فصل 8

CHAPTER 8

Cancer, Heart Attacks, and a Shorter Life

Sleep Deprivation and the Body

I was once fond of saying, “Sleep is the third pillar of good health, alongside diet and exercise.” I have changed my tune. Sleep is more than a pillar; it is the foundation on which the other two health bastions sit. Take away the bedrock of sleep, or weaken it just a little, and careful eating or physical exercise become less than effective, as we shall see.

Yet the insidious impact of sleep loss on health runs much deeper. Every major system, tissue, and organ of your body suffers when sleep becomes short. No aspect of your health can retreat at the sign of sleep loss and escape unharmed. Like water from a burst pipe in your home, the effects of sleep deprivation will seep into every nook and cranny of biology, down into your cells, even altering your most fundamental self—your DNA.

Widening the lens of focus, there are more than twenty large-scale epidemiological studies that have tracked millions of people over many decades, all of which report the same clear relationship: the shorter your sleep, the shorter your life. The leading causes of disease and death in developed nations—diseases that are crippling health-care systems, such as heart disease, obesity, dementia, diabetes, and cancer—all have recognized causal links to a lack of sleep.

This chapter describes, uncomfortably, the many and varied ways in which insufficient sleep proves ruinous to all the major physiological systems of the human body: cardiovascular, metabolic, immune, reproductive.

SLEEP LOSS AND THE CARDIOVASCULAR SYSTEM

Unhealthy sleep, unhealthy heart. Simple and true. Take the results of a 2011 study that tracked more than half a million men and women of varied ages, races, and ethnicities across eight different countries. Progressively shorter sleep was associated with a 45 percent increased risk of developing and/or dying from coronary heart disease within seven to twenty-five years from the start of the study. A similar relationship was observed in a Japanese study of over 4,000 male workers. Over a fourteen-year period, those sleeping six hours or less were 400 to 500 percent more likely to suffer one or more cardiac arrests than those sleeping more than six hours. I should note that in many of these studies, the relationship between short sleep and heart failure remains strong even after controlling for other known cardiac risk factors, such as smoking, physical activity, and body mass. A lack of sleep more than accomplishes its own, independent attack on the heart.

As we approach midlife, and our body begins to deteriorate and health resilience starts its decline, the impact of insufficient sleep on the cardiovascular system escalates. Adults forty-five years or older who sleep fewer than six hours a night are 200 percent more likely to have a heart attack or stroke during their lifetime, as compared with those sleeping seven to eight hours a night. This finding impresses how important it is to prioritize sleep in midlife—which is unfortunately the time when family and professional circumstances encourage us to do the exact opposite.

Part of the reason the heart suffers so dramatically under the weight of sleep deprivation concerns blood pressure. Have a quick look at your right forearm and pick out some veins. If you wrap your left hand around that forearm, just below the elbow, and grip it, like a tourniquet, you will see those vessels start to balloon. A little alarming, isn’t it? The ease with which just a little sleep loss can pump up pressure in the veins of your entire body, stretching and distressing the vessel walls, is equally alarming. High blood pressure is so common nowadays that we forget the deathly toll it inflicts. This year alone, hypertension will steal more than 7 million people’s lives by way of cardiac failure, ischemic heart disease, stroke, or kidney failure. Deficient sleep is responsible for many of these lost fathers, mothers, grandparents, and beloved friends.

As with other consequences of sleep loss we’ve encountered, you don’t need a full night of total sleep deprivation to inflict a measurable impact on your cardiovascular system. One night of modest sleep reduction—even just one or two hours—will promptly speed the contracting rate of a person’s heart, hour upon hour, and significantly increase the systolic blood pressure within their vasculature.I You will find no solace in the fact that these experiments were conducted in young, fit individuals, all of whom started out with an otherwise healthy cardiovascular system just hours before. Such physical fitness proves no match for a short night of sleep; it affords no resistance.

Beyond accelerating your heart rate and increasing your blood pressure, a lack of sleep further erodes the fabric of those strained blood vessels, especially those that feed the heart itself, called the coronary arteries. These corridors of life need to be clean and open wide to supply your heart with blood at all times. Narrow or block those passageways, and your heart can suffer a comprehensive and often fatal attack caused by blood oxygen starvation, colloquially known as a “massive coronary.”

One cause of a coronary artery blockage is atherosclerosis, or the furring up of those heart corridors with hardened plaques that contain calcium deposits. Researchers at the University of Chicago studied almost five hundred healthy midlife adults, none of whom had any existing heart disease or signs of atherosclerosis. They tracked the health of the coronary arteries of these participants for a number of years, all the while assessing their sleep. If you were one of the individuals who were obtaining just five to six hours each night or less, you were 200 to 300 percent more likely to suffer calcification of your coronary arteries over the next five years, relative to those individuals sleeping seven to eight hours. The deficient sleep of those individuals was associated with a closing off of the critical passageways that should otherwise be wide open and feeding the heart with blood, starving it and significantly increasing the risk of a coronary heart attack.

Although the mechanisms by which sleep deprivation degrades cardiovascular health are numerous, they all appear to cluster around a common culprit, called the sympathetic nervous system. Abandon any thoughts of love or serene compassion based on the misguiding name. The sympathetic nervous system is resolutely activating, inciting, even agitating. If needed, it will mobilize the evolutionarily ancient fight-or-flight stress response within the body, comprehensively and in a matter of seconds. Like an accomplished general in command of a vast military, the sympathetic nervous system can muster activity in a vast assortment of the body’s physiological divisions—from respiration, immune function, and stress chemicals to blood pressure and heart rate.

An acute stress response from the sympathetic nervous system, which is normally only deployed for short periods of time lasting minutes to hours, can be highly adaptive under conditions of credible threat, such as the potential of real physical attack. Survival is the goal, and these responses promote immediate action to accomplish just that. But leave that system stuck in the “on” position for long durations of time, and sympathetic activation becomes deeply maladaptive. In fact, it is a killer.

