The impact of a standardized micronutrient supplementation on PCOS-typical parameters: a randomized controlled trial

Marlene Hager, Kazem Nouri, Martin Imhof, Christian Egarter, Johannes Ott, Marlene Hager, Kazem Nouri, Martin Imhof, Christian Egarter, Johannes Ott

Abstract

Purpose: To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS).

Methods: The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the "multinutrient supplementation group" (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the "control group" (two unlabeled soft capsules containing 200 μg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol.

Results: In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable.

Conclusion: A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).

Keywords: Anti-Mullerian hormone; Micronutrients; Polycystic ovary syndrome; Testosterone.

Conflict of interest statement

M. Imhof and J. Ott received speaker honorarium for lecturing from Lenus Pharma GesmbH.

References

    1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–2749.
    1. McCartney CR, Marshall JC. Clinical practice. Polycystic ovary syndrome. N Engl J Med. 2016;375(1):54–64.
    1. Diamanti-Kandarakis E, Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Nestler JE. A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills. J Clin Endocrinol Metab. 2003;88(5):1927–1932.
    1. Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER, Network Cooperative Multicenter Reproductive Medicine. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356(6):551–566.
    1. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH (2012) Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, d-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev CD003053
    1. Sills ES, Perloe M, Tucker MJ, Kaplan CR, Genton MG, Schattman GL. Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports. BMC Womens Health. 2001;1(1):3.
    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(1):500.
    1. Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update. 2013;19(3):268–288.
    1. 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):1–8.
    1. Mejia-Montilla J, Reyna-Villasmil E, Domínguez-Brito L, Naranjo-Rodríguez C, Noriega-Verdugo D, Padilla-Samaniego M, Vargas-Olalla V. Supplementation with omega-3 fatty acids and plasma adiponectin in women with polycystic ovary syndrome. Endocrinol Diabetes Nutr. 2018;65(4):192–199.
    1. Jamilian M, Shojaei A, Samimi M, Afshar Ebrahimi F, Aghadavod E, Karamali M, Taghizadeh M, Jamilian H, Alaeinasab S, Jafarnejad S, Asemi Z (218) The effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome. J Affect Disord 229:41–47.
    1. Mirmasoumi G, Fazilati M, Foroozanfard F, Vahedpoor Z, Mahmoodi S, Taghizadeh M, Esfeh NK, Mohseni M, Karbassizadeh H, Asemi Z. The effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome: a randomized, double-blind placebo-controlled trial. Exp Clin Endocrinol Diabetes. 2018;126(4):222–228.
    1. Ebrahimi FA, Samimi M, Foroozanfard F, Jamilian M, Akbari H, Rahmani E, Ahmadi S, Taghizadeh M, Memarzadeh MR, Asemi Z. The effects of omega-3 fatty acids and vitamin E co-supplementation on indices of insulin resistance and hormonal parameters in patients with polycystic ovary syndrome: a randomized, double-blind placebo-controlled trial. Exp Clin Endocrinol Diabetes. 2017;125(6):353–359.
    1. Rahmani E, Samimi M, Ebrahimi FA, Foroozanfard F, Ahmadi S, Rahimi M, Jamilian M, Aghadavod E, Bahmani F, Taghizadeh M, Memarzadeh MR, Asemi Z. The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression of lipoprotein(a) and oxidized low-density lipoprotein, lipid profiles and biomarkers of oxidative stress in patients with polycystic ovary syndrome. Mol Cell Endocrinol. 2017;439:247–255.
    1. Mohammad Hosseinzadeh F, Hosseinzadeh-Attar MJ, Yekaninejad MS, Rashidi B. Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: a randomized, double blinded, placebo controlled clinical trial. J Trace Elem Med Biol. 2016;34:56–61.
