RHR: Chronic Fatigue—Treating the Cause Not the Symptoms

Symptoms are important because they can give us clues to what the underlying mechanisms might be that are contributing to a health problem. However, if you focus on the underlying mechanisms and causes the symptoms tend to resolve on their own. When treating a nonspecific symptom like fatigue, you have to investigate all seven of the primary mechanisms that lead to disease.

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I’m going to talk a little bit about the difference between conventional and functional medicine and how they would approach something like this, and how that relates to this overall discussion about conventional versus functional medicine because it is fresh on my mind. I’ve been thinking a lot about these things in preparation for my clinician training program. And then I want to talk a little bit about the model that I use in my clinic and how I approach a nonspecific symptom like fatigue.

In this episode, we cover:

1:58 What Chris ate for lunch
8:04 The functional medicine process
16:04 7 primary mechanisms that lead to disease
20:54 How Chris structures treatment in the clinic

Steve Wright: Good morning, good afternoon, good evening. You are listening to the Revolution Health Radio Show. I’m your host, Steve Wright, co-author at SCDlifestyle.com. This episode of RHR is brought to you by 14Four.me. 14Four.me is a 14-day healthy lifestyle reset program. So if you’re struggling with any area of the four main quadrants that Chris is typically talking about on the RHR podcast — we’re talking about diet, sleep, movement, and stress — all these areas are areas that I typically struggle with, I know Chris has struggled with in the past, and so they really make up the foundation of our health. 14Four.me is Chris’ solution to how do you implement them all at the same time in our modern world, which can be challenging, to say the least. So if you haven’t yet, check it out. It’s a great sort of reset program. If, for instance, maybe your goals for the new year are already sort of sliding to the wayside and you want to get started again, check out a program like this. Chris, you are an integrative medical practitioner. You’re the healthy skeptic and a New York Times bestselling author. Thanks for being with us.

Chris Kresser: Good to be here. It would be weird if I wasn’t, wouldn’t it?

Steve Wright: It would be weird. I was just running with that one. I have a lot of energy today, and I swear I’m only running on Perrier.

Chris Kresser: Perrier? Alright. Nobody slipped anything in there?

Steve Wright: No, not yet.

Chris Kresser: Yeah.

Steve Wright: Before we get into today’s question, we’ve been forgetting to ask you what you’ve been eating.

What Chris Ate for Lunch

Chris Kresser: Ah, right. Today I had leftover ground beef from last night, some salad, and some plantains, which I usually have for breakfast, as you know, Steve. I had them for lunch today. Call me crazy.

Steve Wright: Watch out! That sounds like a weird diet, my friend. Just totally weird.

Chris Kresser: Yeah. And then I had some water kefir from Three Stone Hearth to wash it down.

Steve Wright: Alright then. Simple but effective.

Chris Kresser: Yeah.

Steve Wright: I like it.

Chris Kresser: It works. Yeah, well, we have another great question. This one is from Yvette. I hope I’m pronouncing that correctly. It’s not only just a good question that we get asked a lot in terms of the content of the question, but it points to a larger issue that I’ve been thinking a lot about as I prepare to offer clinician training, so I’m going to use this as an opportunity to kind of have a larger discussion about functional medicine and how it can be used to treat chronic conditions. So maybe I’ll stop talking and let Yvette take over!

Question from Yvette: Hi. My name is Yvette, and my question is, how do you go about — I guess, at a high level — treating chronic fatigue syndrome when no one really understands sort of the root cause of it or what it is? And the reason why I’m asking is that I’ve been sick for nearly a year without a diagnosis. I have a doctor who thinks I might have Lyme disease even though I had some inconclusive results from IGeneX, and I’m finishing a month of antibiotics, don’t feel any better, and considering continuing with more of an herbal antibiotic route, but I worry that if my issue is more autoimmune that that type of approach might not be the best, and I don’t have any answers from a rheumatologist either. So I guess my question is, what would you do in this situation, when you don’t really know yet whether the underlying issue is infection versus autoimmune in treating someone?

Steve Wright: Alright, Chris, before you jump into answer this question, I just want to let all the listeners know that if you’d like your question answered on this podcast, please go to ChrisKresser.com/PodcastQuestion, and go ahead and call in and record your question there. Thank you.

