Research Summary

NAD⁺ Precursors and Physical Function: Can NMN Improve Endurance?

Summary ID02-HA-RS-00056

Research Summary

Original Publication

Domain-specific effects of NAD⁺ precursors on fatigue and functional performance: a systematic review and network meta-analysis

Journal

Frontiers in Nutrition, .

Category
02Healthy Aging
Evidence
Systematic Review and Network Meta-Analysis
Summary Type
Latest

What Was Studied?

NAD⁺ precursors are being investigated for their potential effects on energy metabolism and physical function.

But physical function includes several different abilities. Endurance, muscle strength and the feeling of fatigue are not the same thing.

This 2026 systematic review and network meta-analysis examined them separately.

The researchers included 27 studies with 1,599 adults:

25 randomized controlled trials

2 quasi-experimental studies

Four NAD⁺-related compounds were studied:

NR: 12 studies, 459 participants

NMN: 7 studies, 370 participants

NADH: 6 studies, 224 participants

NAM: 2 studies, 546 participants

Participants ranged from 24 to 83 years and included both healthy adults and people with different health conditions.

Most interventions lasted 4–12 weeks.

The researchers examined endurance, muscle strength, perceived fatigue, cognitive performance, quality of life and sleep.

Key Findings

1. NMN showed the clearest positive result for endurance

The most promising finding involved aerobic capacity and endurance.

This analysis included 14 studies with 540 participants.

In the network meta-analysis, compared with placebo:

medium-dose NMN showed a significant improvement in endurance-related performance: SMD 0.66

high-dose NMN showed a larger estimated improvement: SMD 1.02

low-dose NMN did not show a significant benefit

In simple terms, the clearest positive functional signal in the entire analysis was for NMN and endurance-related performance.

This does not mean that NMN improved every aspect of physical fitness.

2. The endurance result was encouraging, but not definitive

The researchers also performed a more conventional pairwise meta-analysis.

Medium-dose NMN remained significantly associated with better endurance performance.

For high-dose NMN, the estimated benefit was still positive, but it narrowly missed conventional statistical significance.

Sensitivity analyses generally supported the direction of the findings, although removing some key high-dose studies weakened the effect.

So the results suggest a possible dose-related pattern, but they do not yet establish a simple rule that more NMN always produces a greater benefit.

3. Muscle strength did not significantly improve

The strength analysis included 20 studies with 619 participants.

No NAD⁺ precursor showed a statistically significant improvement in neuromuscular strength compared with placebo.

For NMN, the estimated effect was small and not statistically significant.

This is an important distinction.

Better endurance does not necessarily mean stronger muscles.

4. People did not consistently feel less tired

Perceived fatigue was evaluated in 16 studies involving 1,126 participants.

No NAD⁺ precursor produced a statistically significant improvement compared with placebo.

This shows another important difference:

objective physical performance and the subjective feeling of fatigue are not the same outcome.

A person may potentially perform better on an endurance test without necessarily feeling less tired.

5. Other outcomes were more mixed

Quality of life was assessed in 6 studies involving 722 participants.

Some NMN groups showed modest improvements, but the pattern was not consistent enough to establish a straightforward dose-response relationship.

For cognitive performance, 24 studies with 788 participants were analyzed. NADH produced the strongest positive signal, particularly in people with cognitive impairment.

However, this finding was sensitive to individual studies and should therefore be interpreted cautiously.

Sleep was evaluated in only 4 studies with 231 participants, and no significant overall improvement was found.

Why It Matters for Longevity

Maintaining endurance and physical capacity is an important part of healthy aging.

This study therefore adds something important to the broader NAD⁺ evidence.

Earlier research shows clearly that NAD⁺ precursors can change NAD-related biomarkers. This analysis suggests that NMN may also produce a measurable functional benefit in humans, particularly for endurance.

But the effect appears selective.

The study does not show that NMN improves overall physical fitness, prevents age-related decline or slows the aging process.

And because most trials were short, it cannot tell us whether these effects translate into better long-term health.

The next question is therefore not simply whether NMN changes NAD⁺ levels.

It is whether improvements in specific functions such as endurance can be reproduced in larger and longer trials — and whether they ultimately help people remain healthier and physically capable as they age.

Clinical Perspective

This study provides a useful lesson for longevity medicine:

NAD⁺ precursors do not appear to have one universal effect.

The clearest positive finding was for NMN and endurance-related performance.

At the same time, the analysis found no consistent improvement in muscle strength or perceived fatigue.

The study itself was relatively strong methodologically. It was prospectively registered in PROSPERO and conducted according to PRISMA-NMA standards.

Among the 27 included studies:

66.7% were rated at low overall risk of bias

22.2% had some concerns

11.1% were rated at high risk of bias

There are still important limitations.

The studies involved different populations, doses and treatment durations. Most lasted only weeks or a few months.

Also, many comparisons in a network meta-analysis are indirect. Instead of directly comparing two supplements in the same trial, researchers may compare each of them with a common placebo group and then estimate how they compare with each other.

This is scientifically useful, but it provides less certainty than large direct head-to-head randomized trials.

Key Takeaway

NMN shows promising human evidence for improving endurance-related performance. It has not yet been shown to broadly improve physical aging or extend healthy lifespan.

Reviewed and Summarized by

Monika Mikulicz-Pasler, MD, PhD

Monika Mikulicz-Pasler, MD, PhD

Specialist in Cardiology

Specialist in Internal Medicine

KCM Longevity Clinic

Source Publication

Title:
Domain-specific effects of NAD⁺ precursors on fatigue and functional performance: a systematic review and network meta-analysis
Authors:
Yixuan Gao, Shengnian Li, et al.
Journal:
Frontiers in Nutrition, September 2026.
Direct Link

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