Carnitine

• How It Works

  Some clinical trials show that carnitine supplementation is helpful for patients with angina, heart disease, or peripheral vascular disease. However, guidelines recommend against a particular form, acetyl-l-carnitine, for chemotherapy-induced peripheral neuropathy.

  Carnitine is a nutrient found naturally in the body and in foods such as meat and dairy products, beans, and avocados. It plays an important role in energy production by delivering fatty acids that are processed within the cells to be used as fuel. It also helps to prevent damaging effects that can occur when fatty acids build up outside of cells.

  L-carnitine is more readily absorbed in the body if obtained from food rather than supplements. However some people, such as those with a genetic deficiency who are fatigued because energy production is greatly reduced, respond well with carnitine supplements. In addition, studies in some patients with heart conditions show improved heart function and ability to exercise after taking carnitine.

  There is less evidence for the use of carnitine supplements for other conditions. In clinical trials, cancer patients who have higher blood levels of carnitine generally have higher functioning and more energy. However, one particular form, acetyl-L-carnitine, is known to increase chemotherapy side effects, so it is important to discuss any use of this supplement with your oncologist.

• Purported Uses
  • To manage heart disease
    Several clinical trials suggest that carnitine can enhance physical performance, increase exercise tolerance in patients with stable angina, reduce heart damage after a heart attack, and possibly increase survival in patients with heart disease. It may improve circulation in peripheral vascular disease. However, results from one large trial of patients who had a heart attack found no reductions in heart failure events or death with carnitine therapy.
  • To relieve some side effects of chemotherapy
    Data are mixed on whether carnitine helps chemotherapy-related fatigue. In addition, a processed form of carnitine known as acetyl-L-carnitine, has been shown to increase nerve pain. Therefore, additional studies are needed to determine whether carnitine supplementation can benefit cancer patients.
  • To gain weight and prevent weight loss in patients with advanced cancer
    There is some initial evidence that carnitine supplementation may improve nutritional status in patients with advanced pancreatic cancer while improving quality of life. However, additional studies are needed to confirm these effects.
  • To treat chronic fatigue syndrome
    One clinical trial supports this use.
  • To treat diabetes
    In one clinical trial, carnitine given by infusion decreased insulin resistance in patients with type 2 diabetes, but more research is needed to confirm this effect with oral dosages. A few studies also suggest that carnitine may be helpful for diabetic nerve pain.
  • 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
    Studies show mixed results in treating male infertility.
  • To increase strength and stamina
    Studies of oral carnitine for enhanced exercise performance in healthy individuals are poorly designed and show no consistent benefit.
  • To treat Alzheimer’s disease
    Some clinical trials show benefit with a processed form of carnitine known as acetyl-L-carnitine to improve brain function, but two large long-term studies did not find any benefit. In addition, a review of studies on various forms of carnitine to enhance brain function found the current evidence lacking.
• Do Not Take If

  You are taking warfarin: L-carnitine may increase bleeding risks.

• Side Effects
  • Upset stomach
  • Heartburn
  • Flu-like syndrome
  • Sore throat
  • Headache
  • Diarrhea
  • High blood pressure
  • Unpleasant body odor with high doses

  Case Report

  Low blood sugar: In a patient with a rare genetic metabolic disorder who took carnitine supplements.

• Special Point
  • Over-the-counter carnitine supplements may not be well absorbed by the body.
  • L-carnitine may inhibit the action of thyroid hormone, but it is not known whether it interacts with thyroid supplements.
  • L-carnitine should not be confused with acetyl-L-carnitine, which can increase chemotherapy side effects such as nerve pain.
• Scientific Name

  Beta-hydroxy-gamma-trimethyl-amino-butyric acid

• Clinical Summary

  Carnitine is a nutrient that plays an important role in fatty acid absorption and mitochondria function. It can be found in diets that include meat, or synthesized endogenously from lysine and methionine. Deficiencies can be caused by genetic disorders, malnutrition, malabsorption, and kidney dialysis. These can affect the heart, skeletal muscles, liver, nerve, and endocrine functions. Carnitine is marketed as a dietary supplement to enhance physical performance and to treat fatigue, cardiovascular disease, diabetes, obesity, chronic fatigue syndrome, liver disorders, and cancer.

  Animal models suggest that L-carnitine has cardioprotective ^(8) (14) and antioxidant effects ⁽³¹⁾. It may help prevent cardiovascular disease in hemodialysis patients ⁽²⁴⁾. Long-term carnitine supplementation in humans is correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance ⁽⁷⁾. However, L-carnitine administration did not improve risk of death or heart failure in patients with anterior acute myocardial infarction ⁽³⁶⁾.

