NAD+ and the brain: long-COVID, mice and IV tests

Long-COVID: the placebo comparison

The 24-week randomised long-COVID trial enrolled 58 people. Neither participants nor staff knew who received NR or placebo. NR significantly increased NAD+, but the randomised comparison showed no significant group-level difference in cognitive scores.

People receiving NR improved within their group on fatigue, sleep, depression and executive function, which includes planning and organising tasks. The decisive question is how those changes compare with the placebo group. I trust the randomised comparison here. It tests the treatment’s contribution more directly than changes within the NR group.

This result does not settle every possible brain question about NAD+. It does make a broad claim of clearer thinking difficult to sustain from this trial.

Parkinson’s disease and brain NAD+

The Parkinson’s research review describes interest in restoring energy production in neurons, improving protein quality control and modifying immune responses. Preliminary NR findings include increased cerebral and whole-blood NAD+ alongside early clinical signals. Dedicated trials are needed to establish useful effects on symptoms.

Measuring inside the brain is a meaningful advance over inferring its contents from blood. Even then, the next question remains functional: did movement or thinking improve because of the intervention? A measurement inside the organ gets the investigation closer to that question, while the clinical comparison still has to answer it.

Alzheimer’s-model mice

In the APP/PS1 mouse study, NR in drinking water for 5 months increased brain NAD+ and improved memory and synaptic function. The mice also had less neuroinflammation, DNA damage, cell death and cellular senescence, a state in which cells cease dividing. The work implicated cGAS-STING, an immune-signalling pathway involved in responses to DNA.

Human Alzheimer’s skin cells showed a similar NAD+ depletion pattern. These were cell observations, separate from a treatment trial in people with dementia. I see a substantial experimental story here: several measures changed in an animal model. The human memory question remains open.

The NAMPT review adds a reason to investigate the brain’s supply system. NAMPT helps recycle material into NAD+, and its high expression in the hippocampus connects it to NAD+ production in neural stem and progenitor cells. The hippocampus is involved in memory. That is biological rationale for research.

NAD IV therapy and cognitive tests

The intravenous NAD+ cognition pilot gave 750 mg/day for 5 consecutive days. Scores improved on 6 of 8 neuropsychological tests in the NAD+ group and on 2 of 8 in the saline group. Those counts describe tests showing improvement; they supply no percentage improvement in memory and no measure of easier everyday remembering.

I think this finding merits a larger, rigorous follow-up with outcomes that people can recognise in daily life. The small pilot leaves lasting benefit unresolved. Oral NR trials and an infusion of NAD+ test different interventions, so the pill results cannot fill that gap.

NAD injection evidence and safety

An NAD injection delivers NAD+ itself. Published discussion covers intravenous delivery and injections into muscle or beneath the skin, with little peer-reviewed evidence about how the latter routes are handled in people. Controlled evidence for IV treatment is especially limited.

Compounded NAD+ injections are unapproved. One product was recalled by FDA for elevated bacterial endotoxin, with a Class I designation, FDA’s most serious recall level. Infusion reports also describe chest or abdominal discomfort, flushing and nausea when NAD+ is given too quickly.

Anecdotal accounts of energy or brain fog are personal reports, not clinical evidence. They cannot resolve the treatment effect. The dosage and side-effect page separates the tested amounts, the short safety observations and the remaining questions.