N-ACETYL CYSTEINE (NAC): A Natural Insulin-Sensitizer for PCOS?

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N-Acetyl Cysteine, also known as NAC may offer help to women with PCOS.  In this article, we examine the research between NAC and women with PCOS and what influence it may or may not have on fertility, inflammation, and improving metabolic markers like insulin.

NAC is both an antioxidant and amino acid (building blocks of protein). Specifially, NAC is a derivative of the amino acid L-cysteine, an essential precursor used by the body to produce glutathione. Glutathione is an extremely important and powerful antioxidant produced by the body to help protect against free radical damage and oxidative stress, and is a critical factor in supporting a healthy immune system. NAC has been shown to increase glutathione levels as well as protect insulin receptors. NAC may also influence insulin receptor activity.

NAC is widely sold in Europe as a treatment for the common cold and it has other numerous uses from being a treatment for bronchitis to removing heavy metals and environmental pollutants from the body. NAC has also been found to reduce inflammation, heart disease and most recently, insulin.

NAC vs. Metformin in PCOS

Three studies have compared the effects of NAC or Metformin in women with PCOS.

In the most recent study published in Gynecological Endocrinology, a randomized double-blind clinical trial involving 94 women with PCOS compared NAC 600 mg, three times a day with 500 mg oral metformin, three times a day for 24 weeks.

The researchers found that NAC can improve lipid profile and fasting blood sugar and fasting blood insulin better than metformin.

These results are confirmed with an earlier study, published in the European Journal of Obstetrics, Gynecology and Reproductive Biology which compared the effects of NAC and metformin on insulin levels. In this prospective trial, 100 women with PCOS were divided to receive metformin (500mg three times daily) or NAC (600mg three times daily) for 24 weeks.

The results: Both treatments resulted in a significant decrease in body mass index, hirsutism, fasting insulin, free testosterone and menstrual irregularity, and both treatments had equal effectiveness. Furthermore, NAC led to a significant decrease in both total cholesterol and low-density lipoprotein levels, whereas metformin only led to a decrease in total cholesterol level.

This research supports findings published in the Journal of Fertility and Sterility in 2002 where researchers reported significant improvement in insulin levels among women with PCOS who took 1.6-3g/day of NAC and who had elevated insulin levels before the start of study. Women also showed improvements in testosterone, cholesterol and TG levels.

NAC and Fertility in PCOS

When used with clomid, NAC has been shown to improve ovulation and pregnancy rates in PCOS women by thickening endometrial lining. 100 women with PCOS who randomly received NAC plus clomid had more endometrial thickness and ovulatory follicles than women who just took clomid or clomid plus metformin.

NAC was also shown to improve oocyte and embryo quality in Iranian women undergoing intracytoplasmic sperm injection.

Conclusions of Systematic Review

A systematic review published in Obstetrics and Gynecology, involving eight randomized controlled trials with 910 women that compared effects of NAC with placebo or metformin in women with PCOS, concluded:

“NAC had significant improvement in pregnancy and ovulation rate as compared to placebo.”

NAC was not associated with greater benefits to metformin for improving pregnancy rate, spontaneous ovulations, and menstrual regularity.”

“No evidence showed the effects of NAC on improving acne, hirsutism, BMI, fasting insulin, or fasting glucose.”

Both NAC and Metformin improved BMI, total testosterone, insulin, and lipid levels compared to NAC.

“Compared with Metfrormin, NAC significantly reduced BMI, total testosterone.”

“Compared with Metformin or placebo, NAC significantly reduced fasting blood glucose in women with PCOS.”

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Side Effects

Overall, NAC is well tolerated but can cause gastrointestinal adverse effects including nausea, abdominal pain, vomiting, constipation, and diarrhea, particularly when used in high doses. The therapeutic dosage of NAC to improve insulin levels based on the published studies is 1.6-3 grams/day. If you are overweight, you may benefit from the higher end of the dose range. Fulghesu et al found that obese patients with PCOS did not respond to doses under 3 grams/day. You should not exceed 7grams/daily. As with any nutrition supplement, it is important to discuss use with your physician before taking.

Bottom line: More research needs to be conducted on the potential benefits of NAC in PCOS women. So far, the evidence does show NAC can improve pregnancy and ovulation rates. NAC is a safe and well tolerated antioxidant which has potential to help women with PCOS improve their insulin and inflammation.

