Top Evidence-Based Supplements for PCOS

September is Polycystic Ovarian Syndrome (PCOS) awareness month!

Throughout this post, we will explore the current literature on supplementation for PCOS management.

For more information, regarding PCOS diagnostic criteria, symptoms, and underlying mechanisms of pathology, see our previous post titled, “What is PCOS?”.

Before we delve deep into the science, it is important to note that there are different types of PCOS, and therefore symptom presentation varies on an individual basis (1). It is important to take this into consideration when determining the course of treatment, or management of PCOS. Lastly, always speak with your primary health care provider before making changes, or introducing any new supplements into your health regime. So… what does the science say?

1. Myo-inositol

Myo-inositol is one of the most well-researched supplements for PCOS. Several studies support myo-inositol as an insulin sensitizer with comparable results to metformin, a pharmaceutical drug used to treat insulin resistance (2 – 4). Myo-inositol has also been shown to regulate the menstrual cycle and ovulation, resulting in improved fertilization rates and fertility (5, 6). Taking myo-inositol prior to in-vitro fertilization (IVF) has been found to improve clinical pregnancy rates and reduces miscarriage (7).

2. N-acetyl cysteine (NAC)

NAC is a precursor to glutathione (one of the most powerful and naturally occurring antioxidants), and also promotes detoxification of the liver. NAC has been compared to metformin to assess outcomes of metabolic health in PCOS patients. In a human trial performed in 2015, NAC was found to improve metabolic markers (cholesterol levels, fasting blood sugar and fasting insulin) more than metformin (8). Women with PCOS taking NAC while trying to conceive, were found to have higher odds of many stages of pregnancy – from improved egg quality, to ovulation, to getting pregnant and having a live birth (9).

3. Vitamin D

Did you know, vitamin D deficiency appears to be more common in women diagnosed with PCOS? Vitamin D has the ability to correct the metabolic disturbances (insulin resistance, dyslipidemia) that are often present in women diagnosed with PCOS (12). Vitamin D supplement has also shown to improve fertility in PCOS by correcting the hormonal disturbances within the ovaries, reducing inflammation, and improving antioxidant defense (13). Vitamin D is a fat soluble vitamin - meaning that there is a risk of toxicity, thus it is crucial to test serum levels prior to starting supplementation.

4. Omega 3 Fatty Acids

Omega-3 fatty acids are known for their many benefits - mostly coming from the anti-inflammatory properties. Several human trials have examined the effects of omega-3 supplementation on antioxidant status and metabolic health in PCOS patients. One study found that after 12 weeks of supplementation, the patient's glutathione – a marker of antioxidant capacity – increased statistically significantly (14). Omega-3 supplementation has also been shown to decrease insulin resistance, an increase in insulin sensitivity and a reduction in total and free testosterone after 12 weeks (15). The anti-inflammatory and antioxidant properties boosts the body’s ability to become resilient and reactive to stress, improves egg quality, supports hormone synthesis, implantation rates and fetal development.

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Article written by: Riley Forbes, BSc

Peer-Reviewed by: Dr. Cassandra Paiano, ND, BSc.

Resources:

1. Toosy S, Sodi R, Pappachan JM. Lean polycystic ovary syndrome (PCOS): an evidence- based practical approach. J Diabetes Metab Disord. 2018;17(2):277-285. Published 2018 Nov 13. doi:10.1007/s40200-018-0371-5

2. Tagliaferri V, Romualdi D, Immediata V, et al. Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study. Clin Endocrinol (Oxf). 2017;86(5):725-730. doi:10.1111/cen.13304

3. Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017;33(1):39-42. doi:10.1080/09513590.2016.1236078 4. Mishra N, Verma R, Jadaun P. Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study. Cureus. 2022;1

4(1):e21781. Published 2022 Jan 31. doi:10.7759/cureus.21781

5. Gerli S, Papaleo E, Ferrari A, Di Renzo GC. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci. 2007;11(5):347-354.

6. Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig. 2018;34(2):/j/hmbci.2018.34.issue-2/hmbci-2017-0067/hmbci- 2017-0067.xml. Published 2018 Mar 2. doi:10.1515/hmbci-2017-0067

7. Zheng X, Lin D, Zhang Y, 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. doi:10.1097/MD.0000000000008842

8. Javanmanesh F, Kashanian M, Rahimi M, Sheikhansari N. A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome. Gynecol Endocrinol. 2016;32(4):285-289. doi:10.3109/09513590.2015.1115974

9. Thakker D, Raval A, Patel I, Walia R. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. 2015;2015:817849. doi:10.1155/2015/817849