Poor Sleep, Circadian Disruption and Autoimmunity

Sleep disturbances significantly impact quality of life in patients with autoimmune disease, but they are often overlooked.¹ Poor sleep may be both a cause and a consequence of autoimmunity, contributing to a perpetuating cycle of symptoms.

Multiple sclerosis patients often struggle to get a good night’s sleep, while 55-85% of systemic lupus erythematosus (SLE) and 61-78% of rheumatoid arthritis (RA) patients report sleep disturbances.²

Conversely, a nationwide study revealed patients with chronic insomnia had a 70% higher risk of developing autoimmunity.³ Sleep deprivation has also been found to exacerbate symptoms of RA and SLE, negatively impacting health.¹

Considered an epidemic of sleep disturbance, approximately 20% of the industrialised world has disrupted or insufficient sleep.³ Whether poor sleep predisposes, precipitates or is a consequence of chronic inflammatory conditions is still being elicidated.²

The Importance of a Good Night’s Sleep

Sleep is a physiological restorative process that helps the body maintain homeostasis, particularly in the neuro-immunological, cardiometabolic, and neurocognitive systems.³ Without quality sleep, your body cannot function at its physiological best.

How Sleep Influences Autoimmune Development

Sleep disruption and deprivation alters circadian cycles, challenging regulatory mechanisms, making immune responses vulnerable and leading to imbalances in melatonin and cortisol. In those with a genetic predisposition and the presence of certain environmental factors, circadian clock genes influence the development of autoimmune disorders via regulation of innate and adaptive immunity (see Figure 1).¹

Figure 1. Disruptions in circadian regulation in the suprachiasmatic nucleus and its general effects on immune cell responses and sleep deprivation.¹

Tired and Inflamed

Sleep deprivation creates a proinflammatory environment and may induce expression of autoimmune-associated proteins including T-helper 17 (Th17).¹ Increased serum TNF-α levels have been observed in patients with insomnia, narcolepsy, and obstructive sleep apnoea, while prolonged sleep restriction increases IL-6 levels.⁴ The increase in inflammatory cytokines and leukocytes may heighten the potential for a breach in self-tolerance, particularly when regulatory T cells (Tregs) are dysregulated.¹

Sleep Deprivation Increases Symptom Severity

Sleep disturbance can increase pain sensitivity, mediated by inflammation. In patients with RA, sleep loss induced heightened pain and activation of arthritis-related joint pain,⁵ as well as higher disease activity, depression, and anxiety scores.² Studies show that poor sleepers with SLE experience lower self-assessed quality of life scores, affecting physical and emotional health, energy levels, and intimate relationships.¹

Patients with significant pain report less total sleep time, long sleep latency, more awakenings, non-restorative sleep, and daytime sleepiness and fatigue.² Autoimmunity also increases the risk of developing other sleep disorders including obstructive sleep apnoea and restless leg syndrome.⁴

Herbal Heroes Support a Sound Night’s Sleep

Educating patients about factors compromising sleep and providing practical sleep hygiene tips are important first steps in resetting circadian cycles (see Figure 2).

Figure 2. Sleep hygiene tips⁶

Dietary and lifestyle measures help patients wind down at the end of the day, however many will benefit from specific herbal medicines. Lavender (Lavendula angustifolia), Passionflower (Passiflora incarnata), and California poppy (Eschscholzia californica) are a herbalists’ prescribing favourites to support restful sleep.

In adults with insomnia disorder, Passionflower extract (60 mg taken nightly for two weeks) significantly improved total sleep time compared with placebo (p=0.049) in a double-blind, placebo-controlled trial. Compared to baseline scores, sleep efficiency and ‘wake after sleep onset’ significantly improved in the Passionflower group (p=0.008 and p=0.025, respectively).⁷

Lavender is traditionally used in Western herbal medicine to relieve restless sleep and sleeplessness. In a randomised, controlled trial in postmenopausal women, Lavender flower extract (500 mg BID for eight weeks) significantly improved mean sleep scores (Pittsburgh Sleep Quality Inventory) compared with controls (p=0.003). Of those taking Lavender, 83.7% reported good or very good improvements in sleep quality.⁸

California poppy has traditionally been used by Native American cultures to improve sleep and relieve pain.⁹ Animal studies suggest that California poppy’s sedative effects are mediated via benzodiazepine receptors.¹⁰ It’s analgesic properties¹⁰ [BF1] make it a particularly useful herb for insomnia associated with pain, a common feature of autoimmune conditions. However it should be used with caution alongside strong analgesic medication if these are being used to manage pain.¹¹

Supporting patients

Sleep disturbances significantly impact quality of life in patients with and at risk of autoimmune disease, but they are often overlooked. Assessing and addressing sleep is an important part of case-taking and therapeutic management.

Interventions that treat insomnia have the potential to interrupt the effects of sleep disturbance on inflammation, pain sensitivity and symptomatic progression in patients with autoimmunity.⁵

References

1. Awuah WA, Huang H, Kalmanovich J, Mehta A, Mikhailova T, Ng JC, et al. Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review. Medicine (Baltimore). 2023 Aug 11;102(32):e34614. doi: 10.1097/MD.0000000000034614.
2. Shaver JL, Iacovides S. Sleep in women with chronic pain and autoimmune conditions: a narrative review. Sleep Med Clin. 2018 Sep;13(3):375-394. doi: 10.1016/j.jsmc.2018.04.008. 
3. Kok VC, Horng JT, Hung GD, et al. Risk of autoimmune disease in adults with chronic insomnia requiring sleep-inducing pills: a population-based longitudinal study. J Gen Intern Med. 2016 Sep;31(9):1019-26. doi: 10.1007/s11606-016-3717-z.
4. Gómez-González B, Domínguez-Salazar E, Hurtado-Alvarado G, et al. Role of sleep in the regulation of the immune system and the pituitary hormones. Ann N Y Acad Sci. 2012 Jul;1261:97-106. doi: 10.1111/j.1749-6632.2012.06616.x. 
5. Irwin MR, Straub RH, Smith MT. Heat of the night: sleep disturbance activates inflammatory mechanisms and induces pain in rheumatoid arthritis. Nat Rev Rheumatol. 2023 Jul 24. doi: 10.1038/s41584-023-00997-3.
6. Kelley, Mary & O'brien, Jacob. (2019). Clean up your sleep hygiene.  doi: 10.13140/RG.2.2.12857.11362.
7. Lee J, Jung HY, Lee SI, Choi JH, Kim SG. Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol. 2020 Jan;35(1):29-35. doi: 10.1097/YIC.0000000000000291
8. Kamalifard M, Farshbaf-Khalili A, Namadian M, Ranjbar Y, Herizchi S. Comparison of the effect of lavender and bitter orange on sleep quality in postmenopausal women: a triple-blind, randomized, controlled clinical trial. Women Health. 2018 Sep;58(8):851-865. doi: 10.1080/03630242.2017.135357
9. Bone K, Mills S. Principles and practice of phytotherapy: modern herbal medicine. Elsevier Health Sciences; 2012 Dec 31.
10. Rolland A, Fleurentin J, Lanhers MC, Misslin R, Mortier F. Neurophysiological effects of an extract of Eschscholzia californica Cham.(Papaveraceae). Phytother Res. 2001 Aug;15(5):377-81.
11. Mills SY, Bone K. The essential guide to herbal safety. Elsevier Health Sciences; 2005.

    12. Recommend to include a safe prescribing comment, as concomitant prescribing with other strong   
         analgesics is not recommended as a precaution (Mills & Bone 2005)