CHAPTER 9 - Allostatic Overload: Stress “breaking bad”
The TV show “Breaking Bad” told the story of Walter White, a high school chemistry teacher and average family man, who is diagnosed with terminal lung cancer. To support his wife and disabled son after he’s gone, he uses his knowledge of chemistry to launch himself into an underworld career manufacturing crystal meth.
Allostatic overload is stress breaking bad. Stress moves from an agent of growth and change to an agent of disease and death.
Remember from section 2, we discussed that stress is actually more of a positive than a negative. It’s not that stress can’t be bad, because we know from the stress-productivity curve and from Yerkes-Dodson Law that too much stress overwhelms our capacity to cope with it. But the majority of stress is actually beneficial – stress is to our mind what gravity is to our physical body. Without it, we become weak and unproductive. As I outlined in chapter 4, studies in animals show that chronic, manageable stress levels enhanced new nerve cell growth in the brain, and another study showed acute levels of stress actually enhances the immune system, rather than weakens it.
Dr Leaf relies on the General Adaptation Model of stress first proposed by Selye in the 1930’s - a three-stage process of alarm, adaptation, then exhaustion. While it held sway with researchers for most of the 20th century, the weaknesses of the model were exposed more than a decade ago. For example, the General Adaptation Syndrome suggests that the effects of stress are the same no matter what caused it, yet modern research has shown that the different stress systems have different patterns of response depending on what caused the stress. Second, the “fight or flight” response does not apply equally to both sexes; males “fight or flight” whereas females “tend-and-befriend”. Also, “exhaustion”, the third stage of Selye's model, has been superseded by newer knowledge that the stress mediators can have both protective and damaging effects, depending on their pattern of secretion over time .
So the basis of Dr Leaf’s understanding and application of the stress concept throughout her books is based on a largely outdated model of stress that cannot be used in a general way. Because of this, and a generous dose of exaggeration, Dr Leaf’s “toxic pathway” theory diverges from the current accepted idea that prolonged or chronic stress is not always harmful, but can be beneficial. Her discussion on stress also has a number of errors relating to the causes of, and the effects of, “toxic” stress.
The purpose of this chapter is to provide a reality check to Dr Leaf’s “toxic pathway” model of stress.
The Allostatic Model of Stress
If Dr Leaf’s theory relies on an outdated model of stress, then it’s fair to ask what the currently accepted model of stress is? McEwen and his colleagues proposed a concept that he called allostasis.
All living things maintain a complex dynamic equilibrium - a balancing act of the many different physiological systems that all rely on the other systems working at an optimal range. Imagine trying to stack ten spinning tops on top of each other while trying to keep them spinning. The body does the chemical equivalent of this very difficult combination of balance and dexterity every day. It’s called homeostasis. This balancing act is constantly challenged by internal or external events, termed stressors. Both the amount of stress and amount of time that the stressor is applied is important. When any stressor exceeds a certain threshold (“too strong, or too long”), the adaptive homeostatic systems of the living thing activate responses that compensate.
The theory of allostasis is related to these homeostatic mechanisms, although not just in terms of stress, but broadly to the concept of any change of the optimal range of these homeostatic balancing processes, in response to a change in the environment or life cycle of an organism .
McEwen and Wingfield give an example of some bird species, which change their stress response to facilitate their breeding capacity during mating season. They note that the benefit of the increased chance of breeding is important to the bird, but also comes at a cost of increased susceptibility to some diseases because of the weakening of the stress response at the time .
When it comes to stress, we adapt in a similar way. A lack of stress, or an excess of a stressor in some way (either too long or too strong) results in adaptation, which is beneficial, but can come at a cost. This is demonstrated by that broadly applicable U-curve, the stress productivity curve.
Chrousos wrote, “The interaction between homeostasis disturbing stressors and stressor activated adaptive responses of the organism can have three potential outcomes. First, the match may be perfect and the organism returns to its basal homeostasis or eustasis; second, the adaptive response may be inappropriate (for example, inadequate, excessive and/or prolonged) and the organism falls into cacostasis; and, third, the match may be perfect and the organism gains from the experience and a new, improved homeostatic capacity is attained, for which I propose the term ‘hyperstasis’.”  And as noted by McEwen, “Every system of the body responds to acute challenge with allostasis leading to adaptation.” 
