Mark C. Kelley, MD MMHC

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Sleep

Jul 01, 202421 min read

Sleep is a beautiful symphony of rest, cleansing, repair, and growth conducted by the brain to promote the health and well-being of all systems in the body. Like a fine maestro, the brain directs the precise timing and scope of changes to multiple systems including temperature regulation, hormone release, and nervous system control to repair and rejuvenate cells and systems from the previous day’s work, facilitate memory and learning, and prepare the body for maximal functioning the next day. Sleep has been highly preserved throughout evolution in animal species, which confirms that it is essential to health.

Sleep is broadly separated into 2 categories: non-REM sleep and REM sleep. These stages cycle approximately every 90 minutes throughout the night. The ratio or proportion of time spent in each or the stages varies across the night as one will experience primarily non-REM sleep during the first part of the night and primarily REM sleep the last part of the night.

Sleep stages: Non-REM (NREM) Sleep

Deep sleep is essential for your body’s repair and restoration processes. It helps boost your immune system, regulates metabolism, improves memory, and cleans your brain of harmful substances.

Non-REM (NREM) sleep is a type of sleep that is separated into four distinct stages. These stages are characterized by changes in brain electrical activity, which can be measured using an electroencephalogram (EEG). Stage 1 and Stage 2 of NREM sleep are considered to be the light stages of sleep. During these stages, brain electrical activity slows down compared to wakefulness. Stage 2 sleep is characterized by the presence of “sleep spindles,” which are short, synchronous bursts of electrical activity in the brain, typically around 12-15 Hz.123

As an individual progresses from Stage 2 to Stage 3, the frequency of brain waves further slows to about 1-2 Hz. Stages 3 and 4 are collectively referred to as “deep” sleep stages. During these stages, the brain’s electrical activity transitions from faster, short-amplitude waves to slower, high-amplitude waves, known as delta waves.456 Stage 4 sleep is the deepest stage of NREM sleep, and it is crucial for physical restoration, memory consolidation, and maintaining overall health and well-being.123

During deep sleep (Stages 3 and 4 of NREM sleep), the body experiences several changes in its physiological function which have important health benefits:

Physiological changes during deep sleep:

  1. The autonomic nervous system switches from sympathetic control (associated with the “fight or flight” response) to parasympathetic control (associated with “rest and digest” functions).123

  2. The activity of the cardiovascular system decreases, leading to a decrease in heart rate and blood pressure. This allows the heart and blood vessels to rest and recover. These changes are primarily due to the changes in autonomic nervous system activity noted above.123

Deep sleep benefits:

  1. Improved immune system function: Deep sleep is crucial for maintaining a strong immune system. During this stage, the body increases the production of immune cells, such as T cells and Natural Killer cells, which help fight off infections and diseases. Additionally, cells and systems become more sensitive to signals from the immune system, enhancing the ability of the body to respond to potential threats.78

  2. Improved metabolic regulation: Deep sleep helps regulate metabolic functions, including the control of blood sugar levels and insulin release. During this stage, the body’s cells become more sensitive to insulin, which helps maintain stable blood sugar levels and reduces the risk of developing metabolic disorders like diabetes.123

  3. Learning and memory consolidation: Deep sleep plays a vital role in the regulation of learning and memory functions. During this stage, the brain processes and consolidates newly acquired information, transferring it from short-term to long-term memory. This process is essential for learning, problem-solving, and overall cognitive performance.123

  4. Brain “cleansing”: Recent research suggests that during deep sleep, the brain undergoes a “cleansing” process which is mediated by the glymphatic system. This system removes toxins, proteins, and metabolites that accumulate in the brain during wakefulness, including beta-amyloid and tau proteins. The buildup of these proteins has been linked to the development of neurodegenerative disorders like Alzheimer’s disease. By clearing these substances, deep sleep helps maintain brain health and may reduce the risk of developing such conditions.91011

Sleep Stages: Rapid Eye Movement (REM) sleep

REM sleep is when most vivid dreaming occurs. It’s important for memory, emotions, and thinking, and makes up about a quarter of your total sleep.

