Dietary supplements for polycystic ovary syndrome
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Keywords

Polycystic ovary syndrome
Curcumin
Vitamin D
Inositol
CoQ10

Abstract

Polycystic ovary syndrome (PCOS) is one of the most prevalent female endocrine reproductive disorders, affecting between 4 to 18% of the women in their reproductive age. It is generally characterized by several clinical aspects, among which anovulation, inflammation and infertility. Moreover, PCOS has several health implications, including increased metabolic, reproductive, and psychological risks. Previously, metformin and to some extent thiazolidinediones were considered as drug of choice for PCOS management, but they had several side-effects, and controversial results were obtained about their efficiency, especially in non-insulin-resistant non-obese patients. Thus, alternative treatment options are now being studied for PCOS, including different natural molecules and complementary medicines (CM) for the improvement of their health, wellbeing and fertility. Recently, treatment of PCOS patients with different natural molecules, coming from nutritional supplements and herbal medicines, has attained satisfactory results with the absence of any side effects. In this review, four natural molecules, curcumin, vitamin D, inositol and CoQ10 are discussed for their therapeutic ability. These molecules proved to decrease insulin sensitivity and inflammation, to improve the restoration of ovarian function, and they could restore hormonal balance and regulate the menstrual cycle, all of which are the main features and major concerns for women suffering from PCOS.

https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2762
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References

[1] Arentz S, Smith CA, Abbott J, Bensoussan A. Nutritional supplements and herbal medicines for women with polycystic ovary syndrome; a systematic review and meta-analysis. BMC Complement Altern Med 2017;17:500. https://doi.org/10.1186/s12906-017-2011-x
[2] Orio F, Muscogiuri G, Palomba S. Could the Mediterranean diet be effective in women with polycystic ovary syndrome?A proof of concept. Eur J Clin Nutr 2015;69:974. https://doi.org/10.1038/ejcn.2015.53
[3] Guido M, Romualdi D, Giuliani M, Suriano R, Selvaggi L, Apa R, Lanzone A. Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab 2004;89:2817-23. https://doi.org/10.1210/jc.2003-031158
[4] Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod (Oxford, England), 2007;22:2967-73. https://doi.org/10.1093/humrep/dem271
[5] Amini L, Tehranian N, Movahedin M, Ramezani Tehrani F, Ziaee S. Antioxidants and management of polycystic ovary syndrome in Iran: A systematic review of clinical trials. Iran J Reprod Med 2015;13:1-8.
[6] Ji Y, Tan S, Xu Y, Chandra A, Shi C, Song B, Qin J, Gao Y. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis. Neurology 2013;81:1298-307. https://doi.org/10.1212/WNL.0b013e3182a823cc
[7] Bazarganipour F, Taghavi SA, Montazeri A, Ahmadi F, Chaman R, Khosravi A. The impact of polycystic ovary syndrome on the health-related quality of life: A systematic review and meta-analysis. Iran J Reprod Med 2015;13:61-70.
[8] Abdelazeem B, Abbas KS, Shehata J, Baral N, Banour S, Hassan M. The effects of curcumin as dietary supplement for patients with polycystic ovary syndrome: An updated systematic review and meta-analysis of randomized clinical trials. Phytother Res 2022;36:22-32. https://doi.org/10.1002/ptr.7274
[9] Sohrevardi SM, Heydari B, Azarpazhooh MR, Teymourzadeh M, Simental-Mendía LE, Atkin SL, Sahebkar A, Karimi-Zarchi M. Therapeutic effect of curcumin in women with polycystic ovary syndrome receiving metformin: a randomized controlled trial. Adv Exp Med Biol 2021;1308:109-17. https://doi.org/10.1007/978-3-030-64872-5_9
[10] Dennett CC, Simon J. The role of polycystic ovary syndrome in reproductive and metabolic health: overview and approaches for treatment. Diabetes Spectr 2015;28:116-20. https://doi.org/10.2337/diaspect.28.2.116
[11] Chien YJ, Chang CY, Wu MY, Chen CH, Horng YS, Wu HC. Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with Meta-Analysis and Trial Sequential Analysis. Nutrients 2021;13:684. https://doi.org/10.3390/nu13020684
[12] Gao XY, Liu Y, Lv Y, Huang T, Lu G, Liu HB, Zhao SG. Role of androgen receptor for reconsidering the “True” polycystic ovarian morphology in PCOS. Sci Rep 2020;10:8993. https://doi.org/10.1038/s41598-020-65890-5
[13] Derosa G, Maffioli P, Simental-Mendía LE, Bo S, Sahebkar A. Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2016;111:394-404. https://doi.org/10.1016/j.phrs.2016.07.004.
