فصل 2

CHAPTER 2

Caffeine, Jet Lag, and Melatonin

Losing and Gaining Control of Your Sleep Rhythm

How does your body know when it’s time to sleep? Why do you suffer from jet lag after arriving in a new time zone? How do you overcome jet lag? Why does that acclimatization cause you yet more jet lag upon returning home? Why do some people use melatonin to combat these issues? Why (and how) does a cup of coffee keep you awake? Perhaps most importantly, how do you know if you’re getting enough sleep?

There are two main factors that determine when you want to sleep and when you want to be awake. As you read these very words, both factors are powerfully influencing your mind and body. The first factor is a signal beamed out from your internal twenty-four-hour clock located deep within your brain. The clock creates a cycling, day-night rhythm that makes you feel tired or alert at regular times of night and day, respectively. The second factor is a chemical substance that builds up in your brain and creates a “sleep pressure.” The longer you’ve been awake, the more that chemical sleep pressure accumulates, and consequentially, the sleepier you feel. It is the balance between these two factors that dictates how alert and attentive you are during the day, when you will feel tired and ready for bed at night, and, in part, how well you will sleep.

GOT RHYTHM?

Central to many of the questions in the opening paragraph is the powerful sculpting force of your twenty-four-hour rhythm, also known as your circadian rhythm. Everyone generates a circadian rhythm (circa, meaning “around,” and dian, derivative of diam, meaning “day”). Indeed, every living creature on the planet with a life span of more than several days generates this natural cycle. The internal twenty-four-hour clock within your brain communicates its daily circadian rhythm signal to every other region of your brain and every organ in your body.

Your twenty-four-hour tempo helps to determine when you want to be awake and when you want to be asleep. But it controls other rhythmic patterns, too. These include your timed preferences for eating and drinking, your moods and emotions, the amount of urine you produce,I your core body temperature, your metabolic rate, and the release of numerous hormones. It is no coincidence that the likelihood of breaking an Olympic record has been clearly tied to time of day, being maximal at the natural peak of the human circadian rhythm in the early afternoon. Even the timing of births and deaths demonstrates circadian rhythmicity due to the marked swings in key life-dependent metabolic, cardiovascular, temperature, and hormonal processes that this pacemaker controls.

Long before we discovered this biological pacemaker, an ingenious experiment did something utterly remarkable: stopped time—at least, for a plant. It was in 1729 when French geophysicist Jean-Jacques d’Ortous de Mairan discovered the very first evidence that plants generate their own internal time.

De Mairan was studying the leaf movements of a species that displayed heliotropism: when a plant’s leaves or flowers track the trajectory of the sun as it moves across the sky during the day. De Mairan was intrigued by one plant in particular, called Mimosa pudica.II Not only do the leaves of this plant trace the arching daytime passage of the sun across the sky’s face, but at night, they collapse down, almost as though they had wilted. Then, at the start of the following day, the leaves pop open once again like an umbrella, healthy as ever. This behavior repeats each and every morning and evening, and it caused the famous evolutionary biologist Charles Darwin to call them “sleeping leaves.”

Prior to de Mairan’s experiment, many believed that the expanding and retracting behavior of the plant was solely determined by the corresponding rising and setting of the sun. It was a logical assumption: daylight (even on cloudy days) triggered the leaves to open wide, while ensuing darkness instructed the leaves to shut up shop, close for business, and fold away. That assumption was shattered by de Mairan. First, he took the plant and placed it out in the open, exposing it to the signals of light and dark associated with day and night. As expected, the leaves expanded during the light of day and retracted with the dark of night.

Then came the genius twist. De Mairan placed the plant in a sealed box for the next twenty-four-hour period, plunging it into total dark for both day and night. During these twenty-four hours of blackness, he would occasionally take a peek at the plant in controlled darkness, observing the state of the leaves. Despite being cut off from the influence of light during the day, the plant still behaved as though it were being bathed in sunlight; its leaves were proudly expanded. Then, it retracted its leaves as if on cue at the end of the day, even without the sun’s setting signal, and they stayed collapsed throughout the entire night.

It was a revolutionary discovery: de Mairan had shown that a living organism kept its own time, and was not, in fact, slave to the sun’s rhythmic commands. Somewhere within the plant was a twenty-four-hour rhythm generator that could track time without any cues from the outside world, such as daylight. The plant didn’t just have a circadian rhythm, it had an “endogenous,” or self-generated, rhythm. It is much like your heart drumming out its own self-generating beat. The difference is simply that your heart’s pacemaker rhythm is far faster, usually beating at least once a second, rather than once every twenty-four-hour period like the circadian clock.

Surprisingly, it took another two hundred years to prove that we humans have a similar, internally generated circadian rhythm. But this experiment added something rather unexpected to our understanding of internal timekeeping. It was 1938, and Professor Nathaniel Kleitman at the University of Chicago, accompanied by his research assistant Bruce Richardson, were to perform an even more radical scientific study. It required a type of dedication that is arguably without match or comparison to this day.

Kleitman and Richardson were to be their own experimental guinea pigs. Loaded with food and water for six weeks and a pair of dismantled, high-standing hospital beds, they took a trip into Mammoth Cave in Kentucky, one of the deepest caverns on the planet—so deep, in fact, that no detectable sunlight penetrates its farthest reaches. It was from this darkness that Kleitman and Richardson were to illuminate a striking scientific finding that would define our biological rhythm as being approximately one day (circadian), and not precisely one day.

In addition to food and water, the two men brought a host of measuring devices to assess their body temperatures, as well as their waking and sleeping rhythms. This recording area formed the heart of their living space, flanked either side by their beds. The tall bed legs were each seated in a bucket of water, castle-moat style, to discourage the innumerable small (and not so small) creatures lurking in the depths of Mammoth Cave from joining them in bed.

The experimental question facing Kleitman and Richardson was simple: When cut off from the daily cycle of light and dark, would their biological rhythms of sleep and wakefulness, together with body temperature, become completely erratic, or would they stay the same as those individuals in the outside world exposed to rhythmic daylight? In total, they lasted thirty-two days in complete darkness. Not only did they aggregate some impressive facial hair, but they made two groundbreaking discoveries in the process. The first was that humans, like de Mairan’s heliotrope plants, generated their own endogenous circadian rhythm in the absence of external light from the sun. That is, neither Kleitman nor Richardson descended into random spurts of wake and sleep, but instead expressed a predictable and repeating pattern of prolonged wakefulness (about fifteen hours), paired with consolidated bouts of about nine hours of sleep.

The second unexpected—and more profound—result was that their reliably repeating cycles of wake and sleep were not precisely twenty-four hours in length, but consistently and undeniably longer than twenty-four hours. Richardson, in his twenties, developed a sleep-wake cycle of between twenty-six and twenty-eight hours in length. That of Kleitman, in his forties, was a little closer to, but still longer than, twenty-four hours. Therefore, when removed from the external influence of daylight, the internally generated “day” of each man was not exactly twenty-four hours, but a little more than that. Like an inaccurate wristwatch whose time runs long, with each passing (real) day in the outside world, Kleitman and Richardson began to add time based on their longer, internally generated chronometry.

Since our innate biological rhythm is not precisely twenty-four hours, but thereabouts, a new nomenclature was required: the circadian rhythm—that is, one that is approximately, or around, one day in length, and not precisely one day.III In the seventy-plus years since Kleitman and Richardson’s seminal experiment, we have now determined that the average duration of a human adult’s endogenous circadian clock runs around twenty-four hours and fifteen minutes in length. Not too far off the twenty-four-hour rotation of the Earth, but not the precise timing that any self-respecting Swiss watchmaker would ever accept.

Thankfully, most of us don’t live in Mammoth Cave, or the constant darkness it imposes. We routinely experience light from the sun that comes to the rescue of our imprecise, overrunning internal circadian clock. Sunlight acts like a manipulating finger and thumb on the side-dial of an imprecise wristwatch. The light of the sun methodically resets our inaccurate internal timepiece each and every day, “winding” us back to precisely, not approximately, twenty-four hours.IV

It is no coincidence that the brain uses daylight for this resetting purpose. Daylight is the most reliable, repeating signal that we have in our environment. Since the birth of our planet, and every single day thereafter without fail, the sun has always risen in the morning and set in the evening. Indeed, the reason most living species likely adopted a circadian rhythm is to synchronize themselves and their activities, both internal (e.g., temperature) and external (e.g., feeding), with the daily orbital mechanics of planet Earth spinning on its axis, resulting in regular phases of light (sun facing) and dark (sun hiding).

Yet daylight isn’t the only signal that the brain can latch on to for the purpose of biological clock resetting, though it is the principal and preferential signal, when present. So long as they are reliably repeating, the brain can also use other external cues, such as food, exercise, temperature fluctuations, and even regularly timed social interaction. All of these events have the ability to reset the biological clock, allowing it to strike a precise twenty-four-hour note. It is the reason that individuals with certain forms of blindness do not entirely lose their circadian rhythm. Despite not receiving light cues due to their blindness, other phenomena act as their resetting triggers. Any signal that the brain uses for the purpose of clock resetting is termed a zeitgeber, from the German “time giver” or “synchronizer.” Thus, while light is the most reliable and thus the primary zeitgeber, there are many factors that can be used in addition to, or in the absence of, daylight.

The twenty-four-hour biological clock sitting in the middle of your brain is called the suprachiasmatic (pronounced soo-pra-kai-as-MAT-ik) nucleus. As with much of anatomical language, the name, while far from easy to pronounce, is instructional: supra, meaning above, and chiasm, meaning a crossing point. The crossing point is that of the optic nerves coming from your eyeballs. Those nerves meet in the middle of your brain, and then effectively switch sides. The suprachiasmatic nucleus is located just above this intersection for a good reason. It “samples” the light signal being sent from each eye along the optic nerves as they head toward the back of the brain for visual processing. The suprachiasmatic nucleus uses this reliable light information to reset its inherent time inaccuracy to a crisp twenty-four-hour cycle, preventing any drift.

