Stress Induced Inflammation and the NEM Stress Response

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

stress induced inflammation caused by a stressful jobStress has been shown time and again to be a major influence on mood, physical health, mental health and behavior. Persistent stress can make you generally more susceptible to physical and psychological problems, and it can be a precursor to many illnesses. Stress induced inflammation is something that everyone should be made aware of so that the prevention of many diseases, as well as recovery from them, can happen at the causal level.

Chronic Illness and Stress Induced Inflammation

We are all equipped with the ability to neutralize stress through a series of stress responses that are fast and efficient enough to prevent damage to our physical and psychological health. However, when acute stress turns into chronic stress, it increases our health risks significantly.

There are many physical disorders that have been connected to stress, including:

  • Cardiovascular problems like hypertension, strokes and heart attacks
  • Immune system disorders like HIV and AIDs, herpes, colds and flus
  • Different types of cancers
  • Autoimmune disorders like multiple sclerosis and lupus
  • Skin problems like rashes, hives and dermatitis
  • Gastrointestinal (GI) disorders like irritable bowel syndrome, ulcers, ulcerative colitis, gastroesophageal reflux disease (GERD)
  • Neurological disorders (like Parkinson’s)
  • Sleep disturbances

Psychological problems like depression, anxiety, and panic attacks are also very commonly linked to chronic stress.

The interesting thing that not many people are made aware of by their doctors is that the inflammation that is induced by the chronic stress is actually what creates the environment for these problems to develop, including the psychological issues mentioned above.

But, what exactly is stress?

How stress induced inflammation is createdStress is a force or state of tension, pressure or strain imposed by a stressor. A stressor is the stimulus that creates stress and it can be psychological or physical. All kinds of stress will have a physiological effect on the body in the form of the body’s stress responses.

Not all stress is bad. In fact, some types of stress are healthy and needed, such as stress caused by moderate exercise. For our purposes, we are going to focus on unhealthy and excessive stress.

Physical stressors include:

  • Injury
  • Viral or bacterial infections
  • Hormonal changes
  • Unstable sugar levels
  • Dehydration
  • Consumption of caffeine, sugar
  • Consumption of allergenic foods (gluten, dairy)
  • Certain medications
  • Alcohol, drugs or smoking
  • The effects of an illness
  • Aches and pains (like migraines or dental problems)
  • Environmental toxins
  • Unhealthy diets
  • Extreme dieting
  • Lack of sleep

Psychological stressors include:

  • Financial worry
  • Work pressure
  • Academic exams
  • Family problems
  • Relationship problems
  • Death or loss of loved ones
  • Dealing with difficult people
  • The psychological stress of being physically unwell
  • Going through a traumatic event (theft, violence)

All of these stressors can elicit an acute stress response, but if they are not resolved and the stress response is constantly switched on, the stress becomes chronic and opens the body up to many problems, including stress induced inflammation.

Stress and Homeostasis

One very important factor in health, and even survival, is the ability of the body to maintain homeostasis – the equilibrium between different organs and systems. Stress is a threat to the maintenance of this homeostasis.

Depending on the stressor, different patterns of stress responses are elicited. Also, different people will have different stress responses to the same situation.

For example, some people will have a more averse reaction to a stressful situation, especially if the situation does not allow for an active response like fight or flight to actually be effective. These aversive reactions will typically involve the sympathetic nervous system, an inhibition of movement and the blood shunting from the periphery of the body. This is also called a vigilance response.

On the other hand, some people will have a more active coping mechanism to stress, such as the fight or flight response, which helps them either defend themselves or run away from a threat by increasing hormonal, metabolic and autonomic functions that enhance their muscular capabilities.

Stress induced inflammation reductionMost stress responses are integrated, and everyone is capable of both types of response. Although the pattern of the stress response that shows up largely depends on the situation itself, there is a certain personal tendency that is determined by genetic, developmental and environmental factors.

Studies in rats and dogs have shown that those that were nurtured consistently by their mothers early on have lowered stress responses and less anxiety than those that were not.

The mechanisms of homeostasis are sophisticated enough to help the body deal with acute stress without much damage to the system, especially for younger, healthier people. Those who suffer from illnesses already, are in weak health or are older tend to have a higher health risk when exposed to stress.

This is especially true if the stress becomes more consistent. Even younger, healthier individuals are at risk of disease and psychological issues in that case.

Other elements also play a role in how susceptible an individual becomes to the diseases and stress induced inflammation. Hereditary factors, upbringing, early life experiences, the meanings given to certain situations, constitutional composition, and access to health care (including psychological support) all have a part in how vulnerable an individual is to the harmful effects of stress.

