Can Berberine Live Up to the Claim That It's 'Nature's Ozempic'?

Lori Youmshajekian

Disclosures

July 12, 2023

Berberine, a plant-derived compound historically used in traditional Chinese medicine, is experiencing increased popularity thanks to social media, especially TikTok, where the hashtag #berberine has more than 75 million views at the time of writing. Social media influencers are promoting the compound, calling it "Nature's Ozempic," saying they lost weight taking the supplement.

Off-the-shelf berberine comes as a yellowy-orange powder usually encased in a capsule or mixed into tablet form. It's extracted from the roots, stems, and leaves of various plants, including goldenseal and barberry.

Its use is additionally promoted for insulin resistance, polycystic ovary syndrome, and even cancer, but medical experts are warning potential users that it lacks robust evidence to support its use.

"There's not that much data on it," says Reshmi Srinath, MD, director of the Mount Sinai Weight and Metabolism Management Program, New York, NY. "It's sort of shocking now that it's popped up into the media, to be frank."

In response to berberine's online popularity, the National Center for Complementary and Integrative Health issued a warning, stating that "there isn't enough rigorous scientific evidence to determine whether it is effective."

Overstated Claims, Lack of Scientific Research?

Other endocrinologists and weight management experts agree. "The claims are pretty overstated when it comes to the impact on weight loss, based on the evidence in the literature that's currently available," says Jaime Almandoz, MD, medical director of the UT Southwestern Weight Wellness Program, Dallas, Texas.

A review of 12 randomized controlled trials evaluating berberine's effects on obesity concluded that the treatment moderately decreased body weight. The trials included were conducted only over a few months, had small numbers of participants, and weight loss was not the primary outcome measure.

"There are few randomized controlled trials," says Ivania Rizo, MD, an endocrinologist at Boston University's Chobanian & Avedisian School of Medicine. "It appears that they all have some low quality of methods which essentially can lead to an increased risk of bias."

Another review, of 35 studies — most of them on animals and human cells and similarly underpowered — concluded that berberine showed promise for reducing blood glucose. A separate study found that berberine treatment actually increased the body weight and appetite of rats.

How exactly berberine elicits these effects is not entirely clear. Several studies point to its activation of AMP-activated protein kinase, which improves glucose tolerance in rats, as the mechanism for weight loss. Metformin, a drug used to improve glycemic control in people with type 2 diabetes, works in a similar way. Other researchers have hypothesized a link between berberine and the gut microbiome to explain its effect on type 2 diabetes and weight loss, though the clinical data to substantiate this link are shaky.

"I caution my patients about dietary supplements for weight management because we do not have high-quality data demonstrating efficacy," Katherine Saunders, MD, DABOM, an obesity expert and co-founder of Intellihealth, a platform for obesity management, said in an email.

Experimenting With Berberine

Despite the lack of substantial evidence supporting berberine's use for weight management and obesity, interest in the supplement seems to be increasing. One reason could be that lifestyle interventions aren't sufficient for most people with obesity to lose a significant amount of weight, with many requiring medical intervention, according to Saunders.

But access to treatment providers is limited. "As a result, it is not uncommon for individuals with obesity to experiment with dietary supplements like berberine," she observed.

Srinath, the Mount Sinai doctor, says many patients have asked for her thoughts on berberine as a weight loss supplement. "I say, you know, it's something you're welcome to try, but we don't have enough data at this time to recommend it."

The hype surrounding the supplement isn't all that surprising. About 42% of adults in the United States have obesity, according to 2019-2023 National Health and Nutrition Examination Survey (NHANES) data, pointing to a serious need for accessible drugs to address the condition. Berberine is available over the counter and is far cheaper than most of the newer US Food and Drug Administration (FDA)-approved drugs for weight loss.

Wegovy, semaglutide approved to treat obesity, can cost as much as $1300 per package; and Ozempic, semaglutide approved to treat type 2 diabetes, can cost more than $1000 per month. "That's a very steep price to pay," says Srinath.

Many insurance companies won't cover the drugs, curbing access to Americans who need them, says Almandoz. Federally sponsored programs such as Medicare and Medicaid also don't cover the drugs which are approved for obesity and weight management. "That's been a huge hole in our healthcare system," says Srinath. "That's sort of what's been driving interest in supplements and things like that."

Among adults trying to lose weight, only about 3% said they took prescription medication for weight loss, according to a report from the US Government Accountability Office. This report includes 2013-2016 data, predating Wegovy's approval for chronic weight management.

"These classes are notorious for being quite pricey and not well covered by insurance," says Almandoz. "It's easy to see why someone would promote something that someone may have more access to."

Comparing Ozempic or Wegovy with berberine can be misleading. Those drugs work by mimicking the effect of the hormone GLP-1 to help reduce appetite.

A clinical trial assessing the efficacy of semaglutide found that adults with obesity who took the drug for 68 weeks lost approximately 15% of their body weight in combination with lifestyle changes. The FDA approval was based on this trial and three others which showed similarly substantial reductions in weight.

The trials also document the many side effects of taking the drugs, primarily gastrointestinal in nature. The short- and long-term effects of berberine, on the other hand, are less clear. Some of the clinical trials reported diarrhea and stomach upset as the most common adverse effects.

Its perception as a naturally derived option for weight loss, though, might encourage people to overlook the potential interactions that berberine could have with other drugs, according to Almandoz.

He says clinicians considering natural products or nutraceuticals for patients should check for potential side effects and find reliable database sources to determine any potential medication interactions for patients. But the unregulated nature of berberine makes this challenging, Almandoz adds.

The dosage, formulations, and quality of berberine vary in each study and each product because supplements don't need to pass through the checks and balances of the FDA to land on shelves.

The lack of regulation could incentivize some companies to add stimulants to enhance any weight loss effect that the supplement may have. Those additives might interact with other health conditions or cause side effects like anxiety, says Almandoz.

Berberine should also not be taken during pregnancy or while breastfeeding, and it is unsafe for young children; in newborns and children, the supplement can cause higher levels of bilirubin in the blood, worsening any jaundice at birth and posing a greater risk for kernicterus.

Before they ask for berberine, Rizo urges patients to first ask for safe and effective interventions they can access. "I don't want to have people not use effective interventions that are currently available to them, and instead use something that needs to be better studied and needs to be better regulated," she says.

While the "Nature's Ozempic" catchphrase could be drawing in potential users with its dubious comparison, berberine's escalating popularity might also be a symptom of people seeking a quick fix, the experts worry.

"That's my fear," says Srinath. "'Let me get this medicine, let me lose the weight fast,' but at the end of the day, weight management is a long-term journey. It takes time, it takes effort, it is not easy, and there is no quick fix."

This is another concern for doctors; for people who've struggled with losing weight for years, not seeing results from berberine could feel like another failure.

"It will give them another opportunity to feel like they are being unsuccessful or that they are failing at weight loss again," says Almandoz. "It feeds into the hopelessness that many people with obesity have around their weight management."

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