Several years ago, I was self-experimenting with different dietary attempts to lower my blood sugar and raise my ketones, the energy source that our liver makes when our blood sugar drops. This study had nothing to do with stress and cancer, I was merely attempting to expand on my recently published series of patients who were on a similar diet while receiving treatment for brain tumors.1 Several studies have shown that the higher a cancer patient’s blood sugar, the shorter they seem to live.2–4 Our initial study hinted that a very low-carbohydrate and high-fat ketogenic diet may potentially offset the rise in blood sugar that often occurs when patients are treated with chemoradiation for brain tumors.1 Efforts are even underway to block sugar uptake as a form of cancer treatment, which leaves cancer cells more sensitive to treatments like chemotherapy and radiotherapy.5 Cancer cells seem to love sugar.
During my self-experimentation, I found myself fasting for hours at length, eating miniscule amounts of sugar and carbohydrates, eating massive amounts of fat, and trying different herbs and supplements known to lower blood sugar. As expected, my blood sugar dropped and my ketone levels rose. Some mornings, my blood sugar was so low that if I had checked into the hospital, they would have questioned why I was not experiencing some serious symptoms of hypoglycemia (I had no symptoms, felt great, and was running on ketones). I also lost some belly fat and felt a sensation of mental clarity. I had done this plenty of times before, however during this experiment, I pricked my finger to test for glucose and ketone levels continuously throughout the day. I kept a journal logging all my food and activities. I even pricked my finger in the corner of the gym during my workouts, eliciting some strange looks from the other members.
I fasted in the mornings, drank coffee with heavy cream and some coconut oil (which is high in medium chain triglycerides, a type of fat that aids the liver in ketone production), and ate mostly fat. I changed no other aspects of my day-to-day and assumed that my blood sugar would be most affected by the food I ate.
I was wrong.
After several weeks of my self-experimentation, I noticed some unexpected findings from my many finger-sticks. My food had a small effect on ketones and blood sugar. My exercise routine seemed to transiently affect them a little more. However, my blood sugar levels were most affected by my drive to work. While my sugar levels seemed to scoff at any dietary changes, a 10-12-minute morning ride to work during the week spiked my blood sugar from an average of 76 mg/dl up to 98 mg/dl (normal is 70-99). On several occurrences when my road rage was at its highest, my blood sugar levels rose by more than 30 mg/dl and almost doubled.
I increased my ketone/glucose checks to the mornings during the weekend. No changes.
I increased the number of checks before and after my drive home from work, where I drive equally as fast. My blood sugar was barely affected.
Stress and Cancer – The Physiologic Response
The instant we are met with severe stress, an intricate interplay of brain signals, hormone release, and organ activation that has evolved over millions of years is activated in a fraction of a second as our brain leaps into action. Several parts of the brain communicate with each other, triggering the fight-or-flight response, signaling several chain reactions. Hormones leave the hypothalamus from within the brain and force the adrenal glands, from atop our kidneys, to secrete adrenaline into the bloodstream.
The body instantly responds with the release of several hormones, including:
- Epinephrine (adrenalin)
- Cortisol (the opposite of insulin, it increases blood sugar)
This response to stress has been imbedded within our physiology over millions of years. The forms of stress may have migrated from lions and tigers and bears to screaming bosses, but our body’s physical responses to increase our chances of surviving an encounter with them has remained the same. We have all felt that feeling when we get yelled at by a supervisor (or getting pulled over for speeding) – our heart starts pounding and we are overwhelmed with adrenaline.
The increased heart rate, breathing rate, blood pressure, and amount of blood pumped to our muscles provides them a rich source of oxygen and nutrients to enable a quick escape. The release of sugar, fats, and cholesterol from our reserves enrich our blood with nutrients to fuel these contracting muscles. The oxygen in our blood provides high octane fuel and our vessels constrict to ensure a speedy delivery to oxygenate our muscles. Our brain also benefits from the rapid delivery of oxygen and nutrients, as the sudden surge enhances its acuity as it coordinates our muscles to navigate and escape the dangerous situation.
During this period of “fight-or-flight,” our body shuts off its inessentials. For instance, there is no time for digestion and stomach acid production is shut off (though increased afterwards). Even certain parts of our vital immune system are inactivated during the encounter.
