Ulcer Related Quotes

Medicine is a social science, and politics nothing but medicine on a large scale,

A large percentage of what we think of when we talk about stress-related diseases are disorders of excessive stress-responses.

In a world of stressful lack of control, an amazing source of control we all have is the ability to make the world a better place, one act at a time.

It takes surprisingly little in terms of uncontrollable unpleasantness to make humans give up and become helpless in a generalized way.

Something roughly akin to love is needed for proper biological development, and its absence is among the most aching, distorting stressors that we can suffer.

Subjected to enough uncontrollable stress, we learn to be helpless—we lack the motivation to try to live because we assume the worst; we lack the cognitive clarity to perceive when things are actually going fine, and we feel an aching lack of pleasure in everything.

The defining feature of a major depression is loss of pleasure. If I had to define a major depression in a single sentence, I would describe it as a “genetic/neurochemical disorder requiring a strong environmental trigger whose characteristic manifestation is an inability to appreciate sunsets.

Everything in physiology follows the rule that too much can be as bad as too little. There are optimal points of allostatic balance. For example, while a moderate amount of exercise generally increases bone mass, thirty-year-old athletes who run 40 to 50 miles a week can wind up with decalcified bones, decreased bone mass, increased risk of stress fractures and scoliosis (sideways curvature of the spine)—their skeletons look like those of seventy-year-olds. To put exercise in perspective, imagine this: sit with a group of hunter-gatherers from the African grasslands and explain to them that in our world we have so much food and so much free time that some of us run 26 miles in a day, simply for the sheer pleasure of it. They are likely to say, “Are you crazy? That’s stressful.” Throughout hominid history, if you’re running 26 miles in a day, you’re either very intent on eating someone or someone’s very intent on eating you.

Fear is the vigilance and the need to escape from something real. Anxiety is about dread and foreboding and your imagination running away with you. Much as with depression, anxiety is rooted in a cognitive distortion. In this case, people prone toward anxiety overestimate risks and the likelihood of a bad outcome.

Whenever you inhale, you turn on the sympathetic nervous system slightly, minutely speeding up your heart. And when you exhale, the parasympathetic half turns on, activating your vagus nerve in order to slow things down (this is why many forms of meditation are built around extended exhalations).

if you want to increase your chances of avoiding stress-related diseases, make sure you don’t inadvertently allow yourself to be born poor.

growing strong from adversity is mostly a luxury for those who are better off.

This is the critical point of this book: if you are that zebra running for your life, or that lion sprinting for your meal, your body’s physiological response mechanisms are superbly adapted for dealing with such short-term physical emergencies. For the vast majority of beasts on this planet, stress is about a short-term crisis, after which it’s either over with or you’re over with. When we sit around and worry about stressful things, we turn on the same physiological responses—but they are potentially a disaster when provoked chronically. A large body of evidence suggests that stress-related disease emerges, predominantly, out of the fact that we so often activate a physiological system that has evolved for responding to acute physical emergencies, but we turn it on for months on end, worrying about mortgages, relationships, and promotions.

As Beck and other cognitive therapists have emphasized, much of what constitutes a depression is centered around responding to one awful thing and overgeneralizing from it—cognitively distorting how the world works.

the average level of happiness increases in old age; fewer negative emotions occur and, when they do, they don’t persist as long. Connected to this, brain-imaging studies show that negative images have less of an impact, and positive images have more of an impact on brain metabolism in older people, as compared to young.

Males who do extreme amounts of exercise, such as professional soccer players and runners who cover more than 40 or 50 miles a week, have less LHRH, LH, and testosterone in their circulation, smaller testes, less functional sperm. They also have higher levels of glucocorticoids in their bloodstreams, even in the absence of stress. (A similar decline in reproductive function is found in men who are addicted to opiate drugs.)

by the year 2020, depression is projected to be the second leading cause of medical disability on earth.

This is thought to reflect the killer combination that these folks are often burdened with, namely, high work demands but little autonomy—responsibility without control.

Genes are rarely about inevitability, especially when it comes to humans, the brain, or behavior. They’re about vulnerability, propensities, tendencies

Memory can be dramatically disrupted if you force something that’s implicit into explicit channels. Here’s an example that will finally make reading this book worth your while—how to make neurobiology work to your competitive advantage at sports. You’re playing tennis against someone who is beating the pants off of you. Wait until your adversary has pulled off some amazing backhand, then offer a warm smile and say, “You are a fabulous tennis player. I mean it; you’re terrific. Look at that shot you just made. How did you do that? When you do a backhand like that, do you hold your thumb this way or that, and what about your other fingers? And how about your butt, do you scrunch up the left side of it and put your weight on your right toes, or the other way around?” Do it right, and the next time that shot is called for, your opponent/victim will make the mistake of thinking about it explicitly, and the stroke won’t be anywhere near as effective. As Yogi Berra once said, “You can’t think and hit at the same time.

Brain-imaging studies of drug users at that stage show that viewing a film of actors pretending to use drugs activates dopamine pathways in the brain more than does watching porn films. This

Cognitive therapists, like Aaron Beck of the University of Pennsylvania, even consider depression to be primarily a disorder of thought, rather than emotion, in that sufferers tend to see the world in a distorted, negative way.

Freud was fascinated with depression and focused on the issue that we began with—why is it that most of us can have occasional terrible experiences, feel depressed, and then recover, while a few of us collapse into major depression (melancholia)? In his classic essay “Mourning and Melancholia” (1917), Freud began with what the two have in common. In both cases, he felt, there is the loss of a love object. (In Freudian terms, such an “object” is usually a person, but can also be a goal or an ideal.) In Freud’s formulation, in every loving relationship there is ambivalence, mixed feelings—elements of hatred as well as love. In the case of a small, reactive depression—mourning—you are able to deal with those mixed feelings in a healthy manner: you lose, you grieve, and then you recover. In the case of a major melancholic depression, you have become obsessed with the ambivalence—the simultaneity, the irreconcilable nature of the intense love alongside the intense hatred. Melancholia—a major depression—Freud theorized, is the internal conflict generated by this ambivalence. This can begin to explain the intensity of grief experienced in a major depression. If you are obsessed with the intensely mixed feelings, you grieve doubly after a loss—for your loss of the loved individual and for the loss of any chance now to ever resolve the difficulties. “If only I had said the things I needed to, if only we could have worked things out”—for all of time, you have lost the chance to purge yourself of the ambivalence. For the rest of your life, you will be reaching for the door to let you into a place of pure, unsullied love, and you can never reach that door. It also explains the intensity of the guilt often experienced in major depression. If you truly harbored intense anger toward the person along with love, in the aftermath of your loss there must be some facet of you that is celebrating, alongside the grieving. “He’s gone; that’s terrible but…thank god, I can finally live, I can finally grow up, no more of this or that.” Inevitably, a metaphorical instant later, there must come a paralyzing belief that you have become a horrible monster to feel any sense of relief or pleasure at a time like this. Incapacitating guilt. This theory also explains the tendency of major depressives in such circumstances to, oddly, begin to take on some of the traits of the lost loved/hated one—and not just any traits, but invariably the ones that the survivor found most irritating. Psychodynamically, this is wonderfully logical. By taking on a trait, you are being loyal to your lost, beloved opponent. By picking an irritating trait, you are still trying to convince the world you were right to be irritated—you see how you hate it when I do it; can you imagine what it was like to have to put up with that for years? And by picking a trait that, most of all, you find irritating, you are not only still trying to score points in your argument with the departed, but you are punishing yourself for arguing as well. Out of the Freudian school of thought has come one of the more apt descriptions of depression—“aggression turned inward.” Suddenly the loss of pleasure, the psychomotor retardation, the impulse to suicide all make sense. As do the elevated glucocorticoid levels. This does not describe someone too lethargic to function; it is more like the actual state of a patient in depression, exhausted from the most draining emotional conflict of his or her life—one going on entirely within. If that doesn’t count as psychologically stressful, I don’t know what does.

By not talking about death with our loved ones, not being clear through advanced directives, DNR (do not resuscitate) orders, and funeral plans, we are directly contributing to this future ... and a rather bleak present, at that. Rather than engage in larger societal discussions about dignified ways for the terminally ill to end their lives, we accept intolerable cases like that of Angelita, a widow in Oakland who covered her head with a plastic bag because the arthritic pain of her gnarled joints was too much to bear. Or that of Victor in Los Angeles, who hung himself from the rafters of his apartment after his third unsuccessful round of chemotherapy, leaving his son to discover his body. Or the countless bodies with decubitus ulcers, more painful for me to care for them even babies or suicides. When these bodies come into the funeral home, I can only offer my sympathy to their living relatives, and promise to work to ensure that more people are not robbed of a dignified death by a culture of silence.

Perhaps the best way to begin is by making a mental list of the sorts of things we find stressful. No doubt you would immediately come up with some obvious examples—traffic, deadlines, family relationships, money worries. But what if I said, “You’re thinking like a speciocentric human. Think like a zebra for a second.” Suddenly, new items might appear at the top of your list—serious physical injury, predators, starvation. The need for that prompting illustrates something critical—you and I are more likely to get an ulcer than a zebra is.

It is never really the case that stress makes you sick, or even increases your risk of being sick. Stress increases your risk of getting diseases that make you sick, or if you have such a disease, stress increases the risk of your defenses being overwhelmed by the disease.

Now we have hundreds of carefully engineered, designed, and marketed commercial foods filled with rapidly absorbed processed sugars that cause a burst of sensation that can’t be matched by some lowly natural food. Once, we had lives that, amid considerable privation and negatives, also offered a huge array of subtle and often hard-won pleasures. And now we have drugs that cause spasms of pleasure and dopamine a thousand-fold higher than anything stimulated in our drug-free world.

