The Science Behind Milk Thistle and Berberine for Liver and Metabolic Support

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Protecting the body against excesses and toxins associated with daily living

There are many herbs with a history of use for supporting liver function and metabolic regulation with exposure to toxins or excessive consumption of alcohol or food. Modern analytical techniques and clinical studies have helped us to further understand the potential health benefits of two important botanically-derived substances: silymarin and berberine.

Milk thistle (Silybum marianum)

Milk thistle is possibly the best-known botanical for its potent liver-protective benefits. Silymarin, a mixture of the active constituents of milk thistle, and silibinin, the most active compound found within it, have been shown in animal studies to reduce liver injury caused by acetaminophen, alcohol, iron overload, and radiation among other known liver-toxic substances.[1] Silymarin has also been shown to increase levels of glutathione, a powerful antioxidant, in both the liver and intestines, and reduce lipid peroxidation, which leads to damage of the cellular (lipid) membranes, altering their function, and possibly causing cellular death.[2],[3]

Silymarin has also been shown to increase levels of glutathione, a powerful antioxidant, in both the liver and intestines, and reduce lipid peroxidation, which leads to damage of the cellular (lipid) membranes.

Silibinin and silymarin have been shown to activate a nuclear bile acid receptor known as farnesoid X receptor (FXR) which down-regulates inflammatory pathways.[4] FXR is a key regulator of bile acid, glucose, and lipid balance in the body – all of which are important for metabolic health.[5] Not surprisingly, with activation of FXR in mice, milk thistle ameliorated insulin resistance (the hallmark of diabetes), dyslipidemia (high cholesterol), and inflammation due to high-fat diet (HFD) feeding. Medications which interact with FXR similarly to these milk thistle derived compounds are also being investigated for the treatment of non-alcoholic fatty liver disease (NAFLD) and its associated hepatic changes.[6]

Clinical studies have also shown benefits to liver health and function with milk thistle supplementation. A 2017 meta-analysis found that treatment with milk thistle significantly reduces alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by −5.08IU/L and −5.44IU/L, respectively, in patients with NAFLD.[7] Dosages used in the studies surveyed in this meta-analysis ranged from 140 mg once a day to 200 mg three times a day, for a duration of 8 to 24 weeks. Additional parameters that were observed to be improved included fasting blood sugar, lipid profile, and serum insulin levels.

Berberine

Berberine, the orangish-yellow alkaloid found in botanicals such as Oregon grape root and bark, goldenseal, and barberry, is another substance that has numerous mechanisms by which it may help protect the liver, particularly against NAFLD.[8],[9],[10]

Berberine reduces intestinal permeability and improves tight junction integrity, reducing the passage of lipopolysaccharide (LPS) into circulation.

Berberine is well known for its antidiabetic and lipid-balancing effects,[11] both of which impact fatty liver changes. The direct actions of berberine, however, do not stop there. Berberine has been shown to alter hepatic metabolism-related gene expression, supporting bile acid metabolism via FXR-related pathways.[12] In animal studies, berberine has been shown to have the effect of preventing HFD-associated obesity and liver triglyceride accumulation (a hallmark of NAFLD) in wild-type (normal) mice, but not in those that had the genetic elimination of intestinal FXR expression.

Berberine also reduces intestinal permeability and improves tight junction integrity, reducing the passage of lipopolysaccharide (LPS) into circulation.[13],[14] High systemic levels of LPS (known as endotoxemia) plays a significant role in cholestasis and the related liver damage.[15],[16] Berberine has also been shown to suppress obesity-associated inflammation and hepatic steatosis in mice via pathways related to an inflammatory complex known as JNK1,[17] a protein kinase implicated in the development of steatohepatitis.[18] JNK1 is strongly activated by environmental stressors and pro-inflammatory cytokines.

The benefits of berberine in NAFLD have also been demonstrated clinically in a randomized, parallel controlled, open-label clinical trial.[19] In patients with NAFLD, berberine was shown to restore normal hepatic architecture, lipid, and blood sugar metabolism, with significant improvements seen over the population who only implemented lifestyle changes.

In our modern world, where the toxins we take in are often related to the foods we eat and beverages we consume, both milk thistle and berberine may be of benefit in supporting health on a long-term basis.

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