Rapid Eye Movement (REM) sleep is a unique stage of sleep characterized by several distinct features that set it apart from non-REM sleep stages. The characteristics of REM sleep are:

  1. Rapid eye movements: As the name suggests, during REM sleep, the eyes move rapidly beneath closed eyelids, darting back and forth in a seemingly random pattern. This is one of the most recognizable features of REM sleep and can be easily observed.121314

  2. Dreaming: REM sleep is the primary stage in which vivid, narrative, and emotionally charged dreaming occurs. While some dreaming may happen during non-REM stages, most memorable and complex dreams are experienced during REM sleep.12131415

  3. Temporary loss of voluntary muscle tone: During REM sleep, the brain sends signals to the spinal cord to temporarily paralyze most of the body’s voluntary muscles, particularly those in the limbs. This is known as REM atonia and is thought to prevent individuals from physically acting out their dreams, which could lead to injury. However, some small muscles, such as those controlling eye movements and breathing, remain active.121316

  4. Increased brain activity: In REM sleep, the brain becomes highly active, with brain waves becoming more variable and resembling those seen during wakefulness. This heightened brain activity is associated with the vivid and complex nature of REM sleep dreams, as well as the processing and consolidation of emotional memories.121314

  5. Elevated heart rate: Unlike non-REM sleep, where the heart rate typically slows down, REM sleep is characterized by an increase in heart rate. The heart rate may become more variable and can even resemble the patterns seen during wakefulness.1213

  6. Changes in respiratory patterns: Breathing during REM sleep becomes more rapid, irregular, and shallow compared to non-REM sleep stages. This can contribute to the increased heart rate and overall physiological arousal observed during REM sleep.1213

REM sleep is essential for cognitive functions, emotional regulation, and memory consolidation. It is believed to play a crucial role in learning, creativity, and problem-solving. Adults typically spend about 20-25% of their total sleep time in REM sleep, with the duration of REM periods increasing throughout the night.1213

Factors that determine the health benefits of sleep: What is a “good night’s sleep”?

Good sleep is defined by four key factors: how much you sleep, how well you sleep, how consistently you sleep, and when you sleep relative to your body’s natural rhythm. Optimizing these factors can significantly improve your overall health and well-being.

A good night’s sleep is essential for maintaining physical and mental health and overall well-being. Four key characteristics determine the health benefits of sleep. These can be considered to be the “macros” of sleep and are known as QQRT: Quantity, Quality, Regularity, and Timing.

  1. Quantity:

    This describes the amount of time asleep. Most adults require an average of 7-9 hours of sleep each night to function optimally. However, individual sleep needs may vary slightly, with some people needing slightly more or less sleep to feel fully rested and get the most physiological benefits of sleep.174

  2. Quality:

    This describes how optimal the sleep pattern is. Sleep quality is often measured in terms of continuity, which refers to the degree of fragmentation in sleep. Highly fragmented sleep with many waking points is considered lower quality. Sleep tracking devices often use the term “sleep efficiency” to describe the percentage of time spent asleep compared to the total time spent in bed. Healthy sleep is usually classified as having an efficiency of 85% or above. It’s important to note that while wearable trackers can measure sleep efficiency, they cannot yet assess the electrical quality of deep sleep, which can also vary.1819

  3. Regularity:

    This describes the consistency of sleep timing. Maintaining a consistent sleep schedule by going to bed and waking up at approximately the same time every day (within a 30-minute window), including weekends, is crucial for optimal sleep. This consistency allows you to stay in sync with your circadian rhythm, the internal biological clock that regulates sleep-wake cycles and various physiological processes.5

  4. Timing:

    This describes how the time you go to sleep is matched to your biological clock. Each individual has a unique chronotype, which refers to the body’s preferred time to sleep and wake each day. Chronotypes are primarily determined by genetics and can be classified as early birds (morning types), night owls (evening types), or somewhere in between. In sleep science, there are 5 categories of chronotypes:6

    • Extreme Morning - to bed around 8/8:30 pm and wake up 4/4:30 am
    • Morning - to bed 9:30/10 pm and wake up 5:30/6am
    • Neutral - to bed 10:30/11pm and wake up 7:30/8am
    • Night - to bed 12:30/1am and wake up 9/9:30 am
    • Extreme Night - to bed 2:30/3 am and wake up 10:30/11 am

To determine your chronotype, you can take an online quiz called the Morningness-Eveningness Questionnaire (MEQ). Simply search for “Chronotype MEQ” on Google to find the quiz. Understanding your chronotype can help you optimize your sleep schedule and daily activities to align with your body’s natural preferences.

