Cortisol – Еverything you need to know about it

Cortisol a steroid hormone produced by the adrenal glands, plays a complex role in the immune system. Its functions are intricately tied to maintaining an appropriate balance in the immune response. Understanding cortisol’s role sheds light on the body’s innate stress response mechanisms, unveiling the intricate interplay between hormones and the nervous system. This exploration lays the foundation for grasping the significance of cortisol in maintaining physiological balance and resilience in the face of life’s challenges.

The Adrenal Mechanism:

Situated atop the kidneys, the adrenal glands act as the command center for cortisol release. Triggered by the hypothalamus-pituitary-adrenal (HPA) axis, cortisol production is part of the intricate process between the brain and adrenal cortex. This understanding extends to the feedback loop regulating cortisol release, providing a nuanced perspective on how the body finely tunes its stress response to maintain balance. Recognizing this mechanism is essential for grasping how the body mobilizes resources to cope with stressors of varying intensities, safeguarding its equilibrium. By delving into the intricate mechanics of cortisol production, we gain a deeper appreciation for the body’s ability to adapt and respond to environmental demands.

Understanding Cortisol:

Beyond its reputation as a stress hormone, cortisol serves a spectrum of functions. From regulating metabolism and influencing immune response to orchestrating the body’s natural rhythm, cortisol is a versatile player in maintaining homeostasis. This section explores the multifaceted nature of cortisol, emphasizing the need for a delicate balance for optimal physiological functioning. As we delve into cortisol’s diverse roles, it becomes clear that its influence extends beyond immediate stress response, impacting various aspects of daily life and overall health. Recognizing cortisol as a dynamic regulator, not just in stress but also in metabolism and immune function, broadens our understanding of its importance in maintaining overall well-being.

Here are some key aspects of cortisol’s function in the immune system:


  1. Anti-Inflammatory Effects: Cortisol has potent anti-inflammatory properties. It works to suppress the immune system’s inflammatory response, preventing an excessive release of pro-inflammatory substances. This is crucial for preventing chronic inflammation, which can lead to various health issues.
  2. Immunosuppressive Action: Cortisol acts as an immunosuppressant, particularly in high concentrations. It inhibits the activity of immune cells, such as T cells and B cells, and reduces the production of pro-inflammatory cytokines. This immunosuppressive action helps prevent the immune system from overreacting and causing damage to the body’s own tissues.
  3. Regulation of Immune Cell Trafficking: Cortisol regulates the migration of immune cells to different tissues. It can inhibit the movement of immune cells to areas of inflammation, controlling the intensity and duration of the immune response. This is crucial for preventing excessive immune activity in specific regions of the body.
  4. Balance in Th1 and Th2 Responses: Cortisol helps maintain a balance between the T-helper 1 (Th1) and T-helper 2 (Th2) immune responses. An appropriate balance between these responses is necessary for effective immune function. Cortisol can shift the immune response towards Th2 dominance, which is associated with antibody production and allergic responses.
  5. Modulation of Cytokine Production: Cortisol influences the production of cytokines, which are signaling molecules that regulate immune responses. It tends to suppress the production of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), while promoting the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10).
  6. Stress-Related Impact on Immunity: In situations of acute stress, cortisol levels can rise rapidly. While short-term increases in cortisol may enhance certain aspects of immune function, chronic stress and prolonged elevation of cortisol levels can lead to immunosuppression. This underscores the importance of managing stress for overall immune health.

It’s crucial to note that while cortisol is essential for regulating immune responses, prolonged or excessive cortisol levels, as seen in chronic stress, can have detrimental effects on immune function. Chronic stress-related cortisol elevation may contribute to increased susceptibility to infections and other immune-related disorders. The intricate balance in cortisol levels is vital for a properly functioning immune system.

