Why Sleep Is Critical for Immune Health

There’s no doubt this is a time of uncertainty. COVID-19 has changed the way most of us live, and it’s not clear when or if we’ll be able to resume the activities we took for granted just a year ago. Rather than waiting for the government to figure it all out, our best defence against infectious disease is optimising metabolic health and immune function. For that, sleep is arguably the keystone behaviour.

Today I’m joined again by our resident sleep expert, Greg Potter, PhD to talk about the effects of sleep on the immune system. Greg explains how poor sleep and sleep disorders profoundly impact the body’s ability to combat infections, including the common cold, pneumonia, and COVID-19. He also discusses the importance of getting enough sleep in the days leading up to vaccination and offers pandemic-specific tips for better sleep.

Here’s the outline of this interview with Greg Potter:

[00:02:01] Resilient Nutrition; Long Range Fuel.

[00:07:05] Changes in sleep since COVID.

[00:08:50] COVID dreams.

[00:11:19] Changes in sleep timing and patterns.

[00:11:45] Effects of COVID-19 lockdowns on sleep and activity; Study: Blume, Christine, Marlene H. Schmidt, and Christian Cajochen. "Effects of the COVID-19 lockdown on human sleep and rest-activity rhythms." Current Biology 30.14 (2020): R795-R797.

[00:12:34] Changes in sleep behaviors amongst university students; Study: Wright Jr, Kenneth P., et al. "Sleep in university students prior to and during COVID-19 stay-at-home orders." Current Biology 30.14 (2020): R797-R798.

[00:13:17] Sleep disorders; insomnia.

[00:13:36] Greg’s previous podcasts on entraining circadian rhythm: How to Entrain Your Circadian Rhythm for Perfect Sleep and Metabolic Health and time cues: Morning Larks and Night Owls: the Biology of Chronotypes

[00:14:15] Sleep apnea.

[00:15:23] Sleep apnea associated with increased mortality due to COVID-19; Study: McSharry, David, Michael T. Lam, and Atul Malhotra. "OSA as a probable risk factor for severe COVID-19." Journal of Clinical Sleep Medicine 16.9 (2020): 1649-1649.

[00:16:11] Sleep apnea treatment; continuous positive airway pressure (CPAP).

[00:21:13] How the immune system works.

[00:24:50] TNF-alpha blockers improve sleep in rheumatoid arthritis; Detert, Jacqueline, et al. "Effects of treatment with etanercept versus methotrexate on sleep quality, fatigue and selected immune parameters in patients with active rheumatoid arthritis." Clin Exp Rheumatol 34.5 (2016): 848-856.

[00:32:23] Cytokine storms.

[00:33:38] Mice more susceptible to infection administered during sleep hours; Study: Lundy, Stephanie R., et al. "Effect of time of day of infection on Chlamydia infectivity and pathogenesis." Scientific reports 9.1 (2019): 1-12.

[00:34:37] Better response to BCG vaccine when administered in the morning; Study: de Bree, L. Charlotte J., et al. "Circadian rhythm influences induction of trained immunity by BCG vaccination." The Journal of clinical investigation 130.10 (2020): 5603-5617.

[00:35:19] Different dimensions of sleep: SATED - satisfaction, alertness, timing, efficiency, duration.

[00:37:58] Associations between sleep and chronic disease.

[00:39:20] People who report short sleep are at higher risk of metabolic syndrome; Meta analyses: 1. Xi, Bo, et al. "Short sleep duration predicts risk of metabolic syndrome: a systematic review and meta-analysis." Sleep medicine reviews 18.4 (2014): 293-297; 2. Iftikhar, Imran H., et al. "Sleep duration and metabolic syndrome. An updated dose–risk metaanalysis." Annals of the American Thoracic Society 12.9 (2015): 1364-1372; 3. Lian, Ying, et al. "Association between sleep quality and metabolic syndrome: A systematic review and meta-analysis." Psychiatry research 274 (2019): 66-74.

[00:40:02] Sleep disturbance as a risk factor for type-2 diabetes; Meta analysis: Wang, Fei, et al. "Sleep duration and patterns in Chinese patients with diabetes: A meta‐analysis of comparative studies and epidemiological surveys." Perspectives in psychiatric care 55.2 (2019): 344-353.

[00:41:04] The brain’s glymphatic system; Maiken Nedergaard, MD.

[00:41:53] Study: Fultz, Nina E., et al. "Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep." Science 366.6465 (2019): 628-631.