    1. Razavi M, Jamilian M, Kashan ZF, Heidar Z, Mohseni M, Ghandi Y, Bagherian T, Asemi Z. Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Horm Metab Res. 2016;48(3):185–190.
    1. Sirmans SM, Weidman-Evans E, Everton V, Thompson D. Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications. Ann Pharmacother. 2012;46:403–418.
    1. Sadeghi A, Djafarian K, Mohammadi H, Shab-Bidar S. Effect of omega-3 fatty acids supplementation on insulin resistance in women with polycystic ovary syndrome: meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2017;11(2):157–162.
    1. Hajishafiee M, Askari G, Iranj B, Ghiasvand R, Bellissimo N, Totosy de Zepetnek J, Salehi-Abargouei A. The effect of n-3 polyunsaturated fatty acid supplementation on androgen status in patients with polycystic ovary syndrome: a systematic review and meta-analysis of clinical trials. Horm Metab Res. 2016;48(5):281–289.
    1. Rahmani E, Jamilian M, Samimi M, Zarezade Mehrizi M, Aghadavod E, Akbari E, Tamtaji OR, Asemi Z. The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome. Gynecol Endocrinol. 2018;34(3):217–222.
    1. Samimi M, Zarezade Mehrizi M, Foroozanfard F, Akbari H, Jamilian M, Ahmadi S, Asemi Z. The effects of coenzyme Q10 supplementation on glucose metabolism and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf) 2017;86(4):560–566.
    1. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008;89:505–522.
    1. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23(3):462–477.
    1. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22:141–146.
    1. Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A, Formigli L, Zecchi-Orlandini S, Orlandini G, Carella G, Brancato R, Capaccioli S. Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem. 2003;278(30):28220–28228.
    1. Armanini D, Bonanni G, Palermo M. Reduction of serum testosterone in men by licorice. N Engl J Med. 1999;341:1158.
    1. Armanini D, Bonanni G, Mattarello MJ, Fiore C, Sartorato P, Palermo M. Licorice consumption and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes. 2003;111:341–343.
    1. Barbieri RL, Rein MS, Hornstein MD, Ryan KJ. Rat Leydig cell and granulosa cells 17-keto reductase activity: subcellular localization and substrate specificity. Am J Obstet Gynecol. 1988;159:1564–1569.
    1. Bogovich K, Payne AH. Purification of rat testicular microsomal 17-ketosteroid reductase. Evidence that 17-ketosteroid reductase and 17 beta-hydroxysteroid dehydrogenase are distinct enzymes. J Biol Chem. 1980;255:5552–5559.
    1. Latif SA, Conca TJ, Morris DJ. The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. Steroids. 1990;55:52–58.
    1. Sakamoto K, Wakabayashi K. Inhibitory effect of glycyrrhetinic acid on testosterone production in rat gonads. Endocrinol Jpn. 1988;35:333–342.
    1. Takahashi K, Yoshino K, Shirai T, Nishigaki A, Araki Y, Kitao M. Effect of traditional herbal medicine (Shakuyaku-Kanzo-To) on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound. Acta Obstet Gynaecol Jpn. 1988;40:789–792.
    1. Takeuchi T, Nishii O, Okamura T, Yaginuma T. Effect of paeoniflorin, glycyrrhizin and glycyrrhetinic acid on ovarian androgen production. Am J Chin Med. 1991;19:73–78.
    1. Yu PL, Pu HF, Chen SY, Wang SW, Wang PS. Effects of catechin, epicatechin and epigallocatechin gallate on testosterone production in rat leydig cells. J Cell Biochem. 2010;110(2):333–342.
    1. Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr. 2003;133:3275–3384.
    1. Farahi N, Zolotor A. Recommendations for preconception counseling and care. Am Fam Physician. 2013;88:499–506.
    1. Bahmani F, Karamali M, Shakeri H, Asemi Z. The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial. Clin Endocrinol (Oxf) 2014;81(4):582–587.
    1. Asemi Z, Karamali M, Esmaillzadeh A. Metabolic response to folate supplementation in overweight women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Mol Nutr Food Res. 2014;58(7):1465–1473.

Source: PubMed

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