With few exceptions over the past half century, every experiment that has investigated the impact of deficient sleep on the human body has observed an overactive sympathetic nervous system. For as long as the state of insufficient sleep lasts, and for some time thereafter, the body remains stuck in some degree of a fight-or-flight state. It can last for years in those with an untreated sleep disorder, excessive work hours that limit sleep or its quality, or the simple neglect of sleep by an individual. Like a car engine that is revved to a shrieking extreme for sustained periods of time, your sympathetic nervous system is floored into perpetual overdrive by a lack of sleep. The consequential strain that is placed on your body by the persistent force of sympathetic activation will leak out in all manner of health issues, just like the failed pistons, gaskets, seals, and gnashing gears of an abused car engine.

Through this central pathway of an overactive sympathetic nervous system, sleep deprivation triggers a domino effect that will spread like a wave of health damage throughout your body. It starts with removing a default resting brake that normally prevents your heart from accelerating in its rate of contraction. Once this brake is released, you will experience sustained speeds of cardiac beating.

As your sleep-deprived heart beats faster, the volumetric rate of blood pumped through your vasculature increases, and with that comes the hypertensive state of your blood pressure. Occurring at the same time is a chronic increase in a stress hormone called cortisol, which is triggered by the overactive sympathetic nervous system. One undesirable consequence of the sustained deluge of cortisol is the constriction of those blood vessels, triggering an even greater increase in blood pressure.

Making matters worse, growth hormone—a great healer of the body—which normally surges at night, is shut off by the state of sleep deprivation. Without growth hormone to replenish the lining of your blood vessels, called the endothelium, they will be slowly shorn and stripped of their integrity. Adding insult to real injury, the hypertensive strain that sleep deprivation places on your vasculature means that you can no longer repair those fracturing vessels effectively. The damaged and weakened state of vascular plumbing throughout your body now becomes systemically more prone to atherosclerosis (arteries furring up). Vessels will rupture. It is a powder keg of factors, with heart attack and stroke being the most common casualties in the explosive aftermath.

Compare this cascade of harm to the healing benefits that a full night of sleep normally lavishes on the cardiovascular system. During deep NREM sleep specifically, the brain communicates a calming signal to the fight-or-flight sympathetic branch of the body’s nervous system, and does so for long durations of the night. As a result, deep sleep prevents an escalation of this physiological stress that is synonymous with increased blood pressure, heart attack, heart failure, and stroke. This includes a calming effect on the contracting speed of your heart. Think of your deep NREM sleep as a natural form of nighttime blood-pressure management—one that averts hypertension and stroke.

When communicating science to the general public in lectures or writing, I’m always wary of bombarding an audience with never-ending mortality and morbidity statistics, lest they themselves lose the will to live in front of me. It is hard not to do so with such compelling masses of studies in the field of sleep deprivation. Often, however, a single astonishing result is all that people need to apprehend the point. For cardiovascular health, I believe that finding comes from a “global experiment” in which 1.5 billion people are forced to reduce their sleep by one hour or less for a single night each year. It is very likely that you have been part of this experiment, otherwise known as daylight savings time.

In the Northern Hemisphere, the switch to daylight savings time in March results in most people losing an hour of sleep opportunity. Should you tabulate millions of daily hospital records, as researchers have done, you discover that this seemingly trivial sleep reduction comes with a frightening spike in heart attacks the following day. Impressively, it works both ways. In the autumn within the Northern Hemisphere, when the clocks move forward and we gain an hour of sleep opportunity time, rates of heart attacks plummet the day after. A similar rise-and-fall relationship can be seen with the number of traffic accidents, proving that the brain, by way of attention lapses and microsleeps, is just as sensitive as the heart to very small perturbations of sleep. Most people think nothing of losing an hour of sleep for a single night, believing it to be trivial and inconsequential. It is anything but.

SLEEP LOSS AND METABOLISM: DIABETES AND WEIGHT GAIN

The less you sleep, the more you are likely to eat. In addition, your body becomes unable to manage those calories effectively, especially the concentrations of sugar in your blood. In these two ways, sleeping less than seven or eight hours a night will increase your probability of gaining weight, being overweight, or being obese, and significantly increases your likelihood of developing type 2 diabetes.

The global health cost of diabetes is $375 billion a year. That of obesity is more than $2 trillion. Yet for the under-slept individual, the cost to health, quality of life, and a hastened arrival of death are more meaningful. Precisely how a lack of sleep sets you on a path toward diabetes and leads to obesity is now well understood and incontrovertible.

DIABETES

Sugar is a dangerous thing. In your diet, yes, but here I’m referring to that which is currently circulating in your bloodstream. Excessively high levels of blood sugar, or glucose, over weeks or years inflicts a surprising harm to the tissues and organs of your body, worsens your health, and shortens your life span. Eye disease that can end in blindness, nerve disease that commonly results in amputations, and kidney failure necessitating dialysis or transplant are all consequences of prolonged high blood sugar, as are hypertension and heart disease. But it is the condition of type 2 diabetes that is most commonly and immediately related to unregulated blood sugar.

In a healthy individual, the hormone insulin will trigger the cells of your body to swiftly absorb glucose from the bloodstream should it increase, as happens after eating a meal. Instructed by insulin, the cells of your body will open special channels on their surface that operate like wonderfully efficient roadside drains at the height of a downpour. They have no problem dealing with the deluge of glucose coursing down the transit arteries, averting what could otherwise be a dangerous flood of sugar in the bloodstream.

