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Health Protocols

Stress Management

Although the human body is relatively adept at managing acute physical and/ or psychological stressors, chronic psychological stress can produce a variety of adverse effects.

Chronic unremitting stress can increase our risk of suffering from a barrage of anxiety- and pressure-related diseases ranging from high blood pressure and dementia to depression. Chronic stress also increases our risk for some types of cancer (Thaker 2007; Jacobs 2000; Saul 2005; McEwen 1998; Liu 2010; Eiland 2010). According to reports by the American Academy of Family Practice and the Russian Department of Family Care, nearly two-thirds of doctor’s office visits are related to stress (Mechanic 1978; Servan-Schreiber 2000; Saleeby 2006).

Regrettably, while chronic stress produces significant adverse health effects, conventional medicine often relies upon psychoactive drugs to mask stressed patients’ symptoms. At the same time, mainstream stress management strategies often fail to address biochemical abnormalities, such as imbalanced adrenal hormone levels, that contribute to the detrimental health effects of chronic stress (Strous 2003; Wolkowitz 1997, 1999).

At the core of chronic stress is deregulation of the hypothalamic-pituitary-adrenal (HPA) axis, an interconnected network of physiologic command terminals that governs the production of stress hormones like cortisol and catecholamines like epinephrine and norepinephrine. Chronic stress leads to desynchronization of the HPA axis and subsequent imbalances in stress hormone levels, a critical feature of stress-related illness.

Upon reading this Life Extension protocol, you will appreciate the dangers of chronic stress, understand how it contributes to various diseases, and know how you can optimize your stress response by combining healthy lifestyle habits with scientifically studied natural therapies.

The Deadly Consequences of Chronic Stress

The consequences of chronic stress can be devastating. A chilling example is stress cardiomyopathy, a spontaneous weakening of the heart that predisposes victims to arrhythmia and even sudden cardiac death. While the mechanism is not clearly understood, it is thought that chronic stress-induced elevations in epinephrine (adrenaline) over-stimulate the cardiac muscle, altering its function and causing atrial remodeling (Sakihara 2007; Korlakunta 2005).

Another striking example is a condition the Japanese refer to as Karoshi (death from overworking); this condition was recognized in post-World War II Japan. Overworked and severely emotionally and physically stressed Japanese high level executives suffered strokes and heart attacks at alarming rates at relatively young ages. Researchers discovered that the death of these otherwise healthy men was due to chronic, unremitting stress. Government estimates in 1990 put the number of men dying each year from Karoshi at over 10,000 (Kondo 2010; Saleeby 2006).

Prolonged stress has been linked with elevated circulating markers of inflammation, and increased intima media thickness, a measure of atherosclerosis progression (Gouin 2011; Roepke 2011). Chronic stress considerably increases the risk of anxiety and depression by causing structural and functional changes in the brain as well (McEwen 2004; Liu 2010). Moreover, those who do not properly manage and adapt to chronic stress are more likely to be overweight and develop sexual dysfunction (Kyrou 2008).

TABLE 1: Health Risks Associated with Chronic Stress

Stressor Health Outcome Increased Risk
Sleep Disturbances (Nilsson 2001) Early Death from All Causes 170%
Occupational Injuries 38% (Men)
Perceived Stress (Nielsen 2008) Early Death from All Causes 32%
Death from Respiratory Disease 79%
Death from Heart Attacks 159%
Death from External Causes 207%
Suicide 491%
Adverse Childhood Experiences (Brown 2009) Death by Age 65 140%
Stress at Work (Heraclides 2009; Laszlo 2010; Heraclides 2011) Risk of Type 2 Diabetes in Women 100%
Death from Heart Attack 181%
Early Death from All Causes 65%
Not Enough Reward for Effort at Work (Salavecz 2010) Poor Self-Rated Health Up to 280%
Divorce (Matthews 2002) Total and Cardiovascular Death 37% (Men)
Major Negative Life Events (Kruk 2011) Breast Cancer 533%

How the Body Responds to Stress

When an individual experiences a stressor, physical or emotional, internal or environmental, the body initiates a complex system of adaptive reactions to help cope with the stress. This reactive response results in the release of glucocorticoids, also known as stress hormones, and catecholamines, which stimulate adaptive changes in a variety of bodily systems.

