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A review on the role of l-carnitine in the management of tamoxifen side effects in treated women with breast cancer

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Tumor Biology

Abstract

l-carnitine is an antioxidant and is found to be a protective agent against many diseases including cancer. This review illustrates the possible role of l-carnitine as an add-on therapy to breast cancer patients maintained on tamoxifen. The objectives of carnitine treatment are diverse: improving tamoxifen-related side effects, offering better cancer prognosis by reducing the risk of developing cancer recurrence or metastasis, and modulating the growth factors which may be, in part, a prospective illustration to overcome tamoxifen resistance. So, it could be recommended to supplement l-carnitine to breast cancer patients starting tamoxifen treatment.

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References

  1. Ahmad S. l-carnitine in dialysis patients. Semin Dialysis. 2001;14(3):209–17.

    CAS  Google Scholar 

  2. Aja S, Landree LE, Kleman AM, Medghalchi SM, Vadlamudi A, McFadden JM, et al. Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight. Am J Physiol Regul Integr Comp Physiol. 2008;294:R352–61.

    PubMed  CAS  Google Scholar 

  3. Alagozlu H, Cindoruk M, Unal S. Tamoxifen-induced severe hypertriglyceridaemia and acute pancreatitis. Clin Drug Investig. 2006;26(5):297–302.

    PubMed  Google Scholar 

  4. Al-Majed AA. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats. Basic Clin Pharmacol Toxicol. 2007;100(3):145–50.

    PubMed  CAS  Google Scholar 

  5. Al-Rejaie SS, Aleisa AM, Al-Yahya AA, Bakheet SA, Alsheikh A, Fatani AG, et al. Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats. World J Gastroenterol. 2009;15(11):1373–80.

    PubMed Central  PubMed  CAS  Google Scholar 

  6. Andreasen EB, Tranholm M, Wiinberg B, Markussen B, Kristensen AT. Haemostatic alterations in a group of canine cancer patients are associated with cancer type and disease progression. Acta Vet Scand. 2012;54(1):3–30.

    PubMed Central  PubMed  CAS  Google Scholar 

  7. Ariazi EA, Cunliffe HE, Lewis-Wambi JS, Slifker MJ, Willis AL, Ramos P, et al. Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time. Proc Natl Acad Sci USA. 2011;108:18879–86.

    PubMed Central  PubMed  Google Scholar 

  8. Behr GA, Moreira JC, Frey BN. Preclinical and clinical evidence of antioxidant effects of antidepressant agents: implications for the pathophysiology of major depressive disorder. Oxid Med Cell Longev. 2012;2012:609421–34.

    PubMed Central  PubMed  Google Scholar 

  9. Biolo G, Toigo G, Ciocchi B, Situlin R, Iscra F, Gullo A, et al. Metabolic response to injury and sepsis: changes in protein metabolism. Nutrition. 1997;13:52S–7S.

    PubMed  CAS  Google Scholar 

  10. Borghi-Silva A, Baldissera V, Sampaio LM, Pires-DiLorenzo VA, Jamami M, Demonte A, et al. l-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs. Braz J Med Biol Res. 2006;39(4):465–74.

    PubMed  CAS  Google Scholar 

  11. Breuer B, Anderson R. The relationship of tamoxifen with dementia, depression, and dependence in activities of daily living in elderly nursing home residents. Women Health. 2000;31(1):71–85.

    PubMed  CAS  Google Scholar 

  12. Brocker C, Thompson DC, Vasiliou V. The role of hyperosmotic stress in inflammation and disease. Biomol Concepts. 2012;3(4):345–64.

    PubMed Central  PubMed  CAS  Google Scholar 

  13. Browne BC, O'Brien N, Duffy MJ, Crown J, O'Donovan N. HER-2 signalling and inhibition in breast cancer. Curr Cancer Drug Ther. 2009;9:419–38.

    CAS  Google Scholar 

  14. Campbell CI, Petrik JJ, Moorehead RA. ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis. Mol Cancer. 2010;9:235–50.

    PubMed Central  PubMed  Google Scholar 

  15. Cao Y, Qu HJ, Li P, Wang CB, Wang LX, Han ZW. Single dose administration of l-carnitine improves antioxidant activities in healthy subjects. Tohoku J Exp Med. 2011;224(3):209–13.

