Pomegranate-linked compound improves heart function by 80% in lab — and scientists now know why

A compound your gut quietly manufactures after you eat a pomegranate has improved heart function by up to 80 percent in animal models of one of cardiology's most stubborn problems — a form of heart failure that affects roughly half of all heart failure patients and has resisted almost every drug thrown at it.

The compound is urolithin A, produced when gut bacteria break down ellagitannins found in pomegranates, walnuts, and some berries. Researchers at King's College London, publishing in Science Advances, have now identified for the first time how it acts on the heart: by activating a protein called PKGIα at a specific site — a cysteine molecule known as Cys42 — which in turn improves how heart muscle cells handle calcium, allowing the heart to relax more effectively between beats.

The condition at the centre of the research is heart failure with preserved ejection fraction, or HFpEF. Unlike the more familiar image of a weakened, poorly pumping heart, HFpEF involves a heart that contracts normally but has become too stiff to relax and fill with blood properly. The result — breathlessness, fatigue, reduced exercise capacity, poor quality of life — is just as debilitating, but the underlying biology is far harder to target. Major clinical trials of drugs aimed at related signalling pathways have largely failed.

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.— Dr. Joseph Burgoyne, senior author, King's College London

In mice given a diet- and hormone-induced version of HFpEF, a week of urolithin A treatment improved measures of diastolic heart function, reduced fibrosis — the scarring that stiffens heart tissue — limited enlargement of heart muscle cells, and increased the animals' running activity. When the researchers tested the same compound in genetically modified mice that lacked a functional Cys42 site, the benefits disappeared entirely, confirming the effect depended on that specific molecular mechanism.

To test whether the results might extend to human biology, the team applied urolithin A to engineered human heart tissue grown from stem cells — a laboratory model designed to closely mimic real heart muscle. The compound significantly improved how quickly the tissue contracted and relaxed, suggesting the animal findings could be relevant to human cardiac function.

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.— Dr. Joseph Burgoyne, senior author, King's College London

Burgoyne told Newsweek that while urolithin A is associated with pomegranates, it is not present in the fruit itself in significant amounts — it is produced by gut bacteria metabolising compounds in the food. He also stressed that eating a particular quantity of pomegranate is not equivalent to receiving a defined dose of urolithin A, meaning the findings do not translate into a dietary prescription.

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, senior author, King's College London

One practical advantage urolithin A has over many experimental compounds is that it has already been evaluated in human studies and shown a favourable safety profile, which Burgoyne said supports the feasibility of moving toward a clinical trial. The study identifies the Cys42 site on PKGIα as a drug target that could potentially be addressed either through urolithin A itself or through compounds designed to act on the same mechanism.

The British Heart Foundation, which funded the research, welcomed the findings while urging caution about how far they can currently be taken.

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.— Professor James Leiper, Director of Research, British Heart Foundation

One gap the researchers themselves acknowledge: the mouse study used only male animals, even though women tend to suffer from HFpEF more than men. Preclinical studies suggest there are sex-dependent differences in how rodent hearts respond to metabolic and hypertensive stress, so whether the results extend to female biology remains unclear.

HFpEF accounts for roughly half of all heart failure cases and affects nearly half a million people in the UK alone. It is driven by a combination of aging, high blood pressure, obesity, and diabetes — factors that make a single-drug solution unlikely and have caused previous large trials to fail. The identification of PKGIα's Cys42 site as a targetable mechanism represents a new avenue that bypasses the pathways those earlier trials addressed.

Why it matters — HFpEF is one of the most common and least treatable forms of heart disease, and this study identifies the first molecular mechanism by which urolithin A could address its root cause — opening a path to new drugs and, eventually, clinical trials.

Reported by goodnewsnetwork.org, sciencedaily.com, sci.news, newsweek.com, sciencealert.com