NMN benefits

How is a ‘benefit’ of NMN separated from a rise in NAD level?

NAD+ is a coenzyme that takes part in processes such as energy metabolism and DNA repair, and its level in tissues declines with age; according to the review authors, it is still unknown whether reversing this decline by raising NAD+ would benefit aging humans. ^[1] Three steps should therefore be kept separate: a rise in NAD level (biomarker), improvement of a measurable function, and that improvement being clinically meaningful.

Does NMN raise NAD+ levels?

Yes. In prediabetic postmenopausal women, NAD+ content in blood mononuclear cells rose in the NMN group after 10 weeks. ^[2] In the study of 42 healthy men aged 65 and over, whole blood NAD+ and its metabolites rose at 6 or 12 weeks with 250 mg/day. ^[3] In the 60-day study in 80 healthy middle-aged adults, the 300, 600 and 900 mg groups raised blood NAD level more than placebo; the highest levels were in the 600 and 900 mg groups. ^[4]

Limit: This is a laboratory indicator. The Yi study was funded entirely by two companies that manufacture NMN, and three of its authors are employees of these companies; the Igarashi study was funded by a company that supplies NMN and which provided the NMN; three authors are employees of this company. ^{[4] [3]} Evidence grade: B (for the biomarker).

Does NMN improve blood sugar and insulin sensitivity?

A single positive RCT. Twenty-five overweight or obese, prediabetic postmenopausal women (12 placebo, 13 NMN; 250 mg/day) were followed for 10 weeks. Insulin-stimulated glucose uptake measured with the clamp method and muscle insulin signaling (AKT and mTOR phosphorylation) rose in the NMN group and did not change in the placebo group. ^[2] This finding belongs only to this group.

No benefit shown in the meta-analysis. The meta-analysis pooling eight RCTs (342 middle-aged and older adults, mostly without diabetes; 250–2,000 mg/day, 14 days–12 weeks) found no significant benefit in fasting glucose, fasting insulin, HbA1c, HOMA-IR and lipid profile; the authors state that the result is limited because of the small number of RCTs and relatively healthy participants. ^[5] In the Yi study, HOMA-IR did not differ from placebo on day 60. ^[4]

Evidence grade: C for muscle insulin sensitivity in prediabetic women (single RCT); for blood sugar and lipids in mostly healthy adults, no benefit shown (E).

Does NMN improve walking and muscle strength?

Favorable findings. In the Yi study, distance in the six-minute walk test was significantly greater than placebo in the 300, 600 and 900 mg groups on days 30 and 60. ^[4] In the Igarashi study, ‘nominally significant’ improvement was reported in gait speed and the left-hand grip test with 250 mg/day; the authors stated that the findings need to be confirmed in larger trials, and no significant effect was seen on body composition. ^[3]

Conflicting meta-analyses. In a meta-analysis pooling 9 trials (412 people) in middle-aged and older adults, gait speed rose in favor of NMN (SMD 0.34; 95% CI 0.03–0.66; the lower limit of the confidence interval is very close to zero). ^[7] In another meta-analysis examining participants with mean ages of 60.9–83, NMN did not make a significant difference in skeletal muscle index, grip strength, gait speed (4 trials; mean difference −0.01; 95% CI −0.08 to 0.06) and the 5-repetition chair stand test. The authors concluded that the available evidence does not support NMN or NR supplementation for preserving muscle mass and function above age 60. ^[6]

Evidence grade: D — small trials, conflicting meta-analyses.

Does NMN lower liver enzymes?

In the meta-analysis by Wang and colleagues, ALT level was lower in the NMN group (SMD −0.29; 95% CI −0.55 to −0.03), but the effect is small and the confidence interval is close to zero. ^[7] This is a laboratory value; it is not a liver disease outcome.

Does NMN increase general well-being and energy?

In the Yi study, the change in SF-36 (general health perception questionnaire) scores was better than placebo in all three NMN groups on days 30 and 60 (except day 30 in the 300 mg group). ^[4] This is a subjective outcome reported by participants; the study is manufacturer-funded and has not been confirmed in an independent study.

Evidence grade: D.

Does NMN slow aging or extend lifespan?

There is no study in humans showing an effect on lifespan or aging. Findings from animal models cannot be transferred directly to humans; the introduction to the Yi study reports that in animal studies NMN increased NAD level and improved healthy lifespan and longevity, but leaves it uncertain whether this can be translated to humans. This sentence is background information, not a finding of that study. ^[4] In the same study, the value measured as a secondary outcome with the ‘blood biological age’ calculator rose in the placebo group and did not change in the NMN groups; this is not lifespan or a disease outcome but the output of a calculator. ^[4]

Evidence grade: E — no human data; no benefit shown.

Why do the studies give different results?

Participants range from prediabetic postmenopausal women to healthy older men and healthy middle-aged adults; doses are 250–900 mg/day and durations range from 6 weeks to 12 weeks. ^{[2] [3] [4]} The authors of the glucose and lipid meta-analysis state that the result is limited to a small number of RCTs and mostly relatively healthy participants; the authors of the muscle meta-analysis say that dose, baseline NAD+ deficiency and combined interventions need to be investigated in the future. ^{[5] [6]} That the two muscle meta-analyses gave different results shows that study selection and differences in outcome measures can affect the result; new and larger trials may clarify this question.

Summary table