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Why We Get Sick—and How to Get Well


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If you have one of the many chronic health problems that people suffer from today—such as IBS, fibromyalgia, chronic fatigue, and autoimmune disease—you will likely be given a drug to manage your symptoms and not much else. The key to successfully treating these conditions, however, is addressing their underlying cause. This is the promise of Functional and evolutionary medicine.

why we get sick
Getting to the root of why we get sick is how we determine how to get well. Okea/iStock/Thinkstock

We’re in the midst of the most serious epidemic of chronic disease humans have ever faced. Six in 10 adults in the United States have a chronic health condition, and four in 10 have two or more. (1) Seven of the top 10 causes of death in 2010 were chronic diseases, and two of them—heart disease and cancer—together accounted for almost half of all deaths. (2)    

While some of these problems (like heart disease) are fairly well-understood by conventional medicine, others are more mysterious. Conditions like Irritable Bowel Syndrome (IBS), chronic fatigue, diverticulosis, fibromyalgia, and autoimmune disease together affect hundreds of millions of people around the world, but in most cases, patients are told that the causes of their condition are unknown and simply prescribed drugs to manage the symptoms.

But is it really true that we don’t know what causes chronic illness? Certainly, there are particulars related to each specific illness that we don’t yet understand. But I would argue that we do, in fact, have a solid grasp on the most important factors that contribute to virtually all chronic disease. This means that it is within our power now to prevent, and even reverse, many of these conditions.

Do you know the eight underlying causes of most chronic disease? Check out this article to find out and learn how Functional Medicine can solve them. #functionalmedicine #unconventionalmedicine #kresserinstitute

The Functional Medicine Systems Model

As many of you know, I train clinicians in Functional Medicine through the ADAPT Practitioner Training Program. In preparing for that program, I created a “unified theory” of what causes disease that I call the Functional Medicine Systems Model. I’d like to share that with you here, and use it as a springboard for our discussion.

exposome + genome copy

As the diagram illustrates, the interaction between an individual’s genome, epigenome, and exposome is at the core of what determines our health.

The genome is our complete set of DNA, containing all of the information needed to build and maintain the human organism.

The epigenome consists of chemicals that modify the genome in a way that tells it what to do, where to do it, and when to do it. These modifications do not change the underlying genes, but they can be passed on to future generations.

The exposome represents the sum total of all non-genetic exposures an individual experiences from the moment of their conception through the end of their life. It includes the food we eat, the water we drink, the air we breathe, the chemicals we’re exposed to, the social connections we have, and the environment we live in.

To use an analogy, the genome is like a piano; the epigenome is like the sheet music, and the exposome is what determines how the music is written and performed. The quality of the piano will certainly affect the sound that it produces. But the finest piano in the world will still sound terrible if the sheet music and performance are terrible. Likewise, a virtuoso pianist performing a Mozart piece will not be at her best playing a poor-quality piano.

In the same way, genetics do play an important role in human health and disease. However, we now know that the exposome (and its influence on the epigenome) is far more significant in most cases. In fact, it is responsible for more than 90 percent of human disease. That is why the exposome is at the core of the Functional Medicine Systems Model, and should always be the first thing addressed regardless of the patient’s complaint.

The modern diet, lifestyle, and environment affect the expression of our genes and lead to pathology, which in turn cause disease and symptoms in the patient.

But what are those pathologies?

The Eight Core Pathologies That Underlie All Chronic Disease

I believe that virtually all diseases and symptoms that we experience are caused by one or more of the following eight core pathologies:

1. Gut Dysfunction

Gut dysfunction includes small intestine bacterial overgrowth (SIBO), infections (e.g. parasites, pathogenic bacteria, viruses), low stomach acid, bile, and enzyme production, intestinal permeability, and food intolerances.

2. Nutrient Imbalance

Nutrient imbalance includes deficiency of nutrients like B12, iron, folate, magnesium, zinc, EPA/DHA and fat-soluble vitamins (most common), and excess of nutrients like iron (less common).

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Chris Kresser in kitchen

3. HPA Axis Dysregulation

HPA axis dysregulation includes regulating the communication between the hypothalamus, pituitary, and adrenal glands, and balancing the production of hormones associated with those glands (e.g. DHEA, cortisol)

4. Toxic Burden

Your toxic burden includes exposure to chemicals (e.g. BPA, phthalates, etc.), heavy metals (e.g. mercury, arsenic), biotoxins (e.g. mold/mycotoxins), or impaired detoxification capacity due to nutrient deficiency, GI issues, or other causes.

