Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial

Chao-Yi Wu and colleagues ran a single-centre, double-blind, placebo-controlled trial in Boston between August 2021 and September 2023. Fifty-eight community-dwelling adults with long COVID were randomised 2:1 after a placebo lead-in. Thirty-seven took nicotinamide riboside for 20 weeks. Twenty-one took placebo for 10 weeks and then nicotinamide riboside for 10 weeks. The dose was 2000 mg per day and total follow-up was 24 weeks.

Cognition was the primary outcome, measured three ways: the Everyday Cognition scale, the Repeatable Battery for the Assessment of Neuropsychological Status, and Trail Making Test part B. None of the three showed a significant difference between groups. The reported p-values span 0.47 to 0.74. Fatigue, sleep and mood also showed no between-group difference.

The supplement did what it is sold to do biochemically. NAD+ rose within five weeks. That change did not carry through to any clinical outcome the trial was designed to detect. Exploratory within-group analyses after 10 weeks of active treatment suggested benefit, but a within-group change without a control comparison is the weakest form of signal in a randomised trial and the authors present it as a reason for larger studies rather than a result.

Charles Brenner, who discovered the nicotinamide riboside pathway and is a paid adviser to ChromaDex, is a co-author. Rudolph Tanzi and Steven Arnold at Massachusetts General Hospital are also co-authors.

This is the second published nicotinamide riboside trial to raise NAD+ without improving cognition, after the 42-person mild cognitive impairment pilot in Alzheimer's & Dementia. Both used a symptomatic population. Neither supports a cognitive claim.

In long-COVID, NR increased NAD+ within 5 weeks but did not significantly improve cognition, fatigue, sleep, or mood vs. PBO. Exploratory analyses suggested within-group benefits after 10 weeks of NR, supporting the need for larger trials.