A Comprehensive Review on L-carnitine: A Promising Nutraceutical

Authors

  • AA Gunjal Department of Pharmacology, Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, India
  • AV Kulkarni Department of Pharmacology, Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, India
  • PK Bairagi Department of Pharmacology, Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, India
  • VY Chavan Department of Pharmacology, Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, India

DOI:

https://doi.org/10.25004/IJPSDR.2024.160325

Keywords:

Carnitine, L-carnitine, Nutrition, Health Benefits, Supplement

Abstract

L-carnitine (LC), which is a type of quaternary amine, is an essential element for energy metabolism in mammals, plants, and specific bacteria. Originating from the amino acid methionine and lysine, it is primarily synthesized in the kidneys and liver. L-carnitine is a pharmacologically active form of carnitine that plays a vital role in energy generation and the breakdown of fatty acids via β-oxidation in metabolism. Deficiencies in organic cation transporter-2 (OCTN2) can arise due to gene mutations or in conjunction with other conditions like renal or hepatic disorders. Deficiency in carnitine regulation results in several diseases, including cardiomyopathy, cirrhosis, diabetes, endocrine disorders, malnutrition, aging, sepsis, and malnutrition. LC is known for its anti-inflammatory and antioxidant properties. Research indicates that incorporating LC into the diet can ameliorate inflammatory ailments by decreasing the presence of inflammatory agents. Supplementation with LC is particularly useful for individuals with predominant carnitine deficiencies, which can be life-threatening, as well as certain subsidiary deficiencies like organic acid disorders, muscle wasting, and weakness. Moreover, emerging evidence suggests that LC may have therapeutic benefits for various diseases, including renal diseases, liver diseases, neurodegenerative disorders, cardiovascular diseases (CVDs), cancer, diabetes, cachexia, obesity, depression, and epilepsy.

Downloads

Download data is not yet available.

References

Almannai M, Alfadhel M, El-Hattab AW. Carnitine Inborn Errors of Metabolism. Molecules. 2019;24(18):3251. Available from: https://doi.org/10.3390/molecules24183251.

Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Role of carnitine in disease. Nutr Metab (Lond). 2010;16(7):30. Available from: https://doi.org/10.1186/1743-7075-7-30.

Ringseis R, Keller J, Eder K. Basic mechanisms of the regulation of L-carnitine status in monogastrics and efficacy of L-carnitine as a feed additive in pigs and poultry. J Anim Physiol Anim Nutr (Berl). 2018;102(6):1686–719. Available from: https:// doi.org/10.1111/jpn.12959.

Alhasaniah AH. l-carnitine: Nutrition, pathology, and health benefits. Saudi J Biol Sci. 2023;30(2):103555. Available from: https://doi.org/10.1016/j.sjbs.2022.103555.

Cave MC, Hurt RT, Frazier TH, Matheson PJ, Garrison RN, McClain CJ, et al. Obesity, Inflammation, and the Potential Application of Pharmaconutrition. Nutrition in Clinical Practice. 2008;23(1):16–34. Available from: https://doi.org/10.1177/ 011542650802300116.

Roseiro LC, Santos C. Carnitines (Including l-Carnitine, Acetyl-Carnitine, and Proprionyl-Carnitine). Nonvitamin and Nonmineral Nutritional Supplements. 2019;45–52. Available from: https://doi.org/10.1016/B978-0-12-812491-8.00006-0

Ed (Edgar181). Chemical structure of carnitine. Wikimedia Commons. 2014. https://commons.wikimedia.org/wiki/File:Carnitine.svg

Bonomini M, Zammit V, Pusey CD, De Vecchi A, Arduini A. Pharmacological use of l-carnitine in uremic anemia: Has its full potential been exploited? Pharmacol Res. 2011;63(3):157–64. Available from: https://doi.org/10.1016/j. phrs.2010.11.006.

Ribas GS, Vargas CR, Wajner M. l-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene. 2014;533(2):469–76. Available from: https://doi.org/10.1016/j.gene.2013.10.017.

Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM. Significance of l-carnitine for human health. IUBMB Life. 2017;69(8):578–94. Available from: https://doi.org/10.1002/iub.1646

Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiol Aging. 1995;16(1):1–4. Available from: https://doi.org/10.1016/0197-4580(95)80001-8.

Malaguarnera M. Acetyl-L-carnitine in hepatic encephalopathy. Metab Brain Dis. 2013;28(2):193–9. Available from: https://doi.org/10.1007/s11011-013-9376-4.

Jin M, Pan T, Cheng X, Zhu TT, Sun P, Zhou F, et al. Effects of supplemental dietary l-carnitine and bile acids on growth performance, antioxidant, and immune ability, histopathological changes, and inflammatory response in juvenile black seabream (Acanthopagrus schlegelii) fed high-fat diet. Aquaculture. 2019;12(4):199–209. Available from: https://doi.org/10.1016/j. aquaculture.2019.01.063.

Gao X, Sun G, Randell E, Tian Y, Zhou H. Systematic investigation of the relationships of trimethylamine N-oxide and L-carnitine with obesity in both humans and rodents. Food Funct. 2020;11(9):7707–16. Available from: https://doi.org/10.1039/d0fo01743d.

