Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

Author(s): Fiammetta Romano*, Giovanna Muscogiuri, Elea Di Benedetto, Volha V. Zhukouskaya, Luigi Barrea, Silvia Savastano, Annamaria Colao and Carolina Di Somma

Volume 26 , Issue 21 , 2020

Page: [2492 - 2496] Pages: 5

DOI: 10.2174/1381612826666200310145935

Price: $65

Abstract

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle.

Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders.

Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders.

Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome.

Conclusion: Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

Keywords: Sleep, vitamin D, sleep regulation, sleep disturbance, sleep disorders, sun.

[1]
McCarty DE, Reddy A, Keigley Q, Kim PY, Marino AA, Vitamin D. Vitamin D, race, and excessive daytime sleepiness. J Clin Sleep Med 2012; 8(6): 693-7.
[http://dx.doi.org/10.5664/jcsm.2266] [PMID: 23243403]
[2]
Mete T, Yalcin Y, Berker D, et al. Obstructive sleep apnea syndrome and its association with vitamin D deficiency. J Endocrinol Invest 2013; 36(9): 681-5.
[PMID: 23558409]
[3]
Çakır T, Doğan G, Subaşı V, et al. An evaluation of sleep quality and the prevalence of restless leg syndrome in vitamin D deficiency. Acta Neurol Belg 2015; 115(4): 623-7.
[http://dx.doi.org/10.1007/s13760-015-0474-4] [PMID: 25904436]
[4]
Kerley CP, Hutchinson K, Bolger K, McGowan A, Faul J, Cormican L. Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome. Sleep (Basel) 2016; 39(2): 293-300.
[http://dx.doi.org/10.5665/sleep.5430] [PMID: 26414899]
[5]
Bikle DD. Extraskeletal actions of vitamin D. Ann N Y Acad Sci 2016; 1376(1): 29-52.
[http://dx.doi.org/10.1111/nyas.13219] [PMID: 27649525]
[6]
Bikle DD. Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential. Endocr Rev 1992; 13(4): 765-84.
[PMID: 1459048]
[7]
Bikle DD. Extra renal synthesis of 1,25 dihydroxyvitamin D and its Health Implications. Clin Rev in Bone and Min Metab 2009 June; 7: 114-25.
[8]
Balden R, Selvamani A, Sohrabji F. Vitamin D deficiency exacerbates experimental stroke injury and dysregulates ischemia-induced inflammation in adult rats. Endocrinology 2012; 153: 2420. e35
[9]
Zakon HH. The effects of steroid hormones on electrical activity of excitable cells. Trends Neurosci 1998; 21(5): 202. e7
[http://dx.doi.org/10.1016/S0166-2236(97)01209-5]
[10]
Shipton EA, Shipton EE. Vitamin D and pain: vitamin D and its role in the aetiology and maintenance of chronic pain states and associated comorbidities. Pain Res Treat 2015; 2015 904967
[http://dx.doi.org/10.1155/2015/904967] [PMID: 26090221]
[11]
Stumpf WE, O’Brien LP. 1,25 (OH)2 vitamin D3 sites of action in the brain. An autoradiographic study. Histochemistry 1987; 87(5): 393-406.
[http://dx.doi.org/10.1007/BF00496810] [PMID: 2828283]
[12]
Stumpf WE. Drug localization and targeting with receptor microscopic autoradiography. J Pharmacol Toxicol Methods 2005; 51(1): 25-40.
[http://dx.doi.org/10.1016/j.vascn.2004.09.001] [PMID: 15596112]
[13]
Stumpf WE, Bidmon HJ, Li L, et al. Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain of Siberian hamster (Phodopus sungorus) assessed by autoradiography. Histochemistry 1992; 98(3): 155-64.
[http://dx.doi.org/10.1007/BF00315874] [PMID: 1333462]
[14]
Musiol IM, Stumpf WE, Bidmon H-J, Heiss C, Mayerhofer A, Bartke A. Vitamin D nuclear binding to neurons of the septal, substriatal and amygdaloid area in the Siberian hamster (Phodopus sungorus) brain. Neuroscience 1992; 48(4): 841-8.
