CARNITINE

L-Carnitine (L-b-hydroxy-g -N,N,N-trimethylaminobutyric acid) is a non-essential organic nutrient required for entry of long-chain fatty acids (as acylcarnitine esters) into mitochondria. It also facilitates removal of short-chain organic acids from mitochondria, thereby freeing intramitochondrial coenzyme A to participate in the b-oxidation and tricarboxylic acid cycle pathways. Carnitine is a substrate for carnitine palmitoyltransferases I and II and carnitine acetyltransferase, enzymes that participate in and regulate fatty acid utilization. Carnitine and its esters are transported across the inner mitochondrial membrane specifically by carnitine-acylcarnitine translocase. The D-isomer of carnitine is biologically inactive. Carnitine is concentrated in most tissues of the body, with about 97% in skeletal muscle. L-Carnitine is synthesized from the essential amino acids lysine and methionine. In humans, the last enzymatic reaction in the pathway occurs primarily in liver and kidney, but not in skeletal and heart muscle. The normal rate of carnitine synthesis in humans is 0.16 to 0.48 mg/kg body weight/day.

Deficiencies: Carnitine deficiency occurs as a primary genetic defect of carnitine transport and secondary to a variety of genetic and acquired disorders. These disorders often are associated with fasting hypoglycemia, lethargy and cardiomyopathy. A murine model of systemic carnitine deficiency (the jvs mouse) has been studied in some detail. Reports of nutritional carnitine deficiency are rare, and in the few cases described, other genetic causes were not specifically excluded. Infants are particularly susceptible to carnitine depletion, because the demands of tissue accretion associated with rapid growth exceed the ability of the infant to synthesize carnitine. However, the substantially lower plasma carnitine concentrations (and, presumably, lower tissue carnitine concentrations) do not impair growth rates or other indicators of normal development.

Diet recommendations: Carnitine is not required in the diet of normal humans. Daily intakes of omnivores and strict vegetarians are 20 mg to 200 mg and <1 mg for a 70 kg (154 lb.) person, respectively. Infant formulas (including total parenteral nutrition solutions) that do not contain carnitine (e.g., non-milk-based formulas) should be supplemented with carnitine to the levels found in human milk, 11.3 mg/L (70 mmol/L).

Food sources: Red meats are the best sources of carnitine (50 to 120 mg/100 g). Fish, chicken and milk are good sources (1.6 to 6.4 mg/100 g). Vegetables, fruits, grains, and other plant-derived foods contain very little carnitine (<0.05 mg/100 g). Approximately 65 to 75% of dietary carnitine is absorbed. Unabsorbed carnitine is almost entirely degraded by bacteria in the large intestine. No dietary components are known to impair absorption. There is no known toxicity associated with ingestion from normal dietary components. Supplements that provide more than 3,000 mg (19 mmol) of carnitine per day may cause diarrhea and/or "fish odor" syndrome.

Recent research: Carnitine may have functions in cellular metabolism independent of its role in fatty acid oxidation, such as plasma membrane fatty acid remodeling, gene regulation (modulation of the transcriptional response to triiodothyronine of genes for malic enzyme and fatty acid synthase), and modulation of cytokine concentrations in experimental sepsis and cancer cachexia. Esters of carnitine (acetyl- and propionylcarnitine) may have pharmacological value, by virtue of their antioxidant properties and/or ability to deliver readily oxidizable carbon units to mitochondria, in chronic disorders such as Alzheimer's disease and ischemia-induced myocardial dysfunction in angina pectoris. Carnitine, by virtue of its role in fatty acid oxidation, may diminish modulation of transcription of urea cycle enzymes by long-chain fatty acids, suggesting a mechanism for its ammeliorating effect on experimentally-induced hyperammonemia.

For further information:

Rebouche, C. J. (1998) Carnitine. In: Modern Nutrition in Health and Disease (Shils, M. E., Olson, J. A., Shike, M. & Ross, A. C., eds.), 9th ed., pp. 505-512. Williams & Wilkins, Baltimore, MD.

Tomomura, M., Tomomura, A., Dewan, A. A. M. & Saheki, T. (1996) Long-chain fatty acids suppress the induction of urea cycle enzyme genes by glucocorticoid action. FEBS Lett. 399: 310-312.

Prepared By:

Alan T. Davis, Ph.D.
Associate Professor and Director
Clinical Nutrition Laboratory
515 Michigan Street NE, Suite 102
Grand Rapids, MI 49503
Phone: 616-454-9960
FAX: 616-454-9227
Email: davisa@pilot.msu.edu

Charles Joseph Rebouche, Ph.D.
Associate Professor
Department of Pediatrics
University of Iowa
100 Oakdale Research Park, Rm A138
Iowa City, IA 52242-5000
Phone: 319-335-4567 FAX: 319-335-4347
Email: charles-rebouche@uiowa.edu