I. ME/CFS and Freeze: A Metabolic State of Hibernation That is Not in Your Head (The Cell Danger Response and Polyvagal Theory)

• Chitty: Chapter 6, (2013)
• Fredrickson (2013)
• Levine, Chapter 4, (2010)
• Ogden, Chapter 5, (2006)
• Porges (1992, 1995, 2001, 2004, 2009)
• Schore (1994, 2001)

Sympathetic Nervous System (SNS) Fight / Flight

We are most familiar with the sympathetic branch of the autonomic nervous system, which is the branch that can feel like having a foot on the gas pedal. The sympathetic nervous system enables us to take action in everyday life, and also in the event of threat.

In danger, we can fight, chase off the predator, or flee the hurricane.

In the first minutes and hours of a fight flight responses to stress, our bodies release adrenaline, increase blood pressure and heart rate, augment body temperature and breathing, enhance blood sugar availability to fuel muscles for fighting and fleeing, and increase our immune response (Dhabhar, 2018). This is all aimed at maximizing energy levels to support fight and flight.

And it is all part of the healthy cell danger response.

These changes optimize our ability to survive through escape mechanisms and by warding off infections, healing wounds by clotting more efficiently, and increasing speed and strength.

“[The CDR is a] coordinated set of cellular responses … that evolved to help the cell defend itself from microbial attack or physical harm … and at its most fundamental and most ancient role: to improve cell and host survival after viral attack (Naviaux 2014, p. 7).

The actions of the acute fight flight response are consistent with Naviaux’ acute cell danger response, which is the opposite of what he found in ME/CFS (paraphrased from his 2016 article on ME/CFS):

The acute CDR is found in acute infection, during acute inflammation and in the metabolic syndrome (a cluster of conditions that include high blood pressure, high cholesterol, insulin resistance and high blood sugar levels, and increased fat around the waist area. These symptoms, also known as Syndrome X, are associated with increased risk for heart disease, stroke and diabetes).

In this acute sympathetic nervous system response, our bodies also decrease or suppress functions that aren’t important for immediate survival, such as digestion and rest.

If stress continues for a long time, an increased degree of fight flight arises in which cortisol is released, the immune system is suppressed, inflammation rises and symptoms can occur.

In health, our bodies return to baseline when the stressor goes away or the threat disappears.

In health, at rest, and in play and safety, the sympathetic nervous system coordinates with the other branches of the autonomic nervous system to constantly tweak and maintain just the right levels of blood pressure, heart rate, oxygen consumption, mitochondrial function and other basics that support our ever changing activities of daily life.

In some circumstances, which I’ll discuss later, the sympathetic nervous system remains turned “on” and this acute CDR contributes to disease (Naviaux, 2014).

The Social Nervous System (“The Vagus”)

As introduced in an earlier post by Tim Vaughan on Health Rising, psychophysiologist Stephen Porges’ polyvagal theory  shows that the parasympathetic portion of the autonomic nervous system is comprised of two branches rather than one.

This more evolved branch of the parasympathetic nervous system is present in mammals and humans and is called the social nervous system or the ventral vagus complex (VVC).

The social nervous system is regulated by the parasympathetic nervous system branch called the ventral vagus complex because of where it originates in the brainstem (in the nucleus ambiguous on the ventral or belly-like surface of the brain in the brainstem). Also known as Cranial Nerve X (Ten), the ventral vagus travels from the brain to the facial muscles down to the gut.

It is the faster of the two branches and supports safety and survival in the most metabolically energy efficient capacities we have: those of connection and communication.

If you’ve heard of the ventral vagus, it’s because it is “The Vagus” we refer to when we:

• incorporate mind body practices such as yoga nidra, mindfulness, or meditation to protect or improve our health
• use vagal stimulation as a treatment tool
• take up a hobby or other activity for pleasure
• go on a vacation to slow down and catch our breath

You may also have heard of it because this is the branch that facilitates the survival response of “tend and befriend” (Taylor, 2000).

In health, our social nervous systems are in charge of autonomic nervous system functions and can inhibit fight, flight as well as freeze.

