L-Carnitine

Abstract

This information is compiled by the Anticancer Fund and is based on the professional information.
 Last Updated: January 2015

 

L-Carnitine is a naturally occurring compound which is present in cells and tissues  and is mostly located within skeletal muscles, where it is critical for the supply of energy. L-Carnitine is essential to the transportation of fatty acids into mitochondria, which are membrane-enclosed organelles that function as a sort of cellular power plants. In the human body, it also plays an important role in the stress response. L-Carnitine is not regarded as an essential nutrient because humans obtain it from both endogenous (produced within the body) synthesis and dietary sources. Only in certain situations (e.g. increased renal loss) could the need exceed the capacity of the body’s own production. As a commercial product, L-carnitine is made by cell cultures (in the laboratory) and usually sold as a supplement for oral use.

Preliminary evidence suggests that L-carnitine may protect from chemotherapy-induced neurotoxicity and may improve sexual dysfunction in patients after prostatectomy. The evidence that L-carnitine is effective in the treatment of cancer-related fatigue and cancer anorexia-cachexia syndrome is weak. There is no evidence sustaining that L-carnitine has direct antitumor effects.

All clinical data suggest that L-carnitine is well tolerated and has been safely used in clinical trials at doses from 250 milligrams up to six grams per day for up to six months.

What is it?

L-Carnitine is a naturally occurring compound which is present in humans, most animal species, numerous microorganisms and plants. The vital metabolic functions of L-carnitine are to facilitate the transport of fatty acids across the mitochondrial membranes, which function as a sort of cellular power plants, providing energy to cells. Further functions being discussed are: regulation of cell death and inflammation, protection from free radicals and modulation of proteins, cellular stress response, and gene expression.

Humans obtain L-carnitine from both endogenous synthesis ( the body’s own production) and their diet. Meat, fish and dairy products are rich in L-carnitine and valuable dietary sources. A well-balanced Western diet provides about 100-300mg L-carnitine per day. However, not all of the consumed L-carnitine is absorbed by the body. In healthy adults with a balanced diet, the body’s own production is capable of covering the required amount of L-carnitine.

The synthesis of L-carnitine occurs primarily in the liver, whereas heart and skeletal muscles, the target organs, are incapable of producing L-carnitine. Circulating L-carnitine is excreted via the kidneys. Renal tubules contain a highly efficient L-carnitine transport system that reabsorbs more than 98% of the L-carnitine.This mechanism is effective in conserving L-carnitine body stores even during L-carnitine-poor diets. If tubular reabsorption is affected by kidney disease or inhibited by other compounds or drugs, the increased urinary loss can result in depletion of L-carnitine body stores.


Scientific and other names

Carnitine was named from the Latin word for ‘flesh’ as it was discovered from muscle tissue. Other names used include: Levocarnitine, carnitor, carnitene, Karnitin, and Vitamin BT.

Does it work?

Cancer-related fatigue (CrF) and other patient-reported outcomes

The evidence that L-carnitine has beneficial effects on CrF and other patient-reported outcomes (quality of life, quality of sleep) in patients with advanced cancers is rather weak.

 

Cancer anorexia-cachexia syndrome (CACS)

There is evidence that L-carnitine has beneficial effects on parameters related to CACS, based on the results of one randomized controlled trial and one uncontrolled study including 12 patients with advanced cancers.

 

Sexual dysfunction

One study on the effectiveness of interventions for sexual dysfunction found some positive effects when L-carnitine was combined with other drugs that improve sexual dysfunction.

 

Chemotherapy-induced peripheral neuropathy (CIPN)

There is evidence from two uncontrolled studies including 52 patients with different grades of CIPN that acetyl-L-carnitine is beneficial in the treatment of chemotherapy-induced peripheral neuropathy.
Evidence that acetyl-L-carnitine or L-carnitine might protect from CIPN comes from two RCTs and is contradictory. The findings from the most recent trial introduce a note of caution in that there are indications that ALC could even increase CIPN.