If the cells of your body stop responding to insulin, however, they cannot efficiently absorb glucose from the blood. Similar to roadside drains that become blocked or erroneously closed shut, the rising swell of blood sugar cannot be brought back down to safe levels. At this point, the body has transitioned into a hyperglycemic state. Should this condition persist, and the cells of your body remain intolerant to dealing with the high levels of glucose, you will transition into a pre-diabetic state and, ultimately, develop full-blown type 2 diabetes.

Early-warning signs of a link between sleep loss and abnormal blood sugar emerged in a series of large epidemiological studies spanning several continents. Independent of one another, the research groups found far higher rates of type 2 diabetes among individuals that reported sleeping less than six hours a night routinely. The association remained significant even when adjusting for other contributing factors, such as body weight, alcohol, smoking, age, gender, race, and caffeine use. Powerful as these studies are, though, they do not inform the direction of causality. Does the state of diabetes impair your sleep, or does short sleep impair your body’s ability to regulate blood sugar, thereby causing diabetes?

To answer this question, scientists had to conduct carefully controlled experiments with healthy adults who had no existing signs of diabetes or issues with blood sugar. In the first of these studies, participants were limited to sleeping four hours a night for just six nights. By the end of that week, these (formerly healthy) participants were 40 percent less effective at absorbing a standard dose of glucose, compared to when they were fully rested.

To give you a sense of what that means, if the researchers showed those blood sugar readings to an unwitting family doctor, the GP would immediately classify that individual as being pre-diabetic. They would start a rapid intervention program to prevent the development of irreversible type 2 diabetes. Numerous scientific laboratories around the world have replicated this alarming effect of short sleep, some with even less aggressive reductions in sleep amount.

How does a lack of sleep hijack the body’s effective control of blood sugar? Was it a blockade of insulin release, removing the essential instruction for cells to absorb glucose? Or had the cells themselves become unresponsive to an otherwise normal and present message of insulin?

As we have discovered, both are true, though the most compelling evidence indicates the latter. By taking small tissue samples, or biopsies, from participants at the end of the above experiments, we can examine how the cells of the body are operating. After participants had been restricted to four to five hours of sleep for a week, the cells of these tired individuals had become far less receptive to insulin. In this sleep-deprived state, the cells were stubbornly resisting the message from insulin and refusing to open up their surface channels. The cells were repelling rather than absorbing the dangerously high levels of glucose. The roadside drains were effectively closed shut, leading to a rising tide of blood sugar and a pre-diabetic state of hyperglycemia.

While many in the general public understand that diabetes is serious, they may not appreciate the true burden. Beyond the average treatment cost of more than $85,000 per patient (which contributes to higher medical insurance premiums), diabetes lops ten years off an individual’s life expectancy. Chronic sleep deprivation is now recognized as one of the major contributors to the escalation of type 2 diabetes throughout first-world countries. It’s a preventable contribution.

WEIGHT GAIN AND OBESITY

When your sleep becomes short, you will gain weight. Multiple forces conspire to expand your waistline. The first concerns two hormones controlling appetite: leptin and ghrelin.II Leptin signals a sense of feeling full. When circulating levels of leptin are high, your appetite is blunted and you don’t feel like eating. Ghrelin, in contrast, triggers a strong sensation of hunger. When ghrelin levels increase, so, too, does your desire to eat. An imbalance of either one of these hormones can trigger increased eating and thus body weight. Perturb both in the wrong direction, and weight gain is more than probable.

Over the past thirty years, my colleague Dr. Eve Van Cauter at the University of Chicago has tirelessly conducted research on the link between sleep and appetite that is as brilliant as it is impactful. Rather than depriving individuals of a full night of sleep, Van Cauter has taken a more relevant approach. She recognized that more than a third of individuals in industrialized societies sleep less than five to six hours a night during the week. So in a first series of studies of healthy young adults of perfectly normal weight, she began to investigate whether one week of this societally typical short sleep was enough to disrupt levels of either leptin or ghrelin or both.

If you are a participant in one of Van Cauter’s studies, it feels rather more like a one-week stay at a hotel. You will get your own room, bed, clean sheets, a television, Internet access, etc.—everything except free tea and coffee, since no caffeine is allowed. In one arm of the experiment, you will be given an eight-and-a-half-hour sleep opportunity each night for five nights, recorded with electrodes placed on your head. In the other arm of the study, you are only allowed four to five hours of sleep for five nights, also measured with electrode recordings. In both study arms, you will receive exactly the same amount and type of food, and your degree of physical activity is also held constant. Each day, your sense of hunger and food intake are monitored, as are your circulating levels of leptin and ghrelin.

Using precisely this experimental design in a group of healthy, lean participants, Van Cauter discovered that individuals were far more ravenous when sleeping four to five hours a night. This despite being given the same amount of food and being similarly active, which kept the hunger levels of these same individuals under calm control when they were getting eight or more hours of sleep. The strong rise of hunger pangs and increased reported appetite occurred rapidly, by just the second day of short sleeping.

At fault were the two characters, leptin and ghrelin. Inadequate sleep decreased concentrations of the satiety-signaling hormone leptin and increased levels of the hunger-instigating hormone ghrelin. It was a classic case of physiological double jeopardy: participants were being punished twice for the same offense of short sleeping: once by having the “I’m full” signal removed from their system, and once by gaining the “I’m still hungry” feeling being amplified. As a result, participants just didn’t feel satisfied by food when they were short sleeping.

From a metabolic perspective, the sleep-restricted participants had lost their hunger control. By limiting these individuals to what some in our society would think of as a “sufficient” amount of sleep (five hours a night), Van Cauter had caused a profound imbalance in the scales of hormonal food desire. By muting the chemical message that says “stop eating” (leptin), yet increasing the hormonal voice that shouts “please, keep eating” (ghrelin), your appetite remains unsatisfied when your sleep is anything less than plentiful, even after a kingly meal. As Van Cauter has elegantly described to me, a sleep-deprived body will cry famine in the midst of plenty.

