A healthy thyroid is a critical component of one’s overall health, and many people are struggling with thyroid disorders such as hypothyroidism, specifically Hashimoto’s autoimmune thyroiditis. In this autoimmune condition, the immune system attacks the thyroid gland, with the resulting inflammation leading to an underactive thyroid gland or hypothyroidism. Hashimoto’s disease is the most common form of hypothyroidism and was the first condition ever to be classified as an autoimmune disease.

I’ve written extensively about thyroid health, focusing on a multitude of environmental factors that may affect thyroid function, including gluten, gut health, stress, excess iodine, and vitamin D deficiency. I’ve also discussed why dietary changes are always the first step in treating Hashimoto’s, and why replacement thyroid hormone is often necessary for a successful outcome.

There is yet another nutritional factor that may play a role in thyroid health: selenium.

Selenium deficiency is not thought to be common in healthy adults, but is more likely to be found in those with digestive health issues causing poor absorption of nutrients, such as Crohn’s or celiac disease, or those with serious inflammation due to chronic infection. (1, 2) It is thought that selenium deficiency does not specifically cause illness by itself, but that it makes the body more susceptible to illnesses caused by other nutritional, biochemical or infectious stresses, due to its role in immune function. (3) Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage from excessive iodine exposure. (4)

Several research studies have demonstrated the benefits of selenium supplementation in treating autoimmune thyroid conditions. One study found that selenium supplementation had a significant impact on inflammatory activity in thyroid-specific autoimmune disease, and reducing inflammation may limit damage to thyroid tissue. (6) This may be due to the increase in glutathione peroxidase and thioredoxin reductase activity, as well as the decrease in toxic concentrations of hydrogen peroxide and lipid hydroperoxides which result from thyroid hormone synthesis. (7)

Another study followed patients for 9 months, and found that selenium supplementation reduced thyroid peroxidase antibody levels in the blood, even in selenium sufficient patients. (8) While these studies show promise for the use of selenium supplementation in preventing thyroid tissue damage, further research is needed to determine the long-term clinical effects of selenium treatment on inflammatory autoimmune thyroiditis.

Additionally, selenium is also essential for the conversion of T4 to T3, as deiodinase enzymes (those enzymes that remove iodine atoms from T4 during conversion) are selenium-dependent. As I’ve explained before, T3 is the active form of thyroid hormone, and low T3 can cause hypothyroid symptoms. A double-blind intervention study found that selenium supplementation in selenium deficient subjects modulated T4 levels, theoretically by improving peripheral conversion to T3. (9) In cases of severe selenium deficiency, conversion of T4 to T3 may be impaired, leading to hypothyroid symptoms. As T3 conversion is not performed by the thyroid, the dependence on selenoproteins for this conversion demonstrates how significant selenium deficiency could lead to hypothyroid symptoms.

So the question is, should you start supplementing with selenium if you have hypothyroidism, Hashimoto’s thyroiditis, or low T3 levels?

As the answer often is, it depends. These preliminary studies show the positive effects of selenium supplementation on inflammatory activity in autoimmune thyroid conditions, but the long term effects of supplementation on thyroid health are still unknown. And we know that selenium is an essential component of the enzymes that convert T4 to T3, but whether supplementation will increase serum T3 levels is unclear.

While it seems that selenium supplementation would be an obvious solution to poor thyroid function, long term consumption of high doses of selenium can lead to complications such as gastrointestinal upsets, hair loss, white blotchy nails, garlic breath odor, fatigue, irritability, and mild nerve damage. (10) Additionally, supplementing selenium in the context of low iodine status may actually aggravate hypothyroidism. Mario Renato Iwakura discusses this particular topic extensively on Paul Jaminet’s Perfect Health Diet blog.

For now, the best option for most people may be to include selenium-rich foods in the context of a healthy Paleo diet. Great sources of selenium include: brazil nuts, crimini mushrooms, cod, shrimp, tuna, halibut, salmon, scallops, chicken, eggs, shiitake mushrooms, lamb, and turkey. For those concerned with the high level of omega-6 fats in brazil nuts, it may be worth considering the fact that it only takes one or two brazil nuts per day to improve your selenium status and boost immune function. (11)

For those who choose to supplement, I consider 200 micrograms of selenium to be a safe supplemental dose for people with thyroid issues. The brand of selenium I recommend is Life Extension Super Selenium Complex, which has four different forms of selenium, totaling 200 micrograms. It also provides vitamin E, which works synergistically with selenium as an antioxidant. This dosage is enough to be therapeutic for treating selenium deficiency, but has a lower risk of causing overdose symptoms.

Making sure your selenium intake is optimal may give your immune system and thyroid the boost it needs to help it function better. Whether through selenium-rich foods or supplements, it is especially important for those managing thyroid conditions to ensure their selenium status is adequate.

Has anyone had any experience with selenium supplementation? Was it a positive or negative experience? Let me know in the comments below.

**Special announcement: you’ll notice we’re now providing a full transcript for each new episode of the show.  Special thanks to Lindsey Gosling from our community for volunteering to do this.  She’s my hero.

One of the most hotly debated subjects in the Paleo-sphere over the last several months has been the causes and treatment of obesity and overweight.  Some claim that it’s simply a matter of “calories in, calories out”, and weight loss is just a question of “eating less, and exercising more”.  Others claim that it’s all about macronutrients (fat, carbs & protein), and calories don’t make a difference at all.

Over the last two decades a more sophisticated theory of weight regulation has emerged that encompasses the seeming contradictions in the prevailing paradigms.  This theory holds that the brain is the primary driver of weight gain and loss, and that environmental and genetic factors that influence this neurobiological system are what account for the alarming rise in obesity we’ve seen in the Western world since the early 80s.

2:57 Why it’s so hard to lose weight and keep it off
8:00 The truth about food reward, calories in vs. calories out, and “the metabolic advantage”
13:32 The Body Fat Setpoint making you “gain the all weight back”
21:06 Why leptin is the master fat hormone and what happens when you’re leptin resistant
26:05 The link between inflammation and obesity
31:00 Are modern foods engineered to make us fat?
49:48 The one thing any successful weight loss intervention must have

Links We Discuss:

• Stephan Guyenet: Author of The Whole Health Source Blog
• Stephan Guyenet: Body Fat Setpoint Series
• “The End of Overeating”

Full Text Transcript:

Steve Wright:  Hi everyone, and welcome to the Revolution Health Radio Show.  I’m Steve Wright from SCDlifestyle.com, and with me is Chris Kresser, health detective and creator of ChrisKresser.com.  How are you doing, Chris?

Chris Kresser:  I’m pretty good.  I have to confess to being quite sleep deprived.  Sylvie is usually a pretty good sleeper actually, but the last several nights she has been — I don’t know what’s happening, maybe a growth spurt or something, but she has just been squirrelling around the bed like a little monkey all night.  Yeah, so if I start slurring my speech or just have large pauses or gaps, you’ll know what’s going on.  How are you doing, Steve?

Steve Wright:  We’ll be a pretty good tag team today then, because I’m working one-handed here, so I can basically only talk.  I had shoulder surgery nine days ago, and everything went well.  It appears to be good.  I had a labrum tear, but I do have an arm in a sling for four weeks, so that kinda slows down life.

Chris Kresser:  Oh, wow.  Well, all right, so we’re injured and impaired, but we’re still here.

Steve Wright:  That’s right.  We can still talk!

Chris Kresser:  Yeah, thank God for the radio show!  So, let’s see, we have one announcement to make before we get started.  Some people are already aware of this, I’m sure, but we now have full transcripts for all of the Revolution Health Radio and previous Healthy Skeptic podcasts in the works, which is really exciting.  We loved you so much that we just decided that we were finally gonna do it, and we have a volunteer from the community, Lindsey, who is helping us with this on an ongoing basis, and we’re really grateful to her.  She’s doing an awesome job, and so we’ve already put some of the transcripts up on the website, on the actual episode posts, and some of the older ones are in progress right now, and we’ll be adding them as we get them done.  But in the future, I think we’re gonna be able to have the transcript up there right as the podcast or the radio show goes live, so that’s really exciting, and I hope you enjoy the transcripts, all of those who have been asking for them.  I hope you enjoy it!

Steve Wright:  Yeah, it will make things much easier to find with the Ctrl+F function.

Chris Kresser:  Yeah, definitely.

Why is it so hard to lose weight and keep it off?

Chris Kresser:  So, today I decided to review a study that was recently published by a friend of mine who I’m sure many of you know and a colleague, Stephan Guyenet, from Whole Health Source, one of my favorite blogs, and if you don’t know his work, I would highly recommend checking it out.  I think it’s WholeHealthSource.blogspot.com.  And Stephan published this paper with his mentor, Michael Schwartz.  Both of them are at the University of Washington School of Medicine.  And Stephan is an obesity researcher.  He has spent his career studying the mechanisms involved in particularly the neurobiology of weight regulation, and he just published a paper called Regulation of Food Intake, Energy Balance, and Body Fat Mass:  Implications for the Pathogenesis and Treatment of Obesity.  And we’ll put a link to the paper in the show notes.  Unfortunately the full text is not available for free, but the abstract is, and if you’re really interested you can cough up the, I think, 30 bucks or 35 bucks for the full text.  I want to talk about it because Stephan’s been on the show twice already to discuss obesity and all the various factors involved in obesity, but I wanted to take another opportunity to revisit this because I think it’s much misunderstood.  I think our understanding of it is continually evolving, and this paper, I thought, was the most concise and thorough synopsis of all of the various mechanisms that are supported in the scientific literature in terms of what causes weight gain and what might cause weight loss and keeping the weight off, because as everybody knows, losing weight is hard and keeping it off is even harder, and I want to explain in some detail why that is because, again, I think there is a lot of misunderstanding about that.  So, we’re gonna spend quite a bit of time talking about this.  It might even take the whole show.  If we have a chance, we’ll answer some questions at the end, and I’m sure we’ll come back to this again.  I’m not gonna get too far into what this means in terms of practical mechanisms because we’ll probably devote another show to that later, so this is just gonna be more of the background theory.

Steve Wright:  Sounds good.

Chris Kresser:  OK, shall we do it?

Steve Wright:  Yeah, are you gonna start with a high-level overview or just dive right in?

Chris Kresser:  Yeah, I’m gonna do a high-level overview, and so I’ll just give you kind of the basics of what we’re gonna be talking about, and then we’ll get into more detail about each point.  The high-level overview, I’ve written about this on my blog as well, and as most of you know, I think, obesity is a multifactorial disease, and I think pretty much anybody who researches it seriously agrees with that.  Anybody who says obesity is as simple as, you know, too much fat or too much carbohydrate or something like that is either misinformed or is intentionally misleading you.  It’s far more complex than that, but I can boil it down into one simple phrase, which is modern lifestyle + genetic predisposition = obesity.  And this is supported by the fact that obesity is virtually unheard of in populations that still follow their traditional diet and lifestyle.  In modern hunter-gatherer societies, it is basically nonexistent.  And then on the other hand, we know that there must be some genetic predisposition because not everyone who adopts a modern lifestyle becomes obese.  I mean, surely we all have friends or family members that eat like crap and they’re still really lean, so there are obviously some genetic and epigenetic factors, as well.

Steve Wright:  And lifestyle is food, stress, environment, everything?

Chris Kresser:  Yeah, exactly, so everything from the food we eat to our — I mean, actually it starts even before that.  It starts with our mother’s diet while she was pregnant with us, and it’s our gut flora particularly at the time of birth, whether we were breastfed.  So, that’s maybe kind of depressing news for some people because we obviously didn’t have any control over that, but it turns out that those things can have a very significant impact on our risk for obesity as we get older.

The truth about food reward, calories in vs. calories out, and “the metabolic advantage”

Chris Kresser:  One thing I want to talk about right up front is this whole — many of you who follow the Paleo blogs and are involved in this kind of thing have been aware of this debate that has been going on about food reward and calories in / calories out vs. the metabolic advantage or the idea that carbohydrates in particular predispose people to weight gain.  You know, on one end of the spectrum you have people say that calories don’t matter at all; it’s more a matter of carbohydrate density and the type of carbohydrates that you eat, and if you eat a low-carb diet, for example, you can eat as many calories as you want and you won’t gain weight.  And then you have on the other end of the spectrum people that say it’s all about calories, and as long as you’re in a negative energy balance, meaning as long as you expend more calories than you eat, then you will lose weight, and if you have an energy balance where you eat and expend about the same amount of calories, then you’ll maintain your weight.  That’s a little bit of a false dichotomy, and I’ll explain why in a second, but I just want to say for the record that I think that calories do matter, and I think the research definitely supports the idea that calories matter.  If you look at per capital energy intake — there’s actually a great graph in this study — in the U.S. it has increased about 20% since 1980, and that increase in energy intake or food intake over that period has closely paralleled the rapid rise we’ve seen over this past 30 years in obesity.  I think where people get confused about this is that they mistake the idea that calories matter with the idea that eating less and exercising more is effective weight loss advice; and it’s not.  And, you know, I absolutely agree with that.  That’s been a monumental failure.  The idea that you can just tell somebody to eat less and exercise more to lose weight is ridiculous and doesn’t work in the vast majority of cases, and we’re gonna talk a lot about why that is in the show today.  But that doesn’t mean that calories aren’t a factor and that some interventions that reduce caloric intake wouldn’t contribute to long-term weight loss.  This will be more clear as we get into it.  I’m already kind of ignoring my own top-line review thing here.

Steve Wright:  Hey, Chris, what was the 20%?  Was that 300 extra calories a day or 400?

Chris Kresser:  I don’t know the exact number, actually.  Let me look here.  I don’t know the exact number.  I’d have to look it up.  I just the percentage.

Steve Wright:  OK.

Chris Kresser:  So, another thing that we’re gonna focus on here is that over the last 20 years or so, research has shown that food intake and body fat regulation are primarily orchestrated by the brain.  And of course, the brain gets input from another of other body systems, but it turns out that the hypothalamus in particular, and other regions of the brain play a really essential role in regulating weight and body fat mass and that obesity involves the biological defense of an elevated body fat mass, or another way of putting that is an increased setpoint, and we’ll talk more about this.  And the increase in the setpoint, in turn, is mediated by interactions between the hedonic or pleasure/reward-seeking system and the homeostatic or energy-regulating system.  And these, in turn, are influenced by inflammation, both peripherally, like in the gut and other parts of the body, and then in the brain, by leptin resistance and by other mechanisms that impair the function of the hypothalamus or those other parts of the brain that are involved in regulating weight.  So, that’s the birds-eye view of what we’re gonna talk about, and it unfortunately gets a little bit complex in certain areas, so bear with me, and I hope it’s not overwhelming in those parts, but since we do have a transcript, you can go back and read it if it gets to be too much.  So, all clear, Steve?  Shall we go on?

Steve Wright:  Yeah, I think one more time really fast do that crescendo of the various parts.

Chris Kresser:  Well, basically obesity = modern lifestyle + genetic predisposition, and one of the ways that that is mediated, and the primary focus that we’re gonna talk about today, is the interaction between the hedonic and the homeostatic weight regulation mechanisms, and those are governed primarily by the brain.  So, that’s kind of the gist of what we’re gonna get to today.

Steve Wright:  OK, and then a bunch of things, like inflammation, affect the brain.

Chris Kresser:  Yeah.

Steve Wright:  Gotcha.  Cool.

The Body Fat Setpoint making you “gain all the weight back”

Chris Kresser:  OK, so let’s talk about the body fat setpoint.  I mean, I don’t know if anyone has thought about this, but if you’ve wondered how most lean people stay the exact same weight or within a couple of pounds for years or maybe their whole life without counting calories or weighing what they eat, it’s actually a pretty remarkable system if you think about it.  I mean, if it is true that the amount of calories you take in and the amount of calories you expend is what determines your weight, then it’s a pretty exquisitely regulated system to be able to maintain a range of weight within this 1 or 2 pounds without the person even thinking about it at all.  So, this happens because survival in a natural environment is threatened by either too little or too much fat.  If we have too little fat, we can’t survive periods of food scarcity and we starve; and if we have too much fat and we become obese, then we aren’t as fit to hunt and gather food and evade predators and survive.  So, the body has a system for maintaining a level of fat that’s appropriate for the human ecological niche, and this is called the energy homeostasis system or the homeostatic regulation of weight, and it’s this system that’s one of the main reasons it’s so hard to keep weight off once you lose it, because the homeostatic system responds to any reduction in fat.  Like if you lose 20 pounds, let’s say, this homeostatic system will increase hunger, it will decrease your resting energy expenditure, so even when you’re just sitting down the number of calories that you’ll burn will be lower, and it extract more calories from the food that you eat, so your metabolic efficiency goes up.  So, it has all of these mechanisms that are basically working against you when you lose weight to get you back to that body fat setpoint or what it thinks is the ideal weight for you.  On the other hand, if you were to gain 10 or 15 pounds, the body responds in the opposite way.  It would decrease hunger, it would increase your resting energy expenditure, so you burn more calories just sitting there, and it would extract fewer calories from the food that you eat, and by doing that your weight would also fall back down to the setpoint.  And so, a good analogy for this setpoint is a thermostat, and everyone knows how a thermostat works.  Let’s say the thermostat is set at 70 degrees, and that’s the setpoint for the temperature in the house.  And, you know, overnight the temperature drops down to 60 degrees, the heating system kicks in, and it brings it back up to 70 degrees.  And then during the day the sun comes out, maybe the temperature goes up to 80 degrees, and then the air conditioner kicks in and brings it back down to 70 degrees.  So, likewise, that’s how the body fat setpoint regulates our weight.  That’s what happens in a normal-weight person, but what happens in obesity is that the thermostat, or the body fat setpoint, gets thrown off and the body defends a higher setpoint, which corresponds to a higher fat mass.  And then when that person tries to lose weight, all of their efforts to reduce the fat mass are fought pretty strenuously by the body in the same way that a lean person maintains their normal weight.  So, it’s an extremely effective system, and anyone who has tried to lose weight and keep it off knows exactly what I’m talking about.  It’s really an up-hill battle, and that’s the depressing part about weight loss, and it’s probably why after all these years nobody has come up with the magic bullet.  You know, weight loss is a billion dollar industry, it’s still a huge hot topic in the research literature, and really it still hasn’t been cracked, and that’s because we’re talking about some very old, very powerful, innate evolutionary mechanisms that are working against us, and any time we’re up against mechanisms like that, you know, that are mediated by our brain and not in our conscious control, it’s a challenge.

