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Stress

Not unlike vitamin D metabolism, the human stress response is governed by a sophisticated hormonal system, one which is also dysregulated in patients with chronic inflammatory diseases. Successful management of both stressors and a patient's stress response can temper disease symptoms while the Marshall Protocol (MP) is facilitating recovery from disease. These diseases cannot be cured or resolved through lifestyle modifications including “stress management” any more than HIV, tuberculosis, polio, or any of the other forms of infectious disease can.

Physical stress or trauma has also been accepted as a partial contributor for several chronic diseases. However, psychological or physical stress does not appear to play any greater role than many factors which drive disease. There appears a difference between stress causing disease and stress being one of many factors which can influence the progression of disease. Other factors such as the presence of microbial pathogens appear to play a more prominent role.

Psychological stress and immune function

Researchers have shown that stress has certain detrimental effects on immune function, including reduced natural kill cell activity, lymphocyte populations, lymphocyte proliferation, antibody production and reactivation of latent viral infections.1) Such effects on the immune system have some effect on health which include, but are not limited to, delayed wound healing, impaired responses to vaccination and development and progression of cancer.2)

Psychological stress and disease

Some researchers have concluded that stressors may trigger disease in susceptible individuals. These researchers point to retrospective studies, which have found that a high proportion of certain kinds of patients reported uncommon emotional stress before disease onset.3) Indeed, a relationship between stress and disease has been identified in at least the following diseases:

  • periodontal disease 4)
  • Graves' disease5)
  • cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, and musculoskeletal disorders6)
  • many of the common autoimmune diseases including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease.7) 8)

On the other hand, there is good reason to believe that people with higher bacterial loads are more likely to respond to stressors with an elevated stress response. In this respect, stress may merely accelerate the inevitable onset of clinically observable disease.

Patients in the later stages of the MP have reported increased resilience, an observation which suggests that bacterial pathogens drive the stress response.

Mechanisms by which the stress response promotes infection

Some bacterial pathogens directly respond to stress-induced neuroendocrine hormones, reacting to stress in parallel to host immune cells. For example, when catecholaminergic nerves within the gut release norepinephrine, the local population of gram-negative bacteria, mainly Escherichia coli, increases by as much as 105-fold.9) Stress hormones not only enhance growth, but also modulate expression of virulence-associated genes in some bacterial pathogens. As a result, stress-mediated changes may shift the microbial colonization patterns on the mucosal surface and alter the susceptibility of the host to infection.10)

Stress hormones promote iron availability

According to Sandrini et al., stress hormones form complexes with iron-sequestering proteins such as transferrin and lactoferrin, reducing their affinity for iron and thus allowing bacteria to obtain iron from these ordinarily inaccessible host stores.11)

A second mechanism is independent of host iron and, instead, involves synthesis of a novel growth stimulator among many different species of bacteria. This autoinducer restores active growth for several pathogens, including E. coli O157:H7 and Salmonella enterica, and it also induces Bacillus anthracis spores to germinate. Several investigators have attempted to understand the global response of bacteria to stress hormones by looking at gene expression profiles. Interpreting these microarray analyses of enteric bacteria such as E. coli and Salmonella becomes complicated in part because of the diversity of media on which these bacteria are grown and of the varied physiological states of the cultures being profiled.12)

Epinephrine as a quorum sensing molecule

Epinephrine, a hormone produced in response to stress, is produced by at least one bacteria, E. coli, for communication with other members of the species (quorum sensing).13) A pathogen which uses the same signaling molecule the body uses for stress makes sense: E. coli would be able to spread more effectively during times when the body is weakened. The shared use of the epinephrine molecule may also explain, at least in part, by why those with chronic diseases (who carry high pathogenic loads) are sensitive to stress.

Pseudomonas aeruginosa PA14 offers another example of how stress hormones can aid microbes.14)

However, the stress response by the host does not appear to be detrimental in all respects. In Salmonella bacteria, epinephrine has been found to reduce Salmonella's defense systems against antimicrobial peptides.15)

Physical stress and disease

In susceptible individuals, physical stress or trauma has been accepted as a trigger for chronic disease for at least the following diseases:

  • psoriasis and vitiligo 16)
  • fibromyalgia 17) 18)

Motor vehicle collision trauma appears capable of triggering FM, but generally not through direct biomechanical injury. Instead, the evidence suggests that MVC trauma can act as a “stressor”… The evidence that motor vehicle collision trauma may trigger fibromyalgia meets established criteria for determining causality.

Samuel A. McLean, et al. 19)

Microbes in combination with physical stress have been shown to induce memory dysfunction in mice. Mice were infected with the non-invasive intestinal pathogen, Citrobacter rodentium in the presence or absence of acute stress. No behavioural abnormalities were observed, either at the height of infection or following bacterial clearance. After infection clearance, however, when one group of infected mice were exposed to acute stress, however, memory dysfunction was apparent.20)

War – a crucible for chronic disease

War offers a number of circumstances which contribute to the incidence and prevalence of chronic disease as evidenced by epidemiological studies.

Factors driving chronic disease

There are a number of circumstances inherent to war which appear to drive the prevalence of chronic disease.

  • Acquisition of new pathogens – As discussed in a recent book, among American servicemen stationed overseas during World War II, those who served in the Pacific were 1.5 times more likely to have died by 2000 than overseas personnel in other theaters.21) 22) There are a number of possible explanations for this phenomenon, but one compelling one is exposure to infections. Any event which brings together diverse groups of humans in new environments allows for the acquisition and sharing of chronic pathogens – especially war with its close quarters, and unsanitary and undersanitary conditions. Studying metabolites in urine, Dumas et al showed that three geographically distinct populations seemed to each have a distinct microbiota. Interestingly, people who recently moved between regions began to take on the metabolic profile of that region – an observation which implies the sharing of bacteria.23)
  • Physical trauma and stress – Fibromyalgia patients are more likely to report significant physical trauma prior to disease onset.24) 25) as are patients with psoriasis.26) Trauma, of course, is more common during wartime.
  • Psychological stress – Studies have linked traumatic stress exposures to a wide variety of conditions.27) 28) American Gulf War veterans have high rates of anxiety disorders.29) One study of World War II prisoners of war found that those who suffered posttraumatic stress disorder were at higher risk of cardiovascular disease including hypertension and chronic ischemic heart disease.30)
  • Use of vaccines

Diseases shown to be exacerbated by war

Epidemiological evidence that war predisposes combatants, their families, and other noncombatants to increased rates of certain chronic diseases. These conditions include:

  • Hypertension and obesity – Among, displaced Croatians who survived the Croatian War of Independence, there were significantly higher rates of hypertension, hyperlipidemia and obesity as compared to a control group.31)
  • Cancer – Another study also looking at Croatians found that those who got breast cancer during the war, as opposed to the time before and after the war, were significantly more likely to get it earlier in life and to survive for less time.32)
  • Chronic Fatigue Syndrome – Fourteen years after deployment, 1991 Gulf War veterans continue to report a higher prevalence of many adverse health outcomes, compared with Gulf Era veterans including unexplained multi-symptom illness, chronic fatigue syndrome-like illness, posttraumatic stress disorder, and functional impairment.33)

Perhaps it is more than coincidence that those diseases for which there is a demonstrated association with war – cancers, hypertension, obesity, and many of the other forms of cardiovascular disease – saw an increase in the aftermath of World War II, particularly in the United States. Given the discrepancy with which the genders have traditionally enlisted, it would be speculative to suggest that war plays a role in the onset of predominantly “male” chronic diseases, but that possibility may be worth further study.

Management

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Mast cell activation plays an important role in stress-mediated disease pathogenesis. 34)

===== Notes and comments =====

  • explain car accidents, etc. as disease triggers1 2 Blaney: “I have observed in many patients that an important precipitator of increased Th1 disease is physical injury. My speculation is that the physical trauma further activated AT1 due to the wound response, suppressing the immune system further and allowing increased bacterial growth.”

=====References=====

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