But feeling hungry and actually eating more are not the same thing. Do you actually eat more when sleeping less? Does your waistline really swell as a consequence of that rise in appetite?

With another landmark study, Van Cauter proved this to be the case. Participants in this experiment again underwent two different conditions, acting as their own baseline control: four nights of eight and a half hours’ time in bed, and four nights of four and a half hours’ time in bed. Each day, participants were limited to the same level of physical activity under both conditions. Each day, they were given free access to food, and the researchers meticulously counted the difference in calorie consumption between the two experimental manipulations.

When short sleeping, the very same individuals ate 300 calories more each day—or well over 1,000 calories before the end of the experiment—compared to when they were routinely getting a full night of sleep. Similar changes occur if you give people five to six hours of sleep over a ten-day period. Scale that up to a working year, and assuming one month of vacation in which sleep miraculously becomes abundant, and you will still have consumed more than 70,000 extra calories. Based on caloric estimates, that would cause 10 to 15 pounds of weight gain a year, each and every year (which may sound painfully familiar to many of us).

Van Cauter’s next experiment was the most surprising (and devilish) of all. Fit, healthy individuals went through the same two different conditions as before: four nights of eight and a half hours’ time in bed, and four nights of four and a half hours’ time in bed. However, on the last day if each of the experimental conditions, something different happened. Participants were offered an additional food buffet stretched across a four-hour period. Set out in front of them was an assortment of foods, from meats, vegetables, bread, potatoes, and salad to fruit and ice cream. Set to one side, however, was access to a bonus snack bar filled with cookies, chocolate bars, chips, and pretzels. Participants could eat as much as they wanted in the four-hour period, with the buffet even being replenished halfway through. Importantly, the subjects ate alone, limiting social or stigmatizing influences that could alter their natural eating urges.

Following the buffet, Van Cauter and her team once again quantified what participants ate, and how much they ate. Despite eating almost 2,000 calories during the buffet lunch, sleep-deprived participants dove into the snack bar. They consumed an additional 330 calories of snack foods after the full meal, compared to when they were getting plenty of sleep each night.

Of relevance to this behavior is a recent discovery that sleep loss increases levels of circulating endocannabinoids, which, as you may have guessed from the name, are chemicals produced by the body that are very similar to the drug cannabis. Like marijuana use, these chemicals stimulate appetite and increase your desire to snack, otherwise known as having the munchies.

Combine this increase in endocannabinoids with alterations in leptin and ghrelin caused by sleep deprivation and you have a potent brew of chemical messages all driving you in one direction: overeating.

Some argue that we eat more when we are sleep-deprived because we burn extra calories when we stay awake. Sadly, this is not true. In the sleep-restriction experiments described above, there are no differences in caloric expenditure between the two conditions. Take it to the extreme by sleep-depriving an individual for twenty-four hours straight and they will only burn an extra 147 calories, relative to a twenty-four-hour period containing a full eight hours of sleep. Sleep, it turns out, is an intensely metabolically active state for brain and body alike. For this reason, theories proposing that we sleep to conserve large amounts of energy are no longer entertained. The paltry caloric savings are insufficient to outweigh the survival dangers and disadvantages associated with falling asleep.

More importantly, the extra calories that you eat when sleep-deprived far outweigh any nominal extra energy you burn while remaining awake. Making matters worse, the less an individual sleeps, the less energy he or she feels they have, and the more sedentary and less willing to exercise they are in real-world settings. Inadequate sleep is the perfect recipe for obesity: greater calorie intake, lower calorie expenditure.

Weight gain caused by short sleep is not just a matter of eating more, but also a change in what you binge eat. Looking across the different studies, Van Cauter noticed that cravings for sweets (e.g., cookies, chocolate, and ice cream), heavy-hitting carbohydrate-rich foods (e.g., bread and pasta), and salty snacks (e.g., potato chips and pretzels) all increased by 30 to 40 percent when sleep was reduced by several hours each night. Less affected were protein-rich foods (e.g., meat and fish), dairy items (such as yogurt and cheese), and fatty foods, showing a 10 to 15 percent increase in preference by the sleepy participants.

Why is it that we lust after quick-fix sugars and complex carbohydrates when sleep-deprived? My research team and I decided to conduct a study in which we scanned people’s brains while they were viewing and choosing food items, and then rated how much they desired each one. We hypothesized that changes within the brain may help explain this unhealthy shift in food preference caused by a lack of sleep. Was there a breakdown in impulse-control regions that normally keep our basic hedonic food desires in check, making us reach for doughnuts or pizza rather than whole grains and leafy greens?

Healthy, average-weight participants performed the experiment twice: once when they had had a full night of sleep, and once after they had been sleep-deprived for a night. In each of the two conditions they viewed eighty similar food images, ranging from fruits and vegetables, such as strawberries, apples, and carrots, to high-calorie items, such as ice cream, pasta, and doughnuts. To ensure that participants were making choices that reflected their true cravings rather than simply choosing items that they thought would be the right or most appropriate choice, we forced an incentive: after they came out of the MRI machine, we gave them a serving of the food they told us they most craved during the task, and politely asked them to eat it!

Comparing the patterns of brain activity between the two conditions within the same individual, we discovered that supervisory regions in the prefrontal cortex required for thoughtful judgments and controlled decisions had been silenced in their activity by a lack of sleep. In contrast, the more primal deep-brain structures that drive motivations and desire were amplified in response to the food images. This shift to a more primitive pattern of brain activity without deliberative control came with a change in the participants’ food choices. High-calorie foods became significantly more desirable in the eyes of the participants when sleep-deprived. When we tallied up the extra food items that participants wanted when they were sleep-deprived, it amounted to an extra 600 calories.