A healthy ventral vagus allows us to connect to ourselves and the world, and to empathize and bond with others, which supports safety through numbers and strength. It also enables people to read others’ facial expressions to assess whether they are safe to approach or should be avoided. This is all part of a highly evolved and built-in survival mechanism.

The ventral vagus allows us to sense into our gut feelings that warn us of safety vs danger, and to communicate using energy-sparing actions through our voices, gestures and facial muscles that show and express our feelings and boundaries.

Through the ventral vagus, for example, babies draw their parents towards them with their big, curious, beautiful eyes, their smiles, and their cries of hunger or discomfort. In health, babies pull at our heart strings to elicit bonds of love and the desire to nurture and protect them. This is all facilitated by the ventral vagus, which stimulates behaviors (cooing, smiling, eye contact), hormones (oxytocin and vasopressin), feelings (love, comfort, pleasure) and more that support feelings of love in both babies and their parents.

This is important because human babies and mammals are born at a very immature stage of development, when it is critical to draw in the proximity and care of adults as a requirement for survival.

Children and adults communicate affection and form protective, supportive alliances through touch, a smile or a conversation. These are actions of the ventral vagus. The social nervous system also supports our defenses with verbal boundaries like “no” or gestures, such as hand signals inviting approach or conveying “stop.”

The social nervous system facilitates all of these functions through the nerves that connect to our eyes, ears, mouths and facial muscles, to our hearts and voices, and through our endocrine, immune and other organ systems.

The ventral vagus makes survival and defense actions possible by placing a gentle brake on our baseline heart rates, which helps us feel more connected and relaxed. This occurs at the cellular and physiological levels and can often be enhanced through mind body practices.

Defenses that use words, eye contact and gestures are energy efficient.

Babies avert their gaze and look away when they are getting too much input, signaling the communicator to stop or slow down. When you talk someone down from raging at or firing you rather than fleeing the office, you are engaging your ventral vagus. The same is true when you stay present and engaged in the middle of a heated or painful argument with a spouse rather than attacking them physically, or disappearing (which would be sympathetic nervous system functions of fight and flight). Our ventral vagus also enables us to use the tone of our voices, such as to soothe a baby who is distressed or calm down a scared animal so that it doesn’t attack. And you may signal “stop” to a stranger who is approaching closer or faster than you are comfortable with before deciding if you need to flee.

This is the way of the social nervous system.

In health, the ventral vagus gently suppresses fight and flight unless it’s truly needed.

In health, our ventral vagus subtly immobilizes us so we can hold still long enough to make love, bond, or snuggle with and care for our babies and children – which is how the most vulnerable among us engage protection through connection.

In health, the ventral vagus can release its gentle brake so our heart rates can rise a little for activities such as standing, walking and playing. This enables us to shift gears without resorting to the higher energy functions of SNS fight and flight systems with releases of adrenaline or cortisol.

The ventral vagus is a critical player in keeping us healthy through energy efficient means.

When ventral vagus functions get interrupted, however, we can end up in states of prolonged fight and flight, hibernation and freeze, or some combination of both.

This is what happens when we have an illness like ME/CFS and feel as though we have one foot on the gas and one foot on the brake. It means that we each have our own, unique, individual version of the same disease. I’ll discuss this a little more after the next section on the freeze response.

The Parasympathetic Nervous System (PNS) Freeze / Hibernation

If you’ve ever gotten light-headed or fainted at the sight of blood or at the sight of a needle (Bracha, 2004), felt as though everything went into slow motion; felt rooted to the ground and unable to move, such as during or after a stressful or scary event (hearing a loud, unexpected sound; witnessing something horrifying; surviving a car accident), you’ve experienced a moment of physiological “freeze.”

As you know, this state was not something you did on purpose, through conscious control, or to “get attention.”

This state is facilitated by the branch of the PNS that acts as a brake in an even stronger manner than the ventral vagus.

Going into states of freeze happens when our other two forms of self protection, fight flight and tend and befriend, described above, are either unsuccessful or unlikely to succeed.

