A compound found in pomegranates, transformed by gut bacteria, can shrink artery plaques and drive down heart disease risk.
For about $1.50 at an average grocery store, you could buy a pomegranate and give your gut bacteria the raw material they need to produce a natural compound that, according to new research, shrinks artery plaque and calms inflammation.
Pomegranates contain high levels of the heart-healthy polyphenol punicalagin, but the body barely absorbs it. Instead, gut bacteria break it down into urolithins, smaller molecules that circulate in the blood and affect tissues throughout the body.
When researchers tested punicalagin, ellagic acid, and several other urolithins on human cells, urolithin A (UA) stood out as the most effective weapon against atherosclerosis, the dangerous plaque buildup that affects more than 18 million Americans and heart disease, afflicting 126 million.
UA reduced oxidative stress, lowered inflammatory gene activity, limited immune cell movement and decreased cholesterol uptake by macrophages, all central processes in the formation of dangerous artery plaques.
Cardiff University researchers tested UA in mice genetically prone to plaque buildup. After 12 weeks on a high-fat diet, the mice that got UA had fewer and smaller plaques, less inflammation, and more stable plaque structure than untreated mice.
While not tested in humans, the UK team’s findings suggest that this pomegranate-derived, gut-activated molecule could become a future tool for heart disease prevention by targeting inflammation and plaque stability in ways statins do not.
For now, eating pomegranates and other ellagitannin-rich foods is a low-risk way to support the gut’s production of UA.
Pomegranates contain heart-healthy punicalagin, but the body barely absorbs it. Gut bacteria break it into smaller molecules that circulate in the blood and reach other tissues (stock)
Heart disease is the nation’s leading killer, claiming roughly 700,000 American lives each year. That is one in every five deaths, or one person every 33 to 40 seconds.
Atherosclerosis is the leading precursor to heart attacks. Fatty cholesterol plaques build up in the arteries, narrowing them silently over time.
If a plaque ruptures, a blood clot forms that can fully block the artery, cutting off oxygen and triggering a heart attack or stroke, often within minutes.
The Cardiff University researchers ran two sets of experiments: one in lab dishes using human tissues and one in mice.
First, they tested pomegranate’s main compound, punicalagin, along with its breakdown products, ellagic acid and five different urolithins, on human immune cells and human blood vessel cells.
They measured whether these compounds could block key drivers of artery disease. UA stood out.
It reduced oxidative stress, the cellular damage caused by harmful molecules that can trigger plaque formation.
It calmed inflammation, tamping down the overactive immune responses that wear down artery walls. It also blocked immune cells from migrating into blood vessel linings, a key step in seeding new plaque.
The mice on a high-fat diet and urolithin A (UA) supplementation (HFD+UA in red) reduced arterial blockage by a statistically significant margin compared to mice on that diet but without treatment with UA (green), meaning more of the artery remained open for blood flow
And it cut back on how much cholesterol immune cells called macrophages could take in, which stops those cells from transforming into the foam-filled cells that form the core of artery plaques.
The researchers chose only UA to move forward into the animal study.
They fed genetically modified mice made to be more prone to high cholesterol and atherosclerosis a high-fat diet for 12 weeks. Half of the mice received daily UA supplementation; the other half did not.
At the end of the study, the researchers analyzed the mice’s arteries for plaque size, composition and stability, along with blood immune cell profiles, short-chain fatty acid levels and genetic changes in the aorta using RNA sequencing.
All plaque analyses were done blind, meaning the researchers did not know which mice had received UA when measuring results.
The mice that received UA fared substantially better. They had smaller plaques with fewer inflammatory cells.
Their plaques had more collagen and smooth muscle cells, which stabilize the fibrous cap and make rupture less likely. Ruptured plaques trigger heart attacks and strokes.
The treated mice also showed lower blood levels of inflammatory immune cells, including monocytes and natural killer cells.
Mice that received urolithin A (UA) with their high-fat diets (red) had significantly smaller artery plaques than untreated mice on high-fat diets (green), as measured by plaque area
UA achieved all of this without changing the animals’ cholesterol levels, suggesting it works through a different mechanism than statins.
While eating the fruit provides fiber, vitamin C and the precursor compounds, individual results depend heavily on an individual’s gut microbiome.
Dr Dipak Ramji, senior author of the study published in the journal Antioxidants and a professor of cardiovascular science at Cardiff University, said: ‘These results help explain why diets rich in fruits like pomegranates are associated with cardiovascular benefits, but also why responses can vary between individuals.
‘Not everyone’s gut microbiome produces urolithin A efficiently.’
Some people naturally produce more UA than others. Direct UA supplements are also available, though they are significantly more expensive — around $3.50 per dose and up to $125 for a month’s supply — than a pomegranate or two.
‘This study opens the door to the use of urolithin A and microbiome‑driven strategies for cardiovascular disease prevention,’ Ramji added.
Current treatments for atherosclerosis include statins to lower cholesterol, antiplatelet drugs like aspirin to prevent blood clots and blood pressure medications.
In more advanced cases, doctors may use procedures such as angioplasty with stenting or bypass surgery to restore blood flow.
During a heart attack, which strikes 805,000 Americans annually, doctors thread a tiny balloon into the blocked artery, inflate it to clear the plaque, and place a small metal stent to keep the vessel open.
The average age of a person at the time of their first heart attack in the United States is 65.5 years for men and 72 years for women.
Heart attacks remain rare in young people, but the American College of Cardiology reports they are becoming more common among those under 40, with a two percent rise over the past decade.
