Aidan:
And welcome to the Ideal Nutrition podcast. My name is Aidan. I’m here with my co-host, Torwen. And this is episode 249. We’re going to be talking about berberine and doing a bit of a deep dive on it.
Torwen:
Berberine is a naturally occurring compound, particularly an alkaloid, found in several plants. These include goldenseal, barberry, Oregon grape, and tree turmeric. It is pretty well known in traditional Chinese and Ayurvedic medicine. However, recently it has increased in popularity a little bit.
It is known as Nature’s Metformin. What it does is activate an enzyme called AMPK. That plays a key role in energy metabolism and blood sugar. It increases glucose uptake into cells. It suppresses glucose produced in the liver. And also improves insulin sensitivity by reducing inflammation and lipid accumulation.
Metformin does similar things. This is why people have started saying that it’s Nature’s Metformin.
Aidan:
And in addition to that, from a cholesterol standpoint, it kind of upregulates LDL receptors on liver cells. That is how it plays a role in that too. Then, as you said, there’s a few mechanisms around inflammation. So yeah, I also think it’s interesting when we consider switching something from alternative to Western medicine, so to speak.
One of the key distinctions is consistent evidence in randomised controlled trials and stuff like that. That’s when it kind of tends to make that switch over. It also becomes kind of an accepted option here. However, we will talk about all the research and support for or against it as well.
Torwen:
Let’s start with diabetes then. Research does seem pretty positive across the board in diabetes. Specifically, this makes a lot of sense because of the mechanisms relevant for insulin sensitivity and glucose metabolism. The potential for berberine to lower blood glucose has been tested in a study by Zhang et al.
In that study, 116 participants with type 2 diabetes and dyslipidaemia were either allocated to a placebo or berberine. They took a one gram daily dose of berberine for three months. They then assessed changes in plasma glucose and serum lipid concentrations.
The one gram of berberine per day group found a reduction in fasting blood glucose levels of around 20%. They also found reductions in HbA1c.
Aidan:
Yeah, so that’s super promising. That was also the first study I read on it as well. Obviously, with any kind of thing like this, you can be like, that is just one study. It’s promising, but should we recommend it? We fortunately have heaps more than just that as well. There’s a review looking at 37 relevant studies.
It found that it consistently helps with the management of diabetes. It all kind of lined up with that. So it actually is an area where the research seems pretty consistent.
Torwen:
In terms of cholesterol, it has also been proposed to reduce cholesterol by inhibiting PCSK9 specifically. That is a protein that normally helps destroy LDL receptors on liver cells. So when there’s less of this activity, more LDL receptors end up surviving. That means they allow them to be pulled out of the bloodstream for clearance.
The study I just mentioned also looked at blood lipid concentrations. In the group taking one gram a day of berberine, triglycerides, total cholesterol, and LDL cholesterol were all lowered. That’s pretty significant.
Aidan:
Yeah, in terms of average numbers seen across the research, I’ve included this in the show notes as always. There was a review that found the average drop across a lot of studies looking at this. That makes the assumption they had elevated cholesterol at the start. The average drop was 0.5 millimole per litre for total cholesterol.
There was a 0.4 millimole per litre drop for LDL cholesterol. It was 0.3 for triglycerides. Then there was a small increase in HDL as well. It’s just pretty good news across the board.
Torwen:
In terms of weight, that’s another interesting one because it has similar effects to something like metformin. People are comparing it to weight loss medication and how it can support that. And it has been seen that it potentially could help. The question is whether or not it’s better than other weight loss medications.
Aidan:
I’ve got a lot of thoughts on this. Like how you referred to it as Nature’s Metformin, the TikTok trend I’d been seeing was Nature’s Ozempic. When we’re looking at weight loss, that kind of makes it an even bolder claim.
If we look at research on metformin and weight loss, we often do see small, consistent weight losses. It is emphasis on small. That’s probably what you would expect from a lot of things. That is if the mechanism is related to insulin and glucose. Fortunately, again, we do have research looking at this. Probably the most famous study looking at this had about 80 participants. They compared berberine versus placebo for three months.
The average weight loss was around 1.5 kilos. And the thing that stands out to me most is this. We do a lot of research and prep for these podcasts. I read a lot of research. I listen to podcasts. I read a lot of general articles to see what people are saying. The amount of times I opened a general article and saw hyperbole about berberine for weight loss was huge.
