Nicotinamide Riboside (NR)

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.

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.

Funded by the company that sells the ingredient, with two of the three authors on its staff and the third the inventor of its licensed patents. Eight weeks, in healthy overweight adults. Every number reported is a blood or safety measurement, so the curve describes how much of the pill turns up, not how much it does.

The outcome is a marker in spit, not a symptom: nothing was reported about breathlessness, flare-ups, lung function or quality of life. The confidence interval runs from a 76 percent reduction to a 7.6 percent one, so the size of the effect is barely pinned down. Inflammation in the blood did not change, so the effect did not travel beyond the airway. Two authors are employees and shareholders of the company selling the compound.

Twenty people over four weeks, in a phase one safety trial. Its apparent improvement in Parkinson's symptom scores is not an efficacy finding: the authors traced it to participants on the compound having taken their levodopa more recently before assessment. Four weeks establishes the highest dose tested, not a dose anyone has certified for long-term use.

Men only, all obese and insulin-resistant, so this does not describe healthy or older users, and twelve weeks is not years. The mitochondrial half is a sub-study of the same forty men rather than an independent replication, and the two count once. The trial did not report whether NAD actually rose in these participants, so a failure of delivery cannot be fully separated from a failure of the mechanism.

Twelve men over 21 days is a mechanistic study, not an efficacy trial. What rose was the NAD metabolome, the family of related compounds including clearance products; the paper does not report that muscle NAD itself rose in proportion. The gene-expression changes ran downward in the energy and mitochondrial pathways, the opposite direction to the one the rationale predicts. One author invented the licensed patents behind the product and holds stock in the company selling it.

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.

Thirteen people is very small even for a crossover design, which makes the two positive results the fragile half and the long list of nulls the sturdy one. The fat-free mass change was one of many outcomes tested, exactly the setup in which a chance finding appears. Six weeks, in healthy overweight and obese volunteers.

Twenty-four people in a crossover design, six weeks per arm, all of them healthy, so this is an early tolerability and target-engagement study rather than a test of anything. NAD was measured in blood, which shows the pill is absorbed and metabolised, not that it reached the tissues where ageing is supposed to slow. The trial was investigator-initiated at a university with no declared competing interests, which sets it apart from most of this literature.