Allostatic Load

Inflammation: Pathway to Chronic Diseases

Inflammation is activation of the immune system in response to threat or injury to the body. Acute inflammation mobilizes the immune system to repair an injury or fight an infection. Once healing takes place the immune system goes back to baseline. Chronic inflammation, however, involves long term activation of the immune system caused by some ongoing stress to the body. More and more, researchers are beginning to show that chronic inflammation is the common pathway to many diseases. There are multiple causes of chronic inflammation. In this post I will write about the causes of chronic inflammation. I will also do a series of posts about the many diseases that chronic inflammation causes. These posts will be based on the structure of an excellent book: Inflamed – Deep Medicine and the Anatomy of Injustice. It is not easy to read because it is disturbing but I highly recommend it. I will also write about a test to measure chronic inflammation. I will write about things you can do to decrease chronic inflammation if you have it and how to prevent it if you don’t. There are many causes of chronic inflammation that have to do with the structure of our society. These are things an individual cannot control. These societal causes will take ongoing efforts by all of us to change some of the toxic structures of society.

The Process of Inflammation

The inflammatory process starts with damage or threat of damage to the body. That can be an infection, a wound, or perceived threat of such. The immune system mobilizes white blood cells called macrophages to the injured area or site of infection. The cells of the immune system also release a cascade of messenger molecules called cytokines that amplify inflammation. These include interleukin 1ß, interleukin- 6 and tumor necrosis factor -α. The liver also releases a protein called c-reactive protein. When the threat is neutralized the immune system helps the body start to heal by releasing anti-inflammatory cytokines including interleukin (IL)-1 receptor antagonist, IL-4, IL-10, IL-11, and IL-13.

In chronic inflammation the pro-inflammatory cytokines continue to predominate and the c-reactive protein continues to be elevated.

Causes of Chronic Inflammation

Causes an individual can do something about

  • Low levels of physical activity.
  • Having a BMI at or above 30 , especially when excess weight is deep within your belly (visceral fat). The best way to measure belly fat is to use a tape measure to measure your waist at the widest point. Increased belly fat is greater than 35 inches for women or greater than 40 inches for men
  • An imbalance of healthy and unhealthy bacteria in your intestine (dysbiosis). Dysbiosis can be caused by antibiotics and by eating foods low in soluble fiber.
  • Regularly eating foods that cause inflammation, especially highly processed foods, or foods high in sugar or salt
  • Inadequate sleep
  • Using tobacco products.
  • Regularly drinking too much alcohol
  • Periodontal disease (gum infection) and tooth decay
  • Perceived stress

Societal Causes

  • Experience of racism (structural or personal)
  • Poverty
  • Homelessness
  • Worry about debt
  • Work stress
  • Exposure to air pollution
  • Exposure to chemicals (pesticides and herbicides for farm workers, glyphosphate (RoundUp) for everyone, microplastics in our bloodstreams for everyone. Every day, we are surrounded by thousands of synthetic chemicals. They are in our food, clothes, tools, furniture, toys, cosmetics and medicines. We know the health effects of only a few of these).

Diseases caused by chronic inflammation

  • Cardiovascular Disease (coronary artery disease, heart attacks, congestive heart failure)
  • Strokes
  • Type 2 diabetes
  • Cancer (multiple types)
  • Inflammatory bowel disease (crohns disease, ulcerative colitis)
  • Rheumatoid Arthritis
  • Lupus and similar autoimmune diseases
  • Asthma
  • COPD
  • Pulmonary fibrosis
  • Depression

Tests to measure chronic inflammation

All of the inflammatory cytokines can be measured but those are expensive tests. A simple inexpensive test that measures inflammation, both acute and chronic is high sensitivity CRP. It will also be high with an acute infection or injury, but will return to normal after the infection or injury have resolved. If it remains elevated when you are not sick or injured it is a sign of chronic inflammation. It may be worth asking your doctor to order this test if you have any of the individual or societal risk factors for chronic inflammation. A normal hs-CRP is less than 0.55 mg/dl in men and less than 1.0 mg/dl in women. If your hs-CRP is high in the absence of acute infection or injury, that can serve as motivation to make lifestyle changes to decrease your chronic inflammation and put you in a population that has less risk of developing any of the diseases associated with chronic inflammation.