The encouraging news is that getting enough sleep will help you control body weight. We found that a full night of sleep repairs the communication pathway between deep-brain areas that unleash hedonic desires and higher-order brain regions whose job it is to rein in these cravings. Ample sleep can therefore restore a system of impulse control within your brain, putting the appropriate brakes on potentially excessive eating.

South of the brain, we are also discovering that plentiful sleep makes your gut happier. Sleep’s role in redressing the balance of the body’s nervous system, especially its calming of the fight-or-flight sympathetic branch, improves the bacterial community known as your microbiome, which is located in your gut (also known as the enteric nervous system). As we learned about earlier, when you do not get enough sleep, and the body’s stress-related, fight-or-flight nervous system is revved up, this triggers an excess of circulating cortisol that cultivates “bad bacteria” to fester throughout your microbiome. As a result, insufficient sleep will prevent the meaningful absorption of all food nutrients and cause gastrointestinal problems.III

Of course, the obesity epidemic that has engulfed large portions of the world is not caused by lack of sleep alone. The rise in consumption of processed foods, an increase in serving sizes, and the more sedentary nature of human beings are all triggers. However, these changes are insufficient to explain the dramatic escalation of obesity. Other factors must be at play.

Based on evidence gathered over the past three decades, the epidemic of insufficient sleep is very likely a key contributor to the epidemic of obesity. Epidemiological studies have established that people who sleep less are the same individuals who are more likely to be overweight or obese. Indeed, if you simply plot the reduction in sleep time (dotted line) over the past fifty years on the same graph as the rise in obesity rates across the same time period (solid line), shown in Figure 13, the data infer this relationship clearly.

Figure 13: Sleep Loss and Obesity

We are now observing these effects very early in life. Three-year-olds sleeping just ten and a half hours or less have a 45 percent increased risk of being obese by age seven than those who get twelve hours of sleep a night. To set our children on a pathway of ill health this early in life by way of sleep neglect is a travesty.

A final comment on trying to lose weight: let’s say that you choose to go on a strict, low-calorie diet for two weeks in the hopes of losing fat and looking more trim and toned as a consequence. That’s precisely what researchers did to a group of overweight men and women who stayed in a medical center for an entire fortnight. However, one group of individuals were given just five and a half hours’ time in bed, while the other group were offered eight and a half hours’ time in bed.

Although weight loss occurred under both conditions, the type of weight loss came from very different sources. When given just five and a half hours of sleep oppurtunity, more than 70 percent of the pounds lost came from lean body mass—muscle, not fat. Switch to the group offered eight and a half hours’ time in bed each night and a far more desirable outcome was observed, with well over 50 percent of weight loss coming from fat while preserving muscle. When you are not getting enough sleep, the body becomes especially stingy about giving up fat. Instead, muscle mass is depleted while fat is retained. Lean and toned is unlikely to be the outcome of dieting when you are cutting sleep short. The latter is counterproductive of the former.

The upshot of all this work can be summarized as follows: short sleep (of the type that many adults in first-world countries commonly and routinely report) will increase hunger and appetite, compromise impulse control within the brain, increase food consumption (especially of high-calorie foods), decrease feelings of food satisfaction after eating, and prevent effective weight loss when dieting.

SLEEP LOSS AND THE REPRODUCTIVE SYSTEM

If you have hopes of reproductive success, fitness, or prowess, you would do well to get a full night’s sleep every night. Charles Darwin would, I’m sure, cleave easily to this advice, had he reviewed the evidence I now present.

Take a group of lean, healthy young males in their mid-twenties and limit them to five hours of sleep for one week, as a research group did at the University of Chicago. Sample the hormone levels circulating in the blood of these tired participants and you will find a marked drop in testosterone relative to their own baseline levels of testosterone when fully rested. The size of the hormonal blunting effect is so large that it effectively “ages” a man by ten to fifteen years in terms of testosterone virility. The experimental results support the finding that men suffering from sleep disorders, especially sleep apnea associated with snoring, have significantly lower levels of testosterone than those of similar age and backgrounds but who do not suffer from a sleep condition.

Uttering the results of such studies will often quell any vocal (alpha) males that I occasionally come across when giving public lectures. As you may imagine, their ardent, antisleep stance becomes a little wobbly upon receiving such information. With a genuine lack of malice, I proceed to inform them that men who report sleeping too little—or having poor-quality sleep—have a 29 percent lower sperm count than those obtaining a full and restful night of sleep, and the sperm themselves have more deformities. I usually conclude my response with a parenthetical low blow, noting that these under-slept men also have significantly smaller testicles than well-rested counterparts.

Rare podium fracases aside, low testosterone is a clinically concerning and life-impacting matter. Males with low testosterone often feel tired and fatigued throughout the day. They find it difficult to concentrate on work tasks, as testosterone has a sharpening effect on the brain’s ability to focus. And of course, they have a dulled libido, making an active, fulfilling, and healthy sex life more challenging. Indeed, the self-reported mood and vigor of the young men described in the above study progressively decreased in lockstep with their increasing state of sleep deprivation and their declining levels of testosterone. Add to this the fact that testosterone maintains bone density, and plays a causal role in building muscle mass and therefore strength, and you can begin to get a sense of why a full night of sleep—and the natural hormonal replacement therapy it provides—is so essential to this aspect of health and an active life for men of all ages.

Men are not the only ones who become reproductively compromised by a lack of sleep. Routinely sleeping less than six hours a night results in a 20 percent drop in follicular-releasing hormone in women—a critical female reproductive element that peaks just prior to ovulation and is necessary for conception. In a report that brought together findings from studies over the past forty years of more than 100,000 employed women, those working irregular nighttime hours resulting in poor-quality sleep, such as nurses who performed shift work (a profession occupied almost exclusively by women at the time of these earlier studies), had a 33 percent higher rate of abnormal menstrual cycles than those working regular daytime hours. Moreover, the women working erratic hours were 80 percent more likely to suffer from issues of sub-fertility that reduced the ability to get pregnant. Women who do become pregnant and routinely sleep less than eight hours a night are also significantly more likely to suffer a miscarriage in the first trimester, relative to those consistently sleeping eight hours or more a night.

