NMN Human Clinical Trials: Complete Evidence Review
What this page answers
This is the central evidence page of this hub: what has actually been demonstrated in humans, by randomized or otherwise controlled NMN intervention trials? It is not a list of positive results. Every trial below is shown with its actual primary endpoint, its actual secondary findings, and — where relevant — its null results, design limitations, and funding. Where a trial's headline finding was a secondary or exploratory outcome rather than its prespecified primary endpoint, that is stated explicitly, because the two are not equivalent evidence.
Master trial table
16 completed, published human NMN intervention studies were identified through a systematic literature review current through August 30, 2026 (PubMed/NCBI, primary publisher records, and existing systematic reviews/meta-analyses of this literature), plus one additional registered trial with no published results yet (shown separately below the table) — 17 entries in the inventory in total. This is not necessarily exhaustive of every NMN study ever conducted anywhere, but reflects a deliberate, repeated search rather than a static list. Full population, dose, and safety detail for each trial is on NMN Dosage and NMN Safety and Side Effects; this table adds design rigor and outcome-type detail those pages don't repeat.
Every entry also carries a verification tier, reflecting how thoroughly this review was able to independently confirm it — not how strong the evidence is. A small, weak trial can still be Tier A (its primary record was directly inspected); a large trial could in principle be Tier C if its record couldn't be located. Tier A = the primary publication itself was directly inspected and its core identity and outcomes verified. Tier B = an authoritative primary record was verified, but some outcome detail could not be independently checked. Tier C = the study appears to exist but its primary identity, full text, or indexing could not be sufficiently verified; Tier C findings are not used to support any efficacy conclusion on this hub.
| Study | N (random./compl.) | Design | Primary endpoint | Primary result | Key secondary findings | Funding/COI | Verification |
|---|---|---|---|---|---|---|---|
| Yoshino et al. 2021, Science[1] | 25 / 25 | RCT, DB, PC, parallel | Muscle insulin sensitivity (hyperinsulinemic-euglycemic clamp) | Positive — insulin-stimulated glucose disposal and muscle insulin signaling increased vs. placebo | No significant change in whole-body glucose tolerance, fasting glucose, HbA1c, or body weight/composition reported | Industry ties disclosed (co-author patent-licensing fees) | Tier A |
| Igarashi et al. 2022, npj Aging[2] | 20 / 20 | RCT, DB, PC, parallel | Blood NAD+ and muscle-function measures | Mixed — NAD+ ↑ (primary biomarker met); no effect on insulin sensitivity, muscle mass, or visceral fat | Nominal (non-robust) gait-speed and grip improvements; cognitive function directly assessed via MMSE-J and the Japanese Montreal Cognitive Assessment (MOCA-J) — the intervention had no observable effect on overall cognitive function on either instrument | Industry funded / author employment | Tier A |
| Okabe et al. 2022, Frontiers in Nutrition[3] | 30 / 29 | RCT, DB, PC, parallel | Safety and blood NAD+ | Positive for biomarker — NAD+ nearly doubled; no serious adverse events | Minor GI symptoms in both arms (not clearly attributable) | Industry funded / author employment | Tier A |
| Katayoshi et al. 2023, Scientific Reports[4] | 36 / N/R | RCT, DB, PC, parallel | NAD+ metabolism and arterial stiffness (PWV) | Null on primary — PWV trended lower, not statistically significant | Serum nicotinamide ↑; well tolerated | No competing interests reported | Tier A |
| Akasaka et al. 2023, Geriatrics & Gerontology International[5] | 14 / N/R | RCT, DB, PC | Grip strength and walking speed | Null — no significant improvement vs. placebo in a small, likely underpowered sample | Safe, tolerable | Funding/COI not independently verified | Tier A |
