The 7 Best Supplements for Patients with PCOS

by Krista Russ

As a provider who treats PCOS, you are probably aware of the conventional protocol for managing this disorder, such as birth control pills, spironolactone, and sometimes ovulation induction medications. And while these medications do have their place in certain situations (artificial insemination, in vitro fertilization, acne, and hirsutism treatment, etc.), they do not prevent long-term complications of PCOS such as heart disease, as they fail to address the root causes of the disorder like hyperinsulinemia, insulin resistance, and low-grade inflammation. 

Numerous evidence-based supplements have entered the spotlight recently that address these important root causes. You may be wary about prescribing over-the-counter supplements for managing PCOS, especially when most clinicians are trained to treat PCOS with drugs alone, but the supplements to be discussed have robust scientific backing. They have demonstrated efficacy in controlled clinical trials published in prestigious medical journals such as the International Journal of Endocrinology and the European Journal of Endocrinology.  

Seeing as PCOS is best managed with a comprehensive, multidisciplinary approach, supplements certainly have their place in a PCOS treatment plan when the evidence supports their efficacy. The supplements to be discussed for treating PCOS fall into one of two categories: insulin-sensitizing and anti-inflammatory.  

In this article, we introduce four insulin sensitizers and three anti-inflammatory supplements used for treating PCOS with the most robust evidence–both in vitro and clinically. Anti-inflammatory supplements will be discussed in the future as a separate topic. These seven supplements are considered the best for managing PCOS based on the latest research with regards to infertility, secondary symptoms like hirsutism, and long-term complications like type two diabetes.  

Insulin Sensitizing Supplements 

1. Inositol  
2. Magnesium  
3. Berberine  
4. N-Acetyl-Cysteine (NAC)

Anti-Inflammatory Supplements (to be discussed in future article) 

1. Fish Oil 
2. Vitamin D 
3. CoQ10 

Defining Insulin Sensitizers

Supplements and drugs that promote insulin sensitivity allow insulin to work better so that smaller amounts are needed. Since hyperinsulinemia can cause the ovaries to produce excessive testosterone in some women (though not all) and disrupt other important hormones (Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), estradiol, progesterone, etc.), reducing both fasting and postprandial insulin levels will improve PCOS. The supplements below work in different ways, but they all improve the body’s responsiveness to insulin, which in turn improves PCOS.   

Inositol

Inositol is a sugar alcohol and vitamin-like compound that has been shown to improve the function of insulin receptors [1]. There are two different isomeric forms–Myo (MI) and D-Chiro Inositol (DCI). Taking them both in the correct ratios offers more benefits than taking either alone. In fact, taking the wrong ratio of MI to DCI, especially too much DCI, can potentially worsen PCOS. That’s why you should take our PCOS course to learn how to prescribe inositol. 

In addition to decreasing insulin resistance, inositol has been shown to reduce inflammation, improve oocyte and embryo quality, increase fertilization and pregnancy (implantation) rates, and decrease the risk of gestational diabetes [2]. One study found it could even reduce insulin resistance by up to 70 percent in postmenopausal women with metabolic syndrome [1], [3]!  

Lastly, a meta-analysis and systematic review of seven studies with 935 women included linked inositol to a significant increase in clinical pregnancy rates in patients undergoing ovulation induction in preparation for ICSI or IVF-ET reproductive assistance procedures [1] [4].  

Inositol is one of the most heavily researched supplements for PCOS and probably the single most important.  

Magnesium

Many women with PCOS are lacking in this essential mineral that serves as an important coenzyme for hundreds of chemical reactions in the body, including those involved in handling sugar. Magnesium supplementation has been shown to improve insulin resistance, lower blood pressure, improve sleep, and even mellow bothersome PMS symptoms such as cramping and mood swings [1]. It even improves symptoms of anxiety like anxiousness and heart palpitations, which women with PCOS are at increased risk for. Furthermore, women with PCOS are nearly twenty times more likely to be deficient in magnesium [5].  

Magnesium is the most abundant mineral in the human body and plays a vital role in glucose and insulin signaling [5]. Deficiency has been associated with an increased risk for type two diabetes.  

You can assess your patients’ magnesium level with a simple blood test [6], which can be a helpful tool for determining if your patient is getting enough from their diet and/or supplement regimen and by assessing common symptoms of magnesium deficiency like heart palpitations, muscle spasms, and headaches [5]. Good food sources of magnesium include dark leafy greens, avocados, dark chocolate, legumes, meat, fish, and whole grains–all whole foods.  

In one randomized interventional study, magnesium supplementation (250 mg Magnesium Oxide q.d.) for eight weeks resulted in favorable decreases in both BMI and testosterone levels compared to placebo in PCOS patients [7].  

To get the most benefit from magnesium, it’s important that your patients take a highly absorbable form–especially one that does not cause GI distress–which you’ll learn about in the PCOS Course. 

Berberine

The benefits of berberine–an alkaloid isolated from various herbs like Oregon grape and goldenseal–are comparable to the drug metformin [6]. In one three month study, berberine reduced fasting glucose and insulin levels as well as metformin when taken at the same dosage: 500 mg, TID [6] [8]. However, berberine increased the live birth rate more than metformin and did so with fewer side effects than metformin.  

In a second randomized study, berberine resulted in reduced free testosterone, HOMA-IR, and increased sex-hormone binding globulin (SHBG) comparable to metformin [9].  

