Sleep and Health

Question 1

Sleep as a pillar of health:
1- a trend of?
2- what has been found for those sleeping less than 8 hours?
3- short and long sleepers finding?

Answer 1

1- A trend of sleeping fewer hours than the recommended
2- Prospective studies have reported a higher risk for cardiovascular events, metabolic disease and obesity in those sleeping less than 8 and those sleeping more than 9 hours (Ayas et a, 2003)
3- Prospective study in the UK found increased risk for cardiovascular problems in short and long sleepers even if they took into consideration existing problems (Ferrie et al 2007)

Question 2

Systematic Review and Meta-analysis by Gallicchio and Kalesan (2009) finding

Answer 2

Analysed 23 prospective studies that examined the association between sleep duration and all-cause and/or specific mortality

• In both men and women , there was an increased risk in short and long sleepers for all-cause mortality compared to those who slept 7-8h
• Specific risk for cardiovascular disease and cancer

Question 3

Sleep, Morbidity and Mortality(Kallicchio and Kalesan, 2009)

Answer 3

There is a moderate increased risk for short and long sleepers compared to those who are sleeping 7-8 hours

U shaped relationship between time we spend asleep and the risk factor associated with it

Question 4

Sleep and Obesity:
- what is a risk factor for obesity in children and adults?
- UCLA Energetics Study (2014)

Answer 4

• Using self-reports in 223 adults between 21-69y
• Asked questions about their sleep and measured calories indirectly (using double-labelled water which measures CO2 expenditure)
• Only 12 responses of less then 5 hours of sleep and only 4 responses for more than 10 so these were combined with 6 and 9 respectively, in a cross-sectional study
• Objective measures for calories but subjective measures for sleep

Question 5

The Association between sleep duration with BMI, Sleep, Energy Intake and Physical Activity

Patterson et al, 2014

Answer 5

Higher BMI is found in those that are sleeping fewer hours than those 7-8 hours

Same for energy intake- people sleeping less were taking in more calories

Physical activity was not significant

Those who are under-sleeping or oversleeping can suffer from morbidity, increased risk of dying. People who sleep less are more likely to consume more food

Question 6

1- what is poor sleep associated with?
2- what are behaviours which contribute to obesity?
3- implication of those who sleep sufficiently?
4- Eve Van Cauter (U Chicago) suggested?
5- what do studies provide strong evidence in support of?

Answer 6

1- Poor sleep is associated with greater morbidity and mortality
2- Behaviours that contribute to obesity are modifiable: sedentary lifestyle, overeating or poor diet, and delayed meal patterns
3- Those who sleep sufficiently, tend to be physically more active and have better diet
4- Eve Van Cauter (U Chicago) suggested that the current obesity epidemic may be due to sleep deprivation as well as the increased consumption of sugar, as 40% of American adults are considered obese
5- Studies provide strong evidence in support of the role of sleep in body-weight regulation

Question 7

What are the mechanisms that can account for sleep and obesity findings?

Answer 7

Mostly focused on leptin and ghrelin although not always consistent findings

— Leptin – an anorexigenic signal released from adipocytes. Hormone produced by adipose tissue. Making us not eat. Reduced when we don’t sleep well.

— Ghrelin- an orexigenic signal released from the stomach. Tells us we should eat. Increases when sleeping.

• Short sleepers (5h/night) secrete lower leptin and higher ghrelin than normal sleepers (8h/night) (also correlated with reports of hunger and appetite)
• Neuroimaging studies also find greater activation of regions involved in reward such as the nucleus accumbens, insula etc

Question 8

Meal Timing:
1- Does it matter when we eat?
2- when is sleep most efficient?
3- who are most susceptible to weight gain and obesity?
4- example

Answer 8

1- Timing of sleep can affect our risk for obesity
2- Most efficient sleep when conducted in sync with the circadian rhythm
3- Adolescents and adults with a delayed rhythm are more susceptible to weight gain and obesity.
4- Freshmen college students who were evening types gained sig more weight over an 8-week period compared to morning types.
- Severely obese adults undergoing bariatric surgery, evening types weighed more before surgery, lost less weight after surgery and regained more weight at follow-up

Question 9

1- what have delayed meal times also been linked to?
2- what may impact when we eat- findings of when this has been impacted

Answer 9

1- Delayed meal-times have also been linked to increases in BW– even when the total calories are the same, it makes a difference if consumed early in the day vs later in the day

2- Sleep duration may impact when we eat – when bedtime was delayed in a sleep-restriction study (4h total time in bed x 5 nights), participants took 500+ calories during the late-night hours when they were kept awake instead of going to bed (10pm-4am) and fewer calories (~100) the next morning (8am-3pm).

• This led to a shift in the timing of caloric intake depending on sleep. Those in the non-restricted sleep group ate mostly before 3pm and those in the sleep-restricted group ate mostly after 3pm
• The food consumed late at night (10pm-4am) was correlated with the weight gained and was higher in fat (may have greater impact on body weight) (Spaeth et al, 2015)

Question 10

Fonken et al. (2010) study on circadian disruption and body weight

Findings

Answer 10

Both bright light (LL) / dim light (DM) increased body mass and reduced glucose tolerance despite equivalent caloric intake and activity levels.

Animals in DM conditions consumed most of their food during the light phase instead of the dark phase (55% for DM vs 35% for LD)

This was prevented if feeding was restricted only duringthe active phase of the DM

Question 11

Sleep and diabetes:
1- what is secreted, why, function
2- restricted sleep and diabetes
- findings

Answer 11

1- Insulin is secreted when glucose levels rise, in order for the liver, muscle and fat cells to absorb the excess glucose from the blood and convert it to glycogen or fat, for longer term use

2- When sleep is restricted, to only 4 hours of sleep for 5 nights, healthy college students began to look pre-diabetic (Spiegel, Leproult and Van Cauter, (1999) The Lancet)
- The rate in which their bodies cleared glucose from their blood dropped by 40% compared to controls (getting 8h of sleep a night)
- After an acute administration of insulin their bodies’ response was similar to that seen with aging or in pregnancy-related diabetes

Question 12

Mimicking shift-work in animals (Salgado-Delgado et al 2008)
how / findings

Answer 12

• Motivating animals to be active during their rest phase by slowly rotating drums to force activity (‘forced work’) for 5 days/week
• Revealed internal desynchronization at the metabolic and behavioural level:
  – Ate less during their active phase
  – Less active during their active phase
  – Gained more weight under these conditions by the 4th week

Question 13

Salgado-Delgado et al. (2008)

Activity results

Answer 13

1) had a few days of baseline (which showed a big difference between their activity levels during the light phase and during the dark phase)

2) time off work showed - they tend to be active more equally during the day time and night time. SO their circadian rhythms have been disrupted.

Question 14

Salgado-Delgado et al. (2008)

Mean food intake in control animals, work during the sleep phase (W-SP) and work during the active phase (W-AP)

Answer 14

• In control conditions they are eating more during the night (dark bars are significantly higher)
• When they are working during their sleep phase it is kind of reversed. Their food intake decreases when they go to work. This changed their glucose levels.

Question 15

The Effects of Feeding during the Light or Dark Phase:

What did Arble et al. (2009) and Adamovich et al. (2014) find?

Answer 15

Arble et al 2009: Mice fed with a high-fat diet only during the 12-h light phase gained significantly more weight than mice fed only during the 12-h dark phase.

Adamovich et al 2014: Night-restricted feeding leads to reductions in triglyceride levels in mice

At baseline started off with the same body weight but animals who slept during rest phase gained more weight even though the food was the same

Question 16

factors considered for eating patterns in humans?

Answer 16

• Assumption that we generally eat 3 meals per day
• Focus on calories in and calories out monitoring to control body weight and associated health issues

Question 17

Gill & Panda (2015)

study and findings

Answer 17

1. Asked people to take a picture of what they’re eating/ drinking and send it
2. They did a baseline eating pattern to get this information for 3 weeks
3. findings: people do not really consume three meals per day as we thought. They found erratic daily eating patterns spread over day and night. Weekend eating patterns delayed from weekdays. There is a lot of variation and it is not consistent.
4. Then they took a number of overweight individuals and decided to restrict the time they would eat (10-12h every day). They gave feedback through Feedograms. No recommendation on nutrition or calories.
5. findings: weight loss; improved sleep

Question 18

Gill & Panda (2015)

Answer 18

• baseline (3 wks) - 8 subjects with >14h eating duration and BMI >25 - intervention (16 wks) - no monitoring (36 wks)
• eating behaviour (caloric containing eating duration). For the 16 week intervention the bars are shorter so they’re eating food in a smaller period throughout the day.
• overall there was a decrease in body weight after 16 weeks and then after a year of follow up
• decrease in body weight after the intervention
• subjective score of how energetic they feel (in morning, overall, ect…) They felt more energetic in the morning when they were on this restrictive feeding pattern. They had more energy overall, hunger at bed time dropped and sleep satisfaction was higher.

sum- improved eating patterns reduced body weight in healthy overweight individuals

Question 19

The Effects of Time-Restricted Feeding

Zarrinpar, Chaix & Panda, 2016

Answer 19

Time-restricted feeding is beneficial for our health and body weight

Animals are becoming obese and they are disrupting all bacteria in their gut and it leads to many diseases.

Eating in active phase is associated with many benefits

Question 20

Sleep and cardiovascular health:

Hoevenaar-Blom et al. (2011) study and findings

Answer 20

Sleep Duration: Those who slept ≤6 hours had a 15% higher risk of CV disease (CVD) incidence and a 23% higher risk of Coronary Heart Disease (CHD) incidence compared to people who slept 7-8 hours.

Sleep quality: Those with short sleep duration and poor subjective sleep had a 63% higher risk of CVD and 79% higher risk of CHD than those with normal sleep duration and good sleep quality

*FYI: Whitehall II study in London followed people for ~years

Question 21

Insufficient sleep and cardiovascular disease risk

Answer 21

Insufficient sleep ←→ sympathetic hyperarousal → heart rate & blood pressure, vascular dysfunction & insulin resistance

Insufficient sleep ←→ systematic inflammation → vascular dysfunction & insulin resistance, lipids & obesity

Insufficient sleep ←→ hypothalamic-pituitary-adrenal axis dysregulation → vascular dysfunction & insulin resistance, lipids & obesity

Question 22

Sleep and Blood Pressure
1- blood pressure change in evening/ morning, name?
2- what is short sleep predictive of?
3- what is short sleep associated with?
4- what is insomnia associated with?
5- insomnia and risk?

Answer 22

1- Naturally, there is a 10-20% drop in blood pressure in the evening followed by a morning surge – ‘non-dippers’** (don’t have circadian rhythm of blood pressure dipping in evening) **are considered to be at greater risk for hypertension

2- Short sleep is predictive of hypertension for those younger than 60 but not those older

3- Short sleep is associated with increased risk for high blood pressure even if obesity is factored in

4- Insomnia, such as difficulty initiating sleep, maintaining sleep and non-restorative sleep have all been associated with increased risk for myocardial infarction (MI) in men and women, especially difficulty initiating sleep

5- Insomnia is also associated with a greater risk for stroke

Question 23

The day/night pattern of adverse cardiovascular events

Answer 23

Epidemiological studies find that adverse cardiovascular events including myocardial infarction (MI), sudden cardiac death (SCD), and ischemic stroke have increased frequencies in the morning hours compared with other times of the day and night

(Thosar, Butler and Shea, 2018)

Question 24

Could it also be that heart disease is causing disruptions in sleep?

Answer 24

bad sleep → heart problems

bad sleep ← immune system activation - heart problems

Question 25

What is impacted by Heart Disease?

Ziegler et al 2023, Science

Answer 25

Collected postmortem pineal glands from heart disease patients (N=7) and heart-healthy controls (N=9) and stained them for the enzyme tyrosine hydroxylase. In patients, pineal gland tissue had significantly reduced axonal density

Could this finding explain the diminished levels of melatonin in these patients?

(- pineal glands release melatonin when its dark
- you can see the difference between heart healthy and heart disease- heart disease have less neurons that reach the pineal gland and release melatonin.)

Question 26

Ziegler et al 2023, Science

Findings for echocardiography

Answer 26

Looked at superior cervical ganglia (in necks) in healthy and heart patients

Heart healthy → echocardiography → upper neck ganglion ultrasound

For the heart disease patients it was swollen. SO they believed these were swollen because they were inflamed

Question 27

Heart dysfunction linked to sleep

Answer 27

Heart disease: (steps feed into one another)
1. cardiac dysfunction
2. activated macrophage infiltration
3. superior cervical ganglia neuron loss
4. Pineal gland denervation
5. less melatonin release and disordered sleep

Question 28

Immune system:
1- what is tis primary function
2- important to?
3- what can poor sleep do?

Answer 28

1- Immune System – primary function is to recognize self from non-self (external pathogens) but also to recognize internal (self) pathological challenges that arise in cells and tissues that could lead to disease
2- Important to balance the immune response, in order to prevent self-damage caused by excessive reaction
3- Poor sleep can impair both innate and adaptive (acquired) immunity

Question 29

What did Cohen et al 2009 do and what has a similar study also found?

Answer 29

• Exposure to rhinovirus in the lab
  – Participants were quarantined in a hotel, and given a rhinovirus
  – Viral-specific antibody measures are obtained 21-28 days after
• Found that shorter sleep duration and poorer sleep efficiency assessed by 14-day sleep diary significantly predicted a greater chance for developing a cold

A similar study found that those that slept less than 6 hours had 4X greater chance of developing a cold than those with 7h+ of sleep (Prather et al 2015)

Question 30

Sleep and Innate Immunity
1- during exam periods, what is there an association between?
2- finding from the National Health and Nutrition Examinations Survey (NHANES) spanning from 2005-2012
3- Important experimental paradigms that shed light in this area are those using _____?

Answer 30

1- Association of decreased sleep and getting sick, during exam periods

2- short-sleep duration (5 hours or less), disturbed sleep or having a sleep disorder was associated with increased rates of colds as well as infection compared to long sleepers

3- Important experimental paradigms that shed light in this area are those using exposure to pathogens in a controlled environment while monitoring sleep

Question 31

Sleep and Immunizations: Hepatitis studies and findings

Answer 31

A study on Hepatitis A vaccine (Lange, et al 2003):
- Method: Half were allowed to sleep the night after the vaccine and half were sleep-deprived
- Findings: Those deprived produced only half the antibody levels of controls at 4 weeks post-vaccination

A similar study found that even a year later, those who slept the night before the vaccine had more antibodies than those who didn’t

Prather et al 2012
Method: used wrist actigraphy and measured vaccination response to hepatitis B vaccination in healthy adults

Findings:
— Shorter average sleep duration was associated with fewer specific antibodies to the vaccination
— There was a 56% increase in antibody production with every additional hour of sleep
— Short sleepers (less than 6h) were nearly 12x more likely to be left unprotected 6 months after the vaccination compared to those who slept 7h or more

Question 32

Sleep and Immunizations:
- acute sleep loss findings
- Prather et al 2021

Answer 32

• Acute sleep loss can impair antibody responses compared to undisturbed sleep
• Prather et al 2021 – sleep before and after influenza vaccine and antibody levels
• the two nights preceding vaccination were the most important for immunity, even four months later

Question 33

Sleep and Immune System Readiness:
1- what do circulating lymphocytes (T and B cells) do?
2- what has production of antibodies been associated with?
3- thus….

Answer 33

• Circulating lymphocytes (T and B cells) peak early in the evening and then during sleep they migrate in the lymphoid organs where they may come into contact with new antigens and get activated
• Production of antibodies has been associated with SWS which is characterized by increased secretion of GH and reduced levels of cortisol.
• Thus, sleep loss may hinder the ability of the immune system to tackle pathogens

Lympocytes recognise proteins we have encountered and start to create antibodies for this and tackle infections

Question 34

Inflammatory Risk:
1- inflammation link to sleep?
2- what have meta-analysis on sleep and inflammation found?
3- what can insufficient sleep also provoke?

Answer 34

1- Inflammation is a common pathway that leads to several conditions that have been associated with sleep
2- Meta-analysis on sleep and inflammation find that sleep disturbances (short and long sleep durations) were associated with higher levels of C-reactive protein (CRP)
3- Insufficient sleep can also provoke a pro-inflammatory response via increased cytokine secretion such as circulating IL-6, IL-1, tumor necrosis factor (TNF) etc (Vgontzas et al., 1999; 2004)

Question 35

Effects of acute sleep deprivation on C-reactive protein (CRP) and systolic blood pressure (SBP) in Meier-Ewert et al 2004

Answer 35

impact on inflammation levels which then makes us more susceptible to heart disease.

Increase of CRP and SBP (particularly SBP)

Question 36

inflammation in the gut:
1- what do flies and mice deprived of sleep show?
2- what do mice deprived for 5 days show?
3- what do studies find for humans?

Answer 36

1- Flies and mice deprived of sleep show accumulation of reactive oxygen species in the gut

2- Mice deprived for 5 days show accumulation of reactive oxygen species in the small and large intestine that causes cell damage and leads to death

3- In humans several studies find association of gastrointestinal problems and risk of colon cancer to be elevated in those with chronic insufficient sleep

Question 37

Impacts of sleep deprivation

Answer 37

Sleep deprivation leads to reactive oxygen species (ROS) accumulation in the fly and mouse gut
|
ROS trigger oxidative stress in the gut but this is prevented by the administration of antioxidants
|
prevention of ROS accumulation in the gut allows animals to survive even after prolonged sleep deprivation

(If they gave antioxidants it could reverse effects such as premature death)

Question 38

Solute and fluid clearance from the brain
(Iliff et al 2012)

Answer 38

• Flushing out waste from the brain using the flow of the CSF and astrocytes, thus, glymphatic system
• A large proportion of soluble Aβ is removed by bulk flow along the gliovascular clearance system rather than locally across the BBB - fluorescent-tagged Aβ moved rapidly along the vasculature when injected in the striatum
• Especially important for larger molecules such as proteins and peptides that may not readily diffuse into the subarachnoid space

AQP4- pores of astrocytes which are forming the channels (ways for csf to be flushed out). If they block this or pores aren’t working, fluid isn’t flushed out. They tested it and found a new way that we can get rid of anything.

studies have shown even one night of going to sleep → amyloid beta levels increased

so sleeping allows you to remove things which could cause inflammation

Question 39

What did Xie et al (2013) find in relation to sleep and amyloid beta

Answer 39

When we are awake there is a lot of amyloid beta it and when we are asleep it is cleared

Question 40

Sleep and cleansing away waste

Answer 40

• Waste material such as β-amyloid is removed much more quickly while we sleep
• After just one night of sleep deprivation, the level of β-amyloid increases by 5%
• The clearance of waste is linked to the flow of CSF which washes over the cells in the brain and carries away waste products (Xie et al., 2013).
• This flow occurs in pulses and the pulses are timed to the slow waves of NREM sleep (Fultz, et al, 2019, Science, 366, 628-31)

Question 41

Glymphatic System and Aging

Answer 41

When we are young we spend a lot of time in SWS but when we get older our sleep becomes more disrupted and we’re spending less time in deep sleep.

So when we are older this could be a reason we are more likely to develop neurological conditions because everything might not be cleared out the way that it used to.

