Q: What is L-carnitine and what is it good for? - Technical

A: L-Carnitine is a derivative of the amino acid, lysine. Its name is derived from the fact that it was first isolated from meat (carnus) in 1905. Because L-carnitine appeared to act as a vitamin in the mealworm (Tenebrio molitor), it was called vitamin BT. Vitamin BT turned out to be a misnomer when scientists discovered that humans and other higher organisms synthesize L-carnitine. Under certain conditions, the demand for L-carnitine may exceed an individual's capacity to synthesize it, making it a conditionally essential nutrient .

L-Carnitine is synthesized primarily in the liver and also in the kidneys, and must be transported to other tissues. It is most concentrated in tissues that use fatty acids as their primary dietary fuel, such as skeletal and cardiac (heart) muscle. In this regard, L-carnitine plays an important role in energy production by chaperoning activated fatty acids (acyl-CoA) into the mitochondrial matrix for metabolism and chaperoning intermediate compounds out of the mitochondrial matrix to prevent their accumulation.

The transport of long-chain fatty acids by L-carnitine into the mitochondrial matrix where they can be metabolized to generate energy requires three enzymes located on the mitochondrial outer and inner membranes. On the outer mitochondrial membrane of skeletal and cardiac muscle cells, carnitine-palmitoyl transferase I (CPTI) catalyzes the formation of acylcarnitine (a fatty acid + L-carnitine) from acyl-CoA (a fatty acid + coenzyme A). A transporter protein called carnitine:acylcarnitine translocase (CT) transports acylcarnitine across the inner mitochondrial membrane. Carnitine-palmitoyl transferase II (CPTII) is associated with the inner mitochondrial membrane and catalyzes the formation of acyl-CoA within the mitochondrial matrix where it can be metabolized through a process called beta-oxidation, ultimately yielding propionyl-CoA and acetyl-CoA .

The enzyme, pyruvate dehydrogenase (PDH), catalyzes the conversion of pyruvate to acetyl CoA, a pivotal reaction in glucose metabolism. In the mitochondrial matrix, decreased free CoA, relative to acetyl CoA, inhibits the activity of PDH. Carnitine acetyl-transferase (CAT) catalyzes the transfer of the acetyl group from acetyl CoA to L-carnitine, freeing CoA to participate in the PDH reaction. Acetyl-L-carnitine can be exported from the mitochondria through the activity of CT.

Within the mitochondrial matrix, short- and medium-chain fatty acids can be transferred from CoA to L-carnitine, allowing short and medium-chain acyl-carnitines to be exported from the mitochondria. This process provides free CoA needed for energy metabolism, as well as a mechanism to export excess acetyl and acyl groups from the mitochondria. This mechanism may also play a role in the depletion of L-carnitine during the metabolism of certain drugs.

Primary carnitine deficiencies

The primary carnitine deficiencies, systemic carnitine deficiency and myopathic carnitine deficiency, are relatively rare hereditary disorders.

Myopathic carnitine deficiency: Primary myopathic carnitine deficiency is also a genetic disorder in which carnitine deficiency is limited to skeletal and cardiac muscle. Serum L-carnitine levels are generally normal. The symptoms of myopathic carnitine deficiency include muscle pain and progressive muscle weakness. Symptoms may begin in childhood or adulthood. The myopathic form of primary carnitine deficiency is generally less severe than the systemic form.

Secondary carnitine deficiencies

Secondary carnitine deficiencies may be hereditary or acquired. In all cases, they are characterized by decreased availability of free L-carnitine. In such cases, total L-carnitine levels may be normal, but free L-carnitine levels are decreased. 

Hereditary causes: Hereditary causes of secondary carnitine deficiency include genetic defects in amino acid degradation (e.g., propionic aciduria) and lipid metabolism (e.g., medium chain acyl-CoA dehydrogenase deficiency). 

Increased L-carnitine loss: Hemodialysis, Fanconi syndrome, and the metabolism of some medications may result in substantial L-carnitine loss, resulting in L-carnitine deficiency. 

Insufficient L-carnitine synthesis: Malabsorption syndromes and diets that chronically lack L-carnitine and its precursors may increase the risk of secondary carnitine deficiency. Premature infants may be at risk of secondary L-carnitine deficiency when fed soy-based formulas without added L-carnitine. Therefore, it is recommended that non-milk based infant formulas be fortified with the amount of L-carnitine normally found in human milk (11 mg/liter). Although dietary L-carnitine comes mainly from animal sources, even strict vegetarians can generally synthesize enough L-carnitine to prevent deficiency.

