Can Berberine Damage the Liver? Debunking Myths and Revealing Facts


Concerns about the liver safety of supplements are warranted, and berberine is no exception. Can berberine damage the liver? This article examines the latest research to address the safety of berberine for liver function. Expect a straightforward review of what clinical studies and trials show regarding the hepatic effects of this supplement.

Key Takeaways

  • Berberine has been historically used in traditional medicine and is being studied for its effects on liver health, including its interaction with liver enzymes and activation of AMPK, which influences liver metabolism.
  • Clinical evidence suggests Berberine can manage conditions like NAFLD by improving metabolic parameters, regulating lipid metabolism, and offering hepatoprotective effects through its antioxidative action.
  • While Berberine is largely considered safe for liver health, with no strong association with liver injury, its interactions with other medications and potential side effects, like gastrointestinal issues, necessitate cautious use and medical oversight.

1 Understanding Berberine’s Role in Liver Health

Various plants containing berberine such as goldenseal, coptis, Oregon grape, barberry, and tree turmeric

Berberine has a long history in traditional medicine. It’s been used in Ayurvedic and traditional Chinese medicine for treating various ailments, including infections, diarrhea, bronchitis, and digestive complaints. This versatile compound is found in a variety of plant species, including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). This widespread occurrence in plants underscores its historical importance in holistic applications.

Chemically speaking, Berberine is classified as an isoquinoline alkaloid, indicating a specific biochemical profile with diverse therapeutic potentials. But what does this chemical identity mean for liver health? We begin by looking at the interaction of Berberine with liver enzymes.

Investigating Berberine’s Impact on Liver Enzymes

An important aspect of assessing liver health is examining liver enzymes. These enzymes serve as key markers, and any changes in their levels can provide insights into the state of liver health. Some studies have shown a reduction in the levels of AST, a liver enzyme, with Berberine treatment. However, these results are not consistent across all studies, indicating a need for further research to confirm these findings.

Determining the safety profile of Berberine, particularly its impact on liver function, calls for in-depth research, inclusive of clinical trials. Despite some positive findings, more research is needed to fully understand Berberine’s overall effect on liver enzyme levels and liver health. The AMP-activated protein kinase (AMPK) is a critical player in this process.

The Role of AMP-Activated Protein Kinase

AMPK plays a significant role in regulating liver metabolism, and Berberine’s ability to activate this protein has wide-reaching implications for liver health. When Berberine activates AMPK, it lessens hepatic lipid synthesis and boosts fatty acid β-oxidation, aiding in the reduction of obesity and hepatic steatosis.

Notably, when Berberine activates AMPK, it also increases CD36 expression, aiding the uptake of fatty acids into hepatocytes. This can result in lipid accumulation and possible development of fatty liver, including alcoholic fatty liver disease. The link between the effects of AMPK activation on liver enzymes, fatty acid oxidation, and its role in regulating CD36 expression underscores the complex interplay of these factors in liver health.

Berberine’s Effect on Hepatic Steatosis

Regulation of lipid metabolism in the liver by berberine

Hepatic steatosis, characterized by excessive fat storage in the liver, is a common liver condition. The way that berberine improves lipid dysregulation, particularly in the context of hepatic steatosis, is indeed impressive. It:

  • Regulates lipid metabolism
  • Increases the expression of LDL receptors
  • Promotes cholesterol excretion into bile
  • Decreases liver cholesterol and triglyceride levels

By inhibiting lipogenesis, gluconeogenesis, and lipid synthesis, as well as suppressing fatty acid uptake and β-oxidation, Berberine contributes to the reduction of liver fat content and improvement of glucose regulation. Additionally, Berberine’s ability to modulate gut microbiota offers another mechanism by which it manages hepatic steatosis.

Insights from Randomized Controlled Trials

Clinical trials offer important information on the therapeutic effects of Berberine. A meta-analysis of randomized controlled trials indicated that Berberine is effective in the treatment of nonalcoholic fatty liver disease (NAFLD) and its complications, with a safety profile comparable to first-line medications.

While these findings are promising, the need for more high-quality clinical trials persists, given current limitations like the limited number of trials, brief study durations, and subpar quality. These trials provide evidence that Berberine may positively affect obesity parameters and inflammation, but its influence on liver enzyme levels and direct liver function outcomes may be minimal.

Berberine in the Management of Fatty Liver Disease NAFLD

NAFLD, a prevalent liver condition, can greatly benefit from Berberine. Berberine has demonstrated the ability to:

  • Improve metabolic parameters by enhancing insulin sensitivity through the PPAR-γ pathway
  • Reduce lipid levels
  • Lower blood glucose in NAFLD patients Furthermore, reductions in liver enzymes such as ALT, AST, and GGT due to Berberine treatment suggest a positive effect on liver health in NAFLD patients.

Clinical trials have validated Berberine’s efficacy in treating NAFLD, either solo or combined with lifestyle changes, leading to substantial reductions in hepatic fat content and enhancements in patient lipid profiles over 12-16 week periods. Berberine’s influence on NAFLD may be attributed to its ability to:

  • Inhibit enzymes responsible for lipogenesis and gluconeogenesis
  • Upregulate glucose transporters
  • Aid in the reduction of hepatic steatosis
  • Improve glucose homeostasis

Berberine’s Protective Mechanisms Against Liver Injury

Hepatoprotective effects of berberine against liver injury

Beyond its effectiveness in managing NAFLD, Berberine also exhibits protective mechanisms against liver injury. It has potent antioxidative action against liver oxidative stress, as indicated by decreased malondialdehyde levels, a marker of lipid peroxidation, and increased activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione in the liver and serum.

The antioxidative activities of Berberine contribute to the reduction of reactive oxygen species (ROS) production in the liver, further highlighting its hepatoprotective effect. In addition, Berberine intake is associated with a significant reduction in C-reactive protein (CRP) levels, highlighting its potential to mitigate inflammation and thereby protect the liver from inflammatory injury.

The genomic modulation of Berberine could also be vital to its protective effects against liver injury.

Modulation of Lipid Synthesis

Berberine's impact on hepatic lipid metabolism and cholesterol levels

Berberine regulates hepatic lipid metabolism directly, a fundamental mechanism for its therapeutic effects on NAFLD. It impacts cholesterol metabolism by lowering blood lipid levels and promoting the excretion of cholesterol from the liver into the bile.

Berberine also downregulates key enzymes in hepatic lipid synthesis, such as stearoyl-CoA desaturase 1 (SCD1), fatty acid-binding protein 1 (FABP1), and CD36, contributing to reduced lipid accumulation in the liver. Given the role of defects in lipid metabolism pathways, insulin resistance, and inflammation in the pathophysiology of NAFLD, Berberine’s engagement with these players showcases its crucial role in the management of NAFLD.

Stabilizing Blood Glucose Levels

Berberine’s part in stabilizing blood glucose levels is another important component of its influence on liver health. Berberine increases the amount of glucose transporter 4 (Glut-4), enhancing glucose uptake and leading to reduced blood glucose levels. This reduction in blood glucose levels is crucial for the maintenance of hepatic lipid homeostasis, indicating its implications for liver health.

However, patients taking Berberine, particularly those with diabetes, should monitor their blood sugar levels as Berberine lowers blood glucose to prevent them from dropping too low.

Next, we examine berberine’s reduction of insulin resistance, a significant factor in multiple metabolic disorders, including metabolic syndrome and NAFLD.

Reducing Insulin Resistance

Insulin resistance, particularly hepatic insulin resistance, significantly contributes to the development and pathogenesis of NAFLD, which can lead to liver inflammation. Berberine improves insulin sensitivity by influencing the PPAR-γ pathway and enhancing tyrosine phosphorylation in the insulin receptor substrate (IRS), which can aid in reducing insulin resistance associated with liver function.

