The Evidence for Berberine

For thousands of years, herbalists have prized certain plants for fighting infections and fevers. It turns out that many of these herbs contain a yellow alkaloid known as berberine. Among these plants are popular botanical remedies like goldenseal, Oregon grape, barberry, Chinese golden thread (coptis), amur cork tree bark (phellodendron), and yellow root.

Herbs containing berberine have long been used topically on cuts and other wounds. They have also been used internally for gastrointestinal issues, including traveler’s diarrhea and food poisoning, in various cultures. They have also been used to reduce fever and inflammation caused by infection, stimulate digestion, and help with urinary tract infections.

Research on Berberine

Thousands of studies about the benefits of berberine are available on PubMed. The research confirms the traditional value of berberine-containing plants for infections, showing that berberine has antibacterial, anti-inflammatory, and immune-enhancing properties. Studies suggest that berberine (and therefore the herbs that contain it) are effective against a wide range of bacteria, protozoa, and fungi.

But the research doesn’t stop at berberine’s anti-infective abilities. It turns out that berberine has numerous other benefits and may have efficacy in the treatment of insulin resistance, diabetes, arthritis, and cancer. There is evidence that it may also help prevent heart disease by lowering cholesterol and triglyceride levels. Berberine may even be helpful for hypertension (high blood pressure), brain health, immune dysfunction, low bone density, and weight control.

How Berberine Works

Berberine helps to activate the enzyme AMPk (Adenosine Monophosphate-activated Protein kinase). This enzyme functions like a metabolic master switch inside the cells of your body. It does this by regulating biological activities that normalize lipid, glucose, and energy imbalances.

Low AMPk activity can lead to accelerated aging, chronic inflammation, high blood cholesterol and triglycerides, insulin resistance, poor blood sugar regulation, increased visceral belly fat, obesity, neurodegeneration, and mitochondrial insufficiency and dysfunction. Boosting AMPk activity helps shift energy toward cellular repair and maintenance, leading to homeostasis and improved health.

In other words, berberine turns idle cells on, thereby helping them to use glucose more efficiently. In fact, researchers have suggested that berberine can produce similar health benefits to engaging in regular exercise and restricting calorie intake—two foundational pillars of health and longevity.

Berberine also supports healthy gut function to help combat endotoxins. High-carbohydrate diets have been shown to alter the microflora of the gut, increasing endotoxin-producing bacteria. These endotoxins are released into the bloodstream and interfere with normal glucose metabolism. Berberine supports gut health by inhibiting the ability of endotoxins to bind to muscle cells, thus helping to support proper glucose metabolism.

According to Jacob Schor, ND, berberine holds tremendous promise for major conditions such as metabolic syndrome, inflammation, and cancer.”₁ The Natural Medicine Journal goes a step further by stating, “Any condition that would be favorably impacted by a patient losing weight and/or exercising more may be impacted favorably with oral berberine supplementation. It makes sense to consider berberine for clients with insulin resistance, pre-diabetes, diabetes, metabolic syndrome, hypertension, heart disease, dyslipidemia, cancer, depression, and other neuropsychiatric diseases.”₂

Here’s a closer look at what berberine may do for some of these problems.

Metabolic Syndrome and Diabetes

Berberine may help with both metabolic syndrome and diabetes. The journal Metabolism reported the results of two three-month human trials in which patients diagnosed with type-2 diabetes were treated with either berberine (500 mg three times a day) or the same dose of Metformin. The studies showed that berberine reduced blood glucose levels similarly to the drug and also reduced hemoglobin A1c, another important marker of glucose metabolism.₃

A recent meta-analysis by Dong et al combined data from 14 randomized trials involving 1,068 participants. Patients treated with berberine and lifestyle modification experienced a significant reduction in blood sugar levels. The effects were virtually identical to those obtained by the standard hypoglycemic drugs metformin, glipizide, or rosiglitazone.₄ Besides directly reducing blood sugar, berberine may also help with some of the side effects of diabetes, such as diabetic nephropathy.

This research helps justify the use of berberine-rich goldenseal in many formulas for diabetes. Goldenseal has been traditionally by herbalists to lower blood sugar levels in type-2 diabetics.

Inflammation

Chronic inflammation lies at the heart of many degenerative diseases, and berberine has been shown to have anti-inflammatory action. While the mechanism is not fully understood, berberine does downregulate proinflammatory responses in macrophages. It also affects cellular kinases and other inflammatory signaling mechanisms.₅ Some researchers believe that berberine also acts as a COX-2 protein inhibitor without reducing enzyme activity.

