NAC for Fertility: What N-Acetylcysteine Can and Can’t Do

NAC is sold as a supplement for PCOS and for sperm health, and some small trials look encouraging. But the evidence is thin, and for PCOS it has not matched standard treatment. Here is the evidence, graded.

What is NAC?

N-acetylcysteine (NAC) is a modified form of the amino acid cysteine that acts as an antioxidant; studies in men measure its effect on markers of oxidative stress.³

It has an unusual legal status. The FDA considers NAC excluded from the legal definition of a dietary supplement. In August 2022, the FDA issued final guidance saying it intends to exercise enforcement discretion for NAC products labeled as dietary supplements that are otherwise lawful.⁵ Like other supplements, those products are not FDA-approved; by law the FDA does not approve supplements before they are marketed.⁸

NAC for fertility: the evidence at a glance

Does NAC help with PCOS fertility?

It beat placebo in small trials, but not metformin. A 2015 meta-analysis pooled eight randomized trials with 910 women with PCOS.¹ Compared with placebo, women taking NAC had higher odds of live birth, pregnancy and ovulation. Compared with metformin, they were less likely to ovulate or get pregnant.¹ There was no difference from placebo in miscarriage, menstrual regulation, acne, hirsutism, BMI, testosterone or insulin.¹ Two trials had high risks of selection, performance and attrition bias, and four had high risk of reporting bias, so the authors called for better trials with live birth as the outcome.¹

Cochrane’s review of antioxidants for subfertile women, which includes NAC trials, pooled 63 trials with 7,760 women. It found very low-quality evidence for higher live birth rates with antioxidants as a group (OR 1.81) and concluded there is limited support for oral antioxidants in subfertile women.² It could not single out NAC as better or worse than the others.

For context, the 2023 international PCOS guideline names letrozole as the first-line medicine for ovulation induction in anovulatory women with PCOS who have no other infertility factors.⁶ NAC is not part of that recommendation. If you have PCOS and irregular or absent ovulation, our guide to PCOS and getting pregnant covers the treatments with stronger evidence, and myo-inositol covers the other popular supplement option.

Does NAC help sperm?

The data are limited. In a 2019 Iranian study, 50 infertile men with low motility and abnormal morphology took 600 mg of NAC a day for three months.³ Afterward, sperm count and motility were higher, abnormal morphology, DNA fragmentation and protamine deficiency were lower, and markers of oxidative stress improved.³ But the comparison was with each man’s own results before treatment, with no placebo group, so the improvement cannot be separated from natural variation.

Another frequently cited trial of selenium and NAC in infertile men, published in 2009, is now subject to an expression of concern issued by the Journal of Urology in January 2023.⁷ We do not rely on it.

The 2022 Cochrane review of antioxidants for male subfertility found very low-certainty evidence that antioxidants may increase live births; the effect disappeared when trials at high risk of bias were removed.⁴ Sperm take about three months to develop, which is why trials run that long; see our 90-day sperm health plan.

Is NAC safe?

Doses of around 600 mg a day were used in the sperm study above.³ In the PCOS meta-analysis, adverse events did not differ from placebo.¹ In the Cochrane review of antioxidants for men, antioxidants as a group were linked to more mild stomach upset.⁴ Check with your doctor or pharmacist about interactions with any medicines you take, and ask before continuing it in pregnancy.

Questions to ask your doctor about NAC

• Am I ovulating, and if not, is a prescription such as letrozole a better first step?
• Could NAC interact with any medicine or supplement I already take?
• Should my partner have a semen analysis before taking anything? Our guide to semen analysis results explains the numbers.
• Should I stop taking it after a positive pregnancy test?

Should you take NAC?

For most people trying to conceive, NAC is optional at best. If you have PCOS, discuss proven options first. If your partner has abnormal semen results, NAC is one of several antioxidants with weak evidence. Antioxidants such as CoQ10 have a similar evidence profile. For everything else to do before trying, visit the Prepare hub.