Stress, Consequences and Overall Health

By Fabio Comana, MA, MS, NASM-CPT, CES, PES,

Director, Continuing Education, National Academy of Sports Medicine

Stress stimulates appetite, it increases abdominal fat, it increases risks for disease and it can even play a role in our intimate relationships. The list could keep going, but what exactly is stress and how is it connected to all these consequences? Examine the concept of stress and discover how chronic stress can negatively impact specific physiological systems within our body.

Stress can be is defined as a nonspecific response to any stimulus that overcomes, or threatens to overcome, the body’s ability to maintain homeostasis or allostasis (state of equilibrium of the body’s internal biological mechanisms) (1). In other words, when the body is exposed to, or anticipates a stress, regardless of the source of the stress (e.g., lack of sleep, starvation, financial or emotional hardship, exercise, fighting to survive), it initiates a response mechanism to help restore a state of equilibrium. However, it is important to remember that this biological response is essentially the same regardless of the type of stress we impose upon ourselves, and only differs by magnitude of the response needed. Furthermore, the term allostasis refers to the concept whereby the entire body is involved in this adaptive response and therefore it is our weakest response mechanism (i.e., from one particular system,) that can become problematic as the body attempts to cope with the stress (1).

Nonetheless, if we have this built-in, biological stress-response mechanism, then why is it that medical experts are expressing more concern over stress and its association with disease and pre-mature death?  One major explanation lies with the type of stress we are exposed. Our stress-response mechanism is designed to respond to acute physiological stresses – ones that place stress upon our body for only short periods of time (e.g., escaping a sabre-tooth tiger) where we respond with physical work. We often refer to this mechanism as our ‘fight-or-flight’ response. We either confront the stressor or remove ourselves from it (1). The stress is short-lived and allows ample time for the body to recover from the stress response.

Our lives have evolved. The creation of an industrialized world has dramatically altered the nature of the stress we experience. We face less physiological stress and now deal with a new stressor that has become more significant in our lives; namely smaller bouts of continual psychological stress (e.g., work schedule, responsibilities, traffic, finances, environmental toxins, etc.) that ordinarily do not require physical work. Though our stress has changed, but our biological stress-response mechanism has not (2). Growing concern is not necessarily with the stressing agents, but more so related to the cumulative effect of our stress-response mechanism and how the body recovers from this stress-response. In modern times we are exposed to frequent bouts of psychological stress (i.e., chronic stress), the answers medical experts and researchers seek revolve around recovery from these responses. If we are unable to fully recover, the body becomes weak and vulnerable. Stress therefore does not necessarily cause disease, but simply exacerbates the potential for disease (2).

Takeaway

Primary change associated with our stress-response mechanism is with the nature of the stressor where we have experienced a shift from less frequent, acute bouts of intense physiological stress to more frequent, smaller bouts of psychological stress from which the body struggles to recover.

To better understand this difference, it may be helpful to first review key stress-response mechanisms. Our biological stress response was designed for survival and is regulated by both the neural and endocrine (hormonal) systems. Fundamentally, both systems are communication systems that receive sensory information from various sources (eyes, ears, skin, blood, etc.) and transmit appropriate responses to specific targets once information has been processed to re-establish balance.

• The nervous system is a rapid-acting, but short-lived communication system that functions by transmitting nerve impulses – it reacts very quickly to stimuli, but its effects do not last very long (e.g., the sudden, short-lasting elevation of heart rate when startled).
• The endocrine system is a slower-acting, but longer-lasting communication system that functions by hormonal action – it is activated more slowly (sometimes by nerve activity) and its effects may last longer (e.g., the sustained elevation of heart rate during a 60-minute run).

Many of our nerve responses are governed by our autonomic (ANS) or involuntary nervous system, which forms part of our peripheral nervous systems (i.e., nerve system excluding the brain and spinal cord). As illustrated in Figure 1-1, the ANS is further sub-divided into the parasympathetic (PNS) and sympathetic (SNS) nervous systems that operate independently and cooperatively with each other. The SNS is considered a rapid-acting, mobilizing system aimed at helping the body prepare itself to tolerate stress (sometimes called excitatory) whereas the PNS is considered a slower, dampening system that dominates during periods of calm or recovery (3).

