnitine body pool is in skeletal muscle and the heart (Rebouche and Engel, 1983). Flores et al. (1996) recently reported that the small intestine is a considerable and previously unrecognized pool in suckling rats.
Carnitine is required for transport of long-chain fatty acids into the matrix compartment of mitochondria from cytoplasm for subsequent oxidation by the fatty acid oxidase complex for energy production. The oxidation of long-chain fatty acids in animal tissues is dependent on carnitine because it allows long-chain acyl-CoA esters to cross the mitochondrial membrane, which is otherwise impermeable to CoA compounds. Carnitine facilitates the beta-oxidation of long-chain fatty acids in the mitochondria by transporting the substrate into the mitochondria. Carnitine acyltransferase is the enzyme responsible for this shuttle mechanism. It exists in two forms, carnitine acyltransferase I and carnitine acyltransferase II. After the long-chain fatty acid is activated to acyl-CoA, it is converted to acylcarnitine by the enzyme carnitine acyltransferase I and crosses to the matrix side of the inner mitochondrial membrane. Carnitine acyltransferase II then releases carnitine and the acyl-CoA into the mitochondrial matrix. Acyl-CoA is then catabolized via beta-oxidation (Borum, 1991). Thus, utilization of long-chain fatty acids as a fuel source depends on adequate concentrations of carnitine. The role of carnitine in the transport of long-chain fatty acids across the inner mitochondrial membrane is known, but liver medium-chain fatty acid (MCFA) metabolism has been considered carnitine independent owing to MCFAs’ passive diffusion through the inner mitochondrial membrane and intramitochondrial activation (Bremer, 1990). However, evidence suggests that MCFA metabolism may be affected by supplemental carnitine (Van Kempen and Odle, 1993; 1995). Recently, dietary carnitine was shown to enhance the lymphatic absorption of fat and alpha-tocopherol in ovariectomized rats (Zou et al., 2005). Another role of carnitine may be to protect cells against toxic accumulation of acyl-CoA compounds of either endogenous or exogenous origin by trapping such acyl groups as carnitine esters. These may then be transported to the liver for catabolism or to the kidney for excretion in the urine. Carnitine also has functions in other physiological processes critical to survival, such as lipolysis, thermogenesis, ketogenesis and possibly regulation of certain aspects of nitrogen metabolism (Borum, 1985). Carnitine was found to be beneficial in detoxification of aflatoxins (Yatim and Sachan, 2001). For rats there was a modification of aflatoxin binding to proteins and DNA by carnitine, which reduced the carcinogenic and hepatotoxic potential of aflatoxins.
In mammals, gamma-butyrobetaine, the immediate precursor of carnitine, can be synthesized from the essential amino acids lysine and methionine in most tissues. The four-carbon chain comes from lysine; the methyl groups come from methionine. The ultimate conversion of gamma-butyrobetaine to carnitine occurs in the liver (Olson and Rebouche, 1987).
Carnitine is an essential growth factor for some insects, such as the mealworm (T. molitor). However, most insects and higher animals, as well as poultry, can synthesize carnitine. For common livestock species, there are no established nutritional requirements for carnitine. Recent studies have indicated that the biosynthesis of carnitine may be limited or inadequate in certain classes of humans and animals. No requirement data are available for poultry but some positive responses have resulted from carnitine supplementation. Supplemental L-carnitine at 50 mg per kg (22.7 mg per lb) has improved body weight gain and feed conversion and decreased abdominal fat of broilers (Iben and Meinhart, 1997; Rabie et al., 1997a, d; Rabie and Szilagyi, 1998; Kidd et al., 2005). Egg quality and hatchability also have been favored by carnitine supplementation (Leibetseder, 1995; Rabie et al., 1997b, c).
In general, foods of plant origin are low in carnitine, whereas animal-derived foods are rich in carnitine (Mitchell, 1978; Rebouche, 2006). Red meats and dairy products are particularly rich sources. In general, the redder the meat, the higher the concentration of carnitine. Typical concentrations of carnitine could be 600 µg per kg (272.7 µg per lb) for beef, 45 to 90 µg per kg (20.5 to 40.9 µg per lb) for chicken and 75 µg per kg (34.1 µg per lb) for lamb (Mitchell, 1978). Carnitine is located principally in skeletal muscle, which has about 40 times the concentrations of carnitine in blood. On the contrary, grains such as barley, corn and wheat have undetectable or negligible concentrations. Most plant foods that are low in carnitine are also likely to be low in lysine and methionine, the precursors of carnitine.
Carnitine in milk is essential for the nursing mammal. Although carnitine is synthesized in the growing young and adult animals, previous studies in humans provide evidence that exogenous carnitine is necessary to maintain normal fat metabolism during infancy. Studies by Davis (1989) indicated that up to 50% of tissue carnitine in suckling rats is derived from the mother’s milk. Studies with neonatal rabbits (Penn and Schmidt-Sommerfeld, 1988) and rats (Floreset al., 1996) demonstrated that body tissues of carnitine are greatly diminished in newborns deprived of milk during early life. Coffey et al. (1991) showed that diminished dietary intake is associated with decreased levels of carnitine compared with piglets receiving carnitine supplementation. These observations indicate the importance of milk. The demand for carnitine during the suckling period may exceed the capacity for its synthesis.
