Recently, the US Food and Drug Administration (FDA) said that beta-nicotinamide mononucleotide (Β-NMN) — a popular longevity supplement ingredient — is under investigation as a potential new drug. Therefore, companies can no longer market it as a dietary supplement. This decision has sparked concern among those who use NMN and the dietary supplement industry.
NMN is an ingredient used in supplements and food products that research suggests can raise levels of NAD, an important coenzyme for metabolism.
NAD levels decrease as a person ages, leading some scientists to believe that NMN can promote longevity.
Recently, the FDA concluded that because it is under investigation by pharmaceutical companies as a potential new drug, supplement companies can no longer market NMN.
This decision has raised concerns among industry leaders about federal dietary supplement policies.
Beta-nicotinamide mononucleotide (β-NMN), also referred to as NMN, is a forerunner to nicotinamide adenine dinucleotide (NAD+) — a compound that repairs and protects DNA and mitochondria in the body. As people age, NAD levels decrease, which is associated with reduced energy levels, DNA damage, cognitive impairments, and inflammatory conditions.
NMN is an ingredient in dietary supplements like Hello100 that research suggests may raise NAD levels in the body. Because of this, it has gained popularity as an over-the-counter anti-aging health product. As NMN dietary supplements are no longer sold in the US, NAD+ injections may become a good alternative.
The FDA had previously accepted NMN as a New Dietary Ingredient (NDI), which allowed supplement manufacturers to market it. But, on October 11, 2022, they revoked the NDI, so companies can no longer sell it in the United States.
This decision has created concern among proponents of natural supplements, practitioners, and the dietary supplement industry.
What happened to NMN?
On July 25, 2022, Inner Mongolia Kingdomway Pharmaceutical Limited voluntarily submitted an NDI for NMN because the company planned to market an NMN-containing dietary supplement.
However, on October 11, 2022, the FDA sent a letter to Kingdomway regarding the company’s NDI. The FDA document states that “NMN has been authorized for investigation as a new drug” and “may not be marketed as a dietary supplement or as a food.”
The FDA can do this because of the preclusion provision of Section 201(ff) of the Federal, Food, Drug, and Cosmetic Act. Officials created this provision to protect the commercial interests of pharmaceutical companies developing new drugs. It also prevents unscrupulous individuals or groups from bypassing the drug approval process by categorizing their ingredients as dietary supplements.
The provision states:
"The term 'dietary supplement' ... (3) does ... (B) not include - (i) an article that is approved as a new drug under section 355 of this title ... or (ii) an article authorized for investigation as a new drug ... for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, which was not before such approval ... or authorization marketed as a dietary supplement or as a food unless the Secretary, in the Secretary’s discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under this chapter."
However, the FDA does not disclose when a pharmaceutical company submits an Investigational New Drug (IND) application. So, it is unclear when NMN was authorized for investigation. This led Kingdomway to question the FDA’s decision.
In a supplemental letter explaining its decision, the FDA wrote, “the evidence on which Kingdomway relies to show that Β-NMN was marketed as a dietary supplement or food before it was authorized as a new drug is too recent, not relevant, or both.”
The FDA cites February 16, 2021, as the first date on which another manufacturer could have marketed its Β-NMN product lawfully after submitting an NDI notification to the agency on December 3, 2020. However, the FDA noted that it’s unclear whether Β-NMN was actually marketed on that date.
The second timeframe the FDA points out is September 2021 — the month that Kingdomway first marketed its NMN-containing whey protein concentrate.
“Both of these dates are after the first date on which Β-NMN was authorized for investigation as a new drug,” the FDA wrote.
Pharmaceutical companies interested in NMN
Metro International Biotech is one privately owned pharmaceutical company currently involved in studies examining MIB-626— a pharmaceutical grade Β-NMN formulation.
One study looking at Β-NMN’s effect on Alzheimer’s disease was first publicly posted on September 10, 2021. Another investigation MIB-626 treatment in adults with COVID-19 and kidney injury was posted on September 9, 2021. A third study, first posted on March 25, 2021, is testing the safety of MIB-626 in adults with Friedreich's Ataxia (FA).
