The long-running debate surrounding the dietary supplement status of N-acetyl-cysteine (NAC) may soon come to a close as the U.S. Food and Drug Administration (FDA) completes a critical safety review of the ingredient. In a move that has been closely watched by the supplement industry, the FDA has announced that its findings on NAC will now go through a peer review process, which could shape the future regulatory landscape for this popular antioxidant.

A Long History of Controversy

NAC has been a staple in the dietary supplement world, widely promoted for its antioxidant properties and its ability to replenish the body’s glutathione levels, which play a key role in detoxification and immune defense. However, a regulatory cloud has hung over the ingredient since the FDA issued warning letters in 2020 asserting that NAC was ineligible to be marketed as a dietary supplement. The reason? NAC had been approved as a drug back in 1963, putting it at odds with the Dietary Supplement Health and Education Act (DSHEA), which prohibits substances from being classified as supplements if they were first approved as drugs.

The FDA’s decision sparked uproar across the supplement industry, with several organizations—including the Council for Responsible Nutrition (CRN) and the Natural Products Association (NPA)—filing petitions and even lawsuits to challenge the FDA’s stance. Their argument hinged on the fact that NAC has been sold as a supplement for decades, with no major safety concerns. Supplement manufacturers and advocates pushed for the FDA to reconsider its position, and after years of legal wrangling, the agency agreed to exercise enforcement discretion. This allowed NAC products to remain on the market while the FDA conducted a full safety review.

FDA Findings and the Peer Review Process

Now, the FDA’s safety review is complete, and the results are promising for NAC proponents. The agency found no significant safety concerns when NAC is used under typical conditions in healthy adults. This finding aligns with the supplement’s longstanding safety record and could pave the way for NAC’s continued availability as a supplement, depending on the outcome of the next step: peer review.

Peer review is a critical part of the scientific process, where independent experts assess the validity of the FDA’s findings. The agency’s decision to submit its review to this rigorous evaluation shows that it is committed to transparency and scientific integrity. The review will focus on whether NAC can be safely marketed as a supplement despite its previous classification as a drug. If the peer review supports the FDA’s findings, it could lead to formal rulemaking that would allow NAC to be legally sold as a dietary supplement.

Implications for the Supplement Industry

The FDA’s handling of the NAC controversy has broader implications for the supplement industry. Over the past few years, the agency has taken a harder line on supplements that may conflict with pharmaceutical products, invoking the drug preclusion clause of the DSHEA. This has affected not just NAC but also other popular ingredients like cannabidiol (CBD) and nicotinamide mononucleotide (NMN), both of which have faced similar regulatory challenges.

Supplement industry leaders have argued that the FDA’s stance creates uncertainty for manufacturers and consumers alike. Products like NAC, which have been safely used for years, could be abruptly pulled from the market due to technicalities in the law. This, they argue, stifles innovation and limits consumer access to beneficial supplements.

The outcome of the NAC case could set a precedent for how the FDA handles future disputes over ingredients that straddle the line between supplements and pharmaceuticals. If NAC is allowed to remain on the market as a supplement, it could provide a roadmap for other ingredients facing similar challenges.

Industry Response and What’s Next

So far, the industry’s response to the FDA’s decision has been cautiously optimistic. The Natural Products Association (NPA), which had previously filed a lawsuit against the FDA, expressed relief that the agency is moving forward with a scientific review rather than outright banning NAC. The lawsuit was dropped after the FDA issued its guidance on enforcement discretion, but the NPA continues to advocate for a clearer regulatory framework that would allow manufacturers to bring safe, beneficial products to market without fear of sudden regulatory action.

“The FDA’s decision to complete a safety review and move into peer review is a step in the right direction,” said an NPA spokesperson. “But we need more clarity to avoid future regulatory disruptions.”

The peer review process could take several months, and industry experts are keeping a close eye on the outcome. If the peer review upholds the FDA’s findings, the next step could be formal rulemaking, which would finally provide regulatory certainty for NAC and potentially other ingredients facing similar scrutiny.

Until then, NAC remains on the market under the FDA’s enforcement discretion policy. Supplement manufacturers are hopeful that this process will ultimately confirm what they’ve long known—that NAC is a safe and beneficial ingredient that deserves its place in the supplement aisle.