More often than not, we adapt to the stressor, either the same as before, or possibly better. It’s only if the response to the stressor is inadequate, excessive and/or prolonged that stress ends up causing us trouble. This is what people normally think of when they think of stress – called allostatic overload – simply stress breaking bad.
The number one killer!
The problem with using such an outdated model of stress like the General Adaptation Model is that it mislabels nearly every form of stress as harmful. Dr Leaf, and indeed, the popular press, all fall into this trap. It doesn’t matter what the problem is, there’ll be an article somewhere claiming that stress caused or exacerbated it. The way the media describe stress, you’d think it was our number one killer! Blood pressure? Stress. Anxiety? Stress. Cancer? Stress. Flatulence? Stress!
This saturation of the media with negative messages about stress is so pervasive that the negative messages become self-perpetuating. Then when Dr Leaf writes that, “A massive body of research collectively shows that up to 80% of physical, emotional and mental health issues today could be a direct result of our thought lives” [1: p15] or “75 to 98 percent of mental and physical illnesses comes from ones thought life” [2: p37] we assume it must be true, since it sounds so similar to what everyone else says about stress. This is known in scientific circles as Confirmation Bias [185, 186].
Definition and Causality
The difference between sensationalism and reality is two-fold: perception and causality.
As we saw in section 2, there are a number of ways to conceptualise stress - mechanical, old-style, modern or toxic. Each concept can highlight either the protective or damaging side of stress. Studies have shown that if we view stress as entirely negative, then any stress is likely to have a maladaptive outcome, whereas viewing stress as potentially positive is associated with an adaptive response to stress . In this sense, our perceptions of stress become like a self-fulfilling prophecy. If all we’re told about stress is that stress is negative, then of course stress will be bad for us.
Defining each disease is also important. Talking about disease in vague, ill-defined terms ensures you’ll be in the ballpark, but the trade-off is that whatever assertion your broad statement contains is diluted by error. Saying, “Heart disease maybe caused by stress”, maybe technically true, but it’s so vague that it becomes devoid of meaning. The media messages about stress are often like this: broad, vague and impotent.
The other issue is causality. Correlation does not equal causation, which means that just because two things occur together, one does not always cause the other.
In other words, just because symptom B always occurs with disease A doesn’t mean that A causes B. There’s often a common underlying cause, C.
A simple example would be that itchy red eyes and sneezing often go together. Do my itchy red eyes cause my sneezing? No! They have an association, (or correlation*), but one does not cause the other. The common underlying cause of both my itchy red eyes and my sneezing is the cat that I’ve been patting, and my allergy to cats.
It’s easy to think that something that always happens with another must be cause and effect, but such thinking leads to some pretty crazy assumptions. Williams cleverly demonstrated this with a graph showing that the US road toll is inversely correlated with the importation of lemons from Mexico .
When it comes to stress, we know that stress is associated with an eclectic bunch of diseases. But correlation does not equal causation. Just because stress is associated with these diseases doesn’t mean that stress caused these diseases.
Take the relationship between stress and cardiovascular disease. There’s no doubt that stress and heart disease are associated [189, 190], but does stress cause cardiovascular disease? If it does, how does it do it?
If stress were to cause heart attacks, it would either be directly (by directly stopping or reducing the blood flow to the heart to critical levels) or indirectly (by accelerating the other disease processes that lead to the blockage of the coronary arteries, which then causes a heart attack).
I don’t know of any evidence that shows that stress directly blocks the coronary arteries. So if stress were to cause heart attacks, it would be indirectly - accelerating the other risk factors for heart disease, like high cholesterol, high blood pressure, diabetes or chronic inflammation. Lets look at the relationship between stress and these different risk factors.
The causes of high cholesterol are diet and genetics. Diets high in fat are likely to give people high blood cholesterol. But it isn't as simple as that. Some people eat huge amounts of fat but have normal cholesterol, and some people live on a diet of lentils and bean broth and still have cholesterol through the roof. This is because of genetics, and the efficiency of their liver to metabolise their cholesterol. Genes account for 40-60% of the risk for high cholesterol .
Stress has very little to do with cholesterol directly. A recent paper showed that chronic stress in caregivers of relatives with Alzheimer's affects the expression of one form of a gene coding for a cholesterol transport protein. This changed the average lipid profile, but only resulted in a small overall risk increase .
Some studies show that people who are stressed will tend to eat fatty, salty foods  but in terms of cholesterol and heart attack risk, it’s likely that stress will only affect those who are already genetically vulnerable .
Diabetes Mellitus, the best-known form of diabetes, is a disease of insulin dysfunction. Insulin is a hormone that is secreted from nests of cells in the pancreas. Normally, there is a predictable rise and fall of insulin with a surge of blood sugar. Insulin acts like a key, unlocking a protein 'gate' that lets glucose into a cell.
Type 1 diabetes is an autoimmune disease. The body mounts an immune reaction to its own proteins, attacking the cells in the pancreas that produce insulin. 88% of cases of type 1 diabetes are caused by genetic factors. Environmental factors only contribute the other 12% . These environmental risk factors include possible viral or bacterial infections, and possibly early introduction of cows milk or gluten into the infant diet. Stress is not listed .
Type 2 diabetes is considered multifactorial, with a number of influences affecting its course. There is a strong genetic component with 62 to 70% being attributable to genes, and only 30 to 38% being caused by independent environmental factors [194, 195]. Of these other factors, there are some shared genes that increase the risk of type 2 diabetes and obesity together. Sedentary lifestyles and high fat diets predispose to developing type 2 diabetes. But even then, large trials show that overweight pre-diabetic adults can achieve a 58% reduction in their development of type 2 diabetes, but despite intensive dietary and lifestyle modification, 11% go on to develop the disease anyway within four years .
Of the others, environmental pollutants may play a minor role. Again, stress is not listed as a major contributing factor .
So diabetes is mostly genetic in origin. Stress isn’t documented as a significant environmental risk factor.
Smoking is linked with nearly every disease that affects human beings. There are more than 7000 different chemicals released in cigarette smoke, including over 60 carcinogens and other poisons. These include Cyanide, Benzene, Formaldehyde, Methanol (wood alcohol), Acetylene (the fuel used in welding torches), and Ammonia . These chemicals in cigarette smoke irritate the lining of the blood vessels, which allows more cholesterol into the walls of the arteries to form plaques. Smoking accelerates the damage from other risk factors like the high blood sugar in diabetes.
The damage done by smoking is partly a dose dependent response  although it is a complicated pathway for cardiovascular damage .
Initiation of smoking is mediated by genetic risk factors . And nicotine addiction that underlies the habit of smoking is also strongly genetically determined [200-202].
So while most people think it’s purely a conscious choice to take up smoking, there is more scientific data to support the opposite notion, that genetics plays a stronger role than choice does in influencing people to take up smoking, and which people become addicted to nicotine. For example, people with the genetic tendency are more likely to take up smoking and/or more likely to become addicted to smoking. While there is still some choice, it is less of a choice than the person without the genetic predisposition. It is not a level playing field for the person with the genetic tendencies for smoking.
High blood pressure
High blood pressure, known in the medical field as hypertension, and as the name suggests, is defined by having blood pressure that is too high.
The physiological regulation of blood pressure is a complex interaction between the heart and blood vessels, brain, and kidneys [5: p227]. There is also new evidence of the role of the immune system in the onset of high blood pressure and in the way that it causes damage to the vascular system .
The interplay of genes and the environment in the development of high blood pressure isn’t as clear as other heart attack risk factors , but the immune response to stress is important. However, in the latest research in animal models, the role of high levels of autonomic nerve activity, and the immune system in high blood pressure, are significantly influenced by a gene deficiency .
So stress may be a risk factor in the development of high blood pressure, but it seems more likely that, rather than stress being the cause of high blood pressure, it is only an association, through a shared link with specific genes.
The effect of stress on the risk factors for heart disease and other illnesses
So in short, risk factors for heart disease are not significantly influenced by stress, if at all. They are mostly genetically determined [10, 168, 184]. There is a strong association of depression with heart disease, but depression is mainly influenced by genetics as well [149, 168, 205], and stress and depression are two separate entities. Table 5 of the INTERHEART psychological study provides one example, where clear differences were noted in those who were stressed and who were depressed. Interestingly, it also shows a protective effect of having mild to moderate stress compared to the other extremes .
No matter which way you cut it, genetics has a significant impact on all of the risk factors for heart disease including depression and stress. Stress itself is influenced by our biology. So even if it were true that stress leads to physical and mental illness, this phenomenon is influenced significantly on a genetic level.
This same pattern is shown in a number of illnesses. Genetics influence 30 to 50% of the risk for nearly every chronic disease. Some diseases have an even higher genetic influence. Prostate cancer, for example, the commonest form of cancer in men (with an incidence higher than the rate of breast cancer in women) , has no known risk factors other than genetics [207, 208].
So stress is associated with some illnesses, but not all. But given the influence of genetics over the complex interplay all risk factors, the actual influence of stress is probably minimal, and it’s likely that common genetic or other environmental vulnerabilities may cause both physical illness and stress, making stress just another symptom rather than a cause.
The “effects” of the “Toxic Pathway”
If stress is just another symptom, then how can Dr Leaf list so many conditions in which stress is a “major contributor” [1: p40-3]? Is stress more powerful than I’ve just made out, or is Dr Leaf’s list misinformed?
Lets flesh out Dr Leaf’s list a bit, and compare it to the evidence.
Dr Leaf starts with the heart and the vascular system. By listing five serious diseases, stress sounds like it’s a killer. But as we’ve discussed, stress is an association with hypertension (high blood pressure), rather than a cause. The others, angina, coronary artery disease, strokes or cerebrovascular insufficiency, and aneurysm (well, at least the abdominal aortic type) are all variations of the same disease process, and all related to hypertension and the other risk factors such as high cholesterol and diabetes. As we’ve just discussed, most of these risk factors are strongly related to genetics, while stress failed to feature as a significant environmental influence for any of them.
Dr Leaf suggests that anger is one of the many toxic emotions that lead to stress [1: p39] and, by implication, causes heart disease. In fact, the opposite may be true. Nakamura et al only demonstrated a small association between anger and heart disease progression, while noting that other authors had found that anger had a protective effect on heart disease, or no difference at all . So rather than being toxic as she suggests [1: p39], anger may be harmless or even protective for your heart.
The Immune System
Dr Leaf proposes that the immune system is “neurologically sensitive to your thought life.” She says that, “When the immune system faces an attack, such as when your thought life is toxic, it generates blood proteins called cytokines, which are known to produce fatigue and depression. In this way, toxic thoughts and the emotions they generate interfere with the body’s natural healing processes. They compound the effects of illness and disease by adding new negative biochemical processes that the body must struggle to overcome.” [1: p41]
Dr Leaf also says that, “A sudden burst of stress lowers immunity (one way to ‘catch a cold’).” [1: p42] Although the experimental evidence shows the opposite, that short term stress actually enhances the body’s immune response [210, 211].
With regard to the role of cytokines, there is evidence that activation or injection of high doses of some cytokines will cause depressive symptoms . However, the same article noted that, “NF-κB and IL-6 responses to psychosocial stress have been shown to be exaggerated in patients with depression, consistent with findings that depressive symptoms are associated with amplified IL-6 responses to antigenic challenge.”  In other words, it’s likely that cytokines only cause depression in people who are biologically vulnerable to depression in the first place (that is, genetically predisposed).
It’s also important to understand that the usual trigger of the immune system is not toxic thoughts, or stress, but infection. To fight off an acute infection, the body mounts a behavioural response called sickness behaviour. Sickness behaviour is an adaptive response . The fever, pains, lethargy, loss of appetite and overwhelming need for sleep may make you feel like garbage, but the enforced rest allows more energy to be diverted to the immune system so that it can fight off the invading infection more effectively.
Sickness behaviour is mediated by the same cytokines that are associated with depression, which is why other than fever, many of these same symptoms of sickness behaviour are shared by depression . So of course giving people high doses of cytokines will make them feel “depressed”. It’s just a different way of describing a normal, functional, adaptive response. True depression is much more complicated, influenced by a number of factors other than cytokines.
The immune system is more complicated on the surface, because while stress does influence the specific functions of the immune system in the lab and in some clinical trials , the stress responses seems to enhance some parts of the immune system (such as inflammation and allergic diseases) while suppressing other parts (like the while blood cells).
New thinking on the immune system, backed up by data in animal models, has lead to the Stress Spectrum model . The Stress Spectrum model suggests that the response of the immune system to any stress depends on a number of factors including the duration of stress, the timing of stress relative to the stage of the immune response, and the concentration, duration and nature of the cortisol exposure. It is also influenced by the health of the individual and their genetic and cognitive coping ability . While it requires confirmation with human data, the model sounds remarkably like the model of allostasis as I outlined earlier in the chapter.
The Stress Spectrum model suggests that stress usually enhances the immune response. Ongoing stress may lead to a state where the negative effects of stress are actually the body’s normal feedback mechanism trying to protect itself further. The odds of changing from immune enhancement to immune dysfunction is determined by genes and then cognitive coping styles (which in themselves are strongly genetically determined). But fundamentally, stress is not toxic, it’s protective.
The Digestive Tract
You’ve heard it said that, “The way to a man’s heart is through his stomach”? Food has an effect on our bodies and minds that we as humans have known for aeons.
Dr Leaf believes that the digestive tract bears the brunt of the “toxic pathway” of stress. She says that carbohydrates are comfort foods because they boost serotonin levels, and that any improvements dissipate within 20 minutes. She also says that thoughts can make comfort foods toxic. She claims that “dietitians and nutritionists tell you (or should tell you) never to eat when you’re angry” because “It’s almost as if the anger seeps into the food you eat as your body tries to digest it.” [1: p42-3]
As a family physician on the front line, I hear all sorts of odd health beliefs that people have, and believe me, I’ve heard some pretty bizarre ones. But I have never heard anyone say “never eat when you are angry”, let alone a dietician. Even a Google search only showed up a couple of relevant hits, all of them from pseudoscientific alternative bloggers, without a shred of evidence to back themselves. In actual fact, there is reasonably good evidence that eating may be good around times of extreme emotions, as sucrose (ie: sugar) has been shown to decrease pain experienced by newborn babies undergoing painful procedures .
The analgesic effect may be partially related to the fact that a load of pure sugar will increase the levels of tryptophan in the blood stream, which then leads to a rise in serotonin levels , which then improves mood. However, Dr Leaf’s statement that carbohydrates are comfort foods because they stimulate serotonin is an overstatement, because a small amount of dietary protein consumed at the same time (as little as 4% of the food) blocks this process . Nearly all foods high in carbohydrates have more than 4% protein, the only exceptions being pure sugar, jelly beans or soft drink/soda. So your serotonin is not going to be enhanced unless you’re binging on jelly beans and Coke. More often than not, comfort eating tends to involve consuming chocolate, which is more influential on the hedonistic rewards pathways requiring dopamine, not serotonin .
Dr Leaf then compiles a list of disorders that gives the impression that stress really is toxic to the gut. But like her list of heart problems in the previous section, her list of digestive disorders have very little to do with stress. “Leaky Gut Syndrome” isn’t even a recognised disorder.
Irritable Bowel Syndrome
Of the others on her list, the one that has the strongest relationship to psychosocial stress is Irritable Bowel Syndrome. But IBS is a very complicated disorder that has only recently begun to be pinned down by medical science.
Irritable bowel syndrome (IBS) is “a chronic condition characterized by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. The degree of symptoms varies in different patients from tolerable to severe, interfering with daily activity.” 
Essentially, IBS patients have a gut that is oversensitive. Something sets it off, and it slows right down (causing constipation) or goes ballistic. The diarrhoea and flatulence from IBS was once described to me as “like an explosion in a sewerage treatment plant.” I’ll leave that one to your imagination!
IBS is now recognised as a disorder of the Neuro-Endocrine System of the gut. This combination of hormone producing cells scattered throughout the gut lining, and the mesh of nerve cells in the wall of the gut, control the intestinal tracts rhythmical muscular contractions, the flow of secretions (“juices”), and the sensory perception of the gut to noxious agents. There are a number of influences that all converge on the NES, including genetics and low-grade inflammation , the microbes that live naturally in our gut , and dietary factors .
The evidence for the relationship of stress to IBS is mixed. Some researchers who study in this field believe that stress is largely responsible for a number of functional bowel disorders, IBS being one of them . However, other authors have reviewed the published literature on stress and IBS, and while it is true that stress can influence the neuro-endocrine system of the gut in patients with irritable bowel syndrome, stress does not cause symptoms in the control groups used in the experimental studies .
