NMN Human Trials: Published Clinical Evidence Mapped and Explained

NMN human trials now include randomized placebo-controlled studies, dose-ranging trials, crossover pharmacokinetic work, disease-specific studies and several meta-analyses. This page tracks the published clinical evidence while separating genuinely independent trials from secondary papers and post-hoc analyses of the same cohorts.

This page is our audit trail of the published human NMN evidence as of September 19, 2026.

Published human NMN studies at a glance

Year	Study / population	Dose and duration	Main result	Independence note
2020	Irie — healthy Japanese men	100–500 mg single dose	Early human safety/metabolite data; generally tolerated	Independent primary study
2021	Yoshino — postmenopausal women with prediabetes	250 mg/day, 10 weeks	Improved muscle insulin sensitivity; limited whole-body metabolic change	Independent RCT
2021	Liao — amateur runners	300–1,200 mg/day, 6 weeks	Aerobic-capacity signal with training	Independent RCT
2021	Niu — pre-aging adults	300 mg/day, 60 days	Exploratory metabolism, microbiome and telomere findings	Single-arm human component
2022	Kim — older adults	250 mg/day, 12 weeks	Selected sleep/drowsiness and physical-function signals	Independent RCT
2022	Okabe — healthy adults	125 or 250 mg/day, 12 weeks	Raised blood NAD+; safety focus	Independent RCT
2022	Fukamizu — healthy adults	High-dose β-NMN	Short-term high-dose safety data	Independent RCT
2022	Huang / Uthever — middle-aged and older adults	300 mg/day, 60 days	NAD-related and wellness/6-minute-walk signals	Independent multicenter RCT
2022	Igarashi — healthy older men	250 mg/day, 12 weeks	Raised NAD+; gait/grip signals; major week-12 supply error	Independent RCT
2023	Katayoshi — adults	Long-term NMN	NAD metabolism / arterial-stiffness endpoints	Independent RCT
2023	Akasaka — older adults with diabetes and impaired performance	250 mg/day	Physical-performance study	Independent RCT
2023	Pencina PK — overweight/obese older adults	1,000 or 2,000 mg/day, 14 days	Dose-dependent NAD pharmacology	MIB-626 program
2023	Pencina physiologic study	MIB-626	Detailed physiologic and cardiometabolic outcomes	Related MIB-626 program
2023	Qiu — hypertension mechanistic study	NMN intervention embedded in mixed study	Vascular/CD38/NAD biology	Mixed mechanistic human study
2023	Yi — healthy middle-aged adults	300/600/900 mg/day, 60 days	Dose response; NAD+ and selected physical outcomes	Independent multicenter RCT
2024	Yamaguchi — middle-aged men	Longer-term daily NMN	Safety, sleep, metabolism, NAD biosynthesis	Single-arm study
2024	Morifuji — older adults	250 mg/day, 12 weeks	NAD+, walking and sleep secondary signals	Independent RCT
2024	Kuerec personalized-response analysis	Parent randomized cohort	Baseline NAD predicts response patterns	Post-hoc; not independent trial
2025	Nakajima — healthy adults	Overdose-intake safety design	High-dose safety assessment	Independent RCT
2025	Pencina COVID/AKI	MIB-626 in hospitalized patients	Raised NAD+; acute-illness safety/feasibility	Independent acute-care RCT
2025	Ge — human NAD-capped RNA study	NMN supplementation	Molecular/epitranscriptomic endpoints	Human biomarker trial
2025	Fukumoto — middle-aged women	500 mg/day, 12 weeks	Hair diameter/appearance signals	Single-arm; no placebo
2026	Christen et al. — NMN vs NR vs nicotinamide	1,000 mg/day, 14 days	NMN and NR produced comparable roughly two-fold baseline whole-blood NAD+ increases	Independent four-arm randomized trial; metabolic endpoint study
2026	Berven et al. — direct NMN vs NR crossover	1,200 mg/day each, 8 days per precursor	NR produced a larger short-term blood total-NAD rise; neither significantly changed cerebral total NAD during the short crossover	Independent randomized crossover; only six participants in the direct comparison
2026	Yang BFR exercise	1,200 mg/day, 7 days	Altered acute muscle inflammatory/remodeling response	Small randomized crossover
2026	Kuerec lab-parameter analysis	Yi parent trial	NAD associations with laboratory markers	Post-hoc; not independent trial
2026	Wakabayashi oral vs sublingual	Route crossover	Different early 2PY/4PY kinetics	Independent crossover PK trial
2026	Li — immune thrombocytopenia	Low-dose oral NMN	Phase 1/2 disease-specific safety/efficacy signal	Single-arm disease trial
2026	Shiraki — diabetic retinal thickness	Parent diabetes RCT	Retinal secondary analysis	Secondary analysis; not independent trial
2025	Prokopidis — NMN/NR skeletal-muscle meta-analysis	Older-adult RCTs	No significant NMN benefit for muscle index, grip strength, gait speed or five-chair-stand	Systematic review/meta-analysis; synthesis, not a new cohort
2026	Gao — fatigue/performance network meta-analysis	7 NMN studies within 27 NAD+ precursor studies	Endurance signal at medium/high NMN dose; no consistent strength, perceived-fatigue, sleep or NMN cognitive benefit	Systematic review/network meta-analysis; search ended Jan 1, 2026, so later 2026 trials are absent
2026	Hong et al. — topical nano-NMN split-face study	10% topical nano-NMN for 4 weeks; device-assisted side vs topical-only side	Device-assisted side improved measured wrinkles, pores, elasticity, pigmentation and hydration more than topical NMN alone	Human topical/procedural intervention; not an oral NMN trial, no vehicle-only control, fixed side allocation
2026	Zhao — acute NMN/PQQ exercise trial	NMN 300 mg once, 60 min pre-exercise	No significant exercise-capacity benefit from NMN; PQQ drove the significant interoception signal	Independent four-arm acute RCT
2026	Nishimura — collegiate endurance trial	NMN 500 mg/day, 8 weeks	Raised NAD+ but NMN alone did not improve the primary endurance endpoint	Industry-funded RCT; all authors company employees/patent applicants

