Sleep
"When you have insomnia, you're never really asleep, and you're never really awake."
- From the movie Fight Club
Everyone experiences sleep deprivation now and again but an unhappy subset of these people additionally suffer from a symptom of severe sleep deprivation called insomnia; full-blown insomnia is defined by difficulty with one or more of falling asleep, maintaining sleep, waking up too early, or non-restorative sleep despite adequate opportunities to do so that results in daytime impairment, and the difficulty must occur at least three times a week for one month or longer (1). Insomnia denotes that the human body is conflicted; instead of being either asleep or awake, it tries to be both asleep and awake. Since it is impossible to do both concurrently, the result is a sort of "walking dead" predicament - never really asleep, never really awake.
Sleep deprivation heralds many negative sequelae including fatigue, reduced immune function, impaired perception, difficulty concentrating, worsened memory, slowed reaction times, heightened aggressiveness, and an increased rate of errors and accidents (2). Regarding that last point, a prospective, randomized study looking at the effects of sleep deprivation in medical training showed that interns working a traditional schedule made 36% more serious medical errors compared to interns under a schedule that included more sleep (3), and one rather large study looking at motor vehicle accidents showed that 20% of them resulted from driver sleepiness (4). In addition to these sequelae of sleep deprivation, people with full-blown insomnia additionally suffer from reduced pain tolerance, an increased risk of diabetes and cardiovascular disease, and psychiatric conditions (2). It has been estimated that a whopping 40% of insomniacs have a coexisting psychiatric condition, depression and anxiety disorders being the most common (5).
Sleep deprivation is global. Its prevalence depends upon the population studied, but survey results across many different countries show that 30-40% of all adults report experiencing semi-regular difficulties in one or more of falling asleep, staying asleep, waking up too early, or non-restorative sleep resulting in daytime sleepiness (1,6,7) indicating that billions of people are semi-regularly sleep deprived. The prevalence of specific insomnia disorders is 5-10% (1,8,9) indicating that hundreds of millions of people suffer from full-blown insomnia.
Sleep deprivation and insomnia are clearly bad and afflict far too many people. So the million-dollar question is "How do we treat them?" To answer this question we must first understand normal sleep and the reason it evolved.
Purpose Of Sleep
Many studies define sleep as a natural and reversible state of reduced responsiveness and relative inactivity (10,11). Sleep in mammals consists of two core stages, non-rapid eye movement (NREM) sleep (absent eye movements, reduced muscle tone, and thought-like dreams) and rapid eye movement (REM) sleep (rapid eye movements, absent muscle tone, and emotionally laden dreams). On an electroencephalogram (EEG), NREM sleep is hallmarked by slow, high-amplitude oscillations whereas REM sleep differs considerably and is characterized by fast, low-amplitude oscillations similar to quiet wakefulness (10).
Sleep is vital. If it were not, one would expect to find animals that do not sleep; since sleep makes an animal vulnerable to predators, evolution would have selected against it long ago unless it served an essential function. Yet there is no strong evidence of any animal that does not sleep (11), although not every animal sleeps in the same way. Dolphins move continuously, yet are capable of unihemispheric sleep whereby they put half of the brain to sleep at a time and sleep in a stereotyped circular manner with one eye open so that they can detect threats and periodically surface for air (11,12). Mallard ducks also engage in unihemispheric sleep; ducks located on the edge of a group keep the open eye directed outwards to detect predators (13). Sleep behaviour has been shown in all vertebrate classes including reptiles, amphibians, and fishes as well as many invertebrates, such as insects and worms (14,15,16,17,18,19).
If sleep serves an essential purpose that cannot be eliminated by evolution, what is it? There are many theories. Some are unlikely and only worth mentioning in passing. Some are more substantial and worth contemplating.
We'll discuss some of the unlikely theories first. In the energy conservation theory, sleep is submitted to be a means of saving energy (20). However, sleep only marginally decreases metabolism by 5-10% (14,21) while hibernating animals such as bears can drop their metabolic rates by as much as 75% (22), yet bears still need to go into rebound sleep after the hibernation period which suggests that they need sleep for something other than energy conservation. The preservation theory posits that sleep protects an animal during the night, when being awake and roaming around might place them at great risk (23). However, a sedentary non-sleeping animal can achieve the same thing. Moreover, carnivores on the top of the food chain sleep the most - for example, adult male lions sleep up to twenty hours a day (24) but they aren't threatened by much, so all that sleep must be needed for something else. Finally, the restitution theory proposes that sleep is a time of total body growth and repair, the key argument of which is the observation that hormones released during sleep such as growth hormone, prolactin, and testosterone exhibit predominantly anabolic functions whereas hormones released during wakefulness such as cortisol are predominantly catabolic (25). However, since this theory was proposed it has been shown that human total body protein synthesis is actually greater during wakefulness than sleep (26), and it is more affected by feeding than by anything else (27), so this theory also fails to explain sleep's purpose.
