Berberine is found in the roots, stems, and bark of various plants, including goldenseal, barberry, and Oregon grape, and has potent anti-inflammatory, antioxidant, and antimicrobial properties. But one of its most exciting properties is that it activates an enzyme in our cells called adenosine monophosphate-activated protein kinase (AMPK). AMPK is sometimes referred to as a metabolic “master switch” and regulates how energy is produced and used in the body; activation of the enzyme increases glucose uptake, fat burning for energy, and mitochondrial biogenesis. Mitochondria are the energy-producing organelles of our cells, and increased production (i.e., biogenesis) of mitochondria is important to maintain overall health and wellbeing.

Because of AMPK’s influence on metabolism, researchers consider it a potential therapy in controlling metabolic diseases like diabetes and cancer. As Jacob Schor, ND, writes in the Natural Medicine Journal, “activating AMPK can produce the same benefits as exercise, dieting, and weight loss—the lifestyle modifications considered beneficial for a range of maladies.”^v Berberine is one of only a handful of compounds that activate AMPK, making it a valuable tool in treating an array of modern day diseases. 

Metabolic Disorders

Rates of metabolic disorders such as type-2 diabetes, obesity, and metabolic syndrome have skyrocketed in modern times, and dysregulation of blood sugar, insulin, and triglycerides are hallmarks of these types of disorders. Much of the research conducted with berberine has investigated its role in blood sugar control, and the results are impressive. Berberine lowers fasting glucose and insulin levels, post-prandial glucose (glucose levels after eating), HbA1c (a marker of long-term blood sugar levels), and triglycerides.^{vi vii} It improves insulin resistance, inhibits glucose production in the liver, stimulates the breakdown of glucose, and regulates lipid (fat) metabolism. Research has found that berberine is as effective as metformin (a common diabetic drug) at lowering fasting blood glucose and HbA1c, and even more effective than the drug at reducing triglycerides.^{ix x} It has also been shown to be as effective as metformin in reducing insulin resistance in polycystic ovary syndrome (PCOS).

The bulk of berberine’s positive effects on blood sugar are likely through its activation of AMPK, but there’s another novel way that berberine may help—through its ability to modulate the gut microbiota. Negative changes in gut bacteria have been connected to metabolic diseases, including type-2 diabetes and obesity. Bacteroidetes and Firmicutes are two types of gut bacteria that play a role in regulating fat storage and metabolism, and some studies have found that obese individuals have more Firmicutes and less Bacteroidetes compared to lean controls. One animal study found that berberine not only significantly lowered blood glucose, lipid levels, and body weight but also significantly reduced the number of Firmicutes in the gut.

Cardiovascular Disease

Cardiovascular disease (including heart disease, stroke, and hypertension) is the number one cause of death in the U.S., killing more than 800,000 people annually. Along with its blood-sugar regulating abilities, berberine has also been found to have a positive impact on several other markers of cardiovascular health, including improving the ratio of LDL to HDL cholesterol, reducing triglycerides, improving endothelial function, and suppressing inflammatory cytokines. One study investigating berberine’s effect on patients with congestive heart failure (CHF) found that supplementing with berberine, in addition to conventional therapy, significantly increased left ventricular ejection fraction (the amount of blood pumped out of the heart with each heartbeat), exercise capacity, and improved the dyspnea-fatigue index, a measurement of labored breathing and fatigue in CHF patients compared to those who received conventional therapy alone. In a two-year follow-up, there was also a significant decrease in death in the berberine-treated patients compared to those only receiving conventional therapy.

Non-Alcoholic Fatty Liver

Metabolic disorders like metabolic syndrome and type-2 diabetes are intricately linked with cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). These often occur together, or one may be a precursor to another. With its antioxidant, anti-inflammatory, and AMPK-activating properties, berberine is proving to be a valuable multifunctional intervention. A recent randomized, controlled trial including 184 patients with NAFLD compared lifestyle intervention (diet and exercise), lifestyle intervention plus pioglitazone (a diabetic drug, that should be noted, can cause or worsen heart failure), or lifestyle intervention plus berberine (500 mg, three times daily). Lifestyle intervention plus berberine resulted in a significant reduction in liver fat (57% compared to 36% in the lifestyle intervention group), a “remarkable” decrease in body weight, and better reductions in blood glucose, triglycerides, and cholesterol. Berberine was more effective than the drug in reducing body weight and improving triglyceride levels. To explore berberine’s mechanism of action on NAFLD in humans, the researchers looked at an animal model of NAFLD and found that berberine favorably collects in the liver—with a concentration 50 times higher than in the blood—where they propose it directly affects genes related to energy metabolism, including activating liver AMPK. Previous research has found similar results.

Ancient practitioners knew there were special properties in the plant compound berberine, and now modern research is shedding light on just how remarkable this compound’s effect is in the human body. With berberine’s unique and multiple modes of action, it is looking to be a modern-day panacea when it comes to metabolic disorders. Berberine is rapidly metabolized, so it’s best taken in divided doses throughout the day. Most studies have used between 1,000 and 1,500mg daily. 

References available upon request