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Cited by 79Liver Disease Diagnosis and TreatmentMetabolism and Genetic DisordersAlcohol Consumption and Health Effects

Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update

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Li, Na, Zhao, Hui·2021·Frontiers in Medicine
DOI 10.3389/fmed.2021.689042PMC PMC8381051
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Abstract

Carnitine is an amino acid-derived substance that coordinates a wide range of biological processes. Such functions include transport of long-chain fatty acids from the cytoplasm to the mitochondrial matrix, regulation of acetyl-CoA/CoA, control of inter-organellar acyl traffic, and protection against oxidative stress. Recent studies have found that carnitine plays an important role in several diseases, including non-alcoholic fatty liver disease (NAFLD). However, its effect is still controversial, and its mechanism is not clear. Herein, this review provides current knowledge on the biological functions of carnitine, the “multiple hit” impact of carnitine on the NAFLD progression, and the downstream mechanisms. Based on the “multiple hit” hypothesis, carnitine inhibits β-oxidation, improves mitochondrial dysfunction, and reduces insulin resistance to ameliorate NAFLD. L-carnitine may have therapeutic role in liver diseases including non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, alcoholic fatty liver disease, and viral hepatitis. We also discuss the prospects of L-carnitine supplementation as a therapeutic strategy in NAFLD and related diseases, and the factors limiting its widespread use.

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  • Detected differences in metabolites between HRX215- and vehicle-treated groups were related to carnitines and hypoxanthines, offering a mechanistic explanation for the observed antisteatotic effects.

    “Detected differences in metabolites between the HRX215- and vehicle-treated group were related to carnitines and hypoxanthines, offering a mechanistic explanation for the observed antisteatotic effects35,36 (Figures S3A–S3C).”

    From First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure (2024) · cites this paper as [36]

    The section on carnitine and the “multiple hit” hypothesis explains how carnitine can promote fatty-acid oxidation and reduce liver fat accumulation, supporting a possible antisteatotic mechanism. It does not address hypoxanthines or connect HRX215-related metabolite differences to that mechanism; those specific findings are not supported by this source. (LLM, conf=0.85)

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  1. [1]Almannai M Alfadhel M El-Hattab AW. Carnitine inborn errors of metabolism. Molecules. (2019) 24: 3251. 10.3390/molecules24183251 PMC6766900 31500110 · DOI
  2. [2]Ribas GS Vargas CR Wajner M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene. (2014) 533: 469– 76. 10.1016/j.gene.2013.10.017 24148561 · DOI
  3. [3]Lee B-J Lin J-S Lin Y-C Lin P-T. Effects of L-carnitine supplementation on oxidative stress and antioxidant enzymes activities in patients with coronary artery disease: a randomized, placebo-controlled trial. Nutr J. (2014) 13: 79. 10.1186/1475-2891-13-79 25092108 PMC4125592 · DOI
  4. [4]Komlósi K Havasi V Bene J Süle N Pajor L Nicolai R. Histopathologic abnormalities of the lymphoreticular tissues in organic cation transporter 2 deficiency: evidence for impaired B cell maturation. J Pediatr. (2007) 150: 109– 111.e2. 10.1016/j.jpeds.2006.09.042 17188629 · DOI
  5. [5]Modanloo M Shokrzadeh M. Analyzing mitochondrial dysfunction, oxidative stress, and apoptosis: potential role of L-carnitine. Iran J Kidney Dis. (2019) 13: 74– 86. 30988244