Berberine also increased spontaneous ovulation by 25 percent in yet another study on 98 anovulatory women with PCOS. A forth study confirmed that the hypoglycemic effects from berberine were comparable to metformin with regards to HbA1c, fasting, and postprandial glucose levels, which decreased by ~ 7.5 percent, 6.9 percent, and 11.1 percent respectively [10].  

A review of six randomized controlled trials including over 500 participants concluded that berberine was even a good therapy for steatohepatitis–a common long-term complication of PCOS–because it significantly reduced liver fat, triglycerides, and liver enzymes [6], [11].   

N-Acetyl-Cysteine (NAC)

This antioxidant is both insulin sensitizing and anti-inflammatory. Similar to berberine, research shows that NAC may even be more effective than metformin for improving insulin sensitivity and fasting blood sugar [1].  

NAC can also help to reduce high testosterone levels, which helps to promote ovulation and reduce bothersome secondary symptoms like facial hair growth. It can also improve pregnancy and live birth rates.  A study [12] concluded “NAC may be a new treatment for the improvement of [circulating insulin levels] and insulin sensitivity in hyperinsulinemia patients with polycystic ovarian syndrome.”  

Lastly, a systematic review and meta-analysis [13] of eighteen randomized controlled trials involving 2,185 women with PCOS demonstrated a significant reduction in total testosterone and significant increases in FSH levels. This is an important finding because many women with PCOS have far greater LH than FSH, limiting follicle growth at the start of a cycle and resulting in either anovulation or release of an immature egg that cannot be fertilized.  

The Bottom Line

While supplements will not cure PCOS (there is no cure to date), they are an integral tool in any quality toolbox for managing PCOS in your patients.  

To learn more about these supplements, such as dosage and best form to use, be sure to read our EBook: Your Ultimate PCOS Toolkit

References  

1. By CNY Fertility. The Ten Best Supplements for PCOS. CNY Fertility. Updated on December 15, 2021. Accessed August 14, 2023. https://www.cnyfertility.com/pcos-supplements/   
2. Grassi A. White R. 6 Things to Know About Taking Inositol for PCOS. Verywell Health. November 7, 2022. Accessed August 3, 2023. https://www.verywellhealth.com/inositol-for-pcos-info-2616286  
3. Asimakopoulos, G., Pergialiotis, V., Anastasiou, E. et al. Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial. J Trials 21, 633 (2020). https://doi.org/10.1186/s13063-020-04561-2 https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04561-2 
4. Zheng X, Lin D, Zhang Y, Lin Y, Song J, Li S, Sun Y. Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. J Medicine (Baltimore). 2017 Dec;96(49):e8842. doi: 10.1097/MD.0000000000008842. PMID: 29245250; PMCID: PMC5728865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728865/ 
5. Grassi A, Schlanger L. What Women With PCOS Should Know About Magnesium. Verywell Health. Updated on November 09, 2022. Accessed August 15, 2023. 
6. https://www.verywellhealth.com/pcos-and-magnesium-4145000 
7. Grassi A. King K. Berberine for PCOS: Benefits and Side Effects. Verywell Health. Updated on January 21, 2023. Accessed August 4, 2023. https://www.verywellhealth.com/pcos-and-berberine-4136324 
8. Farsinejad-Marj M, Azadbakht L, Mardanian F, Saneei P, Esmaillzadeh A. Clinical and Metabolic Responses to Magnesium Supplementation in Women with Polycystic Ovary Syndrome. J Biol Trace Elem Res. 2020 Aug;196(2):349-358. doi: 10.1007/s12011-019-01923-z. Epub 2020 Jan 20. PMID: 31960275. https://pubmed.ncbi.nlm.nih.gov/31960275/ 
9. Wei Wei and others, A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome, European Journal of Endocrinology, Volume 166, Issue 1, Jan 2012, Pages 99–105, https://doi.org/10.1530/EJE-11-0616 https://academic.oup.com/ejendo/article-abstract/166/1/99/6659259?redirectedFrom=fulltext&login=false 
10. An, Y., Sun, Z., Zhang, Y., Liu, B., Guan, Y. and Lu, M. (2014), The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. J Clin Endocrinol, 80: 425-431. https://doi.org/10.1111/cen.12294 https://onlinelibrary.wiley.com/doi/10.1111/cen.12294 
11. Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. J Oncotarget. 2017 Sep 11;9(11):10135-10146. doi: 10.18632/oncotarget.20807. PMID: 29515798; PMCID: PMC5839379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839379/#:~:text=It%20was%20found%20that%20hypoglycemic,the%20end%20of%20the%20trial 
12. Chang, X., Wang, Z., Zhang, J. et al. Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. J Transl Med 14, 266 (2016). https://doi.org/10.1186/s12967-016-0982-x https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0982-x 
13. Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. J Fertil Steril. 2002 Jun;77(6):1128-35. doi: 10.1016/s0015-0282(02)03133-3. PMID: 12057717. https://pubmed.ncbi.nlm.nih.gov/12057717/ 
14. Shahveghar Asl Z, Parastouei K, Eskandari E. The effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysis. Br J Nutr. 2023 Jul 28;130(2):202-210. doi: 10.1017/S0007114522003270. Epub 2023 Jan 4. PMID: 36597797. https://pubmed.ncbi.nlm.nih.gov/36597797/