The Body Fat – Immune Function Link with Alex Leaf & Ari Whitten

head_shot_ari
Content By: Ari Whitten

In this podcast, I am speaking with Alex Leaf — a nutrition expert, researcher, and teacher of nutrition at the University of Western States. We will talk about the little known link between body composition and viral infections.

Table of Contents

In this podcast, Alex will cover:

  • The sixth highest cause of death in the US
  • How your body composition influences your risk of disease
  • The link between obesity and chronic low-grade inflammation
  • How chronic low-grade inflammation impacts on your ability to fight off infections
  • The benefits of weight gain
  • How society facilitates overweight and obesity
  • The power of happiness at every size

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Transcript

Ari: Hey, everyone. Welcome back to the energy blueprint podcast. I’m your host Ari Whitten. Today, I have with me a very special guest, my good friend and now partner in the energy blueprint, somebody who works with me, who I hired because he is absolutely brilliant at what he does as a researcher. He’s one of the most knowledgeable people in nutrition and health science that I have ever met literally in my entire life. He brings a level of understanding of nuance and complexity and understanding of the different perspectives and an ability to cut through myths and pseudoscience and speak to the actual evidence that is just absolutely world-class.

Funny story. I actually a little more than a year ago, maybe a year and a half ago, I posted in an evidenced based group on Facebook saying, “Hey, I’m really looking to hire a researcher to help me out with some projects. Basically, the person that I’m looking to hire is someone just like Alex Leaf.” I literally said that in the post that I wrote and at the time, Alex was the senior researcher at examine.com. I was very familiar from a couple of years of reading his posts online, I was always very impressed with his level of knowledge. I said, I want to hire somebody just like this. Then about six months later, as luck would have it, he reached out to me and said, “Hey, you still interested because I’m interested too?”

It’s been a beautiful working relationship ever since. He’s been helping me a ton. Co-writing the next book I’m coming out with on sunlight, which is epic and he’s done a phenomenal job helping me with the research in some areas. He’s someone I have the highest level of respect for and I’m excited to introduce you all to him in what is the first of many, many podcasts to come that we’ll be doing on a regular basis. He, just a couple of quick formal credentials. He’s got a master’s degree in nutrition. He’s on the teaching staff at the University of Western States in the human nutrition and functional medicine program, and as I said, he’s the former senior researcher at examine.com.

One more thing I want to mention in addition to helping me co-write the next book, he also has been a huge help in building out a program that’s going to be released in a couple of weeks, which I’m very excited about, which is advanced fat loss strategies. Basically, it’s a no BS, no pseudoscience approach to fat loss, here’s the evidence. We are assuming you understand the basics of what fat loss is about good nutrition, good lifestyle habits, and yet you’re stuck at a plateau and you’re looking for next level cutting edge advanced fat loss strategies to take your results to the next level.

That’s what this whole program is about. It’s really is phenomenal. Anyway, enough of me glowing about how awesome and brilliant he is. Alex, welcome to the show. Such a pleasure.

Alex: Thank you. I’m really the one over here glowing. That was too kind of an introduction. I don’t have anything to say, that was awesome.

The biggest factors that control our health and immune function

Ari: It’s not too kind. You are brilliant, my friends. We’re going to be talking in this podcast something related to fat loss, something related to fat gain and fat loss, and tying that together with immunity, which is the topic that no one can stop talking about right now. We’re all very focused on infectious disease and immunity and it’s the coronavirus outbreak. This is a critical piece of the story that I think a lot of people are not really that clued into because they’re not hearing about it in the media. What we’re hearing about in the media is like how many people it’s killing, what’s the new death count of today, the shortage of ventilators, and how far away we are from a vaccine.

What’s not really talked about is, Hey, what are the big factors that control our health and our immune function. Talk to me about the broad overview of the relationship of being overweight, having excess body fat and how that relates to immune function.

Alex: When it comes to immunity and body weight, there’s really a huge focus on people being underweight. At a global level, infectious diseases are responsible for something like 15% of all deaths every year. Most of that is in less developed in nations– the ones where there still aren’t as good a sanitation practices, hygiene just isn’t the greatest medical treatments and antibiotics aren’t as readily available.

