The NMN and NAD+ precursor research landscape has moved quickly over the past two years, with several trials publishing findings that refine — and in a few cases meaningfully complicate — the picture that earlier research established. This update covers the most significant new findings from 2024–2025, what they add to our understanding of NAD+ supplementation, and where the research is heading next.
As with any research update in a fast-moving field, these findings should be read in context with the fuller evidence base reviewed in the articles on what human clinical trials on NMN actually show and what human clinical trials on NR actually show. Individual trials rarely overturn established findings; they add nuance and extend the picture.
Contents
- The NMN vs. NR vs. Nicotinamide Head-to-Head Trial
- NMN and Blood Pressure in Older Adults
- NR in Werner Syndrome: A Rare Disease Window Into Accelerated Aging
- NR in Long-COVID: A Null Finding Worth Noting
- A 2025 Meta-Analysis: Muscle Function in Older Adults
- Ongoing and Upcoming Trials to Watch
- The Overall Trajectory of the Evidence
The NMN vs. NR vs. Nicotinamide Head-to-Head Trial
One of the most practically useful questions in the NAD+ precursor space — which compound raises NAD+ most effectively? — was addressed by a significant head-to-head trial published by Christen et al. (2025) in Nature Metabolism. The study, conducted by researchers at Nestlé Health Science and Swiss research institutions, directly compared NMN, NR, and nicotinamide (Nam) in healthy adults over 14 days of supplementation.
The headline finding: NMN and NR approximately doubled circulating NAD+ levels after 14 days of supplementation, while nicotinamide only increased NAD+ acutely at four hours after supplementation but had no significant sustained effect at 14 days. The conclusion that NR and NMN are comparable in their ability to chronically increase baseline whole-blood NAD+ levels, while nicotinamide provides only an acute transient effect is practically important: it directly addresses the ongoing debate about whether NMN offers meaningful advantages over NR, and it resolves the nicotinamide question decisively in favor of the two precursors over plain nicotinamide for sustained NAD+ elevation.
An additional finding from this trial has generated interest in gut biology circles: the data show that NMN and NR modulate gut bacteria to increase the concentrations of short-chain fatty acids (SCFAs), which are believed to strengthen the gut barrier and reduce systemic inflammation. The gut microbiome dimension of NAD+ precursor supplementation is emerging as a potentially important secondary mechanism distinct from the primary sirtuin and mitochondrial pathways — and one that may partly explain why the metabolic benefits of NR and NMN in human trials are sometimes larger than the direct NAD+ effects alone would predict.
NMN and Blood Pressure in Older Adults
A 2025 trial examining NMN and blood pressure in a specific older adult subgroup added an important piece to the cardiovascular evidence picture. The findings suggest NMN may serve as a viable avenue for blood pressure management in adults with elevated blood pressure, particularly for systolic blood pressure among individuals aged 60 and older. This age-specific finding is consistent with the broader pattern across NAD+ precursor trials: cardiovascular effects are most pronounced in people with elevated baseline values, and older adults show larger responses than younger ones — the pattern that the foundational Martens NR trial established is extending to newer NMN-specific research.
NR in Werner Syndrome: A Rare Disease Window Into Accelerated Aging
A trial from Chiba University in Japan, published in Aging Cell in June 2025, examined NR supplementation in patients with Werner syndrome — a rare genetic disorder that causes dramatically accelerated aging, with patients typically developing cataracts, gray hair, diabetes, and skin ulcers from their twenties. The researchers found that Werner syndrome patients have depleted NAD+ levels, and that NR supplementation in this population produced measurable benefits in this pilot randomized, double-blind, placebo-controlled trial.
This finding is worth attention for two reasons. First, Werner syndrome is one of the clearest human models of accelerated aging available — it essentially compresses decades of NAD+ depletion and aging biology into a shortened lifespan. Demonstrating NR efficacy in this population provides compelling disease-context evidence for the NAD+ decline → aging outcomes mechanism. Second, as the commentary on this trial correctly notes, the results do not straightforwardly generalize to healthy adults — Werner syndrome involves a specific, severe NAD+ depletion mechanism from a known genetic defect that differs from normal aging. The finding supports the biological framework; it is not evidence that NR produces equivalent effects in generally healthy people with normal aging trajectories.
NR in Long-COVID: A Null Finding Worth Noting
A 24-week randomized controlled trial published in eClinicalMedicine (The Lancet) in late 2025 examined NR at 2,000 mg/day in patients with long-COVID — a condition characterized by cognitive difficulties, fatigue, and immune dysregulation that has attracted interest as a potential NAD+ depletion context. The trial enrolled 58 community-dwelling participants with long-COVID and evaluated cognitive and symptom outcomes. The findings suggest that increasing NAD+ levels with NR does not meaningfully improve cognitive functioning in long-COVID.
This null cognitive finding in a long-COVID population is an honest part of the current evidence picture. It joins the Dollerup and Remie metabolic null findings as a reminder that NAD+ elevation does not uniformly produce measurable functional improvements in every disease or condition studied. The complexity of long-COVID — involving multiple overlapping pathologies beyond NAD+ depletion — likely explains the absence of a cognitive signal, but the trial result deserves acknowledgment rather than minimization.
A 2025 Meta-Analysis: Muscle Function in Older Adults
A 2025 meta-analysis pooling data from 10 randomized controlled trials of NMN and NR in older adults examined muscle mass, muscle strength, and physical function outcomes. The analysis found no benefit for muscle mass, strength, or physical function in older adults across the pooled data.
This finding requires careful contextual interpretation. The meta-analysis pools trials that varied substantially in dose, duration, population characteristics, and outcome measures — including some trials not specifically designed to measure muscle outcomes. The Yi et al. (2023) trial, which found significant strength and endurance improvements at 1,000 mg/day alongside exercise in older adults, represents one of the stronger individual trials in this domain and may be obscured in a pooled analysis by smaller trials at lower doses or in less suitable populations. Meta-analyses of this literature are still limited by the relatively small number and heterogeneous design of included trials. The finding is a signal for caution about overstating NMN’s muscle effects; it is not a finding that the Yi trial’s results were wrong.
Ongoing and Upcoming Trials to Watch
Most of the upcoming human trials involving NAD+ supplementation revolve around neurodegenerative disorders like Alzheimer’s and Parkinson’s disease. There is also a handful of trials testing the effects of boosting NAD+ on obesity and type 2 diabetes. Whether healthy and fit individuals will benefit from NAD+ may be answered with a new and upcoming trial.
The neurodegenerative disease trials are the most eagerly anticipated in the NAD+ field. The mechanistic case for NAD+ in Alzheimer’s and Parkinson’s is among the most developed in the application landscape, and larger, better-powered trials in these populations would provide the kind of disease-outcome evidence that could significantly strengthen the overall NAD+ supplementation rationale. Results from these trials are expected to begin appearing in the 2025–2027 timeframe.
The TAME trial (Targeting Aging with Metformin) — the large randomized trial testing whether metformin slows biological aging in healthy older adults — continues its enrollment and follow-up. While not an NMN trial, its results will provide important context for the broader question of whether AMPK-activating compounds produce measurable longevity benefits in healthy adults, which has direct implications for how to interpret berberine’s and NMN’s potential in this context.
The Overall Trajectory of the Evidence
The 2024–2025 research period has produced several important clarifications alongside the new findings. The head-to-head NMN vs. NR vs. nicotinamide comparison confirms that NMN and NR are functionally equivalent for sustained NAD+ elevation and both are meaningfully superior to plain nicotinamide for this purpose. The blood pressure finding in older adults reinforces the cardiovascular application. The Werner syndrome NR results strengthen the biological framework even while not generalizing to healthy aging.
At the same time, the null cognitive finding in long-COVID and the muscle function meta-analysis serve as honest reminders that the field has not yet demonstrated broad, reliable functional benefits across all applications and populations. The evidence base is maturing — it is no longer just pharmacokinetics and safety; it now includes multiple functional outcome trials with real results in both directions. That is progress, even when the results are mixed.
The most significant gaps remain: no large, long-duration trials in healthy adults; no lifespan or healthspan endpoint trials that could directly demonstrate longevity benefits; and limited head-to-head comparison between NAD+ precursors and established lifestyle interventions on comparable functional outcomes. These are the trials that will ultimately determine where NMN and NR sit in the hierarchy of longevity interventions. They are coming, but they are not yet here.