Towards personalized nicotinamide mononucleotide supplementation: nicotinamide adenine dinucleotide concentration

Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40 to 65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NAD{Delta}) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NAD{Delta} was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NAD{Delta} for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NAD{Delta} after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization. HighlightsO_LILarge interindividual variability in blood NAD response to NMN supplement was observed. C_LIO_LIThe median effective dose of blood NAD concentration improvement to achieve clinically significant improvement in functional outcome and quality of life was around 15 nmol/L. C_LIO_LIA close monitoring of NAD concentration change and personalized regimen of NMN supplements is needed. C_LI