Lynn’s Clinical Pearl on Stress – July 24th, 2016 


Nutritional Endocrinology Practitioner Training (NEPT)
Clinical Pearl
July 24th, 2016 




Lynn’s Clinical Pearl on Stress

Over the last few days, I’ve been speaking with people, either in a coaching capacity or on a call, and as they explain the messages their body is giving them, they usually tell me it involves hormone-deficiency symptoms such as hot flashes, vaginal dryness, decreased libido, difficulty sleeping, increased anxiety, etc. In asking the questions that we learn through our Nutritional Endocrinology Practitioner Training, a basic theme comes through – stress.

As in many responses, stress begins in the brain. As we come upon a situation, it enters our brain response through either sight, sound, smell, or the other sensory receptors. Our brain then tells us what it thinks is the appropriate behavioral and/or physiological response to actual or perceived stressors. The brain has its own set of stressors – glucocorticoids and catecholamines are the two main fight-or-flight stress response hormones, but there are also pro- and anti-inflammatory cytokines along with the parasympathetic nervous system.

While we occasionally may need the catecholamines for those occasional times of a fright – increased heart rate and blood pressure – to help us cope with a situation, chronic elevation of our heart rate and blood pressure will produce wear and tear on our cardiovascular system resulting, eventually, in heart attack or stroke. The active process by which the body responds to daily events and maintains homeostasis is called allostasis. Allostasis literally means “achieving stability through change” and is not intended to replace “homeostasis.” There is now a term “allostatic load or overload” to refer to the wear and tear that results from either too much stress or from inefficient management of allostasis, e.g., not turning off the response when it is no longer needed. Allostatic overload refers to the chronic behavior, such as poor eating patterns, whereas chronic stress has other references that could come from situations outside of your own behavior.

The common experience of being “stressed out” has as its core the elevation of some of the key systems that lead to allostatic overload – e.g., cortisol, sympathetic activity, and pro-inflammatory cytokines, with a decline in parasympathetic activity. Nowhere is this better illustrated than for sleep deprivation, which is a frequent result of being “stressed out”. Sleep deprivation produces an allostatic overload that can have harmful consequences (McEwen, 2006; McEwen, 2007). The effects include elevated evening cortisol, insulin, and blood glucose, elevated blood pressure, reduced parasympathetic activity, and elevated levels of proinflammatory cytokines, as well as the gut hormone, ghrelin, which increases appetite. Hunger for comfort foods and increased caloric intake are one result, along with depressed mood and cognitive impairment (Dallman, 2003;McEwen, 2006). In contrast to these potentially dysfunctional consequences, the same mediators are involved in the natural world in adaptation to environmental changes (McEwen and Wingfield, 2003).

The brain is the key organ of the stress response because it determines what is threatening and, therefore, potentially stressful, and also controls the behavioral and physiological responses, and resulting lifestyle, as I pointed out earlier, which are as important to development of allostatic load and overload as the stressful experiences themselves. Many other things can affect this perception – experiences within our early upbringing, genes and epigentics, different alleles in genetics – are among the environmental triggers.

One of the ways that stress hormones regulate function within the brain is by changing the structure of neurons. The hippocampus is one of the most sensitive and pliable regions of the brain, and is also very important in cognitive function. Within the hippocampus, the input from the entorhinal cortex to the dentate gyrus has complicated consequences by the connections between the dentate gyrus and the CA3 pyramidal neurons. The dentate gyrus-CA3 system is believed to play a role in the memory of sequences of events, although long-term storage of memory occurs in other brain regions, too. The dentate gyrus-CA3 system is balanced in its function and is susceptible to damage, there is also adaptive structural plasticity, in that new neurons continue to be produced in the dentate gyrus throughout adult life, and CA3 pyramidal cells undergo a reversible remodeling of their dendrites in conditions such as hibernation and chronic stress (Popov et al., 1992; Popov and Bocharova, 1992; McEwen, 1999). The role of this plasticity may be to protect against permanent damage. As a result, the hippocampus undergoes a number of adaptive changes in response to acute and chronic stress.

Adrenal steroids are important buffers of remodeling of hippocampal neurons during repeated stress, and adrenal steroids can also cause remodeling in the absence of an external stressor. The role of adrenal steroids involve many interactions with neurochemical systems in the hippocampus, including serotonin, GABA, and excitatory amino acids (McEwen, 1999; McEwen and Chattarji, 2004). Probably the most important interactions are those with excitatory amino acids such as glutamate. Excitatory amino acids released by the fiber pathway play a key role in the remodeling of the CA3 region of the hippocampus, and regulation of glutamate release by adrenal steroids may play an important role (McEwen, 1999).

Repeated stress also causes changes in other brain regions such as the prefrontal cortex and amygdala. Repeated stress causes dendritic shortening in medial prefrontal cortex (Sousa et al., 2000; Wellman, 2001; Vyas et al., 2002; Kreibich and Blendy, 2004; Cook and Wellman, 2004; Radley et al., 2004; Brown et al., 2005; Radley et al., 2005) but produces dendritic growth in neurons in amygdala (Vyas et al., 2002), as well as in orbitofrontal cortex (Liston et al., In Press). Along with many other brain regions, the amygdala and prefrontal cortex also contain adrenal steroid receptors; however, the role of adrenal steroids, excitatory amino acids, and other mediators has not yet been studied in these brain regions. Nevertheless, in the amygdala, there is some evidence regarding mechanism, in that tissue plasminogen activator (tPA) is required for acute stress to activate not only indices of structural plasticity but also to enhance anxiety (Melchor et al., 2003). These effects occur in the medial and central amygdala and not in basolateral amygdala, and the release of CRH acting via CRH1 receptors appears to be responsible (Matys et al., 2004).

Although there is very little evidence regarding the effects of ordinary life stressors on brain structure, there are indications from functional imaging of individuals undergoing ordinary stressors, such as counting backwards that there are lasting changes in neural activity (Wang et al., 2005). Another study, using voxel-based morphometry, has uncovered a relationship between shrinkage of grey matter volume in the hippocampus and orbitofrontal cortex and prospective reports of chronic life stress over a 20 year period (Gianaros et al., 2007).

Another important factor in hippocampal volume and function is glucose regulation. Outright Type 2 diabetes and poor glucose control as measured by glycosylated hemoglobin is associated with reduced hippocampal volume (Gold et al., 2007). Furthermore, poor glucose regulation is associated with smaller hippocampal volume and poorer memory function in individuals in their 60’s and 70’s who have “mild cognitive impairment” (Convit et al., 2003), and both mild cognitive impairment and Type 2, as well as Type 1, diabetes are recognized as risk factors for dementia (Ott et al., 1996; de Leon et al., 2001; Haan, 2006).

Having a positive outlook on life and good self-esteem appear to have long-lasting health consequences (Pressman and Cohen, 2005), and good social support is also a positive influence on the measures of allostatic load (Seeman et al., 2002). Positive affect, assessed by combining momentary experiences throughout a working or vacation day, was found to be associated with lower cortisol production and higher heart rate variability (showing higher parasympathetic activity), as well as a lower fibrinogen response to a mental stress test (Steptoe et al., 2005).

I have given you some scientific information to back up some basic principles. A major goal should be to try to improve sleep quality and quantity, to have good social support and a positive outlook on life, to have a positive self-esteem, to maintain a healthy diet, to avoid smoking, and to engage in regular moderate physical activity. Concerning physical activity, it is not necessary to become an extreme athlete, and seemingly any amount of moderate physical activity helps (Bernadet, 1995; Rovio et al., 2005).


Foundations, foundations, foundations.