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The Dangers of Sleep Deprivation

“The best bridge between despair and hope is a good night sleep” - E. J. Cossman

Introduction

“So let me get this straight. You just decided that you’re going to sleep half of what is evolutionarily programmed? … Does it strike you as odd that evolution would have designed us to spend a third of our life, not mating, not watching out for predators, not hunting for food, but doing this thing for some other purpose? Do you think that thing must have been important?” - Kirk Parsley, M.D. to Peter Attia, M.D.

The current leading expert and proponent of sleep is Matthew Walker, Ph.D., at the University of California Berkley. He believes sleep is undertaught in medical school relative to its health effects. Large epidemiological studies show that humans need 7 to 9 hours of sleep a night [1]. Two of the current major theories on why we need to sleep is memory formation and toxin removal:

  • Glymphatic system “washes away” toxins like beta amyloid after a restful night sleep (during deep sleep glial cells shrink by 60% allowing CSF to clear debris) [2]

  • An n=26 study showed that morning CSF beta-amyloid concentrations decreased 6% (25.3 pg/ml) by getting a restful night sleep. There was no decrease in a group that was subjected to 24 hours of sleep deprivation. Moreover, CSF beta-amyloid were 75.8 pg/ml higher in the 24-hour sleep deprivation group than the restful night sleep group [3]


Sleep and Cardiovascular/ Metabolic Disease

1.) Data from 5,172,710 participants from 153 studies: short sleep (generally defined as <5 or <6 hours of sleep per night) was associated with increased mortality outcome (RR, 1.12; 95% CI, 1.08–1.16), diabetes (1.37, 1.22–1.53), hypertension (1.17, 1.09–1.26), cardiovascular diseases (1.16, 1.10–1.23), coronary heart diseases (1.26, 1.15–1.38), and obesity (1.38, 1.25–1.53). [19]


2.) When controlling for traditional risk factors for heart disease, sleeping less than 6 hours was associated with a 27 percent increased risk of having atherosclerosis compared to those who slept 7-8 hours per night.

  • In the same study, those with poor quality of sleep (number of awakenings at night and frequency of movement during sleep) were 34 percent more likely to have atherosclerosis than those with good quality of sleep. [4]

3.) For sleep deprived patients, one more hour of sleep decreased the odds of coronary artery calcification by 33% [5]

  • One additional hour of sleep decreased the risk of calcification similar to reducing systolic blood pressure by 16.5mmHg [5]

4.) There is a 24% increase in Acute Myocardial Infarction (AMI) the Monday following spring time changes (ie, losing an hour of sleep) and a 21% reduction in AMI the Tuesday following fall time changes (ie, gaining an hour of sleep) [6]


5.) Sleeping for less than 6 hours per night increases odds ratio for hypertension by 1.66 [7]


6.) In a systematic review and meta-analysis published in Nature, energy intake was increased by 385 kcal (95% CI (252, 517); p <0.00001) following partial sleep deprivation. [42]

  • Sleep deprivation blunts human frontal and insular cortex activity while increasing reactivity in the amygdala when making food decisions, leading to a theoretical increase in calories consumed by 600 kcal [8]

7.) Sleeping less than four hours for one week increases insulin resistance [9,10]


8.) 5 hours of sleep deprivation for 1 week decreases testosterone level by 10-15% [11]


9.) Creating light/ day cycles in the NICU improved weight gain, sleep, and led to earlier discharge in neonates [12]



Sleep and the Immune System

1.) Sleeping 4-5 hours caused a 70% reduction in natural killer cells with concomitant increase in colon, prostate, and breast cancer [13]


2.) Sleeping <7 hours for 2 weeks increased risk of catching a cold by 2.94x (CI[95%]=1.18–7.30). [14]



Sleep and Caffeine

1.) Adenosine in CNS neurons promotes drowsiness and sleep. Upon awakening, there is little to no adenosine in CNS neurons. However, adenosine builds up throughout the day as a by-product of wakefulness. Caffeine is an adenosine receptor blocker, thus decreasing the drowsiness feeling that increases with increasing levels of adenosine.


