Health Care Professional Information

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

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

Brand Name

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

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 AIDS. Endogenous treatment is thought to enhance mitochondrial integrity and function.

Preliminary results indicate benefits of l-carnitine in improving symptoms of Chronic Fatigue Syndrome (22) and improving physical performance in patients undergoing dialysis for end-stage renal disease (9) but data of its benefits in alleviating atigue associated with multiple sclerosis are inconclusive (21). 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).

L-carnitine supplementation was shown to improve quality of life in patients with pancreatic cancer (27).
Preliminary data indicate its benefits in ameliorating chemotherapy-related fatigue (15) (23). However, in another study supplementation did not improve fatigue in cancer patients (28). More research is needed.

Food Sources

Meat, dairy products, beans, and avocado.

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
  • AIDS-associated wasting
  • Infertility
  • Strength and stamina
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).
A few mechanisms that result in the anti-catabolic effects and the improvement of fatigue following l-carnitine supplementation include affecting improved nitrogen balance either due to increased protein synthesis or reduced protein degradation, inhibition of apoptosis and abrogation of inflammatory processes. Animal studies indicate that carnitine supplementation prevents oxidative stress and ameliorates mitochondrial function (29).

In a study of mice metabolism of dietary l-carnitine by intestinal microbiota produced trimethylamine-N-oxide (TMAO), a proatherogenic species, which accelerated atherosclerosis (30). Clinical trials are needed to determine the implications of this study in humans.
Long-term carnitine supplementation in humans is correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance (7). In one study carnitine was shown effective in reversing hyperthyroidism by acting as a peripheral antagonist of thyroid hormone action (3).

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).

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)

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).
High doses of oral l-carnitine may cause unpleasant body odor (5).

Literature Summary and Critique

Kraft M, Kraft K, Gärtner S, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)—a randomized multicentre trial. Nutr J. 2012 Jul 23;11:52.
This multicentre study involved 72 patients with advanced pancreatic cancer. Patients were randomized to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At the start of the trial, patients reported a mean weight loss of 12 ± 2.5 (SEM) kg. During treatment there was an increase in the body-mass-index by 3.4 ± 1.4% in patients on L-carnitine. But it decreased in the placebo group (-1.5 ± 1.4%) (p < 0.05). Further, researchers observed an improvement in the nutritional status and quality of life in the L-carnitine group. There also was a trend toward increased overall survival (median 519 ± 50 d versus 399 ± 43 d, not significant) and reduced hospital stay (36 ± 4d versus 41 ± 9d,n.s.) in the L-carnitine group.
Data from this study suggest benefits of L-carnitine for patients with advanced pancreatic cancer. However, more trials are needed to confirm these observations.

Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012 Nov 1;30(31):3864-9.
In this trial, 376 patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of oral L-carnitine supplementation or a placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). Researchers report that fatigue improved in both groups compared with baseline (L-carnitine: -0.96, 95% CI, -1.32 to -0.60; placebo: -1.11, 95% CI -1.44 to -0.78); there was no statistically significant difference between the groups (P = .57). There were also no differences between the groups in the secondary outcomes including fatigue, depression, and pain.
Four weeks of supplementation with 2 g L-carnitine did not improve fatigue in patients with cancer.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
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 April 12, 2013.
  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. Tejani AM, Wasdell M, Spiwak R, Rowell G, Nathwani S. Carnitine for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2012 May 16;5:CD007280.

  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.
  27. Kraft M, Kraft K, Gärtner S, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)—a randomized multicentre trial. Nutr J. 2012 Jul 23;11:52.
  28. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012 Nov 1;30(31):3864-9.
  29. Ringseis R, Keller J, Eder K. Mechanisms underlying the anti-wasting effect of L-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies.Eur J Nutr. 2013 Mar 19. [Epub ahead of print]
  30. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 Apr 7. [Epub ahead of print]

Consumer Information

How It Works

Bottom Line: Clinical trials show that carnitine is helpful in patients with angina, heart disease, and peripheral vascular disease.

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: carnitine “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.

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
    Data are mixed on carnitine's benefits against chemotherapy-related fatigue.
  • To treat chronic fatigue syndrome
    One clinical trial supports this use.
  • 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.
Research Evidence

Cancer-associated Fatigue:
A multicentre study was conducted on 72 patients with advanced pancreatic cancer. Patients were randomized to receive oral L-Carnitine (4 g) or placebo for 12 weeks. Researchers reported an increase in body-mass index, and an improvement in the nutritional status and quality of life in the L-carnitine group but not in the placebo group. There also was a trend toward increased overall survival and reduced hospital-stay in the L-carnitine group.

In another trial, 376 patients with cancer and fatigue were randomly assigned to either 2 g of oral L-carnitine supplementation daily or a placebo. Researchers reported that fatigue improved in both groups compared to the baseline. There were no statistically significant differences in fatigue, depression, or pain between the groups.
Four weeks of supplementation with 2 g L-carnitine did not improve fatigue in patients with cancer.

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).
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.
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.
E-mail your questions and comments to aboutherbs@mskcc.org.