Sleep-Cycle

Sleep – Why It’s Important, with Proven 21 Health Benefits

Introduction

Sleep is defined as a natural and reversible state of reduced responsiveness to external stimuli and relative inactivity, accompanied by a loss of consciousness (R).

Sleep occurs in regular intervals and there is a consistent need for sleep, so a loss or delay of sleep results in subsequently prolonged sleep (R).

There are two types of sleep non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep.

Rapid Eye Movement (REM) Sleep:

REM sleep is characterized by high-frequency low-voltage brain activity (as measured by an electroencephalogram) and bursts of rapid contractions of the eye muscles, causing the eyes to move rapidly. 

A healthy young person’s normal night of sleep typically includes 4-5 distinct REM periods, accounting for 20% of the total time spent asleep (TSA) (R).

Non-Rapid Eye Movement (NREM) Sleep:

Most of the night is spent in non-REM sleep, which is further divided into 4 sub-stages (stages I-IV).

Stage I is the lightest stage of sleep

Stage II sleep is defined by the emergence of specific peaks in the electroencephalogram (EEG) (K-complexes and sleep spindles) and typically accounts for more than half of the night’s sleep.

Stage III and IV, the deepest states of sleep are characterized by slow brain waves, also called delta brain wave. Together stages III and IV are also referred to as “Slow wave sleep” (SWS).

For a healthy young person, the first progression through the four nonREM sleep stages typically takes 70-100 minutes.

z9j0021326560001

Typical human sleep profile and sleep related signals

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768102/

Over the course of a period of sleep both REM and NREM alternate cyclically.

Irregular cycling and/or the absence of sleep stages are associated with sleep disorders (R).

Sleep Disorders

Primary sleep disorders include those not attributable to another medical or psychiatric condition and these include (R):

  • Insomnia
  • Narcolepsy
  • Obstructive sleep apnea
  • Central sleep apnea
  • Parasomnias (abnormal activities during sleep, which could be walking, eating or sex)

Insomnia

Insomnia is a common sleep disorder. People who have insomnia have trouble falling asleep, staying asleep or both (R). As a result, they may get too little sleep or have poor-quality sleep.

It is more common in women, with prevalence ranging from 10 to 30% of the population (R1, R2).

Insomnia can be acute or chronic. Acute insomnia lasts for few days or weeks and is often brought on by psychological stresses such as work and family pressures etc.

Chronic insomnia which lasts for a month or longer is mostly secondary to other health issues (R).

The most important causes of chronic insomnia are medications, drug or alcohol  abuse, psychiatric disorders like depression or anxiety and other diseases, including (R):

  • Arthritis
  • Asthma
  • Hyperthyroidism
  • Parkinson’s disease
  • Kidney disorders
  • Heart failure
  • Rhinitis (irritation and inflammation of mucous membrane inside the nose)
  • Prostate hypertrophy (enlarged prostate gland).

Obstructive Sleep Apnea (OSA)

Ongoing obstructive sleep apnea is a sleep disorder that is marked by pauses in breathing for 10 seconds or more during sleep, causing unrestful sleep. Symptoms include loud or abnormal snoring, daytime sleepiness, irritability and depression (R).

OSA affects 4% of men and 2% of women (R) and is strongly linked to the current obesity epidemic (R).

Central Sleep Apnea

Central sleep apnea (CSA) is defined by the cessation of airflow without breathing effort (R).

This condition is different from obstructive sleep apnea in which ongoing the breathing effort is present during respiratory events (R). The patient simply stops breathing during sleep because the nervous system does not send proper signals to the breathing muscles during sleep. 

Narcolepsy

Narcolepsy is a disorder that causes periods of extreme daytime sleepiness even after adequate sleep during the night (R).

Some narcoleptic patients fall asleep suddenly, even if they are in the middle of talking, eating or another activity.

Health Benefits of Sleep

1) Sleep Improves Memory

Sleep is essential for effective cognitive functioning (R).

Naps can reduce sleepiness and improve cognitive performance (R).