The “Fight or Flight” Response

Under short-term circumstances, stress-induced changes prioritize functions involved in escaping danger; for example – redirection of blood flow to the muscles from most other body parts, increased blood pressure and blood sugar levels, dilation of pupils, and inhibition of digestion for energy conservation. During this time, fatty acids and glucose (blood sugar) are liberated from storage sites into the bloodstream where they become readily available for utilization by the muscles. This is known as the fight-or-flight response. This reactive and adaptive protection system originates in the brain.

Upon perception of stress, specialized neurons in the paraventricular nucleus of the hypothalamus (a major endocrine-regulating brain region) respond by releasing, among other compounds, corticotrophin releasing hormone (CRH) and vasopressin (VP). Subsequently, these hormones stimulate the release of adrenocorticotropic hormone (ACTH) from the pituitary gland.

After entering circulation and reaching the adrenal glands, ACTH stimulates the production of glucocorticoids and catecholamines, which then act throughout the body to induce the adaptive changes mentioned in the opening paragraph of this section. Cumulatively, this brain-endocrine coordination comprises the hypothalamic-pituitary-adrenal (HPA) axis.

While the fight-or-flight response is undoubtedly necessary to initiate an autonomous response to impending danger in an acute situation (the “rush” you feel when you hear an unexpected loud noise, for example, is the fight-or-flight response in action), it can become devastating when active, even at a low-level, for a protracted period of time (Innes 2007).

We modern humans live in an environment filled with emotional stressors, such as financial worries, and deadline pressures at work or school. All of these modern worries chronically activate the HPA axis in an evolutionarily unnatural way, leading to elevated stress hormone levels, and accompanying physiologic changes, throughout the day.

A few components of the fight-or-flight response are especially damaging to health when the stress response is active over a prolonged timeframe – insulin resistance, and high blood pressure (Lehrke 2008).

The elevation in blood pressure and deteriorating insulin sensitivity contribute, along with several other stress-related physiologic irregularities, to a compromised health state that predisposes chronically stressed individuals to an onslaught of age-related diseases.

Eventually, chronic elevations in glucocorticoid levels damage and destroy neurons in the region of the hypothalamus responsible for regulating CRH release (Siegel 2006). This gives rise to erratic or insufficient HPA axis activation and may lead to the mood disorders, such as depression and anxiety, and fatigue commonly observed in individuals who have been under great stress for a long time.

A Closer Look at Cortisol

Cortisol is, in many ways, a paradoxical hormone. A certain amount of cortisol is necessary for optimal health, but too much or too little can be unhealthy. As mentioned above, during acute episodes of stress, more cortisol is released to help the body cope with physical or psychological stressors (Tomlinson 2004). Its primary functions in the body are:

  • regulation of blood glucose levels by a process called gluconeogenesis in the liver
  • regulation of the immune system;
  • regulation of carbohydrate, protein and lipid metabolism

Essentially, cortisol is regarded as an anti-inflammatory hormone, a blood glucose modulator, an immune-modifier, and an adaptation hormone (Chrousos 2000). Depending on diet, exercise, stress, and time of day, serum levels of cortisol can vary.

During healthy conditions, cortisol levels peak in the early morning hours (usually around 8AM) and dip to their lowest between midnight and 4AM. The complex process of cortisol biosynthesis and release is sensitive to disruption by both internal and external factors (Beishuizen 2001; Tomlinson 2004; Weerth 2003). In the face of chronic psychological stress, for example, the adrenal glands excrete an abnormal amount of cortisol in an abnormal rhythm.

Cortisol, being a catabolic hormone (a hormone that breaks down tissues), when out of balance and unregulated, can have detrimental effects on body composition. Moreover, too much cortisol can suppress the immune system, while too little can lead to autoimmunity and rheumatologic disorders (Chrousos 2000; Wu 2008; Muneer 2011; Sapolsky 2002; Tak 2011).

Cortisol receptors are expressed throughout the body, including in the brain; therefore, derangement of the biosynthesis, metabolism and release of cortisol can disrupt many physiologic systems (Beishuizen 2001; Tomlinson 2004; Weerth 2003).