Steve Wright:  So, when it comes to the setpoint, do we know anything about, like, how long it takes to slowly reset?  Because there are a lot a people who do lose the weight.  I’m not sure how many.  There are people who lose the weight and keep it off, and then there are definitely plenty of people who lose the same amount of weight but then gain half of it back, so is it more of a time-based thing, do you think?

Chris Kresser:  There are a number of factors that control what dysregulates the setpoint, which we’re gonna talk about, and as you say, there are some people who seem to be able to lose weight and keep it off, but statistically speaking, there is only really one treatment that we know of that reliably and substantially and durably lowers the setpoint in pretty much everybody that tries the treatment, or a vast majority of the people, and we’ll talk about that towards the end of the show.  But in answer to your question, I don’t think that it’s an easy formula and certainly not black or white, and it depends on so many factors, beginning with genetics, you know, gene mutations, single gene mutations, which are relatively minor, and then epigenetic and developmental factors like I just was talking about, maternal status, maternal weight, birth weight, exposure to initial bacteria, gut flora, breast feeding, food, environmental toxins.  I mean it’s so vastly complex that I don’t think there will ever be an easy, straightforward answer to that question.

Steve Wright:  OK, and then did you say that the homeostatic system basically will also stimulate more hunger, as well?

Chris Kresser:  Yeah, if you lose weight and you’re below what your setpoint is, then you’ll get hungrier.  And that’s one of the ways that the homeostatic system regulates energy balance.  You know, it’s one of the ways it tries to get you back to what it considers to be your normal weight.  And that’s fine, that’s exactly how it should work in a lean person, but the problem in obesity is that the setpoint has become too high, and so the weight that the body is defending is inappropriate, and that’s again, of course, why weight loss and keeping it off is so difficult.

Why leptin is the master fat hormone and what happens when you have too much

Chris Kresser:  So let’s talk about leptin because, as I’m sure most people have heard by now, leptin is really the master control hormone in this process.  It is made by fat cells in proportion to body fat mass, so more body fat means you’ll be producing more leptin.  And leptin basically informs the brain of changes in energy balance and the amount of energy stored as fat, so it’s a communication system where leptin signals to the brain how much energy is stored as fat, how much fat mass you have.  And that leptin signal acts primarily on the hypothalamus in the brain.  The hypothalamus is a little, pea-shaped gland kind of right between your eyes; if you were to extend back beyond that, that’s about where it would be.  But there are also other more specific areas like the arcuate nucleus; the paraventricular nucleus; the ventromedial hypothalamic nucleus; and the lateral hypothalamic area, which is often referred to as the LHA; and then other parts of the brain that are leptin sensitive.  So, clearly we know now from the last 20 years that leptin acts on several different areas of the brain, and that’s probably the main nexus of where leptin acts.  So, in a normal-weight person, here’s what happens:  When fat mass increases — if you go through a period of overfeeding or overeating, for example — leptin goes up, and then the brain gets the message to constrain the fat mass by reducing food intake and increasing energy expenditure, all of those mechanisms that we already talked about.  And then, on the other hand, when fat mass decreases, leptin will go down, and then the brain will stimulate mechanisms that increase food intake and reduce energy expenditure and cause body fat accumulation.  And so that’s how leptin regulates that homeostatic system.  But in obesity, what we see is an increase of fat mass and a corresponding increase then in circulating leptin, but the appropriate response of reducing food intake and increasing energy expenditure doesn’t happen, and this suggests a state of leptin resistance, where increasing amounts of leptin are required to overcome the insensitivity to leptin in the brain.  For people have heard of insulin resistance, and that’s a condition where the liver or the fat cells or the muscles cells become resistant to insulin, and the pancreas has to just continue to make more insulin in order to have the same response, in order to perform the functions that insulin should perform, because it’s basically like somebody is knocking on the door and nobody is answering, and so then they have to knock louder and louder or you have to get a couple more people to knock on the door before the person inside can actually hear it and open the door.  So, that’s possible with the pancreas and insulin resistance because the pancreas can just make more insulin, right?  But what happens with leptin resistance and in obesity, because leptin is produced by body fat, when there’s leptin resistance in the brain, the only way for the message to get through is for the body to increase fat stores, and that’s what will lead to a higher amount of leptin so that the message can finally get through.  So, this is how leptin resistance promotes the defense of a higher setpoint for body fat mass, and we see this borne out in studies that show the genetic interventions that prevent leptin resistance in the hypothalamus will also prevent obesity, diet-induced obesity.  We see this in rat studies, and we also have seen that leptin resistance precedes weight gain, so for example it can be detected in the brain even after relatively short periods of overfeeding, which suggests that it’s the leptin resistance that comes first, not the obesity.

Steve Wright:  So, once you’re obese then, you don’t want to focus on more leptin, you want to focus on the leptin resistance and making new receptors.

Chris Kresser:  Yeah, decreasing the factors that cause leptin resistance — and inflammation is a big one, improving leptin sensitivity, and decreasing fat mass because that’s part of what caused the problem in the first place.

The link between inflammation and obesity

Chris Kresser:  Let’s talk about what causes leptin resistance then, because we just touched on it.  So, one of the main causes is inflammation, and Stephan has written some good articles about this on his blog.  Maybe we can link to them, as well, in the show notes.  But we know that proinflammatory cytokines inhibit leptin signalling in a whole bunch of different cell types, so leptin is getting to the brain, again, but the hypothalamus can’t hear it, and then the fat mass has to increase to produce more leptin.  This inflammation can be caused by a lot of different factors.  There are, of course, a lot of foods that promote inflammation:  processed and refined foods in particular and sugar and some unprocessed, improperly prepared grains.  Gut infections that produce an increase in endotoxins like lipopolysaccharide and then intestinal permeability, which allows those endotoxins to get out of the gut and into the blood stream, that promotes inflammation and has been implicated in hypothalamic leptin resistance.  Then certain micronutrient deficiencies and fatty acid imbalances can also promote inflammation and leptin resistance in the brain.  And finally, another cause of leptin resistance is injury to the neurons that is, in turn, caused by accumulation of free fatty acids in the brain, and this has been shown in experiments with rodents, where researchers overfeed them, you know, they feed them a purified, which means processed, high-fat diet, and then they observe the damage to the neurons prior to the onset of obesity.  So, just like leptin resistance seems to precede obesity, then the damage to the neurons also precedes obesity.  So, let’s talk about now what else increases the body fat setpoint.  We just discussed inflammation, and inflammation is a pretty broad term that can include causes like gut infections and intestinal permeability and environmental toxins and food toxins and micronutrient deficiencies, etc.; but there’s another main cause, I think, and this is one that Stephan has really spent a lot of time and energy highlighting on his blog, and he has taken a lot of flack for it, which I don’t really understand why.  I mean, I understand people’s reaction, but I think he has presented really solid evidence supporting this.  I mentioned before that the modern lifestyle is one of the primary causes of obesity, and one aspect of that lifestyle that affects weight regulation is the availability of highly energy-dense and palatable and rewarding foods.  So, again, we have two systems that interact to regulate fat mass, and one is the hedonic or pleasure-seeking system and the other is the homeostatic system.  And we’ve talked a bit about the homeostatic system, but the hedonic system evolved to help our hunter-gatherer ancestors seek out and take advantage of any highly palatable, energy-dense foods they happened to come upon, and its job is to make it hard to resist those foods because they’ve been so rare for most of evolutionary history.  You know, having a 7-Eleven on the corner and being able to access extremely calorie-dense, rewarding, palatable foods is a very recent development on the overall scale of human history, so the hedonic system evolved at a time where that wasn’t the case, and it was to our survival advantage to be naturally drawn to those energy-dense foods and eat pretty much as much as we could of them and then store them because inevitably there were would be times where those foods were scarce and possibly even most of the time.

Are modern foods engineered to make us fat?

Chris Kresser:  But, like I said, over the last 50 years in particular, there has been a huge increase in the availability of these foods and actually a systematic effort by food manufacturers to increase the reward value of food, and there’s a book that’s all about this that Stephan referenced in one of his blog posts.  I can’t remember the title off the top of my head, but the book covers the intentional effort on the part of food manufacturers who hire scientists, people who really understand all of these mechanisms in depth, and they purposely engineer the food to be highly rewarding.  And reward in this context is actually a term borrowed from psychology literature, which means that it reinforces a particular behavior in response to a stimuli; in this case, eating.  So, eating a rewarding food makes you want to eat more of it, and there are a number of factors that influence the reward value of food — and believe me, the processed food industry has, like I said, teams of scientists that study these factors — and they include caloric density, the texture of food, the content of fat and starch and simple sugar and salt and free glutamate.  They talk about it with terms like ‘mouth feel,’ like when you put a food into your mouth, how it feels in the mouth; and they study the neurobiology of it, like what centers in the brain are stimulated when you eat that particular food.  It’s really quite insidious, and if you study it and become aware of how much effort has gone into this, it starts to become obvious, at least from this perspective, why there is such a dramatic increase in obesity.

Steve Wright:  Is that book The End of Overeating?

Chris Kresser:  It might be.  Is it?  Have you read it?

Steve Wright:  I think it is.  I’ve read that one.  There’s also Mindful Eating, I believe.

Chris Kresser:  I don’t think it’s Mindful Eating.  It could be The End of Overeating.  We’ll look it up and put it in the show notes.

Steve Wright:  Yeah, if it’s that book, that book just literally blew my mind.  It talks all about that, about the chemistry and the various — I think they have five variables that they rate food on.

Chris Kresser:  Right, so this is a highly developed science, right?  I mean, they talk about that in the book.

Steve Wright:  Yeah.  I think they talk about — I think it’s over a billion dollars that is kind of spent in R&D, or it’s some astronomical number that’s spent in R&D just to make us like the food, and they call it a craveability.  So, they want to create foods that just — like, for some people maybe it’s a Dorito, like the Cool Ranch Doritos, or something — and they’re only looking to promote foods that are craveable.  In a capitalistic, you know, consumer marketplace, that’s the only thing that’s gonna survive is that one food where you’re like, “Man, I just want some of that Cool Ranch,” or something like that.

Chris Kresser:  Yeah, exactly.  So, like I said, it’s an insidious and very highly developed industry.  Well, we know from many animal and human studies that the reward value of a food has repeatedly been shown to influence food intake and body fatness in both animals and humans; whereas, palatability, on the other hand, is defined as the pleasure or the hedonic value associated with a food.  So, when Stephan was writing this series, people got reward and palatability really confused, so let’s say again reward value reinforces a particular behavior; in this case, eating more of it; so eating a rewarding food makes you want to eat more.  Whereas, a palatable food is just one that tastes good, and you know, of course, they often are related.  Like, a highly palatable food might be one that is highly rewarding, in that since it tastes so good, you want to eat more of it.  But it’s not necessarily to the same degree.  A good example of this is steak.  Steak, in my opinion, is a pretty palatable food.  It tastes great.  I love it.  But how often do you hear somebody say, “I’m really addicted to steak.  I can’t get enough steak”?  People like it, they eat it, but it doesn’t tend to stimulate addictive eating behavior, right?  But you do often hear people say that about chocolate or ice cream or chips and crackers.  I mean, the whole Pringles thing, right?  What was their slogan?  “I bet you can’t eat just one.”

Steve Wright:  Perfect.

Chris Kresser:  Yeah!  There’s a reason for that, because the scientists have designed it that way, and their marketing department is even making a baldfaced bet against you in their advertising slogan.  They’re betting that your hedonic system’s evolutionary effectiveness is gonna override any willpower that you might have and that you won’t be able to eat just one, and so they’re doing everything they can to make sure that’s possible, and they’re capitalizing on our innate, you know, our evolutionary mechanism here that was designed from the beginning to be a survival advantage, but in an obesogenic environment where you have access to all these super-energy-dense, palatable, rewarding foods, that system kind of backfires.

Steve Wright:  So, let me repeat that back really quick.  So, palatability is just all about the food in itself and our judgement of whether it tastes good.

Chris Kresser:  Right.  It’s the pleasure and taste.  If you find a food to be palatable, that means you like it and it tastes good.

Steve Wright:  And then the reward that we’re talking about is multilevel — it’s a chemical in the brain, it’s psychological in our actions, and it potentially is also driven from, like, our ancestors in a deeper lizard brain as far as seeking certain nutrients, as well?

Chris Kresser:  Well, I think they’re both driven by neurobiological mechanisms, which we’re gonna talk about a little bit more.  I think that the easiest way to simplify it is that palatability doesn’t necessarily imply a change in behavior.  It just means that it tastes good and you like it and you get pleasure from eating it.  Whereas, food that’s rewarding will make you want to eat more, so it will actually influence your behavior.  And I think, again, the really good way to piece that out in your mind is just to think of certain foods that you like the taste of but you don’t have any kind of addictive relationship with them, like steak or something.  And those would tend to be foods that taste good and they’re probably part of our evolutionary history in terms of eating them, you know, like a plain sweet potato.  I think most people would think a plain sweet potato tastes pretty good.  It’s sweet and it’s pleasurable to eat, but how many people, again, do you know that just would go crazy eating plain sweet potatoes?  It just doesn’t really happen.  On the other hand, chips that have fat and salt and a particular mouth feel all engineered to stimulate the centers in your brain that motivate a particular behavior, that’s gonna have a really high reward value.  Does that make sense?

Steve Wright:  Yeah, it totally makes sense, and I think a lot of people listening probably in the Paleo crowd or the Specific Carbohydrate Diet crowd will relate, because I know that previously if I ate mashed potatoes or sweet potatoes I never thought of them as particularly intensely flavorful, and I think that’s just because I was eating that other stuff.  Then once you drop off and you eat something that has some more carbs in it like that, you can definitely taste the sweetness and it’s much more subtle.

Chris Kresser:  You got it, and I’m glad you brought that up, because one of the reasons I love this overarching theory is that it can explain why both low-carb and low-fat diets can be effective for weight loss and why when people tend to start adding carbs back if they have been on a low-carb diet or they start adding fat back when they’ve been on a low-fat diet that they tend to gain the weight back, and that’s because carbohydrates and fat have reward value on their own.  And so, when you remove or really limit a whole entire class of macronutrients, that reduces the reward value of that diet.  And then when you bring them back in, that increases the reward value and it tends to make you want to eat more of that.  So, in your example that you just used, if you’re on a low-carb diet, which the SCD and GAPS typically are, and then you start eating carbohydrates, you’re adding reward value back to your diet, and if you had a weight problem before and the setpoint hadn’t been actually adjusted, then the chances are that you’ll gain weight back.  We’re gonna talk a litte bit more about that in a moment here.  So, one of the best examples of how reward and palatability affect weight regulation is something called the cafeteria diet model of rodent obesity, and this is where they give rats a bunch of human junk food, so you know, just chips, crackers, candy — it’s all human, processed food — and then they also give them an unlimited amount of the standard rat chow, which compared to the human junk food is pretty boring.  And what do you suppose happens?  I mean, you can probably guess.  They over consume the junk food, and they don’t even touch the rat chow.  And the rats that are genetically susceptible become obese, and how addicted do they get to the junk food?  Well, the rats that are put on this cafeteria diet will voluntarily endure foot shocks and extreme cold just to obtain the cafeteria diet, even when the standard rat chow is freely available.

Steve Wright:  That’s how good those researchers are.