Why the “number of NMN trials” changes depending on the review

Reviews use different inclusion rules. Some count only randomized placebo-controlled adult trials. Others include nonrandomized interventions, single-arm studies, secondary analyses, MIB-626 formulations or disease-specific studies. A publication count can also overstate the number of independent participant cohorts.

The 2026 systematic review/meta-analysis included 15 randomized trials under its eligibility criteria. ^[1] A 2023 narrative review had earlier mapped 10 published human trials plus completed and ongoing registry records. ^[2]

Our database keeps the paper-level records but marks post-hoc and secondary analyses so readers do not mistake them for replication.

Human NMN evidence by study type

The first human study: safety before efficacy

Irie and colleagues gave single oral NMN doses to healthy Japanese men and measured clinical parameters and nicotinamide metabolites. It was an early safety/pharmacology study, not an anti-aging efficacy trial. ^[3]

The 2021 metabolic milestone

Yoshino and colleagues randomized postmenopausal women with prediabetes to 250 mg/day NMN or placebo. The standout result was improved muscle insulin sensitivity, accompanied by molecular changes in skeletal muscle. ^[4]

This study is often generalized into “NMN improves diabetes.” That is too broad: the population was specific, and later meta-analyses do not show consistent pooled improvement in fasting glucose or HbA1c.

Exercise and physical function trials

Liao reported improved aerobic-capacity measures in amateur runners receiving NMN alongside training. ^[5] Igarashi later reported NAD+ elevation and selected gait/grip signals in older men, though a supplement-supply crossover error materially reduced valid week-12 data. ^[6]

Yi's 300/600/900 mg/day trial added dose-ranging physical-performance data. ^[7] Morifuji found secondary walking-speed signals in older adults, while the primary stepping-test result was less compelling. ^[8]

In 2026, Yang's BFR-exercise crossover trial showed that high-dose short-term NMN can also dampen acute inflammatory/remodeling pathways after resistance exercise. ^[9]

Sleep and fatigue

Kim's 2022 randomized study and Morifuji's 2024 study provide the main controlled sleep-related signals, both in older adults. ^{[10] [11]}

These are small clinical signals rather than evidence that NMN is an insomnia treatment.

NAD+ pharmacokinetics and the 2026 head-to-head trial

The MIB-626 program established strong dose-dependent NAD pharmacology for a specific pharmaceutical-grade microcrystalline β-NMN formulation. ^[12]

The 2026 four-arm trial then directly compared NMN, NR, nicotinamide and placebo. NMN and NR at 1,000 mg/day both roughly doubled baseline whole-blood NAD+ after 14 days. ^[13]

This is one of the most important modern studies because it replaces pathway speculation with direct comparative human data.

Route-of-administration research

The 2026 oral-versus-sublingual randomized crossover study found higher early 2PY/4PY exposure after sublingual administration. ^[14] No clinical-outcome superiority was established.