How cortisol reflects on metabolism:

  1. Glucose Metabolism: Cortisol is known to influence glucose metabolism. It stimulates gluconeogenesis, a process in which the liver produces glucose from non-carbohydrate sources, such as amino acids and glycerol. This helps maintain blood glucose levels during fasting or stress. Elevated cortisol levels can lead to increased glucose production, contributing to higher blood sugar levels.
    ( A study published in the journal “Diabetes” (2015) titled “Cortisol Counteracts Insulin-Stimulated Glucose Transport in Human Skeletal Muscle” found that cortisol has an inhibitory effect on insulin-stimulated glucose transport in human skeletal muscle, highlighting its role in glucose metabolism.)
  2. Protein Metabolism: Cortisol also influences protein metabolism. It promotes protein catabolism, where proteins are broken down into amino acids. These amino acids can then be used for gluconeogenesis or as an energy source during stressful situations. Increased cortisol levels may lead to muscle protein breakdown, impacting overall protein balance.
    (Research published in the “American Journal of Physiology – Endocrinology and Metabolism” (2012) demonstrated that cortisol increases the rate of protein degradation in skeletal muscle, indicating its role in protein metabolism.)
  3. Lipid Metabolism: Cortisol is involved in lipid metabolism, particularly in promoting the breakdown of triglycerides into fatty acids. These fatty acids can be used as an energy source. However, prolonged elevation of cortisol levels, as seen in chronic stress, is associated with increased visceral fat deposition.
    (A study published in the “Journal of Clinical Endocrinology & Metabolism” (2008) investigated the impact of chronic stress on abdominal fat distribution and found a positive association between chronic stress, cortisol levels, and visceral fat accumulation.)
  4. Insulin Sensitivity: Cortisol has a complex relationship with insulin. While it is necessary for normal insulin function, chronically elevated cortisol levels can contribute to insulin resistance. This can lead to impaired glucose uptake by cells, resulting in elevated blood sugar levels and increased risk of type 2 diabetes. (In a study published in “Diabetes Care” (2005), researchers observed that higher cortisol levels were associated with insulin resistance in men, emphasizing the link between cortisol and impaired insulin sensitivity.)
  5. Appetite Regulation: Cortisol is implicated in appetite regulation. It can influence food intake by interacting with brain regions involved in appetite control. Stress-induced cortisol release may lead to changes in eating behavior, potentially contributing to weight gain. (A systematic review published in “Psychneuroendocrinology” (2017) examined the impact of acute stress on appetite and found evidence supporting cortisol’s role in modulating food intake, particularly in stressful situations.)

In summary, cortisol significantly influences various aspects of metabolism, including glucose, protein, and lipid metabolism, as well as insulin sensitivity and appetite regulation. While acute cortisol release is a normal part of the body’s stress response, chronic elevation can have detrimental effects on metabolic health. The evidence suggests that maintaining a balanced cortisol response is crucial for overall metabolic well-being.

How elevated cortisol levels may lead to increased body weight?cortisol-_weight-problems

  1. Increased Appetite and Cravings: Cortisol is associated with the regulation of appetite and food intake. Elevated cortisol levels, particularly in response to chronic stress, can lead to increased appetite, particularly for energy-dense and palatable foods. This can result in overeating and, consequently, weight gain. (A study published in “Appetite” (2010) investigated the relationship between cortisol and food intake in response to stress. The findings suggested that stress-induced cortisol release was associated with increased energy intake and a preference for high-fat and sugary foods.)
  2. Promotion of Abdominal Fat Deposition: Cortisol has been linked to the redistribution of fat, favoring its deposition in visceral or abdominal areas. High cortisol levels, especially in the context of chronic stress, can lead to the accumulation of fat around the abdomen. (Research published in “Psychoneuroendocrinology” (2000) explored the relationship between cortisol and fat distribution. The study found that higher cortisol levels were associated with increased abdominal fat in both men and women.)
  3. Stimulation of Lipogenesis: Cortisol promotes the process of lipogenesis, where excess glucose is converted into fat. This is part of the body’s response to chronic stress, where cortisol signals the storage of energy in the form of fat. (A study published in “Obesity” (2014) investigated the impact of cortisol on lipogenesis and found that cortisol increased the activity of enzymes involved in fat storage, providing insights into its role in promoting fat accumulation.)
  4. Insulin Resistance and Glucose Dysregulation: Elevated cortisol levels can contribute to insulin resistance, impairing the ability of cells to respond to insulin. Insulin resistance can lead to increased blood sugar levels and the storage of excess glucose as fat. (A study published in “Psychosomatic Medicine” (2000) examined the relationship between cortisol, insulin sensitivity, and body composition. The findings suggested that cortisol was associated with insulin resistance, which may contribute to fat accumulation.)
  5. Impact on Physical Activity: Chronic stress and elevated cortisol levels can also influence physical activity patterns. Some individuals may experience fatigue or a lack of motivation to engage in regular physical activity, which can contribute to weight gain.(Research published in “Medicine and Science in Sports and Exercise” (2004) investigated the relationship between stress, cortisol, and physical activity. The study found that higher cortisol levels were associated with lower levels of physical activity.)