 

Cardiotoxicity

There is currently insufficient evidence that L-carnitine protects from anthracyclin-induced cardiotoxicity. The evidence that L-carnitine might prevent cancer patients with concomitant heart diseases from cardiac toxicity is weak.

Is it safe?

The oral or parental (other route dan the digestive tract, e.g.: intravenous) use of L-carnitine is regarded as “likely safe when used appropriately according to FDA approved prescriptions". Oral L-carnitine has been safely used in children for up to 2 months and intravenously in preterm infants. For pregnant women, there is insufficient reliable information available to date. L-Carnitine is secreted in the breast milk, but use during breast-feeding is regarded as safe because supple-mental doses of L-carnitine were administered to children in formula diets without reported adverse effects. One up to six grams L-carnitine per day has been safely used in clinical trials lasting from 4 weeks to 6 months.

 

Adverse effects

L-carnitine used orally or intravenously has been less frequently associated with nausea and gastrointestinal upset of minor intensity.

 

Contraindications

Patients under thyroid medications should not take L-carnitine except under a physician's supervision. Individuals with low or borderline-low thyroid levels should avoid L-carnitine because it might impair the action of thyroid hormones.

 

Interactions

It has been observed that long-term treatment with ementine, pivalic acid and the anticonvulsant valproic acid leads to secondary carnitine deficiency. One animal study alsoindicates that combining acetyl-L-carnitine with mitoxantrone might be inappropriate.

 

Quality issues

The use of supplements containing D-enantiomers of carnitine or DL racemats should be avoided.

More info

Application and dosage

As L-carnitine is not regarded  an essential nutrient, no values for dietary reference intake or recommended daily allowance have been set. For supplementation or pharmacological purposes, L-carnitine is available as capsules, tablets or powder for oral use and as solutions for intravenous (into the vein) administration. Typical doses investigated in clinical trials ranged from 250 mg/kg/day up to 6g per day.

 

Claims of efficacy and alleged indications

Supplementation with L-carnitine is claimed to exert benefits in cancer patients as complementary therapy: to protect organs from chemo- and radiotherapy-related toxicities and to counteract cancer related fatigue (CRF) and cancer-associated cachexia syndrome (CACS), which referes to the loss of body mass that cannot be reversed nutritionally.

 

Prevalence of use

There are no data available on the prevalence of use of carnitine in cancer patients.

 

Legal issues

Carnitor® (L-carnitine) is FDA approved for the treatment of carnitine deficiencies of genetic origin. In the EU, L-carnitine is approved for use in all foodstuffs intended for particular nutritional uses. According to the Office of Dietary Supplements, L-carnitine and acetyl-L-carnitine are approved dietary supplements in the US. In the EU, propionyl-L-carnitine is also approved.

 

Costs and expenditures

Good quality L-carnitine supplements cost about € 0.30 per 1000mg. Taking into account the typical daily doses of 10-50mg/kg, costs for a 70kg patient would amount to about € 8 to 30 per month.

Abstract

This information was compiled and reviewed by the CAM-Cancer consortium. Last Updated: January 2015.

  • L-carnitine is a biosynthesized compound which is also obtained from dietary sources
  • L-carnitine is essential for the transportation of fatty acids into mitochondria and maintains homeostasis in key mitochondrial lipids and proteins
  • Preliminary evidence suggests that L-carnitine might protect nervous tissue from chemotherapy-induced toxicity, improves cancer anorexia-cachexia syndrome and helps against erectile dysfunction after prostatectomy
  • There is evidence that patients with advanced cancer and cancer-related fatigue do not benefit from L-carnitine supplementation
  • Supplementation of L-carnitine is safe with only minor adverse events

Carnitine is the generic term for a compound occurring naturally in humans, most animals, plants and microorganisms. It is part of the group of compounds that includes acetyl-L-carnitine and propionyl-L-carnitine. Most of the body’s carnitine is located within skeletal muscles, where it is critical for the supply of energy by the beta-oxidation of fatty acids. It also plays an important role in the stress response by modulating inflammatory and oxidative processes.

