A substance that can be produced in the human body from, among other things, components found in pomegranates, walnuts, and certain berries is taking center stage in cardiovascular research.
Scientists at King’s College London have now investigated whether urolithin A could improve the function of a stiff heart. In experiments using animal models of a specific form of heart failure, the substance improved the heart muscle’s ability to relax between heartbeats. At the same time, pathological changes in the heart tissue decreased. The researchers also observed positive effects in artificially generated human heart tissue.
The results are interesting but are still based on experimental research. Clinical trials are still needed to determine whether urolithin A can actually be used therapeutically in people with heart failure.
When the Heart Pumps But Does Not Relax Properly
Previous studies have already examined the potential health benefits of pomegranates. A meta-analysis published in 2025 evaluated 53 randomized studies involving more than 2,300 participants and found, among other things, evidence of improvements in blood pressure and several other cardiometabolic risk factors. However, the results pertain to pomegranates or related supplements and not specifically to urolithin A or the treatment of heart failure.
The current study focuses on heart failure with preserved ejection fraction, or HFpEF for short. In this form of heart failure, the heart is generally still able to pump blood out of the ventricles sufficiently. The problem lies rather in the relaxation phase. A healthy heart contracts and then relaxes again. During this relaxation phase, the ventricles can fill with blood. However, if the heart muscle becomes stiffer, this filling process can be impaired. The heart must then work at a higher pressure to draw in enough blood and subsequently pump it into the circulatory system.
The term “preserved ejection fraction” can therefore be somewhat misleading. It does not mean that the heart is healthy overall. The ejection fraction merely describes what proportion of the blood present in the ventricle is ejected with each heartbeat. In HFpEF, this value may fall within the normal range, even though the heart muscle’s ability to relax and fill with blood is already impaired. For those affected, this can manifest, among other things, as shortness of breath, fatigue, reduced physical endurance, and a lower quality of life. Symptoms often first appear during physical exertion but can become more pronounced in everyday life as the disease progresses.
HFpEF is particularly common in older adults and is also associated with conditions and risk factors such as high blood pressure, obesity, and diabetes. Changes in the blood vessels and chronic metabolic processes can also play a role. As a result, there is no uniform clinical picture: in different patients, various factors can contribute to the heart muscle becoming stiffer and less able to relax.
Treatment is therefore challenging. Rather than targeting a single pathological mechanism, it is often necessary to address multiple underlying factors. This is precisely where current research is focused: Scientists are searching for new molecular mechanisms directly involved in the impaired relaxation of the heart muscle that may be specifically targeted for treatment.
A Metabolic Byproduct Takes Center Stage
Urolithin A is not a substance that simply enters the bloodstream unchanged from a pomegranate. Rather, it is first produced in the gut: Certain plant compounds, particularly so-called ellagitannins and ellagic acid, are metabolized by gut bacteria. This process can result in the formation of urolithins—including urolithin A.
The actual amount produced can vary from person to person. Key factors include which bacteria are present in the gut and how they process the ingested plant compounds. Therefore, it is not possible to predict how much urolithin A is produced in the body based solely on the amount of a particular food consumed.
This makes the substance particularly interesting for research. In recent years, urolithin A has been studied primarily in connection with mitochondria, cellular metabolism, and healthy aging. One area of focus is what is known as mitophagy. Put simply, this is a cellular recycling process in which damaged mitochondria are identified and broken down. Mitochondria are often referred to as the “powerhouses” of cells. They provide a large portion of the energy that cells need to function. Heart muscle cells are particularly energy-dependent because the heart works around the clock and must constantly contract and relax.
That is why scientists are interested in whether changes in energy metabolism and mitochondrial quality are also linked to heart muscle diseases. The current study, however, takes a slightly different approach: The researchers investigated whether urolithin A influences a signaling pathway that is directly involved in the relaxation of the heart muscle.
