New page on NMN

    Does it help with aging?

    I’m Bill Willis, PhD. I’m a scientist at an academic medical center as well as a personal trainer and long-time researcher for Examine.

    Although my work in the lab involves studying how the body develops autoimmunity so that we can develop new treatments to stop it, I closely follow supplements in the anti-aging space because I get a lot of questions about it from my training clients and also out of personal interest. (Hey, who wants to age?)

    The good news is that there’s been some progress in the development and discovery of supplements in this space, such as nicotinamide mononucleotide (NMN). I’m reaching out because we’ve started a page on NMN that you might want to check out. We gave it the full Examine treatment: a careful analysis and weighing of the evidence to date, void of sensationalism or commercial influence.

    What are NMN and NAD+?

    Nicotinamide mononucleotide is a form of a B vitamin that increases levels of nicotinamide adenine dinucleotide (NAD+) in the body. NAD+ is an important compound that other enzymes require to function (i.e. a coenzyme), and does quite a bit of work on its own as an oxidizing agent in biochemical reactions. NAD+ is pretty much a powerhouse of biological activity, participating in a variety of processes, including DNA repair, immunity, redox signaling, and cell metabolism, to name a few.

    What we know about how it works: NMN is converted to NAD+ in the body after supplementation. The effects of NMN in research models are also driven by increased NAD+. Boosting levels of this co-enzyme increases the activity of sirtuins, a family of enzymes with possible anti-aging effects. Although positive effects have been observed in human trials (improved physical ability, reduced disease biomarkers in older people) the results have been subtle and have not matched the performance of NMN in rodent studies, where there’s clear evidence that it can slow aging-associated decline.

    NMN safety and efficacy in humans

    NMN achieved high marks for safety in early phase human trials, with no reported safety concerns. However, the doses of NMN tested to date have been on the low to moderate side in short-term trials, typically at 3-fold lower equivalent dosages compared to rodent trials. The long-term safety of taking NMN has not been tested, and some scientists highlighted theoretical interactions that warrant caution.

    As far as efficacy, NMN supplements clearly increase NAD+ levels in the body. There also has been evidence of positive outcomes in human trials, mostly in middle aged or older participants. The effects seem to be dose-dependent, though, and the dose required for health-promoting effects in different populations is still being worked out.

    Has NMN been shown to work in healthy adults? Or does it mostly shine in the context of a pathological condition?

    Nobody knows for sure, but there’s evidence for both. In theory, we might expect NMN to help healthy adults, since NAD+ becomes scarcer with aging due to increased consumption and reduced production.

    What’s up with the legal status of NMN in the U.S.?

    The short answer is that NMN legal status is murky. NMN seems to be in a state of legal limbo in the U.S., and there are many twists and turns to this emerging story.

    NMN had been granted GRAS (Generally Regarded As Safe) status by an FDA panel in 2018, which technically made it legal for use as a food additive. However, GRAS designation applies to food or food additives, not dietary supplements. In order for a supplement to be marketed and sold, manufacturers need to submit premarket notification of a “New Dietary Ingredient” (NDI) to the FDA, which, among other things, contains information for the basis of concluding that the supplement is reasonably safe.

    A company successfully (warning: PDF download) submitted an NDI for approval to the FDA in 2022, paving the way for sales as a dietary supplement. Later that year, the FDA changed their stance on NMN’s dietary supplement status. Companies testing NMN in clinical trials successfully lobbied the FDA to get NMN classified as an investigational drug, which, according to the formal definition of a dietary supplement defined by the FDA in 21 U.S.C. § 321(ff) (section 321(ff) of the Federal Food, Drug, and Cosmetic Act) prevents the sales or marketing of NMN as a dietary supplement.

    So the FDA then revoked the NDI, effectively banning the sale or marketing of NMN as a supplement in the U.S. Whether or not it may still be marketed as a food additive under the original GRAS designation is not clear, since the GRAS status was not affected by the withdrawal of NMN NDI approval. Technically, NMN could still be sold as a food ingredient in the U.S., but most online retailers have pulled their products with NMN in response to its unclear legal status.

    The evidence on NMN is still evolving, and thus our page on it will evolve as well. We’ll let you know what we find out as we flesh out more pages on aging related supplements, like nicotinamide riboside or NR, a compound related to NMN.

    In the meantime, and as always, be wary of fantastical claims!


    Bill Willis, PhD