5. Chronic Infections

These include “stealth” infections by tick-borne organisms (e.g. Borrelia, Babesia, Bartonella, Erlichia), intracellular bacteria (e.g. Mycoplamsa, Chlamydophila), viruses (e.g. HHV-6, HPV), and dental bacteria.

6. Hormone Imbalance

Hormonal imbalance can include those associated metabolism (e.g. insulin, leptin), thyroid, and gonads (e.g. estrogen, progesterone, testosterone).

7. Immune Dysregulation

This includes autoimmunity, underactive immune function, and chronic, systemic inflammation. 

8. Cellular Dysfunction

Cellular dysfunction can refer to impaired methylation, energy production, and mitochondrial function, and oxidative damage.

These pathologies (and the exposome-genome-epigenome interactions that lead to them) are at the root of everything from obesity, to Hashimoto’s thyroiditis, to asthma, to autism spectrum disorders, to depression. The understanding that the same eight core pathologies underlie most modern, chronic diseases has profound implications for how we should address these conditions.

In conventional medicine, the focus is often on diseases and the symptoms; it works “from the outside in.” For example, let’s say that you go to the doctor for your annual exam and your blood tests reveal that you have “high cholesterol”. The most likely outcome in this situation is that you’ll be prescribed a statin, and in some cases be told to exercise more and eat better. There is rarely any serious investigation into what caused the high cholesterol in the first place.

In Functional Medicine, however, we work “from the inside out.” We pay less attention to the symptoms and more attention to the pathology that produces those symptoms.

High cholesterol is a symptom, not a pathology. The pathologies that can lead to high cholesterol include poor thyroid function, intestinal permeability, disrupted gut microbiome, chronic viral or bacterial infections, insulin and leptin resistance, and nutrient imbalances—to name a few. If I find high cholesterol in a patient, we will examine all of these potential pathologies, and of course, we will also look at how the individual’s genetics, diet, lifestyle, and other factors related to the exposome may be contributing to them. Once we have addressed all of the core pathologies, the cholesterol levels typically normalize on their own.

Whether the patient’s main complaint is infertility, fatigue, sinusitis, or skin problems, I will focus on these eight core pathologies because I know (from both clinical experience and research) that they are the most likely underlying causes of their condition. In my practice, most of my patients are dealing with not just one of these pathologies, but several.

As you can see, this is a fundamentally different approach than what is typically done in the conventional setting. The downside is that it requires a lot more testing and investigation up front, which can be costly and time-consuming. The upside—which obliterates any of the downside considerations—is that it becomes possible to not only prevent but even reverse many chronic disease conditions without the need for taking medication for the rest of your life.

Unfortunately, the Functional Medicine approach is not yet embraced within the conventional healthcare model. But I believe that is changing. The prestigious Cleveland Clinic established the Center for Functional Medicine, directed by Functional Medicine pioneer Dr. Mark Hyman. This is a big step toward mainstream acceptance of Functional Medicine, and the research the center is engaged in will almost certainly lead to even broader recognition.

I think health insurance companies will also see the benefits of Functional Medicine. They’ll recognize that spending a little more money up front to properly diagnose and treat the root of the problem will lead to enormous savings down the line.

These changes aren’t going to happen overnight, and we still have a lot of work to do. But the tide really is starting to turn!

If you’re a healthcare practitioner and you’re interested in training in this approach, learn more about the ADAPT Practitioner Training Program.

If you’re struggling with a chronic health problem and are interested in learning more about this approach, click here to learn more about how the team at the California Center for Functional Medicine can help. The membership-based health transformation service offered by CCFM is 100 percent virtual, and it’s designed to offer you the support, tools, and team you need to get well.

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Join the conversation

  1. First, I did not read all the comments above (sorry; not enough time). Instead, I searched for “intolerance” on the page but found nothing relevant on the 3 instances that came up.

    I want to share our family experience with food intolerance. This developed in the males (father first, son at similar age later) as adult-onset. The symptoms (the same for both) were getting worse, serious and disabling. The first time, an intelligent doctor said “No, it is not cancer or a parasite or whatever, it looks like something you are eating.” The patient, being an experimental scientist, conducted 2 years of experimentation, with the result of excluding all grains, big or small, from his diet. Examples of excluded: wheat, corn, rice, peas, beans, black pepper, grain spices, coffee, chocolate, all “vegetable” oils (except olive virgin first press), annato, food additives such as emulsifiers etc, … Bingo: end of problem. That was almost 30 years ago. Since then, provided we shop carefully and cook at home with safe ingredients, the patient is healthy.

    Clearly, we rarely (if ever) “go out” as a family to eat. We also have built quite a repertoire of how to shop and cook at home (but nobody “outside” seems to care much; I mentioned this by email to an acquaintance in the Nutrition program at the local U and got not even a response). When invited to something that includes food, our men typically take along their food (cannot expect others to understand such restrictions; some have tried, and included things that hurt, not knowing enough to ask). I have known people with celiac, this helped (these would be fine on our “diet”). Basically, we cook much like our rural grandparents did, using what we have and what works (root, bark, leaf; meat, eggs, dairy; we de-seed tomatoes, etc).

    • You are describing my life. It’s a challenge to do social things as almost everything social involves food.
      I also had to do my own research and experiment s as Doctors had no idea and recommended things that made me much worse.
      Life is getting easier thanks to the paleo movement. Not that I follow any “diet” as such but for going out Paleo would be the closest thing I could eat if I’m caught out.
      The social isolation is hard, and being treated as if this is my lifestyle choice harder.
      Thanks for sharing your experience. It helps to know I’m not alone.

  2. Actually, I’m this article highlights the causes and indeed but very little is said about How to Get Well.

    The Jury is out on Mr Kresser for 4 reasons.

    Firstly, his articles on the acid/alkaline myth are mythical, basically summarising that urine acid levels only reflect the acidity of the urine and aren’t indicative of levels in the body. The whole article tries to debunk acidity in the body, which is an acidic stance in itself. Whilst alkalinity may not be the answer to everything, of course over acidity can create a toxic load. Also, why eating bacon and beef can be good for you if it’s super grass-finished and killed humanly, no one size fits all, especially different people with different problems and at different levels of health. Someone with impaired glutathione conjugation, and missing genes for Methylation, with heavy metal burden, and yeast overgrowth, may find any additional acidic input from food extremely damaging to tissues. Of course it matter, it’s ignorance to claim acidity is not extremely important in some cases.

    Secondly, his interviews are on occasion extremely negative, I’ve heard him talk on R. Arthritis, and what he would do in that circumstance, basically giving very little hope tojjjuu those who have it. It’s in a par with Karazzians “when we see x, y, and z together, we get very very nervous” comments, frightening to most who are already anxious about their health. Hyman never reveals a chink of darkness regarding the possibility of reversibility nor lack of hope and nor should any seriously positive, healthy, health professional.

    Thirdly, I’m not convinced Kresser has addressed his own mitochondrial challenges. He comes across very low energy, monotone and down beat and one wonders, if his methods are not working for him……………??

    Lastly, this article is just a list of causes, which in fact conventional pharmaceutical medicine doesn’t really disagree with albeit they don’t have the resources nor sanctions to test for all of these things….that’s coming with Theranos. However, the article makes the claim that it communicate how people can get well…..where?? All I learned is an elongated list of testing I might have to do…..and the second bit…..getting well?

    Not convinced about Kresser’s abilities nor underlying PMA at all.

    People believe because they do a bit of good, that damage has to be overlooked if it is minimal. This is not the case. One has to take a very good look at the overall all net product of ones efforts, and assess, honestly and deeply whether the net, net, net toll on the universe is indeed positive or not. Sometimes, doing nothing is a more compassionate stall, this applies to many who just don’t care to look and intuit.

  3. Hi Chris,

    I listen to your podcast and read your articles and am so grateful for all of the information and help I receive. I have a question that I can’t seem to get an answer to. I’m hoping you can help! How much mercury in the blood is dangerous? I am having neurological problems (likely peripheral neuropathy) and diagnosed Erythromelalgia (rare). My neurologist ran a slew of blood tests including mercury, which was 11. The “normal” range is 0-10. My PCP referred to my result as “sub clinical”. Tell me please, would you be concerned with a mercury level of 10? The only advice I received from the neurologist was to avoid fish that are high on the food chain like swordfish, halibut, grouper, etc. I love fish and eat fish 3-4 times a week and have been avoiding the big fish but would very much appreciate your advice. Thank you.

    • check out the Quicksilver tests from Colorado. Lots of docs and dentists order them now, you can also ask them who. It uses blood hair and urine to give a much better heavy metals testing. I had my first one in 2010 and second in 2015 (I know Chris uses this test now with his patients).