A Quick Guide to Berberine: Top Health Benefits, How to Use Berberine Supplements, and More

A powerful compound with use dating back to 650 B.C., berberine has been utilized for millennia in both ancient healing practices and textile dyes for its characteristically yellow hue. Prior to the identification and isolation of berberine itself in 1918, health practitioners primarily from China and India recognized the therapeutic potential of the plants that this compound comes from, including barberry, Chinese goldthread, and goldenseal.  

In recent decades, berberine's popularity as a supplement has grown alongside the collection of research on how it supports health. In this quick yet comprehensive guide, find out more about berberine’s benefits and uses as a supplement, from managing blood sugar to maintaining a healthy weight to modulating aging.    

What is Berberine?

Berberine’s health-supporting powers come primarily from its chemical structure as an alkaloid — a nitrogen-containing, plant-derived compound that supports antioxidant, antimicrobial, and anti-inflammatory activity. Alkaloids in plants are produced as a defense response to environmental stressors, providing pharmacological-like support in the human body.

What Does Berberine Do in the Body?

One of berberine’s leading ways it supports health is through its antioxidant activity. With age or poor health, our bodies can accumulate inflammatory compounds called reactive oxygen species (ROS) or free radicals. These reactive molecules damage cells, proteins, and fats in our body and create a state called oxidative stress; antioxidants like berberine can neutralize the harm. 

Research has found that berberine is as effective as the well-known antioxidant vitamin C in fighting ROS and free radicals. Berberine may also increase levels of other antioxidants in the body, including our body’s master antioxidant, glutathione. 

Second, berberine impacts various systems in the body by activating AMP-activated protein kinase (AMPK), an enzyme that acts as a sensor for low levels of energy, or ATP, inside cells. When this occurs, AMPK works quickly to restore intracellular energy levels, which it does by redirecting carbohydrate and fat metabolism to take glucose from the blood and pull it into cells. Essentially, AMPK acts as a “metabolic master switch” in the body, and berberine supports this process. 

Lastly, berberine can support a healthier inflammatory response in the body. Although not all inflammation is harmful, chronic or dysregulated inflammation plays a role in many, if not all, age-related disorders. Research in cell cultures has found that berberine reduces several pro-inflammatory compounds called cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE2), and cyclooxygenase-2 (COX-2). 

Top Health Benefits of Berberine

By regulating oxidative stress and supporting AMPK activity, berberine may benefit several aspects of health that can deteriorate with age. 

Supports Healthy Blood Sugar

Berberine activates the AMPK pathway, which pulls glucose (sugar) from the blood into cells for energy, allowing the compound to show support for maintaining healthy blood sugar levels. In addition, berberine has been found to increase glucokinase activity, an enzyme that supports healthy glucose metabolism. 

One recent study found that individuals who took berberine for one month experienced significant reductions in fasting blood glucose and blood glucose two hours after a meal compared to those taking a placebo. These results indicate that berberine supplementation does not need to be taken long before experiencing blood sugar management.

Notably, both human and animal studies have found that taking 500 milligrams (mg) of berberine three times per day is equally as effective as several leading pharmaceutical drugs for blood sugar management, which also target the AMPK pathway.

Supports Cardiometabolic Health

Poor heart and vascular health are increasingly common in older adults, affecting up to 90% of those over age 80. One way to support cardiovascular and metabolic health with age is with berberine. 

​​Berberine increases the production of nitric oxide — a compound known as a vasodilator, meaning it relaxes blood vessels and supports healthy blood pressure. Plus, berberine has been found to reduce plaque buildup in the arteries by supporting a healthier antioxidant and inflammatory response. 

In addition to blood pressure, vascular function, and inflammation, cardiometabolic health is also affected by blood lipid (fat) and cholesterol levels. In a 2013 study involving 144 healthy adults, those who took 500 mg of berberine twice a day for three months saw significant reductions in total cholesterol, triglycerides (fat in the blood), and LDL (“bad”) cholesterol, with increases in HDL (“good”) cholesterol. 

Supports Healthy Aging

Berberine may increase the activity of the sirtuin protein called SIRT1, which plays a role in supporting longevity and the health of various organs, including the heart and brain. This antioxidant-rich compound may also support healthier aging by protecting DNA and limiting cellular senescence — a buildup of dysfunctional cells that can no longer replicate but remain in the body, causing harm and inflammation. 

One recent study found that both yeast colonies and aged mice treated with berberine had extended lifespans by 28% and 16%, respectively. The berberine-supplemented mice also showed significantly improved health markers at their old age, including thicker fur and better behavioral function. 