When I tell you that the suprachiasmatic nucleus is composed of 20,000 brain cells, or neurons, you might assume it is enormous, consuming a vast amount of your cranial space, but actually it is tiny. The brain is composed of approximately 100 billion neurons, making the suprachiasmatic nucleus minuscule in the relative scheme of cerebral matter. Yet despite its stature, the influence of the suprachiasmatic nucleus on the rest of the brain and the body is anything but meek. This tiny clock is the central conductor of life’s biological rhythmic symphony—yours and every other living species. The suprachiasmatic nucleus controls a vast array of behaviors, including our focus in this chapter: when you want to be awake and asleep.

For diurnal species that are active during the day, such as humans, the circadian rhythm activates many brain and body mechanisms in the brain and body during daylight hours that are designed to keep you awake and alert. These processes are then ratcheted down at nighttime, removing that alerting influence. Figure 1 shows one such example of a circadian rhythm—that of your body temperature. It represents average core body temperature (rectal, no less) of a group of human adults. Starting at “12 pm” on the far left, body temperature begins to rise, peaking late in the afternoon. The trajectory then changes. Temperature begins to decline again, dropping below that of the midday start-point as bedtime approaches.

Figure 1: Typical Twenty-Four-Hour Circadian Rhythm (Core Body Temperature)

Your biological circadian rhythm coordinates a drop in core body temperature as you near typical bedtime (figure 1), reaching its nadir, or low point, about two hours after sleep onset. However, this temperature rhythm is not dependent upon whether you are actually asleep. If I were to keep you awake all night, your core body temperature would still show the same pattern. Although the temperature drop helps to initiate sleep, the temperature change itself will rise and fall across the twenty-four-hour period regardless of whether you are awake or asleep. It is a classic demonstration of a preprogrammed circadian rhythm that will repeat over and over without fail, like a metronome. Temperature is just one of many twenty-four-hour rhythms that the suprachiasmatic nucleus governs. Wakefulness and sleep are another. Wakefulness and sleep are therefore under the control of the circadian rhythm, and not the other way around. That is, your circadian rhythm will march up and down every twenty-four hours irrespective of whether you have slept or not. Your circadian rhythm is unwavering in this regard. But look across individuals, and you discover that not everyone’s circadian timing is the same.

MY RHYTHM IS NOT YOUR RHYTHM

Although every human being displays an unyielding twenty-four-hour pattern, the respective peak and trough points are strikingly different from one individual to the next. For some people, their peak of wakefulness arrives early in the day, and their sleepiness trough arrives early at night. These are “morning types,” and make up about 40 percent of the populace. They prefer to wake at or around dawn, are happy to do so, and function optimally at this time of day. Others are “evening types,” and account for approximately 30 percent of the population. They naturally prefer going to bed late and subsequently wake up late the following morning, or even in the afternoon. The remaining 30 percent of people lie somewhere in between morning and evening types, with a slight leaning toward eveningness, like myself.

You may colloquially know these two types of people as “morning larks” and “night owls,” respectively. Unlike morning larks, night owls are frequently incapable of falling asleep early at night, no matter how hard they try. It is only in the early-morning hours that owls can drift off. Having not fallen asleep until late, owls of course strongly dislike waking up early. They are unable to function well at this time, one cause of which is that, despite being “awake,” their brain remains in a more sleep-like state throughout the early morning. This is especially true of a region called the prefrontal cortex, which sits above the eyes, and can be thought of as the head office of the brain. The prefrontal cortex controls high-level thought and logical reasoning, and helps keep our emotions in check. When a night owl is forced to wake up too early, their prefrontal cortex remains in a disabled, “offline” state. Like a cold engine after an early-morning start, it takes a long time before it warms up to operating temperature, and before that will not function efficiently.

An adult’s owlness or larkness, also known as their chronotype, is strongly determined by genetics. If you are a night owl, it’s likely that one (or both) of your parents is a night owl. Sadly, society treats night owls rather unfairly on two counts. First is the label of being lazy, based on a night owl’s wont to wake up later in the day, due to the fact that they did not fall asleep until the early-morning hours. Others (usually morning larks) will chastise night owls on the erroneous assumption that such preferences are a choice, and if they were not so slovenly, they could easily wake up early. However, night owls are not owls by choice. They are bound to a delayed schedule by unavoidable DNA hardwiring. It is not their conscious fault, but rather their genetic fate.

Second is the engrained, un-level playing field of society’s work scheduling, which is strongly biased toward early start times that punish owls and favor larks. Although the situation is improving, standard employment schedules force owls into an unnatural sleep-wake rhythm. Consequently, job performance of owls as a whole is far less optimal in the mornings, and they are further prevented from expressing their true performance potential in the late afternoon and early evening as standard work hours end prior to its arrival. Most unfortunately, owls are more chronically sleep-deprived, having to wake up with the larks, but not being able to fall asleep until far later in the evening. Owls are thus often forced to burn the proverbial candle at both ends. Greater ill health caused by a lack of sleep therefore befalls owls, including higher rates of depression, anxiety, diabetes, cancer, heart attack, and stroke.

In this regard, a societal change is needed, offering accommodations not dissimilar to those we make for other physically determined differences (e.g., sight impaired). We require more supple work schedules that better adapt to all chronotypes, and not just one in its extreme.

