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Berberine for Diabetes and Metabolic Syndrome

May 23, 2012 Written by JP    [Font too small?]

Berberine is a naturally occurring plant alkaloid found in a number of medicinal herbs including barberry, goldenseal and oregon grape root. In China, a significant amount of money and time has been applied to investigating the potential of this phytochemical in managing a host of conditions and diseases. Diabetes and heart disease top the list of health concerns presently being evaluated. The findings of a current batch of studies may very well catapult berberine supplements into the bestseller category in China, the United States and beyond. Whether or not this turns out to be a positive development remains to be seen.

The latest trial evaluating berberine’s effect on human health was conducted in a group of patients diagnosed with metabolic syndrome – a condition characterized by cardiovascular and diabetic risk factors. After 3 months of supplementation, an improvement in insulin sensitivity, leptin levels and weight loss was noted. Of late, other studies have determined that berberine is capable of: a) correcting endothelial dysfunction and excessive levels of oxidative stress; b) decreasing liver abnormalities associated with nonalcoholic fatty liver disease; c) modulating hormonal and metabolic derangements in women with polycystic ovary syndrome; d) reducing blood sugar, insulin and lipids in type 2 diabetics. In fact, one study comparing berberine (500 mg, thrice daily) to the popular antidiabetic drug metformin reported that the two “drugs” provided similar benefits. A lower dosage of 1,000 mg/day has also been shown effective and safe in previous experiments. Mild to moderate constipation is the predominant adverse reaction noted in approximately 10% of participants receiving berberine.

Some natural health authorities would have you believe that berberine is completely safe and should be broadly used by anyone concerned about diabetes and heart disease. I disagree. One reason is that emerging data reveals that berberine intake may alter metabolic processes that affect how medications and other supplements are excreted and/or retained by the body. This is a significant factor since very few people are likely to use berberine as a stand alone agent. In addition, diet and lifestyle factors are still, by far, the most important considerations for addressing blood sugar and cardiovascular concerns. Berberine and other similar supplements are not replacements for a low-glycemic, whole food diet accompanied by adequate exercise and stress management. What’s more, berberine should only be considered after essential supplements including minerals, omega-3 fats and vitamins are present in optimal amounts. These are substances that are needed by the body to thrive. Without them, deficiency states often become apparent. Berberine may be a helpful adjunct for certain at-risk individuals but, it’s not a requirement.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 – Berberine Improves Insulin Sensitivity by Inhibiting Fat Store and … (link)

Study 2 – Berberine Improves Endothelial Function by Reducing Endothelial … (link)

Study 3 – Research on Therapeutic Effect and Hemorrheology Change of (link)

Study 4 – A Clinical Study on the Short-Term Effect of Berberine in Comparison … (link)

Study 5 – Berberine Lowers Blood Glucose in Type 2 Diabetes Mellitus Patients (link)

Study 6 – Efficacy of Berberine in Patients with Type 2 Diabetes … (link)

Study 7 – Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant … (link)

Study 8 – Repeated Administration of Berberine Inhibits Cytochromes P450 in … (link)

Study 9 – CYP2D Plays a Major Role in Berberine Metabolism in Liver of Mice (link)

Study 10 – Effects of Cinnamon Granules on Pharmacokinetics of Berberine in (link)

How Berberine May Support Improved Health

Source: World J Cardiol. 2010 April 26; 2(4): 71–77. (link)

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Posted in Alternative Therapies, Diabetes, Nutritional Supplements

11 Comments & Updates to “Berberine for Diabetes and Metabolic Syndrome”

  1. JP Says:

    Another option: tomato juice …


    Food Chem Toxicol. 2014 Sep 3.

    Dietary supplementation with tomato-juice in patients with metabolic syndrome: A suggestion to alleviate detrimental clinical factors.

    Lycopene, a carotenoid, is known for its antioxidant properties. Little is known, though, about the relationship of dietary tomato-juice intake and risks factors, like inflammation, insulin resistance and hyperlipidemia, implicated in metabolic syndrome. In the present study, we examined whether supplementation with tomato-juice has any implication on the risk status of patients with metabolic syndrome. A comparative study was conducted in 27 individuals diagnosed with metabolic syndrome. Fifteen of them were instructed to use commercially available tomato-juice as refreshment 4 times a week over a period of two months and twelve individuals served as the control group. Several parameters reflective of the metabolic syndrome were monitored both in the group supplemented with tomato juice and in the control group (ADMA for entdothelial function, TNF-α and IL-6 for inflammation, FIRI for insulin resistance). There was a significant improvement in the inflammation status and the endothelial dysfunction of the tomato-juice supplemented patients. At the same time, insulin resistance improved and a pronounced decrease in LDL was recorded, along with a slight increase in HDL. The results of the present study suggest an alleviating effect of tomato-juice with regard to risk factors associated with metabolic syndrome.

    Be well!


  2. JP Says:

    Update 04/20/15:


    BMC Complementary and Alternative Medicine 2015, 15:52

    Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome?: A double blind, placebo controlled randomized trial

    Background: Metabolic syndrome (MetS) comprises a spectrum of clinical phenotypes in which dyslipidemia, dysglycemia and hypertension are clustered and where all share a high level of oxidative stress and an increased risk of cardiovascular disease. This study examines the effect of a nutritional supplement combining red yeast rice and olive fruit extract on the lipid profile and on oxidative stress in a population of patients with MetS.

    Methods: In a double blind placebo controlled randomized trial, 50 persons with MetS, as defined by the ATPIII criteria, received the study product or placebo for 8 weeks. The study product contained 10.82 mg of monacolins and 9,32 mg of hydroxytyrosol per capsule, and is commercialized as Cholesfytol plus. The primary outcome measure was the difference in LDL reduction between intervention and control groups. Furthermore, differences in changes of CH, HDL, ApoA1, ApoB, HbA1c and oxLDL were measured, as well as side-effects, CK elevation, changes in clinical parameters and in cardiovascular risk.

    Results: In the intervention group, LDL cholesterol was lowered by 24% whereas it increased by 1% in the control group (p < 0.001). Other effects observed were a change in total cholesterol (−17% in the intervention group vs +2% in the control group, p < 0.001), apolipoprotein B (−15% vs +6%, p < 0.001), and TG (−9% vs + 16%, p = 0.02). Oxidized LDL decreased by 20% vs an increase of 5% in the control group (p < 0.001). Systolic and diastolic arterial blood pressure decreased significantly by 10 mmHg (vs 0% in the control group, p = 0.001) and 7 mmHg (vs 0% in the control group, p = 0.05) respectively. One person in the intervention group, who suffered from Segawa’s syndrome, dropped out because of severe muscle ache. Conclusions: The combination of active products in this study may be an alternative approach to statins in people who do not need, or cannot or do not want to be treated with chemical statins. Side effects, effects on oxidative stress and on glucose metabolism need to be examined more thoroughly. Be well! JP

  3. JP Says:

    Update 04/21/15:


    J Diabetes Metab Disord. 2015 Apr 9;14:22.

    Improvement of glucose and lipid profile status with Aloe vera in pre-diabetic subjects: a randomized controlled-trial.

    BACKGROUND: Pre-diabetes is a disturbing trend in the population, who are at risk of developing type-two diabetes. The aim of this study was to determine the effects use of Aloe vera in different doses on glucose and lipid profile in pre-diabetic subjects.

    METHODS: This study was a double blind randomized controlled trial (72 subjects) with pre-diabetes symptoms in 3 groups consumed capsules twice a day: Aloe vera 300 mg (AL300), 500 mg (AL500) and placebo (PL). Fasting blood glucose (FBS), HbA1C and lipid profile were evaluated in baseline, 4 or 8 weeks. On-way ANOVA, Friedman, Wilcoxon, Kruskal-Wallis , Mann-Whitney and Chi-square tests were used for within or between groups statistical analysis.

    RESULTS: FBS level in group AL300, showed significantly decreased in fourth week after the intervention, compared to PL in the same time (p = 0.001). Also, HbA1C level in this group at the eighth week after the intervention (p = 0.042), had a significant decrease. The levels of Total cholesterol and LDL-C, only in the group AL500 (p < 0.001 and p = 0.01), was significantly reduced, along with HDL-C level improvement just after eight weeks (p = 0.004). Triglyceride level showed a significant decrease (p < 0.045) just after four weeks use of AL500. CONCLUSIONS: The Use of Aloe vera extract in pre-diabetic patients, could revert impaired blood glucose within four weeks, but after eight weeks could alleviate their abnormal lipid profile. Be well! JP

  4. JP Says:

    Updated 08/08/15:


    PLoS One. 2015 Aug 7;10(8):e0134172.

    Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease.

    OBJECTIVES: A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.

    METHODS: A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.

    RESULTS: As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.

    CONCLUSION: BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.

    Be well!


  5. JP Says:

    Updated 11/27/15:


    Atherosclerosis. 2015 Sep 30;243(2):449-461.

    Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies.

    Berberine (BBR) is an isoquinoline plant alkaloid endowed with several pharmacological activities, including anti-microbial, glucose- and cholesterol-lowering, anti-tumoral and immunomodulatory properties. The main mechanism by which BBR exerts a protective role in atherosclerosis relates to its cholesterol-lowering activity. BBR significantly increases hepatic low density lipoprotein receptor (LDLR) expression and reduces the expression and secretion of the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9). In addition to this, several other atheroprotective effects have been ascribed to BBR, including anti-inflammatory and anti-oxidant properties, inhibition of vascular smooth muscle cell proliferation and improvement of endothelial dysfunction. BBR also increases glucose utilization in adipocytes and myocytes, while decreases glucose absorption in intestinal cells, resulting in a net hypoglycemic effect. In hypercholesterolemic animals, BBR significantly decreases LDL-C and total cholesterol (TC) levels and reduces aortic lesions, an effect similar to that of statins. In diabetic animals, BBR significantly reduces glucose levels, improves glucose tolerance, reduces body weight gain and adipose tissue mass. Several clinical studies have also tested the efficacy of BBR in humans. In hypercholesterolemic subjects, BBR induces a significant reduction of TC, triglycerides and LDL-C levels and a significant increase of HDL-C levels, without major adverse effects. BBR also reduces glycemia and plasma cholesterol in diabetic patients, improves lipid and glucose profile and decreases body mass index and waist circumference in subjects with metabolic syndrome. These findings, together with the good tolerability, suggest that BBR administration might be considered a potential therapeutic approach for the treatment of hypercholesterolemia or diabetes. Given the level of evidence available to date well-designed randomized controlled trials to test safety and efficacy of BBR are warranted.

    Be well!


  6. JP Says:

    Updated 09/26/16:


    J Transl Med. 2016 Sep 15;14:266.

    Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease.

    BACKGROUND: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment.

    METHODS: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment.

    RESULTS: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate.

    CONCLUSIONS: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease.

    Be well!


  7. JP Says:

    Updated 08/11/17:


    Medicine (Baltimore). 2017 Aug;96(32):e7697.

    Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial.

    BACKGROUND: Due to increasing antimicrobial resistance, a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori (H pylori) eradication. However, different results are varied greatly and the availability of bismuth was limited in some countries. We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication.

    METHODS: In a randomized, open-label, non-inferiority, phase IV trial between November 25, 2014, and October 15, 2015, 612 treatment-naive patients were randomly assigned to 14-day berberine-containing (n = 308) or 14-day bismuth-containing (n = 304) quadruple therapy. The primary outcomes were eradication rates determined by the C urea breath test (C-UBT) 28 days after the end of treatment. The secondary outcomes were adverse events and compliance.

    RESULTS: The baseline demographic data including age, gender, body mass index (BMI), general condition and severity score were not statistically different in both groups. The eradication rates in bismuth and berberine groups were 86.4% (266/308) and 90.1% (274/304) in intention-to-treat (ITT) analysis (P = .149), and 89.6% (266/297) and 91.3% (273/299) in per-protocol (PP) analysis (P = .470), respectively. No statistically significant difference was found in the overall incidence of adverse events between both groups (35.7% vs 28.6%, P = .060).

    CONCLUSIONS: Both regimens achieved the recommended efficacy for H pylori eradication. The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region.

    Be well!


  8. JP Says:

    Updated 12/12/18:


    Am J Cardiol. 2018 Nov 23.

    Short-Term Effects of Dry Extracts of Artichokeand Berberis in Hypercholesterolemic Patients Without Cardiovascular Disease.

    Hypercholesterolemia represents one of the main reversible cardiovascular risk factors. In this pilot clinical trial, we have tested the short-term efficacy and safety of a new combined cholesterol-lowering nutraceutical containing artichoke dry extract and berberine at enhanced bioavailability in subjects with moderate polygenic hypercholesterolemia in primary prevention for cardiovascular disease. After 2 months of treatment, the tested nutraceutical induced a significant reduction in plasma total cholesterol (-19%), low-density lipoprotein cholesterol (-16%), non-high-density lipoprotein cholesterol (-19%) and triglyceride levels (-15%), in association with a standardized control diet. No side effect has been observed during the trial. In conclusion, on the short-term, the tested nutraceutical has been shown to be well tolerated and effective, even if not containing any statin-like compound.

    Be well!


  9. JP Says:

    Updated 12/18/18:


    Zhonghua Yi Xue Za Zhi. 2018 Dec 11;98(46):3756-3761.

    [Effects of berberine on the serum cystatin C levels and urine albumin/creatine ratio in patients with type 2 diabetes mellitus].

    Objective: To investigate the effects of berberine on urine albumin/creatine ratio (UACR) and serum cystatin C (Cys C) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 114 T2DM inpatients or outpatients, including 46 males and 68 females aged (55±14) years between January 2015 and January 2016 were randomly divided into two groups: the control group (n=57) only with hypoglycemic agents, and the intervention group (n=57) with berberine (0.4 g, 3 times a day) on the basis of treatment from the control group. Both groups were treated and followed up for six months. All the clinical and biochemical parameters were routinely evaluated before and after treatment. And the safety of berberine was assessed. Results: After the treatment, the improvement of glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), systolic pressure (SP), high sensitive C-reactive protein (hs-CRP), rythrocyte sedimentation rate (ESR), estimated glomerular filtration rate (eGFR) in the intervention group were significantly better than those in the control group (all P<0.05), as well as the UACR[47(26, 120) mg/g vs 103(42, 267) mg/g, P<0.001]and serum Cys C[(0.83±0.30) mg/L vs (0.98±0.25) mg/L, P=0.031]. However, there was no statistically significant difference of UACR and Cys C between before and after treatment in the control group (all P>0.05). Compared to the control group, the patients in the intervention group had lesser UACR[47(26, 120) mg/g vs 68(28, 158) mg/g, P=0.039], and lower serum Cys C[(0.83±0.30) mg/L vs (0.96±0.30)mg/L, P=0.041]. Berberine had no obvious adverse effects. Multiple linear regression analysis revealed that the berberine administration was independently associated with the reduction of UACR (β=-0.051, P=0.041) and Cys C (β=-0.068, P=0.033) in T2DM patients. Conclusion: Berberine improves diabetic kidney disease by reducing UACR and serum Cys C in T2DM patients, and it was safe.

    Be well!


  10. JP Says:

    Updated 01/13/19:


    Phytother Res. 2019 Jan 10.

    Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

    The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta-analysis of the available randomized, double-blind, placebo-controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random-effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: -25.3, 95% CI [-39.2, -11.4] mg/dl; p < 0.001), TG (MD: -28, 95% CI [-35.3, -20.6] mg/dl; p < 0.001), HDL-C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL-C (MD: -29.1, 95% CI [-39.7, -18.6] mg/dl; p < 0.001), and FPG (MD: -7.5, 95% CI [-13, -1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health. Be well! JP

  11. JP Says:

    Updated 05/02/19:


    Theranostics. 2019 Mar 16;9(7):1923-1951.

    Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics.

    Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

    Be well!


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