Sleep Deprivation: A Deeper Dive Into Clinical Screenings, Mitochondrial Impact, and Therapeutic Interventions

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Sleep is essential for mental, physical, and emotional well-being. In addition, adequate sleep promotes healthy immune function by bolstering the body’s response to stress, helping to fight off possible infection, and potentially minimizing the risk of illness. Even with the demonstrated value of sleep, nearly one-third of adults in the United States report short sleep, or sleeping less than seven hours per night.1 An increasing trend of self-reported short sleep notably started in 2013, and this trend was more pronounced among African-American and Hispanic adults.1 In 2018, however, the National Sleep Foundation’s survey suggested a potentially positive trend. While sleep duration reporting was consistent with previous results, sleep quality showed some improvement, with an increased number of people feeling well-rested.2

While there are indications that more US adults have an increased awareness of sleep’s benefits for better health,2 for some patients, sleep quality and habits are not ideal, and they may feel tired throughout the day. And fatigue isn’t the only consequence of a poor night’s sleep. Adults who sleep less than seven hours per night are more likely to report 10 chronic health conditions, including depression, arthritis, diabetes, and asthma.3

Understanding a patient’s sleep quality is an important part of clinical screening to ultimately help a patient adopt healthy sleep habits and to address health concerns associated with sleep dysfunction. In the following video, IFM educator Kristi Hughes, ND, IFMCP, shares her methods for conducting a deeper dive assessment into a patient’s sleep history, quality, and needs.

Kristi Hughes, ND, IFMCP talks about the methods and tools she uses to help her patients understand their sleep quality and needs, and to address health concerns associated with sleep dysfunction.

A Deeper Dive Into the Cell – Mitochondria

Over the past several years, researchers have begun to examine what happens at a cellular level when the body is deprived of sleep. Some studies suggest a connection between limited sleep and oxidative stress, pointing to mitochondria as a possible target of the physiological effects of sleep deprivation.4-6

Mitochondria, the cellular source of energy production, play an important role in cellular energy metabolism and homeostasis via generation of several metabolites, including ATP. Acute and chronic stressors influence various aspects of mitochondrial biology, and chronic stress exposure can lead to molecular and functional recalibrations among mitochondria.7 Mitochondria have a potential role at two levels: as a target of stress and as a mediator of stress pathophysiology,7 suggesting that one of the biological functions of sleep may be to protect against oxidative stress.5-8

Circadian Rhythm & sleep deprivation

Over the years, a growing body of evidence has emerged suggesting that energy metabolism and cellular antioxidant mechanisms defending against oxidative damage are coordinated by the circadian clock, the mechanism that keeps bodies attuned to the day/night cycle.9

In 2018, a study using a combination of in-vitro and in-vivo models of human skin fibroblasts and mice established a molecular link between circadian control of mitochondrial morphology and oxidative metabolism.9 Also in 2018, researchers used the fruit fly Drosophila melanogaster (which shares many key characteristics with mammalian sleep) to measure how mitochondria function under sleep deprivation.4 Analysis showed that sleep deprivation affected mitochondrial bioenergetics capacity, decreasing respiration and oxidative phosphorylation.4

The first-ever study to analyze the combined effect of physical exercise and sleep deprivation on oxidative stress in humans found that oxidative stress was likely to be a consequence of exposure to not only physical, but also psychological stressors related to, among other things, sleep deprivation. The 36-hour survival training in young, healthy men with sleep deprivation showed impaired enzymatic antioxidant defense, increased lipid peroxidation, and muscle damage.10

Therapies for Sleep & Mitochondrial Health

Clearly, sleep is a physiological necessity, and being deprived of it has many deleterious health effects. How can clinicians help their patients get more rest and limit the maladaptive mitochondrial changes that occur during states of stress?


Certain nutrients have been shown to protect against oxidative damage to mitochondria, including:5

  • Omega-3 fatty acids
  • Antioxidants (including vitamin C and zinc)
  • Members of the vitamin B family (including vitamin B12 and folic acid)
  • Magnesium5

In addition, dietary sources of melatonin may promote improved sleep quality. A 2020 review evaluated randomized placebo-controlled trials conducted through 2019 that assessed sleep quality and the intake of two melatonin food sources, milk and cherry juice, in children, adults, and elderly participants.11 While only eight studies dated through 2017 met the inclusion criteria, the analysis suggested that food sources of melatonin may promote healthy sleep.11 One specific study in the review found that after participants in the test group consumed tart cherry juice concentrate for a seven-day period, their total urinary melatonin content significantly increased, and they reported a significant increase in sleep duration and sleep quality.12

Mind-Body Therapies & Exercise

A 2019 systematic review and meta-analysis of 49 studies covering 4,506 participants found that mind-body therapies can be effective in treating insomnia and improving sleep quality for both healthy individuals and patients.13 The tested therapies included:13

