Berberine: Thin Body, or Thin Evidence?

by Brian Dunning
August 29, 2023

Let's say you're on the Internet, and say you're browsing around seeing if there's anything new in weight loss. Maybe there's a new diet, a new exercise, or something you might be able to try. Well, if you do that these days, one of the things you're liable to stumble upon is berberine, a natural compound touted as Nature's Ozempic; Ozempic being one of the hot-ticket weight loss pharmaceuticals on the market right now. It all sounds pretty promising! A natural version of a hot product, no doctors or prescriptions needed, that you can go right out and buy today? It sounds too good to be true. Well, maybe it is, maybe it isn't. Today we're going to find out.

First let's take a quick look at Ozempic. Ozempic, and another drug called Wegovy with the identical active ingredient, contain semaglutide. Semaglutide mimics a hormone called GLP-1 that tells your brain that you're full, making you want food less; this also slows your digestion and causes food to stay in your stomach longer, thus making you actually literally full, and you're often unable to finish a complete meal. Ozempic was originally approved to treat type 2 diabetes, while Wegovy is approved to treat obesity. Although the dosages are slightly different, in practice both drugs treat both conditions; it's just that one is approved for one and the other is approved for the other.

So let's now have a look at berberine. Is it indeed a naturally occurring version of Ozempic? Is berberine a GLP-1 receptor agonist? Well, let's see. It is a naturally occurring compound found in a number of plants, including the barberry, goldenseal, and the Oregon grape. Chemically, it's an isoquinoline alkaloid, and in the past it's been used as a yellow dye. If none of this sounds like it's a GLP-1 receptor agonist, that's because it's not. Some naturopaths and other alternative practitioners have tried to sidestep this by claiming that berberine may enhance the body's natural production of GLP-1, but there's never been either evidence or biochemically plausible basis for this. Chemically, berberine and semaglutide have nothing to do with one another. Pharmacologically they're about as different as two compounds can get. So we have one answer very early in this episode: No, berberine is not a natural form of Ozempic, not remotely, not even a tiny bit. Berberine does not mimic GLP-1, and does not have any of the effects that Ozempic or Wegovy might have.

Firm no. Hard pass. Next question.

While it's one thing to establish that berberine doesn't do what Ozempic and Wegovy do, that says nothing about the larger and more important question: Does it help you lose weight, perhaps through some other mechanism?

According to countless videos and influencers on TikTok and other social media, berberine does cause you to lose weight, but it also treats just about everything else. Influencers say berberine treats high cholesterol, insulin resistance, and more. On the websites of companies selling berberine supplements, I found:

• Increases energy levels
• Improves cardiovascular health
• Supports your immune system (of course, one of the classic standbys)
• Promotes gastrointestinal microbial balance
• Regulates cholesterol levels
• Healthy aging (whatever that means)
• Decreases abdominal fat and waist:hip ratio
• Helps your liver metabolize fat
• Promotes healthy skin
• Promotes hormone balance, like insulin and testosterone

These are from only two web pages; I'm sure I could easily find more. But note that really none of these are claiming to treat a disease or a problem. They are the usual vague "wellness" claims — and we run into a familiar bit of nonsense, which is the entire concept of wellness. If there's nothing wrong with you, you're healthy, by definition; a supplement can't make you healthier than healthy. Health is the absence of disease. And, in the absence of disease, you've nothing to treat. The only reason to take any "wellness" supplement would be in hopes of achieving Super Health, Weller Than Well, Less Than Zero Disease. Be skeptical.

So, how can we find out if berberine actually provides any useful pharmaceutical benefit for people who are suffering from some condition? One way is to search public health databases to see what papers have been published about berberine, and to see what clinical trials might be underway to study its usefulness.

Unsurprisingly, much of what you will find is published by naturopaths or other alternative practitioners, and the bulk of it comes out of China, where berberine is considered a part of traditional Chinese medicine. I did find two meta analyses of many studies that tried berberine as a treatment for a variety of conditions, including type 2 diabetes and obesity. Both studies found a statistically significant benefit from using berberine for weight loss.

And here is where we find out exactly what statistical significance means. On average across all of those studies that looked at berberine for weight loss, study participants dropped an average of one quarter of a point of BMI (body mass index, one popular metric for obesity). That equates to roughly two pounds of body weight or a bit less, depending on your height and weight for a typical large, chunky person. And this is without any context: what else was being done for these participants? Did they exercise? Did they diet? How was it managed? What was the dosage and for how long did they take it? Things like that were different in all the studies.

