I’m a supplement junkie. If you refer to my ttc cv, you can see that I tried for over a year, long before we even started trying to have a baby, to regulate my cycles naturally. I’ve tried everything that I am aware of that is advocated for as a natural solution to PCOS. I’ve tried all of the following, alone and in combination, including both high intensity and low intensity and somewhere in-between exercise, herbal tinctures, supplements, acupuncture, Chinese herbs, a low Glycemic Index diet, a stricter diet from the PCOS diet e-book, and bioidentical hormones.
I’ve found it frustrating and confusing to track down an appropriate list of supplements for someone with PCOS. In an attempt to help others, I wanted to provide the supplements I take linked to the research that convinced me it was an important supplement to include in my regimen.
Disclaimer: I am not an Eastern or Western medical practitioner, nor do I have a degree in pharmacology. The information provided below is simply a review of medical literature, and is not to be construed as medical advice.
N-Acetyl-Cysteine (NAC): NAC is an antioxidant that is most commonly used as an antidote to acetaminophen overdose and as a anti-mucolytic for the treatment of chronic bronchitis. Since 2002, medical research has explored the efficacy in treating PCOS with NAC. The earliest study that I’ve found explores NAC’s ability to increase insulin sensitivity in women with PCOS (Fulghesu et al, 2002). The trial found that NAC has a statistically significant effect in increasing insulin sensitivity and decreasing androgens. The study used women with varying BMI’s including overweight women and women with a BMI within the normal range.
It appears as if the aforementioned article was the starting point for research exploring the efficacy of NAC in treating PCOS. Studies found that NAC assists in inducing ovulation in both clomid-resistant women with PCOS, as well as women not previously diagnosed as clomid-resistant (Rizk et al, 2005 & Badawy et al, 2010). Research also reveals that NAC is just as effective as Metformin in reducing androgens, BMI, and hirsutism, in addition to having a positive effect on menstrual irregularity and fasting insulin levels (Oner & Muderris, 2011).
Additionally, NAC has been found to reduce oxidative stress which results in inflammation and increases the risk of miscarriage (Amin et al, 2008). Researchers hypothesize that women with PCOS have an increased level of oxidative stress (Zhang et al, 2008), and have determined that the oxidative stress is the reason why women with PCOS are at increased risk for cardiovascular disease (Sabuncu et al, 2001).
This is just a small summary of the literature regarding NAC and PCOS. Most of the research utilized a dose of 1200 to 1800 mg/day. While most of the literature I’ve reviewed shows a positive and statistically significant effect, not all studies reported significant results ( e.g. Elnashar et al, 2005).
Lastly, I find it really interesting that NAC is a known anti-mucolytic and PCOS, as an Eastern diagnosis, is phlegm-damp, which results in excessive mucus.
Vitamin D: Studies reveal that Vitamin D is involved in the production of sex hormones, assisting in the fertility of both men and women (Lerchbaum & Obermayer-Pietsch, 2012). In regards to PCOS, research reveals that a Vitamin D deficiency is negatively related to insulin resistance and glucose intolerance in Type II diabetics (Song and Manson, 2010). Further, PCOS women are at increased risk for Vitamin D deficiency, resulting in increased risk of metabolic disorders (Raymond et al, 2011 & Wehr et al, 2009). Research does not provide as strong of an effect as NAC, but still provides evidence that Vitamin D is effective in improving insulin sensitivity and menstrual regularity(Selimoglu H. et al, 2010, & Wehr E. et al, 2011).
L-Arginine: L-Arginine is an amino acid best know for its vasodilatory properties. LAG also produces Nitric Oxide (NO), which is thought to reduce inflammation due to free radicals and assist in the regulation of ovulation, including follicular development, and implantation (Westphal et al, 2004). Supplementation with LAG was found to increase blood flow to the organs, in addition to aiding the response to gonadotrophins in poor responder women (Battaglia et al, 1999). LAG in combination with NAC has been found to increase the amount of Nitric Oxide, which decreases the number of free radicals, typical in women with PCOS. Combined supplementation of NAC and LAG was found to increase insulin sensitivity and menstrual regularity in women with PCOS (Masha et al, 2009). The research I’ve read utilized 1200 mg/day.
Returning to the Eastern diagnosis of phlegm-damp, circulation to the reproductive organs is often not optimal due to excess production of mucus. Supplements and acupuncture, as well as castor oil packs, are helpful in increasing blood flow to the uterus and ovaries, reducing inflammation, and assisting in ovulation.
Inositol: Inositol is a insulin-sensitizing agent that can be described as a sugary carbohydrate that is part of the B Vitamin family. There are up to nine different types of inositol, but two, in particular, have insulin-sensitizing capabilities: myo-inositol and d-chiro-inositol (Unfer et al, 2012).
Due to its insulin-sensitizing ability, inositol is almost as magical as NAC, if not more so. The prevalence of research studies number in the 70′s, but recent research demonstrates that myo-inositol may be more effective than d-chiro-inositol in treating PCOS (Galletta et al, 2011). As a result, I will focus on the myo-inositol literature.
Of the 70 articles, approximately half focus on myo-inositol and of those there are six randomized control studies looking at the effect of myo-inositol on PCOS indicators such as hormonal levels, egg quality, and ovarian function. Randomized control studies are the gold standard in evidence based research. Across the six studies, myo-inositol was effective in reducing LH, prolactin, estradiol, testosterone, and insulin/blood sugar (Genazzani et al, 2008; Gerli et al, 2007); in restoring ovulation and decreasing the length of cycles (Constantino et al, 2009; Genazzani et al, 2008; Gerli et al, 2007; Gerli et al, 2007; Papaleo et al, 2007; Raffone et al, 2010); and decreasing blood pressure, cholesterol and triglycerides (Constantino et al, 2009; Gerli et al, 2007, Gerli et al, 2007).