If these changes sound drastic, it’s because they are. The physiologic response to stress is much like Bruce Banner’s rapid change to the Incredible Hulk – pupils are dilated, sweat pours from the skin, and our heart beats out of our chest. These mechanisms kept us away from danger and alive as a species over the past million years, when drastic was necessary. These acute stressful events even rewire our brain to help performance and cognition.6,7 They also leave our brains with an enhanced response to similar future situations. The next time that lion comes around the corner, we are familiar with the dangerous situation and escape before our brain even needs to process it. After these events happened a couple billion times over a couple million years, they became embedded within our normal physiology. The stress response became part of us.
Stress and Cancer – The Types of Stress
Before we dig too deep into the connections between stress and cancer, let’s take a step back and discuss the different types of stress. Simply put, we encounter two types of stress, acute and chronic. To some degree, both are a normal part of daily life.
Acute stresses have been described as three different types: acute time-limited stressors (like mental math problems or public speaking), brief naturalistic stressors (a test at school or a quick dash from a grizzly bear), 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 acute stresses can fluctuate in severity, we usually see an end in sight and these stresses will subside or at least largely diminish.
But what happens when the encounter we are trying to escape is inescapable? Chronic stresses often lack that end in sight. They seem to stick around for the long-term and result in restructuring of our lives. We have less knowledge of when and if these types of stresses will end, and some may not.
Being frightened, put on the spot at work, running several sets of sprints, or lifting heavy weights at the gym are all acute stresses. Chronic stress, on the other hand, are physical and emotional stresses that occur frequently or over long periods of time. For instance, a general baseline of work-induced anxiety, concerns over money, annoying family members, or prolonged physical overexertion like ultramarathon running are chronic stressors that wear the body down both physically and emotionally. Other chronic stresses that can affect us are less obvious, like chronic infections.
The cortisol release from my “stressful” daily drive to work resulted in a large and significant increase in my blood sugar. My ten-minute drive signaled to my brain to go engage the sympathetic “Incredible Hulk” response, ruining my nice clothes while releasing a slew of stress hormones. Apparently I am not the only one with this issue, as driving is a documented potent stress and cortisol trigger8 and fast driving may be even worse. Even traffic noise can raise cortisol.9
What should stand out here is the cause of the stress and the response to it. Commonly, acute stressors are perceived by the body as acute danger and the response is immediate, acute physical activity. In other words, the event ends with us sprinting, climbing, screaming – just getting away. Instant adrenaline is released, we run away, we are safe, and the body goes back to normal.
There is, however, a lasting effect from the acute stress, as it seems to intensify our body’s humoral immune system, leading to the release of immune proteins, antibodies, and antimicrobial peptides to help our body fight the stress.10 These changes increase our ability to fight things like skin infections,11 which may occur from all of the scrapes and bruises as we run and climb away from our potential threat. The humoral immune system affects the body fluids, named so by Hippocrates 2,500 years ago when he described the body humors: phlegm, yellow bile, black bile, and blood. Hippocrates, not surprisingly, knew of the connection between stress and health, and is one of the first recorded physicians theorizing this connection. Hippocrates knew that health was depending on a complex interplay of physical and mental responses. Some stress was good for the system. Too much stress was bad.
Besides providing safety and aiding in Houdini-like escapes from potentially lethal situations, the stimulation of our immune systems from acute stress to fight infections and inflammation may have provided the extra benefit of fighting cancer. Chronic stress, on the other hand, transiently raises our blood sugar during a stressful episode, but if this release occurs too often, we may find ourselves with habitually elevated blood sugar. This state – similar to a poorly controlled diabetic – may lead to metabolic dysfunction and cancer.12,13 Much like my morning drive, studies confirm that stress can raise blood glucose levels to double their normal amount.14
Depression, a common form of chronic stress, causes hyperactive responses to stress and chronically elevated levels of cortisol, which undoubtedly will lead to chronically elevated levels of blood sugar.15 This extra sugar is worrisome, as higher serum glucose levels are associated with increased risks of cancer.16
Early on, it was understandably thought that all stress was bad, as initial studies suggested that it suppressed the immune system, decreasing the release of antibodies and response of immune cells.17 However, keep in mind these studies were mostly looking at chronic stress, i.e. worrying about jobs and not running from those bears.