By focusing on these four sleep “macros”—quantity, Quality, Regularity, and Timing—individuals can work towards achieving a good night’s sleep, which is essential for physical and mental well-being, cognitive function, and overall health.

Strategies to improve the quality and health benefits of sleep

Sleep hygiene involves practices that promote good sleep, including consistent sleep schedules, managing light exposure, and controlling bedroom temperature. Good sleep habits also include avoiding late meals, limiting caffeine and alcohol, and not staying in bed when you can’t sleep.

Sleep hygiene refers to a set of practices, habits, and environmental factors that are conducive to achieving high-quality sleep consistently. Just as dental hygiene involves using tools and following practices to maintain oral health, sleep hygiene involves implementing strategies to optimize sleep, leading to numerous health benefits.202122 Here are some key elements of proper sleep hygiene:

  1. Quantity:

    Plan for 7-9 hours of sleep every night. Sleep of under 7 hours and over 9 hours is associated with impaired metabolic function, increased inflammation, decreased immune function, and decreased cognitive function, memory, and performance.23

  2. Regularity: Maintaining a consistent sleep schedule by going to bed and waking up at approximately the same time every day, even on weekends, is crucial for optimizing sleep. This regularity helps anchor the brain’s sleep-wake cycle and can improve both the quantity and quality of sleep by reinforcing the body’s internal clock.24 Sleep regularity may have an even greater impact on metabolic health than sleep quantity.2526

  3. Timing: Choosing a sleep time that is matched to your body’s natural circadian clock will maximize the health benefits of sleep.24

  4. Quality: The following factors can affect the quality of sleep:

    A. Light and dark exposure:

    The visual system plays a significant role in regulating the release of melatonin, a hormone that helps control the timing of sleep onset.

    Darkness signals the brain to release melatonin, preparing the body for sleep. To facilitate this process, it’s essential to dim the lights by 50% or more in the last hour before bedtime. Avoiding blue light from cell phones, computers, and TV screens is also important. This can be achieved by avoiding screen time in the last hour before bed or using blue light-blocking apps or glasses. Keeping the sleep environment as dark as possible during sleep may improve sleep quality.24272829

    Exposure to light in the morning helps slow the release of melatonin, promoting wakefulness. Morning light exposure, particularly bright sunlight, stimulates the release of cortisol, a hormone that helps regulate the sleep-wake cycle and provides an energy boost when it is most beneficial. Exposure to morning light through the cells in the back of the eye (retina) is crucial for regulating the circadian rhythm, the body’s internal 24-hour clock that governs various physiological processes, including sleep.272829

    B. Temperature regulation:

    The body’s core temperature plays a significant role in the sleep-wake cycle. To initiate and maintain sleep, the body and brain core temperature needs to drop by 2-3 degrees Fahrenheit. This temperature drop is part of the natural circadian rhythm and helps signal the body that it’s time to sleep. As the body prepares to wake up, its core temperature begins to rise, helping to promote alertness and wakefulness. Ensuring a cool and comfortable sleep environment can help facilitate this natural temperature regulation process.3031

    Sleep scientist Dr. Matthew Walker recommends the following way to think about regulating your temperature for sleep:

    • “Warm up to cool down to fall asleep”. Your body must reduce its core temperature to fall asleep. It does this by directing blood to the surface of your skin, especially your hands and feet. These must warm up for your core to cool down. Things like a warm bath, sauna or putting socks on can facilitate this. Lying down also helps as this position makes it easier for the body to move blood from the core to the skin to release heat.
    • ”Stay cool to stay asleep”. Keeping the room cool is very helpful; an ideal sleeping temperature is around 67 degrees Fahrenheit
    • ”Warm up to wake up.” Your core temperature must rise again to wake up. Once up, a warm beverage often helps with alertness as it contributes heat internally.

By implementing these sleep hygiene practices, allowing adequate time for sleep, maintaining regularity in your sleep schedule, properly timing light and dark exposure, and optimizing sleep environment temperature, individuals can significantly improve their sleep. This, in turn, can lead to a wide range of health benefits, including improved cognitive function, better emotional regulation, and enhanced overall well-being.

