Roughly half of all heart failure patients have a form doctors call HFpEF, short for heart failure with preserved ejection fraction.
The heart squeezes normally but cannot relax and refill between beats, and drugs have struggled to touch it.
A new study points to a natural compound made in the gut, and the effect in animals was striking.
Researchers at King's College London tested urolithin A, a molecule your gut bacteria produce after you eat pomegranates, walnuts and some berries. In mice bred to mimic HFpEF, and in miniature human heart tissue grown from stem cells, the compound eased the stiff heart's ability to relax.
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It also reduced scarring and abnormal enlargement of the heart muscle.
The study was published in Science Advances in September 2026 and was funded by the British Heart Foundation.
Why this form of heart failure is so hard to treat
HFpEF accounts for about half of all heart failure cases, according to the American College of Cardiology.
In the United States, that adds up to more than 3 million people. Symptoms include shortness of breath, fatigue and a sharp drop in the ability to exercise.
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The problem is not pumping strength. It is stiffness. A stiff left ventricle cannot draw in enough blood between beats, so the body gets shortchanged.
Major trials of drugs aimed at the usual blood-vessel signaling pathways have mostly failed to change patient outcomes.
"This type of heart failure remains one of the most challenging forms of heart disease to treat," said Dr. Joseph Burgoyne, the senior author and a cardiovascular biologist at King's College London.
What the compound actually did
Urolithin A works on a protein called PKGIα, which helps blood vessels and heart muscle relax. In the study, the compound switched on that pathway by modifying a specific building block of the protein, a site called cysteine 42.
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In mice with HFpEF, one week of treatment improved diastolic function, reduced fibrosis and cut abnormal thickening of the heart.
In engineered human heart tissue, the tissue relaxed measurably better after treatment. In the strongest measurements reported by the researchers, heart function improved by up to 80 percent compared with untreated controls.
To confirm the compound was working through that exact site, the team repeated the experiment in mice genetically altered to lack a functional cysteine 42. In those mice, the benefit vanished.
What this means for people
Nothing in this study was done in patients. The results come from mice and lab-grown tissue, which is why the researchers are careful about how they talk about food.
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"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," Burgoyne said.
Professor James Leiper, associate medical director at the British Heart Foundation, put it plainly. "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."
The foods that feed urolithin A production
Your body does not eat urolithin A directly. Gut bacteria make it from a family of plant compounds called ellagitannins. The main food sources include:
- Pomegranates and pomegranate juice
- Walnuts and pecans
- Raspberries, strawberries and blackberries
Not everyone produces the compound in equal amounts. The mix of bacteria in the gut differs from person to person, so two people eating the same handful of walnuts can end up with very different levels in the blood.
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Pomegranate juice has been studied on its own for effects on blood pressure in small trials, though findings there have been mixed.
Anyone with symptoms of heart failure, such as unexplained breathlessness, fatigue or swollen ankles, should talk to a doctor rather than reach for a supplement bottle.
A clinical trial of urolithin A in HFpEF patients has not yet been announced.
This article is made and published by Mie Hermansen, who may have used AI in the preparation.