A compound connected with foods such as pomegranates and walnuts could point scientists toward a new treatment for one of the most stubborn forms of heart failure.
Researchers found that urolithin A helped stiff heart tissue relax and reduced several damaging changes linked to the disease.
Urolithin A is not simply a nutrient that comes directly from a pomegranate. Instead, certain bacteria living in the gut can turn natural substances in pomegranates, walnuts and some berries into urolithin A after the foods are eaten.
The new research comes from scientists at King’s College London. Their study will be published in Science Advances and focuses on heart failure with preserved ejection fraction, commonly called HFpEF.
Heart failure is often imagined as a heart that has become too weak to pump properly. HFpEF is different because the heart’s squeezing ability can remain relatively normal while the muscle becomes unusually stiff.
Between heartbeats, a healthy heart relaxes and fills with blood. A stiff heart cannot fill as easily, so pressure can build up and patients may become breathless or exhausted, particularly when walking or exercising.
HFpEF accounts for around half of heart failure cases and is especially common among older adults. It often occurs alongside high blood pressure, obesity, diabetes and kidney problems, making the condition complicated to treat.
Doctors can treat some of the diseases that contribute to HFpEF, and newer heart-failure medicines have improved care. Even so, there remains a need for therapies that directly tackle stiffness, scarring and other changes inside the heart muscle.
Dr. Joseph Burgoyne and his colleagues investigated whether urolithin A could do this. Previous research had already created interest in the compound because of possible effects on healthy aging and the tiny structures inside cells that produce energy.
The team discovered a different way that urolithin A may help the cardiovascular system. It switched on a protein that helps control the relaxation of heart muscle and the normal function of blood vessels.
That discovery gave the researchers a possible explanation for what they saw in their experiments. When animals with features of HFpEF received urolithin A, some measures of heart performance improved by as much as 80% compared with untreated animals.
The compound also reduced fibrosis in the heart. Fibrosis is a process in which excessive scar-like material builds up between cells, making tissue harder and less flexible.
Another improvement involved the size of heart muscle cells. These cells can become enlarged when the heart is under long-term stress, but urolithin A reduced this harmful enlargement in the experimental models.
Animal results alone are not enough to predict what will happen in people, so the researchers also used engineered human heart tissue. They created heart-like tissue from human stem cells and tested how it responded to the compound.
The treated human tissue relaxed better than untreated tissue. Although a laboratory-grown piece of heart tissue cannot reproduce the complexity of a living patient, the result gives researchers another reason to investigate urolithin A in clinical trials.
Urolithin A has previously been tested in human studies, which means researchers already have some information about its safety. That could potentially make future development easier, but heart-failure patients may have very different health needs from participants in earlier studies.
The research also does not show that eating pomegranates can cure or treat HFpEF. Not everyone produces the same amount of urolithin A after eating these foods, and the amount produced naturally may differ greatly from the doses used in experiments.
Professor James Leiper of the British Heart Foundation described the work as promising but emphasized that the benefits have so far been demonstrated in experimental models rather than patients. Human clinical trials will be necessary before doctors know whether the approach can genuinely improve heart failure.
The study’s main strength is that the researchers found similar signs of benefit using several approaches, including disease models and engineered human tissue. They also identified a possible biological pathway explaining why the compound improved relaxation rather than simply reporting an unexplained effect.
Its main weakness is equally important: there is no evidence yet that urolithin A helps people living with HFpEF. An improvement in laboratory measurements does not automatically mean patients will breathe more easily, exercise longer, avoid hospital stays or live longer.
The findings therefore represent an early but interesting step rather than a new treatment ready for use. If clinical trials confirm that urolithin A can safely reduce heart stiffness and improve patients’ health, the discovery could eventually provide another option for a condition that remains difficult to treat.
Source: King’s College London.
