Key Points:
- 500 mg or 1000 mg of urolithin A increases muscle strength.
- 1000 mg of urolithin A improves muscle endurance and reduces inflammation.
- The most likely side effect of UA is muscle aches.
Animal studies demonstrate that supplementing with urolithin A (UA) prevents age-related muscle decline, and even prolongs lifespan by 18%. Whether these benefits apply to humans remains an open question, but it is becoming more apparent. Recently, researchers from the National University of Singapore reviewed the latest clinical trials testing the effects of UA supplementation on humans. The researchers highlighted the promise of UA in reducing inflammation and enhancing muscle strength and endurance. However, they also say the impact of UA on human lifespan requires further investigation.
Benefits of Urolithin A
The researchers searched all registered human trials examining the effects of UA on age-related physiological changes and incidence of disease. Based on the five studies found, they highlighted that UA may reduce inflammation and enhance muscle function.
Reducing Inflammation
In a study by Singh et al., 2022, middle-aged adults were given 500 mg or 1000 mg of UA for 4 months. The 500 mg dose led to a significant decrease in the inflammatory marker IL-1β. Furthermore, the 1000 mg dose decreased three inflammatory markers (i.e., CRP, INF-γ, and TNF-⍺) but not IL-1β. However, in contrast to middle-aged adults, in a study by Liu et al., 2022, older adults given 1000 mg of UA for 4 months did not exhibit a decrease in CRP. These findings suggest that UA reduces inflammation in middle-aged adults but not older adults, especially with a higher dose of 1000 mg.
Enhancing Muscular Strength and Endurance
Signh et al., 2022 showed that 500 mg of UA increased hamstring muscle strength by 12% and 1000 mg of UA increased hamstring strength by 10%. However, UA did not significantly increase quadriceps muscle strength. Furthermore, Liu et al., 2022 showed that 1000 mg of UA improved muscle endurance after 2 months of supplementation but this improvement disappeared after 4 months. These studies show that UA could help improve muscle strength in middle-aged adults and temporarily improve muscle endurance in older adults.
Other Positive Outcomes
Based on animal studies, UA is thought to exert its beneficial effects on the body by improving the health of our mitochondria and promoting autophagy. Autophagy is the process our cells use to get rid of unnecessary material like dysfunctional mitochondria and misfolded proteins. From the muscle of older adults, Andreux et al., 2019 showed that 500 mg but not 1000 mg of UA increased genes related to autophagy. It was also shown that 500 mg or 1000 mg of UA can improve genes related to mitochondrial health.
Additionally, a recent study showed that 500 mg of UA increased HDL cholesterol in heart failure patients. Moreover, another recent study showed that 1000 mg of UA improves the immune system of middle-aged adults.
Negative Results
UA is a metabolite produced by the microbes living in our gut — the gut microbiome. When we eat foods containing a molecule called ellagitannin (e.g., pomegranates, berries, and nuts), our gut microbiome converts ellagitannins to UA. Based on a study (Nishimoto et al., 2022) of individuals who cannot convert ellagitannin to UA, the Singapore-based researchers reported that UA does not change the composition of the gut microbiome.
Bringing into question whether UA improves mitochondrial health, Liu et al., 2022 showed that cellular energy (ATP) production was not increased by UA. The older adults who participated in the study had low levels of cellular energy before the study began, suggesting their mitochondria were not healthy. If mitochondrial health was improved by UA supplementation, then cellular energy production is expected to increase.
Negative results were also reported for measures of physical function, including grip strength, gait speed, and maximum oxygen consumption (VO2 max). Additionally, Nishimoto et al., 2022 showed that 10 mg of UA for 10 weeks does not significantly improve blood vessel function. The authors say,
“Taken together, current evidence does not support the beneficial effects of UA on physical function in healthy individuals. However, this conclusion should be considered in light of several limitations: small sample sizes, short intervention durations, and a wide participant age range (45–85 years), which includes both middle-aged and older individuals who may not be ideal candidates for geroprotection.”
The authors go on to conclude,
“There is very limited evidence on the effect of UA in human aging. UA showed some improvement in mitochondrial activity and autophagy. It decreased inflammatory markers and increased muscle strength and endurance, however, it did not affect gut microbiota composition and physical function. Further research across a wider range of physiological systems, higher number of individuals and longer intervention periods is required.”
Dosage (500-1000 mg)
A dose of 500 mg or 1000 mg of UA was shown to improve muscle strength in middle-aged adults while a dose of 1000 mg was shown to temporarily improve muscle endurance in older adults. Therefore, a 500 mg dose seems sufficient for increasing muscle strength while 1000 mg may be needed to improve resistance to fatigue.
A dose of 500 mg of UA reduced one marker of inflammation while 1000 mg reduced three markers of inflammation, suggesting 1000 mg of UA reduces inflammation more potently. Overall, it would seem that 1000 mg of UA for 4 months could reduce inflammation and improve muscle function in middle-aged or older adults. Whether these benefits also occur in younger adults remains to be studied.
Side Effects
No serious adverse events attributed to UA supplementation were reported in any of the clinical trials. A mild adverse event classified as “possibly” related to UA is myalgia — muscle aches and pains. Mild to moderate events classified as “unlikely” related to UA are as follows:
- Headache
- Limb discomfort
- Diarrhea
- Back pain
Key Takeaways
There are not many clinical trials testing the effect of UA on physiological aging. Two studies (Denk et al., 2024 and Singh et al., 2022) show that UA improves the immune system and reduces inflammation. One study shows (Singh et al., 2022) that UA increases muscle strength, and one study (Lin et al., 2022) shows that UA temporality improves hand muscle endurance. If more studies replicate these findings, it will seem more likely that UA can reduce inflammation and improve muscle function.
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