You may be wondering why Mother Nature would program this variability across people. As a social species, should we not all be synchronized and therefore awake at the same time to promote maximal human interactions? Perhaps not. As we’ll discover later in this book, humans likely evolved to co-sleep as families or even whole tribes, not alone or as couples. Appreciating this evolutionary context, the benefits of such genetically programmed variation in sleep/wake timing preferences can be understood. The night owls in the group would not be going to sleep until one or two a.m., and not waking until nine or ten a.m. The morning larks, on the other hand, would have retired for the night at nine p.m. and woken at five a.m. Consequently, the group as a whole is only collectively vulnerable (i.e., every person asleep) for just four rather than eight hours, despite everyone still getting the chance for eight hours of sleep. That’s potentially a 50 percent increase in survival fitness. Mother Nature would never pass on a biological trait—here, the useful variability in when individuals within a collective tribe go to sleep and wake up—that could enhance the survival safety and thus fitness of a species by this amount. And so she hasn’t.

MELATONIN

Your suprachiasmatic nucleus communicates its repeating signal of night and day to your brain and body using a circulating messenger called melatonin. Melatonin has other names, too. These include “the hormone of darkness” and “the vampire hormone.” Not because it is sinister, but simply because melatonin is released at night. Instructed by the suprachiasmatic nucleus, the rise in melatonin begins soon after dusk, being released into the bloodstream from the pineal gland, an area situated deep in the back of your brain. Melatonin acts like a powerful bullhorn, shouting out a clear message to the brain and body: “It’s dark, it’s dark!” At this moment, we have been served a writ of nightime, and with it, a biological command for the timing of sleep onset.V

In this way, melatonin helps regulate the timing of when sleep occurs by systemically signaling darkness throughout the organism. But melatonin has little influence on the generation of sleep itself: a mistaken assumption that many people hold. To make clear this distinction, think of sleep as the Olympic 100-meter race. Melatonin is the voice of the timing official that says “Runners, on your mark,” and then fires the starting pistol that triggers the race. That timing official (melatonin) governs when the race (sleep) begins, but does not participate in the race. In this analogy, the sprinters themselves are other brain regions and processes that actively generate sleep. Melatonin corrals these sleep-generating regions of the brain to the starting line of bedtime. Melatonin simply provides the official instruction to commence the event of sleep, but does not participate in the sleep race itself.

For these reasons, melatonin is not a powerful sleeping aid in and of itself, at least not for healthy, non-jet-lagged individuals (we’ll explore jet lag—and how melatonin can be helpful—in a moment). There may be little, if any, quality melatonin in the pill. That said, there is a significant sleep placebo effect of melatonin, which should not be underestimated: the placebo effect is, after all, the most reliable effect in all of pharmacology. Equally important to realize is the fact that over-the-counter melatonin is not commonly regulated by governing bodies around the world, such as the US Food and Drug Administration (FDA). Scientific evaluations of over-the-counter brands have found melatonin concentrations that range from 83 percent less than that claimed on the label, to 478 percent more than that stated.VI

Once sleep is under way, melatonin slowly decreases in concentration across the night and into the morning hours. With dawn, as sunlight enters the brain through the eyes (even through the closed lids), a brake pedal is applied to the pineal gland, thereby shutting off the release of melatonin. The absence of circulating melatonin now informs the brain and body that the finish line of sleep has been reached. It is time to call the race of sleep over and allow active wakefulness to return for the rest of the day. In this regard, we human beings are “solar powered.” Then, as light fades, so, too, does the solar brake pedal blocking melatonin. As melatonin rises, another phase of darkness is signaled and another sleep event is called to the starting line.

You can see a typical profile of melatonin release in figure 2. It starts a few hours after dusk. Then it rapidly rises, peaking around four a.m. Thereafter, it begins to drop as dawn approaches, falling to levels that are undetectable by early to midmorning.

Figure 2: The Cycle of Melatonin

HAVE RHYTHM, WON’T TRAVEL

The advent of the jet engine was a revolution for the mass transit of human beings around the planet. However, it created an unforeseen biological calamity: jet planes offered the ability to speed through time zones faster than our twenty-four-hour internal clocks could ever keep up with or adjust to. Those jets caused a biological time lag: jet lag. As a result, we feel tired and sleepy during the day in a distant time zone because our internal clock still thinks it is nighttime. It hasn’t yet caught up. If that were not bad enough, at night, we are frequently unable to initiate or maintain sleep because our internal clock now believes it to be daytime.

Take the example of my recent flight home to England from San Francisco. London is eight hours ahead of San Francisco. When I arrive in England, despite the digital clock in London’s Heathrow Airport telling me it is nine a.m., my internal circadian clock is registering a very different time—California time, which is one a.m. I should be fast asleep. I will drag my time-lagged brain and body through the London day in a state of deep lethargy. Every aspect of my biology is demanding sleep; sleep that most people back in California are being swaddled in at this time.

The worst, however, is yet to come. By midnight London time, I am in bed, tired and wanting to fall asleep. But unlike most people in London, I can’t seem to drift off. Though it is midnight in London, my internal biological clock believes it to be four p.m., which it is in California. I would normally be wide awake, and so I am, lying in bed in London. It will be five or six hours before my natural tendency to fall asleep arrives . . . just as London is starting to wake up, and I have to give a public lecture. What a mess.

This is jet lag: you feel tired and sleepy during the day in the new time zone because your body clock and associated biology still “think” it is nighttime. At night, you are frequently unable to sleep solidly because your biological rhythm still believes it to be daytime.

Fortunately, my brain and body will not stay in this mismatched limbo forever. I will acclimatize to London time by way of the sunlight signals in the new location. But it’s a slow process. For every day you are in a different time zone, your suprachiasmatic nucleus can only readjust by about one hour. It therefore took me about eight days to readjust to London time after having been in San Francisco, since London is eight hours ahead of San Francisco. Sadly, after such epic efforts by my suprachiasmatic nucleus’s twenty-four-hour clock to drag itself forward in time and get settled in London, it faces some depressing news: I now have to fly back to San Francisco after nine days. My poor biological clock has to suffer this struggle all over again in the reverse direction!

You may have noticed that it feels harder to acclimate to a new time zone when traveling eastward than when flying westward. There are two reasons for this. First, the eastward direction requires that you fall asleep earlier than you would normally, which is a tall biological order for the mind to simply will into action. In contrast, the westward direction requires you to stay up later, which is a consciously and pragmatically easier prospect. Second, you will remember that when shut off from any outside world influences, our natural circadian rhythm is innately longer than one day—about twenty-four hours and fifteen minutes. Modest as this may be, this makes it somewhat easier for you to artificially stretch a day than shrink it. When you travel westward—in the direction of your innately longer internal clock—that “day” is longer than twenty-four hours for you and why it feels a little easier to accommodate to. Eastward travel, however, which involves a “day” that is shorter in length for you than twenty-four hours, goes against the grain of your innately long internal rhythm to start with, which is why it is rather harder to do.

West or east, jet lag still places a torturous physiological strain on the brain, and a deep biological stress upon the cells, organs, and major systems of the body. And there are consequences. Scientists have studied airplane cabin crews who frequently fly on long-haul routes and have little chance to recover. Two alarming results have emerged. First, parts of their brains—specifically those related to learning and memory—had physically shrunk, suggesting the destruction of brain cells caused by the biological stress of time-zone travel. Second, their short-term memory was significantly impaired. They were considerably more forgetful than individuals of similar age and background who did not frequently travel through time zones. Other studies of pilots, cabin crew members, and shift workers have reported additionally disquieting consequences, including far higher rates of cancer and type 2 diabetes than the general population—or even carefully controlled match individuals who do not travel as much.

Based on these deleterious effects, you can appreciate why some people faced with frequent jet lag, including airline pilots and cabin crew, would want to limit such misery. Often, they choose to take melatonin pills in an attempt to help with the problem. Recall my flight from San Francisco to London. After arriving that day, I had real difficulty getting to sleep and staying asleep that night. In part, this was because melatonin was not being released during my nighttime in London. My melatonin rise was still many hours away, back on California time. But let’s imagine that I was going to use a legitimate compound of melatonin after arriving in London. Here’s how it works: at around seven to eight p.m. London time I would take a melatonin pill, triggering an artificial rise in circulating melatonin that mimics the natural melatonin spike currently occurring in most of the people in London. As a consequence, my brain is fooled into believing it’s nighttime, and with that chemically induced trick comes the signaled timing of the sleep race. It will still be a struggle to generate the event of sleep itself at this irregular time (for me), but the timing signal does significantly increase the likelihood of sleep in this jet-lagged context.

SLEEP PRESSURE AND CAFFEINE

Your twenty-four-hour circadian rhythm is the first of the two factors determining wake and sleep. The second is sleep pressure. At this very moment, a chemical called adenosine is building up in your brain. It will continue to increase in concentration with every waking minute that elapses. The longer you are awake, the more adenosine will accumulate. Think of adenosine as a chemical barometer that continuously registers the amount of elapsed time since you woke up this morning.

One consequence of increasing adenosine in the brain is an increasing desire to sleep. This is known as sleep pressure, and it is the second force that will determine when you feel sleepy, and thus should go to bed. Using a clever dual-action effect, high concentrations of adenosine simultaneously turn down the “volume” of wake-promoting regions in the brain and turn up the dial on sleep-inducing regions. As a result of that chemical sleep pressure, when adenosine concentrations peak, an irresistible urge for slumber will take hold.VII It happens to most people after twelve to sixteen hours of being awake.

You can, however, artificially mute the sleep signal of adenosine by using a chemical that makes you feel more alert and awake: caffeine. Caffeine is not a food supplement. Rather, caffeine is the most widely used (and abused) psychoactive stimulant in the world. It is the second most traded commodity on the planet, after oil. The consumption of caffeine represents one of the longest and largest unsupervised drug studies ever conducted on the human race, perhaps rivaled only by alcohol, and it continues to this day.