Figure 1-1: Neural Organization

When activated, the SNS triggers numerous responses intended to help the body optimize its chances for success during the ‘fight-or-fight’ response. Many of these are mediated by hormones listed in Table 1-1. These responses include:

• Increased cardiopulmonary responses (e.g., blood pressure, heart rate, dilation of breathing tubes to move more air).
• Increased mobilization of fuels (i.e., breakdown of stored fat and stored carbohydrates – glycogen to make more readily available for energy production).
• Increased vasodilation of vessels to the brain and exercising muscles – needed to increase attention, recall and memory; and increase nutrient and oxygen delivery.
• Increased blood clotting ability– needed to stop one from bleeding to death during a‘fight-or-flight’ response.
• Decreased pain perception (analgesia) – needed to tolerate discomfort during a‘fight-or-flight’ response.
• Decreased growth, repair and maintenance.
• Decreased reproduction capacity.
• Decreased salivary and digestive enzyme secretion and digestion – this may explain why one experiences dry mouth when nervous (i.e., public speaking).
• Decreased stomach and small intestinal contractility.
• Increased large intestinal contractility (evacuates bowels to help chances of survival during ‘fight-or-flight’ responses) – this explains why diapers are used on prisoners when executed.
• Increased bladder contractility (removes urine to help chances of survival during‘fight-or-flight’ responses) – this explains why people and animals urinate when scared.
• Increased immune function – needed to fight off pathogens.
• Increased sweat rates – stimulation of the eccrine and appocrine (primarily under the arms) to remove heat.

Table 1-1: Hormones Influenced by SNS Activation

Connect: A Difference in Women?

Research by Shelley Taylor, a psychology professor from the University of California, Los Angeles (UCLA) has explored differences in the female response-mechanism to stress that resulted in the creation of a ‘tend-and-befriend’ response model rather than ‘fight- or-flight’ response (4). This response involves protection of offspring (tending) and seeking out social groups for mutual defense (befriending) as a coping mechanism to stress.This unique response appears to be regulated by the female hormone oxytocin, which in turn is regulated by the hormone estrogen. Oxytocin has been connected to a variety of social relationships and activities, including peer bonding, breast feeding and affiliative behaviors – including maternal tending and social contact with peers. Researchers believe these social responses help reduce biological responses such as elevated heart rate and blood pressure, and the release of certain stress hormones like cortisol (5).

Stress and Cardiovascular Responses

Each time we respond to stress, the release of epinephrine increases platelet adhesiveness to help blood clot.  Likewise, under stress the body aims to increase blood volume to offset any potential loss of blood volume from sweating or bleeding by increasing the release of antidiuretic hormone (ADH) from the anterior pituitary gland that re-absorbs fluid from the kidneys. However, without any loss of blood volume (i.e., no exercise-induced sweating), the end result is an increase in blood pressure. Higher blood pressure results in a gradual thickening of the arterial walls to withstand increased pressure, resulting in a loss of vessel elasticity needed for dilation and constriction, and increased damage to the vessel’s interior lining. This in turn increases vessel inflammation, as evidenced by increased levels of C-reactive protein (CRP) (an inflammatory marker) in the blood during periods of, and following stress (6). One adaptive response to elevated blood volume and pressure is that the body attempts to push fluid back to the kidneys, taking calcium with it, which increases calcium losses from the blood and increases the risk of osteoporosis.

Under stress, the mobilization of fats from fat cells elevates circulating levels within the blood, increasing the likelihood that these lipids will be deposited on the damaged vessel walls. This escalates risks for heart disease and stroke (6). Furthermore, if these fats, mobilized from all regions of the body, are not utilized by cells due to the psychological nature of the stress, many of these circulating fats are re-deposited in the abdominal region and not within subcutaneous fats cells. This shift of fat stores to the more dangerous abdominal region (visceral fat) also increases risk for heart disease.

Therefore, exposure to acute, shorter bouts of stress that reduce blood volume (i.e., sweating) and utilize circulating fats is tolerable to the body, but it is the repeated exposure of chronic stress that ultimately results in health issues.

Stress, Metabolism, Appetite and Intestinal Health

The body releases insulin, an anabolic (storage) hormone, in response to food or in anticipation of the arrival of food, but during periods of stress, the body will inhibit the release of insulin as it favors catabolic or breaking down processes. These specific functions provide fuel during periods of stress and then allow the body to restore energy reserves during periods of recovery or calm (PNS dominance). However, during periods of chronic stress where there is no increase of energy utilized, these mobilized fuels are not utilized (baring a small energy cost to breakdown and restore energy reserves), but our biological response mechanism kicks in to increase the desire for food although we really have no need to eat. This response may override our regulatory processes of hunger and may help explain why two thirds of people experience an increase in appetite when stressed. As the body strives to replace its primary fuel (carbohydrates), this offers some insight to why carbohydrates (e.g., sugars) are often desired (7).

With the onset of stress, the release of corticotropin-releasing hormone (CRH) from the hypothalamus (the body’s master gland) occurs within seconds. This activates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary to activate the release of glucocorticoids (GC) from the adrenal cortex gland (cortisol is the primary GC). Glucocorticoids, particularly cortisol are considered primary stress hormones.  Likewise, within seconds of the removal of an acute stress, levels of CRH and ACTH disappear quickly but GC levels may remain elevated for some time. The prime reason why GC levels remain elevated during recovery is to stimulate appetite to replenish lost energy stores, which in turn elevate insulin to help push food into the cells. Elevating blood glucose levels following food consumption (especially sugar) lowers GC levels, helping explain why eating sugar is sometimes viewed as an anti-stress or stress-coping mechanism (8). As some people release more GC or have a slower process to restoring GC levels back to baseline, appetite levels vary with stress. Furthermore, some people also undergo small adaptations where repeated exposure to chronic stress results in a blunted GC (cortisol) release (8).

Under stress, gastrointestinal (GI) function is reduced and while tolerable over shorter durations, it will compromise GI health and nutrient intake under conditions of chronic stress. Functional bowel disorders (e.g., spastic colon, irritable bowel syndrome – IBS) are all associated with prolonged exposure to stress. Similarly, stomach ulcers caused byHelicobacter pylori bacteria in the stomach are highly correlated with stress levels. Although 50% of adults harbor these bacteria in their upper GI, and 80% of people are asymptomatic, it is those exposed to higher levels of chronic stress that experience a greater incidence of ulcers. Normal GI function and our body’s natural immune response appear to control these bacteria, but with reduced stomach activity and compromised immune function under stress, these bacteria flourish.

The thyroid gland releases two important hormones called thyroxine (T4) and triiodothyronine (T3) that regulate our metabolism, accounting for 60 – 75 % of all calories expended in a day. Thyroid stimulating hormone (TSH) released by the pituitary gland acts to stimulate thyroid gland production of T3 and T4, but under increased levels of chronic stress, elevated GC levels hinder TSH production, which in turn reduces the quantities of T3 and T4 needed to regulate metabolism.

Takeaway

Our physiological stress-response is intended to replace lost energy reserves, but with the changing nature of stress where energy is not expended, it may trigger over-eating. Overall intestinal health and nutrient uptake are both directly impacted by repeated bouts of stress.

Stress and Immune Function

Moderate amounts of sustained stress and short term exposure to acute stress increase GC release. This is actually beneficial to our immune function because while it temporarily suppresses immune function during the stress-response, it helps restore baseline (normal) immune function after the stress has been removed. Concern exists with exposure to chronic stress where frequent and sustained levels of elevated GC result in immune system levels returning to sub-baseline levels (7). Chronic stress initially produces elevated GC levels, but prolonged exposure also decrease levels over time if the adrenal glands become chronically fatigued (known as adrenal insufficiency or adrenal fatigue).

Connect: Cortisol

Cortisol is the primary glucocorticoid hormone in the body and often referred to as the key ‘stress hormone’ that helps maintain homeostasis by mediating various physiological responses that include:

• Regulating blood sugar levels
• Influencing macronutrient utilization to maintain blood glucose levels (e.g., stimulating gluconeogenesis)
• Fat deposition
• Having anti-inflammatory and some immuno-stabilizing effects
• Influencing hormonal and nerve system responses

As cortisol is our primary stress hormone, it responds during periods of stress (e.g., exercise, missed meals or starvation, following insufficient sleep), but returns to baseline when the stress is removed. However, with our continual exposure to psychological stress, this recovery or return to baseline may not occur. Health concerns exist, as seen in Table 1-2, with elevated levels of cortisol associated with chronic stress or from suppressed levels of cortisol. Levels generally fluctuate throughout the day, usually reaching the lowest levels 2 – 4 hours after falling asleep (e.g., 2 – 4 am) as we transition into deep sleep and reaches the highest levels in the hours immediately prior to waking (e.g., 6 – 7 am) as the body enters a prolonged fasted state and prepares itself to wake-up and increase metabolism.