  6. [6]Bene J Hadzsiev K Melegh B. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr Diabetes. (2018) 8: 8. 10.1038/s41387-018-0017-1 29549241 PMC5856836 · DOI
  7. [7]Xu Y Jiang W Chen G Zhu W Ding W Ge Z. L-carnitine treatment of insulin resistance: a systematic review and meta-analysis. Adv Clin Exp Med. (2017) 26: 333– 8. 10.17219/acem/61609 28791854 · DOI
  8. [8]Jamilian H Jamilian M Samimi M Afshar Ebrahimi F Rahimi M Bahmani F. 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. (2017) 33: 442– 7. 10.1080/09513590.2017.1290071 28277138 · DOI
  9. [9]Malek Mahdavi A Mahdavi R Kolahi S. Effects of l-Carnitine supplementation on serum inflammatory factors and matrix metalloproteinase enzymes in females with knee osteoarthritis: a randomized, double-blind, placebo-controlled pilot study. J Am Coll Nutr. (2016) 35: 597– 603. 10.1080/07315724.2015.1068139 26933897 · DOI
  10. [11]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: 578– 94. 10.1002/iub.1646 28653367 · DOI
  11. [12]Vashistha VK Bhushan R. Bioanalysis and enantioseparation of dl-carnitine in human plasma by the derivatization approach. Bioanalysis. (2015) 7: 2477– 88. 10.4155/bio.15.155 26457589 · DOI
  12. [13]Li J-M Li L-Y Zhang Y-X Jiang Z-Y Limbu SM Qiao F. Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model. Br J Nutr. (2019) 122: 625– 38. 10.1017/S000711451900148X 32124711 · DOI
  13. [14]Sayed-Ahmed MM Darweesh AQ Fatani AJ. Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model. Oxid Med Cell Longev. (2010) 3: 266– 74. 10.4161/oxim.3.4.12859 20972373 PMC2952087 · DOI
  14. [15]Arafa HMM. Carnitine deficiency aggravates carboplatin nephropathy through deterioration of energy status, oxidant/anti-oxidant balance, and inflammatory endocoids. Toxicology. (2008) 254: 51– 60. 10.1016/j.tox.2008.09.010 18852009 · DOI
  15. [16]Zhu C Petracci M Li C Fiore E Laghi L. An untargeted metabolomics investigation of Jiulong Yak (Bos grunniens) meat by H-NMR. Foods. (2020) 9: 481. 10.3390/foods9040481 PMC7230376 32290528 · DOI
  16. [17]Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J. (1992) 6: 3379– 86. 10.1096/fasebj.6.15.1464372 1464372 · DOI
  17. [18]Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. (2004) 1033: 42– 51. 10.1196/annals.1320.004 15591002 · DOI
  18. [19]Tein I Bukovac SW Xie ZW. Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts. Arch Biochem Biophys. (1996) 329: 145– 55. 10.1006/abbi.1996.0203 8638946 · DOI
  19. [21]Bremer J. Carnitine–metabolism and functions. Physiol Rev. (1983) 63: 1420– 80. 10.1152/physrev.1983.63.4.1420 6361812 · DOI · Paper page
  20. [22]Vaz FM Wanders RJA. Carnitine biosynthesis in mammals. Biochem J. (2002) 361 (Pt 3): 417– 29. 10.1042/bj3610417 11802770 PMC1222323 · DOI
  21. [23]Strijbis K Vaz FM Distel B. Enzymology of the carnitine biosynthesis pathway. IUBMB Life. (2010) 62: 357– 62. 10.1002/iub.323 20306513 · DOI
  22. [24]Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. (2004) 1033: 30– 41. 10.1196/annals.1320.003 15591001 · DOI
  23. [25]Schooneman MG Vaz FM Houten SM Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance? Diabetes. (2013) 62: 1– 8. 10.2337/db12-0466 23258903 PMC3526046 · DOI · Paper page
  24. [26]Lahjouji K Mitchell GA Qureshi IA. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab. (2001) 73: 287– 97. 10.1006/mgme.2001.3207 11509010 · DOI
  25. [27]Koch A König B Luci S Stangl GI Eder K. Dietary oxidised fat up regulates the expression of organic cation transporters in liver and small intestine and alters carnitine concentrations in liver, muscle and plasma of rats. Br J Nutr. (2007) 98: 882– 9. 10.1017/S000711450775691X 17524183 · DOI
