Therapeutic Roles and Safety Profiles of Non-Vitamin Antioxidant Supplements in Female Infertility: A Narrative Review
Abstract
Objective: Treatment of female infertility consists different strategies including metabolic, hormonal and surgical therapeutic modalities. Non-vitamin supplements with antioxidant activity as carnitines, Inositols, Poly Unsaturated Fatty Acids (PUFAs), coenzyme Q10 and melatonin are among those with most popularity, but their prescription may confer some warnings.
Materials and methods: This review narrates the antioxidant mechanism of these supplements, beside their effect on outcomes of infertility treatment while considering side effects, warnings and ranges of doses.
Results: Carnitines are used for energy production and fat metabolism, while they have anti-aging and antioxidant effects. Supplementation with carnitines improve obesity outcomes, especially in Poly Cystic Ovarian Disease (PCOS) patients. Rare cases have shown increasing risk of seizure with levocarnitine. Coenzyme Q10 (Ubiquinone) has shown benefit in patients with PCOS or poor ovarian responders. It significantly increased live birth rate and the side effects are minimal even in higher doses. Poly Unsaturated Fatty Acids (PUFAs) have shown impact on follicular development and embryo quality. The hazard is increasing lipid low density lipoprotein (LDL) in high doses. Use of inositols in female infertility treatment is due to its metabolic effect and insulin resistance in PCOS patients resulting in decreasing use of gonadotropins. They have produced acceptable results about count of follicles and oocyte quality. Hypoglycemic effects of inositols have been reported as side effect, especially in combination with other hypoglycemic agents. Melatonin can increase the clinical pregnancy rate, and improve the outcomes about oocyte and quality of embryo via receptor- and non-receptor- action. Dizziness, drowsiness, and headache are reported in higher doses of melatonin.
Conclusion: The attitude that all supplement can be prescribed without restriction endangers susceptible patients. Hence, increasing our knowledge about efficacy and safety profile can help individualize prescription of supplements for female infertility.
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5. Bhardwaj JK, Panchal H, Saraf P. Ameliorating effects of natural antioxidant compounds on female infertility: a review. Reprod Sci. 2021;28(5):1227-1256.
6. Taylor CT. Antioxidants and reactive oxygen species in human fertility. Environ Toxicol Pharmacol. 2001;10(4):189-198.
7. Hosseini B, Eslamian G. Association of micronutrient intakes with female infertility: review of recent evidence. 2015. Thrita. 2015;4(1):e25586.
8. Pandey C, Maunder A, Liu J, Vaddiparthi V, Costello MF, Bahri-Khomami M, et al. The role of nutrient supplements in female infertility: an umbrella review and hierarchical evidence synthesis. Nutrients. 2025;17(1):57.
9. Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci. 2022;23(5):2717.
10. Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet. 2012;51(9):553-572.
11. Modanloo M, Shokrzadeh M. Analyzing mitochondrial dysfunction, oxidative stress, and apoptosis: potential role of L-carnitine. Iran J Kidney Dis. 2019;13(2):74-86.
12. Lopez-Maldonado A, Pastoriza S, Rufián-Henares JA. Assessing the antioxidant and metabolic effect of an alpha-lipoic acid and acetyl-L-carnitine nutraceutical. Curr Res Food Sci. 2021;4:336-344.
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35. Wang R, Feng Y, Chen J, Chen Y, Ma F. Association between polyunsaturated fatty acid intake and infertility among American women aged 20-44 years. Front Public Health. 2022;10:938343.
36. Giorgi VSI, Ferriani RA, Navarro PA. Omega-3 fatty acids and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with endometriosis: an experimental study. JBRA Assist Reprod. 2023;27(4):610-618.
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46. Sene AA, Saeedzarandi M, Yazdizadeh M, Ghaffari SR, Amjadi F, Zandieh Z, et al. The effect of myo-inositol on assisted reproductive technology outcomes in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized clinical trial studies. Int J Reprod Biomed. 2025;23(5):353-366.
