Last week I wrote about the #MeToo hashtag and discussed the way that abuse influences biology. I mentioned that ‘fight, flight or freeze’ are our default responses to threats – and that these responses don’t just take place on the surface level. Instead, the instinct to fight, flee or freeze emanates from deep within the nervous system and, as such, permeates throughout the body, having widespread physiological consequences. This instinct can also leave scars.
The fight/flight/freeze reaction changes biochemical patterns. Our bodies learn how to interact with the world through the interactions we have with it. When we are exposed to threats, the default approach to life itself becomes fear-based. Sympathetic nervous system reactivity becomes the norm. We learn that life itself is threatening and we react accordingly – having a whole-being response to life which is one of fight, flight or freeze.
Last week I discussed ‘fight’ – the first response of the sympathetic nervous system. This mode affects the immune system, the sentry guard of the body – the system of the body which fights external invaders to keep us safe. When this system is upregulated by the presence of external, invading threats (abusers) this creates immune dysregulation and dysfunction. This can lead to autoimmunity (self attacks) and hyper-immunity (attacking everything you come into contact with).
Today, I want to discuss the ‘freeze’ response – entering into a pattern of stagnation as a means of self-protection. This isn’t just about standing still, this is about how such stagnation responses can become cellular, changing our biochemistry.
This is the realm of epigenetics: where external experiences and environmental triggers alter gene expression and cellular function. When it comes to the epigenetic cellular reaction to extra stress we are talking about the “Cell Danger Response”.
A Primer on Cell Danger Response
One of the best papers providing an overview of the Cell Danger Response is linked here. I will provide an overview below.
The Cell Danger Response is described as an “evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical or biological threats that exceed the cellular capacity for homeostasis.”
Homeostasis is best thought of as the body’s innate ability to bring itself back to centre, or balance, after facing a stressor or situation which creates off-balance states. Homeostasis is what keeps your temperature within a fairly narrow band, irrespective of the temperature outside. It is what keeps the level of glucose in your blood at about the level of a teaspoon, irrespective of what you eat. It is the way we revert to the mean after we’re pushed to the extremes.
When something is distressing enough to create metabolic or chemical dysregulation, homeostasis is lost. This, in and of itself, is not an issue – we are designed to be pushed beyond our limits and we have a whole host of mechanisms in place to fight/defend/protect, should this cellular capacity for homeostasis be exceeded and these were discussed in my last article about the immune system. The ability to pull ourselves back into balance, to turn OFF stress responses, is as important a part of our biology as the mechanisms which turn ON the responses.
But beneath a release of immune and inflammatory chemicals, when our bodies are under threat the very cellular function and biology is altered. The paper cited above gives a very complex explanation, but the simple version is that all cells work on signalling pathways which involve the uptake and release of compounds into and out of the cell.
Human bodies regulate metabolism and energy production using intricate feedback mechanisms based on “if this, then that” reactions. One of the most important of these signalling pathways is purinergic signalling. This is the alarm bell response of cells – it’s how cells are informed that there is a threat and they need to fight.
Purinergic signalling tells cells to release ATP and ADP (these are the energy currency of the cell), Krebs cycle intermediates (the Krebs cycle is what makes the energy within the cell), oxygen and reactive oxygen species (these are ‘free radical’ compounds which are sometimes referred to as pro-oxidants). So far, so normal – this cellular signalling and response is literally called the “Cell Danger Response”, or CDR.
As I said above, this is a biologically advantageous mechanism that has been preserved throughout human evolution.
The problem with the CDR is that there is a delicate interplay between this response, and the response that is designed to bring down the CDR. Anti-inflammatory and restorative/regenerative pathways exist to change the signals, bind and eliminate the reactive oxygen species – and essentially reverse the efflux (rapid exiting) of all of the energy molecules (ATP, ADP and the bits for the Krebs cycle which can make ATP) from the cell.
It is postulated that prolonged CDR leads to a drastic change in cellular biology. Instead of taking in nutrients and making energy, cells become stuck in a kind of stasis which minimises energy influx and efflux. Cells stop taking up energy, stop creating energy. Things get stuck. We are, effectively, ‘frozen’.
To describe the CDR I often use the analogy of an animal ‘playing dead’ in order to hide from predators. The cells are stuck in a halfway house between living and dying, maintaining life but respirating only minimally so they could pass for being dead, thereby protecting them from external threats.
A dysregulated CDR is one that remains active long after the actual threat has passed – and one that keeps the cells in this minimally-active state for MUCH longer than is appropriate or necessary. The consequences of this are mass dysregulation – most notably chronic illnesses such as chronic fatigue, mitochondrial dysfunction and the whole host of illnesses which stem from this.
Epigenetics, Chronic Illness and the Cell Danger Response
The profound impact of CDR and its link to chronic illness may be obvious from the scientific explanation above. However, it is always extraordinary to me whenever I look at this response just how many functions are affected. It shouldn’t be surprising – we are literally all made up of cells and cell signalling. But when you look at how biology and biochemistry change when this “I am under threat” switch is left in the ‘on’ position, it becomes more apparent than ever how important the messages we get from the outside environment are.
It is external signals – cues from the world that surrounds us – that can tell our biochemistry how to react, how to behave: how to keep us safe. This relationship between how the outside affects our internal workings is known as ‘epigenetic regulation’ and it can literally change the way our DNA behaves. We are learning more and more about the epigenetic regulation of cellular function – and the impact is much broader than just CDR and stress responses.
However, when it comes to looking at CDR, it is the presence of epigenetic stressors which entrains this response.
The precise “how” CDR shifts energy flux is phenomenally complex. It involves understanding mitochondria, electrons, voltage potential of cells, calcium and sodium shuttling, electrolyte balance and a whole host of factors which can be read in this linked article, but are far too detailed for here.
The consequences of this cellular shift, however, are that through cell membrane stiffening, the swapping of electrons, the upregulation of the production of reactive oxygen species and the loss of calcium regulatory control – mitochondrial efficiency is drastically reduced. A cell whose mitochondria starts functioning more slowly is a cell which does not create energy.
A cell which does not create energy creates a human in a kind of stasis. Here, we have the ‘freeze’ of the threatened response.
The illnesses that occur when cells enter into the CDR state might be (this is still speculative) anything from the following list:
- Chronic fatigue syndrome
- Mast cell activation syndrome
- Attention Deficit Hyperactivity Disorders
- Gluten and many other food and chemical sensitivity syndromes
- Tourette’s syndrome
- Bipolar disorder
- Post-traumatic stress disorder (PTSD)
- Chronic traumatic encephalopathy (CTE)
- Traumatic brain injury (TBI) – the lasting effects
- Suicidal ideation
- Alzheimer and Parkinson diseases
- Autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis
Yes… really… when cells get threatened they can isolate themselves from the rest of the body. Cellular senescence – where the immune system kills self-cells it realises are damaged – fails and the normal regulation systems of the body go awry. This can lead to literally any condition – mitochondrial dysfunction is at the heart of every condition listed above. Obviously, all of the above conditions can stem from other ‘causal’ factors – but as they are all linked with mitochondrial dysfunction this means that CDR can also lead to these illnesses.
The Messages Which Stimulate Cell Danger Responses
One of the major triggers for excess upregulated CDR is viral load and toxin overload. This is the classic post-viral fatigue story, common after infection with Epstein-Barr Virus, or Glandular Fever. It is also the common response after exposure to mould or biotoxins, or a lot of pesticides or organophosphates. It’s a cellular response which gets turned on in response to threat and stays on as long as that threat is felt to be there – occasionally long beyond.
But then there are the other environmental triggers – the subtle societal ones that perhaps aren’t validated in the literature, but in all honesty can be more pernicious. These are the #MeToo moments – the abuse moments. This is where the Cell Danger Response gets triggered because an individual’s sovereignty over their body is literally under threat.
Worryingly, the threat doesn’t need to keep happening in order for the CDR to be left ‘on’. If the body believes that the only safe state is to stay alert, which is a common response after a serious threat has been experienced, the continued presence of the threat is immaterial. The damage is done.
When I deal with CDR in my clinic I find myself more often being drawn into the patients’ abuse and trauma histories, as opposed to their viral exposure. In fact, in my experience, when the complex protocols and supplements we have to fight viral loads, historic toxicity, heavy metal burdens and gastrointestinal endotoxin levels fail, it is always because the CDR response was really triggered long before the viral/toxin load hit.
In fact, I would argue that the strength of hold that any viral or toxin load can have on individuals is, in part, genetic – but in larger part it is to do with cellular patterning already in place due to abuse, trauma or adverse child experience history.
I have also found that this CDR response is most pronounced in those for whom an original trauma experience was accompanied by the sense of being trapped, unable to fight, not allowed to escape. The sense of impotence in the face of threat is a powerful conditioning force – and one that I have seen, time and time again, to lead to an upregulated CDR.
When abuse is prolonged, or even when different threats crop up over a period of time, the impression that life is unsafe is confirmed. The need to retain the state of CDR is confirmed with every exposure to threat. In the climate that we have recently learned is prevalent – the environment in which people cannot trust those around them to respect their personal space – it is easy to see how CDR has become common. Couple emotional trauma with the ever-increasing toxic load in the environment – and you have the perfect recipe for chronic illnesses.
This is how the #MeToo movement can play a large role in the illnesses that I see in my clinic – in particular those which revolve around fatigue states and the susceptibility and vulnerability to the viral and toxic load in the modern environment.
Next week I will cover how #MeToo experiences lead to the third manifestation of the sympathetic nervous system – flight. Running away may seem to be the opposite to freezing, but in truth it emanates out of the same cellular need to change metabolism in order to self-preserve.
And if anything within this article, or last week’s, has resonated for you – do sign up to receive my updates. My fourth article in this #MeToo series is going to discuss what to actually DO about these responses and how to change the biochemical patterning – whether fight, flight or freeze – that can happen in response to #MeToo abuse.