Like c. elegans and other living creatures, shutting down and going into hibernation and other freeze-like hypometabolic states is a CDR pathway designed to maximize survival when fighting, fleeing and connecting are not available options.

As Naviaux asserts in his 2016 article, the state of freeze

is an evolutionarily conserved, genetically regulated, hypometabolic state similar to dauer that permits survival and persistence under conditions of environmental stress but at the cost of severely curtailed function and quality of life (2016, p. e5477).

In other words, the option to freeze has persisted in life forms of all kinds as an evolutionary adaptation to maximize survival.

As mentioned in this video of an opossum in freeze, states of freeze are neither psychological nor manufactured.

In states of freeze, our bodies use the same physiology and produce the same metabolites as c. elegans when it goes into hibernation to wait out a threat it cannot successfully outrun or outgun.

States of freeze and hibernation are facilitated by the second branch of the parasympathetic nervous system, the dorsal vagal complex (DVC).

The dorsal vagus, like the ventral vagus, originates in the brainstem (Porges, Chitty).

The Dorsal Vagal Complex (DVC)

In health, the dorsal vagus interacts with the other branches of the autonomic nervous system and uses its braking function to gently decrease blood pressure, heart rate, and oxygen use. It supports digestion so that we are operating at maximum efficiency, just like an air conditioner that turns on and off to maintain a comfortable temperature rather than perpetually staying on and making it too cold.

In health, the dorsal vagus coordinates its functions with the social nervous system branch and the sympathetic nervous system to support changes in activity levels that takes us from activity to rest, eating to digesting, and back.

In health, the dorsal vagus functions to help us feel calm and available for play and work and rest.

Under threat, the dorsal vagus intensifies its brake.

Even more than fight and flight, the state of freeze is not a conscious choice. It is not a psychological ploy. It is an unconscious autonomic nervous system response of last resort in circumstances we are relatively helpless to address and towards threats that cannot be overcome.

In freeze, the opossum’s heart rate, blood pressure and body temperature actually go down (Gabrielsen, 1985).

These aspects of the freeze state are what the opossum and many other creatures have evolved as a primary defense strategy to fool predators into thinking they are already dead. Predators are less likely to attack when prey is unmoving and already looks dead.

In freeze, our own blood pressure, heart rate, temperature and oxygen levels can also go down. We may feel slow or foggy headed; we may disconnect and watch the event unfold as if we’re standing outside of our bodies or watching from the ceilng; or we may feel numb, limp or unable to move. We may also feel exhausted or too weak to stand.

Freeze states can also flood a body with feel-good hormones and numbness or even euphoria. This is nature’s way of supporting humans (and other animals) so that the pain of a broken bone or a physical assault do not prevent trying to escape and engaging fight and flight if an opportunity arises.

When humans experience states of freeze, our physiologies use the same CDR pathways as opossums and bears and c. elegans.

In freeze / hibernation, our bodies divert energy from eating and digesting to hunkering down and conserving as many resources as possible. Just like c. elegans.

As in c. elegans, the dorsal vagal complex takes humans into states of freeze when other options for survival in the face of threat aren’t available. Our bodies can also go “dorsal vagal” if we’ve had experiences of being unsuccessful at surviving or escaping using fight, flight or ventral vagal functions in the past.

Naviaux explains that dauer / freeze / hibernation physiology occurs as an intelligent strategy, not as a random mistake, mutation or a problem with faulty hardware or software:

• Entry into dauer confers a survival advantage in harsh conditions.
• Entering a hypometabolic state during times of environmental threat is adaptive, even though it comes at the cost of decreasing the optimal functional capacity.
• When the dauer response is blocked by certain mutations, animals are short-lived when exposed to environmental stress (p e5477).

In other words, when the freeze response is not an option, we don’t live as long.

This is the definition of Dauer, which means “persistence or long-lived in German” (Naviaux, 2016, p. e5477).

As Naviaux further explains, when we live in states of relative freeze for prolonged periods, it comes with a recognizable set of changes in our bodies and physiologies.

