Stress: The Basics

Hawaiian Sunset

Caveman Doctor recently was asked the question by loyal reader, Cristina, “Does stress cause cancer?”  Caveman Doctor isn’t sure what stress is, so he did some research. Apparently there are different kinds of stresses like acute and chronic stress. Caveman Doctor understood what acute stress was, as he deals with this every day when he is running after animals hunting, running from animals when hunting goes awry, lifting heavy animals that he drags back to camp, talking to cavelady about her feelings, and dealing with drastic weather changes in his little shelter.  However, Caveman Doctor was really confused when he read about causes of chronic stress and what people worry about, including webpages on celebrities like Kim Kardashian, The Jersey Shore, and many on where to get the latest iPad, iPod or Blackberry, as he rarely encounters these in his life. Caveman Doctor is spoiled in this way, as he doesn’t need to call anyone, does not have a computer with an inevitable 100 emails a day waiting for him to respond, and he also has no boss to report to after the hunt. He only reports to his stomach, to make sure it’s full. Also, this topic is so large (like the number of websites dedicated to Kim Kardashian), Caveman Doctor decided to do several posts on it.
 

Hawaiian Sunset

Sunset on the Beach = Stress Alleviator

 

Stress: The Good, the Bad and the Ugly

 
There are several types of stress that we all encounter. Acute stress involves both physical and emotional events, such as being frightened or put on the spot at work, running several sets of sprints, or lifting heavy weights in the gym. We also encounter physical and emotional chronic stress that persists over a longer period of time. This stress would be anxiety concerning your job, financial worries, an annoying mother or father-in-law, frequent long distance running, or general over-exercising. Many, however, often fail to consider the stress, both acute and chronic, from trauma, infections, and foreign pathogens entering our body.
 

Our body responds to stress by releasing two main hormones:

 
1. Epinephrine (adrenalin)
2. Cortisol (the opposite of insulin, it increases blood glucose)
 
These hormones make us react to the stress with increased strength and speed through increasing our blood pressure, heart rate, and even our blood glucose levels. If you were to picture a potential robber attacking you (or a bear attacking Caveman Doctor), this increase in heart rate and blood pressure will get your blood pumping throughout your body to get oxygen to your brain as you figure out your method of escape and to all your muscles during your sprint away from the danger. The increase in blood glucose gives your muscles and brain a quick source of energy. This is also why you often hear stories of people eliciting super human strength to lift heavy objects in a time of crisis and even why you have seen Hines Ward, threatened by one of the Raven’s defensive backs, run over them and acquire super speed into the end zone as he led the Steelers to multiple Super Bowls in the past couple years. Many of you know this as the “fight or flight” response.
 
There are two important points to note here – the cause of the stress and the response to it. The cause is acute danger, and the response is acute physical activity. Keep this in mind as we will revisit in later in the post.  Also, while stress can be emotional or physical, and acute or chronic, over 300 studies show that both emotional and physical stress can elicit a response from our immune system that helps our body “fight” the stress.1
 

Acute Stress

 
Acute stresses have been described as three different types: acute time-limited stressors (mental math problems or public speaking), brief naturalistic stressors (a test at school or doing sprints), and finally stressful event sequences (stresses that lead to the development of further stresses, such as a death in the family leading to more stressful situations). While extremely stressful, you usually can see an endpoint in sight and know that these stresses will subside or largely decrease. Assuming it does not cause physical injury, there may be some actual health advantages to acute stressors, our body’s response, and the overexertion from running from a bear (or sprinting in a workout), or lifting massive amounts of weight. Early on, it was understandably thought that all stress was bad, as studies of chronic stress showed it to be immunosuppressant, resulting in decreased release of antibodies and response of immune cells.2 However, keep in mind these studies were mostly looking at chronic stress, i.e. worrying about Kim Kardashian and the latest cellphone, not running from bears.
 

