# The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation

## TL;DR

This study examines how oral NAD precursors affect NAD levels in blood and brain over time, showing that steady-state is reached after about two weeks with slow decline after stopping.

## Contribution

The study provides first-in-human pharmacokinetic data on oral NAD augmentation in both healthy individuals and Parkinson’s disease patients.

## Key findings

- Blood NAD levels plateau after two weeks of treatment and decline slowly with a half-life of ~6.25 days.
- Cerebral NAD levels increase measurably after four weeks of treatment.
- NAD augmentation shows significant interindividual variation but is not influenced by sex or Parkinson’s disease status.

## Abstract

Nicotinamide adenine dinucleotide (NAD) augmentation therapy (NAD-AT) is increasingly explored in clinical trials across multiple indications, especially neurological diseases, yet its human pharmacokinetic profile remains incompletely defined. We report findings from a phase I pharmacokinetic trial assessing systemic and cerebral responses to oral NAD precursors in healthy individuals (n = 6) and persons with Parkinson’s disease (n = 6) receiving 1,200 mg/day nicotinamide riboside or nicotinamide mononucleotide. Blood NAD increased slowly, plateauing after approximately two weeks of treatment, and declined with similarly slow kinetics following treatment discontinuation. Cerebral NAD levels increased measurably after four weeks of treatment. NAD-related metabolites showed faster increase and washout dynamics compared to NAD itself. Collectively, these data suggest that effective NAD-AT requires sustained oral administration over at least 2–4 weeks and that once-daily dosing is sufficient to maintain stable NAD levels. NAD responses exhibited considerable interindividual variability, but were not influenced by disease status or sex, indicating broad applicability.

•Oral NAD-augmentation with NR or NMN requires ∼2 weeks to reach steady-state•Elevated NAD declines slowly with a half-life of approximately 6.25 days in blood•The extent of NAD augmentation shows substantial interindividual variation•The extent of NAD augmentation is independent of sex and Parkinson’s disease status

Oral NAD-augmentation with NR or NMN requires ∼2 weeks to reach steady-state

Elevated NAD declines slowly with a half-life of approximately 6.25 days in blood

The extent of NAD augmentation shows substantial interindividual variation

The extent of NAD augmentation is independent of sex and Parkinson’s disease status

Biopharmaceuticals; Health sciences; Pharmaceutical compounds formulation; Pharmaceutical preparation; Pharmaceutical science