In addition to the previously discussed elements of sleep hygiene, there are several other important factors to consider when optimizing your sleep:

  1. Avoid staying in bed if you can’t sleep:

    The brain is highly associative, and it’s crucial to maintain a strong connection between your bed and sleep rather than wakefulness. If you find yourself awake in bed and unable to fall asleep or fall back asleep, it’s best to get up and move to another location. Engage in a relaxing activity, such as reading a book or listening to calming music, while keeping the lighting low. Only return to bed when you feel sleepy.

  2. Avoid late meals:

    The timing of the last meal relative to bedtime may affect sleep quality, with earlier meal times generally promoting better sleep. The biological mechanisms responsible for this include the synchronization of circadian rhythms, gut hormone regulation, glucose homeostasis, and digestive efficiency. Avoiding meals within 2-4 hours of bedtime can improve sleep quality.

  3. Be mindful of caffeine and alcohol consumption:

    Caffeine impairs sleep and can remain in your body for several hours after consumption. To maximize the quality and duration of sleep, it is best to limit caffeine intake before your bedtime. For example, limit coffee to 1-3 cups, consumed 8-10 hours before you go to bed. While alcohol may make you feel sleepy and help you fall asleep quickly, it has negative effects on sleep quality. Alcohol fragments sleep, inducing awakenings throughout the night that you may not be aware of. Alcohol also changes the amount and electrical activity of deep sleep and is a potent blocker of REM sleep, which is essential for cognitive function, emotional regulation, and memory consolidation. Even if you feel that you slept through the night, alcohol consumption can negatively impact sleep architecture and quality.

  4. Consider the effects of THC and CBD:

    THC, the psychoactive compound in cannabis, can help people fall asleep. Like alcohol, THC can impair REM sleep, leading to less restorative sleep. When stopping THC use, individuals may experience significant withdrawal symptoms related to sleep, including insomnia. There is limited data regarding the effects of CBD on sleep. Different dosages of CBD may have either sleep-inhibiting or sleep-promoting properties.

By being mindful of these additional factors, avoiding staying in bed when unable to sleep, and carefully managing meal timing, caffeine, and alcohol intake, individuals can further optimize their sleep hygiene practices. Combining these strategies with the previously discussed elements of sleep duration, regularity, proper timing of light and dark exposure, and optimal sleep environment temperature can help promote high-quality, restorative sleep and its associated health benefits.

Good sleep is essential for good health and feeling well, and perhaps, in some ways, it is the “low-hanging fruit” of your health journey. It is like having an expert personal staff clean, repair, organize, and prepare you to make the most of the next day. You just provide them with the tools and an appropriate environment and they do all the work!

Relationship Between Sleep and Metabolic Health

Sleep significantly affects metabolic health by regulating glucose processing, hormones that control hunger, and energy balance. Poor sleep can lead to weight gain, increased risk of diabetes and cardiovascular diseases, and disruption of the body’s natural rhythms.

Sleep impacts metabolic health through multiple interrelated mechanisms:

  1. Impact on Glucose Metabolism: Both total and partial sleep deprivation impair glucose tolerance and insulin sensitivity, meaning the body becomes less efficient at processing glucose. This can contribute to hyperglycemia, diabetes, and other disorders associated with impaired glucose regulation.32333435

  2. Hormonal Regulation: Sleep affects the balance of ghrelin and leptin, two hormones that regulate hunger and satiety. Sleep deprivation increases ghrelin (stimulates appetite) and decreases leptin (signals satiety), leading to increased hunger and overeating. Lack of sleep elevates cortisol levels, a stress hormone that can promote fat storage and increase appetite, further contributing to weight gain and metabolic dysregulation.3233

  3. Energy Balance and Weight Management: Sleep deprivation can lower the basal metabolic rate (BMR), reducing the number of calories burned at rest. This can lead to weight gain over time. Poor sleep quality and short sleep duration are associated with increased cravings for high-calorie, high-carbohydrate foods and a tendency to eat more frequently, especially late at night. This can disrupt the body’s circadian rhythm and lead to weight gain.3233

  4. Metabolic Syndrome and Cardiovascular Health: Both short and long sleep durations are linked to an increased risk of metabolic syndrome. Sleep disorders such as obstructive sleep apnea (OSA) are associated with higher risks of cardiovascular diseases, including hypertension, stroke, coronary artery disease, and heart failure. Poor sleep quality and inadequate duration can increase these risks by promoting inflammation and oxidative stress.363738