Dauer is comprised of an evolutionarily conserved and synergistic suite of metabolic and structural changes.

This state makes it possible to live efficiently by altering a number of basic mitochondrial functions, fuel preferences, behavior, and physical features.

Changes linked with hypometabolism run in the opposite direction of the acute CDR (Naviaux, 2016), which, as mentioned earlier, is consistent with sympathetic states of fight and flight.

The metabolites Naviaux identified in ME/CFS patients reflect a fundamental reset in our physiology (to use Cort’s term) that is consistent with freeze. This pathway, opposite to the acute CDR, includes the following:

• energy conservation and death-like states whose primary goal is survival despite the cost
• organism geared towards survival via inaction rather than action, to wait out overwhelming threat
• altered Th1/Th2 imbalance
• decreased immune system ability to fight infection
• loss of antibacterial and antifungal activity
• a “decrease in the ability to restore high-energy phosphate stores after exertion” (this relates to mitochondrial ATP and energy production)
• normal or low blood pressure
• aversion to glucose as a fuel with preference for fat as a fuel (Naviaux, 2016; Lant, 2010) [this suggests why people with ME/CFS may do better with ketogenic diets that use fat as the primary fuel]
• loss of intestinal mucosal integrity and leaky gut
• decreased gut absorption as part of a hypometabolic survival response
• changes in DNA methylation and histone modification that alter gene expression (epigenetic changes, Naviaux, 2014. p. 10)
• stress-induced cholesterol pathways, which are different from routes used in health
• altered mitochondrial function and the finding that:

Mitochondria represent the front lines in cellular defense and innate immunity … Their rapid metabolism makes [them] “canaries in the coal mine” for the cell.” (Naviaux, 2014, p. 9-10)

Low cortisol is another shift that happens as part of nervous system response to threat. Low cortisol is common in late phases of PTSD and in adults with a history of adversity in childhood as well as in their parents’ lives.

Cortisol is measured as part of a physiological / biological response. Like other physiological effects of environmental stressors including psychological trauma and adversity, it is not a psychological effect but a biological effect.

Low cortisol is seen in many chronic diseases such as fibromyalgia, cardiovascular and gastrointestinal diseases, rheumatoid arthritis, psoriasis, and thyroid disease (Lehrner, 2016, p. 268).

Low levels of cortisol are not a problem of adrenal exhaustion but the result of a body responding to prolonged threat in a directed rather than accidental way.

To reiterate, just like Naviaux’ findings, this physiological response is not a psychological effect of trauma. It is one that is driven by changes in the nervous system and linked to unconscious, unresolved perceptions of threat.

Naviaux explains that the high cost of being in a prolonged state of freeze, hibernation or dauer expresses itself as symptoms.

The changes in function listed above translate to many of the problems that are well-known characteristics of this disease.

The dorsal vagal survival state

• reduces energy levels to death-like states
• inhibits mobilization at cellular, mitochondrial, and other physiological levels.
• conserves energy by suppressing states of fight and flight.

Freeze states in humans also inhibit the social nervous system.

Low blood pressure, exhaustion, and other altered physiological processes are all NORMAL aspects and functions of the state of freeze. They are aimed at reducing the body’s energy consumption in order to preserve life as long as possible while we outwait the threat.

So what Naviaux is saying, and what research in the cell danger response and into polyvagal theory and hypometabolic states is saying, is that while the following signs and symptoms can occur in a chronic illness like ME/CFS and are all entirely real, these are not the CAUSE of ME/CFS.

In other words, a hypometabolic cell danger response is an intelligent, physiological, biological, chemical and epigenetic process that has gotten prolonged.

It is a state that has gone from a single location, group of cells, or tissue alarm to a system-wide state of defense that is guided and directed by the nervous system and by functions within our cells.

As a result, ME/CFS, like type 1 diabetes, POTS, fibromyalgia, celiac disease, MS, lupus, asthma, Parkinson’s, autism, Alzheimer’s and a 100 other diseases that Naviaux refers to, reflects a nervous system pattern that is deliberately inciting one or more different types of cell danger responses and all the changes this entails.