There is a very, very clear and well established link between being undernourished, malnourished and infectious risk because in somewhat of a vicious cycle, being undernourished, completely tanks the immune system and increases your susceptibility to infections and the severity of any infections you do get. Then those infections in turn reduce your appetite, cause muscle wasting and lead to malnourishment. That’s basically one of the most well understood relationships out there is the relationship between being underweight and having a greater risk of infectious disease burden.

What I think a lot of people, because of that very strong relationship, something that is less well known is the relationship between being overweight or obese and increasing your risk of infections. Believe it or not, in the US, infections, specifically respiratory infections like the flu are still the sixth leading cause of death and the seventh leading cause of lost life because of premature mortality. This is in the US where like being undernourished is basically unheard of. In fact, two thirds of the population are either overweight or obese based on BMI.

Some researchers, when they combine body composition with more accurate measures like waist circumference and DEXA scans, and they combine that with markers of metabolic health they estimate that about nine in 10 American adults are considered over fat because they’re carrying so much fat around, it’s damaging their health. You have this weird juxtaposition where most of the nation is definitely not undernourished, and yet, the sixth leading cause of death is respiratory infections like the flu. How do you explain that discrepancy?

That’s like this broad overview of infectious disease and how we can start to churn into the research on overweight and obesity. When we do that, what’s most surprising is that no one actually looked at how being obese impacts your risk of infections until around 2009 with the H1N1 flu pandemic. I think that many people today are seeing reports about how having poor metabolic health and being overweight or obese is a risk factor for the current pandemic we’re in with the COVID-19 and this isn’t a unique circumstance because that was the exact same association that researchers identified during the H1N1 flu pandemic.

Then from that point forward have since confirmed this association between obesity and an increased risk of infections from just the flu in general and other respiratory infections. Probably the only risk factor that is stronger than being obese when it comes to the risk of something like the flu is either being underweight marginally, but equivalent to being underweight, having a chronic metabolic disease like cardiovascular diseases, diabetes, basically the diseases that being overweight or obese increases your risk of getting.

We see that this infectious risk operates on a U-shaped curve where both being underweight and being overweight or obese, and especially, having impaired metabolic health increases your susceptibility of infections.

The link between obesity, blood lipid dysregulation, and insulin resistance

Ari: Very interesting. For people that don’t know, there’s obesity, there’s insulin resistance and type two diabetes, there’s blood lipid dysregulation and there’s hypertension, high blood pressure, and these are all very much connected. I think there’s a tendency in the general public to see these all as very distinct, very separate things, but there’s some people who have argued that to a large extent, this is really the same thing.

It’s really the same set of causes and it might manifest differently in different individuals depending on their genetics or the specifics of their particular health status or where along in the progression they are. What are your thoughts on just the link between all of these different things? Just connect the dots for people.

Alex: At a fundamental level, the link between all of the chronic diseases and obesity is going to be chronic inflammation, chronic low grade inflammation. There’s a subtle irony here because for influence– well, I guess, let me start here. Inflammation is a word that gets thrown around and a lot of people are familiar with it. When they hear inflammation, they’re like, oh, I’ve heard that before. I know what inflammation is, but they might not be able to describe it.

We can basically just think of inflammation as an immune response against damaged tissue, an infection or metabolic dysfunction. Dysfunctional tissues put out signals that cause your innate immune system to respond to it with inflammation. When we think about obesity and it stimulating chronic low grade inflammation, it basically stems from the fact that in people with obesity, in the majority, not all, but in the vast majority of them, their fat cells contain so much fat that the body perceives those fat cells as being dysfunctional.

In response, it sends immune cells to the area to try and clean up those damaged cells but all this ends up doing is creating a immune response in that area that then leaks into circulation. The obese individual has this systemic low grade state of inflammation. It’s not anything remotely close to what you would see if you actually had an infection or if you became ill with something. It’s much lower than that, but it’s high enough to be noticeable on tests that it’s outside of the normal range.

We call it low grade inflammation because it’s nowhere near an infection, but it’s definitely elevated. They have this 24/7. They have this chronic immune response and that is one of the fundamental drivers of actually why obesity is associated with an increased infectious risk and also, why many of these metabolic diseases are associated with that risk because they all share this commonality of chronic low grade inflammation.