El-Hattab AW, Scaglia F. Disorders of carnitine biosynthesis and transport. Mol Genet Metab. 2015;116(3):107–12. Available from: https://doi.org/10.1016/j.ymgme.

Luo H, Zhang Y, Guo H, Zhang L, Li X, Ringseis R, et al. Transcriptional regulation of the human, porcine, and bovine OCTN2 gene by PPARα via a conserved PPRE located in intron 1. J Eur Acad Dermatol Venereol. 2014;33(8):1569-1576. Available from: https://doi.org/10.1186/s12863-014-0090-y.

Hu C, Lancaster CS, Zuo Z, Hu S, Chen Z, Rubnitz JE, et al. Inhibition of OCTN2-Mediated Transport of Carnitine by Etoposide. Mol Cancer Ther. 2012;11(4):921. Available from: https://doi.org/10.1158/1535-7163.MCT-11-0980

Tamai I, Ohashi R, Nezu JI, Yabuuchi H, Oku A, Shimane M, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem. 1998;273(32):20378–82. Available from: https://doi: 10.1074/jbc.273.32.20378.

Elimrani I, Lahjouji K, Seidman E, Roy MJ, Mitchell GA, Qureshi I. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2003;15(5):863–871. Available from: https://doi:10.1152/ajpgi.00220.2002.

Nezu JI, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nature Genetics. 1999;21(1):91–4. Available from: https://doi.org/10.1038/5030.

Mayatepek E, Nezu J, Tamai I, Oku A, Katsura M, Shimane M, et al. Two Novel Missense Mutations of the OCTN2 Gene (W283R and V446F) in a Patient with Primary Systemic Carnitine Deficiency. Human Mutation. 1999;15(1):118. Available from: https://doi.org/10.1002/(sici)1098-1004(200001)15.

Reuter SE, Faull RJ, Evans AM. L-carnitine supplementation in the dialysis population: Are Australian patients missing out? Nephrology. 2008;13(1):3–16. Available from: https:// doi.org/10.1111/j.1440-1797.2007.00817.x.

Magoulas PL, El-Hattab AW. Systemic primary carnitine deficiency: An overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2012;7(1):1–6. Available from: https://doi.org/10.1186/1750-1172-7-68.

Amat di San Filippo C, Taylor MRG, Mestroni L, Botto LD, Longo N. Cardiomyopathy and carnitine deficiency. Mol Genet Metab. 2008;94(2):162–166. Available from: https:// doi.org/10.1097/HCR.0b013e3181f1fd65.

de Boer L, Kluijtmans LAJ, Morava E. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency. JIMD Rep. 2013;10:39. Available from: https://doi.org/10.1159/000465531.

Scaglia F, Longo N. Primary and secondary alterations of neonatal carnitine metabolism. Semin Perinatol. 1999;23(2):152–61. Available from: https://doi.org/10.1177/2333794X19830696.

II JLM, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018;6(24):473–473. Available from: https://doi.org/10.1016/ j.clnu.2018.06.1187.

Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, et al. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999;291(2):778–784. Available from: https://doi. org/10.1111/j.1742-7843.2009.00480.x.

Giammarioli S, Boniglia C, Carratù B, Ciarrocchi M, Chiarotti F, Mosca M, et al. Use of food supplements and determinants of usage in a sample Italian adult population. Public Health Nutr. 2013;16(10):1768–81. Available from: https://doi. org/10.1017/S1368980012004314.

Santini A, Novellino E. Nutraceuticals: Beyond the Diet Before the Drugs. Curr Bioact Compd. 2014;10(1):1–12. Available from: https://doi.org/10.2174/ 157340721001140724145924.

Lordan R. Dietary supplements and nutraceuticals market growth during the coronavirus pandemic – Implications for consumers and regulatory oversight. PharmaNutrition. 2021;18:100282. Available from: https://doi.org/10.1016/j.phanu.2021.100282.

Kepka A, Ochocinska A, Borzym‐kluczyk M, Skorupa E, Stasiewicz‐jarocka B, Chojnowska S, et al. Preventive Role of L-Carnitine and Balanced Diet in Alzheimer’s Disease. Nutrients. 2020;12(7):1987. Available from: https://doi.org/ 10.3390/nu12071987.

Lovells H, FedEx B. GRAS Notice (GRN) No. 993. U.S. Food and Drug Administration. 2021. https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory Hogan Lovells. 2021.

Rigault C, Mazué F, Bernard A, Demarquoy J, Le Borgne F. Changes in l-carnitine content of fish and meat during domestic cooking. Meat Sci. 2008;78(3):331–5. Available from: https://doi.org/10.1016/j.meatsci.2007.06.011.

Rospond B, Chłopicka J. [The biological function of L-carnitine and its content in the particular food examples]. Przegl Lek. 2013;70(2):85-91. Available from: https://doi.org/ 10.1161/01.CIR.65.1.115.

Lenk K, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2010;1(1):9–21. Available from: https://doi.org/10.1007/s13539-010- 0007-1.

