SPOTLIGHT ON NAC (N-ACETYL CYSTEINE): THE ONE THAT ALMOST GOT AWAY

NAC (N-Acetyl Cysteine) is a well-researched amino acid supplement with a wide range of clinical applications.

It remains a staple in my clinical toolkit and is something I frequently recommend to clients and use personally.

NAC is the acetylated form of L-cysteine. This form is more stable and better suited for use in supplements than L-cysteine itself. NAC serves as a precursor to cysteine, which, along with glutamic acid and glycine, is required to synthesize glutathione. Each glutathione molecule contains one of each of these amino acids. The synthesis of glutathione takes place in the cell and depends on the enzyme glutathione synthetase, with magnesium acting as a necessary cofactor.

Why not take glutathione directly?

There are a few considerations when comparing NAC to glutathione supplementation:

• NAC is typically more affordable

• NAC is better absorbed in the gastrointestinal tract and can enter cells 

Glutathione, being a tripeptide, is broken down during digestion into its component amino acids unless delivered through specialized formats such as intravenous (IV), sublingual, or liposomal preparations. These delivery systems tend to be more expensive and still may not effectively increase intracellular glutathione levels.  

Even with improved delivery methods, intact glutathione is unlikely to enter cells efficiently. By contrast, NAC provides cysteine, the rate-limiting substrate for endogenous glutathione production inside cells.

Moreover, there is a larger body of primary research on NAC than on supplemental glutathione — approximately three times more, according to literature databases.

Clinical relevance of glutathione production

Glutathione is a major intracellular antioxidant and plays a central role in Phase II detoxification processes. It helps neutralize free radicals and supports the elimination of various toxins, including heavy metals, mycotoxins, and persistent organic pollutants. It also contributes to DNA stability, mitochondrial function, metabolic regulation, and protein synthesis.

Evidence-base for NAC

• A meta-analysis of liver transplant donors and recipients reported that NAC may help reduce liver enzyme levels

• A clinical trial in Italy found that while NAC did not lower influenza incidence, it appeared to reduce symptom severity

• Positive data exist on NAC's role in male fertility (sperm quality) and hormone regulation in PCOS (e.g., effects on testosterone and FSH)

• In patients with COPD, doses up to 1800 mg/day have been linked to fewer symptom exacerbations

Dosage and clinical application

Common dosages range from 600 mg to 2400 mg daily. Most commercial capsules contain 500–600 mg. In clinical practice, I generally begin adults at 500–600 mg twice daily.

Other clinical applications

In my practice, NAC is used in several contexts:

• To support Phase II detoxification when glutathione demand may be elevated, such as during exposure to wildfire smoke, mold, or environmental toxins

• As part of general detoxification protocols, including for fatty liver and hormone-related concerns

• As a mucolytic agent in respiratory conditions (e.g., bronchitis, bronchiectasis, and excessive mucus production)

• As a biofilm disruptor in antimicrobial protocols, including in collaboration with Lyme-literate physicians

Regulatory context: Why NAC was “almost” removed from supplements

During the COVID-19 pandemic, NAC was incorporated into several hospital protocols, largely due to its role in respiratory support and mucus clearance.

In August 2020, the FDA issued a warning letter asserting that NAC did not meet the definition of a dietary supplement, based on its previous approval as a drug for acetaminophen overdose and as a mucolytic. This raised concerns about the future availability of NAC in the supplement market.

In response, two industry groups — the Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA) — filed citizen petitions. In August 2022, the FDA issued a new policy indicating that while NAC remains excluded under current definitions, the agency would not take enforcement action against products making only structure/function claims.

This decision has allowed NAC to remain on the market, though its regulatory status continues to be closely watched.

References

1. Ghanizadeh A, Moghimi-Sarani E. A randomized double-blind placebo-controlled clinical trial of N-acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry. 2013;13:196.

2. Jia D, et al. N-acetylcysteine in the donor, recipient, or both in liver transplantation: A systematic review and meta-analysis. Transplantation. 2023;107(9):1976–1990.

3. Jiang C, et al. Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Ann Palliat Med. 2021;10(6):6564–6576.

Gain confidence in your clinical nutrition skills in our monthly Clinical Working Group! Led by an experienced CNS supervisor and clinical nutritionist: share a case from your functional medicine clinic, gain health and nutrition resources and insights, collaborate with your supervisors and other nutrition graduates, and learn how to incorporate functional nutrition coaching skills with your clients to help them meet their long-term health goals.

Have questions?  We’ve got you! Check out our Frequently Asked Questions  about our personalized nutrition Mentorship Program and meeting the SPE requirements.