The action of Berberine on mitochondrial function, particularly the inhibition of complex I, leads to better glucose metabolism and a reduction in insulin resistance. While berberine may indirectly alleviate clinical symptoms in metabolic disorders, it may not have a significant impact on liver enzymes.

Assessing the Risk of Liver Damage from Berberine

Considering the extensive benefits of Berberine for liver health, it’s natural to ask: Could Berberine potentially harm the liver? The good news is that Berberine has not been associated with serum aminotransferase elevations during therapy nor with instances of clinically apparent liver injury.

Berberine has been assigned a likelihood score of E for causing clinically apparent liver injury, indicating it is an unlikely cause, and no significant changes in ALT levels or hepatotoxicity have been reported in controlled trials. Although available data generally deem Berberine safe, comprehensive studies on its short-term effects on liver metabolism are lacking.

Myths vs. Reality: Berberine’s Side Effects

Berberine's side effects and its association with liver injury

Despite Berberine being generally safe, it’s vital to dispel some misconceptions and clarify the reality of its side effects. Clinical evidence does not associate Berberine with liver injury, as there have been no published instances of clinically apparent liver damage attributed to its use.

Most side effects of Berberine are gastrointestinal, such as:

  • diarrhea
  • constipation
  • gas
  • upset stomach

However, Berberine can interact with certain medications processed by the liver, altering their efficacy and side effects.

Special caution is advised against the use of Berberine in the following cases:

  • Newborns, due to the risk of kernicterus
  • Pregnant women, because of the potential harm to the fetus
  • Breastfeeding women because of the potential harm to the infant.

Optimizing Berberine Use for Liver Health

To fully utilize Berberine’s potential for liver health, optimizing its usage is pivotal. Berberine is possibly safe for most adults when taken orally, in doses up to 1.5 grams daily for six months. However, it’s important to note that Berberine can interact with certain medications processed by the liver, thus requiring careful management of dosages and side effects.

Berberine may cause drowsiness and slowed breathing, and its use alongside sedative medications could be problematic due to potential additive effects. As such, it is advised to seek a healthcare provider’s counsel to ascertain the suitable type and dose of Berberine for individual liver health needs.


Throughout this blog post, we’ve delved into the multi-faceted role of Berberine in liver health, exploring its historical use, its impact on liver enzymes, its effect on hepatic steatosis, and its role in the management of NAFLD. We’ve also examined its protective mechanisms against liver injury, its effect on lipid synthesis and blood glucose levels, and its potential to reduce insulin resistance.

While Berberine is not associated with liver injury, and its side effects are generally limited to gastrointestinal issues, it’s crucial to consult a healthcare provider to optimize its use for liver health. Armed with the insights gained from this post, you’re now better equipped to harness the potential of this remarkable compound for your liver health.

Frequently Asked Questions

What is the danger of taking berberine?

The danger of taking berberine includes potential side effects such as constipation, upset stomach, and low blood sugar levels, especially when combined with other blood sugar-lowering medications. It may also lead to altered liver function, gastric troubles, and damage to immune cells.

What happens if you take berberine for too long?

Long-term use of berberine may cause digestive side effects such as upset stomach, constipation, and diarrhea. It’s important to be cautious and discuss any prolonged use with a healthcare professional.

What is Berberine, and what is its historical use?

Berberine is an isoquinoline alkaloid found in numerous plants and has been historically used in Ayurvedic and traditional Chinese medicine for treating infections, diarrhea, bronchitis, and digestive complaints.

How does Berberine influence liver enzymes?

Berberine has been found to reduce AST, a liver enzyme, but further research is needed due to inconsistent results from studies.

What are the side effects of Berberine?

Berberine may cause gastrointestinal side effects like diarrhea, constipation, and upset stomach, and it can also interact with certain medications processed by the liver. Be cautious of these potential effects.


Social Share Buttons