Anti-inflammatory lifestyle

  • Exercise regularly. The CDC recommends 30 minutes of moderate exercise (walking briskly) for 30 minutes at least 5 days a week.
  • Eat mostly unprocessed or minimally processed foods and avoid sugary drinks or foods with added sugar or high fructose corn syrup. Also include foods with high soluble fiber such as beans, carrots, sweet potatoes, nuts, berries and most fruits (not fruit juice). Organic foods, while more expensive, have no residual pesticides or herbicides. If you eat meat buy grass fed beef, and pasture raised chicken and pork. Eat more plant-based foods than meat.
  • Avoid taking antibiotics as much as possible
  • Sleep. Average at least 8 hours a night
  • Floss your teeth daily, brush twice a day and see your dentist every 6 months
  • If you don’t smoke, don’t start and if you do smoke quit.
  • It is better not to drink alcohol at all, but if you do limit it to 1 drink a day or less.
  • Learn meditation or self hypnosis to manage stress. There are good books and videos, but an in person course is best if it is available.
  • Drink only filtered water and not bottled water in plastic bottles
  • Gas stoves cause significant indoor air pollution. If possible switch to an electric stove. Induction type burners actually heat more quickly than gas. If you have to use a gas stove, be sure to turn the ventilator fan on and open a window if possible.

Bottom Line

Chronic inflammation is the common pathway for many chronic diseases. There are many individual strategies that reduce or prevent chronic inflammation. Many of these strategies are not possible for people with socioeconomic problems. The stress black people experience from structural and individual racism, homelessness or inadequate housing, anxiety over debt, exposure to environmental synthetic chemicals, and exposure to air pollution are societal problems that we all have a responsibility to address.

My next post will deal with chronic inflammation and cardiovascular disease.

Update on Diagnosis and Treatment of Alzheimers Disease

There are some new developments in the diagnosis of Alzheimer’s disease. These developments mean more people may be eligible for the new treatments for Alzheimer’ disease. In this post I will write about the new blood tests for Alzheimer’s disease and also revisit the available treatments. This will be an update of my previous post New Treatment for Early Alzheimer’s Disease – What You Need to Know.

Blood tests for Alzheimer’s disease

The monoclonal antibody treatments for Alzheimer’s disease only work if patients have evidence of amyloid proteins in their brains. Prior to the new blood tests, the only way to tell if patients had the amyloid protein was either to measure it in spinal fluid (which means a spinal tap) or to see it on a PET scan (which is a very expensive type of scan). The FDA has approved a new blood test that has been shown to work as well as a spinal tap or PET scan. It measures a protein called ptau217. The test is called the ALZpath ultra-sensitive pTau217  test. Because it requires just a blood sample, that means a lot more people will get the test and if positive will be eligible for treatment with the new monoclonal antibody treatments. This is a somewhat mixed blessing as I will outline below.

Theories of the cause of Alzheimer’s disease

On November 3, 1906, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported “A peculiar severe disease process of the cerebral cortex” to the 37th Meeting of South-West German Psychiatrists in Tubingen, Germany. He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain at autopsy. In 1909 he presented two more patients with a similar history and pathology in the brain after death. These were all relatively young patients, so the name Alzheimer’s disease originally was applied to patients who developed dementia in their 50’s and 60’s (it was also called “pre-senile dementia.”

In later years it was discovered that many people who developed dementia at any age, including advanced age had the same plaques and neurofibrillary tangles when their brains were examined after they died. It turned out that 90 % of people who had dementia had these plaques and neurofibrillary tangles in their brains found at autopsy..

The Toxic Protein Hypothesis

The composition of the plaques turned out to be a protein called amyloid protein and the neurofibrillary tangles were composed of another protein called tau. The theory was that accumulation of these proteins was toxic to brain cells and that this toxic effect caused dementia. Because dementia is associated with age, it was hypothesized that in predisposed individuals gradual accumulation of these proteins in brain cells over many years eventually results in dementia.

There is one problem with this hypothesis. Several studies have followed aging people over time and measured the presence or absence of dementia. People in all these studies have agreed to have their brains studied after they died. In all of these studies anywhere from 12% to 30% of people who never had dementia during their long lifetimes (many were in their 80’s or older when they died) had plaques and neurofibrillary tangles that met the criteria for Alzheimer’s disease. It appears that the accumulation of amyloid and tau proteins is associated with Alzheimer’s dementia, but not necessarily the main cause of it.