Chris Kresser:  Exactly!  So, I mean, it’s pretty amazing, and it works the other way around, and again, we’re gonna talk about that in a second, but before we do that, I want to back up a little bit and talk at least a little about how food reward and the central nervous system interact and the regions of the brain that are involved in this, because I thinks it’s important to have a basic understanding of it.  So, there are a lot of regions of the brain involved in evaluating and reinforcing the reward value of food, including the corticolimbic system, the hypothalamic system, and parts of the midbrain, and we know that signalling of dopamine and opioid peptides is especially important in the reward and hedonic value.  And this kind of gets at what you were asking before, Steve.  Dopamine signalling is thought to contribute particularly to reward, to the wanting of food and to the motivation to obtain food, and this is supported by the observation that changes in dopamine signalling are associated with other kinds of addictive behavior like drugs and alcohol and other substance abuse.  There are lots of studies showing in drug addicts or alcoholics that there is a problem in the dopamine signalling system.  We also know that interventions that alter dopamine signalling in the central nervous system have been shown to powerfully influence food intake and body fat mass, and we know that inherited or acquired reduction of dopamine signalling favors the accumulation of body fat.  And one theory on this is that overexposure to these highly palatable, rewarding, and energy-dense foods desensitizes the dopamine circuits, although there is some controversy about that.  Now on the other hand, opioids are connected to the liking or the hedonic value or palatability of food, and studies have shown that opioid receptor agonists — an agonist is a substance that mimics the action of a natural substance, so an opioid receptor agonist would be something that increases the effect of opioids.  They strongly increase intake of palatable food in rats, so if you stimulate the opioid receptors, rats will really go crazy for palatable food.  Whereas, on the other hand, opioid antagonists have the opposite effect.  So, we’ve talked a lot about low-dose naltrexone on the show, but full-dose naltrexone at 50 mg is an opioid antagonist, so it completely blocks the opioid receptors, and that’s why it was used for opiate and heroin and alcohol withdrawal, because if a heroin addict, for example, is on 50 mg of naltrexone and they shoot heroin they’ll feel absolutely nothing.  So, the naltrexone has been shown in clinical trials to reduce body weight because when people are taking it, they’re not inclined to eat as much palatable food, so that’s more evidence that these parts of the brain are involved.

Steve Wright:  I was just going to repeat that back:  So, dopamine is the craving, it’s the wanting, and then opioids are the high?

Chris Kresser:  Opioids are the liking.  Yeah, the hedonic — it goes to palatability.  So, dopamine is connected to reward and the motivation and the behavior, and opioids are connected to the liking or the experience of pleasure or the high, yeah, if you want to put it that way.  Definitely.

Steve Wright:  So, that’s how LDN works, is by taking away the high, then all you’re left with is craving, and you could eat a case of chocolate and –

Chris Kresser:  Well, that’s how full-dose naltrexone would work, but the problem with that is that it also, I mean, opioids are what regulate our sense of pleasure overall, so if you’re taking 50 mg of naltrexone, yeah, you won’t experience pleasure when you shoot heroin, and you won’t experience pleasure when you eat that bowl of ice cream, but you’re not going to experience much pleasure any other time.  So, there are pretty obvious problems with that.

Steve Wright:  Yeah.

Chris Kresser:  And then a third neurochemical that’s involved in this whole process are the endocannabinoids.  These are involved in the brain reward area, and of course, they earn their name after it was discovered that marijuana acts primarily through the CB1 endocannabinoid receptor.  Stimulating that receptor selectively increases the consumption of highly palatable foods, and this explains, of course, why people get the munchies when they smoke pot.  So, if they smoke pot and then those endocannabinoid receptors are activated, then they’re gonna want to increase palatable foods, and when people get the munchies they’re seeking out particularly palatable foods, right?  They’re usually not getting the munchies for, I don’t know, brussels sprouts.  I mean some people find them to be palatable.  I actually like them, but it’s not the food that people tend to eat when they get the munchies, right?  They’re going for the more palatable and probably more rewarding foods, as well.  On the other hand, just like naltrexone, drugs that block the endocannabinoid receptors have been shown to cause weight loss and selectively suppress the consumption of highly palatable foods in rodents.  So, that means it didn’t suppress consumption of all food across the board; it just selectively suppressed the consumption of the highly palatable foods.  But, again, there are some problems with using this as a treatment for human obesity because these drugs are known to have psychiatric side effects including an increased risk of suicide because the endocannabinoid system probably, again, plays a role in our overall experience of pleasure and enjoyment or life.  So, you have a drug that blocks those receptors, it does serve the goal of reducing consumption of palatable food, but it also, you know, really screws up people’s mood.  And, of course, that’s often the problem with drugs is they suppress function.  So, they suppress symptoms, but they also suppress functions, and that means that in solving one problem, they end up causing several others, because the receptors and proteins and things that drugs affect in the body don’t tend to have just one effect; they tend to have several different effects.  And so, when you suppress something, you’re not just suppressing the one effect that you want to get rid of.  You’re suppressing multiple effects, many of which are beneficial.  So, when you put all of this together, it suggests that in an environment where humans are exposed to food that’s way more palatable and way more rewarding than what we’re adapted to, that’s when you get obesity.  And I just want to reiterate that I don’t think that food reward and palatability is the only environmental factor involved in the obesity epidemic by a long shot.  We’ve already talked about other factors like food environmental toxins and genetics and micronutrient deficiencies and gut flora and birth weight, etc.  But I do think that reward and palatability is definitely a factor, and I think the research pretty clearly supports that it is.

The one thing any successful weight loss intervention must have

Chris Kresser:  So, let’s wrap all of this up and talk a little bit about what it means for people who are trying to lose weight, and as I said in the beginning, we’re not gonna — you know, we’re already getting to the end of the show here, so we’re not gonna have time to cover this in detail, but we will revisit it later.  At the simplest level, what it means is that any successful weight loss intervention has to involve lowering the setpoint.  And if it doesn’t lower the setpoint, the effect is just flat-out not gonna work at all or it’s gonna work for a short period of time and then the weight will come back, and of course, that explains why something like over 90% of people who go on calorie-restricted diets end up gaining the weight back at some point, and oftentimes they gain more weight back than they lost in the first place.  There is some evidence that low-carb diets and Mediterranean diets have been shown to induce moderate fat loss over the long term, and I think Paleo Diets can do that, too.  There are a few studies that suggest that, but we don’t have any long-term Paleo Diet studies yet on weight loss.  I certainly, you know, anecdotally in my practice have seen that, and I’m sure a lot of other people have had that experience, as well.  But on the other hand, I have a lot of patients in my practice who come to me for weight loss, and they’ve been on a Paleo Diet, they lost weight to begin with, sometimes quite a bit of weight, and then they either plateau and can’t lose the last 10 or 15 pounds or they start gaining the weight back and eventually gain it all back.  So, even though the Paleo Diet, I think, helps a lot of people and in some cases is the only thing that people need to lose weight and keep it off, there are clearly a lot of people whom that’s not enough for, and that’s one of the reasons I wanted to do this show, is I wanted to explain some of the mechanisms involved and help people appreciate how deeply rooted those mechanisms are, that they’re evolutionary in nature and that it’s not a failure of willpower, it’s not your fault that these systems are in place and that they work so strenuously against our efforts to lose weight.  So, getting back to the setpoint, right now, as I mentioned earlier in the show, the only intervention that we know that substantially and consistently and durably, meaning in a lasting way, reduces the defended level of body fat or the setpoint is bariatric surgery or gastric bypass.  So, this is a surgery where they divide the stomach into a small upper pouch and a much larger lower remnant pouch, and then they rearrange the small intestine to connect to both of these chambers.  In the most popular variation of this, the small intestine is divided about 18 inches below the lower stomach outlet, and then it is rearranged into a Y-configuration, and that enables outflow of food from the small upper stomach, and what it does is it causes a rapid onset of satiation, which is feeling full.  So, people who have had this surgery will feel full very quickly after they start eating, and then that is followed by growing satiety, which is an indifference to food or a lack of appetite after you’ve started eating.  So, people who have had gastric bypass, on average, they lose about 60% of the excess body weight that they were carrying — at least, morbidly obese people do, and those are the ones who generally have this surgery.  And in contrast to calorie restriction and other weight loss programs, the bariatric surgery causes a reduction in hunger and reduced cravings for energy-dense foods, and it doesn’t cause any change in circulating thyroid hormones that would suggest a compensatory homeostatic response to fat loss.  In other words, the body doesn’t respond to this surgery in the same way that it responds to caloric restriction that I described earlier by increasing hunger and decreasing resting energy expenditure and decreasing the conversion of T4 to T3 and all of those things.  And then we have studies that suggest that gastric bypass alters food reward processing in the brain, and so it’s changing the food reward system in some way, but those mechanisms aren’t entirely clear at this point.  So, at this point, it may seem like I’m recommending gastric bypass, and –

Steve Wright:  Are you?

Chris Kresser:  I’m not really.  I think it has some use in people who are extremely obese and who have tried every other way of losing weight and haven’t been able to because morbid obesity along with extreme, you know, metabolic syndrome is a real significant risk factor for a number of different diseases that can kill you.  So, in those situations, gastric bypass might actually be a valid alternative, but I’m not bringing it up to suggest it for people who are just trying to lose a little bit of weight or are even 10, 20, 30, 40, 50 pounds overweight.  I don’t think it’s a viable alternative in that situation.  There are risks, of course, associated with any invasive procedure like that, and you know, I’m more talking about this as a way of, first of all, just sharing what this surgery and what happens after it can tell us about the setpoint and other interventions that might help to lower the setpoint, because at this point that’s not altogether clear.  And that’s the million dollar question, really.  I talked earlier about how we just haven’t cracked the nut yet in this whole weight loss thing, and whoever figures out what nonsurgical method can reliably lower the setpoint is gonna get the Nobel Prize and be a multi-billionaire — if there even is such a, I mean, I frankly don’t think that there is gonna be just one thing and that it’s that simple because this is so complex.

Steve Wright:  Yeah, I think you made it pretty clear that this is pretty complex, and any thought that a surgery could just magically turn things around — because I think there is a lot of new stuff coming out now about long-term studies with the bypass surgeries, and they’re having onset of other diseases because of lack of nutrients now and that kind of thing.

Chris Kresser:  Absolutely.  Those are the complications that I was referring to, so there’s no magic bullet.  It does work for weight loss, that’s for sure, but as you pointed out, there are a lot of other problems that the surgery causes, and there is a lot more to health than weight.  There are some other interventions, though, that might lower the setpoint that research supports, and Stephan, again, of course, has written about this.  Just as increased food reward and palatability can increase the setpoint, there are studies that suggest that decreased reward and palatability lowers it in both rodents and humans.  And Stephan blogged about a really great 1965 paper that was published in the Annals of the New York Academy of Sciences, and in this study researchers developed a machine that basically dispenses bland liquid food through a tube at the push of a button, and it was kind of like sci-fi, if you look at the picture; it’s pretty funny.  And the formula was 50% carbohydrate, 20% protein, and 30% fat.  So, at first they fed two lean people with no weight problems for 16 and 9 days, respectively, and both people maintained their typical caloric intake and weight eating this really bland liquid food.  And then they fed morbidly obese volunteers, and over the first 18 days, one obese volunteer ate only 275 calories a day, and the second volunteer ate even less, 144 calories a day over 12 days, and that person lost 23 pounds in 12 days.  The first volunteer continued eating from the machine for 70 more days in the ward and lost 70 pounds total in that 70 days, and then he was sent home with the formula and instructed to eat about 400 calories a day with it for another 185 days, and he ended up losing 200 pounds in that 185-day period and, remarkably, never complained of hunger or GI discomfort.  So, some people might say, yeah, big deal; of course you’re gonna eat less food when it’s not palatable or rewarding.  But that doesn’t explain why the lean people maintained their weight and their caloric intake on that diet, because if both lean and obese people ate less of it, then you would expect the lean people to lose weight, but they ate the same amount of it, and they maintained their weight over that period of time.  And then there was another study in 1976 that confirmed that reducing food reward by feeding bland food lowers the body fat setpoint in humans.  So, all of this implies that, of course, highly rewarding food can increase the body fat setpoint in certain susceptible people, not in everybody, and that food with few rewarding properties can allow them to return to a lean state, and that doesn’t happen necessarily with everybody either.  And there’s also some evidence that suggests another technique called the protein sparing modified fast may reset the setpoint, but we’re out of time here, so we can’t talk about that in any detail.  Before we close, I just want to say a brief word about genetics.  There’s absolutely no doubt, as I’ve said a few times already, that genetics play a role in fat gain and fat loss, but how much is the question.  We know that heritable factors, when you combine genetics and epigenetics, are estimated to account for somewhere between 45% and 75% of body mass index variability.  But we also know that monogenic disorders, which mean mutations of one single gene, account for less than 5% of obesity, and some estimates say it’s even less than 2%.  So, this means, of course, that obesity is a polygenic trait, which means that it involves both developmental and epigenetic factors, as well as genetics, and we’ve talked about some of those before.  Things like low birth weight and maternal obesity and maternal overnutrition can increase subsequent obesity risk.  And likewise, prepregnancy fat loss, like women who have had the bariatric surgery before they get pregnant, tends to reduce the future risk of obesity.  So, this suggests that genetics do play a role, but that role is pretty small on its own but pretty large when you combine genes with environmental and developmental factors.  So, again, it’s the interaction of the genes and the environment that really makes a difference.  OK, I think that’s it!

Steve Wright:  Yeah, that’s pretty powerful!  So, the moral of the story is that you could have been set up from the beginning, unbeknownst to you, from genetics.  And there are a bunch of scientists and a large, billion dollar industry that are trying to set you up on the corner, and so you definitely need to get some help, right?

Chris Kresser:  That’s it!  I hope that the effect of this — one interpretation of this is to get really depressed and say, “Wow!  It’s just pointless to even try to lose weight.”  But I hope that’s not the result of this.  My intention was that people who have been having a hard time might be able to find some more compassion for themselves, because if you think about the forces you’re up against — as you pointed out, so you’ve got genetics, genetic predisposition.  Then you’ve got epigenetic factors that start from before you were even born.  I mean they basically start at conception or even before conception with your mom’s nutritional status during her pregnancy and then your birth and the manner of your birth and whether you were breastfed and your early exposure to all of these environmental factors.  And then you encounter the food industry, which, like you said, is on every corner, trying to get you to eat these highly energy-dense, palatable foods, and that is interacting with all kinds of neurobiological mechanisms, opioids, endocannabinoids, dopamine, and the whole hedonic, pleasure-seeking system that we’ve had as part of our wiring for millions of years.  So, when you put all that together, I hope it leads to just an appreciation of the difficulty of the task and maybe some compassion for yourself if you’re struggling with this for why it is so difficult, and hopefully in the future we’ll get a chance to dive more into what can be done about it, and I will frankly say that weight loss is difficult.  It’s one of the hardest things for me to treat in my practice.  I’m experimenting with some different programs designed to reduce the body fat setpoint, and sometimes they’re successful and sometimes they’re not.  And I’d be really suspicious of anybody who claims to have a program that works for everybody.

Steve Wright:  Yeah, I hope this isn’t depressing either.  I hope this is eye-opening, as you said, and I think it should be eye-opening in the fact that there is no magic pill.  There’s not a magic pill that’s even in testing that could come, and the appreciation that it’s a multifaceted problem, which means that the answer is likely multifaceted.  So, it’s a food problem; therefore, there’s gonna be a food answer.  It’s potentially a psychological problem; there might be a psychological component. It’s a chemical problem; there’s probably a chemical answer.  And altogether, I think it should be encouraging to take multiple steps in every area.

Chris Kresser:  Yeah, that’s very well said, and the takeaway is that it’s extremely individual, and it’s really important to first identify what all the mechanisms are in each individual case and then address those one by one, and that’s, of course, why there is, again, no magic bullet that works for everybody in the same way.  OK, so thanks everybody for listening, and we’ll see you next time!

Steve Wright:  Yeah, it’s been a great show!  OK, so if you’re confused about what to eat, which, after the show, you might be, check out the PersonalPaleoCode.  It’s a 3-step program designed to help you discover your own ideal diet and create highly customized meal plans with a few clicks of a button.  You can visit PersonalPaleoCode.com to learn more.  And if you’re trying to get pregnant or are already pregnant or nursing, don’t miss out on The Healthy Baby Code.  It guides you through the essential steps to naturally boost fertility and promote lifelong health for you and your baby.  Find out more at HealthyBabyCode.com.

Thanks for listening, and keep sending us your questions at ChrisKresser.com using the podcast submission link.  If you enjoyed listening to the show, please head over to iTunes and leave us a review.

The podcast is back! Only now it’s not a podcast, it’s a radio show (Revolution Health Radio), and we have a new host: Steve Wright. Everyone say “hi” to Steve!

We had a few growing pains on this first episode, so the audio is not quite as good as it normally is. We’ve got it ironed out now, though, so expect studio quality sound from here on out.

