Researchers at King’s College London report that urolithin A, a molecule the body can make after eating pomegranates, walnuts and some berries, improved measures of heart function by up to 80% in laboratory models of a form of heart failure that has few good treatments. The team, led by Dr. Joseph Burgoyne, tested the compound in mice and in engineered human heart tissue grown from stem cells. No patient received it, and the group says the work does not support eating pomegranates to treat the disease.
The condition at issue is heart failure with preserved ejection fraction, usually shortened to HFpEF. The heart still ejects a normal share of its blood with each beat, but the muscle has stiffened and cannot relax and refill properly. It accounts for roughly half of all heart failure cases. Burgoyne said that “this type of heart failure remains one of the most challenging forms of heart disease to treat,” and that the findings “identify a completely new therapeutic target.”
Urolithin A and the PKGIα switch at Cys42
Urolithin A does not sit in the fruit itself. It is a postbiotic compound produced when gut bacteria break down plant chemicals in pomegranates, walnuts and berries, which is why the King’s team describes it as something the body makes rather than something the diet supplies directly.
The study traces its effect to a single protein, PKGIα, a kinase involved in how blood vessels behave and how heart muscle relaxes. Urolithin A activates it through one specific amino acid, a cysteine at position 42 (Cys42), and does so without triggering the disulfide bonding seen with related compounds. An earlier preprint version of the work described the same finding: targeting Cys42 in PKGIα alleviates diastolic dysfunction, the filling problem at the center of HFpEF. Diastolic dysfunction is what makes the heart resist relaxing between beats, so a drug that loosens it addresses the defining fault of the disease rather than a downstream symptom.
A test of that mechanism came from genetically modified mice whose PKGIα lacked a functional Cys42 site. In those animals, according to the Sci.News account of the paper, the benefits disappeared, which the authors read as evidence that the compound works through that site and not through some more general effect.
Mouse models and engineered human tissue
In mice with HFpEF induced by a combination of diet and hormone treatment, one week of urolithin A improved diastolic function, reduced heart enlargement and fibrosis, and increased how much the animals ran. Heart tissue engineered from human stem cells also contracted and relaxed faster after treatment. The King’s release, carried by ScienceDaily, sums up the central result as improvements in measures of heart function of “up to 80%” in experimental models.
Two details matter when reading that number. “Up to” marks the best result among the measures tested, not an average across them, and neither the release nor the summaries of the paper identify which measure reached 80%. The figure also describes animals and lab-grown tissue, where conditions are controlled, doses are fixed and the disease is induced on a schedule, rather than people who have lived with a stiff heart for years alongside other illnesses.
Limits stated by the King’s team and the British Heart Foundation
The British Heart Foundation funded the work, and Professor James Leiper of the charity was explicit about its limits. “While these findings are promising, the benefits have so far been seen in animals and engineered human tissue, so clinical trials involving people are needed,” he said.
Burgoyne drew the same line on diet. “While there isn’t enough evidence to suggest that people should eat pomegranates to treat heart failure,” he said, the findings open the possibility of future approaches built on the pathway. The distinction is practical. The fruit supplies precursors and gut microbes do the conversion, so the study’s results come from giving animals and tissue the finished compound directly, which is a very different exposure from a bowl of fruit.
The paper, published in Science Advances (volume 12, issue 34, DOI 10.1126/sciadv.aec8088), lists Jie Su, Yue Zhao, Pierre Coleman, Xiaoping Yang, Mark Holt, Janice Raabe, Friederike Cuello, Ajay Shah, Michael J. Shattock and Min Zhang alongside Burgoyne. A separate report on the August publication frames it the same way, as early tests pointing to a stiff-heart failure pathway rather than a treatment.
The next step that both the authors and the funder name is a clinical trial in people with HFpEF. Until patients receive urolithin A under controlled conditions and show a change in how their hearts fill, the 80% stays what Leiper called it: a benefit seen so far in animals and engineered human tissue.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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