The main function of L-carnitine is to transfer long-chain fatty acids in the form of their acyl-carnitine esters across the inner mitochondrial membrane before beta-oxidation. In humans, it is synthesized in the liver, kidney, and brain and actively transported to other areas of the body. For example, 98% of the total body L-carnitine is confined to the skeletal and cardiac muscle at concentrations approximately 70 times higher than in the blood serum. Supplementation may be necessary in rare cases of primary carnitine deficiency, which may be caused by a defect in carnitine biosynthesis, a defect in carnitine active transport into tissue, or a defect in renal (kidney) conservation of carnitine. Known conditions of secondary deficiency of carnitine (insufficiency), in which L-carnitine is effective, include chronic stable angina and intermittent claudication characterized by distinct tissue hypoxia (low oxygen levels). Another condition that may benefit from carnitine supplementation is decreased sperm motility. Although use in preterm infants suggests carnitine supplementation may aid in maintaining or increasing plasma carnitine levels and possibly weight gain, carnitine is not routinely added to preterm total parenteral nutrition (TPN). However, soy-based infant formulas are fortified with carnitine to levels found in breast milk. In 1986, the U.S. Food and Drug Administration (FDA) approved L-carnitine for use in primary carnitine deficiency. D-carnitine or DL-carnitine may cause secondary L-carnitine deficiency and should not be used.