[http://dx.doi.org/10.1016/0306-4522(92)90272-4] [PMID: 1321365]
[15]
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005; 29(1): 21-30.
[http://dx.doi.org/10.1016/j.jchemneu.2004.08.006] [PMID: 15589699]
[16]
Muzur A, Pace-Schott EF, Hobson JA. The prefrontal cortex in sleep. Trends Cognit Sci 2002 Nov 1; 6(11): 475. e81
[http://dx.doi.org/10.1016/S1364-6613(02)01992-7]
[17]
Macey PM, Henderson LA, Macey KE, et al. Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med 2002; 166(10): 1382-7.
[http://dx.doi.org/10.1164/rccm.200201-050OC] [PMID: 12421746]
[18]
Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 2001; 435(4): 406-17.
[http://dx.doi.org/10.1002/cne.1040] [PMID: 11406822]
[19]
Guzman-Marín R, Suntsova N, Stewart DR, Gong H, Szymusiak R, McGinty D. Sleep deprivation reduces proliferation of cells in the dentate gyrus of the hippocampus in rats. J Physiol 2003; 549(Pt. 2): 563. e71
[20]
Stoffers D, Altena E, van der Werf YD, et al. The caudate: a key node in the neuronal network imbalance of insomnia? Brain 2014; 137(Pt 2): 610. e20
[http://dx.doi.org/10.1093/brain/awt329]
[21]
Marks GA, Roffwarg HP, Shaffery JP. Neuronal activity in the lateral geniculate nucleus associated with Ponto-geniculo-occipital waves lacks lamina specificity. Brain Res 1999; 815(1): 21.e8
[http://dx.doi.org/10.1016/S0006-8993(98)01008-7]
[22]
Lima MM, Andersen ML, Reksidler AB, Vital MA, Tufik S. The role of the substantia nigra pars compacta in regulating sleep patterns in rats. PLoS One 2007; 2(6) e513
[http://dx.doi.org/10.1371/journal.pone.0000513] [PMID: 17551593]
[23]
Iranzo A, Lomena F, Stockner H, et al. Sleep Innsbruck Barcelona (SINBAR) ~ group. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2010; 9(11): 1070. e7
[24]
McKinley MJ, Yao ST, Uschakov A, McAllen RM, Rundgren M, Martelli D. The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis. Acta Physiol (Oxf) 2015; 214(1): 8. e32
[http://dx.doi.org/10.1111/apha.12487]
[25]
Lu J, Greco MA, Shiromani P, Saper CB. Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep. J Neurosci 2000; 20(10): 3830. e42
[26]
Jirikowski GF, Kaunzner UW, Dief Ael E, Caldwell JD. Distribution of vitamin D binding protein expressing neurons in the rat hypothalamus. Histochem Cell Biol 2009; 131(3): 365. e70
[http://dx.doi.org/10.1007/s00418-008-0540-6]
[27]
Solomonova E, Lee YEA, Robins S, et al. Sleep quality is associated with vasopressin methylation in pregnant and postpartum women with a history of psychosocial stress. Psychoneuroendocrinology 2019; 107: 160-8.
[http://dx.doi.org/10.1016/j.psyneuen.2019.05.010] [PMID: 31132568]
[28]
Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002; 13(3): 100-5.
[http://dx.doi.org/10.1016/S1043-2760(01)00547-1] [PMID: 11893522]
[29]
Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357(3): 266-81.
[http://dx.doi.org/10.1056/NEJMra070553] [PMID: 17634462]
[30]
Lucock M, Jones P, Martin C, et al. Vitamin D: beyond metabolism. J Evid Based Complementary Altern Med 2015; 20(4): 310-22.
[http://dx.doi.org/10.1177/2156587215580491] [PMID: 25878189]
[31]
Vitaterna MH, Takahashi JS, Turek FW. Overview of circadian rhythms. Alcohol Res Health 2001; 25: 85. e93
[32]
Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 2010; 72: 517. e49
[http://dx.doi.org/10.1146/annurev-physiol-021909-135821]
[33]
Shipton EA, Shipton EE. Vitamin D and pain: vitamin D and its role in the aetiology and maintenance of chronic pain states and associated comorbidities. Pain Res Treat 2015; 2015 904967