| Morifuji et al. 2024, GeroScience[6] | 60 / N/R | RCT, DB, PC, parallel | Stepping-test performance | Null on primary — no significant difference from placebo at 4 or 12 weeks | Secondary: shorter 4-m walking time and improved sleep quality (PSQI) vs. placebo; NAD+ ↑ | Industry funded / author employment | Tier A |
| Liao et al. 2021, J Int Soc Sports Nutr[7] | 48 / N/R | RCT, DB, 4-arm, PC | Aerobic-capacity measures under combined training | Mixed — certain submaximal/ventilatory-threshold oxygen-uptake measures improved more at medium/high doses; VO2max itself did not significantly differ between groups | Well tolerated | No competing interests reported | Tier A |
| Yi et al. 2023, GeroScience[8] | 80 / N/R | RCT, multicenter, DB, PC, dose-dependent | Blood NAD+ (dose-response) | Positive for biomarker — dose-dependent NAD+ ↑ | Secondary: ↑ 6-minute walk distance, improved self-reported wellbeing at 30/60 days | Industry funded / author employment | Tier A |
| Pencina et al. 2023 (pilot)[9] | 32 / N/R | RCT, DB, PC, block-randomized | Blood NAD+ (dose-response, safety) | Positive for biomarker | No severe adverse events | Funding/COI not independently verified for this specific paper | Tier A |
| Fukamizu et al. 2022, Scientific Reports[10] | 31 / N/R | RCT, DB, PC, parallel (safety design) | Safety at high dose | Null on efficacy measures — no changes exceeding normal physiological variation | No severe adverse events | Industry funded / author employment | Tier A |
| Christen et al. 2026, Nature Metabolism[11] | 65 / N/R | RCT, open-label, PC, 4-arm | Circulating NAD+ vs. NR and nicotinamide | Positive for biomarker — comparable to NR; nicotinamide did not raise NAD+ similarly | Gut-microbiome/SCFA changes observed | Funding/COI not independently verified | Tier A |
| Pencina et al. 2023, JCEM[12] | 30 / N/R (21 active/9 placebo) | RCT, DB, PC, 2:1 randomization | Physiologic effects at 2,000 mg/day | Mixed — NAD+ ↑; ↓ body weight, LDL/non-HDL cholesterol, diastolic BP; no significant change in muscle strength, fatigability, aerobic capacity, or stair-climbing power | 24 on-treatment AEs in 15/30 (2 moderate, rest mild); no serious AEs | Industry funded / author employment (sponsor funded; senior author equity) | Tier A |
| Huang 2022, Frontiers in Aging (Uthever)[13] | 66 / N/R | RCT, multicenter, DB, PC, parallel | NAD+/NADH and quality of life | Positive — NAD+/NADH ↑38% vs. 14.3% placebo; SF-36 quality-of-life score ↑; HOMA-IR stable vs. worsened in placebo | Not detailed in the abstract | Industry funded / author employment | Tier A |
| Qiu et al. 2023, Signal Transduct Target Ther[14] | 21 / 19 (9 NMN / 10 lifestyle-only) | Prospective, randomized, open-label, active-comparator (lifestyle modification) — not blinded, not placebo-controlled; human pilot arm within a primarily mechanistic (mouse/cell) paper (NCT04903210) | Blood pressure and NAD+ in hypertensive patients | Positive — NAD+ in PBMCs ↑~43% vs. lifestyle-only group; systolic BP ↓6.11 mmHg and diastolic BP ↓3.56 mmHg vs. lifestyle-only group at 6 weeks (significant) | Flow-mediated dilation ↑0.6%; brachial-ankle pulse-wave velocity ↓116.66 cm/s | Funding/COI not independently verified | Tier A |
| Zhao et al. 2022, Am J Transl Med[15] | 58 / N/R | RCT (blinding not confirmed) | Insomnia/sleep measures | Not used in this evidence synthesis — see verification note below the table | Not used in this evidence synthesis — see note | Funding/COI not independently verified | Tier C |
| Kawakami et al. 2025, Ann Clin Med Case Rep[16] | 15 (5/arm: liposomal, non-liposomal, placebo) | RCT, double-blind, extremely small (n=5/arm) | Blood NAD+ (liposomal vs. non-liposomal vs. placebo) | Positive for biomarker — at 4 weeks, liposomal NMN raised NAD+ significantly more than placebo (p=0.000) and more than non-liposomal NMN (p=0.001); non-liposomal NMN vs. placebo was not significant (p=0.545) | Statistical limitations: n=5 per arm, no confidence intervals reported alongside the p-values, single-site/single-study result not independently replicated, and the placebo group itself showed an unexplained statistically significant NAD+ rise 4 weeks after supplementation ended (p=0.025) | Funding/COI not independently verified; liposomal NMN test material was supplied free of charge by a commercial liposomal-NMN manufacturer | Tier A |
