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NOTE:   The studies we will review are tagged with citation numbers like this: [2]
If you “click” on that red number, you will be transported to the actual study.
Many of the graphics can also be enlarged by clicking on them.


Stress ~ The Silent Killer

Hans Selye, M.D., PhD first posited the relationship between stress and disease in 1936. [1]   He went on to conduct the first clinical studies on “stress” and “stressors” during the 1950s. The term stress included everything, from prolonged food deprivation to a good exercise workout; by "stress," Selye was not simply referring to “nervous stress”; he also included all “nonspecific responses of the body to any demand”.


His work led to the discovery that steroid hormones, originating from the adrenal cortex, played a crucial role in the stress response. He also introduced the first classification system for the steroids produced by various organs, and that system is still in use today, 70 years later. [2]   A more comprehensive analysis of his career is available online. [3]


The Stress Response

Selye proposed that the human response to stress, which he termed the “general adaptation syndrome”, involved four distinct stages. This complex neurohormonal model revealed that over-activation of the pituitary and adrenal glands are associated with the onset of many chronic diseases, including hypertension [4] , peptic ulcers [5] , renal (kidney) disease [6] , arthritis, asthma, and cancer. [7]

This is how the body responds to stress:

  • The first phase is the alarm reaction, where the nervous system and the adrenal glands provide an almost instantaneous response to a stressor (or threat), by initiating the “fight or flight” response. [8]

  • The second or resistance phase occurs when stressors persists for several days. During this phase, the body attempts to normalize hormonal response.

  • The third, or tissue response phase, happened when the body can’t extinguish the stress response. This leads to adrenal gland hypertrophy (enlargement) [9], decline in gastrointestinal function [10], and thymus gland [11] and lymphoid atrophy. [12]

  • If stress remains protracted, the body enters the exhaustion phase, where we lose the physiologic ability to adapt to stress. In this final stage, our health begins to deteriorate and illness begins to develop.



“Stress is the trash of modern life.
We all generate it. 

But if we don’t dispose of it properly,
it will pile up and overtake our lives.”


      -- Dr. Nina Radcliff, M.D.   [13]



One recent study [14] measured how stress anxiety impacts the health outcomes in a group of 1,000 San Franciscans with pre-existing, but stable coronary heart disease (CHD). These individuals were tracked over a 6 year period.

Three hundred seventy-one cardiovascular events occurred during the follow-up period. The most remarkable finding of this study (and remember that all these individuals ALREADY had CHD) was that those individuals who were also diagnosed with generalized anxiety disorder (GAD) experienced a 62% higher rate of cardiovascular events. This trend was so dramatic that the authors titled their study: “Scared to death?” [14] This is pretty strong evidence that stress contributed to reduced cardiovascular health and eventual death.


Job Stress

A recent new study reviewed the job stress of bank employees. [15] Researchers tracked the impact of what they term subjective mental workload on employees who must constantly adapt to changing technologies while also being polite to their customers.

Imagine this: You work at a busy Bank, and someone approaches your teller cage on their Smartphone, and then asks YOU to wait while they finish their call. Meanwhile, you see a line of people, restlessly waiting to approach you. Grin and bear it, right?

These neuroscientists found that 78% of these employees suffer from musculoskeletal disorders of the neck (48%), low back (44%) and the upper back (36%) directly attributable to their job stress, and those individuals who worked these jobs more than 10 years (10-20 yr.) were 3 times more likely to suffer from musculoskeletal complaints.

The authors discussed how job activities that demand very high concentration and attention levels, so that they can provide quality service, translated to increased job stress.


Stress Studies

Researchers at the University of Michigan assessed 1,300 married couples, and found a direct relationship between marital stress and increased (prolonged) high blood pressure. [16] Another recent study at the University of Colorado [17] found that marital stress contributes to the onset of metabolic syndrome (MetS), a constellation of disorders that includes central obesity, dyslipidemia, elevated blood pressure, and poor blood sugar management. MetS also leads to increased risk for developing cardiovascular disease, diabetes, and stroke.

Earlier studies at Ohio State University found that couples experiencing marital stress also exhibited reductions in natural immunity. [18] Another study at Yale University provided overwhelming evidence that stress has a detrimental effect on natural killer (NK) cells cyto-toxic activity. [19] This means that “killer” cells lose their capacity for destroying invaders. These researchers also demonstrated that severe, or prolonged stress, was associated with a 50% reduction of NK cell activity. [20] Because NK cells play such a vital role in immune surveillance against viruses and cancer cells, one can ill afford a sustained decrease in this aspect of immune performance.

Another recent study at the University of Occupational and Environmental Health demonstrated that prolonged stress reduces bone density, leading to osteoporosis. [21]

Stress also has a significant impact on the balance of our intestinal microflora. Moore et al. found that “the composition of the intestinal flora was not significantly affected by drastic changes in diet, but statistically significant shifts in the proportions of beneficial species were noted in individuals experiencing prolonged anger or fear stressors”.  This shift in the intestinal milieu leads to increased production and absorption of toxins, and a shift towards production of “metabolites that are potentially cancer producing” [22]

The most recent study of 468 military veterans found a strong association between anger and hostility and telomere shortening. Although this article was tipped towards chemical management of stress, it does provide additional insights into the relationship between stress and disease. [23]


Stress Consequences


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