NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 38016950 · doi:10.1038/s41467-023-43514-6
What was done
A single-center, randomized, double-blind, placebo-controlled phase I trial evaluated high-dose nicotinamide riboside (NR) in 20 individuals with Parkinson's disease at Haukeland University Hospital, Norway. Participants were randomized 1:1 to receive NR 1500 mg twice daily (3000 mg/day, n = 10) or matching placebo (n = 10) for 4 weeks. The primary outcome was safety (frequency of moderate and severe adverse events). Secondary outcomes included tolerability (mild adverse events), changes in the blood and urine NAD metabolome, and disease severity measured by the MDS-UPDRS.
What was found
All 20 participants completed the 4-week trial. No moderate or severe adverse events were reported, and mild adverse events did not differ significantly between groups. NR supplementation led to up to a 5-fold increase in blood NAD+ levels. A slight initial increase in serum homocysteine occurred without compromising the methyl donor pool. Clinical improvement in total MDS-UPDRS scores was observed in the NR group, though this coincided with a shorter interval since the last levodopa dose; exact numerical score differences were not reported in the abstract.
Why it matters
This trial establishes initial human safety and strong target engagement for NR at 3000 mg/day—exceeding previously studied 2000 mg/day limits—providing pharmacokinetic and safety support for higher dosing in phase II neurodegenerative disease trials.
Limits
The sample size was very small (n = 20), the treatment duration was short (4 weeks), and the study was conducted at a single center. The apparent clinical improvement in MDS-UPDRS was confounded by levodopa timing, precluding any conclusions regarding therapeutic efficacy.
Cited by
- supports Nicotinamide riboside has been tested for safety at doses up to 3 grams per day in clinical studies.