Scientists have found that a natural substance made by the body after eating certain foods may help the heart relax and work better in a difficult-to-treat form of heart failure.
In experimental models, the compound improved some measures of heart function by as much as 80%.
The substance is called urolithin A. The body can produce it when bacteria in the gut break down substances found in foods such as pomegranates, walnuts and some berries.
Researchers at King’s College London studied whether urolithin A could help people with a condition called heart failure with preserved ejection fraction, or HFpEF. The research will be published in the journal Science Advances.
Heart failure does not always mean that the heart has stopped working or has become too weak to pump. In HFpEF, the heart can still squeeze out a relatively normal amount of blood, but the heart muscle becomes stiff and has trouble relaxing between beats.
This matters because the heart needs to relax so its chambers can fill with blood before the next heartbeat. If filling becomes difficult, the body may not receive enough blood during activity, even though the heart’s pumping strength appears normal.
People with HFpEF may experience shortness of breath, tiredness, swelling and difficulty exercising. These symptoms can greatly reduce quality of life and may lead to repeated hospital stays.
The condition is becoming more common as populations grow older. High blood pressure, obesity, diabetes and other long-term health problems can all contribute to the changes that make the heart stiff.
Treating HFpEF has been difficult because it does not have a single cause. Some newer medicines can reduce hospital admissions and improve outcomes for certain patients, but researchers are still searching for treatments that directly improve the heart muscle’s ability to relax.
In the new study, the King’s College London team investigated how urolithin A affects the heart. The researchers discovered that the compound activates a protein involved in helping heart muscle and blood vessels function normally.
Activating this pathway appeared to make heart tissue better able to relax. It also reduced fibrosis, which is the buildup of stiff scar-like tissue that can make the heart less flexible.
Urolithin A also reduced abnormal enlargement of heart muscle cells. This enlargement can develop when the heart has been working against high pressure or other stresses for a long time.
In animal models of HFpEF, treatment with urolithin A improved some measurements of heart function by up to 80% compared with untreated animals. The researchers also saw less scarring and other harmful changes in the heart.
The team then tested the compound in human heart tissue grown in the laboratory from stem cells. These engineered tissues are designed to behave in some ways like real heart muscle, allowing scientists to study how human cells respond to possible treatments.
Urolithin A significantly improved the ability of the engineered human heart tissue to relax. This result is encouraging because it suggests the effect may not be limited to animals.
Another advantage is that urolithin A has already been studied in people for other purposes and has shown a generally favorable safety profile. However, that does not prove it is safe or effective as a treatment for heart failure.
Senior author Dr. Joseph Burgoyne said the study identifies a new pathway that researchers may be able to target when developing treatments for HFpEF. The results also suggest urolithin A itself deserves further investigation.
The findings should not be interpreted as evidence that eating large amounts of pomegranates, walnuts or berries can treat heart failure. People differ greatly in their ability to produce urolithin A from food because their gut bacteria are different.
The biggest limitation is that the heart-failure benefits have not yet been demonstrated in patients. Animal experiments and engineered human tissues can reveal how a treatment might work, but clinical trials are needed to find out whether it improves symptoms, hospital admissions or survival in people.
Overall, the study provides a promising new direction for a form of heart failure that remains challenging to manage. The biological results are strong enough to justify human research, but it is far too early to consider urolithin A a proven heart-failure treatment.
Source: King’s College London.