ME/CFS is therefore

• not caused by adrenal exhaustion even as adrenal function can be low (low adrenal function supports states of freeze while high function is supportive of fight/flight; both or alternating functions can be seen in ME/CFS)
• not due to a thyroid that is out of whack even as our thyroid activity may be low (low or high thyroid activity supports states of freeze and low energy or fight / flight for survival)
• not primarily from a lack of Vitamin D, nutrients or building blocks that enable mitochondria to function well even as these states can cause symptoms (we may have low building blocks because of poor absorption but many, such as Vitamin D, are intentionally low because the body is more or less sensitive to them in states of freeze, is conserving energy by not producing chemicals that are not absolutely necessary for survival, or is actively removing molecules and chemicals in order to create and preserve a freeze state that needs these factors to be low or absent for optimum function and self-protection) [Naviaux, 2014]
• not directly the result of leaky gut (cell walls in the body and gut are intentionally less boundaried during states of dauer / freeze / hibernation)
• and so on

The question in ME/CFS thus becomes, how do humans get stuck in a state of ME/CFS and freeze, especially if there’s no obvious threat in the present or at the time of onset?

This is where the science of traumatic stress offers important clues. This draws from research findings that most health care professionals and medical care have not yet caught up with – which includes the finding that ME/CFS and freeze are effects of environmental stressors even as they are not psychological.

Individual Expressions of Freeze and CDRs (“Tired” vs “Wired and Tired”)

There are many different versions of freeze and combinations in which freeze can be the dominant problem manifesting as disease and other symptoms.

Tired or more “Pure Dorsal Vagal”

Some types of freeze are the collapsy, death-like, shock-like states that Dr. Peter Levine refers to as “fold,”( p. 49) and that others describe as “faint,” along with many other terms such as shock etc. These states are characterized by feeling tired / exhausted / death-like , having low body temperature, low blood pressure etc, and are the more “pure” form of just the hypometabolic CDR or dorsal vagal state. There are additional variations of freeze I don’t go into here.

Some people with ME/CFS are more purely dorsal vagal.

In addition to the physiologic / immune / gut and metabolic abnormalities mentioned elsewhere, the dorsal vagal state can show up in behaviors, emotions, relationships, dreams as well as in other ways. This is, to be clear, not because it is psychological but because the effects of environmental stressors on nervous system function influence all types of health.

As one example, I regularly had dreams of being completely immobilized for many decades. These night terrors started in childhood long before the onset of my ME/CFS. I would awaken within the dream, thinking it was real, and feel terrified but unable to move, cry out, or wake myself up (dorsal vagal state). I had this dream regularly well into adulthood and it only gradually began to change as I began to heal my unconscious nervous system perceptions of threat. My sleep paralysis states started to shift in parallel with improvements in my ME/CFS.

After a while, in these dreams, I started being able to wake myself up with some effort. Over time, while still in the dream, I was able to sometimes make a sound (social nervous system) and eventually to begin to move. At first, these movements were slow, rubbery and without strength (still a dorsal vagal response).

Eventually I was able to mobilize and run in some dreams. In others I was actually able to strike the attacker in a solid, strong, effective way (sympathetic fight / flight). It’s been a long time now since I’ve had any versions of this dream and my ME/CFS is doing much better as well.

Wired and Tired: A Combination of Freeze and Underlying Fight/Flight

Other people experience a combination of both fight / flight AND freeze, in which freeze is the dominant and most visible form and set of symptoms, but suppresses an underlying state of heightened fight /flight.

This makes some people with ME/CFS feel both wired AND tired at the same time.

If you have ME/CFS and also have high blood pressure, diarrhea instead of or in addition to constipation, the metabolic syndrome with insulin resistance or high cholesterol or being overweight etc, or if you tend to feel more “wired and tired” than “tired,” this is consistent with a freeze state that dominates over a state of overactive fight/flight.

This is an example of a system that has components of both types of CDRs: both the hypometabolic and the acute CDR sympathetic nervous system response.

