The Hidden Toxin that Causes Insulin Resistance

This yogurt— I know, you can almost taste it, that tang on your tongue. That tang comes from a molecule called lactate. Lactate is made by bacteria that turn the lactose sugar into lactate, and a similar process is going on in your muscles right now. But here's something I didn't know until I read this new paper: lactate has a biomolecular twin, a dirty doppelgänger that's not fueling muscles but causing metabolic chaos. And this dirty doppelgänger builds up in people with obesity, contributing linked to metabolic dysfunction. But here's the twist: scientists have just discovered a way to trap this dirty doppelgänger, this biomolecular evil twin, opening up whole new avenues for metabolic therapy. So in this video, we're gonna do like fermentation and break it down, and I promise by the end you'll never see a bowl of yogurt the same way again. Here's something I bet you don't know. So in this video, I'm introducing the right hand of lactate. D-lactate led to significant increases in blood sugar. We're beginning to see this isn't just a correlation the de-lactate crap improved blood glucose, insulin levels, and the fatty liver scores. Make your own yogurt, specifically L. reuteri yogurt at home. That could ultimately change your metabolism. Science is only beginning to unpack the story. Let's back up to start. I'm gonna give you some background you need to understand these data. You've likely encountered the term lactate or lactic acid in the context of exercise. Lactate is a molecule that can serve as a fuel and signal throughout the body. But here's something I bet you don't know. The type of lactate you've heard of before is almost certainly a form called L-lactate. The L refers to the molecule's orientation or handedness, like a left hand. It's as if you maybe had seen hands before in the world, but you'd only ever seen a left hand until now, not a right hand. So in this video, I'm introducing the right hand of lactate. Let's be clear, in biology, That handedness matters a lot. Mirror image molecules can have completely different biological effects. And in this case, the mirror image of L-lactate is D-lactate. And D-lactate is the star, or more correctly the villain, of today's metabolic story. "I am your father." It is a bit of an oversimplification, but to anchor you and emphasize the distinction, think about it like this. L-lactate fuels your muscles during exercise, whereas D-lactate fuels metabolic chaos. That said, the researchers behind this new study have also discovered a way to quiet that metabolic chaos. So, like a spoon diving into yogurt, let's dive into these data. The researchers began by measuring both L-lactate and D-lactate in humans with and without obesity. And interestingly, people with obesity had much higher levels of D-lactate in their blood, that's shown here in pink, while L-lactate levels remained the same between lean and obese individuals. So specifically, D-lactate was increased in obesity. But here's the real question: is D-lactate merely a bystander, or is it actually driving obesity? To answer this, the researchers turned to mouse models, animal models. They administered obese mice with either L-lactate or D-lactate and observed the metabolic effects. Only D-lactate, shown here in red, led to significant increases in blood sugar. And in the fed state, D-lactate also increased triglycerides, fat in the blood, whereas L-lactate didn't. So we're beginning to see this isn't just a correlation. D-lactate specifically, not L-lactate, has negative metabolic effects. It increases blood glucose and increases triglycerides, two hallmarks of metabolic dysfunction and metabolic syndrome. But where is D-lactate primarily coming from? Well, it's generally thought L-lactate comes largely from your body's synthesis, and also to some extent the microbiome, whereas D-lactate is primarily made by the microbiome. So, using experiments with germ-free mice, animals raised without any microbes in their system, the researchers were able to show that the main source of D-lactate in mammals was indeed the microbiome, at least in mice. I suspect this translates to humans as well, but you can't really make germ-free humans. Anyway, that aside, to prove that variations in microbiome composition could contribute to D-lactate variations and knock-on variations in metabolic health markers, the researchers colonized mice with specific Lactobacillus bacterial strains. One group received Lactobacillus intestinalis, a high D-lactate producer. —shown in red—another received Lactobacillus reuteri, which makes far less D-lactate—shown in blue. Mice colonized with the high D-lactate microbes developed worse blood sugar control. Now, a quick aside, but an important one. For those wondering about how D-lactate increases blood sugar, it's not entirely clear yet, but what is clear is that while lactate can actually be converted into glucose, that alone does not explain the full effect. D-lactate's influence on glucose may be 10 to 100 times greater than can simply be explained by just a conversion, a lactate-to-glucose conversion. Thus, D-lactate is acting more like a metabolic signal than a fuel source itself. This is not unusual in nutritional biochemistry. Often molecules that are themselves sources of energy—think ketone bodies like beta-hydroxybutyrate or omega-3 fats like EPA and DHA— they have their primary metabolic effects not just through serving as metabolic gas, but through rewiring the engine itself. That's a whole separate kettle of fish, but I did want to make that point. Now, let's get back on track and summarize what we've learned so far. First, D-lactate is the mirror image version of L-lactate. D-lactate is primarily made by gut microbes, and variations in the microbiome can lead to variations in D-lactate levels. D-lactate is elevated in obesity in both humans and mice. And D-lactate appears to have harmful metabolic effects that are distinct from L-lactate, raising blood sugar and increasing triglycerides— hallmarks of metabolic syndrome. Now, I'm sure you're wondering, what about solutions? Well, the researchers envisioned a D-lactate trap that would prevent D-lactate from being absorbed, literally trap it in the intestines, thereby avoiding metabolic damage. You just poop it out. This trap takes the form of polymers—chains of either D-lactate or L-lactate. And interestingly, polymers of the L-lactate bound together can trap D-lactate and lead to its excretion. These polymers also are already used in resorbable, safe medical devices such as sutures, implants, and various drug delivery systems used in humans, and they're biodegradable and non-toxic. Therefore, in theory, these existing tools, these existing materials could be repurposed to trap D-lactate and improve metabolic health. So the researchers tried that out. The researchers found