Nutrients · Oct 23, 2026
Unlocking the Healthy Aging Potential of Novel NMN-Based Nutritional Formulations: Cardiopulmonary, Cognitive, and Aging-Related Outcomes in a 42-Day Open-Label Study
By Abe T, Yoshida N, Abdelhakim M et al.
Background: Nutritional strategies targeting NAD+ metabolism, mitochondrial function, and metabolic resilience are gaining attention as potential approaches to healthy aging. This study investigated the short-term physiological, cognitive, and aging-related responses to NMN-based nutritional formulations, including combinations with β-hydroxybutyrate, ginsenosides, and complementary metabolic modulators. Methods: In this 42-day, open-label, four-arm exploratory clinical study, 40 Japanese adults aged 45–65 years were included in the final analysis: placebo (n = 10), NMN alone (n = 9), a core combination (n = 10), and an expanded eight-component formulation (n = 11). Cardiopulmonary exercise testing (CPET) and computerized cognitive assessments (CogniTrax) were performed at baseline and week 6. Additional exploratory analyses evaluated immune and inflammatory biomarkers and model-derived functional-age estimates in a placebo-versus-expanded-formulation subset. DNA methylation and transcriptomic profiles were independently assessed in a separate eight-participant pilot. Results: The intervention was associated with high recorded adherence and no reported serious adverse events. Although between-group comparisons did not demonstrate statistically significant improvements in the selected cardiopulmonary or cognitive outcomes, several cognitive measures showed favorable descriptive changes in the expanded-formulation group relative to placebo, including the Neurocognitive Index (+3.09 vs. −1.90), composite memory (+5.82 vs. −5.30), and verbal memory (+9.00 vs. −2.50). Exploratory biomarker analyses identified nominal between-group differences in CTACK (p = 0.015) and GDF-15 (p = 0.022), without adjustment for multiple testing; the direction of these changes does not establish clinical benefit. A model-derived functional-age composite decreased by 2.79 years in the expanded-formulation group compared with 0.63 years in placebo. In the separate uncontrolled molecular pilot, DNAm PhenoAge relative to chronological age decreased by approximately 4.1 years, accompanied by nominal transcriptomic changes. These exploratory age-related measures do not establish biological age reversal. Conclusions: This exploratory study demonstrates the feasibility of short-term administration of NMN-based multi-ingredient nutritional formulations and provides multidomain descriptive observations across cognitive, physiological, inflammatory, and molecular measures. While the findings do not establish clinical efficacy or ingredient-specific effects, they offer a foundation for hypothesis development and the design of larger, randomized, double-blind trials with prespecified outcomes.