Supplement · graded by use, three uses
NMN (Nicotinamide Mononucleotide)
Muscle insulin sensitivity in prediabetic postmenopausal women.
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 →
NMN is sold for healthy aging. The body turns it into a molecule called NAD. Studies show that NMN raises NAD in the blood, which shows the pill is absorbed, not that health improves. Every one of those studies was run or paid for by a company that sells NMN. One small study found that muscles handled sugar better in older women with prediabetes. No study shows that NMN slows aging or helps people live longer.
The C belongs to one of the three uses graded on this record. The other two carry their own letters.
As studied, and the trials
Yoshino et al. (Science, 2021; 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): 25 postmenopausal women with prediabetes, 13 on 250 mg/day for 10 weeks; clamp-measured muscle insulin sensitivity rose with NMN and not placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received., 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 A study that pools the numbers from several trials into one combined estimate. of NMN trials found no effect on fasting glucose, insulin, HbA1c A blood test that reflects average blood sugar over the previous two to three months. 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.
As studied, and the trials
Raising blood NAD is the most consistently replicated 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. 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 Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries. 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.
As studied, and the trials
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.
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A letter describes the human evidence, not the product, the manufacturer, or the ingredient's worth.
See the full evidence record →Funding: All four randomized trials replicating this Grade C for Blood NAD+ concentration in healthy middle-aged adults were funded by industry: Multicenter, India and USA (PMID 36482258) by Abinopharm and Aba Chemicals, the makers of the product it tested; Brigham and Women's Hospital, USA (PMID 36740954) by Metro International Biotech, the maker of the product it tested; Meiji, Japan (PMID 38789831) by Meiji Holdings, the maker of the product it tested; DHC Corporation Laboratories, Japan (PMID 36797393) by DHC Corporation, the maker of the product it tested. The funder's role in design and analysis is not stated here, because the full trial reports could not be read. The letter stands because each trial met the grading rules on its own; the funding is stated here so it can be weighed alongside it.
Muscle insulin sensitivity in prediabetic postmenopausal women on one small trial; blood NAD+ rises in maker-run trials, a mechanistic marker.
Why this gradeGrade C, small or unreplicated trials. The reasoning, and what the grade does not cover.
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 COVERlongevity, 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.
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 →
Who responds: this record's trial reading reports no subgroup that identifies who responds.
As studied: dose, form, population and duration for every use
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
The trial that would change this grade.
Positive trials of this shape from independent research groups would move this entry to A.
Why the current trials fall short
The cited trials are short and end at surrogates: muscle insulin sensitivity in one trial of 13 treated women, and blood NAD+ in four trials. Raising NAD+ is established. Benefit from raising it is not, and no trial cited here tests it. The headline C rests on a blood level, which shows absorption and qualifies for nothing above C. Moving to A would take randomized trials with a hard or objective functional endpoint, from independent research groups and independent of NMN makers; no NMN trial has measured one.
Why people believe itThree human sources; no published case reports of benefit; no reports of harm.
The case for NMN rests on the idea that NAD+, which falls with age, can be topped up, and that topping it up slows aging. Mouse work supports the idea; in people, NMN reliably raises NAD+ in the blood, and one small trial found a metabolic benefit.
What supporters point to, and what each source actually shows. None of it is enough to move this letter higher; the trial described above under Evidence wanted is what would.
- Human trial, blood or body markerIn healthy middle-aged adults, NMN raised blood NAD+ in a randomized trial, as it has in several others. This shows the supplement is absorbed. It does not show a health benefit. PMID 36482258
- Human trial, a different useMuscle insulin sensitivity improved in prediabetic postmenopausal women, 13 of whom took NMN, over 10 weeks. This is the trial the Grade C rests on, and it has not been repeated. PMID 33888596
- Human trial, blood or body markerIn a maker-run trial in older adults, blood NAD+ rose and walking speed was maintained. PMID 38789831
A case report describes what happened to one or a few patients. It cannot show the treatment caused the change, and reports of success are published more often than reports of failure.