Disease-specific studies

NMN research is now moving beyond healthy adults. Akasaka studied older patients with diabetes and impaired physical performance. ^[15] A later secondary analysis examined retinal thickness in older diabetic patients. ^[16]

MIB-626 has been tested in hospitalized patients with COVID-19 and acute kidney injury. ^[17] A 2026 phase 1/2 single-arm study examined low-dose NMN in immune thrombocytopenia. ^[18]

These trials should not be pooled mentally with healthy-aging supplementation. Disease context, dose, monitoring and risk-benefit calculus differ.

Registered trial to watch: NMN and immune recovery in HIV

A separate proof-of-concept study, NCT06889142, is testing 1,000 mg/day of NMN for 12 weeks in virologically suppressed adults with HIV who have persistent immunological failure despite antiretroviral therapy. The planned enrollment is only seven participants, the design is open-label and single-arm, and the primary endpoint is change in CD4+ T-cell count. Secondary outcomes include NAD+ levels, CD38 and HLA-DR immune-activation markers, TNF-alpha, IL-6, hs-CRP, quality of life, and safety/tolerability.

DoNotAge.org is listed publicly as a collaborator on the registry. The public ClinicalTrials.gov intervention is described generically as NMN, so we do not treat this registration as evidence for the exact retail DoNotAge Pure NMN product. The registry currently says “Not yet recruiting” and posts no results. This belongs in the ongoing-trial map, not in the published-efficacy count.

Secondary and post-hoc analyses: useful, but not replication

Kuerec and colleagues have published analyses exploring personalized NAD response and laboratory associations using parent randomized-trial data. ^{[19] [20]}

These papers add information but should not be counted as two new independent NMN trials. The same principle applies to secondary retinal analyses and other outcome-specific publications from existing cohorts.

What the meta-analyses say when studies are pooled

The 2026 synthesis found reassuring short-term safety but mostly null pooled results for weight, BMI, fasting glucose, HbA1c, lipids and systolic blood pressure, with a small diastolic blood-pressure signal. ^[21]

A dedicated blood-pressure meta-analysis similarly found a modest pooled DBP reduction and an age-subgroup SBP signal. ^[22]

Two glucose/lipid meta-analyses reached broadly cautious conclusions about routine metabolic outcomes. ^{[23] [24]}

What is still missing?

• Large multi-center trials powered for hard clinical outcomes rather than NAD biomarkers.
• Multi-year randomized safety data.
• Independent replication of several positive physical-function and sleep signals.
• Robust trials in diverse ethnic populations and age groups.
• Head-to-head formulation trials that connect pharmacokinetics to clinical outcomes.
• Human trials measuring validated biological-age endpoints with prespecified interpretation.
• Human cancer-safety data during active malignancy or chemotherapy.

Route matters: the table includes one 2026 topical/device-assisted NMN study because it is a genuine human intervention, but it is not evidence for oral NMN supplementation. Human oral, sublingual, topical and intravenous NMN studies should not be pooled conceptually as if route and formulation were interchangeable.

How the NMN evidence developed

How Biohack Blueprint counts trials without inflating the literature

An evidence database can count papers, trial registrations or independent participant cohorts. These are not the same thing. One randomized trial may produce a primary publication followed by analyses of laboratory parameters, retinal outcomes or personalized response.

Our Data Center stores each peer-reviewed paper because each can support a different claim. But our synthesis identifies when papers come from the same parent trial so they are not mistaken for independent replication.

How the field grew: 2020–2022

The earliest human work was dominated by safety, NAD pharmacology and small proof-of-concept studies. Irie 2020 focused on single-dose safety. ^[25] Yoshino 2021 then supplied a landmark metabolic efficacy signal in prediabetic postmenopausal women. ^[26]

Liao added exercise-performance data, while 2022 produced several older-adult and safety studies, including Kim, Okabe, Fukamizu, Huang/Uthever and Igarashi. This period established that oral NMN repeatedly changes human NAD biology and is generally tolerable over short study windows.

2023: dose response and specialized physiology

Yi's multicenter trial compared 300, 600 and 900 mg/day, providing one of the clearest dose-ranging datasets. ^[27]

Pencina's MIB-626 program characterized high-dose pharmaceutical-grade β-NMN pharmacokinetics and physiology in older overweight/obese adults. ^[28] Qiu and Katayoshi expanded the vascular/NAD literature.

2024–2025: secondary outcomes and a maturing evidence base

Morifuji added older-adult walking and sleep data. ^[29] Kuerec used an existing randomized cohort to examine personalized NAD response rather than creating a new independent trial. ^[30]

Meta-analyses began to outgrow the narrative-review stage. Chen and Zhang pooled glucose/lipid outcomes and found mostly null conventional metabolic effects. ^{[31] [32]}

Additional publications broadened the landscape to hair quality, acute illness, molecular biomarkers and high-dose safety.