[14] Sahebkar A, Cicero A, Simental-Mendía LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res 2016;107:234-
42. https://doi.org/10.1016/j.phrs.2016.03.026
[15] Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer-Pietsch B. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 2009;161:575-82. https://doi.org/10.1530/EJE-09-0432
[16] Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007;92:2017-29. https://doi.org/10.1210/jc.2007-0298
[17] Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011;164:741-9. https://doi.org/10.1530/EJE-11-0134
[18] Alvarez JA, Ashraf A. Role of vitamin d in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol 2010;351385. https://doi.org/10.1155/2010/351385
[19] Menichini D, Facchinetti F. Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review. Gynecol Endocrinol 2020;36:1-5. https://doi.org/10.1080/09513590.201 9.1625881
[20] Angellotti E, D’Alessio D, Dawson-Hughes B, Nelson J, Cohen RM, Gastaldelli A, Pittas AG. Vitamin D supplementation in patients with type 2 diabetes: the vitamin D for established type 2 diabetes (DDM2) Study. J Endocr Soc 2018;2:310-21. https://doi.org/10.1210/js.2018-00015
[21] He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D Levels and polycystic ovary syndrome: a systematic review and meta-analysis. Nutrients 2015;7:4555-77. https://doi.org/10.3390/nu7064555
[22] Łagowska K, Bajerska J, Jamka M. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients 2018;10:1637. https://doi.org/10.3390/nu10111637
[23] Plymate SR, Matej LA, Jones RE, Friedl KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 1988;67:460-4. https://doi.org/10.1210/jcem-67-3-460
[24] Precone V, Notarangelo A, Marceddu G, D’Agruma L, Cannarella R, Calogero AE, Cristofoli F, Guerri G, Paolacci S, Castori M, Bertelli M. A simultaneous next-generation sequencing approach to the diagnosis of couple infertility. Minerva Endocrinol (Torino) 2022;47:4-10. https://doi.org/10.23736/S2724-6507.21.03477-1
[25] Kiani AK, Paolacci S, Scanzano P, Michelini S, Capodicasa N, D’Agruma L, Notarangelo A, Tonini G, Piccinelli D, Farshid KR, Petralia P, Fulcheri E, Chiurazzi P, Terranova C, Plotti F, Angioli R, Castori M, Bertelli M. Complications related to in vitro reproductive techniques support the implementation of natural procreative technologies. Acta Biomed 2020;91:e2020018. https://doi.org/10.23750/abm.v91i13-S.10525
[26] Guerri G, Maniscalchi T, Barati S, Gerli S, Di Renzo GC, Della Morte C, Marceddu G, Casadei A, Laganà AS, Sturla D, Ghezzi F, Garzon S, Unfer V, Bertelli M. Non-syndromic monogenic female infertility. Acta Biomed 2019;90:68-74. https://doi.org/10.23750/abm.v90i10-S.8763
[27] Wdowiak A, Filip M. The effect of myo-inositol, vitamin D3 and melatonin on the oocyte quality and pregnancy in in vitro fertilization: a randomized prospective controlled trial. Eur Rev Med Pharmacol Sci 2020;24:8529-36. https://doi.org/10.26355/eurrev_202008_22649
[28] Monastra G, De Grazia S, De Luca L, Vittorio S, Unfer V. Vitamin D: a steroid hormone with progesterone-like activity. Eur Rev Med Pharmacol Sci 2018;22:2502-12. https://doi.org/10.26355/eurrev_201804_14845
[29] Voulgaris N, Papanastasiou L, Piaditis G, Angelousi A, Kaltsas G, Mastorakos G, Kassi E. Vitamin D and aspects of female fertility. Hormones (Athens, Greece) 2017;16:5-21. https://doi.org/10.14310/horm.2002.1715
[30] Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril 2014;102:460-468.e3. https://doi.org/10.1016/j. fertnstert.2014.04.046
[31] Kiani AK, Paolacci S, Calogero AE, Cannarella R, Di Renzo, GC, Gerli S, Della Morte C, Busetto GM, De Berardinis E, Del Giudice F, Stuppia L, Facchinetti F, Dinicola S, Bertelli M. From Myo-inositol to D-chiro-inositol molecular pathways. Eur Rev Med Pharmacol Sci 2021;25:2390-2402. https://doi.org/10.26355/eurrev_202103_25279
[32] Facchinetti F, Espinola M, Dewailly D, Ozay AC, Prapas N, Vazquez-Levin M, Wdowiak A, Unfer V, Expert Group on Inositols in Preclinical and Clinical Research Breakthroughs in the Use of Inositols for Assisted Reproductive Treatment (ART). Trends Endocrinol Metab 2020;31:570-9. https://doi.org/10.1016/j.tem.2020.04.003
