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Health Protocols

Stress Management

Determining if Stress May be Affecting Your Health

Although the effects of chronic stress can vary among individuals, several laboratory and clinical assessments can help determine if stress may be contributing to health problems. Objective tests that may be helpful in assessing the extent to which stress is affecting overall health include cortisol, DHEA level, salivary alpha-[α] amylase and immunoglobulin A (IgA) levels, and heart rate variability.


Measuring cortisol levels can be helpful in assessing HPA axis function. Cortisol levels in saliva, blood, urine, and hair have been shown to be reliable markers of adrenal cortisol output.98,99 These tests are widely available and are sometimes used as indicators of HPA axis function. In general, long-term increased cortisol output, reflecting over-activity of the HPA axis, is typical in major depression, while decreased cortisol output, reflecting under-activity of the HPA axis, is typical in chronic fatigue syndrome and post-traumatic stress disorder.100

  • Salivary cortisol is a non-invasive test that may be helpful in determining whether the circadian rhythm of adrenal gland function is intact or disturbed. Late night salivary cortisol is sometimes used to diagnose Cushing syndrome (a condition caused by excess exposure to cortisol or drugs that mimic cortisol), but tests that measure cortisol levels at multiple times in a day, creating a curve that reflects the diurnal pattern of cortisol release, may have broader usefulness in assessing stress.101,102 One research review found that flatter diurnal cortisol curves are correlated with poorer health.103

    Cortisol levels rise gradually with age and are affected by gender, especially around puberty and in the elderly. Although every lab determines its own reference ranges, peak salivary cortisol levels (within the first hour after waking) in adults appear to range from 1.8 to 26 nanomoles per liter (nmol/L), and evening trough levels (about 16 hours after waking) range from 0.2 to 3.5 nmol/L.104

  • Hair cortisol concentration is a novel and non-invasive method of evaluating long-term cortisol exposure over months to years. Because stress levels can fluctuate over time, cortisol is generally measured in the three centimeters of hair closest to the scalp (reflecting HPA axis activity during the previous three months).105 Cortisol concentrations in scalp hair have been found to vary with psychological and physical stressors, and have been correlated with perceived stress and stress-related symptoms and illnesses, including obesity, metabolic syndrome, and cardiovascular disease.99,106

Salivary Alpha [α]-Amylase and Immunoglobulin A (IgA)

α-amylase is a starch-digesting enzyme produced in the salivary glands as well as the pancreas. Production of salivary α-amylase increases under stimulation by the sympathetic nervous system, which triggers the “fight or flight” reaction and has a critical role in the stress response. On the other hand, production of salivary proteins like α-amylase and the antibody IgA is inhibited by the parasympathetic nervous system, which controls resting body functions. Therefore, salivary α-amylase and salivary IgA have been proposed as markers of the balance of nervous system regulation and objective measures of stress.107-109

Numerous studies show that α-amylase increases as a result of physical and psychological stress, and high levels have been seen in stress-related conditions such as anxiety.107,110 It is sometimes tested along with salivary cortisol, which reflects HPA axis activity, to provide a more comprehensive assessment of stress. Although not performed routinely, evidence suggests this combination of salivary tests may be useful for non-invasively and objectively evaluating the contribution of stress in patients with chronic conditions111 and monitoring the effects of stress-reducing therapies.112

Salivary secretory IgA (sIgA) has also been proposed as a marker of stress. A number of studies have shown that acute stress can increase levels of this important antibody.113-115 With chronic stress, however, sIgA appears to be depleted and salivary levels drop,116,117 possibly increasing risk of oral, gastrointestinal, and respiratory infections.118 Interpretation of salivary sIgA is somewhat challenging due to its sensitivity to other factors in the oral environment.119

Salivary sIgA and α-amylase tests are commercially available and frequently recommended and interpreted by integrative health care providers. In general, standardization of these salivary tests and more information about factors that interfere with their interpretation, such as smoking, food and beverage consumption, and medication use, will help increase their usefulness and acceptance.108,119,120


Dehydroepiandrosterone (DHEA) is an adrenal hormone that opposes some of the actions of cortisol in many tissues. Acute stress can increase production of both DHEA and cortisol in healthy individuals, but chronic stress has been correlated with low DHEA and high cortisol output.8 In one study, levels of DHEA-S (DHEA-Sulfate, the form of DHEA typically measured in the blood) were 23% lower in healthy adults with the highest perceived work-related stress compared to those with the lowest work-related stress.121 The balance between cortisol and DHEA production also varies dramatically with age: DHEA release is lowest in older age, and it is thought that the unabated action of cortisol in the presence of declining amounts of DHEA may contribute to age- and stress-related diseases.8,122,123

Evidence suggests blood levels of DHEA-S that generally correspond with optimal health are 350–500 µg/dL for men and 275–400 µg/dL for women. Measuring the ratio of serum cortisol to DHEA-S may also provide some insights into the function of the adrenal gland and stress resilience.8

Heart Rate Variability

The heartbeat is not a precisely regular rhythm but instead oscillates unpredictably over time in response to dynamic shifting in the balance of sympathetic and parasympathetic regulation. Heart rate variability is the fluctuation in the length of time between heartbeats.124 In a healthy person at rest, when the parasympathetic nervous system is the predominant heart rhythm regulator, heart rate variability increases, but during times of stress, when the sympathetic nervous system is strongly activated, heart rate variability decreases. Like salivary α-amylase, heart rate variability at rest provides information regarding the stress-related activity of the nervous system.125 Greater variability in the heart rate reflects more robust ability to adapt to changing conditions.124

A growing body of evidence shows that resting heart rate variability is a meaningful reflection of cardiac and nervous system activity.124,125 Low heart rate variability has been noted to be closely correlated with other measures of stress and is an indicator of low stress-resilience and increased risk of heart attack and overall mortality.125-128 Furthermore, stress management strategies like exercise and mindfulness practices can improve heart rate variability.128,129 Taken together, the evidence suggests heart rate variability may prove helpful in predicting risk of stress-related physical and psychological disorders.126,130

Heart rate variability is measured during long (24-hour), short (five-minute), or ultrashort (shorter than five-minute) monitoring periods. At this time, 24-hour data sets are considered the “gold standard” and seem to offer a better reflection of health status. Questions remain about the significance of short- and ultrashort-term heart rate variability measurements, ideal timing of data collection, frequency of oscillations, and the influence of individual factors such as gender, disease status, and medication use on heart rate variability measurements.124 Nevertheless, devices that measure heart rate variability are increasingly commercially available.

The Issue of “Adrenal Fatigue”

An alternative medicine term that often finds its way into discussions about stress is “adrenal fatigue.” Although “adrenal fatigue” is not a recognized diagnosis in conventional medicine, the symptoms often attributed to “adrenal fatigue” may arise from multifactorial pathological processes involving, among other systems, the HPA axis.131,132

On the other hand, Addison’s disease, sometimes referred to as “adrenal insufficiency,” is a medical condition that can be life threatening. Addison’s disease is typically the result of an autoimmune disorder, but can arise due to genetic abnormalities as well. Consequences of Addison’s disease are much more severe and acute than those induced by stress and the condition should be closely monitored by a qualified healthcare professional.133 Those interested in learning more about Addison’s disease can do so by reviewing Life Extension’s Adrenal Disease protocol.