Carnitine metabolic disorders and novel clinical approaches: Mechanistic insights from deficiency management to liver and kidney disease treatment

Mitochondrial dysfunction can lead to the accumulation of fatty acids and excessive production of reactive oxygen species (ROS), ultimately resulting in impaired energy production. Carnitine is essential for transporting fatty acids into mitochondria for oxidative energy generation. Carnitine deficiency commonly occurs in primary carnitine deficiency (PCD) and secondary carnitine deficiency (SCD). The latter can be triggered by liver and kidney diseases, endocrine imbalances (such as diabetes), sepsis (or septic shock), heart failure, cancer, chronic alcoholism, and certain medications. Extensive preclinical and clinical studies have confirmed the broad therapeutic potential of l -carnitine in treating PCD and SCD. Furthermore, l -carnitine is considered a safe supplement with a low incidence of adverse effects. It has demonstrated synergistic or complementary effects when combined with other drugs in the treatment of various diseases. Carnitine has also been widely reported as the potential biomarker for certain clinical diseases. Furthermore, carnitine supplementation offers clinical benefits by enhancing fatty acid β-oxidation and alleviating ferroptosis, thereby exerting antioxidant effects and reducing the accumulation of toxic lipid precursors. This review focuses on the sources, transport, and deficiency of carnitine, as well as its therapeutic potential in treating clinical diseases (particularly liver and kidney disease), aiming to provide a theoretical basis for the rational clinical supplementation of carnitine. • Carnitine is essential for transporting fatty acids into mitochondria for oxidative energy generation. • Carnitine exhibits a broad spectrum of therapeutic potential in treating primary and secondary carnitine deficiency. • Carnitine is recognized as a safe supplement with a low incidence of adverse effects. • Carnitine has therapeutic benefits for clinical conditions, particularly liver and kidney diseases.