Additionally, it should be mentioned that when compared with metformin, myo-inositol had greater success in restoring ovulation (65% v. 50%). Of those taking myo-inositol, 30% became pregnant versus 18% within the met group (Raffone et al, 2010). The authors of this article recommended using myo-inositol over metformin for first line treatment of PCOS. Bananas, right?
And, finally, my-inositol was also helpful in achieving weight loss and lowering BMI (Gerli et al, 2007).
The dose for the trials ranged from 2000 to 4000 mg a day. The easiest way to get this dose is to take it as a powder. I’ve done it, and it isn’t bad. I probably measures at about 1/2 teaspoon, and it doesn’t flavor the water. It is slightly sweet. You wouldn’t notice it if you popped it into a drink, breakfast cereal, yogurt, smoothie, etc. The exception to the dosage is Gerli et al, 2007. They used a 200 mg/day dose and achieved the same results.
Essential Fatty Acids (EFA): EFAs used to intimidate me. DHA, ELA, GLA, 3, 6, 9, what?! OMG, am I consuming the right amounts, during the correct time of my cycle, to gain the benefits of the EFA’s?! I then embarked upon a journey to demystify EFAs. I will try to do the same for you in just a few paragraphs.
EFAs are unsaturated fats that are integral to good health and come in the form of Omega 3, Omega 6 and Omega 9 fatty acids. The former two cannot be produced by our body, and, thus, must be obtained through food consumption or supplementation. Our bodies do have the ability to create Omega 9, so let’s focus on 3 and 6.
Omega 3 and 6 are both integral to the production of eicosanoids. Eicosanoids are signaling molecules present in every cell of the body that control different functions related to inflammation and immunity. Ideally our consumption of EFAs would be at a ratio of 2:1 Omega 6s to Omega 3s; However, diets in the US typically consume EFAs at a ratio of 10-20: 1 (Mirkin, 2012). Decreased levels of Omega 3s results in an imbalance of eicosanoids, which results in a host of problems including infertility. It has been found that an increase in the level of Omega 3′s results in increased blood flow to the uterus and ovaries (Saldeen & Saldeen, 2004). Additionally, decreased levels of Omega 3s decreases insulin sensitivity and increases blood sugar levels (Mirkin, 2012).
Women with PCOS tend to have an unbalanced ratio of Omega 6s to Omega 3s, and a higher level of Omega 6s is correlated with increased androgen levels. A cross-sectional study revealed that supplementation of Omega 3s balanced the ratio while also reducing androgens in women with PCOS (Phelan et al, 2011). Omega 3s are also conducive to reducing inflammation in women with PCOS (Liepa et al, 2008). Women with PCOS also have higher rates of non-alcoholic fatty liver disease. Omega 3s have been found effective in improving the condition and reducing cardiovascular risk factors such as triclycerides and blood pressure (Cussons et al, 2009; Sathyapalan & Atkin, 2011).
There are three types of Omega 3s – ALA, DHA, and EPA. ALA primarily comes from plant sources, whereas DHA and EPA are found in fish. DHA is the powerhorse that is integral to brain function, and it is recommended that pregnant women take up to 1100 mg of DHA + 800 mg of EPA daily while pregnant. The aforementioned PCOS trials used 4000 mg of Omega 3s in the form of fish oil capsules with a ratio of 1.5:1 of EPA to DHA.
Supplementation with fish oil is a great way to consume Omega 3s, and it appears to be fairly common throughout the world of fertility and infertility. I’ve been warned by a number of practitioners to be careful about the choice of fish oil; However, third party testing resulted in negligible levels of mercury in major brands of supplements.
Vitamin B Complex: The B Vitamin family is integral to cell metabolism, and the B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) are related to cellular health, metabolism, immune system, nervous system, skin, hair and muscles, mood, and, last but not least, fetal development. Most women are fully aware of the benefits of folic acid (B9) for fetal development, especially in regards to the prevention of neural tube defects. B vitamins are also helpful for women with PCOS. In particular, B6, B9, and B12 are helpful in addressing the unique issues surrounding PCOS due to their relationship with homocysteine (HC).
HC is an amino acid found in the blood and is typically ingested through the consumption of meat. Increased HC is linked to low levels of B6, B9, and B12. In addition, high levels of HC are negatively related to cardiovascular health as well as being linked to inflammation and oxidative stress. Low levels of B vitamins and high levels of homocysteine appears to be a problem with egg quality in women undergoing IVF, male factor infertility, endometriosis, and PCOS (Forges et al, 2007). Additionally, insulin resistance, increased androgens, and increased levels of HC are correlated with one another (Yarali et al, 2001).
As a result, it should be no surprise that women with PCOS commonly have elevated levels of homocysteine and low levels of B vitamins (Forges et al, 2007; Yilmaz et al, 2005; Yarali et al, 2001). This has been found to negatively affect women with PCOS undergoing IVF by impacting egg quality, embryo quality and fertilization rates (Berker et al, 2009). Treatment with B vitamins improves insulin sensitivity and decreases the levels of HC (Bargiota & Diamanti-Kandarakis, 2012). With that said, it should be noted that metformin is known to be related to increased levels of HC and decreased B vitamins, possibly due to the fact that metformin creates a deficiency in folates and B12 (Vrbikova et al., 2002; Kilicdag et al., 2005). God bless the Met. However, this can be counteracted by supplementing with B vitamins. The referenced studies used 500 mg of B1, 500 mg B6, and 2000 mcg B12 (Kilicdag et al., 2005), which are much higher than the levels found in prenatal vitamins.