While we don’t know for sure if berberine supplements would also extend lifespan in humans, these initial results are promising and warrant more research. 

Supports Healthy Liver Function

Berberine has been shown to reduce an accumulation of fat in the liver, which is a well-known marker of poor liver health. In addition to lowering hepatic fat levels, berberine may also support liver health by encouraging a healthy inflammatory response and scavenging for harmful ROS and free radicals in the liver.

Clinical research supports these claims, as seen in a study of berberine supplementation in people with excess fat in the liver. After 16 weeks, those supplemented with 1500 mg of berberine per day experienced significant reductions in liver fat content, especially when paired with healthy lifestyle changes. The group with berberine supplements added saw a decrease in liver fat content by 53%, compared to a 36% reduction in the lifestyle modification group. Plus, the berberine group had significant improvements in metabolic health, as measured by body weight, blood sugar, and blood fat levels. 

Supports a Healthy Weight

With all of these reported mechanisms related to metabolism and inflammation, many people wonder about using berberine for weight loss. Similar to how berberine reduces fat in the liver, the compound may also support healthier body weight and fat levels.

Although becoming overweight or obese is multifactorial, inflammation and dysregulated glucose metabolism are both known to play a role — and, as we’ve seen, berberine may help to support these processes. In addition, berberine has been found to reduce adipocyte (fat cell) maturation by regulating the activity of specific genes involved in that process.

In a study with mildly overweight adults, those who took berberine for one month had reductions in body weight and increases in brown adipose tissue activity. Also known as brown fat, this type of fat tissue is more metabolically active and increases energy expenditure. Essentially, brown fat is a beneficial type of fat, and having more of it supports healthier body weight and metabolism.

Supports Brain Health

There are several potential ways that berberine may support brain health, including its role as an antioxidant and its ability to facilitate a healthier inflammatory response in the brain. 

Berberine can cross the highly selective blood-brain barrier and facilitate the clearing of dysfunctional neuronal proteins by inducing autophagy — our body’s way of removing damaged cells and cell parts. 

In a comprehensive review of 15 animal studies, berberine supported a healthier memory and inflammatory response. While we don’t know for sure if these results would translate to humans, the cell- and animal-based research is encouraging for using this compound to support brain health with age.

FAQs About Berberine Supplements

Now that we know all of the potential benefits of berberine, let’s dive into some frequently asked questions about berberine supplements. 

Can Berberine Be Harmful?

Berberine is generally safe in moderate doses, but higher or excessive doses may cause some issues. Berberine has a high potential to interact with other medications — especially those designed to lower blood sugar — so check with your health care provider if you’re unsure. 

Another potential side effect of high doses of berberine is gastrointestinal upset. Splitting it up into three doses, with meals, is a way to combat these effects. Although the dosage will vary by individual, the available research uses anywhere from 900 to 2,000 mg of berberine per day, split into three or four doses with meals. 

Is It Safe To Take Berberine Daily?

For most people, it is safe to take berberine daily. However, if you take medications for blood sugar, it’s highly recommended to talk to your doctor to find a dosage that is right for you. 

What Is The Best Time To Take Berberine?

Berberine is best utilized when taken with a meal or shortly after eating to ensure that the compound can support healthy blood sugar and lipid management. Plus, splitting up the dose can help to reduce any potential adverse gastrointestinal-related side effects, like upset stomach, cramping, and diarrhea.

Can You Combine Berberine and NMN?

The health-supporting effects of berberine can become even more pronounced when combined with NMN (nicotinamide mononucleotide). NMN is a precursor to NAD+ (nicotinamide adenine dinucleotide), a coenzyme that is vital to life but decreases with age. Another compound that can augment berberine’s benefits is resveratrol, a polyphenol and antioxidant-loaded compound found in red wine and grapes. 

Both NMN and resveratrol activate the expression of sirtuins, and both berberine and resveratrol activate the AMPK pathway. When taken together, this powerful trio works synergistically to facilitate pathways that support anti-aging, heart, brain, and metabolic health.

Key Takeaway: 

• The plant alkaloid berberine is rich in antioxidants and anti-inflammatory action, and it supports the AMPK pathway that regulates metabolism.
• Berberine is most well-known for its ability to support healthy blood sugar and lipid levels, supporting cardiovascular and metabolic health. 
• Berberine has also been studied for its ability to support liver function, brain health, and maintaining a healthy weight. 
• Combining berberine with resveratrol and nicotinamide mononucleotide (NMN) may further support health, as this trio activates several anti-aging and longevity pathways.

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