INL Articles - Berberine and Metabolic Syndrome

Berberine is better than Metformin for Metabolic Syndrome

Type 2 diabetes mellitus (T2DM) and Metabolic Syndrome are increasingly contributing to the global and local burden of disease. 

Metformin, sulfonylurea and thiazolidinedione may temporarily improve blood glucose control, yet despite the continuing introduction of hypoglycemic drugs, metabolic syndrome and its related complications (obesity, hypertension, CVD, gout) remain a puzzle needing to be solved. (1)

Berberine is an isoquinoline alkaloid extracted from Berberis vulgaris L. (barberry root), traditionally indicated for treating diarrhoea and is still in use for managing gut dysbiosis such as small intestinal bacterial overgrowth (SIBO). (2) Berberine has long been used in herbal medicine as a cholagogue, supporting liver function and elimination. For a monograph on its wide use in traditional medicine click here.

Ongoing experimental and clinical studies have illuminated great potential of berberine extract, the concentrated most active phytonutrient, in regulation to glucose and lipid homeostasis, as well as in cancer growth and inflammation. (3)

This article makes the proposition that Berberine can contribute in treatment of metabolic syndrome – the glycemic, and hypertensive and lipid-cardiovascular aspects - at a lower cost than do pharmaceuticals, and in ways that assist the wider metabolic syndrome issues better than does metformin (plus statins).

It has been reported that berberine has activity comparable to sulphonureas and metformin in reducing blood glucose in diabetic patients, and additionally performs as well as a statin in lipid management. (4)

Like Metformin, Berberine also significantly activates AMPK (AMP-activated protein kinase).

Obesity, type 2 diabetes and the metabolic syndrome are disorders of energy balance, which AMPK manages at both cellular and whole body levels. (5) One of the ways it does this is by monitoring the AMP/ATP ratio. Activation of AMPK in skeletal muscle and adipose tissue leads to increased glucose uptake (insulin independently). (6)

Some studies report that activation of hepatic AMPK leads to increased fatty acid oxidation (fat burning) and simultaneously the inhibition of hepatic glucose production and lipogenesis, triglyceride and cholesterol synthesis. (7)

It has been consistently demonstrated that AMPK is a target for berberine in the regulation of glucose metabolism. The most recognised theory for the activation of AMPK by berberine is via increasing AMP/ATP ratio through the inhibition of ATP biosynthesis in mitochondria. Berberine is shown to inhibit NAD-linked respiration (Complex I) in isolated liver mitochondria. This, along with increased AMPK activity increases glycolysis, glucose uptake and consumption in muscles, lowering HbA1c. (8)


Berberine improves glucose metabolism through induction of glycolysis

Berberine also reduces the fasting serum insulin and decreases the blood sugar by improving insulin sensitivity of insulin receptors, rather than by stimulating the pancreatic β cells to secrete insulin. 

In 2008 Yin et al reported on administration of Berberine:

  • In study A, 36 adults with newly diagnosed type 2 diabetes were randomly assigned to treatment with berberine or metformin (0.5 g t.i.d.) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (HbA1c; from 9.5% ± to 7.5% P<0.01), fasting blood glucose (from 10.6 to 6.9 mmol/L,  P<0.01), postprandial blood glucose (from 19.8 to 11.1 mmol/L, P<0.01) and plasma triglycerides (from 1.13 to 0.89 mmol/L, P<0.05) were observed in the berberine group. (9)
  • In study B, 48 adults with poorly controlled type 2 diabetes were supplemented with berberine in a 3-month trial. Berberine acted by lowering FBG and PBG from one week to the end of the trial. HbA1c decreased from 8.1% to 7.3% (P<0.001). Fasting insulin and HOMA-IR were reduced by 28.1% and 44.7% (P<0.001), respectively. (10)


Metformin and berberine, two versatile drugs in treatment of common metabolic diseases:

The meta-analysis of 21 clinical trials revealed that berberine has therapeutic effects on T2DM, hyperlipidemia and hypertension, comparable to other therapeutic regimes. Studies have indicated that, similarly to metformin, berberine executes its functions by regulating a variety of effectors including AMPK, MAPK, PKC, PPARα, PPARγ. (11)

In a meta-study assessing 27 experiments comparing berberine, oral hypoglycemic, studies using lipid lowering drugs and others comparing hyoptensive drugs, there was no statistical significance between berberine and oral hypoglycaemics. Berberine compared with lipid lowering drugs showed no statistical significance in reducing the level of total cholesterol and LDL-C, but berberine shows better effect in lowering the level of triglyceride and raising the level of HDL-C. Berberine also showed a hypotensive benefit. (12)

Berberine as a lipid and cardiovascular therapy

In relation to cholesterol berberine the mechanism of action appears to be downregulation of low-density lipoprotein cholesterol (LDL-C) by upregulation of LDL receptor (LDLR) expression. This mechanism is distinct from how statins work but comparable in effect. An example of 116 patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (500mg bid) or placebo for 3 months.