In the first episode of Revolution Health Radio (RHR), we cover:

• 1:17 How Steve, the new RHR host, came to be here
• 5:13 The latest study showing the concrete connection between chronic stress and the immune system
• 10:38 Can arguing with your significant other trigger inflammation and cause disease?
• 16:51 Recommendations for benchmarking your inflammation from chronic stress
• 21:18 The latest Fasano paper: could healing the gut prevent and cure autoimmune disease?
• 27:02 Why fixing leaky gut can stop and reverse autoimmunity
• 36:59 Will the latest intestinal permeability drug trial lead to Celiac’s eating gluten again?
• 44:12 How to overcome IgG food sensitivity to eggs and milk
• 54:07 The 3-step process for figuring out the right diet changes that work for you and your body… once and for all

Links We Discuss:

1. Study: Chronic Stress, Immune Dysregulation, and Health
2. Study: Leaky Gut and Autoimmune Diseases
3. Diabesity: The #1 Cause Of Death And Disease
4. 9 Steps To Perfect Health: Manage Your Stress

In this episode we discuss the gut-brain axis: the relationship between digestive health and cognitive function, memory, depression, anxiety and other mental and behavioral health issues. We cover:

• the basic physiology involved
• how inflammation in the gut affects the brain
• how decreased brain activity compromises gut function
• how to recognize the signs and symptoms of gut-brain axis dysfunction
• studies demonstrating gut-brain dysfunction and its effects on health
• dietary and lifestyle modifications to improve gut-brain function.

I think the gut-brain axis is one of the most important and least recognized factors in human health. If you follow a good diet (Paleo, Primal, Perfect Health Diet, etc.) and you’re still experiencing gut symptoms, it’s likely you have a gut-brain axis issue.

Full Text Transcript:

DANNY RODDY: Hello everyone and welcome to the Healthy Skeptic podcast. My name is Danny Roddy and with me is Chris Kresser, health detective and creator of thehealthyskeptic.org, a blog challenging mainstream myths about nutrition and health. Chris, how are you doin buddy?

CHRIS KRESSER: I’m pretty good Danny, how bout you?

DANNY RODDY: I’m doing really great, but when I walked into my garage, my podcasting studio, I forgot to plug in my deep freezer from two weeks ago, so there was spoiled beef fat that smelled absolutely terrible.

CHRIS KRESSER: You’re bringing this whole garage band thing to a new level huh.

DANNY RODDY: Cleaning out the deep freezer was one of the worst moments of my life, also because it was a ton of expensive spoiled meat.

CHRIS KRESSER: Yeah that’s what I was gonna say.

DANNY RODDY: But the smell, oh my God.

CHRIS KRESSER: That would be catastrophic for us, we buy like, a quarter of a cow at a time, it’s like $500-600 bucks of meat, if that happened I would be really really upset.

DANNY RODDY: Every single time we podcast I tell myself, you need to like make a note because you’re totally gonna forget and I forgot.

CHRIS KRESSER: Maybe we need the Danny Roddy grass-fed beef fund.

DANNY RODDY: It’s okay I’ll get by. It was mostly fat, which I’m more happy about, cause I think it’s like, way less expensive.

CHRIS KRESSER: Yeah, definitely. Good.

DANNY RODDY: What’s new with you?

CHRIS KRESSER: Um, ya know just slowly getting settled in to our new place, and when I say slowly I mean it. My office probably still has probably 14 unpacked boxes that I’m surrounded by. I’ve just been too busy to unpack em and it’s gonna stay like that for the next couple weeks until we get the healthy baby product out, which, I’ll talk a little bit about at the end, cause it’s coming up. I’m pretty excited about that. Yeah otherwise I’m happy to see the spring here it’s a beautiful, sunny, windy, crisp day in the bay area, I like that kinda day, so I’m good.

DANNY RODDY: That’s exactly how it is down here too. Awesome so this week’s episode is gonna specialize in the gut-brain axis. Do you wanna tell us a little more about it?

The basic Gut-Brain Axis physiology involved

CHRIS KRESSER: The gut-brain axis, the axis of evil. Sounds kind of sci-fi, but actually it’s probably one of the most important and most often ignored aspects of health and I think the more I see patients and the more I get into this research, the more important I’m seeing it and the more significant I think it is, especially in people who are doing all the right things in terms of gut health and they’re not improving. And that’s actually a significant percentage of the patients I see, fall into that category, so it’s one of the reasons I’ve been pursuing this as an avenue of research.

DANNY RODDY: It seems like it’s kind of a black box mysterious thing to treat, I hear everybody talking about but it seems very up in the air, is it just because it’s so new, do you think?

CHRIS KRESSER: Um, I think that’s partly it but I actually think that it’s related to what we’ve been talking about a lot that some of the treatments for it are, involve lifestyle changes that are a lot more difficult to make than just switching up your supplement regime or the percentage of carbohydrates you eat every day.  I know people are probably getting tired of hearing me say this but, the whole stress management piece is so crucial and yet I think it’s the hardest thing we can do in terms of making changes in our health. We’ll talk about that at the end when we talk about how to work with gut-brain axis issues.

I’ll talk a little bit generally about what I mean when I say the gut-brain axis cause it’s complex but it’s also completely simple. It’s probably obvious but I’ll say it anyways, everything we’ve ever done in life, or everything we ever will do depends on the brain. Anything from our capacity to taste food or appreciate art or music or smell, to feel the sun or the wind on our skin. To enjoy activities, to read, to record a podcast, it depends on our brain. And if the brain’s not functioning well, nothing else in the body will function well, period. And that’s so important to get. It’s one of those really obvious things that’s so obvious maybe that we overlook it.

DANNY RODDY: Is it the chicken or the egg syndrome though, because I feel like foods I eat specifically make me happy or sad, or is that a mental thing? Do you know which comes first?

CHRIS KRESSER: I think the sooner we get rid of this idea of linear causality in the body the better. One of the coolest things about Chinese medicine (and Chinese philosophy in general) is that they don’t really tend to see things in linear fashion. They see things in a cyclical way. And they way they look at the body, they would never say ‘this causes that’, like from A to B. It’s always ‘this and that’. Or, ‘and both’. For example, they’ve always recognized that the emotions, psychology, and physiology are one in the same. In fact they don’t even really have a separate word for emotions, like in the medical sense. Of course they do in language, but they look at systems of the body. The liver system, or the lung system, or the heart system. Each system includes both physical symptoms and also emotional and psychological and even psycho-spiritual aspects. So it’s a pretty cool way of looking at the body and I think in that sense it’s more advanced than our way of looking at it, which is ya know, like a car, with a bunch of separate parts. We understand that they’re related but we still talk about them as being and distinct. But the truth is, you can’t really talk about emotion without talking about physiology. And you can’t talk about physiology without talking about emotion. They’re not connected, they’re  the same system. So I think that’s important to understand and it kinda makes the chicken and egg thing a moot point. In the sense that it’s really difficult, if it’s all part of the same system it’s really difficult to say which came first and which followed. Once you’re in the cycle you’re in the cycle. So, that’s good news, bad news because it means that when it comes to treating it, you don’t have to figure out which one. You do both and both will improve. But you can figure out which one you havn’t been focusing on, which in most cases for most people is the brain. And so you might get more milage by focusing on one area because you’ve been neglecting it.

DANNY RODDY: I like that cyclical thing, I’ve never heard that before.

CHRIS KRESSER: Yeah Chinese medicine, they’re amazingly far, far ahead of they’re time. They figured this stuff out 2500, 3000 years ago. While we were still thinking about things in terms of phlegm and bile, western medicine was just a totally archaic understanding the body.

DANNY RODDY: Phrenology?

CHRIS KRESSER: Yeah, you were a phlegm type, or a bile type, and you know even up until the middle ages we were bleeding buckets full of blood from people to make them better. Ya know George Washington was killed by his physician who just kept bleeding him and bleeding him. He was sick but he just kept bleeding him til he died. Anyways I don’t know where the heck we’re going with this, but lemme get back on track here.. the brain.

How inflammation in the gut affects the brain

When the brain’s not functioning well nothing else in the body functions well. So you have to also remember that neurons are post-mitotic which means they don’t go through  cell division, they don’t regenerate. They’re like heart tissue in that respect which is the only other post-mitotic tissue in the body. So when neurons die that’s it. You don’t get new ones, game over. So for example by the time you finish listening to this podcast you’ll probably have lost about 7,000 neurons. Sorry to say, it depends what you’re doing while you’re listening too but, and the day that we’re born we have more neurons than we’ll ever have in our life. So that’s the bad news but the good news is that the neurons can develop plasticity, which means that when you lose neurons, other neurons can adapt to communicate with each other so you can form these new connections that can take the place in some cases of the loss of neurons.

What all this means is that protecting the brain from neuro-degeneration, which is happening for all of us all the time, and when I say protecting I don’t mean stopping cause you can’t, at least we don’t know how to yet. I mean slowing it down as much as possible. This is one of the most important and again overlooked steps we can take in protecting our health.

So let’s talk a little bit more specifically about the brain-gut axis and how it all works. The 50,000 foot overview, which somebody on the facebook page asked for, is this… 90% of our brain’s output goes into something called the pontomedullary area, it’s the lower two-thirds of the brain stem, and that goes into the vagus, or the pneumogastric nerve, which innervates the digestive tract. Now one of the earliest signs of the brain not firing well is poor vagal activity, which will manifest as decreased pancreatic enzyme secretion, poor gallbladder function, and poor gut function overall. And it basically works like this, you have decreased activity in the brain, and we’re gonna talk about how that can happen in a second, and that decreases the activation of the vagal motor nuclei, which in turns suppresses the intestinal immune system and decreases intestinal blood flow. And when that happens you get an increased growth in pathogenic yeast and bacteria, that cause intestinal permeability or leaky gut, which we’ve talked about a lot, and leaky gut causes a state of chronic low grade inflammation. Then the inflammatory cytokines produced in the gut travel through the blood and they cross the blood-brain barrier. One of the problems with inflammation is that it makes the blood-brain barrier leaky so you get leaky brain. And then those inflammatory cytokines once they get into the brain activate the microglial cells, which are the second type of cell in the brain. You have neurons and then you have microglial cells. The microglial cells are the immune cells of the brain and once they’re activated by these inflammatory cytokines this is basically inflammation of the brain. So your brain gets inflamed, you get a leaky brain and then you get inflamed brain. And that’s no fun, definitely. Cause one of the problems is that unlike the rest of the immune system in the body that has T-regulatory cells that can turn off inflammation in the brain, the microglial cells don’t get turned off. So, when you’ve got an inflamed brain it can be really tricky to reduce that inflammation without some outside help. So, you’ve got an inflamed brain and the inflammation in the brain decreases nerve conductance and that in turn causes depression and reduced activity of the vagal motor nuclei, and of course then we’re back where we started. That reduced activity of the brain reduces the output into the vagus, and that causes more digestive problems, more inflammation in the gut, more inflammatory cytokines to be in the bloodstream and up into the brain and we’re stuck in this really viscous cycle.

DANNY RODDY: Cyclical

CHRIS KRESSER: Cyclical, exactly, more cycles, it’s all cycles baby! So, this is also why digestive symptoms are typically the main symptom of brain issues. I don’t know if you’ve ever thought about this, but two of the populations that most commonly have gut symptoms are seniors and autistic kids. I mean, show me an autistic kid and I’ll show you someone that’s got a screwed up gut. As Datis Kharazzian likes to say. And seniors typically have problems chewing, they have hypochloridia or atrophic gastritis where they don’t produce stomach acid, they’re constipated. It’s very very common to see digestive problems in seniors and it’s not a coincidence, it’s not, there’s a mechanism here and that mechanism is neurodegeneration and neuroinflammation. The other thing that’s important to recognize about all this, which we already alluded to, is that when gut symptoms persist even in the context of a healthy diet, like let’s say you’ve done the 30-day challenge or your on a paleo diet and you’re still having a lot of symptoms, that could indicate a brain-gut axis problem. It may also indicate a parasite or something like that, but let’s say you’ve been tested for a parasite and you don’t have any but you’re still having all these gut symptoms, that’s the brain-gut axis or the gut-brain axis right there.

DANNY RODDY: Could  heavy metals be another factor?

CHRIS KRESSER: Sure,  I mean any kind of environmental toxin, including metals, could be a factor in terms of agitating the gut and causing inflammation. And also, I think as you’re suggesting, causing issues in the brain. But, the body is equipped to deal with some level of metal toxicity and of course there certainly are people who have more exposure to toxic metals than they can handle, but I think heavy metal toxicity is also one of these diagnoses that fall into that sort of like, candida, chronic fatigue, lime disease category.

DANNY RODDY: I couldn’t agree more, just because the amount of people with amalgams in their mouth and that are unaffected by them is huge so it’s like some people it affects really badly and then other people it’s like totally okay.

CHRIS KRESSER: Right so my mantra lately is ‘it’s the environment stupid’. Which is like, we’re always trying to find the answer for everybody, but the truth is, and I was just talking to a patient about this yesterday, there is no answer for everybody because everyone’s internal environment is different. So for example, you take one person and they have Blastocystis hominis, which is the most common parasite in humans and they have no symptoms, they’re completely healthy, completely symptom free. Take another person and they have blasto and they’re totally sick. They’re like on death’s door. So is Blastocystis pathogenic or not? Well yes and no, it depends on what’s happening in the host. Depends on the internal environment of the gut, and the innate immunity of that person. As usual it’s a lot more gray than we’d like it to be.

Just a little personal story here, lately I’ve been overworking. Between my very full practice, and the blog, and facebook and twitter, and I’m spending a lot of time on this healthy baby product which I’m really excited about, it’s gonna be ready soon. I’m just like, I’m working too much, there’s no other way to put it, not taking my own advice. I have been exercising, doing my sitting practice, those pretty much are bulletproof, they never go away, but  a lot of the other things I usually do to keep my brain functioning well, like just resting, surfing, going out in the sun, listening to music, doing yoga and other stress management stuff, having fun, watching a funny TV show or movie or something like that. I havn’t been doing that stuff.

DANNY RODDY: You better watch out cause Durian Rider is gonna write a post about you like he did Robb. Did you see that?

CHRIS KRESSER: No I don’t pay attention to that stuff.

DANNY RODDY: Well no doubt he’s crazy but he wrote a really mean article about Robb and then Robb responded with something really funny but I don’t remember what it was.

CHRIS KRESSER: I try to take the high road with that stuff, I don’t even have time to bother with those people. So anyways I was noticing a flare up in gut symptoms, ya know I have this history of digestive issues from when I got parasites and amoebas and a bunch of other stuff in Asia a long time ago, some of you know that story. I was starting to have gut symptoms, I hadn’t made a single change in my diet, a single change in the supplement regime (which is pretty minimal anyways), nothing else had changed except for the level of work I was doing and the amount of time I was spending taking care of myself so I switched some things up over the past week or ten days and even in that short period of time I’ve noticed huge differences, I feel like I’m back on my normal track again, so just a little cautionary tale.

How to recognize the signs and symptoms of gut-brain axis dysfunction

Okay so what are the symptoms of a brain-gut axis problem? Well, fatigue and brain fog are a big indicator. We’ve talked about chronic digestive problems and especially those that don’t respond to dietary changes. Then we have things like progressive cognitive decline or memory problems, which we see in the elderly of course, but also an increasingly large number of twenty-five year olds. I have so many people in their twenties and thirties who are losing brain function, which is just kinda scary. It’s something that you don’t want to be happening when you’re twenty five years old. Anxiety, depression, ADHD, autism spectrum disorder, behavioral problems, and then here’s an interesting one, cold hands and feet. Especially if you have toenail fungus, because what’s happening there is that you’ve got reduced blood flow, reduced circulation to your peripheral tissues and the brain when you think about it is a peripheral organ. So, cold hands and feet, and toenail fungus can be an indicator of a brain-gut axis problem. I see that a lot actually, in my practice.

DANNY RODDY: Does it have anything to do with the thyroid? and the brain down-regulating things?

CHRIS KRESSER: It could, it could also just be a simple result of reduced blood flow. And that can happen in all kinds of inflammatory processes. So the basic physiology here is that in the brain the key players (in this gut-brain axis) are the frontal cortex, the insular cortex, the vagal motor nuclei (which I’ve already talked about) and the hypothalamus. The frontal cortex basically stimulates the vagal nuclei to activate gut motility (intestinal peristalsis), which is what moves the contents of our gut through the digestive tract and out the other end, and enzyme secretion. The insular cortex contains the somatotopic map, which is basically what lets the brain know where the gut is. And then the vagal motor nuclei activate intestinal motility, and they modulate blood flow, which we just talked about, but in this case to the gut. And then the activate the release of hydrochloric acid  and digestive enzymes. The brain primarily communicates with the gut via neuronal projections and then hormones that are secreted via the hypothalamus.  But in the gut the key players are the enteric nervous system, the intestinal immune system, which is the gut-associated lymphoid tissue and the gut flora, and then the intestinal microglia.

