CELL DANGER RESPONSE : RETHINKING MAST CELL ACTIVATION

April 30, 2022 7:00 am

Alison Vickery FDN-P

The science of healing, particularly in understanding the cell danger response, is growing rapidly.

For instance, Dr. Naviaux published a journal article that organises the current knowledge.

It is a seminal work that forms the basis of how I restore health.

histamine intolerance, mast cell activation, medicines, cell danger response, antidepressants, brain fog, nervous system EMF Health Effects

Health On A Spectrum: Understanding The Role of The Cell Danger Response

Health occurs on a spectrum.

At one end, the body seamlessly maintains health through what Naviaux calls the health cycle. For example, if you have pricked your finger with a lancet or seen it bleed and repair itself.

Conversely, at the other end of the spectrum, the body can no longer address stressors because cells and organs have stopped functioning, and a disease process is underway. This is where medicine excels.

In the middle of these two extremes, the body attempts to restore health by running cell danger response programs. 

I like the analogy of a sailing boat rocking under 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.

Ultimately, once the cell danger response is completed, the health cycle resumes, allowing the boat to sail upright once again.

Naviaux's Stages of Healing: The Cell Danger Response

Naviaux has suggested four stages with distinct cellular characteristics.

The four stages are;

  • Firstly, the health cycle,
  • Secondly, cell danger response 1 (CDR1),
  • Thirdly, cell danger response 2 (CDR 2), and
  • Finally, cell danger response 3 (CDR3)

Moreover, Naviaux has provisionally organized over 100 conditions into each stage. This organization provides a working hypothesis on where targeted solutions can promote healing.

Cell Danger Response, Health Cycle

The Health and Cell Danger Response Cycles

The health cycle was not designed to handle continual exposure to sources of threats and stress.

Therefore, when the total stressor load exceeds the health cycle’s ability to restore health, the body consequently progresses through three stages of the cell danger response.

These stages are characterised by:

1. The HPA Axis And The Cell Danger Response

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

Therefore, 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.

Indeed, adrenal support is frequently needed as part of the first stage of the cell danger response.

2. The Mitochondria And The Cell Danger Response

The mitochondria generate the energy-rich molecule adenosine triphosphate (ATP). 

ATP has two roles. Firstly, within the cell, it produces energy. Secondly, outside the cell, it signals a threat that starts the cell danger response and triggers inflammation within the body.

Naviaux categorises these into three mitochondrial responses:

  • Firstly, glycolysis (CDR1 blockage)
  • Secondly, aerobic glycolysis/pyruvate (CDR2 blockage)
  • Thirdly, citric acid cycle and oxidative phosphorylation (CDR3 blockage)

In conclusion, during stage 2 of the cell danger response, the mitochondria struggle and need support.

3. The Autonomic Nervous System And The Cell Danger Response

The autonomic nervous system identifies whether a cell is functional or not.

Specifically, when the cell is stressed, the autonomic nervous system initiates the cell danger response, and when the cell is repaired, it restores the health cycle. 

In other words, at CDR1, the cell quarantines itself to run the cell danger response programs. Then, CDR3 requires the cell to re-establish communication via the autonomic nervous system. Only then can the health cycle be re-established. 

In conclusion, the autonomic nervous system it vital to restoring health.

Naviaux's Stages of Healing: A Practical Framework

Naviaux’s four distinct stages provide a hierarchy.

Additionally, he has provisionally organised over 100 conditions into each stage, offering a working hypothesis on what support is needed.

  • Firstly, for Cell Danger Response 1 (CDR1), the support includes pyrroles, acetylation, methylation, uric acid, and adrenal support.
  • Secondly, for Cell Danger Response 2 (CDR2), the focus is on mitochondrial support.
  • Finally, for Cell Danger Response 3 (CDR3), anti-purigenic support is typically provided, often using suramin.

In my practice, I observe a very high correlation between these stages and what I see in my client base.

Notably, many clients have pyrrole and acetylation issues triggered by the cell danger response and resolved once homeostasis is restored, rather than being permanent diagnoses.

Anti-Purigenic Support and Cell Danger Response 3

Naviaux popularised the concept of anti-purinergic support.

Purinergic receptors plays a crucial role in the cell danger response and mast cell activation. Specifically, these receptors, located on cell surfaces, respond to extracellular ATP released by stressed or damaged cells.

When ATP binds to purinergic receptors, it triggers the cell danger response, thereby amplifying inflammation. 

Furthermore, when ATP binds to purinergic receptors on mast cells, it causes these cells to degranulate, releasing histamine and other inflammatory mediators, thus further perpetuating the cycle of inflammation and cellular distress.

Therefore, anti-purinergic support involves interventions that inhibit the actions of purinergic receptors. Consequently, this approach reduces inflammation, stabilises mast cells, and supports healing.

For instance, Suramin has been used to block the effects of ATP on purinergic receptors and has been widely successful in my client base.

Conclusion

The importance of the cell danger response is not in identifying medicines or mast-cell stabilisers but in providing a clear pathway to restore health.

Diagnoses and medications make for lifetime clients and are good for business. They are not necessarily good for health.

Having worked within this model since this paper was first published, it provides a hierarchy that explains how ill health progresses and how we can heal.

We can either wait and do nothing or wait for a disease process. Or we can get busy supporting our body to restore health.

To learn more about the health cycle, read the companion blog post, How to Heal.

Follow me on Instagram and Facebook to continue the conversation.

Additional Reading

Cell Danger Response Theory

Puregenic Receptors

Suramin

Wareham, Kathryn J., and Elizabeth P. Seward. “P2X7 receptors induce degranulation in human mast cells.” Purinergic signaling 12.2 (2016): 235-246.

Sibaev, A., et al. “Iberis amara L. constituents reduce excitatory cholinergic and inhibitory purinergic neurotransmission.” Planta Medica 76.12 (2010): P618.

Zhang, Jun, et al. “Study of baicalin on sympathoexcitation induced by myocardial ischemia via P2X3 receptor in superior cervical ganglia.” Autonomic Neuroscience: Basic and Clinical189 (2015): 8-15.

Shemon, Anne N., et al. “Chelerythrine and other benzophenanthridine alkaloids block the human P2X7 receptor.” British journal of pharmacology 142.6 (2004): 1015-1019.

Ruprecht, Ruth M., et al. “Suppression of retroviral propagation and disease by suramin in murine systems.” Proceedings of the National Academy of Sciences 82.22 (1985): 7733-7737.

Balzarini, Jan, et al. “Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T cell lymphotropic virus (HTLV-III)/lymphadenopathy?associated virus (LAV).” International journal of cancer 37.3 (1986): 451-457.

Hamidpour, Rafie, et al. “Antipurinergic therapy with suramin as a treatment for autism spectrum disorder.” J. Biomed. Sci5.14 (2016): 10-4172.

Mahoney, C. W., et. al “Effects of suramin, an anti-human immunodeficiency virus reverse transcriptase agent, on protein kinase C. Differential activation and inhibition of protein kinase C isozymes.” Journal of Biological Chemistry265.10 (1990): 5424-5428.