There are three theories with more grit to them. They relate sleep to the immune system and brain.
(1) Immune Function Theory.
Sleep and immunity are tightly linked - sleep loss impairs immune function, and immune challenge alters sleep (28). Many studies have shown that sleep deprivation impairs the immune system. In rats, sleep restriction for 21 days significantly reduces spleen weight and total white blood cell numbers compared to a control group (29), and rats totally sleep deprived develop bacterial infections within days followed by overwhelming infections and death after a few weeks (30). An analysis of 26 mammalian species showed that those with more total sleep have higher numbers of white blood cells but not red blood cells, and a further analysis of twelve species revealed that a ten hour increase in sleep results in a massive 24-fold reduction in parasitism (31). In addition to sleep deprivation impairing the immune system, the reverse association is also true, that immune challenges affect sleep - for example, rabbits infected by live bacteria show altered sleep patterns over the next two days (32). These observations suggest that sleep is involved in regulating the effectiveness of the immune system.
(2) Waste Clearance Theory.
In the human brain, metabolic waste products such as amyloid proteins accumulate during wakefulness and must be removed lest they reach toxic levels (33). They are removed by a waste clearance pathway called the glymphatic system which consists of a route for cerebrospinal fluid to enter brain tissue, coupled to a clearance mechanism for the removal of interstitial fluid and its metabolic waste products. Sleep is associated with a 60% increase in the interstitial space volume, resulting in a striking increase in the removal of waste products from the brain (33), especially in the lateral sleeping position (34). If the brain remained awake at all times then its metabolic waste products would reach toxic levels resulting in death, so sleep may have evolved to regulate this process.
(3) Neural Reorganization Theory.
Many people believe that sleep is the price paid by the brain for its neuroplasticity, which is its ability to reorganize neural networks in the creation and modification of memories (35). In humans, many studies have shown that sleep deprivation significantly impairs attention and working memory (36,37,38). However, it also impairs long-term memory consolidation, a process that occurs during sleep and involves the transfer of memories of actual experiences from the hippocampus into the neocortex for long-term storage; during long-term memory consolidation, the critical "gist" of a memory is retained while the details are forgotten (36). Many studies have shown that sleep deprivation impairs long-term memory (37) whereas sleep after learning improves long-term memory (36). Furthermore, sleep deprivation impairs stress adaptation - in humans subjected to a stressful experience, restricting REM sleep results in greater anxiety and emotionality compared to control groups (39,40). These observations all suggest that sleep is crucially involved in reorganizing the neural networks of the brain.
Taken together, the immune function theory, waste clearance theory, and neural reorganization theory all hold merit, suggesting that the purpose of sleep is to calibrate the immune system and brain against past waking experiences so that these two systems remain effective during future waking experiences. Thus, when the animal is awake, much of its finite energy reserves are devoted to using the immune system and brain so that it may survive and interact in the world during the present, and when the animal is asleep, much of its energy reserves are devoted to calibrating the immune system and brain so that it may become better at surviving and interacting in the world in the future.
Restoration Of Sleep
The goal of sleep restoration is the establishment of regular, nocturnal sleep periods of sufficient duration and quality such that the symptoms of sleep deprivation are eradicated. First, sleep should be nocturnal, which means no shift work during the night - many studies have shown positive associations between shift work and chronic diseases such as diabetes, cardiovascular disease, and cancer (41,42,43), and while a specific conclusion cannot yet be drawn the strength of the evidence prompted the International Agency for Cancer Research to classify shift work as a probable carcinogen in 2007 (44). Second, the ideal sleep duration for most people is seven to eight hours - sleep of less than six hours or more than nine hours is associated with a modestly increased risk of diabetes, cardiovascular disease, and mortality (45,46). Third, sleep should be of high enough quality that one wakes up feeling refreshed - poorer self-reported sleep quality is associated with a slight increase in mortality (47).
Sleep deprivation and insomnia are clearly associated with problems at night, but certain activities during the day may also help or hinder sleep. Therefore the best approach to sleep restoration includes not only bedtime strategies, but daytime strategies too.
