Is this the REAL Root Cause of Autoimmune Disease?

What if all autoimmune diseases were stemming from the same source? From a seed planted 2 billion years ago that is just beginning to flower? That might sound wild, but it's actually the central thesis of a new paper published in Nature, which proposes that many autoimmune diseases, if not all of them, may be driven by the failure of a relationship that began 2 billion years ago, the one between your body and your mitochondria. For me, this idea carries personal weight since I suffered from debilitating inflammatory bowel disease, a form of autoimmune disease, which went into remission on June 1st, 2019 when I started a ketogenic diet. And I've seen many others put similar diseases, IBD, lupus, multiple sclerosis, rheumatoid arthritis, into remission with lifestyle change. And I desperately want to know how it all works. But enough chitchat. The paper in question is entitled "A break in mitochondrial endosymbiosis as the basis for inflammatory diseases." I'm going to decode what this means, then tell you what it means for you and give you a list of practical advice to help out your immune system. Okay, About 2 billion years ago, a cell consumed another smaller bacteria-like cell. Technically, it was an Asgard archaeon. Anyway, that smaller cell didn't just get digested and pooped out, but it was integrated into the larger one. This is what is meant by endosymbiosis. Endo means within, and symbiosis derives from the Greek word meaning to live together, where two different organisms are associated in a close, prolonged, and often mutually beneficial relationship. And you guessed it, that smaller cell was the precursor to our very own mitochondria, the engines and the powerhouse of most of the cells in our bodies and the center of your metabolism. But your mitochondria are far, far more than just little engines. They are also informational hubs and communication stations, signaling all over your body to cue and coordinate a near infinite set of pathways and processes. And how mitochondria do this derives, at least in part, from their foreign origins. Truly, mitochondria retain many of the signatures of their foreign origins that mark them much like bacteria or even viruses, and apart from other components of, well, you. Quoting from the authors, "We can also consider mitochondria as pseudobacterium bricked in behind the mitochondrial outer membrane." And your body's immune system is great at recognizing the other, the foreign invaders. Mitochondria, for the most part, are shielded within the cell so they don't get targeted and attacked. However, the body can selectively release mitochondrial components or mitochondria-derived signaling molecules to trigger certain events. Again, in the author's words, "The endosymbiotic relationship"—remember what endosymbiotic means—"the endosymbiotic origins of mitochondria mark them apart apart from the rest of the cell in a way that can be co-opted to produce key messages pertaining to cell fate. For example, in response to certain cell stressors, mitochondria can release proteins from the intermembrane space, like cytochrome c, which is involved in metabolism, to trigger a form of organized cell death, which you might have heard of, called apoptosis. Mitochondria also retain their very own DNA called mitochondrial DNA, which is separate from the DNA in your cell's nuclei. And they can also release this DNA to trigger immune reactions. In some cases, the inner portion of the mitochondria can swell, and components can literally herniate out of the mitochondria, pushing components, including mitochondrial DNA, out of the mitochondria and triggering an immune reaction, an inflammatory reaction. The core idea of this paper is that inflammatory and autoimmune diseases derive from the breakdown of this endosymbiotic relationship. In other words, mitochondria and their components are exposed and/or leak more than they should, triggering an inflammatory reaction in the body. This could be the real cause of autoimmune diseases. And this is really important because the two obvious questions that follow: first, what causes this breakdown in endosymbiosis? And two, what can we do to fix it? Now, as you can see here, clearly illustrated in the central figure of this paper, the authors hypothesize And I agree, quite honestly, that environmental factors common to modern living, including prevalent obesity, processed food intake, lack of exercise, disrupted circadian rhythm, disrupted sleep, and environmental pollutants are what trigger the breakdown in endosymbiosis, which triggers downstream inflammation and autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and so on. Now, if you want specifics of the pathways discussed in this paper, feel encouraged to read the paper itself. I always encourage that. But to reinforce the point, the authors write, "Might the pressure on mitochondria caused by obesity, chronic stress, certain foodstuffs like processed food, disrupted circadian rhythm, or damage to mitochondria caused by various environmental toxins—" we're going to review some more specifics later on in the video, exacerbate a process whose homeostatic goal is to drive inflammation, but in a beneficial way. In other words, they're saying things go awry, the current environment is mismatched to how we've evolved with our mitochondria, and that's leading to autoimmune diseases. But now I want to move on to telling you how