It’s important to note that the relationship between cortisol and body weight is complex and can be influenced by various factors, including individual differences in stress response, genetics, and lifestyle. While acute cortisol release is a normal physiological response to stress, chronic elevation can have detrimental effects on metabolic health and contribute to weight gain. Stress management strategies and lifestyle interventions are often recommended to help mitigate the impact of chronic stress on cortisol levels and overall well-being.

The connection between depression and high levels of cortisol

  1. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis: The HPA axis is a key component of the body’s stress response system, involving the hypothalamus, pituitary gland, and adrenal glands. Chronic stress and depression can lead to dysregulation of the HPA axis, resulting in elevated cortisol levels. (Numerous studies, including a meta-analysis published in “Psychological Medicine” (2014), have consistently demonstrated HPA axis dysregulation in individuals with depression, characterized by increased cortisol secretion and altered feedback mechanisms.)
  2. Persistent Activation of the Stress Response: In depression, there is often a persistent activation of the stress response, leading to prolonged elevation of cortisol levels. This chronic exposure to cortisol can have detrimental effects on the brain, impacting neural structures associated with mood regulation and contributing to depressive symptoms. (Research published in “Biological Psychiatry” (2003) examined the relationship between cortisol and depression. The study found that individuals with depression exhibited higher cortisol levels and a blunted cortisol response to stress, indicating a dysregulated stress response.)
  3. Impact on Neurotransmitters and Neuroplasticity: Cortisol can influence neurotransmitter function and neuroplasticity, which are crucial for maintaining mood stability. Prolonged exposure to elevated cortisol levels may contribute to alterations in the levels of neurotransmitters such as serotonin and impair neuroplasticity, both of which are implicated in depression. (A review published in “Journal of Neuroendocrinology” (2019) discussed the impact of cortisol on neurotransmitter systems and neuroplasticity, emphasizing the potential role of cortisol dysregulation in the pathophysiology of depression.)
  4. Inflammation and Immune Dysregulation: Elevated cortisol levels in depression are associated with increased inflammation and immune dysregulation. Chronic inflammation has been implicated in the development and maintenance of depressive symptoms. (Studies, including a review in “Current Pharmaceutical Design” (2017), have explored the relationship between cortisol, inflammation, and depression. The evidence suggests that cortisol dysregulation may contribute to a pro-inflammatory state associated with depression.)
  5. Structural Changes in the Brain: Prolonged exposure to elevated cortisol levels can lead to structural changes in the brain, particularly in areas such as the hippocampus, which is crucial for mood regulation. Reduced hippocampal volume has been observed in individuals with depression. (Neuroimaging studies, including a meta-analysis in “Biological Psychiatry” (2018), have consistently reported structural changes, including reduced hippocampal volume, in individuals with depression, suggesting a potential impact of cortisol on brain structure.)

It’s important to note that the relationship between cortisol and depression is bidirectional, meaning that while depression can contribute to cortisol dysregulation, elevated cortisol levels can also exacerbate depressive symptoms. Treatment approaches for depression often involve addressing both psychological and physiological factors, with interventions such as psychotherapy, medications, and stress management techniques aiming to modulate the stress response and normalize cortisol levels. Additionally, research in this field continues to evolve, providing deeper insights into the intricate mechanisms linking depression and cortisol dysregulation.

The measurement of cortisol levels


  1. Blood Cortisol Test: A blood cortisol test is commonly used to measure the total amount of cortisol in the blood. It is usually done in the morning when cortisol levels are typically at their highest. In some cases, multiple samples may be taken throughout the day to assess the diurnal rhythm of cortisol.
  2. Salivary Cortisol Test: Salivary cortisol testing is often used to assess the free, unbound cortisol in the saliva. It is a non-invasive test that can be done at various times throughout the day, providing information about the diurnal variation of cortisol. This test is particularly useful for assessing cortisol levels in response to stress.
  3. Urine Cortisol Test: A urine cortisol test measures the total cortisol output over a 24-hour period. This test is often used to assess cortisol production over a more extended period and can be helpful in diagnosing conditions such as Cushing’s syndrome or Addison’s disease.
  4. Corticotropin-Releasing Hormone (CRH) Stimulation Test: This test involves injecting synthetic CRH to stimulate the release of cortisol. It is used to assess the responsiveness of the adrenal glands to CRH and can help differentiate between different causes of adrenal insufficiency or excess cortisol production.
  5. Low-Dose Dexamethasone Suppression Test: The low-dose dexamethasone suppression test is used to diagnose conditions such as Cushing’s syndrome. It involves taking a low dose of the synthetic glucocorticoid dexamethasone and measuring cortisol levels the next day to assess the suppression of cortisol production.
  6. High-Dose Dexamethasone Suppression Test: Similar to the low-dose version, the high-dose dexamethasone suppression test is used to diagnose Cushing’s syndrome. However, it involves a higher dose of dexamethasone to further suppress cortisol production.
  7. ACTH Stimulation Test: The adrenocorticotropic hormone (ACTH) stimulation test is used to evaluate adrenal gland function. It involves administering synthetic ACTH and measuring cortisol levels in response. This test helps distinguish between primary and secondary adrenal insufficiency.