Las Vegas casinos to keep defibrillators handy.

glucocorticoids in

The impact of social relationships on life expectancy appears to be at least as large as that of variables such as cigarette smoking, hypertension, obesity, and level of physical activity.

Science provides us with some of the most elegant, stimulating puzzles that life has to offer. It throws some of the most provocative ideas into our arenas of moral debate. Occasionally, it improves our lives. I love science, and it pains me to think that so many are terrified of the subject or feel that choosing science means that you cannot also choose compassion, or the arts, or be awed by nature. Science is not meant to cure us of mystery, but to reinvent and reinvigorate it.

Another study that winds up in half the textbooks makes the same point, if more subtly. The subjects of the “experiment” were children reared in two different orphanages in Germany after World War II. Both orphanages were run by the government; thus there were important controls in place—the kids in both had the same general diet, the same frequency of doctors’ visits, and so on. The main identifiable difference in their care was the two women who ran the orphanages. The scientists even checked them, and their description sounds like a parable. In one orphanage was Fräulein Grun, the warm, nurturing mother figure who played with the children, comforted them, and spent all day singing and laughing. In the other was Fräulein Schwarz, a woman who was clearly in the wrong profession. She discharged her professional obligations, but minimized her contact with the children; she frequently criticized and berated them, typically among their assembled peers. The growth rates at the two orphanages were entirely different. Fräulein Schwarz’s kids grew in height and weight at a slower pace than the kids in the other orphanage. Then, in an elaboration that couldn’t have been more useful if it had been planned by a scientist, Fräulein Grun moved on to greener pastures and, for some bureaucratic reason, Fräulein Schwarz was transferred to the other orphanage. Growth rates in her former orphanage promptly increased; those in her new one decreased.

What Wilkinson and others have shown is that poverty is not only a predictor of poor health but, independent of absolute income, so is poverty amid plenty—the more income inequality there is in a society, the worse the health and mortality rates.

Interestingly, traumatic stress early in life (abuse, for example) greatly increases the risk of IBS in adulthood. This implies that childhood trauma can leave an echo of vulnerability, a large intestine that is hyperreactive to stress, long afterward.

This is great. But what I’m grasping at is an idea about a subtler goal. This thinking owes a lot to conversations with Manjula Waldron of Ohio State University, an engineering professor who also happens to be a hospital chaplain. This feels embarrassingly Zen-ish for me to spout, being a short, hypomanic guy with a Brooklyn accent, but here goes: Maybe the goal isn’t to maximize the contrast between a low baseline and a high level of activation. Maybe the idea is to have both simultaneously. Huh? Maybe the goal would be for your baseline to be something more than the mere absence of activation, a mere default, but to instead be an energized calm, a proactive choice. And for the ceiling to consist of some sort of equilibrium and equanimity threading through the crazed arousal. I have felt this a few times playing soccer, inept as I am at it, where there’s a moment when, successful outcome or not, every physiological system is going like mad, and my body does something that my mind didn’t even dream of, and the two seconds when that happened seemed to take a lot longer than it should have. But this business about the calm amid the arousal isn’t just another way of talking about “good stress” (a stimulating challenge, as opposed to a threat). Even when the stressor is bad and your heart is racing in crisis, the goal should be to somehow make the fraction of a second between each heartbeat into an instant that expands in time and allows you to regroup. There, I have no idea what I’m talking about, but I think there might be something important lurking there. Enough said.

One last bit of bad news. We’ve been focusing on the stress-related consequences of activating the cardiovascular system too often. What about turning it off at the end of each psychological stressor? As noted earlier, your heart slows down as a result of activation of the vagus nerve by the parasympathetic nervous system. Back to the autonomic nervous system never letting you put your foot on the gas and brake at the same time—by definition, if you are turning on the sympathetic nervous system all the time, you’re chronically shutting off the parasympathetic. And this makes it harder to slow things down, even during those rare moments when you’re not feeling stressed about something. How can you diagnose a vagus nerve that’s not doing its part to calm down the cardiovascular system at the end of a stressor? A clinician could put someone through a stressor, say, run the person on a treadmill, and then monitor the speed of recovery afterward. It turns out that there is a subtler but easier way of detecting a problem. Whenever you inhale, you turn on the sympathetic nervous system slightly, minutely speeding up your heart. And when you exhale, the parasympathetic half turns on, activating your vagus nerve in order to slow things down (this is why many forms of meditation are built around extended exhalations). Therefore, the length of time between heartbeats tends to be shorter when you’re inhaling than exhaling. But what if chronic stress has blunted the ability of your parasympathetic nervous system to kick the vagus nerve into action? When you exhale, your heart won’t slow down, won’t increase the time intervals between beats. Cardiologists use sensitive monitors to measure interbeat intervals. Large amounts of variability (that is to say, short interbeat intervals during inhalation, long during exhalation) mean you have strong parasympathetic tone counteracting your sympathetic tone, a good thing. Minimal variability means a parasympathetic component that has trouble putting its foot on the brake. This is the marker of someone who not only turns on the cardiovascular stress-response too often but, by now, has trouble turning it off.