A PubMed search in October 2026 found no published case report of benefit for this use.
Searched PubMed, October 2026: 7 case report record(s) returned. None of the seven records describes a person taking NMN for aging or for any graded use. They concern inherited enzyme disorders and one veterinary report.
Animal and laboratory workTwo studies in animals or cells. Not counted toward the letter.
None of this is human evidence and none of it counts toward the letter. It is listed so the reader can see what the idea rests on. Most findings in animals do not hold up when tested in people.
- MouseTwelve months of oral NMN in normally aging mice reduced age-associated weight gain and improved energy metabolism, physical activity, insulin sensitivity, plasma lipids and eye function, with no toxicity seen. Lifespan was not measured. PMID 28068222 Two of the authors list an affiliation with Oriental Yeast Company, a commercial NMN producer.
- MouseNMN restored tissue NAD+ and improved glucose intolerance and hepatic insulin sensitivity in mice made diabetic by a high-fat diet or by age. PMID 21982712
How this letter has changed · latest: October 2026 · Downgraded
Four randomized trials agree that oral NMN raises blood NAD (Yi et al., GeroScience, 2023; PMID 36482258; Pencina et al., J Clin Endocrinol Metab, 2023; PMID 36740954; Morifuji et al., GeroScience, 2024; PMID 38789831; Katayoshi et al., Sci Rep, 2023; PMID 36797393). The editor settled the open question of what counts as a qualifying biomarker in October 2026 and added it to 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. Blood NAD is that kind of level, so the use and the headline move to C, the same reasoning that holds nicotinamide riboside at C. This supersedes the correction of earlier the same day that confirmed the B. Editor decision, Arnold Sandlow, D.C., October 2026.PMID 36482258 PMID 36740954 PMID 38789831 PMID 36797393
The use rose C to B in October on four randomized trials that agree on higher blood NAD+ (PMIDs 36482258, 36740954, 38789831, 36797393), every one run or funded by an NMN maker, which the replication funding rule of September counts as replication and states beside the letter. Replicated randomized evidence on a surrogate is B, and the surrogate is what keeps it from A; a blood level is not a health outcome, which the record states. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).
Text corrections after the letters were set earlier today. The Route 1 longevity row cited a blood-pressure meta-analysis (Zhang et al., 2026; PMID 41901064), which now sits in the ref described as what it is: diastolic pressure about 2 mmHg lower, systolic unchanged. The insulin-sensitivity row omitted the one other direct measurement, null at 2,000 mg/day (Pencina et al., 2023; PMID 36740954), and three meta-analyses finding no effect on glucose, insulin, HbA1c or HOMA-IR (PMIDs 39531138, 39116016, 42514320), now stated. The dose line said sublingual may improve absorption; the only randomized comparison (Wakabayashi et al., 2026; PMID 42304075) found no NAD+ difference between routes. The liposomal claim had no trial and is removed. The industry authorship of Yi 2023 (PMID 36482258) is stated. Letters unchanged. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 36482258 PMID 36740954 PMID 41901064 PMID 42304075
Kane et al. (bioRxiv preprint, 2024; PMID 38979132), in a version revised in 2026, gave NMN to mice from middle age for life. Frailty accumulated more slowly in both sexes, but median lifespan rose 8.5 percent in females only, and the female control mice were short-lived, so the result may reflect correcting poor baseline health. It is a mouse study and not peer reviewed. No human trial has tested NMN against lifespan, healthspan or mortality, so that use stays D.PMID 38979132
The blood NAD use held a C on one dose-ranging trial, Yi et al. (GeroScience, 2023; PMID 36482258; 80 adults). Three further randomized placebo-controlled trials report the same result: Pencina et al. (J Clin Endocrinol Metab, 2023; PMID 36740954; 30 adults, 28 days), Morifuji et al. (GeroScience, 2024; PMID 38789831; 60 older adults, 12 weeks) and Katayoshi et al. (Sci Rep, 2023; PMID 36797393; 36 adults, 12 weeks). A replicated surrogate reaches B under the written rule. Every one of the four was run or funded by a company that sells NMN, so the funding and investigator line prints beside the letter under the rules of September and October. The pooled metabolic endpoints across NMN trials (Yang et al., Nutrients, 2026; PMID 42514320) show no clear clinical benefit, which the record states. Moved October 2026 by editor adjudication (Arnold Sandlow, D.C.) of a use-specific literature search, every trial re-fetched from PubMed before the letter rose; the search is recorded on the record.PMID 36482258 PMID 36740954 PMID 38789831 PMID 36797393 PMID 42514320
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 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
The headline Grade B sat above per-use grades of C, C and D. A headline letter may not exceed the best use it rests on, so the headline is now C. The longevity, healthspan and mortality use remains D: no cited trial measures it.