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 Life Extension believes that symptoms often attributed to “adrenal fatigue” arise from multifactorial pathological processes involving, among other systems, the HPA axis, and that these conditions must be treated as such.

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. For those who would like more information, Addison’s disease is discussed in our Adrenal Disease protocol.

Recognizing When Stress is Getting the Best of You

Everyone has an inborn ability to handle stress. However, tolerance is variable as some people can handle only low levels and short durations of stress, while others adapt and can accommodate higher levels stress for more prolonged periods. Dr. Hans Selye, in 1935, devised the term stress as a factor that induced behavioral changes in mammals. He then furthered this notion to include higher level organisms (humans) as being effected by stress in a harmful way (Viner 1999).

According to Dr. Selye, there are three states the body faces when dealing with stress. The first being the alarm state early on in the process, followed by the resistance state where the body attempts to adapt to the added stress (release of cortisol), and finally, after stress overwhelms and weakens the system, the exhaustion state (Kalaitzakis 2011; Tak 2011). These three “states” can be analogously detailed as physiologic mechanisms:

1) Alarm state: adaptation to acute stress; “fight-or-flight” response;

2) Resistance state: emergence of consequences of prolonged stress response activation (i.e. insulin resistance)

3) Exhaustion state: decline in responsiveness and sensitivity of primary relays of the HPA axis (i.e. hypothalamic deterioration / dysfunction leading to erratic / insufficient stress hormone and catecholamine production and subsequent mood disorders and fatigue).

The same imbalances in the HPA axis and stress response mechanisms that contribute to these signs and symptoms also contribute to the deadly sequelae of more serious stress-related illness. Therefore, recognizing that you are experiencing some or all of the following symptoms is an important initial step towards achieving better overall health and mitigating your risk for various diseases.

Signs that You are Suffering the Effects of Chronic Stress May Include:

  1. Excessive fatigue after minimal exertion; feeling “overwhelmed” by relatively trivial problems
  2. Trouble awakening in the morning, even after adequate sleep
  3. Relying on coffee (caffeine) and other “energy” drinks for a pick me up
  4. Perceived energy burst after 6:00 PM
  5. Chronic low blood pressure
  6. Hypersensitivity to cold temperatures
  7. Increased premenstrual symptoms (PMS) symptoms
  8. Depression and/or labile mood swings
  9. Mental “fog” and poor memory
  10. Decreased sex drive
  11. Anxiety
  12. Craving sugar and salty foods
  13. Decreased appetite
  14. Imbalanced immune system
  15. Chronic allergies
  16. Generalized weakness and dizziness upon standing
Some of these symptoms may mimic, or overlap, with dysfunction of the thyroid gland, gonadal (sex) hormones, malnutrition, depression, chronic fatigue states, chronic illness, infections, alcohol and drug abuse, and heavy metal toxicity (Ng 1990; Gagnon 2006). Therefore, it is very important to rule out other possible causes before attributing symptoms to chronic stress alone.


Impaired Stress Response: A Major Cause of Anxiety and Depression

Often, chronic stress is accompanied by mood disorders, particularly anxiety and depression. In fact, depression and anxiety can both be viewed as manifestations of an impaired stress response; the underlying physiology of both is similar.

In fact, the chronic elevation in glucocorticoids caused by chronic stressors in modern society can lead to physical changes in brain structure.

For example, dendrites, the branches of neurons that receive signals from other neurons, are shifted into less functional patterns upon chronic exposure to glucocorticoids. This has been documented in key brain regions associated with mood, short-term memory, and behavioral flexibility (Krugers 2010). Furthermore, glucocorticoids cause receptors for the mood-regulating neurotransmitter serotonin to become less sensitive to activation (van Riel 2003; Karten 1999). Other detrimental effects of chronic stress include both increased susceptibility to neuronal damage and impaired neurogenesis, the process by which new neurons are “born” (Krugers 2010).

Interestingly, emerging research suggests that certain psychoactive drugs, like those used to treat anxiety and depression, may stabilize mood not only by acting upon neurotransmitter levels, but by modulating the action of glucocorticoids receptors within the brain (Anacker 2011). These new findings strongly support the idea that in order to alleviate mood disorders, controlling stress response is an important aspect of treatment. Indeed, several genetic and epidemiological studies have linked excessive stress, and the inability to efficiently adapt to stress, to increased rates of anxiety and depression (Strohle 2003; Binder 2010).

