The Stress Continuum and NEM Response

By: Dr. Michael Lam, MD, MPH; Dr. Justin Lam, ABAAHP, FMNM



The stress continuum and your doctorOne of the greatest challenges in clinical medicine is the clinician’s ability to take clues from the body’s stress continuum, presented as signs and symptoms, and translate them into a diagnosis that accurately reflects the underlying pathology. Once a proper diagnosis is made, a solution is relatively straightforward for the most part. The most challenging cases are often those which appear to defy conventional medical logic, cannot be compartmentalized, and where laboratory tests appear to be normal or insufficiently strong to pronounce a straightforward verdict.

For example, it is relatively easy to make a diagnosis of diabetes if the fasting blood sugar is over 140 mg/dl (normal under 125 mg/dl) and the HBA1C exceeds 7.0 (normal under 6.5 mg/dl) What about those who are otherwise normal but with a slight hypertensive history, a positive family history of diabetes, and generally in good health, but have fasting blood sugar of 120 mg/d; and HbA1C of 6.3 mg/dl? In the past, these factors were considered “normal”. Patients were sent home. In recent decades, research has shown that many chronic diseases exist in a continuum of ranges from mild to severe – whether it be diabetes, chronic fatigue, depression, hypertension, autism or even Alzheimer’s’ Disease. The compartmentalization approach of “all or nothing” is an incomplete thought process when it comes to such conditions because it is too simplistic a view of how a diseased state affects the body.

Until recently, fibrocystic breast disease, endometriosis, uterine fibroids, and PCOS were thought of as independent entities. We now know they are all an expression of the same underlying condition called estrogen dominance. It is clear that chronic disease does not exist in a vacuum. The progression, whether it be classified in stages, phases, or steps, all point to the same psychological construct, that disease and conditions are progressive in nature. Autism has now been renamed Autism Spectrum Disorder, for example.

Such progression has been researched in great detail with regards to Adrenal Fatigue Syndrome, where the body progressively advances through various symptoms from stages one through four as the condition worsens. Each stage of the condition presents with different but overlapping symptoms. Reversal and recovery efforts are necessarily different because in each stage, the body’s underlying health and response may be very different. Using the same approach, regardless of what stage a sufferer is in, is a sure recipe for failure. In fact this is a common clinical mistake and accounts for the majority of clinical and self navigation errors.

There are multiple components and circuits that govern the body’s overall response to stress. It is way more than the adrenal glands and sympathetic nervous system that is involved. While the adrenals are an important anti-stress regulatory center, the body has additional systems in place concurrently. Indeed, such systems appear complex and convoluted on the surface. However, on deeper study, one can see that there is a logical and systematic holistic response available to the body to help restore harmony. Focusing on a single organ or system dysfunction can blind us to the big picture. This narrow focus is a common clinical mistake.

The big picture is the stress continuum responsesLet us accept that the body is seldom (if ever) wrong. It is us who have failed to see the forest because we are so focused on the trees. Our specialization has blinded us at a time when we need to be a generalist. If we are able to let go of our pretenses and look from afar at the big picture, it is crystal clear that the body’s staged NEM response to stress is a defense system masterpiece fortified with redundancy to ensure survival of our species. Symptoms can range from annoying to downright unpleasant and incapacitation can even result ultimately, but these are the body’s only ways to alert us of a problem within.

Our body, when it comes to handling stress, is far more wise and comprehensive we think. Multiple systems and organs are involved. This is in stark contrast to our myopic vision of assigning it only one system such as the hypothalamic-pituitary-adrenal (HPA) hormonal axis, for example. As far as the body is concerned, the fact is that no single organ or system can fully do all that is necessary, all by itself, in times of stress. Overcoming stress is a team sport, requiring each player to contribute to the overall success. The body’s orchestration of the neuroendocrine and metabolic components and their circuits simultaneously and collectively is miraculous and amazing – to say the least.

The proper assessment of the NEM response stress continuum requires that we first understand that our body’s response to stress spans a continuum from mild to severe, with different responses at each point of the spectrum. Secondly, we need to know that the body uses and place different emphasis on its neuroendocrine component and its metabolic component, depending on the stage of stress. Understanding these two fundamental concepts is the first step towards the healing process.

NEM Stress Continuum

Fatigue and low energy is a physician’s office most frequent complaint and accounts for more than fifty percent. Our body’s built in NEM stress response is activated when stress arrives on our doorstep.

