Berberine, a plant-derived compound used in traditional medicine, has attracted interest as a potential supplement for non-alcoholic fatty liver disease (NAFLD). Whilst early research suggests berberine may improve liver enzymes and reduce fat accumulation through metabolic pathways, the evidence in humans remains limited and of low to moderate quality. Importantly, berberine is not a licensed medicine in the UK for treating liver conditions and is not recommended by NICE or the NHS for NAFLD management. This article examines the current evidence, safety considerations, and how berberine compares to established lifestyle interventions for fatty liver disease.

What Is Berberine and How Does It Work?

Berberine is a naturally occurring alkaloid compound extracted from various plants, including Berberis species (barberry), goldenseal, and Chinese goldthread. Traditionally used in Chinese and Ayurvedic medicine for centuries, berberine has gained attention in recent years as a dietary supplement for metabolic health conditions.

The compound works through several mechanisms at the cellular level. Berberine activates an enzyme called AMP-activated protein kinase (AMPK), often referred to as the body's "metabolic master switch". This activation influences how cells process glucose and lipids, potentially improving insulin sensitivity and reducing fat accumulation. Additionally, berberine appears to modulate gut microbiota composition, which may contribute to its metabolic effects.

In terms of liver-specific actions, berberine has been shown in laboratory and animal studies to reduce hepatic lipid accumulation through multiple pathways. It may inhibit fatty acid synthesis, enhance fatty acid oxidation (breakdown), and reduce inflammation within liver tissue. The compound also appears to influence cholesterol metabolism and may help lower circulating triglyceride levels.

Evidence in humans is limited. Small randomised controlled trials and meta-analyses have reported modest improvements in liver enzymes (ALT, AST) and lipid profiles in people with non-alcoholic fatty liver disease (NAFLD), but the quality of evidence is low to moderate, with significant heterogeneity between studies. Larger, well-designed trials are needed to confirm these findings.

It is crucial to note that berberine is not a licensed medicine in the UK for treating liver conditions and is not recommended by NICE or the NHS for NAFLD management. It is available as a food supplement, regulated under food law rather than medicines legislation. The Medicines and Healthcare products Regulatory Agency (MHRA) does not evaluate supplements for efficacy in treating specific medical conditions unless medicinal claims are made. Whilst emerging research is promising, berberine should not replace conventional medical treatment for fatty liver disease without discussion with a healthcare professional.

Understanding Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a condition characterised by excessive fat accumulation in the liver (hepatic steatosis) in people who consume little to no alcohol. It has become increasingly common in the UK, with estimates suggesting it affects approximately one in three adults to some degree, though prevalence varies by population and diagnostic criteria. The condition exists on a spectrum, ranging from simple steatosis (fat accumulation without significant inflammation) to non-alcoholic steatohepatitis (NASH), which involves inflammation and liver cell damage that can progress to fibrosis, cirrhosis, and liver failure. (Note: newer international terminology uses MASLD—metabolic dysfunction-associated steatotic liver disease—and MASH, though UK guidance currently retains NAFLD/NASH.)

The primary risk factors for NAFLD include obesity, type 2 diabetes, insulin resistance, high cholesterol, and metabolic syndrome. The condition is strongly associated with central (abdominal) obesity and is considered the hepatic manifestation of metabolic syndrome. Most people with NAFLD have no symptoms in the early stages, and the condition is often detected incidentally through abnormal liver function tests or imaging performed for other reasons.

Diagnosis and risk stratification typically involve blood tests to assess liver enzymes (ALT, AST, GGT), imaging such as ultrasound to detect fat accumulation, and assessment of fibrosis risk. In UK primary care, NICE guidance (NG49) recommends using non-invasive fibrosis scores such as the FIB-4 index or NAFLD fibrosis score to triage patients. Indicative thresholds for FIB-4 in adults under 65 years are: <1.3 suggests low risk of advanced fibrosis; >3.25 suggests high risk; intermediate values warrant further assessment. (Thresholds differ for those aged 65 and over.) The Enhanced Liver Fibrosis (ELF) blood test may be used in secondary care or specialist settings to further assess fibrosis risk. Transient elastography (e.g., FibroScan) can measure liver stiffness as a marker of fibrosis. Referral to a hepatologist is advised for high or indeterminate fibrosis scores (e.g., FIB-4 >3.25, ELF ≥10.51), suspected advanced liver disease, or when alternative liver pathology is suspected.

NICE guidance emphasises that lifestyle modification remains the cornerstone of NAFLD management, focusing on weight loss, dietary changes, and increased physical activity. There is currently no licensed pharmacological treatment specifically for NAFLD in the UK, though medications for associated conditions (diabetes, high cholesterol) are used.

The natural history of NAFLD varies considerably. Whilst many people with simple steatosis remain stable, approximately 20% may progress to NASH, and a smaller proportion develop advanced fibrosis. Regular monitoring and addressing underlying metabolic risk factors are essential to prevent disease progression and reduce cardiovascular risk, which is the leading cause of mortality in NAFLD patients.