Treatments based on the toxic protein hypthesis

There are three monoclonal antibodies now approved by the FDA for the treatment of Alzheimer’s disease. They newest ones are lecanemab and donanemab. They both target the amyloid beta protein that accumulates in people with Alzheimer’s disease. They are both used in people with mild cognitive impairment and they do reduce the beta amyloid protein as shown by follow up spinal fluid testing and/or PET scanning. Unfortunately, they only have a modest effect on slowing progression from mild cognitive impairment to Alzheimer’s disease. The cognitive test used in the studies of both drugs is called the Clinical Dementia Rating–Sum of Boxes. The range of this test is 0-18. Only people with mild cognitive impairment were included in the trials. The treatment group in the lecanemab trial got lecanemab, which has to be given by iv infusion every two weeks for 18 months. The placebo group got a saline infusion every two weeks. In both the placebo group and the treatment group, the scores on the dementia test got worse by 18 months, but the dementia scores for the treatment group did not increase as much as the placebo group. The absolute difference in the scores was about 14%. This was a statistically significant difference in slowing the progression of mild cognitive impairment to Alzheimer’s disease, but it’s not a very big difference.

Side effects of monoclonal antibody treatment

Both approved monoclonal antibody treatments attack the amyloid beta protein and produce an inflammatory response in the brain. This resulted in brain edema and/or micro hemorrhages in 17% of the treatment group vs 9% of the placebo group. Also nearly a quarter of the treatment group had reactions to the infusion. Most of the people with brain hemorrhages or edema did not have symptoms but some had headache, visual disturbance and confusion.

Expense of monoclonal antibody treatment

Lecanemab, which goes by the trade name Leqimbi is priced by the manufacturer at $26,500 per year. The other approved monoclonal antibody, aducanumab is priced at $28,200 per year. The UK has not approved either of these drugs because they don’t feel the modest benefit justifies the cost. The UK also points out that we have no idea what the long term effects of either one of these drugs might be.

Other treatments for Alzheimer’s disease

The other major class of drugs that has been used for Alzheimer’s disease are the cholinesterase inhibitors. The theory behind using these drugs is that nerve cells that produce a neurotransmitter called acetyl choline are diminished in Alzheimer’s disease. The cholinesterase inhibitors have the effect of increasing levels of acetyl choline in the brain because they inhibit the enzymes that break it down. These drugs are donazepil (Aricept), rivastigmine (Excelon), memantine in combination with donazepil (Namzeric), galantamine (Razadyne) and tacrine (Cognex).

These medicines don’t work very well Fourteen out of 100 patients with mild to moderate Alzheimer’s disease have some improvement in thinking skills. Side effects, especially nausea and vomiting are common. None of these medicines has been shown to work any better than the others in the class.

Genetics

There is no specific Alzheimer gene. Almost 80 genetic sequences have been identified that either decrease or increase the risk of Alzheimer’s disease. If you have a first degree relative who has had or has Alzheimer’s disease, then your risk is increased somewhat. Each of these sequences has only a minimal effect by itself, so you would have to have a lot of them to substantially increase the risk of Alzheimer’s disease. It is estimated that genetics accounts for less than 5% of Alzheimer’s disease.

Integrated theory of cause of Alzheimer’s disease

In doing research for this post, I discovered a very interesting paper by Richard Armstrong that reviews current theories of the cause of Alzheimer’s disease and proposes a new integrated theory that accounts for everything we know about Alzheimer’s disease so far. Here is a link to that paper if you would like to read the whole thing: Review article: What causes alzheimer’s disease?. It is from a Polish neurological journal, but the article is in english.

On the basis of current evidence Dr Armstrong believes that the primary factor in Alzheimer’s disease is an age-dependent breakdown of anatomical systems and pathways within the brain and the consequent loss of synapses. The degree of this aging effect depends on the amount of lifetime stress (also called allostatic load). The brain is the ultimate recipient of stress through hormonal changes resulting from high blood pressure, diabetes, cardiovascular disease, and immunological problems. The result of all this is gradual disconnection of synapses, degeneration of nerve cells, and the expression of genes determining various reactive and breakdown products such as Aβ and tau. The brain has a protective mechanism that removes breakdown products, and this protective mechanism continues to function and prevents the accumulation of Aβ and tau. As a person enters old age and the effects of excessive body stress accumulate, then senile plaques and neurofibrillary tangles begin to form as the brain’s protective systems get overwhelmed. In this theory, accumulation of Aβ and tau are the result of loss of synapses and connections in the brain rather than the cause. By the time these proteins can be detected in the spinal fluid or blood, the process of brain degeneration is already well underway. It is no wonder that targeting these proteins with monoclonal antibodies only modestly slows but does not reverse the progression of mild cognitive deficit to full blown Alzheimer’s disease.