In December 2021, Metro Biotech posted a comment to the FDA regarding NMN. The company wrote:
"As a company that has instituted publicly available clinical trials on β-Β-NMN, we request that FDA take the preclusion provision of Section 201(ff) of the Federal, Food, Drug, and Cosmetic Act seriously to protect the right of companies that have spent significant time and research to develop drugs products from competition from dietary supplements that are clearly new dietary ingredients that have never filed a new dietary ingredient notification prior to the institution of substantial clinical trials."
Industry reactions to the decision
Steve Mister, President & CEO of the Council for Responsible Nutrition (CRN), a leading trade association for the dietary supplement and functional food industry, told Healthnews:
“We are very disappointed with the FDA decision here. We think it is the wrong decision. We think it has a potential negative precedent for other ingredients in the space.”
“This issue is part of a much bigger concern for the industry around something called drug preclusion,” he said.
“There's a provision in the statute in the Food Drug and Cosmetic Act that says that if an article is either marketed as a pharmaceutical or substantively studied as a pharmaceutical prior to it being introduced as a dietary supplement, the pharmaceutical side of the industry gets a monopoly over the article,” Mister explained.
According to Mister, if the dietary supplement industry markets an ingredient first, then the ingredient is shared with the pharmaceutical industry.
“One of the best examples of that has been omega-3 fish oils,” he explained. “Because we marketed that as supplements going back decades, and now you can buy highly purified versions of omega-3s as prescription pharmaceuticals. But we did not lose it just because they decided to start marketing highly purified versions of it,” Mister said.
Mister suggests that the statute sets up a one-sided monopoly for pharmaceuticals. “I think the industry will be looking for a long-term solution that goes beyond NMN and looking to actually amend the statute because this is not working,” he said.
Mister told Healthnews:
“This same provision is what is keeping cannabidiol off the market. The FDA says that it was first marketed by pharmaceutical companies, so we can't bring CBD to market as a supplement. It's not a safety question for the agency — they're relying on drug preclusion language.”
Mister is concerned because the FDA does not disclose when a pharmaceutical company submits an IND application. So, it becomes a transparency issue.
“We are fighting against something that we can't even get transparency to see when […] the pharmaceutical monopoly begin[s]. We had to take [the] FDA on their word — we know there's this magic date that's behind the curtain,” Mister told Healthnews.
Moving forward, “we have not decided what our response is going to be,” Mister said. “Our board of directors will be meeting next week, and this will be one of the topics.”
A doctor weighs in
According to Jeff Gladd, MD, practicing integrative medicine physician and chief medical officer at Fullscript, sudden FDA decisions to exclude existing ingredients from being defined as dietary supplements are frustrating for practitioners, consumers, and retailers alike.
“While I support investments in clinical research to prove the claims for dietary supplements, protecting the pharmaceutical industry often leads to very high-priced options that are difficult for the average patient to consider,” he told Healthnews.
“I have concerns about the potential for other dietary supplement ingredients to become pharmaceutical industry targets of FDA’s efforts to exclude them from the marketplace, and I support the work being done by advocacy groups to petition [the] FDA,” he said.
Is NMN banned?
According to Mister, when the FDA decides an ingredient no longer meets its definition as a dietary supplement, they issue a letter to companies that market it.
“But […] unless the FDA decides to then go out and exercise some enforcement, it does not require that the companies pull the ingredients,” he explained.
For example, when the FDA decided that companies could no longer market [N-acetyl cysteine] NAC, “most retailers continued to sell it because the warning letter was only directed to one company, it was not enforced against the rest of the industry,” Mister said.
“I think that's what you will see happen again with NMN,” he added. “Many companies will continue to market it until they see whether [the] FDA is really so confident in its decision that it is ready to actually exercise enforcement against the products.”
Healthnews reached out to the FDA for clarification on its decision but did not receive a response.
Putting it in perspective
However, regardless of NMN’s fate, Dr. Gladd suggests that although many people take it for its potential role in healthy aging, it’s unclear whether it has significant benefits.
“While supplements may provide benefits, they should never be at the top of one's health and healthy aging plan,” he noted. “A heavy focus on whole foods eating, regular exercise, and high-quality sleep are essential and higher priorities.”