L-Carnitine

Category

Herbs & Supplements

Synonyms

AcCn, acetyl-L-carnitine, B (t) Factor, β-hydroxy-gamma-N-trimethylamino butyrate, carnitene, carnitine, carnitor, canitor, D-carnitine, D,L-carnitine, LAC, L-acetyl-carnitine, LCLT, L-carnitina, L-carnitine L-tartrate, L-CARNIPURE, levacecarnine, levocarnitine, levocarnitine chloride, LK-80, L-propionylcarnitine, propionil-L-carnitine, propionyl-L-carnitine, total parenteral nutrition, TPN, VitaCarn®, vitamin B(t), vitamin Bt.

Background

The main function of L-carnitine is to transfer long-chain fatty acids in the form of their acyl-carnitine esters across the inner mitochondrial membrane before beta-oxidation. In humans, it is synthesized in the liver, kidney, and brain and actively transported to other areas of the body. For example, 98% of the total body L-carnitine is confined to the skeletal and cardiac muscle at concentrations approximately 70 times higher than in the blood serum.

Supplementation may be necessary in rare cases of primary carnitine deficiency, which may be caused by a defect in carnitine biosynthesis, a defect in carnitine active transport into tissue, or a defect in renal (kidney) conservation of carnitine. Known conditions of secondary deficiency of carnitine (insufficiency), in which L-carnitine is effective, include chronic stable angina and intermittent claudication characterized by distinct tissue hypoxia (low oxygen levels). Another condition that may benefit from carnitine supplementation is decreased sperm motility.

Although use in preterm infants suggests carnitine supplementation may aid in maintaining or increasing plasma carnitine levels and possibly weight gain, carnitine is not routinely added to preterm total parenteral nutrition (TPN). However, soy-based infant formulas are fortified with carnitine to levels found in breast milk.

In 1986, the U.S. Food and Drug Administration (FDA) approved L-carnitine for use in primary carnitine deficiency. D-carnitine or DL-carnitine may cause secondary L-carnitine deficiency and should not be used.

Evidence

DISCLAIMER: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Nutritional deficiencies (primary and secondary carnitine deficiency in adults): Carnitine supplementation, both intravenous (injection) and oral (by mouth), is indicated for cases of primary and secondary carnitine deficiency. Use of L-carnitine in primary carnitine deficiency restores plasma carnitine levels to nearly normal levels. Muscle carnitine levels may rise only slightly; however muscle function can be normalized.
Grade: A

Angina (chronic stable): Evidence from clinical trials suggests that L-carnitine and L-propionyl-carnitine (propionyl-L-carnitine) are effective in reducing symptoms of angina. Carnitine may not offer further benefit when patients continue conventional therapies. Additional study is needed to confirm these findings.
Grade: B

Attention-deficit hyperactivity disorder (ADHD): Only one study has examined the effects of L-carnitine in boys with ADHD. Although results were promising, additional study is needed before a strong recommendation can be made.
Grade: C

AIDS: Carnitine may be beneficial in AIDS treatment by increasing proliferation of mononuclear cells and increasing CD4 counts. Additional study is needed to make a firm recommendation.
Grade: C

Alcoholism: L-carnitine or acetyl-L-carnitine may be of benefit to alcoholics. Additional study is needed to make a firm recommendation.
Grade: C

Alzheimer's disease: Early evidence suggests the effectiveness of L-carnitine and/or acetyl-L-carnitine for Alzheimer's disease. However, the evidence is mixed.
Grade: C

Arrhythmia (abnormal heart rhythms): Although preliminary results are promising, there is insufficient available evidence to recommend for or against this use.
Grade: C

Cerebral ischemia (lack of adequate blood flow to the brain): There are a limited number of studies showing a positive effect of L-acetyl-carnitine on cerebral blood flow and metabolism of the brain in patients who have suffered from stroke. Additional study is required before a firm recommendation can be made.
Grade: C