If Doctor Armstrong’s theory is correct, then we should see a markedly increased risk of developing Alzheimer’s Disease with aging in people with certain chronic conditions. Here are some numbers:

Metabolic Syndrome

Metabolic syndrome is defined by having at least three of the following five conditions:

  1. Excess abdominal fat (Waist circumference greater than 40 inches for men or 35 inches for women)
  2. High blood pressure (Systolic greater than 140 or diastolic greater than 90)
  3. High blood sugar (fasting blood sugar greater than 100 mg/dl)
  4. high blood triglycerides (fasting triglycerides greater than 150 mg/dl)
  5. Low HDL cholesterol (less than 40 mg/dl)

People with metabolic syndrome have 11.5 times the risk of developing Alzheimer’s disease as they age as people without metabolic syndrome. About one in every three adults in the US has metabolic syndrome.

Type 2 diabetes

A recent review of the literature found that type 2 diabetes increases the risk of eventually developing Alzheimer’s disease by 56%.

Coronary artery disease

People with coronary artery disease, especially at a relatively young age have a 26% increased risk of eventually developing Alzheimer’s disease.

Sedentary Lifestyle

In a study from the UK the more hours a person spent sedentary, the higher the risk of all cause dementia. Since Alzheimer’s disease accounts for the vast majority of dementia, we can assume that the more hours per day you spend on the couch, the greater the risk of eventually developing Alzheimer’s disease.

Social Networks

Many longitudinal studies show that maintenance of supportive social networks (family, friends) decreases the risk of development of Alzheimer’s disease. Conversely loneliness increases the risk of developing Alzheimer’s disease

Heavy alcohol consumption

Light to moderate alcohol consumption (2 drinks a day for men and 1 drink a day for women actually decreases the risk of developing Alzheimer’s disease. Heavy alcohol consumption (4 drinks a day or greater for men and 3 drinks a day or greater for women) increases the risk of developing Alzheimer’s disease by 300%!

Bottom Line

The new blood tests help diagnose people with mild cognitive impairment who are at high risk of progressing to Alzheimer’s disease. This is only helpful if there are good treatments to prevent progression to Alzheimer’s disease. Unfortunately, the best current treatments modestly slow the progression from mild cognitive impairment to Alzheimer’s disease but do not reverse or prevent the progression. These monoclonal antibody treatments have significant side effects that include microhemorrhages and brain edema. At present there is no medical treatment to reverse or prevent Alzheimer’s disease.

Dr. Armstrong has proposed a theory that the non-hereditary form of Alzheimer’s disease results from loss of synaptic connections in the brain from chronic lifetime body stress and that the amyloid protein accumulations are the result rather than the cause of loss of synaptic connections in the brain. This theory is supported by the fact that people with lifestyle related chronic diseases (metabolic syndrome, diabetes, heart disease, sedentary lifestyle, lack of meaningful mental activity, loneliness, heavy alcohol intake) have a markedly increased risk of developing Alzheimer’s disease as they age.

The best treatment for Alzheimer’s disease is prevention. Risk of developing Alzheimer’s disease with age is decreased by maintaining normal body weight, eating mostly unprocessed foods, exercising regularly, staying mentally active, maintaining supportive social networks, and avoiding heavy alcohol intake.

Chronic Stress Response: It Can Make You Sick or Kill You

All mammals, including humans have an innate response to perceived threat or stress. The more common name for it is the “flight or fight” response. Our remote ancestors faced many real threats. Let’s say for example one encountered a saber tooth tiger. As soon as he (or she) saw the tiger, several things happened. Epinephrine and norepinephrine were released, speeding up the heart rate in preparation for running away. A surge of cortisol was also released, which increased glucose in the bloodstream for fuel for muscles and the brain. Cortisol also increases mental alertness. Inflammatory molecules were released to promote wound healing should that be needed.

This kind of acute stress response is a good thing. People or animals with this kind of response were more likely to survive and reproduce. Once the acute threat was over, all the hormones and neurotransmitters quickly returned to their baseline levels.

