Cortisol

Stress hormone produced by adrenal glands

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What is Cortisol?

Cortisol is the primary stress hormone produced by your adrenal glands in response to physical or psychological stress, low blood sugar, inflammation, or circadian rhythm. It's often called the "fight-or-flight"hormone, but this oversimplifies its role. Cortisol is essential for survival:it regulates metabolism, blood pressure, immune function, and helps your body respond to stress. Problems arise when cortisol is chronically elevated (from chronic stress, Cushing's syndrome) or deficient (adrenal insufficiency).

Here's the critical insight:cortisol follows a strong circadian rhythm. It's highest in the morning (peak around 8 AM) to help you wake up and get moving, then gradually declines throughout the day, reaching its lowest point around midnight to allow sleep. Disruption of this rhythm—high cortisol at night, low cortisol in the morning, or chronically elevated levels—is associated with insomnia, weight gain, insulin resistance, immune dysfunction, and accelerated aging.

A single cortisol measurement isn't very informative without context of timing. Morning cortisol should be tested between 7-9 AM. A 4-point salivary cortisol test (morning, noon, evening, bedtime) better captures the daily rhythm and is useful for assessing chronic stress, adrenal dysfunction, or HPA axis dysregulation. Serum cortisol is standard for diagnosing Cushing's or Addison's disease, while salivary cortisol is better for functional assessment.

Why Cortisol Balance Matters for Longevity

Metabolic regulation:Cortisol raises blood sugar by promoting gluconeogenesis. Chronic elevation causes insulin resistance, visceral fat accumulation, type 2 diabetes.
Immune function:Physiologic cortisol is anti-inflammatory and modulates immune response. Too high suppresses immunity (infections, poor wound healing);too low causes autoimmune flares.
Bone density:Chronic high cortisol increases bone resorption and decreases bone formation, leading to osteoporosis.
Muscle mass:Elevated cortisol is catabolic, breaking down muscle protein for glucose. Chronic stress accelerates sarcopenia.
Sleep and circadian rhythm:Cortisol should be low at night to allow deep sleep. High nighttime cortisol causes insomnia and disrupts recovery.
Longevity:Chronic cortisol elevation accelerates aging, shortens telomeres, and increases mortality from cardiovascular disease and metabolic syndrome.

Optimal vs Standard Ranges

Range Type	Level	Significance
Optimal (Morning 7-9 AM)	10-20 mcg/dL	Healthy morning cortisol. Peak should occur within 30 min of waking (cortisol awakening response).
Optimal (Evening/Bedtime)	<5 mcg/dL	Cortisol should be low at night to allow restful sleep and overnight recovery.
Suboptimal (Morning)	5-10 mcg/dL	Low morning cortisol suggests blunted cortisol awakening response, adrenal dysfunction, or chronic stress/burnout.
High (Morning)	>25 mcg/dL	Elevated morning cortisol. May indicate acute stress, Cushing's syndrome, or HPA axis dysregulation. Retest with dexamethasone suppression test if persistently high.

Standard lab range: anxiety

How to Optimize Cortisol

1. Very Low (<5 mcg/dL morning)

2. Adrenal insufficiency (Addison's disease or secondary adrenal insufficiency). Requires urgent evaluation with ACTH stimulation test.

High (Bedtime/Night)

3. >5 mcg/dL

Cortisol should be low at night. Elevated nighttime cortisol impairs sleep, recovery, and drives metabolic dysfunction.

4. Manage Chronic Stress (Most Common Cause of Cortisol Dysregulation)

Meditation and mindfulness:10-20 min daily meditation reduces cortisol by 20-30% in studies. Apps:Headspace, Calm, Insight Timer.

Deep breathing:4-7-8 breathing (inhale 4 sec, hold 7 sec, exhale 8 sec) activates parasympathetic nervous system, lowering cortisol.

Sleep optimization:7-9 hours nightly. Sleep deprivation raises cortisol. Prioritize consistent sleep/wake times, dark room, cool temp.

Exercise (but not too much):Moderate exercise lowers cortisol. Overtraining (>90 min high-intensity daily) raises cortisol chronically.

Social connection:Loneliness and social isolation chronically elevate cortisol. Prioritize relationships, community.

5. Adaptogenic Herbs (Moderate Evidence)

Ashwagandha:300-600 mg/day reduces cortisol by 25-30% in stressed individuals. KSM-66 and Sensoril are well-studied extracts.

Rhodiola rosea:200-600 mg/day may reduce stress-induced cortisol spikes and improve mental performance under stress.

Phosphatidylserine:300-800 mg/day may blunt exercise-induced cortisol elevation.

Holy basil (tulsi):300-600 mg/day may reduce cortisol and stress markers.

L-theanine:200-400 mg/day (from green tea or supplement) promotes relaxation without sedation, may modulate cortisol response.

Symptoms of Abnormal Cortisol

Low Cortisol

Nutritional Support

High Cortisol

Treat Adrenal Insufficiency (if very low cortisol)

Causes of Abnormal Cortisol

Low Levels

Evaluate and Treat Cushing's Syndrome (if persistently high)

High Levels

If morning cortisol >25 mcg/dL or loss of circadian rhythm (high at night), evaluate for Cushing's:
24-hour urinary free cortisol (elevated in Cushing's)
Late-night salivary cortisol (should be <0.09 mcg/dL;elevated in Cushing's)
Dexamethasone suppression test (cortisol fails to suppress in Cushing's)
If confirmed, determine cause:pituitary adenoma (Cushing's disease), adrenal tumor, or ectopic ACTH production. Treatment:surgery, medications (ketoconazole, metyrapone), or radiation.