Chris Kresser: OK, so fatigue. Super, super common, obviously. I’d say it’s probably the number one complaint. We always ask people to list their top five complaints when they come in to our clinic, and I would say fatigue is part of the clinical picture in probably 80% of cases, if not more. The trouble is it’s a very nonspecific symptom, which means that you can’t easily attribute it to any one particular condition. There are other symptoms, for example, like the thinning of the outer third of the eyebrow, that are more specific. That tends to be a sign of hypothyroidism. There are other things that could potentially cause that, but that’s kind of a red flag for hypothyroidism. Whereas, with fatigue, someone tells you that you have fatigue, you really can’t say much about what might be causing it. There’s a whole world of possibilities that need to be explored, and that’s really, I think, the difficulty that Yvette is pointing to and the difficulty that we all face as those of you who work with people who are health care practitioners. If that’s all you have to go on, it can be a challenging place to start because you really have to cast a wide net.

So what I’m going to do here is I’m going to talk a little bit about the difference between conventional and functional medicine and how they would approach something like this and how that relates to this overall discussion about conventional versus functional medicine because this is fresh on my mind. Like I said, I’ve been thinking a lot about these things in preparation for the clinician training program. And then I want to talk a little bit about my kind of model that I use in my clinic and how I approach a nonspecific symptom like fatigue, and then I’ll talk even a little bit more specifically about Yvette’s situation, like what we know of it, at least, and what I might do there with the limited information that we have.

In conventional medicine, one of the biggest problems with it is that they mostly focus on symptoms and diseases. If you go to a doctor and you have high cholesterol, you get a drug to lower your cholesterol. If you go to a doctor with high blood pressure, you typically get a drug to lower your blood pressure, and there’s often little investigation into why your cholesterol or blood pressure are high in the first place. The intent is to just bring them down, and that’s generally the end of the story. In functional medicine, it’s often flipped. It would be an exaggeration to say that we don’t care about symptoms, because we do care about people’s symptoms and suffering. Symptoms are important in as much as they can give us clues as to what the underlying mechanisms might be that are contributing to the problem, but they’re not as important because when you focus on the underlying mechanisms and causes and you address those, the symptoms tend to resolve on their own, so you don’t have to worry about going after each and every symptom individually. You just address the root causes and the symptoms resolve.

The Functional Medicine Process

So that’s the difference. Conventional medicine kind of works from the outside in, and functional medicine tends to work from the inside out. Actually I’ve been working on this series of concentric circles that’s a functional medicine systems model that I’m going to talk about during the clinician program, and it starts with the recognition that the core of all disease starts with the interaction between our genes and the way that our genes express, and the way that our genes express is primarily controlled by what’s been called the exposome.

Let’s break all those terms down quickly. Our genetic code is the basic template that we come into this world with. Another way to think of it is like the script that provides the instructions for the production of our life, if you want to use that metaphor. And there are certain genetic mutations in genes that can either guarantee that something is going to happen to us — that’s a lot more rare — or make it more likely that we’re going to have a problem in a certain area of physiology or function. An example would be, mutations in genes that are involved with methylation don’t necessarily guarantee methylation problems, but they increase the risk that you might methylate poorly, especially if you are exposed to certain environmental factors.

Epigenetics, on the other hand, is the study of changes in gene expression that don’t involve changes to the underlying genes themselves but can be passed on to one or more generations. What we know now is that epigenetics is probably much more of a determinant of our health than genes themselves because genetics account for 10% or less of disease, and the remaining 90% is controlled by our gene expression and how our genes interact with environmental factors.

That brings us to the exposome, and the exposome is a term coined by Dr. Christopher Wild in 2005, and it encompasses the sum total of all of our non-genetic exposures that we experience from the moment of conception to the end our life. This could be our mother and father’s health at the time of our conception, our mother’s health during pregnancy, and then things like our diet, our lifestyle, physical activity, stress, social status and environment, external environment, like the air that we breathe, the water we drink, chemicals that we’re exposed to, whether we live in an urban or rural environment, and then our internal environment, which would be our microbiome and our hormones and metabolic health, inflammation, oxidative damage, all that sort of stuff.

So again, if we imagine a circle, this whole interplay between our genes and epigenetics and the exposome is at the core. This is really what drives health and disease.