In today’s world, threats from predators are not a problem for the vast majority of people. The threats we perceive are things like poor work conditions; experiencing discrimination, hate, or abuse; poverty; homelessness; divorce or other family discord; having little control over outcomes; feeling overwhelmed.

These are all things that produce the stress response, but unlike our remote ancestors, these threats are chronic. They are either lifelong or at least last a long time. Instead of returning to normal, the stress hormones and neurotransmitters stay elevated for long periods of time. A chronic stress response is definitely not a good thing!

Allostatic Load

The medical term for the acute stress response is called allostasis. Here is the definition of allostasis from Wikipedia: “Allostasis is the efficient regulation required to prepare the body to satisfy its needs before they arise by budgeting those needed resources such as oxygen, insulin etc., as opposed to homeostasis, in which the goal is a steady state.” Allostasis is an adaptive response to acute stress. Allostatic load on the other hand is the long-term result of failed allostasis, resulting in dysregulation (abnormal function) of multiple systems including the neuroendocrine, cardiovascular, immune, and metabolic systems.

Allostatic load is measured traditionally by 10 indicators of chronic stress. Primary indicators are the hormones and neurotransmitters released by stress. Secondary outcomes are measurements of the systemic effects of the primary indicators. All of these indicators are associated with the perception of stress. Below is a table showing the 10 indicators, how they are measured, and which body systems are affected. Here is a link to the full article from which this table comes: Allostatic Load: Importance, Markers, and Score Determination in Minority and Disparity Populations

CategoryMarkerFunctional purpose
Primary mediatorsDehydroepiandrosterone sulfate (DHEA), serumSecreted by the adrenal glands. When high with stress it tends to lower cortisol and be protective in the stress response.
Cortisol, urinaryIntegrated measure of 12-hour hypothalamic–pituitary–adrenal axis activity. Secreted by the adrenal glands. Has multiple effects in stress response.
Epinephrine, urinaryIntegrated indices of 12-hour sympathetic nervous system activity. Sympathetic nervous system activation increases heart rate and blood pressure.
Norepinephrine, urinary
Secondary outcomesSystolic blood pressureIndices of cardiovascular activity and major risk factor for vascular disease
Diastolic blood pressure
Waist–hip ratioIndex of long-term levels of metabolism and adipose (fat) tissue deposition. High value means fat around internal organs which increases inflammation and increases LDL (bad cholesterol) and triglycerides.
High-density lipoprotein cholesterolIndex of atherosclerotic risk protection. Low value increases risk of heart disease.
Total cholesterolIndex of long-term atherosclerotic risk
Hemoglobin A1CIntegrated measure of high blood sugar over 2–3 months

Each indicator that is a certain distance out of the normal range counts as one point. The score can range from zero to ten. The higher the score, the greater the risk of illness or death.

Other Indicators

Although the ten indicators were the ones described in the original papers about allostatic load, other indicators have been used as well.

  • Heart rate variability is the normal beat to beat variability in the heart rate. In a healthy heart there is slight variation in the timing of one heartbeat to the next. Chronic stress reduces or even eliminates this beat to beat variation.
  • High sensitivity C-reactive protein (CRP). This is a measure of systemic inflammation that can result from chronic stress.

How is the stress reaction triggered?

The stress reaction begins in the brain. Something in the environment is perceived in a part of the front of the brain called the prefrontal cortex. This is the executive decision maker in the brain. If the prefrontal cortex perceives something in the environment as a threat, then it sends messages to the limbic system (the part of the brain that is involved with emotions). It also sends messages to centers lower in the brain, especially the hypothalamus. The hypothalamus sends messages to the adrenal glands which secrete cortisone, norepinephrine and epinephrine. The hypothalamus secretes DHEA. Messages from the hypothalamus are also sent to the white blood cells which secrete inflammatory chemicals called cytokines. All of this prepares the body to deal with the perceived threat. Different people may perceive different things as a threat. It is the reaction to perceived threats that causes allostatic load. If another person experiences the same thing in the environment as not a threat, then there is no stress reaction.

Diseases associated with high allostatic load (high chronic stress)

A high allostatic load score is not disease in itself, but if chronic stress continues then disease in the cardiac, metabolic, neuroendocrine and immune system can occur. Here is a list of diseases associated with persistent high allostatic load.