    PubMed  CAS  Google Scholar 

  16. Cappuzzo F, Toschi L, Tallini G, Ceresoli GL, Domenichini I, Bartolini S, et al. Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib. Ann Oncol. 2006;17:1120–7.

    PubMed  CAS  Google Scholar 

  17. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology. 2004;63(4):641–6.

    PubMed  CAS  Google Scholar 

  18. Cave MC, Hurt RT, Frazier TH, Matheson PJ, Garrison RN, McClain CJ, et al. Obesity, inflammation, and the potential application of pharmaconutrition. Nutr Clin Pract. 2008;23:16–34.

    PubMed  Google Scholar 

  19. Chan AL, Leung HW, Wang SF. Multivitamin supplement use and risk of breast cancer: a meta-analysis. Ann Pharmacother. 2011;45(4):476–84.

    PubMed  CAS  Google Scholar 

  20. Chang B, Nishikawa M, Nishiguchi S, Inoue M. l-carnitine inhibits hepatocarcinogenesis via protection of mitochondria. Int J Cancer. 2005;113:719–29.

    PubMed  CAS  Google Scholar 

  21. Corrales RM, Luo L, Chang EY, Pflugfelder SC. Effects of osmoprotectants on hyperosmolar stress in cultured human corneal epithelial cells. Cornea. 2008;27:574–9.

    PubMed  Google Scholar 

  22. Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Shaiova L, et al. l-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Ann N Y Acad Sci. 2004;1033:168–76.

    PubMed  CAS  Google Scholar 

  23. Cui J, Shen Y, Li R. Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends Mol Med. 2013;19(3):197–209.

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Davison Z, de Blacquiere GE, Westley BR, May FE. Insulin-like growth factor-dependent proliferation and survival of triple-negative breast cancer cells: implications for therapy. Neoplasia. 2011;13:504–15.

    PubMed Central  PubMed  CAS  Google Scholar 

  26. De Falco FA, D'Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G. Effect of the chronic treatment with l-acetylcarnitine in Down's syndrome. Clin Ter. 1994;144(2):123–7.

    PubMed  Google Scholar 

  27. De Grandis D, Minardi C. Acetyl-l-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D. 2002;3(4):223–31.

    PubMed  Google Scholar 

  28. De Vivo DC, Bohan TP, Coulter DL, Dreifuss FE, Greenwood RS, Nordli Jr DR, et al. l-carnitine supplementation in childhood epilepsy: current perspectives. Epilepsia. 1998;39(11):1216–25.

    PubMed  Google Scholar 

  29. Dossus L, Kaaks R. Nutrition, metabolic factors and cancer risk. Best Pract Res Clin Endocrinol Metab. 2008;22(4):551–71.

    PubMed  CAS  Google Scholar 

  30. Duffy LS, Greenberg DB, Younger J, Ferraro MG. Iatrogenic acute estrogen deficiency and psychiatric syndromes in breast cancer patients. Psychosomatics. 1999;40:304–8.

    PubMed  CAS  Google Scholar 

  31. Dutta A, Ray K, Singh VK, Vats P, Singh SN, Singh SB. l-carnitine supplementation attenuates intermittent hypoxia-induced oxidative stress and delays muscle fatigue in rats. Exp Physiol. 2008;93(10):1139–46.

    PubMed  CAS  Google Scholar 

  32. Eisner A, Luoh SW. Breast cancer medications and vision: effects of treatments for early-stage disease. Curr Eye Res. 2011;36(10):867–85.

    PubMed Central  PubMed  CAS  Google Scholar 

  33. Erbas H, Aydogdu N, Usta U, Erten O. Protective role of carnitine in breast cancer via decreasing arginase activity and increasing nitric oxide. Cell Biol Int. 2007;31:1414–9.

    PubMed  CAS  Google Scholar 

  34. Federighi G, Macchi M, Bernardi R, Scuri R, Brunelli M, Durante M, et al. Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-l-carnitine treatment. PLoS One. 2013;8(1):e53605–11.

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-l-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005;219(3):154–66.

    PubMed  CAS  Google Scholar 

  36. Fidler MJ, Shersher DD, Borgia JA, Bonomi P. Targeting the insulin-like growth factor receptor pathway in lung cancer: problems and pitfalls. Ther Adv Med Oncol. 2012;4(2):51–60.

