Towards personalized nicotinamide mononucleotide (NMN) supplementation: nicotinamide adenine dinucleotide (NAD) 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 Δ ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NAD Δ 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 Δ 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 Δ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization. Highlights Large interindividual variability in blood NAD response to NMN supplement was observed. The 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. A close monitoring of NAD concentration change and personalized regimen of NMN supplements is needed.