That subtle irony I mentioned earlier is because you would think that having this enhanced immune activity would actually grant you greater protection against an infection because it’s like your defenses, your military forces within your body are on higher patrol. They’re more alert to anything that might go wrong but that’s not what happens.

The role of stress in immune function

Ari: I think a good way to think about it is like, hey, if you’re chronically stressed all the time, if you have that high baseline levels of stress and anxiety 24/7 on an ongoing basis as a result of just your lifestyle and your financial stress, job stress, relationship stress, that’s just at that high baseline level relative to somebody who’s not under so much stress, and then you’re met with a challenge, some new stressors, there’s some crisis, something bad happens, now you’ve got to deal with that new stress.

Who’s going to be more resilient? The person that was under chronic stress all the time and is already at the tipping point where they’re ready to explode with any new thing that comes across their path or the person who is in a much lower baseline state of stress and anxiety?

Alex: Yes, that is definitely one component of it. I’ll go a little– I’ll talk a little more about this in a bit. It’s an idea called immunosenescence, but another related aspect to what you just said with your example is that when your body is constantly operating up here, it becomes accustomed to operating up here and so when your– let’s say you do get the flu or another respiratory infection and your tissues, your cells that become infected with that virus are going to start pumping out things like interferon that try to recruit your immune cells to that area to say, hey, we have an infection over here. We need you to do your job.

They’re sending off this alert signal, but your immune system is like, well, we’re already over here. We can’t see the signal that you’re sending off because we’re in so much combat already. We’re not as keen to it. It’s like if you’re in a battlefield and there’s buildings on fire, things blowing up around you, but there’s one explosion you’re supposed to be paying attention to, how are you supposed to recognize that explosion that actually matters in light of all the other damage going around?

Ari: The classic tale of the boy who cried Wolf.

Alex: Exactly. Your immune system basically becomes desensitized to the initial signals that your body puts out to alert it that there’s a problem. This has tremendous consequences downstream because a delayed immune response means that that virus or bacteria or parasite can start to do more damage, can start to spread further before it ever gets contained. That initial ability to spread could really be the breaking point between even life and death because all it takes is it spreading to the right area and then you’re done.

One of the fundamental aspects of our innate immune system is to contain an infection before it spreads too far and then our adaptive immune system can come in and target it and destroy it, but you can’t do that effectively if you have chronic low grade inflammation going on because it becomes desensitized to those signals.

The other part of it though is what I’d mentioned, the immunosenescence and this plays into exactly what you’re doing with your bucket being already so full and then you’re just ready to go off the edge. Immunosenescence is the idea of the immune system essentially becoming aged and dysfunctional. Some of the listeners might be familiar with telomeres and the cell cycle and how there’s basically little like shoelace protectors on the ends of DNA strands of every cell called telomeres.

These get shorter and shorter every time the cell reproduces and creates and divides. Once they get too short, the cell can’t divide any further and it enters a state called senescence because if it tried to divide further, the DNA would become damaged and then you’re just increasing your risk of getting cancer and having cellular dysfunction and that doesn’t help anyone.

The same thing happens in immune cells. When you have chronic low grade inflammation, your immune cells are constantly reproducing, fighting this battle. All it does is it shortens their lifespan, so that ultimately in the future, your immune system is aged and less powerful than it should be. This has been actually demonstrated in studies in mice where it’s been suggested that obese mice are a animal model for premature aging of the immune system.

I can’t think of the details at the moment, but there’s at least one study that shows that. If the studies in mice do translate to humans being obese at the age of 21 would cause you to have an immune system that’s as old as a 55 year old that was normal weight their whole life. Just to give you an idea of the magnitude and we already know that elderly individuals are at an increased risk of infections as well and that’s precisely because of immunosenescence. They’ve been alive for so long their immune system has had so many battles, that as you age, it eventually just gets to a point where the immune system cannot continue to divide and produce cells to fight off these infections.

That’s one of the reasons why infectious risk is so large in the elderly. It’s the same concept in obesity. Chronic low-grade inflammation basically causes immunosenescence.