    PubMed Central  PubMed  CAS  Google Scholar 

  37. Forloni G, Angeretti N, Smiroldo S. Neuroprotective activity of acetyl-l-carnitine: studies in vitro. J Neurosci Res. 1994;37(1):92–6.

    PubMed  CAS  Google Scholar 

  38. Gallicchio L, Lord G, Tkaczuk K, Danton M, Lewis LM, Lim CK, et al. Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer. Breast Cancer Res Treat. 2004;85(1):89–97.

    PubMed  CAS  Google Scholar 

  39. Giancaterini A, De Gaetano A, Mingrone G, Gniuli D, Liverani E, Capristo E, et al. Acetyl-l-carnitine infusion increases glucose disposal in type 2 diabetic patients. Metabolism. 2000;49(6):704–8.

    PubMed  CAS  Google Scholar 

  40. Gjerde J, Gandini S, Guerrieri-Gonzaga A, Haugan Moi LL, Aristarco V, Mellgren G, et al. Tissue distribution of 4-hydroxy-N-desmethyltamoxifen and tamoxifen-N-oxide. Breast Cancer Res Treat. 2012;134(2):693–700.

    PubMed Central  PubMed  CAS  Google Scholar 

  41. Gjerde J, Geisler J, Lundgren S, Ekse D, Varhaug JE, Mellgren G, et al. Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer. BMC Cancer. 2010;10:313–25.

    PubMed Central  PubMed  Google Scholar 

  42. Gülçin I. Antioxidant and antiradical activities of l-carnitine. Life Sci. 2006;78(8):803–11.

    PubMed  Google Scholar 

  43. Gunes D, Kirkim G, Kolatan E, Guneri EA, Ozogul C, Altun Z, et al. Evaluation of the effect of acetyl l-carnitine on experimental cisplatin ototoxicity and neurotoxicity. Chemotherapy. 2011;57(3):186–94.

    PubMed  CAS  Google Scholar 

  44. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, et al. Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA. 2002;99(4):1870–5.

    PubMed Central  PubMed  CAS  Google Scholar 

  45. Hansen MV, Madsen MT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, et al. The effect of melatonin on depression, anxiety, cognitive function and sleep disturbances in patients with breast cancer. The MELODY trial: protocol for a randomised, placebo-controlled, double-blinded trial. BMJ. 2012;2(1):e000647–55.

    Google Scholar 

  46. Hayashi T. Estrogen, SERM. Nihon Rinsho. 2011;69(7):1270–4.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  48. 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.

    PubMed  CAS  Google Scholar 

  49. Huiart L, Bouhnik AD, Rey D, Tarpin C, Cluze C, Bendiane MK, et al. Early discontinuation of tamoxifen intake in younger women with breast cancer: is it time to rethink the way it is prescribed? Eur J Cancer. 2012;48(13):1939–46.

    PubMed  Google Scholar 

  50. Husain S, Crosson CE. Role of PKCepsilon in PGF2alpha-stimulated MMP-2 secretion from human ciliary muscle cells. J Ocul Pharmacol Ther. 2008;24(3):268–77.

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Jeukendrup AE, Randell R. Fat burners: nutrition supplements that increase fat metabolism. Obes Rev. 2011;12(10):841–51.

    PubMed  CAS  Google Scholar 

  52. Jirillo E, Altamura M, Munno I, Pellegrino NM, Sabato R, Di Fabio S, et al. Effects of acetyl-l-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study. Immunopharmacol Immunotoxicol. 1991;13(1–2):135–46.

    PubMed  CAS  Google Scholar 

  53. Khalil RM, Darwish H, El-Ashmawy NE, El-Bahrawy HA. l-carnitine ameliorates tamoxifen-associated adverse effects in breast cancer women. Int J Cancer Res. 2013;47(2):1149–57.

    Google Scholar 

  54. Khalil RM, El-Ashmawy NE, El-Bahrawy HA, Darwish H. l-carnitine supplement to tamoxifen-treated breast cancer patients: protection against cardiovascular risk. Int J Med Sci. 2013;46(2):1245–54.

    Google Scholar 

  55. Khalil RM, El-Bahrawy HA, El-Ashmawy NE, Darwish H. l-carnitine decreases Her-2/neu in breast cancer patients treated with tamoxifen. IOSR-JPBS. 2013;5(2):91–8.

    Google Scholar 

  56. Kumaran S, Subathra M, Balu M, Panneerselvam C. Supplementation of l-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res. 2005;31(1):55–67.

