Metabolic Features and Regulation of the Healing Cycle (The theory of everything expanded)

To provide context for this new information, please re-read my blogs on Naviaux’s work from May 2016 and October 2016.  In the May 2016 blog, I summarize Naviaux’s 2014 paper on the Cell Danger Response (CDR) which I call the “Theory of Everything” (Robert K Naviaux, 2014).  In the October blog, I summarize Naviaux’s metabolomics study of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) showing that ME/CFS may be a manifestation of the CDR (R. K. Naviaux et al., 2016).

3 Phases of Healing in a Systematic Way

Phase 1: Containment and Innate Immunity

Cells move from a state of health to the Cell Danger Response (CDR) when confronted with many different triggers including infection, injury, chemical exposure, oxidative stress and psychological stress. Once in the CDR, cells follow a programmed path regardless of what the illness trigger was. In Containment and Innate Immunity, the first phase of the CDR, cells stop communicating with their neighbors and decrease their metabolism. The innate immune system is activated in an attempt to contain the damage.  The slowed metabolism protects cells from death but at a cost of decreased function of organs and organisms.  Cells become blocked in phase I if the damage cannot be contained.  Naviaux believes that chronic infections such as tuberculosis and ecosystem disorders such as colony collapse disorder in honey bees may result from a failure to progress past phase I.

Phase 2: Healing Cycle

In Proliferation, the second phase of the healing cycle, metabolism increases and stem cells are recruited to multiply and replace the damaged cells. All of the damaged cells and cell components need to be replaced.  If cells become blocked in phase II while rapid growth is occurring, proliferative disorders such as cancer can result.  Conditions including diabetes and non-alcoholic fatty liver disease (NAFLD) are also considered disorders of blockage at phase II.

Phase 3: New cells created in phase

In Differentiation and Development, the third and final phase of healing, the new cells created in phase II mature and “learn” their roles.  They begin communicating again with their neighbors and with distant organs. If cells become blocked in phase III, disorders reflective of poor communication result.  Naviaux believes that disorders resulting from a block at phase III include psychiatric, autoimmune and energy disorders including ME/CFS and FM.

Each cell responds individually to injury and stress and each injured cell is at a different point in the healing cycle at any given point in time.  If the majority of cells are healing then the organism will heal.  If cells encounter blocks to healing, chronic disorders result.

A very important aspect of Naviaux’s healing hypothesis is that the original cause of the cellular injury is unimportant.  Once a cell enters the CDR, it progresses through the phases in a predetermined manner (or not) regardless of the initial injury.  Successful healing does return the organism (us) to its original state.  We arrive at a new healthy state, different from before.  Therefore, it is more important to find a way to change the metabolic and signalling pathways that are maintaining the block to healing than to identify the cause.

If Naviaux’s Cell Danger Response theory is correct, cures for chronic conditions are possible if a way can be found to overcome blocks in the healing cycle.  Naviaux predicts that the successful approaches will be different for blocks at each phase of the healing cycle and that one approach may be successful for many chronic conditions. As mentioned in the October 2016 newsletter, Naviaux and others are exploring strategies to help move animals and patients past healing blocks in phase III.  In 2017, Naviaux’s team published a very small, modestly successful 3 month trial of the drug suramin in children with autism.  The positive results provide proof of the concept that if a suitable intervention can be found to help move cells (and patients) past blocks in the healing cycle, chronic diseases can be cured rather than merely managed.  I believe a study is underway using suramin in ME/CFS.

Naviaux mentions that just as the body can become addicted to external substances such as alcohol or drugs, it can also become addicted to internally produced chemicals reflective of metabolic states of the Cell Danger Response.  As a result, even after healing, there is a tendency to relapse to the illness state.  How then can we assist our bodies and minds to heal and stay healed?

Healing requires the brain to feel safe.  If we are stressed and scared the brain is less likely to send signals to the healing cells that it is safe to proceed. This may be one connection between stress and chronic illness. Anything that helps calm the nervous and autonomic nervous systems may assist with healing.

Healing is most likely to take place in the context of a conducive lifestyle. What does this mean?  Naviaux suggests eating a seasonally appropriate diet during daytime hours, getting regular exercise during the day and enough slow-wave deep sleep at night.  In health, there is a balance between the two limbs of the vagus nerve.  One limb gets the organism ready for fight or flight and leads to chronic illness, the other activates feeding, sleep and reproduction.

For more on the critical role that the vagus nerve plays in health and illness, I recommend listening to one of Stephen Porges’s shorter Youtube videos.  His book “The polyvagal theory” is pretty heavy going and likely more information than most people need.  Porges’s website lists some of his publications and talks.  There are a growing number of strategies to calm and balance the vagus nerve and the autonomic nervous system.

Naviaux predicts that with environmental degradation and increasing toxic exposure, chronic diseases will increase.  Just as hygiene (clean water supply) had a huge impact on health and life expectancy in the last century, he recommends attention to the environment and to our individual toxic exposures as the single most helpful action to heal our species and ourselves.

Naviaux, R. K. (2014). Metabolic features of the cell danger response. Mitochondrion, 16, 7-17.

Naviaux, R. K. (2018). Metabolic features and regulation of the healing cycle-A new model for chronic disease pathogenesis and treatment. Mitochondrion, 09, 09.

Naviaux, R. K., Naviaux, J. C., Li, K., Bright, A. T., Alaynick, W. A., Wang, L., et al. (2016). Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America, 113(37), E5472-5480.

Author: Eleanor (Ellie) Stein MD FRCP(C)

I am a psychiatrist with a small private practice in Calgary and am an assistant clinical professor in the faculty of medicine at the University of Calgary. Since 2000, I have worked with over 1000 patients, all with ME/CFS, FM and ES. My passion for this field comes from my own struggle with these diseases, my desire to improve my health and then pass on what I learn. My goal is for every patient in Canada to have access to respectful, effective health care within the publicly funded system. 

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