When to Retest

Fatigue, exhaustion, low energy (especially morning)
Difficulty waking up, non-restorative sleep
Low blood pressure, dizziness upon standing (orthostatic hypotension)
Salt cravings
Weight loss, loss of appetite
Hypoglycemia, low blood sugar episodes
Muscle weakness, joint pain
Darkening of skin (hyperpigmentation in Addison's disease)
Depression, low mood, apathy
Frequent infections (impaired immune function)

Scientific Evidence

Low cortisol <5 mcg/dL in morning suggests adrenal insufficiency (Addison's disease or secondary insufficiency). This is a medical emergency if severe.

Weight gain, especially abdominal/visceral fat|Moon face, buffalo hump (fat redistribution)|Muscle weakness, muscle wasting (especially proximal muscles)|Thin skin, easy bruising, purple striae (stretch marks)|Insomnia, difficulty falling or staying asleep|High blood pressure|High blood sugar, insulin resistance, type 2 diabetes|Osteoporosis, fractures|Mood changes:anxiety, irritability, depression|Poor wound healing, frequent infections|Irregular menstrual periods (women)|Erectile dysfunction (men)

Source:Chronic elevation of cortisol drives metabolic syndrome, visceral obesity, insulin resistance, bone loss, and immune suppression.

Primary adrenal insufficiency (Addison's disease):Autoimmune destruction of adrenal cortex (most common in developed countries). Can't produce cortisol or aldosterone.|Secondary adrenal insufficiency:Pituitary or hypothalamic failure (tumor, surgery, radiation, Sheehan syndrome) causes low ACTH→low cortisol.|Chronic exogenous steroid use:Long-term prednisone/dexamethasone suppresses HPA axis. If stopped abruptly, adrenal glands can't produce cortisol (iatrogenic adrenal insufficiency).|Adrenal hemorrhage:Waterhouse-Friderichsen syndrome (meningococcal sepsis), trauma.|Chronic stress and burnout:Prolonged HPA axis activation may lead to blunted cortisol response (controversial "adrenal fatigue"concept).|Medications:Ketoconazole, etomidate, megestrol can suppress cortisol production.

Cushing's syndrome:Excess cortisol from pituitary adenoma (Cushing's disease), adrenal tumor, ectopic ACTH production (small cell lung cancer), or exogenous steroids.|Chronic stress:Psychological stress, overtraining, sleep deprivation chronically activate HPA axis.|Severe depression:Major depressive disorder often associated with HPA axis dysregulation and elevated cortisol.|Alcoholism:Chronic alcohol use disrupts HPA axis, raising cortisol.|Obesity:Visceral fat produces cortisol locally and amplifies systemic cortisol response.|Obstructive sleep apnea:Intermittent hypoxia and sleep fragmentation raise cortisol.|Medications:Estrogen (oral contraceptives, HRT) increases cortisol-binding globulin, raising total cortisol.

Source:Morning cortisol (7-9 AM):Baseline to assess adrenal function and circadian rhythm. Optimal 10-20 mcg/dL.|If very low (<5 mcg/dL):Perform ACTH stimulation test to confirm adrenal insufficiency.|If very high (>25 mcg/dL):Retest and consider dexamethasone suppression test, 24-hour urinary free cortisol, late-night salivary cortisol to evaluate for Cushing's.|4-point salivary cortisol:Morning, noon, evening, bedtime. Best for assessing circadian rhythm and chronic stress. Look for blunted morning rise or elevated nighttime levels.|If treating adrenal insufficiency:Monitor for adequate replacement and stress-dose adjustments. Retest during illness.|If optimizing stress management:Retest 3-6 months after implementing lifestyle changes (meditation, sleep, adaptogens) to assess improvement in cortisol rhythm.

Cortisol Circadian Rhythm

Cortisol follows strong circadian rhythm:peaks 30-45 min after waking (cortisol awakening response, CAR), then declines throughout the day, reaching nadir at midnight. Disruption of this rhythm (low morning cortisol, high evening cortisol, or flattened rhythm) is associated with metabolic syndrome, depression, insomnia, and increased mortality.

Source:Adam EK, et al. Diurnal cortisol slopes and mental and physical health outcomes. Psychoneuroendocrinology. 2017;83:25-41.

Chronic Stress and Cortisol Elevation

Chronic psychological stress causes sustained HPA axis activation and elevated cortisol. This drives visceral fat accumulation, insulin resistance, hypertension, immune suppression, bone loss, and accelerated aging. Mindfulness meditation reduces cortisol by 20-30% and improves HPA axis regulation.

Source:Epel ES, et al. Accelerated telomere shortening in response to life stress. PNAS. 2004;101(49):17312-17315.

Cushing's Syndrome Diagnosis

Cushing's syndrome (chronic cortisol excess) is diagnosed with:(1) 24-hour urinary free cortisol >3x upper limit, (2) late-night salivary cortisol >0.09 mcg/dL, (3) failure to suppress cortisol after dexamethasone. Most common cause is iatrogenic (exogenous steroids), followed by pituitary adenoma (Cushing's disease).

Source:Nieman LK, et al. The diagnosis of Cushing's syndrome:an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.

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