Ari: It would be interesting I think for listeners to have some of the dots connected here with coronavirus, specifically. So translating theory and the mechanisms that Alex is explaining to some real-world data of what’s going on right now. We know that within the US, 86% of the people that have died from coronavirus, generally, they’re older. Okay? So more immunosenescence is a factor, but pre-existing conditions, type 2 diabetes or insulin resistance, hypertension, high blood pressure, and cardiovascular disease, which are all connected, as you explained to excess body fat are– it’s 86% of the people who have died have at least one of those pre-existing conditions.

In Italy, the numbers are more like 99% of the people who have died are people who have at least one of those pre-existing conditions, as well as COPD and a couple of other risk factors, smoking and so on. Again, cardiovascular disease, insulin resistance, type 2 diabetes, high blood pressure, which are all directly connected to the accumulation of excess body fat are major risk factors for coronavirus. This isn’t just theory and speculation. There is real-world data that’s coming in right now with coronavirus that directly connects to the mechanisms that Alex is explaining here.

Alex: Yes, and to really solidify this idea, there was actually a study that came out just in March of this year by Dr. Stacy Schultz-Cherry. She used the very, very pathogenic H1N1 flu strain, as well as several other strains of the flu. What she did is she inoculated mice several times with them, and the mice were either obese caused through eating a high-fat diet or they were normal weight, they were normal mice. What she found as she inoculated them on a regular basis, and she tracked the viruses within them to see if the obese body doesn’t just affect the immune system, but if it actually has a specific effect on the viruses themselves.

She found that she could only infect the obese mice five times. She could only do five infection cycles before they just died because it became so pathologic, this virus. It mutated to such an extent that it just became ridiculously pathogenic. Whereas she could inoculate the normal-weight mice 10 to 15 times before it reached that level. Just to give you an idea of the type of environment the obese body allows for the virus to spread and mutate. In fact, when she took out the virus of the obese mice and put it in the normal-weight mice, that virus was three to five-fold more lethal than the viruses that were developed in the normal-weight body.

Ari: What explains–

Alex: What was that?

Ari: What explains that?

Alex: Basically, this idea of immunosenescence, the immune system in the obese mice was just so incapable of containing this infection. This is just theoretical mechanisms that need further follow up, but also the weakened immune system that allowed the virus to more easily spread and replicate, combined with the obese environment, where the immune cells or leptin resistant, where there is readily available fat in the bloodstream and glucose were able to just kind of feed this virus and make it much more lethal than it would be otherwise. Basically, the obese body is the perfect microenvironment for obese replication.

Studies in humans confirm this idea, like when you look at the duration of illness in people with obesity, not only are obese people normally more contagious and infected for a longer period of time than normal-weight people, but you also see higher levels of viral shed. Viral shed is basically whenever a virus successfully reproduces within a cell and then explodes the cell to release all of its viral copies out into the bloodstream to go infect new cells. That’s viral shed.

Obese people not only have higher levels of viral shed, they also stay contagious and stay infected for longer periods of time. All of this comes back to theoretically, the obese bloodstream being rich in nutrients that viruses and bacteria and other pathogens can use for their own purposes, but most definitely, an immunosenescence and a weakened immune system and an inability to contain and fight off infections.

Ari: You talked about the link with inflammation and tissue damage. Obviously, there’s probably a few different mechanisms of how that might occur. For example, in the context of insulin resistance that the chronically high blood sugar itself could be a factor that causes damage. The inflammatory cytokines, I think at some point, it becomes unclear whether the inflammation is just there as a beneficial reparative force or the inflammation is also now a cause and contributor to the problems. We’ve heard obviously lots of stories in the media about inflammation is the cause of disease, but then it’s like, “Okay, well, what causes the inflammation to go up in the first place.”

At some point, at least it seems to me like there’s a vicious cycle and you have both things occurring. You have the tissue damage, root causes causing tissue damage, inflammation is responding but the chronic effects itself now becomes the causative factor. What’s your take on that kind of landscapes?

Alex: I think what you said is exactly right. At a fundamental level, when you follow the chain of events from what causes low-grade inflammation, what causes systemic inflammation, what causes insulin resistance and metabolic dysfunction, when you follow that chain of events, it all really starts for, I would say, probably 99% of the time. Definitely, for anyone, that’s overweight or obese, it all starts in their fat tissue, simply exceeding what’s called the personal fat threshold, which is something that we talked about in the previous podcast that we did together.

