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Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis

Wenyu Yang, Jun Huang, Zihan Tang, Cong Chen, Yanan Sun
Nutrients 2026 18, 2251

Bibliography

PubMed
PMID 42514320
PubMed Central
PMC13414721
DOI
10.3390/nu18142251
Funding
The research received no external funding.
Competing interests
The authors declare no conflicts of interest.

Study snapshot

DesignSystematic review and random-effects meta-analysis of parallel randomized controlled trials; protocol registered prospectively in PROSPERO and reporting followed PRISMA 2020.
ModelAdults aged 18 years or older across healthy, metabolic-risk and clinically distinct populations; included oral NMN or NMN-related preparations compared with placebo or other eligible controls.
Sample15 randomized trials included in the review; 10 contributed to the safety analyses. The paper notes that the total evidence base remains small.
InterventionAcross included trials, oral NMN or NMN-related preparations ranged from 250 to 2000 mg/day and intervention durations ranged from 14 days to 24 weeks.
DurationIncluded trials: 14 days to 24 weeks; literature search through 13 May 2026.
EndpointsTotal and serious adverse events; Withdrawals due to adverse events; System-specific adverse events; ALT and AST; Body weight and BMI; Fasting glucose, HbA1c and HOMA-IR; HDL-C, LDL-C, total cholesterol and triglycerides; Systolic and diastolic blood pressure

What the study showed, in plain terms

This 2026 review pooled the available randomized adult trials of oral NMN or NMN-related formulations, with safety as its primary interpretive focus. Fifteen trials met the review criteria and 10 contributed to pooled safety analyses.

Across short-term trials, NMN did not clearly increase overall adverse events, serious adverse events, withdrawals, system-specific adverse events, ALT or AST. Conventional metabolic outcomes were mostly null: body weight, BMI, fasting glucose, HbA1c, lipids and systolic blood pressure did not show significant pooled improvement.

A small reduction in diastolic blood pressure was observed and HOMA-IR trended downward without statistical significance. The authors emphasized that small samples, heterogeneous populations/formulations and short follow-up prevent firm conclusions about long-term safety, rare adverse events or broad metabolic efficacy.

Key findings

  • Fifteen randomized trials were included; 10 contributed to safety analyses. Doses ranged from 250 to 2000 mg/day and durations from 14 days to 24 weeks.
  • Pooled analyses found no clear increase in overall adverse events, serious adverse events, withdrawals due to adverse events or system-specific adverse events.
  • ALT and AST were not significantly elevated, supporting a favorable short-term hepatic biochemical safety profile.
  • No significant pooled effects were observed for body weight, BMI, fasting glucose, HbA1c, lipid profiles or systolic blood pressure.
  • Diastolic blood pressure decreased slightly, while HOMA-IR showed a non-significant downward trend.
  • The review used Cochrane RoB 2 for risk of bias and GRADE to assess certainty for major safety and metabolic outcomes.

What this study can and cannot tell us

The evidence base is dominated by small, short-term trials, limiting conclusions about long-term efficacy, rare adverse events and population-specific safety signals.

Populations, doses, formulations and intervention durations varied substantially, including studies of MIB-626 that may not be pharmacokinetically equivalent to ordinary free NMN.

Most original trials did not comprehensively assess visceral/liver fat, mechanistic insulin sensitivity, inflammatory markers, mitochondrial function, endothelial function or NAD+ metabolic status, limiting phenotype-specific conclusions.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology