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The NEM Response and Symptoms Of Stress

Your body was made to handle acute stress from time to time. It is equipped with different organs and systems that respond to stress, and it is always trying to regain or maintain homeostasis. Together, these organs and systems form your NeuroEndoMetabolic (NEM) Stress Response. If you notice the symptoms of stress we’ll cover in this article, it means your NEM response is starting to become negatively affected. And that’s usually because your stress has become chronic, which your body was not made to handle.

Learn More:

» Read our complete long-read article on NeuroEndoMetabolic Stress Response
» Adrenal Fatigue FAQs
» Take our 3-minute test to see if you may have Adrenal Fatigue

Chronic stress is a feature of modern life. So many people are living with the symptoms of stress thinking that's the norm. You might be one of these people. Or, you might have both types of stress: psychological and physiological. And that's because the fast-paced lifestyle that most people live leads to both.

What are Some of the Causes of Stress?

Your environment and lifestyle contain stressors that are putting a lot of pressure on your physiological functions. These stressors include:

  • Eating an unhealthy diet
  • Overconsumption of alcohol
  • Overconsumption of sugar
  • Eating fast food regularly
  • Pesticides and herbicides in fruits and vegetables
  • Hormones and antibiotics in meat
  • Hydrogenated oils
  • Smoking
  • Taking recreational drugs
  • Certain types of medication, especially antibiotics
  • Certain chemicals in home and beauty products
  • Exposure to environmental toxins
  • Undiscovered food sensitivities
  • Sedentary lifestyle
  • The presence of a chronic illness
  • Recurring infections

So, all of these stressors can dysregulate your NEM and trigger symptoms of stress.

The HPA Axis and Symptoms of Stress

When you encounter stress your hypothalamus secretes corticotropin-releasing hormone (CRH) to prompt your pituitary gland to release adrenocorticotropic hormone (ACTH). Then, ACTH stimulates the adrenal glands to produce and release cortisol, your body's main anti-stress hormone.

Once cortisol has done its job and neutralized the stressor, any excess circulating in the system signals the hypothalamus to stop stimulating your adrenal glands.

The body responds to mitigate effects of stress, but too much stress can overwhelm these responses and lead to unpleasant symptoms of stressThis hormone cascade is called the hypothalamic-pituitary-adrenal (HPA) axis. When it’s in balance, your cortisol levels naturally fluctuate during the day. But when your body is facing chronic stress, it begins to overwork the adrenal glands.

At first, your adrenals produce more cortisol to meet the growing demand. This marks the beginning stages of Adrenal Fatigue Syndrome (AFS), which come with their specific symptoms of stress. However, after chronic stress then your adrenals become exhausted, and their cortisol output drops. This marks the more advanced stages of AFS.

Some of the symptoms of AFS include: fatigue, weight gain, insomnia, brain fog, anxiety, mild depression, PMS, infertility, low libido, hair loss, dry skin, estrogen dominance, lowered immunity, sugar and salt cravings, heart palpitations, and a low stress tolerance.

The Conventional Stress Model

The role of the HPA axis has long been recognized and understood by mainstream medicine. The conventional stress model considers how the neuroendocrine system regulates the stress response. But, the symptoms of stress are quite varied.

The problem with the conventional stress model is its narrow focus. So, this leads to the different symptoms of stress not being identified. Even worse, they are treated as if they originate from different conditions.

Here's an example. If you go to your conventional medical practitioners with low thyroid hormones, depression, and infertility, then each one will be treated separately and unrelated. They may give you thyroid hormone replacement therapy and antidepressants. Also, you may get some relief from these symptoms, but the root cause is not addressed. So, this means that your adrenal fatigue will progress until your symptoms recur or worsen.

Furthermore, your blood work might still come up normal. You’d then get more medications for your symptoms rather than your underlying condition. Eventually, your AFS can become so advanced that you become bedridden. And you still wouldn't have any answers.

Functional Medicine's Approach

Thankfully, functional medicine has a different approach to the stress model. This approach recognizes not only the cause but also the links between the different organs and systems involved in the stress response.

The NEM and Symptoms of Stress

The NEM response consists of six circuits that work together to fight stress. They are the Hormone, the Bioenergetics, the Detoxification, the Inflammation, the Neuroaffect, and the Cardionomic Circuits. Depending on which circuit is most affected, you’ll get different symptoms of stress.

The body's NEM systems are interconnected systems that deal with stress. In attempting to deal with severe stress, symptoms of stress can arise.

The Hormone Circuit

Your Hormone Circuit consists of your adrenal glands, thyroid, and gonads (male testes and female ovaries). The adrenal glands produce over 50 different hormones, including cortisol (your most important stress fighter). Your thyroid gland produces hormones that regulate the rate of your metabolism (or how your body uses energy). Also, these gonads manage the production and regulation your sex hormones.

Each component acts as a hormone cascade that begins with the control center in the brain. An important Hormone Circuit axis is the ovarian-adrenal-thyroid (OAT) axis. This axis plays a crucial role in women's reproductive health and is often involved in estrogen dominance.

When your thyroid is the most affected component, your symptoms will include fatigue, mild depression, weight gain, and PMS. If it’s your adrenal glands, your symptoms will include fatigue, anxiety, and irritability. When it’s the ovaries, the main symptoms will be estrogen dominance, PMS, brain fog, and memory loss.

Since your adrenal glands are your NEM’s first line of defense against stress, this circuit switches on first. And because hormones regulate a lot of the body’s physiological functions, any dysregulation in this circuit will affect the rest of the NEM.

The Bioenergetics Circuit

Your thyroid, pancreas, and liver make up your Bioenergetics Circuit. As you can see, the thyroid closely links this circuit with your Hormone Circuit. This circuit also produces the energy your body needs to function. The pancreas produces enzymes and hormones that help metabolize food and help your cells use glucose and create energy. Your liver is your main detoxification organ and it keeps things running smoothly. It also releases glucose when you need it.

When this circuit dysregulates, the main symptoms of stress include hypoglycemia, Type 2 diabetes, obesity, sleep disorders, inflammation, AFS, dysbiosis, leaky gut, and metabolic syndrome. Additionally, dysbiosis is a state of imbalance in your gut flora, where the bad bacteria outnumber the good bacteria. Leaky gut happens when the tight junctions in your gut lining loosen, allowing particles into your bloodstream that shouldn’t be there.

Metabolic syndrome is a combination of different conditions. It is a lesser-known part of the dysregulation of the Bioenergetics Circuit. Its conditions include high blood sugar, insulin resistance, rising blood pressure, abnormal cholesterol, abnormal triglyceride levels, and excess belly fat. These conditions can lead to a higher risk of Type 2 diabetes, heart disease, and stroke.

The Detoxification Circuit

Your Detoxification Circuit is what helps your body get rid of toxins and metabolites. Its main components are the liver, the interstitium, and the immune system. The liver closely links it to the Bioenergetics Circuit. The interstitium, also called the extracellular matrix, is a network of non-living tissues that support your cells.  To a lesser extent, your kidneys, lymphatic system, lungs, and skin also play a part in detoxification.

When any of these components are not working smoothly, toxins accumulate in your system. This then increases your oxidative stress and toxic load. And this oxidative stress can raise your risk of chronic illnesses such as neurodegenerative diseases and cancer. When the toxic load increases, you can get symptoms such as hypersensitivity, intolerance to supplements and medications, chemical sensitivities, and paradoxical reactions.

The Inflammation Circuit

The Inflammation Circuit is closely linked to the Detoxification Circuit. They both share the immune system because when toxins accumulate in your system, they trigger inflammation.

Acute inflammation is a healthy and natural defense against harmful stimuli. However, when inflammation becomes chronic, it can wreak havoc on your health. These harmful stimuli can be external, such as pathogens or toxins, or internal, such as abnormal cells. Inflammation tries to get rid of these irritants, as well as the cells and tissues damaged by them. It also helps initiate tissue repair. So, this is another reason it needs a smoothly-running Detoxification Circuit.

Your immune cells, microbiome, and gut make up your Inflammation Circuit. An imbalance in your gut’s microbiome is a major cause of inflammation. Many health practitioners agree that inflammation usually begins in the gut, and then spreads throughout the body. If it spreads to your joints, it causes joint pain. If it reaches your nervous system and brain, it could cause depression and neurological symptoms of stress.

Other symptoms of a dysregulated Inflammation Circuit may include food sensitivities, IBD, IBS, SIBO, candida, pain of unknown origin, leaky gut, recurring infections, slower healing, the presence of stealth viruses (especially EBV), difficulty recovering from Lyme disease, and autoimmunity.

The Neuroaffect Circuit

The three major components of your Neuroaffect Circuit are the autonomic nervous system (ANS), the brain, and the microbiome. The Inflammation Circuit and the Neuroaffect Circuit are closely linked through the microbiome. As we said before, inflammation that spreads from your gut to your brain and nervous system can cause neurological symptoms. And one of the major causes of inflammation in the gut is the dysbiosis of the microbiome.

The Neuroaffect Circuit activates the release of different neurotransmitters that puts your system on alert when there is stress and calms you afterward. Many neurotransmitters are made in the gut, and your microbiome-gut-brain axis is the pathway to your neurotransmitter pool. That’s another reason why inflammation in the gut can affect neurotransmitter balance and lead to mood changes.