    PubMed  CAS  Google Scholar 

  57. Lambrechts S, Decloedt J, Neven P. Breast cancer prevention: lifestyle changes and chemoprevention. Acta Clin Belg. 2011;66(4):283–92.

    PubMed  CAS  Google Scholar 

  58. Landree LE, Hanlon AL, Strong DW, Rumbaugh G, Miller IM, Thupari JN, et al. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism. J Biol Chem. 2004;279:3817–27.

    PubMed  CAS  Google Scholar 

  59. Lango R, Smoleński RT, Rogowski J, Siebert J, Wujtewicz M, Słomińska EM, et al. Propionyl-l-carnitine improves hemodynamics and metabolic markers of cardiac perfusion during coronary surgery in diabetic patients. Cardiovasc Drugs Ther. 2005;19(4):267–75.

    PubMed  CAS  Google Scholar 

  60. Legault C, Maki PM, Resnick SM, Coker L, Hogan P, Bevers TB, et al. Effects of tamoxifen and raloxifene on memory and other cognitive abilities: cognition in the study of tamoxifen and raloxifene. J Clin Oncol. 2009;27(31):5144–52.

    PubMed Central  PubMed  CAS  Google Scholar 

  61. Li H, Li QD, Wang PZ, Wang MS, Cui J, Diao TY, et al. The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line. Lipids Health Dis. 2011;10:108–18.

    PubMed Central  PubMed  CAS  Google Scholar 

  62. Lien EA, Anker G, Ueland PM. Pharmacokinetics of tamoxifen in premenopausal and postmenopausal women with breast cancer. J Steroid Biochem Mol Biol. 1995;55(2):229–31.

    PubMed  CAS  Google Scholar 

  63. Macciò A, Madeddu C. Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. Sci Wor J. 2011;11:2020–36.

    Google Scholar 

  64. Maestri A, De Pasquale CA, Cundari S, Zanna C, Cortesi E, Crinò L. A pilot study on the effect of acetyl-l-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy. Tumori. 2005;91:135–8.

    PubMed  CAS  Google Scholar 

  65. Malaguarnera M, Pistone G, Astuto M, Vecchio I, Raffaele R, Lo Giudice E, et al. Effects of l-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial. Dig Dis Sci. 2006;51(12):2242–7.

    PubMed  CAS  Google Scholar 

  66. Micheletti R, Giacalone G, Bianchi G. Effect of propionyl-l-carnitine on the mechanics of right and left papillary muscles from volume-overloaded rat hearts. J Cardiovasc Pharmacol. 1996;27(1):52–7.

    PubMed  CAS  Google Scholar 

  67. Mintz M. Carnitine in human immunodeficiency virus type 1 infection/acquired immune deficiency syndrome. J Child Neurol. 1995;10(2):S40–4.

    PubMed  Google Scholar 

  68. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-l-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003;18(2):61–71.

    PubMed  Google Scholar 

  69. Mook D, Felger J, Graves F, Wallen K, Wilson ME. Tamoxifen fails to affect central serotonergic tone but increases indices of anxiety in female rhesus macaques. Psychoneuroendocrinology. 2005;30(3):273–83.

    PubMed  CAS  Google Scholar 

  70. Moon YW, Park S, Sohn JH, Kang DR, Koo JS, Park HS, et al. Clinical significance of progesterone receptor and HER2 status in estrogen receptor-positive, operable breast cancer with adjuvant tamoxifen. J Cancer Res Clin Oncol. 2011;137(7):1123–30.

    PubMed  CAS  Google Scholar 

  71. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006;3:269–80.

    PubMed  CAS  Google Scholar 

  72. Naini AE, Sadeghi M, Mortazavi M, Moghadasi M, Harandi AA. Oral carnitine supplementation for dyslipidemia in chronic hemodialysis patients. Saudi J Kidney Dis Transpl. 2012;23(3):484–8.

    PubMed  Google Scholar 

  73. Nazarewicz RR, Zenebe WJ, Parihar A, Larson SK, Alidema E, Choi J, et al. Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase. Cancer Res. 2007;67:1282–90.

    PubMed  CAS  Google Scholar 

  74. Neuhouser ML, Schenk J, Song YJ, Tangen CM, Goodman PJ, Pollak M, et al. Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. Prostate. 2008;68(13):1477–86.