By contrast, people on a prescription regimen of semaglutide (Ozempic or Wegovy) lose an average of 4.61 BMI units in a year. That's 18 times as much weight lost, or for our hypothetical large chunky person, almost 40 pounds. When someone drops 40 pounds, you notice it. When someone drops 2 pounds, on the other hand — well, most of us fluctuate that much just during a normal day without it being noticeable. Statistical significance, at least in this case, still doesn't even mean noticeable, and is certainly not the results that anyone who takes berberine for weight loss is hoping for.

Unlike a lot of supplements that people take, berberine is actually pharmacologically active. It does interact with your body biochemically, and can make things happen. That means that it has side effects, and it also means that interactions — potentially dangerous ones — are possible. Nausea and diarrhea are the most common side effects (paradoxically, attempting to treat diarrhea is one thing some people take it for), but it's when you're already taking other medications that the real problems arise. Metformin is another drug that some people with diabetes take, and it's also prescribed more and more often for weight loss. Someone thinking they might wish to turbocharge those effects by taking berberine on top of their metformin, could be asking for real trouble with a severe drop in blood sugar.

Cyclosporine is one immunosuppressive given to some transplant patients to help prevent organ rejection, which requires very carefully balancing the immune system to not attack the transplant, but to also continue attacking the other bad things your body wants it to. Studies show that berberine can increase the effects of cyclosporine, thus suppressing the immune system more than is wanted, leaving the body vulnerable to all manner of infections, which can be lethal for a transplant patient.

Beyond causing drug interactions, berberine is also actively counterproductive to some things that people take it for, which is what can happen when you get your medical recommendations from TikTok. Some people take it for the vague wellness promise of "improved gastrointestinal flora" or some such thing. In fact, one thing that berberine is actually decent at is as an antimicrobial. Meaning it might just kill whatever flora you have in your gut that you're trying to improve the wellness of. This is actually why berberine causes diarrhea: kill your gut microbes, end up with a bad case of the runs.

Also pregnant and breastfeeding mothers, and also newborns, should definitely not take berberine for anything. Berberine can cross the placenta, and what it might do to the fetus is something we don't have a lot of data for. There is some anecdotal data that berberine may cause a type of brain damage called kernicterus in young children, so it's probably best to avoid it altogether in those situations.

However, berberine may not be all bad. As it is pharmacologically active and can do things, it continues to be studied in three main areas:

1. Some data indicates that it can lower cholesterol, specifically, LDL (the "bad" cholesterol), and thus your total cholesterol. How much? Not clear yet. As well as existing medications? Still don't know.
   
   
2. It may still be a treatment for type 2 diabetes. Data is still very preliminary, but some of the most promising shows that berberine may be as effective, or nearly as effective, as metformin at controlling blood sugar in diabetics. Research is definitely ongoing.
   
   
3. It may help women with PCOS (polycystic ovary syndrome) fight the insulin resistance that often comes along with it.

It's important to stress that all of this is fairly preliminary, and more study is needed before we can say that berberine does have some medical potential. And even if it does turn out to work as well or better than established drugs, we'd still need to do the drug development work to establish doses and treatment courses, and all the stuff that goes into finding an effective treatment regimen. You don't just go buy supplement pills off the shelf that are of unknown doses and purities and swallow them.

That best case scenario is that berberine — like all of the many natural compounds that eventually form the basis of some medical treatment — might one day become a treatment for some bodily dysfunction. As the concept of a wellness supplement — the promise of fixing something when there's nothing to fix — is fundamentally a marketing scam, don't look to berberine for any supposed wellness benefits.

I do want to make one final point that is, I don't think, mentioned often enough in articles debunking miraculous claims for certain supplements and alternative therapies, and that's that in all probability, a normal person taking a normal amount of berberine for any of the usual reasons is very unlikely to have any ill effects. It's probably not going to do you any harm. Nevertheless, you're getting no known benefit, and you're taking a nonzero risk; so there truly is no compelling argument to be made for why you should spend your money on berberine supplementation. Maybe one day this will no longer be the case, and some berberine formulation will be found to have some medical value for those suffering from some defined condition. But that day is not today. Save your money.

By Brian Dunning
Follow @BrianDunning