[34]
Moretti R, Morelli ME, Caruso P. Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact. Int J Mol Sci 2018; 19(8) E2245
[http://dx.doi.org/10.3390/ijms19082245] [PMID: 30065237]
[35]
Zhao D, Yu Y, Shen Y, et al. Melatonin Synthesis and Function: Evolutionary History in Animals and Plants. Front Endocrinol (Lausanne) 2019; 10: 249.
[http://dx.doi.org/10.3389/fendo.2019.00249] [PMID: 31057485]
[36]
Kaneko I, Sabir MS, Dussik CM, et al. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J 2015; 29(9): 4023-35.
[http://dx.doi.org/10.1096/fj.14-269811] [PMID: 26071405]
[37]
Golan D, Staun-Ram E, Glass-Marmor L, et al. The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis. Brain Behav Immun 2013; 32: 180. e5
[http://dx.doi.org/ 10.1016/j.bbi.2013.04.010]
[38]
Toujani S, Kaabachi W, Mjid M, Hamzaoui K, Cherif J, Beji M. Vitamin D deficiency and interleukin-17 relationship in severe obstructive sleep apnea-hypopnea syndrome. Ann Thorac Med 2017; 12(2): 107-13.
[http://dx.doi.org/10.4103/atm.ATM_301_16] [PMID: 28469721]
[39]
Okura K, Lavigne GJ, Huynh N, Manzini C, Fillipini D, Montplaisir JY. Comparison of sleep variables between chronic widespread musculoskeletal pain, insomnia, periodic leg movements syndrome and control subjects in a clinical sleep medicine practice. Sleep Med 2008; 9(4): 352-61.
[http://dx.doi.org/10.1016/j.sleep.2007.07.007] [PMID: 17804292]
[40]
Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep 2007; 30(9): 1145-52.
[http://dx.doi.org/10.1093/sleep/30.9.1145] [PMID: 17910386]
[41]
Yokoe T, Minoguchi K, Matsuo H, et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 2003; 107(8): 1129-34.
[http://dx.doi.org/10.1161/01.CIR.0000052627.99976.18] [PMID: 12615790]
[42]
Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 2003; 89(5): 552-72.
[http://dx.doi.org/10.1079/BJN2003837] [PMID: 12720576]
[43]
Huang W, Shah S, Long Q, Crankshaw AK, Tangpricha V. Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. Clin J Pain 2013; 29(4): 341-7.
[http://dx.doi.org/10.1097/AJP.0b013e318255655d] [PMID: 22699141]
[44]
Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR. 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 2011; 57(1): 63-9.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.160929] [PMID: 21115878]
[45]
Feldman D, Krishnan A, Moreno J, Swami S, Peehl DM, Srinivas S. Vitamin D inhibition of the prostaglandin pathway as therapy for prostate cancer. Nutr Rev 2007; 65(8 Pt. 2): S113-5.
[http://dx.doi.org/10.1301/nr.2007.aug.S113-S115] [PMID: 17867384]
[46]
Krueger JM, Majde JA, Rector DM. Cytokines in immune function and sleep regulation. Handb Clin Neurol 2011; 98: 229-40.
[http://dx.doi.org/10.1016/B978-0-444-52006-7.00015-0] [PMID: 21056190]
[47]
Barceló A, de la Peña M, Barbé F, Pierola J, Bosch M, Agustí AG. Prostaglandin D synthase (beta trace) levels in sleep apnea patients with and without sleepiness. Sleep Med 2007; 8(5): 509-11.
[http://dx.doi.org/10.1016/j.sleep.2006.10.005] [PMID: 17512779]
[48]
Jung YS, Chae CH, Kim YO, et al. The relationship between serum vitamin D levels and sleep quality in fixed day indoor field workers in the electronics manufacturing industry in Korea. Ann Occup Environ Med 2017; 29: 25.
[http://dx.doi.org/10.1186/s40557-017-0187-7] [PMID: 28652922]
[49]
Massa J, Stone KL, Wei EK, et al. Vitamin D and actigraphic sleep outcomes in older community-dwelling men: the MrOS sleep study. Sleep (Basel) 2015; 38(2): 251-7.