2.) 400mg caffeine three times a day for 7 days caused changes in sleep architecture including increased “arousals and awakenings at the expense of reductions in both stage-2 and stage-4 sleep” [22]


3.) Caffeine increases the duration of stage-1 sleep earlier in the night and reduces the amount of NREM stage 3 and 4 over the course of the night [27]

  • Sleep latency and wake time after sleep onset were prolonged, whereas sleep duration, and sleep efficiency (percentage of total time asleep per total time in bed) were reduced with caffeine consumption. [27]

  • Interestingly, subjective measures of sleep quality did not match the objective findings, ie sleep fragmentation that occurs from caffeine consumption is not easily perceived by the sleeper and underestimated its negative effects on sleep. [27]

  • Less individuals who drink large amounts of coffee (>5cups/day) believe evening coffee ingestion would disrupt their sleep than those who drink 0-1 cups/day [27]

4.) The half-life of caffeine is near 6 hours

  • A tall (12oz) Starbucks coffee has 270 mg caffeine, which when consumed at noon: 135 mg of caffeine is still in your system at 6pm and 67.5 mg is present at midnight


Sleep and Alcohol

1.) Ethanol fragments your sleep, prevents ideal REM sleep, and increases light sleep [22, 23]


2.) Insomnia and sleep problems are a predictor of relapse after controlling for severity of alcohol dependence, depression severity, and wake time after sleep onset [24, 25]


3.) Alcohol fragments REM sleep, increases heart rate variability and increases core body temperature [20,21]



Sleep and Work Place Wellness

1.) Under-slept employees use less effort in group settings and impaired decision-taking ability [15,16, 28]


2.) Under-slept employees were more likely to lie and be unprofessional [15,16, 28]


3.) Under-slept employees take on less challenging tasks and develop fewer creative solutions

[15,16]


4.) Sleep doubles brain plasticity and strength of connections in the brain [17]


5.) 35 hours of sleep deprivation increased reactivity to negative images by 60% with concomitant changes on brain scans in the prefrontal lobe [18]


7.) Sleep apnea and anxiety are positively correlated, and 3 months of treatment with CPAP decreases anxiety in those with sleep apnea [28]



The nonbenzodiazepine hypnotic sleep medications inhibit natural sleep architecture

1.) In a double-blind, placebo-controlled, four-way cross-over trial in which nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG: temazepam and zolpidem significantly reduced slow wave activity (marker of sleep depth) compared with placebo. Zolpidem also decreased REM duration [32]

  • Prolonged release melatonin also suppressed slow wave activity during the first third of the night but not total duration over the entire night

2.) In cats: zolpidem reduced cortical plasticity by about 50%, however, triazolam and ramelteon had no effect on plasticity [29]


3.) Nonbenzodiazepines hypnotics are associated with increased risk of falls in older men [30]


4.) FDA Box warning for eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien) due to reports of sleepwalking, sleep driving, engaging in activities while not fully awake – leading to some deaths and serious accidents [26]


5.) The American Academy of Sleep Medicine and the European Sleep Research Society have completed systematic reviews and concluded that insomnia-specific cognitive behavioral therapy (CBTi) should be the first line treatment for insomnia [31]

  • Increases bed-sleep connection, homeostatic mechanisms and the circadian rhythm, and decreases anxiety and rumination about sleep [31]

  • CBTi does better than hypnotic medications for sleep and less adverse events [31]


What Can We Do To Optimize Our Sleep? Basic Sleep Hygiene

1.) Set rigid sleep and wake times for all seven days of the week


2.) In a crossover trial, wearing orange-tinted blue light-blocking glasses from 6 pm until bedtime compared to control glasses reduced LED-induced melatonin suppression, decreased vigilant attention, and subjective alertness before bedtime [37]

3.) Blue-enriched light exposure caused significantly greater suppression of melatonin compared to standard full-field fluorescent light 70.9 ± 19.6% and 42.8 ± 29.1%, respectively, p < 0.05 [34]

  • However, they both significantly suppressed melatonin

  • Another study comparing dim light (lux <3) vs. room light (<200 lux) for 8 hours before bed found that exposure to room light resulted in a later melatonin onset in 99% of participants and shortened melatonin duration by about 90 minutes [35]

  • A study in young adults found 5 hour LED screen exposure in the evening suppressed melatonin secretion and increased both subjective and objective alertness [38]

4.) Reading on an iPad vs. a book before bed delayed slow wave activity by 30 minutes and reduced slow wave activity after sleep onset [36]

  • In another study comparing an electronic book with reading a printed book a few hours before bed found the e-book readers had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next morning alertness [39]

  • However, another study showed no difference between groups reading from a tablet versus reading from a book two hours before bed in parameters such as salivary melatonin and polysomnography readings. This study used photic preload of 569 lux over 6.5 hours before bed which may explain these results. [40]

