Urolithin A improves stiff-heart function by up to 80% in animal models

In a dish at King’s College London, engineered heart tissues grew between fixed posts. When researchers tested them with urolithin A, a compound the body produces after consuming foods such as pomegranates, walnuts and some berries, the tissue relaxed more effectively. In animal models of heart failure with preserved ejection fraction, or HFpEF, measures of heart function improved by up to 80%.

HFpEF is the stiff-heart form of heart failure. The heart retains its ability to pump blood but becomes less able to relax and fill between beats, causing breathlessness, fatigue and reduced exercise capacity. The condition accounts for around half of all heart failure cases and affects nearly half a million people in the UK. Treatment remains difficult because aging, high blood pressure and diabetes can all contribute to it.

The researchers found that urolithin A activates PKGIα, a protein involved in blood-vessel function and heart-muscle relaxation. The compound targets a specific amino acid on that protein, setting off a pathway that improved relaxation in the engineered human tissue. In the laboratory tests, it also reduced fibrosis, or harmful scarring, and limited the enlargement of heart muscle cells.

So what changes, concretely? The study offers a possible drug target for patients whose hearts pump normally but fill poorly, a group with relatively limited treatment options. Urolithin A has already been evaluated in human studies and has a favorable safety profile, but this does not make pomegranates a treatment: Joseph Burgoyne of King’s College London said there is not enough evidence to recommend eating them to treat heart failure.

The boundary is clear. The reported gains come from animal models and engineered human heart tissue, not from clinical trials. James Leiper of the British Heart Foundation said the results are promising but that studies involving people are needed to determine whether urolithin A works for patients. For now, the finding is a laboratory lead, not a therapy in service.