Heart failure sounds like a heart that has simply stopped working.
But that isn’t always what happens.
In one increasingly common form of the disease, the heart can still squeeze surprisingly well. The problem appears when it tries to do the opposite.
It cannot relax properly.
The heart muscle becomes stiff. Its chambers have difficulty filling normally between beats. Pressure builds inside the heart and can eventually back up into the lungs and other parts of the body.
Someone may become breathless walking across a room, climbing stairs, or even lying flat at night. Legs can swell. Everyday activities that once required no thought suddenly demand effort.
This condition is known as heart failure with preserved ejection fraction, or HFpEF.
It is notoriously difficult to treat.
Now researchers have uncovered an unexpected possible avenue involving a compound called urolithin A—a substance the human body can produce after gut bacteria metabolize compounds found in foods including pomegranates, walnuts, and certain berries.
In experimental animal models of HFpEF, urolithin A improved several measurements of heart function, in some cases by as much as 80%. It helped stiff heart muscle relax more effectively, reduced abnormal enlargement and scarring, and improved important aspects of cellular energy production.
Researchers then tested it in engineered human heart tissue.
There too, the tissue relaxed better.
The findings are early and do not yet establish urolithin A as a treatment for people with heart failure. But they point toward something researchers have increasingly suspected:
Sometimes helping a failing heart isn’t about making it squeeze harder.
It may be about helping the heart relax again.
A Heart Has Two Jobs
We tend to notice only one half of every heartbeat.
The squeeze.
With each contraction, the heart pushes blood forward through the circulation.
But before the next beat can happen, something equally important must occur.
The muscle has to relax.
As the heart relaxes, its chambers expand and fill with blood. Only then can they contract again and send that blood back out.
Imagine repeatedly squeezing a sponge.
If you allow it to expand completely between squeezes, it fills with water.
But if the sponge becomes stiff and cannot fully expand, each squeeze begins with less water inside.
Something conceptually similar can happen in HFpEF.
The heart may retain much of its ability to contract, yet filling becomes impaired because the muscle has become unusually stiff.
That’s Why “Preserved Ejection Fraction” Can Be Confusing
One of the standard measurements of heart function is called ejection fraction.
It describes the proportion of blood inside the main pumping chamber that is pushed out during a contraction.
In many forms of heart failure, ejection fraction falls because the heart has become weak and cannot contract effectively.
But people with HFpEF may have an ejection fraction within a relatively normal range.
On paper, the heart still appears capable of squeezing.
Yet the person can have very real heart failure.
Why?
Because ejection fraction doesn’t tell us everything about what happens between contractions.
A stiff ventricle can have difficulty accepting blood.
Pressure rises.
And those abnormal pressures can produce severe symptoms even when the percentage of blood being ejected looks relatively preserved.
The Heart Can Gradually Become Stiffer
HFpEF usually doesn’t result from one single problem.
Aging, high blood pressure, obesity, diabetes, kidney disease, inflammation, and other conditions can contribute to the biological environment in which it develops.
Over time, the heart may undergo structural changes.
The muscle can thicken.
Cells can enlarge.
The extracellular material surrounding those cells can change.
Fibrous tissue can accumulate.
That process is called fibrosis.
Think of healthy heart tissue as something flexible enough to expand and recoil repeatedly.
Fibrosis makes that tissue less compliant.
The heart increasingly resembles a pump enclosed within material that doesn’t want to stretch.
Scar Tissue Is Particularly Important
Fibrosis isn’t the same as the visible scar left after cutting your skin.
Inside an organ, fibrosis involves excessive accumulation of structural proteins such as collagen.
Some collagen is essential.
Without structural support, tissues would have no strength.
But too much can make them rigid.
In the heart, excessive fibrosis can interfere with normal relaxation.
That is one reason the urolithin A findings attracted attention.
In the animal models, treatment was associated with less cardiac fibrosis.
Researchers weren’t merely seeing a temporary change in heart rate or blood pressure.
They were observing differences in the structure of diseased heart tissue.
Then There Was the Abnormal Enlargement
A heart working under chronic stress can remodel itself.
Individual heart muscle cells may become enlarged, and the walls of the heart can thicken.
Initially, some of this adaptation may help the heart cope with increased workload.
But eventually, excessive enlargement can become part of the problem.
The thickened heart becomes less flexible.
Its oxygen and energy requirements change.
Normal electrical and mechanical behavior can be disrupted.
In the experimental study, urolithin A reduced aspects of this abnormal enlargement as well.
That suggested the compound might be affecting several interconnected processes rather than one isolated symptom.
But What Exactly Is Urolithin A?
This is where the story becomes unusual.
You don’t necessarily eat urolithin A directly when you eat a pomegranate.
Instead, certain foods contain natural plant compounds known as ellagitannins and related molecules.
These compounds occur in foods including:
pomegranates,
walnuts,
and several types of berries.
When they reach the digestive system, gut microorganisms can transform them through a series of chemical steps.
One of the compounds that may eventually emerge is urolithin A.
In other words, part of this molecule’s story begins not in the heart—
but in the intestine.
Your Gut Bacteria Help Make It
Two people can eat similar foods and produce different amounts of urolithin A.
Why?
Their gut microbiomes aren’t identical.
The enormous microbial ecosystem inside the intestine differs from person to person.
Some people harbor microbial communities capable of efficiently converting ellagitannin-derived compounds into urolithin A.
Others produce much less.
Some may produce little or none.
That makes statements such as “eat pomegranate to get urolithin A” more complicated than they initially appear.
The food provides the raw materials.
The microbes perform part of the chemistry.
And not everyone’s microbial factory works exactly the same way.
Scientists Were Already Interested in Urolithin A for Another Reason
Urolithin A has attracted scientific attention because of its effects on mitochondria.
Mitochondria are often described as the powerhouses of cells.
The phrase is almost painfully overused, but in heart muscle it is especially appropriate.
Your heart contracts approximately once every second throughout your entire life.
That requires an enormous and continuous supply of energy.
Heart cells therefore contain large numbers of mitochondria.
But mitochondria don’t last forever.
They become damaged.
Cells need ways to identify poorly functioning mitochondria and remove them.
One such quality-control process is called mitophagy.
Think of Mitophagy as Cellular Housekeeping
Imagine operating a factory twenty-four hours a day for eighty years.
Machines inevitably wear out.
If broken equipment simply accumulates on the factory floor, production eventually suffers.
A good factory continually identifies damaged machinery, removes it, and replaces or repairs what is needed.
Cells face a similar challenge.
Mitophagy helps remove dysfunctional mitochondria before they accumulate and interfere with cellular function.
Urolithin A has been studied for its ability to influence mitochondrial quality-control pathways.
That makes it particularly interesting in organs with enormous energy requirements.
Few tissues fit that description better than the heart.
A Stiff Heart May Also Be an Energy Problem
Relaxation sounds passive.
It isn’t.
Heart muscle requires energy not only to contract but also to relax properly.
Calcium ions move through heart cells during every heartbeat.
When the muscle contracts, calcium helps activate the machinery that produces force.
For relaxation to occur, calcium must then be moved back into appropriate cellular storage compartments.
That process consumes energy.
If cellular energy production and calcium handling become impaired, relaxation can suffer.
So HFpEF isn’t merely a structural disease of stiff tissue.
It also involves abnormalities in metabolism, inflammation, cellular signaling, blood vessels, and energy use.
A compound influencing mitochondrial quality could therefore potentially affect several parts of the problem.
The Improvements in Animals Were Striking
In experimental models designed to reproduce important features of HFpEF, researchers observed substantial improvements after treatment with urolithin A.
Depending on the measurement examined, some aspects of cardiac performance improved by up to approximately 80%.
Numbers that large naturally attract attention.
But “80% improvement” does not mean an animal’s heart failure was 80% cured.
Different measurements quantify specific aspects of heart function, and percentages can sound much more dramatic when removed from that context.
The meaningful finding is broader:
Multiple indicators moved in a favorable direction.
The heart relaxed better.
Abnormal enlargement decreased.
Fibrosis decreased.
