Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

This randomized, double-blind, placebo-controlled trial tested 250 mg/day of oral NMN for 12 weeks in 30 healthy Japanese adults. Fifteen participants were assigned to NMN and 15 to placebo; 29 completed the study. The primary outcome was safety and tolerability, while secondary outcomes included whole-blood NAD-related metabolites and amino acids.

No serious adverse events were reported. One participant in each group had an intervention-related gastrointestinal symptom; the NMN-group event was transient abdominal pain that resolved without treatment. Body weight, BMI, blood pressure, pulse rate, liver and kidney measures, and most other safety laboratory values did not differ significantly between groups.

Whole-blood NAD+ increased significantly in the NMN group at 4, 8, and 12 weeks and returned toward baseline four weeks after supplementation stopped. NAMN showed a similar pattern, while measured NMN itself did not increase and several other NAD-related metabolites were unchanged.

The trial did not demonstrate significant effects on glucose or lipid measures, uric acid, body composition, or whole-blood amino acids. It therefore provides short-term safety and NAD-metabolism evidence for the tested dose and formulation, not evidence of a clinical anti-aging or functional benefit.

• Thirty healthy adults were randomized 1:1 to NMN or placebo; 29 completed the trial after one placebo-group dropout.
• No serious adverse events occurred. Intervention-related adverse events occurred in one participant in each group; the NMN-group event was transient abdominal pain that resolved without medication.
• Whole-blood NAD+ was significantly increased in the NMN group at 4, 8, and 12 weeks and returned toward baseline by the 16-week follow-up after supplementation had stopped.
• NAMN increased significantly during NMN supplementation, while measured NMN itself did not increase. NR, nicotinamide, nicotinic acid, NAR, NAAD, and MNAM were not significantly changed between groups.
• Body weight, BMI, blood pressure, pulse rate, glucose-related measures, lipid measures, uric acid, and body-composition changes did not show significant between-group effects.
• Whole-blood amino-acid levels, including branched-chain amino acids, did not significantly change.
• Exploratory analyses found a strong positive correlation between baseline pulse rate and the 4-week increase in NAD+ in the NMN group (R = 0.768); this was not a randomized treatment comparison.

• The sample was small: 30 participants were randomized and 29 completed the study, limiting precision and the ability to detect uncommon adverse events.
• Participants were healthy Japanese adults aged 22–64, so the findings may not generalize to other populations, people with chronic disease, or substantially older adults.
• The intervention lasted 12 weeks at one dose, 250 mg/day; the study does not establish longer-term safety or outcomes at other doses.
• The primary outcome was safety and the main secondary outcomes were blood metabolites. The trial was not designed to establish anti-aging, longevity, disease-treatment, or functional benefits.
• NAD+ was measured in whole blood, not in tissues such as skeletal muscle, and the study did not establish the physiological consequences of the observed rise in blood NAD+.
• Several metabolic and body-composition outcomes were null; non-significant trends should not be interpreted as demonstrated benefits.
• The study was funded by Mitsubishi Corporation Life Sciences Limited, which also manufactured and supplied the NMN and placebo; four authors were company employees.
• COVID-19 vaccination occurred in both groups during the trial and contributed to some reported fever, joint pain, and fatigue, complicating interpretation of those adverse-event reports.