In a placebo-controlled, double blind clinical trial to assess the effect of NMN and aerobic sport. We showed that oral NMN supplementation (500 mg/day or 1000 mg/day) for 30 days can significantly increase whole-blood NAD+ levels in a dose-dependent manner, and aerobic sport can further increase NAD+ levels both in control group and NMN treated group.
In the 1000mg/day NMN treated group, we found some subjects non-response towards the NMN administration. We then performed bulk RNA sequencing for the peripheral blood mononuclear cells (PBMCs) of four responders and non-responders from the 1000 mg/day group and mapped the expression levels of genes involved in NAD+ metabolism. Responders featured a higher expression of NAD+-synthesizing enzymes such as IDO2, NAPRT, NMNAT2 and NAMPT, as well as a nucleoside transporter SLC29A3; while non-responders have more expressions of NAD+-consuming enzymes such as SIRT4, PARP14, CD38 and PARP2 etc.
Study design for evaluating effects of oral NMN supplementation. Daily supplementation of 500 mg (n= 19) and 1000 mg NMN (n= 22) for 1 month significantly increased the venous NAD+ concentration compared to the placebo group (n= 25). Error bars represent SD of the respective group. Significance was determined using one-way ANOVA analysis, * p< 0.05, ** p< 0.01, *** p< 0.001, **** p< 0.0001.
Study design for evaluating effects of oral NMN supplementation in combination with moderate level of sport. Effect of aerobic sport with oral NMN supplementation (n= 20) and aerobic sport alone (n= 21) on venous NAD+ level. Error bars represent SD of the respective group. Significance was determined using t-test for, * p< 0.05, ** p< 0.01, *** p< 0.001, **** p< 0.0001.
Relative expression level of NAD+ metabolism-related genes for subjects responsive and inert to NMN supplementation. (a) Whole blood NAD+ levels measured from NMN responders and non-responders after 30 days of 1000 mg/day NMN supplementation. (b) The expression profile of NAD+ metabolism-related genes were obtained by sequencing PBMCs isolated from venous blood at the end of the clinical study for 4 subjects responsive and inert to NMN supplementation based on measured NAD+ levels. Error bars represent SD, significance was calculated using t-test for (a), **** p < 0.0001.
