Mitochondria control cellular fate by various mechanisms and are key drivers of cellular metabolism. Although the main function of mitochondria is energy production, they are also involved in cellular detoxification, cellular stabilization, as well as control of ketogenesis and glucogenesis. Conditions like neurodegenerative disease, insulin resistance, endocrine imbalances, liver and kidney disease are intimately linked to metabolic disorders or inflexibility and to mitochondrial dysfunction. Mitochondrial dysfunction due to a relative lack of micronutrients and substrates is implicated in the development of many chronic diseases. L-carnitine is one of the key nutrients for proper mitochondrial function and is notable for its role in fatty acid oxidation. L-carnitine also plays a major part in protecting cellular membranes, preventing fatty acid accumulation, modulating ketogenesis and glucogenesis and in the elimination of toxic metabolites. L-carnitine deficiency has been observed in many diseases including organic acidurias, inborn errors of metabolism, endocrine imbalances, liver and kidney disease. The protective effects of micronutrients targeting mitochondria hold considerable promise for the management of age and metabolic related diseases. Preventing nutrient deficiencies like L-carnitine can be beneficial in maintaining metabolic flexibility via the optimization of mitochondrial function. This paper reviews the critical role of L-carnitine in mitochondrial function, metabolic flexibility and in other pathophysiological cellular mechanisms.

Kidney disease is associated with a wide variety of metabolic abnormalities that accompany the uremic state and the state of dialysis dependence. These include altered L-carnitine homeostasis, mitochondrial dysfunctions, and abnormalities in fatty acid metabolism. L-carnitine is essential for fatty acid metabolism and proper mitochondrial function. Deficiency in kidney disease and dialysis is caused by a reduction in endogenous renal synthesis, impaired fatty acid metabolism, a lower intake due to dietary restrictions, and nonselective clearance by the dialysis procedure. Free carnitine levels <40 µmol/L in dialysis patients can lead to dialysis-related complications, such as anemia that is hyporesponsive to erythropoietin therapy, intradialytic hypotension, cardiovascular disease, and skeletal muscle dysfunction manifested as muscle weakness and fatigue. L-carnitine deficiency is also seen in acute kidney injury (AKI) resulting from trauma and/or ischemia, drugs such as cisplatin, and from infections such as covid. A persistent state of L-carnitine deficiency can further damage kidneys and lead to multi-organ failure. Carnitine supplementation has been shown to be safe and effective in improving kidney disease-related complications resulting from drug-induced toxicity, trauma, ischemic injury, infection, and dialysis, by replenishing adequate carnitine levels and rebalancing carnitine homeostasis. In this review, we will examine the protective role of L-carnitine in reducing cellular oxidative damage and maintaining mitochondrial function together with the clinical evidence for its potential use in the management of kidney disease.