Randomized Controlled Trial

NR-SAFE Trial - Nature Communications

Berven et al./Nature/2023

Why It Matters

This paper caught my attention because it's the first human trial testing NR doses this high — 50% higher than previous studies. For anyone experimenting with NAD+ boosters, this establishes that 3000 mg/day appears safe short-term, though we still don't know if it actually helps Parkinson's or other conditions long-term. The clinical improvement seen could just be timing of medication, not the NR itself.

Key Findings

  • 20 participants took either 3000 mg NR daily or placebo for 4 weeks — zero moderate or severe side effects in either group, no difference in mild side effects
  • Blood NAD+ levels increased up to 5-fold in the NR group, confirming the supplement actually does what it's supposed to do at the biochemical level
  • Parkinson's symptom scores (MDS-UPDRS) improved in the NR group, but this correlated with shorter time since last levodopa dose — suggesting it might just be medication timing, not NR effect
  • Small initial increase in homocysteine (a cardiovascular risk marker) in NR group, but methyl donor pool stayed intact — worth monitoring but not alarming at 4 weeks
  • This was a safety trial with only 20 people for 4 weeks — way too small and short to know if NR actually helps Parkinson's, only that this dose doesn't cause obvious harm