Following are my top four bedtime strategies for restoring sleep, in sequential order.
(1) Reduce artificial light sources one hour before bedtime.
Darkness is best for sleep, but it has been banished by artificial light over the last two centuries. In 1792, the engineer and inventor William Murdoch first used coal gas to light his house and in 1879, the inventor Thomas Edison's electric light bulbs first illuminated a New York street followed by the modern era of electric lighting (44). Humans are now so inundated with artificial light that when a 1994 earthquake knocked out the power in Los Angeles, many anxious residents called local emergency centers to report seeing a strange “giant, silvery cloud” in the dark sky. What they were seeing, for the first time, was the Milky Way Galaxy, long obliterated by the urban sky glow (44). Exposure to room light before bedtime suppresses the level of melatonin, a hormone released during the biological night that anticipates darkness and sleep, compared to dim light (48). While dimming the lights in the evening is ideal it may not be practical, so a viable alternative is to wear amber-lensed glasses which preferentially block melatonin-suppressing blue light and have been proven to improve sleep quality and mood in a randomized trial (49). The brightness of a television or a computer screen also interferes with melatonin release (50) and it has been shown that watching television before bedtime, or even just having a television in the bedroom, negatively impacts sleep in children (51). Therefore wear amber-lensed glasses, turn off the television, and put away the computer one hour before bedtime.
(2) Drink tart cherry juice 30 minutes before bedtime.
There is only one food that has been shown to unequivocally benefit sleep - tart cherry juice, which is naturally and stratospherically high in melatonin, particularly Montmorency cherries. In a randomized, placebo-controlled trial it was shown that eight ounces of cherry juice twice a day over two weeks significantly increased melatonin levels, reduced napping, and increased sleep time and efficiency in the experimental group compared to the control group (52). Many other studies suggest that small protein or carbohydrate meals half an hour before bedtime may benefit sleep and have positive effects on weight and cardiometabolic parameters (53,54,55), but the evidence is not as strong as it is for tart cherry juice. There are also those who swear by small fat meals to improve sleep (56), but again the evidence is lacking. Therefore drink tart cherry juice 30 minutes before bedtime.
(3) Lower the body and room temperature right before bedtime.
Cooler temperatures are best for sleep. It is well established that sleep onset is most likely to occur when the core body temperature is declining at its maximum rate (57). Perhaps for this reason, a cold shower before bed can enhance sleep quality (53). Moreover, heat exposure decreases both NREM sleep and REM sleep throughout the night (58). Assuming that one is wearing pajamas and is covered by at least one sheet, the ideal temperature for sleep is 16-19 degrees Celsius (53,59). Therefore skip the hot bath, take a cold shower, and set the room temperature to 16-19 degrees Celsius right before bedtime.
(4) Replace distracting noises with peaceful ambient noises at bedtime.
Peaceful ambient noises are beneficial for sleep as they mask the perception of distracting night-time noises. Even at low exposure levels, night-time noises such as traffic and voices induce sleep arousals and are associated with cardiovascular disease and stroke in the elderly (60). Possibly the worst offenders in this category are mobile phones, with high mobile phone use associated with sleep disturbances and symptoms of depression among young adults (61). Peaceful ambient noises include music and white noise. It has been shown that 45 minutes of listening to relaxing music such as classical music before sleep significantly improves sleep quality and reduces depressive symptoms compared to control groups in young adults (62). Exposure to white noise, which is any low intensity, consistently random sound such as a rushing waterfall or wind blowing through trees has been proven to induce sleep in neonates (63) and improve sleep quality in adults after surgery (64). Therefore ditch the phone and listen to relaxing music or white noise at bedtime.
Following are my top four daytime strategies for restoring sleep, in sequential order.
(1) Get bright light, especially in the morning.
Bright light in the morning is good for sleep as it appears to regularize one's circadian rhythms. Sunlight is great but may not be available depending on the weather. Two studies have demonstrated that exposure to artificial light from 9 am to 11 am for four weeks increases total sleep times from 5-18% in patients with dementia (65,66). Morning bright light is particularly good for treating sleep onset difficulties, including those induced by eastward air travel jetlag (as an aside, evening bright light is good for treating early morning awakenings, including those induced by westward air travel jetlag) (67). Therefore get that bright light first thing in the morning.
(2) Swap stressful experiences for relaxing experiences during the day.