2026: the comparison era

The field changed materially in 2026 because direct precursor comparisons and larger evidence syntheses arrived.

The Nature Metabolism trial randomized healthy adults to NMN, NR, nicotinamide or placebo and found comparable baseline whole-blood NAD+ increases with 1,000 mg/day NMN and NR after 14 days. ^[33]

The Berven NAD-brain phase I study used a six-person randomized crossover and found a larger eight-day blood total-NAD response to 1,200 mg/day NR than equal-dose NMN, while neither significantly changed cerebral total NAD during the short crossover. ^[34]

Different analytes, time windows and sample sizes help explain why the studies should be read together rather than reduced to opposite headlines.

2026 systematic reviews and meta-analyses

The NMN-specific 2026 meta-analysis synthesized 15 randomized trials and found short-term safety broadly reassuring but most conventional metabolic outcomes neutral. ^[35]

The dedicated blood-pressure meta-analysis found a small diastolic signal and no significant overall systolic benefit. ^[36]

The broader PRISMA-guided NAD-augmentation review included 33 human intervention studies across NMN, NR and related strategies and concluded that biochemical target engagement is consistent while clinical outcomes remain heterogeneous. ^[37]

How strong is the human evidence?

Primary trials versus secondary analyses

Publication type	Example	How we count it
Independent randomized trial	Yi 300/600/900 mg study	Independent cohort
Post-hoc analysis	Kuerec personalized NAD response	New paper, not new cohort
Secondary disease endpoint	Shiraki retinal-thickness analysis	New paper, not independent replication
Systematic review/meta-analysis	Yang 2026	Synthesis, not a trial
Single-arm intervention	Fukumoto hair study	Human evidence, lower causal strength
Registry only	Unpublished ClinicalTrials.gov record	Research activity, not efficacy evidence

Why trial size still matters

Many NMN RCTs enroll dozens rather than hundreds of participants. Small trials can detect large biomarker changes but are less reliable for modest clinical outcomes and rare adverse events. Positive secondary endpoints are especially vulnerable to chance when many outcomes are measured.

This is one reason pooled estimates and independent replication become increasingly important as the literature grows.

How long are the trials?

Most randomized studies span approximately two weeks to several months. The 2026 meta-analysis included trials up to about 24 weeks. ^[38]

That window is enough to study NAD pharmacology and some functional endpoints. It is not long enough to demonstrate human lifespan extension or confidently quantify rare long-term harm.

Who has been studied?

• Healthy middle-aged and older adults.
• Postmenopausal women with prediabetes.
• Older adults with diabetes and impaired physical function.
• Amateur runners and young male exercise participants.
• Overweight/obese middle-aged and older adults.
• Hospitalized patients with COVID-19 and acute kidney injury.
• People with immune thrombocytopenia in a phase 1/2 program.
• Healthy adults in direct precursor pharmacokinetic comparisons.

Who remains underrepresented?

Pregnant and breastfeeding people, children, many non-Asian ethnic populations, very frail older adults, people with advanced organ disease and long-term cancer survivors remain underrepresented or unstudied.

Funding and conflicts of interest

The NMN literature includes academic funding, government support, product-company funding, supplied study product and investigator commercial relationships. These disclosures belong in evidence interpretation rather than being ignored.

Our individual Research pages record funding and competing interests when available so the reader can inspect the evidence source behind every claim.

What would the next decisive trial look like?

The field does not need only more 30-person studies showing NAD rises. A decisive program would enroll hundreds of participants, use independent replication, run at least a year, prespecify clinically meaningful healthspan outcomes and track safety carefully. If NMN ultimately has major longevity value, that is the scale of evidence needed to demonstrate it.

What we deliberately exclude from the ordinary NMN trial count

Not every paper containing the letters “NMN” belongs in a β-NMN clinical evidence table. In August 2026, a randomized phase I preprint reported results for reduced β-nicotinamide mononucleotide calcium salt (NMNH-Ca). That is a chemically different reduced precursor, and the report is a preprint rather than a peer-reviewed β-NMN trial.

We therefore track it as adjacent NAD-precursor research, not as evidence that ordinary NMN supplements have another positive 90-day RCT. The same rule applies to registry-only studies: a ClinicalTrials.gov record shows research activity, not a published efficacy result.

Related NMN guides

• NMN benefits by evidence level
• trial doses
• human safety evidence
• NMN mechanism
• blood-pressure evidence
• insulin-sensitivity evidence

Bottom line

The NMN human evidence base is now substantial enough for serious synthesis, but still too small and short-term for broad longevity claims. The strongest consistent result is NAD+ augmentation; clinical outcomes are mixed, endpoint-specific and often preliminary.