Stress and Cancer and the Immune System – Nurturing our Granules
No discussion on the connection between stress and cancer would be complete without an explanation of our body’s defense system. Our immune system is the police force comprised of the organs and cells within our body that serve to protect us from harmful pathogens. Each immune cell plays an important role. It’s all very detailed and interesting, but five cups of Starbucks’ coffee couldn’t keep me up when lectured about it in medical school, so I will keep it brief.
- Granulocytes: These cells contain granules, as the name would imply, which work like little grenades to defend against foreign invaders. Some of them look like pacman and roam throughout the body engulfing foreign elements. These neutrophils contain caustic granules comprised of enzymes that digest and destroy bacteria. Eosinophils have granules that kill parasites. Basophils and mast cells have granules that contain histamine and other inflammatory elements. They blitzkrieg areas of infection, turning it into a war zone and increasing blood flow to aid in immune cell reinforcements to eliminate the potential threat.
- Lymphocytes: These cells act like hired hitmen found within our lymph tissue. They include T cells, B cells, and natural killer cells (NK cells). Generally, B cells tag foreign bacteria and viruses with antibodies, enabling T cells to recognize and assassinate them, also with the help of granules. The B and T cells then pass their information onto memory cells to ensure that if these foreign elements trespass again, the next response will be quicker and more effective. They are part of the adaptive immune system, or in other words, they adapt to these threats and when called upon, charge into action against known enemies.
- NK killer cells are part of the innate immune system, and simply go buck wild on cells infected by viruses and tumor cells. If you remember the enemy-revealed-father of the main characters in Boondock Saints, he was basically a natural killer cell in the flesh.
Stress and Cancer – Inflammation: Cancer’s Fertilizer
When it comes to fighting cancer, we want our NK cells and T cells (specifically helper T cells) healthy, functioning, and ready to take down any abnormal cells that may resemble cancer. Other cells chip in as well. For instance, when macrophages are called to the crime scene, they release cytokines and inflammatory signals, calling for more reinforcements. Thus, a local battle becomes a full-scale war to tilt the odds of victory in our favor.
Before we know it, the area is bombarded with inflammation, fevers, increased blood flow, and preparation for wound healing. These changes create an uncomfortable feeling for us, but an inhospitable environment for bacteria. Cytokines are created as messengers to the rest of the body, and the most common include interleukin-1 (IL-1), 2, 4, 6, and 10, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) from neutrophils.
In the acute setting, inflammation is vital to spark up a war against a potential cancerous or infectious threat. However, repeated and lingering inflammation starts to cause problems. For instance, chronically elevated levels of IL-6 are felt to be partially responsible for many of the problems of old age, including muscle loss, bone loss, anemia, and even Alzheimer’s disease.18 (As a side note, heavy lifting and muscle stimulation is a great way to lower serum levels of IL-6). Accompanying these issues are elevated levels of other factors that accompany chronic inflammation, like C-reactive protein (CRP). Elevated CRP levels are associated with a higher risk of death from cardiovascular disease, high blood pressure (hypertension), diabetes,19 depression, and stroke.20
When neutrophils release their ammunition against harboring enemies, other cells are called to the scene. Macrophages, for instance, arrive ready to engulf any foreign objects. While certainly beneficial to fight infections and cancer, they can also be used against us. They can even help cancer cells grow and spread through their promotion of inflammation. Simply put, inflammation serves as the fertilizer of cancer cells, and if too much is produced, we may find ourselves in trouble. When macrophages release TNF – remember tumor necrosis factor – several changes occur in cancer cells that promotes their growth, ability to avoid death by our normal cells, and create even more inflammation by increasing IL-6 and other inflammatory compounds.21 To top it off, they attract more blood vessels to the cancer cells, which attracts more inflammation, tumor growth factors, and glucose to fuel these tumors.22
In fact, macrophages become so helpful to tumors that the cancer cells start signaling and inviting more to migrate nearby and contribute to their growth and spread. Like many aspects of our physiology, a little inflammation and immune response is a good thing, but a lot may be detrimental. The stress and immune response, and the entire immune system, is extremely adaptable, with the capacity for large changes and fluctuations to help keep us alive. The overarching conclusion is that each aspect of our stress response, however inflammatory at times, is necessary to defeat potentially dangerous and deadly threats. Some aspects of the response can be viewed as beneficial over the long-haul, as it prepares our body for future attacks. What becomes clear is that the collateral damage from the inflammatory response and the message to the rest of the body to become involved, can become detrimental over the long term. The double-edged sword is that stress can both activate and strengthen the immune system, but over time, can wear it down, weaken it, and leave us susceptible to illness.23
From the example of immune cells above, it is clear that they are extremely beneficial, but carry much risk. Much like a lethal swat team, when given appropriate direction they can eliminate a potential threat. However, when used inappropriately, can create much collateral damage.
