Cortisol

Cortisol, often dubbed the "stress hormone," plays a pivotal role in the body's response to various stressors, regulating metabolism, immune function, and overall well-being. 

Produced by the adrenal glands, cortisol levels fluctuate throughout the day, following a circadian rhythm. While essential for survival, chronic elevation or depletion of cortisol levels can lead to a range of health issues, making it crucial to maintain cortisol levels within a healthy range. 

This article explores the significance of cortisol, its production and regulation, testing methods, normal and abnormal levels, and strategies to manage cortisol levels effectively. Understanding cortisol and its implications can empower individuals to take proactive steps towards better stress management and overall health.

Definition and Function of Cortisol

What is Cortisol?

Classified as a glucocorticoid hormone, cortisol is a crucial component of the body's stress response system.

It is synthesized from cholesterol through a series of enzymatic reactions in the zona fasciculata of the adrenal cortex.  Cortisol is produced in the steroidogenesis pathway, which encompasses the biosynthesis of steroid hormones from cholesterol. 

Cortisol Production and Regulation

Cortisol production and regulation are tightly controlled processes orchestrated by the hypothalamic-pituitary-adrenal (HPA) axis.  

The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then prompts the zona fasciculata of the adrenal cortex to synthesize and release cortisol into the bloodstream. 

Once the circulating cortisol level reaches a certain threshold it negatively feeds back to inhibit the release of CRH and ACTH, effectively regulating its own production. This feedback loop ensures that cortisol levels remain within a narrow physiological range, adapting dynamically to stressors and maintaining homeostasis throughout the body.

Cortisol has free and bound fractions: cortisol is bound to a carrier protein (often cortisol-binding globulin or albumin).  The free fraction is the biologically active pool of cortisol; the bound pool of cortisol becomes biologically active when it is released from its carrier protein.  Only 3-5% of circulating cortisol is available in its free, unbound form.  [5.]

Function of Cortisol: What Does Cortisol Do?

As a glucocorticoid hormone, cortisol exerts its effects by binding to glucocorticoid receptors in target tissues.  Because glucocorticoid receptors are present in almost every tissue of the body, cortisol has far-reaching effects in influencing gene expression and regulating metabolism, immune function, inflammation, and stress response.

Some specific functions of cortisol include:

Regulates metabolism: cortisol influences glucose metabolism by promoting gluconeogenesis, the production of glucose from non-carbohydrate sources, and inhibiting glucose uptake in peripheral tissues.  [20.]

Modulates immune response: cortisol has anti-inflammatory properties and suppresses immune function by inhibiting the release of pro-inflammatory cytokines and reducing the activity of immune cells including lymphocytes and macrophages.

Supports stress response: cortisol is often referred to as the "stress hormone" because it helps the body cope with physical and psychological stressors by mobilizing energy reserves, increasing alertness, and suppressing non-essential functions during times of perceived danger.  It does this through complex interactions between the brain and autonomic nervous system.  [20.]

Regulates blood pressure: cortisol contributes to blood pressure regulation by enhancing vasoconstriction, the narrowing of blood vessels, and increasing the sensitivity of blood vessels to other vasoconstrictors like adrenaline.  [23.]

Influences fluid and electrolyte balance: cortisol regulates fluid balance by enhancing the reabsorption of sodium and water in the kidneys while promoting the excretion of potassium, helping to maintain electrolyte balance.  [3.]

Affects mood and behavior: cortisol can influence mood, cognition, and behavior by interacting with neurotransmitter systems in the brain, particularly those involved in stress response and emotional regulation. [10.]

Supports fetal development: cortisol plays a crucial role in fetal lung maturation and surfactant production during pregnancy, aiding in the development of the respiratory system.

Regulates sleep-wake cycle: cortisol follows a diurnal rhythm, with levels typically peaking in the early morning hours to help facilitate wakefulness and declining throughout the day to promote relaxation and sleep at night.

Maintains bone health: cortisol modulates bone turnover by inhibiting bone formation and promoting bone resorption, which can lead to bone loss and increase the risk of osteoporosis when chronically elevated.  [4.]

