N-Acetyl-L-Cysteine for Hormone Support:

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NAC is an amino acid supplement that may support increased fertility in a variety of ways.

The acronym PCOS (sometimes pronounced “peek-ohs”) stands for polycystic ovarian syndrome. It’s a fairly common hormonal disorder, which occurs in about 10% of women at some point between menarche and menopause, during the reproductive years [1]. Unfortunately for some, although these should be “the reproductive years”, PCOS can stand in the way of fertility and successful pregnancy. In fact, 55-75% of PCOS patients are infertile due to anovulation [2]. In those with PCOS who are able to conceive, rates of spontaneous abortion are also high [3]. Those suffering from PCOS may have irregular, infrequent, or extended menstrual periods, and may express very high levels male hormones such as testosterone resulting in excess body hair, acne, or male pattern baldness [4]. Some experience ovarian inflammation and fluid-filled follicles that fail to regularly release eggs.

There is no known cause of PCOS, although diagnoses often follow a significant weight gain. There may be a hereditary tendency towards the disorder, or it may be brought on by excess insulin and androgen production [4]. Whatever the cause, excessive insulin levels and/or insulin insensitivity due to the disorder appear to be causing the majority of the reproductive endocrine disruptions observed in PCOS patients [3]. At present, there is no known cure for the disorder, but it can be treated and managed throughout a woman’s lifetime with the help of endocrinologists and health care experts. Clomiphene citrate (CC) is the standard drug for inducing or augmenting ovulation, but it doesn’t work for all patients [4]. In the last few years, many research efforts have been focused on optimizing nutritional support for women with PCOS. One positive finding has been the noted effects of NAC supplementation.

NAC is N-acetyl-cysteine, the acetylated version of the amino acid L-cysteine [2]. Cysteine is considered a semi-essential or conditionally essential amino acid, as it can be made within the body, but only under ideal homeostatic conditions. There are multiple pathologic conditions where the body does not produce sufficient levels of certain amino acids, including cysteine. NAC is more stable than L-cysteine and may be easier for the body to absorb. It is a necessary precursor for glutathione, arguably the most important antioxidant in the body, and also plays a role in its regulation. Glutathione helps to fight cellular damage and aids in immune health [5]. NAC aids the body’s phase II detoxification pathways, glutathione conjugation, and sulphation. NAC is so well known for its detoxification properties, that it is commonly used in hospitals to prevent kidney and liver damage from acetaminophen overdose or to prevent damaging side effects from ingestion of drugs or environmental toxins [6,7].

NAC also exerts an effect on both the insulin secretion of pancreatic cells and on insulin receptors on human red blood cells [2]. Because of its role as an insulin sensitizer, NAC was suggested as an adjuvant to CC to regulate ovulation in patients with PCOS. The fact that NAC also protects cells against apoptosis, preserves vascular integrity and has an immunologic effect all add to its candidacy as an excellent nutrient for those with PCOS-related infertility [2]. It was demonstrated that patients with PCOS taking both NAC and CC have had stronger rates of normal ovulation than those taking CC alone [2]. This finding has been attributed, in part, to NAC’s antiapoptotic effects on the ovary and protection against follicular atresia, in combination with an increase in insulin sensitivity.

NAC supplementation, as an adjuvant to CC, was shown to outperform metformin (a commonly-prescribed insulin-sensitizing agent) in the improvement of lipid profiles, fasting blood sugar, and fasting blood insulin levels of women with PCOS [8]. It has also been reported to support improved hormonal profiles, and help to regulate ovulation and fertility in hyperinsulinemic patients, specifically women with PCOS for whom CC alone was not effective [9]. Another study found that the rate of successful pregnancies (after IUI) increased by adding NAC to the nutritional regimen of patients taking CC for long-standing, unexplained infertility [10]. NAC has been shown to improve the number and quality of mature oocytes for ovulation, improve embryo quality after fertilization, and decrease the rate of immature oocytes in women under the same conditions [11].  

There is long-standing and significant evidence to show NAC supplementation is associated with a shortened duration of respiratory tract/bronchial infections, as NAC thins mucus for easier expectoration [12,13]. The ovulation study by Badawy, et al. reported a related and likely beneficial effect of NAC in combination with CC on fertility. As a known mucolytic, in the case of the cervix, NAC was found to improve the character of the cervical mucus without additional estrogen supply [2].

NAC is not a drug and has not been evaluated by the FDA. Supplementation with NAC is not intended to treat, cure or prevent any disease. It is, however, a naturally occurring amino acid and an effective antioxidant that plays a number of crucial roles in the endocrine and metabolic systems. It is intended to supplement the nutrition from your diet and support your body’s systems by providing extra substrate for natural processes. As always, please discuss the benefits of NAC with your healthcare provider before adding another nutrient to your dietary health regimen.

References

  1. Rizk A, Bedaiwy M, Al-Inany H. N-Acetyl cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate resistant patients with polycystic ovary syndrome. Fertil Steril. 2005; 83:36770.
  2. Badawy, Ahmed, Omnia State, and Soma Abdelgawad. “N‐Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross‐over trial.” Acta obstetricia et gynecologica Scandinavica 86.2 (2007): 218-222.
  3. Kumar, Pratap, and Sameer Farouk Sait. “Luteinizing hormone and its dilemma in ovulation induction.” Journal of human reproductive sciences 4.1 (2011): 2.
  4. The Mayo Clinic. Polycystic Ovarian Syndrome. Aug. 29, 2017. https://www.mayoclinic.org/diseases-conditions/pcos/symptoms-causes/syc-20353439
  5. Cascella, Roberta, et al. “S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans.” Free Radical Biology and Medicine 73 (2014): 127-135.
  6. Mokhtari, Vida, et al. “A review on various uses of N-acetyl cysteine.” Cell Journal (Yakhteh) 19.1 (2017): 11.
  7. Quig, David. “Cysteine metabolism and metal toxicity.” Alternative Medicine Review 3 (1998): 262-270.
  8. Javanmanesh, Forough, et al. “A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome.” Gynecological Endocrinology 32.4 (2016): 285-289.
  9. Nemati, M., et al. “Comparison of metformin and N-acetyl cysteine, as an adjuvant to clomiphene citrate, in clomiphene-resistant women with polycystic ovary syndrome.” Journal of gynecology obstetrics and human reproduction 46.7 (2017): 579-585.
  10. Bedaiwy MA, Rizk A, A Inany H, Falcone T. N-Acetylcysteine improves pregnancy rates in long standing unexplained infertility: a novel mechanism of ovulation induction. Fertil Steril. 2004;82(Suppl):S228.
  11. Cheraghi, Ebrahim, et al. “N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin.” Reproduction, Fertility and Development 28.6 (2016): 723-731.
  12. Arranz, Lorena, et al. “The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women.” Free radical biology & medicine 45.9 (2008): 1252-1262.
  13. De la Fuente, Macarena. “Effects of antioxidants on immune system ageing.” European Journal of Clinical Nutrition 56.S3 (2002): S5.