This is what is seen in the gazelle that suddenly shifts from running at full tilt (sympathetic flight) and collapses just before the cheetah pounces on her (dorsal vagal fold).

Her body shifts into parasympathetic when her nervous system perceives that she cannot survive the chase by running. Her nervous system tells her body to shut down, she collapses and immobilizes, and this provides a numbness and disconnection that make death painless, even if she gets munched.

Underneath this immobility, however, her body is primed to go from 0 to 60 in a moment’s notice should the cheetah get distracted long enough for her to escape (you see an example of this shift out of immobility to escape in this video of the gazelle).

Naviaux does not talk about this combination of CDRs in his 2016 article but does refer to 3 different types of disease states based on which type of CDR and which stage of healing the body is in (2018). Such mixed states are well known in the trauma literature.

Oscillating Between Freeze and Flight/Flight

While some people with ME/CFS have symptoms that are predominantly purely dorsal vagal or dorsal vagal combined with fight flight, some oscillate between various combinations of fight flight, and freeze / faint / fold.

This has been found in PTSD research, where a person can be in a state of fight flight (hypervigilance, high blood pressure, states of high blood clotting factors, or rage) in one moment, and in exhaustion, collapse, immobilization, low blood pressure, cold body temperature or depression, in the next. I’ve felt it in myself and seen it happen with clients when I was still learning how to catch early warning signs or anticipate this reaction that could happen very suddenly.

But the science is showing that such variations in symptoms are an effect of environmental stress and resulting perceptions of threat in the nervous system that are not psychological.

In other words, nervous system changes towards hibernation and freeze as well as fight flight are just as real in humans with ME/CFS and other chronic diseases as they are in c. elegans and other animals.

To offer another example, I have long had a predominantly dorsal vagal imprint with my own ME/CFS with a long history of low blood pressure as one example (varying between about 90/60 to 100/70 when normal is considered 120/80).

As I recover, my blood pressure has very gradually increased to within the more common ranges (It was 118/76 at my annual exam in September 2018, which is the highest it’s been in 20 years since the onset of ME/CFS). I also have had more and more irritability alongside the fatigue as my health has improved (emergence of an underlying state of fight flight).

Another impulse seen in the ME/CFS community is a profound impulse to escape, such as to some quiet place. I had such an impulse when I practiced medicine and life was too overwhelming and hectic and stressful.

The craving arose around the onset of my first fatigue attacks 20 years ago. I fantasized about finding a job in the middle of a national park somewhere, monitoring for forest fires and holing up in a tiny tower high up on stilts, away from everyone and everything except the quiet of nature.

This has components of flight but as a strong component of the health within the dorsal vagal freeze response that craves quiet, stillness and avoidance of social contact, which can support the process of healing (see Levine, 2010, Chapter 4).

What Causes Prolonged States of ME/CFS and Freeze / Hibernation?

Our defenses are adaptive and occur at multiple levels, including the cellular level and through physiology such as heart rate, energy levels and gut function. These mechanisms are meant to ensure our survival.

But while humans, like other animals, are designed to recover from infections, exposures to toxins and life’s other adversities given enough time and support, experiences severe enough to trigger a freeze response put people at risk of getting stuck and resetting into prolonged physiological states of survival. The result is a body caught in CDR pathways with symptoms that express themselves as chronic diseases such as ME/CFS.

When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results (Naviaux, 2014).

The field of trauma research in humans and animals has found that bodies and physiologies can get stuck in states of defense when the nervous system does not realize the threat is gone and the danger is past.

In the wild, animals that have just escaped their predators discharge their states of fight, flight and freeze, often by shaking or trembling. We experience this as humans too. It may be barely visible to the naked eye or overt as in this youtube video of a gazelle in a freeze state, emerging from the immobility with chaotic-looking shaking movements and then escaping by running away.