that when they gave these D-lactate traps, which are L-lactate polymers, sorry if that's confusing, to mice with obesity, fecal output of D-lactate was indeed increased, while fasting blood glucose, fasting insulin, and insulin resistance scores, HOMA-IR, all improved. And this provides poop of principle— sorry, proof of principle that repurposing these already existing non-toxic L-lactate polymers, the D-lactate traps, could have positive effects on metabolic health. This was shown in mice, but there's no reason to think it wouldn't work in humans as well. The researchers then went on one step further to test the ability of a variant of this polymer, the D-lactate traps, in a fatty liver disease model, another mouse model. Impressively, in these fatty liver mice, the D-lactate trap improved blood glucose, insulin levels, insulin resistance scores, and the D-lactate trap reduced inflammation and improved fatty liver scores. You can even see the improvement on imaging. The white blobs are actually themselves fat cells, with more white blobs representing more full fat cells. The control mouse has very little liver fat, that's healthy, whereas the fatty liver mouse here called the MASH mouse, shows a large accumulation of liver fat. But when the D-lactate trap is administered to the fatty liver mouse, there's a marked improvement in the liver fat. So to recap, D-lactate is the mirror image of lactate, but unlike its twin, D-lactate exerts harmful metabolic effects, raising blood glucose, worsening insulin resistance, and even contributing to fatty liver disease linked with metabolic dysfunction. But encouragingly, at least in preclinical trials, blocking the absorption of D-lactate with D-lactate traps improves to improve blood sugar, insulin sensitivity, and liver health. But as with all emerging science, many questions remain. How exactly does D-lactate alter metabolism? Through what particular receptor signals or gene expression patterns? What are the further consequences of chronically elevated D-lactate over the years, particularly in human obesity, not just over weeks? And beyond polymer traps, what other interventions—dietary, microbial, or lifestyle—might lower D-lactate and in doing so improve metabolic health? Now that brings us to the final section of this video. Now, as a quick aside, an important caveat, an author's transparency note, this is the part of the video, or the content, where I often struggle. Not with providing information, that's easy, I love to talk, but with providing honest and useful information. The nature of early-stage research like this is that it identifies problems first, and only later points towards or proves solutions in humans. And since this paper is only a few weeks old as I'm recording this, it would be impossible for me to offer surefire ways to act on this knowledge to improve metabolic health in humans. So all I can truly do is offer informed speculation. So please take it as intended: thoughtful guidance that is far more likely to help than harm, but is still provisional. I just wanted to be upfront about that. With that, let's talk about specific probiotic strains. Certain microbes don't produce D-lactate—we already talked about one in this video—and therefore they may help compete with D-lactate producers in the gut, thereby reducing overall D-lactate levels. Two good examples are Lactobacillus reuteri and Lactobacillus rhamnosus, particularly the GG strain. If you take a probiotic, check the labels for these strains. Hi, future Nick here. Now, in the original cut of this video, I admit I was gonna tease you on a specific probiotic that I myself am taking that I also helped to develop that contains low D-lactate producers, but it's actually primarily engineered for another purpose: to be the only probiotic that binds up harmful microplastics that are plentiful, ubiquitous in our environment. You can see this video for more on the science. Anyway, I've been sitting on this video long enough that now I just want to tell you about it because I've been talking with the team for months and was onboarded as a scientific advisor because I'm genuinely interested in the science. So with that That is my disclosure, yes I'm affiliated with this company, this is also the probiotic that I will be using myself, so take that for what it's worth to you and you can check the links below for more information and a discount code. But let's get back to the rest of our video. Another option is to make your own yogurt, specifically L. reuteri yogurt at home. It's pretty easy. Here's how you do it in a nutshell: start with a prebiotic off of which the bacteria can feed, like an inulin powder, add the L. reuteri starter culture, and add your choice of fatty dairy. Like cream or half and half, and mix it all up until smooth. Then just cover it with plastic wrap and ferment it for 24 to 36 hours at 98 to 102°F. The precise temperature is really important for the proper fermentation so you don't kill the bugs, and slightly longer fermentation periods like 36 hours will allow for greater bacterial counts and more probiotic potential. For more specific instructions, again, check out the newsletter in the notes. Now, as another transparency statement, I don't trap the extra details, the nuanced notes, the author Q&As, the methodological and etymological asides in the letter to troll you, but because honestly, newsletter and YouTube audiences, they're distinct. And so I give myself a little bit more liberty to be long-winded in text, and I try to keep things kind of streamlined in the videos. I'm not always good at it, but I try. And also, candidly speaking, the premium subscribers to the letter are what make this channel and my provision of all this free information possible. So I really want to give them a thanks. Anyway, transparency note and plug over, back to yogurt. If you try this yogurt, the result should be a thick, delicious yogurt that you can serve by itself, or stevia if you want a little bit sweetness, wild berries, dark chocolate shavings, or my personal favorite, a sprinkle of Maldon salt. I love salted yogurt. So now I want to return to that image that we started with, the humble bowl of yogurt. It's not just a simple source of calcium, fat, and proteins. It is, or it can be, a microbial cocktail that could shift your microbiome in ways that could ultimately change your metabolism, your blood glucose, and even your liver health. Science is only beginning to unpack the story, and part of that story appears to involve D-lactate. Now, I hope you found this interesting. I hope you also felt the real purpose of this video, which is not to give you direct instructions, but to help you feel a little bit of the scientific awe I feel every day, even looking at a humble bowl of yogurt. Because that's a pretty awesome feeling, and I want you to share it. Stay curious. Thanks.