Urolithin A Improves Muscle Strength and Exercise Performance

This study tested whether oral Urolithin A, a compound linked to mitochondrial health, could improve muscle strength and exercise performance in overweight middle-aged adults with low endurance.

"This study highlights the benefit of Urolithin A to improve muscle performance."

Key Points

  • Urolithin A improved lower-body muscle strength.

  • Higher doses improved aerobic endurance and walking performance.

  • Benefits appeared to affect on muscle function and quality rather than muscle size.

  • Blood biomarker changes suggest improvements in mitochondrial fat metabolism and inflammation.

  • Data supported increased markers of mitophagy and energy metabolism.

“UA was found to be safe and well tolerated during the 120-day (4-month) supplementation period at both doses.”

Study Overview

Eighty-eight overweight, sedentary adults (ages 40–64) with low aerobic fitness were randomized into three groups:

  • Placebo group: 29 people received placebo for four months.

  • UA 500 group: 29 people received 500 mg/day of Urolithin A for four months.

  • UA 1000 group: 30 people received 1,000 mg/day of Urolithin A for four months.

Researchers measured muscle strength, aerobic fitness, walking distance, body composition, blood biomarkers, and muscle tissue changes at the start of the study, after 2 months, and after 4 months.

Woman doing assisted pistol squat

Leg Muscle Strength Improved at Both Doses

Hamstring strength improved significantly in both Urolithin A groups compared with placebo:

  • 500 mg group: 12% improvement

  • 1,000 mg group: 9.8% improvement

  • Placebo group: about 9.8% decline

“Average peak torque in the hamstring skeletal muscle was significantly increased in both UA 500 mg and UA 1,000 mg groups.”

The placebo group lost roughly 9–10% of hamstring strength over 4 months, consistent with the natural trajectory of muscle decline in sedentary middle-aged adults.

“Participants taking the placebo had significant within-group decreases.”

Quadriceps strength showed positive trends with Urolithin A but did not reach statistical significance. Hand-grip strength improved 5.1% within the 1,000 mg group, without reaching between-group significance.

“UA supplementation induced positive, although non-significant, improvements in the average peak torque of the quadriceps muscle and in maximum torque measurement for knee extension.”

Importantly, participants did not gain measurable muscle mass. That means Urolithin A may have improved how well the muscle worked, rather than simply increasing muscle size.

“Lean body mass evaluated… and total fat mass were unchanged across groups after 4 months of supplementation.”

Higher Dose Drove Performance Gains

The 1,000 mg dose appeared to have the strongest effect on whole-body endurance.

“Only the higher dose of UA led to clinically relevant improvements in measures of physical performance (6MWT) and aerobic endurance (peak VO2).”

Peak VO₂, a measure of aerobic fitness, changed as follows:

  • 1,000 mg group: 10.2% increase

  • 500 mg group: 1.6% increase

  • Placebo group: 1.1% decrease

The improvement appeared by 2 months and was still present at 4 months.

“Peak VO2 improved by 10% in the high-dose UA group, with the effect already manifesting at 2-months post-UA supplementation and being maintained at 4 months.”

The 1,000 mg group also improved on the 6-minute walk test:

  • 1,000 mg group: walked 33.4 meters farther

  • 500 mg and placebo groups: essentially unchanged

“The group administered the high dose of UA (1,000 mg) increased their walking distance by >30 m during the 6MWT.”

“In addition, the total cycling distance increased from baseline to end of study in the 1,000 mg UA intervention group (+15%)... as did the time to fatigue during the exercise test.”

Overall, the higher dose seemed more effective for endurance and physical performance.

Pink stained organism under microscope

Inflammation and Mitochondrial Health Improved

At the 500 mg dose, Urolithin A reduced certain acylcarnitines, molecules that build up during inefficient fat processing, which may suggest improved mitochondrial fat metabolism.

“Acylcarnitines were reduced in the UA 500 mg group and middle- to long-chain acylcarnitines were the most downregulated species.”

At the 1,000 mg dose, CRP, a common marker of inflammation in the body decreased.

“UA reduced plasma CRP levels at both doses, with results statistically significant at the 1,000 mg dose.”

The researchers suggested that Urolithin A may support muscle health in two ways:

  • Helping mitochondria function better

  • Reducing chronic, low-grade inflammation linked with aging

“Data indicate how UA supplementation offers a potential dual benefit for muscle health, by improving mitochondrial function, while also acting to reduce age-related chronic inflammation, or inflamm-aging.”

Urolithin A may help cells clear damaged mitochondria, which may reduce inflammatory signals and support healthier muscle metabolism.

Mitophagy and Mitochondrial Activity Increased

Urolithin A appeared to affect pathways related to mitophagy, which is the body’s process for cleaning out damaged mitochondria.

At the 500 mg dose, the strongest signal was related to mitophagy signaling.

“The most significantly enriched pathway induced in the UA 500 mg group was ‘‘Parkin-mediated ubiquitin and proteasomal systems’’.”

At the 1,000 mg dose, the strongest signals were centered on energy metabolism.

“Top pathways enriched at the 1,000 mg dose were associated with improved mitochondrial metabolism.”

In simpler terms, the lower dose seemed to activate mitochondrial cleanup, while the higher dose seemed to support mitochondrial energy production.

“These results indicate that UA-mediated improvement of muscle function associates with both enhanced mitochondrial efficiency and reduced inflammation.”

Woman exercising at gym equipment

Conclusion

This 4-month study found that Urolithin A produced statistically significant improvements in hamstring muscle strength in overweight, middle-aged adults with low aerobic fitness.

Both 500 mg and 1,000 mg doses improved hamstring strength, while the 1,000 mg dose also showed stronger effects on aerobic fitness and walking distance.

“A key finding of the present study is the clinically meaningful impact of UA on improving muscle strength and positively impacting aerobic endurance and physical-performance measures such as walking distance.”

Urolithin A may support muscle function by improving mitochondrial quality control, mitochondrial energy metabolism, and possibly inflammation-related pathways.

"Data revealed UA to impact markers of Parkin-mediated mitophagy and to dose-dependently upregulate levels of mitochondrial TCA cycle and OXPHOS proteins."

The study also reported good tolerability and no major safety concerns over 4 months.

“How UA impacts both mitochondrial health and inflammation is an intriguing question that warrants in-depth mechanistic studies in more suited experimental models.”

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Olivia Harrier

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Olivia is a biochemist and longevity researcher focused the molecular architecture of aging. Her work centers on metabolic health and the systems-level mechanisms that shape how we age. She translates dense research into clear frameworks for improving energy, resilience, and long-term health, grounded in physiology and evidence-driven frameworks that help people align daily habits with cellular performance. If you understand how the system works, you can work with it, and aging becomes something to navigate rather than just endure.

References

Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633. doi:10.1016/j.xcrm.2022.100633