Memory is one of the essential cognitive functions involved in all other cognitive processes.

Sleep helps strengthen and stabilize new memories acquired before sleep (R1, R2, R3).

Sleep actively promotes the reprocessing of fresh memories as well as their integration into the pre-existing network of long-term memories (R1, R2, R3).

A short period of sleep prior to learning can enhance the capacity to encode new information (R).

Sleep loss diminishes a wide variety of cognitive functions such as attention, language, reasoning, decision-making, learning and memory (R1, R2, R3).

In children, shortened sleep duration, especially before the age of 41 months, is associated with lower cognitive performance and developmental tests (R).

Humans totally deprived of sleep showed deficits in motor procedural, implicit memory and working memory (R).

2) Sleep Helps Remove Waste from the Brain

bigstock-d-rendering-of-human-brain-o-163987757-min

Sleep stimulates the clearance of metabolic waste from adult brain (R).

The glymphatic system (the waste clearance system for the nervous system) clears metabolic waste from the mammalian brain while the cerebrospinal fluid removes the beta-amyloid metabolites from the brain (R1, R2).

When individuals sleep well, the glymphatic system can effectively remove cellular waste byproducts that have accumulated outside and inside the brain cells (R).

3) Adequate Sleep Reduces the risk of Heart diseases

bigstock-medical-stethoscope-head-and-r-104167844-min

Sleep influences cardiovascular function both in healthy people and those with heart diseases (R).

Getting enough quality sleep can reduce cardiovascular risk (R).

Sleep duration of <5hr per night was associated with a significantly increased risk of hypertension in subjects between the ages of 32-59 years (R).

The Standardized mortality ratio of Coronary Heart Disease (CHD) was highest among those who worked 67 hr or more a week (R).

Men sleeping 4 hr or less had higher mortality from CHD than those sleeping 7-7.9 hours (R).

Women reporting 9 or more hours of sleep had a relative risk of developing coronary heart disease (CHD) (R).

Hence short and long self-reported sleep durations are independently associated with a modestly increased risk of coronary heart diseases (R).

Hypertension and increased sympathetic nervous system activity may underlie the relationship between sleep deprivation and CHD (R).

4) Sleep Enhances Immune Response

424_2011_1044_fig1_html

Sleep supports the Initiation of an adaptive Immune response

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC325632/

Adequate sleep strengthens Immune function (R1, R2).

Sleep also enhanced the human antibody response to hepatitis A vaccination in healthy people (R).

Mechanism: Sleep presumably enhances lymphocyte proliferation, differentiation, and antibody synthesis.

Good sleep imparts long-lasting immune enhancing effects (R) and sleep after vaccination boosts the effectiveness of the vaccine (R).

Sleep also promotes recovery from infectious diseases and lack of sleep increases susceptibility to infections.

Sleep deprivation in humans changes both circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IL-6, TNF-ɑ etc). Hence the lack of sleep may reduce immunity (R).

5) Sleep Helps Reduce Appetite

The two hormones that play a major role in appetite regulation are leptin and Ghrelin. Leptin is a hormone that decreases your appetite, ghrelin is a hormone that increases your appetite.

In both animals and humans sleep loss is associated with decreased leptin and increased ghrelin levels, and therefore an increased appetite (R1, R2)

In sleep-deprived young men, the decrease in leptin was 18% and an increase in ghrelin was 28% with a total increase in appetite by 23% (R).

6) Sleep May Help with Weight Loss

bigstock-weight-loss-12023894-min

Insufficient sleep and possibly longer sleep are associated with obesity and eating related problems (R).

Sleep duration of <6 hour/night has been associated with higher BMI (Body Mass Index) (R1, R2).

National Health and Nutrition Examination Survey (NHANES) analysis showed that adults who slept less than 7hr were more likely to be obese (R).

People who slept only 5.5 hours lost 55% less body fat and 60% more fat-free mass (e.g bones and muscles) compared to people who slept 8.5 hours (R).

