The Metabolic Roots of Modern Disease: Understanding the Common Thread
- The Facility Denver
- Sep 23
- 13 min read
When we look at the leading causes of death in America today – heart disease, cancer, and Alzheimer's disease – they might seem like separate, unrelated conditions. However, beneath these seemingly distinct illnesses lies a common foundation: metabolic dysfunction. This metabolic disruption serves as fertile soil in which our most feared diseases take root and thrive.
Not All Woo-Woo, Not All Reductionist
The conventional medical world often gets trapped in reductive thinking. Take the ongoing debate about heart disease: is it caused by high LDL cholesterol or inflammation? The reality is that both play crucial roles. LDL cholesterol serves as the raw material for arterial plaque (loading the gun), while inflammation is the destabilizing force that causes plaque rupture (pulling the trigger). This integrated understanding explains why medications targeting either pathway show benefits. Statins reduce LDL levels but also possess anti-inflammatory properties, while newer anti-inflammatory drugs like colchicine demonstrate cardiac benefits even in people with normal cholesterol levels. The question isn't which factor matters more... both are essential pieces of the same puzzle.
Diving deeper into cardiovascular health brings us to the endothelium, which is the critical lining of our blood vessels. Think of healthy endothelium as Teflon, allowing blood to flow smoothly without anything sticking. However, when exposed to chronic stressors like high blood sugar, smoking, poor sleep, or infection, this protective lining transforms into something more like Velcro, where LDL particles begin to adhere, setting the stage for plaque formation. Simultaneously, insulin resistance reduces nitric oxide production, leading to stiff, inflexible arteries. This endothelial dysfunction becomes the launchpad for vascular disease. The quality of LDL particles also matters – it's not just about total LDL, but about ApoB particle count (the total number of "cars on the freeway"), which increases significantly with insulin resistance.
Metabolic Dysfunction: The Ultimate "Root Cause"?
Metabolic syndrome – characterized by central obesity, elevated blood sugar, high triglycerides, low HDL, and hypertension – affects virtually every system in the body. In the cardiovascular system, it drives formation of small, dense LDL, increases inflammation, and damages endothelial function. For cancer risk, elevated insulin and insulin-like growth factors act as fertilizers for tumor growth, while inflammation facilitates spread. In the brain, insulin resistance compromises energy delivery, damages blood vessels, and fuels neuroinflammation (leading some researchers to label Alzheimer's as "Type 3 diabetes.") The metabolic dysfunction particularly impacts the frontal cortex, disrupting its crucial signaling to the brainstem and parasympathetic nervous system, further compromising our stress regulation capacity.
The good news is that metabolic health is remarkably responsive to lifestyle interventions. Exercise improves insulin sensitivity, with muscles acting as a "sink" for glucose. Even simple actions like post-meal walks or squats can help manage blood sugar spikes. Exercise also reduces ApoB particle numbers and boosts nitric oxide, supporting endothelial health. Nutrition plays an equally important role, with Mediterranean-style diets lowering both LDL and inflammation, while processed foods and sugars do the opposite. Adequate sleep maintains insulin sensitivity and endothelial function, while stress management reduces inflammation and blood pressure. Environmental toxin exposure (from mold to PFAS to microplastics) while individually small, collectively overwhelm our detoxification systems and accelerate endothelial aging.
The narrative that medications represent the third leading cause of death oversimplifies a complex issue. While adverse drug events likely contribute to over 200,000 deaths annually in the US, focusing exclusively on this statistic misses the larger point – our need to address the root causes of disease rather than simply treating symptoms. By understanding and targeting the metabolic dysfunction underlying our most feared illnesses, we can potentially reduce medication dependence and address these conditions at their source. The path forward lies not in choosing between conventional and alternative approaches, but in integrating the best of both to restore metabolic health and place the safety on the loaded gun of modern disease.
By understanding and targeting the metabolic dysfunction underlying our most feared illnesses, we can potentially reduce medication dependence and address these conditions at their source.
If you prefer content in audio format, check out Facilitated Episode 27 | Metabolic Health: It's Not About Vanity for a monologue on the real concerns of cholesterol, blood sugar, and medications from Dr. Mitchell Rasmussen | Listen here
Key Takeaways
Heart disease isn’t LDL or inflammation—it’s both. LDL loads the gun, inflammation pulls the trigger, and endothelial dysfunction is where the real action happens.
Particle count matters more than particle size. ApoB testing gives the clearest picture of cardiovascular risk.
