Consistent finding across trials

Dose-dependent RCT — blood NAD+ elevation, physical performance & health scores (n=80)

PubMed ID: 36482258 · Yi et al. · GeroScience (2023) · n=80 · 300, 600, 900 mg/day · 60 days · NCT04823260

NMN supplementation at all three doses (300, 600, 900 mg/day) significantly increased blood NAD+ concentrations versus placebo. Clinical efficacy on blood NAD+ and physical performance (6-minute walking test) peaked at 600 mg/day. All three NMN groups showed statistically significantly better SF-36 health scores versus placebo at day 30 and day 60 (p<0.05) — indicating improved subjective health and wellbeing. NMN was safe and well tolerated up to 900 mg/day.

RCT — NMN maintains walking speed and improves sleep quality in older adults (n=60)

PMC11336149 · Saito et al. · AGE (2024) · n=60 · 250 mg/day · 12 weeks · UMIN000047871

After 12 weeks, the NMN group had a significantly shorter 4-metre walking time than the placebo group — while the placebo group's walking speed significantly declined over the same period (p<0.001). Blood NAD+ and its metabolites were significantly higher in the NMN group. The NMN group also showed significantly improved sleep quality (lower Daytime Dysfunction and Global PSQI scores). A significant negative correlation was observed between the change in walking time and the change in blood NAD+ levels — directly linking NAD+ restoration to physical function maintenance.

RCT — NMN reduces LDL, body weight, and diastolic blood pressure in middle-aged adults

Double-blind, placebo-controlled · n=36 healthy middle-aged participants · 125 mg twice daily · 12 weeks

NMN supplementation significantly reduced total LDL cholesterol, non-HDL cholesterol, body weight, and diastolic blood pressure. Arterial stiffness was reduced, suggesting NMN supplementation potentially improves vascular health in middle-aged adults. NMN intervention specifically reduced diastolic blood pressure in participants with higher-than-mean blood glucose levels — suggesting particular benefit in metabolically challenged individuals.

RCT — NMN enhances aerobic capacity in amateur runners

J Int Soc Sports Nutr (2021) · PubMed ID: 34238308 · Randomised, double-blind · 300 mg/day · 12 weeks

NMN supplementation (300 mg/day for 12 weeks) significantly improved aerobic capacity versus placebo in healthy adult runners — increasing VO2 max and endurance on the treadmill test. Blood NAD+ levels rose substantially, confirming bioavailability. Aligns with rodent data showing NMN increases muscle NAD+ and SIRT1 activity, enhancing mitochondrial function and fatigue resistance.

Evidence quality note: NAD+ elevation in humans is consistently confirmed across multiple RCTs — this is not in doubt. Physical performance benefits (walking speed, aerobic capacity, muscle function) are now supported by multiple positive RCTs in older adults. However, two meta-analyses (PMC11557618; PubMed 39116016) found no significant overall effect of NMN on fasting glucose, HbA1c, or lipid profiles across all trials reviewed — suggesting metabolic benefits may be most pronounced in those with elevated baselines rather than healthy adults. The 500 mg dose in this formula is within the range of doses showing positive physical performance and NAD+ elevation results. NMN is currently restricted as a dietary supplement in the US following FDA drug designation — it remains legally available as a supplement in the UK and Europe.

NAD+ declines ~60% from early to late adulthood across multiple tissues

Multiple population studies · Plasma, skin, liver, and muscle NAD+ measured across age groups

Plasma NAD+ concentrations decline approximately 60% from early to late adulthood, with parallel declines in skin, liver, and muscle tissue. This systemic reduction limits the activity of sirtuins — the longevity-linked enzymes that regulate stress responses, metabolic efficiency, and DNA repair. Healthy ageing and muscle function are positively associated with NAD+ abundance in humans (Janssens et al.), providing direct human correlational evidence for the importance of maintaining NAD+ levels.

Sirtuins, PARPs, and longevity — the NAD+ consumer enzymes

Multiple mechanistic reviews · Song et al. Advances in Nutrition (2023) · PubMed ID: 37619764

Sirtuins use NAD+ to perform deacetylation reactions that regulate gene expression, mitochondrial biogenesis, and inflammation suppression. SIRT1 activation is linked to improved lifespan and healthspan in every model organism studied. PARPs consume NAD+ during DNA repair — declining NAD+ means declining DNA repair capacity, directly contributing to genomic instability. CD38 (an immune enzyme whose activity increases with age) is the largest single consumer of NAD+ in the ageing body, representing a "NAD+ leak" that outpaces biosynthesis. NMN bypasses the rate-limiting NAMPT step to directly restore the NAD+ available to all three enzyme systems.