Protocol
NMN 250–500 mg/day (morning)
Yoshino 2021 (Science, PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 33888596): insulin-stimulated glucose disposal increased with NMN and did not change on placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received., in postmenopausal women with prediabetes.
Grade C: human trials exist, but they are small, mixed or not yet repeated. This is not a finding that it does not work. How to read a grade →
Compare this record with another, side by side →
How this letter has changedLatest: September 2026 · Downgraded.
The NMN supplement record moved to Grade C. The dosing protocol built on the same two trials stayed at B, and its own description said so out loud: one strong randomized trial, replication The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away. still needed. Yoshino 2021 (PMID 33888596) carries the insulin-sensitivity result and Yi 2023 (PMID 36482258) measured blood NAD in a different population, so neither repeats the other. Both records now read C.PMID 33888596 PMID 36482258
Every change to a letter on this site is dated and published. The full evidence log →
This protocol is NMN at 250 to 500 mg a day. In one study of older women with prediabetes, NMN helped muscles take up sugar in response to insulin. In another study, NAD levels in the blood rose with the dose. These are lab measurements, not proof of better health. No outside group has repeated the insulin result.
Yoshino 2021 (Science, PMID 33888596): insulin-stimulated glucose disposal increased with NMN and did not change on placebo, in postmenopausal women with prediabetes. Blood NAD rose dose-dependently in a separate randomized trial (PMID 36482258). Muscle NAD was not measured in either. Grade C: one randomized trial carries the insulin-sensitivity result and no independent group has repeated it, which Rule 03 places at C however strong the trial. TIMING CAUTION: this protocol is named for morning dosing, and no cited trial tested time of day. Neither Yoshino 2021 nor Yi 2023 compared morning against evening administration.
Why this gradeGrade C, small or unreplicated trials. The reasoning, and what the grade does not cover.
Grade C on surrogate metabolic endpoints The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.. Insulin-stimulated glucose disposal increased with NMN in postmenopausal women with prediabetes (Yoshino et al., 2021; PMID 33888596), and blood NAD rose with dose in a separate trial in healthy middle-aged adults (Yi et al., 2023; PMID 36482258). One trial carries the insulin-sensitivity result and no independent group has repeated it, which places it at C.
WHAT THIS GRADE DOES NOT COVERlongevity, healthspan or mortality, which no human trial has tested; muscle NAD, which neither trial measured; and morning dosing, which neither trial compared with any other time of day.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
The evidence, in fullTwo papers, each linked to its PubMed record.
Yoshino et al. (Science, 2021; PMID 33888596): NMN improved muscle insulin sensitivity in prediabetic women. Yi et al. (GeroScience, 2023; PMID 36482258): randomized trial in healthy middle-aged adults. Small, short trials with surrogate or modest functional outcomes, and neither trial repeats the other, so Grade C, matching the NMN supplement record.
If blood NAD+ Nicotinamide adenine dinucleotide, a molecule cells use in energy metabolism. Its level falls with age in some tissues. is measured, the same laboratory assay is used at baseline and follow-up. NAD+ is a mechanistic biomarker A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment., not a clinical outcome. Fatigue or exercise performance is tracked separately with the same validated measure at baseline and follow-up.
Evidence notes: randomized trial
Endpoint graded: Insulin sensitivity and blood NAD (surrogate)
Last reviewed: July 2026
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