Table 1-2: Effects of Elevated or Suppressed Cortisol Levels

Stress in Females

Healthy fetal development is largely dependent upon the health of the mother and those exposed to higher levels of chronic stress may develop babies who are both physically and cognitively compromised (2). The stressed mother has elevated SNS activity and GC levels coupled with decreased levels of HGH (needed for bone and tissue growth), compromised nutrient intake, and lower calcium stores, all of which negatively impact fetal development. Increased GC levels are also associated with increased vulnerability to anxiety and decreased ability to recover from, or cope with, stressful events (2).

The hypothalamic-pituitary-ovarian (HPO) axis regulates estrogen and progesterone levels throughout life and the menstrual cycle. They hypothalamus releases luteinizing hormone releasing hormone (LHRH) to the anterior pituitary gland which in turn releases luteinizing hormone (LH) and follicle stimulating hormone (FSH) to the ovaries to manufacture and release estrogen and progesterone. Under chronic stress however, elevated GC levels negatively impact the hypothalamus, resulting in less LHRH release. Additionally, beta-endorphins (neurotransmitters that act as an analgesic to numb or dull pain sensations), secreted in the hypothalamus are also increased under stress and block the release of LHRH (Table 1-1) (7). Less LHRH results in less LH and FSH being released from the pituitary gland (as the gland becomes less responsive to smaller quantities of LHRH). This in turn:

• Reduces levels of estrogen, which when coupled with the additive effect of GC makes the ovaries less responsive to LH and FSH, decreasing chances for fertilization.
• Reduces levels of progesterone, which decreases uterine wall thickening that normally occurs after fertilization.
• Increases levels of prolactin, which decrease pituitary sensitivity to LHRH and thins the uterine wall. Interestingly, this thinning effect of the uterine wall acts as a natural contraceptive in breastfeeding mothers when prolactin levels are higher to assist with milk secretion (2).

Estrogen plays a role in helping deposit fat in the hips and thighs, and helps prevent deposition in the waist region, thereby reducing the risk of heart disease (10). However, in chronically stressed females, this functionality is reduced due to lowered estrogen levels and females increase their levels of abdominal or android fat (2). Females also make small amounts of testosterone (TST) in the adrenal glands and fat cells possess specific enzymes that can convert some of this TST to estrogen (2). However, under conditions of chronic stress, these enzymes become less active and therefore convert less TST to estrogen.

Lastly, chronic stress also decreases sexual libido. Elevated levels of the reproductive hormones increase a female’s tactile responsiveness (i.e., responsiveness to physical touch). Chronic stress reduces dopamine levels, thus reducing pleasurable experiences associated with sex. Dopamine is a neurotransmitter involved in controlling our reward and pleasure centers.

Stress in Males

The release of LH and FSH stimulate production of TST in the testes, but under stress, elevated GC levels decrease LHRH secretion and diminish the sensitivity of the testes to LH and FSH. Less TST in men leads to many physiological changes that include decreased muscle mass, osteoporosis (low bone density), lowered red blood cell count, and changes in body composition and fat distribution (TST helps oppose cortisol’s effect on depositing fat into the abdominal region).

During sex, where the SNS system generally dominates, it is the co-activation of the PNS that enables a man to have an erection, and continue to maintain that erection until his SNS overwhelms him, resulting in an ejaculation. However, under conditions of stress where a man has greater SNS activity, this interferes with his ability to gain an erection, leading to impotence.

Stress and Aging

One aging theory proposes the existence of telomeres, structures composed of repetitive nucleotide sequences located at the end of our chromosomes (11). They are believed to protect chromosomes from deterioration from various stressors and it is the function of the enzyme telomerase to constantly repair them to help keep cells healthy (12). However, under sustained stress, the activity levels of this enzyme decrease, shortening the telomere and promoting accelerated cellular aging (2).

Stress Management

Given the need to control stress and elevated GC levels, numerous stress-management and coping mechanisms exist, but much of the earlier research in this area examined animal responses to physiological stress that surprisingly still have applications to humans with psychological stress (2). Some proposed strategies include:

