Meta Information
ID:berberine
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine lowers blood glucose by activating AMPK, which can have an additive effect with other diabetes medications (e.g., Metformin, insulin, SGLT2 inhibitors), increasing the risk of hypoglycemia (dangerously low blood sugar).
Actionable advice:
Berberine lowers blood glucose. Monitor closely and have your prescriber reduce your insulin or sulfonylurea dose to avoid hypoglycemia when combining.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models.
Label source:
PubMed: Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. (PMID 19800084)
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors (e.g., Cyclosporine, Tacrolimus)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine inhibits both the CYP3A4 enzyme and the P-glycoprotein transporter, which can significantly increase blood concentrations of these narrow-therapeutic-index drugs, leading to severe toxicity.
Actionable advice:
Berberine should not be taken with cyclosporine or tacrolimus unless under strict medical supervision with drug level monitoring.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The models account for reversible and irreversible (mechanism-based) inhibition of CYP3A enzymes as well as inhibition of the P-glycoprotein transporter.
Label source:
PubMed: Physiologically based pharmacokinetic model predictions of natural product-drug interactions between goldenseal, berberine, imatinib and bosutinib. (PMID 35048143)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine may stimulate uterine contractions and can displace bilirubin from albumin, posing a risk of neonatal jaundice (kernicterus) to the fetus.
Actionable advice:
This should be strictly avoided during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Berberine can change how bilirubin (a yellowish pigment that is made during the breakdown of red blood cells) binds to serum albumin (the main protein in blood plasma).
Label source:
Anecdotal: MotherToBaby
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its ability to displace bilirubin, berberine poses a theoretical risk of causing brain damage (kernicterus) in nursing infants if it passes into breast milk.
Actionable advice:
It should be avoided completely while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
It may raise the risk of bilirubin buildup in a baby’s brain, which can lead to brain damage and other problems, especially in newborns.
Label source:
Anecdotal: MotherToBaby
Action type:
avoid
Target id:
/class/cyp3a4-substrates
Target name:
Drugs Metabolized by CYP3A4
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine moderately inhibits the CYP3A4 enzyme, which can increase blood levels and the risk of side effects from many common drugs, including certain statins, calcium channel blockers, and benzodiazepines.
Actionable advice:
It is a good idea to consult a pharmacist or doctor to check for interactions when taking any prescription medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP3A4 activity was also inhibited, as the C(max), AUC(0-∞), and AUC(0-12) of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after BBR treatment, respectively.
Label source:
PubMed: Repeated administration of berberine inhibits cytochromes P450 in humans. (PMID 21870106)
Action type:
informational_none
Target id:
/class/cyp2d6-substrates
Target name:
Drugs Metabolized by CYP2D6
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine inhibits the CYP2D6 enzyme, which can increase blood levels of various medications like certain beta-blockers (metoprolol), antidepressants (SSRIs, TCAs), and antipsychotics, enhancing their effects or toxicity.
Actionable advice:
Caution is warranted, and it is important to talk to a healthcare provider when combining with drugs metabolized by CYP2D6.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSIONS: Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities.
Label source:
PubMed: Repeated administration of berberine inhibits cytochromes P450 in humans. (PMID 21870106)
Action type:
informational_none
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine may have its own antiplatelet effects and can inhibit the metabolism of warfarin (via CYP2C9), which can potentiate the action of blood thinners and increase the risk of bleeding.
Actionable advice:
Extreme caution is warranted, and it is important to talk to a doctor before combining this with any blood-thinning medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The antiplatelet effect of berberine has been demonstrated in both laboratory research and clinical trials.
Label source:
PubMed: Effect of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. (PMID 12297129)
Action type:
informational_none
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine can lower blood pressure, which adds to the effect of antihypertensive drugs and may cause hypotension (blood pressure that is too low).
Actionable advice:
Blood pressure should be monitored regularly when starting berberine while on blood pressure medication.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These findings suggested that Sanoshashinto has significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine, which were the principal constituents of Scutellariae Radix and Coptidis Rhizoma, were the main antihypertensive constituents in Sanoshashinto.
Label source:
PubMed: Antihypertensive constituents in Sanoshashinto. (PMID 31894475)
Action type:
monitor
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine inhibits the P-glycoprotein (P-gp) transporter responsible for clearing digoxin, which can lead to increased digoxin levels and a higher risk of cardiac toxicity.
Actionable advice:
Berberine and digoxin are best not combined unless under strict medical supervision with drug level monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
For current labeling information, please visit https://www.fda.gov/drugsatfda
In patients with hypertrophic cardiomyopathy (formerly called idiopathic hypertrophic subaortic stenosis), the
positive inotropic effect of digoxin leads to an increased subvalvular outflow gradient and therefore, may
compromise cardiac output.
Label source:
Action type:
avoid
Target id:
/class/statins
Target name:
Statins (HMG-CoA Reductase Inhibitors)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By inhibiting CYP3A4, berberine can increase blood levels of statins like atorvastatin, simvastatin, and lovastatin, raising the risk of muscle-related side effects (myopathy or rhabdomyolysis).
Actionable advice:
It is important to talk to a doctor before combining; statins not metabolized by CYP3A4 (e.g., pravastatin, rosuvastatin) may be safer.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Based on these findings, berberine in combination with statins has a greater inhibitory effect on CYP3A4 activity and CYP3A4 protein and mRNA expression than berberine alone.
Label source:
PubMed: The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. (PMID 30086269)
Action type:
informational_none
Target id:
/procedure/surgery
Target name:
Scheduled Surgery
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
Berberine's effects on blood sugar, blood pressure, and potential antiplatelet activity can interfere with hemodynamic stability during and after surgery and may increase bleeding risk.
Actionable advice:
Berberine should be discontinued at least 2 weeks before any scheduled surgery.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Berberine and coptisine inhibited platelet aggregation in both in vitro and in vivo assays, and berberine inhibited the decline of renal blood flow.
Label source:
PubMed: Japanese journal of pharmacology (1992)
Source url:
Exact phrase from label:
Both baicalin and berberine showed markedly antiplatelet aggregation induced by all activators. The antithrombotic activity of baicalin was relatively higher than that of berberine (35.0-47.8% vs. 20.6-33.5%).
Label source:
PubMed: Pharmaceutical biology (2021)
Source url:
Exact phrase from label:
As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation.
Label source:
PubMed: Toxins (2022)
Action type:
avoid
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking berberine with food can significantly reduce gastrointestinal side effects like cramping and diarrhea, and may also improve its otherwise poor absorption.
Actionable advice:
Berberine is best taken with or immediately after a meal.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The tolerability is high for low dosages, with some gastrointestinal complaints appearing to be associated with use of high dosages.
Label source:
PubMed: Hospital practice (1995) (2012)
Source url:
Exact phrase from label:
Berberine is a natural alkaloid used to improve glycemia but displays poor bioavailability and increased rates of gastrointestinal distress at higher doses.
Label source:
PubMed: Nutrients (2021)
Source url:
Exact phrase from label:
Because berberine is well tolerated aside from transient gastrointestinal (GI) upset in some people and, in particular, has not been reported to cause myopathy or hepatic damage, the combination of RYR and berberine may have the potential to achieve reductions in LDL cholesterol comparable with those achieved with prescription statin therapy, but without the associated risks such as muscle damage and diabetes.
Label source:
PubMed: Alternative therapies in health and medicine (2015)
Action type:
separate
Target id:
/intervention/metformin
Target name:
Metformin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both berberine and metformin activate the AMPK pathway, leading to synergistic improvements in glucose control. However, this combination also increases the risk of hypoglycemia and GI side effects.
Actionable advice:
These are best combined only under medical supervision to monitor blood sugar and adjust dosages to prevent hypoglycemia.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our findings highlight that compared to monotherapies, combination treatment significantly enhanced AMPK activation and inhibited sterol regulatory element-binding protein 1 (SREBP1) expression and that of its downstream target fatty acid synthase (FASN).
Label source:
PubMed: Scientific reports (2025)
Source url:
Exact phrase from label:
Metformin and berberine share many features in actions despite different structure and both could be excellent drugs in treating T2DM, obesity, cardiac diseases, tumour, as well as inflammation.
Label source:
PubMed: Oncotarget (2018)
Source url:
Exact phrase from label:
The potent glucose-lowering effects with minimal hypoglycemia of berberine and metformin may be partially due to their bidirectional regulation of the AMPK signaling pathway.
Label source:
PubMed: Journal of cellular biochemistry (2018)
Action type:
monitor
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine is a weak inhibitor of the CYP2C9 enzyme, which may slightly increase levels of drugs metabolized by this pathway, such as warfarin and losartan.
Actionable advice:
A potential interaction may occur with medications like warfarin or losartan, and watching for effects may help.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses).
Label source:
PubMed: Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. (PMID 22855269)
Action type:
monitor
Target id:
/class/serotonergic-agents
Target name:
Serotonergic Medications (SSRIs, SNRIs, TCAs, Triptans)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Berberine may possess weak monoamine oxidase (MAO) inhibitory properties, which could theoretically increase the risk of serotonin syndrome when combined with other serotonergic drugs.
Actionable advice:
The symptoms of serotonin syndrome (e.g., agitation, rapid heart rate) are worth knowing when combining with antidepressants.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The result of the study showed that untreated STZ-induced diabetic rats have increased acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO) activities, and malonylaldehyde (MDA) level, with concomitant decrease of superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, and glutathione (GSH) level. However, daily treatment with 50 and 100 mg/kg BER and ACA significantly reversed these effects.
Label source:
PubMed/primary literature: https://pubmed.ncbi.nlm.nih.gov/33725758/
Action type:
informational_none
Target id:
/intervention/curcumin
Target name:
Curcumin
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Curcumin and berberine may have synergistic effects on improving insulin sensitivity, reducing inflammation, and supporting metabolic health through complementary pathways.
Actionable advice:
Taking curcumin and berberine together may enhance overall metabolic health benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Natural compounds have become promising candidates for the intervention of diabetes and its complications due to their high safety profile, multi-target synergistic hypoglycemic effects, and protective actions on target organs. This article systematically reviews the antidiabetic effects of five major natural compounds: resveratrol, curcumin, berberine, quercetin, and ginsenosides. Their core mechanisms mainly include improving insulin resistance, protecting pancreatic β-cells, exerting antioxidant and anti-inflammatory effects, regulating mitochondrial function, and repairing the intestinal barrier.
Label source:
PubMed: Research Progress of Natural Compounds in the Treatment of Diabetes and Its Complications. (PMID 41984462)
Action type:
informational_none
Target id:
/intervention/milk-thistle
Target name:
Silybin (from Milk Thistle)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Silybin can inhibit the P-glycoprotein efflux pump in the gut, which may increase the absorption and bioavailability of berberine, enhancing its effectiveness.
Actionable advice:
Consider using a berberine formula that includes a bioavailability enhancer like silybin.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: silybin (milk thistle) is a documented P-glycoprotein inhibitor, so it could increase berberine absorption/bioavailability. FLAG: the cited DOI (10.3390/pharmaceutics12090882) is a berberine mixed-micelle P-gp study with NO silybin - citation mismatch; the silybin-P-gp mechanism is plausible but unsupported by that source.
Label source:
Class inference
Action type:
informational_none