The enteric nervous system is really interesting actually, the gut is basically one big nervous tissue. In fact it’s been referred to as the second brain. There’s a book by that title by Dr. Michael Gershon that’s kind of interesting, it has some flaws but it’s worth reading. The enteric nervous system also generates intestinal motility and enzyme release and then it provides incoming input to the vagus nerve. Someone asked about serotonin in the questions and how much serotonin is in the gut, well 80% of total serotonin in the body is located in the enterochromaffin cells in the gut and this is used primarily to regulate peristalsis and motility. So this is why constipation and depression so often tend to go together. And then the remaining 20% is synthesized in serotonergic

neurons in the central nervous system that regulate mood and appetite, sleep, and muscle contraction, and a whole bunch of other stuff. So the gut communicates with the brain via cytokines and gut opiates and gut peptides like neurotensin and substance-P. Whew. Okay. Everyone who just zoned out for the last five minutes staring out the window while your driving or whatever you can come back now cause we’re gonna talk about some practical applications but I feel like it’s important to understand the basic physiology so that what we’re gonna talk about next makes more sense. Any questions Danny? How you doin?

DANNY RODDY: I’m good.

CHRIS KRESSER: You’re still with us, in your rotten meat smelling garage?

DANNY RODDY: Luckily the smell has subsided, it was bad man.

How decreased brain activity compromises gut function

CHRIS KRESSER: Good. Okay so, how does the brain affect the gut. Well I know everybody’s experienced this in a very personal way, we have  phrases like ‘butterflies in the stomach’ and ‘gut feeling’ that of course suggests the connections have been known for a long time. Maybe we all know somebody that has lost complete bowel control in a state of extreme fear or stress, certainly that’s in the movies and we hear about that sort of thing. But what are some of the mechanisms here. Well, in the intestinal mucosa there are blood vessels that are influenced by the autonomic nervous system. The intestinal mucosa also is infiltrated by the myenteric plexus which is a network of nerve fibers and neuron cell bodies that are in turn influenced by the brain. So as I said before the gut’s basically one big nervous tissue. I think I mentioned this study in a previous podcast or in an article but it was a really interesting study where they induced traumatic brain injury in mice, which is not too nice, but these mice developed leaky gut in less than six hours after having this brain injury. Even more interestingly if the researches stimulated the vagus nerve, which mimics increasing the brain output into the vagus, that actually prevented the leaky gut from developing.

DANNY RODDY: When they did that to the mice, is the root cause like, the brain injury causes stress?

CHRIS KRESSER: It causes decreased output into the vagus, cause remember I said before 90% of the output of the brain goes into the pontomedullary area and then into the vagus. A traumatic brain injury is gonna reduce that output and then they showed that by just stimulating the vagus, which mimics increasing the output, they were able to prevent a leaky gut. So they basically showed, proved that connection between the brain and the vagus and the gut.

Then you have other studies that show that neurotransmitters like serotonin and acetylcholine are involved in preventing or promoting ulcers in the digestive tract. And that alterations in the brain can cause abnormal gastric enzyme secretion. So I wanna talk about a few different studies that I have found over the last couple of years that I think are pretty interesting.

Studies demonstrating gut-brain dysfunction and its effects on health

There was one published last year in the National Review of Gastroenterology & Hepatology and I’ll quote from the conclusion. It said “IBS is thought to be the result of disturbed neural function along the gut-brain axis.” So that makes it pretty clear.

DANNY RODDY: That’s big news.

CHRIS KRESSER: Yeah, there’s an interesting thing here where for a lot of years doctors told people with IBS it was all in their head. And that’s really not a nice thing to say, but it’s true. The thing is it’s not true in the way that the doctors meant it. You know what I’m saying? They meant you just need to get over this, or you’re just imagining it is what they meant.  But what is true is that it is in your head, cause that’s where your brain is. And if the gut is malfunctioning then the brain is involved, and vice-versa. So it is all in our head but not in the sense that we’re to blame for it or we’re just making it up.

Another study in 2005 found that IBS patients have increased activation of pain circuits and decreased activation of pain inhibition circuits. So this is interesting cause, I don’t know if you remember this but when we had Kurt Harris on we were talking about fructose malabsorption and the gas that produces, and the difference  in the way that’s experienced with people with IBS and people without IBS. And they found in that study that people with IBS and without IBS had the same amount of gas produced with fructose malabsorption, but it didn’t even bother the people who didn’t have IBS. It only was painful and uncomfortable in people with IBS. And so that’s what this is about here, people with IBS have a decreased pain threshold, increased activation of pain circuits and then decreased ability to turn off the pain circuits.

DANNY RODDY: So they’re just in a hyper-sensitive state?

CHRIS KRESSER: Exactly. Yeah, so it’s not even necessarily the amount of gas that’s produced, it’s how they experience it. And again it’s not their fault, it’s not something that they are imagining it’s a real neuro-physiological pathway. Journal of Clinical Psychiatry 2001, this is crazy, 50-90% of IBS patients seeking treatment have a psychiatric disorder. Woah. This includes panic disorder, anxiety, social phobia, PTSD or a major depressive disorder. I mean, if that doesn’t sum it all up, give you some strong evidence for an association between the gut-brain connection I don’t know what does.

DANNY RODDY: I hate to put you on the spot here but is there a figure for how many Americans suffer from IBS? It seems pretty common, at least among my peers.

CHRIS KRESSER: The only figure that stuck in my mind about that it’s now the second leading cause of people missing work, behind the common cold. That stuck in me more than whatever the number of millions of people are that have it. It’s causing serious debility and morbidity in the population. It’s right up there with depression in terms of how common it is and how debilitating it is.

DANNY RODDY: And then the third cause just being a normal hangover?

CHRIS KRESSER: And hating their jobs. Okay Biological Psychiatry 2009 they again not very nicely exposed rats to stress by separating them from their mothers early on in their life, and then they challenge them with lipopolysaccharide which is a bacterial endoxtoxin. And the rats that were exposed to the early life stress had increased pain and alteration in their gut flora compared to controls and the conclusion by the researchers was that early life stress alters the gut-brain axis, and in a permanent way, and causes depression, IBD, and IBS. I mean permanent I don’t know, they were suggesting that it’s something that wasn’t passing, it didn’t just last for the early part of the life for these rats, it persisted throughout their life. Whether that’s permanent for humans or can be reversed that’s a whole other question.

DANNY RODDY: Because mice, their lives are so much shorter could they say that it wouldn’t be transferable over to humans because we live so much longer? Would that have anything to do with it?

CHRIS KRESSER: Yeah I dunno, I think this all sort of, fairly gray territory in terms of earlier on it was thought that certain neurological conditions were irreversible and certain neural-pathways once developed couldn’t be undeveloped, but now more recent research suggests there is a lot more plasticity in the brain and in the nervous system than we thought there was, which means that it’s possible to form new connections and for those new connections to take over in terms of importance in the brain and nervous system. My sense is, that significant trauma early on in life probably would predispose somebody for life to certain, to maybe having a sensitive gut-brain axis. And maybe that sensitivity wouldn’t be reversible but by learning strategies for how to cope with it and things to do that manage it they can live a perfectly healthy, happy, normal life. That’s my sense but there’s nothing particularly scientific about that.

Journal of Neurotrauma in 2009 they found that traumatic brain injury can cause gastrointestinal disfunction, we already talked about this, and leaky gut. And then a study in Lancet found that patients with inflammatory bowel disease, which includes chron’s and ulcerative colitis, had focal white matter lesions which are these small areas of dead cells in the brain, with almost the same frequency as patients with multiple sclerosis. So how’s that. Once again extremely clear connection between brain issues and gut issues.

Now we’re gonna talk a little bit about how the gut affects the brain. There’s a lot of different mechanisms here and we only have time to review a couple of the main ones. Our friend Mat Lalonde actually sent me me a study a couple weeks ago that was just published that the gut flora influences the development of behavior and causes neurochemical changes in the brain. So again from the conclusion they said “we conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior and is accompanied by neurochemical changes in the brain.” And they point out that even sub-clinical doses, small doses of pathogenic bacteria infused into the gut of mice can produce anxiety without any overt gut inflammation. So what they’re saying here basically is that the gut flora can not only affect how we digest food and whether our gut lining is permeable, but can actually influence the development of our behavior and one can even argue personality.

DANNY RODDY: I think it was Gershon that said have you ever met somebody with IBS that’s not anxiety prone. I think he said if you were a changed to a toilet you probably wouldn’t be in the best spirits either.

CHRIS KRESSER: That’s a vivid example for sure. Yeah, it reminds me of the fact that bacteria outnumber human cells in the body by 10 to 1. We have a hundred trillion bacteria in our gut that’s 1014, it’s just like an incomprehensible number. And so if you look at it that way you could say that we’re more bacterial than we are human. When you consider it that way it’s not that surprising that the composition of the gut flora can have so many effects on everything from our metabolism to our behavior. So another study by Lee, et al. found that changes in gut bacteria induced by feeding different types of food to mice altered their memory and learning. So they fed half the mice standard rat chow, and then the other lucky half of the mice got a 50-50 blend of rat chow and ground beef. And then they measured the diversity of the gut flora and the mice that ate the beef had significantly more diverse gut flora and significantly higher learning and memory scores. So now we’re talking about healthy gut flora making you more intelligent, essentially.

DANNY RODDY: Like serotonin in the gut, does acetylcholine, could that have somehow been involved? I mean I know we don’t have all the answers…

CHRIS KRESSER: I don’t know the answer to that Danny, actually where the majority of acetylcholine is produced. I don’t think it’s in the gut but I’m not sure.

One of the most interesting examples of how the gut affects the brain is this immune inflammatory cytokine model of depression, and I wanna get Dr. Emily Deans to come on the show and talk about this cause she writes a lot about it and she probably knows a ton more about it than I do. But I’m gonna give you my understanding of it. I like it because it’s the only model of depression that bridges the gap between physical and mental. We talked about this before, in Chinese medicine they don’t see depression as a mental problem they see it as a whole body problem. Mental, emotional, psycho-spiritual, physiological problem. But the immune inflammatory cytokine model from this perspective depression isn’t so much a disease as it is a sign of chronic immune system activation. And that chronic immune activation produces inflammatory cytokines that in turn produce depression I explained that back at the beginning of the show how that works. And this was discovered back in the 80s, that inflammatory cytokines have a huge effect on mood and behavior and you would have thought this would have had a gigantic impact cause it completely changes the way we look at depression. But it didn’t receive much attention at all in the mainstream press or the conventional medical world I suspect because there were no drugs available for treating it in this particular way. But the inflammatory cytokines that are associated with depression include interferon-alpha,   tumor necrosis factor, interleukin-1 and 2, and it’s important to note that elevated cytokines don’t produce depression in everybody and why some people are susceptible and others aren’t isn’t really known. But we do know that inflammatory cytokines produce symptoms of depression in some people. And the best example of this is patients given interferon treatment for hepatitis. I don’t know if you’ve ever heard about this Danny, but interferon is a nasty, nasty drug and basically the idea is to increase the inflammatory response so that the body can deal with the hepatitis and most of the patients who take this drug, they report severe fatigue, complete lack of interest in life, lack of concentration, and just debilitating depression. And suicide rates are higher on interferon than any other drug. In fact one study 65% of patients taking interferon became psychiatric patients during the study.

DANNY RODDY: Holy smokes.

CHRIS KRESSER: Yeah. And the depression didn’t stop immediately after stopping the treatment. So definitely a strong connection between inflammatory cytokines and depression. We also know that depressed people secrete greater quantities of inflammatory cytokines than normal people and this has been extensively studied by… Dr. Michael Maes and his colleagues in Belgium, and they’ve published like 40 papers demonstrating that chronic immune activation and the associated increase in cytokine production is characteristic of depression. So you have all those different ways that the gut can affect the brain and particularly inflammation in the gut can cause inflammation in the brain. So the takeaway here is that anxiety and stress and IBS and IBD, the gut and the brain, they’re all part of the same axis, they always go together. Every stressful event that we experience in life increases the plasticity of stress pathways in the brain which means it makes the brain essentially more efficient at running stress pathways. And there’s a saying in functional medicine, fire in the gut, fire in the brain. Which sums it up pretty well. Digestive function will start to fail immediately after the brain starts to fail, and the inter intestinal gut mucosa in the brain themselves don’t have any pain fibers which is why brain-gut, you don’t see people coming into the clinic going my brain hurts. My brain feels really inflamed can you help me? They come in saying I can’t eat any foods, I’ve got gas and bloating, I can’t remember anything, I used to be able to concentrate for long periods and now I can’t, I’ve got cold hands and feet, and I’ve got this toenail fungus and it won’t go away, this is what people say when they’ve got a gut-brain issue. And as a patient or a clinician if you ignore the role of the brain in addressing gut issues, success is definitely gonna be limited. Probiotics, and HCL, and diet are all very important of course. But it’s possible to do all of that right and still have gut symptoms as I’ve experienced directly myself, and as a lot of my patient’s have experienced. So this is one of the reasons that I’m always harping on the importance of sleep, and stress management, and cultivating pleasure, because these are all things that we can do to help our brain function better.

So let’s talk a little bit more about that. You have a question?

DANNY RODDY: No, I liked your conclusion.

Dietary and lifestyle modifications to improve gut-brain function.

CHRIS KRESSER: Okay, good. So there’s three things that the brain needs, essentially. Glucose, oxygen, and stimulation. As far as stimulation goes that’s why people that stay mentally active as they get older tend to age better. And do a lot better than people who don’t, you know who just sit on the couch and eat jellybeans and watch TV. And this is another reason why blood sugar regulation is so important. When people come to see me in the clinic, the first things that I’m looking for are oxygen deliverability and blood sugar regulation, those are like, the two deal breakers. Once again here as we talk about the brain we see glucose and oxygen being two of the main things that it needs. Alzheimer’s and parkinson’s and other neurological conditions have been called diabetes of the brain, that’s one of the newer theories about it and of course this also illustrates why stress management is so important. Studies show that cortisol rhythm maintains blood sugar stability, so if cortisol doesn’t go down you get insulin resistance and if it goes too low and can’t come up you get hypoglycemia, which is a total disaster for the brain. And then we know that elevated cortisol also damages the hippocampus. And that chronic stress atrophies the brain, it literally atrophies the brain. And this is also why blood flow to the brain is so crucial because blood carries oxygen and glucose and everything else we need to the brain. You could almost say that blood flow equals function.

So two of the best ways to increase blood flow to the brain are exercise and acupuncture. And actually I wrote a whole series about, I believe that one of the main reasons that acupuncture works is that it increases blood flow. That’s kind of a western understanding of how it works but there’s a lot of support for that. And it’s been proven to increase blood flow to the brain. And so anyone with a brain-gut axis issue should definitely be trying acupuncture on a pretty regular basis. And then there are certain nutrients and botanicals like feverfew, ginko, cayenne, and then some limited research suggests that vinpocetine from periwinkle can increase blood flow to the brain. And then you of course would have to deal with any anemias that are present, which of course is compromised oxygen deliverability. The impaired ability of hemoglobin to deliver oxygen to the tissues including the brain. I think anemia is one of the most under diagnosed and misdiagnosed conditions there is, cause I see anemias in 30-40% of my patients and they’re almost all unaware that they have it, and their doctors havn’t told them anything about having it. If they see low hemoglobin they just give them iron, even if iron deficiency is not the cause of anemia but that’s a whole other issue. And then stress management, stress management, stress management. It just keeps coming back to this. Things like mindfulness based stress reduction, Jon Kabot-Zinn’s programs, Feldenkrais, yoga, qi gong or tai chi, whatever it is for you. Different people have different things that work for them. It’s super important to integrate this into your life. You notice that I’m not staying stress reduction, or stress elimination because in the modern world most of us don’t have that luxury or option. Stress management is the key.

Regarding the gut we’ve talked more about this in other podcasts, but a gut-healing protocol might include the GAPS diet, glycine rich bone broths, probiotics, prebiotic foods like sweet potatoes, jerusalem artichokes, stuff like that. And then you’ve got botanicals like marshmallow root, and slippery elm, and chamomile, and spanish moss can be helpful. And if there’s a pathogen you should address that. But really at least in terms of this episode I’m focusing more on the brain because I think that’s the part that people are missing more. There’s a lot out there on how to heal the gut but not that much on how to heal the brain.

And I mentioned before that when the microglial cells become activated it’s hard to turn them off. There are some nutrients that have been demonstrated to do that including curcumins like turmeric, skullcap, green tea extract. In terms of healing the blood-brain barrier you’ve got alpha-lipoic acid, glutathione, which you need to take things that help glutathione synthesis, you can’t take just oral glutathione it’s not effective. And then the omega 6:omega 3 balance is absolutely crucial in blood-brain barrier integrity. Don’t go out and just buy all this stuff and come home with a shopping bag of supplements, try to find someone who can help with this and focus your efforts. It’s definitely worth doing because it’s a really important pattern to manage.

DANNY RODDY: Like Spectracell will actually measure the amount of glutathione in your blood correct?

CHRIS KRESSER: I don’t know about that test.

DANNY RODDY: I don’t know if it’s totally bunk or not, but I remember receiving it, and they didn’t tell me that it measured it but I got it back and it was cool.

CHRIS KRESSER: I’m always naturally skeptical, as you might imagine, of those kind of tests. but anyways I don’t know anything about it so I can’t really say. So let’s take a couple questions, I know we had a long episode last time I don’t wanna go too far this time, but let’s take a few questions and then I have a couple things to end with.

