Carnitine: Benefits, Dosage, and Safety

What carnitine is

Carnitine is the generic term for several related compounds, including L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine, that are derived from amino acids. Per the NIH Office of Dietary Supplements, it is a conditionally essential nutrient: the body synthesizes it endogenously in the liver, kidneys, and brain from the amino acids lysine and methionine, and needs exceed the ability to synthesize it only under certain conditions such as premature birth or kidney dysfunction. It is naturally present in many foods, especially foods of animal origin, and is also sold as a dietary supplement. About 95% of total body carnitine is stored in heart and skeletal muscle, with most of the remainder in the liver and kidney and only about 0.5% circulating in plasma.

What it does

• Acts as an essential cofactor that transports long-chain fatty acids into the mitochondria so they can be oxidized to produce energy as adenosine triphosphate (ATP)
• Helps transport some toxic compounds out of the mitochondria
• Is concentrated in tissues that oxidize fatty acids as a dietary fuel, mainly heart and skeletal muscle
• The body needs about 15 mg per day from a combination of dietary sources and endogenous synthesis

Intake and dosing

Carnitine is not an essential nutrient, so no Recommended Dietary Allowance or Tolerable Upper Intake Level has been set. Doses in studies vary widely. Because supplement doses are not standardised, discuss an appropriate amount with a clinician or pharmacist.

Deficiency and who is at risk

Two deficiency states exist. Primary carnitine deficiency is a genetic disorder of the cellular carnitine transporter and can cause, depending on age, epilepsy and encephalopathy in infants; seizures, irregular heartbeat, and breathing problems in adolescents and young adults; and myopathy, rhabdomyolysis, cardiomyopathy, or sudden death in older people, with increased risk of heart failure, hepatic disorders, and coma. Secondary carnitine deficiency results from disorders such as chronic renal failure or chronic use of pivalate-containing medications and can cause hyperammonemic encephalopathy, hypoglycemia, hypoketonemia, dicarboxylic aciduria, hyperuricemia, muscle weakness, myoglobinuria, cardiomyopathy, and sudden death. Both states can be resolved with high doses (20 to 200 mg/kg/day) of supplemental carnitine. Note: deficiency in otherwise healthy people is not expected because endogenous synthesis meets needs.

Who may need more

• Premature infants, who may require supplemental carnitine in addition to breast milk and fortified formula
• People with end-stage renal disease, particularly those on maintenance hemodialysis, who often become carnitine insufficient
• People with primary or secondary carnitine deficiency, treated under medical supervision with high-dose carnitine
• People taking valproic acid or pivalate-conjugated antibiotics that lower carnitine levels
• Healthy children and adults generally do NOT need supplemental carnitine because the liver and kidneys synthesize sufficient amounts

Food sources

Foods of animal origin, especially red meat, provide most dietary carnitine. Approximate amounts per serving: cooked beef steak, 3 ounces, 42 to 122 mg; cooked ground beef, 3 ounces, 65 to 74 mg; whole milk, 1 cup, 8 mg; cooked codfish, 3 ounces, 3 to 5 mg; cooked chicken breast, 3 ounces, 2 to 4 mg; ice cream, half cup, 3 mg; cheddar cheese, 2 ounces, 2 mg; whole-wheat bread, 2 slices, 0.2 mg; cooked asparagus, half cup, 0.1 mg. Vegetables, fruits, and grains provide negligible amounts. A typical omnivorous diet provides about 24 to 145 mg daily for a 165-pound person, whereas a vegan diet provides about 1.2 mg.

Forms and absorption

The two main supplement forms are L-carnitine and acetyl-L-carnitine (propionyl-L-carnitine is also studied), with product amounts ranging from about 3 mg to 5,000 mg. Dietary carnitine has a bioavailability of about 63% to 75%. Absorption of supplemental L-carnitine is much lower, about 14% to 18%. The bioavailability of acetyl-L-carnitine has not been well studied.

Safety, excess and interactions

Too much

Carnitine has no established tolerable upper intake level. Doses of approximately 3 g/day of carnitine supplements can cause nausea, vomiting, abdominal cramps, diarrhea, and a fishy body odor. It can also cause muscle weakness in people with uremia and seizures in those with seizure disorders. Some research indicates that intestinal bacteria metabolize unabsorbed carnitine to trimethylamine-N-oxide (TMAO) and gamma-butyrobetaine, which might increase cardiovascular disease risk, an effect that appears more pronounced in people who eat meat than in vegans or vegetarians; the implications are not well understood and require more research.

Interactions to know

• Pivalate-conjugated antibiotics (such as pivampicillin) used to prevent urinary tract infections: chronic use can deplete carnitine by reducing its absorption or increasing its excretion
• Valproic acid: reduces blood carnitine levels; combined with the risk of hepatotoxicity and elevated plasma ammonia leading to encephalopathy, intravenous L-carnitine may help treat valproic acid toxicity
• Other anticonvulsants including phenobarbital, phenytoin, and carbamazepine: reduce blood levels of carnitine

How status is measured

Carnitine status is not routinely assessed in clinical practice but can be determined by measuring circulating carnitine. A plasma free carnitine concentration of 20 micromol/L or less, or a total carnitine concentration of 30 micromol/L or less, is abnormally low. An acyl-L-carnitine ester to free L-carnitine ratio of 0.4 or greater in plasma or serum indicates abnormal carnitine metabolism and suggests carnitine insufficiency.

Carnitine is sold as a dietary supplement, which the FDA regulates as food rather than as a drug, so products are not FDA-approved for safety and effectiveness before marketing. Levocarnitine (L-carnitine) is also an FDA-approved prescription drug for carnitine deficiency, and L-carnitine has received FDA orphan drug designations. The Food and Nutrition Board concluded in 1989 that carnitine is not an essential nutrient and did not establish Dietary Reference Intakes for it.

What the evidence supports

We grade the strength of evidence behind each common reason people take carnitine, mirroring how the NIH describes it.