Berberine, Metformin, and an Incredible New Discovery

0:00 Throw out everything you know about berberine and metformin. All right. That's a bit dramatic. Don't throw away all out, but maybe add to your knowledge with this fantastic study that discovered a new way that metformin and berberine, as we'll get to, improve our metabolic health. I mean, metformin is a molecule that we've been using to great effect in staving off type 2 diabetes and reducing overall insulin resistance. Berberine, a bit like a little sibling, has also gained traction for having similar types of effects, though with some nuances. It was believed that both molecules act on the liver. Specifically, since the liver is the site of glucose or sugar production, metformin inhibits the

0:45 ability for your liver to produce that glucose by inhibiting particular enzymes in the mechanism of action. Now, berberine reduces the initial production of the enzymes in the first place, the ones that are responsible for this production of glucose. Thereby, both would then reduce blood sugar levels. Now, regardless of the exact mechanism, we know they work by reducing blood sugar levels. These data are from people with insulin resistance, and you can see that the data is split by those who received berberine or metformin, and the timetable there is about 14 weeks. And we can see that the blood glucose levels, blood sugar on the vertical axis. Here, we want the lines to go down. The white line is the fasting blood glucose, and the black

1:31 line is after consuming a standard meal. You can see, regardless of if it's metformin or berberine, there's a reduction in the blood sugar that typically takes about 2 weeks for it to stabilize to a new low. The effect is substantial, too. So, we know that berberine and metformin may act slightly differently, but they both reduce blood sugar in people with insulin resistance. Now, the paradigm shift here is that we are moving away from a liver-centric understanding of these molecules and turning our attention to the gut. Now, of late, we've been discussing the gut microbiome, but not in this case. We're discussing the actual gut cells, the intestinal cells themselves.

2:17 Intestinal cells themselves. Intestines are made up of epithelial cells, cells that line up next to each other like soldiers in the Revolutionary War. They absorb molecules and spit them into the bloodstream for the rest of our organs to use as nutrients or other functions. Now, metformin is also known to be a mild mitochondrial inhibitor. In this case, that's a good thing because inhibiting the mitochondria means that the cells can't rely on fat metabolism as readily. As a result, they shift to glucose metabolism. Now, if you increase glucose metabolism, that means that more glucose is being used up, keeping it out of the blood to harm the body as we see in diabetes. That's important in this context because while

3:03 we've classically accepted this mechanism in the liver, check out what happens when we test it this in the intestines. I know this doesn't look like much, but it's pivotal data. We're measuring the uptake of glucose into the intestinal cells. The higher the bars, the more uptake. That alone doesn't matter much because the intestines take up glucose and kick it back out into the bloodstream, which is why we see rises in blood sugar or blood glucose when we consume carbohydrates that contain glucose. Nothing new there. The unique part is that there's a second component to this experiment. We're also disinhibiting the mitochondria, or in another way of saying it, we are rescuing mitochondrial function. The vehicle condition there is the control condition, no metformin added.

3:49 The large gray bar there is the glucose uptake in the intestines when Metformin is present. Remember, mitochondria are somewhat inhibited here. Then, the far right condition is the rescue. Mitochondria are functioning again. Notice how with Metformin, the intestines are sucking up glucose. Yet, when we rescue mitochondria, there's no longer that effect. That's because when paired with other data in this paper that I'm omitting just so I don't overwhelm you, the intestinal cells are no longer metabolizing the cells. Said differently, when Metformin comes in contact with the intestinal cells, the cells have to shift their metabolism to glucose metabolism. And low and behold, if a person has trouble with excess glucose, that's an excellent thing

4:36 considering that the intestinal cells can start using the glucose as energy. In short, Metformin is creating a metabolic sink in the intestines. It's activating the intestines to suck up glucose, not just to release it into the bloodstream, but to feed themselves. How freaking cool is that? Now, all of this mechanistic research has been in mice because we can't ethically genetically manipulate humans for experimental purposes. Fortunately, we have other evidence, human evidence that confirms aspects of this research, though not as detailed. We can see glucose uptake in the intestines here. You can ignore the final condition there. The bars close to one another represent before and after. And the green bar there above Metformin

5:21 is after Metformin exposure. Clearly, there's an increase in glucose uptake by the small intestine with Metformin. That's about doubling, in fact. I should note that these data don't tell us about the metabolism of glucose, just the uptake. And the study was done in reverse. So, the injection of glucose in the blood and then measuring the glucose uptake, not the feeding of glucose directly. But considering what we know about Metformin, it seems likely some metabolism is likely happening here through that intestinal metabolic sink that we've been discussing. So, this means that we can confirm there's an increased uptake of glucose with Metformin use in humans. Now, we've been focusing more of our discussion on Metformin, but does this also apply to

6:06 berberine? As some people like berberine more, but do you like it enough to expand your knowledge beyond what is offered in this video that you're watching? I go into using it in combination with Metformin as well as some other metabolic effects of berberine and even more details on mitochondrial inhibition by Metformin and berberine in my full analysis. That's right, the extended version including a full article or if you prefer a monthly podcast going over all of my analysis for each month with actionable takeaways and much more, some of which is shown right here. Anyway, it's all included as a Physionic Insider. The link to join the Physionic Insiders is in the description of this video. Now, back to our regularly

6:53 scheduled programming. Check this out. Here, not to be mistaken with the Metformin experiment, we're measuring blood glucose, not intestinal glucose uptake. So, the lower the bars, the better. You can see again that berberine does reduce blood glucose, but again, when we remove the mitochondrial inhibition in the intestines, we no longer see a reduction in blood glucose. This, including some other data, confirm that the mechanism of beneficial mitochondrial inhibition applies to berberine as well. So, what does this all mean for you? Well, applicably, it doesn't change anything, right? The discovery here is between the lines of should I use berberine or Metformin or not? Doesn't change that answer. The

7:40 answer is yes, if you have insulin resistance and your physician thinks that it's wise. But, it does tell us some wildly fascinating mechanisms and completely shifts how we think about how both molecules work. Not just thinking about the liver, but expanding to other potent intestinal effects in protecting us from metabolic disease like type 2 diabetes. Anyway, you may want to know more on berberine. There's some, in my opinion, even more impressive uses of berberine right here. I will leave you here. Do not weep, for we will not be apart for long, depending on how long you decide to hang out with Physionic. If not, then definitely weep. Thanks for tuning in. I'll catch you in the next

8:25 one. See you.