FDA Reverses Course: NMN Allowed in Dietary Supplements (2025)

Table of Contents

1. What the FDA Did
2. What NMN Is, in the Letter’s Words
3. The Law Behind It: The “Race to Market” Clause
4. How NMN Came to Be Excluded in 2022
5. What the Petition Asked
6. What Changed: “Marketed” No Longer Means “Lawfully Marketed”
7. Which Date Counts, and What “Substantial” Means
8. Marketing Must Still Be in the United States
9. The Parts of the Petition the FDA Denied
10. What the Letter Does Not Do
11. Dates and Status as of 11 October 2026
12. How It Fits Earlier and Later FDA Actions
13. Primary Documents
14. Key Research Papers
15. Connections

1. What the FDA Did

The action is a citizen petition response. A citizen petition is a formal written request that anyone can file asking the FDA to take, change or reverse an action; the agency answers in a letter placed in a public docket (an online file of the petition, comments and the agency’s response, kept on regulations.gov). This response is document FDA-2023-P-0872-2754 in docket FDA-2023-P-0872. It was issued by the FDA’s Human Foods Program and digitally signed on 29 September 2025 by Donald Prater, DVM, Principal Deputy Director for Human Foods. (The letterhead date reads “September 29, 2029”, a misprint; the digital signature is dated 2025.09.29.)

The petition had been filed on 7 March 2023 by a dietary-supplement trade association and a natural-health advocacy group, and amended on 24 December 2024. The FDA states that it considered the petition, its attachments and the comments submitted to the docket, and that it was “granting your petition in part and denying it in part.” It granted the request to “amend” its determination that NMN is excluded from the definition of a dietary supplement, and to explain its thinking on several legal questions. It denied the parts that asked for details it says it is prohibited from disclosing, and the requests it treated as moot.

The central conclusion, in the letter’s words: “In light of FDA’s revised interpretation of the race-to-market clause in section 201(ff)(3)(B), we now conclude that NMN is not excluded from the definition of dietary supplement under section 201(ff)(3)(B).”

No Federal Register document was published for this action; the docket letter is the primary record.

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2. What NMN Is, in the Letter’s Words

The letter describes NMN as “an intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis produced from nicotinamide.” NAD+ is a molecule every cell uses in energy metabolism; nicotinamide is a form of vitamin B3. For that description the letter cites a 2016 study in mice published in Cell Metabolism (listed under Key Research Papers below).

The FDA places NMN in two legal categories:

• A dietary ingredient. The Federal Food, Drug, and Cosmetic Act (FD&C Act) lists the kinds of ingredients a dietary supplement may contain. The FDA says NMN is a dietary ingredient under section 201(ff)(1)(E) of the Act.
• A new dietary ingredient (NDI). An NDI is a dietary ingredient that was not marketed in the United States before 15 October 1994. The FDA says NMN was not, so NMN is an NDI.

Being an NDI matters because of the new dietary ingredient notification (NDIN): a company selling a supplement with an NDI generally has to send the FDA, at least 75 days before marketing, the information on which it has concluded the product “will reasonably be expected to be safe.” The letter explains that the notification is not required when every dietary ingredient in the product has been “present in the food supply as an article used for food in a form in which the food has not been chemically altered,” and that a supplement containing an NDI without a required notification is deemed adulterated (legally unfit for sale).

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3. The Law Behind It: The “Race to Market” Clause

The Dietary Supplement Health and Education Act of 1994 (DSHEA) wrote the legal definition of a dietary supplement into section 201(ff) of the FD&C Act. According to the letter, its drafters added section 201(ff)(3) as a compromise, answering concern in Congress that the original definition “was too broad and would enable manufacturers to escape appropriate safety and efficacy review and FDA oversight for drugs by classifying those products as dietary supplements.”

The resulting provision sets up what the FDA calls “a race to market between drugs and dietary supplements that contain the same ingredient.” In plain terms:

• If a substance is approved as a drug (or licensed as a biologic) after it was already sold as a supplement or food, it can stay a supplement.
• If it was approved as a drug before it was sold as a supplement or food, it is excluded from the supplement definition.
• The same exclusion reaches an article “authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public” — unless it was marketed as a supplement or food before that authorization. This is section 201(ff)(3)(B)(ii), the clause that applied to NMN.
• In either case the HHS Secretary may make an exception through a regulation issued after public notice and comment.

An “authorization for investigation” refers to an investigational new drug application (IND), the filing that lets a company or researcher test an unapproved drug in people. The letter explains that the FDA does not expressly approve an IND; it generally goes into effect 30 days after the FDA receives it unless the agency places the studies on clinical hold. The letter says one purpose of the clause is “to protect the incentives for new drug development.”