Caffeine works by successfully battling with adenosine for the privilege of latching on to adenosine welcome sites—or receptors—in the brain. Once caffeine occupies these receptors, however, it does not stimulate them like adenosine, making you sleepy. Rather, caffeine blocks and effectively inactivates the receptors, acting as a masking agent. It’s the equivalent of sticking your fingers in your ears to shut out a sound. By hijacking and occupying these receptors, caffeine blocks the sleepiness signal normally communicated to the brain by adenosine. The upshot: caffeine tricks you into feeling alert and awake, despite the high levels of adenosine that would otherwise seduce you into sleep.

Levels of circulating caffeine peak approximately thirty minutes after oral administration. What is problematic, though, is the persistence of caffeine in your system. In pharmacology, we use the term “half-life” when discussing a drug’s efficacy. This simply refers to the length of time it takes for the body to remove 50 percent of a drug’s concentration. Caffeine has an average half-life of five to seven hours. Let’s say that you have a cup of coffee after your evening dinner, around 7:30 p.m. This means that by 1:30 a.m., 50 percent of that caffeine may still be active and circulating throughout your brain tissue. In other words, by 1:30 a.m., you’re only halfway to completing the job of cleansing your brain of the caffeine you drank after dinner.

There’s nothing benign about that 50 percent mark, either. Half a shot of caffeine is still plenty powerful, and much more decomposition work lies ahead throughout the night before caffeine disappears. Sleep will not come easily or be smooth throughout the night as your brain continues its battle against the opposing force of caffeine. Most people do not realize how long it takes to overcome a single dose of caffeine, and therefore fail to make the link between the bad night of sleep we wake from in the morning and the cup of coffee we had ten hours earlier with dinner.

Caffeine—which is not only prevalent in coffee, certain teas, and many energy drinks, but also foods such as dark chocolate and ice cream, as well as drugs such as weight-loss pills and pain relievers—is one of the most common culprits that keep people from falling asleep easily and sleeping soundly thereafter, typically masquerading as insomnia, an actual medical condition. Also be aware that de-caffeinated does not mean non-caffeinated. One cup of decaf usually contains 15 to 30 percent of the dose of a regular cup of coffee, which is far from caffeine-free. Should you drink three to four cups of decaf in the evening, it is just as damaging to your sleep as one regular cup of coffee.

The “jolt” of caffeine does wear off. Caffeine is removed from your system by an enzyme within your liver,VIII which gradually degrades it over time. Based in large part on genetics,IX some people have a more efficient version of the enzyme that degrades caffeine, allowing the liver to rapidly clear it from the bloodstream. These rare individuals can drink an espresso with dinner and fall fast asleep at midnight without a problem. Others, however, have a slower-acting version of the enzyme. It takes far longer for their system to eliminate the same amount of caffeine. As a result, they are very sensitive to caffeine’s effects. One cup of tea or coffee in the morning will last much of the day, and should they have a second cup, even early in the afternoon, they will find it difficult to fall asleep in the evening. Aging also alters the speed of caffeine clearance: the older we are, the longer it takes our brain and body to remove caffeine, and thus the more sensitive we become in later life to caffeine’s sleep-disrupting influence.

If you are trying to stay awake late into the night by drinking coffee, you should be prepared for a nasty consequence when your liver successfully evicts the caffeine from your system: a phenomenon commonly known as a “caffeine crash.” Like the batteries running down on a toy robot, your energy levels plummet rapidly. You find it difficult to function and concentrate, with a strong sense of sleepiness once again.

We now understand why. For the entire time that caffeine is in your system, the sleepiness chemical it blocks (adenosine) nevertheless continues to build up. Your brain is not aware of this rising tide of sleep-encouraging adenosine, however, because the wall of caffeine you’ve created is holding it back from your perception. But once your liver dismantles that barricade of caffeine, you feel a vicious backlash: you are hit with the sleepiness you had experienced two or three hours ago before you drank that cup coffee plus all the extra adenosine that has accumulated in the hours in between, impatiently waiting for caffeine to leave. When the receptors become vacant by way of caffeine decomposition, adenosine rushes back in and smothers the receptors. When this happens, you are assaulted with a most forceful adenosine-trigger urge to sleep—the aforementioned caffeine crash. Unless you consume even more caffeine to push back against the weight of adenosine, which would start a dependency cycle, you are going to find it very, very difficult to remain awake.

To impress upon you the effects of caffeine, I footnote esoteric research conducted in the 1980s by NASA. Their scientists exposed spiders to different drugs and then observed the webs that they constructed.X Those drugs included LSD, speed (amphetamine), marijuana, and caffeine. The results, which speak for themselves, can be observed in figure 3. The researchers noted how strikingly incapable the spiders were in constructing anything resembling a normal or logical web that would be of any functional use when given caffeine, even relative to other potent drugs tested.

Figure 3: Effects of Various Drugs on Spider Web Building

It is worth pointing out that caffeine is a stimulant drug. Caffeine is also the only addictive substance that we readily give to our children and teens—the consequences of which we will return to later in the book.

IN STEP, OUT OF STEP

Setting caffeine aside for a moment, you may have assumed that the two governing forces that regulate your sleep—the twenty-four-hour circadian rhythm of the suprachiasmatic nucleus and the sleep-pressure signal of adenosine—communicate with each other so as to unite their influences. In actual fact, they don’t. They are two distinct and separate systems that are ignorant of each other. They are not coupled; though, they are usually aligned.

