NAC Supplementation for Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) affects 5-10 percent of reproductive-age women and is considered the most common cause of anovulatory infertility problems. Women who are afflicted in this way do not ovulate and thus, are unable to get pregnant. This, of course, can be quite emotionally devastating for women who wish to conceive.

To make things worse, PCOS is also associated with pregnancy complications such as recurrent pregnancy loss (RPL), which means having two or more miscarriages. And PCOS can also be extremely painful if the cysts in the ovaries burst and hemorrhage.

With PCOS, women tend to develop ovarian cysts that are comprised of immature egg cells (follicles) in the ovaries that are not being released over time. The follicles keep growing and form multiple cysts. These cysts may be described as appearing like a "string of pearls" in an ultrasound image of the ovaries.

Causes and Complications

Studies show that women with PCOS tend to have a high prevalence of metabolic syndrome, which includes various combinations of obesity, high blood pressure, glucose intolerance (high blood sugar), high triglycerides and decreased blood levels of the good cholesterol, known as HDL (high-density lipoprotein) cholesterol. In fact, up to 70 percent of women with PCOS have insulin resistance.

This profile often produces a hormonal imbalance whereby excess testosterone adversely affects ovulation and fertility and increases the propensity for ovarian cysts to form. Other studies show that women with PCOS have increased propensity for type 2 diabetes and increased risk of blood clots due to a high prevalence of protein C deficiency (a genetic problem that increases risk of blood clots). These factors also contribute to infertility, as they affect a woman's hormonal function, as well as blood viscosity or blood stickiness.^1-3

Drug and Natural Treatment

To help women with PCOS overcome infertility problems a drug called clomiphene citrate (CC) can be used to help induce ovulation. This drug stimulates the pituitary gland to secrete higher amounts of follicle stimulating hormone (FSH) and luteinizing hormone (LH), which prompt the maturation of egg cells in the ovaries and induce ovulation.

Unfortunately, the drug is ineffective in up to 40 percent of women who use it. However, studies beginning in 2010 have shown that taking the natural supplement N-acetylcysteine (NAC), along with the drug CC, increases both ovulation and pregnancy rates in women with PCOS, in cases where the drug CC was previously ineffective.⁴

How NAC Supplementation Helps

Regarding fertility, NAC has been shown to break up the mucus layer on the surface of the cervix. A thick mucus layer on the cervix can impede conception to a significant degree by acting as barrier that prevents sperm cells from gaining access to the uterus and fallopian tubes. One of the negative effects of the drug CC is that it thickens the mucus layer on the cervix, preventing penetration of the sperm to get through this barrier. The mucolytic action of NAC helps to break up this mucus, enabling sperm cells to find their way to the uterus and the fallopian tubes so fertilization of the egg can occur.

NAC also has a sensitizing effect on insulin receptors, which helps to lower blood glucose and thus lowers insulin secretion.¹ More specifically, NAC has been shown to reduce the oxidative stress that is a common feature in diabetes and metabolic syndrome. Increased oxidative stress is a key factor in reducing activity of insulin receptors, creating insulin resistance with resulting higher fasting and postprandial glucose levels.⁴

NAC has been shown to exhibit direct, as well as indirect, antioxidant properties. Its direct effect is due to a free thiol group interacting with and scavenging reactive oxygen species (ROS). Its indirect antioxidant effect is related to its role as a glutathione (GSH) precursor, resulting in increased intracellular GSH concentrations.

These antioxidant effects have been shown to improve function of insulin receptors, which in turn, helps to lower serum glucose and insulin levels in type 2 diabetics, prediabetics and patients with metabolic syndrome.⁵ These factors also help to improve hormone function, ovulation and fertility.

NAC supplementation also enhances a woman's overall antioxidant status, which suppresses free radical damage to throughout the body. Excessive free radical damage (oxidative stress, ROS) has also been implicated in infertility problems in women with PCOS.¹

Show Them the Research

The daily dosage of NAC used in PCOS studies is 1,200 mg, taken once per day, along with the drug clomiphene citrate.⁴ If you have patients who suffer from PCOS, and NAC supplementation is not part of their treatment plan, I suggest you bring this research to their attention and provide them with the references listed below to provide to their medical doctor. Many MDs follow drug research, but are not exposed to and/or do not follow the research showing the efficacy and synergy of natural supplements in the management of specific health conditions ... even though these clinical trials are published in peer-reviewed medical and scientific journals.

References

1. Mokhtari V, et al. A review of various uses of N-acetyl cysteine. Cell J, April 2017;19(1).
2. Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Curr Womens Health Rev, 2010;6:84-95.
3. Nasr A. Effect of N-acetyl cysteine after ovarian drilling in clomiphene citrate-resistant PCOS women: a pilot study. Reprod Biomed Online, 2010;20(3):403-409.
4. Shen FC, Weng SW, Tsao CF, et al. Early intervention of N-acetylcysteine better improves insulin resistance in diet-induced obesity mice. Free Radic Res, 2018;52(11-12):1296-1310.
5. Qianwen Z, Yuanrong J, Yan M, Wong T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia. Medicine, Nov 2018;97(45).