Clinical experience has shown us that the body’s NEM stress response stress continuum is designed to be graded and activated in sequential steps as stress increases. This make perfect sense. The body will not ring multiple alarm bells to warn us of impending danger when only one or a few will do to resolve stress in situations when it is mild – such as having a late night out. The body, however, will relentlessly ring multiple alarm bells available if the fire of stress is rampant and out of control – such as when there is a loss of a loved one or traumatic accident. Different responses are thus activated to match the level of stress perceived by the body. This is good design.

The two major components of the NEM stress response stress continuum, the neuroendocrine and the metabolic responses, are activated in sequential fashion when exposed to stress.

Stage 1 – NEM Response Activation:

the stress continuum keeps us on alertWhen stress is mild, the body’s metabolic response (consisting of the metabolism, detoxification, and inflammation circuits) is engaged automatically in an auto-regulation process, as the first line of defense. Stress induces demand for more energy. This can be accomplished by increasing metabolism. The body does exactly this. Extra energy generated keeps us on alert mentally and physically – ready to escape the threat of stress – whether it be physical or emotional. Our body’s becomes inflamed as part of this response and protection process. The purpose is to remove unwanted and harmful stimuli (including damaged cells, irritants, or pathogens) quickly and begin the healing process. Stress induced free radical damage are quickly and automatically removed by our detoxification system. Reactive metabolites are kept to a minimum, well within the capability of the body to store and handle. The three metabolic circuits collectively help to quickly restore the body back to equilibrium or homeostasis, working within their capacity behind the scenes. Symptoms are mild if any. A sense of tiredness may be experienced, but generally contained with a bit of rest as the body’s metabolic response kick in.

Signs of increased metabolic demand are plentiful if one looks closely. Sugar craving, a early symptom of metabolic derangement, can be overcome with donuts and sweet food. Exercise intolerance is blamed on aging, and food sensitivities viewed as hereditary are passed on.

The neuroendocrine circuits are also activated in this stage, but at a much lesser degree as the metabolic circuits carry out the burden of the work. The HPA axis is on standby waiting to be called into action. The sympathetic nervous system is put on standby. Occasional heart palpitations are passed over as normal after a typical medical work up. Mild insomnia is resolved with over the counter sleep aids. Brain fog is passed over as insignificant.

The neuroendocrine component of this stage incorporates symptoms physiologically consistent with Adrenal Fatigue Stage 1, also referred to as Alarm Reaction. The dominant overall anti-stress response rests with the metabolic auto-regulation component of the NEM response stress continuum.

The NEM response is able to return the body to normal function if and when stress arises in this stage. This is the way the body is designed. Our life continues normally as stress subsides and hopefully stay away. Most people do not even realize they have passed this stage unless it is in retrospect.

Stage 2 – NEM Response Overdrive:

As the assault of stress increases, the workload burden on our metabolic circuits increases as well. The three metabolic circuits – metabolism, detoxification, and inflammation – go into overdrive. If stress is unrelenting, these circuits eventually reach their maximum workload in this stage. Further burden triggers metabolic dysregulation, evidenced by dyslipidemia and central obesity, for example.

As our metabolic circuits get close to or reach capacity in this stage, the marginal benefit decreases. Metabolic dysregulation may begin if the metabolic circuits are not given proper rest and rebuilding time. The body recognizes this and calls upon the neuroendocrine system into action – as stage 2 progresses. Unwanted weight gain can be caused by the stress continuumThis work is the responsibility of the HPA hormonal axis. Starting in the brain and ending in the adrenal glands, the anti-stress hormone cortisol output rises and reaches its peak as the HPA axis is put on overdrive to help the metabolic circuits which are reaching maximum capacity. The HPA axis will drive more cortisol output from the adrenal glands to reduce inflammation and generate energy from within. With regard to neuroendocrinological factors, the body is in stage 2 of Adrenal Fatigue Syndrome, also called Resistance Response.

Clinical symptoms of fatigue in this stage are mild to moderate. Fatigue becomes more frequent. Weekends can be spend at home recuperating. Strong willed sufferers will continue to demand top performance from their body as they refuse to slow down and rest. Many start to come home drained after a full day’s work. This process can go on for years or decades. The body’s nutritional reserve reduces as its resiliency starts a subtle downhill pattern.

Stage 3 – NEM Response Exhaustion:

Unrelenting burden resulting in metabolic dysregulation and HPA axis overdrive cannot go on forever. Our metabolic, detoxification and inflammation circuits have exceeded their functional capacity in this stage. They are overwhelmed and become dysfunctional. In other words, our stress defense system starts to break down from overwork.

If stress is not resolved or at least put under control, the entire NEM response stress continuum enters the exhaustion phase. The body enters stage 3 of adrenal fatigue from a neuroendocrine perspective. Metabolically, the body enters a state of metabolic exhaustion. This stage is perhaps the most dangerous because the velocity of decline can be fast. Fatigue crashes start to be more debilitating as both neuroendocrine and metabolic problems surfaces.

From the neuroendocrine perspective, the body enters a state of hormonal dysregulation beyond the HPA axis. In the female, the OAT axis becomes disturbed. In the male, the AT hormone axis can be damaged. The four phases of adrenal exhaustion (also called neuroendocrine exhaustion or stage 3 adrenal fatigue) take their toll on the body as vitality reduces. Symptoms of neuroendocrine derangement become more severe, including dysmenorrhea, brain fog, anxiety, and reactive hypoglycemia. Our autonomic nervous system will start to flood the body with norepinephrine and adrenaline to prepare us for the “flight or fight” response. The reproductive system will slow down as energy is channeled towards our brain to keep us on full alert in preparation of surviving the worst case scenario. Such neuroendocrine response, utilizing the hormone, cardionomic and neuroaffective circuits, becomes overpowering and overshadows the still ongoing metabolic response. It rises to the forefront – similar to the front line marines landing to establish a beachhead as the battle begins. Symptoms becomes more severe, with reactive hypoglycemia, anxiety, insomnia, and increasing fatigue becoming most bothersome.

Metabolically, the body experiences reactive hypoglycemia, food sensitivities, frequents infection, bloating, and irritable bowel – all signs of a unhappy metabolic system within.

Unwanted symptoms can be resluts of the stress continuumReactive sympathetic overtone and reactive sympatho-adrenal response rule the day as the body comes under full control of the catecholamine – the last resort. Metabolically, metabolic dysregulation of earlier stages progresses now to metabolic exhaustion. The body is unable to keep up with the detoxification process; it becomes more and more inflamed as the progression worsens. Reactive metabolite overload becomes a problem, and the body enters a reactive metabolite response that can be extremely harmful and negative.

Reactive metabolite response, along with reactive sympatho-adrenal response form the hallmark of NEM exhaustion. The body is in a stage of disrepair. Regulatory pathways designed to be self healing have failed. The body is internally in shambles.

These are the body’s further warning signs for us to take action. This is the time where physician’s help is often sought and sufferers starts to lose faith in the healthcare system. Most sufferers are sent home after normal laboratory test and multiple physician visits. Those who complain frequently are put on anti-depressants, stimulatory hormonal replacement, and sleeping medications.

Stage 4 – NEM Response Failure:

Both the metabolic and the neuroendocrine components of the NEM response stress continuum capitulate and surrender. No longer able to restore equilibrium, the body resorts to the only strategy it knows for survival – reducing energy expenditure with the exception of key organs such as the brain. Reproduction and hormonal regulation becomes trivial compared to the immediate need to provide energy for survival at the most basic vegetative state. The body is in a state of disarray. Frequent heart palpation , temperature intolerance, amenorrhea, electrolyte instability, dizziness, breathlessness, dehydration, electrolyte imbalance, severe insomnia, panic attacks grip the body and refuses to let go.

As the neuroendocrine system responses capitulate, the metabolic circuits shutdown process begins as well. All efforts are directly towards survival and conservation of energy. The body starts to lose weight and enters a catabolic state. The gut slows down to avoid unnecessary energy expenditure. Reactive toxic metabolite buildup continues unabated, leading to severe reactive metabolite response that can render the sufferer bedbound. Ambulatory care is needed for daily living.

The body ultimately progresses to a brittle state of vegetative function. This is the state commonly known as the “living dead”.

NEM Response Stage Neuroendocrine Component Response Activity Metabolic Component Response Activities Adrenal Fatigue Syndrome Association
Stage 1: Activation neuroendocrine activation metabolic auto-regulation alarm reaction
Stage 2: Overdrive HPA axis overdrive metabolic dysregulation resistance response
Stage 3: Exhaustion autonomic nervous system overdrive, reactive sympathetic overtone (RSO) and reactive sympatho-adrenal response (RSR) metabolic exhaustion, reactive metabolite overload (RMO) and reactive metabolite response (RMR) adrenal exhaustion (neuroendocrine exhaustion)
Stage 4: Failure neuroendocrine capitulation metabolic shutdown adrenal failure (neuroendocrine failure)

Stage Dependent Symptoms Summary

Stress continuum responses vary from person to personNow that you understand how the body may switch gears in its response to stress progression, we will take a look at how symptoms of each circuit varies and reflect such switches. We hope you can that there is the logical flow behind the symptoms, and that the body is much smarter than we think.

The following table breaks down the six circuit response to stress with their corresponding symptoms and organs involved as NEM response stress continuum progresses through the stages.

Stress Response Circuit Primary Systems and Organs Involved NEM Response stress Continuum Activation (stage 1) and Overdrive (stage 2) NEM Response Stress Continuum Exhaustion (stage 3) and Failure (stage 4)
Hormone Adrenal-Reproductive-Thyroid estrogen dominance, low libido, premenstrual syndrome (PMS), endometriosis, polycystic ovary syndrome (PCOS), amenorrhea, erectile dysfunction low cortisol output, thyroid resistance, brittle adrenal
Metabolism Thyroid-Pancreas-Liver metabolic syndrome, sugar cravings, salt cravings, dyslipidemia, weight gain carbohydrate dependency, carbohydrate intolerance, catabolic state, liver congestion, organ resistance, reactive hypoglycemia
Detoxification Liver-ECM-Immune hypersensitivity to drugs and supplements, paradoxical reactions, sensitivity to food, pain of unknown origin electromagnetic field (EMF) sensitivity, paradoxical reaction ,chemical sensitivities, recurrent crashes, retoxification reaction, paradoxical reaction, reactive metabolite overload
Inflammation Immune-Microbiome-GI food sensitivities, leaky gut, irritable bowel syndrome (IBS), recurrent infections, Epstein-Barr virus (EBV) recurrent and stealth infection, autoimmune disorders, , systemic candida, small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD)
Neuroaffective GI-CNS-ANS mood swings, anxiety, sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), stress intolerance adrenaline rushes, panic attacks, depression, neurotransmitter imbalances
Cardionomic ANS-Heart-Adrenal heart palpitations, tachycardia, sub-clinical postural orthostatic tachycardia syndrome (POTS) shortness of breath, breathlessness, premature ventricular contractions (PVC), atrial fibrillation, clinical POTS

The above table listing is by no means comprehensive or all inclusive. They serve only as general reminders of our body’s systemic and comprehensive approach to handling stress from a functional perspective. The body has multiple avenues of alerting us of danger within. Different signs and symptoms are activated depending on the stage. As stress increases, symptoms worsens. Because each person is unique, no two people respond identically. There is much overlap, depending on the body state of resilience and constitution.

From afar, it is clear that the body’s way to handle stress is comprehensive and holistic in nature. Multiple systems and organs are activated simultaneously because the body does not take chances when it comes to stress. Modulation is automatic (by way of self regulation) through intensity and frequency of activation. Depending on the degree of stress, the body in its infinite wisdom will decide the appropriate course of action and timing. Each person is different. What happens to one person is unlikely to replicate in another, although some general recurrent trends can be seen from our clinical experience.

It is also very important not to jump to conclusions too quickly and make rash decisions based on the above table alone. Many other conditions can present with similar symptoms. A person who is anemic may present with fatigue and low energy, for example. This is why a thorough work up should be carried out and no stone unturned.

Variations on a Theme

The stress continuum can cause heart palpitationsMany signs and symptoms of NEM response stress continuum activation (stage 1) and overdrive (stage 2) carry through to NEM response exhaustion (stage 3) and failure (stage 4). As more severe symptoms surface, milder ones tend to take a back seat. Some symptoms appear in reversed order from those shown in the table. For example, they may have severe palpitations right off the bat. Still others sufferers have some signs and symptoms of each column without a clear and predictable order or sequence. So much depends on the body in real time as it deals with daily stress. Some symptoms can wax and wane with time. For example, panic attack may be followed by calm and relaxation. Such roller coaster rides is not unusual. It reflects the body’s continuous and never ending attempts to rebalance itself, though the weaker the body the higher chances of failure.

Most phase progress and symptoms get worse with time, such as hypersensitivity to drugs and supplements. The weaker the body, the greater the risk. However, the general trend is one towards massive decompensation, as both components of the NEM response stress continuum become dysfunctional as stage 4 approaches, although not necessarily to the same degree – as we shall discuss further in later chapters.

Knowing the key presenting symptoms and component dominance of each stage of the NEM response stress continuum progression helps us to better understand how the body handles stress and what we can expect.

The first step in any healing process is to understand the problem on hand. Knowing the NEM response stress continuum perspective and how the body switches its responsibility from one component to another as stress increases sheds light on and helps us see. What appeared to be convoluted symptoms is actually a systematic approach by the body – using the tools it has – to begin the process of self healing.
© Copyright 2017 Michael Lam, M.D. All Rights Reserved.


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