L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the ‘quasi vitamins’ LC and ALC can be used either individually, or in combination with each other or with other antioxidants.
This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production. They reportedly aid β-oxidation in oocytes, maintain its cell membrane stability by acetylation of phospholipids and amphiphilic actions, prevent free radical-induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl storage as energy supply to maintain the robustness of reproductive cells.
While both LC and ALC have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells. These beneficial effects show great promise in its application as a treatment option for women facing infertility disorders.
Binienda Z, Virmani A. The Mitochondriotropic effects of L-carnitine and its esters in the central nervous system. Curr Med Chem - Cent Nervous Sys Agents. 2003;3:275–82. CrossRef
Abdelrazik H, Agarwal A. L-carnitine and assisted reproduction. Arch Med Sci. 2009;1A:S43–7.
Cheng HJ, Chen T. Clinical efficacy of combined L-carnitine and acetyl-L-carnitine on idiopathic asthenospermia. Zhonghua Nan Ke Xue. 2008;14:149–51. PubMed
Dokmeci D. Oxidative stress, male infertility and the role of carnitines. Folia Med (Plovdiv). 2005;47:26–30.
Samimi M, Jamilian M, Ebrahimi FA, Rahimi M, Tajbakhsh B, Asemi Z. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol. 2016;84:851–7. CrossRef
Genazzani AD, Lanzoni C, Ricchieri F, Santagni S, Rattighieri E, Chierchia E, Monteleone P, Jasonni VM. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea. J Endocrinol Investig. 2011;34:287–91. CrossRef
Latifian S, Hamdi K, Totakneh R. Effect of addition of l-carnitine in polycystic ovary syndrome (PCOS) patients with clomiphene citrate and gonadotropin resistant. Int J Curr Res Acad Rev. 2015;3:469–76.
Samland CJ, Musser RE, Peters JK, Sawyer JT, Owen KQ, Davis DL. Ovulation and fertilization rate of gilts provided additional L-carnitine and chromium nicotinate. In: Kansas Agricultural Experiment Station Research Reports, editor, Swine Day. Manhattan: Agri Exp Station Cooper Ext Service; 1998. p. 25–7.
Pirestani A, Aghakhani M, Tabatabaei SN, Ghalamkari G, Baharlo F. Effects of dietary L-carnitine and choline chloride compound on reproduction indices and udder immune system in Holstein dairy cattle. In: Proceedings of international conference on life Science and Technology; 2011. p. 59–61.
Gulewitch VS, Krimberg R. Zur Kenntnis der Extraktivstoffe der Muskeln. II. Mitteilung: Über das Carnitin. Zeits für Physiol Chem. 1905;45:326–30. CrossRef
Marzo A, Arrigoni Martelli E, Mancinelli A, Cardace G, Corbelletta C, Bassani E, Solbiati M. Protein binding of L-carnitine family components. Eur J Drug Metab Pharmacokinet. 1991;3:364–8.
Infante JP, Tschanz CL, Shaw N, Michaud AL, Lawrence P, Brenna JT. Straight-chain acyl-CoA oxidase knockout mouse accumulates extremely long chain fatty acids from alpha-linolenic acid: evidence for runaway carousel-type enzyme kinetics in peroxisomal beta-oxidation diseases. Mol Genet Metab. 2002;75:108–19. CrossRefPubMed
Christiana K, George T, George F, Margarita T, Anna T, Costas F, Irene A. L-carnitine alters lipid body content in pre-implantation embryos leading to infertility. J Reprod Immunol. 2014;101-102:18–39. CrossRef
Jamilian H, Jamilian M, Samimi M, Afshar Ebrahimi F, Rahimi M, Bahmani F, Aghababayan S, Kouhi M, Shahabbaspour S, Asemi Z. 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. CrossRefPubMed
Meczekalski B, Katulski K, Czyzyk A, Podfigurna-Stopa A, Maciejewska-Jeske M. Functional hypothalamic amenorrhea and its influence on women's health. J Endocrinol Investig. 2014;37:1049–56. CrossRef
MBMR F, Flayyih NK. Effect of L-carnitine administration to pregnant mice on some reproductive hormones and organs. Iraqi J Vet Med. 2012;36:68–74.
