Specifically, the study found no statistically significant improvements in cardiopulmonary or cognitive function outcomes—the study’s primary objectives—between the placebo and NMN groups.
Although the group taking NMN formulated with seven other actives showed favorable improvements in cognitive function, such as composite and verbal memory, compared with placebo, the findings were not statistically significant.
The study also explored the effects of NMN formulations on biological age, which researchers said demonstrated a decrease but did not amount to biological age reversal.
Still, researchers said that the findings provided a foundation for investigating NMN-based nutritional strategies to support healthy aging.
“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,” researchers from Abe Yoan Aging Research Institute and Nippon Medical School Hospital wrote in Nutrients.
Funded by Abe Yoando Pharma Co., Ltd., the open-label, four-arm exploratory clinical study assessed the effects of nicotinamide mononucleotide (NMN), a three-ingredient formulation consisting of NMN, D-beta-hydroxybutyrate (D-BHB) and ginseng-derived ginsenosides, and an eight-ingredient formulation, compared with placebo.
In addition to NMN, D-BHB, and ginsenosides, the eight-ingredient formulation also consisted of berberine, PQQ, CoQ10, trans-resveratrol, and spermidine.
A total of 42 healthy adults aged 45 to 65 took part in the study and took the placebo or NMN formulations as a 50-mL beverage each morning for 42 days.
The study was designed to assess changes in cardiopulmonary functions, such as exercise capacity, workload, and ventilation, as well as biological age based on DNA methylation clocks and gene expression.
Favorable changes but not significant
Overall, the study found no significant changes in the aforementioned cardiopulmonary or cognitive outcomes.
For example, cardiopulmonary exercise testing (CPET) showed no statistically significant differences between placebo and the group taking the eight-ingredient NMN formulation in exercise oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), minute ventilation (VE), maximal ventilation (VEmax), anaerobic threshold (AT) and achieved workload.
In the placebo group, for instance, achieved workload changed by −5.71 ± 15.23 W and −1.19 ± 11.79 W in the eight-ingredient NMN formulation group.
On the other hand, exercise VO2 changed by +0.0018 ± 0.0846 L/min in the placebo group and −0.0585 ± 0.1013 L/min in the other group, again showing no significant between-group differences.
“The direction of change was mixed rather than consistently favoring the expanded combination,” researchers wrote.
Similarly, the neurocognitive index, composite memory, and verbal memory showed positive changes in the groups taking NMN and NMN supplements.
In contrast, the placebo group showed small negative mean changes.
Commenting on the findings, researchers wrote that the favorable changes were “encouraging but not definitive.”
“Cognitive aging reflects changes in memory, processing speed, executive control, and attention, domains that can also be influenced by learning effects, sleep, motivation, and repeated testing,” they wrote.
They added that the study, being an open-label trial, might have further influenced cognitive performance of individuals taking NMN formulations.
Exploratory findings
On the other hand, the study reported a decrease in functional-age composite and biological age based on the DNAm PhenoAge epigenetic clock.
Specifically, the group taking the eight-ingredient formulation showed a 2.79-year reversal in a model-derived functional-age composite, compared with a 0.63-year reversal in the placebo group.
In a separate uncontrolled molecular pilot, DNAm PhenoAge relative to chronological age also decreased by approximately 4.1 years.
Still, researchers stressed that these changes did not indicate biological age reversal or improved healthspan.
“Nominal biomarker differences, mathematically derived age-equivalent scores, and the separate uncontrolled molecular pilot do not establish improvement in healthspan, effects of individual ingredients, synergy, or biological age reversal,” they wrote. “Future trials require documented concealed randomization, blinded assessment, prespecified primary endpoints, appropriate multiplicity control, verified formulation specifications, and longer safety follow-up.”
The questions this study raises, from cellular aging and NAD+ biology to the design of rigorous longevity trials, sit at the heart of the debate the sector will be working through at the Nutra Healthspan Summit 2026.
Source: Nutrients, 18(21), 3490. doi:10.3390/nu18213490. “Unlocking the Healthy Aging Potential of Novel NMN-Based Nutritional Formulations: Cardiopulmonary, Cognitive, and Aging-Related Outcomes in a 42-Day Open-Label Study.” Authors: Abe, T., Yoshida, N., Abdelhakim, M., & Abe, H.