Stress and Cancer – Is There a Link?
Individuals with chronically stressful states, like depression and a lack of social support, seem to experience an increased risk of cancer.24 Yet, like most population studies, results have been mixed and often contradictory, and narrowing down the cause versus effect of this association has been difficult. Stress from our workplace, which usually includes high work demand, long hours, and a difficult working environment has shown both positive and negative links with cancer.25
Difficult and stressful life events seem to have a stronger association with cancer, and specifically breast cancer.26 For instance, the death of a mother during childhood leaves the child at an increased risk of breast cancer later in life.27 Jewish individuals who were part of the Holocaust experience a higher risk of breast and colon cancer versus the rest of the population.28 Collateral damage from stressful events like death, divorce, or a continued stressful social situation takes a little over a decade to lead to cancer.
Much like the world of dietary studies, studies on stress and cancer are almost always plagued by Monday morning quarterbacking and analyzing cancer occurrence after the fact. To obtain some concrete answers would require the purposeful stressing of individuals over prolonged periods, and these unethical studies will never happen.
Instead, we turn to animal studies for some answers. They can at least point us in the right direction to implicate stress as one of the many smoking guns when it comes to cancer. While mice are not humans, if we take two similar groups, stress one and simply watch the other, we get some answers.
Stress in Mice, Adrenaline, and Cancer
- Chronically stressed mice have a decreased immune system and experience tumor development significantly earlier than non-stressed mice.29
- Chronically stressed mice have an increased risk of cancer growth as well as increased angiogenesis, the process by which cancer forms new blood vessels to feed itself nutrients for growth and metastases (spread to other parts of the body).30
- Epinephrine, the adrenaline hormone released during stress, may disable our body’s ability to kill cancer cells through the process called apoptosis.31,32
- Stress accelerates prostate cancer development in mice.33
- Stress causes prostate cancer cells in mice to spread quicker.34
- Stressed mice experience a 30-times higher risk of their breast cancer spreading.35
- Mice injected with leukemic cells and stressed physically and physiologically with injections of adrenaline, experience enhanced cancer progression.36
- Some scientists even propose that, while necessary in many cases of cancer, undergoing surgery may cause enough stress to lead to tumor promotion and progression.37
- While Peyton Rous was awarded a Nobel Prize for proving that a virus could cause cancer in 1911, more recently several viruses have been implicated in head and neck and cervical cancer. Chronic stress has also been shown to decrease our body’s ability to mount an attack against foreign invaders, including viruses.38
- Studies have yet to take a close look at stress on the effect of cancer-causing viruses, but it does appear that methods to combat chronic stress stimulate our immune system to battle viruses and potentially fight cancer.39
Stress and Cancer – The Why
Much like my “stressful” drive to work, when the brain perceives stress, it releases cortisol. Cortisol triggers a set of chain reactions that pull sugar into the blood, providing a quick source of energy for our muscles and cells. We run away, our muscles use this sugar, the immune system is stimulated, and the body returns to normal. But what happens when we aren’t running from a predator? What happens when we are sitting in our car and follow the “need for speed” ride to work with a seat at our desk for the next several hours? What happens when the “situation” we are escaping is not actually a threat, but rather a made up stressful situation? We get a surge of stress hormones, increased blood pressure, and blood sugar levels that shoot through the roof. Then we sit at our desk.
As far back as 400 BC, Hippocrates, one of the earliest documented physicians, knew of the damage inflammation could cause to the body. He began treating patients with willow tree bark to alleviate their symptoms of pain and fever.40 What Hippocrates may not have realized was that he was actually calming these patients’ inflammatory symptoms with aspirin, which is found in the bark of the willow tree. Over 2,000 years later, we continue to prescribe an array of medications for inflammation, including aspirin. While often these medications are treating the symptoms as opposed to the cause, the treatment of inflammatory diseases has largely broadened our knowledge of the connection with cancer and inflammation.
