The effects of urolithin A supplementation on muscle strength, muscle mass and physical performance in humans - a systematic review

Abstract Background Urolithin A, a stimulator of mitophagy, has been proposed as a therapy to improve skeletal muscle function via its beneficial effect on mitochondrial health. We aimed to systematically review existing evidence of the effect of urolithin A on measures of muscle strength, muscle mass and physical performance in humans. Methods We conducted a systematic review according to a prespecified protocol. Databases (PubMed, EMBASE, CINAHL, Scopus, ISRCTN.com and Clinicaltrials.gov ) were searched from inception to 31 st May 2025, with hits screened by two reviewers. We included randomised controlled trials comparing urolithin A to placebo or usual care. We sought outcomes measuring muscle strength, muscle mass or physical performance. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results were grouped by outcome type and where applicable pooled using random-effects meta-analysis. Results We identified 194 titles, of which three studies were eligible for inclusion. Included studies recruited 174 participants, and mean age ranged from 24 to 72 years. All studies were placebo controlled and examined doses of 500mg/d or 1000mg/d of Urolithin A. Overall risk of bias of included studies was low; urolithin was well tolerated with good adherence to therapy. Four of 12 included outcome measures showed a statistically significant positive effect of urolithin A on muscle strength and physical performance, with a further seven outcomes demonstrating non-significant improvements in muscle strength or physical performance. Pooled analysis of six-minute walk distance from two trials showed a non-significant improvement in walk distance with urolithin A (23m [95% CI −6m to 52m, p=0.12, I 2 =0%]). One study measured muscle mass but found no improvement in mass with urolithin supplementation. Conclusions Insufficient evidence exists to support the use of urolithin A to improve muscle function in any population at present, but existing data support conducting larger randomised controlled trials in a range of target populations.