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 effect 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.

Vita-mix Giveaway

I have a couple of announcements to make. First, I’m switching over to a new Facebook page. My current page is still called “The Healthy Skeptic”, and as it’s not possible to change the name of a Facebook page, I had to create a new one.

In order to entice you to come join us on my new page, I’m giving away a Vitamix blender and free lifetime access to both the Personal Paleo Code and the Meal Plan Generator.

To enter the drawing, just like my new page and fill out the entry form. The contest ends on February 29th at 11:59pm, so make sure to enter before then!

Personal Paleo Code Affiliate Program

I’ve received a lot of inquires about an affiliate program for the Personal Paleo Code, and I’m happy to say that it’s now available. You can sign up by clicking here and filling out the form. We will then contact you with details.

The affiliate program is a great way to help others experience the life-changing benefits of a Paleo diet and lifestyle, while earning a little extra cash for your efforts. Here’s how it works:

• You place banners or links to the Personal Paleo Code on your website.
• If someone purchases the PPC through through your site, you earn a 33% commission.
• If they continue with the Meal Plan Generator after the 30 day trial, you’ll earn a 25% commission on their monthly subscription fee.

If you plan to promote the PPC offline – at your gym or health clinic, for example – you can still be an affiliate and earn commissions. Just make sure you indicate that you will be promoting PPC offline in the “Website/location where you will promote PPC” field on the sign up form, and we will send you special instructions.

Healthy Baby Code Affiliate Program

We also have an affiliate program for the Healthy Baby Code. It works in a similar fashion. You will earn a 33% commission for anyone who purchases through your website or gym/clinic. Click here to sign up.

Exercise is a major component of a healthy lifestyle, and the benefits of regular physical activity are well established. When adopting a Paleo lifestyle, modifying your fitness routine to include more high intensity exercise can bring great benefits to energy, body composition, and overall fitness.

However, there are many people who take their physique and physical fitness to an extreme level, particularly in the Paleo community. Certain styles of exercise take the participant to a state of physical exhaustion on a regular basis, which may do more harm than good.

While a consistent, high intensity workout routine may provide some benefits for those people looking to lose body fat and increase their strength and fitness, there is a fine line between training hard and overtraining. While running fast and lifting heavy may be major components of an active Paleo lifestyle, engaging in these physically demanding activities too regularly or too intensely can contribute to many different symptoms of overtraining.

Overtraining goes beyond just excessive “chronic cardio” or too many hours spent at the gym. Certain high-intensity exercise routines may push the body’s stress response too far, leading to a cascade of biochemical responses that can cause serious damage to one’s health in both the short and long term.

While short, intense workouts can be great for inducing fat loss, increasing aerobic capacity, and reducing risk for cardiovascular disease, excessively intense exercise can cause a variety of health problems, especially for those dealing with other concurrent stressors such as autoimmune disease, gut dysbiosis, or adrenal fatigue.

Overtraining has been shown to affect blood levels of important neurotransmitters such as glutamine, dopamine and 5-HTP, which can lead to feelings of depression and chronic fatigue. The stress caused by intense, excessive exercise can negatively affect the hypothalamic-pituitary axis, possibly causing conditions such as hypothyroidism. Hypothyroidism is known to cause depression, weight gain, and digestive disfunction along with a variety of other symptoms. As we know, high stress in general can cause symptoms of hypothyroidism, and the stress caused by excessive, intense exercise is no exception.

Another major effect that extreme exercise has on our bodies is an immediate increase in cortisol, the hormone that is released when the body is under stress. Heavy-resistance exercises are found to stimulate markedly acute cortisol responses, similar to those responses found in marathon running. Chronically high levels of cortisol can increase your risk for a variety of health issues, such as sleep disturbances, digestive issues, depression, weight gain, and memory impairment. Excess cortisol also encourages fat gain, particularly around the abdomen.

When a goal of exercise is to lose weight or improve energy, overtraining can clearly be a major barrier to achieving those goals.

Overtraining can also have harmful effects on the immune system. Research has shown that the cellular damage that occurs during overtraining can lead to nonspecific, general activation of the immune system, including changes in natural killer cell activity and the increased activation of peripheral blood lymphocytes. This hyperactivity of the immune system following intense overtraining can possibly even contribute to the development of autoimmune conditions.

This type of nonspecific immune response is associated with symptoms such as chronic fatigue, weight loss, decreased appetite, and sleep changes. Altered immune status is also known to affect the hypothalamic-pituitary axis, and may be responsible for the hypothalamic-pituitary dysfunction and hypothyroidism known to occur in overtrained athletes.

Mark Sisson talks about the different signs of overtraining, which may be more common in endurance training but is nonetheless possible in high intensity training as well. Feeling ill or rundown, losing muscle mass, gaining fat, and constant exhaustion can all be signs of excessive exercise of any type. Not only is this counterproductive to most people’s fitness and health goals, but it is also a sign of sickness. In the path to better health, any activity that makes you more fatigued and more prone to infection is definitely something to be avoided.

So does this mean you should quit CrossFit, or stop pushing towards your weightlifting goals? Not necessarily.

Here are a few techniques to avoid overtraining while still enjoying high intensity exercise:

1. Reduce the frequency. While pushing yourself hard at the gym is not inherently problematic, doing it too often during the week is overtraining. High intensity, high stress exercise should be limited to two or three times a week, especially for those who are dealing with other health issues such as autoimmune conditions or digestive troubles. Compounding those stressors with extra stress from your exercise routine will not leave you healthier, and can easily cause you to become more sick.
2. Get adequate rest. I’ve written before about how important sleep quality is for health. Not only is taking breaks from exercise important, but getting adequate sleep to allow recovery from intense exercise is vital to avoiding the overtraining syndrome. Make sure you are getting adequate sleep, particularly on the days you train. Interestingly, one symptom of overtraining is disturbance of sleep, so if you’re feeling restless and having trouble sleeping through the night, you may want to reconsider the intensity of your training schedule.
3. Mix it up. While high intensity exercise may be ideal for losing body fat and improving lean muscle mass, we know that high levels of cortisol can cause the body to hold onto fat. For this reason, you may consider trying a type of exercise that can help modulate your cortisol levels. Some may knock yoga as being too easy to affect weight loss, but regular yoga practice is shown to reduce cortisol levels, which may help in reaching your weight and fitness goals. Instead of doing a fourth day of CrossFit, try doing a yoga class instead. You may find that this stress reducing exercise helps you recover more quickly from your more intense exercise schedule.
4. Eat more carbohydrates. While cutting down carbohydrate consumption is often seen as the best way to decrease body fat, a combination of overtraining and low-carb eating can actually raise cortisol significantly and negatively impact immune function. There is also a possibility that very low carbohydrate (VLC) diets suppress thyroid function, a debate thoroughly discussed by Paul Jaminet on his blog. So if you’re regularly doing high intensity training and want to avoid symptoms of overtraining stress, don’t skimp on the carbs!

High intensity exercise can be a great way to improve body composition and enhance your general health, if done the right way. As with all components of our lifestyle changes, the key is moderation and listening to your body. If you choose to participate in these high intensity training programs, always use your best judgment and don’t let coaches or fellow athletes push you past your comfort zone.

Now, I’d like to hear your experiences with different exercise programs – did your health improve or suffer after increasing the intensity of your training? Have you been able to find a balance between intensity and adequate recovery?

**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.

I’m going to be speaking as well as participating in a couple of mastermind panels at the PaleoFx conference in Austin, TX from March 14th – 16th.

The symposium theme is “Theory to Practice”. PaleoFx is the practical, hands-on, how-to version of the Ancestral Health Symposium. Speakers include myself, Robb Wolf, Mark Sisson, Jack Kruse, Keith Norris, and many others. All of your favorite Paleo & Primal diet and lifestyle folks will be there.

In addition to fitness and healthcare professionals, nutritionists, and research scientists, there will be top strength and conditioning and natural movement coaches giving hands-on demonstrations. The symposium is intended for laypersons, practitioners, researchers, and everyone in between.

Tickets are now on sale. Stay tuned for announcements on ticket giveaways. For full details, visit www.paleofx.com and www.facebook.com/paleofx.

Looking forward to seeing you there! Are any of you planning to go?

GERD is an extremely common problem in the U.S.. 44% of Americans suffer from it at least once a month, and 20% suffer from it weekly. (1) Drug companies make $7 billion a year selling acid suppressing drugs – primarily proton pump inhibitors (PPIs) like Prilosec and Aciphex.

The popularity of these drugs is predicated on the idea that GERD is caused by stomach acid burning the esophagus. This is known as the “chemical burn” theory. It holds that GERD develops from caustic, chemical injury that starts at the surface layers of the esophagus and progresses through the tissue to the deeper layers (the lamina propia and submucosa). (2)

Early animal research seemed to support this. Studies showed large quantities of stomach acid with a pH of less than 2 does damage the esophagus. (3) However, the concentrations of acid used in these studies are much higher than those normally found in human episodes of reflux. In fact, the vast majority of human reflux episodes have a pH of more than 2 and are incapable of causing esophageal damage. (4)

What if GERD is not caused by acid burning the esophagus?

In a 2009 study Souza and colleagues connected the esophagus directly to the duodenum (the upper part of the small intestine) in a group of rats, thus permitting acid to reflux freely into the esophagus. (5) To their surprise, it took 3 weeks for damage to the esophagus to occur. Commenting on the results, senior author Stuart Spechler said:

That doesn’t make sense if GERD is really the result of an acid burn, as we were all taught in medical school. Chemical injuries develop immediately. If you spill battery acid on your hand, you don’t have to wait a month to see the damage.

If acid itself caused the damage, we’d expect to see the damage start at the superficial layers of the esophageal tissue, and then progressively deepen. Instead, this study found the opposite. 3 days after the initial acid exposure, there was no surface damage – but inflammation had already begun to develop at the deepest layer of the tissue. This inflammation didn’t rise to the surface layers until about 3 weeks after the initial acid exposure.

This suggests that GERD is an autoimmune disease.

