What is berberine, and who should take it?

Research suggests the botanical-based supplement berberine affects insulin and glucose, so is it worth taking for better metabolic health?

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Berberine has been used as a natural botanical remedy for thousands of years, but it’s recently experienced a surge in popularity thanks to social media users who have dubbed it “nature’s Ozempic.” (Ozempic is a popular GLP-1 receptor agonist weight loss drug.) And while preliminary studies on berberine’s effect on weight loss are pretty thin, more robust research suggests it can benefit blood sugar, blood pressure, and cholesterol levels.

Research suggests it has some similar mechanisms of action in the body to the Type 2 diabetes drug metformin—and some functional medicine physicians think supplementing could be beneficial.

However, the body of scientific research on berberine is still thin, and supplementation can lead to side effects. Below, we cover berberine’s potential pros and cons and who should consider taking it.

What is berberine and how does it affect metabolic health?

Berberine is a deep yellow compound that may be derived from the roots, stems, and bark of plants such as Indian barberry, Chinese goldthread, goldenseal, and Oregon grape (most berberine supplements on the market feature an extract of Berberis aristata, or Indian barberry). Traditionally, plants containing berberine were used in Ayurvedic medicine and traditional Chinese medicine for various ailments, from treating gastrointestinal disorders to promoting wound healing. In China today, berberine is often used as an adjuvant therapy (i.e., used in addition to typical treatments) for Type 2 diabetes, high blood pressure, and high blood lipids.

Unlike some drugs and supplements with one or two mechanisms of action, berberine appears to interact with multiple targets in the body, impacting a range of physiological processes and conditions.

Are berberine supplements safe?

Berberine supplements appear relatively safe for most adults in doses up to 1.5 grams (1,500 mg) per day for up to 6 months. However, it should not be taken by children or by pregnant or breastfeeding women. Side effects are generally mild and may include diarrhea, constipation, gas, and upset stomach.

Berberine may cause unwanted side effects when combined with many medications. For example, when combined with antidiabetes drugs like metformin, berberine may cause blood sugar levels to dip too low. Berberine may also interact with medications, such as cyclosporine, dextromethorphan (Robitussin DM), blood pressure drugs, anticoagulants, and others. If you take medication, always consult with your doctor before taking berberine.

Like all supplements, berberine supplements aren’t regulated for safety or effectiveness. So choose one that is third-party tested by an independent organization such as NSF International or U.S. Pharmacopeia (USP) to ensure it contains the ingredients listed on the label in the correct quantities and that it doesn’t contain unsafe levels of contaminants. Pure EncapsulationsThorne, and Integrative Therapeutics are established brands that offer third-party testing on some of their products or processes (check the label to see if a given product has it).

While more high-quality clinical trials are needed, here’s what the research to date suggests about berberine and metabolic health.

How berberine impacts health

Insulin resistance, blood sugar, and Type 2 diabetes

Berberine is most well-studied for its beneficial impact on blood glucose and Type 2 diabetes. Research suggests it may support healthy blood sugar levels through a variety of mechanisms, such as improving insulin sensitivity and increasing insulin secretion.

Insulin is a hormone secreted by the pancreas that allows glucose to enter cells. Insulin resistance—when cells become less responsive to the effects of insulin due to factors like chronically elevated blood sugar, physical inactivity, and obesity—initially causes the body to pump out more insulin to compensate. But over time, insulin-producing cells wear out and can’t produce enough insulin, resulting in elevated blood glucose and, eventually, Type 2 diabetes.

Berberine has been shown to boost glucose uptake from the bloodstream and improve insulin sensitivity—in part by enhancing the activation of a metabolism-regulating pathway called AMPK. When activated, AMPK triggers the movement of GLUT4 glucose transporters to cell membranes in skeletal muscle, where they can help usher glucose inside cells to be broken down for energy. Typically, GLUT4 translocation requires insulin, but when AMPK is activated, this can occur independently of insulin. Additionally, research suggests that AMPK activation reduces insulin resistance through various mechanisms, such as lowering inflammation, lowering oxidative stress, and promoting the survival of insulin-secreting pancreatic beta cells. (Besides berberine, exercise and caloric restriction also activate AMPK.)

One small clinical trial found that supplementing with 500 mg berberine three times a day for three months resulted in a 36% reduction in metabolic syndrome, as well as increased insulin sensitivity. Additionally, a 2023 research review on women with polycystic ovarian syndrome (PCOS)—a condition strongly associated with insulin resistance and infertility—found that berberine supplementation appeared to reduce insulin resistance, reduce androgen (male sex hormone) levels, and support healthy ovulation.

Berberine may also help keep blood glucose in check via other mechanisms, such as reducing gluconeogenesis (glucose production by the liver), stimulating glycolysis (metabolism of glucose for energy), promoting insulin secretion, and reducing intestinal glucose absorption.

