Blood NAD did not fall with age in 1,068 healthy adults — it tracked cardiovascular disease instead, in a large human study

Edited by Samael A. Tejada, Founder & Editor-in-Chief

It is one of the most repeated sentences in longevity marketing: your NAD+ falls as you age. This study — over a thousand people, one careful morning blood draw each — measured the claim in blood, and the sentence did not survive contact with the data.

What did the study measure?

Arm 1 was cross-sectional: 1,068 adults (636 females, 432 males) gave a single standardized morning fasting sample, collected as dried blood spots and analysed with an enzymatic cycling assay measuring total whole-blood NAD — the sum of NAD+ and NADH, which closely approximates the NAD+ that dominates liquid blood. The method went through four-tier validation, including blinded cross-validation across three laboratories. Arm 2 was exploratory and longitudinal: within-person variability over a year and over seven days, real-world supplement users, and the blood response to daily oral NMN. The authors are explicit that the programme was not designed to test causality or whether supplementation treats any disease.

What happened to NAD with age — and with disease?

In healthy males, subgroup, significance-matrix and regression analyses all showed no significant association between whole-blood NAD and age. In healthy females, NAD increased significantly with age — a slope of 0.07 µM per year (sensitivity analyses gave 0.043 to 0.09), a subtle effect the team says probably requires a large female cohort to detect. Disease told a different story: in the pooled chronic-disease group (n=243), male NAD declined with age, and stratification showed the reduction was specific to cardiovascular disease — hypertension in particular — in both sexes; in women, disease erased the healthy age-related rise. The reduction persisted even though participants were on medications. The authors note a methodological moral: because hypertension becomes more common with age, cohorts that do not stratify for cardiovascular disease accumulate hypertensive participants and can manufacture a spurious 'age decline' — a plausible explanation for the inconsistent trajectories in earlier, smaller studies.

What did supplementation do to blood levels?

Boosters do move the blood number — that part of the marketing is true and also beside the point. Among healthy participants, the 22 self-reported NAD-booster users (10 men, 12 women) had significantly higher NAD than non-users, and 6 of the 22 (27%) reached 38 to 58 µM, roughly two to three times the unsupplemented range. In the longitudinal supplementation study, oral NMN at 1,000 mg per day raised whole-blood NAD from about 19-20 to about 51-56 µM with first-order kinetics (half-time 3.2 to 4.3 days). Within-person fluctuation over seven days was about 2 to 3 µM — large enough, the authors warn, for a single measurement in a small study to reflect daily noise rather than any real trajectory. None of this shows a clinical benefit from raising blood NAD, and the study tested no IV product: the supplementation arm used oral NMN.

What does this mean for NAD+ IV therapy?

Directly, it removes a premise. IV NAD+ and booster supplements are commonly sold to healthy adults as replacements for an age-related deficit. In the most accessible compartment — blood — this large, carefully validated programme found no such deficit in healthy people, and its authors conclude the data 'provide no broad rationale for NAD-boosting interventions' on that basis. Two honest boundaries apply. First, blood is not tissue: NAD decline has been reported in skeletal muscle, brain and skin, and this study does not contradict those findings — it shows blood dynamics do not necessarily mirror tissue dynamics. Second, association is not mechanism: the cardiovascular link does not prove low NAD causes hypertension, or that raising it would help. What the study does establish is that 'your blood NAD+ is falling with age, so refill it' is not a claim a clinic can make on current evidence.

Where the evidence stands

• Established: NAD is essential to redox metabolism and mitochondrial function, and oral precursors (NMN, NR) reliably raise whole-blood NAD — confirmed again here (1,000 mg/day NMN: ~19-20 to ~51-56 µM).
• Preliminary: The cardiovascular association: cross-sectional and observational, however large and well validated. It does not establish that low NAD causes cardiovascular disease or that raising NAD treats it.
• Absent: Any evidence in this programme that NAD-boosting — oral or IV — improves any clinical outcome, and any test of IV NAD+ at all. Also absent: a universal age-related decline in blood NAD among healthy adults — the study looked for it in 1,068 people and did not find it.