Long work hours could contribute to obesity via a reduction in sleep duration in adults (R).

7) Sleep Increases Growth Hormone

In healthy young adults, pharmacological stimulation of Slow-wave (SW) sleep resulted in an increase in Growth Hormone (GH) release (R).

The mean GH levels were higher during Slow wave sleep  (SWS) compared to other sleep stages (R).

Growth hormone also increases during naps, but more during afternoon naps than morning naps (R).

8) Sleep as Neuronal Detoxification process

Brain tissues and body fluids of sleeping and sleep-deprived animals contain active sleep-inducing factors (sleep-promoting substance) including uridine and glutathione.

Glutathione of SPS may counteract excitotoxic events, hence sleep is a process of neuronal detoxification at the cellular level (R).

Note: Neuronal relates to a neuron or neurons (nerve cells).

Effects of Sleep loss

1) Sleep loss and Diabetes risk

Glucose tolerance was lower in the sleep-deprived young men compared to those who rested well (p<0.02) (R).

Sleep deprivation also results in reduced insulin sensitivity (R).

In a cohort study men reporting short sleep duration (<or= 5 and 6hr) and long sleep duration (>8hr sleep per night) were twice and more than three times as likely to develop diabetes, respectively (R).

Therefore, both short and long sleep duration increases the risk of developing diabetes (R).

13098_2015_18_fig1_html

Metabolic pathways linking Sleep disorders with the development of Type 2 diabetes

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381534/

2) Sleep loss Lowers Testosterone

In young adult men, testosterone levels begin to rise upon falling asleep, peak at about the time of first REM and remain at the same levels until awakening (R).

Animal and human studies have shown that total sleep deprivation/loss lowers testosterone and this effect may be dependent on age (R1, R2).

In a clinical cohort study, men with lower testosterone levels had lower sleep efficiency (R).

3) Sleep Loss May Trigger Autoimmune Diseases

T regulatory cells suppress inappropriate immune and prevent our immune system from attacking our own cells (maintaining self-tolerance) (R). Breakdown of this process can cause autoimmune diseases (R).

In experimentally sleep-deprived healthy people, the suppressive activity of T reg is reduced, providing a link between sleep disorder and autoimmune disease (R).

Sleep deprivation increases proinflammatory cytokines like IL (interleukin)-1, IL-1β, IL-6, IL-17, and TNF-ɑ.

IL-17 remained elevated following sleep deprivation, even after recovery for 7 days (R).

IL-17 has been associated with several autoimmune diseases including Systemic lupus erythematosus (SLE), Rheumatoid Arthritis (RA), Inflammatory bowel disease and multiple sclerosis (R).

Disordered sleep may induce systemic inflammation and activate the function of IL-17-secreting (Th17) cells, thereby leading to autoimmune diseases (R1, R2, R3).

Studies show that mice with chronic sleep deprivation develop an autoimmune disease that strongly resembles Systemic lupus erythematosus (SLE) in humans (R1, R2).

4) Sleep Loss May Lead to Depression

Patients with persistent insomnia have a 2 to 3.5-fold increased risks of developing depression than those without insomnia (R, R2).

Sleep disturbances are also commonly associated with other psychiatric illnesses, including (R)

  • generalized anxiety disorder
  • panic disorder
  • posttraumatic stress disorder

5) Sleep Loss Causes Stomach and Bowel Disorders

The ability of the stomach to defend itself against several potential hazards is because of a number of factors which constitute the “gastric mucosal defense” like (R)

  • mucus and bicarbonate secreted by surface epithelial cells (neutralize HCl)
  • Prostaglandins (act on the stomach wall to inhibit acid secretion)
  • gastric mucosal blood flow (protects mucosa by supplying with oxygen and removing H+ and toxins)
  • Melatonin secretion (stimulates duodenal bicarbonate secretion, which acts against the HCl discharged from the stomach) (R)

During sleep defensive mechanisms against peptic ulcers increase while gastric acid secretion decreases (R, R1, R2).