Before diving into these harmful effects, how they affect each other, how they trigger illness, and how to deal with them, we need to have a good understanding of how your body deals with stress.

The Body’s Global Response To Stress

The body has many different organs and systems that work together to fight stress. They are all part of the NeuroEndoMetabolic (NEM) Stress Response, which is composed of six organ / system circuits that are all affected by chronic stress and stress induced inflammation. We will go through each of these circuits and how each of them respond to stress and their association with inflammation.

The Hormone Circuit and Response

The adrenal glands, the thyroid and the gonads (male testes and female ovaries) regulate, through the hypothalamic-pituitary-gonadal (HPG) axis as well as the hypothalamic-pituitary-adrenal (HPA) axis, the hormone response. The hypothalamus and pituitary gland in the brain send signals to these organs to produce or stop producing their hormones.

As we will discuss in more detail below, the adrenals are responsible for secreting the body’s main anti-stress hormone, cortisol. With consistent stress and stress induced inflammation, your adrenals will weaken and become unable to handle the stress, causing a very common yet usually under-diagnosed condition called Adrenal Fatigue Syndrome (AFS).

The Metabolism Circuit and Response

The metabolism response involves the thyroid, pancreas and liver. The thyroid is responsible for producing thyroid hormones to increase the basal metabolic rate when stress is present so that you can be ready and have the needed energy to deal with whatever threat is present. The pancreas produces insulin to help get your cells the glucose they need to give you a boost of energy when under stress, while the liver clears away excess metabolites generated as a result of metabolism.

Inflammation can affect metabolism and the metabolic response. If the pancreas is chronically inflamed, insulin producing cells may be affected. It will become more difficult as time passes for your body to regulate your blood sugar and reactive hypoglycemia can result. A constantly triggered inflammatory response can also get in the way of thyroid function, which can lower the production of thyroid hormones T3 and T4. At the same time, low T3 and T4 decreases metabolic function and contributes to inflammation.

The Neuroaffective? Circuit and Response

The nervous system and stress induced inflammationThe neuroaffective? circuit consists of the autonomic nervous system (ANS), central nervous system (CNS), and gastrointestinal (GI) system. These systems rely on neurotransmitters to balance your body, mood, and emotions.

Many of these neurotransmitters are actually made in the gut of the GI system, which is why the gut is sometimes called “the second brain.” The gut, brain and ANS form the management team of the neuroaffective? response.

Stress affects the ANS, as well as the brain and gut. For example, when the gut’s health is compromised and there is inflammation present, its production of neurotransmitters is dysregulated and, by connection, the neuroaffective? response. This is one of the reasons why stress induced inflammation and gut health are things to look at if your mood and brain function are not optimal. Inflammation of the brain has also been connected to decreased mood and depression.

The Cardionomic Circuit and Response

Readying the heart, lungs and blood vessels by providing more oxygen-filled blood is part of the fight or flight response. The hormones that turn this response on are cortisol, adrenaline and norepinephrine, which are all produced by the adrenal glands and regulated by the SNS.

When the cardionomic response is triggered, your heart rate goes up, breathing rate is faster and blood pumps through your system more vigorously so that it gives you the best chance at a strong fight or a fast escape. Norepinephrine and epinephrine (also called adrenaline) are the two catecholamines responsible to carry out this responsibility.

Chronic stress and the inflammation induced by it can weaken the adrenal glands and also keep the fight or flight response constantly switched on as the body is flooded with these catecholamines. When this happens, your cardionomic response is on overdrive and you can experience faster resting heart rate, heart palpitations, stronger heartbeats, irritable bowels, anxiety, panic attacks, temperature intolerance, and POTS-like symptoms. In severe cases, this can lead to atrial fibrillation, supraventricular tachycardia, and premature ventricular contractions.

The Inflammation Circuit and Response

Inflammation is one of the most effective and important defense mechanisms that your body has against injury and harmful intrusions by pathogens (such as bacteria, virus, parasites) or toxins. This mechanism involves the immune system, the microbiome, and the gut. The inflammation response creates a hostile environment for the harmful intruders, and it cleans away tissues and cells already damaged by the pathogens, the immune system’s attack, or from injury.

Just like stress induced inflammation, inflammation also affects your brain’s ability to respond to stress. Studies have shown that consistent low-grade inflammation increases the permeability of the gut lining, allowing toxins to enter the system and cause depression in the CNS.

