Berberine
In brief
Section titled “In brief”- Berberine is a plant compound used as dietary supplement (usually 500 mg capsules)
- It can lower fasting glucose, HbA1c, triglycerides and liver enzymes in short-term studies
- Compared to metformin, scientific evidence is limited: smaller, short-term studies, mainly from China, without hard endpoints
- Addition to metformin gives extra metabolic effect on surrogate outcomes, but there is no evidence for fewer complications or better survival
- Within TKB and KMT, berberine is not part of basic treatment; it is at most an additional option for clear residual problems
1. What is berberine?
Section titled “1. What is berberine?”Berberine is a yellow alkaloid from barberry and several other plants.
- Form: usually berberine HCl in 500 mg capsules
- Status: dietary supplement, not a registered medicine
- Quality: purity and actual dosage vary by manufacturer
2. Berberine and metformin
Section titled “2. Berberine and metformin”2.1 Similarities
Section titled “2.1 Similarities”Both agents:
- Lower fasting glucose and HbA1c
- Inhibit glucose production in the liver
- Improve insulin sensitivity
- Affect triglycerides and other lipids
- Act on cellular energy metabolism (including via AMPK)
In short-term studies, the average glucose-lowering effect of berberine is comparable to a mild metformin dose.
2.2 Differences
Section titled “2.2 Differences”| Metformin | Berberine |
|---|---|
| Strictly controlled, registered medicine | Supplement with variable quality |
| Long-term data on complications and safety | Short-term, methodologically weaker studies |
| In guidelines as basic therapy for type 2 diabetes | No comparable place in guidelines |
2.3 Potential added value as addition
Section titled “2.3 Potential added value as addition”In studies of berberine plus metformin versus metformin alone, the following is seen on average:
- Extra reduction of HbA1c (approximately 0.5 to 0.8 percentage points)
- Extra reduction of fasting glucose
- Extra reduction of triglycerides and total cholesterol
- Reduction of liver enzymes and improvement of steatosis scores in MASLD
This is metabolically interesting, but based on small, short-term studies with surrogate outcomes. There is no evidence that adding berberine leads to fewer complications or better survival.
3. Effects in type 2 diabetes, MASLD and dyslipidemia
Section titled “3. Effects in type 2 diabetes, MASLD and dyslipidemia”In type 2 diabetes
Section titled “In type 2 diabetes”- Reduction of fasting glucose and HbA1c in the short term (several months)
In MASLD
Section titled “In MASLD”- Reduction of ALT, AST and GGT
- Improvement of liver fat markers in short-term studies
- No proven effect on liver fibrosis or long-term liver outcomes
In dyslipidemia
Section titled “In dyslipidemia”- Reduction of triglycerides and total cholesterol
- Variable effects on LDL
- Slight increase in HDL possible
Clinical significance depends on the total risk profile and what has already been achieved with lifestyle and metformin.
4. Place of berberine within TKB and KMT
Section titled “4. Place of berberine within TKB and KMT”TKB and KMT usually already provide:
- Clear reduction of insulin and fasting glucose
- Improvement of triglycerides and HDL
- Decrease of abdominal fat and improvement of MASLD
A large part of the metabolic mechanism of berberine is thus already covered by diet and lifestyle. The additional benefit on top of a well-executed TKB or KMT has not been systematically studied and is presumably modest.
5. When to consider berberine?
Section titled “5. When to consider berberine?”Only after consultation with the treating physician, for example:
In type 2 diabetes
Section titled “In type 2 diabetes”HbA1c and fasting glucose remain clearly elevated despite optimal TKB or KMT, metformin (possibly with other agents), weight reduction and exercise.
In MASLD
Section titled “In MASLD”Persistently elevated liver enzymes and metabolic risk factors despite intensive lifestyle intervention and metformin.
In dyslipidemia
Section titled “In dyslipidemia”Triglycerides remain clearly elevated despite diet, weight loss and possible regular lipid treatment.
Metformin intolerance
Section titled “Metformin intolerance”Need for additional, AMPK-targeted metabolic support, preferably under careful supervision and monitoring.
6. When preferably not to use?
Section titled “6. When preferably not to use?”Preferably no berberine:
- During pregnancy or desire for pregnancy
- While breastfeeding
- In newborns and young children (especially with risk of jaundice)
- In severe liver insufficiency or strongly elevated liver enzymes, unless under specialist supervision
- With use of medications with narrow therapeutic margin via similar metabolic routes (including certain immunosuppressants, DOACs, chemotherapy) without involved prescriber
7. Side effects
Section titled “7. Side effects”Often: gastrointestinal complaints (nausea, abdominal pain, diarrhea or constipation)
Less often: fatigue, mild headache and elevation of liver enzymes
8. Use and dosing
Section titled “8. Use and dosing”Always discuss use with the treating physician and bring complete medication list, including supplements. Preferably choose a product from a manufacturer with demonstrable quality control.
General dosing guideline (not an individual prescription)
Section titled “General dosing guideline (not an individual prescription)”| Phase | Dosage |
|---|---|
| Start | 500 mg 1 time per day with meal |
| Build-up (if well tolerated) | 500 mg 2-3 times per day (total 1000-1500 mg/day) |
| Vulnerable/elderly persons | Build up more slowly, stay at lower dose if necessary |
Monitoring
Section titled “Monitoring”Around 3 months: fasting glucose, HbA1c, lipid profile, liver enzymes and kidney function if necessary, with possible adjustment of other antidiabetics.
9. Summary
Section titled “9. Summary”Berberine has demonstrable effects on glucose, triglycerides and liver enzymes in short-term studies, also as addition to metformin. However, the evidence is limited and based on surrogate endpoints, without proof of fewer complications or better survival.
In type 2 diabetes, MASLD and dyslipidemia, berberine can metabolically add something extra on top of metformin and intensive lifestyle. It is an optional, experimental addition for selected cases with residual problems, not a routine standard therapy.
Veelgestelde vragen
What is berberine?
Berberine is a yellow alkaloid from barberry and several other plants. It is sold as a dietary supplement, usually in 500 mg capsules. It is not a registered medicine and quality varies by manufacturer.
Is berberine as good as metformin?
In short-term studies, the glucose-lowering effect is comparable to a mild metformin dose. However, metformin has long-term data on complications and safety, berberine does not. Guidelines position metformin as basic therapy, not berberine.
When can berberine be useful?
Only after consultation with the doctor, for example in type 2 diabetes with persistently elevated glucose despite TKB and metformin, with persistent MASLD, or with elevated triglycerides despite lifestyle. It is not basic therapy but an optional addition.
How much berberine per day?
Start with 500 mg 1x per day with a meal. If well tolerated, build up to 500 mg 2-3x per day (total 1000-1500 mg). In elderly or polypharmacy, build up more slowly. Monitor after 3 months.
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