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Cellular Changes in Chronic Disease Pt 1: The CELL DANGER RESPONSE

This topic is going to be at least a 2-part series as there is a lot of information I want to share. Realistically it should be a 10-part series, but I won’t put you through that.

So as part of my job I have to make sure that I am reading up on what’s going on in the world of medical research. As you might know, I work in an interdisciplinary clinic in Vaughan called The Pain & Wellness Centre (The PWC). As the name implies, we work with people who are experiencing chronic pain for a number of different reasons: headaches, concussions, fibromyalgia, post-motor vehicle accident, pain that occurred with no inciting event, etc. I am a part of the (amazing) nutrition team composed of naturopathic doctors and a holistic nutritionist and we work with our patients to decrease inflammation, optimize their diet, and improve their micronutrient status (ie vitamins/minerals/precursors/co-factors). BUT I DIGRESS.

While sifting through some papers on how inflammation and nutrient status are connected, I came upon one on what’s called the “cell danger response” (CDR), written by Robert Naviaux. Dr. Naviaux is a professor of medicine, pediatrics, and pathology at the University of California San Diego. He is also the founder of the Mitochondrial and Metabolic Disease Center. His interest lies in mitochondrial diseases, which might sound foreign, but actually includes some common conditions as seen in the image below:

Image from:

Naviaux writes a lot about the cell danger response, which is essentially a temporary immune response that is designed to help protect cells and their host (ie the human body) from harm. This activates the inflammatory response. Once the danger has been neutralized, the anti-inflammatory and regenerative responses should kick in and reverse the CDR effects. BUT, when the CDR occurs for longer than its designed to (ie in virtually any chronic disease), it triggers these changes at the cellular level, which then results in whole body changes: the gut microbiome, metabolic processes, nervous system function, organ function. Everything. This is exactly what we see in our chronic pain patients, and it shows up in a multitude of signs and symptoms:

  • Digestive issues

  • Elevated inflammatory markers

  • Fatigue

  • Hormone imbalances

  • Mood changes (anxiety/depressive symptoms)

  • Sleep disturbance

  • Suboptimal nutrient status (ie blood sugar levels, iron, magnesium, vitamin D, vitamin B12, etc)

  • Weight control issues

And the list goes on.

The paper is great in that it reinforces what our team does at The PWC, and really what I do with all my patients: treat the person as more than just the sum of their body parts and understand that their symptoms are a result of changes happening all the way down to the cells. Each system is interconnected and so it is imperative that we get a very good idea of all of the patient’s symptoms, lab results, and physical exam findings to better understand what’s happening.

Some of the nutrients that the author cites in this paper as being important in the CDR and its aftermath include: vitamin D, vitamin B6, vitamin B12, folate, tryptophan, and cholesterol.

In part-2 of this series, I’ll go in to why these things are important to chronic disease.

If you have any questions, feel free to contact me!

Christine Cho, ND

Naturopathic Doctor


Naviaux, RK. Metabolic features of the cell danger response. Mitochondrion. 16 (2014) 7-17. Accessed online November 20, 2018.

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