Stress = Inflammation = Cancer?
Inflammation has been considered the match that ignites the flame of cancer. In fact, it has been recently labeled as one of the hallmarks of cancer.41 Perhaps more appropriately is regarding inflammation as the kindling for the fire, or the fertilizer to nurture cancer initiation and growth. Several diseases of chronic inflammation significantly raise the risk of cancer. For instance, individuals with ulcerative colitis – known as inflammatory bowel disease – have a significantly higher risk of colon cancer.42,43 While acute pancreatitis (inflammation of the pancreas) can be excruciatingly painful, it usually resolves without issue. Chronic pancreatitis, on the other hand, leaves its victims with a much higher risk of deadly pancreatic cancer.44 Cigarette smoke, one of the deadliest substances humans have encountered, chronically inflames the lungs, producing oxidation (free-radicals) while damaging DNA, leaving the lungs scarred and nonfunctioning, eventually leading to chronic obstructive pulmonary disease and cancer.45
Returning to the cancerous impact bowel inflammation has on the colon, stressing animals exacerbates colitis (bowel inflammation)46 and chronic stress from irritable bowel disease decreases immune function, creating a chicken-versus-the-egg situation.47
While acute stress can benefit from its ability to stimulate the immune system, chronic stress induces a state of excess inflammation and eventually diminishing the effectiveness of the immune system. For instance, stress-induced inflammation can activate cellular pathways that favor cancer formation, like the activation of nuclear factor-Kappa B (NF-KB). When our cells lose control of NF-KB after excessive exposure to inflammation, free radicals, or cytokines, it begins to drive cancer cell production. Not surprisingly, it is found in many cancer cells,48 and is associated with breast cancer diagnosis.49
Much like the pancreases of those with chronic inflammation, when surgeons resect precancerous lesions from the inflamed organ, cells are often on the path to becoming cancer. These precancerous lesions are often infiltrated with many of the immune cells listed above and a plethora of inflammation-producing cytokines. These cells can not only cause cancer, but provide it the ability to spread throughout the body,50 create more inflammation, and attract blood vessels to feed them during this journey51 – a deadly combination.
As a result, high levels of chronic inflammation can lead to cancer progression.11 Those inflammatory messengers put out during stress – CRF, TNF, and IL-6 – are seen floating around in high numbers in individuals with cancer.52,53
Stress and Cancer – Aging and the Immune System:
As we age, our immune system loses a step as it attempts to respond to trauma, infections, and inflammation.54 The similarities between the wear and tear of aging and chronic stress are remarkable in the physiologic response: cytokines are secreted, inflammation is increased, disease starts. However, a bigger issue may not be that stress and aging leaves our immune system less able to battle invaders, but that we are less able to regulate this fight. When we have both weaker troops and misdirected troops, the damage increases as our normal cells get bombarded with collateral damage from crossfire and direct attack from our immune cells. If this collateral damage gets too far out of control, we begin to permanently attack our normal cells, a state known as autoimmune disease. Common examples include multiple sclerosis, Crohn’s disease, and rheumatoid arthritis – all diseases that scientists are hurrying to treat and prevent with anti-inflammatory agents.55
Stress and Cancer – The Damage of Chronic Stress
Studies on the dangers of chronic stress are plenty. Not surprisingly, a stressful work environment seems to provide plenty of disease-provoking stress. Chronic emotional stresses of work demands at the job place may lead to atherosclerosis – the state of inflammation throughout the arteries – and ultimately coronary artery disease and heart attacks.56 Taking stress home is just as bad, as daily negative interaction with family and friends is correlated with elevated levels of CRP and atherosclerosis.57 Our vessels function best when blood can smoothly flow through. Inflammation causes buildup along their walls, with an influx of all those immune and inflammatory cells discussed above. The chronic inflammatory responses from these stresses inflames the walls of arteries and bombards them with oxidative, free radical damage. Cholesterol eventually patches up this damage, but over time, adequate blood flow can decrease. Other problems from inflammation-induced inadequate blood flow can surface as well; chronic stress has been linked to delayed wound healing, increased infection, and lingering inflammation.58 Depression, another form of chronic stress, is associated with increased CRP and IL-6, and women seem to be a more common victim of this association.59
While the issues of stress often point to chronic stress, acute stress is not in the clear, as sudden extreme emotional stress has been linked to heart damage.60 As a Pittsburgh native, I was immediately reminded of this when I heard news that a man experienced a heart attack immediately after Jerome Bettis fumbled the football with 1:20 remaining in the 2006 AFC playoffs, just moments before Ben Rothlisberger’s famous shoestring tackle.