For the reasons above, berberine is often compared to the antidiabetic medication metformin, which regulates blood glucose by decreasing glucose production by the liver, decreasing glucose absorption by the intestines, and increasing glucose uptake by muscle cells by activating AMPK. In a 2021 systematic review, berberine showed comparable effectiveness in lowering blood glucose to metformin—and when used in combination with standard diabetes therapies, berberine improved HbA1c, fasting blood glucose, and glucose tolerance.

Weight and body composition

Berberine may have a modest impact on body weight and body composition—one small study found that people taking 750 mg of berberine for three months experienced a 3.4-pound weight loss, on average, while another study found that 500 mg of berberine three times a day resulted in a 3 cm decrease in waist circumference for women. Some experts suspect these changes are due to berberine’s ability to improve glucose uptake and insulin sensitivity since insulin resistance (specifically, elevated insulin levels) is known to promote weight gain and fat accumulation. Additionally, activation of AMPK stimulates catabolic processes like fat oxidation and has an appetite-regulating effect.

Cholesterol and blood pressure

Berberine may also support cardiovascular health. A 2018 systematic review and meta-analysis found that berberine significantly reduced total cholesterol, LDL cholesterol, and triglycerides and increased levels of beneficial HDL cholesterol. Research suggests berberine helps improve blood lipids through several mechanisms: Berberine increases the expression of LDL receptors on the liver, which clears LDL from the bloodstream and thereby lower circulating LDL levels (this is one way statin drugs help lower cholesterol); and it reduces expression of an enzyme called PCSK9 that would otherwise tag LDL receptors in the liver for degradation. The activation of AMPK also inhibits the body’s production of triglycerides and cholesterol.

Berberine has anti-inflammatory and antioxidant effects that support healthy blood vessels, too. Additionally, some sources suggest that berberine in combination with the blood pressure-lowering medication amlodipine may reduce blood pressure more than medication alone, and a clinical trial on adults with metabolic syndrome taking 500 mg of berberine three times a day resulted in decreased systolic blood pressure (along with other metabolic improvements, like lower triglycerides and blood glucose and improved insulin sensitivity). However, other research suggests the relationship between berberine and blood pressure is inconclusive.

Gut health

While it’s hard to determine the exact molecular mechanisms of berberine’s potential health benefits, some research suggests that it may act, in part, by influencing the gut microbiome. For example, research suggests that berberine may positively impact gut bacteria that produce short-chain fatty acids (SCFAs) such as butyrate, which help regulate inflammation, and bile acids, which help regulate cholesterol and triglyceride levels. The gut microbiome of people with obesity also tends to have a higher ratio of Firmicutes to Bacteroidetes (two phyla of bacteria) compared to people without obesity—and some evidence suggests that supplementing with berberine can restore microbial balance by lowering levels of Firmicutes and increasing Bacteroidetes.

In addition to benefiting the microbiome, berberine has been traditionally used in Chinese medicine to treat diarrhea and other GI distress. A recent review of randomized control trials found that berberine did lead to quicker recovery from diarrhea in children and adults, but the researchers called the evidence “promising but inconclusive.”

Do Any Foods Contain Berberine?

Berberine is not found in any common food sources. As mentioned, it’s derived from the roots, stems, and bark of plants such as barberry, Chinese goldthread, goldenseal, tree turmeric, and Oregon grape. Therefore, if you try berberine, it’s best to get it from a supplement.

Who Should Consider Taking Berberine?

Berberine is not an essential micronutrient like vitamins and minerals, so there’s no required intake. But based on the existing research, berberine may benefit people trying to improve insulin sensitivity and regulate blood sugar, lower cholesterol, or improve another aspect of their metabolic health. This might include people with prediabetes, T2DM, hyperlipidemia, PCOS, and other conditions—particularly if they don’t tolerate standard treatments. For example:

  • According to an international panel of experts, berberine may benefit patients with mildly elevated cholesterol who don’t tolerate statins or who have metabolic syndrome.
  • Berberine may be beneficial for T2DM patients who don’t tolerate metformin, according to the authors of a 2022 research review.

That said, by itself berberine is not a magic bullet for any condition, and pairing it with dietary and lifestyle changes is probably necessary to yield any significant improvement. And if you are currently on medication, talk to your doctor about potential interactions before taking berberine.

How Much Berberine Do You Need?

There’s no official recommendation on how much berberine to take. The dose commonly used in research studies that yields positive results is 500 mg of berberine three times a day, timed with meals. Experts like Elizabeth Bradley, MD, a functional medicine specialist at the Cleveland Clinic, support this type of berberine dosing schedule. Dividing your berberine dose throughout the day helps keep blood levels stable since berberine has a relatively short half-life and would otherwise be cleared from your system in a few hours. She recommends starting with 500 mg per day to see how you feel before working your way up.

Of course, these are general suggestions. It’s important to understand that dosing varies based on individual needs. So, work with a medical professional to determine the best dose for you.

 



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