Skip to main content

Advertisement

SpringerLink
Log in

Associations of Multiple Serum Trace Elements with Abnormal Sleep Duration Patterns in Hospitalized Patient with Cirrhosis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The associations of circulating trace elements with sleep health have attracted increasing attention given their potential link. However, there is scant data on the relationship between serum trace elements and abnormal sleep duration patterns in cirrhosis. We aimed to investigate these associations with the purpose of identifying modifiable risk factors. The blood samples were collected from inpatients with cirrhosis, and serum levels of several trace elements were assessed by inductively coupled plasma mass spectrometry. Self-reported sleep duration was categorized to short- (< 7 h/night), optimal (7–8 h/night), and long-sleep duration (> 8 h/night). The dose–response trends and associations of trace elements levels with sleep duration were determined by restricted cubic splines (RCS) and logistic regression, respectively. Cirrhotic patients with optimal sleep duration experienced the highest levels of serum Zinc (Zn) and the lowest values of copper to zinc ratio (CZr). RCS model corroborated non-linear associations of serum Zn and CZr against sleep duration. Multiple regression analysis showed that both CZr (short vs optimal sleep duration: OR 4.785, P < 0.001; long vs optimal sleep duration: OR 4.150, P = 0.019) and serum Zn levels (short vs optimal sleep duration: OR 0.985, P = 0.040; long vs optimal sleep duration: OR 0.956, P = 0.008) serve as independent risk factors for sleep duration abnormalities. In conclusion, our findings unraveled a close relationship of serum Zn and CZr with sleep duration in cirrhosis. Further trace element-based therapy such as Zn supplementation may be novel approach to reverse this sleep problem.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to individual privacy but are available from the corresponding author on reasonable request.

References

  1. Carley DW, Farabi SS (2016) Physiology of sleep. Diabetes Spectr 29(1):5–9

    Article  PubMed  PubMed Central  Google Scholar 

  2. Fernandez-Mendoza J, Vgontzas AN, Liao D, Shaffer ML, Vela-Bueno A, Basta M et al (2012) Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort. Hypertens 60(4):929–935

    Article  CAS  Google Scholar 

  3. Hoevenaar-Blom MP, Spijkerman AM, Kromhout D, Verschuren WM (2014) Sufficient sleep duration contributes to lower cardiovascular disease risk in addition to four traditional lifestyle factors: the MORGEN study. Eur J Prev Cardiol 21(11):1367–1375

    Article  PubMed  Google Scholar 

  4. J. Yin, X. Jin, Z. Shan, S. Li, H. Huang, P. Li, et al., (2017) Relationship of sleep duration with all-cause mortality and cardiovascular events: a systematic review and dose-response meta-analysis of prospective cohort studies, J Am Heart Assoc 6(9):e005947

  5. Marjot T, Ray DW, Williams FR, Tomlinson JW, Armstrong MJ (2021) Sleep and liver disease: a bidirectional relationship. Lancet Gastroenterol Hepatol 6(10):850–863

    Article  PubMed  Google Scholar 

  6. Hui Y, Xu L, Wang X, Feng H, Yu Z, Li C et al (2021) Association between sleep disturbance and multidimensional frailty assessed by Frailty Index in hospitalized cirrhosis. Eur J Gastroenterol Hepatol 33(1):e727–e733

    Article  CAS  PubMed  Google Scholar 

  7. M. Kim, E.M. Liotta, M.B. Maas, R.I. Braun, B. Garcia-Canga, D.R. Ganger, et al., (2021) Rest-activity rhythm disturbance in liver cirrhosis and association with cognitive impairment, Sleep 44(6):zsaa288

  8. T. Himoto, T. (2020) Masaki, Current trends of essential trace elements in patients with chronic liver diseases, Nutrients 12(7):2084

  9. Nordberg M, Nordberg GF (2016) Trace element research-historical and future aspects. J Trace Elem Med Biol 38:46–52

    Article  CAS  PubMed  Google Scholar 

  10. Nangliya V, Sharma A, Yadav D, Sunder S, Nijhawan S, Mishra S (2015) Study of trace elements in liver cirrhosis patients and their role in prognosis of disease. Biol Trace Elem Res 165(1):35–40

    Article  CAS  PubMed  Google Scholar 

  11. H. Nishikawa, K. Yoh, H. Enomoto, Y. Iwata, Y. Sakai, K. Kishino, et al., (2020) Serum zinc level is associated with frailty in chronic liver diseases, J Clin Med 9(5):1570

  12. G. Llibre-Nieto, A. Lira, M. Vergara, C. Sole, M. Casas, V. Puig-Divi, et al., (2021) Micronutrient deficiencies in patients with decompensated liver cirrhosis, Nutrients 13(4)