[33] Pacchiarotti A, Carlomagno G, Antonini G, Pacchiarotti A. Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol 2016;32:69-73. https://doi.org/10.3109/09513590. 2015.1101444
[34] Cirillo F, Catellani C, Lazzeroni P, Sartori C, Tridenti G, Vezzani C, Fulghesu AM, Madeddu E, Amarri S, Street ME. HMGB1 is increased in adolescents with polycystic ovary syndrome (PCOS) and decreases after treatment with myo-inositol (MYO) in combination with alpha-lipoic acid (ALA). Gynecol Endocrinol 2020;36:588-93. https://doi.org/10.1080/09513590. 2020.1725967
[35] Santamaria A, Di Benedetto A, Petrella E, Pintaudi B, Corrado, F, D’Anna R, Neri I, Facchinetti F. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med 2016;29:3234-7. https://doi.org/10.3109/14767058.2015.1121478
[36] D’Anna R, Santamaria A, Giorgianni G, Vaiarelli A, Gullo G, Di Bari F, Benvenga S. Myo-inositol and melatonin in the menopausal transition. Gynecol Endocrinol 2017;33:279-82. https://doi.org/10.1080/09513590.2016.1254613
[37] Dinkova A, Martinov D, Konova E. Efficacy of myo-inositol in the clinical management of patients with asthenozoospermia. Eur Rev Med Pharmacol Sci 2017;21:62-5.
[38] Bertelli M, Paolacci S, Placidi G, Scaccia G, Chiurazzi P, Fulcheri E, Malacarne D, Lichterman B, Petralia P. Combined use of medically-assisted reproductive techniques: a new bioethical issue. Acta Biomed 2019;90:58-61. https://doi.org/10.23750/abm.v90i10-S.8761
[39] Wdowiak A. Myoinositol Improves embryo development in PCOS patients undergoing ICSI. Int J Endocrinol 2016;6273298. https://doi.org/10.1155/2016/6273298
[40] Montanino Oliva M, Buonomo G, Calcagno M, Unfer V. Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women. J Ovarian Res 2018;11:38. https://doi.org/10.1186/s13048-018-0411-2
[41] Vartanyan EV, Tsaturova KA, Devyatova EA, Mikhaylyukova AS, Levin VA, Petuhova NL, Markin AV, Steptsova EM. Improvement in quality of oocytes in polycystic ovarian syndrome in programs of in vitro fertilization. Gynecol Endocrinol 2017;33:8-11. https://doi.org/10.1080/09513590.2 017.1399699
[42] Emekçi Özay Ö, Özay AC, Çağlıyan E, Okyay RE, Gülekli B. Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecol Endocrinol 2017;33:524-8. https://doi.org/10.1080/09513590.2017.1296127
[43] Laganà AS, Vitagliano A, Noventa M, Ambrosini G D’Anna R. Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2018;298:675-84. https://doi.org/10.1007/s00404-018-4861-y
[44] Nordio M, Basciani S, Camajani E. The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci 2019;23:5512-21. https://doi.org/10.26355/eurrev_201906_18223
[45] Mendoza N, Galan MI, Molina C, Mendoza-Tesarik R, Conde C, Mazheika M, Diaz-Ropero MP, Fonolla J, Tesarik J, Olivares M. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol 2020;36:398- 401. https://doi.org/10.1080/09513590.2019.1681959
[46] Nestler JE, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol 2015;31:501-5. https://doi.org/10.3109/09513590.2015.1054802
[47] Unfer V, Carlomagno G, Papaleo E, Vailati S, Candiani M, Baillargeon JP. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci 2014;21:854-8. https://doi.org/10.1177/1933719113518985
[48] Bevilacqua A, Dragotto J, Giuliani A, Bizzarri M. Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol 2019;234:9387-98. https://doi.org/10.1002/jcp.27623
[49] Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, Reiter RJ. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 2009;92:328-43. https://doi.org/10.1016/j.fertnstert.2008.05.016
[50] Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 2002;17:1591-6. https://doi.org/10.1093/humrep/17.6.1591
[51] Unfer V, Raffone E, Rizzo P, Buffo S. Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol 2011;27:857-61. https://doi.org/10. 3109/09513590.2011.564687
[52] Selman H, Pacchiarotti A, Rinaldi L, Crescenzi F, Lanzilotti G, Lofino S, El-Danasouri I. Simultaneous administration of human acidic and recombinant less acidic follicle-stimulating hormone for ovarian stimulation improves oocyte and embryo quality, and clinical outcome in patients with repeated IVF failures. Eur Rev Med Pharmacol Sci. 2013;17:1814-9.
