Carnitine is a nutrient that plays an important role in fatty acid absorption and mitochondrial function. It can be found in diets that include meat, or synthesized endogenously from lysine and methionine. Deficiencies can be caused by genetic disorders, malnutrition, malabsorption, and kidney dialysis. These can affect the heart, skeletal muscles, liver, nerve, and endocrine functions. Carnitine is marketed as a dietary supplement to enhance physical performance and to treat fatigue, cardiovascular disease, diabetes, obesity, chronic fatigue syndrome, liver disorders, and cancer.

Animal models suggest that L-carnitine has cardioprotective ^(8) (14) and antioxidant effects ⁽³¹⁾. A large systematic review and meta-analysis found that L-carnitine supplementation may help improve body weight and BMI in overweight and obese individuals ⁽⁵⁵⁾. Supplementation also alleviates muscle damage in resistance trained and untrained groups ⁽⁵⁶⁾, and helps prevent cardiovascular disease in hemodialysis patients ⁽²⁴⁾. Long-term carnitine supplementation in humans is correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance ⁽⁷⁾. However, L-carnitine administration did not improve risk of death or heart failure in patients with anterior acute myocardial infarction ⁽³⁶⁾.

Preliminary results suggest L-carnitine may improve symptoms of chronic fatigue syndrome ⁽²²⁾ and physical performance in patients undergoing dialysis for end-stage renal disease ⁽⁹⁾, but data of its benefits in alleviating fatigue associated with multiple sclerosis are inconclusive ⁽²¹⁾. Several trials have shown enhanced physical performance ^(17) (20), and improved aerobic capacity and exercise tolerance ⁽³²⁾. Other studies show mixed results ^{(37) (38) (39)} and its clinical value and safety need additional study.

L-carnitine used by itself or in combination with clomiphene citrate may help treat idiopathic male infertility ⁽²⁵⁾, although it did not improve sperm count or motility ⁽⁴⁰⁾. An antioxidant formulation containing L-carnitine was also ineffective in improving semen parameters or DNA integrity ⁽⁵⁷⁾. In women with polycystic ovary syndrome, carnitine supplementation may improve mental health parameters and biomarkers of oxidative stress ⁽²⁾.

Carnitine has also been evaluated for its potential anticancer effects. Supplementation improved nutritional status and quality of life in pancreatic cancer patients ⁽²⁷⁾. Other preliminary data show that L-carnitine by itself ^(15) (23) or in combination with Coenzyme Q10 ⁽³³⁾ may relieve chemotherapy-related fatigue. L-carnitine also demonstrated benefits against fatigue both in younger hypothyroid patients receiving levothyroxine and thyroid cancer patients who have hypothyroidism post-surgery ⁽⁴¹⁾. However, carnitine did not improve fatigue in patients with invasive malignancies ⁽²⁸⁾. In patients with hepatocellular carcinoma, lenvatinib therapy affected the carnitine system, which may result in carnitine insufficiency to increase fatigue ⁽⁵⁸⁾. Other preliminary data suggest l-carnitine may reduce vismodegib-associated muscle spasms ⁽⁵²⁾. Additional studies are needed to determine the cancer populations in which carnitine supplementation may be most beneficial.

An ester derivative, acetyl-L-carnitine, is also available as a dietary supplement and is often used as a neuroprotective agent. It may help to reduce diabetic neuropathy ^(42) (43) or improve cognition in patients with severe hepatic encephalopathy ⁽⁴⁴⁾. In elderly patients with dysthymic disorder, it was found to be comparable with fluoxetine ⁽⁴⁵⁾; however, other studies did not find it effective for Alzheimer’s disease ^(46) (47). In another study, acetyl-L-carnitine increased chemotherapy-induced peripheral neuropathy (CIPN) ⁽³⁵⁾, and this negative effect persisted at long-term follow-up over 2 years ⁽⁵³⁾. Guidelines also do not recommend acetyl-l-carnitine to prevent CIPN because of a possibility of harm ⁽⁵⁴⁾. Therefore, patients receiving chemotherapy should avoid this product.