The short answer
Some ingredients cannot be sold as dietary supplements even if they are natural and safe in food. Under the drug exclusion (or “race to market”) provision of the FD&C Act — section 201(ff)(3)(B) — an article is excluded from the definition of a dietary supplement if it was first:
- approved as a new drug, or
- authorized for investigation as a new drug, with substantial clinical investigations instituted and made public,
— unless it was marketed as a dietary supplement or food in the U.S. before that approval or authorization.
Recent examples
| Ingredient | FDA position |
|---|---|
| NMN (nicotinamide mononucleotide) | FDA said in 2022 that NMN was excluded. On September 29, 2025 it reversed course, finding enough evidence NMN was marketed as a supplement before it was authorized for drug investigation. It is still a New Dietary Ingredient, so NDI notification rules apply. |
| NAC (N-acetyl-L-cysteine) | FDA considers NAC excluded because it was approved as a drug first, but its August 2022 final guidance says it will exercise enforcement discretion for otherwise-lawful NAC supplements while it considers rulemaking. |
| CBD (cannabidiol) | FDA has concluded CBD is excluded from the supplement definition and cannot be added to food. See CBD and hemp rules. |
How to check an ingredient before launch
- 1Search approved drugsIs the ingredient (or a close form) an active ingredient in an FDA-approved drug?
- 2Search clinical trialsHas it been the subject of substantial, public clinical investigations as a drug — and when did they start?
- 3Find the first U.S. supplement or food saleDocumented marketing before the drug date protects the ingredient.
- 4Check NDI status separatelyPassing the drug exclusion test does not remove the need for an NDI notification if the ingredient is new.
- 5Watch FDA responsesFDA states its positions in citizen petition responses, NDI objection letters, warning letters and guidance.
Example: a longevity supplement brand in Singapore
A Singapore brand plans an NMN and resveratrol capsule for the U.S. It confirms FDA’s September 2025 letters say NMN is not excluded, then checks whether its NMN supplier has an NDI notification that FDA acknowledged without objection — or plans its own. It avoids adding CBD, which FDA treats as excluded, and makes only structure/function claims with the FDA disclaimer.
Standard label review (Supplement Facts and structure/function claims) $550. Advanced review with health claims $750. FDA facility registration with U.S. Agent from $300.
Frequently asked questions
What is the drug exclusion rule for supplements?
An ingredient first approved as a drug, or first authorized for substantial public clinical investigation as a drug, cannot be a dietary supplement unless it was marketed as a supplement or food before that.
Is NMN legal in US supplements?
FDA concluded in September 2025 that NMN is not excluded. It is a new dietary ingredient, so NDI notification requirements still apply.
Can NAC be sold as a supplement?
FDA considers it excluded, but under its August 2022 guidance it exercises enforcement discretion for otherwise-lawful NAC supplements.
Can CBD be sold as a dietary supplement?
No. FDA has concluded CBD is excluded from the dietary supplement definition.
Sources
- Venable — FDA declares NMN is a dietary supplement (October 2, 2025)
- Regulations.gov — Comment quoting section 201(ff)(3)(B) and FDA’s 2022 NMN letters (docket FDA-2023-P-0872)
- FDA — Final guidance on enforcement discretion for certain NAC products (August 2022)
Status checked on November 12, 2026. This article is general information, not legal advice.