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4. How NMN Came to Be Excluded in 2022

The letter recounts the FDA’s earlier handling of NMN notifications:

• 2 November 2020. The FDA answered an NMN notification from an ingredient supplier by saying the product described was not a dietary supplement because it was not intended for ingestion in a supplement form, so the agency gave no safety response. A second notification from the same supplier, for a product meant to be swallowed, drew the response that it did “not provide an adequate basis to conclude” the supplement “will reasonably be expected to be safe.”
• 16 May 2022. The FDA acknowledged an NMN notification from another ingredient manufacturer, writing that acceptance for filing “is a procedural matter” and not a finding that the ingredient is safe.
• 28 July 2022. The FDA filed a further NMN notification from a third manufacturer.
• 11 October 2022. The FDA wrote to that manufacturer that NMN is excluded from the definition of a dietary supplement, having determined that “NMN was not marketed as a dietary supplement, except unlawfully without an NDI notification, or as a food before FDA authorized it for investigation as a new drug.” The letter says similar letters went “to all firms that had submitted NDINs for NMN.”
• 4 November 2022. A supplemental response elaborated the reasoning. It said the FDA could not disclose certain facts, including the date NMN was first authorized for investigation as a drug, because of legal limits on releasing information about investigational drugs. It also said that evidence of NMN being sold as a supplement in Japan did not exempt NMN from the U.S. notification requirement.

The 2025 letter also explains how the earlier acknowledgement was overtaken. A supplemental letter of November 2022 had said that “new information that came to light when we were reviewing another notification” led to a review of past NMN responses. The 2025 letter states that information about clinical investigations of a drug candidate known by an industry code name was already available in May 2022, but “it was not readily clear to the staff reviewing the NDIN” that the code name referred to NMN, and the information “was overlooked.” The FDA states that NMN and that code-named drug candidate “have the same chemical structure” and “are the same article.” The letter calls it well established that an agency, on learning of a mistake, may generally correct it.

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5. What the Petition Asked

As the letter summarizes it, the amended petition made three groups of requests:

1. Revoke or amend the determination that NMN is excluded from the supplement definition under section 201(ff)(3), and issue a determination that it is not excluded.
2. In doing so, explain a set of legal points: which date the FDA uses when an investigational drug’s authorization and its public disclosure happen at different times; what makes a clinical investigation “substantial” and whether that term “relates to efficacy”; how the FDA decides whether a supplement was “lawfully” marketed; why “marketing” was read to mean marketing in the United States only; the specific date and clinical investigations the FDA relied on for NMN; and the authority for withdrawing an issued acknowledgement of a notification.
3. If the FDA did not reverse itself, either exercise enforcement discretion for NMN supplements, or recommend that the HHS Secretary start rulemaking declaring NMN lawful in supplements.

The petition also argued that NMN should be “categorically treated as a dietary supplement” because it is a dietary ingredient and because it has “self-GRAS status.” GRAS stands for “generally recognized as safe”, a food-law category; a “self-GRAS” conclusion is one a company reaches on its own without notifying the FDA.

The letter also refers to a second, separate citizen petition on the same issue, filed on 9 May 2023 by another dietary-supplement trade association (docket FDA-2023-P-1867), which challenged the 2022 “lawful marketing” reading. The FDA says it reconsidered the issue “in response to that petition and the petition at issue in this response.”

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6. What Changed: “Marketed” No Longer Means “Lawfully Marketed”

The reversal turns on one phrase in the race-to-market clause: “marketed as a dietary supplement or as a food.” In 2022 the FDA had read it to count only lawful marketing, and so set aside NMN sales made without a new-dietary-ingredient notification. The 2025 letter abandons that reading:

“After careful consideration, we maintain that the best reading of that phrase is that the marketed product must be a dietary supplement or a food, but we agree it need not have been lawfully marketed.”

The reasons the letter gives:

• The phrase does not contain the word “lawful,” and the FDA concluded it is “not sufficiently clear from the context” that Congress meant the agency to judge the lawfulness of the earlier marketing.
• “Lawfully marketed” could mean several things — compliance with every legal requirement, or only with premarket requirements such as the notification — and the statute does not say which.
• Whether a drug was approved or an IND authorized is “a straightforward inquiry,” while whether a supplement sold decades ago needed a notification can be very hard to establish, and the FDA declined “to presume that Congress intended the agency to take on this difficult task for every ingredient.”

The FDA states that the 2022 interpretation “does not reflect the best reading of the statutory language,” and that it “will no longer evaluate whether the dietary supplement or food was lawfully marketed when making a determination under the race-to-market clause.” It still checks two things: that the earlier sales took place in the United States, and that the product sold was actually a dietary supplement or a food. A product labelled as a supplement but containing no dietary ingredient, for example, would not count.

