Pomegranates may boost heart failure recovery by stimulating urolithin A production

Scientists have discovered that a certain compound produced in the body after eating foods like pomegranates, walnuts, and some berries — known as urolithin A — improves heart function by up to 80% in a type of heart failure that has limited treatment options. 

The specific type of heart failure investigated is known as heart failure with preserved ejection fraction (HFpEF). While the heart can still pump blood during this condition, it becomes stiff and does not fill properly, meaning that heart failure treatments are less effective.

When addressing HFpEF, clinicians focus on managing the underlying conditions and advise lifestyle modifications, such as weight loss and controlling blood sugar.

The researchers explain that during HFpEF, urolithin A might improve the heart’s ability to relax, reduce scarring, and prevent its harmful enlargement. It does this by targeting a specific amino acid on the protein, activating a pathway resulting in cardiovascular benefits.

“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,” says Dr. Joseph Burgoyne, senior author of the study at King’s College London, UK.

One of the most difficult heart conditions

Burgoyne underscores 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.”

He believes that the study findings raise the 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.”

More research is needed before the findings can be translated into treatments for patients. However, the study authors believe their findings identify both a promising new drug target and a naturally derived compound that could help address a significant challenge in cardiovascular medicine. 

A “research first” for heart health

Unlike many experimental compounds, the study authors note that urolithin A has already been evaluated in human studies and shows a favorable safety profile. It has attracted growing interest in recent years because of its associations with healthy aging and mitochondrial function, in which the body generates energy.

In what they call a “research first,” funded by the British Heart Foundation, the scientists discovered that urolithin A activates a protein called PKGlα, which plays an important role in blood vessel function and heart muscle relaxation.

Urolithin A has attracted growing interest in recent years due to its link with healthy aging and mitochondrial function.In the upcoming paper to be published in Science Advances, animal models treated with urolithin A had better measures of heart function by up to 80% compared to those that were not.

Compared to controls, the laboratory experiment revealed that urolithin A increased the heart tissue’s ability to relax and reduced harmful scarring, also known as fibrosis.

The compound also reduced the enlargement of heart muscle cells compared to controls, which helped preserve normal cell function, note the study authors.

They also tested urolithin A in engineered human heart tissue created from human stem cells, which is a laboratory model that closely mimics the structure and function of human heart muscle.

The scientists report that urolithin A significantly improved tissue relaxation in these cells, further suggesting that these findings could translate to human cardiac function. 

Expanding limited treatment options

The researchers say that HFpEF can lead to breathlessness, fatigue, reduced ability to exercise, and an overall poor quality of life.

Despite the growing prevalence, effective treatments remain relatively limited. The condition is hard to treat because it is driven by many different factors — including aging, high blood pressure, and diabetes.

“HFpEF makes up roughly half of all heart failure cases in the UK and can be debilitating,” comments professor James Leiper, director of Research at the British Heart Foundation.

“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 scientists note these benefits have so far only been seen in animals and engineered human tissue. They note that 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,” Leiper concludes.