Cellular characteristics improved.
Together, those changes suggested a potentially important biological effect.
The Human Heart Tissue Experiment Made the Story More Interesting
Animal experiments are essential for understanding biology.
But mice aren’t small humans.
Countless treatments that appear promising in animals eventually fail in human trials.
Researchers therefore took another important step.
They studied engineered human heart tissue.
When exposed to urolithin A, the human cardiac tissue also showed improved relaxation.
That doesn’t prove the compound will successfully treat patients.
Engineered tissue lacks the extraordinary complexity of an entire human body.
There is no complete circulatory system.
No kidneys controlling fluid balance.
No liver metabolizing compounds normally.
No full immune system.
No decades of hypertension or diabetes.
But the human-tissue result does provide an important bridge.
It suggests the biological effect isn’t necessarily restricted to the animal model.
Why HFpEF Needs New Ideas
HFpEF represents a particularly difficult problem because it isn’t one simple disease.
Two people can both receive the diagnosis while having very different underlying biology.
One may have longstanding hypertension and severe ventricular thickening.
Another may have obesity and metabolic dysfunction.
Another may have kidney disease.
Another may have atrial fibrillation.
Many have several of these conditions simultaneously.
That heterogeneity makes finding one universally effective therapy difficult.
Modern treatments have improved the outlook, but researchers continue searching for therapies that directly address the structural and cellular abnormalities responsible for impaired relaxation.
Urolithin A is interesting precisely because it may affect some of those deeper mechanisms.
This Doesn’t Mean Pomegranate Juice Treats Heart Failure
This distinction is essential.
The study investigated urolithin A, not a glass of pomegranate juice.
Eating foods containing urolithin A precursors isn’t equivalent to receiving a controlled amount of purified urolithin A in an experiment.
First, individuals produce dramatically different amounts depending on their gut microbiome.
Second, the concentration reaching tissues may differ.
Third, laboratory and animal doses cannot simply be translated into a serving of fruit.
So the research shouldn’t be interpreted as evidence that someone with heart failure can treat the condition by drinking pomegranate juice every morning.
That’s not what the experiment demonstrated.
But the Foods Behind the Molecule Are Still Interesting
That doesn’t make pomegranates, walnuts, and berries irrelevant.
Quite the opposite.
They contain numerous plant compounds being investigated for effects on metabolism, vascular function, inflammation, and the microbiome.
Walnuts also provide unsaturated fats and other nutrients.
Berries contain fiber and diverse polyphenols.
Pomegranates contain a particularly rich mixture of polyphenolic compounds.
These foods can fit naturally into many balanced dietary patterns.
What’s fascinating is that some of their molecules don’t finish their biological journey when we swallow them.
Our microbes transform them into entirely new compounds.
Urolithin A is one example.
The Microbiome Becomes Part of Nutrition
For a long time, nutrition seemed conceptually simple.
Food contains nutrient.
You eat nutrient.
Your body absorbs nutrient.
But microbiome research has revealed a middleman.
Sometimes we eat a compound that our own cells cannot use in exactly that form.
Gut bacteria transform it.
The resulting molecule may then enter circulation and interact with distant organs.
This means two people eating the same food aren’t necessarily exposed to exactly the same biological compounds afterward.
One person’s microbiome may efficiently manufacture urolithin A.
Another’s may not.
Food is therefore interacting with both human metabolism and microbial metabolism.
That is a profound shift in how scientists think about nutrition.
Could Urolithin A Eventually Become a Drug?
Possibly.
But that question requires human clinical trials.
Researchers would need to determine an appropriate dose.
How well is it absorbed?
How long does it remain in circulation?
Does enough reach heart tissue?
Which people with HFpEF are most likely to benefit?
Does it improve exercise capacity?
Does it reduce breathlessness?
Does it decrease hospitalization?
Most importantly, does it improve meaningful outcomes without causing unacceptable side effects?
Those questions cannot be answered by animal models or engineered tissue alone.
Promising biology is the beginning of drug development—not the end.
Human Trials Are Where Many Promising Ideas Change
Biomedical research is full of compounds that produced beautiful laboratory results and disappointing clinical trials.
