L-Carnitine Benefits and Side Effects
L-carnitine supplementation is not recommended for routine use in healthy individuals, as there is insufficient evidence supporting its benefits, while it may cause gastrointestinal side effects and other adverse reactions.
Role and Function of L-Carnitine
- L-carnitine is an endogenous molecule that plays an essential role in fatty acid metabolism by transporting fatty acid chains into the mitochondrial matrix, allowing cells to break down fat and obtain energy from stored fat reserves 1
- L-carnitine is a naturally occurring substance required in mammalian energy metabolism that facilitates long-chain fatty acid entry into cellular mitochondria 2
- L-carnitine is known to be an essential co-factor in fatty acid and energy metabolism 3
Natural Sources and Metabolism
- L-carnitine can be biosynthesized within the human body using amino acids L-lysine and L-methionine as substrates 1
- L-carnitine can also be found in many foods, with red meats such as beef and lamb being the best sources, followed by fish, poultry, and milk 1
- The kidney maintains plasma free L-carnitine levels through selective saturable tubular reabsorption 4
Potential Benefits in Specific Clinical Conditions
Dialysis Patients
- L-carnitine administration may improve subjective symptoms such as malaise, muscle weakness, intradialytic cramps and hypotension, and quality of life in selected maintenance dialysis patients 3
- The most promising application in dialysis patients is treatment of erythropoietin-resistant anemia 3, 4
- Hemodialysis patients often have low serum concentrations of free L-carnitine and decreased skeletal muscle stores due to loss of renal parenchyma and non-selective clearance during dialysis 4, 5
- In selected dialysis patients with left ventricular dysfunction, L-carnitine supplementation has shown improvement in left ventricular ejection fraction 6
Primary and Secondary Carnitine Deficiencies
- L-carnitine is clearly beneficial in primary carnitine deficiencies, which may be life-threatening, and some secondary deficiencies such as organic acidurias 7
- L-carnitine supplementation is indicated for deficiency states including primary systemic carnitine deficiency and secondary deficiencies due to inborn errors of metabolism 2
- Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine (less than 20 μmol/L at one week post term) 2
Side Effects and Adverse Reactions
- At doses of approximately 3 g/day, L-carnitine supplements can cause gastrointestinal side effects including nausea, vomiting, abdominal cramps, and diarrhea 8, 9, 2
- L-carnitine supplementation may cause a fishy body odor at higher doses 8, 9
- Neurological adverse reactions include seizures in patients with or without pre-existing seizure activity, and in patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported 2
- Hypersensitivity reactions such as rash, urticaria, and facial edema have been reported with L-carnitine oral solution 2
- Mild myasthenia has been described in uremic patients receiving D,L-carnitine 2
Recommendations for Use
- There are insufficient data to support the routine use of L-carnitine for maintenance dialysis patients 3
- In selected individuals who manifest symptoms or disorders related to carnitine deficiency and who have not responded adequately to standard therapies, a trial of L-carnitine may be considered 3
- There is no evidence supporting routine L-carnitine supplementation in healthy adults 8, 9
- The European Society of Nutrition Clinical and Metabolism (ESPEN) indicates that carnitine is not an essential nutrient and there is insufficient evidence to support its routine addition in nutrition 9
Dosage and Administration
- When administered intravenously to dialysis patients, the dose of L-carnitine typically ranges from 1 mg/kg body weight to 2 g at the end of each dialysis session 3
- Oral L-carnitine is usually administered in one to three daily doses, ranging from 10 mg/kg body weight per day to 3 g per day 3
- Bioavailability of oral L-carnitine is approximately 15% 2
- Gastrointestinal adverse reactions might be avoided by slow consumption of the solution or by greater dilution, and decreasing the dosage often diminishes or eliminates drug-related body odor or gastrointestinal symptoms 2
Important Considerations and Caveats
- Tolerance should be monitored very closely during the first week of administration and after any dosage increases 2
- The biodisponibility of oral L-carnitine in patients with chronic kidney disease is unknown and may be associated with neurotoxicity 8
- Many studies on L-carnitine supplementation suffer from lack of randomization and control groups, heterogeneity in administration, and non-standardized measures of symptom improvement 4
- Further research is needed to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation 1