Nutrient interactions

The synthesis of L-carnitine is catalyzed by the concerted action of five different enzymes. This process requires two essential amino acids (lysine and methionine), iron (Fe²⁺), vitamin C, vitamin B₆, and niacin in the form of nicotinamide adenine dinucleotide (NAD) (1). One of the earliest symptoms of vitamin C deficiency is fatigue, thought to be related to decreased synthesis of L-carnitine.

Biosynthesis

The normal rate of L-carnitine biosynthesis in humans ranges from 0.16 to 0.48 mg/kg of body weight/day (1). Thus, a 70 kg (154 1b) person would synthesize from 11 to 34 mg/day. This rate of synthesis combined with the reabsorption of about 95% of the L-carnitine filtered by the kidneys is enough to prevent deficiency in generally healthy people, including strict vegetarians.

Food sources

Meat, poultry, fish, and dairy products are the richest sources of L-carnitine. Tempeh (fermented soybeans), wheat, and avocados contain some L-carnitine, while fruits, vegetables, and grains contain relatively little L-carnitine to the diet. Omnivorous diets have been found to provide 20 to 200 mg/day of L-carnitine for a 70 kg person, while strict vegetarian diets may provide as little as 1 mg/day for a 70 kg person. Between 63% and 75% of L-carnitine from food is absorbed, compared to 15%-20% from oral supplements. Non-milk based infant formulas (e.g., soy formulas) should be fortified so that they contain 11 mg/liter. Some carnitine-rich foods and their carnitine content in milligrams (mg) are listed in the table below.

*A 3-ounce serving of meat is about the size of a deck of cards.

Supplements

Intravenous L-carnitine is available by prescription only for the treatment of primary and secondary L-carnitine deficiencies.

Oral L-carnitine is available by prescription for the treatment of primary and secondary L-carnitine deficiencies. It is also available without a prescription as a nutritional supplement. Supplemental doses usually range from 500 mg to 2,000 mg/day.

Acetyl-L-carnitine is available without a prescription as a nutritional supplement. In addition to providing L-carnitine, it provides acetyl groups, which may be used in the formation of the neurotransmitter, acetylcholine. Supplemental doses usually range from 500 mg to 2,000 mg/day.

Propionyl-L-carnitine is available in Europe, but not the U.S. It provides L-carnitine as well as propionate, which may be utilized as an intermediate during energy metabolism.

Age-related declines in mitochondrial function and increases in mitochondrial oxidant production are thought to be important contributors to the adverse affects of aging. Tissue L-carnitine levels have been found to decline with age in humans and animals. Feeding aged rats acetyl-L-carnitine (ALCAR) reversed age-related declines in tissue L-carnitine levels and reversed a number of age-related changes in mitochondrial function, but high doses of ALCAR increased liver mitochondrial oxidant production. More recently, a series of studies in aged rats found that supplementation with either ALCAR or alpha-lipoic acid, a mitochondrial cofactor and antioxidant, improved mitochondrial energy metabolism, decreased oxidative stress, and improved memory. Interestingly, supplementation with the combination of ALCAR and alpha-lipoic acid resulted in significantly greater improvement than either compound alone. While these findings are very exciting, the researchers involved caution that these studies used relatively high doses of the compounds and only for a short time (one month). It is not yet known whether taking relatively high doses of these two naturally occurring substances will benefit rats in the long-term or will have similar effects in humans. Clinical trials in humans are planned, but it will be several years before the results are available.

Conditions related to myocardial ischemia (insufficient blood supply to the heart muscle)

In the studies discussed below it is important to note that treatment with L-carnitine or propionyl-L-carnitine was used as an adjunct (in addition) to appropriate medical therapy not in place of it.