Ari: Quick side note. For everybody who didn’t listen to that previous podcast on the personal fat threshold, the real causes of insulin resistance, highly recommend that. We might touch on a very brief summary of the causes of insulin resistance here at some point but definitely recommend, if you haven’t already, go listen to that episode. Very important to connect all that information with the information here. Sorry, carry on, Alex.

Alex: One of the reasons why we see worse infectious outcomes, especially with the flu and the recent pandemic that we’re having in obesity is because that low-grade inflammation has the immune system be so– I don’t know what the right words are, on edge, that any normal inflammatory damage you might experience is just going to be exacerbated. Inflammation is an immune response toward something. Anti-inflammation, so to speak comes about when the immune system decides that it needs to switch from attack mode to repair and regenerate mode.

So on certain immune cells, like T-helper cells and macrophages, we see very distinct subsets, where they can either pump out inflammatory molecules that tell the immune system to just attack, attack, attack, or they can actually start pumping out anti-inflammatory molecules that alter the activity of the immune system in a way where it will start focusing its efforts on cleaning up any debris from tissue damage and helping facilitate those repair processes.

When you get something like this disease where it’s causing lung damage, the chronic low-grade inflammation now is throughout the body is ultimately impairing any ability to repair damage that’s being done. Over time, that damage just continues to accumulate because you’re never getting the necessary anti-inflammatory repair and regenerate response. You’re just getting this chronic, keep going, keep attacking, keep battling. All that does is lead to worse outcomes down the road when it comes to things like respiratory distress. No different from smoking in that sense.

When you smoke, every time you smoke, you’re causing oxidative stress throughout the lungs and you’re causing damage– or even air pollution, air pollution and smoking are really no different. It’s all just causing oxidative stress and inflammation within the lungs, that causes damage. We know what the long term repercussions of that stuff are. It’s the same way in obesity. It’s just that instead of coming from the outside and going right in, it’s coming from the inside, it’s coming from that fat tissue into the bloodstream and then circulating throughout the entire body.

Ari: I want to address something, this is somewhat of a digression, but it’s important to mention, at least in a very, very succinct way. I don’t want to get really sidetracked in making this a big thing because it could take two, three hours to treat it adequately. Just a couple minutes of treatment I think is worthwhile to make sure that listeners who maybe are, who do have excess body fat do not feel shamed by it or do not feel like, “Hey, you’re just blaming me for it.” Just feeling like they’re at fault or they’ve done something bad. Do you want to speak to that just for a moment?

Alex: Oh, definitely. We can sum it up by saying that being overweight or obese is a very, very complex issue. The modern environment is when you combine the modern environment with evolutionary circuits within our brain, you create the perfect environment to cause overweight and obesity. It’s actually completely normal. In fact, gaining weight itself is a protective mechanism because as long as you can gain weight, you’re keeping energy out of your bloodstream that would otherwise cause damage.

Just look at type 2 diabetes. In type 2 diabetes, everyone or most people listening should be familiar with the notion that having chronically high blood sugar levels is very damaging and can lead to things like neuropathy and retinopathy that can cause like nerve damage and loss of limbs as well as blindness. That’s because having super high levels of energy, having super high levels of glucose and fat in your bloodstream is harmful. The whole reason we have body fat is not only to be a place of long-term energy storage for when we’re fasting or in a famine, but it’s also to protect the rest of the body because fat cells are very good at storing away that energy in a way that’s very benign.

It’s completely normal to gain weight and our current environment facilitates that. It’s when you’re unable to keep gaining weight, when you’ve surpassed your personal fat threshold, that’s when you start to see metabolic dysfunction occur. That’s when you start to see systemic insulin resistance and the deposition of fat in organ tissue as some kind of emergency backup system to try and get it out of your bloodstream because it being in your bloodstream, is so damaging.

Throughout this conversation and probably future conversations that we have when we discuss being overweight and obese, it’s never an attack on the person, it’s just discussing the science around that state of body composition. As hard as it might be for some individuals to hear, there isn’t much controversy around the health consequences of carrying around too much body fat. How much body fat? Like how much is too much depends on the person and it depends on your personal fat threshold.

