○ Evidence tier 4 — Human RCT — biomarker endpoint

Record verify: primary source pending

DesignRandomized, double-blind, placebo-controlled crossover trial (biomarker)
N24
DOI10.1038/s41467-018-03421-7
Citation statusdoi verified via Crossref 2026-07-12 (Nat Commun 2018;9:1286, Martens et al., 'Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults'). NOTE: NCT03821623 is a SEPARATE, later University of Colorado Boulder Phase 2 NR blood-pressure/arterial-stiffness trial — verified via ClinicalTrials.gov v2 API (randomized, triple-masked, n=118 est., RECRUITING as of 2025-02, NO published results) — do NOT conflate it with this 2018 paper. This 2018 trial's own registry id + PMID: needs_primary_fulltext.

Five-qualifier claim

Species / populationHealthy middle-aged and older adults (crossover RCT, ~24 completers).
Exposure, route, scheduleOral NR 500 mg twice daily (1000 mg/day) for 6 weeks.
Comparator / durationPlacebo-controlled, double-blind, randomized crossover; 6-week periods.
Endpoint / numeric resultWell tolerated; roughly doubled whole-blood NAD+; a suggestive reduction in systolic blood pressure and aortic stiffness in a subgroup with elevated baseline.
What it did NOT establishNAD+ is a biomarker; the BP/stiffness signal was secondary/subgroup, not a powered clinical outcome, and there is no lifespan endpoint.

Primary reference

https://doi.org/10.1038/s41467-018-03421-7

Exact identifier confirmed against the primary record via Crossref/ClinicalTrials.gov where stated in the citation status; anything marked needs_primary_fulltext is not yet confirmed.