Incidence of insulin resistance, obesity, and other metabolic diseases have reached massive proportions in our culture. The current popular glucose-lowering drug treatment Metformin comes with some potential serious side effects. Berberine, a natural Metformin alternative, can help the body efficiently process sugar, thereby being safer than pharmaceutical interventions.
What is Berberine and Where Does it Come From?
Berberine is a plant photochemical that’s found in several different plants, including goldenseal, European barberry, phellodendron, goldthread, Oregon grape, and tree turmeric.
- It possesses powerful anti-diabetic properties, as well as being anti-bacterial and immune system enhancing.
- As well as diabetes it can be used as a treatment for a number of other health problems including hyperlipidemia, heart disease, and cancer.
- It can regulate blood glucose, increase insulin sensitivity as well as metabolizing fats (burning fat). It has been widely studied, with nearly 1000 studies published on it in the last 5 years alone. There is a body of evidence supporting it’s efficacy in lowering blood-glucose and increasing insulin sensitivity for both humans and animals.
However, Berberine is not a new discovery. For thousands of years the Chinese and Ayurvedic communities has been aware of the amazing benefits of Berberine. The blood-sugar lowering effects have been documented in China and India for hundreds of years. Although it was primarily used for treating inflammation, infections, and diarrhea, as diabetes was not as common then as it is now (1).
Is Berberine Natural Alternative For Metformin?
However, as the incidence of diabetes has grown, the recent studies have focused on it’s ability to treat the condition. The studies have shown just how safe and effective Berberine is for significantly lowering blood sugar in people with Type 2 diabetes, without all of the harmful side effects that come along with taking pharmaceuticals, such as Metformin.
In this article, we will discuss the mechanisms behind how Berberine works to lower blood-glucose and increase insulin sensitivity. We will also review the research comparing the efficacy of taking Berberine vs. Metformin, and hopefully shed some light as to why Berberine is a natural alternative for Metformin in the treatment of diabetes.
Berberine For Type 1 and Type 2 Diabetes?
Berberine contains significant glucose-lowering properties and improves insulin sensitivity. According to Yin, Ye, and Jia (2012) (1), it was proven to decrease blood glucose, strengthen insulin sensitivity and reduce the weight of both dietary and genetic rodents with type 2 diabetes. The researchers also noted that pancreatic islet function was improved.
“These results indicate Berberine may have a two-way regulation in pancreas islets. In typical type 2 diabetes with notable insulin resistance, Berberine lowered blood insulin level through increasing insulin sensitivity. However, in type 1 diabetes or the late stage of type 2 diabetes characterized by poor β-cell function, Berberine was able to increase insulin secretion via repairing destructed or exhausted islets, which may be related to its antioxidant and anti-lipid peroxidation properties (2).”
Berberine as a Natural Alternative to Metformin and Anti-Diabetic Effects in the Body
There are several molecular mechanisms that take place in order for Berberine to lower blood glucose. It activates the AMPK (adenosine monophosphate-activated protein kinase) pathway. AMPK is like a metabolic master switch in the body, and plays an important role in energy metabolism. Obesity and other energy related imbalances occur when AMPK is suppressed. Berberine helps to activate AMPK, therefore regulating lipid energy and glucose metabolism.
However, Berberine doesn’t just work by activating AMPK. Xu et al. (2014) (2) designed a study to determine if AMPK activation was the only mechanism by which Berberine could lower blood sugar. They did this by chemically blocking AMPK activation. The results showed that even when AMPK was blocked Berberine still lowered blood sugar. The authors went onto suggest that as well as activating AMPK, Berberine also promotes glucose metabolism through the stimulation of glycolysis, which is the breakdown of glucose by enzymes in the body.
AMPK triggers the production of new mitochondria (pictured)
Berberine is also able to work against diabetes because it can also work in the same way in the body as of alpha-glucosidase inhibitor drugs (for example Miglitol and Acarbose). These are medications that prevent the digestion of carbohydrates, and so reduce the impact of eating carbs on blood sugar. They work by inhibiting enzymes called disaccharidases which break down sugars.
They also decrease glucose transportation across the intestinal epithelium layer, (the layer of cells between the intestines and the stomach where food is absorbed into the body). It can also up-regulate expression of insulin receptor genes found in cells, restoring the cell’s ability to be receptive to insulin, thus increasing insulin sensitivity in the body (2).
Berberine has also been found to inhibit gluconeogenesis, or the production of glucose that takes place in the liver. Its ability to work in multiple ways in the body is really the secret to it’s powerful health benefits and anti-diabetic effects (3).