Remels AHV, Gosker HR, Langen RCJ, Schols AMWJ. The mechanisms of cachexia underlying muscle dysfunction in COPD. J Appl Physiol. 2013;114(9):1253–62. Available from: https://doi.org/10.1152/japplphysiol.00790.2012.

Powers SK, Lynch GS, Murphy KT, Reid MB, Zijdewind I. Disease-induced skeletal muscle atrophy and fatigue. Med Sci Sports Exerc. 2016;48(11):2307–19. Available from: https://doi.org/10.1249/MSS.0000000000000975.

Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: A new definition. Clinical Nutrition. 2008;27(6):793–9. Available from: https://doi.org/10.1016/j.clnu.2008.06.013.

Furrer R, Handschin C. Muscle Wasting Diseases: Novel Targets and Treatments. Annu Rev Pharmacol Toxicol. 2019;6(59):315-339. Available from: https://doi.org/ 10.1146/annurev-pharmtox-010818-021041.

Montesano A, Senesi P, Luzi L, Benedini S, Terruzzi I. Potential therapeutic role of L-carnitine in skeletal muscle oxidative stress and atrophy conditions. Oxid Med Cell Longev 2015;2015:646171. Available from: https://doi.org/10.1155/2015/ 646171.

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. European Journal of Nutrition. 2013;52(5):1421–42. Available from: https://doi.org/ 10.1017/S1751731111001327.

Langen RCJ, Haegens A, Vernooy JHJ, Wouters EFM, De Winther MPJ, Carlsen H, et al. NF-κB Activation Is Required for the Transition of Pulmonary Inflammation to Muscle Atrophy. Am J Respir Cell Mol Biol. 2012;47(3):288-97. Available from: https://doi.org/10.1165/rcmb.2011-0119OC.

Busquets S, Serpe R, Toledo M, Betancourt A, Marmonti E, Orpí M, et al. L-Carnitine: An adequate supplement for a multi-targeted anti-wasting therapy in cancer. Clinical Nutrition. 2012;31(6):889–95. Available from: https://doi.org/10.1016/ j.clnu.2012.03.005.

Genazzani AD, Lanzoni C, Ricchieri F, Santagni S, Rattighieri E, Chierchia E, et al. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea. J Endocrinol Invest. 2011;34(4):287–91. Available from: https://doi.org/10.3275/6997.

Vescovo G, Ravara B, Gobbo V, Sandri M, Angelini A, Barbera M Della, 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(3 52-3). Available from: https://doi.org/10.1152/ ajpcell.00046.2002.

Tamilselvan J, Jayaraman G, Sivarajan K, Panneerselvam C. Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: Role of carnitine and lipoic acid. Free Radic Biol Med. 2007;43(12):1656–69. Available from: https://doi.org/10.1016/j. freeradbiomed.2007.08.028.

Di Liberato L, Arduini A, Rossi C, Di Castelnuovo A, Posari C, Sacchetta P, et al. l-Carnitine status in end-stage renal disease patients on automated peritoneal dialysis. J Nephrol. 2014;27(6):699–706. Available from: https://doi. org/10.1007/s40620-014-0076-x.

Keller J, Ringseis R, Koc A, Lukas I, Kluge H, Eder K. Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets. Animal 2012;6(1):70–8.

Wu C, Zhu M, Lu Z, Zhang Y, Li L, Li N, et al. L-carnitine ameliorates the muscle wasting of cancer cachexia through the AKT/FOXO3a/MaFbx axis. Nutr Metab (Lond). 2021;18(1):1–15. Available from: https://doi.org/10.1186/s12986-021-00623-7

Montesano A, Senesi P, Luzi L, Benedini S, Terruzzi I. Potential therapeutic role of L-carnitine in skeletal muscle oxidative stress and atrophy conditions. Oxid Med Cell Longev 2015;2015.

Keller J, Ringseis R, Priebe S, Guthke R, Kluge H, Eder K. Dietary L-carnitine alters gene expression in skeletal muscle of piglets. Mol Nutr Food Res. 2011;55(3):419–29. Available from: https://doi/10.1002/mnfr.201000293

Murata K, Kaji K, Nishimura N, Enomoto M, Fujimoto Y, Takeda S, et al. Rifaximin enhances the L carnitine mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut liver muscle axis. Int J Mol Med. 2022;50(2). Available from: https://pubmed.ncbi.nlm.nih.gov/35686541/

Zhang Z yu, Fan Z kai, Cao Y, Jia Z qiang, Li G, Zhi X dong, et al. Acetyl-l-carnitineameliorates mitochondrial damage and apoptosis following spinal cord injury in rats. Neurosci Lett. 2015;604:18–23.

Aliev G, Liu J, Shenk JC, Fischbach K, Pacheco GJ, Chen SG, et al. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. J Cell Mol Med. 2009;13(2):320–33. Available from: https://doi/10.1111/j.1582-4934.2008.00324.x

Suchy J, Chan A, Shea TB. Dietary supplementation with a combination of α-lipoic acid, acetyl-l-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance. Nutrition Research. 2009;29(1):70–4.