  26. [28]Kou L Sun R Ganapathy V Yao Q Chen R. Recent advances in drug delivery via the organic cation/carnitine transporter 2 (OCTN2/SLC22A5). Expert Opin Ther Targets. (2018) 22: 715– 26. 10.1080/14728222.2018.1502273 30016594 · DOI
  27. [29]Kerner J Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta. (2000) 1486: 1– 17. 10.1016/S1388-1981(00)00044-5 10856709 · DOI
  28. [30]Yan S Yang X-F Liu H-L Fu N Ouyang Y Qing K. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol. (2015) 21: 3492– 8. 10.3748/wjg.v21.i12.3492 25834313 PMC4375570 · DOI
  29. [31]Indiveri C Iacobazzi V Tonazzi A Giangregorio N Infantino V Convertini P. The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology. Mol Aspects Med. (2011) 32: 223– 33. 10.1016/j.mam.2011.10.008 22020112 · DOI
  30. [33]Rinaldo P Cowan TM Matern D. Acylcarnitine profile analysis. Genet Med. (2008) 10: 151– 6. 10.1097/GIM.0b013e3181614289 18281923 · DOI
  31. [34]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: 2178. 10.3390/nu12082178 32708036 PMC7469009 · DOI
  32. [35]Tanphaichitr V Leelahagul P. Carnitine metabolism and human carnitine deficiency. Nutrition. (1993) 9: 246– 54. 8353366
  33. [36]Nicolson GL. Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Integr Med. (2014) 13: 35– 43. 26770107 PMC4566449
  34. [37]Askarpour M Hadi A Dehghani Kari Bozorg A Sadeghi O Sheikhi A Kazemi M. Effects of L-carnitine supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Hum Hypertens. (2019) 33: 725– 34. 10.1038/s41371-019-0248-1 31481697 · DOI
  35. [38]Kinugasa Y Sota T Ishiga N Nakamura K Kamitani H Hirai M. l-Carnitine supplementation in heart failure patients with preserved ejection fraction; a pilot study. Geriatr Gerontol Int. (2020) 20: 1244– 45. 10.1111/ggi.14060 33048437 · DOI
  36. [39]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. (2020). 10.1080/13813455.2020.1797102. [Epub ahead of print]. 32816578 · DOI
  37. [40]Hanai T Shiraki M Imai K Suetugu A Takai K Shimizu M. Usefulness of carnitine supplementation for the complications of liver cirrhosis. Nutrients. (2020) 12: 1915. 10.3390/nu12071915 32610446 PMC7401279 · DOI
  38. [41]Yarizadh H Shab-Bidar S Zamani B Vanani AN Baharlooi H Djafarian K. The effect of L-carnitine supplementation on exercise-induced muscle damage: a systematic review and meta-analysis of randomized clinical trials. J Am Coll Nutr. (2020) 39: 457– 68. 10.1080/07315724.2019.1661804 32154768 · DOI
  39. [42]Askarpour M Hadi A Symonds ME Miraghajani M Omid S Sheikhi A. Efficacy of l-carnitine supplementation for management of blood lipids: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. (2019) 29: 1151– 67. 10.1016/j.numecd.2019.07.012 31561944 · DOI
  40. [43]Hajihashemi P Askari G Khorvash F Reza Maracy M Nourian M. The effects of concurrent Coenzyme Q10, L-carnitine supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial. Cephalalgia. (2019) 39: 648– 54. 10.1177/0333102418821661 30612463 · DOI
  41. [44]Kepka A Ochocinska A Borzym-Kluczyk M Skorupa E Stasiewicz-Jarocka B Chojnowska S. Preventive role of L-carnitine and balanced diet in Alzheimer's disease. Nutrients. (2020) 12: 1987. 10.3390/nu12071987 32635400 PMC7400709 · DOI
  42. [45]Wegermann K Suzuki A Mavis AM Abdelmalek MF Diehl AM Moylan CA. Tackling NAFLD: three targeted populations. Hepatology. (2020) 73: 1199– 206. 10.1002/hep.31533 32865242 · DOI
  43. [46]Draijer LG Froon-Torenstra D van Weeghel M Vaz FM Bohte AE Holleboom AG. Lipidomics in nonalcoholic fatty liver disease: exploring serum lipids as biomarkers for pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. (2020) 71: 433– 9. 10.1097/MPG.0000000000002875 32947564 · DOI
  44. [47]Buzzetti E Pinzani M Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. (2016) 65: 1038– 48. 10.1016/j.metabol.2015.12.012 26823198 · DOI · Paper page