L-carnitine is not regarded as an essential nutrient because humans obtain it through biosynthesis as well as from dietary sources. Only in certain situations (e.g. increased renal loss) can the need exceed the capacity of biosynthesis. The most common commercial production of L-carnitine involves biosynthesis using cell cultures, and it is usually sold as oral supplements. 

There is evidence from four randomized controlled trials (RCTs) indicating that L-carnitine does not reduce cancer-related fatigue in patients with advanced cancer.

There is weak evidence from one small RCT and one uncontrolled study to show that L-carnitine has a positive influence on cancer anorexia-cachexia syndrome and there is also evidence that acetyl-L-carnitine or propionyl-L-carnitine could be of help in reducing erectile dysfunction after prostatectomy.

There is also weak evidence from two uncontrolled studies that acetyl-L-carnitine is effective in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Evidence concerning the prevention of CIPN through acetyl-L-carnitine is contradictory, and findings from the most recent trial introduce a note of caution because it appears possible that acetyl-L-carnitine could even increase CIPN.

There is weak evidence that L-carnitine does not protect against anthracyclin-induced cardiotoxicity, and that it reduces cardiac side effects from interleukin-2.

All clinical data suggest that L-carnitine is well tolerated and has been safely used in clinical trials at doses from 250mg to 6g per day for up to six months.

What is it?

What is it?

L-carnitine (LC) is a naturally occurring compound which is present in humans, most animal species, numerous microorganisms and plants.(1) Together with its short-, medium- and long-chain esters, collectively referred to as acylcarnitines, LC forms the major component of the body’s carnitine pool. Other carnitine compounds include acyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC).

The vital metabolic functions of LC are to facilitate the transport of fatty acids (acyl groups) as acylcarnitines across the mitochondrial membrane for beta-oxidation, to maintaining adequate mitochondrial levels of free coenzyme A and to buffer excess acetyl-coenzyme A. (2) Further functions are: regulation of apoptosis and inflammation, protection from free radicals and modulation of proteins, cellular stress response and gene expression. (3-6)

Humans obtain LC both from endogenous synthesis and their diet. Meat, fish and dairy products are rich in LC and therefore valuable dietary sources; a well-balanced Western diet provides about 100-300mg LC per day. (7) However, in healthy adults with a balanced diet not all of the consumed LC is absorbed intestinally because the body is capable of synthesizing the amount it requires.

Ratios of tissue-to-plasma levels of LC and ALC are high, with a hundredfold difference between concentrations in skeletal muscle and blood plasma. Blood plasma contains both free (~80%) and esterified LC, usually in the form of ALC (20%) and plasma levels of total (free + esterified) LC are kept within narrow limits (40-50 micromole/L in healthy adults). (8, 9)

Circulating LC is excreted via the kidneys as LC or ALC. Renal tubules contain a highly efficient LC transport system that re-absorbs more than 98% of the LC in the glomerular filtrate. This mechanism is effective in conserving LC body stores even during LC-poor diets. If tubular reabsorption is affected by kidney disease, or inhibited by other compounds or drugs, the increased urinary loss can result in depletion of LC body stores. (8)

Scientific and other names

Carnitine was named from the Latin word for flesh (‘carno’) because it was first discovered in muscle tissue. Carnitine is a trimethylated amino acid and its chemical name is (3R)-3-hydroxy-4-(trimethylazaniumyl) butanoate (IUPAC). Carnitine contains a chiral centre and exists in two enantiomeric forms. L-carnitine is the biologically active enantiomer of carnitine. Other names used include: levocarnitine, carnitor, carnitene, karnitin and vitamin BT.

Ingredients

The majority of carnitine supplements contain LC. However, compounds containing the esterized forms ALC and PLC are also available over the counter.

Application and dosage

As LC is not regarded as an essential nutrient, no values for dietary reference intake or recommended daily allowance have been set. For supplementation or pharmacological purposes, LC is available as capsules, tablets or powder for oral use and as solutions for intravenous administration. Typical doses investigated in clinical trials have ranged from 250mg to 6g per day.