Finally, the stressor is over, the lion pursues some other pedestrian, you can return to your dinner plans. The various hormones of the stress-response turn off, your parasympathetic nervous system begins to slow down your heart via something called the vagus nerve, and your body calms down.

A critical realization roared through the research community: the physiological stress-response can be modulated by psychological factors. Two identical stressors with the same extent of allostatic disruption can be perceived, can be appraised differently, and the whole show changes from there.

For the vast majority of beasts on this planet, stress is about a short-term crisis, after which it’s either over with or you’re over with. When we sit around and worry about stressful things, we turn on the same physiological responses—but they are potentially a disaster when provoked chronically

A large body of evidence suggests that stress-related disease emerges, predominantly, out of the fact that we so often activate a physiological system that has evolved for responding to acute physical emergencies, but we turn it on for months on end, worrying about mortgages, relationships, and promotions.

The subject of one experiment is a rat that receives mild electric shocks (roughly equivalent to the static shock you might get from scuffing your foot on a carpet). Over a series of these, the rat develops a prolonged stress-response: its heart rate and glucocorticoid secretion rate go up, for example. For convenience, we can express the long-term consequences by how likely the rat is to get an ulcer, and in this situation, the probability soars. In the next room, a different rat gets the same series of shocks—identical pattern and intensity; its allostatic balance is challenged to exactly the same extent. But this time, whenever the rat gets a shock, it can run over to a bar of wood and gnaw on it. The rat in this situation is far less likely to get an ulcer. You have given it an outlet for frustration. Other types of outlets work as well—let the stressed rat eat something, drink water, or sprint on a running wheel, and it is less likely to develop an ulcer.

Thus wailing and pounding the walls in grief or leaping about and shouting in ecstasy can place similarly large demands on a diseased heart. Put another way, your sympathetic nervous system probably has roughly the same effect on your coronary arteries whether you are in the middle of a murderous rage or a thrilling orgasm.

What the data show: the fewer social relationships a person has, the shorter his or her life expectancy, and the worse the impact of various infectious diseases. Relationships that are medically protective can take the form of marriage, contact with friends and extended family, church membership, or other group affiliations.

when it comes to the bread and butter of human misery, try a major depression. It can be life-threatening, it can destroy lives, demolish the families of sufferers. And it is dizzyingly common—the psychologist Martin Seligman has called it the common cold of psychopathology. Best estimates are that from 5 to 20 percent of us will suffer a major, incapacitating depression at some point in our lives, causing us to be hospitalized or medicated or nonfunctional for a significant length of time. Its incidence has been steadily increasing for decades—by the year 2020, depression is projected to be the second leading cause of medical disability on earth.

Parts of the book describe work carried out in my own laboratory, and these studies have been made possible by funding from the National Institutes of Health, the National Institute of Mental Health, the National Science Foundation, the Sloan Foundation, the Klingenstein Fund, the Alzheimer’s Association, and the Adler Foundation.

Perhaps the best moral is that when doing science (or perhaps when doing anything at all in a society as judgmental as our own), be very careful and very certain before pronouncing something to be the norm—because at that instant, you have made it supremely difficult to ever again look objectively at an exception to that supposed norm.

The health risk of poverty turns out to be a huge effect, the biggest risk factor there is in all of behavioral medicine—in other words, if you have a bunch of people of the same gender, age, and ethnicity and you want to make some predictions about who is going to live how long, the single most useful fact to know is each person’s SES.

when we get into a physiological uproar and activate the stress-response for no reason at all, or over something we cannot do anything about, we call it things like “anxiety,” “neurosis,” “paranoia,” or “needless hostility.” Thus, the stress-response can be mobilized not only in response to physical or psychological insults, but also in expectation of them.

Suppose a major traumatic stressor occurs, of a sufficient magnitude to disrupt hippocampal function while enhancing amygdaloid function. At some later point, in a similar setting, you have an anxious, autonomic state, agitated and fearful, and you haven’t a clue why—this is because you never consolidated memories of the event via your hippocampus while your amygdala-mediated autonomic pathways sure as hell remember. This is a version of free-floating anxiety.