  Preliminary results suggest L-carnitine may improve symptoms of chronic fatigue syndrome ⁽²²⁾ and physical performance in patients undergoing dialysis for end-stage renal disease ⁽⁹⁾, but data of its benefits in alleviating fatigue associated with multiple sclerosis are inconclusive ⁽²¹⁾. Several trials have shown enhanced physical performance ^(17) (20), and improved aerobic capacity and exercise tolerance ⁽³²⁾. Other studies show mixed results ^{(37) (38) (39)} and its clinical value and safety needs additional study.

  L-carnitine used by itself or in combination with clomiphene citrate may help in the treatment against idiopathic male infertility ⁽²⁵⁾, although it did not improve sperm count or motility ⁽⁴⁰⁾. Oral carnitine supplementation may improve mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome ⁽²⁾.

  There are studies looking into the effects of carnitine in cancer patients. L-carnitine supplementation improved nutritional status and quality of life in pancreatic cancer patients ⁽²⁷⁾. Other preliminary data show that L-carnitine by itself ^(15) (23) or in combination with Coenzyme Q10 ⁽³³⁾ may relieve chemotherapy-related fatigue. L-carnitine also demonstrated benefits against fatigue both in younger hypothyroid patients receiving levothyroxine and thyroid cancer patients who have hypothyroidism post-surgery ⁽⁴¹⁾. However, carnitine does not improve fatigue in patients with invasive malignancies ⁽²⁸⁾. Other preliminary data suggest l-carnitine may reduce vismodegib-associated muscle spasms ⁽⁵²⁾. Additional studies are needed to determine the cancer populations in which carnitine supplementation may be most beneficial.

  An ester derivative, acetyl-L-carnitine, is also available as a dietary supplement and is often used as a neuroprotective agent. It may help to reduce diabetic neuropathy ^(42) (43) or improve cognition in patients with severe hepatic encephalopathy ⁽⁴⁴⁾. In elderly patients with dysthymic disorder, it was found to be comparable with fluoxetine ⁽⁴⁵⁾; however, other studies did not find it effective for Alzheimer’s disease ^(46) (47). One study actually showed that acetyl-L-carnitine can increase chemotherapy-induced peripheral neuropathy (CIPN) ⁽³⁵⁾, and this negative effect persisted at long-term follow-up over 2 years ⁽⁵³⁾. Guidelines also do not recommend acetyl-l-carnitine to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm ⁽⁵⁴⁾. Therefore, patients receiving chemotherapy should avoid this product.

• Food Sources

  Meat, dairy products, beans, avocado

• Purported Uses
  • Alzheimer’s disease
  • Cardiovascular disease and symptoms
  • Cancer or AIDS-associated muscle wasting
  • Chemotherapy side effects
  • Chronic fatigue syndrome
  • Diabetes
  • High cholesterol
  • Infertility
  • Strength and stamina
• Mechanism of Action

  Carnitine is a non-essential amino acid, with only the L-isomer utilized in human bodies. It is available in many foods, and bioavailability from dietary sources is much higher (54–87%) than from oral supplements (14%–18%) ⁽⁴⁸⁾. L-carnitine plays a role in the transport of long chain fatty acids across the inner mitochondrial membrane, facilitating beta-oxidation of fatty acids and acting as an intracellular energy reservoir of acetyl groups. In deficiencies, these acyl esters accumulate and cause deleterious effects including inhibition of adenine nucleotide translocase, which impedes ATP production ⁽⁵⁾. Carnitine supplementation prevents oxidative stress and ameliorates mitochondrial function ⁽²⁹⁾. L-carnitine demonstrated a protective effect against statin-induced cellular damage via its anti-oxidative properties in rat hepatocytes ⁽³¹⁾.

  Animal studies show L-carnitine has cardioprotective effects by preventing skeletal muscle myopathy ⁽¹⁴⁾. In hemodialysis patients, carnitine has antiinflammatory and anticoagulation effects which may contribute to its cardioprotective activity ⁽²⁴⁾.

  In cardiac disease models, carnitine supplementation improved cardiac performance including improved myocardial metabolic patterns, reduced necrosis, diminished enzymatic infarct size, and preserved left ventricular function ⁽⁸⁾. Its effects on congestive heart failure-associated myopathy may be due to caspase inhibition and decreased TNF-alpha levels ⁽¹⁴⁾. Metabolism of dietary L-carnitine by intestinal microbiota produced trimethylamine-N-oxide (TMAO), a proatherogenic species, which accelerated atherosclerosis ⁽³⁰⁾.

  Carnitine is often proposed for the treatment of obesity and metabolic syndrome. Possible mechanisms include inhibition of stearoyl-CoA desaturase-1 activity, β-oxidation of fatty acids, and increased storage in the body tissues ⁽⁴⁹⁾.

  Animal studies show L-carnitine has anticatabolic effects by improving nitrogen balance either via increased protein synthesis or reduced protein degradation. Other studies show it prevents oxidative stress and ameliorates mitochondrial function ⁽²⁹⁾. It may help cancer-related cachexia by reducing proteasome activity ⁽⁵⁰⁾. Clinical trials are needed to determine the implications of this study in humans.

