Boosting Cellular Energy: Nicotinamide Riboside Shows Promise for Long COVID Symptoms
Millions worldwide continue to grapple with the debilitating effects of long COVID, and a new study offers a glimmer of hope. Researchers at Massachusetts General Brigham have investigated whether increasing levels of NAD+, a vital molecule for cellular energy, could alleviate some of the most persistent symptoms, including fatigue, sleep disturbances, and “brain fog.” While the trial didn’t yield significant improvements in cognitive scores overall, participants who took a high dose of nicotinamide riboside (NR) for at least 10 weeks reported noticeable improvements in several key areas.
The study, published in eClinicalMedicine, underscores the complex nature of long COVID and points toward a potential therapeutic avenue focused on restoring cellular function and reducing inflammation.
The Long Shadow of COVID-19
Long COVID, characterized by symptoms that linger weeks or months after the initial infection, affects an estimated 400 million people globally. These symptoms can range from mild to severe and significantly disrupt daily life. Neurological issues, particularly brain fog – a frustrating combination of difficulty thinking, memory problems, and reduced mental clarity – are among the most commonly reported and challenging to treat.
“Because these problems can significantly disrupt daily life, researchers are working to find effective treatments,” explained a lead researcher.
Harnessing the Power of NAD+
The research team focused on NAD+, a coenzyme present in all living cells crucial for energy production, immune function, and controlling inflammation. Previous studies suggested that COVID-19 may disrupt NAD+-related biological processes, potentially contributing to the development of neurological symptoms in long COVID patients.
The central question driving the study was whether boosting NAD+ levels through supplementation with nicotinamide riboside (NR) – a form of vitamin B3 – could improve cognitive function and ease common long COVID symptoms.
A Rigorous Clinical Trial
Between August 2021 and September 2023, researchers conducted a 24-week clinical trial at Massachusetts General Hospital. A total of 58 individuals experiencing long COVID were enrolled and randomly assigned to one of two groups:
- One group received 2,000 mg of NR daily for 20 weeks.
- The other group received a placebo for 10 weeks, followed by NR for the subsequent 10 weeks.
To minimize bias, neither the participants nor the researchers initially knew who was receiving the active supplement. Throughout the trial, NAD+ levels were measured through blood tests, and participants completed regular surveys and cognitive assessments evaluating memory, sleep, fatigue, and mood.
Mixed Results, Promising Signals
While the study’s primary endpoints – improvements in thinking and memory – did not show statistically significant differences between the two groups, a closer examination of the data revealed encouraging trends. Of the 58 initial participants, 18 completed the full 22-week protocol, with others leaving the study due to factors like reinfection, relocation, medication changes, or potential side effects.
“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,” a researcher noted.
However, an analysis of participants who took NR for at least 10 weeks showed self-reported improvements in fatigue, sleep quality, and depressive symptoms compared to their baseline levels. Furthermore, some participants demonstrated enhanced performance on tasks measuring executive functioning – the mental skills involved in planning, organization, and task switching.
Implications and Future Directions
The findings suggest that boosting NAD+ levels may offer a potential therapeutic strategy for alleviating certain long COVID symptoms, particularly fatigue and sleep disturbances, in some individuals. The study also confirmed that high-dose NR supplementation is generally safe, with most side effects being mild, such as easy bruising or rash.
“Long COVID affects an estimated 400 million people worldwide, yet its causes remain unclear,” a senior author stated. “In this study, high-dose NR safely boosted NAD+ levels. While results were mixed, findings suggest that boosting NAD+ may play a role in easing symptoms like fatigue and poor sleep for some people. This points to a promising direction for future treatments.”
Future research will focus on larger, more diverse cohorts to confirm these findings and identify which individuals are most likely to benefit from NR supplementation. Researchers also plan to investigate potential differences in response based on factors like sex, baseline NAD+ levels, and inflammation markers. Further analysis of physical activity data and the influence of other supplements taken by participants is also planned.
The study was supported by Niagen Bioscience, the MGH McCance Center for Brain Health, Lavine Brain Health Innovation Fund, MGH ECOR CDI Physician-Scientist Development Award, and the Alzheimer’s Association. Rudolph Tanzi, a co-author, holds equity in Niagen Bioscience but was not involved in the trial’s execution.
