The FDA recently reversed its stance on beta-nicotinamide mononucleotide (NMN) in dietary supplements, now permitting NMN to be marketed in the U.S. as it was before drug investigation authorization, regardless of compliance with the Federal Food, Drug, and Cosmetic Act (FDCA).

This decision is based on a textual interpretation of FDCA § 201(ff)(3)(B), with the FDA determining that, because Congress did not specify “lawfully marketed,” it does not require that standard.

However, this interpretation remains uncertain. It is unclear whether the FDA’s narrow textual approach would hold up under judicial review, particularly since courts might interpret “marketed” as “lawfully marketed” to avoid unreasonable results and to align with the broader statutory framework. The FDCA generally presumes that products in commerce comply with the law, and permitting unlawful marketing could weaken the safety standards Congress intended.

This decision increases regulatory uncertainty. The FDA did not define “substantial investigation” under § 201(ff)(3)(B)(ii) or specify the dates and criteria for drug preclusion. The agency also offered little guidance on compliance for ingredients in drug studies, which may encourage companies to claim that any prior marketing, even if unlawful, is sufficient.

Critically, the FDA had an opportunity to provide genuine clarity and encourage compliance by fully exercising its statutory authority. The relevant statutes offered a clear solution, requiring only a commitment to harmonize provisions for drug-origin ingredients and recognize that many ingredients serve both drug and food/dietary supplement purposes.

An Opportunity for Regulatory Leadership

The NMN decision shows how regulatory confusion can come from narrow legal interpretations instead of a full legal analysis. Creating a single, clear rulemaking system would have given legal certainty, boosted compliance, and lessened incentives for illegal marketing.

The FDA now has a similar chance with NAC and vinpocetine, two widely used ingredients with long histories of safe use but ongoing regulatory uncertainty. Specifically, the FDA should use its authority under FDCA §§ 201(ff)(3)(B) and 301(ll) to initiate concurrent, harmonized rulemakings for NAC and vinpocetine. This process should rely on completed safety reviews, scientific evidence, and stakeholder input to establish a transparent record supporting lawful status for these ingredients.

A harmonized approach, rather than ad hoc policy or narrow interpretations, will provide a durable solution consistent with congressional intent and judicial standards. Applying this framework in future cases, including NMN, will reinforce the FDA’s commitment to regulatory clarity, public health, and legal defensibility. The tools and stakeholder support are in place; decisive agency action is needed.

Indeed, NAC and vinpocetine provide the FDA an opportunity to show regulatory leadership and clear up uncertainty about drug-derived ingredients in dietary supplements. I will concentrate on NAC, though the same principles apply to vinpocetine and NMN.

NAC was approved as a drug before being widely marketed in supplements, leading to exclusion under FDCA § 301(ll) and DSHEA § 201(ff)(3)(B)(i). Importantly, the FDA’s current enforcement discretion for NAC products does not provide lasting regulatory certainty. Simply put, under the law, NAC cannot be used in dietary supplements because it was approved as a drug before being marketed as a supplement. Despite repeated industry requests for clarification and a completed safety review showing no concerns after 30 years of use, the FDA has not issued a final decision.

The Dual ‘Escape Hatch’: Leveraging FDA’s Discretionary Authority

Congress provided the FDA with two mechanisms to address this situation. Both §§ 201(ff)(3)(B) and 301(ll) authorize the FDA to permit the use of otherwise-excluded ingredients through public notice-and-comment rulemaking, offering complementary tools to resolve the regulatory status of NAC and similar ingredients.

Section 301(ll): The FDA may issue a regulation, after public notice and comment, that authorizes NAC for use in food (a category that includes dietary supplements for purposes of § 301(ll)). This provision allows the FDA to determine that a drug or biological product may be added to food despite prior drug or biologic approval or substantial clinical investigations.

Section 201(ff)(3)(B): The FDA may also issue a supplement-specific regulation, again after public notice and comment, to allow NAC legally in dietary supplements if it was not grandfathered by prior marketing. Critically, § 201(ff)(3)(B) requires the FDA to make an affirmative finding that the ingredient “would be lawful under this chapter” when used in or as a dietary supplement. This is a substantive requirement, not just a procedural formality.

