Berberine Supplement Overview: Effects, Uses and Potential Dangers

Berberine supplements have been studied for individuals with metabolic syndrome, diabetes, gastrointestinal disorders, obesity and cardiovascular disease.

Some clinical research has shown berberine to help normalize sugar metabolism as effectively as a commonly-prescribed antidiabetes drug called metformin.

Berberine helps to keep blood sugar levels in check, and to balance lipids (fats) in the blood. This herbal alkaloid is one of very few natural medicines to be supported by a substantial amount of human research. [1]

This article will review what berberine is, how it affects the body, health benefits associated with usage and possibilities for adverse effects and interactions.

Berberine

Herbal Extract

Heart Health

Immunity

Gut Health

How It Works:

• Supports immune function & digestion
• Supports blood sugar metabolism
• Maintain cardivascular health & lipid levels

Dosage:

Between 900 - 1200 mg per day

Safety:

Rated Possibly Safe

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What is Berberine?

Berberine is a yellow, bitter-tasting plant chemical called an alkaloid.

Alkaloids are nitrogenous organic compounds that induce potent physiological effects in humans.

Some alkaloids, like strychnine and atropine, are poisonous. Others, like morphine, quinine and berberine, induce various beneficial effects. [2]

The berberine alkaloid is found in various plants. Its highest concentrations are in Berberis vulgaris (barberry), Hydrastis canadensis (goldenseal), Berberis aquifolium (Oregon grape), Coptis chinensis (coptis or goldenthread), and Berberis aristata (tree turmeric). [2]

Do not confuse berberine with the above plants. It is but one phytochemical constituent of these and some other plants.

Many of these plants have been used for hundreds of years in traditional Chinese medicine and Ayurvedic medicine.

Berberine can be found as an ingredient in oral dietary supplements, herbal teas, topical washes and creams as well as liquid tinctures.

Uses for Berberine Supplements

The University of Maryland Medical Center (UMM) states that barberry root, rhizome and stem bark have been used in traditional Chinese and Indian medicine for more than 2500 years.

It has been used in the past as an anti-fungal and anti-bacterial agent, for fever, diarrhea, poor appetite, stomach upset, low energy and improving overall well-being. [3]

The Natural Medicines Comprehensive Database (NMCD) states that berberine has been used for centuries in the Middle East, Asia and Europe for “multitudes of reasons”. [2]

Berberine was used for a bacterial eye infection called trachoma beginning in 1933. In 1982, Indian researchers showed that this natural alkaloid could slow down growth of various pathogenic fungi. In 1983, berberine was shown to be active against herpes simplex uveitis. [2]

Today, berberine is commonly prescribed by doctors in Iran for improving gallbladder disease and other biliary disorders, and for heartburn. [2]

UMM reports that berberine may be useful in treating high blood pressure (hypertension), rapid heartbeat (tachycardia) – and certain neuronal disorders, like convulsions and epilepsy for instance. [3]

Despite the significant research supporting its use, this plant compound has not been approved by the FDA as a drug for the treatment of any medical conditions. More research is required to evaluate its clinical efficacy.

How does Berberine Work inside the Body?

Berberine has demonstrated an array of pharmacological effects, mostly in animal studies and in vitro cell cultures.

According to NMCD some of the effects of this alkaloid include: [2]

• Antiamoebic
• Antibacterial
• Anticancer
• Antidiabetic
• Antidiarrheal
• Antifungal
• Anti-Inflammatory
• Antilipemic
• Antioxidant
• Antiplatelet
• Antiulcer
• Cardioprotective
• Endocrine
• Hepatic
• Bone
• Behavioral
• Muscle Relaxant
• Sedative
• Renoprotective
• Weight Loss

AMPK effects:

Dr. Joseph Mercola states that berberine induces a wide range of physiological effects; mainly due to activation of an enzyme called AMPK (adenosine monophosphate protein kinase). [1]

According to researchers from University of Copenhagen, Denmark, “AMP-activated protein kinase (AMPK) is a phylogenetically conserved fuel-sensing enzyme that is present in all mammalian cells.”

“When activated, AMPK stimulates energy; generating processes such as glucose uptake and fatty acid oxidation and decreases energy consuming processes such as protein and lipid synthesis.” [4]

Because of its effects on AMPK, berberine is said to be normoglycemic; meaning it only reduces blood glucose levels if they are elevated. It does not seem to reduce them if they are already low, or if they are in the normal range. [5]

P-glycoprotein Effects:

Berberine is also known to alter P-glycoprotein: an ATP (adenosine triphosphate)-dependent drug efflux pump for xenobiotic (foreign) compounds. [5]

According to Stamford University Bangladesh, “P-glycoprotein (P-gp), an efflux membrane transporter, is widely distributed throughout the body and is responsible for limiting cellular uptake and the distribution of xenobiotics and toxic substances.”

“Hundreds of structurally diverse therapeutic agents are substrates to it and it impedes the absorption, permeability, and retention of the drugs, extruding them out of the cells.” [6]

In the body, P-glycoprotein is used to protect tissues and organs from damage from toxic foreign compounds. It does so by preventing the toxins from entering cellular cytosols and by extruding toxins already inside cells to their exteriors. [6]

In these manners, P-glycoprotein also increases the amounts of xenobiotics, and their metabolites, in urine, bile and lumen. [6]

When P-glycoprotein is inhibited, berberine absorption seems to increase. Therefore, some people use this supplement along with known P-glycoprotein inhibitors like chrysin, capsicum, ecdysteroids and milk thistle to name a few. [5]

Berberine is known to have low intestinal uptake, which means it gets absorbs poorly from the gut into the bloodstream. P-glycoprotein inhibitors may help the body to absorb berberine better, much like black pepper enhances the absorption of curcumin. [5]

Some people use excessive doses of berberine to compensate for its poor absorption and low oral bioavailability. However, this can cause adverse effects, like diarrhea and/or stomach cramping for instance. [5]

Berberine slows down activities in CYP2D6, CYP2C9, and CYP3A4 cytochrome P450 hepatic pathways. That means it can interact with a wide variety of pharmaceuticals that are broken down inside the liver. These will be covered in more detail below. [5]

Berberine is considered to be a nootropic, used for enhancing memory and other cognitive functions. It is also considered to be beneficial for bone and joint health. [5]

UMM states that berberine has been shown in recent studies to possess antioxidant properties that may help to reduce risk factors for cancer. It appears to suppress the growth of some tumor cells, based on in vitro research. [3]

In laboratory studies, berberine also demonstrates antibacterial, antiparasitic, antifungal and antiviral effects. [3]

Berberine relaxes smooth muscles that line the inside of the intestines; helping to reduce GI tract pain, and enhance digestion. This alkaloid also is thought to stimulate the immune system. [3]

Berberine Supplement Health Benefits

NMCD rates effectiveness of herbs and supplements in specific health conditions. Each substance can be rated Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective – or Insufficient Reliable Evidence to Rate.

NMCD rates berberine as Possibly Effective for diabetes and hyperlipidemia.

Diabetes:

In people with type 2 diabetes and hyperlipidemia, compared to placebo, berberine seems to moderately reduce blood sugar levels. Some evidence from human trials shows that 500 mg berberine, twice daily for 3 months: [2]

• Reduces postprandial (after-meal) glucose (PPG);
• Reduces fasting plasma glucose (FPG);
• Reduces glycated hemoglobin (HbA1c);

NMCD states that the above dosing schedule “is as effective in regulating glucose metabolism in patients with type 2 diabetes as taking metformin 500 mg 2-3 times daily or rosiglitazone 4 mg daily”. [2]

More research is needed to fully understand how berberine supplements can affect diabetes in humans. Talk with your endocrinologist about how it might be helpful for managing the long-term symptoms of diabetes in your case.

Hyperlipidemia:

Hyperlipidemia is simply defined as having an abnormally high amount of fats (lipids) in the blood. One of the most common types of hyperlipidemia is hypercholesterolemia (high serum cholesterol). Another common type is hypertriglyceridemia (high serum triglycerides).

NMCD states that preliminary clinical evidence suggests that berberine might be able to help lower lipid levels in patients with hypercholesterolemia. Some studies used 500 mg doses, twice daily for 3 months for this purpose. [2]

After 3 months, compared to baseline levels, results suggested decreases in: [2]

• Low density lipoprotein (LDL) cholesterol;
• Total cholesterol;
• Triglycerides;

All other proposed uses for berberine require much more research to validate. Some health conditions that berberine is currently being studied in include: [2]

• Skin Burns;
• CHF (congestive heart failure);
• Diarrhea;
• Glaucoma;
• Helicobacter pylori infection;
• Hepatitis (inflamed liver);
• Liver disease;
• Menopause symptoms;
• Metabolic syndrome;
• Obesity;
• Osteoporosis (brittle, fragile bones);
• PCOS (polycystic ovary syndrome);
• Radiation-induced injuries;
• Thrombocytopenia (blood platelet deficiency);
• Trachoma (Contagious bacterial infection of the eye);

More research is needed to understand the effects of berberine in these and all other health conditions. Ask your doctor about any specific use for this natural compound you have in mind.

Berberine Food Sources

Berberine is known to be found in the following plant foods: [5]

• Phellodendron Amurense (Amur Cork Tree, Huang Bai);
• Coptis Chinensis (Chinese Goldenthread);
• Tinospora cordifolia (Guduchi/Amrita);
• Mahonia aquifolium (Oregon Grape);
• Hydrastis canadensis (Goldenseal);
• Berberis aristata (Tree Turmeric);
• Berberis vulgaris (Barberry);

NMCD states, “Other sources include Mahonia aquifolium (Berberidaceae), Aristolochia taliscana (Aristolochiaceae, locally known as guaco), and Arcangelisia flava.” [2]

Berberine Supplements

UMM states that berberine supplements are available in capsule, fluid extract, tincture and topical ointment forms. Some barberry extracts are standardized to contain 8-12% berberine. [3]

NMCD states that there are 46 different berberine-based dietary supplements available commercially. Shop for berberine supplements that are sourced organically, certified to be toxin-free, and non-genetically modified (non-GMO). [2]

It is recommended to purchase supplements from companies that provide third-party Certificates of Authenticity and that verify their products are manufactured in cGMP-compliant facilities based in the United States.

Berberine Supplement Dosage

There is no standard dosage guideline established by the FDA for the use of berberine supplements.

NMCD reports the following adult oral doses of berberine that have been studied clinically: [2]

• 5 mg berberine bisulfate 3 times daily for 15 days before meals for thrombocytopenia;
• 20 mg/kg/day berberine for 6 weeks for radiation-induced damage to lungs;
• 500 mg/day berberine hydrochloride for 4 weeks for hypercholesterolemia;
• 500 mg berberine hydrochloride 3 times daily for 3 months for PCOS;
• 0.5 g berberine hydrochloride twice daily for 2 months for diabetes;
• 300 mg berberine, 3 times daily for 6 weeks for H. pylori infection;
• 0.5 g berberine twice daily for 3 months for hypercholesterolemia;
• 400 mg berberine sulfate in a single dose for infectious diarrhea;
• 500 mg berberine 3 times daily for 12 weeks for obesity;
• 0.5 g berberine twice daily for 3 months for diabetes;

0.2 mg/kg per minute infusions have also been administered intravenously (in blood vessel) for 30 minutes for heart failure. [2]

0.2% berberine eyedrops have been used as needed for 8 weeks for treating trachoma. [2]

Berberine Supplement Side Effects

According to Healthline, “Overall, berberine has an outstanding safety profile. The main side effects are related to digestion, and there are some reports of cramping, diarrhea, flatulence, constipation and stomach pain.”. [7]

There is insufficient evidence to rate the safety or effectiveness of berberine in children for any purpose. It is not recommended for young children. [3]

It should be avoided by pregnant or nursing mothers as it can be passed to a developing fetus in the uterus or to a newborn through breastmilk.

There have been cases of kernicterus developing in preterm neonates with hyperbilirubinemia after being exposed to berberine.

Like any herbal supplements, high dosages can increase the risk of side effects. Using this product at excessive dosages could result in toxicity. However, in multiple studies, toxic effects on the cardiovascular system, liver, kidneys and blood cells have not been observed.

Berberine Supplement Interactions

As mentioned previously, berberine is known to interact with cytochrome P450 CYP2D6, CYP2C9, and CYP3A4 liver pathways. This can cause interactions with numerous drugs; possibly strengthening, or weakening their effects and/or side effects.

Seek medical advice about using a berberine supplement along with:

CYP2C9 substrate medications including celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), and S-warfarin (Coumadin).

CYP2D6 substrate medications including amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.

CYP3A4 substrate medications including lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous others.

Berberine might affect blood platelet aggregation. Use caution mixing this supplement with anticoagulant/antiplatelet drugs like aspirin, cilostazol (Pletal), clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and others.

Berberine might affect blood glucose levels. Be careful using a berberine supplement along with antidiabetes medications like glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

Berberine might lower blood pressure. Be careful using it along with antihypertensive medications including captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.

Berberine might have sedative effects. Be careful using it along with CNS (central nervous system) depressants like benzodiazepines, pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), thiopental (Pentothal), fentanyl (Duragesic, Sublimaze), morphine, propofol (Diprivan), and others.

Be careful using a berberine supplement along with herbs and supplements with hypoglycemic, hypotensive, antiplatelet and/or anticoagulant potentials.

Some of these include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, alpha-lipoic acid, bitter melon, chromium, devil’s claw, fenugreek, guar gum, horse chestnut, psyllium, Siberian ginseng, andrographis, casein peptides, cat’s claw, coenzyme Q10, fish oil, L-arginine, lyceum, stinging nettle, and theanine.

Berberine is not known to interact with any foods, but may cause false results on laboratory tests that measure bilirubin levels.

Talk with your doctor first about using a berberine supplement if you have diabetes, hyperbilirubinemia and/or hypotension.

Discontinue using any berberine-based supplement at least 2 weeks before you are scheduled for surgery.

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