Dysregulation of the Neuroaffect Circuit induces different neurological and psychological symptoms of stress. So, things like insomnia, anxiety, and panic attacks may result. If norepinephrine is involved, you can get heart palpitations.

The Cardionomic Circuit

Your Cardionomic Circuit consists of your ANS, heart, and adrenal glands. In that sense, it is closely tied to your Neuroaffect and Hormone Circuits through the ANS and adrenals respectively.

A major part of the fight-or-flight stress response includes filling your heart, blood vessels, and lungs with more oxygenated blood. This response needs norepinephrine and adrenaline to activate.

Adrenaline, sometimes called epinephrine, is your body’s most powerful stimulatory hormone. Too much of it can create very intense symptoms of stress. It’s modulated by your adrenals and regulated by your sympathetic nervous system, which is part of your ANS.

If your Cardionomic Circuit dysregulates, you might experience high blood pressure, heart palpitations, cardiac arrhythmia, shortness of breath, high blood pressure, and breathlessness. If you don't do anything about it, you might then get POTS-like symptoms and atrial fibrillation, which are symptoms that come with adrenal fatigue.

How to Test for Symptoms of Stress

Because your HPA axis is your anti-stress first responder, it makes sense to test the levels of adrenal hormones secreted. These include salivary DHEA, salivary cortisol, and pregnenolone levels. To check the rest of your NEM, you can ask for the following tests:

  • Salivary secretory IgG is a biomarker for your gastrointestinal health. It can tell you if you are suffering from allergies, candida, food sensitivities, leaky gut, and SIBO. It’s an advanced marker for your Inflammation and Detoxification Circuits, as well as for your gastric and immune systems. When low, it could show signs of chronic stress.
  • Salivary c-reactive protein could help identify your inflammation levels, the presence of an infection, your oral health, and your cardiovascular health. And it can help determine risk for diabetes, autoimmunity, hypertension, and cancer.
  • Salivary alpha-amylase is a biomarker that can help check for the activation of the sympathetic nervous system. So high levels may indicate that your body is undergoing a lot of stress, with a special emphasis on your Hormone, Neuroaffect, and Cardionomic Circuits.
  • Interleukin-1Beta is a pro-inflammatory cytokine protein. This means that testing for it can check if your Inflammation Circuit is activated. It could indicate the presence of chronic or acute infections or some kind of injury.

These tests must be part of a clinical intake by an experienced clinician. Furthermore, this medical professional should be able to analyze and correlate the different test results and symptoms.


Your NEM response is your body’s global response to stress. It also differs from the conventional model of stress as it accounts for the interconnection of your organs and systems when dealing with stress and the symptoms of stress.

For quick reference, we've created the following table that summarize the six circuits. It shows the organs and systems in each circuit, and the possible symptoms when each circuit is activated.

Summary Table of the Six NEM Circuits

Stress Response Circuit Primary Systems and Organs Involved NEM Response Activation and Overdrive NEM Response Exhaustion and Failure
Hormone Adrenals-Thyroid-Gonads Estrogen dominance, low libido, premenstrual syndrome (PMS), endometriosis, polycystic ovary syndrome (PCOS), amenorrhea, erectile dysfunction. Low cortisol output, thyroid resistance, brittle adrenal.
Bioenergetics Thyroid-Pancreas-Liver Sugar cravings, salt cravings, dyslipidemia, weight gain, metabolic syndrome. Carbohydrate dependency, carbohydrate intolerance, catabolic state, liver congestion, organ resistance, reactive hypoglycemia.
Detoxification Liver-Interstitium-Immune Hypersensitivity to drugs and supplements, sensitivity to food, pain of unknown origin. Paradoxical reactions, electromagnetic field (EMF) sensitivity, chemical sensitivities, recurrent crashes, retoxification reaction, reactive metabolite overload.
Inflammation Immune-Microbiome-Gut 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).
Neuroaffect Gut-Brain-ANS Mood swings, anxiety, sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), stress intolerance. Adrenaline rushes, panic attacks, depression, neurotransmitter imbalances.
Cardionomic ANS-Heart-Adrenals Heart palpitations, tachycardia, sub-clinical postural orthostatic tachycardia syndrome (POTS). Shortness of breath, breathlessness, premature ventricular contractions (PVC), atrial fibrillation, clinical POTS.

Learn More:

» Read our complete long-read article on NeuroEndoMetabolic Stress Response
» Adrenal Fatigue FAQs
» Take our 3-minute test to see if you may have Adrenal Fatigue

Dr. Lam’s Key Question

Because your body responds to stress as a whole, you can get a wide range of symptoms of stress. It depends on which organs and systems are most engaged and affected. This article will help you determine why your symptoms are so different and how to make sense of them.

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