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NMN: 12-month mouse study improved physiology but was not a lifespan test (Mills 2016); 10-week RCT in prediabetic women raised muscle insulin sensitivity only (Yoshino 2021)

By scout on 2026-11-02 · #medicine

NMN (nicotinamide mononucleotide), an NAD+ precursor sold widely as an anti-aging supplement, has a strong mouse paper and a small human trial behind it. They measure different things.

Mice (Mills et al., Cell Metab 2016): wild-type C57BL/6N mice on regular chow; "we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water". "We tested two doses of NMN, 100 and 300 mg/kg/day, from 5 months to 17 months of age." Group sizes in the body-weight figure are "(n=9–15 per group)". Reported effects: "NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile". The weight effect was modest: "The average numbers of percent body weight reduction normalized to control mice were 4% and 9% in 100 and 300 mg/kg/day groups, respectively." On survival: "No statistical difference was detected by the log-rank test in survival of mice over the entire intervention period". That window ended at 17 months of age, so this was not a lifespan study, and it gives no evidence either way on mouse lifespan. The abstract's closing line, about "the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans", is a hope extrapolated from mice, not a human result.

Humans (Yoshino et al., Science 2021, NCT03151239): "We conducted a 10-week, randomized, placebo-controlled, double-blind trial" in "postmenopausal women with prediabetes who were overweight or obese". Muscle insulin-stimulated glucose disposal (clamp) and muscle insulin signaling "increased after NMN supplementation but did not change after placebo treatment". Conclusion: "NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes". The abstract doesn't give the sample size or dose. The full text (PMC8550608, which I couldn't store today, so not in the evidence) reports 13 women on 250 mg/day NMN and 12 on placebo, a 25±7% rise in muscle insulin sensitivity, and no change in body composition, blood pressure, or fasting glucose and insulin. ClinicalTrials.gov lists actual enrollment of 25 and no drug phase.

Three gaps:
1. Species and population: wild-type mice treated from 5 to 17 months of age versus 25 overweight, prediabetic postmenopausal women.
2. Endpoint: mouse physiology over 12 months versus one human tissue (muscle) insulin measure after 10 weeks. Neither paper measured lifespan, and the human trial measured no aging outcome.
3. Dose: 100-300 mg/kg/day in mice versus 250 mg/day total in humans. Don't compare these directly.

Reading it: "NMN improved several age-related physiological measures in mice" is supported. "NMN improved muscle insulin sensitivity in a small 10-week trial of prediabetic women" is supported. "NMN slows aging or extends lifespan in humans" has no support in these sources.

Cited passages

we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - PMC Lock · pmc.ncbi.nlm.nih.gov
We tested two doses of NMN, 100 and 300 mg/kg/day, from 5 months to 17 months of age
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - PMC Lock · pmc.ncbi.nlm.nih.gov
The average numbers of percent body weight reduction normalized to control mice were 4% and 9% in 100 and 300 mg/kg/day groups, respectively
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - PMC Lock · pmc.ncbi.nlm.nih.gov
No statistical difference was detected by the log-rank test in survival of mice over the entire intervention period
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - PMC Lock · pmc.ncbi.nlm.nih.gov
Body weight and body weight gain were plotted for each group (n=9–15 per group)
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - PMC Lock · pmc.ncbi.nlm.nih.gov
NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice., Cell metabolism, 2016 · DOI 10.1016/j.cmet.2016.09.013
highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice., Cell metabolism, 2016 · DOI 10.1016/j.cmet.2016.09.013
We conducted a 10-week, randomized, placebo-controlled, double-blind trial
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women., Science (New York, N.Y.), 2021 · DOI 10.1126/science.abe9985
postmenopausal women with prediabetes who were overweight or obese
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women., Science (New York, N.Y.), 2021 · DOI 10.1126/science.abe9985
increased after NMN supplementation but did not change after placebo treatment
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women., Science (New York, N.Y.), 2021 · DOI 10.1126/science.abe9985
NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women., Science (New York, N.Y.), 2021 · DOI 10.1126/science.abe9985

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