Berberine Supplements and Gut Bacteria
3D Image of Intestinal Bacteria
Berbrine’s effects don’t stop there however. Recent research has associated having too much ‘bad bacteria’ in the gut with type 2 diabetes (4), and Type 2 diabetes has also been associated with a condition of low grade inflammation in the body (5). Researchers have been able to directly connect this inflammation to changes in the gut bacteria (6), so Berberine can also potentially work against diabetes by reducing the level bad bacteria in the gut.
According to Han, Ling, and Wuan (2011) (7), Berberine has been proven to carry heavy antimicrobial activity against bad bacteria, fungi, parasites and worms. Berberine has been shown significantly reduce the levels of ‘bad’ strains of bacteria such as Staphylococcus, Streptococcus, and Salmonella, Klebsiella, Clostridium and Shingella (amongst many others). The interesting part is that berberine inhibits overgrowth of these ‘bad’ organisms, while at the same time having no negative effects on the beneficial bacteria species lactobacilli and bifidobacteria! Therefore modulating the gut microbiota is another way that Berberine works to lower blood-glucose and balance diabetic symptoms.
Berberine vs. Metformin, What is the Research Showing?
Recent research is indicating that Berberine is both safe and effective for the treatment of Type 2 diabetes and has compared it to the effects of Metformin. Berberine taken by itself lowered fasting blood glucose concentrations by 21% to 36%, comparable to the effects of Metformin and Rosiglitazone (3).
Dong H, Wang N, Zhao L, Lu F (8) reviewed randomized trials of Berberine compared with lifestyle modification, placebo, and/or oral hypoglycaemics intervention on treating diabetes. These researchers concluded that Berberine with lifestyle modification was more effective at lowering blood glucose compared with lifestyle intervention alone with placebo. Berberine showed additional hypoglycaemic effects when combined with other pharmaceutical interventions. They concluded that Berberine’s blood sugar lowering abilities were as effective as conventional treatments.
Jun Y, Huili X, and Jianping Y (9), studied the efficacy of Berberine’s blood-glucose lowering abilities. Berberine was given to both newly diagnosed diabetic patients and poorly controlled diabetic patients. Patients were randomly assigned to take either Metformin or Berberine treatment. The researchers measured the blood glucose levels of the participants for a period of three months. Compared with Metformin, Berberine worked just as effectively as Metformin.
Fasting blood glucose was down 30%, and post eating blood glucose went down by 45%. The individuals taking Berberine did not experience severe gastrointestinal distress, like the ones taking Metformin.
However, with regard to the regulation of fat metabolism, Berberine activity was significantly better than that of Metformin. Triglycerides and total cholesterol in the Berberine group had decreased by 21%, and were significantly lower than in the Metformin group. Triglycerides are typically elevated in people with Type 2 diabetes, so this finding is significant in terms of diabetes treatment options! The researchers concluded,
“Berberine is a potent oral hypoglycemic agent, [meaning it is a strong blood sugar lowerer], with modest effect on lipid metabolism [meaning it also improves blood cholesterol and lowers triglycerides]. It is safe and the cost of treatment by Berberine is very low. It may serve as a new drug candidate in the treatment of type 2 diabetes.”
In addition to lowering glucose, animal research is also showing that Berberine may have benefits in treating some of the complications that arise for diabetics, such as diabetic nephropathy. (3)
Berberine Side Effects vs Metformin Side Effects
Berberine is a much safer alternative to chemically created pharmaceuticals, with fewer side effects. Metformin is not considered safe for patients with liver inflammation, because it can contribute to liver disease. However, Berberine actually helps to increase liver function, and may even help with several other diabetic related complications (9).
Metformin is associated with some severe gastrointestinal side effects. Dugic et al. (2015) (10), studied 92 patients with recently developed diabetes, who were taking Metformin. They found that half of the participants (47%) in this study experienced moderate to severe gastrointestinal symptoms while taking Metformin.
Long-term Metformin use is also associated with B12 deficiency and anemia, whereas long-term Berberine use does not come with the same side effects (11). In another recent study by Hertog et al. (2015) (12), the researchers performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment on stroke patients with impaired glucose intolerance. The researchers noted:
“19 patients were randomly assigned Metformin. Nine patients in the Metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3–10 weeks.”
Berberine, however, has been used as a treatment for diarrhea in Chinese medicine for centuries, and so not associated with severe gastrointestinal distress. It’s also safe to take long-term (1).