N-Acetyl Cysteine is now available in the PCOS Nutrition Center Store! Shop now!

We want to hear from you: What has been your experience with NAC?

References

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. 2015 Dec 10:1-5.

Maged AM, Elsawah H, Abdelhafez A, Bakry A, Mostafa WA.The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome. Gynecol Endocrinol. 2015;31(8):635-8.

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.

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.

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. Fertil Steril. 2002 Jun;77(6):1128-35.

Abu Hashim H, Anwar K, El-Fatah RA. N-acetyl cysteine plus clomiphene citrate versus metformin and clomiphene citrate in treatment of clomiphene-resistant polycystic ovary syndrome: a randomized controlled trial. J Womens Health (Larchmt). 2010 Nov;19(11):2043-8. Epub 2010 Oct 12.

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.

 

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Comments (28)
  • Liz

    November 2, 2011 at 2:46 pm

    I have been taking 1000mg a day – 2x 500mg capsules. Unfortunately I can only find one range of vitamins in South Africa which manufactures NAC – and they only make them in 500mg capsules. Do you think I should increase dose to 1500mg? I have noticed better agility – maybe assisting in reducing inflammation. I am excited to see what long term befits will be and will keep you posted. Please send your thoughts on dosage. Ciao

  • Angela Grassi

    November 7, 2011 at 2:46 pm

    If you are having good results with the dosage you are taking now you can stick with that. Heavier people need more in general.

  • Sophie

    June 4, 2012 at 2:47 pm

    I have been using 600 mg NAC twice a day for about a month now. I have had some astounding results. My facial hair growth which was increasing steadily and spreading down towards my neck has almost stopped. I alternate between Puritan’s Pride and GNC brands and find Puritan’s Pride to be slightly more effective. If I miss a dose, I have immense sugar and carb cravings which tells me that the NAC really does help lower insulin levels thereby banishing those cravings. I am now looking to add Chromium and ALA to my regimen. Previous to this, I have used fasting as a means to restore my period, but subsequent bouts of overeating have resulted in gaining back the 40 lbs that I lost and now I am back to my PCOS state. But I am confident that soon I’ll be back on track with my health. For those with hirsutism… please try NAC.

  • Christy

    June 29, 2012 at 2:47 pm

    I am on Amazon as I post this, buying NAC and hoping for some sort of improvement. Thanks for the article!!

  • Natasha

    June 29, 2013 at 2:47 pm

    I started taking 600 mg 3x a day for ten days so far. After day 3 I got my period, which I had not gotten since november (it is June). I can’t wait to see the long term results.

  • thyPCOS

    October 15, 2013 at 2:48 pm

    I have hypothyroidism and PCOS. I take Levothyroxine 50mcg in the morning for hypothyroidism. For PCOS, I take Metformin 500mg in the noon, and Diane-35 in the night. Diane-35 is the brand name of a contraceptive pill. It contains Cyproterone Acetate 2mg and Ethinyl Estradiol 0.035mg. I read NAC is good for hypothyroidism and for PCOS. I just want to make sure it does not interfere with the contraceptive pill. Can I take NAC when am taking the contraceptive pill and metformin?

  • Claudia Rowe

    June 6, 2014 at 2:48 pm

    I no longer have PCOS (strict ketogenic diet, lots of fish and other oils) but continued to have problems with insulin resistance and was eventually diagnosed with Diabetes II, despite a continuing low-carb diet.

    I could never get to a therapeutic dose of Metformin; made me vomit ALL DAY! However, been taking 2400 mg of NAC and the results have been fantastic. Blood glucose lowered and GOTT trsts back to normal ranges.

    Took about three months but really worked.

  • Gemma

    July 13, 2014 at 2:48 pm

    Would you take thus with pregnitude or instead of. I am not ttc but manage my weight and hair loss.

  • Angela Grassi, MS, RDN, LDN

    July 14, 2014 at 2:49 pm

    Gemma, You can take NAC and inositol together but may want to start with one first to see if it helps and to monitor side effects.

  • Laura Ellis

    September 1, 2014 at 2:49 pm

    I am a type 2 diabetic and am taking metformin 500mg daily, along with 400mg of myo-inositol and other supplements. Would it be beneficial to me to take this too? or am I doing enough?

