Berberine: Benefits and Clinical Applications

Berberine is an isoquinolone alkaloid that is bitter and bright golden yellow in color. It is derived mainly from the roots, stems and rhizomes of plants such as Coptis chinensis (Chinese golden thread), Hydrastis canadensis (goldenseal), Berberis aquifolium (Oregon grape), and Berberis vulgaris (barberry). It has been used for thousands of years in traditional Chinese and Ayurvedic medicine and is generally considered safe, though it should be avoided during pregnancy and lactation.


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Gastrointestinal side effects may occur due to berberine’s impact on bowel motility. These include abdominal pain, distention, nausea, vomiting, and constipation. Side effects appear to be dose dependent, with increased symptoms such as low blood pressure, dyspnea, and flu-like symptoms at higher doses.

Berberine is commonly used as an antibacterial, antiviral, antimicrobial, antifungal, and antihyperlipidemic agent. The many therapeutic applications of berberine are due to its antioxidant and anti-inflammatory properties, making it one of the top supplements of choice in clinical practice.

It has traditionally been used for gastrointestinal related issues as well as issues involving liver dysfunction, digestive complaints, blood sugar regulation, inflammation, and infectious diseases.

While berberine has exhibited a bioavailability of <1%, the metabolites of berberine have demonstrated increased absorption in the system. These metabolites contribute to the widespread impact observed from the use of berberine on liver, kidney, muscle, lung and brain.

Gastrointestinal Support

Chen at el (2015) conducted a randomized clinical trial that demonstrated the usefulness of using berberine in treating patients with IBS-D. Berberine (400 mg delivered twice daily) reduced the frequency of diarrhea, abdominal pain, and the urgency of defecation after 8 weeks. They concluded that berberine was well tolerated and was beneficial in treating IBS-D. They also noted that those in the berberine group showed improvements in their depression and anxiety scores and in their IBS quality of life scores.

Berberine has been shown to induce structural and compositional changes in the gastrointestinal microbiota. These changes affect the metabolites dependent on the microbes such as trimethylamine N-oxide (TMAO), short chain fatty acids (SCFAs), bile acids (BAs), branched-chain amino acids (BCAAs), and aromatic amino acids (AAAs).

Yao et al confirmed berberine’s gut modulatory ability in their 2020 study using rats. They showed that berberine caused changes in the GI microbiota that included increased beneficial microbes in the phylum Bacteroidetes and the family Lactobacillaceae. An increase in Lactobacillaceae was also observed to be negatively associated with the risk of Type 2 Diabetes (T2D). A decrease in potentially pathogenic microbes in the phylum Proteobacteria and Verrucomicrobia was noted along with a decrease in aromatic amino acids (AAAs).

The authors concluded that berberine was able to modulate the gut microbiota of the rats in the study. This led to improved glucose tolerance and the alleviation of symptoms associated with T2D, such as abnormal glucose and lipid levels. They recommended the use of berberine in the treatment of T2D in rats.

Glucose and Lipid Regulation

Berberine is useful in conditions associated with metabolic diseases and atherosclerosis due to its ability to decrease inflammation, improve glucose and lipid metabolism, and improve energy homeostasis, making it beneficial as a treatment option for those with T2D. The hypoglycemic effects of berberine have been shown comparable to Metformin.

An important mechanism of action that occurs with the use of berberine is the activation of AMPK. Drugs such as Metformin work by stimulating this AMPK pathway. Turner et al (2008) concluded, in their study on IR mice, that berberine inhibited Complex I in the respiratory chain and ATP synthesis. The inhibition of ATP synthesis activated AMPK in the mice studied.

The beneficial effects of AMPK activation are far reaching as it is the key energy sensor in eukaryotes. Some of the benefits include improved energy homeostasis, inhibition of mTOR signaling, increased mitochondrial biogenesis via PGC1a, inhibition of the NLRP3 inflammasome, increased lipid oxidation, decreased lipid and glucose synthesis, and increased insulin sensitivity as more insulin binds to the insulin receptor. This cascade of actions contributes to the positive therapeutic effects in glucose and lipid regulation.

Yin, Xing, and Ye (2008) concluded that berberine was an effective treatment for lowering blood glucose and found it beneficial for regulating lipid metabolism. Their two arm, 3-month study demonstrated the ability of berberine to significantly lower fasting blood glucose (FBG), postprandial blood glucose (PBG), hemoglobin A1C (HbA1C), fasting plasma insulin, HOMA-IR, plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol. The authors did observe transient, adverse gastrointestinal effects in 34.5% of the patients.

Cancer Support

Berberine has been shown to display anti-cancer mechanisms as well. These include having the ability to inhibit cell growth and proliferation and to inhibit migration, invasion, and metastasis. Other anti-cancer mechanisms include the induction of mitochondrial apoptosis and autophagy, both necessary in limiting cell growth and proliferation.

Anti-inflammatory and Immune System Support

T regulatory (Treg) cells are necessary for establishing immune system tolerance. They play an important role in preventing the development of autoimmune conditions. The pathogenesis of autoimmunity has been associated with an increase in Th1 and Th17 autoreactive T cell responses. Dendritic cells (DCs) and macrophages, part of the immune system inflammatory response, can also promote autoreactive T-cell responses.

Berberine was shown to suppress Th1 and Th17 proliferation and decrease Th mediated inflammation by modulating DCs and macrophages, and by increasing Tregs. Berberine works by decreasing the inflammatory cytokines (IL-12; TGF-β, IL-6, & IL-23) that trigger the differentiation into Th-1 or Th-17 cells (respectively). Berberine also increases Foxp3 and differentiation into Treg cells.

This reduction in proinflammatory cytokines and inflammation has been shown beneficial in those with rheumatoid arthritis. Huang et al (2021) noted the immune-modulatory ability of berberine to regulate the Th17/Treg balance, inhibit the proliferation of autoreactive T cells, and induce apoptosis of dendritic cells and macrophages. They considered berberine a promising lead drug in the treatment of RA.

Anti-viral Support

Berberine influences both immune and inflammatory pathways present with COVID-19. Wang et al (2021) were able to demonstrate the effectiveness of an orally delivered berberine nanomedicine against SARS-CoV-2. The nanomedicine they developed greatly increased the bioavailability of berberine. They were able to induce apoptosis, enhance protective immunity by inhibiting mast cell histamine release, protect against tissue damage, inhibit pro-inflammatory cytokines, and inhibit viral infection and replication.

Berberine was shown to reduce viral replication by regulation of the signaling pathways involved (MEK-ERK, AMPK/mTOR, and NF-кB). It also demonstrated increased viral clearance by inducing an enhanced immune system response to a virus.

This anti-influenza effect noted by Wang et al is useful for many viruses including Epstein-Barr virus (EBV), human papilloma virus (HPV), respiratory syncytial virus (RSV), herpes simplex virus (HSV) 1&2, severe acute respiratory syndrome coronavirus (SARS-CoV) 1&2, and hepatitis C virus (HCV). It has proven so effective against SARS-CoV-2 that the China National Health Commission for COVID-19 has recommended its inclusion with other therapies in treating this widespread virus.

Anti-Fungal Support

Berberine is well known for its antifungal properties against different strains of Candida. Studies have shown that berberine demonstrated inhibitory effects against Candida biofilm formation and damaged the spatial structures in the Candida spp strains studied. This resulted in a decrease in the biofilm thickness rates.

This was observed even with fluconazole resistant strains such as C. krusei. Da Silva et al (2016) explored the mechanisms behind berberine’s success as an antifungal and discovered that berberine was able to alter the integrity of the plasma and mitochondrial membranes, reducing the mitochondrial transmembrane potential.

The administration of berberine was thought to increase transient pore openings that resulted in the release of proapoptotic factors and eventually cell death. They concluded that berberine offered a promising source of molecules with antifungal properties and the potential to reduce biofilm formation.

Pharmacologic actions include:

  • Metabolic inhibition of certain organisms
  • Inhibition of bacterial enterotoxin formation
  • Inhibition of intestinal fluid accumulation and ion secretion
  • Inhibition of smooth muscle contraction
  • Reduction of inflammation (MAPK, IL-1β, IL-6, NF-кB, TNF-α, COX-2, iNOS, etc.)19
  • Platelet aggregation inhibition
  • Platelet count elevation in certain types of thrombocytopenia
  • Stimulation of bile and bilirubin secretion
  • Inhibition of ventricular tachyarrhythmias

Physiologic results include:

  • Increased energy expenditure [adenosine monophosphate-activated protein kinase (AMPK)]
  • Limited weight gain
  • Improved cold tolerance
  • Enhanced brown adipose tissue activity
  • Improved joint health (uric acid levels, uric acid excretion, xanthine oxidase)
  • Improved insulin sensitivity [insulin resistance (IR), impaired glucose tolerance (IGT) & obesity]
  • Protective of mucus membranes
  • Enhanced intestinal barrier function including decreased intestinal permeability and increased colonic mucosal layer thickness [lipopolysaccharides (LPS), inflammation, tight junction proteins (zonulin & occludin)]
  • Improved bone mineral density
  • Protection of lungs from cigarette smoke induced acute lung inflammation
  • Increased endogenous antioxidant activity [superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS) , etc]
  • Increased gastrointestinal microbial diversity (Akkermansia, Bacteroides, Butyrate-producing bacteria, Faecalibacterium prausnitzii)

Clinical Indications for the use of Berberine

  • Anti-bacterial (Staph, Strep, Shigella, Actinobacillus, Chlamydia trachomatis, Vibrio cholera, E. coli, MRSA)
  • Anti-Fungal (Candida, Microsporum)
  • Anti-parasitic (Giardia lamblia, Trichomonas vaginalis, Entamoeba histolytica, Schistosoma, Leishmania donovani)
  • Anti-viral (EBV, CMV, Herpes 1 & 2, SARS-CoV, Influenza, RSV, HCV, HPV)
  • Autoimmune disease (RA, MS, encephalomyelitis, colitis, IBD)
  • Autoimmune conditions
  • Bile Acid issues
  • Benign Prostatic Hyperplasia
  • Cancer prevention
  • Cardiovascular disease (Atherosclerosis, Heart failure Hypercholesterolemia, Antiarrhythmic, Vasorelaxant, Hypertension, AAA, Stroke, MI Ischemia-reperfusion injuries)
  • Constipation
  • Diabetes, Obesity, and other metabolic disorders
  • Diarrhea
  • Dysbiosis
  • Dyslipidemia
  • Gastric ulcers
  • GERD, Reflux esophagitis
  • Gout
  • Helicobacter pylori
  • Hepatitis
  • IBS (C & D), SIBO, IBD
  • Infection
  • Inflammation—GI issues=elevated calprotectin
  • Kidney stones
  • Leaky Gut—any type of gut barrier issue
  • Memory enhancement
  • Metabolic syndrome
  • Micturition
  • Mood disorders (depression, anxiety)
  • NAFLD & Liver fibrosis
  • Neurodegenerative disease (Alzheimer’s, Parkinson’s)
  • Pain
  • PCOS
  • Renal ischemia/reperfusion
  • Stomatitis
  • Type 2 Diabetes
  • Thrombocytopenia
  • Traumatic brain injury


  • Avoid during pregnancy and lactation
  • Generally considered safe
  • Side effects appear to be dose dependent and are typically not seen if using correct dosage.
  • Gastrointestinal Side effects include abdominal pain, distention, nausea, vomiting, and constipation.
  • Other side effects include low blood pressure, dyspnea, and flu-like symptoms.

Dosage and Frequency Recommendations

Moss Nutrition—Berberine Select
500 mg bid;
Tid in more difficult cases. Watch for bowel tolerance
Use caution if exceeding 1 gram/day for longer than 3 months
Can be taken with or without food. Most people tolerate it better with food

Viral Infection—Moss Nutrition—ImmunoSelect (contains goldenseal along with other antivirals)
1 bid for prevention
2 tid in acute phase
Discontinue with ramping lung inflammation

GI Infections—Moss Nutrition—ParaBotanic Select (contains berberine along with other antimicrobials)
2 bid with food for 4 weeks
Parasites, bacteria, fungi, viruses, bacterial overgrowth, H. pylori

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