5.) Dim lights or use red lights in your house a few hours before bed


6.) Do not eat between dinner (ideally at least 3 hours before bed) and breakfast

  • A recent study showed decreased amplitude and periodicity of PER protein in every cell of the body if intake of calories was before morning cortisol spike [33]. Unknown clinical significance at this time

7.) Basic Sleep Hygiene/ Cognitive behavioral therapy

  • Training your brain to associate your bed with sleep

  • Use blackout shades if you go to bed while it is still bright in your bedroom

  • Upon waking, use sunlight or 10,000 Lux light

  • Ideal sleeping ambient temperature is 68 degrees

  • Taking a hot shower or bath before bed will cause vasodilation to radiate heat and will lower your core body temperature, decreasing sleep latency and increase efficiency [41]

  • Go to another room if you haven’t fallen asleep within 20 minutes

  • Do not use your phone or look at an electronic screen before bed

  • Do not eat food before bed (ideally within 3 hours of bed)


References:

[1] https://www.sciencedirect.com/science/article/pii/S2352721815000157

[2] https://www.sciencedirect.com/science/article/pii/S0166223616300376

[3] https://jamanetwork.com/journals/jamaneurology/article-abstract/1875833

[4]https://www.acc.org/about-acc/press-releases/2019/01/14/13/57/sleeping-less-than-six-hours-a-night-may-increase-cardiovascular-risk

[5] https://jamanetwork.com/journals/jama/fullarticle/183124

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189320/

[7] https://academic.oup.com/sleep/article/29/8/1009/2708444

[8] https://www.nature.com/articles/ncomms3259?message-global=remove&cmsPreview=1

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435718/

[10] https://www.ncbi.nlm.nih.gov/pubmed/10543671/

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445839/

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560620/#R6

[13] https://www.ncbi.nlm.nih.gov/pubmed/7871104

[14] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629403/

[15] https://www.ncbi.nlm.nih.gov/pubmed/27159583

[16] https://psycnet.apa.org/record/2009-00277-004

[17] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572743/

[18] https://www.sciencedirect.com/science/article/pii/S0960982207017836

[19] https://www.sciencedirect.com/science/article/pii/S1389945716301381

[20] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775419/

[21] https://www.ncbi.nlm.nih.gov/pubmed/23347102

[22]https://www.sciencedirect.com/science/article/pii/S1087079216000150?via%3Dihub&fbclid=IwAR27Vi0GTWJXxBvHVUOVKFmz8r56r5gZ3vfLozxf34xgtarVWL4Km41m3K4#bib46

[23] https://www.ncbi.nlm.nih.gov/pubmed/16930215

[24] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008542/

[25] https://pubs.niaaa.nih.gov/publications/aa41.htm

[26]https://www.medscape.com/viewarticle/912402?src=soc_fb_190502_mscpedt_news_psych_insomnia&faf=1

[27] https://www.sciencedirect.com/science/article/pii/S1087079216000150?via%3Dihub

[28]https://www.sciencedirect.com/science/article/pii/S1389945716301368?via%3Dihub&fbclid=IwAR13l-8ixHPpDeoRNft_1GOOp00leIA7RFbHL98-RMpj-ReFOn8ipne4L-E

[29] https://www.ncbi.nlm.nih.gov/pubmed/18853935

[30] https://www.ncbi.nlm.nih.gov/pubmed/25587493

[31] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803038/

[32]https://journals.sagepub.com/doi/full/10.1177/0269881115581963?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

[33]https://www.cell.com/cell/fulltext/S0092-8674(19)30166-7?fbclid=IwAR0AG6XWG2bDjq20q5aLfoeG3mJVKsSo2C7zB85yoSliebLtzDxhRqutKfI

[34] https://www.ncbi.nlm.nih.gov/pubmed/30296404

[35] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047226/

[36] https://www.ncbi.nlm.nih.gov/pubmed/27448477

[37] https://www.jahonline.org/article/S1054-139X(14)00324-3/fulltext

[38] https://www.ncbi.nlm.nih.gov/pubmed/21415172?dopt=Abstract

[39] https://www.ncbi.nlm.nih.gov/pubmed/25535358

[40] https://www.sciencedirect.com/science/article/pii/S1389945716300818?via%3Dihub

[41] https://www.ncbi.nlm.nih.gov/pubmed/28691581

[42] https://www.nature.com/articles/ejcn2016201

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