| Registered / no published results: a multicenter, randomized, double-blind, placebo-controlled trial of oral NMN (320 mg/day, 60 days) for chronic insomnia in 400 participants has a published protocol but no results identified as of this review. Not counted among the 16 completed studies above and not used in any efficacy conclusion.[17] | |||||||
Verification note on Zhao et al. 2022: this study's title, authors, journal, volume, issue, and page range were confirmed directly on the journal's own publication page, and that page states a specific result (a higher "total effectiveness rate" and improved PSQI sub-scores in the NMN group, both reported as p<0.05). However, the journal carries no PMID, no DOI, and no confirmed MEDLINE/PubMed/Scopus indexing, and its blinding procedure is not stated. Because this study cannot be identified through any authoritative bibliographic record — the standard every other source on this hub meets — its specific numeric findings are not used to support any conclusion about NMN and sleep on this hub. It is retained here only as a study that was identified but could not be independently verified to that standard.
Inventory summary: 16 completed, published studies identified — 15 Tier A (primary-verified), 0 Tier B, 1 Tier C (Zhao, identified but not independently verified; excluded from synthesis) — plus 1 registered trial with no published results.
Systematic reviews and meta-analyses (pooled evidence, not additional trials)
These are analyses of the trials above and others, not new primary evidence. They are shown separately and are not counted toward the 16-trial total.
- Safety/tolerability (Yang et al. 2026, Nutrients): 15 pooled trials; no increase in overall, serious, or system-specific adverse events; no significant ALT/AST elevation.[18]
- Glucose and lipid metabolism (Zhang et al. 2025, Crit Rev Food Sci Nutr): 12 studies, 513 participants; NAD+ rose significantly, but most clinically relevant metabolic outcomes were not significantly different from control; risk-of-bias assessment found "some concerns" in 7 studies and "high risk of bias" in 5; authors explicitly caution against exaggerating benefits.[19]
- Physical performance (Wen et al. 2024, Cureus): 10 studies, 437 participants, mean follow-up 9.6 weeks; grip strength and skeletal muscle index changes were non-significant pooled.[20]
- Skeletal muscle mass/function (Prokopidis et al. 2025, J Cachexia Sarcopenia Muscle): pooled NMN/NR trials in adults averaging over 60 years; no significant effect on skeletal muscle index, grip strength, or gait speed; authors conclude current evidence does not support NMN/NR for preserving muscle mass and function.[21]
- Blood pressure (Zhang et al. 2026, Nutrients): 10 RCTs, 11 arms, 349 participants; a modest, statistically significant diastolic-BP reduction pooled (WMD −2.15 mmHg); systolic BP reduction was not significant overall, but was significant in the subgroup aged 60+ (WMD −3.94 mmHg); authors call the evidence "preliminary and suggestive," requiring larger long-term trials.[22]
Several of these reviews draw on overlapping trial populations — for example, Yoshino 2021, Okabe 2022, and Yi 2023 appear in more than one meta-analysis above. Pooled participant counts across different reviews should not be added together, since the same individual trials, and in some cases the same participants, recur across them.
Synthesis: what the evidence actually supports
What human trials support with reasonable confidence
Oral NMN, across doses from 250–2,000 mg/day and durations from 14 days to 24 weeks, reliably and reproducibly raises blood NAD+ or related metabolites, across many independent trials and research groups.[2][3][8] Short-term tolerability at these doses is well supported, with no serious adverse events reported across any trial identified.
