Free Cortisone Waking

Cortisone, the inactive form of the adrenal steroid hormone cortisol, is primarily converted from cortisol in the kidneys but also in the liver, salivary glands, adipose tissue, and colon. 

The enzyme 11-beta-hydroxysteroid dehydrogenase (11β-HSD), which has two isoforms, is responsible for this conversion. While 11β-HSD Type 1 converts inactive cortisone to active cortisol, Type 2 converts active cortisol to inactive cortisone. 

Free waking cortisone levels refer to the amount of cortisone in the body upon waking, measured through urine or saliva tests. These levels provide insight into adrenal function and the body's stress response. 

Testing both cortisol and cortisone levels offers a comprehensive view of adrenal health, as diurnal rhythms influence these hormones. Understanding and optimizing these levels can aid in diagnosing and managing adrenal-related disorders.

Understanding Cortisone

What is Cortisone?

Cortisone is the inactive form of the adrenal steroid hormone cortisol.  For more information on cortisol including its function as the active form of cortisone, click here.

Where is Cortisone Produced?

The primary site of cortisol conversion to cortisone is in the kidneys.  However, this conversion also occurs in the liver, salivary glands, adipose tissue and colon.  [14.]  

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) is the primary enzyme responsible for the cortisol/cortisone interconversion.  [22.] It has also been shown to be active in the human placenta, possibly to protect the fetus from the effects of excessive maternal glucocorticoid production.  [21.]

The enzyme 11-beta-HSD has two isoforms, type 1 and type 2. 11-beta-HSD Type 1 primarily converts  inactive cortisone to active cortisol, while 11-beta-HSD Type 2 converts active cortisol to inactive cortisone. [14.] 

Physiological Functions of Cortisone

Cortisone is the inactive form of cortisol; its physiological effects are apparent when cortisone is converted to active cortisol.  For more information on the functions of cortisol, click here.

What is Free Cortisone Waking?

Free cortisone waking refers to the amount of free cortisone in the body upon waking. 

Cortisol, an active glucocorticoid, follows a diurnal rhythm. While serum cortisone may not follow a diurnal rhythm, urine and saliva cortisone are believed to. [1., 23.] 

Clinical Significance of Free Cortisone Waking

Testing free waking cortisone levels in the urine or saliva provides additional information about adrenal function.

Simply testing free waking cortisol levels may miss important information in the setting of increased conversion of cortisol to cortisone.

In some cases, increased cortisol-to-cortisone conversion may be occurring, so testing only cortisol levels would give a false picture of adrenal insufficiency.

While diurnal levels of cortisol and cortisone may fluctuate throughout the day and night, the cortisol:cortisone ratio remains relatively constant. This ratio provides additional insight into adrenal function. [11.]

Testing cortisone levels alongside cortisol levels allows the clinician to confirm an individual’s adrenal function. 

Testing Waking Free Cortisone Levels: Testing Methods

Blood Testing for Cortisone

Blood testing for cortisone does not provide accurate reflection of free, or bioavailable, cortisone levels; it can only measure total cortisone.  [2.]

Urine Testing for Cortisone

Urine testing for cortisone involves collecting a urine sample over a specified period, usually 24 hours, to measure the total cortisone excretion. This method provides an integrated measure of total cortisol production, and free cortisol and cortisone over time. Also, urine testing 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 Cortisone

Saliva testing for cortisone involves collecting saliva samples at specific times throughout the day, typically upon waking, before lunch, before dinner, and before bedtime. 

This method measures free cortisone levels, which represent the biologically active form of cortisone available to tissues.

Benefits:

• Non-invasive and painless sample collection

• Saliva testing provides the ability to assess diurnal cortisol rhythms

Drawbacks:

• Potential variability in saliva collection technique

• Oral health may have an effect on cortisone measurements

Understanding Cortisone Levels

Optimal Range for Cortisone Levels

Cortisone levels may vary throughout the day, typically peaking in the Waking and decreasing gradually throughout the day, alongside cortisol levels. 24 hour salivary and urine tests will capture the diurnal rhythm.

It is essential to understand that lab values may vary. In blood, urine, and saliva, normal cortisol and cortisone levels can vary throughout the day.  

According to one lab company, typical salivary values range from:  [16.] 

• Waking: 6.8-14.5 ng/mL

• Waking + 30 min: 12.4-19.4 ng/mL

• Waking + 60 min: 9.4-15.3 ng/mL

• PM: 2-7.1 ng/mL

• Nighttime:0-4.8 ng/mL

In urine, they range from: [17.]

• Waking: 40-120 ng/mg

• Waking: 90-230 ng/mg 

• Afternoon: 32-110 ng/mg

• Nighttime: 0-55 ng/mg

How to Optimize Waking Free Cortisol and Cortisone Levels

Cortisol and cortisone are intimately linked. High waking cortisone levels may be seen alongside high waking cortisol levels.

Fortunately, there are several lifestyle modifications and supplementation strategies that can help regulate cortisol and cortisone and promote a balanced stress response.

Strategies to Lower Free Cortisol and Cortisone

• Practice mindfulness-based stress reduction techniques, including meditation, deep breathing exercises, and yoga.  [24.]

• Engage in regular physical activity and ensure adequate sleep each night to support cortisol regulation.  [3.]

• 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.  [4., 6., 9.] 

Supplements for Lowering Free Cortisol and Cortisone:

• Herbal adaptogens: incorporate adaptogenic herbs like ashwagandha and holy basil into your routine to regulate cortisol levels and enhance stress resilience.  [8., 15.] 

• Explore supplements such as phosphatidylserine to support adrenal health, reduce inflammation and maintain cortisol balance.  [20.]

• Vitamin C: Supports adrenal gland function and cortisol production.  [13.]

• 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.  [10.]

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.

Strategies to Increase Cortisol-to-Cortisone Ratio

Conversely, sometimes an individual will have low Waking cortisol alongside high Waking cortisone levels. In this setting, increasing cortisol-to-cortisone conversion may be desired. 

Both licorice and carbenoxolone are competitive inhibitors of 11-beta-HSD Type 2. Ingestion of these substances can inhibit 11-beta-HSD Type 2 activity, leading to decreased conversion of cortisol to cortisone, thus increasing the cortisol-to-cortisone ratio.

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