They cited research. This was the one that was cited. And they’d use really strong words, like really powerful for weight loss. Then you read the thing and it’s like 1.5 kilos. What are we talking about here?
Torwen:
That’s not so significant. We know other weight loss medications can support 10 to 20% of body weight. That is much larger than just 1.5 kilos.
Aidan:
It’s absolutely not an equivalent. Looking at a broader range of studies, the average weight loss seems to be about two kilos. So it does fall into that category of small, consistent improvements. I wouldn’t rule it out for this. However, I do have a caveat that I want to add here. There are quite a few options that potentially cause nausea or GI issues.
People report one to two kilos. Well, it’s not report, sorry. The measurements come out as one to two kilos. And that is a common side effect of berberine as well. There’s a lot of GI issues that occur. I might add some context around that later. I wouldn’t be shocked if that plays some role in that one to two kilo drop as well.
Torwen:
Moving on then, should we have a chat about non-alcoholic fatty liver disease? Or, as it’s now known, metabolic dysfunction-associated steatotic liver disease? That is an absolute mouthful. We’ll go with M-A-S-L-D. In terms of this, when it comes to berberine, the research is, again, pretty encouraging.
It might even be better than looking at just weight loss on its own. I had a look at a 2024 meta-analysis. It compiled 10 randomised controlled trials and looked at over 800 participants. The results all showed some pretty meaningful improvements. They found reductions in liver enzymes.
These included ALT, AST, and GGT. We normally look at those as markers of liver health. That, along with improved insulin sensitivity and potentially a bit of supported weight loss, is pretty positive for MASLD.
Aidan:
Absolutely. And when I was looking at this, that stood out really clearly. What I was curious on is this. Is there a decrease in fat in and around the liver? Is it more so than what you’d expect from one to two kilos of weight loss? From the research that we do have, it does seem like that is the case.
However, it’s a bit too early for me to have a strong take on it. It does seem to be hard to spot reduce fat anywhere. So I’m not going to claim berberine is magical for that. However, what we have looks promising there too.
Torwen:
How to take it. Do you want to start with this one?
Aidan:
Sure. Gold standard, it seems very consistently to be around 500 milligrams three times per day. That is approximately 30 minutes before meals. It also has a relatively short half-life. It typically peaks in the blood somewhere between one and four hours. This is another factor as to why we’d be doing it multiple times per day.
Torwen:
And before meals as well. Weaving into that too, it is a relatively poorly bioavailable substance. That means taking it pre-meals, as well as splitting the doses, actually does help improve absorption. I think I read somewhere that it’s around 1% absorption, potentially. That is low for a supplement.
Aidan:
Yeah, I think that’s one small factor in why it’s not super popular. It’s very easy to dismiss it because the bioavailability is super low. I did go deep looking at protocols and how you can improve that. It really does just seem like the timing of meals is the simplest and easiest way. That seems to really move the needle on that.
The other sense I do have on this, though, is this. All the research we’ve spoken about is occurring despite the bioavailability being super low. It’s almost like, if you forgot about that, and didn’t pay attention to the bioavailability, these benefits are still existing.
Torwen:
I did read a few things that might come out in the future. That was about whether they can combine berberine with other substances to improve the bioavailability. That would be huge. However, I think there needs to be a little bit more research in that space first.
Aidan:
Yeah, absolutely. Another thing we had on our list was whether the supplements contain what they say they contain. I don’t know where I got this before we even started prepping. This is a pretty common theme, particularly with less common supplements. A US study from 2017 found that the average berberine content was about 75% of what the label listed.
Their standard allowable percentage discrepancy is anywhere between 90 and 110%. So 75% obviously falls outside of that. And 60% of the products tested would have failed to meet that standard. Hard to say whether this is a big deal or not. Then it raises the next question of what has been used in research.
Have they been using products that contain 75% of what the label listed? Or are they using completely accurate products? I don’t know the answer to that question. However, I still think it’s interesting to know this. Many times, you could purchase this and it has noticeably less berberine than expected.
Torwen:
So if you’re listening along, we want to chat about why it may not be as popular. That is despite it seemingly having so many positive advantages for overall metabolic health. So, one of my thoughts, which I’d mentioned before, is common side effects. Gastrointestinal symptoms like diarrhoea, nausea, and constipation tend to happen. That can occur even at the standard dose of 1.5 grams a day. That can be a pretty big barrier for people wanting to use substances like this.
