Berberine supplement benefit, side effects by Ray Sahelian, M.D.
April 9 2014
Role in diabetes, cholesterol and other medical conditions

Berberine is a plant alkaloid isolated from the roots and bark of several herbs. Some of these herbs include:

Barberry (Berberis vulgaris), Berberis integerrima. Berbamine and berberine are found in the plant barberry.
Coptis chinensis or Berberis aristata
Goldenseal (Hydrastis canadensis)
Oregon Grape (Berberis aquifolium)
Phellodendron Amurense
Yerba mansa (Anemopsis californica). 

The berberine alkaloid can be found in the roots, rhizomes, stem, and bark of the plants. Berberine-containing plants are used medicinally in many traditional medical systems, including Ayurvedic herbal and Chinese herbal medicine.

Coptis chinensis rhizome -- Golden Thread -- Huang Lian -- Intense yellow color most likely due to high content of berberine, which is very bitter in taste.

Benefits
Some people claim berberine is useful for fungal, candida, yeast, parasites, bacterial and viral infections. Berberine extracts and decoctions have demonstrated antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. Currently, the predominant clinical uses of berberine include bacterial diarrhea, intestinal parasite infections, and ocular trachoma infections.
   Berberine has been tested in diabetes, prostate cancer, cardiac arrhythmia and leukemia.

Cancer
Mol Carcinog. 2011. Dietary administration of berberine or Phellodendron amurense extract inhibits cell cycle progression and lung tumorigenesis.

Liver cancer
Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukemia cell growth.
Clin Exp Pharmacol Physiol. 2004.
The present study was conducted to evaluate the cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents on hepatoma and leukemia cells in vitro. Four human liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and four leukemia cell lines. Of the two crude drugs, Coptis chinensis exhibited the strongest activity against SK-Hep1  and Raji cell lines. Icariin (the major compound of E. sagittatum) showed no inhibition of either the hepatoma or leukemia cell lines. The results of the present study suggest that the Coptis chinensis extract and its major constituents berberine and coptisine possess active antihepatoma and anti leukemia activities.

Prostate cancer
Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells.
Mol Cancer Ther. 2006. Department of Dermatology, University of Alabama at Birmingham, Volker Hall, University Boulevard, Birmingham, AL
Berberine, a naturally occurring isoquinoline alkaloid, has been shown to possess anti-inflammatory and antitumor properties in some in vitro systems. Here, we report that in vitro treatment of androgen-insensitive and androgen-sensitive (LNCaP) prostate cancer cells with berberine inhibited cell proliferation and induced cell death in a dose-dependent and time-dependent manner. The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy.

Diabetes and blood sugar
A collaboration between Chinese, Korean, and Australian scientists at Sydney's Garvan Institute indicates berberine could be helpful. They say "Our studies in animal models of diabetes show that berberine acts in part by activating an enzyme in the muscle and liver that is involved in improving sensitivity of the tissue to insulin. This in turn helps lower blood sugar levels. In addition, it seems berberine can help reduce body weight". "Berberine has been used for decades, if not centuries, with few reported side effects. Given the limitations of existing medicines we are excited to have evidence that berberine may be a helpful new treatment for type 2 diabetes; however, despite its widespread use in traditional medicine practices, it will still have to be evaluated properly following the defined clinical trials process", said Professor James, head of the Garvan's Diabetes & Obesity Research Program and co-author of the Diabetes paper.

Blood sugar, cholesterol, and blood pressure
Berberine may be helpful in maintaining healthy blood sugar and cholesterol levels in those with type 2 diabetes. Dr. Guang Ning, of Shanghai Jiao Tong University School of Medicine in Shanghai and colleagues randomized 116 diabetes patients to receive one gram of berberine daily or placebo for 3 months. Average hemoglobin A1C -- a measure of long-term blood sugar control -- dropped from 7.5 percent to 6.6 percent in those taking berberine supplements. Patients taking berberine also showed significant reductions in total and "bad" LDL cholesterol. Blood pressure also fell in patients taking berberine. Patients on berberine lost 2.3 kilograms (5.1 pounds), on average, compared to 1.3 kilograms (2.9 pounds) for the placebo group. Patients taking berberine were more likely to have a side effect of constipation, and two patients in the berberine group had their dosage reduced for this reason. Journal of Clinical Endocrinology and Metabolism, 2008.

Radiation induced colitis
Med Oncol. 2010. Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

Research, multiple benefits
Scientific World Journal. 2012. Interaction of herbal compounds with biological targets: a case study with berberine. Department of General Surgery, The First People's Hospital of Shunde, Southern Medical University, Shunde, Guangdong, China. Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways.

