NAD+ Supplement Shows Early Promise for Long COVID Fatigue and Brain Fog in Clinical Trial
核心洞察
A randomized controlled trial at Massachusetts General Hospital tested nicotinamide riboside (NR (搜索)), a form of vitamin B3, in 58 long COVID (搜索) patients over 24 weeks to boost NAD+ levels and improve symptoms.
While primary cognitive outcomes showed no significant differences between treatment and placebo groups, exploratory analyses revealed improvements in self-reported fatigue, sleep, and depressive symptoms after 10 weeks of NR (搜索) supplementation.
The study safely demonstrated that high-dose NR (搜索) (2,000 mg daily) can boost NAD+ levels in long COVID (搜索) patients, with only mild side effects reported and few discontinuations due to adverse events.
Researchers at Massachusetts General Hospital have completed the first randomized controlled trial testing nicotinamide riboside (NR (搜索)), a form of vitamin B3, as a potential treatment for long COVID (搜索) symptoms. The study, published in eClinicalMedicine, found mixed but promising results for addressing persistent fatigue and cognitive issues affecting millions of COVID-19 (搜索) survivors worldwide.
The 24-week clinical trial, conducted between August 2021 and September 2023, enrolled 58 people with long COVID (搜索) and tested whether boosting NAD+ levels through supplementation could improve cognitive function and ease common symptoms. NAD+ is a molecule present in all human cells that is essential for energy production, immune function, and inflammation control.
Trial Design and Patient Population
Lead author Chao-Yi Wu, PhD, OT, from the Department of Neurology, and senior author Edmarie Guzmán-Vélez, PhD, of the Department of Psychiatry at Mass General Brigham (搜索), designed the study as a double-blind, placebo-controlled trial. Participants were randomly divided into two groups: 37 people started taking 2,000 mg of NR (搜索) daily for 20 weeks, while 21 began with a placebo for 10 weeks before switching to NR for the next 10 weeks.
The researchers measured NAD+ levels through blood tests and assessed participants using surveys and cognitive tests evaluating memory, sleep, fatigue, and mood at baseline, 10 weeks, and 20 weeks. However, only 18 people completed the full 22-week protocol, with others leaving due to reinfection with COVID-19 (搜索), relocation, medication changes, or possible side effects.
Primary Outcomes Show Limited Differences
When comparing the two groups directly, the study did not demonstrate major differences in thinking or memory scores, which were the primary focuses of the investigation. Other symptoms including fatigue, sleep quality, and mood also showed no significant differences between the treatment and placebo groups in the main analysis.
"When we compared the two groups, we didn't see major differences in thinking or memory scores, which were the main focuses of the study," Wu explained. "Other symptoms like fatigue, sleep and mood also didn't show big differences between groups."
Exploratory Analysis Reveals Potential Benefits
Despite the lack of significant primary outcomes, exploratory post hoc analyses with a larger sample size of all participants who took NR (搜索) for at least 10 weeks revealed more encouraging results. Researchers observed improvements in self-reported fatigue, sleep, and depressive symptoms after 10 weeks of NR supplementation compared to baseline measurements.
Additionally, some participants performed better on executive functioning tasks, which involve mental skills such as planning, organizing, and switching between tasks. "This suggests that some people may benefit from the use of NR (搜索), even if the overall results didn't show clear differences between groups," Wu noted.
Safety Profile and Side Effects
The study demonstrated that high-dose NR (搜索) supplementation safely boosted NAD+ levels in long COVID (搜索) patients. The most common side effects were mild, including easy bruising and rash. No serious adverse events were reported, and only a few participants discontinued the study due to side effects.
Clinical Implications and Future Directions
Long COVID (搜索) affects an estimated 400 million people worldwide, yet its underlying causes remain unclear. The current findings suggest that boosting NAD+ levels may play a role in easing symptoms like fatigue and poor sleep for some patients, pointing to a promising direction for future treatments.
"While results were mixed, findings suggest that boosting NAD+ may play a role in easing symptoms like fatigue and poor sleep for some people," Guzmán-Vélez said. "This points to a promising direction for future treatments."
The researchers emphasize that future studies should include larger and more diverse patient populations to confirm these findings and identify which patients benefit most from NAD+ supplementation. Key questions for future research include whether men and women respond differently, and whether people with lower baseline NAD+ levels or higher inflammation are more likely to improve.
The research team also plans to analyze physical activity data collected during the trial and examine whether other supplements taken by participants influenced NR (搜索)'s effects. Given that long COVID (搜索) often involves inflammation, an important future question is whether boosting NAD+ can help reduce inflammatory markers in affected patients.