    PubMed Central  PubMed  Google Scholar 

  75. Ng VL. Prothrombin time and partial thromboplastin time assay considerations. Clin Lab Med. 2009;29:253–63.

    PubMed  Google Scholar 

  76. Ntukidem NI, Nguyen AT, Stearns V, Rehman M, Schott A, Skaar T, et al. Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen. Clin Pharmacol Ther. 2008;83(5):702–10.

    PubMed Central  PubMed  CAS  Google Scholar 

  77. Owen L, Sunram-Lea SI. Metabolic agents that enhance ATP can improve cognitive functioning: a review of the evidence for glucose, oxygen, pyruvate, creatine, and l-carnitine. Nutrients. 2011;3(8):735–55.

    PubMed Central  PubMed  CAS  Google Scholar 

  78. Palva T, Ranta H, Koivisto AM, Pylkkänen L, Cuzick J, Holli K. A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo—a substudy for IBIS I Breast Cancer Prevention Trial. Eur J Cancer. 2013;49(1):45–51.

    PubMed  CAS  Google Scholar 

  79. Porter NS, Jason LA, Boulton A, Bothne N, Coleman B. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia. J Altern Complement Med. 2010;16(3):235–49.

    PubMed  Google Scholar 

  80. Pritchard KI, Abramson BL. Cardiovascular health and aromatase inhibitors. Drugs. 2006;66(13):1727–40.

    PubMed  CAS  Google Scholar 

  81. Puca FM, Genco S, Specchio LM, Brancasi B, D'Ursi R, Prudenzano A, et al. Clinical pharmacodynamics of acetyl-l-carnitine in patients with Parkinson's disease. Int J Clin Pharmacol Res. 1990;10(1–2):139–43.

    PubMed  CAS  Google Scholar 

  82. Puig T, Relat J, Marrero PF, Haro D, Brunet J, Colomer R. Green tea catechin inhibits fatty acid synthase without stimulating carnitine palmitoyltransferase-1 or inducing weight loss in experimental animals. Anticancer Res. 2008;28(6A):3671–6.

    PubMed  CAS  Google Scholar 

  83. Queiroga FL, Perez-Alenza MD, Silvan G, Pena L, Lopes CS, Illera JC. Crosstalk between GH/IGF-I axis and steroid hormones (progesterone, 17β-estradiol) in canine mammary tumours. J Steroid Biochem Mol Biol. 2008;110:76–82.

    PubMed  CAS  Google Scholar 

  84. Radhakrishnan Y, Busby Jr WH, Shen X, Maile LA, Clemmons DR. Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells. J Biol Chem. 2010;285(21):15682–95.

    PubMed Central  PubMed  CAS  Google Scholar 

  85. Rosca MG, Lemieux H, Hoppel CL. Mitochondria in the elderly: is acetylcarnitine a rejuvenator? Adv Drug Deliv Rev. 2009;61(14):1332–42.

    PubMed  CAS  Google Scholar 

  86. Samaddar JS, Gaddy VT, Duplantier J, Thandavan SP, Shah M, Smith MJ, et al. A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance. Mol Cancer Ther. 2008;7(9):2977–87.

    PubMed  CAS  Google Scholar 

  87. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 western prospective studies. Circulation. 2007;115(4):450–8.

    PubMed  CAS  Google Scholar 

  88. Sener G, Ekşioğlu-Demiralp E, Cetiner M, Ercan F, Sirvanci S, Gedik N, et al. l-carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol. 2006;22(1):47–60.

    PubMed  CAS  Google Scholar 

  89. Sharma S, Neetu S, Wiseman DA, Carter L, Kumar S, Hou Y, et al. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2008;294:L46–56.

    PubMed Central  PubMed  CAS  Google Scholar 

  90. Silvério R, Laviano A, Rossi Fanelli F, Seelaender M. l-carnitine and cancer cachexia: clinical and experimental aspects. J Cachexia Sarcopenia Muscle. 2011;2(1):37–44.

    PubMed Central  PubMed  Google Scholar 

  91. Singh B, Bhat NK, Bhat HK. Partial inhibition of estrogen-induced mammary carcinogenesis in rats by tamoxifen: balance between oxidant stress and estrogen responsiveness. PLoS One. 2011;6(9):e25125–36.