Now, that may seem like a no-brainer, since by definition, control groups are picked because they don’t have the disease. But what it shows is that the effect of stress on the function of the intestines is only linked to people with IBS. Ninety percent of the population have stress and don’t get irritable bowel symptoms of constipation, diarrhoea or abdominal cramping. At best, stress exacerbates the pre-existing condition, but does not cause IBS.
But there are experts who go one step further, and believe that stress doesn’t even exacerbate the disease. El-Salhy explains, “Many patients with IBS ignore their symptoms and regard them as a normal part of everyday life. IBS patients with anxiety, depression, somatisation or hypochondria are more liable to seek healthcare than other IBS patients. Unless this is borne in mind, incorrect conclusions can be drawn. A hospital-based case-control study showed that patients with IBS have a comparable health-related quality of life, level of psychological distress and occurrence of recent stressful life events to age-matched IBD (inflammatory bowel disease) patients.” 
He goes on: “Two percent of patients diagnosed with IBS among the adult residents of Olmsted County, Minnesota, United States, were found to suffer from depression compared to the 16.2% incidence of depression in the entire population of the United States. In conclusion, there is no convincing evidence to show that psychological factors play a role in the onset and/or progression of IBS.” 
In trying to marry all of the facts about stress and IBS together, the most logical explanation is that stress does not cause IBS. Stress and IBS may be linked by a common causative factor, such as genetics and possibly early life stress, which predisposes the patient to have both more frequent stress and irritable bowel syndrome. Stress, then, is one small part of a wider disease complex involving inflammation, diet, and changes to the gut bacteria.
The remaining disorders on her list can be tenuously linked to stress, but only because they are symptoms of irritable bowel syndrome. Outside of IBS, constipation is caused by a lack of dietary fibre and water although there are a plethora of other causes, none of which are related to stress [224, 225]. Diarrhoea is usually caused by infections, foods or digestive disorders, not stress . Nausea and vomiting can be caused by anything from irritation of the stomach or duodenum from physical toxins as well as other infections or inflammation throughout the body, severe pain, vertigo, medications, and even pregnancy [5: p803-4]. Cramping is a symptom that co-occurs with other symptoms like diarrhoea and constipation. It’s uncommon to have cramping by itself.
In times gone by, ulcers were always thought to be directly associated with stress and lifestyle factors. That was until Dr Barry Marshall, from the University of Western Australia, underwent an endoscopy to prove he was ulcer-free, and then drank a petri-dish full of Helicobacter pylori. After about a week, he had an endoscopy which showed massive amounts of inflammation of his stomach lining, and was positive for Helicobacter infection [227, 228]. Subsequent work has proven that up to 80% of stomach ulceration (and 90% of duodenal ulcers) are caused by Helicobacter pylori . The use of NSAIDs (non-steroidal anti-inflammatory drugs, such as aspirin and ibuprofen) is the next most important cause . “Stress ulcers” are actually erosions of the stomach lining, caused by a lack of blood flow to the lining of the stomach in patients who are critically ill , not because of any toxic thought process.
Summary of the “Toxic Pathway”
So when the recent scientific and medical literature is applied to Dr Leaf’s assertions about stress, it becomes clear that rather than being uniformly detrimental, stress is often beneficial. Dr Leaf also confuses correlation and causation. Stress may be associated with various disorders, but it does not cause them. Dr Leaf lists multiple overlapping symptoms as separate disorders, which also confuses the issue. She incorrectly links comfort foods and serotonin, and incorrectly assumes that the “stress” of stress ulcers is psychological stress. She even lists a “disease” that doesn’t exist in the medical literature.
The fundamental problem is Dr Leaf’s use of an outdated model of stress as the basis for her understanding. Therefore, her conceptualization of stress and its effects is inaccurate. She suggests that all long term stress is negative, and that stress can be caused by toxic thoughts when there is no evidence for this, while not considering the evidence for the positive effects of stress on your health.
In short, Dr Leaf teaches that stress is toxic. In reality stress is usually beneficial, rather than breaking bad.
 The terms “Association” and “Correlation” tend to be used interchangeably.