A Specific Protein Plays a Central Role
The researchers focused on the protein PKGIα, which functions within heart muscle cells as part of an important signaling system. Such signaling pathways ensure that external or internal stimuli within the cell are translated into specific responses. Among other things, PKGIα is involved in processes that influence the tension of muscle cells and, consequently, the relaxation of the heart muscle. Of particular interest was a small but crucial site within the protein: the amino acid cysteine 42. The scientists found evidence that urolithin A interacts with this site and can thereby influence the activity of PKGIα.
This is relevant because impaired signal transmission at this site can contribute to impaired relaxation of heart muscle cells. If, on the other hand, the corresponding signaling pathway is activated, the cells can more easily return to a relaxed state after contracting.
The researchers see this as a possible link between urolithin A and the improved heart muscle relaxation they observed in their experimental models. The compound may therefore not simply have a general effect on the heart, but rather specifically influence a molecular switch that is relevant to the function of heart muscle cells.
The study thus also provides a potential starting point for the development of new medications. Instead of treating only the symptoms of HFpEF, future efforts could focus on specifically targeting signaling pathways involved in the pathologically altered relaxation of the heart muscle. However, it remains to be investigated whether this mechanism can actually be utilized for treatment in humans.
Improved Heart Function in the Experimental Models
The scientists then investigated what happens when urolithin A is administered in various experimental models. In the treated animals, measures of cardiac function improved significantly. In some studies, the improvement compared to the untreated models was as high as 80 percent.
In addition, the researchers observed less fibrosis. This refers to pathological scarring of heart tissue, which can make the tissue stiffer and impair its normal function. The enlargement of individual heart muscle cells was also less pronounced. Such changes can occur when the heart is exposed to increased strain over an extended period.
The results thus suggest that urolithin A may not only influence the relaxation of the heart muscle but also potentially mitigate some of the structural changes associated with HFpEF.
Human Heart Tissue Was also Examined
Another part of the study is particularly interesting. The researchers tested urolithin A not only on animals but also on artificially generated human heart tissue. This tissue was produced from human stem cells and serves as a laboratory model for studying certain properties of the human heart muscle.
Here, too, urolithin A showed a measurable effect: the artificial heart tissue was able to relax more effectively under the treatment. In addition, changes were observed in both relaxation and contraction. This makes the results interesting for further research. However, this is still a laboratory model and not a treatment for patients.
Does this Mean that Pomegranates Protect Against Heart Failure?
No, the study explicitly does not allow for this conclusion. While urolithin A can be produced in the body through metabolism after consuming certain foods, the amount of urolithin A actually produced depends, among other things, on an individual’s gut bacteria.
Furthermore, the current study did not simply examine whether people with HFpEF become healthier by eating pomegranates. Rather, the researchers investigated the effect of the isolated compound urolithin A in experimental models.
Therefore, no recommendation can currently be derived from the results to use pomegranates or other sources of urolithin A for the treatment of heart failure. Experts also emphasize that there is not yet sufficient evidence to support this.
An Interesting Approach – But Not Yet a Treatment
The study provides new evidence that the PKGIα signaling pathway could be of therapeutic interest in HFpEF. Urolithin A could serve as a starting point for the development of new active compounds. At the same time, the study clearly highlights the limitations of current knowledge: The positive effects have so far been observed in animal models and in artificially generated human heart tissue. Whether urolithin A also improves heart function in humans, what dosage would be necessary, and which patients might benefit from it remains to be seen. Clinical trials are needed to answer these questions.
Before the current findings can be translated into a potential treatment, several questions must be answered. These include, among other things, whether urolithin A actually reaches the signaling pathway under investigation in sufficient quantities in humans and whether the changes observed in the laboratory can be translated to the heart’s actual performance.
Equally important is the question of long-term safety and efficacy. Although urolithin A has already been studied in humans in other contexts and has demonstrated a favorable safety profile, this does not yet indicate efficacy against HFpEF.
The new study therefore primarily provides an interesting starting point for further research. It shows that a molecular mechanism that has received little attention to date could potentially help influence the impaired relaxation of the heart muscle in HFpEF.
For people with heart failure, a balanced diet remains an important component of a heart-healthy lifestyle. However, based on current knowledge, a single food or plant compound cannot prevent or treat heart failure.