Combine these deleterious effects on reproductive health in a couple where both parties are lacking in sleep, and it’s easy to appreciate why the epidemic of sleep deprivation is linked to infertility or sub-fertility, and why Darwin would find these results so meaningful in the context of future evolutionary success.

Incidentally, should you ask Dr. Tina Sundelin, my friend and colleague at Stockholm University, how attractive you look when sleep-deprived—a physical expression of underlying biology that alters your chances of pair bonding and thus reproduction—she will inform you of an ugly truth. Sundelin isn’t the one doing the judging in this scientific beauty contest. Rather, she conducted an elegant experiment in which members of the public did that for her.

Sundelin took a group of healthy men and women ranging from eighteen to thirty-one years old. They were all photographed twice under identical indoor lighting conditions, same time of day (2:30 p.m.), hair down, no makeup for the women, clean-shaven for the men. What differed, however, was the amount of sleep these individuals were allowed to get before each of the photo shoots. In one of the sessions, the participants were given just five hours of sleep before being put in front of the camera, while in the other session, these same individuals got a full eight hours of sleep. The order of these two conditions was randomized as either first or second across the unwitting models.

She brought another group of participants into the laboratory to act as independent judges. These individuals were naïve to the true purpose of the experiment, knowing nothing about the two different sleep manipulations that had been imposed on the people featured in the photographs. The judges viewed both sets of the pictures in a jumbled order and were asked to give ratings on three features: perceived health, tiredness, and attractiveness.

Despite knowing nothing about the underlying premise of the study, thus operating blind to the different sleep conditions, the judges’ scores were unambiguous. The faces pictured after one night of short sleep were rated as looking more fatigued, less healthy, and significantly less attractive, compared with the appealing image of that same individual after they had slept a full eight hours. Sundelin had revealed the true face of sleep loss, and with it, ratified the long-held concept of “beauty sleep.”

What we can learn from this still burgeoning area of research is that key aspects of the human reproductive system are affected by sleep in both men and women. Reproductive hormones, reproductive organs, and the very nature of physical attractiveness that has a say in reproductive opportunities: all are degraded by short sleeping. One can only imagine Narcissus being a solid eight- to nine-hour sleeper on the basis of the latter association, perhaps with an afternoon nap for good measure, taken beside the reflection pool.

SLEEP LOSS AND THE IMMUNE SYSTEM

Recall the last time you had the flu. Miserable, wasn’t it? Runny nose, aching bones, sore throat, heavy cough, and a total lack of energy. You probably just wanted to curl up in bed and sleep. As well you should. Your body is trying to sleep itself well. An intimate and bidirectional association exists between your sleep and your immune system.

Sleep fights against infection and sickness by deploying all manner of weaponry within your immune arsenal, cladding you with protection. When you do fall ill, the immune system actively stimulates the sleep system, demanding more bed rest to help reinforce the war effort. Reduce sleep even for a single night, and that invisible suit of immune resilience is rudely stripped from your body.

Short of inserting rectal probes to measure core body temperature in certain sleep research studies, my good colleague Dr. Aric Prather at the University of California, San Francisco, has performed one of the most fetid sleep experiments that I am aware of. He measured the sleep of more than 150 healthy men and women for a week using a wristwatch device. Then he quarantined them, and proceeded to squirt a good dose of rhinovirus, or a live culture of the common cold virus, straight up their noses. I should note that all participants knew about this ahead of time, and had surprisingly given full consent to this snout abuse.

Once the flu virus had been satisfactorily boosted up the nostrils of the participants, Prather then kept them in the laboratory for the following week, monitoring them intensely. He not only assessed the extent of immune reaction by taking frequent samples of blood and saliva, but he also gathered nearly every glob of nasal mucus that the participants produced. Prather had the participants regimentally blowing their noses, and every drop of the product was bagged, tagged, weighed, and analytically pored over by his research team. Using these measures—blood and saliva immune antibodies, together with the average amount of snot evacuated by the participants—Prather could determine whether someone had objectively caught a cold.

Prather retrospectively separated the participants into four sub-groups on the basis of how much sleep they had obtained in the week before being exposed to the common cold virus: less than five hours of sleep, five to six hours of sleep, six to seven hours of sleep, and seven or more hours of sleep. There was a clear, linear relationship with infection rate. The less sleep an individual was getting in the week before facing the active common cold virus, the more likely it was that they would be infected and catch a cold. In those sleeping five hours on average, the infection rate was almost 50 percent. In those sleeping seven hours or more a night in the week prior, the infection rate was just 18 percent.

Considering that infectious illnesses, such as the common cold, influenza, and pneumonia, are among the leading causes of death in developed countries, doctors and governments would do well to stress the critical importance of sufficient sleep during the flu season.

Perhaps you are one of the responsible individuals who will get a flu shot each year, boosting your own resilience while adding strength to the immunity of the herd—your community. However, that flu shot is only effective if your body actually reacts to it by generating antibodies.

A remarkable discovery in 2002 demonstrated that sleep profoundly impacts your response to a standard flu vaccine. In the study, healthy young adults were separated into two groups: one had their sleep restricted to four hours a night for six nights, and the other group was allowed seven and a half to eight and a half hours of time in bed each night. At the end of the six days, everyone was given a flu shot. In the days afterward, researchers took blood samples to determine how effective these individuals were in generating an antibody response, determining whether or not the vaccination was a success.