  • Angela Grassi, MS, RDN, LDN

    September 2, 2014 at 2:49 pm

    Hi Laura,

    I can’t advise you on what dose you take because I don’t know what other supplements and medications you take. If you are interested, we do provide nutrition counseling through the web or phone and can give you the right advice. Contact us at info@PCOSnutrition.com. If you are feeling well and managing your blood sugars ok, you may be doing enough.

  • Mary

    September 15, 2015 at 2:49 pm

    I have taken my first nac capsule 600 mg at noon I am type 1 diabetic and my sugar is very high 400 at 3pm and after taking a lot more insulin it’s not going down very much . I always have great numbers with my sugar. I am taking it because it’s a very good antioxidant . Has anyone had a problem like this while taking it would like some feed back

  • Jessica

    September 23, 2015 at 2:50 pm

    I have been directed to take 1800 mg daily and am also taking Co-enzymeQ10 (600 mg daily) – is it safe to take both?

  • Angela Grassi, MS, RDN, LDN

    September 29, 2015 at 2:50 pm

    Yes, you can take NAC and CoQ10 together.

  • Monika Andersson

    November 21, 2015 at 2:50 pm

    I have PCOS, and have been on Metformin for about 16 years now. I had very few periods as a young woman (about once a year) and low fertility, and treated with hormones to get pregnant in my early 30’s. (Got twins!). Yet, it took my sister who is a gynecologist to point out that I probably had PCOS, and sure enough. That’s when I went on Metformin for my heart health. About two years ago I started taking green coffee bean extract. It worked so well that I could cut my Metformin dose in half. When I excitedly told my endocrinologist about it she was completely uninterested in my comments about the green coffee bean extract, and thought instead it was all diet related. I tried to tell her that my diet had not changed, but she would not listen. I just found out about N-acetylcysteine and am eager to try that as well. Be well, all of you. There are ways to get better, and sometimes we have to do research on our own to find some answers… And thank you to the researcher who try to help!

  • Theresa

    July 20, 2016 at 8:11 pm

    Can this be taken safely along with metformin and ovasitol?

  • Angela Grassi

    July 21, 2016 at 11:07 am

    Yes, you can take NAC, metformin and ovasitol together.

  • M.C.

    October 3, 2016 at 12:56 pm

    Can this be taken in conjunction with ovasitol?

  • M.C.

    October 3, 2016 at 1:00 pm

    Disregard this comment I see the answer above. Thank you!

  • Dana

    October 29, 2016 at 7:33 am

    I’m 52 and post menopausal with insulin resistance and male pattern baldness due to high androgen. Will NAC help me? My daughter suffers with PCOS as well. I had a heart attack at 39 they don’t know what cause I. Now I believe it was PCOS. I would love to decrease my stomach size.

  • Trish

    January 4, 2017 at 7:22 pm

    I’m so excited to try this but I’m wondering if it’s safe to use while nursing?Thx so much for helping those of us who are seriously struggling with this.So many people just ask why I can’t loose the weight…can’t I just start a healthier lifestyle? It’s so frustrating to have to explain PCOS all the time

  • Angela Grassi

    January 5, 2017 at 9:48 am

    Yes, you can take it with nursing but I would check with your pediatrician before starting it.

  • Sarah

    February 20, 2017 at 3:28 am

    Hi Angela,

    Thank you for all of your thorough research and many articles. I am newly diagnosed with PCOS though I did suspect it for nearly 5 years now! I am currently taking the ovasitol and am thinking about adding in Berberine and/or NAC, is one better than the other? They both seem similarly beneficial but would adding both be redundant? Thanks so much!

  • Angela Grassi

    February 20, 2017 at 8:26 pm

    Hi Sarah! Thank you for your kind words. There is definitely more research on NAC for PCOS so I would advise starting there and see how you do with it. Berberine is more aggressive, and isn’t for long term use.

  • Robyn

    September 2, 2017 at 5:47 pm

    Is it safe to continue to use the NAC while pregnant?

  • Angela Grassi

    September 19, 2017 at 4:35 pm

    Yes it is, but we recommend checking with your doctor first.

  • Bri

    January 3, 2018 at 11:51 am

    Hi I was wondering what dose I should take of nac. I weigh 235lbs and I’m 5”6 height wise. I’m taking 2 900 mg pills a day now I was wondering if it’s safe to take 3 a day?

  • Angela Grassi

    January 9, 2018 at 5:45 pm

    Yes you can take 600mg 3x/day. There was a study that showed bigger women needed more NAC to be effective-up to 3,000 mg daily.

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