Stress and Cancer – The Benefits?
The near constant chastising of stress over the past several decades has caused us to miss the potential upside. Dealing with stress is a natural part of our evolution, health, and physiology. It has been ingrained within our cells for millions of years. Acute stress stimulates our immune system, which has potential upside.
Studies even show that individuals with stress may not be as affected as we think. While individuals that worry about stress can have substantial health problems, researchers from Stanford have shown that those of us who view stress as a normal and potentially helpful part of daily life have better emotional and physical health, and are even more productive.61 Other benefits of stress have been shown:
Mental Acute Stress Stimulates our Immune System:
A recent analysis revealed that mental arithmetic and public speaking between 5 and 100 minutes increases killer T cells and large granular lymphocytes. Stress from the speech causes the immune system to redistribute its cells to fight a potential threat.10 However, this task did not increase the immune cells that favor responses to chronic stresses.
Stress May Help Prevent Cancer:
When genetically engineered mice prone to skin tumors are acutely stressed via 2.5 hour restraints three times per week and then exposed to ultraviolet light, the stressed group experiences significantly less skin cancers (and significantly higher numbers of activated T cells).62
Metabolic Stress Helps Fight Cancer:
Metabolic stress, i.e. fasting, carbohydrate restriction, a ketogenic diet, and intense exercise all stress our mitochondria (the powerhouses of our cells), which causes our cells to engage in the recycling of faulty parts and faulty cells undergo programmed cell death, reducing the risk of them becoming cancer.63
With chronic stress comes a plethora of both direct and indirect damage. Direct injury 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.64 It is similar to the roller-coaster of craving-eating-regretting that often happens with sugary foods and simple carbohydrates; they only lead to further detrimental behavior and emotions.
Avoiding the chronic stresses can be as simple or as complicated as we make it; some are easily avoidable while others are near-impossible to avoid. Much like the inevitability of inflammation and free-radicals that bombard us whether we like it or not, all we can do is attempt to build up our defenses to withstand the barrage. Stress is no different.
My Simple Methods to Counter Stress-Induced Inflammation:
- Always push for eight hours of sleep per night for optimal recovery.
- Surround ourselves with people who help reduce stress and avoid those that cause it.
- Avoid exercises that wear and tear the body down and stick with ones that build it up.
- Take adequate days off in-between heavy workouts to recover.
- Eat a diet that limits inflammatory foods and contains leafy greens and cruciferous vegetables to help offset inflammation, free radicals, and cancer causing chemicals.
- Spend time in a meditative-like state cooking all whole foods meals, providing stress relief.
- Replace empty activities, like late-night TV-watching, with enriching activities like conversation with friends and family, meditation, reading, or long walks.
- If unavoidable stresses are overwhelming your job, take some advice from Adam Grant, in his book Originals. We have four options when in a sub-optimal work situation: actively attempt to change the bad situation, leave if it is unchangeable, persist at the bad job through grit, or neglecting the current job to be able to mentally deal with it. The first two may lead to less chronic stress, while the latter two will likely increase it.
- Don’t stress too much about stress and remember it is a normal part of daily life (sometimes easier said than done).
Stress and Cancer – In Conclusion:
Stress is a normal part of daily life that we have encountered for millions of years. It is ingrained within our physiology. If we appropriately channel these natural stresses it may decrease our risk of cancer and infection and improve our overall health. Furthermore, if we approach acute stress head-on, we may find ourselves no longer fearful of it. We may even begin to enjoy it.
Dwell on those chronic stresses, and it may wear us down until we are left with illness. Stress is a natural part of the human environment and the response to stress is a natural part of our physiology. It only stands to reason that it has been adapted to provide benefits. To deny it, would be denying those potential benefits.
To channel it, however, seems wise.
Stress and Cancer – References:
- Champ, C. E. et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J. Neurooncol. 117, 125–31 (2014).
- Derr, R. L. et al. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 27, 1082–1086 (2009).