Chronic Stress

 
Chronic stresses are those that stick around for the long-term and result in changes and restructuring of your life. Also, you are never quite sure if and when these types of stresses will end (and they may not). While acute stress may provide us with many health benefits, chronic stress appears to be the ugly stepchild. It has been shown to cause obesity, heart disease, depression, and a whole slew of other diseases. But, does it cause cancer? More to come on this…
 

Stress and the Immune System

 
Our immune system is the group of organs and cells within our body that serve to protect us from harmful pathogens.  There are several types of immune cells, including lymphocytes (like cytotoxic killer T-cells that attack foreign invaders) and granulocytes, like macrophages and neutrophils, which engulf foreign invaders. These cells actually work through inflammatory processes, i.e. they travel to the affected site, release their toxic ammunition (often oxidizing free radicals) and then eat the hopefully dead infectious material as well as the damaged tissue. A good example of this would be a pimple (the white is often more macrophages than bacteria).
 
When macrophages are called to the scene of the crime, they release cytokines, which send the signal out for help and stimulate wound healing, but also increase inflammation and cause fevers. The most common cytokines include interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNFα) from granulocytes and IL-2, 4, 10 and interferon gamma (IFNγ) from neutrophils.
 
However, the immune system, like the rest of the human body, is extremely adaptable and can undergo large changes and fluctuations in order to keep us alive. This is likely why even though we know that suppression of the immune system by stress3 can increase disease susceptibility in animals, little data exists in humans. In fact, in studies when mice were predisposed to social stress (mice get stressed out too apparently), they had increased susceptibility to endotoxic shock, glucocorticoid resistance (which raise blood glucose for the “fight or flight” response), and increased production of those cytokines mentioned above, all from increased stress.
 
Several common markers of inflammation are ESR (erythrocyte sedimentation rate), TNF (tumor necrosis factor), and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)).4  However, the markers that are receiving most of the attention these days are:
 

IL-6

 
IL-6 is a cytokine that is normally low, expect during trauma, infection, and, you guessed it, stress.  Interestingly, IL-6 is lowered by estrogen and testosterone, and as we age and these hormones decrease, IL-6 gradually rises5. Not a coincidence, many feel that IL-6 is responsible for several of physical changes that accompany both old age and chronic inflammation, including loss of lean body mass, osteopenia, low red blood cells (anemia), and decreased cholesterol. Accompanying these decreases are elevated levels of the inflammatory C-reactive protein (CRP) and serum amyloid A. IL-6 levels have also been correlated with diseases of old age, including osteoporosis, multiple myeloma, and Alzheimer’s disease.
 

CRP

 
A prime player in stress is CRP, a serum marker which rises in response to inflammation, acute stress, infectious elements within the body, inflammatory and autoimmune diseases (when the body attacks itself), tissue damage, and cancer (just one of the many links between inflammation and cancer). It can be measured as quickly as two hours of the initial insult. It also binds to dead or dying cells, marking them to be destroyed (the complement system).  People with elevated CRP are at increased risk of cardiovascular disease, high blood pressure (hypertension), diabetes,6 depression, and stroke.7
 

Aging and the Immune System

 
When we age, our immune systems become less able to respond to trauma, infections, and inflammation,8 and the similarities between aging and chronic stress (which are often synonymous for many of us) are remarkable in both the physiologic response (cytokines secreted, increased inflammation, etc.) and physical response (weight loss, disease, etc.).
 
Unfortunately, while stress and aging leaves our immune systems less able to battle invaders, we are also less able to regulate this fight. Accordingly, we have weaker troops and in a sense dumber troops that often do not fight the right enemy. As a result, our own body often gets attacked by both crossfire and direct attack from our immune cells, a state known as autoimmune disease. Common examples include multiple sclerosis, Crohn’s disease, and rheumatoid arthritis. This is similar to what happens when gluten sensitive people consume wheat and other grains and find their immune system attacking both the gluten in grains and their own body.
 

Back to Chronic Stress

 
Studies have linked the chronic emotional stresses of work demands at the job place with atherosclerosis.9 Even negative interactions with family and friends on a daily basis has been correlated with elevated levels of CRP, a risk factor for atherosclerosis10. The chronic inflammatory responses from these stresses likely cause inflammatory and oxidative damage to the walls of arteries. As we already know, cholesterol then comes in to patch up the damage (don’t shoot the messenger!). Chronic stress has also been linked to delayed wound healing, increased infection, and chronic inflammation.11 Depression, another form of chronic stress has been shown to be associated with increased CRP and IL-6, more so among women than men.12 While we have been steadily bashing chronic stress, acute stress is not totally in the clear, as sudden extreme emotional stress has been linked to heart damage13 (likely when it demands that the heart pump blood a little too hard), and I even remember reading a story of a guy having a heart attack after Jerome Bettis fumbled the football with 1:20 remaining in the 2006 AFC playoffs, right before Big Ben’s infamous shoestring tackle.
 

Acute Vs. Chronic

 
As alluded to above, the initial models showing decreased immunity with stress were built around chronic stress.  Short term stress, on the other hand, may actually have some benefits, and as stress models in the medical world changed, newer versions had acute stress stimulating the immune system and chronic stress suppressing it.
 
This model was later modified even further, and the next generation version went caveman on us, describing the activation of natural immune responses during acute stress as aiding in the management of rapid life-threatening responses as they evolve quickly, providing our muscles and brain with the ability to escape.1 Importantly, these responses avoid the specific responses that occur from repeated chronic stress and become ingrained in our system.
 
A recent meta-analysis showed that mental arithmetic and public speaking between five and 100 minutes resulted in a significant increase in killer T cells and large granular lymphocytes, for which the authors cited as the immune system redistributing itself in the most effective way to fight whatever unknown insult lie ahead.1 Interestingly, the immune cells that play a larger part in adaptive immune response that would be necessary for specific repeated or chronic insults were not significantly increased. Basically, acute stress causes an acute response and then the immune system goes back to its other functions.
 
The same study looked at chronic stressors, such as unemployment, having a handicap, and caring for a loved one with dementia. Universally, these had negative effects on the immune system. The “natural” and nonspecific immunity increased in acute stressors was decreased. However, specific immunity, which was decreased in acute stress, was elevated. Just as chronic stresses cause remodeling of one’s life, the immune system seems to follow suit by making more permanent changes to deal with the repeating nature of chronic stress. Also, while the example here looked at specific stresses (unemployment, etc.) the study also found that those events that people perceived as chronically stressful reduced killer T cells activity. The authors summed this up quite nicely:

“The results of this meta-analysis support this assertion in one sense: Stressors with the temporal parameters of the fight-or-flight situations faced by humans’ evolutionary ancestors elicited potentially beneficial changes in the immune system. The more a stressor deviated from those parameters by becoming more chronic, however, the more components of the immune system were affected in a potentially detrimental way.”1

With stress comes a plethora of maladies from a variety of direct and indirect methods. Direct damage was discussed above, however, indirectly, when stress bears its ugly face, it leads to overeating unhealthy foods, possibly drinking excess alcohol, abusing drugs (prescription or illegal), and general behavior that often leads to more stress and stress-related pathology.14 It is similar to the roller-coaster of craving-eating-regretting eating of simple carbohydrates; they only lead to further detrimental behavior and emotions. Stress also can lead to further unhealthy behaviors, such as overeating, smoking, or abusing drugs or alcohol, that may affect cancer risk.
 
Avoiding the chronic stresses can be as simple or as complicated as you make them, and some are easily avoidable while others are near-impossible. Much like the inevitability of inflammation and free-radicals that are going to bombard us whether we like it or not, all we can do is attempt to build up our defenses as we withstand the barrage. Stress is no different.
 

Simple Methods to Counter Stress-Induced Inflammation:

 

  1. Get enough sleep to recover.
  2. Take adequate days off in-between heavy workouts to recover.
  3. Eat a Caveman-like diet to increase antioxidants and decrease the stress and dips and peaks in moods that come with a carb-laden diet.
  4. Workout like a caveman and replace the triathlons, marathons, and chronic workouts that tear the body down (without giving it the ability to build back up) with intense periodic workouts.
  5. Supplement these workouts with low-intensity walks and fun activities.
  6. Avoid as many stress-inducing activities as realistically possible and replace them with activities that melt your stress away (i.e. instead of staying up watching TV, get up early and take a long walk or work out.  I guarantee you will feel less stressed out).
  7. Avoid people that raise your level of stress (as much as realistically possible).

 
Fishing in Florida

Go fishing and watch your stress melt away.

 
The theme of these steps is to make a realistic attempt to reduce those elements of daily life that stand in the way of decreasing stress and recovering from it. These can include the easier chip-shot changes, like sleeping more, being more active, and watching less television (or even cancelling your cable!), to the much harder tasks of avoiding financial stresses and asking yourself if the objects you obsess over are actually that important.
 
Also, as crazy as cancelling cable sounds, I found that when I cancelled my cable, I was more efficient at completing my work on time, going to bed earlier (and getting more sleep), and having a lot more time left over for the gym, reading, and walks outside – all activities that decrease stress. Sometime one simple change can result in eliminating several other areas of stress.
 

Give It a Trial Run

 
One thing I found beneficial with different foods and stressors is conducting a personal trial run eliminating them.  I did a similar trial with checking the news online after reading an article on a favorite blog of mine (James Altucher). I felt that I spent a lot of time reading the news online and it always fired me up. For the trial, I basically avoided all news websites for a week. I found that this actually gave me about an extra 30 minutes during work days and even up to an hour during the weekend to do other things that I enjoy. At the end of the week, I checked my favorite news website, and found that it was reporting on similar topics as the week before. I then extended this to a month. There was no difference. I then extended this to three months, with once again, all the same topics and a ton of them still ticked me off to see. I no longer read the news, which gives me 30-60 minutes per day to work on my blog and some other projects, all the time while eliminating that area of stress in my life.
 

In Conclusion:

 
A simple way to think about stress is that acute stresses (that don’t cause injury) allow our body to recover, possibly even become stronger, whereas chronic stresses merely beat down our immune system over time until it can no longer adequately and appropriately respond.
 
One theme you will notice throughout this post on stress: avoid chronic stressors. Obviously try to keep your acute stresses from being too extreme (though we don’t always have control), and give yourself time to adequately recover in-between the acute stresses. This was when Caveman Doctor would go hang out in his cave or walk around the jungle to eliminate stress. Find your stress-eliminating activity and do it!
 

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References:

1. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130:601-630.
2. Cohen S, Miller GE, Rabin BS. Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med 2001;63:7-18.
3. Quan N, Avitsur R, Stark JL, et al. Social stress increases the susceptibility to endotoxic shock. J Neuroimmunol 2001;115:36-45.
4. Ballantyne CM, Nambi V. Markers of inflammation and their clinical significance. Atheroscler Suppl 2005;6:21-29.
5. Ershler WB, Keller ET. Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty. Annual Review of Medicine 2000;51:245-270.
6. Dehghan A, Kardys I, de Maat MP, et al. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 2007;56:872-878.
7. Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol 2005;4:371-380.
8. Boucher N, Dufeu-Duchesne T, Vicaut E, Farge D, Effros RB, Schachter F. CD28 expression in T cell aging and human longevity. Exp Gerontol 1998;33:267-282.
9. Everson SA, Lynch JW, Chesney MA, et al. Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study. Bmj 1997;314:553-558.
10. Fuligni AJ, Telzer EH, Bower J, Cole SW, Kiang L, Irwin MR. A Preliminary Study of Daily Interpersonal Stress and C-Reactive Protein Levels Among Adolescents From Latin American and European Backgrounds. Psychosom Med 2009;71:329-333.
11. Gouin J-P. Chronic Stress, Immune Dysregulation, and Health. American Journal of Lifestyle Medicine 2011;5:476-485.
12. Brummett BH, Boyle SH, Ortel TL, Becker RC, Siegler IC, Williams RB. Associations of Depressive Symptoms, Trait Hostility, and Gender With C-Reactive Protein and Interleukin-6 Response After Emotion Recall. Psychosom Med 2010;72:333-339.
13. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539-548.
14. Whiteman MC, Deary IJ, Fowkes FG. Personality and social predictors of atherosclerotic progression: Edinburgh Artery Study. Psychosom Med 2000;62:703-714.
 

© 2015 CDR Health and Nutrition, LLC. All Rights Reserved.

13 Comments

  1. Tom and Diane

    When you have a physical, what tests do you have done? CRP? Il6? Blood sugar?
    My doctor didn’t question it when I asked for my CRP test. My husband’s doctor said it was an interesting request but the medical field doesn’t know what to do with the test once they get the result.
    In my opinion, if someone has an elevated CRP test, their first stop should be to their dental hygienist! 😉 Of course, a hygienist would say that.

    Reply
  2. CN

    Thank you!

    Reply
    1. cavemandoctor (Post author)

      You’re welcome! Hope you like it!

      Reply
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