47. Akbari Sene A, Tabatabaie A, Nikniaz H, Alizadeh A, Sheibani K, Mortezapour Alisaraie M, et al. The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial. Arch Gynecol Obstet. 2019;299(6):1701-1707.
48. Fitz V, Graca S, Mahalingaiah S, Liu J, Lai L, Butt A, et al. Inositol for polycystic ovary syndrome: a systematic review and meta-analysis to inform the 2023 update of the international evidence-based PCOS guidelines. J Clin Endocrinol Metab. 2024;109(6):1630-1655.
49. Corrado F, D'Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011;28(8):972-975.
50. Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, et al. Melatonin: pharmacology, functions and therapeutic benefits. Curr Neuropharmacol. 2017;15(3):434-443.
51. Roy D, Belsham DD. Melatonin receptor activation regulates GnRH gene expression and secretion in
GT1-7 GnRH neurons: signal transduction mechanisms. J Biol Chem. 2002;277(1):251-258.
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2. Awonuga AO, Camp OG, Biernat MM, Abu-Soud HM. Overview of infertility. Syst Biol Reprod Med. 2025;71(1):116-142.
3. Vitagliano A, Petre GC, Francini-Pesenti F, De Toni L, Di Nisio A, Grande G, et al. Dietary supplements for female infertility: a critical review of their composition. Nutrients. 2021;13(10):3552.
4. Feng J, Wang J, Zhang Y, Zhang Y, Jia L, Zhang D, et al. The efficacy of complementary and alternative medicine in the treatment of female infertility. Evid Based Complement Alternat Med. 2021;2021(1):6634309.
5. Bhardwaj JK, Panchal H, Saraf P. Ameliorating effects of natural antioxidant compounds on female infertility: a review. Reprod Sci. 2021;28(5):1227-1256.
6. Taylor CT. Antioxidants and reactive oxygen species in human fertility. Environ Toxicol Pharmacol. 2001;10(4):189-198.
7. Hosseini B, Eslamian G. Association of micronutrient intakes with female infertility: review of recent evidence. 2015. Thrita. 2015;4(1):e25586.
8. Pandey C, Maunder A, Liu J, Vaddiparthi V, Costello MF, Bahri-Khomami M, et al. The role of nutrient supplements in female infertility: an umbrella review and hierarchical evidence synthesis. Nutrients. 2025;17(1):57.
9. Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci. 2022;23(5):2717.
10. Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet. 2012;51(9):553-572.
11. Modanloo M, Shokrzadeh M. Analyzing mitochondrial dysfunction, oxidative stress, and apoptosis: potential role of L-carnitine. Iran J Kidney Dis. 2019;13(2):74-86.
12. Lopez-Maldonado A, Pastoriza S, Rufián-Henares JA. Assessing the antioxidant and metabolic effect of an alpha-lipoic acid and acetyl-L-carnitine nutraceutical. Curr Res Food Sci. 2021;4:336-344.
13. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine in female infertility. Reprod Biol Endocrinol. 2018;16(1):5.
14. 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 (Oxf). 2016;84(6):851-857.
15. Fenkci SM, Fenkci V, Oztekin O, Rota S, Karagenc N. Serum total L-carnitine levels in non-obese women with polycystic ovary syndrome. Hum Reprod. 2008;23(7):1602-1606.
16. Ismail AM, Hamed AH, Saso S, Thabet HH. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2014;180:148-152.
17. Latifian S, Hamdi K, Totakneh R, Totakneh R. Effect of addition of L-carnitine in polycystic ovary syndrome patients with clomiphene citrate and gonadotropin resistant. Int J Curr Res Acad Rev. 2015;3(8):469-476.
18. Shukri MFM, Norhayati MN, Badrin S, Kadir AA. Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis. PeerJ. 2022;10:e13992.
