LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that can significantly improve key indicators of heart performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. In animal studies, Urolithin A enhanced certain measures by up to 80% compared to untreated controls. Additionally, the compound promoted relaxation of cardiac tissue, decreased scarring, and limited abnormal expansion of heart muscle cells. The team also observed improved relaxation in engineered human heart tissues derived from stem cells.
In the UK, HFpEF occurs when the heart maintains a near-normal pumping fraction but encounters difficulty relaxing and filling between beats. This condition can cause symptoms like breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, it accounts for approximately half of all heart failure cases in the country. Urolithin A is produced naturally in the body when gut bacteria metabolize compounds present in foods such as pomegranates, walnuts, and certain berries, although its production level can vary among individuals.
The research team identified that urolithin A interacts with a protein called PKGIα, which plays a role in controlling blood vessel function and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on PKGIα, activating a pathway associated with cardiovascular health. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published in Science Advances. The work was led by researchers from King’s College London, with Joseph Burgoyne serving as the senior author.
Compound mitigates fibrosis and abnormal heart enlargement
During animal testing, urolithin A improved diastolic function, which assesses the heart’s ability to relax and fill with blood. Researchers also noted a reduction in fibrosis, the formation of scar tissue that can impair normal cardiac function. Moreover, treatment lessened the enlargement of heart muscle cells compared to controls. The reported improvement of up to 80% pertained to specific heart function measurements in the experimental setting; it does not imply an 80% improvement in patients or a complete reversal of heart failure.
Further testing involved engineered human heart tissue derived from stem cells. These lab-grown tissues replicate key features of human heart muscle and enable precise measurement of contraction and relaxation. Urolithin A showed enhancement in both processes within this model. The researchers highlighted that urolithin A has already been tested in humans for other uses and demonstrated a favorable safety profile. Nonetheless, the HFpEF results stemmed from animal studies and engineered tissue, not from clinical trials involving patients.
Validation in human heart failure patients remains essential
British Heart Foundation, the organization funding this research, stated that these initial findings suggest urolithin A could help improve the heart’s relaxation and filling phases. However, they emphasized that benefits in humans with HFpEF have yet to be demonstrated. Similarly, King’s College London advised against interpreting these results as evidence that consuming pomegranates can treat heart failure. The study does not establish that any single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising biological target for ongoing HFpEF investigations and clarifies how urolithin A activates this pathway in experimental settings. As HFpEF remains a prevalent form of heart failure, often co-occurring with conditions like high blood pressure, obesity, and diabetes, these molecular insights deepen understanding of how heart relaxation might be influenced via this mechanism. To determine if urolithin A could produce similar benefits in patients, clinical trials will be necessary.