When this natural process of releasing a defense response is interrupted, delayed or prevented from happening – as frequently occurs in our human lives, such as when we fill out a police report after an accident, when childhood abuse or emotional neglect persists through many years, or when we undergo surgery and wake up to bright lights and bustling, efficient personnel that don’t quite connect with us – our brains may not get the message that we’ve survived the threat. In such events our bodies can default to freeze states as an adaptation response, just as c. elegans does in a drought or conditions of low oxygen:

These [prolonged metabolic CDR] pathways … suggest a postexposure adaptation in response to pathologically persistent or recurrent cell danger signaling (2016, p. e5477).

What we’ve learned from research in traumatic stress is that, when our brains don’t recognize that the threat is gone or the danger has passed, they maintain their states of defense to maximize self-protection and survival. This is what stimulates our brains to reset from healthy social nervous system functions to temporarily lose the ability to suppress and regulate fight, flight and freeze.

A symptom of this reset often includes a loss of our sense of connection to ourselves, to others or to our sense of belonging in the world. In other words, when our nervous systems shift into defense responses, our brains often disconnect and we feel alone.

These changes in physiology reflect a persistence of the CDR pathways. They don’t usually happen out of the blue but instead occur following a gradual accumulation of exposures throughout our lifetimes. The reset happens after one final “last straw,” which is the exposure that resets our nervous systems.

The CDR shows up in slightly different ways for each of us based on our accumulation of life exposures and adversities.

It may look like ongoing states of of fight and flight for some of us (metabolic syndrome, type 1 diabetes and others per Naviaux, 2014), as prolonged states of freeze for others (ME/CFS, depression, and other chronic illnesses), or as some combination of the two in which we either alternate between too much gas and too strong of a brake, or feel both at the same time even as the brake covers over symptoms of ready-for-fight-flight-in-the event-of-an-opportunity (also experienced in some of us with ME/CFS; Fibromyalgia? ).

In time, CDRs create symptoms of ME/CFS and other chronic diseases. We can have more than one set of symptoms and diseases based on the characteristics of the CDR our autonomic nervous system is expressing.

The CDR is initially adaptive and coordinated by the close interplay of mitochondria and the cell, but becomes maladaptive once the environmental danger is gone.

ME/CFS and Freeze are States of Adaptation That Come at High Cost in Humans

As Naviaux describes (2016), c. elegans expresses metabolites of hibernation in situations that it cannot outrun or successfully overcome through action – conditions such as cold, lack of food or oxygen, and other threats.

Our autonomic nervous systems use the same CDR pathway in situations we cannot escape or successfully overcome either. Experiences such as

• environmental stressors such as exposures to infections, toxins or chemicals, especially early in life are risk factors for many autoimmune and other diseases. They also trigger the cell danger response (Naviaux, 2014; 2016; 2018) and increase risk for autonomic nervous system perceptions of threat and the possibility of developing prolonged defensive responses (Naviaux; Chitty, 2013; Levine, 2010; Porges, 2004; Ogden, 2006; Schore, 2001, and others)
• a difficult environment in the womb (low oxygen, maternal emotional stress and fight flight freeze in her own system, or maternal physical illness, etc, which babies in the womb cannot escape by “connecting”, fighting, or fleeing, other than through premature birth) (Calkins, 2011; Sandman, 2018)

• a difficult or premature birth (these represent inescapable stressors that can be life threatening) (Sandman, 2018; Ridout, 2018)
• incubator care after birth and other events that increase separation of mothers from their babies (which can therefore interrupt the ventral vagus and elicit dorsal vagal complex responses in both individuals) (Hofer, 1994; Klaus & Kennell, 1976; Madrid, 2005; Moore, 2017;
• losing a parent in childhood (such as through divorce or death, which elicits feelings of loss and potential life threat to a child and cannot be fought or escaped) (Felitti, 1998; Hughes, 2017; Jackson Nakazawa, 2015)
• growing up with a depressed parent (depression is generally associated with significant distress that makes it difficult to offer the safety of nurturing, loving connection or even physical care)
• overt trauma, such as childhood physical, sexual, emotional abuse or parent who is an alcoholic (Dube, 2009; Romens, 2017)
• having a debilitating or life-threatening illness such as ME/CFS (Alonzo, 2000)
• and more.