History/providers

Carnitine was discovered in 1905, isolated from muscle tissue. (1) Its chemical structure and major physiological functions were elucidated in the 1920s–1950s and investigations from the 1960s onwards have  led to the uncovering of its biosynthetic pathway, transport mechanisms and deficiency syndromes. (10) Today, leading manufacturers use prokaryotic biotransformation processes analogous to the natural biosynthetic pathway of carnitine, which yield pure LC with high efficiency. (11)

Claims of efficacy and alleged indications

Supplementation with LC is claimed to protect organs from chemo- and radiotherapy-related toxicities and to counteract cancer-related fatigue (CrF)and cancer anorexia-cachexia syndrome (CACS).

Mechanisms of action

The following explanations for the molecular mechanisms of action of LC are currently under discussion:

  1. Results from animal studies indicate that cancer-related cachexia is associated with liver-acinus lipid-metabolism zonation and decreased activity of carnitine palmitoyl transferases (CPT I and CPT II) (12).Signs of cachexia have been found to be ameliorated in mice by modulating the expression and activity of CPTs and by regulating cytokines. (13, 14) This is in line with findings that malnourished and cachectic patients have reduced plasma concentrations and stores of carnitine in the body.(15-18) However, observations in carnitine-deficient patients with lower carnitine stores suggest that these did not affect resting energy expenditure or total food intake. (19)
  2. Long-chain fatty acids are the most energy-rich substrates for beta-oxidation, and increased skeletal muscle LC content has been reported to delay muscular fatigue in rats (20).It could be speculated that increases in ALC levels would have a significant impact on energy production, thus reducing fatigue.
  3. Findings in rats suggest that ALC could protect nervous tissue from chemotherapy-induced toxicity, through protein kinase C-related signalling pathways, by modulating the activities of nerve growth- and glial-derived neurotrophic factors, (21, 22) and by protecting the mitochondria of peripheral nerves. (23)
  4. Animal studies also suggest that LC and PLC could decrease the duration and severity of radiation-induced mucositis because of their capacity to scavenge reactive oxygen species, activate antioxidant enzymes and protect DNA from cleavage. (24, 25)
  5. There is evidence from rats that carnitine deficiency might aggravate carboplatin nephropathy (26) and that patients with decreased dietary carnitine uptake develop carnitine deficiency when treated repeatedly with chemotherapy, including platinum derivatives. (27, 29)
  6. There is evidence from two mouse models with carcinogen-induced cancers that dietary carnitine might inhibit the development of precancerous and neoplastic lesions.(30, 31)

Prevalence of use

There are no data available on the prevalence of use of carnitine in cancer patients.

Legal issues

In the USA,LC is approved by the Food and Drug Administration for the treatment of carnitine deficiencies and according to the Office of Dietary Supplements, LC and ALC are approved dietary supplements.(7) In the EU,LC and PLC are approved for use in foodstuffs for particular nutritional uses.(51)

Costs and expenditures

Good quality LC supplements cost about €0.30 per 1000mg. Taking into account typical daily doses of 10–50mg/kg, costs for a 70kg patient could amount to anything between €8.00 and €30.00 per month.

Does it work?

Please see Table 1 for details of clinical trials of LC, ALC and PLC.

Cancer-related fatigue

There is evidence from four recent randomized trials (RCTs), involving >800 participants with sufficiently robust measures of CrF that LC does not reduce moderate to severe CrF(35-37) or that ALC prevents from CrF occurring during taxane-based chemotherapy.(38)These findings contradict those from several uncontrolled studies suggesting that L-carnitine (LC) might help against CrF. (32-34)

 

Cancer anorexia-cachexia syndrome

There is evidence that LC has beneficial effects on parameters related to CACS, based on the results from one RCT (n=72) (36) and a prospective, uncontrolled study including 12 patients with advanced cancers (32).