Adabi SG, Moghaddam G, Taghizadeh A, Nematollahi A, Farahvash T. Effect of L-carnitine and vegetable fat on broiler breeder fertility, hatchability, egg yolk and serum cholesterol and triglyceride. Int J Poult Sci. 2006;5:970–4. CrossRef
Tselekidou A, Athanassakis I. PGE1 versus PGE2: protective rather than inducing agent for endometriosis. Eur J Immunol. 2009;81:165.
Dionyssopoulou E, Anagnostaki E, Tselekidou A, Vassiliadis S, Athanassakis I. Establishment or aggravation of endometriosis-induction process. In: Arici A, Matalliotakis I, editors. Endometriosis-adenomyosis. Greece: PM Publications; 2011.
Virmani MA, Zerelli S, Vitullo P, Cossetti C. Effect Of nutrients on ovulation and oocytes quality in mice. In: Proceedings of 11th congress of the European Society of Gynecology. Roma: Edizioni Internazionali; 2015. p. 212–4.
Virmani MA, Virtullo P, Cossetti C. Improving Oocyte and Sperm Quality by L-Carnitine, Acetyl-L-carnitine and Other Nutrients as Major Determinant in Pregnancy Success. Journal of Perinatal Medicine. 45 Supplement. 2017;1:3.
Canbolat EP, Sagsoz N, Noyan V, Yucel A, Kisa U. Effects of l-carnitine on oxidative stress parameters in oophorectomized rats. Alex J Med. 2017;53:55–60. CrossRef
Corduk M, Sarica S. Effects of L-carnitine in layer diets containing different fat sources and energy levels on hen performance and egg quality. South Afr J Anim Sci. 2008;38:260–70.
Musser RE, Dritz SS, Davis DL, Tokach MD, Nelssen JL, Goodband RD, Owen KQ. Effects of L-carnitine in the gestating sow diet on fetal muscle development and carcass characteristics of the offspring. J Appl Anim Res. 2007;31:105–11. CrossRef
Scholz H, Heimendahl EV, Menn F, Ahrens A. Application of Protected L-Carnitine in Dairy Cows during Transition and High Lactation Period. Global J Sci Front Res. 2014;XIV:41–6.
Somfai T, Kaneda M, Akagi S, Watanabe S, Haraguchi S, Mizutani E, Dang-Nguyen TQ, Geshi M, Kikuchi K, Nagai T. Enhancement of lipid metabolism with L-carnitine during in vitro maturation improves nuclear maturation and cleavage ability of follicular porcine oocytes. Reprod Fertil Dev. 2011;23:912–20. CrossRefPubMed
Moawad AR, Xu B, Tan SL, Taketo T. L-carnitine supplementation during vitrification of mouse germinal vesicle stage-oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. Hum Reprod. 2014;29:2256–68. CrossRefPubMed
Bedaiwy MA, Falcone T. Peritoneal fluid environment in endometriosis. Clinicopathological implications. Minerva Ginecol. 2003;55:333–45. PubMed
Glabowski W, Kurzawa R, Wiszniewska B, Baczkowski T, Marchlewicz M, Brelik P. Growth factors effects on preimplantation development of mouse embryos exposed to tumor necrosis factor alpha. Reprod Biol. 2005;5:83–99. PubMed
Zare Z, Masteri Farahani R, Salehi M, Piryaei A, Ghaffari Novin M, Fadaei Fathabadi F, Mohammadi M, Dehghani-Mohammadabadi M. Effect of L-carnitine supplementation on maturation and early embryo development of immature mouse oocytes selected by brilliant cresyle blue staining. J Assist Reprod Genet. 2015;32:635–43. CrossRefPubMedPubMedCentral
Bareh GM. The effect of endometriosis on the DNA integrity of different stages of Embryos' development and the role of L- carnitine in preventing damage to early stages. J Minimal Inv Gynecol. 2010;17:S51. CrossRef
Phongmitr T, Liang Y, Srirattana K, Panyawai K, Sripunya N, Treetampinich C, Parnpai R. Effects of L-carnitine supplemented in maturation medium on the maturation rate of swamp buffalo oocytes. Buffalo Bulletin. 2013;32:613–6.
