Discussion
prediabetic, skeletal muscle
ADVERSE EVENTS, SECONDARY, OBESE, INSULIN SENSITIVITY
This randomized, double-blinded, placebo-controlled trial investigated the efficacy and safety of NMN supplementation with 300 mg, 600 mg, and 900 mg daily oral doses in healthy adults of 40-65 years old. The primary objective was to evaluate blood NAD concentration. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring six-minute walking test, blood biological age (Aging.Ai 3.0 calculator), HOMA-IR, and SF-36 scores.In mice, oral NMN can be quickly absorbed through the intestine, efficiently transported into blood circulation, and immediately converted into NAD at various tissues, such as blood, liver, and skeletal muscle [This trial showed that NMN supplementation is safe and well tolerated at up to 900 mg oral daily doses. There were no NMN treatment-related adverse events and dropouts. Lab parameters and physical examination did not show significant abnormal changes during the 60-day NMN treatments of all three doses. Our safety and tolerability observations are consistent with results of other published human clinical trials [It was reported that NMN supplementation in aged mice increased NAD concentrations and improved physical activity [Biological age has been gaining attention including epigenetic clock and blood biological age [One previous human clinical trial reported that NMN supplementation can increase the skeletal muscle insulin sensitivity of prediabetic and obese female adults [Previous human clinical trials reported that NMN supplementation had no effect on sleep quality [This trial was completed without dropout and by strictly following our trial protocol and GCP guidelines. We achieved positive results on many of our trial end points on efficacy and safety of NMN supplementation. However, an even higher number of participants and longer trial duration might have given even more insightful results of trial end points. Furthermore, additional biological age clocks and longer trial duration are needed to confirm our results. It will also be very interesting to conduct a larger study to assess the impact of gender on many of our trial end points since males and females could respond differently to NMN supplementation. Finally, our trial measured the total “NADIn conclusion, blood NAD concentration was significantly and dose-dependently increased during the NMN treatment. Oral administration of NMN up to 900 mg/day for 60 days was safe and well tolerated. NMN supplementation had a positive impact on the physical endurance and general health conditions of healthy adults as demonstrated in the significant improvement of six-minute walking test, blood biological age, and SF-36 scores. The 900 mg/day oral dose did not give significantly better efficacy than 600 mg/day dose.