19. Abu-Zaid A, Alghamdi GA, Alharbi AS, Baradwan S, Saleh SAK, Adly HM, et al. Effect of L-carnitine supplementation on fertility outcomes among patients with polycystic ovary syndrome: a systematic review and dose-response meta-analysis of randomized clinical trials. Obstet Gynecol Sci. 2025;68(4):260-272.
20. Genazzani A, 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. Journal of endocrinological investigation. 2011;34(4):287-91.
21. Li J, Liu L, Weng J, Yin T l, Yang J, Feng H L. Biological roles of l-carnitine in oocyte and early embryo development. Molecular Reproduction and Development.2021;88: 673–685.
22. Zeiler F, Sader N, Gillman L, West M. Levocarnitine induced seizures in patients on valproic acid: a negative systematic review. Seizure. 2016;36:36-39.
23. Cirilli I, Damiani E, Dludla PV, Hargreaves I, Marcheggiani F, Millichap LE, et al. Role of coenzyme Q10 in health and disease: an update on the last 10 years (2010-2020). Antioxidants (Basel). 2021;10(8):1325.
24. Raizner AE. Coenzyme Q10. Methodist Debakey Cardiovasc J. 2019;15(3):185-191.
25. Barcelos IP, Haas RH. CoQ10 and aging. Biology (Basel). 2019;8(2):28.
26. Zhang T, He Q, Xiu H, Zhang Z, Liu Y, Chen Z, et al. Efficacy and safety of coenzyme Q10 supplementation in the treatment of polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Sci. 2023;30(4):1033-1048.
27. Florou P, Anagnostis P, Theocharis P, Chourdakis M, Goulis DG. Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. J Assist Reprod Genet. 2020;37(10):2377-2387.
28. Lin G, Li X, Jin YSL, Xu L. Clinical evidence of coenzyme Q10 pretreatment for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis. Ann Med. 2024;56(1):2389469.
29. Ikematsu H, Nakamura K, Harashima SI, Fujii K, Fukutomi N. Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trial. Regul Toxicol Pharmacol. 2006;44(3):212-218.
30. Mititelu M, Lupuliasa D, Neacșu SM, Olteanu G, Busnatu ȘS, Mihai A, et al. Polyunsaturated fatty acids and human health: a key to modern nutritional balance in association with polyphenolic compounds from food sources. Foods. 2024;14(1):112.
31. Fekete M, Szarvas Z, Fazekas-Pongor V, Lehoczki A, Tarantini S, Varga JT. Effects of omega-3 supplementation on quality of life, nutritional status, inflammatory parameters, lipid profile, exercise tolerance and inhaled medications in chronic obstructive pulmonary disease. Ann Palliat Med. 2022;11(9):2819-2829.
32. Jerab D, Blangero F, da Costa PCT, de Brito Alves JL, Kefi R, Jamoussi H, et al. Beneficial effects of omega-3 fatty acids on obesity and related metabolic and chronic inflammatory diseases. Nutrients. 2025;17(7):1253.
33. Zhu Y, Mierau JO, Riphagen IJ, Heiner-Fokkema MR, Dekker LH, Navis GJ, et al. Types of fish consumption differ across socioeconomic strata and impact differently on plasma fish-based omega-3 fatty acids: a cross-sectional study. Eur J Nutr. 2024;63(2):435-443.
34. Kermack AJ, Wellstead SJ, Fisk HL, Cheong Y, Houghton FD, Macklon NS, et al. The fatty acid composition of human follicular fluid is altered by a 6-week dietary intervention that includes marine omega-3 fatty acids. Lipids. 2021;56(2):201-209.
35. Wang R, Feng Y, Chen J, Chen Y, Ma F. Association between polyunsaturated fatty acid intake and infertility among American women aged 20-44 years. Front Public Health. 2022;10:938343.
36. Giorgi VSI, Ferriani RA, Navarro PA. Omega-3 fatty acids and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with endometriosis: an experimental study. JBRA Assist Reprod. 2023;27(4):610-618.