DANNY RODDY: Alright cool, this one I believe was on your facebook page, from Stephanie Alexander. I would like to understand the connection between acute emotional stress and the onset of gut issues, and the progression to additional health issues.

CHRIS KRESSER: Okay well I think probably we’ve covered that mostly but early studies suggested that a stressful evert would trigger hormonal and neuronal reflexes in the brain that influence the gut, and that does happen but recent reports have also shown that the gut produces the same stress peptides that are present in the brain and the central nervous system. These peptides regulate intestinal motility which is the rate at which digested material passes through the intestines. So we’re getting back to that extreme fear stress event that causes diarrhea. During a stressful event the normal amount of those peptides gets totally thrown out of whack and that affects digestion and motility. And when that happens repeatedly over time it can evolve into a gut-brain axis disorder like IBS or IBD.

DANNY RODDY: Awesome, the next question, kind of a two-pronged question from Lisa Rose. I would love to hear your take on probiotics. Should everyone be taking them? or can it do more harm for some. Which brands do you recommend? And the roll enzymes play to help digest food while the gut heals, also highlighting the power of foods for a healthy gut, like fermented foods. What other foods help? And then an additional question from Laura that’s kind of in the same vain, should people with healthy gut digestion take probiotics? What happens if you take too much? How do you determine the right amount?

CHRIS KRESSER: I don’t see any need for healthy people to take probiotic supplements but I think incorporating fermented foods into your diet is a good idea for everybody. Number one it tends to help with digestion, number two it can just help normalize the gut flora and protect us against overgrowth of pathogenic bacteria or parasites that we might take in through food, and number three they’re tasty and I like them. Number four they tend actually to have even more microorganisms in them than a lot of the commercially available probiotics. Number five I think some common sense and maybe studies suggest that they are more likely to survive the stomach acid and make it to the colon which is where they’re needed. So, I don’t typically recommend probiotic supplements as a matter of course, I do recommend probiotic foods so we’re talking about dairy ferments like kefir, yogurt, and creme fraiche, fermented cream which basically is creme fraiche but there are different ways to do it. And then you’ve got fermented vegetables like kimchee and sauerkraut, and saueruben and fermented beverages like beet kvass. There’s a great book called Wild Fermentation by Sandor Katz that has like, every possible fermented food you can imagine and how to make it. Full Moon Feast by Jessica Prentice is really great for that too, as is Nourishing Traditions by Sally Fallon from the Weston A. Price Foundation.

DANNY RODDY: Yeah food not pills.

CHRIS KRESSER: Yeah but I use probiotics and prebiotics therapeutically in my practice for sure, because for some people the food doesn’t seem to be enough.

DANNY RODDY: Totally. Okay the next one’s gonna be from Mike Zemrose, please discuss psychosomatic reactions to food and how this complicates diagnosis of gut related problems.

CHRIS KRESSER: I’m not totally sure what he means by psychosomatic reactions to food but I’ll take a guess. The Chinese have a great saying, I think I mentioned this before when I wrote the article on the 80/20 rule, which is that it’s better to eat the wrong food with the right attitude than the right food with the wrong attitude. And of course it’s best to eat the right food with the right attitude, but that’s not always possible or it doesn’t always happen that way. And this is in part why I do suggest an 80/20 rule or 90/10 rule for most people and for those of you who don’t know what that is, that means that 80 or 90% of the time you eat a paleo plus raw dairy type of diet, or whatever you wanna call it, Perfect Health Diet, Paleo 2.0. And then the other 10-20% of the time you eat whatever you want. And for a lot of people whatever they want still just is the paleo type of diet, but some people might have a food that they really associate with happy times, when they were a kid, or they’re out with friends and they wanna get some ice cream, or whatever. And the pleasure that that experience can create, and the stress and feeling of deprivation and stuff that that can prevent will actually, according to this Chinese saying is actually better, will have a more beneficial effect on the body. So I think that’s a good rule to follow if you’re generally healthy. If you’re gluten intolerant or celiac for example you don’t get the 80/20 rule with gluten, with bread. It’s 100%/0, you never get to have it. Anyways back to the question, there was an interesting study where they hypnotized patients and put them into four different emotional states. Relaxation, anger, happiness, or excitement. And then they observed the gut after they ate. Relaxation and happiness increased the distension volume required to produce discomfort meaning that, going back to what we were talking about IBS and hypersensitivity that when people are relaxed and happy they’re less likely to experience discomfort while eating. And then when the patients were angry it decreased the distension volume that was required to produced discomfort. So I don’t think this is a surprise to anybody that when you’re happy and relaxed you’re gonna digest your food better, when you’re angry you’re not. But it’s definitely in the scientific literature.

How we feel when we eat alters the secretion of hormones and peptides and neurotransmitters, and that effects not only our digestive function but also things like cardiovascular function. Dr. Malcolm Kendrick talks about this and he points to some studies in his book The Cholesterol Con, that postprandial or after meal stress is one of the most significant risk factors for heart attack. So those French that have those leisurely two hour meals, they know what they’re doing. Whereas here we eat, and we’re eating in front of the computer, or we’re chomping down an egg mcmuffin while we’re changing lanes on the freeway or whatever. That’s kind of a disaster.

DANNY RODDY: Well speaking of the French, our next question is from Pierre Brode. His question is I’m interested in how stress eating throws off the physiology/ body chemistry and how the brain-gut axis amplifies it, and what are some ways of resetting it caught in the cycle. Big question.

CHRIS KRESSER: I think we’ve hopefully covered this during the podcast, but I’ll just mention a few… stress eating we havn’t talked about particularly. Sugar and carbs and fat can mitigate the effects of stress via increasing opiates and dopamine, other neurotransmitters like serotonin that make us feel good, feel like life’s okay and everything’s gonna be fine. But if you do this regularly during times of stress you can cause adaptations in those pathways that can lead to overeating. Other studies have shown that food reward and sensitivity is decreased during stress, which leads to overeating. In other words when you’re really stressed out you don’t actually enjoy the food that you’re eating as much as you do when you’re not. And then you keep eating because you’re not getting that food reward that you’re expecting. And then, I don’t know if you saw this but Stephan Guyenet over at Whole Health Source wrote a post today about food reward. It showed that mice eating chocolate ensure but not vanilla or strawberry ensure, these are these elemental diet drinks that they give people that are just disgusting I can’t believe that mice would even eat them at all, it’s surprising to me. But the mice eating the chocolate ensure could overeat and become obese, whereas the ones eating strawberry and vanilla didn’t. So what this suggested was that the flavor of food actually influences body fat and body fat set point. And then the last thing is, I guess we talked about this before but elevated cortisol can lead to increased food intake. That’s an evolutionary mechanism probably designed to make sure that we get enough food to fuel our metabolic needs during times of stress or maybe when a food shortage is on the way or something like that. So the way to deal with this, is as I said to take steps to manage stress throughout the day and throughout the week and to find other ways of coping with stress when it becomes overwhelming aside from eating. That’s a topic beyond the scope, we can’t cover that in significant detail right now at the end of the show. But I think the key is to manage stress regularly so that you don’t get to that place where you’re just so overwhelmed that the only solution is a half of a chocolate cake.

DANNY RODDY: Cool Chris, do you have anything else to throw in about the gut-brain axis?

CHRIS KRESSER: I don’t think so, did I miss anything? I’m sure I did.

DANNY RODDY: No I thought it was fantastic, you covered everything.

CHRIS KRESSER: Well I wanna talk a little bit about this healthy baby home study course that’s coming out soon. I’m super excited about it, we actually renamed it it’s now called the Healthy Baby Code. Very secret code.

DANNY RODDY: That makes me think of the History Channel’s Bible Code that I used to watch in high school.

CHRIS KRESSER: The Da Vinici code? No it doesn’t have anything to do with that. It’s based on, I was giving these live presentations, for those of you who aren’t aware of this, on nutrition for fertility, and pregnancy and breastfeeding. And they sold out, there was huge demand for them locally, and a lot of people on my blog and facebook and twitter were asking if I could make it available to people who didn’t live locally here in the bay area. It’s a super important topic, I feel really passionate about getting the information out there so what I did is I turned the presentation, which was about three hours, into this home study course. I actually expanded it considerably, and there’s gonna be six video modules that are like screencasts from the presentation, covering things like the basics on how proper nutrition contributes to the lifelong health of your baby, which I just wrote a blogpost on called the developmental origins theory. The sacred fertility foods that have been used by traditional cultures around the world. And then module two we talk about macronutrients, protein, fat and carbohydrate. Not necessarily how much of each but what type of each which I wrote about in my 9 steps series and Kurt’s talked about a lot.  Find out which types of fat and carbohydrate and protein are best for you and your baby. And we talk about micronutrients, essential vitamins and minerals, which ones are critical during the developmental period, during pregnancy, and also for fertility. Where to find them in foods and when it’s necessary to supplement and what dosage of each you might need to supplement with. And then in module four we talk about food toxins, we learn about the four neolithic agents of disease which I’m sure many of you are already familiar with. Cereal grains, industrial seed oils, excess fructose and soy, modern processed soy. And then in module five we talk about breastfeeding and first foods, which a lot of people have questions about. How long should you breastfeed, when should you introduce foods, and how do you introduce them safely to try to minimize the risk of food allergies and reactions, autoimmune conditions and stuff like that. And then in module six we kind of put everything together and into a focused strategy for really supercharging your fertility and promoting healthy pregnancy and then raising a vibrant, healthy, beautiful baby. Of course this is very, my personal motivation for doing this too because my wife is six months pregnant, we’re expecting a baby in july and we had kind of a long road, difficulty conceiving at first. My wife has autoimmune thyroid disease and a lot of doctors just told us not even to bother. Of course that didn’t sit well with me so, I did tons and tons of research in my typical obsessive compulsive way, into what nutrients were really necessary to support a healthy pregnancy and the magic happened last october and we conceived so I’m really excited to share this with people. In addition to the video modules which are by the way gonna be transcribed into pdf’s cause I know some people don’t like video and they learn better by reading, I happen to be one of them. And then there’ll also be MP3 recordings of each module so if you drive a lot and you wanna listen to them in the car you can do that.

And then I’ve added a whole bunch of bonus stuff which we’re excited about. There will be quick reference charts, an easy to follow nutrient chart that lists all the essential nutrients and what foods they’re in and what dose to supplement with if you need to. There’ll be a two week meal plan, which both my wife and I worked pretty hard on from collecting recipes from places like health bent and the cheese slave and the paleo diet lifestyle, a lot of great recipes on the web and then our own recipes, we’re not too shabby cooks ourselves. And then there’s gonna be an interview, of frequently asked questions with me, some of the most frequently asked questions about nutrition for fertility, pregnancy and breastfeeding. There’s gonna be a list of recommended supplement brands, dosages. And then of course it wouldn’t be complete without come stress management, because that’s obviously a huge factor for women trying to get pregnant and women who are pregnant. My wife, Elanne is a Feldenkrais practitioner and has also done a lot of somatic experiencing training which is a particular approach to dealing with stress and trauma. So she is recording some stress management audio programs for women who are trying to get pregnant and men for that matter, and women who are pregnant and breastfeeding. So that’s the whole kit, and now you can see why I’ve been working so hard.

DANNY RODDY: No doubt.

CHRIS KRESSER: So that’s gonna hopefully be available in like, I want it to be available in two weeks but maybe more realistically three weeks and please don’t shoot me if it’s the end of may. I’m working as hard as I can to get it out there. So if you’re not already on the list for this you should go to growahealthybaby.com that’s the old name for it but that’s where the sign up list is and I know it’s a little but confusing, it’s kind of in transition to the new name but if you go to growahealthybaby.com  you can sign up to be on the email list, be notified when it’s released, and one reason to be on that list is that I’m gonna be making a special offer to people that are on that list. We’re gonna do kinda like a beta launch, a smaller launch just to that list. Kick the tires a little bit, and in exchange for people’s feedback I’m gonna offer some pretty cool stuff to people on that list so make sure to join that if you’re interested in this and pass the word on to folks that you think might be interested.

DANNY RODDY: Awesome you can find all my insanity at Dannyroddy.com, keep sending us your questions at thehealthyskeptic.org using the podcast submission link. Chris, what a great episode, thanks.

CHRIS KRESSER: Yeah I had fun, thanks everyone we’ll talk to you next week? are we doing, is it Stephan?

DANNY RODDY: May 20th is Masterjohn.

CHRIS KRESSER: We’ve got some exciting episodes coming up we’ve got Chris Masterjohn, we’re gonna bring cholesterol into the 21st century finally. It’s gonna be like the fully up to date, integrated understanding of cholesterol, all the latest research and cut through the hype and the confusion and you’re finally gonna understand this whole cholesterol thing. And then Stephan Guyenet is gonna come back and make a second appearance, we kicked the whole podcast off with him talking about obesity and he has some very interesting, newly developed theories about obesity and weight regulation that he is gonna share with us which I’m super excited about so, looking forward to that.

DANNY RODDY: Awesome, cool. That brings us to the end of the episode, take care guys.

CHRIS KRESSER: Alright, see ya later, take care of your brain-gut!

There’s no question that regular exercise is essential to health. Our paleolithic ancestors had a different word for exercise: life. For the vast majority of our evolutionary history, humans had to exert ourselves – often quite strenuously – to get food. We naturally spent a lot of time outdoors in the sun, walking, hunting, gathering, and performing various other physically-oriented tasks. We had no concept of this as “exercise” or “working out”. It was just life.

Things are different today. 60% of American adults are not regularly active, and 25% are complete couch potatoes – they get no exercise at all, other than walking back and forth between the car, the cubicle and the refrigerator. This lack of physical activity has profound consequences. Regular movement protects us from disease in several ways, but most importantly it prevents oxidative damage and inflammation – the primary mechanisms underlying most modern, degenerative diseases. This explains why those who are completely sedentary have between 1.5 and 2.5 times the risk of developing heart disease and a higher risk for virtually all modern, degenerative disease.

On the other hand, we’ve got the exercise fanatics. Many Americans have been caught up in the fitness craze over the last 40 years, devoting countless hours to jogging, the Stairmaster or the treadmill in the hopes of slimming down, getting healthy and preventing disease. But while this type of activity may help with stress management, research suggests that it’s useless for weight loss and may in fact be detrimental to health.

If you doubt this, you’ll have to explain why Americans have continually gained weight over the last 40 years, in spite of increased leisure time exercise and increased energy expenditure.

Why “cardio” doesn’t work for weight loss

When I say “cardio”, I’m referring to steady-state, repetitive activity done at a moderate intensity like jogging outdoors, running on a treadmill or climbing the Stairmaster. [Side note: the idea that you have to perform this type of activity to benefit your heart and vascular system is false. Anything that places a demand on the muscles - including so-called anaerobic activities like weightlifting - will also condition the heart and vascular system.]

Most people are surprised to learn that cardio doesn’t work for weight loss. How could this be? There are three main reasons:

• caloric burn during exercise is generally small;
• people who exercise more also tend to eat more (which negates the weight regulating effect of exercise); and,
• increasing specific periods of exercise may cause people to become more sedentary otherwise.

In an example of the first reason, a study following women over a one-year period found that in order to lose one kilogram (2.2 pounds) of fat, they had to exercise for an average of 77 hours. That’s a lot of time on the treadmill just to lose 2 pounds!

In an example of the second reason, a study found that people who exercise tend to eat more afterwards, and that they tend to crave high-calorie foods. The title of this study says it all: “Acute compensatory eating following exercise is associated with implicit hedonic wanting for food.” I love it when researchers have a sense of humor.

In an example of the third reason, one study assigned 34 overweight and obese women to an exercise program for 8 weeks. Fat loss at the end of the study was an average of 0.0kg. Not very impressive. But the researchers noticed that some women did lose weight, while others actually gained. What was the difference? In the women that didn’t lose weight, the increase in specific periods of exercise corresponded with a decrease in overall energy expenditure. Translation: they were more likely to be couch potatoes when they weren’t exercising, which negated the calorie-burning effect of their workouts.

If you’re still not convinced, the Cochrane group did a review of 43 individual studies on exercise for weight loss. Study length ranged from 3 to 12 months, and exercise sessions lasted on average 45 minutes with a frequency of 3-5 times per week. The results? On average, the additional weight loss from exercise averaged about 1 kg (2.2 pounds). Meh. Assuming they worked out for 45 minutes 4x/wk over 6 months, that means they had to exercise 69 hours to lose that 1 kg.

Why cardio may be harmful

Too much cardio exercise has a number of harmful effects on the body:

• increases oxidative damage
• increases inflammation (the root of all disease)
• depresses the immune system
• decreases fat metabolism
• disrupts cortisol levels
• causes neurodegeneration

Overtraining is especially damaging because of its effects on cortisol. We discussed cortisol at length in Step 6: Manage Your Stress, but in this context what’s important to understand is that too much exercise can disrupt our natural cortisol rhythm and drive levels too high initially, and depress them over time. Cortisol dysregulation promotes abdominal fat gain and muscle loss, which in turn causes further weight gain.

