About Herbs, Botanicals & Other Products

Scientific Name
Beta-hydroxy-gamma-trimethyl-amino-butyric acid
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Common Name

Levocarnitine, vitamin BT, vitamin B7, propionyl-L-carnitine

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Brand Name

Carnitor® (approved by FDA), L-Carnipure® (Lonza Ltd.)

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Clinical Summary

Carnitine is an endogenous cofactor in intermediary metabolism. Patients use this supplement to enhance physical performance and to treat fatigue and cachexia associated with carnitine deficiency caused by end-stage renal disease, cardiovascular disease, cancer, diabetes, chronic fatigue syndrome, and HIV/AIDS. Endogenous treatment is thought to enhance mitochondrial integrity and function.

L-carnitine inhibits cisplatin-induced injury of the kidney and small intestine in animal models. Preliminary data suggest efficacy in ameliorating chemotherapy-related (15) (23) and multiple sclerosis (21) related fatigue as well as improving the symptoms of Chronic Fatigue Syndrome (22) and improving physical performance in patients undergoing dialysis for end-stage renal disease (9), but larger trials must be conducted. L-carnitine has been used to prevent skeletal muscle myopathy in heart failure and to block apoptosis (14) and may help prevent cardiovascular disease (24). Several trials have shown enhanced physical performance (6) (17) (20), mitochondrial metabolism (9), or survival (7). Beneficial effects of both carnitine and propionyl-L-carnitine were seen in trials of peripheral arterial disease (1).
L-carnitine used by itself or in combination with clomiphene citrate may help in the treatment against idiopathic male infertility (25).

Reported adverse effects include flu-like syndrome, injection site reaction, pain, pharyngitis, headache, diarrhea, and hypertension (6) (9) (10), while high doses may result in unpleasant body odor (5).

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Food Sources

Meat and dairy products, beans, avocado.

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Purported Uses
  • Alzheimer’s disease
  • Angina
  • Cancer-related cachexia
  • Cardiovascular disease
  • Chemotherapy side effects
  • Chronic fatigue syndrome
  • Chronic obstructive pulmonary disorders
  • Circulatory disorders
  • Diabetes
  • High cholesterol
  • HIV- and AIDS-associated wasting
  • Infertility
  • Strength and stamina
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Mechanism of Action

Carnitine facilitates the transport of long chain fatty acyl CoA esters across the inner mitochondrial membrane, facilitating beta-oxidation of fatty acids and acting as an intracellular energy reservoir of acetyl groups. In conditions of ischemia and carnitine deficiency, these acyl esters accumulate and cause deleterious effects, including inhibition of adenine nucleotide translocase, causing inhibition of ATP production (5). Carnitine modulates the ratio of CoA to CoA-SH, is involved in trapping acyl residues from peroxisomes and mitochondria, and stabilizes cellular membranes (6). Carnitine is a free radical scavenger and may take part in nuclear transcription.

High serum carnitine levels generally correlate with better functional capacity in clinical trials. Exogenous carnitine enhances mitochondrial function in several studies, thought due to an increase in fatty acid oxidation and conservation of glycogen or a decrease in levels of acetyl-CoA, which inhibits pyruvate dehydrogenase (1). In ischemic animal models, carnitine reduces loss of high-energy phosphates, enhances glucose oxidation, preserves myocardial carnitine stores, reduces accumulation of fatty acid esters, and enhances lactate extraction. Numerous studies report that carnitine supplementation improves cardiac performance in animal models of cardiomyopathy or ischemic insult, including improved myocardial metabolic patterns, reduced necrosis, diminished enzymatic infarct size, and preserved left ventricular function (8). L-carnitine has been shown to inhibit cisplatin-induced injury of the kidney and small intestine in animal models (13). One study suggested that L-carnitine inhibits caspases and decreases levels of TNF-alpha (14). Long-term carnitine supplementation in humans is correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance (7). Carnitine administration to rats ameliorates tumor-induced increase in plasma triglycerides. Carnitine is a peripheral antagonist of thyroid hormone action (3).

