Written by the Nuvirox Research Team
Key Points
- A 2025 randomized, placebo-controlled trial tested nicotinamide riboside directly in people with long-COVID over 24 weeks.
- NAD+ levels rose substantially in the treatment group, but cognition, fatigue, sleep quality, and mood showed no significant benefit over placebo on the primary comparisons.
- An exploratory within-group analysis hinted at possible benefit after 10 weeks, which the study authors flagged as needing confirmation in larger trials.
Short answer: this is one of the most direct tests run on NAD+ supplementation, and the honest result is a clean null on the primary outcomes, with an intriguing but unconfirmed exploratory signal. Long-COVID is exactly the kind of condition — post-viral fatigue, brain fog, disrupted sleep, low mood — that NAD+ theories are often applied to, so it's genuinely useful that a real trial tested it directly rather than leaving it to speculation.
Why long-COVID and NAD+ were connected
Long-COVID commonly involves persistent fatigue, cognitive difficulties ("brain fog"), sleep disruption, and mood symptoms, alongside evidence of ongoing immune dysregulation and mitochondrial dysfunction in some patients. Because NAD+ precursors like nicotinamide riboside are thought to support mitochondrial function and reduce inflammation, researchers had a genuine scientific rationale for testing whether raising NAD+ levels could help these lingering symptoms — which is exactly what this trial set out to do.
What the trial actually tested
Published in 2025, this was a 24-week, double-blind, placebo-controlled, parallel-group trial with a placebo lead-in phase, conducted at a single center in Boston. Fifty-eight community-dwelling adults with long-COVID were randomized 2:1 to receive nicotinamide riboside (2,000 mg/day) for 20 weeks, or placebo for 10 weeks followed by NR for the remaining 10 weeks. The primary outcome was cognition, measured with three separate tools: the Everyday Cognition scale, the Repeatable Battery for the Assessment of Neuropsychological Status, and the Trail Making Test-B. Secondary outcomes included fatigue severity, sleep quality, and depression and anxiety symptoms using validated scales.
Study Snapshot — Wu et al., eClinicalMedicine 2025
| Design | Randomized, double-blind, placebo-controlled, PBO lead-in |
| N | 58 adults with long-COVID |
| Dose / duration | 2,000 mg/day nicotinamide riboside, up to 24 weeks |
| Cognition (primary) | No significant difference vs. placebo (p = 0.47-0.74) |
| Fatigue, sleep, mood (secondary) | No significant difference vs. placebo |
The result, stated plainly
NAD+ levels increased substantially within five weeks of starting NR, confirming the supplement did what it's supposed to do biochemically. But on every primary and secondary outcome measured against the placebo group — cognitive test scores, fatigue severity, sleep quality, anxiety, and depression — there was no statistically significant difference between the NR group and the placebo group. This is a genuinely important honest counterweight for anyone hoping NAD+ supplementation might address lingering post-viral symptoms broadly: in this trial, it didn't outperform placebo on any of the outcomes people care most about.
The exploratory finding, and why it doesn't overturn the main result
In a secondary, exploratory analysis, the researchers grouped all participants together during their first 10 weeks of actually taking NR (regardless of which randomization arm they started in) and compared their scores to their own baseline. In this within-group comparison, they found significant improvements from baseline in executive functioning, fatigue severity, sleep quality, and depression symptoms — improvements not seen during the placebo-only phase. This is worth reporting honestly, because it's a real part of the published data. But it's a fundamentally weaker form of evidence than the primary, placebo-controlled comparison: within-group changes over time can reflect natural symptom fluctuation, regression to the mean, or expectation effects, none of which a comparison to one's own baseline can rule out. The study authors themselves described this as supporting the need for larger, confirmatory trials — not as a finding that overturns the null primary result.
What this means if you have long-COVID
If lingering post-viral symptoms are affecting you, this trial's honest message is that a specific, well-tested NAD+ precursor protocol didn't show a clear benefit over placebo across cognition, fatigue, sleep, and mood in a rigorous 24-week study — the most direct test currently available. That doesn't mean nothing can help; long-COVID clinics, when accessible, use a range of approaches including graded activity pacing, symptom-specific treatment, and management of any measurable underlying issues (like postural orthostatic tachycardia or sleep disorders), often through a multidisciplinary team.
What NAD+ won't do
Based on this trial, an NAD+ precursor should not be expected to reliably resolve long-COVID fatigue, brain fog, sleep problems, or mood symptoms. It's reasonable to keep an eye on future, larger trials given the exploratory signal, but current evidence doesn't support a confident claim of benefit for this population.
How this trial was funded, and why that's worth noting
This study was supported in part by Niagen Bioscience, a manufacturer of nicotinamide riboside supplements, alongside academic funding sources including the MGH McCance Center for Brain Health and the Alzheimer's Association. Industry funding doesn't automatically invalidate a trial's findings, especially when the design is rigorous and pre-registered as this one was — but it's relevant context, and it makes the null primary result even more notable: a company-supported trial that still reported no significant benefit over placebo on its primary and secondary endpoints is a stronger, more credible negative finding than if an independent group with no stake in the outcome had found the same thing.
Frequently asked questions
Was this a well-designed trial?
Yes — it was randomized, double-blind, placebo-controlled, with a placebo lead-in phase and validated outcome measures, published in a peer-reviewed journal (eClinicalMedicine, part of The Lancet family). It's one of the more rigorous NAD+ trials run to date.
Does this mean NAD+ supplements don't work for anything?
No — this trial is specific to long-COVID symptoms in this study population. Other trials have found benefits for different outcomes (like blood pressure or walking distance in peripheral artery disease). Each condition and outcome needs its own evidence, and this is simply what the long-COVID evidence shows.
Should I stop taking NR if I have long-COVID and I'm already on it?
This trial didn't find safety concerns with NR at 2,000 mg/day over 24 weeks, so if you're taking it and tolerating it well, there's no specific reason from this trial to stop. But it also shouldn't be relied on as your main long-COVID treatment strategy.
What should I do if long-COVID symptoms are significantly affecting my life?
Seek care from a doctor familiar with post-viral syndromes, or a long-COVID clinic if one is accessible to you. They can screen for specific, treatable contributors and help build a management plan based on your particular symptoms.
FROM NUVIROX
Why we formulated NAD+ Restore
We built NAD+ Restore for general cellular energy support — not as a long-COVID treatment, since the most rigorous trial on that specific use found no significant benefit over placebo. Each 2-capsule serving delivers 500 mg of Nicotinamide Riboside Chloride, one of the two most-researched NAD+ precursors, within the dose range used in published human trials, alongside 150 mg trans-resveratrol and 50 mg quercetin, polyphenols studied alongside NAD+ pathways for cellular health support. 10 mg of galactomannans from fenugreek is included to support absorption.
Backed by a 60-day money-back guarantee — long enough to actually evaluate it the way the research says you should.
Learn more about NAD+ Restore →The bottom line
Long-COVID is one of the few conditions where NAD+ supplementation has been tested in a genuinely rigorous randomized trial — and the honest result is a null primary finding, softened only by an exploratory signal that needs further study. If you're navigating long-COVID, that's useful information for setting expectations, and it points toward working with a knowledgeable clinician rather than treating an NAD+ precursor as a fix. Related reading: lingering fatigue after being sick and NAD+ and the immune system.
References
- Wu CY, Reynolds WC, Abril I, McManus AJ, Brenner C, González-Irizarry G, et al. Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial. eClinicalMedicine. 2025. PMID: 41357333.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is for informational purposes only and is not a substitute for professional medical advice.