Zhou P, Chen Z, Zhao N, Liu D, Guo ZY, Tan L, et al. Acetyl-l-Carnitine Attenuates Homocysteine-Induced Alzheimer-Like Histopathological and Behavioral Abnormalities. 2011;14(6):669–79. Available from: https://doi/10.1089/rej.2011.1195

Zhang H, Jia H, Liu J, Ao N, Yan B, Shen W, et al. Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease. J Cell Mol Med. 2010;14(1–2):215–25. Available from: https://doi/10.1111/j.1582-4934.2008.00390.x

Afshin-Majd S, Bashiri K, Kiasalari Z, Baluchnejadmojarad T, Sedaghat R, Roghani M. Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson’s disease in the rat. Biomedicine & Pharmacotherapy. 2017;89:1–9.

Burks S, Raymick J, Robinson B, Hanig J, Sarkar S. Neuroprotective effects of acetyl-l-carnitine (ALC) in a chronic MPTP-induced Parkinson’s disease mouse model: Endothelial and microglial effects. Neurosci Lett. 2019;703:86–95.

Acosta MF, Muralidhran P, Abrahamson MD, Grijalva CL, Carver M, Tang H, et al. Comparison of l-Carnitine and l-Carnitine HCL salt for targeted lung treatment of pulmonary hypertension (PH) as inhalation aerosols: Design, comprehensive characterization, in vitro 2D/3D cell cultures, and in vivo MCT-Rat model of PH. Pulm Pharmacol Ther. 2020;65:101998.

Di Cesare Mannelli L, Vivoli E, Salvicchi A, Schiavone N, Koverech A, Messano M, et al. Antidepressant-like effect of artemin in mice: A mechanism for acetyl-l-carnitine activity on depression. Psychopharmacology (Berl). 2011;218(2):347–56. Available from: https://doi/10.1007/s00213-011-2326-0

Smeland OB, Meisingset TW, Borges K, Sonnewald U. Chronic acetyl-l-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochem Int. 2012;61(1):100–7.

Hussein AM, Adel M, El-Mesery M, Abbas KM, Ali AN, Abulseoud OA. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70. Brain Sciences. 2018;8(3):45.

Esmail M, Anwar S, Kandeil M, El-Zanaty AM, Abdel-Gabbar M. Effect of Nigella sativa, atorvastatin, or L-Carnitine on high fat diet-induced obesity in adult male Albino rats. Biomedicine & Pharmacotherapy. 2021;141:111818.

Wu T, Guo A, Shu Q, Qi Y, Kong Y, Sun Z, et al. l-Carnitine intake prevents irregular feeding-induced obesity and lipid metabolism disorder. Gene. 2015;554(2):148–54.

Savitha S, Naveen B, Panneerselvam C. Carnitine and lipoate ameliorates lipofuscin accumulation and monoamine oxidase activity in aged rat heart. Eur J Pharmacol. 2007;574(1):61–5.

O’Brien D, Chunduri P, Iyer A, Brown L. l-Carnitine Attenuates Cardiac Remodelling rather than Vascular Remodelling in Deoxycorticosterone Acetate-Salt Hypertensive Rats. Basic Clin Pharmacol Toxicol. 2010;106(4):296–301. Available from: https://doi/10.1111/j.1742-7843.2009.00480.x

Strilakou AA, Lazaris AC, Perelas AI, Mourouzis IS, Douzis IC, Karkalousos PL, et al. Heart dysfunction induced by choline-deficiency in adult rats: The protective role of l-carnitine. Eur J Pharmacol. 2013;709(1–3):20–7.

Tousson E, Tawfeek Zaki Z, Ali Abu-Shaeir W, Hassan H. Methotrexate-induced Hepatic and Renal Toxicity: Role of L-carnitine in Treatment "Methotrexate-induced Hepatic and Renal Toxicity: Role of L-carnitine in Treatment. Biomedicine and Biotechnology. 2014;2(4):85–92.

Ganai AA, Jahan S, Ahad A, Abdin MZ, Farooqi H. Glycine propionyl l-carnitine attenuates d-Galactosamine induced fulminant hepatic failure in Wistar rats. Chem Biol Interact. 2014;214(1):33–40.

Abu Ahmad N, Armaly Z, Berman S, Jabour A, Aga-Mizrachi S, Mosenego-Ornan E, et al. l-Carnitine improves cognitive and renal functions in a rat model of chronic kidney disease. Physiol Behav. 2016;164:182–8.

Gao J, Gu Z, Li M, Xu Y, Gao Y, Wei J, et al. L-Carnitine Ameliorates the Decrease of Aquaporin 2 Levels in Rats with Cisplatin-Induced Kidney Injury. Nephron. 2017;135(4):315–25. Available from: https://doi/10.1159/000455052

Stangenberg S, Nguyen LT, Chan YL, Zaky A, Pollock CA, Chen H, et al. Maternal L-carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking. Clin Exp Pharmacol Physiol. 2019;46(2):183–93. Available from: https://doi/10.1111/1440-1681.13038

Zheng HL, Zhang HY, Zhu CL, Li HY, Cui S, Jin J, et al. L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K/AKT/PTEN signaling. 2020. Available from: https://doi/10.1038/s41401-020-0449-8

C̈ekin AH, GüR G, Türkoǧlu S, Aldemir D, Uǧur Yilmaz, Gürsoy M, et al. The protective effect of L-carnitine on hepatic ischemia-reperfusion injury in rats. Turkish Journal of Gastroenterology. 2013;24(1):51–6.

