Berberine - A panacea for diabetics?
by Tal Friedman, ND
Berberine is a compound that has been garnering a lot of press lately for its numerous positive health effects, specifically for diabetics. Is it deserving of all this praise? Let’s take a look at the science and find out. Berberine is an alkaloid extracted from a wide variety of plants, especially those that have a history of use in traditional Chinese medicine. Some of these plants include berberis aristata, berberis aquifolium, berberis vulgaris, coptis chinensis, and hydrastis Canadensis. Historically these plants were used to treat microbial infections, as an anti-inflammatory and anti-diarrheal substance. More recently, in past few years a number of studies, both in vitro and in vivo, have shown the berberine can have some very potent beneficial effects on human health.
Many of berberine’s effects stem from that fact that berberine can activate and enzyme called adenosine monophosphate-activated protein kinase (AMPK). AMPK, in simple terms is an energy sensor in the cell. When energy levels fall, during fasting states or intense exercise for example, AMPK gets activated. This activation is thought to be responsible for many of the benefits of exercise including, mitochondrial biogenesis (making new mitochondria), increased sugar uptake by muscle cells and increased muscle glycogen stores.
Effects on blood sugar
This action that berberine has on AMPK is one of the main reasons that interest in berberine’s effects on blood sugar management have been studied. AMPK activation is one the main mechanisms of action of the popular diabetes medication metformin (Glucophage). In human trials berberine has been extremely impressive in this regard. Let’s take a look at some of the studies.
In one study 116 persons with newly diagnosed type 2 diabetes were given 500mg of berberine twice a day or placebo.  After three months, participants receiving berberine had impressive reductions in hemoglobin A1c, dropping from 7.5% 6.6%. They also had equally impressive reductions in total cholesterol, LDL cholesterol, triglycerides, and systolic blood pressure.  Five people in the berberine treatment group reported constipation. Two of those five had to reduce their dose to 250mg, twice daily to alleviate symptoms. 
One paper reported on two separate trials. Let’s look at those. Once again this first trial is on persons with newly diagnosed diabetes.  This trial compared berberine at a dose of 500mg, three times daily to the popular diabetes medication metformin.  After thirteen weeks, berberine performed as well as metformin in reducing hemoglobin A1c.  Berberine also had beneficial effects on total cholesterol and triglycerides that metformin did not have. This second trial added berberine to conventional care in persons with poorly controlled type 2 diabetes.  They found that berberine reduced hemoglobin A1c over the thirteen week study period, as well as improved insulin sensitivity and blood lipids.  Mild gastrointestinal symptoms were reported in this trial but again, were resolved with dose reductions. 
In another trial berberine was put up against metformin again, as well as another well-known diabetes medication rosiglitazone.  After 2 months the results showed drops in fasting blood glucose and glycated hemoglobin for berberine which matched the results of both metformin and rosiglitazone. Once again only the berberine group saw a statistical drop in triglyceride levels.
Blood sugar management is not only associated with diabetes but it is also associated with a number of other conditions including obesity and polycystic ovary syndrome. Let take a look a few human studies looking at the use of berberine for these conditions.
One study in persons with newly diagnosed metabolic syndrome noted that 300mg of berberine three times per day (900mg total) for 12 weeks was associated with a significant reduction of BMI from on average 31.5 to 27.4.  This equates to an average decrease of 13 percent, with a significant decrease in overall waist circumference by 5.5%.  Lean mass and fat mass were not measured in this study.  Another study evaluated healthy but obese persons taking 500mg Berberine three times per day (1500mg total) for 12 weeks.  Without any adjustments to exercise there was a noted reduction in body weight of approximately 5lbs, with 3.6 percent body fat lost.  Food intake was not changed overall, but two subjects did report a decrease in appetite. 
PCOS is a condition that is quite common among women that is associated with insulin resistance. Metformin is a common pharmaceutical that is prescribed in the treatment of PCOS, so it would seem appropriate to assess the effectiveness of berberine in the treatment of PCOS. One trial compared Berberine and Metformin, alongside standard therapy (antiandrogens and estrogen).  Both berberine and metformin where given at doses of 1500mg in three divided doses against placebo over 3 months period. The study noted that Berberine was associated with the largest reduction in waist circumference (despite no significant differences in weight) yet no significant differences existed between measures of insulin resistance, blood glucose, or insulin with both berberine and metformin performing better than placebo. 
We always have to remember that any compound with strong, pharmaceutical like effects will probably have some side effects, similar to how powerful drugs have side effects, and berberine is no different. Firstly it seems that berberine can inhibit some liver enzymes, namely CYP3A4 and CYP2D6. [7-9] These studies are confirmed in human subjects and berberine does indeed inhibit liver enzymes. [7-9] This is very important because these liver enzymes are involved in the metabolism of a wide variety of drugs. If you have ever been warned of not taking medications with grapefruit juice, this is a similar warning. If you are taking any medications, it is very important that you check with a health care provider before taking berberine. The chances are high that berberine may interact with your current medications. Always check first.
As we age we all slowly start losing muscle mass, starting for most at the age of 50. This loss is a normal part of aging and is even seen in athletes who continue to train and exercise. Now, those who do exercise experience the loss at much lower degree than those who do not. So why is this important and what does it have to do with berberine?
Earlier we mentioned that berberine induces AMPK and that AMPK is thought to be responsible for some of the benefits of exercise. Well AMPK can increase the protein Atrogin-1.  When this protein level increases it causes muscle breakdown and inhibits new protein synthesis responsible for building muscle. This effect was seen in mice injected with berberine and the mice muscles atrophied. 
You see when you exercise, a number of enzymes and proteins are activated, not just AMPK. These other signals balance out the effects of AMPK, so you get its benefits without the downsides. Exercising, especially resistance type training, would be prudent while taking berberine to negate these muscle suppressing effects.
Lastly we noted before that berberine may cause some mild gastrointestinal distress. [1-2] Check with your healthcare provider about lowering the dose to alleviate these symptoms if you experience them.
Berberine looks to be a very effective as treatment for the management of diabetes. It performs on par with conventional treatments, namely metformin and rosiglitazone. Berberine also has additional benefits for managing metabolic syndrome as it can also lower levels of cholesterol and triglycerides. This is fantastic as diabetes and metabolic syndrome usually go hand in hand.
With this being said, there are some drawbacks to berberine as we mentioned earlier. It can interact with other drugs, it can have detrimental effects on muscle tissue protein synthesis and can cause so gastrointestinal upset. We always have to remember than when any treatment, natural or conventional, is this powerful we can expect it to have some side effects. So caution needs to be taken.
So where does this leave berberine? It is an absolutely fantastic addition to well-rounded diabetes/metabolic syndrome treatment plan which should definitely include dietary modifications, physical exercise and regular monitoring to assess the efficacy of treatment. As always, talk with your health care provider to come up with the best plan of action for you.