In Part 1 of this post, we covered the basic science of the mitochondria and the causes of cell danger response with in the cells and organ systems. Next we are going to help you understand the different stages of this cellular response and the chronic effects of it if it does not naturally resolve. Furthermore, we are going to touch on some ways to support the body (and particularly the mitochondria), through recovery and healing.
The Phases of CDR
CDR, when acting normally in healing and adaptation, undergoes three phases. Once the third phase is completed, you have a genetically more resistant, stronger cell with more adaptability to threats. As we look at the three phases, we will also explore what occurs if we get stuck in one cycle of CDR and don’t complete the healing process.
CDR1 (phase 1)
In the first stage of CDR, the cells activate the innate immunity when they encounter a stressor, pathogen, toxin. By doing this, the hope is to overcome and neutralize the threat and do damage control in the process. The goal of this phase is to clear infections, clean up toxins and repair injuries that occur from them.
During this phase, the mitochondria are changing very rapidly. They switch from their usual anti-inflammatory form/process to a pro-inflammatory form which helps with containment of the threat and damage control. The metabolism switches from using oxygen to storing it and making energy from ANaerobic glycolysis (non-oxygen using energy production), with the goal of preventing cell death.
Disease that occurs when stuck in CDR Phase 1:
(Increased inflammation, damage control, anaerobic (not using oxygen) metabolism dominates)
CDR2 (Phase 2)
For every organ system, we have a specific number and diversity of differentiated cells. When we lose some of those cells by normal cell death in the innate immune response, these have to be replaced with healthy functional cells. During the second stage of CDR, the goal is to provide the resources to replace lost cells and maintain the overall function of the organ.
The process here involves 1.) recruitment of new stem cells containing healthy undifferentiated mitochondria 2.) recruitment of fibroblasts/myofibroblasts to rebuild collagen and renew tissue, 3.) restoration of cell to cell communication.
Stem cells have the ability to differentiate into any cell type depending on the cells in their environment and they also bring with them new mitochondria that can help restore the balance of function back to cell energy production so that new cells can form. These new mitochondria from the stem cells help push the energy production back into its normal dominant form – aerobic glycolysis (oxygen-using energy production).
Once adequate cell formation and restoration is completed, cell to cell communication is restored. This then allows the mitochondria to move into the next phase of cell danger response.
Disease that occurs when stuck in CDR Phase 2
(Cell proliferation predominates to replace lost cells- but the cycle doesn’t stop)
CDR3 (Phase 3)
In this stage, the cells have finished the process of dividing and reestablished communication with their neighbors, but now the new cells need to learn to be incorporated into the organ system. They need to learn metabolic memory and detoxification and all the processes of pain and sensory modulation. They also need to learn from the new information brought on by the changes that occurred when the cell overcame the recent threat. This learning enhances their adaptability to future threats, which is what we call enhanced adaptive immunity.
The mitochondria return to their normal anti-inflammatory stage of energy production and metabolism, gene expression and detoxification.
That’s a lot of cellular science, but the short story is this: the newly created cells need to know how to be a functional part of the whole system. The end of this stage of CDR leads to newer, healthier cells with a better capacity to handle future stress, infection, injury or illness.
Disease related to being stuck in CDR Phase 3
(New cells specialize and learn organ specific functions)
Making it relevant!
To bring it all together simply: when the cells encounter a biological, chemical, physical or psychological stressor the body responds with CDR. What you might feel if your body is in this healing cycle is fatigue, fever, depression. These are natural, short-lived (days to weeks) responses of the body to overcome the threat.
The other big issue is that when the body encounters constant low grade toxins (chemicals, mold, ect), it lowers the threshold for CDR, making it easier for our bodies to quickly cycle into the defensive metabolism of the mitochondria and stay there. So, again we see a pattern emerge about the risk of chronic toxin exposure and our need for healthy detoxification.
Neuroborreliosis/Neurologic Lyme Disease (and CFS/ME)
Lyme Disease is a complex syndrome with three stages: early localized disease, early disseminated and late disseminated disease. The late disseminated disease is characterized by arthritis, severe headaches/ migraines, vertigo, dizziness, insomnia/hypersomnia, brain fog/poor concentration, numbness in the extremities, poor regulation of blood pressure, severe fatigue and cognitive processing issues. These symptoms are similar to those found in Fibromyalgia, Chronic Fatigue Syndrome (CFS)/Myalgic encephalomyelitis (ME), but the difference is that the root cause (infection by the borrelia spirochete) is known.
In this situation, the mitochondria and cells are stuck in CDR (phase 1) and become hypometabolic, not producing ATP for the energy of normal cellular function. The hypometabolism of the cells leads to the symptoms mentioned. What’s worse is that when we get stuck in this state of hypometabolism, we end up with prolonged stimulation of fight or flight. This is worsened when the body encounters additional environmental threats.