    PubMed Central  PubMed  CAS  Google Scholar 

  92. Spichiger E, Müller-Fröhlich C, Denhaerynck K, Stoll H, Hantikainen V, Dodd M. Prevalence of symptoms, with a focus on fatigue, and changes of symptoms over three months in outpatients receiving cancer chemotherapy. Swiss Med Wkly. 2011;141:w13303–13.

    PubMed  Google Scholar 

  93. Thewes B, Meiser B, Duric VM, Stockler MR, Taylor A, Stuart-Harris R, et al. What survival benefits do premenopausal patients with early breast cancer need to make endocrine therapy worthwhile? Lancet Oncol. 2005;6(8):581–8.

    PubMed  CAS  Google Scholar 

  94. Tominaga T, Kimijima I, Kimura M, Takatsuka Y, Takashima S, Nomura Y, et al. Effects of toremifene and tamoxifen on lipid profiles in postmenopausal patients with early breast cancer: interim results from a Japanese phase III trial. Jpn J Clin Oncol. 2010;40(7):627–33.

    PubMed  Google Scholar 

  95. Tsang RY, Finn RS. Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer. Br J Cancer. 2012;106:6–13.

    PubMed Central  PubMed  CAS  Google Scholar 

  96. Tunstall RJ, McAinch AJ, Hargreaves M, van Loon LJ, Cameron-Smith D. Reduced plasma free fatty acid availability during exercise: effect on gene expression. Eur J Appl Physiol. 2007;99(5):485–93.

    PubMed  CAS  Google Scholar 

  97. Uhr JW, Pantel K. Controversies in clinical cancer dormancy. Proc Natl Acad Sci USA. 2011;108(30):12396–400.

    PubMed Central  PubMed  CAS  Google Scholar 

  98. Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004;66(2):276–82.

    PubMed  CAS  Google Scholar 

  99. Vgontzas AN, Bixler EO, Chrousos GP. Obesity-related sleepiness and fatigue: the role of the stress system and cytokines. Ann NY Acad Sci. 2006;1083:329–44.

    PubMed  CAS  Google Scholar 

  100. Wenzel U, Nickel A, Daniel H. Increased carnitine-dependent fatty acid uptake into mitochondria of human colon cancer cells induces apoptosis. J Nutr. 2005;135(6):1510–4.

    PubMed  CAS  Google Scholar 

  101. Westlund KN, Lu Y, Werrbach-Perez K, Hulsebosch CE, Morgan B, Pizzo DP, et al. Effects of nerve growth factor and acetyl-l-carnitine arginyl amide on the human neuronal line HCN-1A. Int J Dev Neurosci. 1992;10(5):361–73.

    PubMed  CAS  Google Scholar 

  102. Winter S, Jue K, Prochazka J, Francis P, Hamilton W, Linn L, et al. The role of l-carnitine in pediatric cardiomyopathy. J Child Neurol. 1995;10(2):S45–51.

    PubMed  Google Scholar 

  103. Xu S, Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Transport of l-carnitine in human corneal and conjunctival epithelial cells. Mol Vis. 2010;16:1823–31.

    PubMed Central  PubMed  CAS  Google Scholar 

  104. Yamada S, Matsuda R, Nishimura F, Nakagawa I, Motoyama Y, Park YS, et al. Carnitine-induced senescence in glioblastoma cells. Exp Ther Med. 2012;4(1):21–5.

    PubMed Central  PubMed  CAS  Google Scholar 

  105. Yuvaraj S, Premkumar VG, Vijayasarathy K, Gangadaran SGD, Sachdanandam P. Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins. Clin Biochem. 2007;40:623–8.

    PubMed  CAS  Google Scholar 

  106. Zhao Y, Zhang J, Zhang J, Wu J. Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values. PLoS One. 2011;6(1):e16470–3.

    PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt

    Nahla E. El-Ashmawy

  2. Biochemistry Department, Faculty of Pharmacy, Delta University, Gamasah, Egypt

    Rania M. Khalil

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  1. Nahla E. El-Ashmawy
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  2. Rania M. Khalil
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Correspondence to Rania M. Khalil.

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El-Ashmawy, N.E., Khalil, R.M. A review on the role of l-carnitine in the management of tamoxifen side effects in treated women with breast cancer. Tumor Biol. 35, 2845–2855 (2014). https://doi.org/10.1007/s13277-013-1477-5

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  • DOI: https://doi.org/10.1007/s13277-013-1477-5

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