 

Sexual dysfunction

The evidence that ALC and PLC could prevent sexual dysfunction in patients after prostatectomy comes from one RCT (39) which has been included and assessed in a Cochrane review on the effectiveness of interventions for sexual dysfunction. The review authors conclude that: ‘(...)there is some evidence suggestive that PDE5 [phosphodiesterase-inhibitor-5] inhibitors are more effective in combination with acetyl-L-carnitine and propionyl-L-carnitine.’(40)

 

Chemotherapy-induced peripheral neuropathy

There is evidence from two prospective, uncontrolled studies including 52 patients with different grades of CIPN that ALC is beneficial in the treatment of paclitaxel- and cisplatinum-induced peripheral neuropathy. (41, 42)

Evidence that ALC or LC might protect from CIPN comes from two RCTs and is contradictory. The findings from the most recent trial, including 409 women receiving adjuvant taxane-containing chemotherapy, introduce a note of caution in that there are indications that ALC could even increase CIPN.(38) The author of a review mentions, however, an unpublished ‘double-blind, placebo-controlled, multicentre trial on 119 cancer patients treated with taxol alone or in combination with other neurotoxic or non-neurotoxic drugs’ in which ‘significant action of AL-carnitine [Acetyl-L-carnitine] in improving vibratory sensation in patients with CIPN, compared with placebo’ was found.(43)

 

Cardiotoxicity

Waldneret al. found no evidence that LC protects against anthracyclin-related cardiotoxicity in an RCT involving 40 lymphoma patients (44), while Lissoniet al. found evidence that LC prevented cardiac adverse effects when high-dose interleukin-2 was used in an RCT with 30 patients.(45)

Is it safe?

The use of LC is regarded as ‘Likely safe when used orally and appropriately and when used parenterally as an FDA-approved prescription medicine’.(46)Oral LC has been used safely in children for up to 2 months and intravenously in preterm infants. For pregnant women, there is insufficient reliable information available to date. Although LC is secreted in breast milk, use during breast-feeding is regarded as safe because supplemental doses of LC have been administered to children in formula diets with no reported adverse effects.(46) Clinical trials lasting from four weeks to six months have used amounts  of LC from under 1g up to 6g per day without any apparent ill effects.

Adverse effects

In the studies discussed above, LC used orally or intravenously has been less frequently associated with nausea, insomnia, vomiting and gastrointestinal upset of minor intensity.

Contraindications

Patients using thyroid medications should not take LC unless supervised by a physician. Individuals with low or borderline-low thyroid levels should avoid taking supplemental LC because it might impair the action of thyroid hormones. (47)

Interactions

It has been observed that long-term treatment with ementine, pivalic acid and the anticonvulsant valproic acid leads to secondary carnitine deficiency. Histological findings of an animal study in mice with Ehrlich tumour indicate that combining ALC with mitoxantrone might be inappropriate. (48)

Quality issues

Supplements containing D-carnitine or dl-racemates should be avoided because D-carnitine can interfere with LC membrane transport, thus increasing the risk of LC deficiency.(49, 50)