What human trials suggest but do not yet establish
A modest reduction in diastolic blood pressure, particularly in adults 60 and older, is suggested by pooled analysis but explicitly labeled preliminary by its own authors.[22] A population-specific improvement in muscle insulin signaling was shown in one trial of prediabetic postmenopausal women, not replicated in a broader population.[1] A blood-pressure reduction was also reported in a small, open-label, non-blinded, non-placebo-controlled pilot in hypertensive patients — a real, directly-verified result, but from a design that cannot rule out placebo or expectation effects the way a blinded trial can.[14] Improved sleep quality by self-report questionnaire appeared as a secondary finding in one well-controlled trial.[6]
What human trials have not demonstrated
A consistent, statistically robust effect on fasting glucose, HbA1c, or lipid profile across pooled trials.[19] A meaningful effect on grip strength, skeletal muscle mass, gait speed, or VO2max, across two independent pooled analyses.[20][21] Any effect on cognitive function — the one trial that directly tested it, using two validated instruments (MMSE-J and MOCA-J), found none.[2] Any human evidence on lifespan, biological-age reversal, or disease prevention, at all.
What remains unknown
Long-term (multi-year) safety and efficacy; effects in populations other than generally healthy or narrowly-defined middle-aged/older adults; the practical significance, if any, of the blood-NAD+ increase that is otherwise well established; and whether any of the preliminary secondary findings above would replicate as a prespecified primary endpoint in a larger, independent, blinded trial. This hub's Limitations of Current NMN Research page addresses these gaps directly, alongside the sample-size, duration, and replication constraints visible throughout the table above.
Related reading
For the full dose-by-dose table, see NMN Dosage. For adverse-event detail, see NMN Safety and Side Effects. For topic-specific deep dives, see NMN and Aging, NMN and Metabolism Research, NMN, Exercise, and Muscle Function, NMN and Cardiovascular Research, NMN and Cognitive Research, and NMN and Sleep Research.
- 17 published human NMN intervention trials were identified, spanning 250–2,000 mg/day and 14 days to 24 weeks.
- Blood NAD+ increase is the most consistently replicated finding across trials; short-term tolerability is well supported.
- Several trials' actual prespecified primary endpoints were null (arterial stiffness, grip strength, stepping-test performance, high-dose safety measures).
- Pooled meta-analyses find no significant effect on fasting glucose, HbA1c, lipids, grip strength, skeletal muscle index, or gait speed.
- No human trial has measured lifespan or biological-age reversal; only one has directly tested cognitive function, and it found no significant effect.
- Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021. doi:10.1126/science.abe9985. PMID: 33888596.
- Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging. 2022. doi:10.1038/s41514-022-00084-z. PMID: 35927255.Full text (PMC9158788) directly verified: cognitive function was assessed via MMSE-J and MOCA-J; no significant effect on overall cognitive function was found on either instrument.
- Okabe K, Yaku K, Uchida Y, et al. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Frontiers in Nutrition. 2022. doi:10.3389/fnut.2022.868640. PMID: 35479740.
- Katayoshi T, Uehata S, Nakashima N, et al. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation. Scientific Reports. 2023. doi:10.1038/s41598-023-29787-3. PMID: 36797393.
- Akasaka H, Nakagami H, Sugimoto K, et al. Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance. Geriatrics & Gerontology International. 2023. doi:10.1111/ggi.14513. PMID: 36443648.
- Morifuji M, Higashi S, Ebihara S, Nagata M. Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults. GeroScience. 2024. doi:10.1007/s11357-024-01204-1. PMID: 38789831.
- Liao B, Zhao Y, Wang D, et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners. Journal of the International Society of Sports Nutrition. 2021. doi:10.1186/s12970-021-00442-4. PMID: 34238308.
- Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults. GeroScience. 2023. doi:10.1007/s11357-022-00705-1. PMID: 36482258.
- Pencina KM, Lavu S, Dos Santos M, et al. MIB-626... Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. Journals of Gerontology: Series A. 2023. doi:10.1093/gerona/glac049. PMID: 35182418.
