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Health Highlight: Stress & HPA Axis

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Physical or psychological stress, including prolonged exposure to cold, hypoglycemia, physical trauma, and emotional distress, activates the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system causing a neuroendocrine response, including the release of epinephrine and norepinephrine and changes in cortisol levels.1,2 The stress response results in increased heart rate, which increases pulse rate, blood pressure, and increases respiration; release of blood glucose stores to provide increased energy; and a reduction in digestive and reproductive functions to increase available energy.1 This is often called the “flight or fight response” due this disruption in homeostasis.1 Homeostasis is the ability of the body to maintain a stable internal environment in response to external stimuli, including temperature, blood pH, blood glucose, heart rate, respiration, organ function, and more.1 While the stress response is helpful in an acute stress situation, such as a car accident, chronic stress can lead to pathological changes.

Chronic activation of the HPA axis can lead to an inability of the body to respond appropriately to environmental changes. Many holistic practitioners call this “adrenal fatigue,” though this term is too simplistic and unscientific for the cascade of problems caused by HPA axis dysfunction. Chronic activation of the HPA axis can lead to alterations in metabolic mediators, autonomic nervous system, immune system, and neuroendocrine system with disruptions in the production of cortisol, epinephrine, DHEA, melatonin, sex hormones, and thyroid hormones.1,2

Symptoms of HPA axis dysregulation and chronic stress include weight gain or loss; fatigue; muscle pain and/or weakness; sleep disorders; anxiety; depression; PTSD; neurodegeneration and cognitive decline; thyroid disease; decreased coping mechanisms; depressed immune system; and metabolic dysfunctions including high blood pressure, impaired glucose metabolism, and insulin resistance which can lead to obesity, type II diabetes, heart disease, stroke, and more.2,3,4

Besides chronic stress, three other drivers of HPA axis dysfunction have been identified: inflammation, circadian rhythm disruption, and blood glucose impairment.4 To improve HPA axis function and reduce chronic stress, these four triggers should be addressed through lifestyle changes including reducing and/or managing physical and psychological stressors; addressing the root causes of inflammation with lifestyle and/or medications; improving circadian rhythm by getting bright light in the morning, reducing blue light after dark, and maintaining a regular sleep pattern; and regulating blood glucose levels by reducing glycemic impact through dietary changes that work best for you.4 Laboratory tests, medications, and supplements for HPA axis dysfunction and associated health issues should be discussed with a qualified healthcare provider.

1. Goldstein DS. Adrenal Responses to Stress. Cell Mole Neurobiol. 2010; 30(8):1433-1440. doi: 10.1007/s10571-010-9606-9.
2. McEwen BS. Neurobiological and Systemic Effects of Chronic Stress. Chronic Stress (Thousand Oaks). 2017; 1. doi: 10.1177/2470547017692328.
3. Herman JP. Neural control of chronic stress adaptation. Front Behav Neurosci. 2013; 7: 61. doi: 10.3389/fnbeh.2013.00061.
4. Guilliams TG, Edwards L. Chronic Stress and the HPA Axis: Clinical Assessment and Therapeutic Considerations. Standard. 2010; 9(2).

Disclaimer: The content herein is not intended to be a substitute for professional medical advice. It is not meant to diagnosis, cure, or treat any medical condition. Always consult a physician or other qualified healthcare provider with questions regarding a medical condition and before starting new diets and dietary supplements. Not all diets or supplements are appropriate for all people or all health conditions.


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