The NAD+ Audit: What Three Years of NAD/NMN/NR Hype Actually Did to Bloodwork

For research and educational use only. Not medical advice.

The NAD+ category has had the longest continuous hype cycle of any longevity compound in the last decade.

Bryan Johnson takes it. Peter Attia had taken it for years — his public position has evolved, but the years of public advocacy moved a large audience. David Sinclair's lab published the foundational rodent work in 2013. A Cell paper showed dramatic lifespan-extension effects in mice, and the community ran with it before the human translation had been tested.

Three years of community bloodwork reports later, the picture is more complicated than the marketing suggested.

This issue is the audit. What does the Tier 1 literature actually show? What do the anonymized community bloodwork reports show? And what should a 38-year-old founder-operator considering NMN or NR actually track before concluding the compound is doing anything?

NAD+ (nicotinamide adenine dinucleotide) declines with age. The mechanism behind most longevity claims: NAD+ is a cofactor for Sirtuin enzymes, which regulate metabolism, DNA repair, and stress response, and for PARP enzymes, which handle DNA damage repair. The theory is that declining NAD+ impairs both systems, and that restoring NAD+ via oral precursors restores some function.

NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are the two primary oral precursors. Both are supposed to raise intracellular NAD+ levels. Both have been sold on the back of the rodent evidence and the Sirtuin mechanism story.

Three questions the literature has been working through for a decade:

The first claim is solid. The second and third are where the audit gets honest.

The Tier 1 literature has produced real data. It is worth reading carefully, because the category has a habit of citing the circulating NAD+ finding as if it validates the downstream claims.

Circulating NAD+ and NAD+ metabolites rise with oral NMN and NR supplementation. This is reproducible across multiple trials. The 2023 Yoshino et al. Nature Aging study is the most rigorous recent example — NMN, 25 postmenopausal women with prediabetes, 10 weeks. Skeletal muscle NAD+ rose. Some insulin-signaling gene expression changes were detected. The 2020 Elhassan et al. NR study in older adults showed a similar circulating NAD+ rise. The compound does what it says at the first step.

Functional outcomes are a different story. The things operators care about — strength, metabolic rate, body composition, cognitive performance — are much less consistent across trials. Where effects are present, effect sizes are small. Several trials that documented circulating NAD+ rise found no meaningful functional endpoint change. The Yoshino 2023 study, often cited as the most positive recent human trial, found gene expression changes, not clinical metabolic outcomes.

The Sinclair rodent work showed dramatic results. The human data has not matched that signal. This was expected — rodent-to-human translation rates are notoriously poor in longevity research — but the marketing proceeded as if the human validation was already in.

The honest summary: the category has Tier 1 evidence for one claim (circulating NAD+ rises) and Tier 3 evidence (rodent, not human) for the primary claim (functional longevity benefit).

What follows is aggregated from anonymized community bloodwork reports across r/longevity, r/biohacking, and related longevity-focused community threads. This is Tier 4 data — uncontrolled, self-reported, unverified. It is useful for pattern recognition, not for conclusions.

The pattern across operators who tracked bloodwork before and after NMN or NR runs:

Circulating NAD+: Rises consistently. This tracks with the RCT literature. The compound is doing what it is supposed to do at the biochemical level.

Fasting glucose, HbA1c, insulin: Mixed. Some operators report modest improvement in fasting insulin, consistent with the Yoshino data signal. Most report no change. The baseline matters — operators with elevated fasting insulin at the start of a protocol report more movement than those with already-healthy metabolic markers.

Lipid panel: Generally unchanged across reports.

Inflammatory markers (CRP, IL-6): Generally unchanged at typical supplementation doses.

Biological age clocks (operators tracking Dunedin PACE or epigenetic clocks): Mixed results, small movements within measurement error for most. No consistent directional signal at the community level.