to start fixing your mitochondrial endosymbiosis to potentially help prevent or even treat autoimmune diseases? The answers and advice can be derived from the presumed causes, kind of obviously. In other words, at a high level, to fix the relationship between your mitochondria and your immune system and potentially quell inflammatory and autoimmune diseases, it's wise to correct obesity, reduce processed food intake, get exercise, sleep enough and sleep well, and at regular hours, and avoid environmental pollutants. That's the high-level view, but it's not super helpful, is it? So I want to dig in to some high-yield specifics going through each of these categories, starting with obesity. Obesity is associated with many autoimmune diseases, including the development of multiple sclerosis and type 1 diabetes. In individuals with obesity, there's a 60 to 90% increased relative risk of developing multiple sclerosis as compared to healthy weight individuals during adolescence and young adulthood. And if you want more on multiple sclerosis and a diet connection, see this video. Some really interesting things in there. And the incidence of type 1 diabetes increases almost linearly with higher birth weight, with a 7.7% increase per pound of birth weight. And as explained in an article published in the prestigious journal Science, metabolic overload, by which they mean excess glucose and lipids, from obesity causes chronic activation of the immune system. The metabolic cascades are really complex, but involve overactivation of inflammatory T lymphocytes immune cells, decreased proliferation of other immune regulatory cells, Tregs, which keep the immune system in check, increased circulating inflammatory molecules, activation of inflammatory signaling cascades, and so on. Now, correcting obesity— really, it's mostly about the destination, not the journey. I'm not here to judge your preferred approach, be that a carnivore diet, a vegan diet, or approaches assisted by medications like GLP-1 receptor agonists. Personally, I think the literature favors approaches that reduce insulin levels, which is a hormone that promotes fat storage. For this, I think lower-carb diets, therapeutic carbohydrate restriction, and ketogenic diets are excellent, and I'll direct you to much more resources on these in the video notes. And just as a quick aside on GLP-1 receptor agonist medications, many don't realize these actually also decrease insulin area under the curve in a mixed macronutrient setting. I.e. when carbs are eaten. A common misperception is that they increase insulin. They don't. They decrease it when people are eating carbs. And there are many very strong opinions on these medications. I get that. I'm not going to get on my soapbox here. But you should check out this video if you want a better mechanistic understanding, a deep understanding of GLP-1 receptor agonists, their role as medications, and their role in overall health. Even beyond obesity. Okay, moving on. Reducing processed food intake. This is a good guideline, a good heuristic. The more you can eat single-ingredient, whole, real foods, and those without labels or long lists of ingredients, the better you'll probably be. However, it's important to note processed foods is a broad and vague category. Some processed foods are formulated quite thoughtfully, I even did a whole video on a few I eat myself. Other processed foods, not so much. But you don't have to be dogmatic about never eating processed foods, but a good rule of thumb is if you don't know what an ingredient is, please do your homework on it and become informed. Personally, I avoid almost all artificial sweeteners, like aspartame, as a general rule, although stevia, monk fruit, and allulose, which are not artificial, are fine. That said, I'll carve out an interesting possible exception for sucralose. Although it has its issues, and it does, research published in Nature in 2023 suggests that sucralose might quell autoimmunity by skewing the differentiation of certain immune cells towards a different ultimate cell fate. I won't overstimulate you with discussions of PLC-gamma-1-dependent induction of intracellular calcium release, But if you're interested, feel free to read the paper and let me know your thoughts. The conclusion reads— it's quite interesting— "These findings suggest that high intake of sucralose can dampen T-cell-mediated responses, an effect that could be used in therapy to mitigate T-cell-dependent autoimmune disorders." And because I do know I'll get asked this question, the paper was not funded by Big Sucralose, and the funding and competing interest statements can be found in the linked paper. I'm no sucralose fan, I have other videos where I'm clearly not a sucralose fan, but these are the data and I think they're interesting. And also, I avoid almost all artificial food dyes like Red 40, Red 3, and Yellow 6. I actually did a video on Red 40 and inflammatory bowel disease here. And I certainly avoid anything with added sugars. Now, getting exercise. Keeping this as high level as possible, it's important to resistance train and get some form of cardiovascular exercise. For resistance training, make sure to work each of your large muscle groups at a minimum twice per week. There are many different training splits, as they're called, depending on your preferences and your recovery time. For example, try Googling a push Push-Pull-Legs routine. This partitions resistance training