- Fukamizu Y, Uchida Y, Shigekawa A, et al. Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports. 2022. doi:10.1038/s41598-022-18272-y. PMID: 36002548.
- Christen S, Redeuil K, Goulet L, et al. The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans. Nature Metabolism. 2026. doi:10.1038/s42255-025-01421-8. PMID: 41540253.
- Pencina KM, Valderrabano R, Wipper B, et al. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults. Journal of Clinical Endocrinology & Metabolism. 2023. doi:10.1210/clinem/dgad027. PMID: 36740954.
- Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement). Frontiers in Aging. 2022. PMID: 35821806.
- Qiu Y, Xu S, Chen X, et al. NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension. Signal Transduction and Targeted Therapy. 2023. doi:10.1038/s41392-023-01577-3. PMID: 37718359.Full text (PMC10505611) directly verified: human component (NCT04903210) was a randomized, open-label, active-comparator (lifestyle modification) design, not blinded or placebo-controlled, N=9 NMN vs N=10 lifestyle-only. Exact figures (NAD+, blood pressure, FMD, PWV) confirmed from the Results section. Funding/COI not independently verified.
- Zhao B, Liu C, Qiang L, et al. Clinical observation of the effect of nicotinamide mononucleotide on the improvement of insomnia in middle-aged and old adults. American Journal of Translational Medicine. 2022.Identified directly on the journal's own publication page (Vol 6, No 4, pp 167-176); no PMID, no DOI, and no confirmed MEDLINE/PubMed/Scopus indexing found; blinding not stated. Because it cannot be identified through an authoritative bibliographic record, its specific findings are not used in this hub's evidence synthesis (Tier C). Funding/COI not independently verified.
- Kawakami S, Maeda Y, Fukuzawa Y. Intervention Study Comparing Blood NAD+ Concentrations with Liposomal and Non-Liposomal Nicotinamide Mononucleotide. Annals of Clinical and Medical Case Reports. 2025.Full primary text directly obtained and inspected (Ann Clin Med Case Rep 2025;V14(11):1-12). n=5/arm; repeated-measures ANOVA with Tukey test; exact p-values verified (placebo vs. liposomal p=0.000; liposomal vs. non-liposomal p=0.001; placebo vs. non-liposomal p=0.545). Statistical limitations described precisely in the hub text rather than characterized as a formal controversy. Liposomal NMN test material was supplied free by a commercial liposomal-NMN manufacturer; funding/COI otherwise not independently verified.
- [Protocol paper, authors not extracted] Oral nicotinamide mononucleotide (NMN) to treat chronic insomnia: protocol for the multicenter, randomized, double-blinded, placebo-controlled trial. (trial protocol). 2023.Study protocol only; no results published as of this review. Registered/no published results — not counted among completed studies, not used in any efficacy conclusion.
- Yang W, Huang J, Tang Z, Chen C, Sun Y. Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis. Nutrients. 2026. doi:10.3390/nu18142251. PMID: 42514320.Systematic review/meta-analysis of 15 trials, not a primary trial.
- Zhang J, Poon ET, Wong SH. Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials. Critical Reviews in Food Science and Nutrition. 2025. PMID: 39116016.Systematic review/meta-analysis of 12 studies, 513 participants, not a primary trial.
- Wen J, Syed B, Kim S, et al. Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials. Cureus. 2024. doi:10.7759/cureus.65961. PMID: 39221308.Systematic review of 10 studies, 437 participants, not a primary trial; despite its title, pooled changes in grip strength and skeletal muscle index were non-significant.
- Prokopidis K, Moriarty F, Bahat G, McLean J, Church DD, Patel HP. The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of Cachexia, Sarcopenia and Muscle. 2025. doi:10.1002/jcsm.13799. PMID: 40275690.Meta-analysis of NMN/NR trials, not a primary trial.
- Zhang M, Chen Y, Jiang N, et al. Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2026. doi:10.3390/nu18060890. PMID: 41901064.Meta-analysis of 10 RCTs, 349 participants, not a primary trial.