Ellagic acid may represent a potential dietary intervention for non-alcoholic fatty liver disease: review

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

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

This rapidly growing epidemic is the most common form of chronic liver disease worldwide.

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

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

There is currently no cure 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, found in a variety of foods such as raspberries, pomegranates, blackberries and pecans, is widely recognized for its antioxidant properties, but also exhibits anti-inflammatory, antifibrotic and anticancer properties,” said University researcher Edith Cowan. Lois Palmer and PhD student Tharani Senaviratna.

„Ellagic acid stands out as a remarkable polyphenolic compound with a wide range of pharmacological properties promising for the treatment of various chronic diseases, including NAFLD.”

„Due to its diverse biological effects, edible plants containing ellagic acid and its derivatives have been recognized as valuable functional foods for improving human health.”

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

The authors were involved in a pilot study previously carried out to investigate 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 by 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.”

„Notably, ellagic acid also suppresses Nf-kB and MAPK pathways, reducing inflammation during NAFLD/NASH.”

„Evidence shows that ellagic acid can lower both triglyceride and cholesterol levels, thereby combating de novo lipogenesis, a significant risk factor in NASH progression.”

„Findings suggest that in vitro, ellagic acid has the ability to attenuate fibrosis.”

„Urolithin, the primary microbial metabolite for ellagic acid, has been shown to improve gut microbiota in several mouse models of obesity.”

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

„There is ongoing debate about the health benefits of ellagic acid and urolithins for NAFLD/NASH, but their biological effect on the liver is still poorly understood.”

Considering the involvement of lipid metabolism, oxidative stress, inflammation, and insulin resistance in the pathogenesis of NASH, the findings of this review may indicate that ellagic acid may represent a potential dietary intervention for NASH that can not only control but also modify pathological manifestations. NAFLD/NASH.”

The study Published in the magazine Antioxidants.

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Dharani Senaviratne and many others. 2024. Unlocking the therapeutic potential of ellagic acid for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Antioxidants 13 (4): 485; doi: 10.3390/antiox13040485