Acid refluxing into the esophagus doesn’t damage the mucosal lining. Instead, it causes the esophagus to release inflammatory cytokines that attract inflammatory cells like interleukin-8, interleukin-6, and others. It is this inflammatory process – and not the initial exposure to stomach acid – that causes the tissue damage characteristic of GERD.

Do you have GERD – or NERD?

The theory that GERD is not caused by chemical injury is supported by the fact that 70% of westerners diagnosed with GERD have no visible tissue damage.

In fact, these people don’t have GERD at all. They have NERD, or Non-Erosive Reflux Disease. Tissue biopsy of their esophagus shows inflammation developing at the base layers of the esophagus like GERD sufferers, but no damage to the surface layers as the conventional theory would predict. It’s unclear at this point why the tissue injury progresses to the superficial layers in GERD – but not NERD – sufferers, but this study suggests that the answer may be an autoimmune mechanism.

So what does this mean for you? How do you avoid GERD and NERD in the first place?

Even if GERD is caused by an autoimmune process as this study suggests, the initial trigger seems to be acid inappropriately moving from the stomach to the esophagus. But that does not mean GERD & NERD are caused by too much stomach acid, as the common dogma holds.

In an earlier series of articles I presented evidence that acid reflux is caused not by too much stomach acid, but by not enough. I argued that low stomach acid causes bacterial overgrowth in the gut, which in turn produces gas that puts pressure on the lower esophageal sphincter, causing it to open and inappropriately allow acid into the esophagus.

I also offered a simple, 3-step protocol for treating reflux and GERD without drugs that thousands of people have now successfully used (check out the 190 comments) – including people that had been on acid suppressing drugs for 20 years or more. This is important because acid-suppressing drugs have numerous side effects and complications.

Why you should think twice about taking acid-suppressing drugs.

Acid stopping drugs promote bacterial overgrowth, weaken our resistance to infection, reduce absorption of essential nutrients, and increase the likelihood of developing IBS, other digestive disorders, and cancer. The pharmaceutical companies have always been aware of these risks. When acid-stopping drugs were first introduced, it was recommended that they not be taken for more than six weeks. Clearly this prudent advice has been discarded, as it is not uncommon today to encounter people who have been on these drugs for decades – not weeks.

What’s more, a recent study showed that proton-pump inhibitors (PPIs) – the most popular class of acid-suppressing drugs – induce “rebound acid reflux” in healthy people. The researchers took a group of people without any history of reflux and put them on PPIs for 8 weeks (where did they find these volunteers???) More than 40% of the healthy volunteers developed rebound acid-related symptoms like heartburn, acid regurgitation and dyspepsia once they stopped taking the drugs. (6) The authors of the study stated:

If rebound acid hypersecretion (RAHS) induces acid-related symptoms, this might lead to PPI dependency and thus have important implications.

I’d say!

If you suffer from acid reflux, make sure to read the entire series, and then follow the 3-step protocol I laid out. In a future article I’ll be covering some additional natural treatments that studies have shown to be just as effective as PPIs, with virtually no side effects or risks.

When addressing our health, many of us tend to focus on the quality of our diet and exercise as the primary methods of improving our overall wellness. We often believe that if we perfectly “dial in” our diet and exercise routine, then optimal health will surely follow. This concentration on perfecting both food and fitness in the quest for well-being can often lead to the neglecting of certain important relationships in our lives, particularly relationships with others.

But what about your relationship with nature?

You may not have considered the possibility of fostering a “relationship” with nature – after all, how can you have a relationship with a non-human entity?

From an anecdotal perspective, how many of us have taken a long walk in the woods, and felt soothed by the sound of the wind in the trees and the crisp smell of leaves? Or have been moved by the beauty of a snow-capped mountain range? Who wouldn’t enjoy an evening watching the sunset at the beach, sand between the toes, with the rhythmic ocean waves lapping at the shore?

Experiencing these profound moments of peace, happiness, or wellness in the context of nature is a universal event, and demonstrates that contact with nature is an integral part of our well-being as humans. In a public health context, exposure to nature has been used as therapy for short-term recovery from stress or mental fatigue, faster physical recovery from illness, and long-term overall improvement on people’s health and well being (1).

Research supports the theory that our relationship with nature is a fundamental component of maintaining good health. This “biophilia hypothesis” suggests that there is an innate affiliation of human beings to other living organisms, both flora and fauna, and perhaps even an innate bond with nature more generally.

The biophilia theory is supported by both common sense and clinical evidence. Many controlled trials and observational studies have demonstrated the positive therapeutic value of both the physical and visual exposure to nature, with benefits shown for a diverse range of diagnoses spanning from schizophrenia to obesity.

This biophilia theory makes sense in an evolutionary context as well.

Many species of animals use habitat selection as a criteria for successful survival, focusing mainly on patterns of tree density and openness of view. Early humans were no different; a preference for living near water and an abundance of green plants would have indicated greater food availability, with both edible vegetation and herbivorous animals in plentitude (2).

The ability to identify relaxing, restorative natural settings would have also allowed paleolithic humans the opportunity to recover from stress or fatigue, and would have been adaptive to survival. Those individuals who were able to settle in these types of environments would have gained a survival advantage, which may explain human beings’ preference for certain landscapes.

While we evolved outdoors and amongst nature for most of the last two million years of our species’ existence, the movement to a largely indoor environment has been a recent development for humans. Much like our diet, our physical environment has changed drastically in a comparatively short amount of time.

We have broken our strong connection with the natural environment very recently, and have not had the chance to adapt to our new life of shelter and confinement. The advent of electricity has been even more recent, allowing our world to be inundated with artificial light at any time of day (or night).

A lack of sunlight and/or excessive amounts of artificial light can have a variety of negative health consequences. (Diane Sanfilippo of Balanced Bites has written an excellent post regarding the problems with artificial light and the different ways you can reduce your exposure.)

Our relationship with nature has been overcome by our relationship with technology.

Recent news stories have focused on the idea of “nature deficit disorder”, suggesting that children who spend too much time staring at screens may develop attention deficits, hyperactivity, or depression (3). While our children may be bearing the brunt of this nature deficit, it stands to reason that those of us that spend forty hours a week or more with our eyes glued to a computer screen may have similar negative health consequences.

While we may not be able to quit our jobs, sell our houses, and move out into the wilderness (or can we?), there are many ways to alleviate our growing nature deficit:

1. Take your exercise outside – Research shows that exercising outside confers even greater physical and mental benefits compared to the same exercise indoors. Take a long walk at your local park (bundle up if it’s cold) rather than plugging away on the treadmill in your fluorescent-lit gym. Take advantage of warmer, sunny days and move your workout into the wilderness. It may take some creativity or extra planning, but the mental and physical benefits will be worth the effort. You may even find yourself enjoying your workout more than usual!
2. Invest in a pet – Companion animal relationships have been essential to the survival of primitive humans, and pet-keeping was common in hunter-gatherer societies. Pet ownership not only gives people a sense of companionship and nurturance, but also provides a connection to nature in a more tangible sense. Contact with animals has been shown to decrease risk of heart disease, lessen anxiety, and reduce depression. Not to mention, there’s nothing more motivating to get outside than a hyperactive dog!
3. Grow an indoor garden – If getting outside on a regular basis is too challenging, consider the addition of indoor foliage to your home’s interior design. Studies show that indoor plants can boost mood, improve air quality, and reduce anxiety and fatigue. Even if you live in an urban environment, bringing green foliage into your living space can greatly benefit your connection with the natural world.

Our relationship with nature is a vital component of our wellbeing, and one often neglected due to the concerns of modern life. In order to more fully address our health and wellness as humans, we must consider the biological appropriateness of our environment to be just as important as that of our diet and exercise choices.

Now I’d like to hear from you. How do you nurture your relationship with nature? What are your favorite ways to interact with the natural world?

The human body has an elaborate system for managing and regulating the amount of key trace metals such as zinc, copper, iron, manganese, chromium.  One of the most common malfunctions of this system is an excess of copper and deficiency of zinc (copper-zinc imbalance), which can lead to hyperactivity, attention deficit disorders, behavior disorders, depression, acne, eczema, sensitive skin, sunburn, headaches, poor immune function and much more.

In this episode of Revolution Health Radio, we cover:

3:07 Can someone without a gallbladder eat a Paleo Diet?
6:39 How to tell if you should avoid coffee, green tea, and caffeine
13:52 If you have this Copper-Zinc imbalance your body could be starving for oxygen…
21:52 Get these tests done if you have nervousness, anxiety, or mood swings
27:43 What to do – and not do – if your copper levels are high
33:46 Is 5-HTP safer than SSRI’s for anxiety and depression?
42:54 Why anti-depressants could permanently alter your brain chemistry… in a bad way
45:37 The surprising cause of depression (and no, it’s not low serotonin)
48:40 Are chocolate cravings related to magnesium deficiency?
53:22 How to get your Vitamin A and D ratio within healthy ranges

Links We Discuss:

• The Depression Series
• Light Therapy Machine for Depression
• Chris Masterjohn’s Vitamin A Article
• Recipes for liver (at the bottom)

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 today, Chris?

Chris Kresser:  I’m pretty good, Steve.  How are you?

Steve Wright:  I’m doing well, as well.  I’m recovering from a chest cold over the holidays that I had, but today has probably been my best day so far, so I’m hoping it’s behind me.

Chris Kresser:  Glad to hear it.  Did you have a good holiday season other than that?

Steve Wright:  Yeah, it was great.  Lots of family time, lots of relaxing, and other than the stress of trying to hit a party every other day, it was great.

Chris Kresser:  Wow.  I kinda remember that, vaguely.

Steve Wright:  How was Canada?

Chris Kresser:  Dark and cold.  No, it was actually not that cold compared to last time; I think I mentioned it was 40 below when we went to visit Elanne’s parents, but this time it was a balmy 25 or 30 degrees, which was not that bad.

Steve Wright:  You could almost wear shorts!

Chris Kresser:  Yeah, right.  It’s interesting because I’m such a daylight person myself.  I’m not a night person.  I’m a day person.  I love being outside during the day and being really active, and up there at this time of year, it doesn’t really even get light until, you know, 8:30 or 9 in the morning, and then it’s already getting dark at 4, so the days are really short, and the good part of that is I ended up resting a lot, you know, and just really doing a lot of nothing, which is not my usual MO, and so it’s nice to have a little bit of time like that.