There’s also some evidence that frequent endurance exercise may promote – rather than prevent – heart disease. Dr. Kurt Harris summarized a study performed on 102 active marathon runners and 102 age-matched controls to determine the effect of aerobic exercise on cardiovascular health.

The marathoners were between 50 and 72 years of age, and they ran an average of 35 miles per week. They had no known history of heart disease or diabetes. The control group was similarly aged and also had no history of cardiovascular or metabolic disease.

You might be surprised to learn that the marathon runners were three times more likely to have heart damage than the non-runners. Among the runners, there were 12 heart attacks vs. 4 attacks in the non-runners.

In another study by the same authors, the more marathoners ran, the higher their likelihood of heart disease. In fact, the number of marathons ran was an independent predictor of the likelihood of irreversible damage to the heart tissue.

No cardio? Then what should we do instead?

In short, we should move like our ancestors. They didn’t strap on a heart monitor and take off for a 45-minute jog, nor did they go down and swim laps for an hour in the local lake. Yet they were extremely fit and almost entirely free of the modern diseases that plague us today.

They performed low-intensity movements like walking, gathering foods or working in other capacities on a regular basis. These periods of low-intensity activity were punctuated by brief periods of much higher-intensity activity – such as going on a hunt, running for a predator or fighting for survival.

This is the type of movement our bodies are adapted for, and thus this is what we should aim for in our daily lives. But how do we do that? As Mark Sisson suggests, we should:

1. Move frequently at a slow pace
2. Lift heavy things and sprint occasionally

Move frequently at a slow pace

Moving frequently at a slow pace means approximately 3-5 hours a week of low level activity like walking, cycling, gardening, hiking, performing manual labor, etc. This mimics our ancestral pattern of movement, helps maintain a healthy weight, promotes proper metabolic function and provides a foundation for more strenuous activity. Another benefit of this type of activity is that it’s often performed outdoors. Spending time outdoors reduces stress, increases vitamin D levels, and brings us pleasure, joy and a sense of connection with the world around us.

I think one of the best ways to do this type of movement is to integrate it into your daily life. This could include commuting to work and doing errands on foot or by bicycle, taking the stairs instead of the elevator, doing your own gardening and yard work, etc.

Lift heavy things and sprint occasionally

In contrast to cardio, this type of exercise involves performing movements at very high intensity for short periods of time – usually between 30 seconds and 2 minutes. This is sometimes referred to as high intensity interval training (HIIT).

Several studies have been done comparing HIIT to low-intensity, steady-state (“chronic cardio”, as Mark Sisson calls it) exercise, and HIIT has been shown to be superior in nearly every meaningful marker.

In this study, one group was assigned to “chronic cardio”, while the other was assigned to intervals of 8-second sprints. After 15 weeks, the researchers concluded:

Both exercise groups demonstrated a significant improvement (P less than 0.05) in cardiovascular fitness. However, only the HIIE group had a significant reduction in total body mass (TBM), fat mass (FM), trunk fat and fasting plasma insulin levels.

A pair of studies done at McMaster University found that “6-minutes of pure, hard exercise once a week could be just as effective as an hour of daily moderate activity“, according to the June 6, 2005 CNN article reporting on the study.

The study itself was published in the Journal of Applied Physiology, and it revealed that HIIT resulted in unique changes in skeletal muscle and endurance capacity that were previously believed to require hours of exercise each week.

A follow-up study confirmed the results. Despite the fact that the more conventional endurance exercise group spent 97.5 percent more time engaged in exercise, both groups of subjects improved to the same degree. The group that exercised 97.5 percent more received no additional benefit whatsoever from doing so. Considering the wear-and-tear and increased risk of injury associated with that much more exercise, there’s absolutely no point to doing “chronic cardio” when you can receive the same benefits with a fraction of the time and risk by doing HIIT.

The Cochrane study I linked to earlier in the article also found that high-intensity exercise was superior to “chronic cardio”. In particular, the researchers found that high-intensity exercise led to a greater decrease in fasting blood glucose levels than low-intensity exercise.

Why high-intensity exercise is better

In his excellent book on high-intensity strength training, Body By Science, Dr. Doug McGuff explains that high-intensity training is superior to chronic cardio because it produces a greater stimulus and thus more effectively empties the muscles and liver of glucose. This stimulus can last several days with HIIT, as opposed to just a few hours with low-intensity training.

HIIT also activates hormone-sensitive lipase (HSL), which mobilizes fatty acids for energy use. This means that during HIIT, both glucose and fatty acids will be burned, leading to greater fat loss and restoration of insulin sensitivity.

High-intensity strength training: best of all?

Both high-intensity running or bicycling sprints and high-intensity strength training are effective. But I believe high-intensity strength training is probably a better choice for most, simply because the wear-and-tear and risk of injury is lower – especially if the strength-training is performed using weight machines as described in Body By Science.

This is, in fact, the method of training I’ve been doing since April of last year. I admit I was somewhat skeptical about it all before I read Body By Science. But the research and the physiology was convincing, so I decided to give it a try.

The results have been incredible. My workout varies in length between 5 and 9 minutes a week. That’s right, I said minutes. With only a few exceptions, I’ve increased the amount of weight I can lift, the time I can lift it, or both, with each successive workout. My strength has increased and my physique is, if anything, better than it was when I was lifting 3x/week for much longer periods.

Where to learn more about HIIT

There are many books on the subject, but these are the two I’d recommend for most people:

• Body By Science, by Doug McGuff. The “bible” on high-intensity strength training. Goes into great detail on the physiological mechanisms and benefits behind this type of exercise, and explains how to put together a routine. Doug also has a great blog with an active community of people using the BBS approach. To see an example of what this type of workout looks like, check out this video on YouTube. For an in-depth video presentation about BBS, watch this video.
• The Power of 10: The Once-A-Week Slow Motion Fitness Revolution, by Adam Zickerman & Bill Schilley. This is more of a nuts-and-bolts book, with less theory than BBS and more focus on teaching you how to do this type of workout. It also has specific routines that can be performed at home, on the road and without access to a gym. The approach is slightly different than what’s advocated in BBS, but the basic idea is the same.

In the previous article in this series, I argued that diabesity is an autoimmune, inflammatory disorder. In this article, we’re going to review the evidence linking inflammation to obesity and type 2 diabetes (T2DM) and learn why inflammation may be the single-most important mechanism driving the diabesity epidemic.

The inflammation-diabesity connection is a hot topic in the scientific literature. A Pubmed search for “inflammation diabetes obesity” turns up more than 1,800 articles. The association between these conditions has been known for decades. In fact, more than 100 years ago high doses of salycilates – a class of anti-inflammatory compounds which includes aspirin – were used to treat T2DM. In 1876, a physician named Ebstein found that sodium salycilate could make the symptoms of diabetes completely disappear. (In case you’re wondering why doctors don’t use this therapy today, it fell out of favor due to the serious side effects caused by high doses of salicylates.)

Though the association between inflammation and diabesity is well-known, questions remain. Does diabesity cause inflammation, or does inflammation cause diabesity? How and why does the body initiate an inflammatory response to diabesity? Does obesity itself cause inflammation, or is inflammation caused by something secondary to obesity (like high blood sugar or triglycerides)?

I’m going to try to answer those questions in this article. Let’s dive in.

How inflammation causes diabesity

There are several lines of evidence that inflammation directly causes obesity and diabetes.

First, inflammation has been shown to precede the development of diabesity. Elevated levels of inflammatory cytokines predict future weight gain, and infusion of inflammatory cytokines into healthy, normal weight mice causes insulin resistance.

The idea that inflammation precedes diabesity is supported by the observation that humans with other chronic inflammatory conditions are at higher risk of developing T2DM. For example, about one-third of chronic Hepatitis C patients develop T2DM, and those with rheumatoid arthritis are also at higher risk.

Second, inflammation begins in the fat cells themselves. Fat cells are the first to be affected by the development of obesity. As fat mass expands, inflammation increases. One mechanism for this may be dysfunction of the mitochondria (the “power plant” of our cells) caused by the additional stress obesity places on cellular function. Another mechanism may be oxidative stress. As more glucose is delivered to the fat cells, they produce an excess of reactive oxygen species (ROS) which in turn starts an inflammatory cascade within the cell.

Third, inflammation of the fat tissue causes insulin resistance, which is the primary feature of T2DM. TNF-α, a cytokine (small protein) released during the inflammatory response, has been repeatedly shown to cause insulin resistance. Several other proteins involved with inflammation, such as MCP-1 and C-Reactive protein, have also been shown to cause insulin resistance.

Fourth, inflammation of the brain (specifically the hypothalamus) causes leptin resistance, which often precedes and accompanies insulin resistance and T2DM. Leptin is a hormone that regulates appetite and metabolism. It does this through its effect on the hypothalamus. When the hypothalamus becomes resistant to leptin, glucose and fat metabolism are impaired and weight gain and insulin resistance result.

Finally, inflammation of the gut causes leptin and insulin resistance. This may occur via an increase in lipopolysaccharide (LPS), an endotoxin produced by Gram-negative bacteria in the gut. LPS has been shown to cause inflammation, insulin resistance in the liver and weight gain.

How diabesity causes inflammation

Up until relatively recently, fat was considered an inert tissue with no biological activity. The idea was that it was just, well, there. It didn’t do much other than store excess energy.

We now know, however, that fat tissue is a metabolically active endocrine organ that secretes hormones and inflammatory cytokines such as IL-6 and TNF-α. The metabolic activity of fat is the key to understanding its role in diabesity.

Why would obesity cause inflammation? There are two basic theories. The first is that obesity-induced inflammation is actually a protective mechanism that prevents the body from losing mobility or fitness. Fat storage is an anabolic process, which means it builds up the organs and tissues. Inflammation, on the other hand, is a catabolic process. Catabolism breaks down organs and tissues. It’s possible that the activation of catabolism via inflammation is the body’s attempt to keep weight within acceptable bounds. Evidence that experimentally induced local inflammation in fat tissue improves insulin resistance and causes weight loss supports this theory.

The second theory is that obesity-induced inflammation is simply a malfunction that was never selected against in human evolution. Obesity and its related disorders have been extremely rare throughout human history, and have only become common in the past 40 years. The surplus of modern, processed foods that accompanies diabesity is also a relatively new phenomenon. It’s possible that the stresses of obesity are similar enough to the stresses of an infection that the body reacts to obesity in the same way it would to an infection: via inflammation. Supporting this theory is evidence that the same intracellular, inflammatory stress pathways are activated in both obesity and infection.

Whichever theory is correct (and they probably both are, to some extent), it’s clear that diabesity causes inflammation. Insulin and leptin resistance impair glucose metabolism. When fat cells become insensitive to insulin, they can’t store any more glucose and hyperglycemia results. Excess sugar in the blood causes glycation, a process where a sugar molecule binds to a protein or a fat, and leads to the formation of advanced glycation endproducts (AGEs). AGEs are inflammatory and are associated with T2DM.

Obesity also contributes to inflammation by up-regulating certain genes involved with the inflammatory response. These genes control the expression of white blood cells called macrophages that play a key role in inflammation. As the concentration of macrophages in the fat tissue increases, the release of inflammatory byproducts such as TNF-α, IL-6 and MCP-1 also increases. This means that the more fat tissue you have, the more inflammation it will produce.

Putting it all together

Collectively, these findings are consistent with the theory I presented in the last article that obesity is an autoimmune, inflammatory disorder.

As we’ve seen, inflammation is both the cause and the result of diabesity. Once obesity and/or insulin resistance have been established, each can further stimulate the production of inflammatory cytokines, forming a vicious cycle of inflammation and diabesity.

It follows, then, that the key to preventing and treating diabesity is reducing inflammation. Unfortunately, few clinicians treating diabesity today understand this. Focusing exclusively on regulating blood sugar and fat hormones without addressing other potential causes of inflammation is bound to produce inferior results.

What are these “other causes” of inflammation? In a phrase: the modern lifestyle. Specifically, dietary triggers (fructose, wheat and industrial seed oils), stress, poor sleep, gut dysbiosis and environmental toxins all cause inflammation on their own. When combined together, they are an explosive mix.

We’ll talk about each of those factors in future articles. For now, the takeaway is that inflammation is probably the single most important mechanism driving the diabesity epidemic. Keep this in mind as we discuss the lifestyle factors that contribute to diabesity, because almost all of them relate back to inflammation in some way.

In this article, I’d like to present a unified model of diabesity. I think it’s helpful to have a “birds-eye view” of how diabesity begins and progresses. It gives us a context for the articles that will follow, each of which will examine specific elements of the model in much more detail.

Two caveats before we dive in. First, remember that all models are imperfect. They’re useful tools, but as the saying goes, a map is never the same as the territory itself.

Second, there is still much about the model I’m going to present that isn’t thoroughly understood. We’re on the bleeding edge here. The science is evolving rapidly, with new articles being published every day. What I’m presenting here is based on my interpretation of the information that is currently available. There are some parts of the model I’m more certain about than others, and I’ll point that out when applicable.

Okay, now that we have that out of the way, take a look at the following diagram. If you click on it a larger version will open in a new window. You might want to print this out or keep it open as we go, because I’ll be referring to it throughout the article.

The model presented in the diagram suggests that diabesity is an autoimmune, inflammatory disorder involving a pathological expression of the innate immune system.

That’s quite a mouthful, so let’s take a closer look at what each part of that statement means.

The innate immune system is the part of the immune system that defends us from infection or foreign substances in a non-specific manner. It’s our first-line of defense against anything the body perceives to be harmful.

Inflammation is the primary response of the innate immune system. In a healthy person, inflammation is temporary and the body eventually returns to homeostasis (“internal balance”). In the case of autoimmunity, however, the body mounts a response against its own cells and tissues and becomes stuck in a continuous loop of chronic inflammation.

Recent research suggests that diabesity is characterized by chronic, low-grade inflammation and a continuous stimulation of the innate immune system. The inflammatory state that accompanies diabesity is not associated with infection or other traditional signs of autoimmunity, and seems to have its own unique features.

If diabesity is an autoimmune, inflammatory disease, the next obvious question is “what causes it?” In a nutshell, the answer is the modern, western lifestyle. Studies clearly show that the incidence of diabesity accompanies its adoption around the world. The features of this lifestyle that have been implicated include:

• Dietary toxins (primarily refined wheat, fructose and industrial seed oils);
• Environmental toxins (chemicals like Bisphenol A, pesticides, phthalates, flame retardants, and heavy metals);
• Micronutrient deficiencies (especially magnesium and vitamin D);
• Chronic stress (emotional, psychological, physiological);
• Altered gut microbiota (caused by antibiotic use, poor diet, formula-feeding during infancy);
• Sedentary lifestyle

Genetics also play a role in diabesity. The evidence suggests, however, that even those with a genetic predisposition to diabesity do not become “diabese” unless they are also exposed to the environmental factors listed above. But genetics likely do explain why some individuals and populations are more likely to develop diabesity when exposed to a modern, western lifestyle.

Environmental factors (together with or independent of genetics) cause both inflammation and obesity, which are both strongly associated with type 2 diabetes (T2DM). But while obesity predisposes people to the metabolic changes characteristic of T2DM, it is not necessarily a feature of diabetes. Evidence is now clear that not all obese people have metabolic dysfunction, and that in some cases, obesity may even protect against metabolic and cardiovascular disease. In this sense obesity may be the body’s attempt to protect against the damage done by a modern lifestyle. (If you’re confused by this, don’t worry – we’ll cover it in more detail later.)

On the other hand, inflammation nearly always accompanies both obesity and diabetes and is independently capable of causing it without overweight – as evidenced by the presence of T2DM in Asian populations that are relatively lean. This explains why thin people can have all of the metabolic problems commonly associated with obesity, including full-fledged T2DM. And in fact these cases of T2DM may be the most severe, because they lack whatever protective adaptation obesity may confer.

Notice that inflammation alone directly contributes to every single metabolic dysfunction associated with diabesity: leptin resistance, impaired fat and glucose metabolism, insulin resistance, and beta-cell destruction. Inflammation can be considered the primary mechanism through which the modern lifestyle and genetics cause diabesity.

Most people are aware that diabetes is characterized by impaired glucose metabolism. What many don’t realize is that diabetes also involves impaired fat metabolism. Fat exists in the body in three primary forms: free fatty acids (FFAs, a.k.a. “non-esterified” fatty acids), triglycerides and phospholipids. Triglycerides and phospholipids are the storage forms of fat. FFAs can be transported in the blood without any carriers.

In healthy people, FFAs are burned in the mitochondria soon after release (lipolysis) from storage forms of fat (triglycerides and phospholipids). But in the diabese, inflammation, leptin resistance and oxidative damage impair the mitochondria’s ability to burn fats. The excess FFAs then “spill over” into non-fat tissue like the liver, pancreas and skeletal muscles. FFAs damage these metabolically active tissues because they don’t belong there. This is called lipotoxicity. Lipotoxicity has been shown in several studies to cause insulin resistance and increase the risk of T2DM.