Every change to a letter on this site is dated and published. The full evidence log →
Commercial disclosure
EBL earns no commission on any supplement it grades. A purchase made through the dispensary link below pays EBL nothing, the practitioner discount goes to you in full. The dispensary is Fullscript, a practitioner dispensary, and many of the professional-grade brands in it are sold mainly through practitioners rather than in health food stores. Grades are assigned by published rubric before any commercial relationship exists and are never influenced by one. Full disclosure.
250 to 1,000 mg/day oral in the trials cited; 2,000 mg/day in the 28-day Pencina trial. The only randomized comparison of oral and sublingual NMN, a single-dose crossover A trial design in which each participant receives both the treatment and the comparison, one after the other, and serves as their own control. in 14 men run by employees of an NMN maker (Wakabayashi et al., Sci Rep, 2026; PMID 42304075), found no difference in blood NMN, nicotinamide or NAD+ between routes, only faster appearance of terminal catabolites after sublingual dosing; no graded trial used sublingual NMN.
Crystalline NMN is the form used in trials. No cited human trial has tested a liposomal form.
In the 60-day trial in healthy middle-aged adults, NMN was taken once daily before breakfast, with water (PMID 36482258). The 10-week trial in postmenopausal women gave 250 mg a day, and its report does not state a time (PMID 33888596).
Checked against the full published reports. What the cited trials did, not a schedule. Every supplement, by trial timing →
How to buy this: quality criteria, not a brand
250–1,000mg/day, crystalline NMN.
Crystalline NMN (the trial form). Liposomal claims are unproven.
A third-party Certificate of Analysis (COA) for purity, NMN purity varies widely.
No COA; “liposomal” claims without data; suspiciously cheap (often impure/underdosed).
The grade and these criteria are set only from human trials. Any purchase link is convenience and does not affect the grade.
Active malignancy, as a precaution rather than a finding: NAD+ is required for cell replication and no trial has tested NMN in cancer patients, so the position is absence of evidence rather than evidence of harm, and it belongs with an oncologist. Pregnancy. The human trials that exist are short, small and aimed at metabolic and functional endpoints, so long-term safety is genuinely unknown rather than reassuring.
No drug interaction has been documented in a human trial. Diabetes medication: NMN has been studied for effects on insulin sensitivity, so additive glucose lowering is plausible and unmeasured. Chemotherapy: an oncology decision, on the same reasoning as the contraindication above.
What the NMN human trials actually cover. The human NMN trials are short, small and directed at metabolic and functional endpoints. They support tolerability over weeks to months and say nothing about long-term safety or about use during malignancy. Yi et al. (GeroScience, 2023; PMID 36482258): randomized, multicenter, double-blind trial of the efficacy and safety of NMN supplementation in healthy middle-aged adults. Fukamizu et al. (Scientific Reports, 2022; PMID 36002548): safety evaluation of oral NMN administration in healthy adult men and women.
Fatigue levels, NAD+ blood test (optional, expensive), biological age markers at 6 months
Primary evidenceTen papers, each linked to its PubMed record.
Yoshino et al. (Science, 2021; PMID 33888596): RCT Randomized controlled trial: people are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect.: 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.
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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
(nicotinamide mononucleotide[tiab] OR NMN[tiab]) AND NAD[tiab] AND randomized controlled trial[pt] AND humans[mesh]Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →