NMN (Nicotinamide Mononucleotide)

The search closed in October 2025, so anything published since is missing. The human trials measured such different things that they could not be pooled, which makes the null conclusion a reading of the literature rather than a calculated number. The review also found no outcomes trial at all of intravenous NAD, which is sold commercially.

Between two and five trials per outcome, so a real effect could still be hiding in an evidence base this thin. What argues against that is how closely the trials agreed with each other: they scattered almost not at all around the null. The nicotinamide riboside results could not be pooled and ran in both directions, longer six-minute walks in peripheral artery disease against worse physical performance scores in mild cognitive impairment.

The over-60 systolic figure is a subgroup finding inside a 349-person pool, which generates a hypothesis rather than confirming one. The analysis assumed one true effect across trials spanning 250 to 2,000 mg a day and 14 days to 24 weeks, which narrows the confidence interval by assumption rather than by evidence. No trial in the pool measured a heart attack or a stroke; the reading on the cuff is the entire result.

Eight trials and 342 people in the metabolic pool, so a modest real effect could be missed. Participants were mostly healthy and not diabetic, which is the population least likely to show a metabolic improvement and leaves the question open in people who already have metabolic disease. Several pooled trials ran fourteen days, far too short for HbA1c, which reflects about three months of blood sugar, to move at all.

The longest trial in the pool ran 24 weeks. Ten trials contributed to the safety analysis, too few to catch a harm affecting one user in a thousand, and most were funded by manufacturers, who historically under-report adverse events. The four-week study establishes the highest dose formally tested, not a dose any regulator has certified. No trial measured a cardiovascular event.

Blood is not tissue. The one trial that biopsied muscle to check delivery found NAD-related metabolites raised there, including the products of clearing the compound away, while the muscle's mitochondria performed no differently. In mice, oral doses of both compounds are taken apart into plain nicotinamide in the liver; the same compounds injected arrive intact.

The notification list records that the FDA responded to each submission on a given date. It does not say whether the response objected, and the agency does not approve dietary ingredients in any case. The submission and response dates come straight from the FDA's own published list; the date of the reversal itself comes from legal and trade reporting, because the agency's letter could not be retrieved.

Open-label, fourteen days, healthy adults, so this establishes a route rather than an outcome. The bacterial step was shown in fermentation vessels seeded with human gut microbes rather than watched in the participants themselves. Nine of the twelve authors work for Nestle, whose health science arm sells NAD-related products.

A narrative appraisal rather than a systematic review, so its selection of evidence cannot be reproduced by anyone else. Its authors include the group running the pharmaceutical NMN trials, which makes this the field appraising itself. Its phrase about raising NAD in blood and some tissues is deliberately narrower than the marketing and should not be read as delivery throughout the body.

Fourteen days and open-label, so the comparison is of absorption, not of benefit, and neither arm measured anything a person would feel. Nine of the twelve authors work for Nestle, whose health science arm sells NAD-related products, which is worth noting mainly because the result cuts against both branded products rather than favouring either.

This was one result among many in a study built to map how fast NAD is made and consumed across tissues, not a comparison it was powered to make. It tracks where the molecule goes, not whether anything follows from its arriving. No equivalent measurement has been made in people.

Thirty-six people is small for a vascular endpoint, so this cannot rule out a modest real effect. The paper's own closing line says NMN showed potential in alleviating arterial stiffness, which is a firmer reading than its numbers support. The work was done in the laboratories of a Japanese supplement company, though the authors declare no competing interests.

Mice, at 100 to 300 mg of NMN per kilogram of body weight a day. A 70 kg adult swallowing a standard 250 mg capsule takes about 4 mg per kilogram, and body-surface scaling narrows that gap without closing it. More was not better even in the mice: the higher-dose group moved around less and reared less than the lower-dose one. The senior author holds NMN patent-licensing interests.

Fourteen men, one dose each, and sixty minutes of blood sampling, so this describes the first hour and nothing about daily use or any outcome. The authors could not say where the extra 2PY and 4PY came from. All three work for Meiji Holdings, which sells NMN.

The cohorts were stable cardiac patients, not supplement users, so the absolute risk does not transfer to anyone taking a capsule. The human half is observational, though 4PY at physiological levels switched on the vascular inflammation machinery in mice and a genetic analysis across 106,000 people pointed the same way. Every trial of these supplements that measured the metabolites ran weeks to months, far too short for a heart attack to be an endpoint.

Twenty-five postmenopausal women with prediabetes who were overweight or obese, at a single site, for ten weeks. The endpoint is insulin sensitivity, a metabolic measure, not an ageing or longevity one. The senior authors hold NMN patent-licensing interests through their university. Later pooled analyses of the wider NMN literature found no metabolic effect, in populations that were mostly not metabolically ill.

Whether NMN improved insulin handling in a 25-person trial is disputed: the women given it began with less than half the liver fat of those on placebo, and liver fat is something NMN is meant to act on. A trial that size cannot settle it.

Twenty people per arm across four arms, analysed per protocol rather than by intention to treat, in healthy adults over sixty days. The first author works for an NMN company and two co-authors for NMN raw-material producers. The trial's biological-age outcome comes from a free online calculator rather than a validated clinical instrument.

Whether NMN helps people walk further is unsettled. The one trial that found it was run by companies selling NMN and tested healthy middle-aged adults; a later pooling in older adults did not repeat it.

A secondary outcome is exploratory unless it was named in advance and corrected for testing many things at once, and this paper reports no such correction. Three of the four authors work for Meiji Holdings, which sells NMN. The authors highlight that walking-time changes tracked changes in blood NAD, 2PY and 4PY, which is an association inside one trial rather than evidence that raising NAD caused the walking.