Infection fighter
Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus.
J Med Food. 2005. Department of Food and Nutrition, Kunsan National University, Kunsan.
Methicillin-resistant Staphylococcus aureus (MRSA) bacteria have been responsible for substantial morbidity and mortality in hospitals because they usually have multidrug resistance. Some natural products are candidates as new antibiotic substances. In the present study, we investigated the antimicrobial activity of berberine, the main antibacterial substance of Coptidis rhizoma (Coptis chinensis Franch) and Phellodendri cortex (Phellodendron amurense Ruprecht), against clinical isolates of MRSA, and the effects of berberine on the adhesion to MRSA and intracellular invasion into human gingival fibroblasts (HGFs). Berberine showed antimicrobial activity against all tested strains of MRSA. These results suggest that berberine may have antimicrobial activity and the potential to restore the effectiveness of beta-lactam antibiotics against MRSA, and inhibit the MRSA adhesion and intracellular invasion in HGFs.

Hepatobiliary excretion of berberine.
Drug Metab Dispos. 2004.
To investigate the detailed pharmacokinetics and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with high-performance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg(-1). Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg(-1) significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation was not obviously affected by probenecid under the present study design.

Heart rhythm
Effect of berberine on regression of pressure-overload induced cardiac hypertrophy in rats.
Am J Chin Med. 2002.
Berberine is the basic chemical component of a Chinese herb, Coptis chinensis, considered to be useful in treating some diseases of the cardiovascular system, such as hypertension and chronic heart failure (CHF). In this study, we investigate the inhibitory effect of berberine on experimental cardiac hypertrophy, which is regarded as a risk factor of CHF and other heart diseases. Forty-two male SD rats were divided into four groups: age-matched control, aortic banding model, berberine-treated group and captopril-treated group. Cardiac hypertrophy was induced by suprarenal abdominal aorta constriction (banding). The drugs were orally administered for 8 weeks starting from 4 weeks after surgery at dosage of berberine 10 mg/kg and captopril 50 mg/kg. Blood pressure (BP) was measured four times during the period of the experiment, and hemodynamic parameters, cardiac index, cell size of left ventricular myocardium and total protein of left ventricular tissue were detected 8 weeks after treatment with drugs. The data from the present study showed that: The BP of the aorta banded rats was increased compared with those of the normal and the age-matched control rats, and berberine showed no significant effect on it. After 8 weeks of treatment with berberine, the elevated left ventricular end diastolic pressure (LVEDP) was slightly decreased compared with the aortic banded rats. Meanwhile, the maximum rates of contraction and relaxation was increased and the time to reach the point of maximum rate from beginning of contraction (t-dp/dt) was shortened, indicating that the functions of heart, both contraction and relaxation, were improved. Cardiac growth was inhibited by treatment with berberine. Both whole heart and left ventricular weight were notably decreased compared with the banded rats. The cell size of left ventricular myocardium was significantly reduced and the total protein of left ventricular tissue was slightly down-regulated by treatment with berberine. These data suggest that berberine can improve abnormal cardiac function and can prevent the development of left ventricular hypertrophy induced by pressure-overload. This indicates that it may have therapeutic potential in the treatment of CHF.

Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
Am J Cardiol. 2003.
This study was designed to assess the efficacy and safety of berberine for chronic congestive heart failure. One hundred fifty-six patients with CHF and >90 ventricular premature complexes (VPCs) and/or nonsustained ventricular tachycardia (VT) on 24-hour Holter monitoring were randomly divided into 2 groups. All patients were given conventional therapy for congestive heart failure, consisting of angiotensin-converting enzyme inhibitors, digoxin, diuretics, and nitrates. Patients in the treatment group were also given berberine 1.2 to 2.0 g/day. The remaining 77 patients were given placebo. Symptoms, a 6-minute walk test, left ventricular (LV) ejection fraction (EF), frequency and complexity of VPCs, and quality of life were assessed after 8 weeks of treatment and during a mean 24-month follow-up. After treatment with berberine, there was a significantly greater increase in LVEF, exercise capacity, improvement of the dyspnea-fatigue index, and a decrease of frequency and complexity of VPCs compared with the control group. There was a significant decrease in mortality in the berberine -treated patients during long-term follow-up (7 patients receiving treatment died vs 13 on placebo). Proarrhythmia was not observed, and there were no apparent side effects. Thus, berberine improved quality of life and decreased VPCs and mortality in patients with congestive heart failure.

Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model.
Biol Pharm Bull. 2003.
Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.

A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species.
Life Sci. 2002.
Roots and barks of various Berberis species are used as folk remedy for the treatment of various inflammatory diseases such as lumbago, rheumatism and to reduce fever. Six isoquinoline alkaloids namely berberine, berbamine, palmatine, oxyacanthine, magnoflorine, and columbamine were isolated as the main components of alkaloidal fraction from the roots of Turkish Berberis species and effects were studied using various in vivo models in mice. All alkaloids inhibited inflammations in varying degrees, among them berberine, berbamine and palmatine were shown to possess significant and dose-dependent inhibitory activity against serotonin-induced hind paw oedema both on oral and topical applications and acetic acid-induced increase in vascular permeability on oral administration. Moreover, these three alkaloids were also shown to possess dose-dependent antinociceptive activity, which assessed by using the model based on the inhibition of p-benzoquinone-induced writhing movements as well as antipyretic activity on FCA-induced increased rectal temperature on subacute administration. However, all alkaloids induced gastric lesions in varying degrees.

Inhibitory effects of berberine on IK1, IK, and HERG channels of cardiac myocytes.
Acta Pharmacol Sin. 2001.
To study the effects of berberine on inward rectifier potassium current and outward delayed rectifier potassium current (IK) of guinea pig ventricular myocytes, and on human ether-a-go-go related gene (HERG) channel expressed in Xenopus oocytes. Berberine prolonged action potential duration (APD) and inhibited IK1 and IK in a concentration-dependent manner. Berberine 100 micromol/L inhibited IK1 by 65 %. Berberine 50 micromol/L inhibited IK by 57 %, IKtail by 53 %. Berberine produced a voltage-dependent block on IK that increased with stronger depolarization. It blocked the HERG channels potently with an IC50 value of approximately 75 micromol/L. This block was voltage-dependent, suggesting that it probably bind to either open or inactivated HERG channels. Berberine prolonged APD and possessed blocking effect on IK1, IK, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine is related to its inhibitory effects on IK1, IK, and HERG channel.

Cardiovascular actions of berberine.
Cardiovasc Drug Rev. 2001.
Berberine, is an alkaloid from Hydrastis canadensis., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Some cardiovascular effects and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.

Effects of berberine of L- and T-type calcium channels in guinea pig ventricular myocytes.
Zhongguo Yao Li Xue Bao. 1997.
Berberine possessed blocking effects on both L- and T-type calcium channels.

Emails
Q. I was traveling in Asia recently and received a bad case of diahrrea and my Chinese colleagues gave me some Berberine HCL as a remedy. The product was 200 mg berberine hcl. It seemed to help over a few days and I ended up taking 2 pills/day for 3-4 days. The amazing thing is that a couple days after I stopped taking the pills I noticed that my PVCs had stopped. I have benign PVCs, a couple every minute, never together. I only notice them when I try to sleep or when I take my pulse so they are just annoying and have no impact on my life. Has there been any serious research on the efficacy of Berberine HCL on treating arrhythmias and PVCs? Is there any danger in my continuing to take this medicine? I have stopped for a few weeks and the PVCs are back to the way they were before. The PVCs returned about 5 days after my last dose of the pills. I never have fully taken the product again as I don't have much left and I'm somewhat concerned with side effects. When I take one pill it seems to have some cardiac effect but I've hesitated to take a second. In china I took 2 to 3 per day for 4 days. The effect seemed to last 3 days after my last pill. I also had taken a bunch of vaccinations for my trip and cipro upon my return, but I believe the berberine was the factor. I also saw some internet data that discusses its affect on ventrical tachycardia.
   A. As with most herbs, it is best to take breaks from use. There has been very little research in humans and berberine, Therefore, the safety and toxicity of berberine in humans is not known well in the West.

Q. I have read that berberine is effective in reducing blood cholesterol levels. However, I am unable to find a source of berberine in a dosage of 0.5 to 1 gram. There are many " berberine complexes " and powdered herb mixtures (goldenseal, oregon grape, etc.), but the actual berberine content is either low or difficult to determine. I am seeking a .5 to 1 g. dosage. I can accept other associated extracts also being included, as long as the berberine is in a sufficient dosage.
   A. We have searched ourselves and have not found such a product.

Different brands and dosages available over the counter in stores or online
Q. I read an email on your site from a person looking for berberine in a 0.5 to 1 g dosage, and your reply indicated that you had researched the question and not found a product in that dosage. Thorne research markets a product called Berbercap wherein the dosage is 0.2 g per capsule, 80% of which is berberine (source oregon grape extract). so each cap contains 0.16 g berberine. one could combine 3 caps to approximate the 0.5 g dosage, and take 6 to approximate the 1 g dosage. Thanks for lots of really good information, nice mix of intuition and real science.
   A. You are right. Berbercap supplement was found on a google search. Berbercap contains berberine (Oregon Grape extract), a major antimicrobial alkaloid present in a number of clinically important medicinal plants, including Hydrastis, Coptis, and Berberis. Berbercap is indicated for parasitic, bacterial and viral infections, including candidiasis, and yeast, urinary tract and bladder infections, intestinal flu, streptococcus and staphylococcus. Current herbal literature also recommends Berberis for liver problems such as hepatitis and jaundice. Each Berbercap Capsule Contains: Oregon Grape extract (root) (Berberis aquifolium) (80% Berberine).

I read the emails from someone who wanted higher dose berberine. Vital Nutrients makes 200 mg caps.

I too had trouble locating a source of pure berberine, but just took delivery in March 2014 of 6 bottles from Swanson Health Products. $9.99 per bottle of 60 caps, 400 mg each.

I came across a page connected with your website on a google search for berberine; there was a lot of very helpful information there. However, I noticed that, while the article was recent, it seemed to indicate that there wasn't half or one gram berberine available. However, I know of 2 brands, Thorne Research and Dr. Whitaker's, both of which are just berberine, that are 500 mg. Both are available on Amazon, Thorne has a few less "other ingredients".

I thought you might want to know that there is another source. It is called Glycosolve and contains 500 mg berberine HCL + 24 mg banaba leaf extract. I have not tried this product yet. Will do so, soon, after I finish Thorne's Berbercap.

You can get berberine up to 500 mg per capsule, from "GOOD STATE" Health Solution out of Flourtown, PA. It's called GlycoX 500 and it also contains 24 mg of Banaba Leaf extract.

Testimonials
I was updating my continued search for information and found your site. Here are a few comments re emailed questions and some observations: I was originally referred to use of berberine by a friend, Dr. Merrily Kuhn of Hamburg, NY. She holds a degree in Physiology among others. She had prior recommended glucosamine with chondrotrin and MSM. (She is listed as Dr Merrily on Solonava site). I have used NEXRUTINE EXTRA form Solonova in this combination for years. My experience has shown that these have reduced joint pain and allowed for greater range of motion. My life style has GREATLY improved. I have made numerous attempts at changed dosages. I find that less than 1000 mg berberine per day allows pain to return. More than 1250 is not needed. I am not sure of any other benefits derived from this therapy. But these are just what I wanted.

I noticed that one user had unintentionally stopped his premature ventricular contractions. I wanted to let you know that i too had unintentionally greatly reduced my PVCs with a immune boosting supplement that had berberine in it. The name of the product is Rainbow light immune response.
    Rainbow light immune response has Sophora, Andrographis, Isatis, elderberry, Berberine Sulfate, oregano oil, Xanthium, Yerba Santa, Platycodon, Chinese Lovage and other vitamins and herbs. So, it is difficult to ascribe the reduction of the heart palpitations to berberine alone.

I read your article. I am interested in lowering pvcs. I am currently taking celexa and enalapril. Can I take berberine also?
    We have not seen studies combining these medications and the herbal extract, so it is not easy to know for certain.

I have PVCs and was put on Tropol XL Beta blocker 25 mg one tablet daily before bedtime. Can I take a product with berberine while taking a beta blocker. Your health and advise will be appreciated.
   Before making a suggestion on what supplements to take and how much, a doctor needs to evaluate the whole history and review of medical exams and lab tests.

I read an article on the net about the many benefits of berberine and, as your name was mentioned in the article. I'm very interested in taking berberine tablets, aiming to lower glycose (I'm prediabetic) and triglycerides levels in my body. However, I'm in doubt as to which brands in the market are trustable and go through quality control procedures. There are particularly two brands that called my attention (since they have positive reviews in Amazon): GlycoX and Huang Lian Su (from a Chinese company with a branch in the US). Since they're not inspected by the FDA, I worry about the possibility of their having contaminants. I wrote their manufacturers: the former told me their product is inspected by an independent lab and therefore has no risk of having contaminants (however, they didn't make the quality report available); the latter didn't reply. If you know any of these brands or any other that you trust and recommend and you feel comfortable in sharing this information, would you be so kind as to let me know about it?
   Without doing an independent analysis by an independent lab, one cannot rely on information provided by any vitamin company or pharmaceutical company. Since I have not seen such testing myself on these products, I am not able to know whether they are of high, or low, quality. Unfortunately this is how it is with purchasing any supplement or product on the market, we have to accept a certain level of uncertainty. There are no 100 percent guarantees. Most of the time, though, the quality of natural supplements are high from most vitamin sellers.