Steve Wright:  Yeah, that’s good.  Sort of a forced outage.

Chris Kresser:  Um-hum, exactly.  And from a sort of Paleo lifestyle perspective, that’s what the winter is supposed to be like, you know?  I mean our ancestors had a natural rhythm and flow throughout the year.  Certainly the spring and the summer were more active times, and the fall, late fall, and winter were times of contemplation and rest, and a lot of us aren’t really in tune with those natural rhythms anymore because of electric light and, you know, there’s often nothing that’s really that different about our lives in the winter and the summer in terms of our work schedule or something else that we’re doing, so it’s always nice for me to get back in touch with those natural rhythms.

Steve Wright:  Yeah, and the added sleep, I think, is a big bonus for me.

Chris Kresser:  Definitely.  Cool.  Well, we have some interesting questions.  Let’s dive in.

Can someone without a gallbladder eat a Paleo Diet?

Steve Wright:  Yeah, thanks everyone for sending in your questions, and let’s start with Angela’s first.  She’s curious how someone without a gallbladder does Paleo.

Chris Kresser:  Well, the common bile duct, which still remains after the gallbladder is removed, actually assumes a lot of the function of the gallbladder once it’s taken out, and that’s why it’s possible to take out the gallbladder and not have somebody just completely fall apart and be unable to digest any fat at all.  So, a lot of people do really well on Paleo without a gallbladder.  Some people may need to moderate their fat intake to some degree, although a lot of people don’t.  The type of fat seems to matter.  Coconut oil is a very good fat for people without a gallbladder because it doesn’t require bile acids for absorption, so it’s rapidly absorbed in the upper part of the small intestine, and it’s transported directly to the liver via the portal vein.  These are medium-chain triglycerides that I’m talking about, and in fact, they’re used in hospital tube-feeding formulas, you know, for people who have had surgery on their intestine or have had parts of their intestine removed because they’re so easy to digest and absorb.  So, coconut oil is definitely your friend if you’re lacking a gallbladder.  Then there are some other things that can be done to improve that function of the bile duct and help emulsify and break down fats.  Dandelion is a very commonly used herb in the Western pharmacopoeia.  It’s bitter and it’s a cholagogue, which means it helps with bile synthesis.  Ox bile can be used if you’re having trouble digesting fats.  You know, that won’t address the underlying cause of the problem, but it will help symptomatically.  It’s a similar approach to using hydrochloric acid when you have low stomach acid, but you’re actually using bile itself in this case.  So, that can be useful for people who don’t have a gallbladder or for anybody who is having trouble digesting fat, because that’s often one of the biggest difficulties that I see when somebody moves from a lower-fat diet to a higher-fat Paleo Diet is if they haven’t been in the habit of eating fat and producing bile that you need to break it down, they can often experience some difficulty with the high fat content, and so ox bile or dandelion root or ginger can all be helpful in breaking down the fat.

Steve Wright:  Well, what about lipase?  Would someone want to take an enzyme like lipase for this?

Chris Kresser:  Sure, that can work too.  You know, we talked before about how I generally prefer HCl to correct the problem at the top, and if the food in the stomach is properly acidified, then the pancreas should secrete all of the necessary enzymes, but the NOW Super Enzymes are a good choice at least temporarily while you’re resolving the underlying issues.  That can be helpful too.

How to tell if you should avoid coffee, green tea, and caffeine 

Steve Wright:  All right, great.  Let’s move on to question #2 from Jeff, and it is, “What is your take on coffee, green tea, and caffeine consumption in general?  Robb Wolf and his cohort seem fine with it, but Mat ‘The Kraken’ Lalonde is against it.”

Chris Kresser:  Well, everyone is probably tired of hearing me say, “It depends,” for questions like this, but I’m gonna have to say it again because I do think it depends.  Caffeine is subject to individual tolerance, just like dairy products and starches, white rice, things like that.  Certainly I don’t think that anyone benefits from drinking, you know, three to five-plus cups of coffee a day and drinking three or four Red Bulls.  That’s not gonna help anybody out, but a single cup of coffee, for example, or a couple of cups of green tea, at least according to the scientific literature, may have health benefit, but it really depends on how somebody responds and what their current circumstances are.  So, let’s just use a couple examples.  Let’s say somebody sleeps well, their energy levels are fine, they don’t have any problems with blood sugar regulation, no adrenal fatigue issues, they’re generally healthy, and they have a cup of coffee each morning.  Is that a problem?  I don’t think so.  I mean there’s no research that shows that that’s a problem really, and if they’re not suffering from it, then I don’t think it’s an issue.  On the other hand, take somebody who is sleeping very poorly, they crash in the afternoon, they have wild blood sugar fluctuations, they feel jittery and agitated, they crave sugar, they’re dealing with depression or anxiety or mood swings, or any number of psychological issues like that.  That person, even one cup of coffee could be a big problem.  It could really prevent them from getting the rest that they need to heal, prevent their adrenals from recovering; and in some cases, even green tea would be too stimulating for them, but they should be able to determine that by going completely caffeine-free for a period of time.  If I was their healthcare practitioner, that’s what I would recommend if we were doing an adrenal protocol.  We’d take them off caffeine completely, with the possible exception of something like kukicha, or twig tea, which is made from the branch of the green tea plant instead of the leaf, and it’s really, really, really low in caffeine.  It provides just a mind-clarifying kind of effect, but it’s rarely stimulating enough to make a difference, so I might allow that.  But if we take them completely off caffeine for a period of time and then they add it back in, they often find that when they get that kind of space from it, it becomes pretty obvious that it’s too much for them to tolerate.  So, it’s really an individual issue.  There are other circumstances to be considered.  Like green tea has shown some benefit, and caffeine in general has shown some benefits, for weight loss, but I’m hesitant to recommend it for weight loss because, in my experience, a lot of people are having difficulty with weight partly because of adrenal issues.  You know, their cortisol is too high or too low or it’s fluctuating inappropriately, and if those people do a caffeine stack for weight loss, it could actually worsen some of those underlying mechanisms.

Steve Wright:  OK, so what about the middle road?  What about the average Paleo person who is on the diet?  They’re doing their best to get some sleep, but they really love, you know, one to three cups of coffee in the morning.  Are they going to be all right on that, or should they take some time off and see what happens?

Chris Kresser:  Yeah, I think everybody benefits from taking some time off and seeing what happens, and that’s true with any other gray-area foods, and I talk about this in the PersonalPaleoCode.  You know, there are a number of foods that are just pretty much safe for most people, and those are what are included in the 30-day Reset, but then there are a bunch of foods that are gray area, which means that they are really subject to individual tolerance.  So, that could be dairy products, it could be starches and then white rice or soured buckwheat, could be caffeine, chocolate, nightshades, eggs, FODMAPs, a lot of the stuff we’ve talked about on the show, and I think nearly everybody would benefit from taking a period of time and going without caffeine.  Now, that can be difficult, of course, as anybody knows who is drinking a lot of caffeine and tries to stop, and I actually don’t recommend that you do it cold turkey because that can be problematic.  You would titrate off of it slowly to make it not as dramatic and difficult.  I don’t think someone who is dealing with potential adrenal issues should be drinking three cups of coffee a day.  One cup, you know, that’s arguable, and maybe if you stop it for a period of time and you add it back in and you really don’t notice that much of a difference, you can make an argument for continuing, but I think most people who are struggling with anything that could be construed as adrenal fatigue should stay away from coffee and should maybe stick with lower-caffeine green teas, green tea that is only steeped for a short period of time so it’s not as strong in caffeine as, you know, a green tea that was steeped for a longer period of time.  Or, if you’re gonna do coffee, maybe doing half decaf and half caffeinated or something like that.

Steve Wright:  OK.  Another thing I want to throw in there is Tim Ferriss, in his book The 4-Hour Body, likes to recommend taking green tea extract that has been decaffeinated, so if someone is looking to stack something for weight loss, that might be a potential avenue to look at.

Chris Kresser:  Um-hum.  Yeah, definitely, although part of the benefit theoretically is the caffeine for weight loss, but I think you’re right.  You get the benefit without the potential downside just by doing the green tea extract.  And there are a lot of other benefits with green tea extract, as well, beyond weight loss in terms of reducing oxidative damage and some other neat stuff.

Steve Wright:  All right, so green tea over coffee, and keep it before noon.

Chris Kresser:  Sounds good.

If you have this Copper-Zinc imbalance, your body could be starving for oxygen…

Steve Wright:  Let’s roll on.  This question is from Allison.  She would love to hear your thoughts about the copper-zinc balance and whether you’ve heard of pyroluria.  What sort of presentations do you see?

Chris Kresser:  Pyroluria.  I wish they would rename that.

Steve Wright:  Me too.

Chris Kresser:  It always sounds funny to say it.  So, let’s talk about this first because I think a lot of people haven’t heard of it, so I need to give a little background about the condition, and then we’ll come back to the copper-zinc ratio and how that relates to pyroluria.  And then we’ll talk about more specifics about copper-zinc imbalance and what to do about it if you’re suffering from it, and how to identify it in the first place.  So, pyroluria is a genetically determined chemical imbalance that involves a defect in hemoglobin synthesis, and hemoglobin is the protein, as I’m sure some of you know, that holds iron in the red blood cell and is responsible for delivering oxygen to the tissues.  So, every cell and tissue in the body needs oxygen and glucose to function properly, and if you’re not getting oxygen to the tissues, as is the case with anemia, nothing is gonna work right.  None of your cells are going to work right.  It’s one of the first things that I look at when I do a case review and I run a comprehensive blood panel on my patients is oxygen deliverability and blood sugar regulation because those two are what I call deal-breaker issues, meaning if they’re are out of whack, nothing else that we do is gonna be very effective until we get those two systems working properly, so it’s really important and this is why pyroluria can be a really challenging condition to experience and to work with.

Steve Wright:  Would I know that I had that from birth, or would I have to get some sort of genetic test?