Ghanem N. L-carnitine improved bovine blastocyst rate and quality when supplemented at different preimplantation stages. Egypt J Anim Prod. 2015;52:89–99.
Manzano PCVJ, Ocampo MB, Ocampo LC, Maylem ERS, Lazaro JV. Improved bovine blastocyst developmental potential by L-carnitine supplementation. Int J Sci Res Knowledge. 2015;3:021–9. CrossRef
Khanmohammadi N, Movahedin M, Safari M, Sameni HR, Yousefi B, Jafari B, Zarbakhsh S. Effect of L-carnitine on in vitro developmental rate, the zona pellucida and hatching of blastocysts and their cell numbers in mouse embryos. Int J Reprod Biomed (Yazd). 2016;14:649–56.
Stojkovic M, Machado SA, Stojkovic P, Zakhartchenko V, Hutzler P, Goncalves PB, Wolf E. Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol Reprod. 2001;64:904–9. CrossRefPubMed
Virmani MA, Krsmanovic LZ, Stojilkovic SS, Catt KJ. Stimulatory effects of L-acetyl carnitine on the pituitary-gonadal axis in female rats. In: Advances in human female reproduction. New York: Sereno Symposium Publication, Raven Press; 1991. p. 291–6.
Amenta F, Cavallotti C, De Rossi M, Bossoni G, Carpi C. Effect of acetyl-L-carnitine treatment on some behavioural, histochemical and histological parameters of methylazoxymethanol microencephalic rats. Int J Tissue React. 1986;8:513–26. PubMed
Bodis-Wollner I. Physiological effects of acetyl-levo-carnitine in the central nervous system. Int J Clin Pharmacol Res. 1990;10:109–14. PubMed
Abo-Ghanema II, El-Nasharty MA, El-Far AH, Ghonium HA. Effect of ginger and L-carnitine on the reproductive performance of male rats. World Acad Sci Eng Technol. 2012;64:980–6.
Abdel-Khalek AE, El-Ratel IT, Wafa WM, El-Nagar HA, Younan GE, Fouda SF. Effect of pre-conception coenzyme Q10 and L-carnitine treatments on ovulatory response, genital characteristics and in vitro embryo characteristics in rabbits. Asian J Anim Vet Adv. 2015;11:53–9. CrossRef
El-Damarawi MA, Salama ME. Obestatin and L-carnitine as a defensive strategy against fertility disorders induced by obesity in male rats. Tanta Med J. 2014;42:103–11. CrossRef
MSH H, Youssef SF, El-bahy MA. Effects of L-carnitine and ascorbic acid supplementation on productive, reproductive, physiological and immunological performance of golden montazah laying hens. Egypt Poult Sci. 2011;31:557–78.
Kacem O, Harzallah M, Zedini C, Zidi I, Meddeb S, Fekih M, Saidi H, Chaib A, Boughizane S, Ali HB, et al. Beneficial effect of an oral antioxidant supplementation (Fertimax2) on IVF-ICSI outcomes: a preliminary clinical study. Adv Reprod Sci. 2014;2:47–56. CrossRef
Genazzani AD, Despini G, Czyzyk A, Podfigurna A, Simoncini T, Meczekalski B. Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA). Gynecol Endocrinol. 2017:1–5.
Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Curr Women's Health Rev. 2010;6:84–95. CrossRef
McDowell LR, Wilkinson N, Madison R, Felix T. Vitamins and minerals functioning as antioxidants with supplementation considerations. In: Florida Ruminant Nutrition Symposium. Gainesville, FL: Best Western Gateway Grand; 2007. p. 30–1.
Sugino N, Karube-Harada A, Taketani T, Sakata A, Nakamura Y. Withdrawal of ovarian steroids stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: potential relevance to menstruation. J Reprod Dev. 2004;50:215–25. CrossRefPubMed
Crha I, Hruba D, Ventruba P, Fiala J, Totusek J, Visnova H. Ascorbic Acid and infertility treatment. Cent Eur J Public Health. 2003;11:63–7. PubMed
- Role of L-carnitine in female infertility
- BioMed Central
Neu im Fachgebiet Gynäkologie und Geburtshilfe
Meistgelesene Bücher aus dem Fachgebiet
Mail Icon II