Gerontologists studying the aging process find increasing evidence that most of us will age with a fair degree of success. There’s far less institutionalization and disability than one might have guessed. While the size of social networks shrink with age, the quality of the relationships improves. There are types of cognitive skills that improve in old age (these are related to social intelligence and to making good strategic use of facts, rather than merely remembering them easily). The average elderly individual thinks his or her health is above average, and takes pleasure from that. And most important, the average level of happiness increases in old age; fewer negative emotions occur and, when they do, they don’t persist as long. Connected to this, brain-imaging studies show that negative images have less of an impact, and positive images have more of an impact on brain metabolism in older people, as compared to young.

Neuropsychologists are coming to recognize that there is a specialized subset of long-term memory. Remote memories are ones stretching back to your childhood—the name of your village, your native language, the smell of your grandmother’s baking. They appear to be stored in some sort of archival way in your brain separate from more recent long-term memories. Often, in patients with a dementia that devastates most long-term memory, the more remote facets can remain intact.

In general, the monkeys under the most social stress were most at risk for plaque formation. Kaplan showed that this can even occur with a low-fat diet, which makes sense, since, as will be described in the next chapter, a lot of the fat that forms plaques is being mobilized from stores in the body, rather than coming from the cheeseburger the monkey ate just before the tense conference. But if you couple the social stress with a high-fat diet, the effects synergize, and plaque formation goes through the roof.

What does clean relations mean? Think of the idea as having enjoyable relationships with those we love in which there are few resentments that are not being talked about. Clean relations are the ones you might describe as having a fair and equitable exchange of love and energy. Chances are, you can name several relationships you are currently participating in that are of a messier nature. Resentments are the natural result of not expressing unmet expectations. When held for too long, they cause internal conditions that I think of as ulcerations of the spirit.

A major depression, these findings suggest, can be the outcome of particularly severe lessons in uncontrollability for those of us who are already vulnerable. This may explain an array of findings that show that if a child is stressed in certain ways—loss of a parent to death, divorce of parents, being a victim of abusive parenting—the child is more at risk for depression years later. What could be a more severe lesson that awful things can happen that are beyond our control than a lesson at an age when we are first forming our impressions about the nature of the world?

Major depression. As will be detailed in chapter 14, major depression is utterly intertwined with prolonged stress, and this connection includes elevated glucocorticoid levels in about half the people with major depression. Yvette Sheline of Washington University and others have shown that prolonged major depression is, once again, associated with a smaller hippocampus. The more prolonged the history of depression, the more volume loss. Furthermore, it is in patients with the subtype of depression that is most associated with elevated glucocorticoid levels where you see the smaller hippocampus.

First, can fetal or childhood exposure to synthetic glucocorticoids have lifelong, adverse effects? Glucocorticoids (such as hydrocortisone) are prescribed in vast amounts, because of their immunosuppressive or anti-inflammatory effects. During pregnancy, they are administered to women with certain endocrine disorders or who are at risk for delivering preterm. Heavy administration of them during pregnancy has been reported to result in children with smaller head circumferences, emotional and behavioral problems in childhood, and slowing of some developmental landmarks. Are these effects lifelong? No one knows.

Obviously, a theme of this book is just how many things can go wrong in the body because of stress and how important it is for everyone to recognize this. However, it would be utterly negligent to exaggerate the implications of this idea. Every child cannot grow up to be president; it turned out that merely by holding hands and singing folk songs we couldn’t end all war, and hunger does not disappear just by visualizing a world without it. Everything bad in human health now is not caused by stress, nor is it in our power to cure ourselves of all our worst medical nightmares merely by reducing stress and thinking healthy thoughts full of courage and spirit and love.

Beginning in the early 1980s, various researchers, including myself, showed that this “glucocorticoid neurotoxicity” was not just a pharmacological effect, but was relevant to normal brain aging in the rat. Collectively, the studies showed that lots of glucocorticoid exposure (in the range seen during stress) or lots of stress itself would accelerate the degeneration of the aging hippocampus. Conversely, diminishing glucocorticoid levels (by removing the adrenals of the rat) would delay hippocampal aging. And as one might expect by now, the extent of glucocorticoid exposure over the rat’s lifetime not only determined how much hippocampal degeneration there would be in old age, but how much memory loss as well.

First, the enormous potential energies of the two elephants are consumed balancing the seesaw, instead of being able to do something more useful, like mowing the lawn or paying the bills. This is equivalent to diverting energy from various long-term building projects in order to solve short-term stressful emergencies. By using two elephants to do the job, damage will occur just because of how large, lumbering, and unsubtle elephants are. They squash the flowers in the process of entering the playground, they strew leftovers and garbage all over the place from the frequent snacks they must eat while balancing the seesaw, they wear out the seesaw faster, and so on. This is equivalent to a pattern of stress-related disease that will run through many of the subsequent chapters: it is hard to fix one major problem in the body without knocking something else out of balance (the very essence of allostasis spreading across systems throughout the body).

By using two elephants to do the job, damage will occur just because of how large, lumbering, and unsubtle elephants are. They squash the flowers in the process of entering the playground, they strew leftovers and garbage all over the place from the frequent snacks they must eat while balancing the seesaw, they wear out the seesaw faster, and so on. This is equivalent to a pattern of stress-related disease that will run through many of the subsequent chapters: it is hard to fix one major problem in the body without knocking something else out of balance (the very essence of allostasis spreading across systems throughout the body). Thus, you may be able to solve one bit of imbalance brought on during stress by using your elephants (your massive levels of various stress hormones), but such great quantities of those hormones can make a mess of something else in the process. And a long history of doing this produces wear and tear throughout the body, termed allostatic load.

You will see that the most powerful and highly placed men let drop remarks in which they long for leisure, acclaim it, and prefer it to all their blessings. They desire at times, if it could be with safety, to descend from their high pinnacle; for, though nothing from without should assail or shatter, Fortune of its very self comes crashing down.8 The deified Augustus, to whom the gods vouchsafed more than to any other man, did not cease to pray for rest and to seek release from public affairs; all his conversation ever reverted to this subject—his hope of leisure. This was the sweet, even if vain, consolation with which he would gladden his labours—that he would one day live for himself. In a letter addressed to the senate, in which he had promised that his rest would not be devoid of dignity nor inconsistent with his former glory, I find these words: "But these matters can be shown better by deeds than by promises. Nevertheless, since the joyful reality is still far distant, my desire for that time most earnestly prayed for has led me to forestall some of its delight by the pleasure of words." So desirable a thing did leisure seem that he anticipated it in thought because he could not attain it in reality. He who saw everything depending upon himself alone, who determined the fortune of individuals and of nations, thought most happily of that future day on which he should lay aside his greatness. He had discovered how much sweat those blessings that shone throughout all lands drew forth, how many secret worries they concealed. Forced to pit arms first against his countrymen, then against his colleagues, and lastly against his relatives, he shed blood on land and sea. Through Macedonia, Sicily, Egypt, Syria, and Asia, and almost all countries he followed the path of battle, and when his troops were weary of shedding Roman blood, he turned them to foreign wars. While he was pacifying the Alpine regions, and subduing the enemies planted in the midst of a peaceful empire, while he was extending its bounds even beyond the Rhine and the Euphrates and the Danube, in Rome itself the swords of Murena, Caepio, Lepidus, Egnatius, and others were being whetted to slay him. Not yet had he escaped their plots, when his daughter9 and all the noble youths who were bound to her by adultery as by a sacred oath, oft alarmed his failing years—and there was Paulus, and a second time the need to fear a woman in league with an Antony.10 When be had cut away these ulcers11 together with the limbs themselves, others would grow in their place; just as in a body that was overburdened with blood, there was always a rupture somewhere. And so he longed for leisure, in the hope and thought of which he found relief for his labours. This was the prayer of one who was able to answer the prayers of mankind.

Some will have a scientific explanation, for example muscle spasms or migraines can be related to low magnesium levels, but some will have a unique meaning to us and it is down to us to decode them. I have a friend that has always said “By the time I get a mouth ulcer, I know that I have pushed myself too hard and my body is not getting enough nutrients to keep going.” I have taken note of that for myself. A cousin said that his stress always shows up as a feeling of toxins built up in knots in his shoulders. I recognize that one too!

I do love Shakespeare, but I relate more to Alexandre Dumas, Victor Hugo, C.S. Lewis. Oh, but Lewis is MAGICAL; reading Lewis is like leaving ground zero and rushing head-on into the universe a child in my heart once more, all ulcers healed and my pain a distant memory...

When it is a question of abuses in political institutions, it is necessary to take great care to judge of them only by their constant effects, and never by any of their causes, of whatever kind, which signify nothing still less by certain collateral inconveniences (if I may so express myself ) which men of limited views readily lay hold of, and are thus prevented from seeing the whole together. Indeed, the cause, according to the hypothesis which seems to be proved, not having any logical relation to the effect; and the inconveniences of an institution, good in itself, being only, as I have just said, an inevitable dissonance in the general key; how can we judge of institutions by their causes and inconveniences?—Voltaire, who spoke of every thing, during an age, without having so much as penetrated below the surface, has reasoned very humorously on the sale of the offices of the magistracy which occurred in France; and no instance, perhaps, could be more apposite to make us sensible of the truth of the theory which I am setting forth. That this sale is an abuse, says he, is proved by the fact, that it originated in another abuse. Voltaire does not mistake here as every man is liable to mistake. He shamefully mistakes. It is a total eclipse of common sense. Everything which springs from an abuse, an abuse! On the contrary; one of the most general and evident laws of this power, at once secret and striking, which acts and makes itself to be felt on every side, is, that the remedy of an abuse springs from an abuse, and that the evil, having reached a certain point, destroys itself, as it ought to do; for evil, which is only a negation, has, for measure of dimension and duration, that of the being to which it is joined, and which it destroys. It exists as an ulcer, which can only terminate in self-destruction. But then a new reality will necessarily occupy the place of that which has disappeared; for nature abhors a vacuum, and the Good. But I diverge too far from Voltaire.

