The Food and Drug Administration (FDA) withdraws new dietary supplement (NDI) status of nicotinamide mononucleotide (NMN) under pharmaceutical industry pressure.
The FDA has issued a statement saying that NMN may not be sold as a supplement, citing its status as being under investigation as a drug. This development is a reversal of the FDA’s previous decision to allow its sale as a new dietary supplement (NDI). Although many vitamin and supplement companies that sell NMN remain concerned with this news, banning NMN’s sale is not currently being enforced.
NMN is a precursor to a vital molecule involved in thousands of reactions for cell energy, DNA repair, and cell stress alleviation called nicotinamide adenine dinucleotide (NAD+). NAD+ levels significantly decline with age, correlating with the onset of age-related diseases like cardiovascular, neurological, and metabolic issues. Taking NMN has been shown to increase blood NAD+ levels in humans and mitigate age-related diseases in animal models. Due to its success in alleviating age-related ailments in animals, namely rodents, pharmaceutical companies like Metro International Biotech have begun trials investigating NMN as a drug for humans.
Pharmaceutical companies’ investigation of NMN as a drug may have spurred the FDA to ban its sale under the label of a supplement. For example, Metro International Biotech sent a letter to the FDA in December 2021 requesting that the FDA revise its classification of NMN to “protect the right of companies that have spent significant time and research to develop drugs products from competition from dietary supplements.” This request likely comes from their development of the NMN-based product MIB-626.
Considering NMN’s popularity, this information has shocked many, especially since the ban isn’t due to NMN’s lack of safety or efficacy. To label a product like NMN as a supplement, a company must file a new dietary ingredient (NDI) notification with the FDA. The FDA’s explicit approval isn’t required for the supplement label, but if the FDA raises objections, this may preclude the compound’s designation as a supplement.
Although NMN has been sold in Asian countries like Japan since 2014, it’s still a newcomer to US markets. In the last two years, numerous companies have filed NDI notifications, which the FDA raised objections to based on a lack of evidence for NMN’s safety.
In 2021 and 2022, new studies examining NMN’s safety may have allayed the FDA’s concerns. As such, in May, 2022, the FDA acknowledged an NDI notification from the Chinese company SyncoZymes without objection. However, more recently, in response to another NDI notification from the company Inner Mongolia Kingdomway, the FDA changed its course on granting NMN an NDI, officially declaring that NMN cannot be marketed as a supplement since it’s already being investigated as a drug.
This FDA decision was based on a provision in the Dietary Supplement Health and Education Act of 1994 (DHSEA). The provision states that a dietary supplement cannot contain an ingredient that has been “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.” This provision applies unless the investigations began after the compound had been approved for use as a supplement.
The FDA can decide whether to enforce its rulings on supplements. However, in a similar instance, with the supplement N-acetyl-L-cysteine (NAC), the FDA excluded the compound from being defined as a dietary supplement on similar grounds in 2021. After a few months of citizen petitions and litigation, though, the FDA decided to exercise enforcement discretion with NAC. Effectively, the FDA has since left the NAC manufacturers alone for now.
As with NAC, there are currently no signs of the FDA taking NMN off the shelves, although it’s still unclear whether it will enforce its ruling. In the meantime, NMN manufacturers will likely continue pressing the FDA to apply enforcement discretion. Pharmaceutical companies like Metro International Biotech may apply pressure in the opposite direction, hoping for enforcement of the decision.