How to Use Berberine Safely for Liver Health

If you are considering berberine supplementation for fatty liver disease, it is essential to consult your GP or hepatologist first. Self-treatment without medical supervision is not advisable, particularly as fatty liver disease requires proper diagnosis, monitoring, and management of underlying metabolic conditions.

Typical berberine supplement dosages in research studies range from 900 to 1,500 mg daily, divided into two or three doses (e.g., 500 mg three times daily with meals). Taking berberine with food may reduce gastrointestinal side effects. However, there is no standardised, evidence-based dosing regimen specifically for liver health, as berberine is not an approved treatment for NAFLD.

Common side effects include gastrointestinal symptoms such as diarrhoea, constipation, abdominal cramping, and nausea, particularly when starting supplementation or at higher doses. These effects are usually mild and may diminish with continued use. Starting with a lower dose and gradually increasing may help minimise discomfort.

Important safety considerations include potential drug interactions. Berberine can affect the metabolism of various medications through its influence on cytochrome P450 enzymes (particularly CYP3A4 and CYP2D6) and P-glycoprotein (P-gp), a drug transporter protein. This may alter blood levels of medications including:

• P-gp substrates such as digoxin and direct oral anticoagulants (DOACs) like apixaban and rivaroxaban

• CYP3A4 substrates including certain statins (simvastatin, atorvastatin), immunosuppressants (ciclosporin, tacrolimus), and some antibiotics

• Warfarin (via CYP2C9 inhibition), potentially increasing bleeding risk

• Antihypertensive medications, which may have additive blood pressure-lowering effects

If you take any regular medications, discuss potential interactions with your pharmacist or doctor before starting berberine.

Berberine may also lower blood glucose levels, which could be problematic for people taking diabetes medications, potentially causing hypoglycaemia. If you have diabetes, coordinate with your clinician on glucose monitoring and possible medication adjustment before starting berberine. Additionally, berberine is not recommended during pregnancy or breastfeeding due to insufficient safety data.

Quality and purity of supplements vary considerably. Choose products from reputable manufacturers that provide third-party testing certificates. Be aware that the actual berberine content may differ from label claims in some products.

Stop taking berberine and seek urgent medical advice if you develop jaundice (yellowing of skin or eyes), dark urine, pale stools, severe abdominal pain, confusion, unusual bleeding or bruising, or persistent worsening of liver function tests. If you experience any suspected adverse reaction to berberine, you can report it via the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk, which helps monitor the safety of all medicines and supplements.

Other Treatments and Lifestyle Changes for Fatty Liver

Weight loss remains the most effective intervention for NAFLD, with evidence showing that losing 7–10% of body weight can significantly reduce liver fat, inflammation, and even fibrosis. NICE recommends a structured weight management programme incorporating dietary modification and increased physical activity as first-line treatment. Even modest weight loss of 3–5% can improve hepatic steatosis.

Dietary approaches should focus on reducing overall calorie intake whilst improving nutritional quality. A Mediterranean-style diet rich in vegetables, fruits, whole grains, legumes, nuts, and olive oil, with moderate fish consumption and limited red meat and processed foods, has shown particular benefit. Reducing intake of refined carbohydrates, added sugars (especially fructose in sweetened beverages), and saturated fats is important. Observational evidence suggests that regular coffee consumption may be associated with reduced liver disease progression, though coffee should not be started solely as a treatment for liver health.

Physical activity is beneficial independent of weight loss. UK Chief Medical Officers' guidance recommends at least 150 minutes of moderate-intensity aerobic activity weekly, such as brisk walking, cycling, or swimming, or 75 minutes of vigorous-intensity activity. Resistance training may also help improve insulin sensitivity and body composition. The key is finding sustainable activities that fit into your lifestyle.

Management of associated conditions is crucial. This includes:

• Optimising diabetes control with appropriate medications (metformin is often first-line)

• Treating dyslipidaemia with statins if indicated (statins are safe in NAFLD)

• Managing hypertension to reduce cardiovascular risk

• Addressing obstructive sleep apnoea if present

Alcohol consumption should be minimised or avoided. UK Chief Medical Officers advise that to keep health risks from alcohol low, it is safest not to drink more than 14 units per week on a regular basis, spread over three or more days with several alcohol-free days. Many liver specialists recommend minimising alcohol intake or abstaining entirely in people with NAFLD, particularly if fibrosis is present, as even moderate amounts may contribute to liver injury.

Avoiding hepatotoxic substances is important. Avoid unnecessary medications and discuss any supplements with your doctor, as some medications, including certain antibiotics and herbal products, can cause liver injury.

When to seek medical review: Contact your GP if you develop new symptoms such as persistent abdominal pain, jaundice (yellowing of skin or eyes), unexplained fatigue, easy bruising, or swelling of the abdomen or legs. Regular monitoring through blood tests and, when appropriate, non-invasive fibrosis assessment (such as FIB-4 score or ELF testing per NICE NG49) helps track disease progression and treatment response. Referral to a hepatologist is recommended if you have high or indeterminate fibrosis risk scores (e.g., FIB-4 >3.25 if under 65 years, ELF ≥10.51), suspected advanced liver disease, or if an alternative cause of liver disease is suspected.

Frequently Asked Questions