Chris Kresser:  Well, you have to get a test.  I can’t remember the name.  I think it’s the mauve something or rather.  So, people who have this condition produce too much of a byproduct of hemoglobin synthesis called kryptopyrrole, and kryptopyrrole has no known function in the body, and it is largely excreted in the urine, so the test that you get tests for the levels of kryptopyrrole, and if it’s too high, then that’s a sign that you have pyroluria.  So, kryptopyrrole binds to vitamin B6 and zinc and makes them unavailable as co-factors in the enzymatic and metabolic processes that they participate in.  And then excess kryptopyrrole also leads to a deficiency of arachidonic acid, or AA, which is an important fatty acid in the tissues.  So, a lot of people with pyroluria will exhibit mild to moderate signs of B6 to zinc deficiency, and so that’s usually what happens.  You know, they go to the doctor and they might be experiencing poor stress control, nervousness, anxiety, mood swings, just a lot of psychological symptoms like feeling really tense, or episodic anger is one of the kind of classic signs, like explosive temper, poor short-term memory, and depression because they can’t create serotonin well.  Serotonin, of course, is a neurotransmitter that reduces anxiety and depression, and vitamin B6 is a rate-limiting factor; it’s an important factor in that last step of the synthesis of serotonin.  So, if you don’t have vitamin B6, you can’t make serotonin properly, and people who have pyroluria don’t have enough B6 usually.  So, let’s get back to the copper-zinc ratio and show how this relates to pyroluria.  So, the body has a pretty elaborate system for managing and regulating the amount of trace minerals like zinc, copper, iron, manganese, and chromium in the blood, and what happens is if blood levels of any of these trace minerals are depleted, then we have a system for absorbing them from the diet, and then they are transported from the blood into cells if the cellular levels are inadequate, or they’re excreted from the body if blood and cell levels are sufficient or overloaded.  That’s the way the system is supposed to work, but in various cases of either genetic diseases or diseases that have environmental causes, that system breaks down, so you get people either absorbing too much of a particular trace mineral more than they need, like with hemochromatosis, which we’ve talked about, or you get people that have deficiency of some of these key minerals, like zinc deficiency with pyroluria.  One of the most common and important imbalances that we see in clinical practice with trace minerals is excess copper and deficient zinc.  So, the ideal ratio between these two, if copper is in the numerator and zinc is in the denominator, would be 0.7 to 1, which means anywhere from 70% as much copper as zinc to even amounts of each.  And one of the ways that you can recognize this or when you might suspect this, and this will tie into a future question that we’re gonna talk about a little bit later in the show, is that copper and zinc are not only minerals, but they’re also regarded as neurotransmitters in the brain.  They have some of the functions of a neurotransmitter, so an imbalance in copper and zinc will lead to things like hyperactivity, ADHD, other kinds of behavioral disorders, and depression; and in fact, a lot of people who are labeled with autism and even paranoid schizophrenia, when they test their copper levels, they find out that they’re elevated.  Then high copper can cause severe PMS.  That’s another red flag for me where I’ll consider it.  It can cause estrogen intolerance, and it can cause skin issues, so people with excess copper have a high incidence of acne or eczema, psoriasis, just sensitive skin in general, sunburn, people who are really apt to get sunburned even if they’re only out for a short period of time, headaches, poor immune function.  Another characteristic sign is white spots under the fingernails, excess copper and deficient zinc, that can happen.  And then elevated copper is a special problem for people with low blood histamine levels and overmethylators, and that can lead to anxiety and even panic disorders and paranoia and, in severe cases, hallucinations.  So, as you can see, most of the effects are nervous system related, nervous and endocrine system, I would say, with particular impact on the brain and behavioral health.  So, those are the things to look for when you’re considering copper-zinc imbalance as a potential issue.

Get these tests done if you have nervousness, anxiety, or mood swings

Steve Wright:  It seems pretty serious, so how would I go about testing for it?

Chris Kresser:  Oh, yeah, it’s definitely serious.  I mean, there’s a syndrome called Wilson’s syndrome that’s a severe excess copper problem.  Actually you’ll see low copper in the blood, but you’ll see very high copper with a 24-hour urine test, and that can cause severe brain damage and difficulties.  I have a friend who had Wilson’s syndrome, and when she first figured out, or when people around her first figured out what was going on, she had lost the ability to speak, and when she gained the ability to speak again, her voice was very slow and deliberate, and it was difficult to understand her, and she’s made a lot of progress and is feeling a lot better and is getting back to normal, but it was a pretty scary thing, and she ended up at the Mayo Clinic.  So, yeah, this is definitely something to pay attention to.

Steve Wright:  Yeah, I’m glad she’s getting better.  You called it Wilson’s disease.  Is that something that can onset in anyone?

Chris Kresser:  Well, there’s a strong genetic predisposition for that, but we don’t fully understand, you know, what all the factors are.  In her case, there was probably a genetic predisposition plus an excess of copper in the diet or copper from other sources, which we’re gonna talk about here in a second.  But Wilson’s is different than just standard copper-zinc imbalance.  They’re not the same thing.  They don’t present in the same way, so I’m not suggesting that copper-zinc imbalance will lead to Wilson’s.  I was just pointing out, using Wilson’s as a way of explaining how serious excess copper can be.  These metals, the trace minerals are potentially lethal.  It’s the same with hemochromatosis, as we talked about before.  That can cause really, really serious problems, including death eventually, so not harmless, for sure.  So, testing for copper and zinc, I use blood tests, just serum testing of copper and zinc.  There is hair mineral analysis, urine testing, other forms of testing.  You know, to be honest, the jury, for me, is still out with hair mineral analysis.  I’ve seen some studies suggesting that it might be accurate in the case of certain nutrients especially, and then I’ve seen a lot of other research indicating that it’s not reliable.  If you look in the mainstream scientific literature, you know, it’s mostly dismissed as not being reliable.  If you search on the Internet, you’ll find lots of kind of random websites saying that it is, but being a little bit of a skeptic myself, I’m not yet convinced that it’s reliable, so I do serum copper and zinc testing and use the ratio above that I just mentioned of 0.7 to 1.

Steve Wright:  I’ve read a lot, or I’ve heard a lot, that zinc serum tests don’t represent the correct number and that you should do, like, a Zinc Tally taste test.

Chris Kresser:  Yeah, I’m not convinced about that either.  I mean if someone has some good, peer-reviewed, placebo-controlled research, if you do, Steve, send it to me.  I’d like to take a look at it, but most of that sort of stuff that I’ve read has been not in the peer-reviewed literature.  It’s just been on, you know, random websites and stuff, so I’m still waiting to see that evidence.

Steve Wright:  OK.

Chris Kresser:  Have you seen it?

Steve Wright:  It’s been a while since I’ve looked into this issue, but I swear it was like one doctor, and my guess is he didn’t publish in a peer-reviewed journal, but he published his own study about it.  So, I’ll try to dig it up and send it to you, but I do know from my own experience that I tried the Zinc Tally taste test, and Thorne Research makes one that you can buy, and I bought the solution, and I put myself through it and I didn’t taste anything.  And then I put several of my family members and friends through it just to see what would happen, and I would say 60% of them right away would, like, spit it out and say, “Ugh, this is gross.”  However, when I put it in my mouth, I was like, “Eh, this tastes like water,” and I supplemented with a lot of zinc over a period of six weeks or eight weeks, and I gradually got that flavor back to the point where it tasted pretty awful.  So, you know, that doesn’t make it right or wrong as far as tests go, but that’s my experience.

Chris Kresser:  Yeah, well, I’ve had patients who have used the Tally, a couple, and one who had no problem with it and the other who absolutely couldn’t handle it at all; it was just revolting immediately, and she was zinc deficient and he wasn’t, according to the blood tests.  So, there was a concordance there, but I’d be curious to see more evidence of how they correlate, those two ways of testing.

What to do — and not do — if your copper levels are high

Chris Kresser:  In any event, people who are eating–well, let me back up.  We’ll talk first about the main sources of copper because if you have excess copper, you’re gonna want to reduce your intake of copper from food, and you’re gonna want to reduce your exposure to copper in the environment.  So, copper is mostly found in vegetarian or plant proteins like nuts and beans and seeds and grains, and meats do contain copper, but they’re balanced by zinc, which competes for the absorption of copper, so a Paleo, Weston A. Price type of diet that’s high in animal protein, it’s unlikely you would develop a copper-zinc ratio just from eating that way because the zinc competes with absorption for copper in those foods.  Chocolate is high in copper, and actually, in some cases, when people are really craving chocolate, you often hear that they’re craving magnesium, and that may be the case, but they may also be craving copper.  Drinking water that is in copper pipes can have copper in it, so if you test high in copper and you’re living in a house with copper pipes, that may be something you want to look into.  There’s copper cookware, which I don’t recommend using.  Some dental materials have copper in them.  Certain vitamins have copper.  If you like multi’s, you want to check and make sure your multi doesn’t have it if you have excess copper.  Fungicides and pesticides have copper residue, and then IUDs and birth control pills have copper, as well.  So, those are the primary sources of copper in the environment and food, and then there are some things that deplete zinc levels, like stress, for example.  Any disturbance of homeostasis or oxidative stress will deplete zinc levels over time.  So, it’s important to manage your stress if you’re dealing with copper imbalance.  One of the first things I would do with patients like this is order a SpectraCell micronutrient analysis, which tests micronutrient levels within the white blood cell, and that can help determine if there are deficiencies of other micronutrients that help reduce copper buildup.  So, these are things like vitamin B1, B3, B6, folate, inositol, and choline, and those are all antagonistic to copper, and then there are some minerals that are antagonistic to copper, like zinc, of course, which we’ve been talking about, manganese, iron, sulfur, and molybdenum.  You want to be careful with the iron, though, of course, because if you are iron-loaded, you have too much iron, and you take iron to reduce copper, that may help solve one problem and cause another, or exacerbate another.  And then there are some studies I’ve seen that suggest that copper might be excreted by binding with glutathione, so yet another reason to maintain healthy glutathione levels; and glutathione levels are often depleted in cases of chronic illness and stress, so that’s another thing to pay attention to.  Then you want to improve the detox function of the liver and the skin.  You can do things like sweats and saunas.  And then, of course, you want to do a diet that is based on animal proteins and lower in the plant proteins that tend to be rich in copper, like the nuts and beans and seeds and grains, like I mentioned earlier.  So, those are the basic steps.

