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

L-carnitine showed cardioprotective ^(8) (14) and antioxidant effects ⁽³¹⁾ in preclinical studies. A large systematic review and meta-analysis found supplementation to improve body weight and BMI in overweight and obese individuals ⁽⁵⁵⁾. Supplementation also alleviated muscle damage in resistance trained and untrained groups ⁽⁵⁶⁾, and prevented cardiovascular disease in hemodialysis patients ⁽²⁴⁾. Long-term supplementation has been correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance ⁽⁷⁾. However, L-carnitine did not improve the 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 on its benefits against fatigue associated with multiple sclerosis are inconclusive ⁽²¹⁾. Some trials reported enhanced physical performance ^(17) (20), and improved aerobic capacity and exercise tolerance ⁽³²⁾ whereas others yielded mixed results ^{(37) (38) (39)}.

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, supplementation may improve mental health parameters and biomarkers of oxidative stress ⁽²⁾.

Small studies in oncology settings found supplementation to improve nutritional status and quality of life in pancreatic cancer patients ⁽²⁷⁾, and to reduce vismodegib-associated muscle spasms ⁽⁵²⁾. L-carnitine by itself ^(15) (23) or in combination with Coenzyme Q10 ⁽³³⁾ may also relieve chemotherapy-related fatigue, reduce fatigue in both younger hypothyroid patients receiving levothyroxine, and in thyroid cancer patients who have hypothyroidism, post-surgery ⁽⁴¹⁾. But it did not improve fatigue in patients with invasive malignancies ⁽²⁸⁾. Confirmatory data are also needed to determine if chemo-induced carnitine insufficiency increases malaise or fatigue ^(58) (59).
In prostate cancer patients initiating androgen deprivation therapy (ADT), a low-carb diet reversed ADT-induced metabolic abnormalities which included reductions in acylcarnitine  ⁽⁶⁰⁾.

Acetyl-L-carnitine, an ester derivative, is also available as a dietary supplement and is often used as a neuroprotective agent. It may help reduce diabetic neuropathy ^(42) (43) and improve cognition in patients with severe hepatic encephalopathy ⁽⁴⁴⁾. In elderly patients with dysthymic disorder, it was found comparable to fluoxetine ⁽⁴⁵⁾, but ineffective against Alzheimer’s disease ^(46) (47). In another study, acetyl-L-carnitine increased chemotherapy-induced peripheral neuropathy (CIPN) ⁽³⁵⁾, which persisted at the 2-year follow-up ⁽⁵³⁾.
Current guidelines do not recommend acetyl-l-carnitine for preventing CIPN because of potential harm ⁽⁵⁴⁾.