Figure 4 encompasses forty-eight hours of time from left to right—two days and two nights. The dotted line in the figure is the circadian rhythm, also known as Process-C. Like a sine wave, it reliably and repeatedly rises and falls, and then rises and falls once more. Starting on the far left of the figure, the circadian rhythm begins to increase its activity a few hours before you wake up. It infuses the brain and body with an alerting energy signal. Think of it like a rousing marching band approaching from a distance. At first, the signal is faint, but gradually it builds, and builds, and builds with time. By early afternoon in most healthy adults, the activating signal from the circadian rhythm peaks.

Figure 4: The Two Factors Regulating Sleep and Wakefulness

Now let us consider what is happening to the other sleep-controlling factor: adenosine. Adenosine creates a pressure to sleep, also known as Process-S. Represented by the solid line in figure 4, the longer you are awake, the more adenosine builds up, creating an increasing urge (pressure) to sleep. By mid- to late morning, you have only been awake for a handful of hours. As a result, adenosine concentrations have increased only a little. Furthermore, the circadian rhythm is on its powerful upswing of alertness. This combination of strong activating output from the circadian rhythm together with low levels of adenosine result in a delightful sensation of being wide awake. (Or at least it should, so long as your sleep was of good quality and sufficient length the night before. If you feel as though you could fall asleep easily midmorning, you are very likely not getting enough sleep, or the quality of your sleep is insufficient.) The distance between the curved lines above will be a direct reflection of your desire to sleep. The larger the distance between the two, the greater your sleep desire.

For example, at eleven a.m., after having woken up at eight a.m., there is only a small distance between the dotted line (circadian rhythm) and solid line (sleep pressure), illustrated by the vertical double arrow in figure 5. This minimal difference means there is a weak sleep drive, and a strong urge to be awake and alert.

Figure 5: The Urge to Be Awake

However, by eleven p.m. it’s a very different situation, as illustrated in figure 6. You’ve now been awake for fifteen hours and your brain is drenched in high concentrations of adenosine (note how the solid line in the figure has risen sharply). In addition, the dotted line of the circadian rhythm is descending, powering down your activity and alertness levels. As a result, the difference between the two lines has grown large, reflected in the long vertical double arrow in figure 6. This powerful combination of abundant adenosine (high sleep pressure) and declining circadian rhythm (lowered activity levels) triggers a strong desire for sleep.

Figure 6: The Urge to Sleep

What happens to all of the accumulated adenosine once you do fall asleep? During sleep, a mass evacuation gets under way as the brain has the chance to degrade and remove the day’s adenosine. Across the night, sleep lifts the heavy weight of sleep pressure, lightening the adenosine load. After approximately eight hours of healthy sleep in an adult, the adenosine purge is complete. Just as this process is ending, the marching band of your circadian activity rhythm has fortuitously returned, and its energizing influence starts to approach. When these two processes trade places in the morning hours, wherein adenosine has been removed and the rousing volume of the circadian rhythm is becoming louder (indicated by the meeting of the two lines in figure 6), we naturally wake up (seven a.m. on day two, in the figure example). Following that full night of sleep, you are now ready to face another sixteen hours of wakefulness with physical vigor and sharp brain function.

INDEPENDENCE DAY, AND NIGHT

Have you ever pulled an “all-nighter”—forgoing sleep and remaining awake throughout the following day? If you have, and can remember much of anything about it, you may recall that there were times when you felt truly miserable and sleepy, yet there were other moments when, despite having been awake for longer, you paradoxically felt more alert. Why? I don’t advise anyone to conduct this self-experiment, but assessing a person’s alertness across twenty-four hours of total sleep deprivation is one way that scientists can demonstrate that the two forces determining when you want to be awake and asleep—the twenty-four-hour circadian rhythm and the sleepiness signal of adenosine—are independent, and can be decoupled from their normal lockstep.

Let’s consider figure 7, showing the same forty-eight-hour slice of time and the two factors in question: the twenty-four-hour circadian rhythm and the sleep pressure signal of adenosine, and how much distance there is between them. In this scenario, our volunteer is going to stay awake all night and all day. As the night of sleep deprivation marches forward, the sleep pressure of adenosine (upper line) rises progressively, like the rising water level in a plugged sink when a faucet has been left on. It will not decline across the night. It cannot, since sleep is absent.

Figure 7: The Ebb and Flow of Sleep Deprivation

By remaining awake, and blocking access to the adenosine drain that sleep opens up, the brain is unable to rid itself of the chemical sleep pressure. The mounting adenosine levels continue to rise. This should mean that the longer you are awake, the sleepier you feel. But that’s not true. Though you will feel increasingly sleepy throughout the nighttime phase, hitting a low point in your alertness around five to six a.m., thereafter, you’ll catch a second wind. How is this possible when adenosine levels and corresponding sleep pressure continue to increase?