Steve Wright:  To summarize those, it’s basically look for any environmental triggers that are adding a lot of copper to your diet, cut out the high-copper foods, and then look to possibly supplement with any other micronutrient imbalances you might have?

Chris Kresser:  Exactly.  And on top of that, improving glutathione levels, improving the detox function of the liver, and improving adrenal function, and managing any form of stress, whether it’s dealing with inflammation or oxidative damage or psychological stress and adrenal stress.

Steve Wright:  OK, so let’s say that I find out that I have high copper and low zinc.  Do I start supplementing with zinc right away?

Chris Kresser:  It’s probably best to get some help from someone who has some experience dealing with this, because it can get a little bit complex, depending on the status of other micronutrients, and you know, I mentioned Wilson’s disease before.  That wouldn’t present with high serum copper.  It usually presents with low serum copper, so they’re not often confused that way, but depending on how you tested for elevated copper, it may be something that you want to rule out, Wilson’s.  But, in general, just following the steps that I outlined for a lot of people should be sufficient.  Zinc is definitely one of the things you would supplement with, especially if the zinc is deficient.  So, it’s important not just to test copper.  You would test copper and zinc at the same time, and if zinc is low, then you definitely would want to bring it back up.

Steve Wright:  OK, so to wrap it up, it’s something you should definitely get tested if you’re exhibiting any of the problems that Chris was mentioning, and I think we’re gonna move on to the next question, unless you have anything, Chris?

Chris Kresser:  No, I think that’s it.

Steve Wright:  OK, copper and zinc.  Got it done.

Is 5-HTP safer than SSRIs for anxiety and depression?

Steve Wright:  All right, this one’s from Breaking All Illusions.  “What do you think about the use of 5-HTP as a natural supplement for anxiety and depression?  Do you consider it safer or more effective than SSRIs?  And do you consider it safe/effective at all?  If so, how would you recommend using it?”

Chris Kresser:  OK, so 5-HTP is an intermediate in the conversion of tryptophan to serotonin, so tryptophan gets converted to 5-HTP, and then 5-HTP gets converted to serotonin.  As I’m sure many people know, some people who are depressed have issues with serotonin synthesis or metabolism, and that can cause depression, and in those cases, 5-HTP might be helpful.  There is some research that’s fairly promising, but I think the jury is still out on it.  But as I pointed out, I wrote an entire series on depression, ChrisKresser.com/depression.  Hopefully that will be updated soon because there’s a lot that I’ve learned since I wrote that.  It’s all still completely valid, but I want to add some information about the inflammatory cytokine model of depression, which I’m gonna talk about in a minute.  But in that series, I pointed out that not all depression is as simple as being a serotonin deficiency, and that is really just a convenient fiction that’s been manufactured by drug companies to sell more antidepressants.  Doctors in 2009 wrote 235 million prescriptions for antidepressants, which is just a mind-boggling number.  It’s a 14 billion dollar market for antidepressant drugs, so it’s a huge business, and the drug companies know that if they create a really simple model for depression, which is basically depression equals serotonin deficiency; therefore, if you take a drug that raises serotonin, that will cure and treat depression.  But the reality is a lot more complex than that, as anybody who works with depression knows or who has experienced it knows, and the drug trials on antidepressants, when you really look at them and you look at careful meta-analyses that have been performed by Kirsch and colleagues and others, you see that for mild to moderate depression and even fairly severe depression, antidepressants are often no more effective than placebo.  And a lot of the natural treatments, which we’re gonna talk about here in a second, are just as effective as antidepressants, with far fewer side effects.  So, 5-HTP may be one of those, but it doesn’t have the research behind it that some of these other natural therapies do.  So, if you’re gonna try 5-HTP, I would recommend starting with a pretty low dose, which would be maybe 20 mg in the morning, and it’s important to take it on an empty stomach.  And then you can continue to increase your dose every few days up to 100 mg, and I wouldn’t go above 100 mg.  Some people out there, some of the studies recommend 200 or 300 mg, but I don’t recommend that for a number of reasons.  So, somewhere between 20 and 100 mg.  If you take it before bed, it can sometimes help with sleep, so that’s another possibility, but I’ve found with patients that it’s more effective for depression if you take it in the morning.  But that’s not the first thing I would try with depression, and in fact, these days I’m looking at it much more as an inflammatory condition, which again I’ll come back to in a moment.  I wanna talk a little bit about some of the natural treatments that have been proven to be effective.  Psychotherapy is, of course, one of them, and it’s often left out when we talk about natural treatments for depression because I think a lot of times we’re thinking of, you know, nutrients or herbs or pills or things that we can take, but psychotherapy, particularly cognitive behavioral therapy, which is a specific type of psychotherapy, has compared favorably with antidepressant drugs in a lot of trials, especially in the short term, even when the depression is severe, and over the long term, it actually appears to be superior to medications.  And then some studies have looked at medication plus psychotherapy versus just medication alone, and of course, that’s almost always more effective, so that’s something to certainly consider, and I would definitely recommend it as part of a protocol for depression in any case.

Steve Wright:  When you say medication, are you talking about SSRIs and SNRIs?

Chris Kresser:  I’m talking, yeah, about both, but primarily SSRIs.  They’re the bigger drug class by far still even though there has been more of a trend to SNRIs lately, but a lot of the research that has been done in the comparisons has been more with SSRIs.  Exercise is at least as effective as antidepressants in treating depression, according to the research literature, and the good news about exercise is the only side effects of exercise are usually other health benefits and reducing your risk for a number of other diseases.  Light therapy, and there was a study in 2005 in The American Journal of Psychiatry that found that it was just as effective as antidepressants.  One of the arguments about that study was that it could have been placebo, and that’s true, but if that’s the case, you know, who cares?  If there’s no negative impact other than spending the 75 bucks or whatever on the machine, actually maybe we can put that in the show notes.  There’s a machine that I recommend on Amazon; I think it’s about 75 bucks.  You know, the only thing you might lose is a little bit of time in the morning and a little bit of money to buy the machine, but there really aren’t any significant side effects associated with it.  St. John’s wort, which I’m sure a number of people have heard of, it’s probably the most popular treatment for depression in Europe.  It’s just as effective as antidepressants in clinical studies, but it has 10 times fewer side effects.  One important thing to keep in kind with St. John’s wort is that it takes several weeks often for the effect to come on fully, so it’s not something that you just start taking and you feel the benefit right away.  It takes about three to four weeks to really get the effect.  Another thing I’ll mention is not to mix these treatments together with drugs.  I mean, exercise and psychotherapy, of course, is fine, and even light therapy, but I would not recommend combining St. John’s wort with antidepressants without supervision.  That can be dangerous.  And the same with 5-HTP and any other nutrient-based or herbal-based remedy.  Acupuncture has been shown to be pretty effective for depression.  In fact, there was a Cochrane review, Cochrane being one of the prestigious group that does meta-analyses of available research on a particular subject.  They found, “There is no evidence that medication was better than acupuncture in reducing the severity of depression.”  And again, just like exercise, acupuncture has very few side effects except feeling better in other ways.  So, those are a number of options for someone who is dealing with depression and doesn’t want to take the drugs or eventually wants to get off the drugs.  Again, it’s really, really important if you are taking a medication for depression not to stop taking it abruptly and to do it under the supervision of someone who is experienced in getting people off SSRIs and other forms of antidepressants, because stopping them cold turkey can really wreak havoc with your brain chemistry, and the problems with suicide that are associated with antidepressants most often occur when people are just starting the medication or just coming off of it.  So, it’s not something to play around with, and it’s really important to find someone who has experience getting people off of those drugs, if you choose to come off of it.

Why antidepressants could permanently alter your brain chemistry… in a bad way

Steve Wright:  Is there also a long-term consequence of staying on the drugs for a number of years?

Chris Kresser:  I think there is, and I wrote about this in my series.  There’s a lot of pretty disturbing research that shows that SSRIs can cause permanent changes in brain chemistry, and it’s difficult to talk about this because, you know, a lot of people are on antidepressants, and some people are helped by them.  Even though the research is pretty equivocal, you have to consider that research is about averages.  You know, when you do a study and statistically at the end of the study there was no difference between placebo and the intervention, in this case an antidepressant, it doesn’t mean that there weren’t some people that benefited from the antidepressant in the study.  It just means that on average, when you take all the results together, there was no statistically significant difference between the two treatments.  I know people that have taken antidepressants and that have benefited from them, and of course, I know people that haven’t, so I’m not saying they never work.  I’m just saying that statistically speaking, from a research perspective, they are not better than other treatments, in general, except in the cases of very severe depression.  So, I’m not making any judgements of anyone who chooses to take antidepressants, and it’s a little bit scary to tell someone that a drug that they’re taking can cause permanent changes in brain chemistry, but I also feel it’s important to get the word out about this so that people think really carefully about going on these drugs before they choose to do so.  So, the research shows essentially that those changes that are made in the brain can basically predispose you to depression more for the rest of your life.  So, they create changes in the brain that make it more likely that you’ll need to be on an antidepressant or have some other kind of treatment for depression indefinitely, and that’s what scares me the most about these drugs, and unfortunately that is not, you know, very few patients are told that before they go on a drug.  I think very few doctors even know about that research, but I wrote about it pretty extensively in the Depression Series.  There are a lot of references there, and there are some great books that I linked to as well, where you can read all about that research if you’re interested in it.