  13. Kaur H, Premkumar M (2022) Diagnosis and management of cirrhotic cardiomyopathy. J Clin Exp Hepatol 12(1):186–199

    Article  CAS  PubMed  Google Scholar 

  14. Ardahanli I, Ozkan HI (2022) Comparison of serum selenium levels between patients with newly diagnosed atrial fibrillation and normal controls. Biol Trace Elem Res 200(9):3925–3931

    Article  CAS  PubMed  Google Scholar 

  15. Ji X, Grandner MA, Liu J (2017) The relationship between micronutrient status and sleep patterns: a systematic review. Public Health Nutr 20(4):687–701

    Article  PubMed  Google Scholar 

  16. Song CH, Kim YH, Jung KI (2012) Associations of zinc and copper levels in serum and hair with sleep duration in adult women. Biol Trace Elem Res 149(1):16–21

    Article  CAS  PubMed  Google Scholar 

  17. Martinez-Peinado M, Rueda-Robles A, Nogueras-Lopez F, Villalon-Mir M, Oliveras-Lopez MJ, Navarro-Alarcon M (2018) Serum zinc and copper concentrations and ratios in cirrhotic patients: correlation with severity index. Nutr Hosp 35(3):627–632

    CAS  PubMed  Google Scholar 

  18. Tsai PS, Wang SY, Wang MY, Su CT, Yang TT, Huang CJ et al (2005) Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects. Qual Life Res 14(8):1943–1952

    Article  CAS  PubMed  Google Scholar 

  19. Jia YN, Sun J, Chen L, Xue Y (2022) Associations of serum zinc, copper, and zinc/copper ratio with sleep duration in adults. Biol Trace Elem Res 200(6):2651–2659

    Article  CAS  PubMed  Google Scholar 

  20. W. Yang, X. Wang, Z. Yu, C. Li, M. Sun, Y. Li, et al., (2021) Low levels of serum zinc associate with malnutrition risk assessed by the Royal Free Hospital-Nutritional Prioritizing Tool in cirrhosis, Biol Trace Elem Res.

  21. Yokoyama K, Araki S, Sato H, Aono H (2000) Circadian rhythms of seven heavy metals in plasma, erythrocytes and urine in men: observation in metal workers. Ind Health 38(2):205–212

    Article  CAS  PubMed  Google Scholar 

  22. Nakhaee S, Amirabadizadeh A, Ataei M, Ataei H, Zardast M, Shariatmadari MR et al (2021) Comparison of serum concentrations of essential and toxic elements between cigarette smokers and non-smokers. Environ Sci Pollut Res Int 28(28):37672–37678

    Article  CAS  PubMed  Google Scholar 

  23. Ji X, Liu J (2015) Associations between blood zinc concentrations and sleep quality in childhood: a cohort study. Nutrients 7(7):5684–5696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Luojus MK, Lehto SM, Tolmunen T, Elomaa AP, Kauhanen J (2015) Serum copper, zinc and high-sensitivity C-reactive protein in short and long sleep duration in ageing men. J Trace Elem Med Biol 32:177–182

    Article  CAS  PubMed  Google Scholar 

  25. Kim NR, Kim KW, Kim HN, Song SW (2018) Associations between serum zinc levels and mental health: findings from the 2010 Korean National Health and Nutrition Examination Survey. Biol Trace Elem Res 181(2):192–198

    Article  CAS  PubMed  Google Scholar 

  26. Zhang HQ, Li N, Zhang Z, Gao S, Yin HY, Guo DM et al (2009) Serum zinc, copper, and zinc/copper in healthy residents of Jinan. Biol Trace Elem Res 131(1):25–32

    Article  CAS  PubMed  Google Scholar 

  27. Gallicchio L, Kalesan B (2009) Sleep duration and mortality: a systematic review and meta-analysis. J Sleep Res 18(2):148–158

    Article  PubMed  Google Scholar 

  28. Zhang C, Dischler A, Glover K, Qin Y (2022) Neuronal signalling of zinc: from detection and modulation to function. Open Biol 12(9):220188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kostin A, Alam MA, McGinty D, Szymusiak R, Alam MN (2019) Chronic suppression of hypothalamic cell proliferation and neurogenesis induces aging-like changes in sleep-wake organization in young mice. Neuroscience 404:541–556

    Article  CAS  PubMed  Google Scholar 

  30. Jones CE, Underwood CK, Coulson EJ, Taylor PJ (2007) Copper induced oxidation of serotonin: analysis of products and toxicity. J Neurochem 102(4):1035–1043

    Article  CAS  PubMed  Google Scholar 

  31. D’Ambrosi N, Rossi L (2015) Copper at synapse: release, binding and modulation of neurotransmission. Neurochem Int 90:36–45