  1. Heart disease, primarily progressive blockage of the coronary arteries. This can lead to angina and/or heart attack. Congestive heart failure and arrhythmia like atrial fibrillation can also occur
  2. Peripheral arterial disease. That is blockage in arteries in the legs and sometime fingers.
  3. High blood pressure
  4. Stroke
  5. Autoimmune diseases like rheumatoid arthritis or lupus
  6. Diabetes
  7. Fibromyalgia
  8. Chronic Fatigue Syndrome
  9. Dementia or decreased cognitive function
  10. Depression
  11. PTSD
  12. Cancer, particularly breast and ovarian cancer. The increase in cancer is probably related to decreased immune system function

Allostatic Load and Mortality

Many studies have shown that people with persistently hight allostatic load have about a 25% higher premature death rate than people with low allostatic load.

Disparities in Health Outcomes

The response to chronic stress (allostatic load) may explain some of the disparities we see in health outcomes. We know, for example that Adverse Childhood Events (ACE), which include things like abandonment and abuse, increase the risk of many chronic diseases in adulthood. Studies have shown that adults with a history of ACE have high allostatic load scores.

African Americans have higher incidence of many cancers, as well as poorer outcomes from those cancers. They also have worse outcomes from heart disease, high blood pressure and diabetes. While a good portion of these poorer outcomes are related to lack of access to health care, these disparities persist to some degree even in middle class and upper middle class African Americans. Almost all African Americans have experienced or still experience racism on a chronic basis. African Americans of all social classes have higher allostatic load scores than caucasians. Chronic stress and response to it may be the common denominator for these disparities as well as for health outcome disparities in other marginalized populations.

How to reduce allostatic load

There is typically a long time between the presence of indicators of allostatic load and illness and death caused by diseases associated with these indicators. That presents an opportunity to reduce allostatic load before the chronic stress response leads to illness and death. So how do we reduce allostatic load?

Some of the things that cause allostatic load can only be reduced by societal changes. Things like poverty, structural racism and homelessness cannot be decreased by individual effort. Even these causes, though, can respond to the mind body methods discussed below. On the other hand, if you don’t have enough to eat, have no home, or have a job that gives you no control of your life, it is not likely that you will have the energy or the will, or the financial means to do many of the mind body methods discussed below. We should not be distracted from working to decrease the inequities that are responsible for societal causes of chronic stress.

Mind-Body Medicine

Remember that an external threat is first received by the peripheral nervous system and transmitted to the pre-frontal cortex. In order to reduce allostatic load we can either reduce the threat perception in the prefrontal cortex (top down) or reduce the transmission of threat in the peripheral nerves (bottom up).

Top Down Treatments

Top down treatments start with intentional activity in the prefrontal cortex. The idea is to decrease activation of the limbic system and the hypothalamus. This can be accomplished by mindfulness meditation, hypnosis (including self hypnosis), mental imagery and progressive muscle relaxation. All of these techniques when done regularly have been found to decrease allostatic load indicators and to reduce the risk of stress related illnesses.

Bottom Up Treatments

Bottom up treatments decrease the threat transmission to the prefrontal cortex. They include yoga, Tai Chi, massage and biofeedback. These treatments have also been shown to decrease allostatic load and to reduce stress related illness.

Bottom up and top down are somewhat of an oversimplification. All of these treatments have some aspects of both top down and bottom up. Yoga, for example includes aspects of meditation. The same goes for Tai Chi. Biofeedback involves some attention from the prefrontal cortex. Massage also includes progressive muscle relaxation.

Bottom Line

The body’s reaction to a perceived threat includes a complex cascade of messages from the executive center in the prefrontal cortex to multiple body systems including the nervous system, the endocrine system, the cardiovascular system and the immune system. All of these things prepare the body to deal with the threat. As long as the threat is short term the stress response is very useful to the organism.

Perception of chronic stress leads to continuous secretion of all the stress hormones and inflammatory cytokines and this leads to dysfunction of multiple body systems and eventually to illness and death.

Mind body treatments, both top down and bottom up can reduce the allostatic load (chronic stress response) and reduce the risk of stress induced illness and death.

Many causes of chronic stress have to do with the structure of our society, such as poverty, homelessness and structural racism. Individual effort is not likely to ameliorate the effect of these causes of chronic stress. All of us should be working toward societal change to reduce chronic stress response in marginalized populations.