  5. Circadian Rhythms and Metabolic Regulation: Circadian Misalignment: Irregular sleep patterns and circadian misalignment can disrupt the body’s natural rhythms, leading to metabolic dysregulation. This includes impaired glucose metabolism, altered lipid profiles, and obesity.3233

  6. Recovery and Reversibility: Short-term recovery sleep can partially, but not completely, reverse the adverse metabolic effects of sleep deprivation. Chronic sleep deprivation may require longer periods of recovery and may produce cumulative changes in metabolism that lead to chronic diseases.3233

Conclusion

Sleep plays a crucial role in maintaining metabolic health by regulating glucose metabolism, hormonal balance, energy expenditure, and appetite. Both insufficient and excessive sleep can disrupt these processes, leading to metabolic disorders such as obesity, type 2 diabetes, and cardiovascular diseases. The metabolic dysfunction associated with chronic sleep disturbance is a key factor in the development of most chronic diseases. Healthy sleep habits and regular sleep patterns are essential for optimal metabolic health.

Relationship between Sleep and Cancer

Sleep patterns, including duration, quality, and timing, may influence cancer risk through effects on hormones, immune function, and DNA repair. While the relationship is complex and not fully understood, improving sleep habits could potentially help reduce cancer risk and improve outcomes for cancer patients and survivors.

Multiple epidemiological studies have demonstrated an association between sleep duration, quality, and timing and the risk of developing certain cancers. The clear link between impaired sleep and poor metabolic health described above provides a strong biological basis for these observations. Other similar studies have not shown a link between sleep disturbance and cancer risk. This may be explained by differences in the populations of people being studied, the cancer types examined, how the information on sleep was collected, and the methods used to analyze the data. Population-based epidemiological studies also have limitations based on other factors (covariates) that may be associated with sleep and cancer. For example, age and other medical conditions, such as obesity and diabetes, impair sleep but are independently associated with the risk of developing cancer. It is difficult to completely separate the effect of poor sleep from these factors. This makes it difficult to definitively conclude that impaired sleep is the cause of the increased cancer risk. However, the numerous associations between sleep, metabolic health, and cancer risk suggest that there is likely a direct effect and support efforts to improve sleep to reduce cancer risk and improve cancer-related outcomes.

Sleep and Cancer Risk

Sleep Duration:

  • Short Sleep Duration: Short sleep duration (less than 7 hours per night) may be associated with an increased risk of certain cancers. For example, short sleep duration has been linked to a higher risk of colorectal and gastric cancers, particularly among individuals with a history of night shift work.39

  • Long Sleep Duration: Conversely, long sleep duration (more than 9 hours per night) has been associated with an increased risk of certain cancers, including colorectal, gastric, and hormone-related cancers (e.g., breast and endometrial cancers) in women.3940 This association may be due to underlying health conditions that both increase the need for longer sleep and elevate cancer risk.

Sleep Quality:

  • Poor Sleep Quality: Impaired sleep quality, including difficulties in falling asleep, staying asleep, and experiencing restorative sleep, has been associated with an increased risk of cancer. A study of older adults found that even moderately impaired sleep quality was associated with a 33% increased risk of cancer, with 58% increase for severely impaired sleep quality.41

Circadian Rhythm Disruption:

  • Shift Work and Circadian Disruption: Disruption of the circadian rhythm, as seen in shift workers, is recognized as a probable carcinogen by the International Agency for Research on Cancer (IARC). Shift work that involves circadian disruption is associated with an increased risk of breast, prostate, and gastrointestinal cancers.42 Circadian disruption can lead to hormonal imbalances, impaired DNA repair, and increased inflammation, all of which can contribute to cancer development.43[^45]

Mechanisms Linking Sleep and Cancer:

Hormonal Regulation:

Melatonin, a hormone that regulates sleep-wake cycles, has anti-cancer properties, including antioxidant effects and the ability to inhibit tumor growth. Reduced melatonin levels due to disrupted sleep or exposure to light at night may increase cancer risk. Elevated cortisol levels due to sleep deprivation can promote cancer progression by increasing inflammation and suppressing immune function.4344

Immune Function:

Adequate sleep is essential for maintaining a robust immune system. Sleep deprivation can impair immune surveillance, reducing the body’s ability to detect and eliminate cancer cells.4344

Inflammation:

Sleep disruption can lead to the upregulation of proinflammatory cytokines, such as IL-6 and CRP, which are associated with increased cancer risk.4344

DNA Repair:

Sleep is crucial for DNA repair processes. Disrupted sleep can impair the body’s ability to repair DNA damage, leading to mutations that can contribute to cancer development.43

Sleep in Cancer Patients and Survivors

Sleep disturbances are highly prevalent among cancer patients and survivors, with issues such as insomnia, circadian misalignment, hypersomnia, and nightmares being common. Poor sleep quality in cancer patients is associated with reduced quality of life, fatigue, depression, and cognitive impairment. Long-term cancer survivors often continue to experience sleep problems, which can affect their overall health and functional status. Addressing sleep issues in survivors is crucial for improving their quality of life and long-term health.44[^45][^46]

Conclusion

The relationship between sleep and cancer is supported by a growing body of evidence indicating that both short and long sleep durations, poor sleep quality, and circadian rhythm disruptions are associated with increased risk of developing cancer and cancer progression. Mechanisms such as hormone imbalances, impaired immune function, increased inflammation, and disrupted DNA repair may play significant roles in this relationship. Addressing sleep issues in cancer patients and cancer survivors is essential for improving their overall health and treatment outcomes. Further research is needed to fully understand the complex interactions between sleep and cancer and to develop effective interventions.

Footnotes

  1. https://www.ncbi.nlm.nih.gov/books/NBK19956/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  2. https://www.ncbi.nlm.nih.gov/books/NBK526132/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  3. https://www.sleepfoundation.org/stages-of-sleep ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  4. https://www.sleepfoundation.org/how-sleep-works/how-much-sleep-do-we-really-need ↩ ↩2

  5. https://www.sleep.com/sleep-health/sleep-schedule ↩ ↩2

  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399511/ ↩ ↩2

  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256323/ ↩

  8. https://www.nature.com/articles/s42003-021-02825-4 ↩

  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/ ↩

  10. https://www.sciencedirect.com/science/article/abs/pii/S2468867319301609 ↩

  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965491/ ↩

  12. https://www.ncbi.nlm.nih.gov/books/NBK526132/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  13. https://www.ncbi.nlm.nih.gov/books/NBK11121/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982729/ ↩ ↩2 ↩3

  15. https://www.nature.com/articles/nrn2716 ↩

  16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579972/ ↩

  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434546/ ↩

  18. https://pubmed.ncbi.nlm.nih.gov/33530453/ ↩

  19. https://www.sciencedirect.com/science/article/pii/S138994570870011X/pdf?md5=e126c8f27a2ce0d3a23f442fe57310c6&pid=1-s2.0-S138994570870011X-main.pdf ↩

  20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400203/ ↩

  21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304732/ ↩

  22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584347/ ↩

  23. https://jcsm.aasm.org/doi/10.5664/jcsm.9476 ↩

  24. https://pubmed.ncbi.nlm.nih.gov/30311830/ ↩ ↩2 ↩3

  25. https://www.sciencedirect.com/science/article/pii/S2211335522001516 ↩

  26. https://academic.oup.com/sleep/article/47/1/zsad253/7280269 ↩

  27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047226/ ↩ ↩2

  28. https://www.nature.com/articles/s41598-019-52352-w ↩ ↩2

  29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717723/ ↩ ↩2

  30. https://pubmed.ncbi.nlm.nih.gov/30454599/ ↩

  31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491889/ ↩

  32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991337/ ↩ ↩2 ↩3 ↩4 ↩5

  33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929498/ ↩ ↩2 ↩3 ↩4 ↩5

  34. https://onlinelibrary.wiley.com/doi/10.1002/dmrr.3667 ↩

  35. https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-015-0018-3 ↩

  36. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.773646/full ↩

  37. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-018-5557-8 ↩

  38. https://www.frontiersin.org/articles/10.3389/fendo.2021.773646/full ↩

  39. https://www.nature.com/articles/s41598-021-91275-3 ↩ ↩2

  40. https://pubmed.ncbi.nlm.nih.gov/24460326/ ↩

  41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953221/ ↩

  42. https://link.springer.com/article/10.1007/s10555-021-01238-6 ↩

  43. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01238-y ↩ ↩2 ↩3 ↩4 ↩5

  44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600154/ ↩ ↩2 ↩3 ↩4

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