Suffice to say, being a normal body composition with relatively low levels of fat mass and high amounts of metabolically active muscle tissue is going to be your best bet for long-term health. That doesn’t mean that there’s anything wrong with you or that there’s anything bad about gaining weight or being overweight or obese. Nothing even close and it doesn’t mean it’s your fault that you got that way.

Ari: We’re products of a world of a modern way of life that is almost perfectly designed in terms of the nutrition habits, environmental exposure to pollutants, toxins, sedentary ways of life, the shift from outdoor physical activity in our jobs to indoor sedentary work. All of these the modern, there’s so many layers, obviously circadian rhythm disruption and sleep deprivation tie into this. There’s many, many layers of just what is the normal way of life in the western world that drive excess body fat gain, that drive people to get overweight.

That’s why it is actually more normal, more common to be overweight than it is to not be overweight. The stats the last time I checked a few years ago were 75% or maybe close to 80% of people are either overweight or obese. If you think about it in those terms, it’s only like 20%, 25% of people are actually not in that category. It’s really just a product of our way of life. It makes it the norm.

Alex: One final point on this I really want to add is that there’s a movement out there called Health at Every Size. I think that the majority of the message they put out is amazing in the sense that you shouldn’t be ashamed of your body, you shouldn’t become obsessed with your food or your diet, and you should definitely have a great mind state about yourself, and you should have high levels of self-esteem.

The only part about it that I really disagree with is the health component. It’s just rather clear that you cannot be healthy at any size, based on the available evidence that we have. I think that frankly, their slogan would be much improved if they would say Happiness at Every Size, because you should definitely, everyone should be happy. There’s no reason to hate yourself or anything. It’s just about taking control, recognizing that if you are overweight or obese, you are likely putting yourself at an increased risk of long-term health consequences. It’s recognizing that and then saying, “I’m going to embrace that and I’m going to now work to improve my long-term health.” That’s awesome.

The link between chronic stress, overweight and energy levels

Ari: Beautifully said. Shifting back into how being overweight and the chronic inflammation that results from that drives different problems. We’ve addressed the immune aspect of it, or maybe we could talk more about that if you want. There’s also some other layers to the story that are worth mentioning, which is how the excess inflammation from excess body fat also contributes to mitochondrial dysfunction, to lower energy levels, to fatigue, as well as some other issues. Do you want to talk about that at all?

Alex: Yes. Actually, it’s funny because there’s a beautiful link between fatigue and reduced immune functionality because one of the primary ways that chronic low grade inflammation causes fatigue is through what’s called sickness behavior. Sickness behavior is an evolutionarily designed mindset and motivational place to be where– The best way to explain it is, if you’ve ever been sick, do you have energy to go out, go for a run, get through your daily chores, or do you just want to lie in bed all day, you don’t have much motivation, you don’t have much of an appetite?

That’s sickness behavior, because the body is saying, look, we got something going on inside and we need to take care of it. So why don’t you stop straining yourself, don’t be active because if you’re being active, that means you could be causing some muscle tissue damage. Just lie down. Let’s take care of this right now.

Especially because your immune system is going right now and it needs energy. The mitochondria in your immune cells are producing a ton of ATP, and we don’t have the resources– we don’t want to delegate resources to other parts of the body. We want your immune system to be functioning optimally. What happens is the inflammatory cytokines that are produced by immune cells that say, “Immune cells, attack”, those actually cross the blood brain barrier and they enter into the brain and they bind to receptors in the brain that cause this downstream effect of killing your motivation, impairing dopamine signaling, basically just making you very groggy and you can’t concentrate. This [unintelligible] of symptoms called sickness behavior.

It’s a beautiful bridge from you’re obese, you have chronic low grade inflammation, you have impaired immune function and that is going to translate into just having chronically low energy levels every day. That chronic inflammation means you have chronic levels of cytokines entering into the brain and saying, hey, we’re battling something so you need to chill out. We’re not going to increase your energy levels. We want you to not move around and we want you to feel like crap, but you’re not fighting anything. It’s just a side effect of your fat cells being dysfunctional and your immune system responding to that.

