LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that enhances key indicators of cardiac performance in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A increased certain metrics by up to 80% in treated animal subjects compared to untreated controls. Additionally, it facilitated relaxation of heart tissue, decreased scarring, and limited the abnormal growth of heart muscle cells. The team also observed improved relaxation in engineered human cardiac tissue derived from stem cells.
HFpEF develops when the heart maintains a normal or nearly normal pumping efficiency but struggles with relaxation and filling between beats. Symptoms can include breathlessness, fatigue, and diminished exercise capacity. According to the British Heart Foundation, it makes up about half of all heart failure cases in the UK. Urolithin A is produced in the human body when gut bacteria process compounds found in foods such as pomegranates, walnuts, and some berries, though individual production levels vary.
The research team identified that urolithin A interacts with a protein called PKGIα, which is involved in regulating blood vessel function and heart muscle relaxation. The compound directly modifies cysteine 42, a specific amino acid on the protein, activating a pathway linked to cardiovascular health. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published by Science Advances. Researchers from King’s College London led the work, with Joseph Burgoyne serving as senior author.
Compound reduces fibrosis and abnormal cardiac growth
In animal models, urolithin A improved diastolic function, reflecting better heart relaxation and filling. The treatment also decreased fibrosis, which is the accumulation of scar tissue impairing cardiac performance, and lessened the enlargement of heart muscle cells compared to untreated controls. The reported improvements of up to 80% pertain to specific measures of heart function in the experimental setting, and do not imply an identical benefit in human patients or a reduction in heart failure rates.
Further testing in engineered human heart tissue made from stem cells showed that urolithin A enhanced both relaxation and contraction processes. Since this compound has already undergone human studies for other uses and demonstrated a good safety profile, these findings are promising. However, the current results are limited to animal models and lab-grown tissues, not yet confirmed through clinical trials.
Human clinical evidence remains essential
British Heart Foundation, the funding organization, highlighted that these early results suggest urolithin A may help improve how heart tissue relaxes and fills. Nonetheless, they emphasized that benefits in actual HFpEF patients have not yet been established. Likewise, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates could treat heart failure. No individual food has been proven by this research to prevent or cure the condition.
The study points to PKGIα cysteine 42 as a biological target for future HFpEF research, demonstrating how urolithin A activates this pathway in experimental systems. HFpEF remains a prevalent form of heart failure, often co-occurring with high blood pressure, obesity, and diabetes. The research adds molecular detail about how heart relaxation could be influenced through this pathway. To confirm if urolithin A can safely produce similar effects in humans, clinical trials would be necessary.