Stressful daytime experiences can worsen sleep (68,69). The media is one of the worst offenders (70). The media largely presents news laced with tones of melodrama creating the perception of a hostile, dangerous world - for example, despite an impressive drop in US crime rates since the 1990s, the media has most people believing that crime rates are rising (71). Besides, does up-to-the-minute knowledge of the most recent plane crash, murder, or political scandal enrich our existence or impair it? The media also exposes people to hundreds of advertisements on a daily basis embedded with messages of fear, power, sex, status, and wealth as well as the perfect fantasy life in which health, home, and work are perfectly balanced - not only does this create unrealistic expectations and a feeling that one never has enough, it spoils our appetites for learning about ourselves. The media is one of most stress-inducing sources on the planet and while it's not conclusively proven, probably worsens sleep.
Fortunately, several relaxing activities have been proven to improve sleep including exercise, massage, yoga, and meditation. Both aerobic and resistance exercise performed at any time of the day improve sleep quality that same night (72,73), although the afternoon might be the best time to exercise (53). Interestingly, better sleep has also been shown to produce better exercise sessions the following day (74). Having a massage for 15-30 minutes a day three times a week has been shown to improve sleep quality in patients with cancer (75), and yoga classes twice a week for three months have also been shown to improve sleep quality in older adults (76). Finally, a randomized clinical trial demonstrated that mindfulness meditation for two hours a week over six weeks improves sleep quality compared to a control group in older adults (77).
Therefore lessen media exposure and replace that time with exercise, massage, yoga, or meditation during the day.
(3) Take a nap in the afternoon.
Taking a nap in the afternoon can combat the effects of sleep deprivation effectively and immediately, even in people who more or less get the sleep they need on a nightly basis (78). Many studies have shown that napping for 10-30 minutes confers considerable benefits in terms of alertness, cognitive performance, and mood in people with either partial or total sleep deprivation (78,79). However, frequent naps longer than 30 minutes are associated with sleep inertia (grogginess) and higher morbidity and mortality, especially among the elderly (79). Therefore take a 10-30 minute nap if tired in the afternoon.
(4) Avoid drugs that mess with the brain, especially in the afternoon and evening.
Several drugs that are often taken for granted - caffeine, nicotine, alcohol, and prescription sedatives - generally impair sleep.
Caffeine is a stimulant that blocks the receptors of adenosine, a molecule that accumulates in the brain during wakefulness to promote sleep (53). It is present in coffee, most teas, colas, and dark chocolate. Taking caffeine an hour before bedtime shortens total sleep time and shortens the time spent in deep sleep (53), and abstaining from caffeine even for a single day has been shown to significantly improve sleep quality (80). Chamomile tea, which does not contain caffeine, is excluded from this list and may slightly benefit sleep, although the evidence isn't really there.
Nicotine is both a stimulant and a sedative and it is commonly found in cigarettes and transdermal patches. Nicotine has a biphasic effect on sleep - at low concentrations it leads to relaxation and sedation but at high concentrations it inhibits sleep (53). In general, cigarette smoking and transdermal nicotine patches appear to impair sleep duration and quality (81,82).
Alcohol is another drug that can act both as a stimulant and as a sedative. A comprehensive review of all scientific studies prior to 2013 examining alcohol and sleep found that alcohol at all dosages before bedtime reduces the time of sleep onset and enhances deep NREM sleep in the first few hours of the night, but it does so at the expense of disrupted REM sleep, particularly in the second half of the night (83). The authors concluded that on the balance, alcohol disrupts sleep, although the effect is minimal at dosages of one to two standard drinks.
Lastly, a meta-analysis of 24 randomized controlled trials showed that sedative hypnotics or "sleeping tablets" such as intermediate-acting benzodiazepines (alprazolam, clonazepam, lorazepam, oxazepam, and temazepam) and non-benzodiazepines (zolpidem, zopiclone, zaleplon, and diphenhydramine) modestly improve sleep quality (84). Unfortunately, these drugs also significantly increase the risk of daytime fatigue, memory loss, confusion, disorientation, and falls, especially in older people. Which in many ways defeats the purpose of taking them in the first place.
Therefore avoid caffeine and nicotine, limit alcohol to two standard drinks, and only take sedative hypnotics as a last resort in the afternoon and evening.
Last Words
Sleep deprivation and insomnia do the immune system and brain a disservice. Ideally, sleep should occur every night for seven to eight hours and it should leave one feeling refreshed in the morning. It's worth summarizing the above strategies for restoring sleep.
Bedtime Strategies(1) Wear amber-lensed glasses, turn off the television, and put away the computer one hour before bedtime.
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Daytime Strategies(1) Get that bright light first thing in the morning.
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