Dr Jeffry Moss did another excellent job on writing about the stress response in his January & February 1998 and August 1999 newsletters which can be found on his web site mossnutrition.com and accessed with mnr for your user name and mnr again for your password. Copies can also be obtained by calling our office. It is worth your time. He goes very deeply into the biochemical pathways of stress. We thank him for his expertise and generosity in sharing his website with us. 

Stress is becoming recognized as one of the primary underlying causes of most disease. As evidenced by the cover of the June 14, 1999 issue of Newsweek, “Stress: How It Attacks Your Body -Fighting Back: What You Can Do”. Also, the major news services are reporting on research relating stress to physical ailments much more often.  Consider this headline from an Associated Press release from Psychosomatic Medicine that appeared in the August 1999: “Study links attitude, heart problems”.  The importance of the stress response in human health and the effects of one of the biochemical changes during stress, is the decrease in the insulin-glucagon ratio. This continued proteolysis (protein breakdown) and gluconeogenesis (sugar producing) is being called ‘autocannibalism’. When patients are under prolonged stress, the biochemical changes cause a situation where the patient starts eating him or herself alive to survive! That most systems in the body are shut down during stress underlines the clinical importance of stress.  

Some of the more important causes of chronic illness in our society include chemical and metal toxicity, compromised epithelial barriers, i.e., “leaky gut,” dysbiosis, and improper nutrition, which includes both micro- and macronutrients. Yet what may be the most important, omnipresent of them all is the malfunctioning stress response. The stress response is always present in all patients, both acute as well as chronic.  If it is working in complementary ways with the treatment plan, almost any well-designed course of action will succeed in improving health.  If the stress response is out of control and at odds with one's efforts, though, virtually anything and everything done to aid the patient will probably fail from a long-term perspective. Most all successful health care practitioners treat psychological stress and the stress response very effectively in their patients.  Unfortunately in terms of health care, most of the time, neither the practitioner nor the patient is actively aware that this very vital therapy is happening.  

The biochemical and physiological power of a thought is one of the most potent molecular forces in nature. Humans exposed to catastrophic stressors utilize the same neurobiological mechanisms that are activated following exposure to a less severe ‘normal’ stressor. In contemporary life, stress is more likely to depend on symbolic stimulus meanings than on physical stimulus features.  It is our personal interpretation of real or imagined objects as actually or potentially harmful to our physical or psychological well being that is most likely to cause us to be anxious and worried and ultimately depressed.  In these cases it is not the stimulus that causes stress so much as the interpretation we apply to it.  We will not understand the psychology or biology of stress until we understand how environmental events come to acquire symbolic significance and thereby gain access to circuits that control so-called stress responses. Too many unconsciously "live" in the response state of a saber-toothed tiger permanently bearing down on them.

Stress will foster Syndrome X. The normal fight-or-flight response raises sugar levels for immediate muscle and brain function to handle the emergency. This immediacy of shifting of energy away from the endocrine, digestive and immune systems, shutting down digestion, repair, healing, is meant to be temporary in order to save the organism. With continued stress the system does not return to normal function. The raised sugar calls for raised insulin. But the system inactivates the increased sugar lowering insulin because the perceived emergency has not been resolved giving stress induced insulin insensitivity.

The stress response has to end so that proper healing can commence and functions such as digestion, reproduction, and sleep can resume. Most of the time, living on this earth should be a relaxed, more harmonious, balanced experience. During the rare periods that would not be, it is biochemically and physiologically justified to radically alter metabolism.  Given its destructive tendencies, it is essential that the stress response be turned off as quickly as possible.  If life on earth were uniformly negative and hostile, the existence of the stress response as it currently functions would make no sense at all. It would tend to act as a primarily destructive force, a double-edged sword effect. But today many live in a world where the stress response never turns off. It often created by an external, uncontrollable situation.  Since as stated, the initiation of the stress response, for the most part, is based on the perception of danger, not on physical contact with the danger. In our modern society, factors other than perceptions of danger can serve as triggers for the stress response. Many, at first glance, seem innocuous. Yet with the stress response as it is becoming to be understood, may be the biggest, most important cause of ill health, yet most ignored of them all.  And unlike many causes of chronic and, sometimes, acute illness, the stress response is omnipresent. The sickest patients will show an out of control stress response in virtually every case. One's ability to address this successfully in a caring manner along with the behavior modifications, dietary changes, nutritional supplements, and/or herbs, etc, will often be a key determinant of whether one is just an average nutritional practitioner or one of the great ones that people come from long distances to see.