[00:43:45] Obstructive sleep apnea - 40% higher risk of developing cancer.

[00:46:27] Research on sleep deprivation in dogs; Study: Bentivoglio, Marina, and Gigliola Grassi-Zucconi. "The pioneering experimental studies on sleep deprivation." Sleep 20.7 (1997): 570-576.

[00:47:01] Sleep deprivation research with rats; Study: Rechtschaffen, Allan, et al. "Sleep deprivation in the rat: I. Conceptual issues." Sleep 12.1 (1989): 1-4.

[00:47:33] Sleep restriction research on fruit flies; Study: Geissmann, Quentin, Esteban J. Beckwith, and Giorgio F. Gilestro. "Most sleep does not serve a vital function: Evidence from Drosophila melanogaster." Science advances 5.2 (2019): eaau9253.

[00:48:23] Sleep deprivation leads to ROS accumulation in the fly and mouse gut; Study: Vaccaro, Alexandra, et al. "Sleep loss can cause death through accumulation of reactive oxygen species in the gut." Cell 181.6 (2020): 1307-1328.

[00:50:25] Effects of circadian disruption on risk of dying in mice: Davidson, A. J., et al. "Chronic jet-lag increases mortality in aged mice." Current biology 16.21 (2006): R914-R916. Likely due to immune disruption; Study: Stowie, Adam, et al. "A reductionist, in vitro model of environmental circadian disruption demonstrates SCN-independent and tissue-specific dysregulation of inflammatory responses." Plos one 14.5 (2019): e0217368.

[00:51:20] Sleep deprivation associated with DNA damage; Study: Carroll, Judith E., et al. "Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans." Brain, behavior, and immunity 51 (2016): 223-229.

[00:52:50] Poor sleep increases pneumonia risk; Study: Patel, Sanjay R., et al. "A prospective study of sleep duration and pneumonia risk in women." Sleep 35.1 (2012): 97-101.

[00:53:55] Sleep habits and susceptibility to colds; Study: Prather, Aric A., and Cindy W. Leung. "Association of insufficient sleep with respiratory infection among adults in the United States." JAMA internal medicine 176.6 (2016): 850-852.

[00:54:26] Swedish study finds no relationship between sleep and cold susceptibility: Ghilotti, Francesca, et al. "Physical activity, sleep and risk of respiratory infections: A Swedish cohort study." PloS one 13.1 (2018): e0190270.

[00:54:47] Sleeping less associated with increased susceptibility to cold virus; Study: Cohen, Sheldon, et al. "Sleep habits and susceptibility to the common cold." Archives of internal medicine 169.1 (2009): 62-67.

[00:55:47] Sleep (assessed with wrist devices) and susceptibility to the common cold; Study: Prather, Aric A., et al. "Behaviorally assessed sleep and susceptibility to the common cold." Sleep 38.9 (2015): 1353-1359.

[00:56:13] Timing of physical activity and sleep and COVID-19 risk; Study: Rowlands AV, Kloecker DE, Chudasama Y, et al. “Association of Timing and Balance of Physical Activity and Rest/Sleep With Risk of COVID-19: A UK Biobank Study.” Mayo Clinic Proceedings. 2020.

[00:57:45] COVID-19 risk higher for shift workers; Study: Rizza, S., et al. "High body mass index and night shift work are associated with COVID-19 in health care workers." Journal of Endocrinological Investigation (2020): 1-5.

[00:58:37] Worse sleep in hospital associated with increased need for ICU (COVID-19); Study: Zhang, Jiancheng, et al. "Poor-sleep is associated with slow recovery from lymphopenia and an increased need for ICU care in hospitalized patients with COVID-19: a retrospective cohort study." Brain, behavior, and immunity 88 (2020): 50-58.

[00:59:05] Accuracy of sleep monitoring devices. 

[01:01:02] Sleep and response to vaccination.

[01:01:40] Antibody response to vaccination reduced with sleep deprivation; Study: Spiegel, Karine, John F. Sheridan, and Eve Van Cauter. "Effect of sleep deprivation on response to immunization." Jama 288.12 (2002): 1471-1472.

[01:02:31] Sleep-deprived men have lower antibody levels 5 days after H1N1 vaccine: Benedict, Christian, et al. "Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination." BMC immunology 13.1 (2012): 1-5.