  45. [48]Tsochatzis EA Papatheodoridis GV Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediators Inflamm. (2009) 2009: 831670. 10.1155/2009/831670 19753129 PMC2694309 · DOI
  46. [49]Shao M Ye Z Qin Y Wu T. Abnormal metabolic processes involved in the pathogenesis of non-alcoholic fatty liver disease (Review). Exp Ther Med. (2020) 20: 26. 10.3892/etm.2020.9154 32934691 PMC7471863 · DOI
  47. [50]Ibrahim SH Kohli R Gores GJ. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. (2011) 53: 131– 40. 10.1097/MPG.0b013e31822578db 21629127 PMC3145329 · DOI
  48. [51]Knottnerus SJG Bleeker JC Wüst RCI Ferdinandusse S Ijlst L Wijburg FA. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev Endocr Metab Disord. (2018) 19: 93– 106. 10.1007/s11154-018-9448-1 29926323 PMC6208583 · DOI
  49. [52]Meex RCR Blaak EE. Mitochondrial dysfunction is a key pathway that links saturated fat intake to the development and progression of NAFLD. Mol Nutr Food Res. (2020) 65: e1900942. 10.1002/mnfr.201900942 32574416 PMC7816225 · DOI
  50. [53]Jun DW Cho WK Jun JH Kwon HJ Jang K-S Kim H-J. Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction. Liver Int. (2011) 31: 1315– 24. 10.1111/j.1478-3231.2011.02602.x 22093454 · DOI
  51. [54]Perez-Carreras M Del Hoyo P Martin M Rubio J Martin A Castellano G. Defective hepatic mitochondrial respiratory chain in patients with non-alcoholic steatohepatitis. Hepatology. (2003) 38: 999– 1007. 10.1002/hep.1840380426 14512887 · DOI · Paper page
  52. [55]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– 18. 10.1007/s00394-011-0284-2 22134503 · DOI
  53. [56]Choi JW Ohn JH Jung HS Park YJ Jang HC Chung SS. Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction. Metabolism. (2018) 78: 43– 51. 10.1016/j.metabol.2017.09.005 28966077 · DOI
  54. [57]Belfiore A Frasca F Pandini G Sciacca L Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. (2009) 30: 586– 623. 10.1210/er.2008-0047 19752219 · DOI
  55. [58]Bailes J Soloviev M. Insulin-like growth factor-1 (IGF-1) and its monitoring in medical diagnostic and in sports. Biomolecules. (2021) 11: 217. 10.3390/biom11020217 33557137 PMC7913862 · DOI
  56. [59]Cubbon RM Kearney MT Wheatcroft SB. Endothelial IGF-1 receptor signalling in diabetes and insulin resistance. Trends Endocrinol Metab. (2016) 27: 96– 104. 10.1016/j.tem.2015.11.009 26712712 · DOI
  57. [60]Li S Tan H-Y Wang N Zhang Z-J Lao L Wong C-W. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. (2015) 16: 26087– 124. 10.3390/ijms161125942 26540040 PMC4661801 · DOI
  58. [61]Muriel P Gordillo KR. Role of oxidative stress in liver health and disease. Oxid Med Cell Longev. (2016) 2016: 9037051. 10.1155/2016/9037051 27092207 PMC4820620 · DOI · Paper page
  59. [62]Cortez-Pinto H Chatham J Chacko VP Arnold C Rashid A Diehl AM. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA. (1999) 282: 1659– 64. 10.1001/jama.282.17.1659 10553793 · DOI
  60. [63]Serviddio G Bellanti F Tamborra R Rollo T Romano AD Giudetti AM. Alterations of hepatic ATP homeostasis and respiratory chain during development of non-alcoholic steatohepatitis in a rodent model. Eur J Clin Invest. (2008) 38: 245– 52. 10.1111/j.1365-2362.2008.01936.x 18339004 · DOI
  61. [64]Limdi JK Hyde GM. Evaluation of abnormal liver function tests. Postgrad Med J. (2003) 79: 307– 12. 10.1136/pmj.79.932.307 12840117 PMC1742736 · DOI
  62. [65]Selimoglu MA Aydogdu S Yagci RV Huseyinov A. Plasma and liver carnitine status of children with chronic liver disease and cirrhosis. Pediatr Int. (2001) 43: 391– 5. 10.1046/j.1442-200X.2001.01423.x 11472585 · DOI
  63. [66]Rudman D Sewell CW Ansley JD. Deficiency of carnitine in cachectic cirrhotic patients. J Clin Invest. (1977) 60: 716– 23. 10.1172/JCI108824 893675 PMC372417 · DOI
