Berberine

Berberine/Drug Interactions:

  • 1,3-bis (2-chloroethyl)-1-nitosurea (BCNU)1,3-bis (2-chloroethyl)-1-nitosurea (BCNU): Based on in vitro study, berberine and 1,3-bis(2-chloroethyl)-1-nitrosourea may have additive effects (99).
  • AcetaminophenAcetaminophen: In vitro and in animal research, berberine has demonstrated hepatoprotective effects when administered pre- and post-exposure to toxic doses of acetaminophen (100; 65).
  • AcetylcholineAcetylcholine: In animal research, berberine increased sensitization to acetylcholine's hypotensive effects (49).
  • AntiarrhythmicsAntiarrhythmics: In vitro, berberine has antiarrhythmic effects (101; 102; 103; 104). However, in a clinical trial, berberine was associated with the development of ventricular arrhythmias in subjects with congestive heart failure (51).
  • AntibioticsAntibiotics: In human research, berberine decreased the efficacy of tetracycline (5). In vitro, berberine in combination with 1% chlorhexidine was comparable in bactericidal activity to 5.25% NaOCl (105).
  • AnticoagulantsAnticoagulants: In human research, berberine bisulfate stimulated platelet formation (55). In vitro, berberine had antiheparin action (56).
  • Antidiabetic agentsAntidiabetic agents: In humans, berberine and berberine hydrochloride have been shown to lower fasting plasma glucose (30; 31; 32; 33; 34), post-prandial plasma glucose (31), post-load plasma glucose (30), and HbA1c levels (30; 31; 32). Berberine, as part of a mixed nutraceutical, has been shown to improve insulin sensitivity in individuals with hypercholesterolemia (93; 94). Moreover berberine hydrochloride has been shown to reduce both fasting insulin level (33) and insulin resistance (33). Similar effects have been documented in animal research (35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47). In vitro, berberine in combination with metformin or 2,4-thiazolodinedione had additive effects on the uptake of 2-deoxyglucose (106).
  • Antihypertensive drugsAntihypertensive drugs: In animal research, berberine caused transient hypotension or reduced blood pressure (48; 49) and bradycardia (48). In human research Armolipid Plus? (berberine, red yeast rice, and policosanol) reduced blood pressure (50). Additionally, propranolol inhibits the increase in slow-response action potential seen with berberine in vitro (107).
  • Antilipemic agentsAntilipemic agents: In humans, berberine and berberine hydrochloride monotherapy have been shown to reduce levels of triglyceride (30; 31; 73; 32; 78; 33; 79), total cholesterol (30; 31; 73; 78; 33; 79), and low-density lipoprotein (LDL) cholesterol (30; 73; 78; 33). Similar total cholesterol- and LDL cholesterol-lowering effects have also been observed following combination berberine therapy (94; 93; 78; 108). Interestingly, although some clinical studies of berberine and berberine hydrochloride monotherapy have observed increased levels of high-density lipoprotein (HDL) cholesterol (73; 78; 33), similar effects have been inconsistent following berberine combination therapy (94; 78). Effects were lacking between groups in other studies (52). Similar effects have been shown in animal research (76; 77; 46).
  • Anti-inflammatory drugsAnti-inflammatory drugs: In animal and in vitro research, berberine had anti-inflammatory effects (109; 110; 111; 112; 112; 113; 114; 115; 110; 116). In human research, berberine reduced levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), hypersensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), and matrix metalloproteinase-9 (MMP-9) vs. baseline (52) and in vitro, berberine reduced the expression of IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), MCP-1, cyclooxygenase-2, and MMP-9 (116).
  • AntineoplasticsAntineoplastics: In vitro, berberine modulated the expression and function of PGP-170 in hepatoma cells (60; 61).
  • Antiobesity agentsAntiobesity agents: In a poor quality study, berberine resulted in weight loss and a reduction in plasma lipids in obese subjects (79).
  • AntipsychoticsAntipsychotics: In vitro, berberine reduced the induction of adipogenesis associated with clozapine or risperidone; down-regulation of mRNA and protein levels of SREBP-1proteins also occurred (117).
  • Carbon tetrachloride (CCl4)Carbon tetrachloride (CCl4): In animal research, berberine has demonstrated hepatoprotective effects when selectively administered pre-exposure to CCl4 (65).
  • COX-2 inhibitorsCOX-2 inhibitors: Based on pharmacological activity and in vitro research, berberine and berberine sulfate had anti-inflammatory effects and may interact with cyclooxygenase-2 (COX-2) inhibitors (112; 114; 110). COX-2 inhibitor drugs include celecoxib (Celebrex?) and rofecoxib (Vioxx?).
  • CyclosporineCyclosporine: In human research, berberine increased the oral bioavailability of cyclosporine A and elevated its concentration level in the blood (118; 119; 24).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: In pre-clinical and clinical research, berberine has been shown to moderately or weakly inhibit various cytochrome P450 enzymes, including CYP2D6, CYP2C9, and CYP3A4 (66; 67; 68; 69).
  • DexamethasoneDexamethasone: In theca cells in vitro, berberine reduced insulin resistance induced by dexamethasone (12).
  • DextromethorphanDextromethorphan: In laboratory research, berberine decreased the CYP2D6-mediated pharmacokinetic activity of dextromethorphan (68). Altered drug effects may be theoretically plausible.
  • FluconazoleFluconazole: Based on in vitro study, there may be a potential for synergism between berberine chloride and fluconazole (71).
  • Hepatotoxic agentsHepatotoxic agents: In a clinical trial, there was a lack of significant differences in AST or ALT (52); however, in a separate study, AST and ALT levels decreased (73; 32) and liver protection has been shown in animal models (18; 65; 120; 46).
  • HeroinHeroin: According to research in humans, levo-tetrahydropalmatine (l-THP), a tetrohydorprotoberberine derivative, has been shown to diminish heroin cravings and reduce heroin withdrawal syndrome symptoms (74).
  • LosartanLosartan: In laboratory research, berberine decreased the CYP2C9-mediated pharmacokinetic activity of losartan (68). Altered drug effects may be theoretically plausible.
  • L-phenylephrineL-phenylephrine: Based on animal study, berberine and L-phenylephrine may have additive effects when administered concurrently (121).
  • MetforminMetformin: In human research, berberine hydrochloride has demonstrated a more potent effect compared to metformin for lowering serum lipids and increasing sex hormone binding globulin (33).
  • MidazolamMidazolam: In laboratory research, berberine decreased the CYP3A4-mediated pharmacokinetic activity of midazolam (68). Altered drug effects may be theoretically plausible.
  • Neostigmine (Prostigmin?)Neostigmine (Prostigmin?): In animal research, berberine reversed the secretory properties of neostigmine (121).
  • PentobarbitalPentobarbital: In animal research, berberine prolonged the sleep-inducing effects of pentobarbital. (65).
  • P-glycoprotein inhibitorsP-glycoprotein inhibitors: Based on in vitro and in vivo study, P-glycoprotein may contribute to the poor intestinal absorption of berberine (122).
  • Renoprotective agentsRenoprotective agents: In a clinical trial, there was a lack of significant differences in BUN and Cr levels between groups (52). However, in animal research, berberine improved negative effects on the kidney in an animal diabetic model (43; 42). Improvements occurred in the glomerular area and volume, as well as BUN, serum Cr, and urinary protein.
  • SedativesSedatives: In animal research, berberine had sedative effects (63; 56; 64; 49; 65).
  • SimvastatinSimvastatin: In animal and human research, berberine and simvastatin have been shown to work synergistically to produce an additive cholesterol-lowering effect vs. either treatment independently (70).
  • StrychnineStrychnine: In animal research, berberine has been shown to potentiate the toxic effects of strychnine (65).
  • VassopressorVassopressor: In an isolated rat mesenteric artery model as well as in vitro, berberine had both vasorelaxant and antiproliferative effects (123).
  • YohimbineYohimbine: In vitro, berberine competitively inhibited the binding of yohimbine to platelets (124).

    • Berberine/Herb/Supplement Interactions:

  • AntiarrhythmicsAntiarrhythmics: In vitro, berberine has antiarrhythmic effects (101; 102; 103; 104). However, in a clinical trial, berberine was associated with the development of ventricular arrhythmias in subjects with congestive heart failure (51).
  • AntibacterialsAntibacterials: In human research, berberine decreased the efficacy of tetracycline (5). In vitro, berberine in combination with 1% chlorhexidine was comparable in bactericidal activity to 5.25% NaOCl (105).
  • AnticoagulantsAnticoagulants: In human research, berberine bisulfate stimulated platelet formation (55). In vitro, berberine had antiheparin action (56).
  • AntilipemicsAntilipemics: In humans, berberine and berberine hydrochloride monotherapy have been shown to reduce levels of triglyceride (30; 31; 73; 32; 78; 33; 79), total cholesterol (30; 31; 73; 78; 33; 79), and low-density lipoprotein (LDL) cholesterol (30; 73; 78; 33). Similar total cholesterol- and LDL cholesterol-lowering effects have also been observed following combination berberine therapy (94; 93; 78; 108). Interestingly, although some clinical studies of berberine and berberine hydrochloride monotherapy have observed increased levels of high-density lipoprotein (HDL) cholesterol (73; 78; 33), similar effects have been inconsistent following berberine combination therapy (94; 78). Effects were lacking between groups in other studies (52). Similar effects have been shown in animal research (76; 77; 46).
  • Anti-inflammatory agentsAnti-inflammatory agents: In animal and in vitro research, berberine had anti-inflammatory effects (109; 110; 111; 112; 112; 113; 114; 115; 110; 116). In human research, berberine reduced levels of IL-6, MCP-1, hsCRP, ICAM-1, VCAM-1, and MMP-9 vs. baseline (52) and in vitro, berberine reduced the expression of IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), MCP-1, cyclooxygenase-2, and MMP-9 (116).
  • AntineoplasticsAntineoplastics: In vitro, berberine modulated the expression and function of PGP-170 in hepatoma cells (60; 61).
  • Antiobesity agentsAntiobesity agents: In a poor quality study, berberine resulted in weight loss and a reduction in plasma lipids in obese subjects (79).
  • AntioxidantsAntioxidants: In animal research, berberine increased activity of superoxide dismutase and decreased levels of malondialdehyde and superoxide anion (42; 43). Antioxidant effects of berberine have been shown in other animal research (125).
  • AntipsychoticsAntipsychotics: In vitro, berberine reduced the induction of adipogenesis associated with clozapine or risperidone; down-regulation of mRNA and protein levels of SREBP-1proteins also occurred (117).
  • Berberine-containing herbsBerberine-containing herbs: According to secondary sources, concomitant use of berberine-containing herbs may increase the risk of berberine toxicity. Berberine-containing herbs include: bloodroot, goldenseal, celandine, Chinese goldthread, goldthread, Oregon grape (Mahonia species), amur cork tree, and Chinese corktree.
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: In pre-clinical and clinical research, berberine has been shown to moderately or weakly inhibit various cytochrome P450 enzymes, including CYP2D6, CYP2C9, and CYP3A4 (66; 67; 68; 69).
  • Hepatotoxic agentsHepatotoxic agents: In a clinical trial, there was a lack of significant differences in AST or ALT (52); however, in a separate study, AST and ALT levels decreased (73; 32) and liver protection has been shown in animal models (18; 65; 120; 46).
  • HypoglycemicsHypoglycemics: In humans, berberine and berberine hydrochloride have been shown to lower fasting plasma glucose (30; 31; 32; 33; 34), post-prandial plasma glucose (31), post-load plasma glucose (30), and HbA1c levels (30; 31; 32). Berberine, as part of a mixed nutraceutical, has been shown to improve insulin sensitivity in individuals with hypercholesterolemia (93; 94). Moreover berberine hydrochloride has been shown to reduce both fasting insulin level (33) and insulin resistance (33). Similar effects have been documented in animal research (35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47). In vitro, berberine in combination with metformin or 2,4-thiazolodinedione had additive effects on the uptake of 2-deoxyglucose (106).
  • HypotensivesHypotensives: In animal research, berberine caused transient hypotension or reduced blood pressure (48; 49) and bradycardia (48). In human research Armolipid Plus? (berberine, red yeast rice, and policosanol) reduced blood pressure (50). Additionally, propranolol inhibits the increase in slow-response action potential seen with berberine in vitro (107).
  • IsoflavonesIsoflavones: In menopausal women, a combination of isoflavones and berberine improved menopausal symptoms (126).
  • P-glycoprotein inhibitorsP-glycoprotein inhibitors: Based on in vitro and in vivo study, P-glycoprotein may contribute to the poor intestinal absorption of berberine (122).
  • PolicosanolPolicosanol: In human research Armolipid Plus? (berberine, red yeast rice, and policosanol) reduced LDL-cholesterol and total cholesterol; significant differences in TG and HDL-cholesterol levels were lacking (108).
  • Red yeast riceRed yeast rice: In human research Armolipid Plus? (berberine, red yeast rice, and policosanol) reduced LDL-cholesterol and total cholesterol; significant differences in TG and HDL-cholesterol levels were lacking (108).
  • Renoprotective agentsRenoprotective agents: In a clinical trial, there was a lack of significant differences in BUN and Cr levels between groups (52). However, in animal research, berberine improved negative effects on the kidney in an animal diabetic model (43; 42). Improvements occurred in the glomerular area and volume, as well as BUN, serum Cr, and urinary protein.
  • SedativesSedatives: In animal research, berberine had sedative effects (63; 56; 64; 49; 65).
  • StanolsStanols: In an animal model, berberine decreased total and non-HDL-cholesterol; addition of plant stanols improved this lowering over plant stanols and berberine alone (127).
  • StrychnineStrychnine: In animal research, berberine has been shown to potentiate the toxic effects of strychnine (65).
  • Tyramine-containing herb/supplementsTyramine-containing herb/supplements: In human research berberine decreased levels of tyramine (62); thus, tyramine-containing foods, such as wine, cheese, and chocolate, may have an interaction with berberine.
  • VassopressorsVassopressors: In an isolated rat mesenteric artery model as well as in vitro, berberine had both vasorelaxant and antiproliferative effects (123).
  • Vitamin BVitamin B: According to secondary sources, berberine may decrease the metabolism of vitamin B therefore the concomitant use of barberry with vitamin B should be avoided.
  • Vitamin DVitamin D: In human research, combination berberine sulfate trihydrate has been shown to increase 25-hydroxyvitamin D levels in the serum (128; 129).
  • YohimbeYohimbe: In vitro, berberine competitively inhibited the binding of yohimbine to platelets (124). In addition, due to the antifertility properties of berberine (98), use of yohimbe for fertility may not be effective.

    • Berberine/Food Interactions:

  • Isoflavone-containing foodsIsoflavone-containing foods: In menopausal women, a combination of isoflavones and berberine improved menopausal symptoms (126).
  • Tyramine-containing foodsTyramine-containing foods: In human research berberine decreased levels of tyramine (62); thus, tyramine-containing foods, such as wine, cheese, and chocolate, may have an interaction with berberine.

    • Berberine/Lab Interactions:

  • AmylaseAmylase: In human research, a combination of Magnolia officinalis and Phellodendron amurense (berberine is a constituent) (Relora?) lacked effect on salivary amylase levels (16).
  • ApolipoproteinsApolipoproteins: In animal research, berberine decreased levels of apolipoprotein B and increased levels of apolipoprotein AI (46).
  • Bilirubin levelsBilirubin levels: In vitro and in animal research, berberine displaces bilirubin from albumin, resulting in an increase in serum total and direct bilirubin concentrations (58).
  • Blood pressureBlood pressure: In animal research, berberine caused transient hypotension or reduced blood pressure (48; 49) and bradycardia (48). In human research Armolipid Plus? (berberine, red yeast rice, and policosanol) reduced blood pressure (50). Additionally, propranolol inhibits the increase in slow-response action potential seen with berberine in vitro (107).
  • Bone markersBone markers: In both animal and human research, berberine monotherapy and combination therapy have been shown to improve various markers of bone health, including bone mineral density, bone resorption, and serum levels of osteocalcin and 25-hydroxyvitamin D (97; 129; 128).
  • CalcitriolCalcitriol: In human research, berberine increased calcitriol levels in all subjects (79).
  • CortisolCortisol: In human research, a combination of Magnolia officinalis and Phellodendron amurense (berberine is a constituent) (Relora?) lacked effect on salivary cortisol levels (16).
  • Cytochrome P450 activityCytochrome P450 activity: In pre-clinical and clinical research, berberine has been shown to moderately or weakly inhibit various cytochrome P450 enzymes, including CYP2D6, CYP2C9, and CYP3A4 (66; 67; 68; 69).
  • Inflammatory markersInflammatory markers: In human research, berberine reduced levels of IL-6, MCP-1, hsCRP, ICAM-1, VCAM-1, and MMP-9 vs. baseline (52) and in vitro, berberine reduced the expression of IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), MCP-1, cyclooxygenase-2, and MMP-9 (116).
  • InterleukinsInterleukins: Berberine has been shown to inhibit IL-1 (113). Berberine has also been shown to decrease IL-8 production (130).
  • Liver enzyme levelsLiver enzyme levels: Based on research in animals and humans, berberine decreased levels of ALT, AST, alkaline phosphatase, and gamma glutamyl transpeptidase (76; 65; 73; 32).
  • Plasma lipid levelsPlasma lipid levels: In humans, berberine and berberine hydrochloride monotherapy have been shown to reduce levels of triglyceride (30; 31; 73; 32; 78; 33; 79), total cholesterol (30; 31; 73; 78; 33; 79), and low-density lipoprotein (LDL) cholesterol (30; 73; 78; 33). Similar total cholesterol- and LDL cholesterol-lowering effects have also been observed following combination berberine therapy (94; 93; 78; 108). Interestingly, although some clinical studies of berberine and berberine hydrochloride monotherapy have observed increased levels of high-density lipoprotein (HDL) cholesterol (73; 78; 33), similar effects have been inconsistent following berberine combination therapy (94; 78). Effects were lacking between groups in other studies (52). Similar effects have been shown in animal research (76; 77; 46).
  • Platelet levelsPlatelet levels: In human research, berberine increased platelet count (55).
  • Renal markersRenal markers: In a clinical trial, there was a lack of significant differences in BUN and Cr levels between groups (52). However, in animal research, berberine improved BUN, serum Cr, and urinary protein (43; 42).
  • Serum glucose levelsSerum glucose levels: In humans, berberine and berberine hydrochloride have been shown to lower fasting plasma glucose (30; 31; 32; 33; 34), post-prandial plasma glucose (31), post-load plasma glucose (30), and HbA1c levels (30; 31; 32). Berberine, as part of a mixed nutraceutical, has been shown to improve insulin sensitivity in individuals with hypercholesterolemia (93; 94). Moreover berberine hydrochloride has been shown to reduce both fasting insulin level (33) and insulin resistance (33). Similar effects have been documented in animal research (35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47).
  • Testosterone levelsTestosterone levels: In human research, berberine hydrochloride has been shown to increase sex hormone binding globulin levels and decrease the free androgen index (33).
  • White blood cell countWhite blood cell count: In human research, berberine increased leukocyte counts (57).