37. Trop-Steinberg S, Gal M, Azar Y, Kilav-Levin R, Heifetz EM. Effect of omega-3 supplements or diets on fertility in women: a meta-analysis. Heliyon. 2024;10(8):e29561.
38. Yang Q, Tao J, Jia S, Fan Z. Association between fatty acids and female infertility: dual evidence from a cross-sectional study and Mendelian randomization analysis. Food Funct. 2025;16(1):249-267.
39. Lepore E, Lauretta R, Bianchini M, Mormando M, Di Lorenzo C, Unfer V. Inositols depletion and resistance: principal mechanisms and therapeutic strategies. Int J Mol Sci. 2021;22(13):6796.
40. Siracusa L, Napoli E, Ruberto G. Novel chemical and biological insights of inositol derivatives in Mediterranean plants. Molecules. 2022;27(5):1525.
41. Kunjara S, Greenbaum AL, Wang DY, Caro HN, McLean P, Redman CWG, et al. Inositol phosphoglycans and signal transduction systems in pregnancy in preeclampsia and diabetes: evidence for a significant regulatory role in preeclampsia at placental and systemic levels. Mol Genet Metab. 2000;69(2):144-158.
42. Merviel P, James P, Bouée S, Le Guillou M, Rince C, Nachtergaele C, et al. Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies. Reprod Health. 2021;18(1):13.
43. Mellonie P, Manivannan A, Thangaraj P, Logeswari B. The effectiveness of myo-inositol in women with polycystic ovary syndrome: a prospective clinical study. Cureus. 2024;16(2):e54308.
44. Palomba S, Seminara G, Aversa A. Myo-inositol in reproductive management of women with PCOS: holy grail for medical practice or demon for scientific evidence? Reprod Biomed Online. 2026;52(2):105269.
45. Zheng X, Lin D, Zhang Y, Lin Y, Song J, Li S, et al. Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine (Baltimore). 2017;96(49):e8842.
46. Sene AA, Saeedzarandi M, Yazdizadeh M, Ghaffari SR, Amjadi F, Zandieh Z, et al. The effect of myo-inositol on assisted reproductive technology outcomes in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized clinical trial studies. Int J Reprod Biomed. 2025;23(5):353-366.
47. Akbari Sene A, Tabatabaie A, Nikniaz H, Alizadeh A, Sheibani K, Mortezapour Alisaraie M, et al. The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial. Arch Gynecol Obstet. 2019;299(6):1701-1707.
48. Fitz V, Graca S, Mahalingaiah S, Liu J, Lai L, Butt A, et al. Inositol for polycystic ovary syndrome: a systematic review and meta-analysis to inform the 2023 update of the international evidence-based PCOS guidelines. J Clin Endocrinol Metab. 2024;109(6):1630-1655.
49. Corrado F, D'Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011;28(8):972-975.
50. Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, et al. Melatonin: pharmacology, functions and therapeutic benefits. Curr Neuropharmacol. 2017;15(3):434-443.
51. Roy D, Belsham DD. Melatonin receptor activation regulates GnRH gene expression and secretion in
GT1-7 GnRH neurons: signal transduction mechanisms. J Biol Chem. 2002;277(1):251-258.
52. Wu D, Zhao W, Xu C, Zhou X, Leng X, Li Y. Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency. BMC Womens Health. 2022;22(1):474.
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| Files | ||
| Issue | Vol 20, No 1 (March 2026) | |
| Section | Review Articles | |
| Keywords | ||
| Antioxidant Female infertility Oxidative damage Drug safety | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Davoudi-Monfared E, Fotouk Kiaie SM, Ebrahimi M. Therapeutic Roles and Safety Profiles of Non-Vitamin Antioxidant Supplements in Female Infertility: A Narrative Review. J Family Reprod Health. 2026;20(1):10-18.
