Insulin Resistance and Fertility: Part 4

Part 4: Supplements for Insulin Resistance and Fertility

Originally published by Dr. Fiona McCulloch in Naturopathic Currents in September 2013, you can read the original article here.

This article has been broken down into a four part series, links to the other parts of this series are listed below:


Myo-inositol as an insulin-sensitizing supplement that is useful in polycystic ovarian syndrome and other insulin resistant fertility concerns. At a dose of 4 grams per day, myo-inositol improves ovarian activity, insulin sensitivity and fertility in patients with PCOS.(1) Myo-inositol also decreases testosterone(2) and is a marker of good egg quality.(3)

  • N-Acetyl Cysteine

A study on 37 women with PCOS found that 1.8 grams daily of NAC improved insulin resistance by reducing insulin levels and increasing insulin sensitivity.(4)

Another study on 100 women with PCOS found that 600mg of NAC three times daily had effects comparable to metformin on lowering insulin, male hormones, and improving menstrual cyclicity.(5) A study on 180 patients with PCOS taking 1.2 grams of NAC daily along with the ovulation inducer Clomid had improved ovulation and pregnancy rates when compared to Clomid alone.(6)

  • Fish Oil

Fish oil may decrease insulin resistance. In a study of 12 overweight men and women who had insulin resistance, 70% of the participants taking fish oil decreased insulin resistance.(7) EPA and DHA from fish oil also increase adiponectin,(8) which improves insulin resistance.

Omega 3 fatty acids from fish oil also lower the inflammatory markers(9) secreted by the fatty tissue in patients with insulin resistance. This improves implantation in patients suffering with infertility.(10)

EPA and DHA also prevent fatty acid oxidation and reduce inflammation in adipose tissue, favouring insulin sensitivity.(11)

  • Vitamin D

Vitamin D is also crucial for treating insulin resistance in patients with fertility concerns. Vitamin D has been found to improve insulin resistance and lower androgen levels in women with PCOS.(12) Low levels of vitamin D are associated with increased insulin resistance markers in PCOS women.(13)

  • Alpha Lipoic Acid (ALA)

Numerous studies exist supporting the use of alpha lipoic acid in insulin resistant and diabetic conditions.(14) ALA has been found to increase peripheral insulin sensitivity,(15) decrease waist circumference(16) and act as an antioxidant.(17) all of which benefit insulin resistance and infertility. A 2010 study administered 600mg bid of controlled release ALA to PCOS patients. At the end of the treatment, there was a 13.5% improvement in insulin sensitivity, an improvement in menstrual cyclicity, and a reduction in triglycerides.

Insulin resistance is one of the most common factors in fertility concerns. It affects the entire reproductive cycle, from egg development and quality, to the implantation and maintenance of a pregnancy. Fortunately, there are effective ways to reduce insulin resistance with diet, lifestyle changes and supplement therapies, allowing conception to happen with greater ease and even better, significantly improved underlying health.

Article References:

  1. Unfer V, Carlomagno G, Dante G, Facchinetti F.Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials.GynecolEndocrinol.2012 Jul;28(7):509-15.doi: 10.3109/09513590.2011.650660. Epub 2012 Feb 1.
  2. Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F.Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial.Eur Rev Med Pharmacol Sci.2011 May;15(5):509-14.
  3. Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ.Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality.Hum Reprod.2002 Jun;17(6):1591-6..
  4. Anna Maria Fulghesu, Mario Ciampelli, Giuseppe Muzj, Chiara Belosi, Luigi Selvaggi, Gian Franco Ayala, Antonio Lanzone.N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome.Fertility and Sterility.June 2002;77(6):1128-1135.
  5. Oner G, Muderris II.Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome.Eur J ObstetGynecolReprod Biol.2011 Nov;159(1):127-31.
  6. Salehpour S, Sene AA, Saharkhiz N, Sohrabi MR, Moghimian F.N-Acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome.J ObstetGynaecol Res.2012 Sep;38(9):1182-6..
  7. Denkins, Y.Experimental Biology 2002 Conference, April 20-24 2002
  8. NalinSiriwardhana, Nishan S. Kalupahana, NaimaMoustaid-Moussa.Chapter 13 – Health Benefits of n-3 Polyunsaturated Fatty Acids: Eicosapentaenoic Acid and Docosahexaenoic Acid.Advances in Food and Nutrition Research.2012;65:211-222.
  9. Kalupahana NS, Claycombe KJ, Moustaid-Moussa N.(n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights.AdvNutr.2011 Jul;2(4):304-16..
  10. Ng SC, Gilman-Sachs A, Thaker P, Beaman KD, Beer AE, Kwak-Kim J.Expression of intracellular Th1 and Th3 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy.Am J ReprodImmunol.2002 Aug;48(2):77-86..
  11. Kalupahana NS, Claycombe KJ, Moustaid-Moussa N.(n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights.AdvNutr.2011 Jul;2(4):304-16.
  12. Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, Tuncel E, Erturk E, Imamoglu S.The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome.J Endocrinol Invest.2010 Apr;33(4):234-8..
  13. Wehr E et alAssociation of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome.Eur J Endocrinol.2009 Jul 23.;
  14. S Jacob, P Ruus, R Hermann, H.J Tritschler, E Maerker, W Renn, H.J Augustin, G.J Dietze, K Rett.Oral administration of rac-a-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.Free Radical Biology and Medicine.August 1999;27(3-4):309-314.
  15. Kamenova P.Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid.Hormones (Athens).2006 Oct-Dec;5(4):251-8..
  16. Udupa AS, Nahar PS, Shah SH, Kshirsagar MJ, Ghongane BB.Study of comparative effects of antioxidants on insulin sensitivity in type 2 diabetes mellitus.J ClinDiagn Res.2012 Nov;6(9):1469-73..
  17. Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C.Direct and indirect antioxidant properties of a-lipoic acid and therapeutic potential.MolNutr Food Res.2013 Jan;57(1):114-25..