Those participants who obtained seven to nine hours’ sleep in the week before getting the flu shot generated a powerful antibody reaction, reflecting a robust, healthy immune system. In contrast, those in the sleep-restricted group mustered a paltry response, producing less than 50 percent of the immune reaction their well-slept counterparts were able to mobilize. Similar consequences of too little sleep have since been reported for the hepatitis A and B vaccines.

Perhaps the sleep-deprived individuals could still go on to produce a more robust immune reaction if only they were given enough recovery sleep time? It’s a nice idea, but a false one. Even if an individual is allowed two or even three weeks of recovery sleep to get over the assault of one week of short sleeping, they never go on to develop a full immune reaction to the flu shot. In fact, a diminution in certain immune cells could still be observed a year later in the participants after just a minor, short dose of sleep restriction. As with the effects of sleep deprivation on memory, once you miss out on the benefit of sleep in the moment—here, regarding an immune response to this season’s flu—you cannot regain the benefit simply by trying to catch up on lost sleep. The damage is done, and some of that harm can still be measured a year later.

No matter what immunological circumstance you find yourself in—be it preparation for receiving a vaccine to help boost immunity, or mobilizing a mighty adaptive immune response to defeat a viral attack—sleep, and a full night of it, is inviolable.

It doesn’t require many nights of short sleeping before the body is rendered immunologically weak, and here the issue of cancer becomes relevant. Natural killer cells are an elite and powerful squadron within the ranks of your immune system. Think of natural killer cells like the secret service agents of your body, whose job it is to identify dangerous foreign elements and eliminate them—007 types, if you will.

One such foreign entity that natural killer cells will target are malignant (cancerous) tumor cells. Natural killer cells will effectively punch a hole in the outer surface of these cancerous cells and inject a protein that can destroy the malignancy. What you want, therefore, is a virile set of these James Bond–like immune cells at all times. That is precisely what you don’t have when sleeping too little.

Dr. Michael Irwin at the University of California, Los Angeles, has performed landmark studies revealing just how quickly and comprehensively a brief dose of short sleep can affect your cancer-fighting immune cells. Examining healthy young men, Irwin demonstrated that a single night of four hours of sleep—such as going to bed at three a.m. and waking up at seven a.m.—swept away 70 percent of the natural killer cells circulating in the immune system, relative to a full eight-hour night of sleep. That is a dramatic state of immune deficiency to find yourself facing, and it happens quickly, after essentially one “bad night” of sleep. You could well imagine the enfeebled state of your cancer-fighting immune armory after a week of short sleep, let alone months or even years.

We don’t have to imagine. A number of prominent epidemiological studies have reported that nighttime shift work, and the disruption to circadian rhythms and sleep that it causes, up your odds of developing numerous different forms of cancer considerably. To date, these include associations with cancer of the breast, cancer of the prostate, cancer of the uterus wall or the endometrium, and cancer of the colon.

Stirred by the strength of accumulating evidence, Denmark recently became the first country to pay worker compensation to women who had developed breast cancer after years of night-shift work in government-sponsored jobs, such as nurses and air cabin crew. Other governments—Britain, for example—have so far resisted similar legal claims, refusing payout compensation despite the science.

With each passing year of research, more forms of malignant tumors are being linked to insufficient sleep. A large European study of almost 25,000 individuals demonstrated that sleeping six hours or less was associated with a 40 percent increased risk of developing cancer, relative to those sleeping seven hours a night or more. Similar associations were found in a study tracking more than 75,000 women across an eleven-year period.

Exactly how and why short sleep causes cancer is also becoming clear. Part of the problem relates back to the agitating influence of the sympathetic nervous system as it is forced into overdrive by a lack of sleep. Ramping up the body’s level of sympathetic nervous activity will provoke an unnecessary and sustained inflammation response from the immune system. When faced with a real threat, a brief spike of sympathetic nervous system activity will often trigger a similarly transient response from inflammatory activity—one that is useful in anticipation of potential bodily harm (think of a physical tussle with a wild animal or rival hominid tribe). However, inflammation has a dark side. Left switched on without a natural return to peaceful quiescence, a nonspecific state of chronic inflammation causes manifold health problems, including those relevant to cancer.

Cancers are known to use the inflammation response to their advantage. For example, some cancer cells will lure inflammatory factors into the tumor mass to help initiate the growth of blood vessels that feed it with more nutrients and oxygen. Tumors can also use inflammatory factors to help further damage and mutate the DNA of their cancer cells, increasing the tumor’s potency. Inflammatory factors associated with sleep deprivation may also be used to help physically shear some of the tumor from its local moorings, allowing the cancer to up-anchor and spread to other territories of the body. It is a state called metastasis, the medical term for the moment when cancer breaches the original tissue boundaries of origin (here, the injection site) and begins to appear in other regions of the body.

It is these cancer-amplifying and -spreading processes that we now know a lack of sleep will encourage, as recent studies by Dr. David Gozal at the University of Chicago have shown. In his study mice were first injected with malignant cells, and tumor progression was then tracked across a four-week period. Half of the mice were allowed to sleep normally during this time; the other half had their sleep partially disrupted, reducing overall sleep quality.

The sleep-deprived mice suffered a 200 percent increase in the speed and size of cancer growth, relative to the well-rested group. Painful as it is for me personally to view, I will often show comparison pictures of the size of these mouse tumors in the two experimental groups—sleep vs. sleep restriction—during my public talks. Without fail, these images elicit audible gasps, hands reflexively covering mouths, and some people turning away from the images of mountainous tumors growing from the sleep-restricted mice.

