Who does Milk Protect from Diabetes? You will never think of milk the same again.

A big new study was just published in Nature Metabolism which explains how some people who drink milk might be protecting themselves against diabetes. Welcome to my channel. Stay curious. First, for some background, there are mixed data on the protective effects of milk on diabetes, in particular type 2 diabetes. Some studies say milk is protective and others provide less convincing results. But often when there are heterogeneity in the data, as there are here, mixed data, it means we're missing a piece to the puzzle. And researchers may have just found that piece and identified who might benefit most from consuming milk with respect to type 2 diabetes risk. The paper itself is entitled Variant of the Lactase Gene Explains Association Between Milk Intake and Incident Type 2 Diabetes. And it includes several sub-studies, a few of which I'll walk through here. But for some more background, the LCT gene is the human gene that codes for the enzyme, the protein lactase, which breaks down the milk sugar lactose. And some people have lactase persistence, LP in the paper, meaning they express the gene throughout life. It persists, the expression, so they can break down lactose throughout life. Their body has that capability. And others are lactase non-persistent, LNP, meaning they don't. They stop expressing this enzyme, so their body itself isn't really good at breaking down lactose. Now, if you actually look at the paper, you'll notice that these two groups, LP and LNP, lactase persistence and lactase non-persistence, are actually coded via letters. AA slash AAG for lactose persistence and GG for lactose non-persistence. And this code, is because the gene expression is determined by variations in the genetic code, nucleotides in the genome, A, C, T, and G. And in this case, it's a variation between A and G. So if you actually look at the figures, when you see GG, that's the lactase non-persistence. And AA/AG is lactase persistence. Really, I want you to focus on, and you'll see why in a minute, the GG, the lactase non-persistence, okay? Now, the first thing the researchers did is look at data from the Hispanic Community Health Study, study of Latinos, to examine an interaction between the host expression, human expression, of LCT gene via their genotype and milk intake on risk of type 2 diabetes. And very interestingly, they found that lactase non-persistence, so when the host, the human, wasn't expressing the lactase gene throughout life, that was actually associated with lower type 2 diabetes risk, the lactase non-persistence, with a relative risk of 0.7, meaning about a 30% risk reduction of type 2 diabetes in people who were lactase non-persistent. And you can see that here in Figure 2C. Hmm, so that's interesting. They also went on to go the extra mile and confirm these findings in another separate cohort the UK Biobank to help solidify their finding, their finding that lactase non-persistence is associated with lower type 2 diabetes risk, particularly in those who consume milk products. Interesting, right? What's more, the researchers then went on to conduct post-hoc meta-analyses of 24 prospective studies with 1.3 million person-years in total to examine the association between milk intake and risk of type 2 diabetes. And what they found is in the meta-analysis of 6 studies in non-white populations where there are high rates of lactase non-persistence, that higher milk intake was associated with lower risk of type 2 diabetes. Whereas by contrast, um, in populations where there are high rates of lactase persistence, there wasn't really an association. There was actually a tiny positive association, almost negligible, between milk intake and lactase, um, milk intake and type 2 diabetes. So basically what they're showing is in this prospective meta-analysis, in populations with high rates of lactase non-persistence, milk intake is associated with lower type 2 diabetes risk, which is consistent with their overall findings thus far. So the next question is why, why is milk intake associated with lower diabetes risk in populations with lactase non-persistence? What could be the mechanism? They then went on to find that various bacteria, including Bifidobacterium, were significantly and positively associated with the abundance of lactose degrading pathways and particular enzymes that are involved in lactose degradation. And that these species were associated with more favorable metabolic profiles in people with lactase non-persistence. And this includes a negative association between the bacteria, the lactase degrading bacteria, and body mass index, waist circumference, and fasting glucose, as you can see in Figure 3E, where blue here is indicative of a negative association, and the GG refers to milk-associated species in lactase non-persistent individuals. So pausing and taking a step back, what they're finding is that in lactase non-persistent individuals, Um, when milk is consumed, there's enrichment of these bacteria, and these bacteria associate with being leaner and having better, better fasting glucose and overall better metabolic profiles. So that's pretty interesting. Now they wanted to move one link further down the chain, not just look at the bacteria, but maybe the metabolites those bacteria produce and how that could maybe mediate the beneficial effects of milk intake On metabolism and type 2 diabetes risk in lactase non-persistent individuals. And what they found was that, um, higher levels of metabolites positively associated with milk intake were generally associated with lower risk of type 2 diabetes. So in lactase non-persistent individuals, more milk intake was associated with increased levels of certain metabolites, and those metabolites were associated with lower risk of type 2 diabetes. These included, for example, indolepropionate, which is a product of tryptophan metabolism, where higher levels of this metabolite were associated with lower risk of type 2 diabetes. And then the converse was true, where higher milk intake was associated with lower levels of other metabolites such as branched-chain amino acids, and those had a positive association with type 2 diabetes risk. So the composite score— they actually went on to generate a composite score of all these metabolites. They called it the GG-specific milk-associated metabolite score. GG again for the lactase non-persistence. Sorry, this is kind of technical. Hopefully you're following along. And what they found was that this score was significantly associated with type 2 diabetes risk, lower type 2 diabetes risk, where, um, and positive metabolic traits. So again, I know this is technical, but pausing, tapping, taking a step back, what they're finding is that in people with lactase non-persistence, they can create a score of the metabolites that are associated with milk intake, and they find that these metabolites are also associated with lower type 2 diabetes risk. So what they're finding, again, to start to kind of put the pieces of the puzzle together, is that in lactase non-persistent individuals, there's a lower risk of type 2 diabetes associated with more milk intake. That in these individuals, milk intake associates with certain bacteria. These bacteria also associate with lower risk of type 2 diabetes. And in these lactase non-persistent individuals Milk intake associates with higher and lower levels of certain metabolites. And when you mush all these metabolites together and create a milk intake score, a milk metabolite intake score, what you find is that higher levels of these metabolites also associate with lower risk of type 2 diabetes, really painting an overall picture of how milk intake in individuals with lactase non-persistence can boost certain bacteria that boost certain metabolites and decrease others, which associates or probably causes lower type 2 diabetes risk, which is super, super cool. So that's more or less the story. This paper also discusses its limitations and how it attempted to control or measure potential confounders. But all in all, I found these data very convincing to suggest to me that people with lactase non-persistence, who are more likely to be lactose intolerant, actually may be the most likely to benefit from milk consumption. That's odd, isn't it? Now, here's how I understand this from a 50,000-foot view. If the body itself, if your human body is lactase non-persistent, then milk creates a selective pressure of sorts on the microbiome to increase species that can handle the milk load. And these species can be beneficial. It's kind of akin to a hormetic stressor like HOT or cold exposure, or exercise even, where you have to stress the body and/or the microbiome, the metaorganism if you will, a word for your body combined with your microbiome, and that causes it to adapt in a positive manner. So here in lactase non-persistent individuals, consumption of milk associates with changes in the microbiome, changes in the metabolome that associates with decreased type 2 diabetes risk, explaining how some people those actually with lactase non-persistent who are more likely to be lactose intolerant might benefit from milk intake. Isn't that cool? So with all that, my last question: Got milk?