References

  1. Bremer J. Carnitine--metabolism and functions. Physiol Rev. 1983;63(4):1420-80.
  2. Bremer J. The role of carnitine in intracellular metabolism. J Clin Chem Clin Biochem. 1990;28(5):297-301.
  3. Chapela SP, Kriguer N, Fernandez EH, Stella CA. Involvement of L-carnitine in cellular metabolism: beyond Acyl-CoA transport. Mini Rev Med Chem. 2009;9(13):1518-26.
  4. Jones LL, McDonald DA, Borum PR. Acylcarnitines: role in brain. Prog Lipid Res. 2010;49(1):61-75.
  5. Famularo G, De SC, Trinchieri V, Mosca L. Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann N Y Acad Sci. 2004;1033:132-8.
  6. Calabrese V, Giuffrida Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. Journal of J Nutr Biochem. 2006;17(2):73-88.
  7. Office of Dietary Supplements. Carnitine. Dietary Supplement Fact Sheet: http://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/. 2006, accessed 27 March 2014.
  8. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. ClinPharmacokinet. 2003;42(11):941-67.
  9. Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet. 2012;51(9):553-72.
  10. Wolf G. The discovery of a vitamin role for carnitine: The first 50 years. J Nutr. 2006;136(8):2131-4.
  11. Meyer HP, Robins KT. Large Scale Bioprocess for the Production of Optically Pure L-Carnitine. Chemical Monthly. 2011;136(8):1269-77.
  12. Kazantzis M, Seelaender MC, Kazantzis M, Seelaender MCL. Cancer cachexia modifies the zonal distribution of lipid metabolism-related proteins in rat liver. Cell Tissue Res. 2005;321(3):419-27.
  13. Laviano A, Molfino A, Seelaender M, Frascaria T, Bertini G, Ramaccini C, et al. Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats. Cancer Invest. 2011;29(10):696-700.
  14. Liu S, Wu HJ, Zhang ZQ, Chen Q, Liu B, Wu JP, et al. L-carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase. Cancer Biol Ther. 2011;12(2):125-30.
  15. Malaguarnera M, Risino C, Gargante MP, Oreste G, Barone G, Tomasello AV, et al. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia. World J Gastroenterol. 2006;12(28):4541-5.
  16. Vinci E, Rampello E, Zanoli L, Oreste G, Pistone G, Malaguarnera M, et al. Serum carnitine levels in patients with tumoral cachexia. European Journal of Internal Medicine. 2005;16(6):419-23.
  17. Sachan DS, Dodson WL, Sachan DS, Dodson WL. The serum carnitine status of cancer patients. J Am Coll Nutr. 1987;6(2):145-50.
  18. Szefel J, Kruszewski WJ, Ciesielski M, Szajewski M, Kawecki K, eksandrowicz-Wrona E, et al. L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia. Oncol Rep. 2012;28(1):319-23.
  19. Rabito EI, Leme IA, Demenice R, Portari GV, Jordao AA, Jr., Dos Santos JS, et al. Lower carnitine plasma values from malnutrition cancer patients. J Gastrointest Cancer. 2013;44(3):362-5.
  20. Brass EP, Scarrow AM, Ruff LJ, Masterson KA, Van LE. Carnitine delays rat skeletal muscle fatigue in vitro. J ApplPhysiol (1985). 1993;75(4):1595-600.
  21. Di Cesare ML, Ghelardini C, Toscano A, Pacini A, Bartolini A. The neuropathy-protective agent acetyl-L-carnitine activates protein kinase C-gamma and MAPKs in a rat model of neuropathic pain. Neuroscience. 2010;165(4):1345-52.
  22. Ossipov MH. Growth factors and neuropathic pain. Curr Pain Headache Rep. 2011;15(3):185-92.
  23. Jin HW, Flatters SJ, Xiao WH, Mulhern HL, Bennett GJ. Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Exp Neurol. 2008;210(1):229-37.
  24. Vanella A, Russo A, Acquaviva R, Campisi A, Di GC, Sorrenti V, et al. L -propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol. 2000;16(2):99-104.
  25. Ucuncu H, Ertekin MV, Yoruk O, Sezen O, Ozkan A, Erdogan F, et al. Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression: a controlled study in a rat model. J Radiat Res. 2006;47(1):91-102.
  26. Arafa HM. Carnitine deficiency aggravates carboplatin nephropathy through deterioration of energy status, oxidant/anti-oxidant balance, and inflammatory endocoids. Toxicology. 2008;254(1-2):51-60.
  27. Haschke M, Vitins T, Lude S, Todesco L, Novakova K, Herrmann R, et al. Urinary excretion of carnitine as a marker of proximal tubular damage associated with platin-based antineoplastic drugs. Nephrol Dial Transplant. 2010;25(2):426-33.