Chronic Stress and Nutrition

Deficiencies, toxicities and life style habits impact the adrenal gland. Deficiencies in vitamin C and vitamin B5, which are essential co-factors in cortisol production and adrenal health, are two examples (Brandt 2012*; Daugherty 2002). Copper is a mineral that is essential in some bodily enzymatic reactions, but may disrupt adrenal function if levels are too high (Veltman 1986).

Even relative imbalances between minerals can affect cortisol levels. It has been documented that abnormal ratios of copper to zinc cause adrenal cortex disruption (Ng 1990; Gagnon 2006). A well balanced multivitamin can complement a healthy diet to help ensure that vitamin and mineral intake is sufficient to support optimal adrenal function.

The fatty acid content of the diet also contributes considerably to stress response physiology. Relative imbalances of omega-6 fatty acids to omega-3 fatty acids create conditions that favor heightened inflammation and impaired stress response (Kiecolt-Glaser 2010).

For example, a clinical trial examined the effects of parenteral fish oil infusions on the stress response induced by injections of an endotoxin called lipopolysaccharide. The group who received fish oil exhibited a much less severe stress response, with plasma norepinephrine levels remaining sevenfold lower and ACTH levels fourfold lower than the control group (Pluess 2007). Upon examination, it was found that the platelet phospholipid omega-3 content had increased substantially in fish oil group, reflecting a lowered omega-6 to omega-3 ratio, a state less conducive of inflammation.

It is believed that a diet high in omega-3 fatty acids may attenuate the effects of chronic stress by limiting the influence of inflammation on stress physiology (Kiecolt-Glasser 2010).

Since cholesterol is a building block of the cortisol hormone, ingestion in the diet of some saturated fat is important. However, the liver will synthesize cholesterol, if poor dietary ingestion occurs, from acetate (Hellman 1954). Of course, too much cholesterol has its drawbacks as well, so a happy medium must be reached. Both extremes of dietary fat ingestion have ill effects on the human body. Life Extension suggests an optimal total cholesterol level of 160-180 mg/dL.

Lifestyle Strategies for Overcoming Chronic Stress

Dr. Thierry Hertoghe, an internationally noted endocrinologist, advises a few lifestyle modifications that one should adhere to before consideration of natural or pharmacological therapies. Lifestyle modifications alone for some with mild to moderate forms of impaired stress response may ease symptoms (Kalaitzakis 2011; Tak 2011; Head 2009). Dietary supplements and/or hormone therapy can complement lifestyle modification to resolve adrenal dysfunction (Hertoghe 1999).

The obvious recommendation of avoiding stressful situations and occurrences goes without saying. If commuter stress, for example, is affecting your body, moving to a home closer to your workplace or finding a job closer to home is an obvious solution. If working third-shift causes disruption in your cortisol levels or circadian rhythm resulting in disease, then change your work schedule to eliminate this stressor (Wirth 2011). Smoking, and extremely vigorous or protracted bouts of exhaustive exercise impact the adrenals in a negative way as well (Peters 2001; Wu 2008; Siddiqui 2001).

With regard to the diurnal biorhythms of cortisol release, a few things increase cortisol at the inappropriate time. The consumption of alcohol and caffeinated beverages such as tea and coffee before bedtime is not recommended as caffeine can increase serum cortisol levels, which is counterproductive during the evening hours when the normal trough is expected (Ping 2012). Additionally, caffeine and alcohol affect the release of melatonin (melatonin counters some of the negative effects of cortisol), causing a relative reduction in melatonin secretion during the night when a spike is usually seen (Lovallo 2006).

Other therapies such as acupuncture, Traditional Chinese Medicine (TCM), Ayurvedic medicine, massage therapy, relaxation, yoga and even music therapy have shown success in stress management (Hanley 2003; Dixit 1993; Field 2005).

Several published studies suggest that owning a pet is associated with improved physical and psychological health (Barker 2008; Friedmann 2009). For chronically stressed individuals, adopting a dog or cat may help ameliorate some of the symptoms and effects of chronic stress (Allen 2001).