Animal studies have shown that partial sleep deprivation (PSD) compromises gastric mucosal integrity by increasing gastric acidity, blood levels of gastrin, histamine, and noradrenaline and decreasing stomach mucosal blood flow (R).

Hence sleep deprivation damages the stomach and could be one of the risk factors for ulcer formation.

Women who sleep more are less likely to get peptic ulcer disease (R).

A cross-sectional study found a nearly 3-fold increased risk of bowel disorders in patients with insomnia (inability to sleep) (R).

Disturbed sleep also could have an adverse effect on bowel functions (R1, R2, R3).

Symptoms of Irritable bowel syndrome (IBS) decreased when subjects slept better (R).

Both extreme short and long duration sleep moderately increased the risk of colorectal cancer in postmenopausal women (R).

6) Poor Sleep May lead to Nonalcoholic Fatty liver Disease (NAFLD)

Short sleep duration and poor sleep quality were significantly associated with an increased risk of nonalcoholic fatty Liver disease (NAFLD) (R).

Results from the Dongfeng-Tongji cohort study showed that long nighttime sleep duration was associated with a modestly increased risk of NAFLD in NAFLD-free subjects (R).

7) Sleep Duration and Cancer risk

In animal studies sleep deprivation altered proteins associated with the proliferation and apoptosis in carcinogenesis like (R).

  • Bcl-2 which prevents the activation of caspases (protease enzymes which help in programmed cell death) and apoptotic process.
  • Bax which activates caspases leading to cell death.
  • p53 which is a tumor suppressor gene.

Meta-analysis studies suggest a positive association between long sleep duration and colorectal cancer (R).

A prospective cohort analysis in women suggests that longer sleep may be associated with increased risks of estrogen-mediated cancers (R).

Less than/equal to 6hr of sleep increases the risk of developing prostate cancer, and sleep greater than/equal to 9 hr has a lower risk (R).

Both short and long sleep duration are associated with a higher risk of breast cancer (R, R2).

Sleep duration may influence breast cancer risk possibly via its effects on melatonin levels (R).

Melatonin prevents tumor initiation, promotion, and progression possibly by (R)

  • Its antiproliferative effects (R1, R2).
  • Its ability to increase protein 53 (p53), a tumor suppressor protein (R).
  • Its capacity to induce cell differentiation (R)
  • Its antimetastatic effects (R)
  • Its antiangiogenic activity (R)
  • Its capacity to decrease telomerase activity (R1, R2)
  • functioning as a free radical scavenger (R).

Melatonin is a hormone which mainly synchronizes the circadian rhythm (R).

Melatonin production may be closely related to sleep duration, night-shift work is expected to disrupt sleep pattern and thus decrease melatonin levels (R, R).

Health Disorders Associated with Sleep Problems

1) Depression and Anxiety

Most depressive disorders patients also have sleep disturbances. Most antidepressant medications suppress rapid eye movement (REM) sleep (R).

Difficulty in initiating or maintaining sleep or both have been reported in about three-quarters of all depressed patients (R).

72.7% of youths with major depression also reported insomnia, and hypersomnia (R).

2) Brain fog

32% of people with brain fog also have a diagnosed sleep disorder, most commonly insomnia, sleep apnea or restless leg syndrome (R).

3) Attention-deficit/Hyperactivity Disorder (ADHD)

In mental health practice settings, children and adolescents with ADHD frequently reported sleep problems, particularly difficulty in initiating and maintaining sleep (R).

4) Cancer

Sleep problems such as difficulty falling asleep, problem maintaining sleep, poor sleep efficiency, early awakening, and excessive daytime sleepiness is prevalent in patients with cancer (R).

Other Effects of Sleep

Oxidative Stress in Obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with increased levels of oxidative stress or antioxidant deficiencies or both (R1, R2, R3, R4).

Oxidative stress contributes to sleep behavior in obstructive sleep apnea patients, and antioxidant intake improves the quality of sleep in them (R).