The answer resides with your twenty-four-hour circadian rhythm, which offers a brief period of salvation from sleepiness. Unlike sleep pressure, your circadian rhythm pays no attention to whether you are asleep or awake. Its slow, rhythmic countenance continues to fall and rise strictly on the basis of what time of night or day it is. No matter what state of adenosine sleepiness pressure exists within the brain, the twenty-four-hour circadian rhythm cycles on as per usual, oblivious to your ongoing lack of sleep.

If you look at figure 7 once again, the graveyard-shift misery you experience around six a.m. can be explained by the combination of high adenosine sleep pressure and your circadian rhythm reaching its lowest point. The vertical distance separating these two lines at three a.m. is large, indicated by the first vertical arrow in the figure. But if you can make it past this alertness low point, you’re in for a rally. The morning rise of the circadian rhythm comes to your rescue, marshaling an alerting boost throughout the morning that temporarily offsets the rising levels of adenosine sleep pressure. As your circadian rhythm hits its peak around eleven a.m., the vertical distance between the two respective lines in figure 7 has been decreased.

The upshot is that you will feel much less sleepy at eleven a.m. than you did at three a.m., despite being awake for longer. Sadly, this second wind doesn’t last. As the afternoon lumbers on, the circadian rhythm begins to decline as the escalating adenosine piles on the sleep pressure. Come late afternoon and early evening, any temporary alertness boost has been lost. You are hit by the full force of an immense adenosine sleep pressure. By nine p.m., there exists a towering vertical distance between the two lines in figure 7. Short of intravenous caffeine or amphetamine, sleep will have its way, wrestling your brain from the now weak grip of blurry wakefulness, blanketing you in slumber.

AM I GETTING ENOUGH SLEEP?

Setting aside the extreme case of sleep deprivation, how do you know whether you’re routinely getting enough sleep? While a clinical sleep assessment is needed to thoroughly address this issue, an easy rule of thumb is to answer two simple questions. First, after waking up in the morning, could you fall back asleep at ten or eleven a.m.? If the answer is “yes,” you are likely not getting sufficient sleep quantity and/or quality. Second, can you function optimally without caffeine before noon? If the answer is “no,” then you are most likely self-medicating your state of chronic sleep deprivation.

Both of these signs you should take seriously and seek to address your sleep deficiency. They are topics, and a question, that we will cover in depth in chapters 13 and 14 when we speak about the factors that prevent and harm your sleep, as well as insomnia and effective treatments. In general, these un-refreshed feelings that compel a person to fall back asleep midmorning, or require the boosting of alertness with caffeine, are usually due to individuals not giving themselves adequate sleep opportunity time—at least eight or nine hours in bed. When you don’t get enough sleep, one consequence among many is that adenosine concentrations remain too high. Like an outstanding debt on a loan, come the morning, some quantity of yesterday’s adenosine remains. You then carry that outstanding sleepiness balance throughout the following day. Also like a loan in arrears, this sleep debt will continue to accumulate. You cannot hide from it. The debt will roll over into the next payment cycle, and the next, and the next, producing a condition of prolonged, chronic sleep deprivation from one day to another. This outstanding sleep obligation results in a feeling of chronic fatigue, manifesting in many forms of mental and physical ailments that are now rife throughout industrialized nations.

Other questions that can draw out signs of insufficient sleep are: If you didn’t set an alarm clock, would you sleep past that time? (If so, you need more sleep than you are giving yourself.) Do you find yourself at your computer screen reading and then rereading (and perhaps rereading again) the same sentence? (This is often a sign of a fatigued, under-slept brain.) Do you sometimes forget what color the last few traffic lights were while driving? (Simple distraction is often the cause, but a lack of sleep is very much another culprit.)

Of course, even if you are giving yourself plenty of time to get a full night of shut-eye, next-day fatigue and sleepiness can still occur because you are suffering from an undiagnosed sleep disorder, of which there are now more than a hundred. The most common is insomnia, followed by sleep-disordered breathing, or sleep apnea, which includes heavy snoring. Should you suspect your sleep or that of anyone else to be disordered, resulting in daytime fatigue, impairment, or distress, speak to your doctor immediately and seek a referral to a sleep specialist. Most important in this regard: do not seek sleeping pills as your first option. You will realize why I say this come chapter 14, but please feel free to skip right to the section on sleeping pills in that chapter if you are a current user, or considering using sleeping pills in the immediate future.

In the event it helps, I have provided a link to a questionnaire that has been developed by sleep researchers that will allow you to determine your degree of sleep fulfillment.XI Called SATED, it is easy to complete, and contains only five simple questions.

I. I should note, from personal experience, that this is a winning fact to dispense at dinner parties, family gatherings, or other such social occasions. It will almost guarantee nobody will approach or speak to you again for the rest of the evening, and you’ll also never be invited back.

II. The word pudica is from the Latin meaning “shy” or “bashful,” since the leaves will also collapse down if you touch or stroke them.

III. This phenomenon of an imprecise internal biological clock has now been consistently observed in many different species. However, it is not consistently long in all species, as it is in humans. For some, the endogenous circadian rhythm runs short, being less than twenty-four hours when placed in total darkness, such as hamsters or squirrels. For others, such as humans, it is longer than twenty-four hours.