The surprising cause of depression (and no, it’s not low serotonin)

Chris Kresser:  So, before we finish up with this question, I want to talk a little bit about a newer perspective on depression that we discussed in an earlier show.  We talked about it in the gut-brain axis program, and this is known as the inflammatory cytokine model of depression, and the theory essentially is that inflammation, which often originates from the gut, produces inflammatory cytokines, and these cytokines travel through the blood, they cross the blood-brain barrier, and then they suppress activity in the frontal cortex, and then that, of course, causes depression, the frontal cortex being responsible for some of the higher brain function.  So, one of the most important things you can do if you’re dealing with depression, if you haven’t already done this, is eat an anti-inflammatory diet and fix your gut.  Anti-inflammatory diet being a Paleo-ish diet, a Personal Paleo Code-ish type of diet, and then all of the steps that we have discussed lots of different times towards healing your gut, and I think that those are kind of the first steps that should be done when somebody is dealing with depression, and then if you eat that diet and you fix the gut and deal with any other potential sources of inflammation like a chronic infection; for example, a viral infection or a bacterial infection that may not be in the gut but outside of the gut.  So, if you deal with all of those sources of inflammation and you’re still experiencing depression, that’s when I would turn to some of these other natural remedies.

Steve Wright:  So, when you start fixing the gut, it’s not necessarily advisable to look towards trying to replace any neurotransmitter losses in the dopamine or serotonin areas?

Chris Kresser:  That’s kind of the last step, maybe.  You know, it’s like fix the gut, reduce inflammation, any other sources of inflammation, then consider some of these other natural treatments that we just talked about that would indirectly regulate brain chemistry:  psychotherapy, acupuncture, St. John’s wort, light therapy, exercise, possibly 5-HTP.  And then there are some products that I might use that improve serotonin or dopamine or acetylcholine or GABA synthesis and metabolism, but even then, they’re a milder, safer, and more natural approach than SSRIs or SNRIs.  I consider those drugs to be a last resort.

Are chocolate cravings related to magnesium deficiency?

Steve Wright:  All right.  Well, let’s roll on here.  You mentioned it earlier in the show, but chocolate cravings — both Martin and Evan were asking about magnesium, and so here’s Evan’s question:  “What are your thoughts about chocolate cravings being related to magnesium deficiency?  As a raw vegan, I didn’t touch chocolate for two years probably, and now I can’t get enough of it.  I’m way beyond your recommendation of a piece about the size of a silver dollar.  A full bar or more is reasonable,” and I think that’s on a daily basis, so he would like to know more about the topic of magnesium, chocolate, and magnesium oil applied topically.

Chris Kresser:  Yeah, OK, so one of the easiest ways to figure that out is just start doing some fairly high-dose magnesium glycinate or malate supplementation.  So, you know, take 600 mg a day for three or four weeks, and if the craving for chocolate disappears, then you could suspect that it had something to do with magnesium deficiency.  But if you’re still eating that full bar of chocolate every day after a month of that kind of magnesium supplementation, then I have a feeling that it has something more to do with something else in the chocolate, maybe the sugar or the caffeine or, you know, some other substance or combination of substances.  Perhaps copper.  I mean, we mentioned that earlier, although copper deficiency is fairly rare in people who are eating a — I just don’t see copper deficiency very often, but you can check for it.  Transdermal magnesium oil — it’s another one that I’m a little bit uncertain about, and when you look in the scientific literature, there are no studies other than studies that are done by companies that sell magnesium oil that show that it’s an effective way of delivering magnesium.  However, I have patients who have not experienced any benefit from taking even the chelated forms of magnesium, like glycinate and malate, but have experienced a fairly dramatic change after using transdermal magnesium oil.  So, I don’t see how it could do any harm, and if you try it and it helps improve your symptoms, then maybe it does work.  And, you know, lack of proof is not necessarily proof against, so it’s possible that we just don’t have the research on this yet.  I remember trying it a while back, and I didn’t really notice that much of a difference, but I don’t think that I was significantly magnesium deficient either, so I’m probably not the best test case.

Steve Wright:  Were you eating a bar of chocolate a day?

Chris Kresser:  No, I wasn’t.  You know, I’m irritating to some people in my discipline around those things.  It’s not even discipline.  I just don’t crave it.  I have sometimes a little piece that size after a meal, and that’s all I really need to satisfy the craving, so I’m no hero of discipline.  I just, for whatever reason, don’t have that kind of relationship with it.

Steve Wright:  It’s interesting.  So, with the magnesium supplementation, would you recommend that before bed?  Is there a certain time there?

Chris Kresser:  Yeah, two times a day usually, so in the morning and then in the evening.  If people are using it for constipation and they want to promote a healthy bowel movement in the morning, you could take two times the dose in the evening and maybe a smaller dose in the morning.  Or, you could even take it all in the evening, maybe with dinner as a good approach.  If you’re using it for muscle pain, muscle fatigue, and just general health, it doesn’t really matter as much when you take it.

Steve Wright:  OK, and with magnesium glycinate, just to remind everyone that there is gonna be an upper level for them at which they’ll start to cause loose stools probably, right?

Chris Kresser:  Yeah, it’s a higher upper level than with oxide or citrate, which is one of the reasons I recommend it, but one approach is dosing intolerance, just like you do with vitamin C.  So, you can keep increasing the dose until you hit the loose stools, and then you can go back a little bit, but I find that for most people, unless they’re severely magnesium deficient, a dose of somewhere between 400 and 600 mg a day will be sufficient.

Steve Wright:  OK.

How to get your Vitamin A and D ratio within healthy ranges

Chris Kresser:  So, I think we have time for one more short one.  How about the vitamin A-D ratio question?

Steve Wright:  Sure.  This comes from Michel, and he or she, I’m sorry, is asking about the ideal ratio between vitamin A and vitamin D.  Should one be higher than the other, and by how much?  They’re worried that vitamin D is being hyped so much that people are going to tend to consume too D and not enough A.

Chris Kresser:  Yeah, I think that’s a valid concern, and one of the reasons that I like the Weston A. Price Foundation approach is they put a lot of emphasis on the importance of fat-soluble vitamins, and that’s not something that’s really discussed in the Paleo world very often.  Fat-soluble vitamins — we’re talking about A, D, K2, and E — they play so many crucial roles in health, and they’re difficult to obtain from food in most cases, particularly K2 and A, you know, and D, if you’re not eating seafood.  But there has been a lot of hype about vitamin D, and then there’s been a lot of hype in the other direction about the danger of vitamin A, particularly for pregnant women or women who are trying to get pregnant; they’re really freaked out, unfortunately, about vitamin A because it’s a crucial nutrient for healthy development of the fetus, which I talk about in The Healthy Baby Code.  The important thing to understand about these fat-soluble vitamins is they exist in a synergistic relationship, and when you have problems with toxicity of one of them, it’s almost always contributed to by, or even only possible in the face of, a deficiency of one of the others.  So, for example, all of the problems with vitamin A toxicity that people are afraid of are only really possible in the presence of concurrent vitamin D deficiency, and Chris Masterjohn has done some great work on this.  I think there’s an article on the Weston A. Price website that he wrote called — I think if you search for vitamin A / osteoporosis in the search engine on their site, you’ll find it, but he talks about a study, and I mention this in The Health Baby Code, too, where when people are supplementing with vitamin D or they have adequate vitamin D levels, the toxicity threshold for vitamin A goes up to like 200,000 IU a day, which is an absurd amount of vitamin A.  Like to put that in perspective, 3 ounces of liver have about 27,000 IU of vitamin A, so you’d have to eat 30 ounces of liver every day to exceed the toxicity threshold, and I don’t know anybody who is eating 30 ounces of liver a day, so that’s just not going to happen.  And likewise, vitamin D toxicity will happen at a lower level if vitamin A and vitamin K2 are deficient, because vitamin A and K2 protect against vitamin D toxicity.  So, as I’ve said on the show before, I think an ideal range for vitamin D is somewhere between 35 ng/mL and maybe 60 or 65 ng/mL.  I don’t see any reason to go higher than that.  I don’t agree with, you know, some of the people pushing vitamin D levels above 100 ng/mL.  Studies show that you’re at risk for hypercalcemia because vitamin D regulates calcium metabolism, so you start to get issues with kidney stones and stiffer arteries, which, of course, increases the risk of cardiovascular disease.  Whereas, vitamin K2, which also has an effect on calcium metabolism, it makes sure that the calcium ends up in the bones and teeth and the hard tissues, and not in the soft tissues.  So, the key thing here is balance and making sure that you have enough of these fat-soluble vitamins.  Vitamin A is only really found in significant amounts in organ meats and cod liver oil.  It’s found to a lesser extent in grass-fed dairy, and that’s why I’m always talking about cod liver oil, especially for people who are on a strict Paleo diet and who aren’t eating grass-fed dairy or organ meats, like liver.  So, getting back to the question, which I’ve kind of gone off on a tangent from, there’s not a lot of research on the ideal ratio between vitamin A and vitamin D, but there was a recent paper by Dr. Holick that suggested that ratios between 4 and 8 times as much vitamin A as D would be ideal, and then the lead author on that paper, Dr. Linda Linday, had used cod liver oil with a ratio in that range to successfully protect against upper respiratory infections, and then there was some other research showing that that range of ratios is ideal in chickens.  I don’t know how applicable that is to humans, but if you look at the amount of vitamin A and D in foods like cod liver oil, then it’s a roughly similar ratio, and that’s, I think, a good ratio to shoot for, and if you eat liver, 2 to 3 ounces of liver once or twice a week, or you’re taking cod liver oil on a daily basis, and then you’re getting exposure to sunlight and maybe taking some supplemental D in the winter, then that’s probably where you’ll end up.  Vitamin K2 you can get from butter oil or ghee and smaller amounts from all grass-fed dairy.  Cheese is actually a particularly high source of vitamin K2, hard cheeses, and goose liver, which is I don’t think a very commonly eaten food, which again, if you’re on a Paleo diet and you’re not eating dairy and you’re not eating goose liver or natto, it’s probably a good idea to supplement with K2.

Steve Wright:  I usually eat natto and goose liver every night.

Chris Kresser:  I bet.  Natto is one of the nastiest things I’ve ever tasted.  Have you tried it?

Steve Wright:  No.  It’s on my list for 2012 to explore.

Chris Kresser:  Oh, God!  Yeah, it’s wrong.  But it’s one of those things where people either like it or absolutely can’t stand it, and that’s kind of what liver is, I think, too.  You know, either people were raised on it and they have a taste for it, or they weren’t and they can’t stand it.

Steve Wright:  Yeah, I think there’s a lot of things you can do to liver to make it taste pretty good.  I started off being a little squeamish with it, and now I actually enjoy it.