Metabolic syndrome is fertile soil for disease. It doesn’t just drive diabetes—it also fuels cancer growth and Alzheimer’s (sometimes called type 3 diabetes).
Lifestyle changes are powerful medicine. Exercise improves insulin sensitivity, lowers ApoB, and boosts nitric oxide. A Mediterranean diet lowers LDL and inflammation. Even small shifts like walking after meals matter.
Chronic stress and toxins accelerate dysfunction. Poor sleep, high cortisol, and environmental exposures (mold, plastics, heavy metals) all damage the endothelium and raise disease risk.
Medications save lives, but headlines can mislead. While adverse drug events cause significant harm, the idea that medications are the “third leading cause of death” oversimplifies the data.
Links & Resources
Episode Transcript | FACILITATED 27 "Metabolic Health: It's Not About Vanity with Dr. Mitchell Rasmussen"
Heart disease, cancer, Alzheimer’s—these are some of the top killers in the United States, and they do seem like separate diseases, but the truth is they all share a common kind of root, which is metabolic dysfunction. Today, I’m going to be sitting down by myself to talk about some topics that I’m passionate about, things that we have discussions with our patients and clients with quite often, and so often I find myself bridging the gap between the conventional and the holistic side. I don’t like to be woo-woo too much and I don’t like to be too Western. I really like to live in the middle, which is often where healing occurs, and unfortunately for social media, this doesn’t make for a ton of clicks, because people tend to get a lot of traction in that way when they’re very extreme, but oftentimes that’s not where healing occurs, and I’m much more interested in helping people get better.
So in this episode, I want to break down this whole LDL cholesterol versus inflammation debate. I want to talk a little bit about how endothelial dysfunction will set the stage for heart attacks, and I also want to show why metabolic syndrome doesn’t just lead to diabetes. It also fuels cancer and neurodegeneration, which, as we’ve talked about before as being such top killers, is a vital aspect of health. I’m even going to tackle that controversial claim that’s been going around social media—are medications really the third leading cause of death? So if you want a little bit of a clearer picture of what’s really driving modern disease and what you can do to protect yourself, this is the episode that you don’t want to miss.
Let’s start with the numbers, and you know, if you’ve been listening for a while, you know that I sometimes like to just shoot from the hip and it annoys Kate. Well, today I’ve actually prepared some notes and some numbers and I’m hoping that we can follow a nice linear path talking you through this. So, according to the CDC, the leading cause of death in the United States—these causes are pretty clear. Number one is heart disease, killing about 680,000 people a year. Number two is cancer, with over 600,000 deaths. And number three is accidents and unintentional injuries—things like car accidents, drug overdoses, falls, stuff like that. Stroke, chronic lung disease, Alzheimer’s, and diabetes come after that. You may have heard people say that medications or medical errors are actually the third leading cause of death. We’re going to dig into that too, because the truth is more nuanced than the headlines. But first, I’d like to help you see the big picture. These top killers are not random, right? They share this common thread, and that thread is metabolic dysfunction.
You’ve probably seen the online fights—some cardiologists yelling that heart disease is all about LDL cholesterol. And others shout back it’s all about inflammation. Here’s how I like to explain it. LDL is like the raw material for a pothole in the road. Without LDL, there’s no plaque. Inflammation is like that jackhammer that cracks that pothole wide open into a sinkhole. That’s when people have heart attacks. So which is it? Both, right. LDL loads the gun and inflammation helps pull that trigger. That’s why statins have a beneficial effect. Yes, they lower LDL, but they also calm inflammation, and this is why there’s a bunch of newer anti-inflammatory drugs, things that have traditionally been used for gout, like colchicine, that actually show benefits in people even if they have low LDL.
So I don’t want you to get trapped in this one versus the other argument. It’s not just LDL or inflammation, right, it’s LDL and inflammation. Like does your car need an engine or gas? Well, obviously you need both, right. Taking that one layer deeper, the real action in heart disease happens at the level of the endothelium, this lining of your blood vessels. A new concept in alternative medicine right now is the endothelial glycocalyx, the support structure for our blood vessels. I like to say that an endothelium is kind of like Teflon. If blood’s flowing smoothly, nothing will stick. But with chronic stressors—I mean, you know, high blood sugar, smoking, poor sleep, chronic infections, oxidative stress beyond the capacity for our innate antioxidant defense systems to protect us—this Teflon will turn into Velcro. LDL starts sticking to the walls, white blood cells move in and plaques form. At the same time, insulin resistance reduces nitric oxide. Nitric oxide is a beneficial compound to help with dilation and opening of blood vessels. So if you’ve got insulin resistance driving poor nitric oxide production, these arteries are going to become stiff and unable to relax. That is endothelial dysfunction, and I like to think about it as kind of being one of these launch pads for vascular disease.