I then have to describe the only news that could be worse in any story of cancer. When Gozal performed postmortems of the mice, he discovered that the tumors were far more aggressive in the sleep-deficient animals. Their cancer had metastasized, spreading to surrounding organs, tissue, and bone. Modern medicine is increasingly adept in its treatment of cancer when it stays put, but when cancer metastasizes—as was powerfully encouraged by the state of sleep deprivation—medical intervention often becomes helplessly ineffective, and death rates escalate.

In the years since that experiment, Gozel has further drawn back the curtains of sleep deprivation to reveal the mechanisms responsible for this malignant state of affairs. In a number of studies, Gozal has shown that immune cells, called tumor-associated macrophages, are one root cause of the cancerous influence of sleep loss. He found that sleep deprivation will diminish one form of these macrophages, called M1 cells, that otherwise help combat cancer. Yet sleep deprivation conversely boosts levels of an alternative form of macrophages, called M2 cells, which promote cancer growth. This combination helped explain the devastating carcinogenic effects seen in the mice when their sleep was disturbed.

Poor sleep quality therefore increases the risk of cancer development and, if cancer is established, provides a virulent fertilizer for its rapid and more rampant growth. Not getting sufficient sleep when fighting a battle against cancer can be likened to pouring gasoline on an already aggressive fire. That may sound alarmist, but the scientific evidence linking sleep disruption and cancer is now so damning that the World Health Organization has officially classified nighttime shift work as a “probable carcinogen.”

SLEEP LOSS, GENES, AND DNA

If increasing your risk for developing Alzheimer’s disease, cancer, diabetes, depression, obesity, hypertension, and cardiovascular disease weren’t sufficiently disquieting, chronic sleep loss will erode the very essence of biological life itself: your genetic code and the structures that encapsulate it.

Each cell in your body has an inner core, or nucleus. Within that nucleus resides most of your genetic material in the form of deoxyribonucleic acid (DNA) molecules. DNA molecules form beautiful helical strands, like tall spiral staircases in an opulent home. Segments of these spirals provide specific engineering blueprints that instruct your cells to perform particular functions. These distinct segments are called genes. Rather like double-clicking open a Word file on your computer and then sending it to your printer, when genes are activated and read by the cell, a biological product is printed out, such as the creation of an enzyme that helps with digestion, or a protein that helps strengthen a memory circuit within the brain.

Anything that causes a shimmy or wobble in gene stability can have consequences. Erroneously over- or under-expressing particular genes can cause biologically printed products that raise your risk of disease, such as dementia, cancer, cardiovascular ill health, and immune dysfunction. Enter the destabilizing force of sleep deprivation.

Thousands of genes within the brain depend upon consistent and sufficient sleep for their stable regulation. Deprive a mouse of sleep for just a day, as researchers have done, and the activity of these genes will drop by well over 200 percent. Like a stubborn file that refuses to be transcribed by a printer, when you do not lavish these DNA segments with enough sleep, they will not translate their instructional code into printed action and give the brain and body what they need.

Dr. Derk-Jan Dijk, who directs the Surrey Sleep Research Center in England, has shown that the effects of insufficient sleep on genetic activity are just as striking in humans as they are in mice. Dijk and his prolific team examined gene expression in a group of healthy young men and women after having restricted them to six hours of sleep a night for one week, all monitored under strict laboratory conditions. After one week of subtly reduced sleep, the activity of a hefty 711 genes was distorted, relative to the genetic activity profile of these very same individuals when they were obtaining eight and a half hours of sleep for a week.

Interestingly, the effect went in both directions: about half of those 711 genes had been abnormally revved up in their expression by the loss of sleep, while the other half had been diminished in their expression, or shut down entirely. The genes that were increased included those linked to chronic inflammation, cellular stress, and various factors that cause cardiovascular disease. Among those turned down were genes that help maintain stable metabolism and optimal immune responses. Subsequent studies have found that short sleep duration will also disrupt the activity of genes regulating cholesterol. In particular, a lack of sleep will cause a drop in high-density lipoproteins (HDLs)—a directional profile that has consistently been linked to cardiovascular disease.IV

Insufficient sleep does more than alter the activity and readout of your genes; it attacks the very physical structure of your genetic material itself. The spiral strands of DNA in your cells float around in the nucleus, but are tightly wound together into structures called chromosomes, rather like weaving individual threads together to make a sturdy shoelace. And just like a shoelace, the ends of your chromosomes need to be protected by a cap or binding tip. For chromosomes, that protective cap is called a telomere. If the telomeres at the end of your chromosomes become damaged, your DNA spirals become exposed and your now vulnerable genetic code cannot operate properly, like a fraying shoelace without a tip.

The less sleep an individual obtains, or the worse the quality of sleep, the more damaged the capstone telomeres of that individual’s chromosomes. These are the findings of a collection of studies that have recently been reported in thousands of adults in their forties, fifties, and sixties by numerous independent research teams around the world.V

Whether this association is causal remains to be determined. But the particular nature of the telomere damage caused by short sleeping is now becoming clear. It appears to mimic that seen in aging or advanced decrepitude. That is, two individuals of the same chronological age would not appear to be of the same biological age on the basis of their telomere health if one was routinely sleeping five hours a night while the other was sleeping seven hours a night. The latter would appear “younger,” while the former would artificially have aged far beyond their calendar years.

Genetic engineering of animals and genetically modified food are fraught topics, layered thick with strong emotions. DNA occupies a transcendent, near-divine position in the minds of many individuals, liberal and conservative alike. On this basis, we should feel just as averse and uncomfortable about our own lack of sleep. Not sleeping enough, which for a portion of the population is a voluntary choice, significantly modifies your gene transcriptome—that is, the very essence of you, or at least you as defined biologically by your DNA. Neglect sleep, and you are deciding to perform a genetic engineering manipulation on yourself each night, tampering with the nucleic alphabet that spells out your daily health story. Permit the same in your children and teenagers, and you are imposing a similar genetic engineering experiment on them as well.