Urolithin A, a compound produced by certain gut bacteria from polyphenols found in pomegranates, walnuts and berries, improved heart relaxation and reversed key features of HFpEF in mice while also enhancing function in lab-grown human heart tissue, although researchers say clinical trials are still needed.
By yourNEWS Media Newsroom.
A molecule created inside the gut after certain people eat polyphenol-rich foods may offer a new path for treating one of the most difficult forms of heart failure, according to research published in Science Advances.
The compound, urolithin A, is produced when intestinal bacteria metabolize ellagitannins and related polyphenols found in foods including pomegranates, walnuts and berries.
Researchers studying heart failure with preserved ejection fraction, or HFpEF, found that urolithin A could influence a molecular pathway involved in the heart’s ability to relax between beats.
In mice with HFpEF, the compound reversed several abnormalities associated with the condition, including excessive stiffness and impaired relaxation.
Experiments using engineered human heart tissue derived from stem cells produced similar signs of improved function, with treated tissue contracting and relaxing more efficiently.
The findings remain preclinical. Researchers have not yet demonstrated that urolithin A can reverse HFpEF in patients, and human clinical trials would be required before the compound could be considered an established treatment.
The work is notable because HFpEF differs from many other forms of heart failure.
About half of the estimated 6.7 million Americans age 20 and older who have heart failure are affected by HFpEF, according to the study.
In these patients, the heart can still contract and eject blood relatively normally. The problem develops during the relaxation phase.
The cardiac muscle becomes abnormally stiff and does not relax sufficiently between beats, reducing the heart’s ability to fill with blood.
Patients can develop symptoms including fatigue and shortness of breath even though the heart’s pumping strength, or ejection fraction, remains preserved.
That distinction has complicated treatment.
Many traditional heart failure medications were developed primarily to improve or compensate for weakened pumping ability. In HFpEF, researchers instead need ways to address the biological processes making the heart rigid and impairing its ability to relax.
The new study suggests urolithin A may act on that underlying mechanism.
Researchers found that the compound activated cysteine 42, a specific site on the PKGI protein involved in regulating relaxation in heart muscle and blood vessels.
Activating that pathway appeared to restore some of the flexibility lost in HFpEF.
In the mouse experiments, treatment improved the heart’s ability to relax and reduced damage associated with cardiac stiffness.
Researchers described the effect as more than simply alleviating symptoms because it appeared to influence molecular processes contributing directly to the disease.
The findings also expand the scientific interest surrounding urolithin A beyond heart failure.
Previous laboratory and animal research has examined the molecule for possible effects involving aging, muscle function, inflammation and cardiovascular health.
In aged mice, earlier research found that urolithin A supplementation improved running endurance by an average of 42%.
Those findings raised interest in the compound’s effects on muscle quality and mitochondrial function.
The newer HFpEF research suggests cardiac muscle may also respond to the molecule.
Other research reported in 2026 linked urolithin A produced from pomegranate polyphenols with reductions in arterial plaque accumulation and inflammation.
Pomegranates themselves contain high levels of compounds including punicalagin and ellagitannins.
A separate 2026 report described those compounds as potentially cardioprotective because of their effects on mitochondrial function and inflammatory pathways.
Pomegranates also contain flavonoids and tannins with antioxidant properties, which a 2024 report associated with cardiovascular support.
A 2025 article similarly highlighted the fruit’s antioxidant content and its ability to help protect cells from oxidative damage.
The important biological step, however, occurs after those plant compounds reach the gut.
Urolithin A is not present in large quantities in the original foods. Instead, certain intestinal microbes convert ellagitannins and related compounds into urolithins after they are consumed.
That makes the gut microbiome an important variable.
Not everyone appears capable of producing meaningful amounts of urolithin A from the same foods.
Dr. Steven R. Gundry wrote in Gut Check that only about 20% of the general population has the particular combination of intestinal bacteria necessary to generate urolithin A efficiently from dietary polyphenols.
If that estimate holds, eating pomegranates or walnuts would not necessarily produce the same urolithin A exposure in every person.
Bioavailability creates an additional complication.
Dave Asprey wrote in Head Strong that polyphenols depend in part on gut bacteria for their metabolism and utilization by the body.
Differences in the microbiome could therefore help explain why people may respond differently to identical polyphenol-rich diets.
Walnuts may have relevance on both sides of that process.
They contain precursors that can be converted into urolithins while also being associated with favorable changes in the intestinal microbiome.
A 2022 study found that walnuts supported both gut and cardiovascular health through effects on beneficial gut bacteria.
Researchers are increasingly studying these food-microbe interactions because the digestive tract can transform dietary compounds into entirely new molecules with biological activity that differs from the original food components.
Urolithin A is one example.
A 2026 review of the broader urolithin family also identified potential neuroprotective effects, suggesting researchers are examining the compounds across multiple organ systems.
The heart study went a step beyond animal testing by using human cardiac tissue created from stem cells.
That model allowed researchers to observe how human heart cells responded to urolithin A under controlled laboratory conditions.
Treated tissue displayed more efficient contraction and relaxation, supporting the possibility that the pathway identified in mice may also operate in human cardiac cells.
Stem cell-derived tissue nevertheless cannot reproduce all of the complexity of a living patient.
Human HFpEF can involve obesity, metabolic dysfunction, high blood pressure, inflammation, aging and multiple other cardiovascular conditions.
Clinical trials would have to determine whether urolithin A can reach relevant concentrations in patients, whether it remains safe with prolonged use and whether improvements seen in experimental tissue translate into meaningful reductions in symptoms or disease progression.
Researchers must also determine whether directly administering urolithin A would be more reliable than attempting to increase its production through diet.
Because only a portion of people may possess the necessary gut organisms, simply recommending more pomegranates, berries or walnuts would not guarantee equivalent exposure to the compound.
The findings therefore should not be interpreted to mean that eating those foods can reverse heart failure.
Instead, they identify a molecular pathway through which a substance ultimately derived from dietary polyphenols may influence diseased heart tissue.
That distinction is especially important for people already diagnosed with HFpEF, who should not replace prescribed treatment with dietary interventions based on preclinical findings.
The study nevertheless adds to evidence that interactions between food compounds and the gut microbiome can produce molecules capable of influencing human biology far beyond the digestive system.
If future clinical trials confirm the results, urolithin A could eventually offer researchers a treatment strategy aimed at restoring the heart’s ability to relax rather than merely compensating for the consequences of impaired filling.
For now, pomegranates, walnuts and berries remain dietary sources of the polyphenol precursors used by some gut bacteria to create urolithin A.
The larger scientific question is whether that microbial conversion can ultimately be harnessed in a predictable and clinically useful way.
The new findings provide an early indication that it may be possible, but researchers emphasized that the transition from mice and laboratory-grown heart tissue to an effective human therapy will require substantially more evidence.
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