Both inflammation and obesity cause leptin resistance. Leptin is a hormone produced by body fat. It tells the brain to decrease appetite, increase metabolic rate and increase physical activity. As you accumulate more fat, you secrete more leptin. This causes more fat to be burned. But if you become leptin resistant, your brain doesn’t hear your fat telling it that it’s already full. Leptin resistance is almost always present in obesity because it’s a precondition of significant fat gain. It’s impossible to gain more than a few pounds without being leptin resistant.

Leptin resistance and inflammation set the stage for impaired fat and glucose metabolism, which in turn cause insulin resistance – the defining characteristic of metabolic syndrome and T2DM.

Beta-cell destruction, which leads to the decline in insulin production seen in some cases of T2DM, can be caused by several mechanisms. These include genetics, inflammation, autoimmunity (i.e. Type 1.5 or Latent Autoimmune Diabetes in Adults [LADA]), and impaired fat metabolism (lipotoxicity) and glucose metabolism.

And here we arrive at our final destination: full-fledged type 2 diabetes. It is an autoimmune, inflammatory disorder triggered by modern lifestyle, influenced by genetics, and characterized by impaired glucose and fat metabolism and fat hormone resistance. The purpose of this article was to give you a broad overview of all of the elements of the model. In the articles that follow, we’ll look at each of them in much more depth.

Hippocrates said: “All disease begins in the gut.” 2,500 years later we’re just beginning to understand how right he was. And, as I’ll explain in this article, hypothyroidism is no exception. Poor gut health can suppress thyroid function and trigger Hashimoto’s disease, and low thyroid function can lead to an inflamed and leaky gut – as illustrated in the following diagram:

The gut-thyroid-immune connection

Have you ever considered the fact that the contents of the gut are outside the body? The gut is a hollow tube that passes from the mouth to the anus. Anything that goes in the mouth and isn’t digested will pass right out the other end. This is, in fact, one of the most important functions of the gut: to prevent foreign substances from entering the body.

Another important function of the gut is to host 70% of the immune tissue in the body. This portion of the immune system is collectively referred to as GALT, or gut-associated lymphoid tissue. The GALT comprises several types of lymphoid tissues that store immune cells, such as T & B lymphocytes, that carry out attacks and produce antibodies against antigens, molecules recognized by the immune system as potential threats.

Problems occur when either of these protective functions of the gut are compromised. When the intestinal barrier becomes permeable (i.e. “leaky gut syndrome”), large protein molecules escape into the bloodstream. Since these proteins don’t belong outside of the gut, the body mounts an immune response and attacks them. Studies show that these attacks play a role in the development of autoimmune diseases like Hashimoto’s.

We also know that thyroid hormones strongly influence the tight junctions in the stomach and small intestine. These tight junctions are closely associated areas of two cells whose membranes join together to form the impermeable barrier of the gut. T3 and T4 have been shown to protect gut mucosal lining from stress induced ulcer formation. In another study, endoscopic examination of gastric ulcers found low T3, low T4 and abnormal levels of reverse T3.

Likewise, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) both influence the development of the GALT. T4 prevents over-expression of intestinal intraepithelial lymphocytes (IEL), which in turn causes inflammation in the gut.

The gut-bacteria-thyroid connection

One little known role of the gut bacteria is to assist in converting inactive T4 into the active form of thyroid hormone, T3. About 20 percent of T4 is converted to T3 in the GI tract, in the forms of T3 sulfate (T3S) and triidothyroacetic acid (T3AC). The conversion of T3S and T3AC into active T3 requires an enzyme called intestinal sulfatase.

Where does intestinal sulfatase come from? You guessed it: healthy gut bacteria. Intestinal dysbiosis, an imbalance between pathogenic and beneficial bacteria in the gut, significantly reduces the conversion of T3S and T3AC to T3. This is one reason why people with poor gut function may have thyroid symptoms but normal lab results.

Inflammation in the gut also reduces T3 by raising cortisol. Cortisol decreases active T3 levels while increasing levels of inactive T3. ¹

Studies have also shown that cell walls of intestinal bacteria, called lipopolysaccharides (LPS), negatively effect thyroid metabolism in several ways. LPS:

• reduce thyroid hormone levels;
• dull thyroid hormone receptor sites;
• increase amounts of inactive T3;
• decrease TSH; and
• promote autoimmune thyroid disease (AITD).

Other gut-thyroid connections

Hypochlorhydria, or low stomach acid, increases intestinal permeability, inflammation and infection (for more on this, see my series on acid reflux & GERD). Studies have shown a strong association between atrophic body gastritis, a condition related to hypochlorhydria, and autoimmune thyroid disease.

Constipation can impair hormone clearance and cause elevations in estrogen, which in turn raises thyroid-binding globulin (TBG) levels and decreases the amount of free thyroid hormones available to the body. On the other hand, low thyroid function slows transit time, causing constipation and increasing inflammation, infections and malabsorption.

Finally, a sluggish gall bladder interferes with proper liver detoxification and prevents hormones from being cleared from the body, and hypothyroidism impairs GB function by reducing bile flow.

Healing the gut-thyroid axis

All of these connections make it clear that you can’t have a healthy gut without a healthy thyroid, and you can’t have a healthy thyroid without a healthy gut. To restore proper function of the gut-thyroid axis, both must be addressed simultaneously.

Healing the gut is a huge topic that can’t be covered adequately in a few short sentences. But I will say this: the first step is always to figure out what’s causing the gut dysfunction. As we’ve reviewed in this article, low thyroid is one possible cause, but often hypochlorhydria, infections, dysbiosis, food intolerances (especially gluten), stress and other factors play an even more significant role. The second step is to address these factors and remove any potential triggers. The third step is to restore the integrity of the gut barrier. My preferred approach for this last step is the GAPS diet.

The influence of thyroid hormones on the gut is one of many reasons why I recommend that people with persistently high TSH and low T4 and T3 take replacement hormones. Low thyroid hormones make it difficult to heal the gut, and an inflamed and leaky gut contributes to just about every disease there is, including hypothyroidism. Fixing the gut is often the first – and most important – step I take with my patients.

In the last post I explained that, for the vast majority of patients, hypothyroidism is an autoimmune disease. This isn’t just an academic distinction. It’s the reason both conventional and alternative treatments are so often ineffective.

In this post I’m going to show you why taking replacement thyroid hormones without addressing the underlying immune imbalance is doomed to fail.

The ultimate effect of hypothyroidism, whether it’s caused by iodine deficiency or autoimmunity, is to decrease the amount of thyroid hormone available to the body. The conventional approach is to simply replace these hormones with either synthetic or bio-identical forms.

On the surface it seems like a reasonable approach. Patient doesn’t have enough hormones? Give more hormones. Simple, right?

Not so much.

Once again the conventional approach falls short because it ignores the underlying cause of the problem. It’s like taking Advil when you’ve got a pebble stuck in your shoe. It might work for a little while, and might even be necessary to dull the pain. But you’d be a lot better off if you took the pebble out of your shoe. Right?

Let’s take a closer look at why thyroid hormones often don’t work, or stop working over time. The following diagram illustrates how autoimmunity affects thyroid metabolism:

Immune dysregulation is another term for autoimmune disease. We still don’t know exactly what causes it, but most researchers agree it’s a mixture of genetic susceptibility and environmental factors such as iodine (excess), infection, pregnancy, diet and intestinal permeability.

In autoimmune disease the body attacks itself. It does this the same way it attacks foreign invaders like bacteria and viruses: with T-cells, B-cells, natural killer cells, and cytotoxic T cells. The immune response also involves proteins called cytokines, chemical messengers that pass messages between cells.

This self-attack by the immune system increases inflammation. And inflammation has a profound effect on all aspects of thyroid metabolism and physiology.

First, inflammation suppresses the hypothalamus-pituitary-thyroid (HPT) axis. One study showed a single injection of the inflammatory cytokine TNF-alpha reduced blood levels of TSH, T3, free T4, free T3 and TRH for 5 days. This shows inflammation disrupts the production and regulatory mechanisms of thyroid hormones. Thyroid medication will increase the levels of T4 (and possibly T3), but it doesn’t address the other effects of HPT axis suppression.

Second, inflammation decreases both the number and sensitivity of thyroid hormone receptors. If there aren’t enough receptors, or they aren’t sensitive enough, it doesn’t matter how much thyroid medication we take. The cells won’t be able to use it. It’s like when my grandpa used to turn down his hearing aids while he was watching the football game. It didn’t matter how much my grandma yelled at him – he couldn’t hear a word she said.

Third, inflammation decreases the conversion of T4 to T3. T4 is the inactive form of thyroid hormone. The body has to convert it to the active T3 form before it can be used. Most synthetic hormone medications on the market are T4. If you give a T4 medication (like Synthroid, Levoxyl, Unithroid, etc.) to someone with inflammation, it’s not going to work because they can’t convert the T4 to T3.

Patients who don’t convert T4 to T3 well do better on bio-identical hormones like Armour, because it contains both T4 and T3 (in a 4.22:1 ratio).

Inflammation disrupts thyroid metabolism in several other ways, but I think these three examples make the point.

Now let’s review.

Inflammation causes HPT axis disruption, decreased receptor function, and decreased conversion of T4 to T3. Thyroid medication only increases the levels of thyroid hormone (usually T4) in the blood. No matter how much we take, it’s not going to restore HPT axis coordination, improve receptor function, or increase conversion of T4 to T3.

The only way to do that is to address the problem at its root by regulating the immune system and decreasing inflammation. Unfortunately, this is rarely done in either conventional or alternative treatment of thyroid disorders.

Before I sign off, I just want to make one thing clear. I’m not saying thyroid medication isn’t necessary or useful. In fact, I think it’s an important part of treating Hashimoto’s – especially when TSH is consistently elevated and T4 and T3 are consistently low. My point is thyroid medication is only one piece of the puzzle, and it won’t be effective on its own unless the autoimmunity and inflammation are addressed.

If thyroid medication is the fantasy magic bullet of conventional medicine, iodine is the equivalent in alternative medicine. In the next post I’m going to explain why supplemental iodine may cause more harm than good in Hashimoto’s patients.

Note: This is the fourth article in an ongoing series. Make sure to read the previous articles before reading this one, and check out the next articles in the series afterwards.

• Chinese Medicine Demystified (Part I): A Case of Mistaken Identity
• Chinese Medicine Demystified (Part II): Origins of the Energy Meridian Myth
• Chinese Medicine Demystified (Part III): The “Energy Meridian” Model Debunked
• Chinese Medicine Demystified (Part IV): How Acupuncture Works
• Chinese Medicine Demystified (Part V): A Closer Look At How Acupuncture Relieves Pain
• Chinese Medicine Demystified (Part VI): 5 Ways Acupuncture Can Help You Where Drugs and Surgery Can’t

In this post we’re going to explore how acupuncture works from a western scientific perspective. As I’ve argued in the previous articles, there is no disagreement between the fundamental anatomical and physiological concepts of western and Chinese medicine. However, as methods of scientific inquiry have progressed, the mechanisms of acupuncture are beginning to be more clearly understood.

Acupuncture effects every major system of the body, including the cardiac, gastrointestinal, circulatory, cerebral, genitourinary, endocrine and immune systems. It would take an entire book to describe all of the mechanisms involved, and in fact there is such a book for those who are interested in that level of detail. In this post my purpose is to summarize that research in a way that’s easy for lay people to understand, while providing links to more technical resources for medical professionals and others that might be interested.

Broadly speaking, acupuncture has three primary effects:

1. It relieves pain.
2. It reduces inflammation.
3. It restores homeostasis.

Homeostasis refers to the body’s ability to regulate its environment and maintain internal balance. All diseases involve a disturbance of homeostasis, and nearly all diseases involve some degree of pain and inflammation. In fact, research over the last several decades suggests that many serious conditions like heart disease previously thought to have other causes are in fact primarily caused by chronic inflammation. If we understand that most diseases are characterized by pain, inflammation and disturbance of homeostasis, we begin to understand why acupuncture can be effective for so many conditions.

Several modes of action have been identified for acupuncture, which I’ll discuss below. The mechanisms can get quite complex. But ultimately acupuncture is a remarkably simple technique that depends entirely upon one thing: the stimulation of the peripheral nervous system. It’s important to point out that when nerves supplying acupoints are cut or blocked there is no acupuncture effect.

A large body of evidence indicates that acupoints, or “superficial nodes” as they are more accurately translated, have abundant supply of nerves. According to Chen Shaozong, “For 95% of all points in the range of 1.0 cm around a point, there exist nerve trunks or rather large nerve branches.” ¹

The following is a list of mechanisms that have been identified so far:

• Acupuncture promotes blood flow. This is significant because everything the body needs to heal is in the blood, including oxygen, nutrients we absorb from food, immune substances, hormones, analgesics (painkillers) and anti-inflammatories. Restoring proper blood flow is vital to promoting and maintaining health. For example if blood flow is diminished by as little as 3% in the breast area cancer may develop. Blood flow decreases as we age and can be impacted by trauma, injuries and certain diseases. Acupuncture has been shown to increase blood flow and vasodilation in several regions of the body.
• Acupuncture stimulates the body’s built-in healing mechanisms. Acupuncture creates “micro traumas” that stimulate the body’s ability to spontaneously heal injuries to the tissue through nervous, immune and endocrine system activation. As the body heals the micro traumas induced by acupuncture, it also heals any surrounding tissue damage left over from old injuries.
• Acupuncture releases natural painkillers. Inserting a needle sends a signal through the nervous system to the brain, where chemicals such as endorphins, norepinephrine and enkephalin are released. Some of these substances are 10-200 times more potent than morphine!
• Acupuncture reduces both the intensity and perception of chronic pain. It does this through a process called “descending control normalization”, which involves the serotonergic nervous system. ² I will explain this process in further detail in the next post.
• Acupuncture relaxes shortened muscles. This in turn releases pressure on joint structures and nerves, and promotes blood flow.
• Acupuncture reduces stress. This is perhaps the most important systemic effect of acupuncture. Recent research suggests that acupuncture stimulates the release of oxytocin, a hormone and signaling substance that regulates the parasympathetic nervous system. You’ve probably heard of the “fight-or-flight” response that is governed by the sympathetic nervous system. The parasympathetic nervous system has been called the “rest-and-digest” or “calm-and-connect” system, and in many ways is the opposite of the sympathetic system. Recent research has implicated impaired parasympathetic function in a wide range of autoimmune diseases, including arthritis, lupus, rheumatoid arthritis and inflammatory bowel disease.

Several other mechanisms have been identified, but the ones I’ve listed above are the most relevant and clearly understood.

Some purists object to acupuncture being described in biomedical terms. They claim that such descriptions are “reductionistic” and narrow-minded, and don’t take into account those aspects of acupuncture that we may not yet understand.

Others who are still committed to the “energy meridian” model are opposed to the biomedical descriptions because, in their eyes, such scientific inquiry “takes the magic” out of acupuncture.

While I agree that there we don’t yet fully understand how acupuncture works, I think it’s vital that practitioners of acupuncture are able to explain what we do know about it from a biomedical perspective to their patients and colleagues in the medical profession. As practitioners we have a moral obligation to provide each patient with the latest medical understanding available in terms they can understand and relate to. Doing this will improve patient outcomes and open the door for acupuncture to be integrated into the healthcare system, which is needed now more than ever.

I would also suggest that explaining the mechanisms of acupuncture in scientific terms should not in any way lessen our appreciation of its uniqueness. The fact that inserting fine needles into the skin can have such a broad range of powerful effects is just as remarkable when those effects are explained in terms of the nervous system as when they are explained in terms of “energy” and “meridians”. When you consider that the Chinese made these discoveries hundreds of years before the birth of Christ, acupuncture is even more impressive.

What’s more, as others have pointed out, acupuncture is inherently holistic even without the “energy meridian” theory because it restores internal homeostasis through the simple act of piercing the skin with a needle.

In the next article I’ll explain the latest theory on how acupuncture relieves pain in more detail. Stay tuned, and as always, I welcome your comments!

A recent study published in the American Journal of Pathology adds to the already considerable body of evidence which suggests that inflammation is a primary cause of heart attacks and strokes.

In an article I wrote last year, Preventing Heart Disease Without Drugs, I reviewed the current scientific understanding of what causes heart disease. If you’ve been following this blog, you know that inflammation and oxidative damage – not saturated fat and cholesterol – are the primary causes of heart disease.

I wrote:

The data from this study provide further support for the “oxidative response to inflammation” hypothesis described above. The researchers found that inflammation leads to a reduction of mature collagen in atherosclerotic plaques, leading to thinner caps that are more likely to rupture. This is important because other studies have shown that it is not atherosclerosis alone, but the rupture of the atherosclerotic plaques, that causes heart attacks and strokes.

It follows, then, that if we want to prevent heart disease we need to do everything we can to minimize inflammation and oxidative damage.

By focusing on reducing or completely eliminating, when possible, the factors in our life that contribute to oxidative stress and inflammation, we can drastically lower our risk for heart disease.

For more in-depth information about each of these factors and how to minimize your risk of heart disease without drugs, please refer to Preventing Heart Disease Without Drugs.