- McGirt, M. J. et al. Persistent outpatient hyperglycemia is independently associated with decreased survival after primary resection of malignant brain astrocytomas. Neurosurgery 63, 286–91; discussion 291 (2008).
- Mayer, A. et al. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther. Onkol. 190, 933–8 (2014).
- Simons, A. L. et al. Enhanced response of human head and neck cancer xenograft tumors to cisplatin combined with 2-deoxy-D-glucose correlates with increased 18F-FDG uptake as determined by PET imaging. Int. J. Radiat. Oncol. Biol. Phys. 69, 1222–1230 (2007).
- Chetty, S. et al. Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus. Mol. Psychiatry 19, 1275–1283 (2014).
- Kirby, E. D. et al. Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2. Elife 2, (2013).
- Tsopanakis, C. Stress Hormonal Factors, Fatigue, and Antioxidant Responses to Prolonged Speed Driving. Pharmacol. Biochem. Behav. 60, 747–751 (1998).
- Prasher, D. Traffic noise increases stress by driving up cortisol. Lancet 352, 1201 (1998).
- Segerstrom, S. C. & Miller, G. E. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol. Bull. 130, 601–630 (2004).
- Dhabhar, F. S. Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking. Ann. N. Y. Acad. Sci. 917, 876–93 (2000).
- Bianchini, F., Kaaks, R. & Vainio, H. Overweight, obesity, and cancer risk. Lancet Oncol. 3, 565–574 (2002).
- Suh, S. & Kim, K. W. Diabetes and cancer: is diabetes causally related to cancer? Diabetes Metab J 35, 193–198 (2011).
- Mathews, E. H. & Liebenberg, L. A Practical Quantification of Blood Glucose Production due to High-level Chronic Stress. Stress Heal. n/a-n/a (2011). doi:10.1002/smi.2415
- de Kloet, E. R., DeRijk, R. H. & Meijer, O. C. Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nat Clin Pr. End Met 3, 168–179 (2007).
- Jee, S. H. et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 293, 194–202 (2005).
- Cohen, S., Miller, G. E. & Rabin, B. S. Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom. Med. 63, 7–18 (2001).
- Ershler, W. B. & Keller, E. T. Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty. Annu. Rev. Med. 51, 245–270 (2000).
- Dehghan, A. et al. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56, 872–878 (2007).
- Kuo, H. K. et al. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol. 4, 371–380 (2005).
- Williams, C. B., Yeh, E. S. & Soloff, A. C. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. npj Breast Cancer 2, 15025 (2016).
- Aronen, H. J. et al. High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas. Clin. Cancer Res. 6, 2189–200 (2000).
- Quan, N. et al. Social stress increases the susceptibility to endotoxic shock. J. Neuroimmunol. 115, 36–45 (2001).
- Antoni, M. H. et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 6, 240–248 (2006).
- Antonova, L., Aronson, K. & Mueller, C. R. Stress and breast cancer: from epidemiology to molecular biology. Breast Cancer Res. 13, 208 (2011).
- Lillberg, K. et al. Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am. J. Epidemiol. 157, 415–23 (2003).
- Jacobs, J. R. & Bovasso, G. B. Early and chronic stress and their relation to breast cancer. Psychol. Med. 30, 669–678 (2000).
- Keinan-Boker, L., Vin-Raviv, N., Liphshitz, I., Linn, S. & Barchana, M. Cancer Incidence in Israeli Jewish Survivors of World War II. JNCI J. Natl. Cancer Inst. 101, 1489–1500 (2009).
- Saul, A. N. et al. Chronic stress and susceptibility to skin cancer. J. Natl. Cancer Inst. 97, 1760–1767 (2005).
- Thaker, P. H. et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat. Med. 12, 939–944 (2006).
- Sastry, K. S. R. et al. Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J. Biol. Chem. 282, 14094–100 (2007).
- Barbieri, A. et al. The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo. Int. J. Oncol. 47, 527–34 (2015).
- Hassan, S. et al. Behavioral stress accelerates prostate cancer development in mice. J. Clin. Invest. 123, 874–86 (2013).
- Palm, D. et al. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by β-blockers. Int. J. Cancer 118, 2744–2749 (2006).
- Sloan, E. K. et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 70, 7042–52 (2010).
- Inbar, S. et al. Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity. PLoS One 6, e19246 (2011).
