Heart failure affects an estimated 64 million people worldwide. Approximately 50% of heart failure cases are classified as heart failure with preserved ejection fraction (HFpEF), a condition in which the heart muscle becomes stiff and cannot relax properly between beats. This stiffness impairs ventricular filling, can cause fluid retention, and leads to symptoms such as fatigue and shortness of breath.
Current management of HFpEF includes medications and lifestyle interventions aimed at risk factors and symptoms, including blood pressure control, weight loss, regular physical activity, and dietary measures such as reduced sodium intake. Despite recent advances, treatment options remain limited and do not fully address underlying mechanisms like increased myocardial stiffness.
In the study reported in Science Advances, researchers screened natural compounds to identify molecules that could target the protein PKG1alpha, which has a known role in facilitating cardiac muscle relaxation. The screening identified urolithin A, a metabolite produced by the gut microbiome after consumption of plant foods containing ellagitannins.
Ellagitannins are polyphenolic precursors present in foods such as pomegranates, certain berries, and walnuts. Urolithin A is not typically consumed directly; rather, it is generated by intestinal microbes metabolizing these dietary precursors.
Lead author Joseph Burgoyne, PhD, described the rationale: targeting PKG1alpha could address the impaired relaxation and increased stiffness that characterize HFpEF. The investigators tested urolithin A in both animal models of HFpEF and in engineered human heart tissue derived from human stem cells.
In the animal model used by the investigators, treatment with urolithin A produced marked improvements in measures of cardiac function related to relaxation and stiffness. The authors reported up to an 80% improvement in heart function in treated animals compared with untreated controls. In parallel, engineered human heart tissue generated from stem cells showed significantly improved tissue relaxation after exposure to urolithin A.
The study authors concluded that urolithin A reduced several markers of heart dysfunction in their HFpEF model, supporting the idea that targeting PKG1alpha could be a viable strategy for addressing the impaired relaxation seen in HFpEF. The investigators also noted that urolithin A or pharmacologic agents designed to act similarly could form the basis for new therapeutic development, while acknowledging that further research is required to determine applicability to patients.
Clinicians and independent experts cited in the source emphasize that these are preclinical findings. Kevin Shah, MD, a board-certified cardiologist who commented on the work, noted the value of concordant results in animal models and engineered human tissue but stressed the necessity of clinical trials to translate these results into patient care. He highlighted that HFpEF is heterogeneous and that treatments may need to be tailored by underlying drivers, such as hypertension or kidney disease.
The next steps cited by experts include clinical studies to assess whether the preclinical benefits of urolithin A translate into measurable improvements in patient-centered outcomes — for example, symptom burden, exercise capacity, and quality of life — as well as longer-term safety and efficacy.
Study authors and nutrition experts caution that the current evidence is insufficient to recommend eating pomegranates or other specific foods as a treatment for heart failure. In a press release, Burgoyne stated that while the findings raise the possibility that dietary approaches that enhance urolithin A production might help, there is not enough evidence to support using pomegranate or related foods as a therapeutic intervention for HFpEF.
Nutrition experts quoted in the source emphasize that urolithin A is a microbial metabolite, not a dietary nutrient consumed in isolation. Production of urolithin A from ellagitannin precursors depends on an individual's gut microbiome composition, which varies markedly between people. Thus, direct supplementation and dietary intake are not equivalent.
The source article summarizes practical dietary guidance from a registered dietitian nutritionist, who framed urolithin A production as a reason to include certain plant foods regularly rather than treating any single food as a medicine. Foods that contain ellagitannins or related precursors include:
Suggested ways to incorporate these foods into a whole-foods dietary pattern include adding berries to oatmeal or yogurt, sprinkling pomegranate arils on grain bowls or salads, including walnuts in salads or snacks, or consuming modest amounts (for example, a small serving) of pomegranate juice as part of a diverse diet.
The dietitian underscored that eating whole foods provides fiber, polyphenols, and micronutrients that support vascular and cardiac health, whereas individual production of urolithin A from those foods will depend on the gut microbiome and can vary considerably. She advised continuing established fundamentals for heart health: varied plant-based foods, physical activity, adequate sleep, adherence to prescribed medications, and further research to clarify mechanisms and clinical utility.