Chronic illnesses or conditions that might be caused and/or influenced, to a greater or lesser extent, by a continuously operating stress response include: Diabetes Mellitus - cardiovascular disease including high blood pressure and elevations in blood fat. Infectious disease - prolonged stress will increase susceptibility to both bacterial and viral infections due to its effects on the immune response. Gastrointestinal illness - increased gastrointestinal permeability (Leaky gut) - sustained sympathoadrenal activation can result in protracted splanchnic (circulatory system of the intestine) flow diversion that may compromise the gut mucosal barrier. Inflammatory (autoimmune) illness - long term exposure to excess cortisol can actually have proinflammatory effects. Effects of stimulant drugs - stress can magnify the effects of drugs and drugs can magnify the effects of stress. Infertility - stress hormones decrease production of both male and female reproductive hormones. Difficulties with growth in children - chronic stress is associated with decreases of both growth hormone and prolactin. Hypothyroidism - cortisol negatively impacts on TSH production and conversion of T4 to T3. Osteoporosis - Under stress the adrenal gland produces cortisol, a hormone which mobilizes calcium from the bone and increases urinary calcium loss. Poor wound repair - Cortisol inhibits fibroblast proliferation and function at the site of an inflammatory response. Amenorrhea - Intensive exercise or psychological stress in women may result in amenorrhea. Detoxification Problems - In the “pathologic detoxifier”, phase I enzymes are elevated and phase II enzymes are depressed.  Cortisol can upregulate phase I (cytochrome P450) enzymes. Reproductive hormone abnormalities in females during puberty - It is suggested that exaggerated adrenal response in early puberty may serve as a predictive marker for the eventual development of polycystic ovary syndrome. Brain damage - prolonged glucocorticoid secretion may cause deficits in memory and cognition through neurotoxic effects on hippocampal neurons. Aphthous stomatitis (Canker sores) - Stress induced high cortisol may play a role in the etiology of recurrent aphthous stomatitis, particularly with an underlying anxiety trait. Chronic fatigue syndrome (CFS) - The stress response is a major causative factor in CFS. Cancer - In a study just published in the Journal of the National Cancer Institute “Researchers at Ohio State University said they found that breast cancer surgery patients with the most anxiety about their medical condition had the lowest levels of white blood cells that normally attack cancer and combat infection.” Gene Expression - One of the hottest topics today in functional medicine is the ability of environmental agents to modify genetic expression, to alter the commands or messages sent out by genes to the rest of the cell. Of the many substances whose genetic expression is modified by glucocorticoids, two are of particular interest.  One is phospholipase A2 (PLA2), which is the major enzyme involved in the production of arachidonic acid derived pro-inflammatory prostaglandins.  The other is serotonin, production of which has gained much attention lately in relation to depression and its treatment with Prozac and St. John’s wort.  The affect of stress-induced glucocorticoids could certainly impact on the efficacy of St. John’s wort as well as anti-inflammatory prostaglandin producing oils such as fish and flaxseed.  
         
Hopefully this is convincing enough that the stress response is a major causative factor in just about every chronic illness that you might encounter in your practices.  Even more sobering, though, is the idea that this is just “the tip of the iceberg.”  Glucocorticoid receptors are found in almost every cell throughout the body. Glucocorticoids are involved in both protection of the organism and damage.  Normal levels of glucocorticoids moderate the primary responses of the body and brain to stressful challenge and buffer them against large or prolonged responses.  Lack of glucocorticoids allows the primary responses to stressful challenge to go unchecked, whereas high levels of glucocorticoids suppress the primary responses to such a degree that the body and brain are adversely affected by the stressful challenge. Some patients have symptoms of high stress without elevations in cortisol and others demonstrated immediate heart pounding and palpitations. The factors that are shared were inappropriate function of epinephrine/ norepinephrine pathways.  Could it be that the underlying biochemistry with certain highly stressed patients involves disturbances in catecholamine activity as opposed to cortisol. GABA tends to counteract the effects of catacholamine neurotransmitters such as dopamine and norepinephrine. Biotics Research product De-Stress pivots in this area so subtly the patient is usually not aware of it effectiveness. Call for the study.