- Ben-Eliyahu, S., Page, G. G., Yirmiya, R. & Shakhar, G. Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int. J. Cancer 80, 880–888 (1999).
- Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B. & Sheridan, J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc. Natl. Acad. Sci. 93, 3043–3047 (1996).
- Davidson, R. J. et al. Alterations in Brain and Immune Function Produced by Mindfulness Meditation. Psychosom. Med. 65, 564–570 (2003).
- Rainsford, K. D., Harris, J. R., Biswas, B. B. & Quinn, P. in (eds. Harris, R. E. et al.) 42, 3–27 (Springer Netherlands, 2007).
- Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
- Ekbom, A., Helmick, C., Zack, M. & Adami, H.-O. Ulcerative Colitis and Colorectal Cancer. N. Engl. J. Med. 323, 1228–1233 (1990).
- Eaden, J. A., Abrams, K. R. & Mayberry, J. F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48, 526–535 (2001).
- Lowenfels, A. B. et al. Pancreatitis and the Risk of Pancreatic Cancer. N. Engl. J. Med. 328, 1433–1437 (1993).
- Brody, J. S. & Spira, A. State of the Art. Chronic Obstructive Pulmonary Disease, Inflammation, and Lung Cancer. Proc. Am. Thorac. Soc. 3, 535–537 (2006).
- Matsunaga, H. et al. Physiological stress exacerbates murine colitis by enhancing proinflammatory cytokine expression that is dependent on IL-18. Am. J. Physiol. – Gastrointest. Liver Physiol. 301, G555–G564 (2011).
- Motzer, S. A., Jarrett, M., Heitkemper, M. M. & Tsuji, J. Natural Killer Cell Function and Psychological Distress in Women with and without Irritable Bowel Syndrome. Biol. Res. Nurs. 4, 31–42 (2002).
- Rayet, B. & Gelinas, C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18, 6938–6947 (1999).
- Sovak, M. A. et al. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J. Clin. Invest. 100, 2952–2960 (1997).
- Solinas, G., Marchesi, F., Garlanda, C., Mantovani, A. & Allavena, P. Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev. 29, 243–248 (2010).
- Kim, S. et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457, 102–106 (2009).
- Barber, M. D., Fearon, K. C. & Ross, J. A. Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer. Clin. Sci. 96, 83–87 (1999).
- Wang, C. S. & Sun, C. F. C-reactive protein and malignancy: clinico-pathological association and therapeutic implication. Chang Gung Med. J. 32, 471–482 (2009).
- Boucher, N. et al. CD28 expression in T cell aging and human longevity. Exp. Gerontol. 33, 267–282 (1998).
- Tabas, I. & Glass, C. K. Anti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities. Science (80-. ). 339, (2013).
- Everson, S. A. et al. Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study. BMJ 314, 553–558 (1997).
- Fuligni, A. J. et al. A Preliminary Study of Daily Interpersonal Stress and C-Reactive Protein Levels Among Adolescents From Latin American and European Backgrounds. Psychosom. Med. 71, 329–333 (2009).
- Gouin, J.-P. Chronic Stress, Immune Dysregulation, and Health. Am. J. Lifestyle Med. 5, 476–485 (2011).
- Brummett, B. H. et al. Associations of Depressive Symptoms, Trait Hostility, and Gender With C-Reactive Protein and Interleukin-6 Response After Emotion Recall. Psychosom. Med. 72, 333–339 (2010).
- Wittstein, I. S. et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N. Engl. J. Med. 352, 539–548 (2005).
- Crum, A. J., Akinola, M., Martin, A. & Fath, S. The role of stress mindset in shaping cognitive, emotional, and physiological responses to challenging and threatening stress. Anxiety, Stress. Coping 1–17 (2017). doi:10.1080/10615806.2016.1275585
- Dhabhar, F. S. et al. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma. Brain. Behav. Immun. 24, 127–137 (2010).
- Jin, S. & White, E. Role of autophagy in cancer: Management of metabolic stress. Autophagy 3, 28–31 (2007).
- Whiteman, M. C., Deary, I. J. & Fowkes, F. G. Personality and social predictors of atherosclerotic progression: Edinburgh Artery Study. Psychosom. Med. 62, 703–714 (2000).
© 2017 CDR Health and Nutrition, LLC. All Rights Reserved.