In a study published in the scientific journal Science Advances, funded by the British Heart Foundation, researchers at King’s College in London discovered that urolithin A, a compound associated with foods such as pomegranates, may help the heart relax more effectively as well as reduce scarring and limit harmful enlargement for normal function.
Urolithin A is a compound produced in the body after consuming food such as pomegranates, walnuts, and some berries when the natural compounds in the food, ellagitannins, are broken down by gut microbes. It’s a compound that scientists have become increasingly interested in due to its uncovered associations with healthy aging and mitochondrial function, which is vital to cell energy production.
In the recent study, the team used animal models to report promising results: The compound improved heart function by as much as 80% compared to those that didn’t receive the experimental treatment. Further lab tests demonstrated similarly positive results by relaxing heart tissue and reducing fibrosis, a harmful scarring that can interfere with normal organ function. With these successes, the researchers moved on to human stem cells to engineer human heart tissue in a lab to mimic the structure and function of human heart muscles, which further reinforced effects of improved relaxation to suggest a connection to the initial success found in the animal model. Their findings were explained by how urolithin A activates the protein PKGLα, which is vital in blood vessel function and relaxing heart muscles by acting on particular amino acids to trigger a pathway associated with cardiovascular benefits.
These findings may be good news for nearly half a million people in the UK suffering from preserved ejection fraction (HFpEF), a form of heart failure that accounts for approximately half of all heart failure cases — characterised by breathlessness, fatigue, reduced ability to exercise, and overall poor quality of life. People with this condition have hearts that can pump effectively, but have difficulty relaxing between beats to fill the organ with blood. At the moment, treatment is relatively limited due to the difficulty in managing the condition’s contributing factors such as aging, high blood pressure, and diabetes — clinicians usually tend to focus on managing underlying conditions with lifestyle changes like weight loss and blood sugar control.
However, despite the apparent positive results and implications, there are still a few caveats yet to be explored. First, while the pomegranate connection is an interesting one, simply eating pomegranates does not guarantee the body will produce certain amounts of urolithin A due to the ways in which the conversion process from ellagitannins depends partly on gut microbiomes that differ from person to person. Additionally, while the lab-made heart is a promising starting point for the treatment’s efficacy, it is limited in the fact that it cannot replicate all biological processes that occur in a living person due to the focused nature of the cells produced. To further prove the effectiveness of urolithin A as a treatment, more research will be conducted through clinical trials to see if the same kind of results are reinforced by human subjects.
Dr. Joseph Burgoyne, senior author of the study and a cardiovascular scientist at King’s College London, reflected on the study in light of its possible treatment benefits by explaining that “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.”
