The science on how to heal is growing rapidly.

Recently, Dr. Naviaux published a journal article that organizes the current knowledge on how to heal. I consider it a seminal piece of work.

We now know that healing happens on a cellular (not an organ) level.

This is hardly news to those who suffer from mast cell activation.  However, the focus of Naviaux’s work is identifying what is blocking the cell.

What if we could remove the blocking factor and restore cellular health rather than perpetually blocking the mast cell's response?

Naviaux has suggested four distinct stages of healing based on distinct cellular characteristics.

The four stages are the;

  • Health cycle,
  • Cell danger response 1 (CDR1),
  • Cell danger response 2 (CDR 2), and
  • Cell danger response 3 (CDR3).

The cell danger response is Naviaux’s term for mast-cell activation.

Importantly, Naviaux has also provisionally organized over 100 conditions into each of these stages, providing a working hypothesis on where targeted solutions can promote healing.



Health happens on a spectrum.

At one end of the spectrum, the body can seamlessly maintain health. It does this through what Naviaux calls the health cycle.

If you have ever pricked your finger with a lancet, seen your finger bleed and repair itself, this is an example of the body seamlessly maintaining health.

At the other end of the spectrum, the body can no longer address stressors as cells and organs have stopped functioning, and a disease process is underway.

It does so when roadblocks degrade organ performance over time as more and more cells fail to be repaired. This is where medicine excels.

In the middle of these two extremes is where the body is attempting to restore health by running the cell danger response cycle.

I like to use the analogy of a sailing boat rocking under the stress of strong winds (stressors) and rough seas (cellular capacity). The boat’s rocking (including releasing histamine) is the boat trying to sail upright (by running the cell danger response cycle).

Unblocking the health cycle allows the boat to sail upright once again.


The body has a pre-programmed health cycle to do everyday running repairs.

Three factors determine whether the health cycle will maintain health; circadian rhythms, neuroplasticity, and the stressor load.

In my experience, this is the most overlooked and misunderstood part of the healing process.


The healing cycle (and even our mast-cells) run on circadian rhythms.

Circadian rhythms are pre-timed hourly biological and seasonal processes.

Active processes (exercise and activity) are programmed for the day, whilst recovery processes (sleep and detoxification) are programmed for the night.

If your lifestyle conflicts with your circadian rhythms, the capacity to heal will be reduced.

Perhaps the most common example of this is interrupting the sleep cycle by shiftwork, which goes against the pre-timed circadian rhythms.

However, many other things can interfere with circadian rhythms.

Working with your body rather than pushing against it is one of the simplest ways to support health. And it costs nothing.


Our brain's capacity to switch (via neuroplasticity) between glucose and ketones for energy expands the capacity of our health cycle.

Specifically, regular moderate exercise and brief intermittent fasting overnight stress the body. Whilst eating, resting, and sleeping restores the body.

The regular stress and repair via the health cycle appear to build the capacity to heal.

What is important is the daily capacity for stress and recovery – not running yourself into the ground.  This area of the health cycle is perhaps one of the most overlooked in my client base.

Runaway blood glucose and insulin are rampant in my client base.

Not only is it incredibly stressful on cells (setting up the cell danger response), but it can stop the switching process (necessary for healing).  Equally, staying only in ketosis, or undertaking long fasts, does not build capacity.

Another common issue is resting and sleep.

In many ways, we have lost the art of rest, and for that matter, sleep.

So often, these are what is left over in the day, rather than a priority. Good quality sleep is not only free but one of the most effective health strategies.

How to Heal

Mattson, Mark P., et al. “Intermittent metabolic switching, neuroplasticity, and brain health.” Nature Reviews Neuroscience 19.2 (2018): 63.


The body is also exposed to many hidden stressors (other than daily activity) that must also be handled by the health cycle.

These include:

  • Metals, especially mercury, aluminum, lead, and copper.
  • Parasites, bacteria, and fungi/candida
  • Mould
  • Retroviruses/viruses
  • Lyme and co-infections
  • Chemical toxins including glyphosate
  • Food and supplement intolerances
  • Unresolved emotional or spiritual trauma
  • Prescription Medicines – many of which impact the mitochondria.

Two of these items, in my experience, are often overlooked.

Unresolved emotional or spiritual trauma is, in my experience, a significant component of not only ill health but also resistance.

It is interesting that few clients when they come to me, have a daily emotional detoxification routine. And yet, emotions are an essential part of all our human journey.

Also, many prescription medicines impact the mitochondria, which are the powerhouse of the cell danger response. For example, many anti-histamine and mast-cell stabilizers appear to interfere with CDR3.

Finally, restoring health involves reducing exposure to environmental risks and ensuring they can be detoxified.

When there is a heavy level of infections, it is common for detoxification pathways to be overwhelmed, blocking the body from detoxification.


Health happens at a cellular level.

Naviaux has identified 3 distinct stages of cell danger response based on its energetics, metabolites, and autonomy. 



The mitochondria produce energy from the nutrients we consume.

Health needs balanced energy production.  The blocks categorize the stage of cell danger response in mitochondrial energy production.

There are four steps; glycolysis (CDR1 blockage), aerobic glycolysis/pyruvate (CDR2 blockage), citric acid cycle, and oxidative phosphorylation (CDR3 blockage).

The health cycle directly links to glycolysis through the ability to utilize glucose efficiently.

An organic acid test or Nutreval test can measure energy production blocks and provide targeted solutions that support mitochondrial function. 



When a cell is stressed, the mitochondria respond by sending alarm signals to over 22 stress response systems.

Changes to the hypothalamic-pituitary-adrenal (HPA) axis are a hallmark of the cell danger response. They commence on CDR1 and resolve on exit from CDR3 to the health cycle.

Other stress signals help differentiate the CDR phase.

The involvement of the HPA axis can be assessed with a DUTCH test.


At CDR1, the cell gains cell autonomy to quarantine and repair the cell.

Healing remains incomplete until CDR3 is completed and cells reintegrate and take up their organ-specific role.

I like to use the analogy of the mitochondria being the fuse, the vagal nerve being the electrical wiring, and the brain being the switchboard.

When a cell is stressed, the mitochondria blow a fuse and blocks communication.

This cell autonomy remains until CDR3.

The last step of CDR3 requires the cell to re-establish bi-directional communication with the brain via the vagal nerve. Only then can the health cycle be re-established.

Naviaux has identified that many conditions, including POTS, Pandas, and mast cell activation, have a vagus nerve component.

Vagus nerve stimulation devices are showing extreme promise. Similarly, dental work can hamper vagal nerve functionality. 


Naviaux’s model provides a framework for how to heal.

This approach provides a fundamentally different approach to the traditional medical model.

Firstly, the health cycle's importance is that it is not possible to restore health without attending to the fundamentals, including circadian rhythms, blood sugar regulation, and stressor load. 

You won’t get well in the same environment that you got sick in. 

Secondly, the cell danger response cycle provides a framework for restoring cellular health through targeted mitochondrial interventions. This requires targeted support to repair (rather than manage biochemical reactions) based on blockages.

Will this approach make medicine traditional redundant? No. But it does provide a framework for a way to heal before an irreversible disease process is underway.


Key References

Naviaux, Robert K. “Metabolic features, and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment.” Mitochondrion (2018).

Naviaux, Robert K. “Metabolic features of the cell danger response.” Mitochondrion 16 (2014): 7-17.

Mattson, Mark P., et al. “Intermittent metabolic switching, neuroplasticity, and brain health.” Nature Reviews Neuroscience 19.2 (2018): 63.


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