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Pharmacokinetics

Absorption:
Endogenous synthesis of carnitine takes place primarily in the liver, and to a lesser extent the kidneys and brain. The dietary precursors for this synthesis are lysine and methionine. Intestinal absorption of dietary carnitine is saturable and can increase in response to carnitine deficiency (1). Intravenous L-carnitine shows linear kinetics and a long time to steady state. Following administration of 2 g L-carnitine for 4 days, Cmax is about 80 ìmol/l and occurs at 3.3 hours. Oral bioavailability is approximately 15%. Mucosal absorption of carnitine is saturated by 2 g doses and oral fractionated treatment is required for higher (10).

Distribution:
Total body carnitine stores have been estimated to be between 20-25 grams. The concentration of free muscle carnitine is approximately 4 mmol/kg. The quantity stored is influenced by muscle mass, nutritional status, and age. The adrenal glands exhibit the highest tissue concentrations of carnitine. Skeletal muscle (98%), liver (1.5%), the heart, and other tissues with fatty acid metabolism also contain high levels of carnitine but are incapable of synthesizing it (5).

Metabolism/Excretion:
More than 95% of dietary carnitine is excreted in the urine. Mean apparent terminal elimination half-life of an intravenous carnitine formulation is 17.4 hours (10).

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Contraindications

A patient with riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic-adipic aciduria type experienced repeated hypoglycemic episodes while taking L-carnitine supplements. Patients with defective oxidation of medium- or short-chain fatty acyl-CoA esters should use carnitine supplementation with caution.
(12)

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Adverse Reactions

Rare: Dyspepsia, heartburn (5), blurred vision, transient hair loss, skin rash, seizures. Mild myasthenia has been reported in uremic patients receiving D,L- carnitine (10).
Reported: Flu syndrome, injection-site reaction, pain, pharyngitis, headache, diarrhea, and hypertension (6) (9).
Toxicity: No notable clinical toxicities have been reported, but high oral doses of L-carnitine may cause unpleasant body odor (5).

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Herb-Drug Interactions
  • L-carnitine can antagonize the action of thyroid hormone (26). Whether it interacts with thyroid supplements is not known.
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Literature Summary and Critique

Graziano F, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 2002;86:1854-7. A prospective evaluation of 4 g daily oral carnitine supplementation in 50 non-anemic patients with solid tumors and good performance status who experienced fatigue during chemotherapy. Chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in 6 patients. All patients had low baseline plasma levels of free carnitine (< 30 mcM). Carnitine was administered in 2 g doses every 12 h for the 7 days of chemotherapy. Patients were evaluated weekly with physical examinations, blood chemistries, and Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaires until the next chemotherapy cycle. After 1 week, all patients had plasma free carnitine levels > 30 mcM and 45 patients reported ameliorated fatigue. Mean FACT-F scores improved significantly from baseline (19.7) to the first week (34.9), (p<0.001). Chemotherapy efficacy was not affected. Randomized, placebo-controlled trials are necessary to verify the efficacy of carnitine in reducing cancer fatigue.

Hurot JM, et al. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002;13:708-14.
An exploratory meta-analysis of 482 patients in 18 randomized, controlled trials from 1978-1999 evaluating effects of L-carnitine supplementation on blood chemistry, erythropoietin (EPO) dose, and symptoms in patients undergoing maintenance hemodialysis. In 9 trials evaluating serum lipid profile, effects on serum triglycerides were heterogeneous and no effect was seen on serum total cholesterol. Carnitine supplementation increased hemoglobin levels in three pre-EPO trials by a clinically significant amount. A significant reduction in EPO dose with constant hemoglobin or hematocrit was seen in carnitine-treated groups in four of six trials. Effect of carnitine on exercise capacity, cardiovascular instability, or quality of life was not assessed because of the heterogeneity in recording methods between trials. Most trials included in this review were small and not double-blind, and the meta-analysis did not take into account route of administration.
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Benvenga S, 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 2001:86:3579-94.
A randomized, double-blind, placebo-controlled, crossover design trial evaluating 4 months of 2 or 4 g daily carnitine supplementation versus 2 months placebo in 50 otherwise healthy women with hyperthyroidism. All patients received TSH-suppressive dose of L-thyroxine. Patients were evaluated clinically and biochemically at baseline and every month thereafter. Bone mineral density was measured at baseline and at the study’s end. Carnitine (any dose) was associated with slight decreases in serum AST, ALT, GGT, SHBG, and ferritin and increases in urinary excretion of OH-P and serum osteocalcin, which are all up-regulated by TH. In all carnitine groups, symptomatology (asthenia, palpitations, nervousness, insomnia, and heart rate) decreased during active treatment and worsened during placebo. Transient nausea and gastralgia were the only adverse events reported.

