Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults

Double-blind, placebo-controlled randomized clinical trial at two centers (University of Washington Medical Center and Fred Hutchinson Cancer Research Center); older adults aged 65–90 years; healthy, ambulatory; mean age 71.7 years; predominantly female (75.8%); all White; 66 randomized (33 per group); intention-to-treat analysis.

Urolithin A, 1000 mg/day, oral, four 250 mg softgels taken in the morning on an empty stomach, for 4 months.

Urolithin A was safe and well tolerated. Primary endpoint (change in 6-minute walk distance) did not differ significantly from placebo. At 2 months, urolithin A significantly improved hand (FDI) and leg (TA) muscle endurance compared with baseline versus placebo; by 4 months, between-group differences in endurance were no longer significant due to parallel improvements in the placebo group. Plasma biomarkers indicated improved mitochondrial health with decreases in acylcarnitines and ceramides, and inflammation marker CRP decreased; urolithin A was bioavailable (detectable urolithin A and metabolite in plasma at 4 months). No serious adverse events occurred. Conclusion: long-term urolithin A may help counteract age-related muscle decline by improving skeletal muscle endurance and mitochondrial-health biomarkers, but larger and longer trials are needed to confirm effects on whole-body performance.

Small, predominantly White, single-site sample; limited generalizability; primary endpoint not significantly different with a notable placebo-like improvement in both groups; modest sample size and COVID-19-related data loss; short duration may not capture long-term effects.