Sleep, Health, and Disease
The science is becoming increasingly clear that this lack of adequate sleep is a threat to our health and safety. Insufficient sleep is linked to 7 of the 15 leading causes of death in the US including cardiovascular disease, hypertension, diabetes, accidents, and cancer.7,8,9
As we discussed in Episode 146 about Metabolic Health, hallmarks of metabolic dysfunction are excess carbohydrate consumption and impaired blood sugar regulation. As it turns out, inadequate sleep results in both.
First, we know that inadequate sleep results in increased food consumption, and particularly sugar. Sleep loss results in a decrease in the satiety hormone Leptin - which signals our brains that we are full,10 and also increases a hunger hormone called ghrelin, which motivates us to eat more. Together, these changes in hormone levels signal that we are both hungry and that we are not full. It’s been shown that those who are sleep deprived have increased hunger and appetite.11,12 Sleep loss has also been shown to result in increased calorie consumption by about 250 cal/day when compared to conditions of normal sleep duration.13 Additionally, those who are sleep deprived have increased preference for calorie-dense, high carbohydrate foods that are especially damaging to our metabolic health.14 This preference for hyperpalatable foods and carbohydrates may be due to changes observed in brain activity in sleep loss states in the areas of cognitive control and reward in the brain.15
Not only are we primed to consume more calories and more energy-dense carbohydrates when sleep deprived, but sleep deprivation also makes our bodies less insulin sensitive,16 meaning we are not able to handle those carbohydrates as well either. Sleep restriction to 4 hours for 1 night17 or 5 hours per night for just one week resulted in significant reductions in insulin sensitivity.18
Together this increased intake paired with impaired glucose regulation (insulin resistance) leads to weight gain19 and metabolic dysfunction. Additionally, even if restricting calories, the fraction of weight loss from fat while sleep deprived is much less, while weight loss from lean body mass is increased.20,21
Sleep loss also increases the activity of the sympathetic nervous system, the chronic effects of which we discussed in our episode on metabolic health and in Episode 139 with Dr. George Slavich on stress. Some effects of chronic sympathetic activation include increased heart rate and blood pressure, increased stress hormones such as cortisol, increased brain activation which may contribute to anxiety or insomnia, and increased low-grade inflammation. Years of inadequate sleep can contribute to the body chronically being stuck in this fight-or-flight state, which can then lead to a host of health problems. Deep sleep combats this sympathetic state by allowing a decrease in heart rate and blood pressure. Inadequate time in a deep sleep state prevents the cardiovascular system from achieving adequate time for rest, repair, and recovery.
Inadequate sleep also contributes to metabolic dysfunction through its epigenetic effects. Each of us is born with DNA which does not change and provides the instructions for our cells, but epigenetics is the description of how those genes are used - which genes are turned on and turned off - and that is mainly controlled by our lifestyle factors and exposures, sleep being an important one. A study restricting men and women to 6 hours of sleep per night for one week compared their gene expression to when they had 8.5 hours of sleep.22 Researchers found a change in the epigenetics, or expression of 711 different genes among these two states. When the researchers looked closer at the genes in the sleep deprived state, they found that the expression of genes linked to chronic inflammation, cell stress, and cardiovascular disease were increased, while those that maintain optimal metabolism and immune function were decreased.
As we’ve discussed previously, the ultimate deadly outcome of metabolic dysfunction as the high blood pressure, inflammation, and sympathetic state continue to spiral out of control is cardiovascular disease culminating in strokes and heart attacks, and sleep deprivation has been associated with greater risk of both.23
Interestingly, even small changes in sleep may impact heart attack risk. For example, one study done at the University of Michigan found a 24% increase in patients presenting with heart attacks to the hospital the Monday after “spring forward” daylight savings time, when they lost an hour of sleep over the weekend.24 After the “fall back” daylight savings time when patients gained an hour of sleep, they observed a 21% drop in heart attacks.
To summarize the effects of chronic sleep loss on metabolism, we know that it:
- Increases appetite and hunger
- Decreases impulse control in the brain
- Increases caloric intake, particularly carbohydrates
- Decreases insulin sensitivity (the ability to control blood sugar)
- Increases sympathetic tone or the “fight-or-flight” state
- Has epigenetic effects, altering the expression of genes toward metabolic dysfunction
Ultimately, this contributes to a metabolically dysfunctional state in which it is more difficult to lose fat even while restricting calories, and ultimately, over the long-term can accelerate progression toward fatal cardiovascular disease.
Our discussion of sleep and Alzheimer’s Disease is an extension of metabolic health, as Alzheimer’s Disease is sometimes referred to as “Type 3 Diabetes.”
We are still just beginning to understand the mechanisms that underlie Alzheimer’s disease, but there does seem to be a relationship between Alzheimer’s disease and poor sleep.25 For example, sleep disturbance affects up to 40% of patients with mild-moderate dementia, sleep changes seem to precede cognitive decline, and the intensity of the sleep disturbance correlates with the severity of dementia symptoms.26
Alzheimer’s is characterized by a buildup of toxic proteins called beta-amyloid in plaques within the brain which impair connections between neurons. Increased buildup of these plaques has been noted even after just one night of sleep deprivation.27 Initial research suggests that deposition of these plaques in areas of the brain involved in sleep result in disrupted deep sleep.28 Because deep sleep is important for memory, this disruption in deep sleep may represent one contributor to memory impairment in those with Alzheimers. It’s a two-way street: without adequate sleep, more amyloid plaques build up in the brain, and the amyloid plaques in certain areas of the brain may lead to less deep sleep. So, getting adequate deep sleep in midlife to prevent amyloid plaque buildup (and to allow for any buildup that does occur to be removed) may be important for the prevention of Alzheimer’s disease.
Sleep is also incredibly important for a properly functioning immune system.29 We’ll review a few of examples of this here:
The first is an example of how sleep affects our susceptibility to infection.30 In this experiment, the sleep of 164 healthy men and women was monitored for one week. Each of them was then given nasal drops containing rhinovirus, a cause of the common cold, and they were observed to see who would develop cold symptoms. The researchers found that those sleeping less than 6 hours per night on average had an increased likelihood of developing cold symptoms compared to those sleeping 7 hours or more per night. About 45% of those getting less than 5 hours of sleep per night developed cold symptoms, while just 18% of those sleeping 7 hours or more per night developed colds. This is especially interesting to think about in the era of COVID-19, when getting enough quality sleep could potentially decrease our risk of infection even if we do get exposed.
The next example discusses our ability to mount an immune response to the flu vaccine.31,32 A study in JAMA in 2002 demonstrated that adequate sleep is important for mounting a response to the flu vaccine. Normally, the flu vaccine works by stimulating the body’s immune system to create antibodies against the flu virus, so that if you do become infected with the flu virus later on, your immune system will be able to fight it off without you getting sick. In this study of young healthy adults, half were allowed to sleep 7.5-8.5 hours while the other half were restricted to 4 hours per night for 6 nights in a row. At the end of this period they were all given a flu shot. The researchers then measured the antibodies in the blood of the two groups in the days following. Those who got the most sleep showed signs of a healthy immune system generating a powerful antibody response. In contrast, those whose sleep was restricted produced less than 50 percent of the antibody response.
Immune function is also important for the prevention of cancer and the natural killer cells of the immune system are particularly important for fighting cancer. Studies have found that even a single night of short sleep (4 hours) results in a 70% reduction in natural killer cells relative to a full night of sleep.33 Observational studies have also shown an increased risk of dying from cancer in those who have shorter sleep duration less than 6 hours.34 Disruptions to circadian rhythms is also at play, and the International Agency for Research on Cancer (IARC) has even classified nighttime shift work as a “probable carcinogen.”35
Testosterone and Fertility
Sleep also has a tremendous impact on testosterone levels and fertility in both males and females. In a study performed on young healthy men who were restricted to 5 hours of sleep per night for 1 week, a 10-15% drop in testosterone was observed compared to their rested state.36 To put this into context, normal aging results in a 1-2% decrease in testosterone per year, so this one week of sleep loss was effectively equivalent to aging 5-15 years. The poor quality and quantity of sleep in men who with obstructive sleep apnea, a common sleep disorder, has also been shown to lead to decreased testosterone levels.37 Finally, short sleep and late bedtimes are also associated with imparied sperm health in men.38
Reproductive function in women is also affected by sleep,39 and levels of Follicle Stimulating Hormone (FSH), an important reproductive hormone in women that stimulates egg growth in the ovaries, was found to be 20% lower in women with chronic sleep deprivation.40
Sleep disruption is also implicated in most major psychiatric conditions, including depression, anxiety, PTSD, bipolar disorder,41 and schizophrenia.42,43 The mechanisms of this are still being worked out, and it is likely not a one way street in which sleep disturbance causes these conditions, but rather sleep may be one of many factors that contribute. Said another way, sleep affects psychiatric conditions and psychiatric conditions affect sleep. Sleep disturbance is also recognized as a universal risk factor for relapse in addictive substance use.44
Another way that inadequate sleep poses a threat to our health and safety is through the impact of sleep loss on car accidents. There is known to be an increased risk of car accidents with increasing sleep deprivation.45 When questioned, 1 in 25 adult drivers report having fallen asleep while driving in the previous 30 days.46,47 It is estimated that up to 6,000 fatal crashes each year in the US may be caused by drowsy drivers.48,49,50 After being awake for nineteen hours, people who were sleep-deprived were as cognitively impaired as those who were legally drunk.51
We’ve spent a lot of time talking about the damaging effects of inadequate sleep on our cognitive function and physical health, but sleep can also be used as a powerful tool to enhance our performance. The International Olympic Committee consensus statement on youth athletic development recognizes the importance of sleep in athletic development as well as the potential consequences of inadequate sleep, and they recommend interventions to support adequate sleep in youth athletes.52 Obtaining adequate sleep has been associated with increased athletic performance in a variety of different domains from aerobic output to vertical jump height, peak and sustained muscle strength.53 Additionally, chronic lack of sleep is associated with a higher risk of injury among athletes.54
Chance of injury decreases with increasing hours of average sleep.55
Performance enhancements seen in an NBA player achieving more than 8 hours of sleep56
How Sleep Works
Now that we’ve reviewed many implications of poor sleep on health, we’ll provide a brief overview of how sleep works.57
When We Sleep
There are two main factors that determine when we sleep: 1. Circadian Rhythms, and 2. Sleep Pressure.
- The first factor that determines when we sleep is our Circadian Rhythm. You can think of this as the biologically built-in rhythm that allows our bodies to function on a 24 hour clock. The length of each person’s circadian rhythm is unique and usually just slightly longer than 24 hours. On average, the adult human’s circadian clock runs around twenty-four hours and fifteen minutes in length.58 An area of the brain called the suprachiasmatic nucleus uses light to reset the circadian rhythm each day, which allows us to stay in tune with a 24-hour cycle and prevents drift over time.The circadian clock is set not just by light but also by food, exercise, temperature fluctuations, and even regularly timed social interaction. The determination of an individual's preferred sleep and wake times, (whether you are a morning or evening person) differs between people as well and is strongly determined by genetics.The hormone melatonin also plays a role. It is released from the pineal gland and helps to signal darkness and the onset of sleep. Melatonin rises a few hours after dusk, peaks around 4am, then drops quickly. Light signals the pineal gland to stop releasing melatonin, and it is undetectable by mid morning.
- The second factor that determines when we sleep is Sleep Pressure. A chemical called adenosine gradually builds up in the brain while you are awake. The longer you are awake the more adenosine builds up. The more adenosine you have circulating in your system, the greater the pressure to sleep. Then when you go to sleep, adenosine is cleared and sleep pressure decreases throughout the night. In the morning the process starts all over again. Interestingly, caffeine works by blocking adenosine receptors. So even though there is increasing adenosine and sleep pressure as the day goes on, while caffeine is in your system you can’t sense this sleep drive.
Together, the circadian rhythm and the sleep-pressure signal of adenosine both work to coordinate sleep and wake times on a 24 hour cycle as seen in the figure below:
It’s important to note that humans also have a genetically hardwired dip in alertness that occurs in the midafternoon hours. Not adhering to this drive for biphasic sleep, or nighttime sleep followed by a short nap in the mid afternoon, seems to lead to increased cardiovascular risk and mortality. Biphasic sleep is still observed in several siesta cultures throughout the world, including regions of South America and Mediterranean Europe. After one of these cultures in Greece transitioned away from a siesta practice, those that abandoned siestas went on to suffer a 37% increased risk of death from heart disease over the following 6 years.59 It may not be a coincidence that in other areas of Greece where siestas still remain commonplace, there are still the highest concentrations of Centenarians. One example is the Greek island Ikaria, with their famous tagline “where people forget to die.”
There are two major stages of sleep, and we alternate between them in approximately 90 minute cycles over the course of the night.
Non-Rapid Eye Movement (NREM) Sleep
Non-rapid eye movement, or NREM, sleep is more predominant earlier in the night. A key function of NREM sleep is storing and strengthening new information while weeding out and removing unnecessary neural connections and waste products. The glymphatic system, which is much like the lymphatic system in the rest of the body, drains waste products from the brain’s tissues and is especially active during deep NREM sleep. The glymphatic system is composed of cells called glia which are distributed throughout the brain. During deep NREM sleep, the glial cells shrink significantly, allowing the cerebral spinal fluid that bathes neurons to clean out toxic waste products that have built up and allows them to drain away. One example of such toxic waste products is the amyloid plaques we discussed above, whose buildup is associated with Alzheimer’s disease.
Rapid Eye Movement (REM) Sleep
Rapid eye movement, or REM sleep, is more predominant later in the night. REM sleep plays a role in integrating new information - this includes integrating new facts and memories with previous experiences, creativity, language learning, and social and emotional learning. REM sleep is also where dreaming takes place. You lose muscle tone during REM sleep, which prevents you from acting out your dreams.
To summarize, you can think of states of wake and sleep like this:
- The waking state is for information perception and gathering
- NREM sleep stores that information and weeds out unnecessary waste and connections
- REM sleep integrates new information together with past experiences allowing you to develop complex functions such as problem solving, language, social interactions, and creativity.
Sleep cycles take place every 90 minutes, and the ratio of NREM sleep to REM sleep within each 90-minute cycle changes dramatically across the night. There is a predominance of NREM sleep in the beginning of the night, and more REM sleep in the second half of the night. Because both cycles are important, and REM is especially important for integrating new information and creativity, missing out on the later sleep cycles by short sleeping can be especially detrimental.
REM sleep is especially important for development of neural connections in the developing brain. In utero, a fetus is almost exclusively in REM sleep, while infants may have closer to 50/50 split between NREM and REM sleep, and by the late teen and adult years most settle into an 80/20 NREM/REM sleep split.
Change in time spent in NREM vs. REM sleep in sleep cycles throughout the night. Figure from Walker, M. Why We Sleep.
Sleep as We Age
Several changes to sleep occur as we age:
- First is a decreased ability to generate deep sleep as we age. This is because areas of the brain responsible for generating deep sleep are some of the same areas that degenerate first with aging.
- Next is reduced sleep efficiency. Teenagers have a sleep efficiency - or the percentage of time that they actually spend asleep while in bed - of about 95 percent. However, sleep efficiency usually drops below 70- 80 percent by the 8th decade of life. This is likely due to increased fragmentation of sleep as we age, often due to medications, diseases, or a weakened bladder.
- Finally, the circadian rhythm shifts throughout different stages of life and there is a change in sleep timing as we age. In teenagers, the circadian rhythm is shifted forward, meaning they naturally fall asleep later and wake up later. This is why forcing teenagers to go to bed early, or asking them to wake up for an early school start time is especially problematic. In contrast, the circadian rhythm shifts backward in older adults resulting in earlier bedtimes and earlier awakenings. Additionally, the overall strength of the circadian rhythm and the amount of nighttime melatonin released also decrease the older we get. Interestingly, melatonin has been shown to help boost the circadian rhythm in the elderly, in contrast to middle-aged adults where it is most helpful only with jet lag.60
How Much Sleep?
Now that we’ve addressed the changes that occur to sleep as we age, let’s try to answer everyone’s favorite question - how much sleep do we really need?
Both the Centers for Disease Control61 and National Sleep Foundation62 recommend 7-9 hours of sleep per night. Years of research indicates that 8 hours is optimal for most adults.63 After 16 consecutive hours of being awake, the brain begins to slow down significantly. A series of experiments showed that ten consecutive days of just seven hours of sleep resulted in the same level of brain dysfunction as pulling one “all nighter” or going without sleep for 24 hours.
Another important distinction to make is that it is almost impossible to “make up” for lost sleep. Performance still suffers even after several full nights of sleep following a night of sleep loss.
Finally, we as humans have a very hard time determining how sleep deprived we actually are, which is what can make inadequate sleep behaviors dangerous especially when it comes to things like driving.
There are very few people (<1% of the population) who truly only need a few hours of sleep per night and do not experience any negative cognitive or other health effects from doing so. This is largely programmed by genetics, which seems to lie in a variant of a gene called BHLHE41, or DEC2.64
Finally, we’ll address some of the ways we can maximize our chances of getting optimal sleep each night.
Give Yourself the Opportunity
The first step in getting enough quality and quantity sleep is to give yourself the opportunity to do so. So often we are going to bed late, knowing that we have to be up early in the morning for work or other obligations. So plan ahead, and try to establish a consistent bedtime and wake time that works for both weekdays and weekends. Alarms can be particularly detrimental because of their propensity to induce a sympathetic fight or flight state immediately upon waking. Even worse is a snoozed alarm inducing that state multiple times in one morning.65 Ideally, when your body is getting enough sleep you should wake up on your own without an alarm.
Maintain a good sleep environment
After allowing adequate opportunity to sleep, it’s important to make sure to have a good sleep environment.
The first aspect of a good sleep environment is the appropriate use of light. Since the advent of artificial, and in particular blue LED lights, the usual changes in natural light throughout the day that helped to train our circadian rhythms and signal the release of melatonin are being overridden. A survey conducted of American adults revealed that 90% of people regularly used some type of electronics within 1 hour of their bedtime.66 When comparing reading an electronic book to a regular paper book before bedtime, those who read the electronic book had less sleepiness in the evening, took longer to fall asleep, reduced melatonin secretion, later timing of their circadian clock, and reduced alertness the following morning.67 There are a few ways to mitigate the damaging effects of constant blue light exposure:
- Avoid bright lights in the evening hours. Dim the lights or use orange-tinted glasses to help filter out the blue light that suppresses melatonin release.
- Programs that can be used on your computer or phone such as F.lux which automatically filter out the blue light as the evening hours approach.
- An eye mask or blackout curtains in the bedroom can also help to maintain complete darkness throughout the night.
- Outdoor sunlight exposure in the morning can also help to train your circadian rhythm appropriately. One easy way to do this is to drink your coffee outside or go for a short walk in the morning.
The next factor to address when it comes to a good sleep environment is temperature.68 Many people think it is mainly the darkness that signals our bodies that it’s time to go to sleep, but a drop in temperature is also very important. In order to successfully initiate sleep, core body temperature needs to drop by about 2-3 degrees F. A bedroom temperature of around 65 degrees F is ideal for sleep of most people, but for those having difficulty falling asleep, dropping their current room temp by 3-5 degrees might be a good strategy. An 18-25% reduction in the time to fall asleep has been reported in adults after dropping their core body temperature.69
In addition to just lowering the thermostat, taking a hot bath can also help to reduce core body temperature. This may seem counterintuitive, but the hot water helps to dilate blood vessels close to the surface of the skin, so that when you get out, heat quickly dissipates from the body resulting in a reduced core temperature. Hot baths prior to bed can also induce 10 to 15 percent more deep NREM sleep in healthy adults.70,71
There are other devices designed to reduce core body temperature to improve sleep onset such as the Chili Pad or 8 Sleep Mattress.
Noise elimination is also important for a good sleep environment. If there is ambient noise, wearing ear plugs or using a white noise or other soothing sound machine can be helpful.
Make your bed a place for sleep only
If you cannot sleep, lying in bed awake looking at the clock can only make things worse. Going into another room and doing something relaxing until feeling sleepy again can help to train your body to recognize your bed as a place for sleep only.
Avoid Substances that Interfere with Sleep
The two most widely used substances that have a substantial impact on sleep are alcohol and caffeine.
Alcohol impacts sleep in two important ways:72
- First, alcohol fragments sleep, meaning it results in numerous brief awakenings which result in poor quality and non restorative sleep.
- Second, alcohol is a powerful suppressor of REM sleep, which we know is incredibly valuable for making new connections and creativity. Aldehydes and ketones are produced when alcohol is metabolized by the body and these block the brain’s ability to generate REM sleep.
Because of its disruption of sleep which is so important for storing and solidifying new memories, alcohol has also been shown to reduce the amount learned in a day by 50%, and drinking 3 days after taking in information still reduces the amount learned by 40%.
Alcohol also has important effects on the sleep of infants when consumed by pregnant and breastfeeding women:
- Alcohol, even in relatively small amounts, reduces the amount of time that the fetus spends in REM sleep and the intensity of REM sleep, which we know is incredibly important for their development.73
- Additionally, infants of breastfeeding mothers who have had alcohol (the equivalent of a drink or two) have more fragmented sleep, spend more time awake, and suffer a 20 to 30 percent suppression of REM sleep.74,75
It’s probably not surprising to hear that caffeine is another substance that can significantly impact our sleep.76,77 As discussed above, caffeine blocks adenosine receptors, which inhibits the brain’s ability to sense sleep pressure. Caffeine levels usually peak approximately 30 min after consumption, and it has an average half-life of about 5-7 hrs. This means that if you finish drinking coffee at 2pm, by 9pm half of the amount of caffeine could still be in your system. Additionally, one cup of decaf coffee usually contains 15 to 30 percent of the caffeine in a regular cup of coffee, so there is still some caffeine there and this can build up if someone is drinking several cups of decaf, or even a cup of decaf later in the day.
Regular exercise can help improve the ability to fall asleep and quality of sleep, but ideally should be done earlier in the day, as exercise done immediately before bedtime can make it more difficult to fall asleep.78
If individuals are still having difficulty sleeping despite these measures, it’s important to work with an experienced physician to determine if there are any underlying sleep disorders that need to be addressed such as sleep apnea, insomnia, circadian rhythm sleep disorders, or others.
In summary, sleep loss is an enormous problem facing our world today that has far-ranging implications on our health from metabolic health to Alzheimer’s disease, immune system function, fertility, psychiatric conditions and car accidents. We have evolved complex biological systems that determine when we sleep, stages and cycles of sleep that play specific roles. However, our modern lifestyle often undermines these natural signals for healthy sleep. We reviewed strategies above that can be used to give ourselves the best opportunity to maximize sleep quantity and quality including sleep opportunity, an optimal sleep environment with regard to light exposure, temperature, and noise, avoiding substances such as alcohol and caffeine that significantly interfere with our sleep, and getting regular exercise.
We also wanted to give a huge shout out to Dr. Matthew Walker, Professor of Neuroscience and Psychology at the University of California, Berkeley, and author of the book, Why We Sleep which helped to direct much of our research and discussion here. If you are interested in learning more about these topics, we highly recommend checking out his book!
Ep 105 - Sleep, Stress, and Brain Health with Dr. Nate Bergman
Ep 139 - Stress: The Elephant in the Room with Dr. George Slavich
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Disclaimer: This podcast is for general information only, and does not provide medical advice. We recommend that you seek assistance from your personal physician for any health conditions or concerns.
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