into push days that work your chest, shoulders, and triceps, pull days that work your back and biceps, and the dreaded leg days which work your quads, glutes, hamstrings, and calves. Getting sleep. Okay, a disclosure on that one. My health report card is probably an A for exercise, A for nutrition, and C-minus if I'm being generous, for sleep. It's something that's hard to tune in for many people, but it's likely relevant to autoimmune diseases. Sleep certainly impacts the immune system. And in population-level studies, sleep disorders have been associated with increased relative risk for autoimmune diseases, a 45% increased risk for rheumatoid arthritis, a 53% increased risk for ankylosing spondylitis, an 81% increased risk for lupus, and a 51% increased risk for Sjögren's Sjögren syndrome. So here's what I suggest at a high level. Again, this is a topic that deserves way more unpacking, but at a high level, sleep in a dark, cool room under 70°F. Have a protected wind-down period before you go to bed where you relax yourself and separate yourself from work. Don't drink caffeine after noon, and don't tell my girlfriend I told you that. Don't eat within 3 hours of getting into bed. Try to get sunlight in your eyes early in the day around when you wake up or when the sun comes up if you get up before the sun. Make sure to exercise if I didn't already mention that in this video. And you can experiment with additional tools like red light lamps and saunas, acoustic neuromodulation. I'll provide links to some devices that I've experimented with below along with one or two discount codes., and some supplements maybe even, like saffron, magnesium threonate, or melatonin. And I'll provide more learning resources below as well. Sleep is really critical. So, do as monkey say, not as monkey do. But I promise you monkey is trying. Okay, now reducing exposure to environmental pollutants. This is a huge topic. To be clear, I'm not trying to be comprehensive here, but here are some high-yield tips. Okay, avoid plastic used for food and drink, especially when it's hot. Plastics often contain BPA, phthalates, and other endocrine disruptors, hormone disruptors, that leach out when heated or degraded. Instead, try to use glass, stainless steel, or ceramic containers for storage and heating. And never microwave plastic. Even if it's labeled microwave safe, I still would not microwave plastic. Okay, avoid non-stick cookware. Many non-stick pans contain PFAS, which stands for per- and polyfluoroalkyl substances. PFAS are also known as the forever chemicals, which are linked to disrupted thyroid, inflammatory bowel disease, and hormone disruption. As a relevant factoid, in one study, the prevalence of ulcerative colitis and inflammatory bowel disease, the one I was diagnosed with, was 186% higher in those with more PFAS exposure, the highest quartile of circulating levels, as compared to those with less PFAS exposure, the lowest quartile of circulating levels. So instead, try to use cast iron cookware, stainless steel, or ceramic. Next, audit and clean up your personal care products. Many conventional cosmetics and toiletries contain phthalates, parabens, triclosan, and synthetic fragrances, all of which can act as endocrine disruptors— again, hormone disruptors. So look for fragrance-free or no synthetic fragrance labels and choose products with short and transparent ingredient lists. Okay, moving on. Avoid canned foods with BPA. This is simple. Simply look for labels that say BPA-free. For me personally, this is critical in my tinned sardine selection, which is quite important and a staple in my diet. Next, try not to touch thermal paper receipts. Receipts are often coated with BPA, which absorbs easily through the skin. So ask for a digital receipt instead. Or no receipt. It's also better for the planet. Less paper, right? Okay, next, reduce indoor dust, which is a hidden reservoir of endocrine disruptors. Household dust can collect phthalates and other endocrine disruptors from furniture, electronics, and flooring. Vacuum regularly using a HEPA filter and try to wet dust rather than dry dust. Again, I'm not trying to be comprehensive in this video, but this will get you started. And post your questions below, because if this video gets a good response, maybe I'll double down on this topic and do deeper dives into each of these elements regulating autoimmunity. So, summing up, could all autoimmune diseases really trace back to a 2-billion-year-old bacterial roommate gone rogue? Maybe. It's possible. But the idea that our ancient mitochondrial alliance could hold the keys to modern inflammatory and autoimmune diseases, it's certainly worth exploring and worth acting on. Now, if you learned something new, or you're just here for mitochondrial drama, and I wouldn't blame you if that's the case, hit the subscribe button. It really helps this channel grow and helps tell the algorithm that science communication should be more than just cat videos. Huh? Although, that said, as a fun fact, mitochondrial DNA from cats is actually useful for forensic analysis because there's less degradation of mitochondrial DNA than nuclear DNA in shed cat hairs. And it's nearly impossible for a perpetrator of a crime to leave a pet owner's home without some pet hair, cat hair, transferred to their clothing. Huh, okay, if you didn't know that, now you have to subscribe. And thanks for watching. Stay curious, and I'll see you in the next one.