Question 42

Exercise and Sleep:
- duration of sleep and impact
- interventions to address sleep?
- regular exercise implementation

Answer 42

• Many adults get less than 6 h of sleep per night and many experience sleep problems such as insomnia
• Interventions to address sleep problems include pharmacological options or psychotherapy like CBT
• Regular exercise is a potential alternative for those with poor sleep
  – Relatively inexpensive safe simple
  – Benefits for longevity and disease prevention

Question 43

Association Between Exercise Sleep Self-reports

Answer 43

• Greater ease of falling asleep
• Greater perceived sleep depth
• Higher morning alertness
• Better overall sleep quality
• Lower prevalence of sleep disorders including insomnia

Question 44

Laboratory studies find more modest associations between exercise and sleep

Answer 44

• Typically measure a single bout of exercise following a night of sleep using polysomnography
• Meta-analysis of these studies find only moderate relationship however studies mainly young population whose quality of sleep is already high
• Randomized controlled studies explored the chronic effects of exercise, using the national guidelines for exercise i.e. 150min per week of moderate to vigorous physical activity
  – Generally find that exercise improved sleep relative to control
  – Stronger effects in self-reported measures in older adults and poorer sleepers

Question 45

Temporal exercise-sleep relationships
1- relationship?
2- when is physical activity lower?
3- exercise and sleep finding?

Answer 45

• Mixed findings, but in general there seems to be a bidirectional relationship between exercise and sleep
• Physical activity is lower during days following sleep restriction compared to days with sufficient sleep – less moderate to vigorous physical activity
• Exercise positively predicted better subjective sleep quality on the subsequent night and better sleep quality predicted higher levels of exercise the next day (Dzierzewski et al 2014)

Question 46

Which type of exercise?

Answer 46

• Aerobic and resistance exercise such as yoga and tai chi have also been associated with better overall sleep, mediated by increases in cardiorespiratory fitness
• Yoga – strong antidepressant and anxiolytic effects
• Resistance exercise may mediate improvements in sleep via growth hormone secretion

Question 47

Impact of sleep deprivation?

Answer 47

• Studies in rats found that REM deprivation resulted in reduced weight and fibre area of the tibialis anterior muscle, accompanied by an increase in corticosterone and decrease in testosterone. Recovery of REM allowed for partial recovery in the muscle
• Acute 24-hour sleep deprivation resulted in abnormality in the architecture of the myofibers compared with the control and recovery groups.
  – Changes in fibre size and myo-phagocytosis after 24-hour sleep deprivation.
  – Even after recovery sleep, a few atrophic and angulated fibres persisted.

Demonstrates that if we look at the muscle tissue itself we can see there are direct effects of not sleeping on the muscle itself

Question 48

Sleep Deprivation and the Neuromuscular Junction

(Sharma et al 2023)- study and findings

Answer 48

Animal on the platform has to keep awake because if they don’t they will fall off into the water

Found that the fibres that make up the muscles were not as they should be compared to healthy control animal

There was a decrease in the nerve terminal branching, the neurons were less innovated, less receptors to respond with ACH compared to controls.

Question 49

Sedentary Behaviour

Answer 49

• Emerging as a novel risk factor for cardiovascular disease, diabetes, mental illness and all-cause mortality
• Defined as sitting or reclining with low energy expenditure
• Little research has explored whether sedentary behaviour is linked to sleep quality independent of physical activity
• In the American Time Use Survey, common sedentary pursuits such as work commute time, television viewing were associated with shortened sleep duration
• In youth, video gaming and computer use have been linked to shortened sleep duration and increased sleep onset latency

people with sedentary lifestyles (sitting down lots), as well as increasing risk for health issues they also sleep less

Should be doing activity during the day to create the contrast (between active and quiet phase)

Question 50

Synergies among sleep, sedentary behaviour and exercise

Answer 50

• Sedentary time is associated with reduced health outcome even after accounting for exercise (Owen et al 2010)
• Buman et al 2014: Demonstrated that reallocating 30min per day of sedentary time for exercise, light physical activity or sleep produced clinically and statistically meaningful health benefits (decrease in obesity, fasting insulin, increase in HDL cholesterol and decreases in triglycerides)