A compound produced in the body after eating pomegranates improves heart function by up to 80% in a type of heart failure with limited treatment options.
Scientists at King's College London have discovered that urolithin A – a natural compound produced in the body after consuming foods such as pomegranates, walnuts and some berries – improves the heart's ability to relax, reduces scarring and prevents harmful enlargement of the heart.
The finding could give hope to nearly half a million people in the UK who have a type of heart failure where the heart retains its ability to pump blood but becomes stiff and less able to relax between beats, making it harder to fill with blood. This is known as heart failure with preserved ejection fraction and accounts for around half of all heart failure cases. The condition can lead to breathlessness, fatigue, reduced ability to exercise and an overall poor quality of life.
Despite its growing prevalence, effective treatments remain relatively limited. The condition is hard to treat because it is driven by many different factors – including ageing, high blood pressure, and diabetes. As the heart can still pump normally, but becomes stiff and does not fill properly, heart failure treatments are less effective. Instead, clinicians focus on managing the underlying conditions and advise lifestyle modifications, such as weight loss and controlling blood sugar.
Dr Joseph Burgoyne, senior author of the study, King's College London, said: "This type of heart failure is becoming increasingly common as populations age and rates of obesity and diabetes rise. Despite its growing burden, treatment options remain limited because the disease is complex and varies considerably between patients."
Urolithin A has attracted growing interest in recent years because of its links to healthy ageing and mitochondrial function, a process in the body which generates energy.
In a research first, the scientists discovered that urolithin A activates a protein called PKGlα, which plays an important role in both blood vessel function and heart muscle relaxation. Urolithin A targets a specific amino acid on the protein, activating a pathway resulting in cardiovascular benefits.
Animal models treated with urolithin A had improved measures of heart function by up to 80% compared to models which were not treated with urolithin A. The laboratory experiment revealed that urolithin A increased the heart tissue's ability to relax and reduced harmful scarring, also known as fibrosis, compared to controls. The compound also reduced enlargement of heart muscle cells compared to controls, helping to preserve normal cell function.
The researchers also tested urolithin A in engineered human heart tissue created from human stem cells. This is a cutting-edge laboratory model that closely mimics the structure and function of human heart muscle. Urolithin A significantly improved tissue relaxation in these cells, suggesting the findings could translate to human cardiac function.
Unlike many experimental compounds, urolithin A has already been evaluated in human studies and shows to have a favourable safety profile.
While more research is needed before the findings can be translated into treatments for patients, the study identifies both a promising new drug target and a naturally derived compound that could help address a significant challenge in cardiovascular medicine.
Dr Joseph Burgoyne, senior author of the study, said: "This type of heart failure remains one of the most challenging forms of heart disease to treat. Our findings identify a completely new therapeutic target and show that urolithin A can activate this pathway to improve heart relaxation and reduce disease severity. This raises the exciting possibility of developing new treatments that improve clinical outcomes and quality of life for people living with the condition.
"While there isn't enough evidence to suggest that people should eat pomegranates to treat heart failure, these findings raise the possibility that dietary approaches that enhance urolithin A production may help alleviate this condition."
Dr Joseph Burgoyne is a cardiovascular scientist at King's College London whose research is uncovering the molecular mechanisms that control the health of the heart and blood vessels. His work focuses on how cells respond to oxidative stress, revealing new ways that blood pressure, heart function and vascular health are regulated. By identifying these fundamental biological processes, his research aims to develop new treatments for cardiovascular diseases such as hypertension and heart failure, with the ultimate aim of improving outcomes for patients.
This study was funded by the British Heart Foundation.
Professor James Leiper, Director of Research at the British Heart Foundation, said: "Heart failure with preserved ejection fraction (HFpEF) makes up roughly half of all heart failure cases in the UK, and can be debilitating. This early-stage study in experimental models suggests that urolithin A may help to improve the heart tissue's ability to relax and fill with blood between beats, reducing the harmful changes to the heart muscle seen in HFpEF.
"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 to test if this approach is effective for patients. In the meantime, a healthy, balanced diet remains one of the best ways to look after your heart. Eating plenty of fruit and vegetables is linked to better heart health, but it's important to remember that no single food can prevent or treat heart disease on its own."
The study will be published in Science Advances.