The next ring out from that would be underlying mechanisms or just mechanisms. These are different than diseases. These are underlying processes that lead to dysfunction. They could be things like SIBO, nutrient deficiency, hormone imbalance, chronic infections, etc. They’re not diseases, per se, but they’re mechanisms that lead to disease.

The next ring out in the circle would be disease, and these are things like Hashimoto’s or type 2 diabetes. Essentially they’re constellations of signs and symptoms that we recognize as a particular disease entity.

And then the final ring out would be symptoms, and this is kind of the ultimate manifestation of everything we’re already talked about so far, and it’s how we experience these mechanisms and diseases on a daily basis, you know, abdominal pain, fatigue, skin rashes, whatever they may be.

Again, in conventional medicine often the outside of the circle is the focus, and in functional medicine the inside of the circle is the starting place, and we move outward from there. So that’s kind of the context for the rest of this conversation.

Steve Wright: That’s a pretty big context, Chris.

Chris Kresser: Yeah. I hope I didn’t lose too many people there. I think it’s really important to understand because, to me, it describes the really key differences between the functional and conventional approach and the limitations of the conventional approach for dealing with chronic illness. If I break my arm, I want to go to the hospital. Conventional medicine is awesome for that kind of thing! In emergency medicine and trauma medicine, there isn’t so much of a need to think about genetics and epigenetics and diet and lifestyle and all those things. It’s just a relatively acute situation that requires an acute intervention, and that’s somewhere where conventional medicine really excels. But as we’re going to see when we go into the next section, with a chronic illness, it’s never that simple, and there’s so much investigation that needs to be done to really get to the bottom of things, and the conventional system is just not set up in a way that makes that even feasible.

Steve Wright: So how do we begin to look at something like fatigue, which could range from somebody who just knows that they used to feel a little bit more energy and now they’re kind of low energy versus somebody who’s maybe stuck in bed?

Chris Kresser: That’s a great question. The simplest answer is, it depends who’s asking and who’s coming in. If somebody comes in and they’re like, Oh, I’m tired, and they’ve been eating a standard American diet and they’re really stressed out and they’re not doing stress management and they’re not exercising enough and their sleep is trashed, I’m going to tell them to do 14Four! Really. That’s why I created that program, because as I said, the core of this whole picture is diet and lifestyle and environment, and so if someone is not attending to those things, that absolutely always the starting place, period. It doesn’t make any sense to do anything else if you’re not addressing those things. I mean, you can do other things, but they’re going to have a limited effect if sleep, diet, stress management, and physical activity aren’t being adequately addressed. That’s the entire reason that I created 14Four. I just wanted to have something where I could say, Here, do this, for someone who’s experiencing all these kinds of nonspecific symptoms but they haven’t addressed those basic things yet, because that’s the starting place for everybody, including people who come to my clinic. Now, because of the nature of my practice and that most people come to my clinic after reading my blog and listening to my podcast for a long time, most of my patients are already on that bandwagon, so we start at a higher level. But in the general population, something like 14Four would always be the starting place if fatigue or any other symptom that’s kind of nonspecific like that were the main complaint. But I assume by Yvette’s question that she’s paying attention to those things. We’ll make that assumption so we can talk about how I would address it in the clinic.

7 Primary Mechanisms that Lead to Disease

When you have a nonspecific symptom like fatigue, you have to investigate all seven of the primary mechanisms that lead to disease. This list is my current list. It’s always changing and evolving. It might change and evolve again by the time I teach the clinician training program, but I think it’s a fairly complete and accurate list at the moment, and the seven primary mechanisms would be:

