Urolithin A Safe in Middle-Aged Adults with Obesity, But Fails to Improve Endothelial Function: JAMA
USA: A new study showed that four weeks of Urolithin A (UA) supplementation did not yield a statistically significant improvement in peripheral endothelial function among middle-aged adults with obesity. Further, Urolithin A supplementation was well tolerated, with no notable safety concerns, demonstrating feasibility for short-term use. However, preliminary observations suggest a potential impact on task-evoked cerebrovascular hemodynamic responses, which warrants further research.
The randomized clinical trial, published in JAMA Network Open, was conducted by Ana Clara da Costa Pinaffi-Langley, Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Center, Oklahoma City, and colleagues. The researchers investigated whether UA, a microbial metabolite derived from dietary polyphenols that activates mitophagy, could improve blood vessel function outside the brain and cerebrovascular responses in adults with obesity.
Obesity is associated with an increased risk of chronic diseases, while impaired mitochondrial function may contribute to vascular dysfunction. Since UA has shown potential benefits for mitochondrial health, the researchers examined whether supplementation could improve vascular function in this population.
The trial included 50 adults aged 40 to 64 years with a body mass index (BMI) of 30 or higher. Participants were randomly assigned to receive either 1,000 mg of UA daily or a placebo for four weeks. The study assessed changes in brachial artery flow-mediated dilation (FMD), a measure of endothelial function, alongside other peripheral vascular measures and cerebrovascular responses during cognitive tasks.
The analysis revealed the following findings:
- No significant improvement in endothelial function: Mean FMD increased by 1.3% in the UA group compared with 0.3% in the placebo group, but the difference was not statistically significant.
- Improved cerebrovascular responses: UA supplementation significantly increased task-evoked cerebrovascular hemodynamic responses compared with placebo, particularly in the left dorsolateral prefrontal cortex, which is involved in working memory.
- No change in cognitive performance: Despite the observed changes in brain hemodynamic responses, participants showed no significant improvement in cognitive task performance.
- Good short-term tolerability: The supplement was well tolerated, with no major safety concerns identified during the intervention.
The researchers noted that the study was limited by its small sample size, short intervention period and single-centre design. Most participants were women, and the wide range of BMI values may have contributed to variability in treatment responses. The findings require validation in larger trials with longer follow-up and a more balanced representation of sexes.
The researchers concluded that four weeks of UA supplementation did not significantly improve peripheral endothelial function in middle-aged adults with obesity. However, the increase in task-evoked cerebrovascular responses suggests a possible effect on brain blood flow regulation that warrants further investigation. Longer studies are needed to establish whether these changes translate into meaningful cognitive or clinical benefits.
Reference:
da Costa Pinaffi-Langley AC, Gulej R, Kaposzta Z, et al. Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(10):e2638047. doi:10.1001/jamanetworkopen.2026.38047
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