Guest post on PCOSdiva Blog – February 2016
NAC, or N-acetyl cysteine, is a form of the essential amino acid cysteine, which is used to make glutathione, the body’s main antioxidant. By raising glutathione levels, your cells are protected from reactive oxygen species, and protected against DNA damage and cancer development. The other main mechanism for NAC is in modulating inflammation both acutely from viruses, and also in chronic inflammatory conditions.
A review of studies with NAC show the following incredible and diverse health benefits for various conditions:
- Replenishing intracellular glutathione levels, which can become deficient with age and chronic illness.
- Protection against flu symptoms, meaning it reduces the severity and likelihood of having flu symptoms when exposed to the flu virus (1).
- Reduction of the frequency and duration of attacks in chronic obstructive pulmonary disease (COPD) and slowing the profession of pulmonary fibrosis.
- Blocks cancer development due to the reduction in oxidative stress and inflammation. NAC also induces cell death in multiple types of human cancer cells, slows tumor growth, protects the lungs from cigarette smoke-induced cancer, and shrinks colon polyps. In these and other mechanisms, NAC is considered a supplement for cancer chemoprevention (2,3,4,5,6).
- Inhibits growth of Helicobacter pylori infection in the stomach and reduces the production of inflammatory cytokines produced by this organism which can lead to gastritis and cancer (7,8).
- Reduction of symptom in obsessive-compulsive syndrome with daily use, including compulsive hair pulling, nail biting, skin picking, and even compulsive gambling (9,10).
Specifically for PCOS, NAC has an impact on insulin resistance, ovulation response and also hormone balance. It is certainly a supplement worth considering, in addition to work with your nutrition, exercise and stress management plan.
Six ways NAC supports your PCOS:
1. NAC improves insulin sensitivity.
Several studies have looked at the role of NAC in women with insulin resistance, and even compared with metformin. A reasonable dosage of 600 mg of NAC daily worked equally well to metformin, where both treatments resulted in lower fasting insulin, a significant decrease in weight, lower free testosterone and hirsutism and improved menstrual regularity. As you read more health benefits of NAC, you will understand why this supplement is likely a superior choice to metformin due to the other positive impacts (11, 12)
2. Lowers testosterone levels and free androgen index
Due to the effect on overall hormone balance, studies also show a significant drop in testosterone levels and also what is called the free androgen index which measures the ratio of testosterone to SHBG (sex hormone binding globulin) as an indicator of how much free testosterone is circulating (11,12). NAC offers an additional support to lower some of the more annoying symptoms of PCOS related to high androgens such as acne, hair loss and hirsutism.
3. Improves menstrual regularity and frequency of ovulation
NAC alone can improve menstrual and ovulation regularity as in the study comparing it to metformin above. Another study combined NAC with l-arginine supplements showing many cases of restored ovulatory cycles. Women with PCOS tend to have higher free radical levels which lowers nitric oxide. Nitric oxide has a positive role in the egg maturation process and ovulation (11, 13).
4. Supports egg quality for fertility
Through increasing intracellular glutathione levels, NAC can protect egg quality. In an additional study looking at egg quality for IVF cycles, and again in comparison to metformin, women treated with NAC for 6 weeks prior to their fertility treatment showed significantly better egg and embryo quality (14), and hence had higher fertility rates. This is worth considering, especially if you are trying to conceive over age 35 and need additional egg quality support.
5. Lowers total cholesterol and LDL levels
An added bonus to reducing insulin resistance and weight loss is a positive change in lipid levels. In women with PCOS, there was also noted a decrease in both total cholesterol and low-density lipoprotein levels (11).
6. Works together with Clomid for improved fertility, better ovulation rate and higher progesterone levels
When Clomid (clomiphene citrate) is combined with NAC for fertility, there is a significantly improved ovulation rate, compared to Clomid alone, along with better endometrial thickness and progesterone levels (15). It is important to note that a very common side-effect of clomid treatment is a thin endometrial lining, which is corrected by the addition of NAC. NAC will also boost ovulation rates in women who are ‘clomid-resistant’, meaning that clomid on its own will not induce ovulation. When combined with NAC, ovulation rates in one study went up from 1% to 49%, which is a very significant change (16).
Dosage and safety:
The therapeutic dosage of NAC in almost all of the published studies is 600 mg 3x daily. If you are significantly overweight, a higher dose, closer to 1000 mg 3x daily may be required to see the benefits.
NAC is considered a very safe supplement. The most common side-effect is stomach upset, usually being acid reflux of gastric irritation. This is usually resolved by taking the supplement with food rather than on an empty stomach, and not combining with coffee. There is some caution in people with asthma.
- De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. The European Respiratory Journal. 1977 July;10(7):1535-41.
- Guan D, Xu Y, Yang M, Wang H, Wang X, Shen Z. N-acetyl cysteine and penicillamine induce apoptosis via the ER stress response-signaling pathway. Mol Carcinog. 2010 Jan;49(1):68-74.
Li J, Tu HJ, Dai G, et al. N-acetyl cysteine inhibits human signet ring cell gastric cancer cell line (SJ-89) cell growth by inducing apoptosis and DNA synthesis arrest. Eur J Gastroenterol Hepatol. 2007 Sep;19(9):769-74.
- Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S. Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetyl cysteine. Int J Cancer. 2010 Mar 1;126(5):1047-54.
- Ponz de Leon M, Roncucci L. Chemoprevention of colorectal tumors: role of lactulose and of other agents. Scand J Gastroenterol Suppl. 1997;222:72-5.
- Estensen RD, Levy M, Klopp SJ, et al. N-acetyl cysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. 1999 Dec 1;147(1-2):109-14.
- Huynh HQ, Couper RT, Tran CD, Moore L, Kelso R, Butler RN. N-acetyl cysteine, a novel treatment for Helicobacter pylori infection. Dig Dis Sci. 2004 Nov-Dec;49(11-12):1853-61.
- Kim MH, Yoo HS, Kim MY, et al. Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells. Int J Mol Med. 2007 Apr;19(4):689-97.
- Grant J, Odlaug BA, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. A double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009; 66(7):756-763
- Grant JE, Kim SW, Odlaug N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiat 2007; 62: 652-657.
- Fulghesu AM, Ciampelli M, Muzj G, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002 Jun; 77(6):1128-35.
- Oner G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2011 Aug 8.
- Masha A, Manieri C, Dinatale S, Bruno GA, Ghigo E. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycistic ovary syndrome. Journal of Endocrinological Investigation. 2009 Dec. 32(11): 870-872.
- Cheraghi E, Mehranjani MS, Shariatzadeh MA, Esfahani MH, Ebrahimi Z. N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin. Reprod Fertil Dev. 2014 Nov 13.
- Badawy A, State O, Abdelgawad S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acts Obstet Gynecol Scand. 2007;86(2):218-22.
- Rizk AY, Bedaiwy MA, Al-Inany HG. N-acetyl-cystein is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovarian syndrome. Fertile Steril. 2005 Feb; 83(2):367-70.