A Harmonized Regulatory Pathway for NAC and Vinpocetine

The optimal pathway forward — one that would provide legal certainty, honor congressional intent, and establish a durable precedent for future drug-origin ingredients — would involve the following coordinated steps:

Step 1: Propose a regulation under Section 301(ll) — The FDA should publish a proposed rule in the Federal Register to authorize NAC and vinpocetine as legal food ingredients, with conditions specific to dietary supplement use. This rule should be based on completed safety assessments, current scientific evidence, market history, and stakeholder input indicating that NAC does not present significant risks when used as labeled.

Step 2: Concurrent Section 201(ff)(3)(B) Rulemaking — The FDA should start rulemaking under § 201(ff)(3)(B) at the same time to officially establish that NAC and vinpocetine are lawful for use in dietary supplements. This step meets legal requirements and clarifies their regulatory status.

Step 3: Robust Public Input and Science-Based Review — The FDA should invite diverse stakeholder participation, including safety data, market history, consumer use patterns, and economic impact details. This process will create a solid administrative record and ensure all viewpoints shape the final decision. The FDA should also release detailed findings explaining the scientific and regulatory basis for its authorizations.

Step 4: Legal Harmony Through Coordinated Final Rules — A final regulation under § 301(ll) establishes the lawfulness required for § 201(ff)(3)(B). Once the FDA determines NAC can be lawfully added to food, this supports the necessary finding for dietary supplements. The two rulemakings together confirm both general and supplement-specific authorization.

This coordinated approach guarantees procedural validity and compliance with statutory requirements. It prevents the authorization of supplement use under § 201(ff)(3)(B) before verifying its legality within the broader FDCA framework.

Why This Harmonized Approach Matters for NAC and Vinpocetine

Regulatory certainty and market stability: A harmonized rulemaking approach eliminates enforcement ambiguity for NAC and vinpocetine. Instead of depending on temporary agency discretion, industry would gain from final regulations that establish lawful status, safeguard investments, reduce litigation risks, and prevent sudden enforcement actions.

Full Statutory Compliance: Meeting both §§ 201(ff)(3)(B) and 301(ll) ensures the FDA meets all legal requirements. This approach lowers legal risks and upholds Congress’s goal to balance drug development with consumer access to safe ingredients.

Public Trust and Transparency: Transparent, science-based rulemaking builds confidence among consumers, industry, public health advocates, and Congress. By inviting public participation, reviewing scientific evidence, and clearly explaining its rationale, the FDA shows accountability and good governance. This method contrasts with the confusion caused by inconsistent enforcement or unclear guidance.

Regulatory Certainty for Future Ingredients: A harmonized regulatory pathway creates a clear framework for addressing other drug-origin ingredients. Instead of relying on ad hoc enforcement or lengthy petition responses, the FDA would have a proven process to balance drug development with supplement availability.

Legal and Policy Implications

This harmonized rulemaking process provides a solid legal foundation for the availability of not only NAC and vinpocetine but also a stronger regulatory basis for including NMN and CBD in dietary supplements. By addressing statutory exclusions together and making necessary findings through public notice and comment, the FDA establishes regulations that can withstand judicial review under the Administrative Procedure Act and recent Supreme Court standards.

This approach establishes regulatory certainty by defining a clear legal status instead of depending on agency discretion. It enhances transparency through stakeholder input and published rationales, thereby building public trust. By authorizing NAC and vinpocetine via coordinated rulemakings, the FDA can address longstanding regulatory uncertainty, provide legal clarity for industry, ensure consumer access, and meet its statutory responsibilities. Most importantly, it shows regulatory leadership by harmonizing complex statutory provisions instead of taking shortcuts that lead to confusion.

In summary, the legal mechanisms are in place, and current safety data support regulatory action. Stakeholders seek clear guidance. The FDA should move beyond its rigid textualist argument outlined in its response to the Natural Products Association petition and utilize its full rulemaking authority to provide the clarity Congress intended and consumers expect. This would set a strong precedent for future decisions and bring certainty to a complex situation, while acknowledging that some ingredients benefit both disease treatment and overall health.

About the Author: Todd Harrison is Partner with Venable, which is located in Washington, D.C. He advises food and drug companies on a variety of FDA and FTC matters, with an emphasis on dietary supplement, functional food, biotech, legislative, adulteration, labeling and advertising issues. He can be reached at taharrison@venable.com.