[01:03:01] Sleep enhances antibody response to vaccination; Studies: 1. Lange, Tanja, et al. "Sleep enhances the human antibody response to hepatitis A vaccination." Psychosomatic medicine 65.5 (2003): 831-835; 2. Lange, Tanja, et al. "Sleep after vaccination boosts immunological memory." The Journal of Immunology 187.1 (2011): 283-290.

[01:03:37] Less sleep associated with worse antibody production after Hep-B vaccine; Study: Prather, Aric A., et al. "Sleep and antibody response to hepatitis B vaccination." Sleep 35.8 (2012): 1063-1069.

[01:04:54] Oxford-AstraZeneca COVID-19 vaccine reduce transmission of COVID-19; Study: Voysey, Merryn, et al. "Single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine." (2021).

[01:06:33] Syndemic, rather than pandemic; Article: Horton, Richard. "Offline: COVID-19 is not a pandemic." Lancet (London, England) 396.10255 (2020): 874.

[01:07:04] CDC: Narcolepsy Following 2009 Pandemrix Influenza Vaccination in Europe.

[01:10:48] Article (11/26/20): Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—let’s be cautious and first see the full data; Follow up article (1/4/21): Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data.

[01:11:12] Paul Offit, MD on Peter Attia's podcast.

[01:12:14] Pandemic-specific tips to sleep better.

[01:12:25] Sleep apnea - STOP-Bang questionnaire; Meta-analysis: Chen, Lina, et al. "Validation of the STOP-Bang questionnaire for screening of obstructive sleep apnea in the general population and commercial drivers: a systematic review and meta-analysis." Sleep and Breathing (2021): 1-11.

[01:15:03] Worsened sleep quality - what to do.

[01:15:58] CBT-Insomnia therapy (CBTI) reduces C-reactive protein (CRP) levels; Study: Irwin, Michael R., et al. "Cognitive behavioral therapy and tai chi reverse cellular and genomic markers of inflammation in late-life insomnia: a randomized controlled trial." Biological psychiatry 78.10 (2015): 721-729.

[01:16:24] Stimulus control.

[01:17:53] Screen time; More smart phone use associated with worse sleep and mood problems; Study: Demirci, Kadir, Mehmet Akgönül, and Abdullah Akpinar. "Relationship of smartphone use severity with sleep quality, depression, and anxiety in university students." Journal of behavioral addictions 4.2 (2015): 85-92.

[01:18:37] Avoiding phone use 30 minutes before bed leads to better sleep, mood, and memory; Study: He, Jing-wen, et al. "Effect of restricting bedtime mobile phone use on sleep, arousal, mood, and working memory: A randomized pilot trial." PloS one 15.2 (2020): e0228756.

[01:19:03] Problem-based coping strategies; scheduled worry time.

[01:20:32] Boosting your slow-wave sleep.

[01:20:53] Hot shower before bed helps with falling asleep faster; Study: Haghayegh, Shahab, et al. "Before-bedtime passive body heating by warm shower or bath to improve sleep: A systematic review and meta-analysis." Sleep medicine reviews 46 (2019): 124-135.

[01:21:24] Lucid dreaming training.

[01:22:00] Managing insomnia using lucid dreaming; Study: Ellis, Jason G., Joseph De Koninck, and Celyne H. Bastien. "Managing Insomnia Using Lucid Dreaming Training: A Pilot Study." Behavioral sleep medicine (2020): 1-11.

[01:25:30] Napping.

[01:26:48] How to get better sleep in a noisy environment (e.g., a hospital).

[01:27:39] Melatonin supplementation.

[01:29:18] Strava 2020 Year in Sport report.

[01:29:43] David Nieman’s J-shaped model of relationship between varying amounts of exercise and risk of upper respiratory tract infection (URTI); Nieman, David C. "Risk of upper respiratory tract infection in athletes: an epidemiologic and immunologic perspective." Journal of athletic training 32.4 (1997): 344.

[01:30:39] Podcast: How to Use Cognitive Behavioral Therapy for Insomnia, with Ashley Mason, PhD.

[01:30:48] Greg's articles on optimising sleep: 1. Having trouble sleeping? A primer on insomnia and how to sleep better 2. Sleep-maintenance insomnia: how to sleep through the night 3. Sleep-onset insomnia: how to get to sleep fast.

[01:31:32] Where to find Greg: Instagram; Greg’s website, Resilient Nutrition, ebook on the Principles of Resilient Nutrition; Blog post: How to Fuel for an Ultramarathon: The Ultimate Guide.