LONDON / RankWire.AI / – Heart failure with preserved ejection fraction (HFpEF) is a condition where the heart maintains its pumping ability but struggles to relax properly between beats, limiting blood filling and leading to symptoms like breathlessness, fatigue, and decreased exercise tolerance. This form of heart failure accounts for roughly half of all cases in the United Kingdom. A naturally occurring compound associated with pomegranates, urolithin A, has demonstrated promising effects on heart function in experimental settings. The compound was found to enable the heart to relax more efficiently during diastole, decrease fibrosis, and reduce abnormal enlargement of cardiac muscle cells. Some parameters showed improvements up to 80% compared to untreated models. Researchers also observed positive effects in engineered human heart tissue, adding further experimental evidence to support these findings.
Urolithin A forms through the action of gut microbes on specific compounds present in pomegranates, walnuts, and various berries, although its production varies among individuals. The research pinpointed its mechanism of action to PKGIα, a protein essential for normal blood vessel function and heart muscle relaxation. Specifically, urolithin A modifies cysteine 42 on the protein, activating a pathway linked to cardiovascular health. The study also investigated how the compound influences the structural integrity of heart tissue. King’s College London researchers reported enhancements in diastolic function, along with less tissue scarring and decreased hypertrophy of cardiac muscle cells in the experimental models treated with urolithin A.
Laboratory models show that Urolithin A enhances cardiac relaxation
The animal experiments primarily focused on diastolic function, which assesses the heart’s ability to relax and fill with blood after each contraction. Treated subjects displayed significantly better performance on several key measures compared to untreated controls. Additionally, the research documented a reduction in fibrosis, a condition that stiffens heart tissue and hampers proper filling. The observed improvement of up to 80% was specific to certain experimental metrics and does not imply that patients would experience an equivalent level of benefit; importantly, the study did not evaluate clinical outcomes in humans.
Further testing involved engineered human heart tissue derived from stem cells, allowing researchers to examine the effects on human cardiac tissue under controlled laboratory conditions. Urolithin A enhanced both relaxation and contraction processes within these tissue samples. Previous human studies involving urolithin A for different purposes have indicated a favorable safety profile. However, the current research on heart failure was limited to animal models and lab-grown tissues, with no clinical trials involving patients diagnosed with HFpEF at this stage.
Further human studies are necessary to confirm heart failure benefits
The British Heart Foundation funded this research and highlighted the impact of urolithin A on heart relaxation during early testing phases. The organization emphasized that these preliminary results do not establish a treatment for HFpEF. Researchers also cautioned against interpreting the findings as evidence that eating pomegranates could cure or prevent heart failure. The study concentrated on urolithin A and its biological activity, not on dietary pomegranate intake. No food tested in the research demonstrated an ability to treat or prevent heart failure.
This work highlights PKGIα cysteine 42 as a specific biological target in HFpEF research, providing laboratory evidence that urolithin A can activate this pathway and improve several indicators linked to cardiac relaxation. HFpEF frequently co-occurs with high blood pressure, obesity, and diabetes, making it a significant contributor to the global burden of heart failure. To determine whether these promising laboratory findings translate into clinical benefits, future trials must evaluate if the compound can produce similar effects in human patients.