  • Meditation
  • Tai chi
  • Qigong
  • Yoga

The therapies resulted in statistically significant improvement in sleep quality and reduction in insomnia severity, but they did not have a significant effect on sleep quantity measurements. Also of note, the researchers found that qigong had a slight advantage over tai chi in the improvement of sleep quality.13

A 2020 study investigated the benefit of qigong exercise, specifically Baduanjin qigong, on self-reported sleep quality and quality of life for elderly adults who regularly experienced sleep disturbances.14 Of the 139 participants, those in the treatment group completed a 45-minute exercise session five times per week for 24 weeks while those in the control group maintained their usual lifestyle.14 At the end of the 24 weeks, per self-reporting, the treatment group noted significant improvements in overall sleep quality compared to the control group.14

A 2021 study also suggests that high intensity interval exercise (HIIE) may mitigate sleep loss–induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms.15 Researchers discovered that in 24 healthy young men, sleep restriction resulted in significantly impaired glucose tolerance, with concomitant changes in skeletal muscle mitochondrial respiratory function, sarcoplasmic protein synthesis, and diurnal rhythms of peripheral skin temperature. However, in those performing three sessions of HIIT during the sleep restriction intervention, these same perturbations were not observed.15


For many, sleep is the cornerstone for leading a healthy, joyous life, and yet sleep often goes unaddressed. Screening for sleep disorders is encouraged as a regular practice in functional medicine, and there is a range of effective lifestyle interventions for patients suffering from poor sleep. Learn more about tools and strategies to help patients achieve sustainable lifestyle change and improve their well-being through IFM’s new course Lifestyle: The Foundations of Functional Medicine.

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  1. Sheehan CM, Frochen SE, Walsemann KM, Ailshire JA. Are U.S. adults reporting less sleep?: Findings from sleep duration trends in the National Health Interview Survey, 2004-2017. Sleep. 2019;42(2). doi:1093/sleep/zsy221
  2. Sleep health index scores: 2018. National Sleep Foundation. Accessed January 27, 2020.
  3. Sleep and sleep disorders: data & statistics. Centers for Disease Control and Prevention. Published May 2, 2017. Accessed May 14, 2021.
  4. Rodrigues NR, Macedo GE, Martins IK, et al. Short-term sleep deprivation with exposure to nocturnal light alters mitochondrial bioenergetics in Drosophila. Free Radic Biol Med. 2018;120:395-406. doi:1016/j.freeradbiomed.2018.04.549
  5. Du J, Zhu M, Bao H, et al. The role of nutrients in protecting mitochondrial function and neurotransmitter signaling: implications for the treatment of depression, PTSD, and suicidal behaviors. Crit Rev Food Sci Nutr. 2016;56(15):2560-2578. doi:1080/10408398.2013.876960
  6. Melhuish Beaupre LM, Brown GM, Braganza NA, Kennedy JL, Gonçalves VF. Mitochondria’s role in sleep: novel insights from sleep deprivation and restriction studies. World J Biol Psychiatry. Published online May 6, 2021. doi:1080/15622975.2021.1907723
  7. Picard M, McEwen BS. Psychological stress and mitochondria: a systematic review. Psychosom Med. 2018;80(2):141-153. doi:1097/PSY.0000000000000545
  8. Hill VM, O’Connor RM, Sissoko GB, et al. A bidirectional relationship between sleep and oxidative stress in Drosophila. PLoS Biol. 2018;16(7):e2005206. doi:1371/journal.pbio.2005206
  9. Schmitt K, Grimm A, Dallmann R, et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. 2018;27(3):657-666.e5. doi:1016/j.cmet.2018.01.011
  10. Jówko E, Ró?a?ski P, Tomczak A. Effects of a 36-h survival training with sleep deprivation on oxidative stress and muscle damage biomarkers in young healthy men. Int J Environ Res Public Health. 2018;15(10):E2066. doi:3390/ijerph15102066
  11. Pereira N, Naufel MF, Ribeiro EB, Tufik S, Hachul H. Influence of dietary sources of melatonin on sleep quality: a review. J Food Sci. 2020;85(1):5-13. doi:1111/1750-3841.14952
  12. Howatson G, Bell PG, Tallent J, Middleton B, McHugh MP, Ellis J. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2012;51(8):909-916. doi:1007/s00394-011-0263-7
  13. Wang X, Li P, Pan C, Dai L, Wu Y, Deng Y. The effect of mind-body therapies on insomnia: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2019;2019:9359807. doi:1155/2019/9359807
  14. Fan B, Song W, Zhang J, et al. The efficacy of mind-body (Baduanjin) exercise on self-reported sleep quality and quality of life in elderly subjects with sleep disturbances: a randomized controlled trial. Sleep Breath. 2020;24(2):695-701. doi:1007/s11325-019-01999-w
  15. Saner NJ, Lee MJ, Kuang J, et al. Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms. Mol Metab. 2021;43:101110. doi:1016/j.molmet.2020.101110


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