  64. [67]Musso G Gambino R Cassader M Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. (2010) 52: 79– 104. 10.1002/hep.23623 20578268 · DOI
  65. [68]Okabayashi T Sui K Mastumoto T Iwata J Morita S Iiyama T. l-Carnitine improves postoperative liver function in hepatectomized patients. J Parenter Enteral Nutr. (2020) 44: 823– 30. 10.1002/jpen.1720 31599019 · DOI
  66. [69]Famularo G De Simone C 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. 10.1196/annals.1320.012 15591010 · DOI
  67. [70]Quillet-Mary A Jaffrézou JP Mansat V Bordier C Naval J Laurent G. Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis. J Biol Chem. (1997) 272: 21388– 95. 10.1074/jbc.272.34.21388 9261153 · DOI
  68. [71]Chapoy PR Angelini C Brown WJ Stiff JE Shug AL Cederbaum SD. Systemic carnitine deficiency–a treatable inherited lipid-storage disease presenting as Reye's syndrome. N Engl J Med. (1980) 303: 1389– 94. 10.1056/NEJM198012113032403 7432384 · DOI
  69. [72]Pike LS Smift AL Croteau NJ Ferrick DA Wu M. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta. (2011) 1807: 726– 34. 10.1016/j.bbabio.2010.10.022 21692241 · DOI
  70. [74]Lheureux PER Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol. (2009) 47: 101– 11. 10.1080/15563650902752376 19280426 · DOI
  71. [75]Mahale RR Mehta A Timmappaya A Srinivasa R. Primary carnitine deficiency as a cause of metabolic leukoencephalopathy: report of one case. Neurol India. (2016) 64: 166– 8. 10.4103/0028-3886.173650 26755012 · DOI
  72. [76]Buist NRM. Historical perspective on clinical trials of carnitine in children and adults. Ann Nutr Metab. (2016) 68(Suppl. 3): 1– 4. 10.1159/000448320 27931034 · DOI
  73. [77]Sachan DS Rhew TH Ruark RA. Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. Am J Clin Nutr. (1984) 39: 738– 44. 10.1093/ajcn/39.5.738 6424429 · DOI
  74. [78]DeCarli LM Lieber CS. Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet. J Nutr. (1967) 91: 331– 6. 10.1093/jn/91.3_Suppl.331 6021815 · DOI
  75. [79]Blomstrand R Kager L Lantto O. Studies on the ethanol-induced decrease of fatty acid oxidation in rat and human liver slices. Life Sci. (1973) 13: 1131– 41. 10.1016/0024-3205(73)90380-9 4762602 · DOI
  76. [80]Jun DW Kim BI Cho YK Kim HJ Kwon YO Park SY. Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study. Clin Mol Hepatol. (2013) 19: 165– 72. 10.3350/cmh.2013.19.2.165 23837141 PMC3701849 · DOI
  77. [81]Jung YW Kim M Kim BK Park JY Kim DY Ahn SH. Influence of besifovir dipivoxil maleate combined with L-carnitine on hepatic steatosis in patients with chronic hepatitis B. J Korean Med Sci. (2020) 35: e104. 10.3346/jkms.2020.35.e104 32356416 PMC7200179 · DOI
  78. [82]Abbasnezhad A Hasanavand A Falahi E Kashkooli S Asbaghi O Choghakhori R. Effect of L-carnitine supplementation on lipid profiles of patients with liver disease: a systematic review and meta-analysis. Prev Nutr Food Sci. (2020) 25: 124– 32. 10.3746/pnf.2020.25.2.124 32676462 PMC7333001 · DOI
  79. [83]Tsukuda Y Suda G Tsunematsu S Ito J Sato F Terashita K. Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection. J Med Virol. (2017) 89: 857– 66. 10.1002/jmv.24692 27664407 · DOI
  80. [84]Mandard S Müller M Kersten S. Peroxisome proliferator-activated receptor alpha target genes. Cell Mol Life Sci. (2004) 61: 393– 416. 10.1007/s00018-003-3216-3 14999402 PMC11138883 · DOI
  81. [85]Couturier A Ringseis R Most E Eder K. Pharmacological doses of niacin stimulate the expression of genes involved in carnitine uptake and biosynthesis and improve the carnitine status of obese Zucker rats. BMC Pharmacol Toxicol. (2014) 15: 37. 10.1186/2050-6511-15-37 25012467 PMC4094635 · DOI