  In one trial, carnitine was shown to be effective in reversing hyperthyroidism by acting as a peripheral antagonist of thyroid hormone action ⁽³⁾.

• Adverse Reactions

  Rare: Dyspepsia, heartburn ⁽⁵⁾.

  Reported: Flu syndrome, injection-site reaction, pain, pharyngitis, headache, diarrhea, and hypertension ^(6) (9). High oral doses may cause unpleasant body odor ⁽⁵⁾.

  Case Report
  Hypoglycemia: In a patient with a rare genetic metabolic disorder who took carnitine supplements ⁽¹¹⁾.

• Herb-Drug Interactions

  Warfarin: L-carnitine may have additive anticoagulant effects when used with warfarin ^(24) (51).

• References

  1. Arsenian MA. Carnitine and its derivatives in cardiovascular disease. Progress Cardiovasc Dis 1997;40:265-86.

  2. Jamilian H, Jamilian M, Samimi M, et al. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol. Jun 2017;33(6):442-447.

  3. 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.

  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).

  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;52(5):1421-42.

  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;19(5):576-85.

  31. Abdoli N, Azarmi Y, Eghbal MA. Mitigation of statins-induced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes. Res Pharm Sci. 2015 Mar-Apr;10(2):143-51.

  32. Gimenes AC, Bravo DM, Nápolis LM, et al. Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy. Braz J Med Biol Res. 2015 Apr;48(4):354-62.

  33. Iwase S, Kawaguchi T, Yotsumoto D, et al. Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01). Support Care Cancer. 2016;24(2):637-46.

  34. Greenlee H, Balneaves LG, Carlson LE, et al. Clinical practice guidelines on the use of integrative therapies as supportive care in patients treated for breast cancer. J Natl Cancer Inst Monogr. Nov 2014;2014(50):346-358.

  35. Hershman DL, Unger JM, Crew KD, et al. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol. Jul 10 2013;31(20):2627-2633.

  36. Tarantini G, Scrutinio D, Bruzzi P, et al. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-223.

  37. Rafraf M, Karimi M, Jafari A. Effect of L-carnitine supplementation in comparison with moderate aerobic training on serum inflammatory parameters in healthy obese women. J Sports Med Phys Fitness. Nov 2015;55(11):1363-1370.

  38. Ahmadi S, Dehghan Banadaki S, Mozaffari-Khosravi H. Effects of Oral L-Carnitine Supplementation on Leptin and Adiponectin Levels and Body Weight of Hemodialysis Patients: a Randomized Clinical Trial. Iran J Kidney Dis. May 2016;10(3):144-150.

  39. Serban MC, Sahebkar A, Mikhailidis DP, et al. Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials. Sci Rep. Jan 12 2016;6:19188.

  40. Sigman M, Glass S, Campagnone J, et al. Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial. Fertil Steril. May 2006;85(5):1409-1414.

  41. An JH, Kim YJ, Kim KJ, et al. L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial. Endocr J. Oct 29 2016;63(10):885-895.

  42. 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. Jan 2005;28(1):89-94.

  43. Li S, Chen X, Li Q, et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. J Diabetes Investig. Sep 2016;7(5):777-785.

  44. Malaguarnera M, Vacante M, Motta M, et al. Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial. Metab Brain Dis. Dec 2011;26(4):281-289.

  45. Bersani G, Meco G, Denaro A, et al. L-Acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine. Eur Neuropsychopharmacol. Oct 2013;23(10):1219-1225.

  46. Thal LJ, Calvani M, Amato A, et al. A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology. Sep 26 2000;55(6):805-810.

  47. Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer’s disease. Neurology. Sep 1996;47(3):705-711.

  48. Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. Nov 2004;1033:30-41.

  49. Panchal SK, Poudyal H, Ward LC, et al. Modulation of tissue fatty acids by L-carnitine attenuates metabolic syndrome in diet-induced obese rats. Food Funct. Aug 2015;6(8):2496-2506.

  50. Busquets S, Serpe R, Toledo M, et al. L-Carnitine: an adequate supplement for a multi-targeted anti-wasting therapy in cancer. Clin Nutr. Dec 2012;31(6):889-895.

  51. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med. Jan 1993;233(1):94.

  52. Cannon JGD, Tran DC, Li S, et al. Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator-initiated trial. J Eur Acad Dermatol Venereol. Jul 2018;32(7):e298-e299.

  53. Hershman DL, Unger JM, Crew KD, et al. Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715). J Natl Cancer Inst. Jun 1 2018;110(6):669-676.

  54. Lyman GH, Greenlee H, Bohlke K, et al. Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline. J Clin Oncol. Sep 1 2018;36(25):2647-2655.