1. Gut dysfunction – This is actually a big category that includes a lot. It would include SIBO, small intestine bacterial overgrowth; leaky gut; low stomach acid; poor digestive enzyme production and malabsorption; parasites; fungal overgrowth; other infections; and then food intolerances, which is a huge category in its own right.
2. Number two would be nutrient imbalance, either deficiency or excess. Now, deficiency is a lot more common, and we just saw data from the NHANES Nurses’ Health Study suggesting that a huge percentage of Americans, almost 50% of Americans, are deficient in things like vitamin A, vitamin D, vitamin C, vitamin E, all the important fat-soluble vitamins. Something like 97% of Americans don’t get enough choline and potassium and fiber. These nutrient deficiencies are widespread, and that’s crucial because nutrients are what fuel our body, our basic metabolic processes, but there are some cases where nutrient excess is a problem. Iron overload, which is something we’ve talked about a lot, is one example of that.
3. Toxicity or toxic overload is another primary mechanism. This can be caused by exposure to toxins like heavy metals or chemicals, phthalates, BPA, etc., and mold or other biotoxins. Or it can be caused by impaired detoxification capacity. So maybe the level of toxic exposure is minimal, but your ability to properly detoxify is impaired for any number of reasons, or you have a combination of both, which is the most likely scenario.
4. Number four would be hormone imbalance. This is another big category. This could include HPA axis dysregulation, aka adrenal fatigue; metabolic hormone disruption, so like, leptin and insulin and hormones that regulate blood sugar; thyroid hormone imbalance; and then sex hormone imbalance both in men and women.
5. Number five would be chronic infections. These could be things like Lyme disease and the various co-infections, mycoplasma; intracellular infections like Chlamydia pneumoniae; and chronic viruses, viral activity.
6. Six would be immune dysregulation, another big category because this includes not only autoimmunity or overactive immune system, but also underactive immune system; poor or weak immune function; inflammation, systemic inflammation and things like chronic inflammatory response syndrome, which is a biotoxin-related illness, and it’s something I’m going to be writing and talking about more in the future. We don’t have time to get into it too much now, but I think it affects a lot of people. That comes from the work of Dr. Ritchie Shoemaker, who we’re going to have on the show at some point.
7. And then the last one would be genetic polymorphisms, single nucleotide polymorphisms or SNPs. These are mutations in genes that can lead to problems with methylation, cellular energy production, mitochondrial function, etc. I think this is probably the most problematic of all of the mechanisms, and there’s still a lot that we’re learning about, but I think we know enough about some of the methylation and detox and cellular energy production mutations to use them to our advantage in the clinic. I used to just list the six mechanisms. That became a seventh pretty recently.

Those are all of the things that need to be investigated with a nonspecific symptom like fatigue, and you can see why functional medicine is as complex as it is, why it takes as long as it takes to learn it, and why it can take as long to address a situation like this as it can in a functional medicine model.

Steve Wright: So are those sort of, like, ranked one through seven specifically, Chris? I’m sure people are going to be wondering who don’t have fatigue, and I know you’re going to give very specific recommendations for fatigue, but I can almost guarantee that your inbox is filling up right now with questions regarding this.

How Chris Structures Treatment in the Clinic

Chris Kresser: Well, it’s a good thing you ask because that’s the next thing we’re going to talk about. This is also an evolving process, but I’ll tell you how I structure things in my clinic, and this will also be, of course, a focus of the clinician training. That’s a tremendous amount of things to do, that I just mentioned, and so we need to focus on what comes first, and again, we’re assuming that diet and lifestyle stuff has already been addressed. That’s kind of going without saying here, but if it has been, then the next thing, for me, I always start with the gut and the HPA axis and nutrient status because those things are often at the root of or contribute to the four other mechanisms that I mentioned: hormone imbalance, immune dysregulation, the effect of genetic polymorphisms, and chronic infections. And the other reason is that even if you have any of those other four mechanisms — toxic overload also — even if you have any of those other mechanisms, addressing the HPA axis and nutrient deficiency and the gut will lead to significant improvement in almost all cases.

An example would be, let’s say someone has a chronic infection like Lyme. This may not be the best example because it’s so complex and intense, but if someone has a chronic infection like Lyme, almost certainly their gut is going to be screwed up, almost certainly their HPA axis is going to be screwed up, and almost certainly they have some nutrient deficiencies. And if you address the gut, the HPA axis, and nutrient deficiencies, that person is almost certainly going to feel better. Now, that won’t be the end of the treatment in that case. You still will have to, obviously, address the infection and the hormone imbalance and other issues that might be present, but I think it’s easier to do that when the person has a basic ability to function because their gut is working a little bit better, they have the nutrients that they need to fuel their body, and their HPA axis has some support. Then after addressing gut, HPA axis, and nutrient deficiency, you might move on to the toxins, detox, infections, hormones, and these genetic polymorphisms that can interact with all of this to cause problems. That’s basically the general template and the approach that we use in our practice.

