Carnitine was first discovered in muscle extracts, independently by Gulewitsch and Krimberg and by Kutscher, in 1905, and the correct structure was assigned in 1927 by Tomita and Sendju (1). Between 1948 and 1952, Fraenkel et al demonstrated the essential nature of this compound for the mealworm, Tenebrio molitor, and assigned the term “vitamin B_T” to carnitine (1). The role of carnitine in fatty acid oxidation was discovered independently by Bremer, and by Fritz and Yue, between 1962 and 1963 (2). The origin of the methyl groups of carnitine was identified by Wolf and Berger and by Bremer in 1961 (2), and the origin of the carbon chain of carnitine from the essential amino acid lysine was first reported by Tanphaichitr et al in 1971 (3). Clinical syndromes associated with carnitine deficiency were first reported by Engel et al in 1973 (4) and 1975 (5), and primary systemic carnitine deficiency associated specifically with a defect in carnitine transport was identified by Treem et al in 1988 (6).

L-Carnitine[R(-)-β-hydroxy-γ-(N,N,N-trimethylammonio) butyrate] is a zwitterionic quaternary amino acid (Fig. 32.1) with a molecular weight of 161.2 g/mol (inner salt). Only the L isomer is biologically active. L-Carnitine is present in biologic systems in both nonesterified and esterified forms. Short-chain (C₂-C₅) organic acids or medium (C₆-C₁₂)- or long (C₁₄-C₂₄)-chain fatty acids are transferred to and from coenzyme A (CoA) and the hydroxyl group of carnitine (see Fig. 32.1). These reversible reactions are catalyzed by a group of enzymes appropriately named carnitine acyltransferases.

Carnitine is abundant in most food products of animal origin. Among all dietary sources, red meats contain the highest concentrations of carnitine. Fruits, vegetables, grains, and other plant-derived foods contain relatively little carnitine (7, 8). Thus, a normal omnivorous diet provides approximately 2 to 12 µmol/kg body weight/day of carnitine, whereas a strict vegetarian diet contains approximately 0.1 µmol/kg body weight/day (7).

Carnitine is not a required nutrient for children and adults. No recommended dietary allowance has been established. Population groups that may be most vulnerable to nutritional carnitine deficiency are strict vegetarians and newborn infants. Strict vegetarians (both adults and children) acquire very little carnitine in their diets. They have somewhat lower plasma carnitine concentrations compared with omnivores, but no indication of clinically relevant carnitine deficiency has been reported (9).

Infants, particularly premature infants, are born with relatively low stores of carnitine, and rapid growth places a demand for carnitine accretion. In the past, but not currently, commercial soy protein-based infant formulas did not contain carnitine. Infants consuming these carnitinefree formulas grew at a normal rate and displayed no evidence of clinical carnitine deficiency, although some biochemical parameters relating to lipid metabolism (e.g., plasma free fatty acid concentration, rate of excretion of
medium-chain dicarboxylic acids) were different, compared with infants consuming the same formulas but supplemented with carnitine (10). An expert panel commissioned by the US Food and Drug Administration’s Center for Food Safety and Applied Nutrition recommended a minimum carnitine content in infant formulas of 7.5 µmol/100 kcal, and a maximum level of 12.4 µmol/100 kcal, a value similar to the upper limit reported for human milk (11). These recommendations were made on the basis of reported biochemical differences when infants were fed carnitine-free diets, compared with similar diets with carnitine, and despite the lack of evidence that carnitine is essential for the term infant.

Carnitine homeostasis in humans is maintained by the dynamic interactions of endogenous synthesis, acquisition from dietary sources, maintenance of concentration gradients across cell membranes, and regulation of renal reabsorption and excretion of carnitine.