Sleep & Immunity

Posted: April 2023
Author: Katie Donnelly, Adv Dip HSc Naturopathy
 

There is a clear link between inadequate sleep patterns, chronic sleep disturbance, and altered immune function. Insomnia, whether chronic or acute, is defined as the inability to commence or maintain sleep, or experiencing chronically poor-quality sleep, despite the appropriate environment or opportunity to do so.¹

Most adults need at least seven hours of sleep per night for well-being, with disturbance to this causing notable changes to immune function and increased likelihood of illness. The microbiome also plays a role in sleep maintenance.² Phytotherapy can help rebalance this response through sleep support and immune system regulation.

Chronic sleep disruption and illness

Studies of sleep disturbance have shown an increase in Tumour Necrosis Factor (TNF), C-Reactive Protein, and Interleukin-6 (IL-6) in chronic sleep loss. This is relative to sympathetic nervous system stimulation triggering norepinephrine and epinephrine, and subsequently activating Nuclear Factor -kappa B (NF-kB) pathways.³ Both TNF and IL-6 have been correlated with perpetual sleep disturbance and depression. As such, increased oxidative stress, inflammation, cellular damage, and altered cellular signalling can occur. Reactive oxygen species and metabolic wastes can accumulate, which would typically be cleared during sleep.

Changes were also noted in the development of Th1 and Th2 cells, with an increased prevalence of Th2 in cases of sleep deprivation, associated with allergies and infection vulnerability. Conversely, Th1 is linked to tumour cell suppression.²

Traditionally used as a sleep aid, Avena sativa (green oat) has displayed notable antioxidant actions in vivo, with reduced oxidative stress and improved cellular protection attributed to beta-glucans. Studies have also shown increased phagocytosis of pathogens with Avena sativa supplementation, regulating the immune response to microbes. Polyphenols and fibre then support detoxification pathways and intestinal health.⁴

Recent studies on the use of Salvia officinalis (sage) for insomnia showed improvements in sleep, with increased alpha wave activity. Reductions in stress levels, snoring, and fatigue were also noted. Commonly used for immune and respiratory support, this study has identified the influence of sage on reducing anxiety and stress, thus positively influencing the microbiome, and lung integrity, and preventing apnoea-related waking.⁵ 

Also, well utilised for immune and sleep support, Prunus serotina (wild cherry) acts as a powerful antioxidant, with higher phenolic compounds than milk thistle or pine.⁶ An anti-inflammatory and antimicrobial, this herb has considerable triterpenoids, including oleanolic, ursolic, and corosolic acids, components that contribute to the sedative actions of this plant.⁷

In acute cases, where sleep was restricted for up to four days, a two-hour nap counteracted much of the immune system changes. However, in chronic cases, inflammatory markers remained high, even when a restorative evening sleep was introduced. Similarly, those with ongoing sleep issues displayed an intensified response of increased TNF and IL-6 when sleep was disturbed for one evening, comparative to healthy controls.⁸ In individuals experiencing insomnia, IL-1β was notably higher in comparison to those with healthy sleep patterns, with lower natural killer cells and naïve T cells.⁹  

Well known for its actions on the respiratory system, Pelargonium sidoides (pelargonium), regulates immune function, decreasing the intensity of symptoms associated with seasonal illness.  Studies on Covid-19 showed pelargonium to reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines.¹⁰ Separate studies have identified a correlation between poor sleep patterns and an increased likelihood of contracting Covid-19 and experiencing intensified symptoms.¹¹

Sambucus nigra (elderflower) has also been shown to reduce levels of nitric oxide, induced by proinflammatory cytokines and additional inflammatory markers, and lower cellular lipopolysaccharide damage.¹² The polyphenols rutin and chlorogenic acid, are attributed to many of these actions. This herb also acts as an antimicrobial, preventing pathogen proliferation associated with reduced immune function, with polysaccharides associated with immune modulating activity.¹³ 

In animal model studies, sleep was also noted to strengthen the response against bacterial infection and was determined as a crucial aspect of innate immunity, with altered monocyte regulation and function in cases of deprivation. Furthermore, there is an increased risk of viral infection, colds, and flu, with poor immune memory development.¹⁴

Microbiome influence

The variation of microbes in the gastrointestinal system impacts sleep via interactions between the microbiome and the gut-brain axis, also impacting immune regulation. Individuals with insomnia displayed different microbiome composition, compared to controls, showing notably higher levels of Prevotella species in recent studies.⁹ Although Prevotella were considered commensal, the potential for opportunistic action has become increasingly prevalent in chronic inflammatory conditions.¹⁵

The role of amino acids is also notable, with significant reductions evident in insomnia patients, including aspartic acid. Further animal model studies on aspartic acid showed hippocampal reductions associated with sleep disturbance. Tryptophan and phenylalanine, required for serotonin and melatonin were also reduced, impacting sleep and mood.¹⁶

Additionally, it is suggested that poor microbiome is an influencing factor in T cell maturation, contributing to the altered response to viral infection.¹⁵ Animal model studies have also noted the translocation of bacteria in subjects of imposed sleep deprivation.¹⁷

One of the most popular immune herbs, Echinacea angustifolia/purpurea (echinacea) has also shown important alterations to the microbiome in animal model studies. In cases of immune suppression, echinacea acted to regulate microbial changes and improve populations of beneficial bacteria. This contributed to modulated cytokine release and protective actions against oxidative stress. Echinacea also improved the function of immune organs, including the spleen, which was also noted as impacting microbe variation.¹⁵  

The essential oils of Angelica archangelica (angelica) also showed microbial regulation through preventing the growth of pathogenic bacteria and opportunistic fungi. Often used for sleep initiation and maintenance in cases of insomnia, and for digestive and respiratory imbalances, this herb acts as an immune, sleep, and microbial support.¹⁸ 

Similarly, saponins from Phytolacca decandra (poke) showed considerable antimicrobial actions in studies, particularly against gram-negative bacteria and Escherichia coli, along with Candida albicans and actions as an anthelmintic.¹⁹

References

1. Kaur H, Spurling BC, Bollu PC. Chronic Insomnia. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526136/
2. Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. Role of sleep deprivation in immune-related disease risk and outcomes. Commun Biol [Internet]. 2021 Nov 18;4(1):1304. Available from: https://doi.org/10.1038/s42003-021-02825-4.
3. Irwin MR, Opp MR. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology [Internet]. 2017 Jan;42(1):129-155. Available from: https://doi.org/10.1038/npp.2016.148.
4. Kim IS, Hwang CW, Yang WS, Kim CH. Multiple Antioxidative and Bioactive Molecules of Oats (Avena sativa L.) in Human Health. Antioxidants [Internet]. 2021 Sep 13;10(9):145 Available from: https://doi.org/10.3390/antiox10091454.
5. Ikeda Y Sr, Nasu M. A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Wild Sage Metabolites in Preventing Snoring, Improving Sleep, and Activating Alpha Wave Brain Frequencies in Healthy Adults. Cureus [Internet]. 2022 Feb 28;14(2):e22714. Available from: https://doi.org/10.7759/cureus.22714.  
6. Telichowska A, Kobus-Cisowska J, Szulc P. Phytopharmacological Possibilities of Bird Cherry Prunus padus L. and Prunus serotina L. Species and Their Bioactive Phytochemicals. Nutrients [Internet]. 2020;12:196 Available from: https://doi.org/10.3390/nu12071966.
7. Wrońska N, Szlaur M, Zawadzka K, Lisowska K. The Synergistic Effect of Triterpenoids and Flavonoids—New Approaches for Treating Bacterial Infections? Molecules [Internet]. 2022 Jan 27;27(3):84 Available from: http://dx.doi.org/10.3390/molecules27030847
8. Irwin MR, Opp MR. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology [Internet]. 2017 Jan;42(1):129-155. Available from: https://doi.org/10.1038/npp.2016.
9. Qinghua W, Bin C, Dashuang S, Junjie Y, Shujie F, Jingwen W, Changying Z, Yihui W, Xiangzhen G, Jianfeng W, Kyle S, Xueyuan H, Honghao M, Lei Z. Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia. American Society for Microbiology[Internet].2023 March 29;10(5):e00998-22. Available from: https://doi.org/10.1128/spectrum.00998-22
10. Papies J, Emanuel J, Heinemann N, Kulić Ž, Schroeder S, Tenner B, Lehner MD, Seifert G, Müller MA. Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs® 7630 in SARS-CoV-2-Infected Human Lung Cells. Front Pharmacol [Internet]. 2021 Oct 25;12:757666. Available from: https://doi.org/3389/fphar.2021.757666.  
11. Ragnoli B, Pochetti P, Pignatti P, Barbieri M, Mondini L, Ruggero L, Trotta L, Montuschi P, Malerba M. Sleep Deprivation, Immune Suppression and SARS-CoV-2 Infection. Int J Environ Res Public Health [Internet]. 2022 Jan 14;19(2):904. Available from: https://doi.org/10.3390/ijerph19020904.
12. Ho GT, Wangensteen H, Barsett H. Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264.7 Macrophages and Dendritic Cells. Int J Mol Sci [Internet]. 2017 Mar 8;18(3):584. Available from: https://doi.org/10.3390/ijms18030584.
13. Mahboubi M. Sambucus nigra (black elder) as alternative treatment for cold and flu. ADV TRADIT MED (ADTM) [Internet]. 2021;21(3):405–14. Available from: https://doi.org/10.1007/s13596-020-00469-z.
14. Hahn J, Günter M, Schuhmacher J, Bieber K, Pöschel S,Schütz M,Engelhardt B,Oster H, Sina C,Lange T, Autenrieth S.E.Sleep enhances numbers and function of monocytes and improves bacterial infection outcome in mice.Brain, Behavior, and Immunity [Internet].2020;87:329-338. Available from: https://doi.org/10.1016/j.bbi.2020.01.001.
15. Lin R, Zhi C, Su Y, Chen J, Gao D, Li S, Shi D. Effect of Echinacea on gut microbiota of immunosuppressed ducks. Front Microbiol [Internet]. 2023 Jan 5;13:1091116. Available from: https://doi.org/10.3389/fmicb.2022.1091116.
16. Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv Nutr [Internet]. 2020 May 1;11(3):709-723. Available from: https://doi.org/10.1093/advances/nmz127
17. Krueger JM, Opp MR. Sleep and Microbes. Int Rev Neurobiol [Internet]. 2016;131:207-225. Available from: https://doi.org/10.1016/bs.irn.2016.07.003  
18. Aucoin M, Cooley K, Saunders PR, Carè J, Anheyer D, Medina DN, Cardozo V, Remy D, Hannan N, Garber A. The effect of Echinacea spp. on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: A rapid review. Adv Integr Med [Internet]. 2020 Dec;7(4):203-217. Available from: https://doi.org/10.1016/j.aimed.2020.07.004.
19. Beressa TB, Ajayi CO, Peter EL, Okella H, Ogwang PE, Anke W, Tolo CU. Pharmacology, Phytochemistry, and Toxicity Profiles of Phytolacca dodecandra L'Hér: A Scoping Review. Infect Dis [Internet]. 2020 Jul 27;13:11. Available from: https://doi.org/10.1177/1178633720943509.