Berberine and Diabetes

 

It is hard not to get too excited about Berberine.  It is a plant alkaloid used to improve intestinal health, lower cholesterol, for anti-inflammatory effects and may also help with body fat loss. Wow – that is a lot to like!

 

However, the biggest excitement for us is its anti-diabetic effects, especially to reduce glucose production in the liver. In fact, both human and animal research indicates that 1500mg of berberine may be as effective as taking 1500mg of metformin or 4mg glibenclamide (two pharmaceuticals for treating type II diabetes).  We’ll look more at that later but first:

 

How Strong is the Evidence?

 

Well, let’s just look at human studies and excludes animal and in vitro studies.  Here is an summary of the possible strength of the effects berberine may have on your body.

 

Condition                         Effect                        

 

Blood Glucose             Strong           

Studies are showing the usage of berberine in reducing blood glucose is comparable to the oral hypoglycemic drugs Metformin or Glibenclamide.  This suggests berberine is one of the more effective supplements for blood glucose reductions.

 

HbA1c                         Strong           

The reduction of HbA1c associated with berberine (with diabetics using 1,000-1,500mg berberine daily) was −0.72% more than a placebo. This reduction appears to be one of the more significant reductions compared to dietary supplements.

 

Insulin                              Minor             

The degree of reduction of fasting insulin according to meta-analysis was SMD −0.50mU/L.  Which is helpful but not overly remarkable.

 

Insulin Sensitivity          Minor             

One study in people with NAFLD has shown mild increases in HOMA-IR when berberine is added to lifestyle changes compared to lifestyle changes alone.

 

Total Cholesterol           Notable         

Total cholesterol appears to be decreased by around −0.58mmol/L.  This is also helpful but not overly potent.

 

HDL, LDL, & Trigs          Minor             

The percent of improvements are usually in the low teens – significant but there are better results from other nutrients.

 

A Look at the Studies

 

Berberine has shown efficacy against some bacteria strains such as cholera, giardia, shigella, and salmonella.  Surprisingly, rough extracts were more potent than isolated berberine extracts suggesting additive effects from other compounds in these plants.¹

 

The most potent sources include Tree Turmeric or Indian Barberry at 5% of the roots or 4.2% of stem and bark.

 

A related compound, Dihydroberberine, found in Coptidis Chinensis, appears to have similar effects to berberine but with lower doses (1 to 5) thus, higher potency.²

 

Absorption with Milk Thistle

 

The bioavailability of berberine is less than 5%. Even then, the studies using 1,000-1,500 mg still appear to get the benefits after absorption.  But, obviously, enhancing absorption would help to reduce the dose of Berberine required to reach these effects.

 

Well, there is a protein molecule, P-Glycoprotein, responsible for approximately 90% of reduced transportation of berberine.³  Thus, adding a P-Glycoprotein inhibitor, such as sodium caprate or the silymarin in milk thistle, greatly increases the absorption of berberine.⁴

 

Mind, Memory and Depression

 

Mental function can be a concern for many long term diabetes sufferers.  The good news is that berberine appears to cross the blood-brain barrier and reach the brain in a dose/time-dependent manner.⁵  This may help in Diabetes-induced memory losses and Learning. Let’s see how this can help people with diabetes.

 

Serotonin – Berberine at 5mg/kg (400 mg / 180#) can raise neural serotonin by 47% in mice. It has been shown to increase serotonin content in some areas of the brains of mice following oral ingestion.⁶

 

Dopamine – Berberine has been shown to increase dopamine concentration in some areas of the brain following oral administration.  Administration of Berberine at 5mg/kg injections can raise neural dopamine by 31% in mice – which increased to 53% over 15 days of administration.⁷

 

Alzheimer’s Disease – Targeting known pathways, berberine yielded 11 targets in the Alzheimer amyloid secretase pathway and 17 targets in the Alzheimer presenilin pathway. This is thought to be therapeutic for Alzheimer’s Disease.⁸

 

Depression – The above helps but a study using 5mg/kg Berberine also noted time-dependent reduction in immobility time in a forced swim test. This indicates anti-depressive effects.  It was also effective at reversing Reserpine-induced depression, enhancing the anti-depressant effects of imipramine, tranylcypromine, fluoxetine, and venlafaxine, and abolishing the depressive effects in the forced swim test.⁹

 

Nutrient-Nutrient Interactions

 

Metformin – Metformin is an anti-diabetic pharmaceutical drug that is known to indirectly activate AMPK. What is interesting is that it does so at a similar potency to Berberine (on an oral dosage basis as well as cellular concentration). This has led to an informal designation of Berberine as ”Herbal Metformin”, and at least one meta-analysis on Berberine noted that they were comparable in efficacy for the treatment of Diabetes.¹⁰   (It should be noted that not all mechanisms are shared between the two compounds.)

 

Statins – Berberine has been shown to reduce cholesterol levels by up to 25% in persons with high cholesterol.¹¹  It also reduces inflammation – leading to it being referred to as “the next statin” by some, with some suggestions of the combination of statin drugs and berberine for the purpose of lipid and cholesterol reduction as they may be synergistic – though it is not our suggestion!¹²

 

Safety and Toxicology

 

(The standard dose of berberine is 900 – 2,000mg a day, divided into three to four doses, with a meal.  Too much berberine at once can result in stomach upset, cramping, and diarrhea. Berberine has a potential to interact with a medications, and some interactions may be serious. Because of this, we use a much smaller amount of berberine in combination with other nutrients.

   

 

References

 

1. Kaneda Y, Tanaka T, Saw T Effects of berberine, a plant alkaloid, on the growth of anaerobic protozoa in axenic culture. Tokai J Exp Clin Med. (1990)

 

2. Turner N, et al Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. (2008)

 

3. Chae HW, et al Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine. Arch Pharm Res. (2008)

 

4. Di Pierro F, et al Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. (2012)

 

5. Zhang Y, et al Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. (2008)

 

6. Wang X, et al The uptake and transport behavior of berberine in Coptidis Rhizoma extract through rat primary cultured cortical neurons. Neurosci Lett. (2005)

 

7. Kulkarni SK, Dhir A On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. (2008)

 

8. Chen XW, et al Interaction of herbal compounds with biological targets: a case study with berberine. ScientificWorldJournal. (2012)

 

9. Kulkarni SK, Dhir A On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. (2008)

 

10. Dong H, et al Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. (2012)

 

11. Kong W, et al Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. (2004)

 

12. Carlomagno G, et al Effects of a nutraceutical combination on left ventricular remodeling and vasoreactivity in subjects with the metabolic syndrome. Nutr Metab Cardiovasc Dis. (2012)