Wang W, Bai M, Jiang T, Li C, Li P, Zhou H, et al. Clozapine-induced reduction of l-carnitine reabsorption via inhibition/down-regulation of renal carnitine/organic cation transporter 2 contributes to liver lipid metabolic disorder in mice. Toxicol Appl Pharmacol. 2019;363:47–56.

Eldamarawi M, Nassef N. Protective effect of the combined use of L-carnitine and L-arginine against hepatic ischemia-reperfusion injury in rats. Bulletin of Egyptian Society for Physiological Sciences. 2022;42(3):2013–230.

Yoshikawa Y, Ueda E, Sakurai H, Kojima Y. Anti-diabetes Effect of Zn(II)/Carnitine Complex by Oral Administration. Chem Pharm Bull (Tokyo). 2003;51(2):230–1.

Guzmán-Guillén R, Prieto AI, Vázquez CM, Vasconcelos V, Cameán AM. The protective role of l-carnitine against cylindrospermopsin-induced oxidative stress in tilapia (Oreochromis niloticus). Aquatic Toxicology. 2013;132–133:141–50.

Bayrak S, Aktaş S, Altun Z, Çakir Y, Tütüncü M, Kum Özşengezer S, et al. Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity. Journal of International Medical Research. 2020;48(8). Available from: https://doi/10.1177/0300060520951393

Samin A, Kury LT Al, KHAN MI, Hussain S, Alattar A, Alshaman R, et al. Acetyl-L-Carnitine protects against LPS induced depression via PPAR-γ induced inhibition of NF-κB/NLRP3 pathway. Archives of Medical Science. 2021.

Jiang F, Zhang Z, Zhang Y, Pan X, Yu L, Liu S. L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. Oncol Res Treat. 2015;38(10):511–6. Available from: https://doi/10.1159/000439550

Silvério R, Laviano A, Fanelli FR, Seelaender M. L-Carnitine induces recovery of liver lipid metabolism in cancer cachexia. Amino Acids. 2012;42(5):1783–92. Available from: https://doi/10.1007/s00726-011-0898-y

You J, Lee J, Hyun SH, Lee E. L-carnitine treatment during oocyte maturation improves in vitro development of cloned pig embryos by influencing intracellular glutathione synthesis and embryonic gene expression. Theriogenology. 2012;78(2):235–43.

Ghanem N. L-carnitine improved bovine blastocyst rate and quality when supplemented at different preimplantation stages. Egyptian Journal of Animal Production. 2015;52(2):89–99.

Reader KL, Cox NR, Stanton JAL, Juengel JL. Effects of acetyl-L-carnitine on lamb oocyte blastocyst rate, ultrastructure, and mitochondrial DNA copy number. Theriogenology. 2015;83(9):1484–92.

Das R, Rauf A, Akhter S, Islam MN, Emran T Bin, Mitra S, et al. Role of Withaferin A and Its Derivatives in the Management of Alzheimer’s Disease: Recent Trends and Future Perspectives. Molecules. 2021;26(12):3696.

Kabir MT, Uddin MS, Jeandet P, Emran T Bin, Mitra S, Albadrani GM, et al. Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential. Marine Drugs. 2021;19(5):251.

Rebouche CJ. Kinetics, Pharmacokinetics, and Regulation of l-Carnitine and Acetyl-l-carnitine Metabolism. Ann N Y Acad Sci. 2004;1033(1):30–41. Available from: https://doi/10.1196/annals.1320.003

Chen N, Yang M, Zhou M, Xiao J, Guo J, He L, et al. L-carnitine for cognitive enhancement in people without cognitive impairment. Cochrane Database of Systematic Reviews. 2015;2015(11). Available from: https://doi/10.1002/14651858.

Wollen KA. Alzheimer’s disease: The pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Alternative Medicine Review. 2010;15(3):223–44.

Gavrilova S, Kalyn IB, Kolykhalov I, Roshchina I, Selezneva N. [Acetyl-L-carnitine (carnicetine) in the treatment of early stages of Alzheimer’s disease and vascular dementia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011.

Parnetti L, Gaiti A, Mecocci P, Cadini D, Senin U. Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type. Eur J Clin Pharmacol. 1992;42(1):89–93.

Zhang Z yu, Fan Z kai, Cao Y, Jia Z qiang, Li G, Zhi X dong, et al. Acetyl-l-carnitine ameliorates mitochondrial damage and apoptosis following spinal cord injury in rats. Neurosci Lett. 2015;604:18–23.