Myocardial infarction (heart attack): Myocardial infarction (MI) occurs when atherosclerotic plaque in a coronary artery ruptures. The resultant blood clot can obstruct the blood supply to the heart muscle, causing in injury or damage to the heart. L-Carnitine treatment has been found to reduce injury to heart muscle resulting from ischemia in several animal models. In humans, the administration of L-carnitine immediately after the diagnosis of MI has resulted in improved clinical outcomes in several small clinical trials. In one trial, half of 160 men and women diagnosed with a recent MI were randomly assigned to receive 4 grams/day of L-carnitine in addition to standard pharmacological treatment. After one year of treatment, mortality was significantly lower in the L-carnitine supplemented group (1.2% vs. 12.5%), and attacks of angina were less frequent. Not all clinical trials have found L-carnitine supplementation to be beneficial after MI. In a randomized, double blind, placebo controlled trial, 60 men and women diagnosed with an acute MI were treated with either intravenous L-carnitine (6 grams/day) for 7 days followed by oral L-carnitine (3 grams/day) for 3 months or placebo. After 3 months, mortality did not differ between the 2 groups, nor did echocardiographic measures of cardiac function. In a larger placebo-controlled trial, 472 patients treated in an intensive care unit within 24 hours of having their first MI were randomly assigned to intravenous L-carnitine therapy (9 grams/day) for 5 days followed by oral L-carnitine (6 grams/day) for 12 months or a placebo in addition to standard medical therapy. Although there were no significant differences in mortality or the incidence of congestive heart failure (CHF), left ventricular volumes were significantly lower in the L-carnitine treated group at the end of one year, suggesting that carnitine therapy may limit adverse effects of acute MI on the heart muscle. Based on these findings, a randomized placebo-controlled trial in 4,000 patients with acute MI is planned to determine the effect of L-carnitine therapy on the incidence of heart failure 6 months after MI.

Heart Failure: Impairment of the heart's ability to pump enough blood for all of the body's needs is known as heart failure. In coronary artery disease, the accumulation of atherosclerotic plaque in the coronary arteries may prevent parts of the heart muscle from getting adequate circulation, ultimately resulting in damage and impaired pumping ability. Myocardial infarction (MI) may also damage the heart muscle, resulting in the development of heart failure. Because physical exercise increases the demand on the weakened heart, measures of exercise tolerance are frequently used to monitor the severity of heart failure. Echocardiography is also used to determine the left ventricular ejection fraction (LVEF), an objective measure of the heart's pumping ability. An LVEF of less than 40% is indicative of systolic heart failure. 

The addition of L-carnitine to standard medical therapy for heart failure has been evaluated in several clinical trials. In a randomized, single-blind, placebo-controlled trial in 30 heart failure patients, oral administration of 1.5 grams/day of propionyl-L-carnitine for 1 month resulted in significantly improved measures of exercise tolerance and a slight but significant decrease in left ventricular size compared to placebo. A larger randomized, double blind, placebo-controlled trial compared the addition of propionyl-L-carnitine (1.5 grams/day) to the treatment regimen of 271 heart failure patients to a placebo in 266 patients for 6 months. Overall, exercise tolerance was not different between the two groups. However, in those with higher LVEF values (greater than 30%), exercise tolerance was significantly improved in those taking propionyl-L-carnitine compared to placebo, suggesting that propionyl-L-carnitine may help to improve exercise tolerance in higher functioning heart failure patients..

Angina pectoris: Angina pectoris is chest pain that occurs when the coronary blood supply is insufficient to meet the metabolic needs of the heart muscle (ischemia). The addition of L-carnitine or propionyl-L-carnitine to pharmacologic therapy for chronic stable angina has been found to modestly improve exercise tolerance and decrease electrocardiographic signs of ischemia during exercise testing in a limited number of angina patients. In a randomized, placebo-controlled crossover trial in 44 men with chronic stable angina, 2 grams/day of L-carnitine for 4 weeks significantly increased the exercise workload tolerated prior to the onset of angina and decreased ST segment depression (electrocardiographic evidence of ischemia) during exercise compared to placebo. In a more recent randomized placebo-controlled trial in 47 men and women with chronic stable angina, the addition of 2 grams/day of L-carnitine for 3 months significantly improved exercise duration and decreased the time required for exercise-induced ST segment changes to return to baseline compared to placebo.

Intermittent claudication in peripheral arterial disease

In peripheral arterial disease, atherosclerosis of the arteries supplying the lower extremities may diminish blood flow to the point that it is insufficient to supply the metabolic needs of exercising muscles, leading to ischemic leg or hip pain known as claudication. In a randomized placebo-controlled study of 495 patients with intermittent claudication, 2 grams/day of propionyl-L-carnitine for 12 months significantly increased maximal walking distance and the distance walked prior to the onset of claudication in patients whose initial maximal walking distance was less than 250 meters. However, no significant response to propionyl-L-carnitine treatment was observed in more mildly affected patients whose initial maximal walking distance was greater than 250 meters. In a double blind, randomized, placebo-controlled trial of 155 patients with disabling claudication in the U.S. and Russia, 2 grams/day of propionyl-L-carnitine for 6 months significantly improved walking distance and claudication onset time compared to placebo. One study compared the efficacy of L-carnitine and propionyl-L-carnitine administered intravenously for the treatment of intermittent claudication, and concluded that propionyl-L-carnitine was more effective than L-carnitine when the same amount of carnitine was provided.