[http://dx.doi.org/10.5665/sleep.4408] [PMID: 25581929]
[50]
Han B, Zhu F-X, Shi C, Wu HL, Gu XH. Association between serum vitamin D levels and sleep disturbance in hemodialysis patients. Nutrients 2017; 9(2) E139
[http://dx.doi.org/10.3390/nu9020139] [PMID: 28216568]
[51]
Cheng TS, Loy SL, Cheung YB, et al. Plasma vitamin D deficiency is associated with poor sleep quality and night-time eating at mid-pregnancy in Singapore. Nutrients 2017; 9(4) E340
[http://dx.doi.org/10.3390/nu9040340] [PMID: 28353643]
[52]
Gunduz S, Kosger H, Aldemir S, et al. Sleep deprivation in the last trimester of pregnancy and inadequate vitamin D: Is there a relationship? J Chin Med Assoc 2016; 79(1): 34-8.
[http://dx.doi.org/10.1016/j.jcma.2015.06.017] [PMID: 26391786]
[53]
Mason C, De Dieu Tapsoba J, Duggan C, Wang CY, Korde L, McTiernan A. Repletion of Vitamin D associated with deterioration of sleep quality among postmenopausal women. Prev Med 93: 166-70.
[54]
Bertisch SM, Sillau S, de Boer IH, Szklo M, Redline S. 25-Hydroxyvitamin D concentration and sleep duration and continuity: multi-ethnic study of atherosclerosis. Sleep (Basel) 2015; 38(8): 1305-11.
[http://dx.doi.org/10.5665/sleep.4914] [PMID: 25669179]
[55]
Kim J, Lee W, Kweon H, et al. Associations between sleep duration and serum vitamin D level in Korean women. Korean J of Fam Pract 2016; 6(6): 586. e91
[http://dx.doi.org/10.21215/kjfp.2016.6.6.586]
[56]
Carlander B, Puech-Cathala AM, Jaussent I, et al. Low vitamin D in narcolepsy with cataplexy. PLoS One 2011; 6(5) e20433
[http://dx.doi.org/10.1371/journal.pone.0020433] [PMID: 21633708]
[57]
Dauvilliers Y, Evangelista E, Lopez R, et al. Vitamin D deficiency in type 1 narcolepsy: a reappraisal. Sleep Med 2017; 29: 1-6.
[http://dx.doi.org/10.1016/j.sleep.2016.05.008] [PMID: 28153207]
[58]
Wali SO, Abaalkhail B, Alhejaili F, Pandi-Perumal SR. Efficacy of vitamin D replacement therapy in restless legs syndrome: a randomized control trial. Sleep Breath 2019; 23(2): 595-601.
[http://dx.doi.org/10.1007/s11325-018-1751-2] [PMID: 30430372]
[59]
Balaban H, Yıldız ÖK, Çil G, et al. Serum 25-hydroxyvitamin D levels in restless legs syndrome patients. Sleep Med 2012; 13(7): 953-7.
[http://dx.doi.org/10.1016/j.sleep.2012.04.009] [PMID: 22704399]
[60]
Archontogeorgis K, Nena E, Papanas N, Steiropoulos P. The role of vitamin D in obstructive sleep apnoea syndrome. Breathe (Sheff) 2018; 14(3): 206-15.
[http://dx.doi.org/10.1183/20734735.000618] [PMID: 30186518]
[61]
Dzik KP, Kaczor JJ. Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol 2019; 119(4): 825-39.
[http://dx.doi.org/10.1007/s00421-019-04104-x] [PMID: 30830277]
[62]
Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int 2002; 13(3): 187-94.
[http://dx.doi.org/10.1007/s001980200012] [PMID: 11991436]
[63]
Sharma V, Borah P, Basumatary LJ, Das M, Goswami M, Kayal AK. Myopathies of endocrine disorders: A prospective clinical and biochemical study. Ann Indian Acad Neurol 2014; 17(3): 298-302.
[http://dx.doi.org/10.4103/0972-2327.138505] [PMID: 25221399]
[64]
Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007; 132(1): 325-37.
[http://dx.doi.org/10.1378/chest.07-0040] [PMID: 17625094]
[65]
Jolliffe DA, Greenberg L, Hooper RL, et al. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet Respir Med 2017; 5(11): 881-90.
[http://dx.doi.org/10.1016/S2213-2600(17)30306-5] [PMID: 28986128]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy