In addition to increasing insulin sensitivity …

Berberine Reduces
Women’s Waistlines

… along with systolic blood pressure, triglycerides, and total insulin secretion

By Will Block

The waist is a terrible thing to mind.
— Tom Wilson

M ost people don’t know much about metabolic syndrome. On the other hand, diabetes has name recognition, yet few understand its underlying causes. All too often, metabolic syndrome plays a large role in determining whether one comes down with diabetes or not.

The Road to Diabetes

The reduction in waist circumference was
about 3 centimeters (over 1 inch less).

Metabolic syndrome is a cluster of endocrine disturbances that include obesity, hyperglycemia, hyperlipidemia, and hypertension. It is strongly correlated to insulin resistance, leading to hyperinsulinemia and visceral obesity. Together, these conditions successively predispose individuals to increased risk for atherosclerosis, cardiovascular events, and eventually to type 2 diabetes.

In addition, visceral adiposity independently predicts insulin resistance, hyperinsulinemia, and metabolic syndrome. Moreover, intra-abdominal fat is metabolically active as a source of free fatty acids and adipokines. Thus, a role for intra-abdominal fat in metabolic syndrome is biologically plausible, and any effort to decrease adiposity, insulin resistance, and hyperinsulinemia in patients with metabolic syndrome is a good thing.

Berberine Hinders Conversion to Diabetes

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Berberine, a naturally occurring isoquinoline alkaloid, is an active component in the roots, rhizomes, and stem barks of many medicinal plants, including Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Berberis aquifolium (Oregon grape), and Coptis chinensis (Chinese goldthread). Historically, berberine has been used as an antibiotic because of its potent antimicrobial activity against many organisms including bacteria, fungi, protozoans, viruses, chlamydia, and helminthes.1 Berberine has a wide range of pharmacological and biochemical effects for various clinical conditions, such as diarrhea, hypertension, arrhythmias, and inflammation.2

Berberine Inhibits Retinopathy

Leukocytes are involved in the mechanism that causes diabetic retinopathy, according to accumulating evidence in animal studies. Leukocytes (aka, white blood cells) are cells of the immune system defending the body against both infectious disease and foreign materials.

In a new study, researchers set out to determine whether leukocytes from diabetic patients could kill retinal endothelial cells, and whether that cytotoxicity could be inhibited in vivo by administration of berberine.1

Human retinal endothelial cells were co-cultured for 24 hours with leukocytes freshly isolated from nondiabetic and diabetic patients. The leukocyte-mediated death of the endothelial cells was analyzed with flow cytometry, a process that characterizes and measures cells and cellular constituents. Inflammatory factors were also investigated, along with the activities of antioxidant enzymes and markers of oxidative stress.

At the same time, leukocytes were isolated from 28 diabetic patients with retinopathy and nondiabetic patients before and after 1 month therapy with berberine. Berberine’s effects on leukocyte-mediated killing of endothelial cells were again assessed.

Leukocytes from diabetic patients induced more cell death of endothelial cells than did cells from nondiabetic patients. This killing occurred primarily via direct cell–cell contact.

Berberine inhibited the leukocyte-mediated killing of human retinal endothelial cells in vitro, the decrease in antioxidant enzyme activities, the nuclear translocation of nuclear factor kappa B, and the increase in intercellular adhesion molecule-1 and inducible nitric oxide synthase expression and malondialdehyde content in retinal endothelial cells cultured in high glucose. Berberine also decreased integrin beta-2 expression of leukocytes in vitro and in vivo. Oral consumption of berberine for 1 month likewise inhibited the diabetes-induced increase in leukocyte-mediated killing of human retinal endothelial cells.

The study’s findings suggest that leukocytes from diabetic patients kill retinal endothelial cells, and that berberine can inhibit this leukocyte-mediated killing of vascular endothelium. Berberine may be a useful therapy against diabetic retinopathy.


  1. Tian P, Ge H, Liu H, Kern TS, Du L, Guan L, Su S, Liu P. Leukocytes from diabetic patients kill retinal endothelial cells: effects of berberine. Mol Vis. 2013 Oct 2;19:2092–105.

After berberine administration,
patients had a 36% reduction of
metabolic syndrome and decreased
waist circumference in females (over
1 inch less!).

Multiple Mechanisms by which Berberine Works in Diabetes

In recent years, berberine has shown that it can help regulate glucose and lipid metabolism and alleviate metabolic syndrome by multiple mechanisms. These include:

  1. Enhancing beta-cell function
  2. Improving insulin secretion
  3. Promoting islet cell regeneration
  4. Reducing lipid levels
  5. Promoting glucose metabolism by stimulating glycolysis
  6. Regulating glucose and lipid metabolism by influencing transcriptional factors expression
  7. Invoking antioxidant and anti-inflammatory activities
  8. Inhibiting reductase to repress oxidative stress and regulate metabolic signal pathways

Berberine Shows Atheroprotective Activities in Macrophages

Macrophages are a kind of white blood cell that engulf and digest cellular debris — Pacman style — microbes, foreign substances, even cancer cells, in a process called phagocytosis. The role of a macrophage helps us to understand atherosclerotic lesions, both their development and thrombogenicity.

Vascular intimal macrophages incorporate modified lipoproteins through the scavenger receptor pathway. This transforms the macrophage into a lipid-rich foam cell, which is a hallmark feature of atherosclerosis. Foam cells lead to lesion expansion. Macrophage activation results in the excretion of proinflammatory and cytotoxic substances, including peroxynitrite, an early inducer of atherosclerosis through the endoplasmic reticulum stress pathway.

In a recent paper, researchers investigated the effect of berberine, showing that it has antiatherogenic properties that go beyond cholesterol-lowering capabilities.1

Using mouse and human macrophage cellular models, the researchers measured cholesterol content by various properties. Exposure of a cholesterol-enriched macrophage to serum in the presence of 1 μM berberine resulted in a reduction of intracellular cholesterol content twice as much as exposure to serum alone, an effect not mediated by an increase of cholesterol efflux, but rather by the inhibition of cholesterol uptake. Consistently, berberine in a dose-dependent manner inhibited cholesterol accumulation in human macrophages exposed to hyper­cholesterolemic serum.

Microscopic analysis revealed that berberine inhibited an independent receptor process involved in LDL internalization. A variety of other responses were significantly inhibited by berberine, along with foiling a cholesterol enrichment process that increased plasma membrane cholesterol by 4.5 fold.

The principal finding of the scientists was that berberine showed novel potentially atheroprotective activities in macrophages, by inhibiting serum-induced cholesterol accumulation.


  1. Zimetti F, Adorni MP, Ronda N, Gatti R, Bernini F, Favari E. The natural compound berberine positively affects macrophage functions involved in atherogenesis. Nutr Metab Cardiovasc Dis. 2014 Aug 30. pii: S0939–4753(14)00276–2. doi: 10.1016/j.numecd.2014.08.004. [Epub ahead of print]

Waist Not, Want Not

Despite all of the accumulated knowledge, what’s really exciting is a new study showing that berberine has an overall effect on metabolic syndrome, insulin sensitivity, and insulin secretion that may reduce waist circumference, especially in women.3 In this randomized, double-blind, placebo-controlled clinical trial — conducted at the University of Guadalajara in Mexico — 24 volunteers with a diagnosis of metabolic syndrome had their glucose and insulin levels measured after a dextrose (sugar) load was given. Also measured at baseline were triglycerides and high-density lipoprotein (HDL, the good cholesterol) concentrations. Twelve subjects received berberine hydrochloride (500 mg) three times daily before meals for 3 months (1.5 g/day); the other twelve received placebo.

According to the Mexican
researchers, the fact that more than
one-third of the patients
had remission of
metabolic syndrome after berberine,
indicates that berberine has
multitherapeutic activities.

After berberine administration, patients had a 36% reduction of metabolic syndrome and decreased waist circumference in females (over 1 inch less!). Also found were reduced systolic blood pressure (about 8 mmHg), lower triglycerides, reduced area under the curve (AUC) of glucose, AUC of insulin, reduced insulinogenic index (a measure of beta cell function; beta cells store and release insulin) and an increase in the Matsuda index (a measure of insulin sensitivity). See Table 1.

  Baseline 3 Months Baseline 3 Months

BMI (kg/m2)
34.2 ± 3.6 34.1 ± 4.0 36.1 ± 2.3 35.5 ± 2.4**
Waist circumference (cm ♀)
108 ± 9 107 ± 8 106 ± 4 103 ± 3*
Waist circumference (cm ♂)
116 ± 10 112 ± 10 121 ± 2 116 ± 1
Systolic blood pressure (mmHg)
118 ± 7 116 ± 7 123 ± 7 115 ± 9**
Diastolic blood pressure (mmHg)
77 ± 7 78 ± 8 80 ± 8 77 ± 6
Glucose (mmol/L)
5.2 ± 0.3 5.1 ± 0.5 5.6 ± 0.8 5.5 ± 0.7*
Triglycerides (mmol/L)
2.1 ± 0.7 2.0 ± 0.8 2.4 ± 0.7 1.4 ± 0.5**
HDL-C (mmol/L ♀)
1.0 ± 0.2 1.0 ± 0.2 1.1 ± 0.4 1.2 ± 0.4
HDL-C (mmol/L ♂)
1.0 ± 0.3 1.0 ± 0.3 0.9 ± 0.2 0.9 ± 0.2
AUC glucose (mmol/L)
989 ± 122 997 ± 200 1182 ± 253 1069 ± 172*
AUC insulin (pmol/L)
67,605±18,730 86,852±57,863 92,056±72,148 67,407±46,441**
Insulinogenic index
0.64 ± 0.23 0.81 ± 0.53 0.78 ± 0.69 0.62 ± 0.46*
Stumvall index
1554 ± 688 1736 ± 783 1506 ± 1392 1483 ± 1207
Matsuda index
2.5 ± 0.6 2.6 ± 1.8 2.1 ± 1.0 3.1 ± 1.6**

*p < 0.05.
**p < 0.01.
BMI, body mass index; HDL, high-density lipoprotein cholesterol; AUC, area under the curve.

Another Diminished Waist Study

This is not the first time that berberine has been associated with waist size reduction. In another study, patients with metabolic syndrome were given a formulation containing berberine (500 mg), policosanol (10 mg), and red yeast rice (containing 3 mg of monacolin) once per day.4 Both women and men in this double-blind placebo-controlled study (64 subjects) taking berberine showed a trend to reduced waist circumference. According to the researchers, “We can postulate that this reflects a better disposal of fat, with a relative reduction of visceral fat in the [active ingredient] arm. The effect on waist circumference confirms previous results in animal models, in which treatment with berberine led to a significant reduction in abdominal fat [Reference excluded].”

The findings described in this article,
along with others, represent a strong
case for the use of berberine as a
treatment option for patients with
metabolic syndrome.

No Single Pathway for Metabolic Syndrome

Returning to the Mexican study, the researchers note that there is no single pathogenic pathway that has been identified to date as a valuable therapeutic target in metabolic syndrome. Furthermore, current medical therapies take aim at the various components individually with both lifestyle modifications and pharmacological therapy, often with a multidrug regimen.

Berberine May Reduce Metastasis
and Angiogenesis of Cervical Cancer


Metastasis is the most common cause of cancer-related death in patients. Epithelial-to-mesenchymal transition is essential for cancer metastasis, which is a complicated multistep process. The process includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination. An increase in vascular density allows easier access of tumor cells to circulation. This represents a rational target for therapeutic intervention.

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Berberine has several anti-inflammation and anticancer biological effects. In a new study, Taiwan researchers provided molecular evidence that is associated with the anti-metastatic effect of berberine by showing a nearly complete inhibition on invasion of highly metastatic cell culture.1

Berberine reversed a transforming growth factor and caused upregulation of epithelial markers. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Notably, in vivo mice treated with berberine showed reduced tumor growth and lung metastasis. Altogether, these findings suggest that berberine could reduce metastasis and angiogenesis of cervical cancer cells, thereby constituting an adjuvant treatment for metastasis control.


  1. Chu SC, Yu CC, Hsu LS, Chen KS, Su MY, Chen PN. Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-induced Angiogenesis in Human Cervical Cancer Cells. Mol Pharmacol. 2014 Sep 12. pii: mol.114.094037. [Epub ahead of print]

The Multitherapeutic Activities of Berberine

According to the Mexican researchers, the fact that more than one-third of the patients had remission of metabolic syndrome after berberine, indicates that berberine has multitherapeutic activities. In their Discussion Section, the authors write that berberine’s effects on glucose metabolism are related to modifications of insulin secretion, glycolysis, and adipogenesis, inhibiting mitochondrial function, activating the AMPK pathway, and increasing glycokinase activity. Berberine also increased glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1) levels.

Consequently, all of these mechanisms may also be associated with the antiobesity effect of berberine. Thus, the results of the study — as well as other reports in diabetic populations — showed that berberine administration improved metabolic control, decreasing fasting, postprandial glucose concentration, and glycosylated hemoglobin (HbA1c) levels.

Increase in Insulin Sensitivity and Decrease in Insulin Secretion

The results were certainly due to an increment in insulin sensitivity and decrease in insulin secretion. Similar findings regarding metabolic control have recently been published with the administration of berberine alone or in combination with other nutraceutical compounds. In accord with other studies, BMI in all groups decreased significantly with the administration of berberine. As implicated in other studies, waist circumference in females decreased. Weight loss may be an influencing factor for the beneficial metabolic results observed with the use of berberine.

Alternatively, unfavorable changes in the secretion of adipokines — considered as an early symptom of impaired adipose tissue function — are the possible link between obesity and insulin resistance, thus influencing the development of metabolic syndrome. The effects of berberine on serum adipokines may mean that inhibiting fat stores and adjusting adipokine profile in human preadipocytes, as well as in those with metabolic syndrome, may improve insulin sensitivity.

Metabolic Syndrome (aka Insulin Resistance Syndrome, Syndrome X, Obesity Syndrome, Dysmetabolic Syndrome) has been estimated to affect over 50 million Americans. It is characterized by obesity, insulin resistance, hypertension and HDL decrease, LDL increase, and triglyceride increase as shown above.

It is disappointing that these inflammatory markers were not measured in the Mexican study. The lipid-lowering effect of berberine appears to be mainly due to stabilization of hepatic low-density lipoprotein receptor (LDL-R). Fundamental to this may be the extracellular signal-regulated kinase-dependent pathway plus increasing transcriptional activity of the LDL-R promoter. Other recently reported explanations include an increment of PPARα receptor expression.

Administration of berberine showed a decrease in systolic blood pressure, as has been the case in other similar investigations with berberine administration in combination with other nutraceutical compounds. Berberine’s vasodilator effect is the result of its action on both endothelium and vascular smooth muscle. Other mechanisms that may explain berberine’s ability to decrease systolic blood pressure include its angiotensin-converting enzyme inhibitor effect, and ability to increase release of nitric oxide/cyclic guanosine monophosphate (NO/cGMP).

Berberine for Remission of Metabolic Syndrome

The findings described in this article, along with others, represent a strong case for the use of berberine as a treatment option for patients with metabolic syndrome — especially when considering its absence of side effects. In summary, berberine use leads to remission of metabolic syndrome and a decrease in waist circumference, SBP, triglycerides, and total insulin secretion, with an increase in insulin sensitivity. Berberine qualifies as an important nutrient to include in your supplement cabinet to achieve and maintain good health.


  1. Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food. 2005 Winter;8(4):454–61.
  2. Rabbani GH, Butler T, Knight J, et al. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. J Infect Dis. 1987 May;155(5):979–84.
  3. Pérez-Rubio KG, González-Ortiz M, Martínez-Abundis E, et al. Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2013 Oct;11(5):366–9.
  4. Affuso F, Mercurio V, Ruvolo A, et al. A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome. World J Cardiol. 2012 Mar 26;4(3):77–83.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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