In humans, the common factor that triggers the persistence of a survival state of fight, flight or freeze is initiated by experiences that elicit a degree of helplessness. This is the inherent definition of trauma that differentiates it from stress.

From neurologist Robert Scaer, MD (2001, 2005):

Any negative life event occurring in a state of relative helplessness—a car accident, the sudden death of a loved one, a frightening medical procedure, a significant experience of rejection—can produce the same neurophysiological changes in the brain as do combat, rape, or abuse. What makes a negative life event traumatizing isn’t the life-threatening nature of the event, but rather the degree of helplessness it engenders and one’s history of prior trauma

Experiences of relative helplessness elicit the freeze response since fight and flight and communication are not effective solutions.

The experience of an infection or exposure to a toxin can trigger a similar biological overwhelm and autonomic nervous system perception that fight flight and ventral vagus are insufficient methods for addressing the threat.

In health our autonomic nervous system responds to threats of all kinds by first using the most evolved survival mechanisms of connection and communication through our ventral vagus. If ineffective, it next implements states of mobilization through fight and flight. When neither are options or effective solutions, our autonomic nervous system resorts to states of freeze.

The science of traumatic stress explains how survival states of nervous system function can persist even after a toxin, infection or other environmental stressor is gone. And even when the threat seems small.

Why Exhaustion and Other Symptoms Persist in ME/CFS

When our brains believe we’re still in danger or under threat, they maintain survival states.

In the case of ME/CFS, this means our brains may insist on remaining in states of hibernation until our autonomic nervous system gets the message that it’s over, that the threat is gone, and that we’re safe.

At that point, our bodies can let go of survival states to come back to the responsive, moment-to-moment dance that reflects ongoing, fluctuating, adaptive interactions and balance between all three branches of the nervous system.

What both Naviaux and trauma science help to explain is that, while a serious disease like ME/CFS may begin after an environment stressor such as an infection, a vaccine or a stressful or traumatic event, this trigger is the final straw in a series of life long exposures rather than the single or actual cause of the disease.

As Naviaux reiterates, the symptoms of ME/CFS are not indications of broken mitochondria, faulty genes or nutrient deficiencies as much as they represent the effects of an organism hell bent on maintaining low energy states of hibernation and freeze in all ways available (cell function, physiology, behavior, emotions and more).

In my next post, I’ll build further on Naviaux’ work to describe what we now understand about how exposures and life experiences – infection, loss of a parent in childhood, abuse, a difficult birth, a vaccine –  can lead to ME/CFS in some of us, and not in others. I’ll describe research that sheds light on why the stressor that triggers onset of ME/CFS can seem completely minor or not even threatening, and why flares can occur with similarly negligible stressors.

Related Posts

IIA. ME/CFS and The Cell Danger Response: How the CDR Gets Stuck in Freeze

IIB. ME/CFS Surveys (The Cell Danger Response and Hibernation Series)

For more, here’s my story with ME/CFS and how this lens makes sense of my symptoms and is helping me to heal. You’ll find a sampling of books and therapies for working with the autonomic nervous system (it’s not because it’s in any way “your fault”). These are not cognitive behavioral therapies nor about will power and can help address effects of environmental stressors even if they happened decades in the past. I’ve also shared how healing complex PTSD (ACREs) helped me recover from food intolerances and how it affects my triggers and flares.

Here’s a detailed summary of the nervous system in chronic illness that is also an overview of my blog. I have additional free downloadables on this page.

Find how to figure out which approaches to use from 11 tools I recommend.  Take a look at the 2020 memoir by Sarah Ramey that skillfully, compassionately, clearly and with humor pulls it all together for those with all kinds of mysterious illnesses from a similar view, including how frequent infections and antibiotic use also contribute to risk, in The Lady’s Handbook for Her Mysterious Illness: A Memoir (which includes a vital perspective on the loss, suppression, blaming of the “softer,” sensitive, feeling, feminine aspect in all of us, men and women).

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