Testing Cortisol Levels: Testing Methods

Blood, urine, and saliva testing are all common methods of cortisol assessment in the laboratory.  Each offers distinct clinical advantages, as listed below:

Blood Testing for Cortisol

Blood testing for cortisol involves drawing a blood sample from a vein, usually in the arm. This method measures the total cortisol concentration in the bloodstream, providing a snapshot of cortisol levels at the time of the test.

Benefits:

• Widespread availability in medical facilities
• Accurate measurement of total cortisol levels
• Considered the gold standard of cortisol measurement

Drawbacks:

• Requires venipuncture, which can be uncomfortable
• Cortisol levels may fluctuate throughout the day, necessitating multiple blood draws, generally at least 2 within a 24 hour period (often at 8 am and 4 pm)
• Does not provide accurate reflection of free, or bioavailable, cortisol levels [5.]

Urine Testing for Cortisol

Urine testing for cortisol involves collecting a urine sample over a specified period, usually 24 hours, to measure the total cortisol excretion. This method provides an integrated measure of cortisol production over time and is less invasive than blood testing. 

Urine testing can show cortisol, cortisone, and metabolized cortisol levels.  

Benefits:

• Non-invasive method
• Samples can be collected at home
• Demonstrates HPA axis function over 24 hours and cortisol metabolism 

Drawbacks:

• Variations in urine volume and dilution can affect cortisol concentrations
• Potential for incomplete sample collection, leading to inaccurate results

Saliva Testing for Cortisol

Saliva testing for cortisol involves collecting saliva samples at specific times throughout the day, typically upon waking, before lunch, before dinner, and before bedtime. This method measures free cortisol levels, which represent the biologically active form of cortisol available to tissues.

Benefits:

• Non-invasive and painless sample collection
• Saliva testing provides the ability to assess diurnal cortisol rhythms
• Saliva testing is comparable to blood levels of free cortisol [12.]

Drawbacks:

• Potential variability in saliva collection technique
• Oral health may have an effect on cortisol measurements

Understanding Cortisol Levels

Normal Range for Cortisol Levels

Cortisol levels vary throughout the day, typically peaking in the morning and decreasing gradually throughout the day. 24 hour salivary and urine tests will capture the diurnal rhythm, while multiple blood tests are required to assess the same information.  

It is essential to understand that lab values may vary. In blood, urine, and saliva, normal cortisol levels also vary throughout the day.  Typical AM values range from : 6.2−19.4 μg/dL; PM: 2.3−11.9 μg/dL.

In urine, they range from 10 to 50 ng/mg upon waking, and rise to 30-130 ng/mg in the morning.  Urine cortisol measurements later in the day are expected to decline to 7-30 ng/mg in the afternoon, and down to 0-14 ng/mg at night.

Salivary cortisol levels are usually around 3.7 to 9.5 ng/mL upon waking and decrease throughout the day, to a low of about 0.4-1.0 ng/ml at night.

Dangerously Low Cortisol Levels

Dangerously low cortisol levels, known as hypocortisolism or adrenal insufficiency, can lead to symptoms such as fatigue, weakness, weight loss, and low blood pressure. Additionally, it is important to understand that symptoms may occur in many systems throughout the body, and that skin pigmentation can be a diagnostic factor between primary vs. secondary adrenal insufficiency.  [1.]

Diurnal rhythm disruptions, where cortisol levels are low in the morning and high in the evening, are also a clue of adrenal insufficiency and can be assessed through cortisol testing throughout the day.

In individuals with diurnal rhythm disruptions and low cortisol levels, the typical cortisol pattern, which is highest in the morning and gradually decreases throughout the day, is often reversed. 

This phenomenon, known as the "cortisol flip," can significantly impact various bodily functions and contribute to symptoms such as fatigue, lethargy, and difficulty coping with stress. 

In some cases, low cortisol levels are a sign of Addison’s disease.  Addison's disease is characterized by insufficient production of cortisol.  This deficiency typically occurs due to damage to the adrenal glands, often caused by autoimmune destruction, infections, or other underlying medical conditions. 