The main negative side effect of Berberine is that if you are currently taking other blood sugar lowering drugs such as Metformin, the combination may cause your blood sugar to go too low. So if you are taking other medications make sure to consult your doctor first. Please also consult your doctor is you are pregnant or breastfeeding. Berberine is, however, a natural alternative to Metformin, so talk to your doctor before you decide to change medications.
Some other minor side effect noticed are some GI discomfort, diarrhea, or constipation. However, these tend to be either in the first week or so or when taking dosages of more than 500mg at one time, which we will discuss in the next section.
Berberine Dosage – How Much Should I Take?
Getting the right dosage and understanding how to take Berberine is really important to make sure that it works for you. Berberine is well absorbed by the body, however it is also metabolized in the liver very quickly. This means that it’s used by the body very quickly. In actual fact it’s used by the body so quickly that blood tests can only measure very small levels of it.
This means that you need to take Berberine after every meal. The recommended Berberine dosage for diabetes is 500mg, so this should be taken 3 times a day, with breakfast lunch and dinner, for a total of 1500mg per day. Don’t take more than 500mg at one time, as this can sometimes produce GI side effects.
Make sure to also choose a pure Berberine supplement as many brands sell weaker complexes that will not be as effective.
How Long Does Berberine Take To Work?
Berberine starts to significantly reduce blood sugar after around 1 week of regular use, and reaches a maximum after around 5-6 weeks (9).
Where To Buy Berberine?
So you’re probably now asking yourself where to buy Berberine. At Intelligent Labs we have produced a ultra pure Berberine supplement formulated in the clinically recognized 500mg capsules.
Berberine as a natural alternative to Metformin, is one of a very few supplements that works effectively as a drug. It is good at reducing blood sugar and increasing insulin sensitivity, and also because it causes far fewer side effects. In fact it has a whole host of positive health benefits outside of it’s anti-diabetic and cholesterol lowering benefits. If you are interested in its other health benefits please read our other article on Berberine benefits.
(1) Yin J, Ye J, & Jia W (2012). Effects and Mechanisms of Berberine in Diabetes Treatment. Diabetes and Obesity. Vol. 2, Issue 4, pp 327-34. doi:10.1016/j.apsb.2012.06.003
(2) Xu M, Xiao Y, Yin J, Hou W, Yu X, Shen L, Liu F, Wei L, & Jia W (2014). Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation. PLoS ONE 9(7): e103702. doi:10.1371/journal.pone.0103702
(3) Yao, J., Kong, W. & Jiang, J. (2015). Learning from berberine: Treating chronic diseases through multiple targets. Science China Life Sciences. 58: 854. doi:10.1007/s11427-013-4568-z
(4) Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010;5:e9085.
(5) Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–67.
(6) Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease.Curr Pharm Des. 2009;15:1546–58.
(7) Han J, Lin H, & Huang W (2011). Modulating gut microbiota as an anti-diabetic mechanism of berberine. Medical Science Monitor 17(7). DOI: 10.12659/MSM.881842
(8) Dong H, Wang N, Zhao L, Lu F (2012). Berberine in the treatment of type 2 diabetes mellitus: A systemic review and meta-analysis. Evidence Based Complementary Alternative Medicine. Volume 2012 (2012), Article ID 591654, 12 pages. http://dx.doi.org/10.1155/2012/591654
(9) Jun Y, Huili X, and Jianping Y (2008). “Efficacy of Berberine in Patients with Type 2 Diabetes” Metabolism. May; 57(5): 712-717.
(10) Dugic T, Causevic A, Bego T, Malenica M, Veliga-Asimi Z, Pearson ER & Semiz S (2016). Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes. Diabetic Medicine. Volume 33, Issue 4, 511 (4).
(11) Aroda VR, Edelsein SL, Goldberb, RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schae DS, Marinella, Temprosa, G, White NH, Crandall JP (2016). Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. The Journal of Clinical Endocrinology and Medicine. V101, Issue 4. DOI: http://dx.doi.org/10.1210/jc.2015-3754
(12) Hertog H, Zandbergen AM, & Achterberg S et al. (2015). Safety and FeasibiLity of Metformin in Patients with Impaired Glucose Tolerance and a Recent TIA or Minor Ischemic Stroke (LIMIT) Trial – A Multicenter, Randomized, Open-Label Phase II Trial. International Journal of Stroke. Vol. 10 (1). 105-9. doi: 10.1111/ijs.12023 Int J Stroke January 2015 vol. 10 no. 105-109.