Obesity supplement boosts brain blood-flow responses, not vascular function

Clinical takeaway: Urolithin A supplementation does not appear to improve peripheral endothelial function over 4 weeks in middle-aged adults with obesity, but it may enhance cerebrovascular responsiveness during cognitive tasks.

Nearly half of US adults in midlife have obesity, a major risk factor for cardiovascular disease, stroke, and later cognitive decline. Urolithin A, a gut microbiome-derived metabolite that promotes mitochondrial quality control, has attracted interest as a potential strategy to counter obesity-related vascular dysfunction and preserve brain health.

In this double-blind trial, 50 adults aged 40-64 years with obesity were randomized to urolithin A 1000 mg daily or placebo for 4 weeks. Participants had a mean BMI of 38, three-quarters were women, and adherence exceeded 95% in both groups. The supplement was generally well tolerated, with headache the most commonly reported adverse event.

The primary endpoint, brachial artery flow-mediated dilation, showed no meaningful benefit with urolithin A. Flow-mediated dilation increased by an average of 1.3 percentage points in the active-treatment group versus 0.3 percentage points with placebo. Other measures of peripheral endothelial and microvascular function likewise did not differ between groups.

Benefits were more apparent in the brain than in the peripheral vasculature. Functional near-infrared spectroscopy showed significantly greater task-evoked cerebrovascular responses among participants receiving urolithin A, particularly in the left dorsolateral prefrontal cortex, a region involved in working memory. However, these physiologic changes did not translate into measurable improvements in cognitive task accuracy or reaction time during the short study period.

The authors noted that “our findings are significant and merit further investigation for the use of UA supplementation as a potential strategy to improve cerebrovascular function in those at increased risk of poor brain health outcomes.”

Source: da Costa Pinaffi-Langley AC, et al. (2026 Oct 9) JAMA Netw Open. Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity: A Randomized Clinical Trial