You don’t actually need to be less active. In fact, being more active would probably benefit your health. In evolutionary terms, no one ever had chronic low grade inflammation. They had spikes when they got injured or infected and then it went back to normal. We developed this very beneficial behavioral response to infections and injuries that now serves a maladaptive purpose because of this chronic low grade inflammatory state that most people are walking around in.

Ari: It’s worth mentioning, mitochondria are not just mindless energy generators that pump out energy. You just pour in carbs and fats and they just pump out energy. They are environmental sensors and they pick up on cues from the environment and they are deciding whether the body is primarily existing in energy mode and they’re going to divert resources towards producing lots of energy in what the way Dr Robert Naviaux, the researcher behind the cell danger response explains it as peace peacetime metabolism or if they’re picking up on cues from the environment that are danger signals, they shift into the cell danger response, which basically shuts down energy mode.

It shifts more into wartime metabolism. The symptoms you’re talking about of sickness behavior are directly related to this mitochondrial shut down. It’s not an on off switch, it’s a spectrum but the inflammatory cytokines themselves are signals to the mitochondria to turn off energy production and shift resources towards dealing with the threat. There’s this very direct tie-in between the degree of immune response and inflammation and the degree to which your mitochondria are either in energy mode or in sickness behavior fatigue mode.

Alex: Yes, exactly. Just to add to that to your mitochondria aren’t like, they don’t operate with one brain like we do. I give sickness behavior based on what Ari has just said is that basically, the rest of your body is receiving the signal. The rest of your body’s getting hit with these inflammatory cytokines that are telling the mitochondria in your muscle tissue, in your brain to go into defense mode and to reduce energy production because it doesn’t want you to burn energy. It wants all that energy to be used in your immune cells.

We actually see during infections, a hypermetabolic state. That’s because your immune cells needs so much energy to be able to fight off these invaders that you’re going to see ramped up energy production in your immune cells and those mitochondria and no energy production anywhere else. Obviously, you’ll have energy production, but relatively speaking, very little energy production in the rest of your body and that just further contributes to this state of chronic fatigue.

As I’m sure, Ari, is familiar and can probably talk to way better than I could, but there’s some huge similarities between people with, for example, chronic fatigue syndrome and people that just have genetic deficits in their mitochondria. They’re almost identical when you look at the fatigue scores between people with chronic fatigue syndrome, they’re like up here, but people who just have mitochondrial diseases are like down here, they’re very close.

Chronic fatigue is a little worse, but they’re very, very close. When you analyze the mitochondria of people with chronic fatigue syndrome, you see things like deficits in carnitine, which is required to transport fats into the mitochondria to use for energy, deficits in coenzyme Q10 which is required to move electrons across the electron transport chain and produce energy.

You have lower concentrations of antioxidants, higher levels of oxidative stress, lower rates of energy production, and you have changes in gene expression of all these functional pathways that impact the mitochondria’s ability to do their job. I think it’s a hundred percent accurate to say that the central issue with fatigue is deficits in mitochondria, but there’s a lot of ways that your mitochondria can accumulate deficits and one of those ways is being in a state of low grade chronic inflammation.

How obesity puts you at risk for viral infections

Ari: Just to extend that one layer further and connect it with these other aspects you’ve been talking about. Fatigue is also directly connected with excess body fat. Having excess body fat contributes at least through one mechanism of the inflammation and mitochondrial shut down, but probably several mechanisms because it’s also contributing to insulin resistance and tissue damage, altering hormones and negative ways. There’s at least a few different ways that it’s going to impact negatively on, of course, health more broadly, but energy specifically and of course immune function.

Tying this back up with immune function, are there any other layers to the story or maybe you just want to summarize what are the really big takeaway points from this in terms of how excess body fat links up with immune health and especially in light of, of course, what’s going on right now with coronavirus?

Alex: Yes, I think if I’m summarizing the relationship between carrying around too much fat and impaired immune function, most of it comes from the state of chronic low grade inflammation and the center piece of it that basically, a state of low grade inflammation caused by being obese causes your immune cells to age prematurely and that weakens their ability to fight off infections.