SSRIs, which are common antidepressants, have anti-inflammatory properties that can help with this. If you suffer from depression, you might want to consider taking up an anti-inflammatory diet alongside your regular therapy. However, you should never discontinue medications in favor of this diet without the consent and supervision of your doctor.

A disruption in your inflammation response can also bring about recurring infections, autoimmunity, candida, GI tract disorders, stealth viruses, musculoskeletal pain, slow healing, and food sensitivities. It also puts a lot of pressure on your body’s detoxification response.

The Detoxification Circuit and Response

stress induced inflammation causing damaged cellsThe debris left over from damaged and dead cells, whether from the inflammation response or oxidative stress, as well as any pathogens or toxins that entered the body, need to be cleared out of the system. The detoxification response involves the liver, extracellular matrix, lymphatic system, kidneys and immune system all working together to ensure anything that is not needed gets removed from the body as quickly and efficiently as possible.

When consistent stress induced inflammation and unrelenting stressors burden your detoxification response, your body’s toxicity levels will inevitably rise as reactive metabolites accumulate. Symptoms of this include intolerance to certain medications, chemicals, foods, and supplements. Paradoxical reactions and brain fog have also been reported.

The HPA Axis and Cortisol

While each of the NEM circuits perform a specific function, the body has a built-in activation sequence when stress arrives at the doorstep. Not all circuits are activated at the same intensity. Some circuits are designed for chronic stress, while others are equipped for more acute situations. The first line of defense within the NEM stress response is the all-important HPA hormonal axis. The HPA axis is composed of the two regulatory control centers in the brain: the hypothalamus and pituitary gland, which secrete stimulatory neurotransmitters that signal the adrenal glands to produce cortisol, the body’s main anti-stress hormone.

Cortisol has many important functions, including regulating blood sugar, regulating heart rate, maintaining heart and blood vessel function, suppressing the immune system, and neutralizing inflammation.

With chronic stress and consistent stress induced inflammation, the adrenal glands begin to increase, and that can ultimately lead to dysregulation. At first, they increase their production of cortisol to meet the growing need for stress/inflammation neutralization. This brings on the symptoms of the first stages of AFS such as sugar craving, hypoglycemia, and low exercise tolerance. After some time, the adrenals become exhausted and their cortisol output drops, bringing about the symptoms of more advanced stages of AFS such as heart palpitations?, anxiety, insomnia, and brain fog.

Without proper cortisol’s anti-inflammatory role, inflammation, including that which is induced by stress, can run rampant. Also, all of the other functions that are under cortisol’s regulation are adversely affected, and that is why AFS can have such a wide range of symptoms.

Symptoms of AFS range from mild to severe. They include fatigue, an inability to fall asleep, waking up in the middle of the night, difficulty getting up in the morning, easily gaining weight and difficulty losing it, low libido, reactive hypoglycemia, food sensitivities, drug sensitivities, PMS, fertility issues, anxiety, heart palpitations, mild depression, and frequent colds and flus.

Many of these symptoms are either directly related to inflammation, or can aggravate the state of inflammation in the body.

So far, we have studied the negative effect of uncontrolled inflammation. Let us back up and examine in more detail now exactly what inflammation is and why it is an important part of our well-being.

What is Inflammation?

Inflammation is the result of the immune system’s cells and their byproducts attacking pathogens or damaged cells. This process increases blood flow to the affected area, creating redness and warmth. The substances the immune system’s cells release can cause a leakage of fluid into the tissues and produce swelling.

Pain and irritation may arise from this process. Other symptoms include fever, stiffness, tiredness, headaches, chills, sweating, dizziness, low appetite, and aches and pains in different areas, like joints.

immune cells and stress induced inflammationImmune cells are found all over the body. Leukocytes (a type of white blood cell) are produced in the bone marrow and lymphocytes (also a type of white blood cell) are found in the lymphatic system.

However, most of the body’s immunity actually begins in the gut. The gut contains two thirds of immune tissue in what is called the GI tract’s immune system – the gut-associated lymphoid tissue (GALT). The GALT is mainly located in the small intestine and is composed of different kinds of immune cells.

The immune system’s response can be divided into these main fields of operation: natural and specific immunity or cellular and humoral immunity.

Natural immunity is the general defense system against pathogens. It works by producing phagocytic cells, cytokines, and killer cells. Phagocytic cells, like neutrophils and macrophages, destroy infectious pathogens. Cytokines stimulate the cells needed in the immune response to move to the affected areas (sites of infections or injuries) and help these cells communicate. Natural killer cells (a subset of white blood cells also called NK) kill infected or cancerous cells.

Specific immunity targets specific “jobs” or threats. It includes NKs, B cells that create antibodies to support humoral immunity, and T helper cells that create cytokines to support cellular immunity.

With regard to cellular and humoral immunity, the difference is that cellular (also called cell-mediated immunity) tags and destroys intracellular pathogens, like viruses. It doesn’t involve antibodies, but antigen-specific Th1 lymphocytes, T cytotoxic cells and NKs.

Humoral immunity on the other hand, which is immunity that involves substances found in extracellular fluids, deals with extracellular pathogens like bacteria or parasites. It does this through Th2 cytokines that stimulate B cells into producing antibodies and antimicrobial peptides that mark extracellular pathogens for disposal.

Stress and high cortisol levels affect the immune system. They promote proinflammatory pathways, especially the activity of Th2 cytokines, creating a Th1 to Th2 shift. This shift suppresses cellular immunity in favor of humoral immunity.

With chronic stress, both Th1 and Th2 classes of cytokines can dysregulate, causing the suppression of both types of immunity and slowing down the healing of wounds, producing less effective defenses against viral and bacterial infections, longer recovery from surgery, and a decrease in the ability to kill cancer cells.

Without an optimally functioning immune response, the risk of low-grade and persistent inflammation is increased, even though the inflammation itself is no longer able to contain infections or help injury recovery as well as it should.

The rise in proinflammatory cytokines involved in stress induced inflammation can also trigger the development of autoimmunity. These cytokines can stimulate the immune system to attack the body’s healthy cells, mistaking them for unhealthy cells or harmful intruders. Depending on which organ or system has been damaged by the immune response, you get a specific disease picture with its own set of symptoms.

For example, if the cytokines stimulate the immune system into attacking the respiratory airways, you can develop asthma. If the immune system attacks the pancreatic cells that produce insulin, you can develop type 1 diabetes.

Stress, when chronic in nature or when it comes at a time when an individual is in a fragile state (such as during certain hormonal changes for women like pregnancy or menopause, or when there is an illness present), can also trigger the development of autoimmunity and chronic disease.

The underlying connection is, as mentioned earlier, that chronic stress induces inflammation, and inflammation is at the root of these problems.

Stress, Inflammation, and Aging

stress induced inflammation and agingStress also has an effect on the aging process because inflammation has an effect on aging. Aging is caused by cellular senescence, which is the irreversible cell cycle arrest that comes from changes in the length and structures of telomeres.

Telomeres are the “caps” at the end of DNA strands; they are there to protect chromosomes. When these telomeres are shortened or changed, they cannot do their jobs as well and the DNA strands are exposed to damage.

Stress induced inflammation can accelerate cellular senescence through progressive telomeric shortening as well as oxidative stress and oncogene activation. Oncogenes are genes that, when activated, have the capacity to cause cancer.

Aging has also been linked to an increase in free radicals, hormonal decline and the decline in mitochondrial adenosine triphosphate (ATP). ATP is thought of as the energy currency of life; it is the molecule that stores the energy needed for all biological processes. Mitochondria, the organelles found in cells, synthesize this life energy by breaking down carbohydrates and fatty acids.

With free radicals, you require antioxidants to neutralize them. If your system is overloaded with free radicals, antioxidants are no longer sufficient. As the cells are exhausted and not producing enough ATP, antioxidants cannot help much. Oxidative medicine may be the better alternative as it puts energy directly into the body again. The use of natural compounds that have metabolic cardiological properties such as ribose, magnesium, CoQ10, and carnitine may be helpful to the mitochondria in optimizing ATP function.

Adrenal Fatigue and Inflammation

As you can see, the interplay between stress, inflammation, and adrenal gland function are closely tied together.

Stress and inflammation is a huge stressor on the body – strong enough to trigger adrenal fatigue or add to its many problematic symptoms like tiredness, depression, brain fog, food sensitivities and general weakness. All systems of the body is affected.

Because the NEM’s inflammation response includes the immune system, brain, and gut, its dysregulation from chronic stress will affect all of these components as well.

When these organs and systems are overworked, you not only get problems with them directly, but the adrenal glands will become overworked as well. When the adrenal glands cannot suppress this stress induced inflammation, the cycle continues.

Throughout the article we have mentioned a few tests and markers for stress, which can also help you determine whether you could develop stress induced inflammation over time. There are also some specific ways to test for inflammation directly, using symptoms as well as markers.

