Evidence Trace, complete trial record
In plain terms
In plain terms: NMN (Nicotinamide Mononucleotide) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
NMN (Nicotinamide Mononucleotide)
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Surrogate biomarker endpoint, Muscle insulin sensitivity in prediabetic postmenopausal women, which is the use the Grade C rests on. Blood NAD+ concentration is also Grade C and is a mechanistic marker, not an outcome. Longevity, healthspan and mortality are Grade D: no human trial has tested them.
The evidence as the record states it
Yoshino et al. (Science, 2021; PMID 33888596): RCT: NMN improved muscle insulin sensitivity in prediabetic women. Zhang et al. (Nutrients, 2026; PMID 41901064): meta-analysis of 10 randomized trials on blood pressure; diastolic pressure about 2 mmHg lower, systolic not significantly changed. Chen et al. (Curr Diab Rep, 2024; PMID 39531138), Zhang et al. (Crit Rev Food Sci Nutr, 2025; PMID 39116016) and Yang et al. (Nutrients, 2026; PMID 42514320): meta-analyses of 8, 12 and 15 NMN trials; blood NAD rises, glucose, insulin, HbA1c, HOMA-IR, lipids and weight do not change, with high or some-concern risk of bias throughout. Yi et al. (Geroscience, 2023; PMID 36482258): randomized, multicenter, double-blind, placebo-controlled dose-ranging trial of NMN in healthy middle-aged adults, run by employees of two NMN suppliers; its secondary six-minute walk, blood biological age and SF-36 findings come from that industry-run trial. Pencina et al. (J Clin Endocrinol Metab, 2023; PMID 36740954), Morifuji et al. (GeroScience, 2024; PMID 38789831) and Katayoshi et al. (Sci Rep, 2023; PMID 36797393): the three further randomized placebo-controlled trials in which blood NAD rose, each run or funded by an NMN maker. Grade C: blood NAD concentration C (replicated across four maker-run trials, but a marker of absorption rather than a validated biomarker), muscle insulin sensitivity C, longevity or mortality D. The headline cannot outrank every use beneath it.
PMID 33888596 PMID 41901064 PMID 36482258 PMID 36740954 PMID 38789831 PMID 36797393 PMID 42304075 PMID 39531138 PMID 39116016 PMID 42514320
Evidence by specific use
Muscle insulin sensitivity in prediabetic postmenopausal women
Grade C
Yoshino et al. (Science, 2021; PMID 33888596): 25 postmenopausal women with prediabetes, 13 on 250 mg/day for 10 weeks; clamp-measured muscle insulin sensitivity rose with NMN and not placebo, while body composition, blood pressure, glucose, insulin and lipids did not change. No independent trial in this population has repeated it. The other trial that measured insulin sensitivity directly, 2,000 mg/day for 28 days in 30 overweight or obese adults, found no change (Pencina et al., J Clin Endocrinol Metab, 2023; PMID 36740954), and three meta-analyses of NMN trials found no effect on fasting glucose, insulin, HbA1c or HOMA-IR (Chen et al., 2024; PMID 39531138; Zhang et al., 2025; PMID 39116016; Yang et al., 2026; PMID 42514320). One small unreplicated positive trial on a surrogate, with the wider glucose evidence null: C.
PMID 33888596 PMID 36740954 PMID 39531138 PMID 39116016 PMID 42514320
Blood NAD+ concentration in healthy middle-aged adults
Grade C
Raising blood NAD is the most consistently replicated NMN result. Yi et al. (GeroScience, 2023; PMID 36482258): 80 healthy adults aged 40 to 65, 300, 600 or 900 mg/day for 60 days; blood NAD rose dose-dependently, highest at 600 and 900 mg. Pencina et al. (J Clin Endocrinol Metab, 2023; PMID 36740954): 30 overweight or obese adults aged 45 and over, 1,000 mg twice daily for 28 days; blood NAD rose, LDL and diastolic pressure fell, insulin sensitivity and liver fat did not change. Morifuji et al. (GeroScience, 2024; PMID 38789831): 60 older adults, 250 mg/day for 12 weeks; blood NAD rose. Katayoshi et al. (Sci Rep, 2023; PMID 36797393): 36 healthy middle-aged adults, 125 mg twice daily for 12 weeks; serum nicotinamide rose, arterial stiffness did not change. Four trials agree that blood NAD rises. The letter is C because blood NAD is a marker that NMN was absorbed, not a validated biomarker of any outcome: the written B definition names validated biomarkers such as HbA1c, LDL and blood pressure, and no trial has shown that raising blood NAD changes health. Nicotinamide riboside is graded C on the same reasoning. Moved from B in October 2026 by applying the written grade definitions. Every one of these trials was run or funded by an NMN maker, which is stated beside the letter.
PMID 36482258 PMID 36740954 PMID 38789831 PMID 36797393
Longevity, healthspan or mortality
Grade D
No human randomized trial has tested NMN against lifespan, healthspan or mortality at any dose. The marketing claim and the evidence base do not meet. The nearest thing to a lifespan result is in mice: Kane et al. (bioRxiv preprint, 2024; PMID 38979132), in a version revised in 2026, gave NMN in drinking water from middle age and found median lifespan rose 8.5 percent in females only, with no lifespan gain in males. It is not peer reviewed, and the female control mice were short-lived, so the gain may reflect correcting poor baseline health rather than slowing aging. Animal data never supports a grade here.
PMID 38979132
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What this grade covers and what it does not
Grade C. Two uses carry the C: muscle insulin sensitivity in prediabetic postmenopausal women, on one trial (Yoshino et al., 2021; PMID 33888596), and blood NAD concentration, which four randomized trials raised (PMIDs 36482258, 36740954, 38789831 and 36797393), every one run or funded by an NMN maker. Blood NAD is C rather than B because it shows the supplement was absorbed, not that health changed: under the B definition a biomarker qualifies only when it is an established stand-in for a clinical outcome, and a blood level of the supplement or of what the body makes from it shows absorption and qualifies for nothing above C. Nicotinamide riboside is graded C on the same reasoning. Moved from B in October 2026 by applying the written grade definitions, closing the review opened October. WHAT THIS GRADE DOES NOT COVER: longevity, healthspan or mortality, graded D because no human trial has tested them; healthy adults outside the populations studied; and any dose or form beyond those in the cited trials.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
Fatigue levels, NAD+ blood test (optional, expensive), biological age markers at 6 months