  82. [86]Ringseis R Wen G Eder K. Regulation of genes involved in carnitine homeostasis by PPARα across different species (rat, mouse, pig, cattle, chicken, and human). PPAR Res. (2012) 2012: 868317. 10.1155/2012/868317 23150726 PMC3486131 · DOI
  83. [87]Mollica G Senesi P Codella R Vacante F Montesano A Luzi L. L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet. Dig Liver Dis. (2020) 52: 314– 23. 10.1016/j.dld.2019.09.002 31607566 · DOI
  84. [88]Scalera A Tarantino G. Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease? World J Gastroenterol. (2014) 20: 9217– 28. 10.3748/wjg.v20.i28.9217 25071314 PMC4110551 · DOI
  85. [89]Zhang C Bjornson E Arif M Tebani A Lovric A Benfeitas R. The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease. Mol Syst Biol. (2020) 16: e9495. 10.15252/msb.209495 32337855 PMC7184219 · DOI
  86. [90]Montesano A Senesi P Vacante F Mollica G Benedini S Mariotti M. L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers. J Endocrinol Invest. (2020) 43: 493– 503. 10.1007/s40618-019-01134-2 31705397 PMC7067714 · DOI
  87. [91]Salic K Gart E Seidel F Verschuren L Caspers M van Duyvenvoorde W. Combined treatment with L-carnitine and nicotinamide riboside improves hepatic metabolism and attenuates obesity and liver steatosis. Int J Mol Sci. (2019) 20: 4359. 10.3390/ijms20184359 31491949 PMC6770226 · DOI
  88. [92]Li N Liu Y Yu S Hu B Zhao H. Composite BMI and waist-to-height ratio index for risk assessment of non-alcoholic fatty liver disease in adult populations. Hepat Mon. (2020) 20: e103607. 10.5812/hepatmon.103607 · DOI
  89. [93]Mahjoubin-Tehran M De Vincentis A Mikhailidis DP Atkin SL Mantzoros CS Jamialahmadi T. Non-alcoholic fatty liver disease and steatohepatitis: state of the art on effective therapeutics based on the gold standard method for diagnosis. Mol Metab. (2021) 50: 101049. 10.1016/j.molmet.2020.101049 32673798 PMC8324680 · DOI
  90. [94]Alavinejad P Zakerkish M Hajiani E Hashemi SJ Chobineh M Moghaddam EK. Evaluation of l-carnitine efficacy in the treatment of non-alcoholic fatty liver disease among diabetic patients: a randomized double blind pilot study. J Gastroenterol Hepatol Res. (2016) 5: 2191– 5. 10.17554/j.issn.2224-3992.2016.05.662 · DOI
  91. [95]Abolfathi M Mohd-Yusof B-N 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. Comp Ther Med. (2020) 48: 102273. 10.1016/j.ctim.2019.102273 31987257 · DOI
  92. [96]Pirmadah F Ramezani-Jolfaie N Mohammadi M Talenezhad N Clark CCT Salehi-Abargouei A. Does L-carnitine supplementation affect serum levels of enzymes mainly produced by liver? A systematic review and meta-analysis of randomized controlled clinical trials. Eur J Nutr. (2020) 59: 1767– 83. 10.1007/s00394-019-02068-4 31385062 · DOI
  93. [97]Somi MH Fatahi E Panahi J Havasian MR Judaki A. Data from a randomized and controlled trial of L-carnitine prescription for the treatment for non- alcoholic fatty liver disease. Bioinformation. (2014) 10: 575– 9. 10.6026/97320630010575 25352725 PMC4209366 · DOI
  94. [98]Lim CY Jun DW Jang SS Cho WK Chae JD Jun JH. Effects of carnitine on peripheral blood mitochondrial DNA copy number and liver function in non-alcoholic fatty liver disease. Korean J Gastroenterol. (2010) 55: 384– 9. 10.4166/kjg.2010.55.6.384 20571306 · DOI
  95. [99]Fujisawa K Takami T Matsuzaki A Matsumoto T Yamamoto N Terai S. Evaluation of the effects of L-carnitine on medaka (Oryzias latipes) fatty liver. Sci Rep. (2017) 7: 2749. 10.1038/s41598-017-02924-5 28584294 PMC5459862 · DOI
  96. [100]Kathirvel E Morgan K French SW Morgan TR. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutr Res. (2013) 33: 932– 41. 10.1016/j.nutres.2013.08.001 24176233 · DOI