For Yvette, to get even more specific, Lyme is a real Pandora’s Box. We’ve talked about it on the show before, and it’s a really difficult and thorny clinical issue. I recommend you go back and listen to the podcast I did with Dr. Sunjya Schweig, who is also my partner and co-director at the California Center for Functional Medicine, our clinic. He has a lot of expertise in treating Lyme and co-infections. In that podcast, we really kind of took an honest look at all of the challenges that are inherent to diagnosing and treating Lyme disease, and we kind of shared our feelings about that, so if you haven’t listened to that podcast or read the transcript, I definitely recommend you do that. And I also recommend you find a very, very experienced clinician and one that — what’s the best way to say this? — one that is open minded and not 100% certain about Lyme, because I’ve found that in the Lyme community there are some practitioners out there who are a little bit overconfident in terms of their ability to accurately diagnose Lyme, and I think a little bit of humility and honesty in terms of the equivocality of some of these tests and the ability to accurately diagnose Lyme in certain situations is a very important quality in a clinician. That’s one of the things I appreciate about Sunjya so much, is that he has a lot of expertise in Lyme and he comes to this with a lot of experience and he has treated a lot of Lyme patients, but he’s not the person who’s going to treat everyone as if they have Lyme, and he will tell you if he is uncertain and if the data coming back is uncertain and kind of give you informed consent in terms of, OK, well, we can go this direction and try a course of treatment and these are the pros and cons of that, or we can not do that and these are the pros and cons of not doing it, because really that’s how it has to be until the testing improves to the point where we have more accurate diagnosis.

For fatigue, I would still focus on the gut, HPA axis, and nutrients if you haven’t already, Yvette. And then my next steps would be looking at methylation, screening for toxins like heavy metals, biotoxins and mold, chronic inflammatory response syndrome, and of course, looking at infections, which it seems like you’re already doing, and then looking at blood sugar and thyroid, seeing if there’s anything that can be done there to help just provide overall support if there is an infection present, or if there’s not an infection present, maybe it’s more related to a thyroid issue or another hormone imbalance of a different kind.

As you can see, this is, again, a lot. There’s, unfortunately, no quick and easy answer here, but this is the method that we use and the way that I think it has to be done in order to really figure it out.

Steve Wright: Well, I’m sure that definitely helps her, Chris, and I hope that she has some good practitioners. Maybe even, Yvette, you could clip this segment out or take the transcript and bring it in to the appointment.

Chris Kresser: I’m just wondering how that’s going to go over!

Steve Wright: Well, I doubt anybody’s practicing this evolved since you haven’t even begun to teach it to too many people.

Chris Kresser: Oh, you know, there are so many good practitioners out there who — well, maybe not so many, but I know of a lot of practitioners who are doing fantastic work, and there are a lot of people out there who just focus entirely on clinical practice and they don’t do anything else and so a lot of folks don’t even know that they’re out there. But I agree, we also do need more people who are embracing both a functional and an ancestral evolutionary approach. That’s the difficult thing to find, really. I think there is at least a growing number of functional medicine practitioners who can do the functional testing and all this stuff, and there is a growing number of people with an ancestral evolutionary nutrition perspective, but there are fewer clinicians that have both of those perspectives at the same time, and that’s what the clinician training program is going to be all about, is kind of bringing those two things together and hopefully creating an army of practitioners that can practice a paleo template based style of functional medicine, because I think that’s where the real power lies in terms of the ability to prevent and reverse disease.

Steve Wright: Yeah, I can’t wait, man. Can’t wait.

Chris Kresser: Alright, that’ll do it.

Steve Wright: Yeah, so if you would like Chris to tackle your question, remember to go to ChrisKresser.com/PodcastQuestion and submit it there. In between episodes, if you’re looking for updates or you’re kind of curious what Chris is reading or how he’s getting his research, he typically is posting stuff that doesn’t necessarily make the cut for the podcast or the blog on Facebook and Twitter. If you use both, obviously follow him on both, but if one is your platform, go to Facebook.com/KresserInstitute and Twitter.com/ChrisKresser. Thanks for listening.

Chris Kresser: Thanks, everyone.