[53] Reyes-Muñoz E, Sathyapalan T, Rossetti P, Shah M, Long M, Buscema M, Valenti G, La Rosa VL, Cianci S, Vitale SG. Polycystic ovary syndrome: implication for drug metabolism on assisted reproductive techniques-a literature review. Adv Ther 2018;35:1805-15. https://doi.org/10.1007/s12325-018-0810-1
[54] Genazzani AD, Shefer K, Della Casa D, Prati A, Napolitano A, Manzo A, Despini G, Simoncini T. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients. J Endocrinol Invest 2018;41:583-90. https://doi.org/10.1007/s40618-017-0782-z
[55] Fruzzetti F, Capozzi A, Canu A, Lello S. Treatment with d-chiro-inositol and alpha lipoic acid in the management of polycystic ovary syndrome. Gynecol Endocrinol 2019;35:506-10. https://doi.org/10.1080/09513590.2018.1540573
[56] Ying Z, Kampfrath T, Sun Q, Parthasarathy S, Rajagopalan S. Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function. Inflamm Res 2011;60:219-25. https://doi.org/10.1007/s00011-010-0256-7
[57] Seyam E, Hasan M, Khalifa EM, Ramadan A, Hefzy E. Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate-resistant polycystic ovary disease. Gynecol Endocrinol 2017;33:892-8. https://doi.org/10.1080/09513590.2017.1320383
[58] González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 2012;77:300-5. https://doi.org/10.1016/j. steroids.2011.12.003
[59] Peng Z, Sun Y, Lv X, Zhang H, Liu C, Dai S. Interleukin-6 levels in women with polycystic ovary syndrome: a Systematic review and meta-analysis. PloS One 2016;11:e0148531. https://doi.org/10.1371/journal.pone.0148531
[60] Taghizadeh S, Izadi A, Shirazi S, Parizad M, Pourghassem Gargari B. The effect of coenzyme Q10 supplementation on inflammatory and endothelial dysfunction markers in overweight/obese polycystic ovary syndrome patients. Gynecol Endocrinol 2021;37:26-30. https://doi.org/10.1080/09513590.2 020.1779689
[61] Ebejer K, Calleja-Agius J. The role of cytokines in polycystic ovarian syndrome. Gynecol Endocrinol 2013;29:536-40. https://doi.org/10.3109/09513590.2012.760195
[62] Repaci A, Gambineri A, Pasquali R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 2011;335:30-41. https://doi.org/10.1016/j. mce.2010.08.002
[63] Farsi F, Mohammadshahi M, Alavinejad P, Rezazadeh A, Zarei M, Engali KA. Functions of Coenzyme Q10 supplementation on liver enzymes, markers of systemic inflammation, and adipokines in patients affected by nonalcoholic fatty liver disease: a double-blind, placebo-controlled, randomized clinical trial. J Am Coll Nutr 2016;35:346-53. https://doi.org/10.1080/0 7315724.2015.1021057
[64] Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, & Döring F. Functions of coenzyme Q10 in inflammation and gene expression. BioFactors 2008;32:179-83. https://doi.org/10.1002/biof.5520320121
[65] Mazidi M, Kengne AP, Banach M, Lipid and Blood Pressure Meta-analysis Collaboration Group Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2018;128:130-6. https://doi.org/10.1016/j.phrs.2017.08.011
[66] Zhai J, Bo Y, Lu Y, Liu C, Zhang L. Effects of coenzyme Q10 on markers of inflammation: a systematic review and meta-analysis. PloS One 2017;12:e0170172. https://doi.org/10.1371/journal.pone.0170172
[67] Schmelzer C, Lorenz G, Rimbach G, Döring F. Influence of Coenzyme Q_{10} on release of pro-inflammatory chemokines in the human monocytic cell line THP-1. BioFactors 2007;31:211-7. https://doi.org/10.1002/biof.5520310308