  97. [101]Bae JC Lee WY Yoon KH Park JY Son HS Han KA. Improvement of nonalcoholic fatty liver disease with carnitine-orotate complex in type 2 diabetes (CORONA): a randomized controlled trial. Diabetes Care. (2015) 38: 1245– 52. 10.2337/dc14-2852 25877813 · DOI
  98. [102]Hong ES Kim EK Kang SM Khang AR Choi SH Park KS. Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study. J Gastroenterol Hepatol. (2014) 29: 1449– 57. 10.1111/jgh.12536 24611967 · DOI
  99. [103]Hamza RT Elkabbany ZA Shedid AM Hamed AI Ebrahim AO. Serum chemerin in obese children and adolescents before and after L-carnitine therapy: relation to nonalcoholic fatty liver disease and other features of metabolic syndrome. Arch Med Res. (2016) 47: 541– 9. 10.1016/j.arcmed.2016.11.010 28262196 · DOI
  100. [104]Malaguarnera M Gargante MP Russo C Antic T Vacante M Malaguarnera M. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis–a randomized and controlled clinical trial. Am J Gastroenterol. (2010) 105: 1338– 45. 10.1038/ajg.2009.719 20068559 · DOI
  101. [105]Ishikawa H Takaki A Tsuzaki R Yasunaka T Koike K Shimomura Y. L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway. PLoS ONE. (2014) 9: e100627. 10.1371/journal.pone.0100627 24983359 PMC4077577 · DOI
  102. [106]Hassan A Tsuda Y Asai A Yokohama K Nakamura K Sujishi T. Effects of oral L-carnitine on liver functions after transarterial chemoembolization in intermediate-stage HCC patients. Mediators Inflamm. (2015) 2015: 608216. 10.1155/2015/608216 26664151 PMC4668308 · DOI
  103. [107]Malaguarnera M Pistone G Astuto M Dell'Arte S Finocchiaro G Lo Giudice E. L-Carnitine in the treatment of mild or moderate hepatic encephalopathy. Dig Dis. (2003) 21: 271– 5. 10.1159/000073347 14571103 · DOI
  104. [108]Malaguarnera M Vacante M Motta M Giordano M Malaguarnera G Bella R. Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial. Metab Brain Dis. (2011) 26: 281– 9. 10.1007/s11011-011-9260-z 21870121 · DOI · Paper page
  105. [109]Malaguarnera M Pistone G Elvira R Leotta C Scarpello L Liborio R. Effects of L-carnitine in patients with hepatic encephalopathy. World J Gastroenterol. (2005) 11: 7197– 202. 10.3748/wjg.v11.i45.7197 16437672 PMC4725086 · DOI
  106. [110]Malaguarnera M Pistone G Astuto M Vecchio I Raffaele R Lo Giudice E. Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial. Dig Dis Sci. (2006) 51: 2242– 7. 10.1007/s10620-006-9187-0 17080254 · DOI
  107. [111]Malaguarnera M Gargante MP Cristaldi E Vacante M Risino C Cammalleri L. Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci. (2008) 53: 3018– 25. 10.1007/s10620-008-0238-6 18357530 · DOI
  108. [112]Iliceto S Scrutinio D Bruzzi P D'Ambrosio G Boni L Di Biase M. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-carnitine ecocardiografia digitalizzata infarto miocardico (CEDIM) trial. J Am Coll Cardiol. (1995) 26: 380– 7. 10.1016/0735-1097(95)80010-E 7608438 · DOI
  109. [113]Van Oudheusden LJ Scholte HR. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. (2002) 67: 33– 8. 10.1054/plef.2002.0378 12213433 · DOI
  110. [114]Ellaway C Williams K Leonard H Higgins G Wilcken B Christodoulou J. Rett syndrome: randomized controlled trial of L-carnitine. J Child Neurol. (1999) 14: 162– 7. 10.1177/088307389901400306 10190267 · DOI
  111. [115]Benvenga S Ruggeri RM Russo A Lapa D Campenni A Trimarchi F. 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. 10.1210/jcem.86.8.7747 11502782 · DOI
  112. [116]Iyer R Gupta A Khan A Hiremath S Lokhandwala Y. Does left ventricular function improve with L-carnitine after acute myocardial infarction? J Postgrad Med. (1999) 45: 38– 41. 10734331
  113. [117]Löster H Miehe K Punzel M Stiller O Pankau H Schauer J. Prolonged oral L-carnitine substitution increases bicycle ergometer performance in patients with severe, ischemically induced cardiac insufficiency. Cardiovasc Drugs Ther. (1999) 13: 537– 46. 10.1023/A:1007883822625 10686664 · DOI