1. Developing an outlet.
   • Stress creates muscle tension. Much like the gazelle that has eluded the cheetah (under intense SNS activation), it proceeds to jump around after the stress is removed (i.e., cheetah leaves) to release muscle tension. In a similar manner, humans also need physical sources to remove our stress (e.g., exercise, punching).
   • Create opportunities to reprioritize matters. After a stressful day, time spent enjoying an activity or person(s) that holds a high priority in your life helps prioritize events and build perspective (e.g., a hug or time with your children after a stressful workday creates that perspective).
   • Displacement of aggression. While not suggested as a coping mechanism, it is a common response in animals and humans. Here, the stressed animal attacks another innocent bystander without provocation. Humans demonstrate similar behaviors by venting their frustrations on an innocent bystander or perhaps worse, by abusing a person as a result of a stressful situation (e.g., financial hardships).
2. Identify and utilize social supports. Animals bond with each other following bouts of stress, offering a social calming effect (e.g., grooming). Likewise, humans should also develop social support systems that offer this same calming effect.
3. Predictability or predictive information. Having awareness or anticipation of the type, magnitude and duration of a stress enables individuals to develop effective coping mechanisms (e.g., asking a dentist how much longer he / she will need to drill may help an individual cope with that stress). The information however, must be relevant (i.e., tied to the stressful event) and must also be time-appropriate (i.e., having information three weeks prior to a procedure or one second prior to a procedure does not offer much solace).
4. Develop a sense of control – creating the impression of, or having actual control of a stressful situation can help reduce stress. Generally, when one has low levels of control, yet perceives the stress (demands) placed upon them to be high or low, stress will prevail. On the other hand, if one has high levels of control, they are more adept to managing their stress. However, for mild-to-moderate levels of stress, increased feelings of control promote self-efficacy, whereas with high levels stress, one may benefit more from less control to avoid extreme pressure, desperation or blame should they not succeed.
5. Interpret things as getting better.
6. Cognitive flexibility, where you develop the ability to remove the stressors that you can, but also learn to adapt to the stressors that you cannot remove. This in essence mirrors the Serenity Prayer by twentieth century American theologian, Reinhold Niebuhr who said, “… grant me the serenity to accept the things I cannot change, the courage to change the things I can, and wisdom to know the difference.”

In closing, as the human body was never designed to tolerate continual psychological stressors, our inability to cope with the biological stress-response mechanism and to adequately recover has emerged as a major health concern. While this article only addressed specific systems and fundamental gender differences, it is clearly evident that the pressures associated with modern living are contributing to major disturbances to homeostasis (allostasis), which in turn exposes us to greater risks for morbidity and mortality. Considering how we all experience some degree of continual stress, the need for effective stress-management techniques and coping strategies is now perhaps bigger than ever.

References:

1. Cannon, W. B., (1926). Physiological regulation of normal states: some tentative postulates concerning biological homeostatics. IN: Pettit, A., & Richet, A.C., Ses amis, ses collègues, ses élèves, Paris, France, Éditions Médicales.
2. Sapolsky, R. (2010). Stress and Your Body. Chantilly, VA., The Teaching Company. http://www.thegreatcourses.com/tgc/courses/course_detail.aspx?cid=1585. Retrieved 2013-01-21.
3. Kenney, W.L, Wilmore, J. H., & Costill (2012). Physiology of Sport and Exercise (5^thEd). Champaign, IL, Human Kinetics.
4. Taylor, S.E., Klein, L.C., Lewis, B.P., Gruenewald, T.L., Gurung, R.A.R., & Updegraff, J.A. (2000). Biobehavioral responses to stress in females: Tend-and-befriend, not fight-or-flight. Psychological Review, 107, 411–429.
5. Tamres, L., Janicki, D., & Helgeson, V.S. (2002). Sex differences in coping behavior: A meta-analytic review. Personality and Social Psychology Review, 6, 2–30.
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7. Sapolsky, R, Romero, M.L., & Munck, A.U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions”. Endocrine Reviews, 21(1): 55 – 89.
8. Tomiyama, J.A., Dallman, M.F., & Epel, E.S. (2011). Comfort food is comforting to those most stressed: Evidence of the chronic stress response network in high stress women. Psychoneuroendocrinology, 36(10):1513 – 1519.
9. Brown, L.M. (2000). Helicobacter pylori: epidemiology and routes of transmission.Epidemiological Reviews, 22 (2): 283 – 97.
10. Cooke, P.S., & Naaz, A. (2004). Role of Estrogens in Adipocyte Development and Function. Experimental Biology and Medicine, 229(11): 1127 – 1135.
11. Puterman, E. & Epel, E. (2012). An intricate dance: Life experience, multisystem resiliency, and rate of telomere decline throughout the lifespan. Social and Personal Psychological Compass, 6(11): 807 – 825.
12. Daubenmier, J., Lin, J., Blackburn, E., Hecht, F.M., Kristeller, J., Maninger, N., Kuwata, M., Bacchetti, P., Havel, P.J., & Epel, E. (2012). Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology, 37(7): 917 – 28.Stress, Consequences and Overall Health