Some also experience freeze syndrome, which occurs when the parasympathetic (rest and digest) and sympathetic (fight/flight) are simultaneously activated. It is what happens when someone describes “being paralyzed with fear.” The brain essentially shuts down for our bodies to cope with the stressor, leading to dissociation.
In both of these situations, prolonged fight or flight or prolonged freeze syndrome, the body is experiencing ongoing perceived threat and continues to cycle in CDR1, unable to ever regain normal cellular function. When this persists, there is a significant increase in risk for disease.
Childhood Behavior Disorders (Autism, ADHD, PANS/PANDA)
If you are the parent or family member of someone with autism, ADHD, PTSD, PANS/PANDAS, you have likely seen that these individuals experienced heightened response to sound, temperature and shock, also demonstrating the increased fight or flight and freeze responses we discussed above. This is due to the connection with being stuck in CDR phase 3 during which the cells learn metabolic memory and detoxification and all the processes of pain and sensory modulation.
Consider in children, whose cells are rapidly dividing for growth- if the mitochondria do not properly return to a stage of energy production and fail to complete the cell danger stage of sensory and pain modulation and memory, you will find an individual who struggle to properly integrate what they are experiencing in the world around them. They also remain in a heightened state of energy producing abnormal amounts of cortisol and adrenaline, leading to chronic inflammation and elevated heart rate, blood pressure and inattention as well as a failure to connect to others.
Remember that the highest concentration of mitochondria are in the brain and nervous system, right?? Well, consider when THOSE CELLS go into cell danger response and do not cycle out of it…This leads to brain inflammation, poor communication between new neurons, disrupted circadian rhythm, poor glymphatic drainage from the central nervous system. (The glymphatic system is responsible for removing toxins from the central nervous system and is activated during REM sleep.)
Prolonged CDR in these situations in children can lead to Autism, ADHD, PANS/PANDAS. In adults, it looks like Parkinsons, dementia, alzheimers. In both situations, it is important to support the mitochondria in completing the normal cycle of CDR, to create more healthy and robust cells.
Addressing Cell Danger Response
Clearly cell danger response has wide reaching effects on the body and predisposes us to chronic disease, so the obvious question is this: “ How do we fix it??” What I hope you see from this series of articles is that the root cause is deep inside the cell and needs to be addressed by supporting the normal health of the cell.
Since we know that the triggers for CDR are biological, chemical and emotional stressors, we need to start there. A little investigation work needs to be done to identify the root cause of the stress- is it viral/ pathogens, nutrient deficiencies, chemical toxins, heavy metals, physical or psychological trauma? Once we address the root cause of the stressor, we can BEGIN to put our body into a healing state.
The mitochondria can be supported to proper health and healing by reducing stress, regular low intensity exercise or movement, intermittent fasting, high density, nutrient rich foods, red light therapy, infrared sauna and supplements to support mitochondrial health. Some supplements that are useful for mitochondrial support include quercetin, co-q-10, alpha lipoic acid, resveratrol, NAC, glucosamine, omega 3 fatty acids, green tea extract, B vitamins and creatine.
For more information or a tailored approach to your personal health concerns, reach out for a free 15 minute health consultation.
If you want to go a little deeper, for our history nerds…..
Some Historical Background- For those who really want to NERD out!
For the few history buffs out there, I have provided some background scientific discoveries which led to our current understanding of CDR. Though cell danger response in name is a relatively new concept, the foundation of this research is not new at all. As our technology improved with things like electron microscopy, which allowed us to see deeper inside the cell, we were able to identify more of what was first
1902: Sir Archibald Garrod’s report of the Mendelian inheritance: This refers to the passing of traits via chromosomes in dominant or recessive manners based on the parental chromosomes. So, the parent’s genetic code, corrupted or uncorrupted, is passed onto the child.
1964: Based on Sir Garrod’s research, an understanding of inborn errors in metabolism developed and was first fully described by Dr. Nyhan, who published the first example of an inherited defect. The defect was in the metabolism of purine, which led to profoundly altered behavior in children. It was given the name Lesch–Nyhan Disease. Just a few years later he published the first example of a child with autism-like behaviors resulting from an inherited increase in purine synthesis. (Lesch and Nyhan, 1964). What is purine? ATP, ADP (and a few more)- those energy-giving foundational elements that are created in…… the mitochondria.
1972: Geoffrey Burnstock described how these same purines can act as independent signaling peptides, like neurotransmitters. The receptors for them were later identified in every cell in the human body.
1994/1998: Polly Matzinger and Ephraim Fuchs developed the cell danger model that described immunoreactivity, which helped show how the cell made certain proteins in response to threatening stimulus. This helped explain why effective adaptive immune responses (good ones) are best mounted under conditions of cell danger and injury. It also gave us an understanding of how CDR- in the right conditions- was a good, helpful function of the cell to develop and adapt in a threatening environment and to create a more resistant, tolerant and healthy cell.This research was important for immunology because expanded our understanding of the way the immune system is affected by CDR.