Sleep and HPA Axis

i1523-5998-003-04-0151-f01

The Hypothalamic-pituitary-adrenal axis

                     Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181180/

HPA axis the Hypothalamic-pituitary-adrenal axis mainly regulates “stress”. During a physical or emotional stress, HPA axis is activated (R).

Sleep in particular slow wave sleep has an inhibitory effect on HPA axis and cortisol secretion (R).

Sleep loss and sleep disruption activate the HPA axis and increase cortisol levels (R).

Sleep and HPT Axis

HPT the Hypothalamic-pituitary-thyroid axis primarily functions to maintain normal circulating levels of thyroid hormone and is responsible for the regulation of metabolism (R1R2).

The hypothalamus senses low circulating levels of thyroid hormone and respond’s by releasing thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary to produce thyroid-stimulating hormone (TSH). TSH further stimulates the thyroid gland to secrete the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine).

Human sleep inhibits TSH secretion (R).

Sleep loss increases TSH (Thyroid stimulating hormone), T4 and T3 (R1, R2).

Sleep and HPG axis

nihms403039f1

GnRH= Gonadotropin-releasing hormone, LH= Luteinizing hormone, FSH=Follicle stimulating hormone

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547681/

The Hypothalamic-pituitary-gonadal (HPG) axis mainly controls development, reproduction, and aging.

Testosterone levels begin to increase with the onset of sleep and reach a peak at REM sleep (R).

The increase in testosterone with sleep and decrease during time awake is stable for an individual, but in turn, there are individual differences (R).

For example old vs young (aging) since in older men there is an objective difference in the amount of nighttime sleep (R).

Studies confirm that total sleep deprivation reduces testosterone levels in males (R1, R2).

Deep sleep stimulates LH (luteinizing hormone) secretion. Entrance into deep sleep might stimulate GnRH (Gonadotropin releasing hormone) and the consequent secretion of LH (weight: 400;”>R1, R2).

Uridine Promotes Sleep

The induction of sleep may be mediated by uridine through uridine receptor in the central nervous system (R).

Uridine binds to the receptors in the areas of the brain which regulate natural sleep.

Uridine, when administered through a systematic route (like intraperitoneally), may pass through the blood-brain barrier to balance sleep (R).

Technical

  • Cohort studies are a type of medical research used to investigate the cause of disease, establishing links between risk factors and health outcomes.
  • A longitudinal study is an observational research method in which data is gathered for the same subjects repeatedly over a period of time.
  • Beta amyloids are peptides of 36-43 amino acids that are crucially involved in Alzheimer’s disease (AD) as the main component of the amyloid plaques found in the brain’s of AD patients.
  • One potential pathway linking sleep duration and cardiometabolic health is via systemic inflammation (R).
  • Hypersomnia or hypersomnolence is a neurological disorder of excessive time spent sleeping or excessive daytime sleepiness (EDS).
  • K-complex is an electroencephalography (EEG) waveform that occurs during stage 2 of NREM sleep. It is the largest event in healthy human EEG. They are more frequent in the first sleep cycles.

350px-stage2sleep_new-svg

  • A sleep spindle is a burst of oscillatory brain activity visible on the EEG that occurs during stage 2 sleep. It consists of 12-14 Hz waves that occur for at least 0.5 seconds. Sleep spindles are generated in the thalamus of the brain.
  • Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal as well as malignant tissues (R).
  • Slow wave sleep (SWS) is considered the most restorative stage of sleep where the greatest impact from immune regulation happens.
  • During SWS smooth muscles in the colon contract less, so this phase of sleep is considered the “rest period” for the colon.
  • So alterations in this phase of sleep can have direct effects on GI (gastrointestinal) physiology (R1, R2).
  • Sleep disorders are generally diagnosed using Electroencephalography (EEG) a method used to record the electrical activity of the brain.
  • Intraperitoneal means administered through the peritoneum which is a thin transparent membrane that lines the walls of the abdominal cavity that encloses the abdominal organs such as stomach and intestines.

Leave a Reply