Natural compound linked to pomegranates targets a hard-to-treat form of heart failure

Some hearts can still squeeze well, yet fail in another way. They become stiff, struggle to relax between beats and leave patients breathless, tired and short of options.

A study from King’s College London points to a possible new approach for that condition, called heart failure with preserved ejection fraction. The work focuses on urolithin A, a natural compound produced in the body after consuming foods such as pomegranates, walnuts and some berries.

In preclinical tests, urolithin A improved measures of heart function by up to 80 percent compared with models that did not receive the compound. It also improved the heart’s ability to relax, reduced scarring and helped prevent harmful enlargement of heart muscle.

The condition affects nearly half a million people in the UK and accounts for around half of all heart failure cases.

Heart failure is often associated with a weak pump. In heart failure with preserved ejection fraction, the problem is different.

The heart can still pump blood normally. But it becomes stiff and less able to relax between beats. That makes it harder for the heart to fill with blood.

Patients can develop breathlessness, fatigue, reduced exercise ability and poor quality of life. The condition is also hard to treat because it has many drivers, including ageing, high blood pressure and diabetes.

Dr Joseph Burgoyne, senior author of the study at King’s College London, said the condition is becoming more common.

“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.”

Because the heart’s pumping ability remains preserved, some standard heart failure treatments are less effective. Clinicians often focus on underlying conditions and lifestyle changes, such as weight loss and blood sugar control.

Urolithin A has attracted attention because of its links to healthy ageing and mitochondrial function. Mitochondria help generate energy inside cells.

The new work identified a different role for the compound. The scientists found that urolithin A activates a protein called PKGIα, which plays an important part in blood vessel function and heart muscle relaxation.

More specifically, urolithin A targets a particular amino acid on that protein. That activates a pathway linked to cardiovascular benefits.

The discovery matters because heart relaxation sits at the center of this form of heart failure. A therapy that improves relaxation could address a core feature of the disease rather than only treating related conditions.

The researchers tested urolithin A in animal models and in engineered human heart tissue created from human stem cells. That tissue model closely mimics the structure and function of human heart muscle.

Animal models treated with urolithin A showed improved measures of heart function by up to 80 percent compared with untreated models.

Laboratory experiments also showed that the compound increased the heart tissue’s ability to relax. It reduced fibrosis, the harmful scarring that can make heart tissue stiffer.

Urolithin A also reduced enlargement of heart muscle cells compared with controls. That helped preserve more normal cell function.

The engineered human heart tissue results added another important signal. Urolithin A significantly improved tissue relaxation in those cells, suggesting the findings could translate to human cardiac function.

That does not mean the compound is already a proven treatment for patients. The research still needs further testing before it can move into medical use for this condition.

But the human tissue result gives scientists a more relevant bridge between animal experiments and future clinical work.

The study identifies both a possible drug target and a naturally derived compound that can activate it.

That target, PKGIα, is involved in the way blood vessels work and how heart muscle relaxes. Activating it through the pathway identified in this research could give scientists a more specific way to address disease severity.

Dr Burgoyne said the finding could open a new direction for treatment.

“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.”

One practical advantage is that urolithin A has already been evaluated in human studies and has shown a favorable safety profile. That does not prove it will work for heart failure. It does mean researchers are not starting with a compound that is entirely unfamiliar in humans.

The findings naturally raise a dietary question. Urolithin A can be produced after eating foods such as pomegranates, walnuts and some berries. But the study does not show that eating those foods treats heart failure.

Burgoyne was careful about that point.

“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.”

That distinction matters. The research points to a biological pathway and a compound with promising effects in preclinical settings. It does not replace clinical evidence in patients.

Future work would need to test whether urolithin A can improve outcomes in people with heart failure with preserved ejection fraction. Researchers would also need to understand dosing, response differences and how the compound fits with existing care.

The work gives cardiovascular researchers a new target for a disease with limited treatment options. By activating PKGIα, urolithin A may help address the relaxation problem that defines heart failure with preserved ejection fraction.

The findings could guide development of drugs that improve heart relaxation, reduce fibrosis and limit harmful heart enlargement. They may also support future studies of dietary approaches that increase urolithin A production, though that remains unproven as treatment.

For patients, the result is not an immediate therapy. Its value is scientific direction. It identifies a pathway that could help researchers move beyond managing related conditions and toward treatments aimed at the stiff, poorly relaxing heart itself.

These resources examine HFpEF biology and treatment while providing clinical context for previous human research involving urolithin A.

Heart failure with preserved ejection fraction: everything the clinician needs to know: Reviews the mechanisms, diagnosis and evolving management of HFpEF, including why its biological diversity makes treatment particularly challenging. (The Lancet, 2024)

Clinical Update in Heart Failure with Preserved Ejection Fraction: Summarizes current understanding of HFpEF pathophysiology and emerging treatment strategies, including fibrosis, abnormal energetics and cardiometabolic disease. (Current Heart Failure Reports, 2024)

Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations: Compares contemporary international guidance for diagnosing and managing HFpEF and highlights areas where treatment recommendations continue to evolve. (European Heart Journal - Quality of Care and Clinical Outcomes, 2024)

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans: Reports a first-in-human study showing that orally administered urolithin A was bioavailable and had a favorable safety profile in healthy older adults. (Nature Metabolism, 2019)

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults: Provides additional human clinical data on urolithin A while examining physical performance and biomarkers related to mitochondrial health. (Cell Reports Medicine, 2022)

Research findings are available online in the journal Science Advances.

The original story "Natural compound linked to pomegranates targets a hard-to-treat form of heart failure" is published in The Brighter Side of News.

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