NAD+ Booster Shows Mixed Results for Long-COVID Brain Fog in Clinical Trial

Long-COVID affects millions worldwide with persistent cognitive difficulties, fatigue, and other debilitating symptoms lasting months after infection. Researchers hypothesized that boosting NAD+ levels—a critical cellular energy molecule depleted by SARS-CoV-2—might help restore normal function.

This rigorous 24-week, double-blind, placebo-controlled trial enrolled 58 community-dwelling adults with long-COVID experiencing brain fog and other persistent symptoms. Participants were randomized 2:1 to receive either nicotinamide riboside (NR, 2000mg daily) for 20 weeks or placebo for 10 weeks followed by NR for 10 weeks. Researchers measured NAD+ levels every 5 weeks and assessed cognitive function, fatigue, sleep quality, and mood every 10 weeks.

NR supplementation dramatically increased NAD+ levels by 2.6-3.1 fold within 5-10 weeks and maintained elevation throughout treatment. However, the primary analysis found no significant differences between NR and placebo groups for cognitive outcomes, fatigue severity, sleep quality, or mood symptoms. The study faced challenges with higher dropout rates in the NR group (32-51%) compared to placebo (14%).

Intriguingly, when researchers combined all participants during their NR treatment phases in exploratory analysis, they observed improvements in executive functioning, reduced fatigue severity, better sleep quality, and fewer depression symptoms after 10 weeks of supplementation. These within-group changes weren't seen during placebo phases.

The findings suggest NAD+ restoration through NR supplementation is achievable in long-COVID patients and may provide some benefits, but the mixed results highlight the complexity of treating this condition. The study's relatively small size and high dropout rates limit definitive conclusions, emphasizing the need for larger, longer trials to fully evaluate NAD+ supplementation's therapeutic potential for long-COVID recovery.