At the same time, you also have an impaired ability to repair any tissue damage that occurs as a byproduct of this chronic immune response. Therefore, you become much more susceptible to damage like lung damage for example, that can lead to the very severe long-term complications and even death from these infections. The obese body is the perfect environment for pathogens to establish a foothold and replicate effectively.

Ari: Beautifully said my friend. I would love to get into practical stuff, practical strategies that we could take away from this and say, okay, well, now basically what do we do with this information? Let’s say somebody does have a lot of excess body fat and they now understand everything that you just said and they go, okay, well maybe now’s a good time to start working on this.

Actually, quick digression, let me speak to that, this is the time. If you’re listening, this is the time to be working on your health. This is the time to be working on your body composition. There is no better time and it is never– you’re not going to be blessed with a greater opportunity and a more important time in your life than right now to work on your health because we have the data to show that your metabolic health and your body composition directly link up with your risk of having severe symptoms and dying from this virus.

Now’s the time. Rather than sitting on your butt and watching Netflix and eating potato chips and ice cream and pizza and being bored and drowning in your sorrows of being locked at home as most people are right now, unfortunately, we need to realize this is a golden opportunity to take control of our health and our body composition. Hopefully, you guys have gathered that I keep putting out that message in podcast after podcast. I think it’s really important to emphasize right now.

Having said that this topic of the practical strategies of fat loss is obviously hours of conversation further. We don’t have time to address it in three minutes right now, but we’re obviously going to do a part two and a part three. We’re going to make this a regular thing, have you come on the podcast, share your knowledge, share your wisdom and start teaching practical strategies. as well.

Hopefully, everybody listening found this really educational to understand the links of excess body fat with immune function with fatigue and immunosenescence and inflammation and all these different layers of the story that Alex explained. Hopefully, you feel inspired to take charge of your health at this point and we have more information coming on how to do that. Alex, is there anything you want to say to– any final words that you want to leave people with?

Alex: Yes, actually. I just want to follow up on your one note about this being the perfect time to lose weight if you’re overweight or obese. The beauty of this current situation, at least, in places where I’m currently living like New York, is that if you’re overweight or obese, exercise is actually less important to get results than if you’re already at a normal weight and trying to push the boundaries of leanness.

Basically, this is the perfect opportunity to just focus on your diet and get those diet things dialed in without having the stress or the little guy in the back of your head trying to get you to do all these other things that are important. Just take this time to get your diet dialed in get your sleep dialed in. Just get these things that you need to be doing when you’re at home anyway dialed in. Work on those.

Ari: Absolutely. Obviously, we’re relying on you at this point to do what you already know. Of course, most people are familiar with the basics of healthy eating and it’s more an issue of lack of doing it all the time than it is lack of knowledge of what foods are healthier than other foods. Nobody’s confused about whether pizza or broccoli is a healthier choice. Do what you already know are healthier habits for now and Alex is going to come back on the show many many more times in the coming months and be sharing lots more knowledge for free.

Also, we have an advanced fat loss program coming out in just a couple of weeks so that’s going to be available to everyone. I’m also going to make it available to people who if you’ve lost your job or something like that, I want to make sure that you have access to this material even if you can’t afford it due to losing your job as I think 20 million 22 million people have now in the United States from this coronavirus outbreak.

I want to make this accessible to everyone regardless of your financial circumstance right now. It is just so critical to work on your health, work on your body composition and we’re going to be providing lots of tools for free to do that as well as the full advanced fat loss program itself.

Alex, thank you so much for coming on and sharing your knowledge. One more thing I want to mention. There is already the podcast number one with Alex Leaf which covers insulin resistance fat loss and protein myths and other good stuff in there. There are some practical tips in there that we didn’t have time to get into in depth today but as I said, more to come. This is just part one and lots more amazing stuff to come. I hope you guys enjoyed this episode and we’ll see you again very soon.

Alex: Thanks, Ari.

Ari: Thank you, Alex. Really a pleasure.

Show Notes

The biggest factors that control our health and immune function (10:38)
The link between obesity, blood lipid dysregulation, and insulin resistance (16:23)
The role of stress in immune function ( 20:30)
The link between chronic stress, overweight and energy levels (43:30)
How obesity puts you at risk for viral infections (51:55)

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