Timing of Tests:

  • Morning Tests: Blood and salivary cortisol tests are often done in the morning, as cortisol levels typically peak within the first few hours after waking.
  • Diurnal Cortisol Rhythm Tests: Salivary cortisol tests throughout the day or a 24-hour urine cortisol test can provide information about the diurnal rhythm of cortisol.
  • Stimulation Tests: Tests involving the administration of substances like CRH or dexamethasone are typically done at specific times during the day, depending on the test protocol.

It’s important to note that the interpretation of cortisol test results should be done in consultation with a healthcare professional, as various factors, including medications, stress, and underlying medical conditions, can influence cortisol levels. The choice of the specific test and timing will depend on the clinical context and the information needed for diagnosis or monitoring.

Managing and reducing high levels of cortisol – recommendations:



  1. Regular Physical Activity:
    Exercise: Engage in regular, moderate-intensity exercise. Activities like walking, jogging, yoga, or swimming can help reduce stress and regulate cortisol levels.
  2. Adequate Sleep:
    Sleep Hygiene: Prioritize good sleep hygiene. Ensure you get enough quality sleep each night, aiming for 7-9 hours. Maintain a consistent sleep schedule, create a relaxing bedtime routine, and keep your sleep environment comfortable.
  3. Stress Management Techniques:
    Mindfulness and Meditation: Practice mindfulness meditation, deep breathing, or progressive muscle relaxation to manage stress. These techniques can help activate the body’s relaxation response, reducing cortisol levels.
    Yoga: Incorporate yoga into your routine, as it combines physical activity with mindfulness and can be beneficial for stress reduction.
  4. Healthy Diet:
    Balanced Nutrition: Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Ensure adequate intake of vitamins and minerals, especially B-vitamins, which play a role in stress management.
    Omega-3 Fatty Acids: Include sources of omega-3 fatty acids, such as fatty fish (salmon, mackerel), flaxseeds, and walnuts, as they have anti-inflammatory properties that may help modulate cortisol levels.
  5. Caffeine and Sugar Moderation:
    Limit Stimulants: Reduce intake of caffeine, especially in the afternoon and evening, as it can contribute to elevated cortisol levels. Similarly, minimize the consumption of refined sugars, as they can lead to blood sugar spikes and crashes, triggering stress responses.
  6. Adaptogenic Herbs:
    Ashwagandha and Rhodiola: Consider incorporating adaptogenic herbs like ashwagandha and rhodiola into your routine. These herbs have been studied for their potential to help the body adapt to stress and modulate cortisol levels.
  7. Social Support:
    Connect with Others: Cultivate strong social connections. Spending time with friends and loved ones and having a support system can contribute to emotional well-being and stress reduction.
  8. Time Management:
    Prioritize Tasks: Manage your time effectively, set realistic goals, and prioritize tasks. Feeling in control of your schedule can help reduce feelings of overwhelm and stress.
  9. Hydration:
    Drink Water: Stay well-hydrated by drinking enough water throughout the day. Dehydration can contribute to stress and impact cortisol levels.
  10. Limit Alcohol Intake:
    Moderation: If you consume alcohol, do so in moderation. Excessive alcohol intake can disrupt sleep patterns and contribute to stress.

It’s important to note that individual responses to stress and cortisol regulation can vary. If you are experiencing persistent stress, anxiety, or symptoms of high cortisol, it is advisable to consult with a healthcare professional. They can provide personalized guidance based on your specific situation, conduct relevant tests, and offer targeted interventions to support stress management and cortisol regulation.

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