Should I take NMN?

Our read is that NMN has been shown to accelerate cancer growth in mice with pancreatic cancer where pro-inflammatory senescence cells drive tumor growth, according to Rhonda Patrick. Peter Attia and Paul Saladino suggest that NMN and NR supplementation can lead to biochemical imbalance by increasing NAM, consuming methyl groups, and destabilizing bodily functions long-term. Andrew Huberman notes that NAD+ precursors like NMN or NR are not a priority for increasing lifespan on a limited supplement budget. Peter Attia also highlights that NMN supplementation in aged mice has been shown to cause kidney inflammation and potential pathology. Paul Saladino argues that remaining metabolically healthy is sufficient to maintain healthy NAD levels, making NMN and NR unnecessary and potentially harmful. Peter Attia and Rhonda Patrick suggest that oral NMN is unlikely to be absorbed intact due to its charged phosphate group and hydrolysis in the small intestine. Peter Attia is not convinced about the efficacy of NAD precursors due to unclear biology and inconsistent personal results, and he, along with Nir Barzilai, has concerns about their biological mechanism in humans. Peter Attia also states there is insufficient data and a lack of well-controlled clinical studies to definitively support the efficacy of NAD+ precursors. Paul Saladino warns that NAD or NMN supplementation may cause issues like anxiety due to potential depletion of methyl groups, and Peter Attia suggests that taking 10 grams of NMN could deplete all one-carbon stores. Paul Saladino also believes that achieving a low carbohydrate state is a more effective approach to increasing NAD+ than NMN supplementation. David Sinclair notes that consumers and scientists should be aware of potential endotoxin contamination in NMN batches. David Sinclair also mentions that NMN enhances the neurotoxicity of vincristine, and that NMN, NAD+, and rapamycin are considered controversial molecules in longevity research. Andrew Huberman notes that taking NMN sublingually may have a laxative effect, the physiological benefit of which is unclear. Peter Attia and Andrew Huberman point out that it is unclear if oral NAD precursors can achieve effective doses in humans due to breakdown to niacin in the gut. Andrew Huberman also states that Rhonda Patrick does not believe that NAD+ precursors will directly increase lifespan, despite potential benefits. Peter Attia notes challenges in replicating NMN and NR efficacy in mouse models and that the stability and biological activity of NMN and NR supplements may be compromised during shipping and storage. Andrew Huberman suggests that taking NAD directly or its precursors may not be a straightforward way to increase NAD levels and slow aging. David Sinclair indicates that the effects of NAD-boosters like NMN in humans are yet to be definitively determined, with human trials pending.

Our read is that definitive human trials demonstrating clear, consistent, and measurable benefits of NMN, along with a better understanding of its absorption, metabolism, and long-term safety, would change the verdict. Addressing concerns about potential side effects, such as kidney inflammation and methyl group depletion, and clarifying its role in cancer progression would also be crucial.