○ Evidence tier 4 — Human RCT — biomarker endpoint

Record verify: primary source pending

DesignFirst-in-human randomized, placebo-controlled safety study (biomarker)
DOI10.1038/s42255-019-0073-4
Citation statusdoi verified via Crossref 2026-07-12 (Nat Metab 2019;1(6):595-603, Andreux et al., 'The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans'). PMID + NCT: needs_primary_fulltext.

Five-qualifier claim

Species / populationHealthy sedentary older adults, first-in-human randomized placebo-controlled study plus a single-dose/repeated-dose safety design.
Exposure, route, scheduleOral urolithin A (single ascending doses and 28-day repeated dosing, up to ~1000 mg/day).
Comparator / durationPlacebo-controlled; short (single-dose and 4-week) exposure.
Endpoint / numeric resultUrolithin A was safe and bioavailable and induced a molecular (gene-expression) signature of improved mitochondrial and cellular health in skeletal muscle; no adverse safety signal.
What it did NOT establishA safety/biomarker first-in-human study — no functional or clinical efficacy endpoint met, and no lifespan or healthy-aging outcome.

Primary reference

https://doi.org/10.1038/s42255-019-0073-4

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.