So you’re sprinting down the street with the lion after you. Things looked grim for a moment there, but—your good luck—your cardiovascular system kicked into gear, and now it is delivering oxygen and energy to your exercising muscles. But what energy? There’s not enough time to consume a candy bar and derive its benefits as you sprint along; there’s not even enough time to digest food already in the gut. Your body must get energy from its places of storage, like fat or liver or non-exercising muscle. To understand how you mobilize energy in this circumstance, and how that mobilization can make you sick at times, we need to learn how the body stores energy in the first place.

It’s Thanksgiving, and you’ve eaten with porcine abandon. Your bloodstream is teeming with amino acids, fatty acids, glucose. It’s far more than you need to power you over to the couch in a postprandial daze. What does your body do with the excess? This is crucial to understand because, basically, the process gets reversed when you’re later sprinting for your life. To answer this question, it’s time we talked finances, the works—savings accounts, change for a dollar, stocks and bonds, negative amortization of interest rates, shaking coins out of piggy banks—because the process of transporting energy through the body bears some striking similarities to the movement of money. It is rare today for the grotesquely wealthy to walk around with their fortunes in their pockets, or to hoard their wealth as cash stuffed inside mattresses. Instead, surplus wealth is stored elsewhere, in forms more complex than cash: mutual funds, tax-free government bonds, Swiss bank accounts. In the same way, surplus energy is not kept in the body’s form of cash—circulating amino acids, glucose, and fatty acids—but stored in more complex forms. Enzymes in fat cells can combine fatty acids and glycerol to form triglycerides (table). Accumulate enough of these in the fat cells and you grow plump. Meanwhile, your cells can stick series of glucose molecules together. These long chains, sometimes thousands of glucose molecules long, are called glycogen. Most glycogen formation occurs in your muscles and liver. Similarly, enzymes in cells throughout the body can combine long strings of amino acids, forming them into proteins. The hormone that stimulates the transport and storage of these building blocks into target cells is insulin. Insulin is this optimistic hormone that plans for your metabolic future. Eat

This grand strategy of breaking your food down into its simplest parts and reconverting it into complex storage forms is precisely what your body should do when you’ve eaten plenty. And it is precisely what your body should not do in the face of an immediate physical emergency. Then, you want to stop energy storage. Turn up the activity of the sympathetic nervous system, turn down the parasympathetic, and down goes insulin secretion: step one in meeting an emergency accomplished.

expend 10 to 20 percent of their energy on digestion.

Along comes stress: turn off the parasympathetic, turn on the sympathetic, and forget about digestion.* End of stress; switch gears again, and the digestive process resumes.

But one of the additional factors is stress. Study after study, even those carried out after the ascendancy of the bacteria, show that duodenal ulceration is more likely to occur in people who are anxious, depressed, or undergoing severe life stressors (imprisonment, war, natural disasters). An analysis of the entire literature shows that somewhere between 30 and 65 percent of peptic ulcers have psychosocial factors (i.e., stress) involved.

The problem is that stress causes people to drink and smoke more. So maybe stress increases the risk of an ulcer merely by increasing the incidence of those lifestyle risk factors.

they also atypically crave sweets. This is an effect that is specific to stress.

So with lots of stress, you get cravings for starchy comfort food and you pack it in the abdomen.

The sympathetic nervous system kicks into action during emergencies, or what you think are emergencies. It helps mediate vigilance, arousal, activation, mobilization. To generations of first-year medical students, it is described through the obligatory lame joke about the sympathetic nervous system mediating the four F’s of behavior—flight, fight, fright, and sex.

The nerve endings of this system release adrenaline.

the American terms, which will be used from now on, are epinephrine and norepinephrine.)

The other half of the autonomic nervous system plays an opposing role. This parasympathetic component mediates calm, vegetative activities—everything but the four F’s. If you are a growing kid and you have gone to sleep, your parasympathetic system is activated. It promotes growth, energy storage, and other optimistic processes. Have a huge meal, sit there bloated and happily drowsy, and the parasympathetic is going like gangbusters

(Steroid is used to describe the general chemical structure of five classes of hormones: androgens—the famed “anabolic” steroids like testosterone that get you thrown out of the Olympics—estrogens, progestins, mineralocorticoids, and glucocorticoids.)

After ACTH is released into the bloodstream, it reaches the adrenal gland and, within a few minutes, triggers glucocorticoid release. Together, glucocorticoids and the secretions of the sympathetic nervous system (epinephrine and norepinephrine) account for a large percentage of what happens in your body during stress. These are the workhorses of the stress-response.