In carnitine deficiency, fatty acid oxidation is reduced, and fatty acids are diverted into triglyceride synthesis, particularly in the liver. Mitochondrial failure develops in carnitine deficiency when there is insufficient tissue carnitine available to buffer toxic acyl-coenzyme (CoA) metabolites. Toxic amounts of acyl-CoA impair the citrate cycle, gluconeogenesis, the urea cycle and fatty acid oxidation. Carnitine replacement induces excretion of toxic acyl groups in the urine (Stumpf et al., 1985). Skeletal muscles are generally involved, with weakness, lipid myopathy and myoglobinuria often aggravated or precipitated by fasting or exercise. For exercising pigeons, L-carnitine supplementation improved fatty acid oxidation efficiency during heavy exercise (Janssens et al., 1998). The increases in plasma and hepatic acylcarnitines in broilers fed 0.5% L-carnitine indicated that supplementary carnitine lessens the load of free acyl groups in the liver by eventual oxidation or excretion (Smith et al., 1994). Barker and Sell (1994) found that carnitine intake of 0, 50 and 100 mg per kg (0, 22.7 and 45.5 mg per lb) of diet did not affect body weight, feed conversion efficiency and proximate composition at 21 days in turkeys and at 45 days in broilers. However, more research indicates liveweight gains and feed efficiency improved with carnitine supplementation (Iben and Meinhart, 1997; Rabie et al., 1997a, d; Rabie and Szilagyi, 1998). Iben and Meinhart (1997) noted that broilers given L-carnitine with optimum lysine and methionine were 2.47% heavier than controls. Amount and percentage of abdominal fat and ether extract in breast meat of 53-day-old broilers were significantly reduced in response to carnitine supplementation (Rabie et al., 1997a). Zhai et al. (2007) concluded that consumption of supplemental carnitine from hatch to 37 weeks of age had no effect on egg production and egg trials, however, egg quality and hatchability have been improved with supplemental carnitine (Leibetseder, 1995; Rabie et al., 1997b, c). L-carnitine had a beneficial effect on albumen quality and could modify the components of the edible part of the egg during the late laying period (Rabie et al., 1997b). With 50 and 100 mg per kg (22.7 and 45.5 mg per lb) in the feed of layer hens, hatchability increased by 4% and 2.9%, respectively (Leibetseder, 1995).
Only the physiological L-carnitine should be used for fortification of diets. Supplementation of 50 to 500 mg per kg (22.7 to 227 mg per lb) of diet have been used as supplementation doses for poultry. Although carnitine has been studied in humans and under laboratory conditions for many years, its effectiveness in promoting the performance and well-being of domestic animals has only recently received attention. A role for carnitine in swine and fish diets has been established and continued research may find that it has a place in the production of poultry and other livestock species. Some studies have found production responses for supplemental carnitine in poultry, while other reports have found no benefits. Rabie and Szilagyi (1998) supplemented broiler diets with 50 mg per kg (22.7 mg per lb) of L-carnitine, which resulted in increased liveweight gain and improved feed efficiency. Weights of breast yield and thigh meat yield were increased, whereas quantity and percentage of abdominal fat were reduced by L-carnitine. In breeder hens fed 25 mg per kg (11.4 mg per lb) L-carnitine, carcass traits of their progeny improved with a decrease in carcass fat and an increase in breast meat (Kidd et al., 2005). L-carnitine fed to broilers at four levels from 0 to 150 mg per kg (0 to 68.2 mg per lb) in diets improved weight gains and reduced abdominal fat (Rabie et al., 1997d). It was concluded that the effectiveness of supplemental carnitine for improving gains and (or) decreasing abdominal fat of broilers may depend on the age at which it is added. Under conditions of this study, L-carnitine at 50 mg per kg (22.7 mg per lb) of diet was effective.
A dietary level of 50 mg per kg (22.7 mg per lb) of L-carnitine had positive effects on interior egg quality during the early stages of egg production (Rabie et al., 1997c). Leibetseder (1995) reported that L-carnitine in the feed of broiler breeder hens affected hatchability of chicks when given a conventional feed with L-carnitine at 0, 20, 50 and 100 mg per kg (0 to 45.5 mg per lb) of diet. After three weeks of feeding, hatchability increased by 4% and 2.9%, respectively, when L-carnitine was provided at 50 and 100 mg per kg (22.7 and 45.5 mg per lb). Carnitine in egg yolk was increased by the supplements.
The supplementation of dietary L-carnitine at levels of 250 or 500 mg per kg (114 or 227 mg per lb) to a basal diet significantly increased sperm viability and decreased multi-nucleated giant cells per testes in mature male Japanese quail breeders (Sarica et al., 2007).
Animal studies are lacking to determine maximum tolerance for carnitine. For human patients, carnitine supplementation at dosages that far exceed the usual dietary intake of carnitine have been administered (Goa and Brogden, 1987). Oral dosages of 100 mg per kg (45.5 mg per lb) have been given to infants and 1 to 3 g daily to adult humans with little problem. Some patients experienced diarrhea, but not if they started with smaller dosages and then increased gradually (Borum, 1991).
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