Another myth that gets thrown out about a bunch when it comes to heart disease is: does LDL particle size matter? Some people laugh at the idea. Right, all LDL is the same. All LDL is a problem because there’s not much difference between the small, dense LDL and the big, fluffy. Well, here’s the deal. Each LDL particle is like a car on the freeway. The real danger—I don’t really care what you’re driving. Are you in an SUV, are you in a sedan? It’s really about how many cars are there total, and that’s what we call your ApoB particle count, and this is something that we now measure in every single person we work with.
Back to this analogy—if you mostly see little cars, it usually means you’re in a bad neighborhood. You’ve got high triglycerides, you’ve got insulin resistance, aka metabolic syndrome. Particle size is a marker, but the real problem is traffic congestion, which is too many particles, and this ties directly back to metabolism. When you’ve got insulin resistance on board, particle counts go up, particles get smaller and this connective protective system within our arteries, the endothelium, really starts to suffer. And this is where it gets really interesting. When we say metabolic syndrome, we think about things like a high waist size, a high fasting blood sugar, high triglycerides, low HDL, high blood pressure. This is not just a diabetes problem. This is the soil in which the big killers grow.
Let’s think about the heart—more small, dense LDL, more inflammation, more endothelial dysfunction if you have metabolic syndrome. If you’ve got metabolic syndrome and we think about cancer, high insulin, high insulin-like growth factor—these are like fertilizers for tumor growth, and inflammation helps it spread.
What about the brain? Glad you asked. Insulin resistance in the brain reduces energy delivery, damages blood vessels and it fuels inflammation. This is why now some people are calling Alzheimer’s disease type 3 diabetes, right? We always say one of the first pieces of the body impacted by insulin resistance is the frontal cortex. Stress is a massive part of this because within the frontal cortex, so much of its job is to signal the brainstem, and the brainstem is where the autonomics, the parasympathetic nervous system, begins. So if we have chronic hyperinsulinemia, we start to have frontal lobe involvement because neurons—again, they need oxygen, they need stimulation and they need fuel. Well, you’re not getting fuel very well if you’re insulin resistant. Now that frontal lobe can’t signal to the brainstem adequately and we’re going to be stuck without that calming effect of that parasympathetic nervous system, simply because it’s not getting the signal.
So if we talk about metabolic health, listen, it’s not all about vanity, right? It’s not just about your weight or your blood sugar. It’s about whether we’re creating fertile soil for these diseases that kill most Americans. Here’s some good news—this isn’t your destiny. Metabolic dysfunction is reversible.
We know that exercise improves insulin sensitivity, right? This is sometimes why we have people with high fasting insulin do squats after they eat. I like to say you know these big, strong muscles, these quads and these hammies and these glutes, they function as a sink for glucose. If your muscles are in need of glycogen, that doesn’t require an insulin transporter in order for those quads, those muscles, to take up glucose. So if you’ve got high insulin after a meal, by simply moving your body a little bit, you will create this hypoglycemic effect, simply because these muscles need glucose and it’s a free sink to absorb glucose. We also know that exercise will lower your ApoB. Particle number goes down and it will boost your nitric oxide, which is key for that endothelium. Even a simple walk after a meal makes a difference.
What about nutrition? This has now been shown that a Mediterranean style diet lowers LDL and inflammation. Okay, it’s both of these factors, it’s not one or the other, it’s all related. As it comes to these top killers, we know that processed foods and sugar literally do the opposite. They increase LDL, they increase triglycerides and they drive chronic, smoldering, low-level systemic inflammation. Poor sleep—you know, when you sleep poorly, you will have worsening insulin resistance and your endothelial matrix will become dysfunctional.
