An estimated 9% of men and 11% of women will experience infertility in the United States. For couples who experience infertility, around one-third of cases are due to male infertility, one-third are due to female infertility, and the remaining third is undeterminable¹. When faced with statistics like these, or experiencing personal struggles with fertility, many men and women seek out natural methods of support — including supplements like N-Acetylcysteine, or NAC. 

Here’s what to know about NAC if you’re considering using it to support your fertility and reproductive health.

What is NAC?

NAC stands for N-Acetylcysteine and is a powerful antioxidant supplement. More specifically, NAC is used by the body to produce antioxidants that can help protect its cells. It stimulates the biosynthesis of glutathione, which is among the most important antioxidants in the body².

In fact, glutathione depletion is reversible with NAC supplementation³. Glutathione helps make DNA and supports immune, enzymatic, and various organ functions.

While cysteine is a semi-essential sulfur-containing amino acid found in foods like eggs, nuts, yogurt, chicken, turkey, and garlic, NAC is its metabolite best found in supplemental form. 

It’s also sold as a prescription drug to counteract acetaminophen overdose. NAC is often used in the treatment of conditions of abnormal and excessive mucus secretions, like cystic fibrosis, bronchitis, and pneumonia⁴. Additionally, there is evidence that NAC can be helpful in the improvement of diseases of the cardiovascular and reproductive systems, as well as disorders of the liver and kidneys⁵.

What the Research Says About NAC and Fertility 

NAC has been a commonly used supplement for several decades, including for reproductive health and fertility among both men and women. 

A 2019 animal study published in PLoS One found that NAC was able to restore the fertility of vitrified-warmed mouse oocytes that were cryopreserved — a common method to preserve fertility and store genetic resources for later use⁶. But does this translate to human studies? 

A 2015 systematic review and meta-analysis of 8 randomized controlled trials involving 910 women with PCOS found that NAC supplementation significantly improved ovulation, pregnancy rates, and live birth rates, versus those who took a placebo⁷.

NAC appears to be especially helpful for men experiencing fertility problems. One of the most studied factors in reduced male fertility is the increase in environmental pollutants all around us⁸. Many of the infertility issues males experience increase when they don’t have enough antioxidants available in their bodies to fight free radicals that influence the reproductive system. When oxidative stress has no boundaries, this can lead to cellular damage and death as well as impaired fertility⁹.

Furthermore, a condition called varicocele — when scrotal veins become enlarged because of free radical damage — also plays a role in male infertility. But a 2016 study published in the International Journal of Fertility & Sterility found that 600 mg per day of NAC given to 35 men with this condition for three months was effective for semen quality as well as their partner’s pregnancy rate compared to the control group¹⁰.

 A 2019 randomized controlled trial among 50 infertile men with reduced sperm motility found that 600 mg/day of NAC supplementation for three months significantly improved their sperm count and motility¹¹.

This is thought to be because infertile men have higher levels of semen-reactive oxygen species than fertile men — which can result in damaged and dysfunctional sperm. Therefore, many of the improvements with NAC are likely due to its antioxidant activity in the body¹²,¹³.

Additionally, a 2009 randomized controlled study published in the Journal of Urology found that semen quality improved after 26 weeks of daily supplementation with 600 mg NAC and 200 mcg of selenium¹⁴. The authors concluded that they would recommend this as a standard combination to support male infertility treatment. 

Finally, there is some evidence that NAC may offer benefits for endometriosis, a painful uterine tissue disorder that can impact fertility. Some studies have found that NAC supplementation could help reduce pain associated with tissue inflammation because of its ability to act as an antioxidant¹⁵. More research is needed, but NAC may also be able to help reduce cyst size and high estrogen levels associated with this condition¹⁶,¹⁷.

NAC Dosing

While dosing varies between supplements and brands, common dosages of NAC fall between 600-1200 mg daily, which has been given in a single dose or split into multiple doses in studies with no major differences in tolerability ¹⁸. However, when given orally, NAC only has a 6-10% bioavailability, so it may be best to split it into a morning and evening dose ¹⁹. Amino acid supplements are sometimes directed to be taken without food to prevent competitive absorption with other amino acids. Still, if you experience digestive side effects of supplementing without food, it may make more sense for you to take NAC with a meal.

It’s always best to speak with your healthcare provider before adding NAC to your routine to ensure it is safe for you and that you take the appropriate dose relevant to reproductive health.

Possible NAC Side Effects

NAC is considered to be likely safe for most adults as an FDA-approved prescription drug²⁰. Keep in mind that supplements do not follow the same regulation as prescription drugs, which means it’s very important to choose high-quality options. Look for NAC supplements that have been independently tested and certified for quality, composition, and safety by third parties such as NSF International, USP, or ConsumerLab. 

With that being said, the side effects of consuming NAC are generally mild but can include the following:²¹

• Fatigue
• Nausea
• Dry mouth
• Diarrhea
• Vomiting
• Eye irritation
• Skin rash

More severe side effects are infrequent but have been reported, including asthma attacks, unexplainable headaches, and a drop in blood pressure²². 

Furthermore, NAC has been known to interact with certain medications. It should not be used with nitroglycerin and may interact with activated charcoal, chloroquine, antihypertensive drugs, and anticoagulant drugs²³. Because NAC can trigger a drop in blood pressure and slow blood clotting, it should not be used in conjunction with herbs that have similar effects. 

Speak with your healthcare provider before starting an NAC supplement and be sure to report any side effects should you experience them.  

Other Potential Benefits of NAC

In addition to supporting fertility and reproductive health, NAC may also offer other benefits. Some of these are outlined below.  

• May improve insulin sensitivity: A 2017 review suggests that NAC supplementation may help increase insulin sensitivity among women with polycystic ovary syndrome (PCOS), which can trigger insulin resistance and disruptions in glucose metabolism²⁴.
• May improve hormonal balance: NAC may help regulate menstrual cycles and reduce androgen levels. A 2011 study found that NAC was as effective as metformin in reducing hirsutism, free testosterone, and menstrual irregularities among women with PCOS²⁵. 
• May support normal inflammatory response: Along with its antioxidant characteristics, NAC may also be helpful in times of inflammation. A 2020 case study found that NAC effectively blocked the inflammatory effects of severe COVID-19 infection, significantly reducing C-reactive protein and likely preventing cytokine storm²⁶. More research is needed on this specific use, but this case study provides interesting insight into how NAC may be beneficial in the inflammatory response process for some people.

The Takeaway

Fertility is a complex issue of reproductive health and there’s generally not one single answer to help individuals and couples who are facing obstacles. A combination of exercise, diet, stress management, and medications when necessary is the best approach. There is also some promising evidence that supplemental products like N-Acetylcysteine may provide fertility benefits, particularly for males. 

Note that while not common, some prenatal multivitamins contain NAC, which will be listed on the ingredient label, FH PRO for women and FH PRO for men are two examples.  NAC is also available as a stand-alone supplement.  Before adding NAC or any supplement to your routine, it’s best to speak with your healthcare provider to make sure it’s safe and appropriate for you to do so. A trusted provider will also be able to offer other guidance and support as you navigate your fertility journey. 

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