Heart Health

Berberine may be beneficial for heart health. A report in the journal, Planta Medica, indicated that berberine may help reduce elevated cholesterol levels. In their analysis of 11 previously published clinical trials with a total of 874 participants, the report’s authors determined that berberine may reduce total cholesterol and bad cholesterol (LDL) levels while increasing levels of good cholesterol (HDL). Berberine was also found to decrease triglyceride levels. It has also been shown to reduce apolipoprotein B, a risk factor for heart disease, by up to 15 percent.₆

For people with heart problems, berberine’s AMPk activation slows the release of free fatty acids, which lowers lipid level and prevents harmful fat deposition, boosts fat burning in the mitochondria, and stimulates the release of nitric oxide, a signaling molecule that relaxes the arteries, increases blood flow and lowers blood pressure, thus protecting against atherosclerosis. In one study, those who took berberine for eight weeks had improved heart function and increased ability to exercise compared to those who took a placebo.₇ 

Cancer

Berberine can slow cancer growth and cause cancer cell death through a variety of mechanisms, namely tumor cell apoptosis and cell cycle arrest. It also inhibits blood vessel growth in tumors while inhibiting tumor cellular invasion and metastases.

NF-kappa B is an important protein transcription factor located in our cells. It is a key switch in the development and progression of inflammation and cancer. When NF-kappa B is active in a cell it prevents programmed cell death (apoptosis) and allows that cell to continue multiplying. Cancerous and precancerous cells often have NF-kappa B permanently activated. Berberine inhibits NF-kappa B which helps the body trigger apoptosis and prevent cancerous cell proliferation.

Additionally, berberine acts as a radio-sensitizer of tumor cells without affecting normal cells. It may actually protect normal cells, potentially making radiation therapy more effective.

Berberine also inhibits the tendency of cancer cells to become drug resistant over time by inhibiting the cellular membrane proteins that pump drugs out of the cell. When berberine is taken with tamoxifen and other chemotherapy drugs, studies show that they work synergistically against cancer cells.₈ Berberine also inhibits the development of cancer from carcinogen exposure.

Weight Loss

At least two studies have examined the effects of berberine on body weight. In a 12-week study in obese individuals, 500 mg taken three times per day caused about 5 pounds of weight loss. The participants also lost 3.6% of their body fat.₉ In another study involving 37 people, taking 300 mg of berberine three times daily for three months resulted in a drop in overall fat and belly fat, as well as other improved health markers.₁₀ The researchers believe the weight loss was caused by improved function of fat-regulating hormones, such as insulin, adiponectin, and leptin.

Because of berberine’s ability to inhibit fat storage and improve the function of hormones such as insulin, leptin, and adiponectin, many researchers have concluded that berberine has potential application in reducing visceral fat and controlling central obesity.

Gut Health and Infection

Berberine can help rebalance the microbiota in the gut, alleviating inflammation and preventing insulin resistance and obesity. One study concluded, “…our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.”₁₁

Polycystic Ovary Syndrome (PCOS)

Berberine may be beneficial to women with polycystic ovary syndrome—a metabolic disorder closely associated with insulin resistance. In a clinical trial published in the European Journal of Endocrinology, women treated with berberine showed greater improvement than women treated a drug used for this condition. What’s more, study members treated with berberine showed greater decreases in cholesterol levels and waist size.

Obtaining the Benefits of Berberine

Berberine is available as a supplement by itself. A dose of around 300-400 mg three times a day is typical. Berberine is generally safe for teenagers and adults, but is not recommended for pregnant or lactating women or for infants. Berberine may be useful for both GI and urinary tract infections, balancing gut microflora, stimulating liver function, reducing blood sugar and lipid levels, and improving general health.

I personally prefer to use whole plants as they contain mixtures of other compounds which often work synergistically to help balance the body. When using herbs that contain berberine, it’s important to remember they don’t just contain berberine. Each has its own unique combination of phytochemicals and therefore its own unique properties. I recommend studying the individual properties of each herb. I’ve already written articles on goldenseal and Oregon grape and will write two more articles on herbs with berberine. I will be writing an article on barberry and another on the other herbs I know that contain berberine.

References

1. Clinical Applications for Berberine, Jacob Schor, ND, FABNO, Natural Medicine Journal, December, 2012.
2. Natural Medicine Journal, December 2012 Vol. 4 Issue 12
3. Yin J, Xing H, Ye J, Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 2008;57₅:712-717
4. Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012; 2012:591654.
5. Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus, Zheng Li et al, 2014.
6. Arzneimittelforschung. 2007;57₁:26-30.
7. Cardiovasc Drug Rev. 2001 Fall;19₃:234-44.
8. Berberine Enhances the Anti‑tumor Activity of Tamoxifen in Drug‑sensitive MCF‑7 and Drug‑resistant MCF‑7/TAM cells, Zhang-X et al, 2016, PMID: 27432642
9. Lipid-lowering effect of berberine in human subjects and rats, phymed.2012.05.009
10. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipo-cytes and metabolic syndrome patients, PMID: 22474499
11. Phytomedicine, July 15, 2012, Volume 19, Issue 2, Pages 861-867