Chris Kresser:  Incidentally, I just published an article today, I mean, you won’t hear this podcast for a little while longer, so on Friday, the 6th, about why you should eat more cholesterol, and the article is about choline and the importance of choline, but at the end of the article there are several recipes for liver from some great blogs.  So, check that out if you want to get some more liver in your diet and you’re wondering about some ways to make it more palatable.  There are some good recipes there on that blog post.

Steve Wright:  So, the biggest takeaway of this A-D conversation is that if you’re just taking a D3 pill, you need to look at adding some liver or some cod liver oil to your diet?

Chris Kresser:  Yep, that’s it, and K2 also, if you’re not doing that.

Steve Wright:  All right.  Well, I think that brings us to the end here.

Chris Kresser:  Yeah, great show!

Steve Wright:  Yeah, this was good.  We dived into a lot of topics I’ve never even heard about.

Chris Kresser:  Cool.

Steve Wright:  OK, so if you’re confused about what to eat, check out the PersonalPaleoCode.  It’s a 3-step program designed to help you discover your own ideal idea and create highly customized meal plans with a few clicks of a button.  Visit PersonalPaleoCode.com to learn more.  And if you’re trying to get pregnant or are already pregnant or nursing, don’t miss 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.

Chris and I would like to thank you for sending in your questions, and invite you to send in more questions at ChrisKresser.com using the podcast submission link.  If you enjoyed listening to the show today, head over to iTunes and leave us a review.

For decades now, the general American population has been neurotically avoiding cholesterol-rich foods for fear of developing heart disease, thanks to the promulgation of the unfortunate Diet-Heart hypothesis. (1)

Those of us that follow a paleo diet are well aware by now that dietary cholesterol does not significantly affect cholesterol levels in the blood or risk for heart disease, and that there is no reason to avoid whole foods with naturally high levels of cholesterol.

However, beyond just ‘not avoiding’ high cholesterol foods, there is a significant reason for us to make a special effort to include many high cholesterol foods in our diet.

The reason? The much under-appreciated B-vitamin called choline, found primarily in cholesterol-rich foods.

If you haven’t heard of choline, or don’t know much about this vital nutrient, you’re not alone. Choline has only been ‘officially’ recognized as an essential nutrient since 1998, when the Food and Nutrition Board of the Institute of Medicine established an Adequate Intake (AI) level of 425 mg per day for women and 550 mg per day for men. (2) Even though it has been deemed a nutrient vital for human health, only 10% of Americans are meeting the conservative AI levels established by the IOM.

If you eat a strict paleo diet, you may be closer to meeting your choline needs than the average American, but only if you are regularly including choline rich foods in your diet. The best whole food sources of dietary choline are egg yolks and liver, which are often avoided by many Americans due to unfounded fear of dietary fat and cholesterol. However, these high cholesterol foods are at the top the choline-rich foods list, followed (albeit distantly) by beef, cod, brussels sprouts, and broccoli. (3)

Why is choline such an important nutrient to consider in one’s diet?

Choline has a variety of functions in the body, including the synthesis of the neurotransmitter acetylcholine, cell-membrane signaling, lipid transport, and methylgroup metabolism. (4) In addition, it is an essential component of the many phospholipids that make up cell membranes, regulates several metabolic pathways, and aids detoxification in the body. During pregnancy, low choline intake is significantly associated with a higher risk of neural tube defects in the newborn.

Choline deficiency over time can have serious implications for our health. Symptoms of choline deficiency include fatigue, insomnia, poor kidney function, memory problems, and nerve-muscle imbalances. Extreme dietary deficiency of choline can result in liver dysfunction, cardiovascular disease, impaired growth, abnormalities in bone formation, lack of red blood cell formation, infertility, kidney failure, anemia, and high blood pressure. Incredibly, choline deficiency is the only nutrient deficiency shown to induce the development of spontaneous carcinoma. (5)

Chris Masterjohn has written extensively about choline deficiency and its relationship to fatty liver disease which affects as many as 100 million Americans and is often attributed to excess alcohol and sugar consumption by conventional practitioners. After a review of the literature, Masterjohn concludes that choline deficiency plays a role in virtually every type of diet-induced fatty liver model, and that adequate dietary choline is essential for proper liver function. He also suggests that high consumption of dietary fat, including saturated fats, increases the amount of choline required to prevent the accumulation of fat in the liver. (6)

This means that if you’re eating a higher fat diet, it is even more crucial that you include a variety of choline rich foods in your diet.

Another important factor to consider is that while humans are able to produce some level of endogenous choline, some people have a common gene variation that further increases the amount of choline they must consume to satisfy their body’s requirements. (7) These particular people are more susceptible to choline deficiency, and must be especially vigilant about including choline rich food in their diets.

As choline is so important, you may be wondering what the best food sources are in order to improve your intake. There are many natural, whole foods that are excellent sources of bioavailable choline, with the best sources being beef liver, poultry liver, and whole eggs. (8) These foods are not only high in choline, but are also very high in many different vitamins and minerals such as as vitamin A, arachidonic acid, DHA, and the B vitamins. (9)

We already know liver is an amazing superfood. Liver from pastured animals is a great source of trace elements such as copper, zinc and chromium, plus highly bioavailable folate and iron. (10)

Liver is also the most potent source of dietary choline that we know of.

For example, a three ounce serving of pan-fried beef liver has over 400 mg of choline in it, compared to less than 80 mg in the same amount of cooked ground beef. (11) While you don’t need to consume beef liver on a daily basis to reap the benefits of this superfood, it should be clear that including pastured liver and other organ meats as part of a nutritionally complete diet is one of the best ways to improve your health and prevent the many types of chronic disease caused by nutrient deficiencies.

If you’re not used to including lots of liver and whole eggs in your regular meal plan, give a few of the following recipes a try. It’s never too late to start incorporating more choline into your diet!

Liver recipes: get your choline!

• http://cavegirleats.com/2011/09/09/baked-liver-pate-yum-seriously-seriously
• http://balancedbites.com/2011/05/easy-recipe-chicken-liver-pate.html
• http://paleodietlifestyle.com/simple-and-delicious-liver-pate-recipes/
• http://www.foodnetwork.com/recipes/ina-garten/chopped-liver-recipe/index.html
• http://www.foodrenegade.com/egg-drop-soup/
• http://nomnompaleo.com/post/1983505174/easy-paleo-frittata
• http://www.theclothesmakethegirl.com/2011/01/17/dont-be-lily-livered-aromatic-chickenlivers/
• http://www.theclothesmakethegirl.com/2010/05/17/scotch-eggs-a-k-a-protein-pellets/
• http://www.primal-palate.com/2011/01/root-vegetable-hash-with-poached-egg.html

We’ve talked a lot about the “gut-brain” axis.  But did you know there’s also a “gut-skin” axis?  And did you know that researchers have been aware of this connection for more than 100 years?  Of course, this early work was forgotten for about 90 years, and it has only received increasing attention in the last decade.  It’s an exciting area of study, and it gives us new strategies for naturally treating skin conditions like acne (vulgaris and rosacea), psoriasis, eczema, dermatitis and others.

And in this episode of Revolution Health Radio, we cover:

2:24  Does the Gut-Brain-Skin Axis hold the secret to naturally get rid of acne?
8:23  The latest study validating 100 year-old research connecting stress, leaky gut, and acne
12:20  Why these ancient gut remedies also treat skin conditions
17:59  Could leaky gut be the hidden cause of acne?
20:55  How to break the vicious constipation-acne cycle
26:00  Why rush-hour traffic can cause low stomach acid, gas, and bloating
29:40  “The first place I look when someone comes to my practice with skin conditions”
34:48  The specific Gut Healing Protocol to naturally eliminate skin problems… for good
40:00  What foods to eat – and not eat – to get rid of migraines (and clear your skin)
44:12  The telltale signs you have low stomach acid… and what to do about it

Links We Discuss

• The Gut-Brain-Skin Axis – Back to the Future? (Full Text Study)
• The HCL Challenge Instructions

First, a confession. I’m a foodie. I enjoy shopping at farmer’s markets, buying meat and dairy directly from local farmers, creating new recipes, and cooking and preparing food. I’ve worked as a chef’s apprentice (way back in my vegan macrobiotic days – if you can believe that!), I pay close attention to where my food comes from, and I know my way around the kitchen.

In the early days of Paleo, it seemed to me that the few cookbooks or Paleo food resources that were available were written by folks that were well-versed in Paleo, but not particularly interested in or experienced with food preparation. An average Paleo recipe might have been Grilled Chicken Breast with Steamed Broccoli.

Now, there’s nothing wrong with eating that way. And in fact, eating simply prepared meals is a very good idea if you’re trying to lose weight (I’ll discuss this more in the future). But for those of us that don’t have weight problems, and have an interest in food, those early Paleo cookbooks just didn’t cut it.

Fortunately, things have changed in the Paleo world. As the Paleo diet has grown in popularity, the number of “gourmet” Paleo cookbooks and recipe sites focused has increased dramatically.

I am often asked which of these I recommend, so I thought I’d write a post listing my current favorites. Originally I planned to do a more comprehensive list, but then I decided to just give you my top two “go-to” sites. This is a subjective list and reflects my personal preferences more than anything else. There are a lot of great cookbooks and sites that aren’t included below that are worth checking out, but I wanted to keep this list focused on “gourmet Paleo”.

So, without further ado…

Nom Nom Paleo

I only recently learned about this fantastic site. If you’re a foodie and into Paleo, I’m sure you already know about it. If not, you need to go over there right now and sign up for her email list or RSS updates or follow her on Facebook.

Every day – or nearly every day – Michelle does a Paleo Eats post where she describes her meals and takes (gorgeous) pictures of them. She also often links to great resources she uses in her meal preparation, like kitchen tools, spice blends, pantry items and cookbooks.

She has a TON of free recipes on her site, and they’re listed in her recipe index here. She doesn’t have a cookbook yet, but in one of her recent posts there was some speculation in the comments section that one might be coming because she’s been taking a lot of pictures of food lately! I’ll be the first in line.