The bloodwork picture for a healthy 38-year-old: the compound raises circulating NAD+, and the downstream metabolic and functional effects do not reliably follow. If your baseline markers are already in a healthy range, it is hard to find a biomarker that moves meaningfully on NMN or NR.

The operators who report the clearest subjective benefit tend to describe better energy and sleep quality. Neither shows up well in standard bloodwork. Whether that is the compound, placebo, or the 12 other variables the typical longevity-stack operator is running simultaneously is the confound that a single-variable protocol would need to isolate. Most operators are not running single-variable protocols.

Issue 1 laid out a five-test framework for evaluating a compound before you build a stack around it. Run the NAD+ category through it.

Is there human RCT data? Yes, for circulating NAD+ rise. Functional outcomes have thinner human data.

Is the rodent-to-human translation validated? No. The Sinclair 2013 rodent findings have not been replicated at scale in healthy human adults. Human trials have been conducted in older adults or metabolically compromised populations.

Is the mechanism plausible? Yes. NAD+ coenzyme biochemistry is well-established. Sirtuins and PARP as NAD+-dependent enzymes is not contested. The mechanism story is real.

What is the evidence tier for the primary claim? The circulating NAD+ claim: Tier 1. The functional longevity claim: Tier 3 at best — rodent, not human, at the effect sizes the marketing implies.

What would it take to change your mind? A properly powered, randomized, placebo-controlled trial showing functional endpoints — strength, metabolic markers, cognitive performance — in healthy 35-to-45-year-olds running NMN or NR as a single variable. That study has not been published. Until it exists, the functional benefit claim in healthy middle-aged adults is a hypothesis, not a finding.

The category passes the mechanism test. It fails the human translation test for its primary claims.

If you are going to run NMN or NR and want to know if it is doing anything in your specific biology, the minimum tracking protocol:

Circulating NAD+ — the one thing that reliably moves. Get a baseline before you start and a retest at 8-to-12 weeks. If NAD+ is not rising, you are not getting the primary biochemical effect.

Fasting insulin and HOMA-IR — the metabolic marker most sensitive to NAD+ in the Yoshino data. If you have any insulin dysregulation at baseline, this is where you would expect to see signal first.

A functional benchmark — pick one: a 5-rep max on a compound lift, a 20-minute cardio benchmark, or a simple grip strength test. Bloodwork alone will not tell you whether the compound is producing functional change.

A structured subjective log — use the five-axis structure from Issue 4's n=1 framework: energy, sleep quality, cognitive clarity, mood stability, and recovery speed. Rate each on the same scale at the same time of day, not a general 1-to-10 number that drifts with whatever else is happening.

Run the protocol for 12 weeks. Hold all other variables constant as much as possible. If circulating NAD+ rises and the functional benchmarks and subjective axes do not move, you have a legitimate n=1 finding: the compound produced the expected biochemical effect and no detectable functional change in your specific biology. That is a real answer. Most operators never get one because they never set up to find it.

The NAD+ hype cycle was built on real biochemistry and genuine rodent evidence. The human translation has been more modest than the marketing implied. Circulating NAD+ rises — that part is well-supported. Functional outcomes in healthy middle-aged adults are inconsistent across the trial literature and in community bloodwork reports.

For a 38-year-old founder-operator with healthy baseline metabolic markers, the most honest framing is: known mechanism, real biochemical effect, contested functional significance. The compound is not snake oil. It is also not what the Sinclair rodent work implied it might be. Track the right markers before concluding it works or does not.

Issue 11 — The Edge Case Issue: Kisspeptin, GHK-Cu, and three compounds worth watching in H2 2026. Mechanism briefings, early-stage literature summaries, and what to track over the next six months if you want to be ahead of where the research is heading.

Colby

For research use only. Not medical advice. Compounds discussed are sold for research purposes; nothing here is a recommendation to use them on humans or animals. The publisher of The Compound has a financial interest in heroxbio.com, an RUO peptide vendor; this relationship may influence which compounds are covered. See the About page for full disclosure.