NAD+ Research

Martens CR, Denman BA, Mazzo MR, et al.

The landmark human trial establishing that oral NR supplementation safely and effectively raises NAD+ levels in middle-aged and older adults. In this 2×6-week randomized, double-blind, placebo-controlled crossover trial, NR supplementation significantly increased whole blood NAD+ metabolism without adverse effects. The study also found initial signals of benefit for blood pressure and arterial stiffness — two key markers of cardiovascular aging — suggesting that NAD+ restoration may have downstream vascular benefits beyond metabolic function. This was the first rigorous human pharmacokinetic study confirming that oral NR meaningfully translates to elevated tissue NAD+ levels in humans.

Igarashi M, Miura M, Williams E, et al.

A randomized, double-blind, placebo-controlled trial of 250mg daily NMN supplementation in healthy older men over 6–12 weeks. NMN significantly elevated whole blood NAD+ and NAD+ metabolite concentrations. There were nominally significant improvements in gait speed and left grip strength — physical performance measures relevant to age-related muscle decline (sarcopenia) — though these require validation in larger trials. The study confirmed NMN’s safety and tolerability while establishing that oral NMN effectively raises NAD+ in humans, mirroring findings seen in animal models that showed broad anti-aging benefits.

Orr ME, Garber G, Ramsay MT, et al.

A pilot randomized controlled trial examining NR’s effects on cognition in 20 older adults with mild cognitive impairment (MCI). NR at 1g/day significantly raised blood NAD+ levels and was well tolerated. While cognitive test scores did not significantly improve over 10 weeks — likely due to the small sample size and short duration — the study documented a reduction in epigenetic age as measured by PhenoAge and GrimAge clocks, a finding with implications for biological aging beyond cognition. The authors called for larger, longer-duration trials to properly assess NR’s cognitive potential. This study represents the state of the human clinical evidence: NAD+ elevation is consistently demonstrated; downstream functional benefits require larger trials to confirm.

PubMed Research Group

A review summarizing the growing human clinical trial pipeline for NMN, covering approximately a dozen trials underway as of 2023. The paper documents how NAD+ levels decline with aging and explains why restoration is theoretically significant — NAD+ is an essential substrate for sirtuins (longevity-associated enzymes), PARPs (DNA repair enzymes), and hundreds of redox reactions governing mitochondrial function. Animal studies show NMN mitigates oxidative stress, DNA damage, neurodegeneration, and inflammatory responses. The review is candid that while preclinical data is compelling, human trials remain early-stage and benefits beyond NAD+ elevation itself need further validation in larger controlled studies.

PubMed Research Group

A 2024 meta-analysis of 12 randomized controlled trials (513 participants) examining NMN’s effects on metabolic health markers. The analysis confirmed that NMN consistently and significantly elevates blood NAD+ levels — but found that most clinically relevant outcomes (fasting glucose, triglycerides, cholesterol) were not significantly different from placebo. The authors noted high risk of bias in several studies and suggested an exaggeration of NMN’s metabolic benefits may exist in the field. This is an important counterbalance to enthusiastic popular coverage — NAD+ elevation is real and consistent, but the clinical translation into measurable metabolic improvements in humans remains to be firmly established.