  28. Heuberger W, Berardi S, Jacky E, Pey P, Krahenbuhl S, Heuberger W, et al. Increased urinary excretion of carnitine in patients treated with cisplatin. Eur J Clin Pharmacol. 1998;54(7):503-8.
  29. Mancinelli A, D'Iddio S, Bisonni R, Graziano F, Lippe P, Calvani M, et al. Urinary excretion of L-carnitine and its short-chain acetyl-L-carnitine in patients undergoing carboplatin treatment. Cancer Chemother Pharmacol. 2007;60(1):19-26.
  30. Roscilli G, Marra E, Mori F, Di Napoli A, Mancini R, Serlupi-Crescenzi O, et al. Carnitines slow down tumor development of colon cancer in the DMH-chemical carcinogenesis mouse model. J Cell Biochem. 2013;114(7):1665-73.
  31. Dionne S, Elimrani I, Roy MJ, Qureshi IA, Sarma DR, Levy E, et al. Studies on the chemopreventive effect of carnitine on tumorigenesis in vivo, using two experimental murine models of colon cancer. Nutr Cancer. 2012;64(8):1279-87.
  32. Gramignano G, Lusso MR, Madeddu C, Massa E, Serpe R, Deiana L, 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.
  33. Cruciani RA, Dvorkin E, Homel P, Malamud S, Culliney B, Lapin J, et al. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage. 2006;32(6):551-9.
  34. Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer. 2002;86(12):1854-7.
  35. Cruciani RA, Zhang JJ, Manola J, Cella D, Ansari B, Fisch MJ. 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. Journal of clinical oncology : official journal of the J Clin Oncol. 2012;30(31):3864-9.
  36. Kraft M, Kraft K, Gärtner S, Mayerle J, Simon P, Weber E, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial. Nutr J. 2012;11:52.
  37. Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Lapin J, et al. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pain Symptom Manage. 2009;37(4):622-31.
  38. Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, 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. 2013;31(20):2627-33.
  39. Cavallini G, Modenini F, Vitali G, Koverech A. Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology. 2005;66(5):1080-5.
  40. Miles CL, Candy B, Jones L, Williams R, Tookman A, King M. Interventions for sexual dysfunction following treatments for cancer. Cochrane Database Syst Rev. 2007(4):CD005540.
  41. Bianchi G, Vitali G, Caraceni A, Ravaglia S, Capri G, Cundari S, et al. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer. 2005;41(12):1746-50.
  42. Maestri A, De Pasquale CA, Cundari S, Zanna C, Cortesi E, Crino L. A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy. Tumori. 2005;91(2):135-8.
  43. De GD. Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. CNS Drugs. 2007;21 Suppl 1:39-43.
  44. Waldner R, Laschan C, Lohninger A, Gessner M, Tuchler H, Huemer M, et al. Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma. J Cancer Res Clin Oncol. 2006;132(2):121-8.
  45. Lissoni P, Galli MA, Tancini G, Barni S. Prevention by L-carnitine of interleukin-2 related cardiac toxicity during cancer immunotherapy. Tumori. 1993;79(3):202-4.
  46. Natural Medicines Comprehensive Database. L-Carnitine.http://naturaldatabase.therapeuticresearch.com (accessed 26.7.2012) . 2012.
  47. Benvenga S. Effects of L-carnitine on thyroid hormone metabolism and on physical exercise tolerance. Horm Metab Res. 2005;37(9):566-71.
  48. Niang M, Soukup T, Zivny P, Tomsik P, Bukac J, Rezacova M, et al. Biochemical and pharmacological effects of mitoxantrone and acetyl-L-carnitine in mice with a solid form of Ehrlich tumour. Chemotherapy. 2011;57(1):35-42.
  49. Negrao CE, Ji LL, Schauer JE, Nagle FJ, Lardy HA. Carnitine supplementation and depletion: tissue carnitines and enzymes in fatty acid oxidation. J Appl Physiol (1985). 1987;63(1):315-21.
  50. Arancio O, Bonadonna G, Calvani M, Giovene P, Tomelleri G, De GD. Transitory L-carnitine depletion in rat skeletal muscle by D-carnitine. Pharmacol Res. 1989;21(2):163-8.
  51. http://www.efsa.europa.eu/en/efsajournal/doc/19.pdf (no longer available)

L-Carnitine

(3R)-3-hydroxy-4-(trimethylazaniumyl) butanoate

Levocarnitine

Carnitor

Carnitene

Karnitin

Vitamin BT