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Pomegranates, Urolithin A, and the Stiff Heart: What a Mouse and Lab-Grown Tissue Study Found

Writer: Joyce Knieff, NMD, LAc
Joyce Knieff, NMD, LAc
4 days ago
5 min read

News that a pomegranate compound improved heart function "by up to 80%" is the kind of thing that gets forwarded to the family group chat within the hour. The study behind it is interesting and very early. The researchers tested a single compound in mice and in lab-grown heart tissue, which means the study involved no pomegranates and no people.


Pomegranate fruit on a brown wooden board
Photo: Alisa Anton / Unsplash

What the King's College London study found


Researchers at King's College London studied heart failure with preserved ejection fraction, usually shortened to HFpEF. In HFpEF the heart squeezes normally, but the muscle is stiff and relaxes poorly between beats, so it has trouble filling with blood. HFpEF accounts for nearly half of all heart failure cases [2].


The team screened natural compounds for one that could act on PKGIα, a protein that helps blood vessels and heart muscle relax, and urolithin A came out of that screen [1]. Your gut bacteria make urolithin A from ellagitannins, plant compounds found in pomegranates, walnuts, and some berries [3, 5, 6]. In a mouse model designed to mimic several features of human HFpEF at once, urolithin A improved diastolic function, meaning the heart relaxed and filled better, and it reduced cardiac remodeling, the structural changes in heart muscle that come with the disease [1]. The researchers showed that the effect depended on one specific spot on the PKGIα protein, called cysteine 42. They then tested urolithin A on engineered human heart tissue, and the tissue relaxed and contracted faster [1].


About that 80%: the figure comes from the press coverage, which reported that some heart function measures improved by up to 80% in treated animals compared with untreated ones [5]. The published abstract does not give that number. "Up to" describes the best result across several measures, so it is the top of a range rather than a typical effect.


What urolithin A has done in people so far


Urolithin A has been tested in people, though never in people with heart failure. In a first-in-human trial in healthy older adults, it had a favorable safety profile whether given once or daily for four weeks [4]. In a four-month trial in 66 adults aged 65 to 90, the researchers found no significant difference on the two main measures, walking distance and muscle energy production. They did find better muscle endurance and lower C-reactive protein, a marker of inflammation, compared with placebo [6]. In a second four-month trial, in middle-aged adults, participants had about 12% better muscle strength, while the main measure, peak power output, did not improve [7]. All three of these trials included authors from the company that makes a commercial urolithin A product [4, 6, 7].


The trial closest to the heart question was published in October. In 50 middle-aged adults with obesity, four weeks of urolithin A did not improve blood vessel function compared with placebo, which was the trial's main outcome [8].


There is also a catch with getting urolithin A from food. Some people's gut bacteria make urolithins and some people's bacteria make none. In a pomegranate extract trial in 49 adults with overweight or obesity, cholesterol and LDL fell only in the group whose bacteria produced a particular urolithin pattern [3]. In a study of 59 Brazilian adults, about 15% made no urolithins at all [9]. In the pomegranate trial, three of the six non-producers started producing urolithins after taking the extract, so this pattern can change [3].


Why your gut bacteria are part of a heart study


Naturopathic medicine starts from the connections between body systems, and in this case the link is between the gut and the heart. Because urolithin A only exists after gut bacteria process food, two people can eat the same handful of walnuts and end up with very different amounts of it [3, 9]. The researchers behind the 2017 pomegranate trial suggested that this difference could explain why pomegranate studies have had conflicting results for years [3]. Heart health, in other words, is connected to what you eat, which microbes you carry, and what those microbes make from your food.


HFpEF itself is a whole-body condition. In a 2024 review, Hamo and colleagues list age, diabetes, high blood pressure, obesity, and atrial fibrillation as risk factors, and they describe inflammation and problems with metabolism and the mitochondria (the energy-producing parts of cells) as contributors [2]. They also note that HFpEF affects skeletal muscle, blood vessels, the lungs, the kidneys, and the brain [2]. That is a root-cause picture of the condition, which is why one compound acting on one protein would be, at best, one part of care.


Should you start eating pomegranates for your heart?


If this study caught your eye, here is how I would use it without getting ahead of what was tested:


  1. Pomegranates, walnuts, and berries are good food on their own merits. They give your gut bacteria the raw material for urolithins. The researchers did not test whether these foods treat or prevent heart failure, and the senior researcher said the evidence so far is not enough to recommend pomegranates for that purpose [5].

  2. The well-studied basics still come first. Abdin and colleagues, in a second 2024 review, recommend exercise for everyone with HFpEF to improve quality of life [10]. Blood pressure, blood sugar, and weight are on the list of HFpEF risk factors, so attention to them is part of protecting the heart [2].

  3. A urolithin A supplement is a different decision from a bowl of fruit. The human trials so far are small and short, and none included people with heart failure [4, 6, 7, 8]. If you take heart or blood-thinning medications, ask your cardiologist how urolithin A would fit with them before you start.

  4. Human trials are still to come. Until they happen, this result applies to mice and lab-grown tissue only [1, 5].


References


  1. Su J, Zhao Y, Coleman P, Yang X, Holt M, Raabe J, Cuello F, Shah A, Shattock MJ, Zhang M, Burgoyne JR. Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction. Sci Adv. 2026;12(34):eaec8088. PMID: 42616901. doi:10.1126/sciadv.aec8088

  2. Hamo CE, DeJong C, Hartshorne-Evans N, et al. Heart failure with preserved ejection fraction. Nat Rev Dis Primers. 2024;10(1):55. PMID: 39143132. doi:10.1038/s41572-024-00540-y

  3. González-Sarrías A, García-Villalba R, Romo-Vaquero M, et al. Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: a randomized clinical trial. Mol Nutr Food Res. 2017;61(5). PMID: 27879044. doi:10.1002/mnfr.201600830

  4. Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595-603. PMID: 32694802. doi:10.1038/s42255-019-0073-4

  5. Original article (press coverage, secondary source): "Pomegranate compound improves heart function by up to 80% in study." ScienceDaily, September 2026. https://www.sciencedaily.com/releases/2026/09/260925093157.htm

  6. Liu S, D'Amico D, Shankland E, et al. Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial. JAMA Netw Open. 2022;5(1):e2144279. PMID: 35050355. doi:10.1001/jamanetworkopen.2021.44279

  7. Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633. PMID: 35584623. doi:10.1016/j.xcrm.2022.100633

  8. da Costa Pinaffi-Langley AC, et al. Urolithin A and endothelial and cerebrovascular function in middle-aged adults with obesity: a randomized clinical trial. JAMA Netw Open. 2026. PMID: 42853569. doi:10.1001/jamanetworkopen.2026.38047

  9. Leite, et al. The effect of jaboticaba peel and seed powder intake for three weeks on urolithin metabotype and excretion in normoweight and overweight/obese Brazilians. Food Res Int. 2026;230:118594. PMID: 41794475. doi:10.1016/j.foodres.2026.118594

  10. Abdin A, Böhm M, Shahim B, et al. Heart failure with preserved ejection fraction epidemiology, pathophysiology, diagnosis and treatment strategies. Int J Cardiol. 2024;412:132304. PMID: 38944348. doi:10.1016/j.ijcard.2024.132304


This post is for education only and is not medical advice. Heart failure needs individual care from your medical team, so please talk with your cardiologist or prescriber before changing your diet in a big way or adding any supplement, especially if you take heart or blood-thinning medications.



If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.




 
 
 

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