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References
  1. Arsenian MA. Carnitine and its derivatives in cardiovascular disease. Progress Cardiovasc Dis 1997;40:265-86.
  2. Brody T. Nutritional Biochemistry. San Diego(CA):Academic Press; 1999.
  3. Benvenga S, et al. Usefulness of L-carnitine, a naturally occuring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2001:86:3579-94.
  4. Breitkreutz R, et al. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases. Br J Cancer 2000:82;399-403.
  5. Lango R, et al. Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass. Cardiovasc Res 2001;51:21-9.
  6. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology 1997;35:16-23.
  7. Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J 2000;139:S120-3.
  8. Atar D, et al. Carnitine - from cellular mechanisms to potential clinical applications in heart disease. Eur J Clin Invest 1997;27:973-6.
  9. Brass EP, et al. Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients. Am J Kidney Dis 2001:37;1018-28.
  10. Food and Drug Administration. Carnitor® (levocarnitine). Accessed December 10, 2009.
  11. Green A, et al. Possible deleterious effect of L-carnitine supplementation in a patient with mild multiple acyl-CoA dehydrogenation deficiency (ethylmalonic-adipic aciduria). J Inher Metab Dis 1991;14:691-7.
  12. Vicari E, Calogero AE. Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis. Human Reprod 2001;16:2338-42.
  13. Chang B, et al. L-Carnitine inhibits cisplatin-induces injury of the kidney and small intestine. Arch Biochem Biophys. 2002;405:55.
  14. Vescovo G, et al. L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol. 2002;283:C802-10.
  15. Graziano F, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 2002;86:1854-7.
  16. Hurot JM, et al. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002;13:708-14.
  17. Ellaway CJ, et al. Medium-term open label trial of L-carnitine in Rett syndrome. Brain Dev 2001:23;S85-9.
  18. Loignon M, Toma E. L-Carnitine for the treatment of highly active antiretroviral therapy-related hypertriglyceridemia in HIV-infected adults. AIDS 2001;15:1194-5.
  19. Benvenga S, 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 2001:86:3579-94.
  20. Cacciatore L, et al. The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exp Clin Res 1991;17:225-35.
  21. Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. J Neurol Sci. 2004 Mar 15;218(1-2):103-8.
  22. Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 Mar-Apr;66(2):276-82.
  23. Gramignano G, Lusso MR, Madeddu C, et al. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 2006 22(2):136-45.
  24. Hakeshzadeh F, Tabibi H, Ahmadinejad M, Malakoutian T, Hedayati M. Effects of L-Carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients. Ren Fail. 2010;32(9):1109-14.
  25. Moradi M, Moradi A, Alemi M, et al. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol J. 2010 Summer;7(3):188-93.
  26. Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci. 2004 Nov;1033:158-67.
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How It Works

Bottom Line: Clinical trials show that carnitine is helpful in patients with angina, heart disease, and peripheral vascular disease. It does not prevent or treat cancer.

Carnitine is a molecule found naturally in the body and in foods such as meat and dairy products, beans, and avocados. Its role in the body is extremely important for the production of energy: carntitine “shuttles” fatty acyl CoA across the membrane of the mitochondria so that they can be metabolized and ATP (the “fuel” of every cell) produced. When there is not enough carnitine in the cells, or when there are not enough nutrients in the cells because blood is not reaching the tissues (i.e., ischemia), fatty acyl coA can accumulate outside of mitochondria and cause damaging effects. In general, people with genetic carnitine deficiency are fatigued because energy production is greatly reduced, and they respond well to carnitine supplements.

The use of carnitine supplements for other conditions is less well established. In clinical trials, cancer patients who have higher blood levels of carnitine generally have higher functioning and more energy, probably because their mitochondria are functioning more efficiently. When rats that have the equivalent of heart disease are fed carnitine, they have increased heart performance and smaller areas of damaged heart muscle than rats with heart disease that were not fed carnitine. Similar results have been shown in humans: patients who take carnitine after having a heart attack generally have increased heart performance and exercise tolerance.

Other effects of carnitine that are under study include a protective effect against the damaging effects of cisplatin on the kidney and small intestine and an ability to suppress thyroid hormone.

