It’s been called “nature’s Ozempic.” It’s touted for everything from fighting cancer to alleviating depression.
In this article, we’ll separate the marketing hype from the evidence-backed benefits. And we’ll look at the one instance where I recommend Berberine to my patients.
Table of Contents
- What is it? What are the claims?
- Sorting Hype from Demonstrated Benefits
- Metformin, Berberine, and Exercise
- Better Options
- References
What is it? What are the claims?
Berberine is a compound naturally found in several plants. It’s been used for centuries in traditional Chinese medicine to treat things like diarrhea. More recently, it’s drawn the interest of researchers for its potential in a wide variety of other areas.
It’s being investigated for its possible effects on blood sugar control, cholesterol levels, weight loss, cancer, and more.
Sorting Hype from Demonstrated Benefits
But what does the current research show? How much of this is hype and how much is grounded in solid evidence?
Let’s consider cancer first. In experiments, berberine has shown an ability to fight cancer cells in a petri dish of breast, colorectal, lung, prostate, and liver cancers [1]. It also seems to enhance the effectiveness of existing cancer treatments, in a petri dish [1].
But the research here is really early. It mostly involves seeing how cancer cells outside the body respond to berberine in the lab. Promising results at this level often don’t translate into effective treatments when tested in humans. For now, we need a lot more clinical evidence before we can get too excited.
We just lack the data.
Next, let’s consider berberine’s impact on blood cholesterol levels. Cholesterol is a worry because of how elevated levels of LDL cholesterol contribute to plaque build-up in our arteries and heart attacks.
We know from separate meta-analyses of over 200 prospective cohort studies and randomized trials including more than 2 million participants with over 20 million person-years of follow-up that the higher our LDL-c levels, the higher our risk of heart disease [2].
Research has found berberine acts on several levels to help. It reduces how much cholesterol from our food gets absorbed in the gut. It also has a dual impact on LDL receptors in the liver [3].
The liver is a key player in how the body regulates cholesterol levels. It has receptors that pull LDL cholesterol from the blood. Think of these receptors as little traps specifically built to capture molecules of LDL cholesterol. The more of these traps there are, the lower the levels of LDL cholesterol in the blood [4].
Berberine stimulates the liver to make more LDL receptors. At the same time, it reduces how much PCSK9 is made. This is a protein whose job is to break down LDL receptors [3].
So how much does this actually help in practice? A meta-analysis in 2018 looked at the results of 16 clinical trials. They found berberine reduced total cholesterol and LDL cholesterol, but the overall effect is relatively small. It also gave a slight boost to HDL (or good) cholesterol [5]. An updated meta-analysis in 2024 yielded similar results [6].
There’s a caution from the researchers in the 2018 analysis, though. They note there are issues with study quality. And different individual studies had wide variation in the results they found. This is a point we’ll return to later [5].
Unfavorable cholesterol levels are just one component of what’s known as metabolic syndrome. It’s a cluster of risk factors that increase our odds of both heart disease and type 2 diabetes. Other important ones are high blood sugar and obesity. There’s been excitement about berberine’s link to these two issues as well.
Consider blood sugar. One of the important effects of berberine is to activate AMPK [7].
AMPK is an enzyme that acts as a cellular energy sensor. It’s like a metabolic master switch. When it’s flipped on, it drives a set of processes to restore energy balance. Normal levels of AMPK keep our blood sugar levels healthy. Impaired AMPK function is an important contributor to type 2 diabetes.
This is one of the mechanisms for how metformin, a drug that I commonly prescribe at the clinic, works.
So how much can berberine help? A meta-analysis in 2021 looked at the effects of berberine supplements in patients with type 2 diabetes. Forty-six trials were included. They found berberine lowered HbA1c levels an average of 0.38 [8].
Let me explain what this means. HbA1c stands for hemoglobin A1c. Checking the level in our blood gives us a measure of the average blood sugar over the past 2–3 months. It’s given as a percentage. A normal level is generally less than 5.7%. Between 5.7% and 6.5% is pre-diabetic. Above 6.5% is considered diabetic. So berberine shaved 0.38% off HbA1c scores. This is borderline clinically meaningful in this context.
In the same analysis, berberine also reduced fasting glucose and the levels measured two hours after a meal [8]. Notice the language researchers use here: it “remarkably” reduced blood sugar levels 2 hours after a meal. In this analysis, this was the strongest effect. It compares favorably to the impact of metformin, which I prescribe every day to my pre-diabetic and type 2 diabetic patients at the clinic.
An intriguing pilot study pushed this even further. It put berberine and metformin head-to-head in a population with type 2 diabetes. Berberine outshone metformin in this trial, slashing HbA1c by 1.99% vs. 1.43%, fasting glucose by 3.78 vs. 2.80 mmol/L, and post-meal glucose by 8.78 vs. 7.67 mmol/L. It also cut triglycerides and cholesterol [9].
Does this mean it’s time to switch from metformin to berberine if we are pre-diabetic or have type 2 diabetes?
Not yet. Here’s why. These results are intriguing. But there’s a big difference between berberine and metformin when it comes to the quality of evidence we have, and this is important.
This is a point that’s often lost online when people compare metformin to berberine.
We have much larger trials with better designs and longer follow-up periods for metformin when compared to berberine.
For instance, we have a trial tracking the impact of metformin on the incidence of diabetes over 10 years with a group of thousands [10]. Compare that to the head-to-head trial of berberine and metformin we just looked at, which enrolled 36 people and lasted just 3 months [9].
Plus, that study is an outlier. The meta-analyses, which group the results of studies together, find a more modest impact for berberine. And the results of individual studies are all over the map.
We could say something similar about risk profile. From results so far, berberine appears to be safe. But we just don’t have the same level of long-term data to know for sure.
All this is why clinical guidelines recommend metformin for pre-diabetic and type 2 diabetic patients, not berberine. Metformin is well-established, effective, and safe. We’ll circle back to the one instance that I recommend Berberine to my patients shortly.
So let’s look at one last element of metabolic syndrome — obesity. Some influencers have been calling berberine “nature’s Ozempic” for weight loss. Is there any truth to this?
A meta-analysis in 2020 took a look at the data. It included 12 studies on berberine’s impact on weight loss. Berberine was found to reduce weight by 2.07 kg and BMI by 0.47 on average [11].
But a more recent meta-analysis, which included more studies, came up with a smaller number. It found the average weight loss was 0.84 kg, though it reached as high as 1.63 for one subgroup [12].
That’s a relatively small effect. For comparison, let’s look at the real Ozempic (or semaglutide). A large randomized controlled trial found the average weight loss over 68 weeks was 15.3 kg. The effect size here is dramatically larger [13].
So for patients who are looking to lose weight, I prescribe GLP-1 meds in addition to a great diet and regular exercise.
Metformin, Berberine, and Exercise
So far I’ve focused on berberine’s impact on people who are pre-diabetic or have type 2 diabetes. But what about others? Something that intrigued me about the initial data on metformin was its potential benefits for non-diabetics. The same question arises for berberine. So let me explain what I was intrigued about and what the data shows.
The key promise was connected to aging. Remember how metformin boosts AMPK, like berberine does? It was thought this could extend lifespan. But the research since the initial promising results has been disappointing. Metformin failed to extend lifespan when it was tested by the Interventions Testing Program [14].
And in humans, when the Diabetes Prevention Program tested metformin in high-risk, but non-diabetic individuals, there was no benefit compared to a placebo for cancer rates, cardiovascular disease, or all-cause mortality over the 21-year follow-up period [15].
In other words, the evidence available today doesn’t suggest metformin counters the effects of aging. It just helps prevent diseases that cause early death. That’s why it makes perfect sense for pre-diabetics or people with type 2 diabetes to take it. It’s also why it doesn’t make sense for someone without the conditions it targets to use it as a supplement.
More troubling, we now have evidence that metformin can have negative impacts as well. And we’ll look at the Berberine data shortly, as well as the instance where I recommend Berberine. In a 2019 study where both groups were exercising, the people who took metformin improved their cardiovascular fitness by only half as much as those who took a placebo [16].
That study was backed up by a 2022 study showing the same thing. Metformin use reduced the improvements in how well the body can use oxygen during exercise by half [17].
One additional problem is that metformin also lowers testosterone levels [18].
So does berberine fare any better? Here the evidence is severely limited. But it looks like we’ll run into similar issues when it comes to exercise. A basic problem is this: when AMPK is ramped up, it acts to conserve energy in the body. One of the key ways it does this is to dial back making proteins. But this is essential to muscle growth. So stimulating AMPK can limit muscle gains.
Do we have evidence of this when it comes to berberine? We are severely limited, but one study looked at the effects of berberine in mice. Berberine decreased protein building and led to a reduction in muscles [19].
On the other hand, a very recent study in mice found a quite different result. Here berberine helped prevent muscles from shrinking. But this was in obese mice [20].
So like metformin, there are benefits for pre-diabetics and those with type 2 diabetes. Otherwise, it may be counterproductive.
This is why I elected not to include Berberine in MicroVitamin. For otherwise healthy people, I don’t want to risk lowering exercise performance or testosterone levels.
Better Options
Instead, here’s what I tend to prescribe in my clinic, and where Berberine fits in.
I need to say upfront that we always address lifestyle factors like exercise and diet. Getting those things right makes a huge difference. But we sometimes find we need additional help to treat metabolic syndrome and diabetes. And that’s when medications have an important role to play.
For controlling blood sugar, the first-line medication is metformin. It’s well-established, it works, and it’s very cheap.
This may be changing soon, however. GLP-1 medications like Ozempic have a powerful lowering effect on blood sugar. The downside is that they’ve been relatively expensive. But as costs come down, we may see these replace metformin as the first-line go-to diabetic treatment.
For now, however, GLP-1s are definitely the first choice for aggressive weight loss. They’ve been a game changer in helping patients achieve and sustain a significant drop in their BMI.
What about when it comes to cholesterol? Here the initial treatment for elevated levels is typically low-dose hydrophilic statins like rosuvastatin 5 mg or pravastatin 20 mg. Sometimes, patients are intolerant to statins or their cholesterol isn’t reduced enough. That’s when we’ll look to add other medications like Ezetimibe. Just like rosuvastatin, Ezetimibe is very cheap.
Failing that, we move to PCSK9 inhibitors and the new medication called Bempedoic Acid.
PCSK9 inhibitors are very expensive, and Bempedoic Acid is under patent. And here’s where Berberine may play a role.
If a patient is intolerant to statins, Ezetimibe isn’t quite cutting the mustard, and it’s not a financial option for PCSK9 inhibitors or Bempedoic Acid, adding Berberine can be considered as a last resort.
It’s a last resort because the cholesterol-lowering effect is much smaller compared to the other medications we have available. Plus, we don’t have outcome data for Berberine. We know that statins, for example, lower the rates of heart disease compared to a placebo [21]. But we don’t have that same data for Berberine.
References
Below are the references cited in the order they appeared:
1. https://onlinelibrary.wiley.com/doi/10.1002/jbt.70073
2. https://pubmed.ncbi.nlm.nih.gov/28444290/
3. https://www.uptodate.com/contents/lipid-management-with-diet-or-dietary-supplements
4. https://www.ncbi.nlm.nih.gov/books/NBK519561/
5. https://pubmed.ncbi.nlm.nih.gov/30466986/
6. https://pubmed.ncbi.nlm.nih.gov/39640489/
7. https://www.sciencedirect.com/science/article/pii/S266703132100052X
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC8696197/
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC2410097/
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC3135022/
11. https://pubmed.ncbi.nlm.nih.gov/32690176/
12. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1013055/full
13. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
14. https://pmc.ncbi.nlm.nih.gov/articles/PMC5013015/
16. https://pmc.ncbi.nlm.nih.gov/articles/PMC6351883/
17. https://pmc.ncbi.nlm.nih.gov/articles/PMC9321693/
18. https://pmc.ncbi.nlm.nih.gov/articles/PMC8740051/
19. https://pmc.ncbi.nlm.nih.gov/articles/PMC2911075/
20. https://pubmed.ncbi.nlm.nih.gov/39930016/
21. https://www.cochrane.org/CD004816/VASC_statins-primary-prevention-cardiovascular-disease
Note: This article is for informational purposes only and is not a substitute for professional medical advice. Always consult with a qualified healthcare provider regarding your individual health needs.