Chronic renal failure/dialysis

L-Carnitine and many of its precursors are removed from the circulation during dialysis. Impaired L-carnitine synthesis by the kidneys may also contribute to the potential for carnitine deficiency in patients with end-stage renal failure on hemodialysis. The U.S. Food and Drug Administration (FDA) has approved the use of L-carnitine in hemodialysis patients for the prevention and treatment of carnitine deficiency. Carnitine depletion may lead to a number of conditions observed in dialysis patients, including muscle weakness and fatigue, plasma lipid abnormalities, and refractory anemia. A systematic review that examined the results of 18 randomized trials, including a total of 482 dialysis patients, found that L-carnitine treatment was associated with improved hemoglobin levels in studies performed before recombinant erythropoietin (EPO) was routinely used to treat anemia in dialysis patients, and that L-carnitine treatment decreased EPO dose and resistance to EPO in studies performed when patients routinely received EPO. Although some uncontrolled studies found that L-carnitine treatment improved blood lipid profiles in hemodialysis patients, the systematic review of randomized controlled trials did not find evidence that L-carnitine improved lipid profiles. The National Kidney Foundation (NKF) does not recommend routine administration of L-carnitine to all dialysis patients. However, the NKF and other consensus groups recommend a trial of L-carnitine for maintenance hemodialysis patients with selected symptoms that do not respond to standard therapy. Those symptoms include persistent muscle cramps or hypotension (low blood pressure) during dialysis, severe fatigue, skeletal muscle weakness or myopathy, cardiomyopathy, and anemia requiring large doses of EPO. In general, intravenous L-carnitine therapy (1-2 grams) at the end of a dialysis session has been recommended for patients on hemodialysis. Oral administration of L-carnitine (1-3 grams/day in divided doses) is more practical for patients on peritoneal dialysis.

Alzheimer's disease (dementia)

Several small controlled clinical trials conducted in the 1990's suggested that acetyl-L-carnitine (ALCAR) treatment (2-3 g/day for 6-12 months) modestly slowed cognitive decline in patients with the clinical diagnosis of Alzheimer's disease. However, a larger multicenter, randomized controlled trial involving 431 patients diagnosed with Alzheimer's disease did not find ALCAR treatment (3 grams/day for 12 months) to be different than placebo in its effects on cognitive decline. Subsequent statistical analyses of that study suggested that patients with early-onset Alzheimer's disease (65 years and younger) experienced more rapid cognitive decline that was significantly slowed by ALCAR treatment. More recently, a multicenter, randomized controlled trial involving 229 early-onset Alzheimer's disease patients between 45 and 65 years of age did not find ALCAR treatment (3 grams/day for 12 months) to affect most measures of cognitive decline with the exception of slightly decreased declines in attention compared to placebo.

HIV/AIDS

One of the hallmarks of infection with the retrovirus, HIV, is a progressive decline in the numbers of critical immune cells known as CD4 T lymphocytes (CD4 cells), ultimately leading to the development of AIDS. Lymphocytes of HIV-infected individuals inappropriately undergo programmed cell death (apoptosis). Limited evidence in cell culture experiments and in humans suggests that L-carnitine supplementation may help slow or prevent HIV-induced lymphocyte apoptosis. In an uncontrolled trial, 11 asymptomatic HIV-infected patients, who had refused antiretroviral treatment despite progressively declining CD4 cell counts, were treated with 6 grams/day of L-carnitine intravenously for 4 months. After 4 months of L-carnitine therapy, CD4 cell counts increased significantly and markers of lymphocyte apoptosis decreased, although there was no significant change in plasma levels of the HIV virus (viremia). Long-term outcomes were not reported in these patients. In a more recent study, 20 HIV-infected individuals were randomly assigned to receive the antiretroviral agents, zidovudine (AZT) and didanosine (DDI), with or without supplemental L-carnitine. Although CD4 cell counts and plasma HIV levels were not different between the two groups after 7 months of therapy, indicators of CD4 cell apoptosis were significantly lower in the group taking L-carnitine. 

Some antiretroviral agents (nucleoside analogues) used to treat HIV-infection appear to cause a secondary L-carnitine deficiency that may lead to some of their toxic side effects. A small cross-sectional study found that nerve concentrations of acetyl-L-carnitine were significantly lower in HIV patients who developed peripheral neuropathy while taking nucleoside analogues than in control subjects. Ten out of 16 HIV patients with painful neuropathies reported improvement after 3 weeks of intravenous or intramuscular acetyl-L-carnitine treatment. Although more controlled research is needed before conclusions can be drawn, L-carnitine supplementation may be a beneficial adjunct to antiretroviral therapy in some HIV-infected individuals.

Decreased sperm motility

L-Carnitine is concentrated in the epididymis, where sperm mature and acquire their motility. Two uncontrolled trials of L-carnitine supplementation in more than 100 men diagnosed with decreased sperm motility in fertility clinics found that oral L-carnitine supplementation (3 grams/day) for 3 to 4 months resulted in significantly improved sperm motility (40, 41). However, no information on subsequent fertility was reported. A cross-sectional study of 101 fertile and infertile men found that L-carnitine concentrations in semen were positively correlated with the number of sperm, the percentage of motile sperm, and the percentage of normal appearing sperm in the sample, suggesting that measuring L-carnitine levels in semen may be useful in the evaluation of male infertility. However, more controlled research on the effects of L-carnitine on sperm motility is required before its utility in treating specific types of male infertility can be determined.

Athletic performance

Interest in the potential of L-carnitine supplementation to improve athletic performance is related to its important roles in energy metabolism. In general, supplementing healthy people with oral L-carnitine for up to 3 months has not been found to result in significant improvements in athletic performance. However, conclusions that can be drawn from this research are limited due to small numbers of participants, short duration of supplementation, and lack of appropriate control groups in most studies.

Toxicity

In general L-carnitine appears to be well tolerated. Toxic effects related to L-carnitine overdose have not been reported. L-carnitine supplementation may cause mild gastrointestinal symptoms, including nausea, vomiting, abdominal cramps and diarrhea. Supplements providing more than 3,000 mg/day may cause a "fishy" body odor. Acetyl-L-carnitine has been reported to increase agitation in some Alzheimer's disease patients and to increase seizure frequency and/or severity in some individuals with seizure disorders. Only the L-isomer of carnitine is biologically active. The D-isomer may actually compete with L-carnitine for absorption and transport, increasing the risk of L-carnitine deficiency. Supplements containing a mixture of the D-, and L-isomers (D,L-carnitine) were associated with muscle weakness in patients with kidney disease. Controlled studies examining the safety of L-carnitine supplementation in pregnant and breastfeeding women are lacking.

Drug Interactions

The anticonvulsant, valproic acid, and nucleoside analogues, used in the treatment of HIV infection, including zidovudine (AZT), didanosine (ddI), zalcitabine (ddC) and stavudine (d4T), may produce secondary L-carnitine deficiencies. Pivalic acid-containing antibiotics used in Europe (pivampicillin, pivmecillinam and pivcephalexin) may also produce secondary L-carnitine deficiencies. The cancer chemotherapy agents, ifosfamide and cisplatin, may increase the risk of secondary L-carnitine deficiency, and there is limited evidence that L-carnitine supplementation may help prevent cardiomyopathy induced by doxorubicin (adriamycin) therapy.

L-carnitine is synthesized in the body from the amino acids lysine and methionine. L-Carnitine is available as a high quality supplement from Bodybuilding.com, as well as from natural and synthetic sources. It is also found in avocados, dairy products, and red meats (especially lamb and beef).

Studies have been conducted on L-carnitine since as early as 1937. They show that the body's cardiovascular system can greatly benefit from its intake. The FDA has approved L-carnitine under the name Carnitor for use in treating heart disease and low energy levels. Also, there are a variety of published studies that show L-carnitine is useful in increasing the heart's output and improving it's functioning, as well as stimulating the heart's energy supply and improving cardiac performance. Moreover, some experts have shown it increases endurance and helps regulating heart arrhythmia.

Although deficiencies are rare, muscle fatigue, cramps, or pre-mature aging are all signs of possible deficiency. A person may also be L-carnitine deficient if their kidneys seem to not function properly after exercise. Other symptoms of possible deficiency are heart irregularities after a heart attack or angina.

Taking L-carnitine is very safe, although the DL form of carnitine may be toxic and is not recommended.