Berberine: Benefits, Side Effects, and Research
We take a look at berberine, a popular supplement in the life extension community that is often touted as being similar to metformin.
What is berberine?
Berberine is an ammonium salt from the protoberberine group of benzylisoquinoline alkaloids. It is part of a group of naturally occurring alkaloids that mostly contain basic nitrogen atoms.
Berberine is usually found in the roots, rhizomes, stems, and bark of barberries and other plants. Due to its rich yellow color, the extract from Berberis species has traditionally been used to dye wool, leather, and wood.
Like many herbs and plants, it has been used in traditional Chinese medicine for centuries. This means that there are numerous anecdotal reports of its usefulness for various purposes.
Fortunately, more recently, berberine has been studied through the lens of modern science, and we can say with more certainty if it is genuinely useful.
Sources of berberine
Berberine is found in various plants, including barberry (Berberis vulgaris), tree turmeric (Berberis aristata), Oregon grape (Mahonia aquifolium), goldenseal (Hydrastis canadensis), yellowroot (Xanthorhiza simplicissima), Amur cork tree (Phellodendron amurense), goldthread (Coptis chinensis), (Tinospora cordifolia), Mexican prickly poppy (Argemone mexicana), Californian poppy (Eschscholzia californica), and greater celandine (Chelidonium majus).
It is, of course, offered as a dietary supplement.
What is berberine used for?
Berberine is commonly used to treat high cholesterol or other fats in the blood, a condition known as hyperlipidemia. It is also used by some people to control blood pressure.
It is also used to treat burns, canker sores, liver disease, and other conditions, though the evidence for its use is limited to nonexistent for such conditions.
As an antimicrobial agent, berberine may also be useful, as it was found to be able to inhibit the growth of Staphylococcus aureus (MRSA) infections .
What does berberine do?
Berberine is a bioactive compound and appears to target an enzyme inside cells called AMP-activated protein kinase (AMPK), which plays a critical role in cellular energy metabolism .
AMPK is one of the four pathways that regulate metabolism and cellular homeostasis (a state of balance), and its deregulation is thought to be one of the reasons we age. This is probably the most interesting aspect of berberine in the context of aging.
Some research suggests that berberine may also have anti-inflammatory properties . Inflammation also plays an important role in the aging process in a more general sense, so if berberine can reduce inflammation this is also potentially useful in relation to aging.
Potential benefits of berberine
There has been quite a varied range of research efforts focusing on berberine, so we will break them down into areas of interest.
Berberine for diabetes
There has been some research focused on berberine for type 2 diabetes, a condition of elevated blood sugar (glucose) levels, either due to increased insulin resistance or a lack of insulin. High blood sugar levels over a long period of time can be highly damaging to tissues and organs and often lead to a shortened lifespan.
A 2015 meta-analysis found that berberine, when combined with lifestyle changes, was more effective at lowering blood glucose levels when compared to just lifestyle changes alone .
A further meta-analysis in 2019 suggested that berberine was more effective at lowering blood sugar levels than a placebo . Data from the same study also appears to suggest that the combination of berberine and blood sugar-reducing drugs is more effective than just the drugs used alone.
Because berberine appears to target AMPK, which regulates metabolism and how the body responds to blood sugar levels, it may help address diabetes and related conditions like obesity.
However, more research is needed, including large-scale clinical studies to properly ascertain berberine’s safety and efficacy. Also, due to its potential interactions with other drugs and medications, speak to your doctor before considering berberine for diabetes.
Berberine for high cholesterol
A high level of LDL cholesterol, which is oversimplified as bad cholesterol, is a risk factor for heart disease and stroke. There is some evidence that berberine may be useful in lowering LDL cholesterol.
A meta-analysis from 2015 suggests that lifestyle changes combined with berberine are more effective than just making lifestyle changes to reduce high cholesterol .
A 2017 review suggests that berberine may help lower LDL cholesterol and triglyceride levels . However, the author concludes that more clinical trials need to be done for establishing the therapeutic effectiveness of berberine.
Berberine for obesity
Obesity can increase the risk of type 2 diabetes, heart disease, high blood pressure, and high cholesterol.
Some researchers believe that berberine works similarly to the drug metformin. In fact, a 2015 animal study even compared berberine and metformin and how they both appear to modify the gut microbiome in ways that may help metabolism .
A 2015 study found that people with metabolic syndrome who took 200 milligrams of barberry three times a day saw a reduction in body mass index .
According to a 2017 review, people who took 750 mg of barberry twice a day for 3 months saw a significant loss of weight . This effect could be due to how berberine interacts with AMPK and the resulting change of metabolism.
A 2018 study suggests that berberine activates brown adipose (fat) tissue . This particular type of fat tissue helps the body to convert nutrients we consume into heat for our bodies. By increasing the activity of brown fat, it may help address metabolic dysfunction and conditions like obesity and metabolic syndrome.
Berberine side effects
Some mild side effects, reported by people taking berberine as a supplement, include upset stomach, constipation, nausea, a rash, and headaches.
While no studies have reported serious adverse effects from berberine, its potential for causing them is high. Berberine can interfere with CYP2D6 and CYP3A4 enzymes, which are involved in metabolism and interact with drugs such as statins [10-11].
More research is needed before it really should be considered, as the potential for dangerous interactions is there. However, if you do decide to take berberine and you experience any adverse effects, cease taking it immediately and consult your doctor.
This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use nor any product or supplement vendor, and all discussion here is for scientific interest.
 Chu, M., Zhang, M. B., Liu, Y. C., Kang, J. R., Chu, Z. Y., Yin, K. L., … & Wang, Y. D. (2016). Role of berberine in the treatment of methicillin-resistant Staphylococcus aureus infections. Scientific reports, 6(1), 1-9.
 Lee, Y. S., Kim, W. S., Kim, K. H., Yoon, M. J., Cho, H. J., Shen, Y., … & Kim, J. B. (2006). Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes, 55(8), 2256-2264.
 Li, Z., Geng, Y. N., Jiang, J. D., & Kong, W. J. (2014). Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evidence-based complementary and alternative medicine, 2014.
 Lan, J., Zhao, Y., Dong, F., Yan, Z., Zheng, W., Fan, J., & Sun, G. (2015). Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. Journal of ethnopharmacology, 161, 69-81.
 Liang, Y., Xu, X., Yin, M., Zhang, Y., Huang, L., Chen, R., & Ni, J. (2019). Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocrine journal, 66(1), 51-63.
 Tabeshpour, J., Imenshahidi, M., & Hosseinzadeh, H. (2017). A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iranian journal of basic medical sciences, 20(5), 557.
 Zhang, X., Zhao, Y., Xu, J., Xue, Z., Zhang, M., Pang, X., … & Zhao, L. (2015). Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Scientific reports, 5(1), 1-10.
 Zilaee, M., Safarian, M., Kermany, T., Emamian, M., Mobarhan, M., & Ferns, G. (2015). Effect of barberry treatment on blood pressure in patients with metabolic syndrome. J Nat Prod, 8, 59-63.
 Hu, X., Zhang, Y., Xue, Y., Zhang, Z., & Wang, J. (2018). Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation. American journal of translational research, 10(11), 3322.
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 Feng, P., Zhao, L., Guo, F., Zhang, B., Fang, L., Zhan, G., … & Li, B. (2018). The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chemico-biological interactions, 293, 115-123.