Just as some glands are activated in response to stress, various hormonal systems are inhibited during stress. The secretion of various reproductive hormones such as estrogen, progesterone, and testosterone is inhibited. Hormones related to growth (such as growth hormone) are also inhibited, as is the secretion of insulin, a pancreatic hormone that normally tells your body to store energy for later use.

A great marker is turning out to be something called C-reactive protein (CRP).

CRP is turning out to be a much better predictor of cardiovascular disease risk than cholesterol, even years in advance of disease onset. As a result, CRP has suddenly become quite trendy in medicine, and is fast becoming a standard endpoint to measure in general blood work on patients.

As noted earlier, your heart slows down as a result of activation of the vagus nerve by the parasympathetic nervous system.

if you are turning on the sympathetic nervous system all the time, you’re chronically shutting off the parasympathetic. And this makes it harder to slow things down, even during those rare moments when you’re not feeling stressed about something.

Whenever you inhale, you turn on the sympathetic nervous system slightly, minutely speeding up your heart.

And when you exhale, the parasympathetic half turns on, activating your vagus nerve in order to slow things down (this is why many forms of meditation are built around extended exhalations).

Large amounts of variability (that is to say, short interbeat intervals during inhalation, long during exhalation) mean you have strong parasympathetic tone counteracting your sympathetic tone, a good thing.

The answer is all the usual suspects—too much sympathetic nervous system arousal, too much secretion of glucocorticoids. But another factor is relevant, one that is wildly controversial, namely estrogen.

mostly thanks to estrogen working as an antioxidant, getting rid of damaging oxygen radicals.

Instead, complex food matter is broken down into its simplest parts (molecules): amino acids (the building blocks of protein), simple sugars like glucose (the building blocks of more complex sugars and of starches [carbohydrates]), and free fatty acids and glycerol (the constituents of fat). This is accomplished in the gastrointestinal tract by enzymes, chemicals that can degrade more complex molecules. The simple building blocks thus produced are absorbed into the bloodstream for delivery to whichever cells in the body need them.

Your body reverses all of the storage steps through the release of the stress hormones glucocorticoids, glucagon, epinephrine, and norepinephrine. These cause triglycerides to be broken down in the fat cells and, as a result, free fatty acids and glycerol pour into the circulatory system.

Just as obviously, you’ll have trouble mobilizing energy in response to the demands of daily life. And that is precisely what is seen in individuals with chronic fatigue syndrome, which is characterized by, among other things, too low levels of glucocorticoids in the bloodstream.

It takes energy to shuttle those nutrients in and out of the bloodstream, to power the enzymes that glue them together (into proteins, triglycerides, and glycogen) and the other enzymes that then break them apart, to fuel the liver during that gluconeogenesis trick.

As is well understood, there is “bad” cholesterol, also known as low-density lipoprotein-associated cholesterol (LDL) and “good” cholesterol (high-density lipoprotein-associated cholesterol, HDL). LDL-cholesterol is the type that gets added to an atherosclerotic plaque, whereas HDL-cholesterol is cholesterol that has been removed from plaques and is on its way to be degraded in the liver. As a result

For reasons that are just being sorted out, in some people the immune system decides that the cells in the pancreas that secrete insulin are, in fact, foreign invaders and attacks them (such “autoimmune” diseases will be discussed in chapter 8). This destroys those cells, leaving the person with little ability to secrete insulin.

you’re diabetic, you never want your insulin levels to get too low—cells are deprived of energy, circulating glucose levels get too high. But you don’t want to take too much insulin. For complex reasons, this deprives the brain of energy, potentially putting you into shock or a coma and damaging neurons.

How does chronic stress affect this process? First, the hormones of the stress-response cause even more glucose and fatty acids to be mobilized into the bloodstream. For a juvenile diabetic, this increases the likelihood of the now-familiar pathologies of glucose and fatty acids gumming up in the wrong places.

Another, more subtle problem occurs with chronic stress as well. When something stressful happens, you don’t just block insulin secretion. Basically, the brain doesn’t quite trust the pancreas not to keep secreting a little insulin, so a second step occurs. As noted earlier, during stress, glucocorticoids act on fat cells throughout the body to make them less sensitive to insulin, just in case there’s some still floating around. Fat cells then release some newly discovered hormones that get other tissues, like muscle and liver, to stop responding to insulin as well. Stress promotes insulin resistance.

In adult-onset diabetes (type 2, non-insulin-dependent diabetes), the trouble is not too little insulin, but the failure of the cells to respond to insulin. Another name for the disorder is thus insulin-resistant diabetes.

With enough fat stored away, the fat cells essentially get full; once you are an adolescent, the number of fat cells you have is fixed, so if you put on weight, the individual fat cells are distended. Yet another heavy meal, a burst of insulin trying to promote more fat storage by the fat cells, and the fat cells refuse—“Tough luck, I don’t care if you are insulin; we’re completely full.” No room at the inn.