Calvani M, Carta A, Benedetti N, Iannuccelli M, Caruso G. Action of Acetyl-L-Carnitine in Neurodegeneration and Alzheimer’s Disease. Ann N Y Acad Sci. 1992;663(1):483–6. Available from: https://doi/10.1111/j.1749-6632.1992.tb38710.x

Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. European Journal of Epidemiology. 2011;26(1):1–58. Available from: https://doi/10.1007/s10654-011-9581-6.

Muangpaisan W, Mathews A, Hori H, Seidel D. A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. J Med Assoc Thai. 2011.

Bahbah EI, Ghozy S, Attia MS, Negida A, Emran T Bin, Mitra S, et al. Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent. Marine Drugs. 2021;19(4):201.

Koppula S, Kumar H, More SV, Kim BW, Kim IS, Choi DK. Recent Advances on the Neuroprotective Potential of Antioxidants in Experimental Models of Parkinson’s Disease. International Journal of Molecular Sciences. 2012;13(8):10608–29.

Sedaghat R, Roghani M, Khalili M. Neuroprotective Effect of Thymoquinone, the Nigella Sativa Bioactive Compound, in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rat Model. Iranian journal of pharmaceutical research. 2014;13(1):227–34.

Chattopadhyaya I, Gupta S, Mohammed A, Mushtaq N, Chauhan S, Ghosh S. Neuroprotective effect of Spirulina fusiform and amantadine in the 6-OHDA induced Parkinsonism in rats. BMC Complement Altern Med. 2015;15(1):1–11. Available from: https://doi/10.1186/s12906-015-0815-0

Afshin-Majd S, Bashiri K, Kiasalari Z, Baluchnejadmojarad T, Sedaghat R, Roghani M. Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson’s disease in the rat. Biomedicine & Pharmacotherapy. 2017;89:1–9.

Hodges H, Fealko C, Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 2020;9(Suppl 1):S55–65.

Goin-Kochel RP, Scaglia F, Schaaf CP, Berry LN, Dang D, Nowel KP, et al. Side Effects and Behavioral Outcomes Following High-Dose Carnitine Supplementation Among Young Males With Autism Spectrum Disorder: A Pilot Study. Glob Pediatr Health. 2019;6. Available from: https://doi/10.1177/2333794X19830696.

Kępka A, Ochocińska A, Chojnowska S, Borzym-Kluczyk M, Skorupa E, Knaś M, et al. Potential Role of L-Carnitine in Autism Spectrum Disorder. Journal of Clinical Medicine. 2021;10(6):1202.

Fahmy SF, El-Hamamsy MH, Zaki OK, Badary OA. L-carnitine supplementation improves the behavioral symptoms in autistic children. Res Autism Spectr Disord. 2013;7(1):159–66.

Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. A review of current evidence for acetyl-l-carnitine in the treatment of depression. J Psychiatr Res. 2014;53(1):30–7.

Di Cesare Mannelli L, Vivoli E, Salvicchi A, Schiavone N, Koverech A, Messano M, et al. Antidepressant-like effect of artemin in mice: A mechanism for acetyl-l-carnitine activity on depression. Psychopharmacology (Berl). 2011;218(2):347–56. Available from: https://doi/10.1007/s00213-011-2326-0.

Falco-Walter J. Epilepsy-Definition, Classification, Pathophysiology, and Epidemiology. Semin Neurol. 2020

Téllez-Zenteno JF, Hernández-Ronquillo L. A review of the epidemiology of temporal lobe epilepsy. Epilepsy Res Treat. 2012;12:1–5.

Hadera MG, McDonald T, Smeland OB, Meisingset TW, Eloqayli H, Jaradat S, et al. Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-L-Carnitine. Neurochem Res. 2016;41(1–2):86–95.

Xia Y, Li Q, Zhong W, Dong J, Wang Z, Wang C. L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function. Diabetol Metab Syndr. 2011;3(1):1–10.

Wu T, Guo A, Shu Q, Qi Y, Kong Y, Sun Z, et al. l-Carnitine intake prevents irregular feeding-induced obesity and lipid metabolism disorder. Gene. 2015;554(2):148–54.

Salic K, Gart E, Seidel F, Verschuren L, Caspers M, van Duyvenvoorde W, et al. Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis. International Journal of Molecular Sciences. 2019;20(18):4359.

Esmail M, Anwar S, Kandeil M, El-Zanaty AM, Abdel-Gabbar M. Effect of Nigella sativa, atorvastatin, or L-Carnitine on high fat diet-induced obesity in adult male Albino rats. Biomedicine & Pharmacotherapy. 2021;141:111818.

Song X, Qu H, Yang Z, Rong J, Cai W, Zhou H. Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2017;2017.

Lipworth B, Skinner D, Devereux G, Thomas V, Jie JLZ, Martin J, et al. Underuse of β-blockers in heart failure and chronic obstructive pulmonary disease. Heart. 2016;102(23):1909–14.

Sidorenkov G, Navis G. Safety of ACE inhibitor therapies in patients with chronic kidney disease. Expert Opin Drug Saf. 2014;13(10):1383–95. Available from: https://doi/10.1517/14740338.2014.951328.