Congestive heart failure: Although preliminary results are promising, there is insufficient available evidence to recommend for or against the use of carnitine for congestive heart failure.
Grade: C

Dementia (elderly): Most of the studies related to dementia suffer from various weaknesses. Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against this use.
Grade: C

Depression: Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against the use of carnitine in the treatment of depression.
Grade: C

Diabetes mellitus: It has been suggested that L-carnitine under constant infusion is able to increase insulin sensitivity in patients with diabetes mellitus type II and enhance glucose oxidation. Carnitine may also decrease fasting blood glucose and Lp(a). Additional study is needed before a firm recommendation can be made.
Grade: C

Diabetic neuropathy: Early evidence suggests that acetyl-L-carnitine may be beneficial for individuals with diabetic neuropathy. Additional study is needed before a firm recommendation can be made.
Grade: C

Dialysis (CAPD): L-carnitine taken by mouth has been used in patients receiving continuous ambulatory peritoneal dialysis (CAPD), but does not appear to lead to the resolution of hypertriglyceridemia. Additional study is needed before a firm recommendation can be made.
Grade: C

Dialysis (hemodialysis): Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against the use of carnitine for hemodialysis patients.
Grade: C

Diphtheria (throat disease): Early studies suggest that carnitine may be beneficial for patients with diphtheria, mainly in terms of myocardial (heart) damage. However, additional study is needed to confirm these findings.
Grade: C

Erectile dysfunction: Preliminary studies suggest that propionyl-L-carnitine, with acetyl-L-carnitine or sildenafil may be beneficial for patients with erectile dysfunction. However, more rigorous trials should be performed in order to recommend carnitine for routine use in erectile dysfunction.
Grade: C

Exercise performance: Overall, the data is mixed in terms of the benefits of L-carnitine for exercise performance. Until confirmed, a strong recommendation for L-carnitine cannot be made for increased exercise endurance.
Grade: C

Fatigue: There are several promising reports on the use of L-carnitine for fatigue. However, additional study is warranted in this area.
Grade: C

Fragile X syndrome: There is insufficient evidence to support the use of carnitine in the treatment of hyperactive behavior of fragile -X children.
Grade: C

Hepatic encephalopathy (brain disease): Preliminary evidence suggests L-carnitine may be of benefit to individuals with hepatic encephalopathy, in terms of ammonia levels and psychometric functioning. Additional study is needed to make a firm recommendation.
Grade: C

Huntington's chorea/disease: One preliminary study showed that L-acetyl-carnitine possesses neither efficacy nor toxicity in patients with Huntington's disease. Further trials are required before a firm recommendation can be made.
Grade: C

Hyperlipoproteinemia (high levels of lipoprotein and cholesterol in the blood): Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against the use of carnitine for hyperlipoproteinemia.
Grade: C

Hyperthyroidism: Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against the use of carnitine for hyperthyroidism.
Grade: C

Infertility (asthenospermia): Early evidence shows a positive effect for carnitine and/or acetyl-L-carnitine in terms of increased sperm motility. However, additional study is needed before a firm conclusion can be made.
Grade: C

Lactic acidosis: Although early evidence appears promising, currently there is insufficient evidence to recommend carnitine in the treatment of lactic acidosis.
Grade: C

Liver disease (cirrhosis): Although early evidence appears promising, currently there is insufficient evidence to recommend carnitine in the treatment of liver cirrhosis.
Grade: C

Memory: There are a limited number of studies relevant to the use of carnitine for memory. Carnitine does not appear to have any effect on memory. Additional study is needed before a firm recommendation can be made.
Grade: C

Myocardial infarction (heart attack): Currently there is insufficient evidence to support the use of carnitine for myocardial infarction. Additional study is needed in this area.
Grade: C

Nutritional deficiencies (adults): Currently there is insufficient evidence to support the use of carnitine in the total parenteral nutrition for adults. Additional study is needed in this area.
Grade: C