That’s not scientific failure.
It’s how the process is supposed to work.
A mouse model simplifies disease enough to investigate mechanisms.
Human disease contains decades of accumulated biology.
Age.
Genetics.
Medications.
Kidney function.
Blood pressure.
Body composition.
Other illnesses.
Different microbiomes.
Different lifestyles.
A successful human treatment must work amid all that complexity.
Urolithin A has passed an intriguing early test.
The difficult tests come next.
The Most Exciting Finding May Be the Relaxation
It’s easy to focus on the dramatic percentage improvement.
But the mechanism may ultimately be more important.
HFpEF has long frustrated researchers precisely because the heart can still contract reasonably well.
Trying simply to make it squeeze harder doesn’t solve the fundamental problem.
The ventricle needs to become more compliant.
Cells need to handle energy and calcium effectively.
Fibrosis needs to be limited.
Abnormal remodeling needs to be addressed.
The fact that urolithin A improved relaxation while also reducing fibrosis and enlargement suggests researchers may have found a pathway touching several features of the disease at once.
That is what makes the findings worth following.
A Food Molecule’s Journey Can Be Remarkably Long
Consider what has to happen before urolithin A can even enter this story naturally.
A pomegranate grows.
You eat its seeds.
Plant compounds pass through your digestive system.
They encounter microorganisms living in your intestine.
Those microbes perform chemical transformations your own cells might not perform in the same way.
A new molecule appears.
That molecule can potentially enter circulation.
And researchers now suspect it may influence something happening inside heart muscle.
Food.
Microbe.
Metabolite.
Mitochondrion.
Heart.
What looks like a simple meal can begin an astonishing chain of biology.
The Heart Is Constantly Repairing Its Machinery
Every day, your heart beats roughly 100,000 times.
Every contraction requires cellular machinery to work.
Every relaxation requires energy too.
This continues while you sleep.
While you exercise.
While you’re stressed.
While you’re reading these words.
There is no scheduled maintenance shutdown.
The heart has to maintain and repair itself while continuing to operate.
That makes cellular quality-control mechanisms especially important.
If urolithin A can meaningfully improve mitochondrial maintenance in human heart disease, it could offer researchers a new way to support the machinery keeping that relentless system running.
But that’s still an “if.”
What This Study Really Gives Us
It doesn’t give us a new heart-failure treatment yet.
It gives us a target.
It suggests that improving mitochondrial health may help heart muscle relax.
It provides evidence that urolithin A can reduce several disease-like changes in experimental HFpEF.
And crucially, it shows that an effect on relaxation can also be observed in engineered human cardiac tissue.
Those findings create enough evidence to justify asking the next question.
Will it work in actual patients?
That is the experiment that matters most.
Sometimes the Heart Doesn’t Need to Beat Harder
We often imagine heart disease as weakness.
A failing heart must be a weak heart.
Therefore, treatment must somehow make it stronger.
HFpEF teaches us why biology is rarely that simple.
A heart can squeeze adequately and still fail because it has become too stiff to relax properly.
Its structure has changed.
Its energy machinery may be impaired.
Fibrosis has accumulated.
The spaces between beats—the moments when the heart should loosen and fill—have become part of the disease.
Urolithin A offers an intriguing experimental way of approaching that problem.
A molecule that can arise from compounds in pomegranates, walnuts, and berries appears capable of improving relaxation, reducing scarring, and limiting abnormal enlargement in experimental models.
Whether those effects will translate into an effective human therapy remains unanswered.
But the discovery gives researchers a new direction—and an unexpectedly elegant one.
Because the future of treating some forms of heart failure may not depend entirely on forcing the heart to work harder.
It may depend on helping it finally relax.
For more fascinating insights, discover how Migraine and Cluster Headaches May Be Closely Tied to Your Body’s Internal Clock or learn about a Migraine Prevention Drug That May Also Help Break the Cycle of Rebound Headaches. And if you’re curious about other health connections, check out how Better Blood Sugar Days May Also Be Better Life Days for People With Diabetes.