  114. [118]Lenzi A Sgrò P Salacone P Paoli D Gilio B Lombardo F. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. (2004) 81: 1578– 84. 10.1016/j.fertnstert.2003.10.034 15193480 · DOI
  115. [119]Brooks JO Yesavage JA Carta A Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychogeriatr. (1998) 10: 193– 203. 10.1017/S1041610298005304 9677506 · DOI
  116. [120]Turpeinen AK Kuikka JT Vanninen E Yang J Uusitupa MI. Long-term effect of acetyl-L-carnitine on myocardial 123I-MIBG uptake in patients with diabetes. Clin Auton Res. (2000) 10: 13– 6. 10.1007/BF02291384 10750638 · DOI
  117. [121]Torrioli MG Vernacotola S Mariotti P Bianchi E Calvani M De Gaetano A. Double-blind, placebo-controlled study of L-acetylcarnitine for the treatment of hyperactive behavior in fragile X syndrome. Am J Med Genet. (1999) 87: 366– 8. 10.1002/(SICI)1096-8628(19991203)87:4<366::AID-AJMG18>3.0.CO;2-F 10588848 · DOI
  118. [122]Dal Lago A De Martini D Flore R Gaetani E Gasbarrini A Gerardino L. Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial. Drugs Exp Clin Res. (1999) 25: 29– 36. 10337502
  119. [124]Longo N Amat di San Filippo C Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. (2006) 142C: 77– 85. 10.1002/ajmg.c.30087 16602102 PMC2557099 · DOI · Paper page
  120. [125]Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr. (2000) 72(2 Suppl.): 618S– 23S. 10.1093/ajcn/72.2.618S 10919968 · DOI
  121. [126]Askarpour M Hadi A Miraghajani M Symonds ME Sheikhi A Ghaedi E. Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: an updated systematic review and dose-response meta-analysis of randomized controlled trials. Pharmacol Res. (2020) 151: 104554. 10.1016/j.phrs.2019.104554 31743774 · DOI
  122. [127]Katalinic L Krtalic B Jelakovic B Basic-Jukic N. The unexpected effects of L-carnitine supplementation on lipid metabolism in hemodialysis patients. Kidney Blood Press Res. (2018) 43: 1113– 20. 10.1159/000491807 30016788 · DOI
  123. [128]Delaney CL Spark JI Thomas J Wong YT Chan LT Miller MD. A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication. Atherosclerosis. (2013) 229: 1– 9. 10.1016/j.atherosclerosis.2013.03.004 23557982 · DOI
  124. [129]Bruls YMH Op den Kamp YJM Phielix E Lindeboom L Havekes B Schaart G. L-carnitine infusion does not alleviate lipid-induced insulin resistance and metabolic inflexibility. PLoS ONE. (2020) 15: e0239506. 10.1371/journal.pone.0239506 32976523 PMC7518598 · DOI
  125. [130]Fujiwara N Nakagawa H Enooku K Kudo Y Hayata Y Nakatsuka T. CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity. Gut. (2018) 67: 1493– 504. 10.1136/gutjnl-2017-315193 29437870 PMC6039238 · DOI

Cited by

Sorted by citations

Authors
Li, N., & Zhao, H.
Affiliations
  • Second Affiliated Hospital of Dalian Medical University (CN)
  • Dalian Medical University (CN)
Corresponding author
Zhao, Hui
ORCID
Venue
Frontiers in Medicine
Publisher
Frontiers Media SA
Published
2021-08-09
Volume
8
Pages
689042-689042
ISSN
2296-858X (ISSN-L)
DOI
10.3389/fmed.2021.689042
PMC
PMC8381051
OpenAlex
W3188724591
Cited by
79
References
4
Citations by year
2026: 12 · 2025: 18 · 2024: 16 · 2023: 12 · 2022: 19 · 2021: 2
FWCI
1.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Chinese Academy of Sciences
  • Dalian Medical University
  • Dalian Institute of Chemical Physics
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
L-carnitine, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, mitochondrial dysfunction, fatty acid beta-oxidation, insulin resistance, oxidative stress, carnitine supplementation, alcoholic fatty liver, viral hepatitis, liver cirrhosis, hepatocellular carcinoma

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