Does berberine make you tired? Whilst berberine—a natural alkaloid compound used in dietary supplements—is generally well-tolerated, some individuals report experiencing fatigue after starting supplementation. This tiredness may relate to berberine's effects on blood glucose regulation, gastrointestinal function, or medication interactions, though fatigue is not consistently documented as a common adverse effect in clinical trials. Understanding the potential mechanisms behind this symptom and how to minimise it can help you make informed decisions about berberine supplementation. This article examines the evidence, explores why some people feel tired when taking berberine, and provides practical guidance on safe use.

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 considerable attention in recent years as a dietary supplement, particularly for metabolic health support.

Mechanism of Action

Berberine appears to work through several mechanisms, with a key pathway involving AMP-activated protein kinase (AMPK), often referred to as the body's 'metabolic master switch'. Current research suggests berberine likely inhibits mitochondrial complex I, which then leads to AMPK activation. This enzyme plays a crucial role in regulating cellular energy balance, glucose metabolism, and lipid homeostasis. Through these pathways, berberine may influence:

• Insulin sensitivity and glucose uptake in cells

• Glucose production in the liver

• Lipid metabolism and cholesterol regulation

• Gut microbiota composition

Berberine also appears to affect mitochondrial function—the cellular powerhouses responsible for energy production. This mitochondrial interaction is particularly relevant when considering potential effects on energy levels and fatigue, though these effects are not fully established in humans.

Berberine has low oral bioavailability, meaning much of the compound remains in the gastrointestinal tract, where it can directly influence gut bacteria and intestinal function. Despite limited systemic absorption, berberine appears to produce measurable metabolic effects, though the precise mechanisms underlying all its actions remain under investigation.

Important safety considerations

In the UK, berberine is classified as a food supplement, not a licensed medicine. This means it has not undergone the rigorous safety evaluation required for pharmaceutical products. Quality and content may vary between products. Berberine should be avoided during pregnancy, when breastfeeding, and in children. It may interact with several medicines through effects on liver enzymes (CYP3A4/CYP2D6) and transport proteins (P-glycoprotein).

Why Some People Experience Fatigue When Taking Berberine

Whilst berberine is generally well-tolerated, some individuals report experiencing tiredness or fatigue after commencing supplementation. Several plausible mechanisms may explain this phenomenon, though it is important to note that there is no official, definitively established causal link between berberine and fatigue in clinical literature.

Blood Glucose Regulation

One possible explanation relates to berberine's glucose-lowering effects. By enhancing insulin sensitivity and reducing hepatic glucose production, berberine can lower blood sugar levels. In individuals unaccustomed to these changes, this glucose reduction may manifest as symptoms including fatigue, light-headedness, or general lethargy. Clinically significant hypoglycaemia (abnormally low blood sugar) is relatively uncommon in people without diabetes, but the risk increases substantially when berberine is combined with glucose-lowering medications.

Gastrointestinal Effects

Berberine's impact on the digestive system represents another potential contributor to tiredness. Common gastrointestinal adverse effects include:

• Abdominal discomfort or cramping

• Diarrhoea or loose stools

• Bloating and flatulence

• Nausea

These symptoms, whilst typically mild, can be uncomfortable and may indirectly contribute to feelings of fatigue or malaise. Gastrointestinal disturbance can affect nutrient absorption and overall wellbeing, potentially leading to reduced energy levels.

Medication Interactions

Berberine can interact with various medicines by affecting their metabolism or transport in the body. This may increase blood levels of certain drugs, potentially leading to enhanced side effects, including fatigue. Medicines that may interact with berberine include some statins, certain antibiotics, immunosuppressants (ciclosporin, tacrolimus), and several others.

Individual Variability

Genetic differences in drug metabolism, baseline metabolic status, concurrent medications, and overall health status all influence how individuals respond to berberine. What one person tolerates well may produce unwanted effects in another, highlighting the importance of personalised assessment.

How to Minimise Tiredness While Taking Berberine

If you are experiencing fatigue whilst taking berberine, several practical strategies may help reduce this unwanted effect whilst maintaining the potential benefits of supplementation.

Dosage Adjustment and Timing

Starting with a lower dose and gradually increasing allows your body to adapt to berberine's metabolic effects. There is no UK-recommended standard dose for berberine, but clinical studies have often used 500 mg two to three times daily:

• Consider beginning with 500 mg once daily for the first week

• Gradually increase if needed and tolerated

• Always follow the specific product label instructions and do not exceed the manufacturer's recommended daily dose

• Take berberine with meals to minimise gastrointestinal effects and moderate glucose changes

• Avoid evening doses if fatigue interferes with daily activities

Dividing the total daily dose across multiple administrations (typically two to three times daily) helps maintain more stable blood levels and reduces the likelihood of pronounced glucose fluctuations.