Stress, as we talked about earlier. Chronic high cortisol literally fuels inflammation and blood pressure. You can become resistant to any hormone, and if you have chronic stress, you will have chronic high cortisol. And what do we know about cortisol? It’s anti-inflammatory, right? Sorry, I didn’t give you enough time to answer. Well, eventually a few things can start happening and I’ve recorded an entire podcast about this, but you will get receptor downregulation to cortisol. So, even if you have high cortisol, after a while the body quits listening to it. So you’ve got the inflammatory driver, whatever that is, and then now you’ve lost the dampening effect of the cortisol that’s meant to be there to suppress the immune response and bring you back to homeostasis. That’s what we might call all gas, no brakes. We also know that chronic stress is going to drive hypertension, which is really not good for heart disease risk stratification.
We also have toxins, right? Toxins? What toxins? Right? People are saying that right now. What toxins? Well, here’s the deal. It’s a little bit of mold, it’s a little bit of PFAS, it’s a little bit of microplastics, it’s a little bit of pesticides in the grass you walk your dog in. It’s a little bit of heavy metals, it’s a little bit of poor sleep, it’s a little bit of shitty food. You know, it’s all these little things that add up and our detox system is not programmed to be able to handle the onslaught that we provide it in this modern world. And if you’re asking what toxins, I mean we can measure these things. We can measure your bisphenols in your urine. We can measure your phthalates and your parabens in your body. We can look at heavy metals. We can look at mold toxins. These are all things that we can quantify for each person to be able to really assess exposure and detoxification capacity. So, yeah, maybe you don’t need an air quote cleanse, but if you’re not supporting phase one, phase two, phase three detoxification in the body, I’m telling you your systems will be impacted and it can possibly lead to systemic, widespread chronic disease. And I also know that the more toxins on board that the body can’t deal with, your endothelium is going to age fast and you’re also going to be more likely to develop hormone problems and gut problems and energy problems and then everything falls. So that is absolutely a vital thing, and every one of these levers improves not just heart risk but cancer risk and brain health too.
I want to circle back here to that claim that you might have heard—that medications are the third leading cause of death. But here’s the reality: the CDC lists accidents as the true number three cause. But, and I found this, some analyses estimate around a quarter million deaths per year from adverse drug events. These include overdoses, prescribing errors as well as side effects. So if you count it that way, like that, they would rival accidents. And actually I found a 2016 British Medical Journal study called “Medical Errors as the Third Leading Cause of Death.” But the methods were shaky. They extrapolated from limited hospital data and a lot of experts have criticized it as inflated. But here’s the truth: adverse drug events are real. They probably kill over 200,000 Americans a year. I just think that calling them the third leading cause of death oversimplifies and sometimes even sensationalizes the data. Again, it grabs headlines and it gets clicks. Here’s my takeaway—we do need safer prescribing, we do need better monitoring and, in my opinion, we need more focus on what’s actually driving these conditions, so that we can eventually reduce dependency on medications wherever possible.
Here’s how it all comes together: heart disease, cancer, Alzheimer’s—the big killers. These all share a common soil: metabolic dysfunction. In the arteries, that dysfunction shows up as endothelial damage, too many LDL particles, and chronic low-level inflammation. In the brain and in cancer biology, it shows up as energy dysregulation, growth signaling and immune dysfunction. Medications help, but they’re not the full answer usually, especially if we ignore lifestyle. So if you want a simple sound bite: LDL loads the gun. Inflammation pulls the trigger. And metabolic dysfunction is the finger on the trigger.
Our job as clinicians, as patients, as a society—put the safety on by restoring metabolic health.
Work with us at The Facility Functional Medicine:
If you’re curious about functional medicine and how it could work for you, we’d love to help. Book an initial consultation with our Denver-based clinic (we see patients locally and via telehealth) and take the first step toward a health journey that doesn’t stop with you.
Meet The Functional Medicine Team behind Facilitated:
Mitchell Rasmussen, DC, CFMP: Mitchell is a certified functional medicine practitioner with a doctorate in chiropractic at The Facility Functional Medicine Clinic in Denver, Colorado.
With lots of letters behind his name, he entered chiropractic with a clear goal: to practice Functional Medicine. His biggest passion is the immune system. He has focused his post-doctoral education on immunology and clinical applications for chronic diseases like Lyme, tick-borne pathogens, viral burden, and mold exposure.
About Kate Daugherty, MS, CNS: Kate is a certified nutrition specialist and functional nutritionist at The Facility Functional Medicine Clinic in Denver, Colorado.
She began her career journey in neuroscience, which seamlessly transitioned into human nutrition. Utilizing food as medicine to treat the mind-body connection is truly remarkable. Kate believes that our eating habits nourish our soul as profoundly as they do our body.
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