Ellagic acid is a polyphenolic, non-flavonoid compound naturally found in a variety of fruits, such as pomegranates, raspberries, strawberries, and grapes, and nuts, such as pistachios, pecans, walnuts, and acorns.

Senavirathna et al. are investigating the effects ellagic acid -- an antioxidant found in some pomegranates, raspberries, strawberries, and grapes, and nuts -- could have on halting and potentially reversing the damage caused by fatty liver disease. Image credit: Engin Akyurt.

Senavirathna et al. are investigating the effects ellagic acid — an antioxidant found in some pomegranates, raspberries, strawberries, and grapes, and nuts — could have on halting and potentially reversing the damage caused by fatty liver disease. Image credit: Engin Akyurt.

Obesity is in epidemic proportions in many parts of the world, contributing to increasing rates of non-alcoholic fatty liver disease (NAFLD).

This fast-growing epidemic is the most prevalent form of chronic liver disease globally.

The prevalence of NAFLD has increased from 25.24% in 2015 to 29.38% in 2021.

NAFLD represents a range of conditions from simple fatty liver (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH), which can progress to more severe fibrosis etc.

There currently exists no treatment for the long-term management of NAFLD/NASH, however, dietary interventions have been investigated for the treatment of NASH, including several polyphenolic compounds. Ellagic acid is one such compound.

“Ellagic acid, which is found in a variety of food such as raspberries, pomegranate, blackberries, and pecan nuts, is widely recognized for its antioxidant properties, but also exhibits anti-inflammatory, antifibrotic and anticancer properties,” said Edith Cowan University researcher Lois Balmer and PhD student Tharani Senavirathna.

“Ellagic acid stands out as a remarkable polyphenolic compound, possessing a wide range of pharmacological properties that hold promise in treating various chronic diseases, including NAFLD.”

“Due to its multifaceted biological effects, edible plants containing ellagic acid, and its derivatives are recognised as valuable functional foods for enhancing human health.”

“Moreover, there is evidence suggesting that ellagic acid, when combined with other antioxidant nutraceuticals, exhibits a synergistic therapeutic effect, making it a potential candidate for combination therapy.”

The authors have been involved in a previously undertaken pilot study investigating the effects of several polyphenolic compounds on NAFLD, with ellagic acid showing the most promise in reducing inflammation.

“Ellagic acid exerts its hepatoprotective properties primarily through scavenging free radicals, modulating cytokine production, and regulating lipid metabolism,” they said.

“As an excellent antioxidant, ellagic acid acts against ROS and activates the NrF2 pathway to reduce oxidative stress to protect the liver.”

“Remarkably, ellagic acid also suppresses Nf-kB and MAPK pathways, mitigating inflammation during NAFLD/NASH.”

“The evidence also shows that ellagic acid can reduce both triglyceride and cholesterol levels, thus combating de novo lipogenesis, which is a significant risk factor in NASH progression.”

“In vitro, findings suggest that ellagic acid has the capability to alleviate fibrosis.”

“The primary microbial metabolite for ellagic acid, urolithin, has been shown to improve the gut microbiome in several mouse models of obesity.”

“Specifically, urolithin A has been shown to lower LDL and increase HDL levels and is also involved in improving lipid metabolism through gene regulation, while urolithin C activates the hepatic AMPK pathway, thus counteracting the pathophysiology of NAFLD.”

“There is an ongoing debate regarding the health benefits of ellagic acid and urolithins for NAFLD/NASH, but there is still a lack of understanding regarding their biological effect on the liver.”

“Given the involvement of lipid metabolism, oxidative stress, inflammation, and insulin resistance in the pathogenesis of NASH, findings from this review suggest that ellagic acid may represent a potential food intervention for NASH, not only to limit but potentially reverse the pathological manifestations of NAFLD/NASH.”

The study was published in the journal Antioxidants.

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Tharani Senavirathna et al. 2024. Unlocking the Therapeutic Potential of Ellagic Acid for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. Antioxidants 13 (4): 485; doi: 10.3390/antiox13040485

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