Applied to NMN: “FDA is aware of evidence that NMN was marketed as a dietary supplement in the United States as early as 2017. This preceded the authorization of NMN for investigation as a new drug.” Because of that evidence, the letter says, it did not need to address the petitioners’ own examples of earlier NMN marketing.

The letter adds that an unlawful head start still has consequences: a supplement rushed to market without a required notification “would be an adulterated dietary supplement,” and the federal government “may take swift action to remove an adulterated dietary supplement from the market.”

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7. Which Date Counts, and What “Substantial” Means

On the legal questions it agreed to answer, the FDA largely kept its earlier positions:

• The date that counts is the authorization date. The petition argued the relevant date should be when clinical investigations were made public. The FDA disagreed: the comparison is with the date the investigational drug application went into effect — specifically “the authorization date of the first IND that is associated with a substantial clinical investigation that was instituted and made public.” The letter acknowledges the petition’s point that outsiders often cannot know when an IND took effect, and says it is “sympathetic to these concerns,” but that the text of the statute points the other way.
• “Substantial” means qualitatively important, not just large. The FDA reads “substantial clinical investigations” as trials “of qualitative importance in the context of new drug development,” with size one consideration among several. It says the term does not mean the “substantial evidence” of effectiveness required to approve a drug, which it calls “a very high bar.” It cites the DSHEA sponsors’ statement that single-patient and compassionate-use applications are not substantial clinical investigations, and says each case is judged individually.

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8. Marketing Must Still Be in the United States

The petition argued that, because the race-to-market clause does not say “in the United States,” marketing abroad should count. The FDA rejected that: “FDA continues to believe that the best reading of the statute is that the phrase ‘marketed as a dietary supplement or as a food’ in the race-to-market clause in section 201(ff)(3)(B) refers to marketing as a dietary supplement or as a food in the United States.”

The letter points to the statute’s U.S.-specific terms, its purpose of letting products already on the U.S. market stay there, and earlier versions of the bill in 1994. It also explains why foreign food use can still matter elsewhere: when the FDA reviews a notification for safety, evidence that an ingredient was eaten in another country can inform that safety review, because that provision “is about safety”, whereas the race-to-market clause is about which product category came first in the U.S. market.

The NMN outcome therefore rests on U.S. sales from as early as 2017, not on sales in other countries.

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9. The Parts of the Petition the FDA Denied

• Investigational-drug details. The FDA declined to give the date NMN was authorized for investigation or to list the clinical investigations it had relied on in 2022, citing regulations that limit disclosure of information about particular INDs. It added that the request was moot now that NMN is no longer excluded, and that the dates investigations became “substantial” or “made public” are irrelevant to the race-to-market comparison.
• How “lawful” marketing is judged. Denied as moot, because the FDA no longer asks that question.
• Enforcement discretion and rulemaking. The fallback requests — that the FDA hold off enforcement against NMN supplements, or that the Secretary issue a regulation declaring NMN lawful — were denied as moot, given the conclusion that NMN is not excluded.
• The “self-GRAS” argument. The FDA disagreed that NMN should be “categorically treated as a dietary supplement.” Being a dietary ingredient satisfies only one part of the definition, and “An ingredient’s ‘self-GRAS status’ is not, in itself, evidence that the ingredient has been present in the food supply as an article used for food in a form in which the food has not been chemically altered” — so self-GRAS status does not remove the notification requirement.

On the petition’s question about the FDA’s authority to revisit an acknowledged notification, the letter answers that its acknowledgement letters state they are not findings of safety, that the agency “is not precluded from taking action in the future,” and that an agency may correct a mistake.

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10. What the Letter Does Not Do

• It is not a safety finding. The letter says so directly: “A product’s safety profile does not determine whether it is ‘marketed as a dietary supplement or as a food’ within the meaning of the race-to-market clause.” The decision concerns which category came first, not whether NMN is safe or effective.
• It does not exempt NMN from new-dietary-ingredient notification. NMN remains an NDI, and the FDA rejected the argument that “self-GRAS status” makes the notification unnecessary.
• It does not give up the FDA’s enforcement tools. The letter states the FDA “may always seek to use the tools available under the FD&C Act (including seizures and recalls) to remove an unsafe or otherwise adulterated dietary supplement from the market.”
• It does not count sales outside the United States toward the race-to-market comparison.
• It does not change the statute. DSHEA’s wording is unchanged; what changed is the FDA’s interpretation of one phrase in it.

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11. Dates and Status as of 11 October 2026

• 7 March 2023 — citizen petition filed (docket FDA-2023-P-0872).
• 9 May 2023 — a second citizen petition on the 2022 interpretation filed by another trade association (docket FDA-2023-P-1867), as cited in the FDA’s letter.
• 24 December 2024 — amended petition filed.
• 29 September 2025 — FDA response letter signed: petition granted in part and denied in part; NMN not excluded from the dietary supplement definition.