Chronic inflammation will have many of the same symptoms of inflammation we have discussed such as swelling, joint pain, stiffness, redness, fatigue, and heat/mood disturbance. Dull ache of unknown origin in the abdomen or migrating discomfort without a known origin can also be a sign of persistent inflammation.

testing and stress induced inflammationStandard laboratory markers such as salivary cortisol and dhea can be helpful. To be even more accurate, markers like c-peptides, c-reactive proteins, and homocysteine levels should also be tested to confirm the diagnosis. A c-peptide test will reveal how much insulin is in the blood, because c-peptides are released into the blood at the same time as insulin. With this test, you can get an idea of whether you have insulin resistance or which type of diabetes (type 1 or 2) you might have.

Testing the blood for c-reactive proteins will show you the level of stress induced inflammation in your body caused by things like infections or inflammatory diseases. Homocysteine (an amino acid) levels will reveal not only inflammation, but also your cardiovascular disease risk.

Advanced markers include IL-beta, SIgA, and alpha amylase are helpful to provide subclinical data points to help formulate a proper clinical assessment of the degree of inflammatory damage within your body in severe cases.

So, let’s say that you’ve checked your stress and inflammation levels and maybe even feel that your inflammation is induced by stress… what’s the next step? The obvious answer might be to reduce stress, and by doing so, you’ll reduce inflammation.

That is true to a certain degree. You really should reduce and manage your stress, especially if you are also suffering from adrenal fatigue. It is the root cause of your AFS as well as a likely causal factor in the inflammation you have. However, in many cases the damage caused by the presence of either, or both, of these conditions has progressed beyond recovery through stress management only.

Rebalancing Stress Induced Inflammation

First of all, if you have any degree of dysbiosis, you will need to make rebalancing your gut flora your first goal. Doing so will increase your immunity, improve any digestive problems you might be suffering from, help with reducing stress induced inflammation and also improve your digestion so that you get the energy and nutrients you’ve been lacking.

You can do this with a healthy diet and exercise program, making sure you follow an anti-inflammatory diet as well as the adrenal fatigue diet if you also have AFS. This can be a little tricky if you’re not used to it, so it bodes well to consider nutritional coaching.

A diet that is right for your condition will help you eliminate any foods you are sensitive to or are detrimental to your state of health, as well as add supportive and nutrient-dense foods.

You may also consider supporting your gut with probiotics, prebiotics and digestive enzymes. Also, you can support your adrenals with adrenal fatigue supplementation.

This can also present a challenge as some supplements that help with one condition may adversely affect another. Some supplements may give favorable results at first and then cause a crash afterwards. This is why it is best to do this with the help of a trained medical professional experienced in adrenal fatigue, gut health, and stress induced inflammation.

Make sure you avoid the shotgun approach with supplementation where you take many vitamins supplements at the same time thinking it will do you good. It will more than likely backfire, and in the end you won’t know which supplements actually were the right ones. A gentle, safe approach is key. Take it one step at a time.

Don’t be surprised that by healing your gut and reducing stress, your condition will improve dramatically. Even psychological issues, like depression, will improve because of the gut-brain connection as well as the lower stress and the inflammation-mood connection.

Strengthening the adrenal glands will also be a great help with your efforts to reduce stress; after all they are the body’s main defense against stress. A fit and healthy stress response that can both neutralize stress as well as “switch off” once the job is done is vital.

stress induced inflammation and yogaConsider doing adrenal breathing exercises and adrenal yoga exercises, depending on the severity of your AFS. Support your recovery by removing as many stressors in your life as you can, without overwhelming yourself. Cut down on sugar, alcohol, caffeine, and any chemical-laden products you might be using.

Getting enough rest and good quality sleep is essential as well. Make sure your room is dark and cool, that your blood sugar is stable before going to sleep (you can eat a small snack before bed), that you don’t eat a big meal at least two hours before bed, that you don’t use electronic devices at least two hours before bed, and that you switch off any devices that might disturb you during the night.

Needing a lot of sleep during your recovery from AFS and stress induced inflammation is natural. Don’t feel bad that you are not capable of being as productive as you used to be. Your body is working hard to get back to normal, so give it all the rest it needs. If you follow these steps, get the right kind of medical support and lead a healthier lifestyle, soon enough you will be able to get your energy back – and do what you want to do!

© Copyright 2017 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Question

We’ve known for years that stress can create physical and psychological disorders, but now we understand the main link is that stress induced inflammation is the underlying cause. Understanding this link and knowing what to do about it is key to good health.

stress induced inflammation