Wang ZY, Liu YY, Liu GH, Lu H Bin, Mao CY. l-Carnitine and heart disease. Life Sci. 2018;194:88–97.

DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: Systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544–51.

Guarnieri G, Situlin R, Biolo G. Carnitine metabolism in uremia. American Journal of Kidney Diseases. 2001;38(4 SUPPL. 1):S63–7.

Eknoyan G, Latos DL, Lindberg J, Willis K. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. American Journal of Kidney Diseases. 2003;41(4):868–76.

Schröder CH, Edefonti A, Fischbach M, Klaus G, Rönnholm K, Schaefer F, et al. The management of anemia in pediatric peritoneal dialysis patients. Guidelines by an ad hoc European committee. Pediatric Nephrology. 2003;18(8):805–9. Available from: https://doi/10.1007/s00467-003-1126-0.

Di Liberato L, Arduini A, Rossi C, Di Castelnuovo A, Posari C, Sacchetta P, et al. l-Carnitine status in end-stage renal disease patients on automated peritoneal dialysis. J Nephrol. 2014;27(6):699–706. Available from: https://doi/10.1007/s40620-014-0076-x.

Bonomini M, Di Liberato L, Zammit V, Arduini A. Current Opinion on Usage of L-Carnitine in End-Stage Renal Disease Patients on Peritoneal Dialysis. Molecules. 2019;24(19):3449.

Koşan C, Sever L, Arisoy N, Çalisşkan S, Kasapçopur Ö. Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients. Pediatric Nephrology. 2003;18(11):1184–8. Available from: https://doi/10.1007/s00467-003-1302-2.

Tousson E, Zaki ZT, Abu-Shaeir WA, Hassan H. Methotrexate-induced Hepatic and Renal Toxicity: Role of L-carnitine in Treatment. Biomedicine and Biotechnology. 2014;2(4):85–92.

Talenezhad N, Mohammadi M, Ramezani-Jolfaie N, Mozaffari-Khosravi H, Salehi-Abargouei A. Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis. Clin Nutr ESPEN. 2020;37:9–23.

Sawicka AK, Hartmane D, Lipinska P, Wojtowicz E, Lysiak-Szydlowska W, Olek RA. l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function. Nutrients. 2018;10(2):255.

Askarpour M, Djafarian K, Ghaedi E, Sadeghi O, Sheikhi A, Shab-Bidar S. Effect of L-Carnitine Supplementation on Liver Enzymes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Arch Med Res. 2020;51(1):82–94.

Talebi SS, Ghasemi M, Etminani-Esfahani M, Mohammadi Y, Haddadi R. Effects of L-carnitine supplementation in patients with mild-to-moderate COVID-19 disease: a pilot study. Pharmacological Reports. 2022;74(6):1296–305. Available from: https://doi/10.1007/s43440-022-00402-y.

Abolfathi M, Mohd-Yusof BN, Hanipah ZN, Mohd Redzwan S, Yusof LM, Khosroshahi MZ. The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 2020;48:102273.

Alam J, Fahim SM, Islam MR, Alam MA, Gazi MA, Ahmed T. Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial. J Nutr. 2024.

Nasiri M, Parmoon Z, Farahmand Y, Moradi A, Farahmand K, Moradi K, et al. l-carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors: a randomized, double-blind clinical trial. Int Clin Psychopharmacol. 2023.

Nachvak SM, Shabanpur M, Mostafai R, Heidari Moghaddam R, Moludi J. L-Carnitine supplementation reduces biomarkers of inflammatory and oxidative stress in patients with coronary artery disease: a randomised controlled trial. Arch Physiol Biochem. 2023;129(1):61–8. Available from: https://doi/10.1080/13813455.2020.1797102.

Yahyapoor F, Keshani M, Sedaghat A, Feizi A, Clark CCT, Bagherniya M, et al. The effects of adjunctive treatment with l-carnitine on monitoring laboratory variables in ICU patients: a double-blinded randomized controlled clinical trial. Trials. 2023;24(1):1–8. Available from: https://doi/10.1186/s13063-022-07010-4.

Ait Tayeb AEK, Colle R, El-Asmar K, Chappell K, Acquaviva-Bourdain C, David DJ, et al. Plasma acetyl-l-carnitine and l-carnitine in major depressive episodes: a case–control study before and after treatment. Psychol Med. 2023;53(6):2307–16.

Asbaghi O, Kashkooli S, Amini MR, Shahinfar H, Djafarian K, Clark CCT, et al. The effects of L-carnitine supplementation on lipid concentrations inpatients with type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials. J Cardiovasc Thorac Res. 2020;12(4):246.

Mazdeh M, Abolfathi P, Sabetghadam M, Mohammadi Y, Mehrpooya M. Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial. Oxid Med Cell Longev. 2022;2022.

Savic D, Hodson L, Neubauer S, Pavlides M. The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients. 2020;12(8):2178.

Enooku K, Nakagawa H, Fujiwara N, Kondo M, Minami T, Hoshida Y, et al. Altered serum acylcarnitine profile is associated with the status of nonalcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma. Scientific Reports. 2019;9(1):1–9.

Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, Ilkayeva O, et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. Journal of Biological Chemistry. 2009;284(34):22840–52.

Isaeva AP, Gapparova KM. The effect of L-carnitine on lipid metabolism in patients with obesity. Clinical Nutrition. 2018;37:S38–9.

Stephens FB, Constantin-teodosiu D, Greenhaff PL. New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol. 2007;581(2):431–44. Available from: https://doi/10.1113/jphysiol.2006.125799.

Vidal-Casariego A, Burgos-Peláez R, Martínez-Faedo C, Calvo-Gracia F, Valero-Zanuy MÁ, Luengo-Pérez LM, et al. Metabolic effects of L-carnitine on type 2 diabetes mellitus: Systematic review and meta-analysis. Experimental and Clinical Endocrinology and Diabetes. 2013;121(4):234–8. Available from: http://doi/10.1055/s-0033-1333688.

Ringseis R, Keller J, Eder K. Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: Evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. Eur J Nutr. 2012;51(1):1–18. Available from: https://doi/10.1007/s00394-011-0284-2.

Hino K, Nishikawa M, Sato E, Inoue M. l-Carnitine inhibits hypoglycemia-induced brain damage in the rat. Brain Res. 2005;1053(1–2):77–87.

Guzmán-Guillén R, Prieto AI, Vázquez CM, Vasconcelos V, Cameán AM. The protective role of l-carnitine against cylindrospermopsin-induced oxidative stress in tilapia (Oreochromis niloticus). Aquatic Toxicology. 2013;132–133:141–50.

Szefel J, Kruszewski WJ, Ciesielski M, Szajewski M, Kawecki K, Aleksandrowicz-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.

Jiang F, Zhang Z, Zhang Y, Pan X, Yu L, Liu S. L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. Oncol Res Treat. 2015;38(10):511–6.

Silvério R, Laviano A, Fanelli FR, Seelaender M. L-Carnitine induces recovery of liver lipid metabolism in cancer cachexia. Amino Acids. 2012;42(5):1783–92. Available from: https://doi/10.1007/s00726-011-0898-y.

Chang BJ, Nishikawa M, Nishiguchi S, Inoue M. L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria. Int J Cancer. 2005;113(5):719–29. Available from: https://doi/10.1002/ijc.20636.

Hoang BX, Graeme Shaw D, Pham P, Levine SA. Neuro-bioenergetic concepts in cancer prevention and treatment. Med Hypotheses. 2007;68(4):832–43.

Hockenberry MJ, Hooke MC, Gregurich M, McCarthy K. Carnitine plasma levels and fatigue in children/adolescents receiving cisplatin, ifosfamide, or doxorubicin. J Pediatr Hematol Oncol. 2009;31(9):664–9.

Olugbodi JO, Samaila K, Lawal B, Anunobi OO, Baty RS, Ilesanmi OB, et al. Computational and Preclinical Evidence of Anti-ischemic Properties of L-Carnitine-Rich Supplement via Stimulation of Anti-inflammatory and Antioxidant Events in Testicular Torsed Rats. Oxid Med Cell Longev. 2021;2021.

Dunning KR, Robker RL. Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci. 2012;134(1–2):69–75.

Aliabadi E, Soleimani Mehranjani M, Borzoei Z, Talaei-Khozani T, Mirkhani H, Tabesh H. Effects of L-carnitine and L-acetyl-carnitine on testicular sperm motility and chromatin quality. Iran J Reprod Med. 2012;10(2):77–82.

Wu GQ, Jia BY, Li JJ, Fu XW, Zhou GB, Hou YP, et al. L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs. Theriogenology. 2011;76(5):785–93.

Samimi M, Jamilian M, Ebrahimi FA, Rahimi M, Tajbakhsh B, Asemi Z. Expression of Concern: Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). 2016;84(6):851–7. Available from: https://doi/10.1111/cen.13003.

Rubin MR, Volek JS, Gómez AL, Ratamess NA, French DN, Sharman MJ, et al. Safety measures of L-carnitine L-tartrate supplementation in healthy men. J Strength Cond Res. 2001;15(4):486–90.

Hathcock JN, Shao A. Risk assessment for carnitine. Regul Toxicol Pharmacol. 2006;46(1):23–8.

Bellamine A, Durkee S. Genotoxicity and subchronic oral toxicity studies of L-carnitine and L-carnitine L-tartrate. J Drug Metab Toxicol. 12(254):253.

Tata 1mg : Buy Tata 1mg Products Online in India. 1mg. Available from: https://www.1mg.com.

Clinical Trials Registry of India| National Portal of India. Available from: https://www.india.gov.in/clinical-trials-registry-india

Home - ClinicalTrials.gov;Available from: https://classic.clinicaltrials.gov/

Downloads

Published

30-05-2024

Issue

Section

Review Article

How to Cite

“A Comprehensive Review on L-Carnitine: A Promising Nutraceutical”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 16, no. 3, May 2024, pp. 517-32, https://doi.org/10.25004/IJPSDR.2024.160325.