Legal status: final. The letter is the FDA’s response to the petition and took effect as the agency’s stated interpretation when issued; it is not a proposal and opened no comment period. No Federal Register document was published for it. No later primary document reviewed for this page withdraws or changes it.

This page covers only the 29 September 2025 letter. Reports of later FDA responses to individual NMN notifications have not been confirmed in a primary document, so they are not described here.

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12. How It Fits Earlier and Later FDA Actions

Before. The letter itself frames the history: notifications answered in 2020 and 2022; the October and November 2022 letters excluding NMN; two citizen petitions in 2023; an amended petition in December 2024. It also quotes the FDA’s draft guidance on new dietary ingredient notifications (August 2016 and April 2024 versions), whose answer on drug-tested ingredients ties the question to “the date the IND went into effect”, and its March 2024 guidance on notification procedures, which says an acknowledgement is not an independent finding of safety. The letter notes that neither version of the draft guidance had said earlier marketing must be “lawful.”

Alongside. The FDA’s rejection of “self-GRAS status” as a route around notification sits next to its broader 2025 moves on self-affirmed GRAS in foods, covered on FDA Moves on Self-Affirmed GRAS and Chemical Reviews (2025), and the 2026 proposal to make GRAS notices mandatory. A different 2025 supplement-market action, on concentrated 7-OH kratom products, is described on FDA Moves Against Concentrated 7-OH Kratom Products (2025).

After. The question of what counts as a dietary ingredient at all — the section 201(ff)(1) list that the letter says NMN satisfies — was the subject of a 2026 FDA public meeting, reported on FDA Public Meeting on What Counts as a Dietary Ingredient (2026).

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13. Primary Documents

1. U.S. Food and Drug Administration, Human Foods Program (2025). Response letter to the citizen petition regarding the regulatory status of beta-nicotinamide mononucleotide (NMN), signed 29 September 2025 by the Principal Deputy Director for Human Foods. Docket No. FDA-2023-P-0872 — regulations.gov FDA-2023-P-0872-2754
2. Public docket FDA-2023-P-0872 (citizen petition dated 7 March 2023, amended 24 December 2024; comments; FDA response) — regulations.gov docket FDA-2023-P-0872
3. Citizen petition dated 9 May 2023 from a second dietary-supplement trade association, cited in the FDA response letter. Docket No. FDA-2023-P-1867 — regulations.gov FDA-2023-P-1867-0001
4. FDA letter and supplemental response of 11 October and 4 November 2022 concluding that NMN is excluded from the dietary supplement definition (NDI 1259), as cited in the 2025 letter — regulations.gov FDA-2022-S-0023-0051
5. FDA acknowledgement of 16 May 2022 and supplemental letter of 4 November 2022 (NDI 1247), as cited in the 2025 letter — regulations.gov FDA-2022-S-0023-0027
6. FDA guidance cited in the letter: Dietary Supplements: New Dietary Ingredient Notification Procedures and Timeframes (March 2024), and the draft guidance Dietary Supplements: New Dietary Ingredient Notifications and Related Issues (August 2016; revised draft April 2024) — fda.gov guidance documents library (fda.gov, Regulatory Information → Guidance Documents)

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Key Research Papers

1. Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism 24(6):795-806 — PubMed PMID: 28068222
2. Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H (2020). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal 67(2):153-160 — PubMed PMID: 31685720
3. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 372(6547):1224-1229 — PubMed PMID: 33888596
4. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M (2021). Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition 18(1):54 — PubMed PMID: 34238308
5. Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T (2022). Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging 8(1):5 — PubMed PMID: 35927255
6. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V (2023). The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 45(1):29-43 — PubMed PMID: 36482258

The first paper, a mouse study, is the one the FDA letter cites (footnote 6) for its description of NMN. The other five are human trials of oral NMN; they are listed for the research context and are not cited in the FDA letter, which makes no finding on NMN’s safety or effects.

PubMed Topic Searches

1. PubMed: nicotinamide mononucleotide randomized controlled trials
2. PubMed: nicotinamide mononucleotide safety in humans
3. PubMed: NAD+ precursors and aging

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Connections

• FDA Actions of 2025
• FDA and Regulation
• FDA Public Meeting on What Counts as a Dietary Ingredient (2026)
• NAD+ and NMN: Cellular Energy and the Science of Aging
• NAD+ Precursors Compared: Niacin vs Niacinamide vs NR vs NMN
• NAD+ and NMN: History and Discovery
• NAD Boosters for Longevity (NMN and NR)
• Vitamin B3 as an NAD+ Precursor
• FDA Moves on Self-Affirmed GRAS and Chemical Reviews (2025)
• FDA Proposal to Make GRAS Notices Mandatory (2026)
• FDA Moves Against Concentrated 7-OH Kratom Products (2025)
• Longevity & Healthy Aging

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