Patients with Addison’s disease may present with fatigue, weight loss, low blood pressure, hyperpigmentation of the skin, salt cravings, and gastrointestinal disturbances. Treatment typically involves lifelong hormone replacement therapy to replace the deficient hormones.

Causes of High Cortisol Levels

High cortisol levels, or hypercortisolism, can be caused by conditions such as Cushing's syndrome, prolonged stress, or excessive corticosteroid medication use. Symptoms may include weight gain, high blood pressure, mood changes, and muscle weakness. 

Additionally, research links chronic inflammation and obesity with elevated cortisol levels.  [6., 22.]  Identifying and addressing the underlying cause is essential for managing high cortisol levels effectively.

How to Stop Cortisol Weight Gain

Chronically elevated cortisol has been associated with increased appetite, particularly for unhealthy foods, as well as with obesity. [9., 11.]

Preventing or reversing cortisol-induced weight gain involves a multifaceted approach that addresses both stress management and lifestyle factors. Incorporating regular exercise into your routine, such as cardiovascular workouts and strength training, can help burn calories and improve metabolism. 

Additionally, adopting a balanced diet that focuses on whole, nutrient-dense foods while limiting processed foods and added sugars can aid in weight management and reduce cortisol levels. 

Implementing stress-reduction techniques like meditation, deep breathing exercises, and adequate sleep can also support healthy cortisol levels and prevent weight gain associated with chronic stress.

The following section explores research-based methods to reduce cortisol levels and stop cortisol-induced weight gain.  

Managing Cortisol Levels

Strategies to Lower Cortisol

• Practice mindfulness-based stress reduction techniques, including meditation, deep breathing exercises, and yoga.  [21.]
• Engage in regular physical activity and ensure adequate sleep each night to support cortisol regulation.  [7.]
• Maintain a balanced diet rich in whole foods, while limiting caffeine, alcohol, and sugar intake to stabilize cortisol levels.
• Foster a supportive social network and seek professional counseling or therapy to address underlying stressors effectively.
• Consume a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats to provide essential nutrients for adrenal health and cortisol regulation.
• Incorporate foods high in magnesium, such as leafy greens, nuts, seeds, and legumes, which may help reduce cortisol levels and promote relaxation.
• Avoid excessive caffeine, refined sugars, and processed foods, as they can spike cortisol levels and contribute to chronic stress.  [8., 9., 14.]

Supplements for Lowering Cortisol:

• Herbal adaptogens: incorporate adaptogenic herbs like ashwagandha and holy basil into your routine to regulate cortisol levels and enhance stress resilience.  [13., 17.]
• Explore supplements such as phosphatidylserine to support adrenal health, reduce inflammation and maintain cortisol balance.  [19.]
• Vitamin C: Supports adrenal gland function and cortisol production.  [16.]
• B Vitamins (B5, B6, B12): Essential for adrenal hormone synthesis and energy metabolism.
• Magnesium: Helps regulate cortisol levels and supports adrenal gland function.  [18.]
• Zinc: Supports immune function and aids in adrenal hormone production.
• Omega-3 fatty acids: Have anti-inflammatory properties and support adrenal health.  [15.]

Prior to initiating any new supplements, it's crucial to consult with a healthcare provider, particularly if you have preexisting health conditions or are currently on medications, to guarantee safety and effectiveness.

Treatment Options for High Cortisol

Treatment for high cortisol levels depends on the underlying cause and severity of the condition. 

In cases of Cushing's syndrome, which is characterized by excessive cortisol production, treatment may involve surgical removal of adrenal tumors or pituitary adenomas, radiation therapy, or medication to suppress cortisol production. 

Lifestyle modifications such as stress management techniques, regular exercise, and a balanced diet can also help regulate cortisol levels. Additionally, medications like ketoconazole, metyrapone, or mifepristone may be prescribed to lower cortisol levels in certain cases. 

Treatment plans should be individualized and overseen by a healthcare professional to ensure optimal outcomes and minimize potential side effects.