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Purported Uses
  • To treat Alzheimer’s disease
    No scientific evidence supports the use of carnitine for Alzheimer’s disease.
  • To treat angina
    Several clinical trials suggest that carnitine can increase exercise tolerance in patients with stable angina.
  • To gain weight and prevent weight loss in patients with cachexia (muscle wasting) from advanced cancer or HIV/AIDS
    No scientific evidence supports this use.
  • To manage heart disease
    Several clinical trials have suggested that carnitine can enhance physical performance, reduce heart damage after a heart attack, and possible increase survival in patients with heart disease.
  • To relieve some of the side effects of chemotherapy
    One clinical trial has suggested that carnitine can help alleviate chemotherapy-related fatigue, but more research is needed to confirm this effect.
  • To treat chronic fatigue syndrome
    One clinical trial weakly supports this use, but because it had design flaws, more research is needed.
  • To manage COPD (chronic obstructive pulmonary disease)
    No scientific evidence supports this use.
  • To improve circulation
    Several clinical trials have shown beneficial effects of both carnitine and propionyl-L-carnitine on peripheral vascular disease.
  • To treat diabetes
    One clinical trial showed that continuous infusion of carnitine decreased insulin resistance in patients with type 2 diabetes, but more research is needed to confirm this effect. Studies generally do not support the use of carnitine or acetyl-L-carnitine for treating diabetic neuropathy.
  • To lower high cholesterol
    Although several clinical trials suggest that carnitine supplements can increase HDL (“good”) cholesterol and reduce blood triglyceride levels, several other clinical trials contradict these findings.
  • To treat infertility
    One study showed that carnitine may be useful in treating idiopathic male infertility. More studies are needed.
  • For increased strength and stamina
    Studies of oral carnitine for enhanced exercise performance in healthy individuals are poorly designed and show no consistent benefit.
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Research Evidence

Cancer Fatigue:
Many cancer patients experience fatigue during chemotherapy, even if they are not anemic. One study gave 4 grams of carnitine by mouth to 50 patients with solid tumors who were experiencing fatigue from chemotherapy and had low blood levels of carnitine. After one week, blood carnitine levels were increased in all of the patients, and 45 of them reported ameliorated fatigue. These results are promising, but one flaw of this study is that it did not have a control group (receiving a placebo pill). Placebo groups are important so that we can compare the effects of carnitine to what would happen if patients were given no treatment at all.

Hemodialysis Fatigue:
Researchers performed a meta-analysis (a systematic review of all the clinical trials performed with a therapy) to assess whether carnitine helps alleviate fatigue in patients undergoing hemodialysis. Their analysis found that carntine had no constant effect on triglycerides, but increased blood hemoglobin levels in three studies and allowed reduction of erythropoietin dose in four studies. However, this analysis did not look at the effects of carnitine on exercise capacity or quality of life, nor did it account for the fact that in some studies carnitine was given intravenously, while in others it was given by mouth.

Hyperthyroidism:
A randomized controlled trial studied the effects of carnitine in 50 women with hyperthyroidism. In this “crossover” design trial, women either took 2 or 4 grams of carnitine for four months, then crossed over to treatment with a placebo for two months, or vice versa. All of the women were also taking L-thyroxine. Any dose of carnitine was associated with changes in blood chemistry that signaled a decreased effect of thyroid hormone. In addition, women reported improved symptoms, such as palpitations, nervousness, and insomnia, while taking carnitine. The women also reported side effects from carnitine, including nausea and stomach upset.

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Patient Warnings
  • This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If
  • You have riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic-adipic aciduria type (One patient with this disorder had repeated low blood sugar while taking carnitine supplements).
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Side Effects
  • Upset stomach
  • Heartburn
  • Blurred vision
  • Temporary hair loss
  • Skin rash
  • Seizures
  • Mild myasthenia (muscle weakness) has been reported in patients with uremia who took carnitine.
  • Flu-like syndrome
  • Pharyngitis (sore throat)
  • Headache
  • Diarrhea
  • High blood pressure
  • High doses of L-carnitine by mouth may cause unpleasant body odor.
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Special Point
  • Over-the-counter carnitine supplements may have poor bioavailability, meaning that they may not be well absorbed into the bloodstream through the gut.
  • L-carnitine may inhibit the action of thyroid hormone. But it is not known whether it interacts with thyroid supplements.
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Dosage (Inside MSKCC Only)
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Last updated: October 19, 2011
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