Nutritional Considerations

Maintaining regular, balanced meals supports stable energy levels when taking berberine. If you have diabetes or are following a specific dietary plan, discuss appropriate carbohydrate intake with your healthcare team rather than making changes independently. Staying well-hydrated is essential, as dehydration can exacerbate feelings of tiredness.

Monitoring and Medical Review

If you have diabetes or take glucose-lowering medications, berberine may potentiate these effects, increasing the risk of hypoglycaemia. Regular blood glucose monitoring becomes particularly important in this context. Consider:

• Checking blood glucose levels if you experience symptoms of hypoglycaemia (shakiness, sweating, confusion, fatigue)

• Consulting your GP or diabetes specialist before starting berberine

• Reviewing all medications and supplements with a healthcare professional

Important safety advice

• Do not use berberine as a substitute for prescribed medications

• Do not stop or adjust prescribed medicines without consulting your doctor

• Avoid berberine if you are pregnant, breastfeeding, or under 18 years of age

• Exercise caution if you take medicines such as ciclosporin, tacrolimus, some statins, certain antibiotics, or anticoagulants

When to Seek Medical Advice

Call 999 immediately if you experience severe symptoms such as loss of consciousness, severe breathing difficulty, or signs of a severe allergic reaction.

Contact NHS 111 or your GP if:

• Fatigue is severe, persistent, or worsening

• You experience symptoms of hypoglycaemia

• Gastrointestinal symptoms are significant or prolonged

• You develop any new or concerning symptoms

Your healthcare provider can assess whether berberine is appropriate for your individual circumstances and may suggest alternative approaches or investigations if fatigue persists.

Does Berberine Make You Tired? Understanding the Evidence

The relationship between berberine supplementation and fatigue remains incompletely characterised in clinical research. Whilst anecdotal reports of tiredness exist, systematic evidence specifically documenting fatigue as a common adverse effect is limited.

Clinical Trial Data

Most clinical trials investigating berberine have focused on metabolic outcomes—glucose control, lipid profiles, and weight management—rather than systematically assessing fatigue or energy levels. In trials that do report adverse effects, gastrointestinal symptoms (diarrhoea, constipation, abdominal discomfort) are most frequently documented, typically affecting 5-15% of participants in systematic reviews. Fatigue is rarely mentioned as a primary adverse event in published literature.

Systematic reviews examining berberine's safety profile across multiple studies have found it to be generally well-tolerated, with most adverse effects being mild and transient. However, the absence of fatigue in formal adverse event reporting does not definitively exclude its occurrence, as mild symptoms may be under-reported or attributed to other causes.

Regulatory Perspective

In the UK, berberine is classified as a food supplement rather than a licensed medicine, meaning it has not undergone the rigorous safety evaluation required by the Medicines and Healthcare products Regulatory Agency (MHRA) for pharmaceutical products. Consequently, comprehensive post-marketing surveillance data on adverse effects, including fatigue, are not systematically collected. Product quality and potency may vary considerably between manufacturers.

Long-term Safety

Most clinical studies of berberine have been relatively short-term (typically 8-12 weeks), so long-term safety data remain limited. This is an important consideration for anyone contemplating extended use.

Clinical Interpretation

For healthcare professionals advising patients, it is reasonable to acknowledge that whilst fatigue is not a well-established or common side effect of berberine in clinical trials, some individuals may experience tiredness, particularly when:

• Initiating supplementation at higher doses

• Taking berberine without food

• Having pre-existing conditions affecting glucose metabolism

• Using concurrent medications that affect blood sugar or that interact with berberine (particularly glucose-lowering medicines and drugs metabolised by CYP3A4 or transported by P-glycoprotein)

Evidence-Based Recommendations

Given the current evidence base, a cautious, individualised approach is warranted. Patients considering berberine should be informed that whilst serious adverse effects are uncommon, mild gastrointestinal symptoms may occur, and some people report fatigue. Starting with lower doses, taking berberine with meals, and monitoring for unwanted effects represents a prudent strategy. Those with diabetes, metabolic conditions, or taking multiple medications should consult their GP before commencing berberine supplementation to ensure safety and appropriateness for their specific circumstances.

If you experience any suspected side effects from berberine, you can report them through the MHRA Yellow Card Scheme, which helps monitor the safety of supplements and medicines.

Frequently Asked Questions