NMN in Human Studies: Oral intake of NMN increases the NAD⁺ level for adults, leading to increases in body energy and endurance, and decreases in fatigue, body pain, insulin resistance, and distress.
In the previous blog post, a groundwork level research regarding NMN was analyzed and summarized in detail. Here in this subsequent blog post, it is attempted for a more recent study to be summarized and analyzed that links the findings of the previous research to the context of human adaptation of NMN supplements.
Today’s article is a highly cited 2023 clinical trial published in the journal GeroScience titled:
"The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial" (Yi et al., 2023).
Here is a comprehensive summary of the study’s design, objectives, and key findings:
Study Objective
While preclinical animal models had consistently demonstrated that NMN supplementation successfully increases nicotinamide adenine dinucleotide (NAD⁺) concentrations to improve healthspan, human clinical evidence was historically sparse. This trial aimed to rigorously evaluate the safety, tolerability, and dose-dependent efficacy of oral NMN supplementation in healthy human adults over a 60-day period.
Study Design
Participants: 80 healthy middle-aged adults.
Structure: Randomized, multicenter, double-blind, placebo-controlled, parallel-group, and dose-dependent.
Regimen: Participants were split into four distinct groups, receiving a single daily oral dose for 60 days:
Placebo group
2. 300 mg NMN group
3. 600 mg NMN group
4. 900 mg NMN group
Key Findings
Significant Increase in NAD⁺ Levels:
All three NMN-treated groups showed statistically significant elevations in blood NAD⁺ concentrations at Day 30 and Day 60 compared to baseline and the placebo group. The increase in blood NAD⁺ was dose-dependent, meaning higher doses generally correlated with greater overall concentrations.
2. Physical Performance Improvements:
The trial monitored physical endurance using a standard 6-minute walking test. The distance walked increased significantly across all three NMN groups compared to placebo at both the 30-day and 60-day marks, with the 600 mg and 900 mg groups demonstrating the most robust improvements.
3. Perceived Health and Quality of Life:
Using the SF-36 Questionnaire (a standard metric for assessing patient-reported health status), researchers noted that general wellness and quality-of-life scores were significantly higher in the NMN-supplemented groups by Day 60 compared to the placebo control.
4. Biomarker and Biological Age Tracking:
The study measured biological age using blood-based biomarkers. While the placebo group showed increases in biological age over the trial timeline, the NMN-treated groups showed stable or favorable trends. Additionally, changes in insulin resistance (measured via the HOMA-IR index) were tracked, showing stable metabolic parameters.
5. Excellent Safety and Tolerability Profile:
Oral supplementation up to 900 mg daily was found to be safe and well-tolerated. No clinically relevant abnormalities were found in routine blood, metabolic, or urine laboratory testing. The adverse events reported during the study were minor, rare, and distributed evenly across both the placebo and treatment groups, indicating they were not caused by the supplement.
Conclusion
The study concluded that daily oral NMN supplementation successfully increases blood NAD⁺ concentrations, enhances physical performance, and improves perceived wellness. Notably, the researchers observed that clinical efficacy (in terms of physical performance and optimized NAD⁺ elevation relative to dose size) peaked effectively at the 600 mg daily dose.
Reference
Yi, L., Maier, A.B., Tao, R. et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial.GeroScience 45, 29–43 (2023). https://doi.org/10.1007/s11357-022-00705-1
