Trial finds nicotinamide riboside supplementation raises NAD+ levels and improves fatigue and sleep, hinting at healthspan links.
Long COVID remains a stubborn reminder that viral infections can echo long after the acute phase has passed; for many, the symptoms are less a coda than a lingering refrain. Fatigue, disrupted sleep, cognitive fog and low mood continue to affect an estimated one in five adults who have had COVID-19, blurring the boundary between infection and chronic condition.
Now, a clinical study published in eClinicalMedicine (The Lancet) suggests that supporting the body’s cellular energy systems may help some of those affected. Led by Dr Edmarie Guzmán-Vélez, Assistant Professor in the Department of Neurology at the Robert Wood Johnson Medical School and the Center for Health Aging Research (CHAR) at the Institute for Health, Rutgers University and funded by the McCance Center for Brain Health at Mass General Hospital and Niagen Bioscience, the trial is the first to evaluate nicotinamide riboside (NR) – a specialized form of vitamin B3 – in individuals experiencing persistent symptoms after COVID-19 infection.
The 24-week, randomized, double-blind, placebo-controlled trial involved 58 participants who received either 2,000 mg per day of Niagen NR or placebo. While between-group differences were not statistically significant, participants taking NR showed within-group improvements in fatigue severity, depressive symptoms and sleep quality after ten weeks of supplementation. NAD+ levels rose up to 3.1-fold, confirming the molecule’s restoration in whole blood [1].
Longevity.Technology: Long COVID has become an unwelcome case study in what happens when the machinery of cellular resilience falters – energy wanes, cognition blurs and recovery stalls. For longevity science, that makes it more than a post-viral syndrome; it is a living laboratory for healthspan under pressure. This study hints that restoring NAD+ may not simply top up metabolic reserves but could help cells regain their composure after insult, offering a glimpse into how biological systems might be coaxed back toward equilibrium. Recovery, after all, is the other side of longevity – maintaining the capacity to rebound from stress as years and challenges accumulate. While the trial’s modest scale and lack of statistical separation from placebo remind us that enthusiasm should be tempered with rigor, the signal of improvement is intriguing. It suggests that interventions designed for healthy aging might also accelerate restoration after disease – a convergence that brings geroscience ever closer to the clinic, one careful step at a time.
The biology of recovery
Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) to give it its proper name, affects multiple organ systems, manifesting as fatigue, breathlessness, ‘brain fog’ and mood disturbance. Emerging evidence points to mitochondrial dysfunction, immune dysregulation and NAD+ depletion as common denominators. NAD+ – nicotinamide adenine dinucleotide – is essential for cellular energy production and DNA repair, yet it declines with both age and illness.
Dr Charles Brenner, Chief Scientific Advisor to Niagen Bioscience and study co-author, said the results were a “compelling indication” that NAD+ biology can be effectively targeted in conditions of metabolic stress such as long COVID.
“Long COVID presents with a wide range of symptoms because coronaviruses disturb NAD+ and thereby disturb multiple organ systems,” he said. “What is encouraging is that despite variability among patients, we observed consistent signals of improvement with elevation of NAD+ levels. This suggests that restoring the NAD+ system can restore multiple biological pathways implicated in long COVID – including mitochondrial function, inflammation, and cellular repair.”
Dr Guzmán-Vélez noted that although between-group statistical differences were not achieved, “We saw encouraging within-group improvements in fatigue, sleep, and mood… These findings suggest that restoring NAD+ remains a promising avenue for recovery and advancing our understanding of how to help individuals affected by long COVID. More research is needed to confirm and expand on these findings.”
A signal for further investigation
Niagen NR was well-tolerated, with no significant difference in adverse events between groups [1]. The investigators attributed the lack of between-group significance to the small sample size and high dropout rates due to reinfection, relocation or medication changes – familiar hurdles in long-term trials conducted during a global pandemic.
Rob Fried, Chief Executive Officer of Niagen Bioscience, said: “These findings demonstrate that ten weeks of Niagen NR supplementation increased NAD+ levels and improved long COVID symptoms of fatigue, sleep quality, and depression, compared to symptoms before treatment. As part of our mission to advance the science of cellular health, we are pleased to see Niagen NR used in research exploring the lasting impact of COVID-19 and look forward to future studies that further our understanding of NAD+ augmentation in recovery and resilience.”
Speaking to Longevity.Technology, Dr Andrew Shao, SVP of global scientific and regulatory affairs at Niagen Bioscience, said the results strengthen the case for NAD+ restoration as a strategy to help cells rebound from physiological stress – whether triggered by infection, inflammation or aging itself.
“Long-COVID continues to affect millions, with no proven treatments for its hallmark symptoms. The findings from this first-of-its-kind clinical trial underscore the importance of NAD+ restoration in supporting cellular recovery following prolonged physiological stress, as seen in long-COVID,” he said. “By safely elevating NAD+, Niagen NR supplementation may represent a promising, well-tolerated approach to re-establishing the cellular energy balance and repair mechanisms that are often disrupted in chronic post-viral or inflammatory states. While more research is needed, these results add to a growing body of evidence suggesting that NAD+ repletion could play a meaningful role not only in recovery from long-COVID, but also in restoring vital cellular energy, reducing fatigue, improving sleep quality, and alleviating depressive symptoms – all key factors in healthy aging.”
Healthspan under pressure
For the longevity field, the implications reach beyond COVID. Long COVID may represent an accelerated form of the biological wear seen in aging, where immune over-activation, oxidative stress and mitochondrial decline converge to diminish cellular resilience and reduce the body’s capacity for renewal. Studying interventions that help patients recover from such post-viral fatigue syndromes could therefore illuminate broader strategies to preserve function and delay physiological decline.
If NAD+ restoration can help cells recover from metabolic stress, it may also inform approaches to sustaining energy balance in older adults or those with chronic inflammatory conditions. The concept of healthspan – not merely the years lived, but the years lived well – depends on resilience: the ability to withstand and rebound from stressors. In that sense, recovery and aging are points on the same continuum.
A measured optimism
The study does not claim victory; rather, it contributes a careful piece to a growing puzzle linking cellular energetics with human resilience. Its modest scope demands replication, yet it hints that rebuilding NAD+ could offer a route toward restoring biological function after infection and perhaps, in time, slowing the attrition of healthspan itself. The longevity community will watch closely as larger, better-powered trials probe whether cellular recovery can indeed be harnessed as a pathway to longer, healthier lives.
[1] https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00567-X/fulltext