In the berberine group:

  • Hemoglobin A1c decreased from 7.5% to 6.6% (~ 12% reduction)
  • FBG decreased from 7.0 to 5.6 mm/L (126 to 100.8 mg/dl, ~ 20%)
  • Triglycerides decreased from 2.51 to 1.61 mm/L (220 to 141 mg/dl, 60%)
  • Total cholesterol decreased from 5.31 to 4.35 mm/L (205 to 168 mg/dl, ~ 23%) 
  • LDL cholesterol decreased from 3.23 to 2.55 mm/L (124.9 to 98.6 mg/dl, ~ 25%) (13)

Note: As a practical clinical note, 500mg bid is insufficient for diabetics, while it is adequate for Metabolic Syndrome in most cases, along with carbohydrate reduction, exercise and improvement in fiber levels and gut health. For diabetics, my clinical recommendation is to use a Designs for Health product Berberine Synergy which has added lipoic acid, at a dose of two capsules twice daily. This adds the relevant antioxidant  lipoic acid protection and will provide an adequate amount of 1600mg of Berberine.)

Berberine is a thrombin inhibitor, approx by 40%, and blood-clotting time, activated partial thromboplastin time, prothrombin time, thrombin time, and decreased fibrinogen and thus has anticoagulant activity. (14)

A 2004 meta-analysis of randomized-controlled clinical trials suggests that metformin has no intrinsic effect on blood pressure, HDL cholesterol or triglycerides in patients with type 2 diabetes. In addition it appeared that while metformin had no effect versus control treatment on triglycerides, there was a significant effect on total and LDL cholesterol, but not on improving HDL-C. (15)

As shown above in the studies, related to lipids, Berberine, but not metformin, reduces blood pressure, and triglycerides and while both reduce LDL-C Berberine is more effective with rising HDL-C than is metformin. Berberine possesses some wider cardiovascular properties.

Unlike Metformin, berberine does not adversely affect vitamin B12 levels. (16)

Unlike metformin berberine has some beneficial effects on gouty inflammation: berberine alleviates monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL-1β expressions. The immune regulatory effects of berberine may be related to the inactivation of NLRP3 inflammasome. (17)

Concluding remarks

Metabolic syndrome has elements of elevated blood glucose, hypertension, low HDL-C and often elevated LDL-C as well. In addition higher rates of gout are encountered along with the obesity. Both metformin and Berberine are comparable in their effects on blood glucose, fatty acid oxidation and insulin resistance.

Berberine has further benefits, being mildly hypotensive and anti-inflammatory and assisting elements of cardiovascular disease, as outlined above.

The largest metastudy being quoted here proposes metformin and berberine share many aspects in actions and mechanisms despite different structure. While metformin is the first line anti-diabetic drug, berberine is not extensively used in treatment of T2DM and metabolic syndrome in Western countries although it is a non-prescriptive medicine, inexpensive and experimental studies show validating results, with “no serious adverse reaction reported in the 27 experiments”. (18)

While Berberine may not be the only treatment needed, it is an excellent way to begin a therapy for patients with the many aspects metabolic syndrome, rivaling metformin in the glucose and fat-burning aspects, and excelling in the cardiovascular area, at the same time supporting improved liver health and gut flora balance. Both plant extracts metformin and berberine are remarkable therapies and both deserve to be used where appropriate.

Berberine Synergy™ supplies high potency berberine combined with alpha lipoic acid to help support optimal blood sugar and insulin levels, cardiovascular health and liver health.** Berberine is an alkaloid compound found in the roots, rhizomes, stems and bark of several plants commonly used in botanical and Chinese medicine, such as goldenseal, Oregon grape, barberry, and Berberis aristata - View Product Here.


Berb-Evail is manufactured using the Designs for Health Evail™ technology, which is an all-natural formulation that improves the absorption and delivery of berberine. This process uses a proprietary blend of MCT oils, non-soy derived lecithin, and vitamin E, without the use of potentially harmful surfactants - View Product Here.