Nutritional deficiencies (full term infants): Despite a large number of studies, it is not clear what effect, if any, the addition of carnitine has on weight gain in full term infants. Additional study is needed.
Grade: C

Nutritional deficiencies (premature infants): Despite a large number of studies, it is not clear what effect, if any, the addition of carnitine has on weight gain in premature infants. Additional study is needed.
Grade: C

Obesity: Early evidence shows that L-carnitine may have no effect on weight loss in obese patients. Further studies are needed before a firm recommendation can be made.
Grade: C

Peripheral neuropathy (nerve damage): Currently there is insufficient evidence to support the use of carnitine for peripheral neuropathy.
Grade: C

Peripheral vascular disease: Propionyl-L-carnitine and L-carnitine may treat peripheral vascular disease, especially in patients with severe limitations in peripheral circulation. The comparative effectiveness of propionyl-L-carnitine and other recognized treatments is unclear. More study is needed to make a firm recommendation.
Grade: C

Peyronie's disease: Although early evidence is promising, more study is needed before a firm recommendation can be made.
Grade: C

Pregnancy (miscarriage): Currently there is insufficient evidence to support the use of carnitine for miscarriage.
Grade: C

Respiratory distress (adults): Currently there is insufficient evidence to support the use of carnitine for respiratory distress in adults.
Grade: C

Respiratory distress (infants): Currently there is insufficient evidence to support the use of carnitine for respiratory distress in infants.
Grade: C

Rett's syndrome: There are promising results on the use of carnitine for this condition. Before a strong recommendation can be made, additional well-designed trials are needed.
Grade: C

Sickle cell disease: Preliminary evidence suggests the absence of any therapeutic effect of propionyl-L-carnitine for sickle cell disease. Additional studies are required before a firm recommendation can be made.
Grade: C

Surgerical uses (bypass): The results of studies on the use of carnitine in improving the functioning of myocardium (heart muscle) during open-heart surgery are controversial. Currently, there is insufficient available evidence to recommend for or against the use of carnitine.
Grade: C

Tuberculosis: A preliminary study suggests antibacterial activity may be increased in patients with tuberculosis given acetyl-L-carnitine. Additional study is needed to confirm these findings.
Grade: C

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Acidosis (acidemia), acne, anorexia, blood circulation, cocaine withdrawal, gonarthrosis (chronic wear of the cartilage in the knee joint), hypertension (high blood pressure), immunomodulator, macular degeneration, metabolic abnormalities (propionate), metabolic disorders (acquired total lipodystrophy), myocarditis/endocarditis (heart infections), neurologic disorders (children), retinal protection.

Dosing

Adults (18 years and older):

The U.S. Food and Drug Administration (FDA) recommends 1 gram of L-carnitine three times per day, intravenously (injected), for primary and secondary carnitine deficiency; this dose should not exceed 3 grams per day. A variety of doses have been used, with 3 grams per day in divided doses for 2-4 months being the most common; however, the doses range from 1 to 9 grams per day. Conditions treated have included AIDS, memory in alcoholics, Alzheimer's disease, angina (chest pain), congestive heart failure, depression, diabetes, diabetic neuropathy, dialysis, exercise performance, hepatic encephalopathy (brain disease), hyperlipidemia (high cholesterol), hyperthyroidism, myocardial infarction (heart attack), peripheral neuropathy (nerve damage), and peripheral vascular disease.

Intravenous (needle into a vein) injections have also been used, with doses typically ranging from 15-50 milligrams per kilogram twice daily. Injections have been given for seven days up to one year. Higher doses (up to 9 grams per day) have been studied. Injections should only be given under the supervision of a qualified healthcare professional.

Children (younger than 18 years):

The U.S. Food and Drug Administration (FDA) does not recommend exceeding 3 grams carnitine daily for primary and secondary carnitine deficiency. A typical dose for these deficiencies, as well as Rett's syndrome, is 100-200 milligrams per kilogram taken daily divided over two or three doses. For hyperlipidemia (high cholesterol), 3 grams L-carnitine for up to six weeks has been used. For total parental nutrition in infants, 50 micromoles per kilogram for two weeks has been used. Injections should only be given under the supervision of a qualified healthcare professional.

Safety

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

Avoid in individuals with a known allergy or hypersensitivity to carnitine.

Side Effects and Warnings

In general, L-carnitine is safe and no significant complications have been reported in available human clinical studies. Minor adverse effects have been reported with the use of L-carnitine or acetyl-L-carnitine, such as skin rash, body odor, "fishy smell," diarrhea, gastric pyrosis (heartburn), nausea, gastralgia (stomachache), loose bowel movement, nonspecific abdominal discomfort, or vomiting. Euphoria, insomnia, nervousness, mania, depression, and aggression have also been reported, but primarily in patients with pre-existing psychiatric conditions.

Transient hair loss was reported in 1% of cases. Less birth weight was regained in low birth weight infants treated with L-carnitine.

Carnitine supplements should be used cautiously in patients with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, low birth weight (infants), diabetics, and patients on hemodialysis.

Pregnancy and Breastfeeding

L-carnitine is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

Interactions

Interactions with Drugs

Several drugs may affect the levels of carnitine in the body. For example, adefovir dipivoxil (Hepsera®), which is given for hepatitis B, may reduce free carnitine levels. Cephalosporin antibiotics may reduce plasma carnitine levels. Anticonvulsants (phenobarbital, phenytoin, carbamazepine) may decrease serum carnitine in children. Cisplastin may increase urinary excretion of carnitine. Ifosfamide (Mitoxana®), a chemotherapy drug, may increase urinary loss of carnitine; however, use of carnitine plus ifosfamide may help reduce fatigue (side effect of ifosfamide treatment). Patients suffering from neuropathy (nerve damage) induced by nucleosides may have reduced levels of acetyl carnitine. Penicillin derivatives (pivaloyloxymethyl esterified, pivampicillin, and pivmecillinam) may decrease the serum carnitine concentration, elevate excretion of acyl-carnitine, and reduce muscle carnitine concentration in adults and children.

L-carnitine may decrease the need for certain drugs, such as glycosides, digoxin, diuretics, beta-blockers, channel blockers, hypolipidemic (cholesterol-altering) drugs, and nitro derivatives.

L-carnitine supplementation may reduce side effects associated with interleukin-2 (IL-2) or nortriptyline (Pamelor®, Aventyl®). It may also improve liver and muscular side effects associated with isotretinoin (Accutane®) in acne patients. Carnitine may reduce nerve damage symptoms associated with paclitaxel (Taxol®) use.

Carnitine may prevent arrhythmias (abnormal heart rhythms) provoked by adriamycin (Doxorubicin®), which is used in chemotherapy. L-carnitine may decrease the need for antiarrhythmics (medications used to treat abnormal rhythms in the heart). Carnitine plus propafenone may improve arrhythmia (heart rhythm) better than propafenone alone.

L-carnitine may decrease the need for anticoagulants ("blood thinners"), such as warfarin (Coumadin®) or heparin.

Several combinations have shown positive interactions. For example, sildenafil and propionyl-L-carnitine may be more effective than sildenafil alone. Although not well studied in humans, L-carnitine used concurrently with antiviral agents such as zidovudin (Retrovir®) or carnitine used with nortryptiline may also have a positive interaction that reduces side effects. L-carnitine plus acetyl-L-carnitine plus cinnoxicam has been found more effective in improving sperm parameters as compared with L-carnitine plus acetyl-L-carnitine alone.

Patients with diabetes should use caution because L-carnitine may decrease blood sugar. However, carnitine levels did not change in diabetics using insulin or sulfonylurea therapy. It is unclear whether L-carnitine would have similar effects when combined with other medications that lower blood sugar. Consult with a qualified healthcare professional, including a pharmacist, before combining therapies.

Although not well studied in humans, carnitine may increase valproic acid concentrations in the brain, which might increase the effects of valproic acid. Caution is advised.

Interactions with Herbs and Dietary Supplements

L-carnitine may decrease the need for herbs or supplements with anticoagulant effects ("blood thinners"). L-carnitine may also decrease the need for herbs or supplements with diuretic effects. Dosing adjustments may be necessary.

Patients with diabetes should use caution because L-carnitine may decrease blood sugar. However, carnitine levels did not change in diabetics using insulin or sulfonylurea therapy. It is unclear whether L-carnitine would have similar effects when combined with other herbs and supplements that lower blood sugar. Consult with a qualified healthcare professional, including a pharmacist, before combining therapies.

Choline supplementation may reduce excretion, renal (kidney) clearance, and fractional clearance of non-esterified carnitine.

L-carnitine chloride and potassium chloride may minimize rhabdomyolysis, a side effect of taking licorice by mouth.

Attribution

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Julie Conquer, PhD (RGB Consulting); Gary Ferguson, ND (Southcentral Foundation); Sayuri Fujita, PharmD (Massachusetts College of Pharmacy); Nicole Giese, MS (Natural Standard Research Collaboration); Mary Giles, PharmD (University of Rhode Island); Richard Liebowitz, MD (Duke University); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Ruslan Voloshin, PharmD (Massachusetts College of Pharmacy); Wendy Weissner, BA (Natural Standard Research Collaboration).

Bibliography

DISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

Bazzato G, Coli U, Landini S, et al. Myasthenia-like syndrome after D,L- but not L-carnitine. Lancet 5-30-1981;1(8231):1209.

Bazzato G, Mezzina C, Ciman M, et al. Myasthenia-like syndrome associated with carnitine in patients on long- term haemodialysis. Lancet 5-12-1979;1(8124):1041-1042.

Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2001;86(8):3579-3594.

Bohmer T, Bergrem H, Eiklid K. Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1-21-1978;1(8056):126-128.

Casciani CU, Caruso U, Cravotto E, et al. Effect of L-carnitine on lipid pattern in haemodialysis. Lancet 12-13-1980;2(8207):1309-1310.

El Beshlawy A, Abd El Raouf, Mostafa F, et al. Diastolic dysfunction and pulmonary hypertension in sickle cell anemia: is there a role for L-carnitine treatment? Acta Haematol. 2006;115(1-2):91-96.

Ellaway C, Williams K, Leonard H, et al. Rett syndrome: randomized controlled trial of L-carnitine. J Child Neurol 1999;14(3):162-167.

Holme E, Greter J, Jacobson CE, et al. Carnitine deficiency induced by pivampicillin and pivmecillinam therapy. Lancet 8-26-1989;2(8661):469-473.

Jirillo E, Altamura M, Munno I, et al. Effects of acetyl-L-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study. Immunopharmacol.Immunotoxicol. 1991;13(1-2):135-146.

Lacour B, Di Giulio S, Chanard J, et al. Carnitine improves lipid anomalies in haemodialysis patients. Lancet 10-11-1980;2(8198):763-764.

Maebashi M, Kawamura N, Sato M, et al. Lipid-lowering effect of carnitine in patients with type-IV hyperlipoproteinaemia. Lancet 10-14-1978;2(8094):805-807.

Persico G, Amato B, Aprea G, et al. The early effects of intravenous L-propionyl carnitine on ulcerative trophic lesions of the lower limbs in arteriopathic patients: a controlled randomized study. Drugs Exp Clin Res 1995;21(5):187-198.

Sima AA, Calvani M, Mehra M, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care 2005;28(1):89-94.

Singh RB, Niaz MA, Agarwal P, et al. A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction. Postgrad.Med J 1996;72(843):45-50.

Thomas S, Fischer FP, Mettang T, et al. Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: A double-blind randomized trial. Am J Kidney Dis 1999;34(4):678-687.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.