Aidan:
Absolutely. In terms of frequency, it seems to be about 15 to 35% of people experiencing that. Particularly the higher up you get with this, the more you can see why people wouldn’t be interested. Maybe it’s having the positive effects, but you don’t want to feel that way as well.
Torwen:
I also think the dosing can be kind of inconvenient for people. Having to take a supplement three times per day before meals can be hard. That is especially true if people aren’t having consistent regular schedules. So that’s just another barrier. Maybe that is why people are not taking it.
Aidan:
Yeah, I don’t know how people who listen to this will perceive that. I think that is a huge factor myself. As somebody who cares a lot about nutrition, sometimes I’m like, well, if a protocol helps, just do it. Something that really shifted my perspective was in 2016. I did a systematic review. I didn’t publish it. It was part of university. It was my project, whatever research project, on calcium and vitamin D supplementation.
Something that massively stood out to me was this. A lot of calcium supplementation studies didn’t noticeably reduce the risk of fractures. That is what I was measuring in elderly populations. If you did a subgroup analysis, and took the people who actually took the supplements, it looked much more promising.
That was compared to intention to treat. That is the people enrolled in it and doing it to a certain standard. The thing with calcium supplementation that stands out is this. You have to take it twice a day. You can’t absorb it fully well at those dosages if you’re having it once. It just really stood out to me, being like, damn.
You get anyone to do anything twice a day and the odds drop off a cliff. The same thing happens with three times a day. So whether my own personal opinion or anything like that, I’m like, this protocol’s not that hard. You just take it, I think, three times a day. It doesn’t really matter. People really do struggle with this. It actually is a big handbrake.
Torwen:
Wonderful. Well, let’s wrap. Anything else you want to add?
Aidan:
I do have one more thing. It’s just the practical kind of thing. Do you ever recommend berberine to people? We’ve just gone through a bunch of research.
Torwen:
Honestly, no. Before we decided this was going to be a topic, I had heard about berberine, but not massively. I think, yeah, it’s not something that I have recommended. However, potentially, if it can help with so many different things, why not give it a try?
Aidan:
Yeah, it is an interesting one. Even just the cholesterol thing. How many people do we work with who have high cholesterol? It’s tricky because there are so many things we can do that can help. It’s always a bit hard to choose. Where I typically stand on berberine with people is this. If I have somebody willing to do a lot of things. They’re always like, more, more, more. What else can I do? I do sometimes think this could be an easy thing that we add in.
Let’s just try it and monitor to see if we are getting GI issues or anything like that. And I’m even more likely to lean towards it if some other options are off the table. I actually had something I was going to come back to. I realised I like to put it in bold in my notes. I kind of skipped over it earlier. That is kind of on that example. It’s a bit of a shame here. However, gestational diabetes, I actually care about this way more than you’d expect.
I did a placement in a gestational diabetes clinic. It made me way more passionate about it than you’d think. I had a really good supervisor too, which probably played a role. In gestational diabetes, unlike type 2 diabetes, you often don’t have the lever of losing weight. That won’t necessarily make you more sensitive to insulin. In many cases, they’ll become more resistant to insulin as pregnancy goes on, right?
Obviously, there are things you can do with your nutrition. However, you can’t just lose weight or whatever. In a situation like that, I would instantly be like, berberine could actually play a role there. The shame I was going to say, though, for that one specifically, is this. There are a few situations where you shouldn’t take berberine.
The first one, unrelated to what I just said, is certain medications. You shouldn’t take it alongside them. So if you were to look at it, I think you should check that first with your doctor. Look it up yourself. Do your own research, whatever. One little thing I would flag on that is this. People often talk about it leading to more hypos. If somebody was hypothetically on certain diabetes medications, it might be more likely to lead to that.
The research doesn’t seem to support that at this stage. It’s a cautious approach. It could make sense. However, at this stage, the research shows it doesn’t seem to lead to more hypos. It just makes people better to a certain point or whatever. The gestational diabetes one is unfortunately not recommended. There are actually documented cases of it being negative for the baby. So you can’t take it during pregnancy. That’s actually a really clear kind of thing. You can’t take it during pregnancy.
Torwen:
That’s a great thing to add on. Well, this has been episode 249 of the Ideal Nutrition podcast. As always, we hope that you enjoyed today’s episode. If you did, we’d appreciate you leaving us a positive review. Thank you.