Here are a few of my favorites:

• Bacon and Guacamole Sammies
• Slow Cooker Thai Yellow Curry With Grass Fed Beef Brisket
• Damn Fine Chicken
• Pork and Spinach Stuffed Kabocha Squash

Health-Bent

Health-bent is another great “gourmet” Paleo recipe site run by my friends Brandon and Megan Keatley. I particularly love Health-Bent because their approach to food is closer to my own, in that they include dairy on occasion and they’re not rigid or dogmatic.

You will never get bored with Health-Bent recipes. They run the gamut from homestyle Southern food to global ethnic cuisine. And for those of you with a sweet tooth, Health-Bent will quickly become your favorite source for dessert recipes.

They don’t have a cookbook, and I’m not sure if they’re planning one, but you can sign up for their RSS feed or follow them on Facebook.

Here are a few of my favorite Health-Bent recipes:

• Thanksgiving Stuffing Hushpuppies
• Pulled Pork Spareribs with Coffee-Molasses Barbecue Sauce
• Braised Short Ribs with Figs
• Chorizo Mini-Meatloaves
• Paleo Coconut Macaroons

Runner-ups

So those are my two favorites. Here are a few others you should check out:

• Paleo Comfort Foods. This cookbook just came out recently, and it’s another that takes a more gourmet Paleo approach. I highly recommend picking up a copy of the book, and checking out their website.
• Everyday Paleo. Another great resource for Paleo foodies. Buy her book and check out her website.
• Well Fed. This is Melissa Joulwan’s new book. I haven’t seen the full book, but she has a free 30-page PDF sampler available on her site, and it looks amazing.

A couple more things before I finish up. Another option – aside from Paleo cookbooks – for those a little more experienced with food is to adapt recipes from non-Paleo sources. My favorite by far for this is the Cook’s Illustrated series of cookbooks. Cooks Illustrated takes a scientific approach to cooking. They try each recipe several times (sometimes more than 50!) with different variations in the process of perfecting it; then they describe what worked and didn’t work (and why) in the intro to the recipe. It’s a science-and-food-lover’s dream.

A lot of the original recipes in the Personal Paleo Code Meal Plan Generator were created this way. But we also have recipes from Nom Nom Paleo, Health-Bent, Everyday Paleo and several other fantastic Paleo recipe sources. In fact, we have more than 450 recipes now that are categorized according to recipe type. But the best part about the Meal Plan Generator is the ability to create customized meal plans that contain only the ingredients you want. Head over to the Personal Paleo Code site to check it out.

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

Since cold and flu season is now upon us (at least in the U.S.), I figured I’d take the opportunity to share my favorite tips for natural prevention and treatment.

Prevention

• A nutrient-dense, toxin-free diet: avoid the foods that tend to weaken the immune system, such as sugar, unprepared grains, industrial seed oils and processed and refined foods.
• Fermented cod liver oil/butter oil blend (FCLO/BO): if there’s only one superfood/supplement you take through the winter, this should be it. It’s rich with fat-soluble vitamins that regulate and support the immune system, and fatty acids like EPA and DHA that reduce inflammation. It also seems to have some kind of synergistic quality above and beyond the individual nutrients it contains that powerfully boosts immunity. I rarely get colds and flus when I’m taking my FCLO/BO. I prefer the Blue Ice brand available at Green Pasture. Dosage: 1 tsp/d or 2 caps per day.
• Liver. Liver is nature’s multivitamin. It’s the most nutrient-dense food on the planet, as I explained here. I recommend eating 3 ounces a week if you’re taking FCLO/BO.
• Bone broth. Grandma knew best! Homemade bone broth is rich with easily absorbable minerals such as magnesium, phosphorus, sulfur, and trace minerals difficult to obtain elsewhere. Check out the Weston A. Price article “Broth is Beautiful” for recipes and more information.
• Fermented foods and/or probiotics: 70-80% of our immune system is in our gut. If you have intestinal dysbiosis or poor gut flora, you’ll be more susceptible to viral and bacterial infections (and colds and flus).
• Vitamin C: I don’t supplement with vitamin C at all times during the year, but when cold and flu season rolls around, I’ll often take 1 g/d as a precaution.
• Vitamin D. Vitamin D plays a powerful immunoregulatory role. For most people, the FCLO/BO blend should be enough to maintain adequate vitamin D levels. However, some people require higher doses of vitamin D to keep their 25D levels in the desired range of 35-60 ng/mL. This is especially true of those with obesity or inflammation, because these conditions impair the conversion of sunlight to vitamin D. Dosage: 2,000 – 4,000 IU/d depending on beginning level and amount of FCLO/BO you’re taking.
• Jade Windscreen Formula. Jade Windscreen (or Yu Ping Feng San in Pinyin Chinese) is an immune system tonic made up of botanicals that enhance the immune system and have anti-viral and anti-microbial properties. The traditional formula contains Astragalus, Actractylodes and Ledebouriella, but modern preparations also add cinnamon, siler root, Chinese yam rhizome, and white peony root. You can often buy Jade Windscreen at a health food store or natural pharmacy. You can also buy it online. I like the Kan Herbs tincture. Dosage: 10-20 drops 2-3x/daily (check with your medical provider if you are pregnant or nursing or have an autoimmune condition)
• Sleep and rest. Getting adequate sleep and rest is perhaps the most important thing you can do to optimize your immune function. Just a few nights of not sleeping well can elevate inflammatory markers and reduce the protective capability of your immune system. That’s why it’s a good idea to go to bed earlier, sleep longer and rest more in the winter season.

Treatment

Sometimes despite our best efforts, a virus slips through our defenses and our immune system is called into action. Here are a few things in addition to the above that you can to do fight off the cold or flu and shorten its lifespan.

• More FCLO/BO: double or even triple your dose to get more immune-boosting fat-soluble vitamins into your system.
• Ginger honey-lemon tea with optional additions: ginger has anti-microbial and can help with nasea and G.I. upset that comes with certain strains of flu. Lemon is a good natural source of vitamin C, and has a soothing quality on a sore throat – especially when combined with honey. Honey is a time-honored cough remedy, and recent research suggests that it may be an effective cough suppressant. (Important note: never give honey to kids under 1-year of age.) Optional additions to this tea could include fresh garlic (anti-microbial), a pinch of cayenne pepper (to help break up mucous) and other warming herbs like cinnamon and clove.
• Sweat: in Chinese medicine, sweating is recommended at the early stages of a cold. The best way to do this is to take a very hot bath. I also recommend adding herbs and essential oils that promote sweating, such as wintergreen, eucalyptus, rosemary and thyme. Dr. Singha’s Mustard Bath is a powder containing these ingredients that you can add to your bath. It’s available at Whole Foods and other health food stores, and also online.
• Increase probiotic intake. I find beet kvaas and kombucha to be particularly helpful at the early stages of a cold.
• Rest, rest, rest. Again, there’s no better remedy for a cold or flu than rest.
• Zinc. Research suggests that zinc can reduce the duration and severity of a cold – but only if it’s started early on.

Now I’d like to hear from you? What are your favorite natural remedies to prevent and treat colds and flus? What do you do during cold and flu season to protect yourself?

In this final article in the series on Low T3 Syndrome, we’ll discuss whether thyroid hormone replacement therapy is an appropriate treatment in these cases.

Unfortunately, there are few studies that have examined this question specifically, and even fewer that have explored the question of whether T4 or T3 (and which type of each) would be the best choice.

As a clinician, my primary concern is always primum non nocere, or “first, do no harm.” From this perspective it’s important to recognize that the changes seen in Low T3 Syndrome may represent a restorative physiological adaptation by the body to chronic illness. In other words, T3 levels are low because the body is attempting to conserve energy and resources to better cope with the challenges it is facing. Increasing thyroid hormone levels in this situation could conceivably have adverse effects.

For example, the changes observed in the thyroid axis in acute illness are similar to those observed in fasting, which can be interpreted as an attempt to reduce energy expenditure and protein wasting. (1) Giving fasting subjects thyroid hormone results in increased catabolism (breakdown). (2)

In cases of chronic illness, however, it is less clear what effect thyroid hormone replacement has. The few studies that have been done produced mixed results. (3)

Some studies show that treatment causes harm, others show no change, and still others show an improvement. After reviewing the literature on this, I’ve come to the following tentative conclusions:

• T4 is rarely, if ever, effective in Low T3 Syndrome and may even cause harm. This is probably due to the decreased conversion of T4 to T3 that is seen in chronic illness.
• T3 replacement has been shown to be consistently beneficial only in cardiac patients who’ve recently had surgery, heart failure or a transplant.

That said, I’ve heard anecdotal reports of improvement from people who have taken replacement T3 hormone for a condition called “Wilson’s Syndrome” (which does not exist in the scientific literature or according to any mainstream medical organizations). Wilson’s Syndrome refers to low basal body temperature and other nonspecific symptoms occurring in the presence of normal thyroid hormones.

I’ll be the first to admit that “lack of evidence is not evidence against”, and as I mentioned earlier, there’s not a lot of research on the effectiveness of T4 and T3 replacement therapy in Low T3 Syndrome. It may be that as we look into this further, we’ll discover a role for thyroid hormone replacement in these conditions.

That said, I think caution is warranted. Taking T3 when you don’t need it is potentially dangerous. It can significantly upregulate the metabolic rate and lead to cardiovascular complications in some patients. And, if the changes seen in Low T3 Syndrome are a compensatory adaptation of the body in response to chronic illness, increasing T3 levels artificially may have undesirable effects.

In the majority of cases of Low T3 Syndrome, I think it’s preferable to identify the underlying cause and treat that. As I discussed in articles #3 and #4 in this series, those causes most often include infections, autoimmunity and inflammation.

Have any of you tried thyroid replacement for Low T3 Syndrome? If so, what was your experience? Please let us know in the comments section.

Articles in this series:

• Low T3 Syndrome I: It’s Not About The Thyroid!
• Low T3 Syndrome II: Myths and Misconceptions
• Low T3 syndrome III: Inflammation Strikes Again
• Low T3 Syndrome IV: An Autoimmune Disease You’ve Never Heard Of?
• Low T3 syndrome V: Should It Be Treated With Thyroid Hormone?