    Article  PubMed  Google Scholar 

  32. Yin D, Dong H, Wang TX, Hu ZZ, Cheng NN, Qu WM et al (2019) Glutamate activates the histaminergic tuberomammillary nucleus and increases wakefulness in rats. Neuroscience 413:86–98

    Article  CAS  PubMed  Google Scholar 

  33. Guo CH, Chen PC, Yeh MS, Hsiung DY, Wang CL (2011) Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis. Clin Biochem 44(4):275–280

    Article  CAS  PubMed  Google Scholar 

  34. Malavolta M, Piacenza F, Basso A, Giacconi R, Costarelli L, Mocchegiani E (2015) Serum copper to zinc ratio: relationship with aging and health status. Mech Ageing Dev 151:93–100

    Article  CAS  PubMed  Google Scholar 

  35. Tsai CF, Chu CJ, Wang YP, Liu PY, Huang YH, Lin HC et al (2016) Increased serum interleukin-6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients. Aliment Pharmacol Ther 44(8):836–845

    Article  CAS  PubMed  Google Scholar 

  36. Sundaram SS, Halbower AC, Klawitter J, Pan Z, Robbins K, Capocelli KE et al (2018) Treating obstructive sleep apnea and chronic intermittent hypoxia improves the severity of nonalcoholic fatty liver disease in children. J Pediatr 198:67-75.e1

    Article  PubMed  Google Scholar 

  37. Hui Y, Wang X, Yu Z, Feng H, Li C, Mao L et al (2021) Relationship between sleep-wake disturbance and risk of malnutrition in hospitalized patients with cirrhosis. Front Nutr 8:719176

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sharonova IN, Vorobjev VS, Haas HL (2000) Interaction between copper and zinc at GABA(A) receptors in acutely isolated cerebellar Purkinje cells of the rat. Br J Pharmacol 130(4):851–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ivanova ID, Pal A, Simonelli I, Atanasova B, Ventriglia M, Rongioletti M et al (2022) Evaluation of zinc, copper, and Cu: Zn ratio in serum, and their implications in the course of COVID-19. J Trace Elem Med Biol 71:126944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang L, Shao J, Tan SW, Ye HP, Shan XY (2022) Association between serum copper/zinc ratio and lung cancer: a systematic review with meta-analysis. J Trace Elem Med Biol 74:127061

    Article  CAS  PubMed  Google Scholar 

  41. Sharma MK, Kainth S, Kumar S, Bhardwaj A, Agarwal HK, Maiwall R et al (2019) Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: a randomized, placebo-controlled trial. Clin Mol Hepatol 25(2):199–209

    Article  PubMed  PubMed Central  Google Scholar 

  42. Spahr L, Coeytaux A, Giostra E, Hadengue A, Annoni JM (2007) Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Am J Gastroenterol 102(4):744–753

    Article  CAS  PubMed  Google Scholar 

  43. Himoto T, Hosomi N, Nakai S, Deguchi A, Kinekawa F, Matsuki M et al (2007) Efficacy of zinc administration in patients with hepatitis C virus-related chronic liver disease. Scand J Gastroenterol 42(9):1078–1087

    Article  CAS  PubMed  Google Scholar 

  44. Bruyneel M, Serste T (2018) Sleep disturbances in patients with liver cirrhosis: prevalence, impact, and management challenges. Nat Sci Sleep 10:369–375

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded in part by the Science and Technology Program of Tianjin, grant number 19ZXDBSY00020 to K.J.

Author information

Author notes

  1. Yangyang Hui, Gaoyue Guo, and Lihong Mao contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Anshan Road 154, Tianjin, 300052, China

    Yangyang Hui, Gaoyue Guo, Lihong Mao, Yifan Li, Mingyu Sun, Xiaoyu Wang, Wanting Yang, Xiaofei Fan, Kui Jiang & Chao Sun

  2. Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Heping District, Anshan Road 154, Tianjin, 300052, China

    Yangyang Hui, Gaoyue Guo, Lihong Mao, Yifan Li, Mingyu Sun, Xiaoyu Wang, Wanting Yang, Xiaofei Fan, Kui Jiang & Chao Sun

  3. Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin Airport Economic Area, East Street 6, Tianjin, 300308, China

    Binxin Cui & Chao Sun

Authors
  1. Yangyang Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaoyue Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lihong Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yifan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingyu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wanting Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaofei Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kui Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Binxin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Y. Y. H., L. H. M., G. Y. G., and C. S.; formal analysis: Y. F. L., M. Y. S., and X. Y. W.; methodology: W. T. Y. and X. F. F.; investigation: K. J. and B. X. C.; writing—review and editing: C. S.

Corresponding author

Correspondence to Chao Sun.

Ethics declarations

Ethics Approval

The current study was approved by the Ethics Committee of TJMUGH and performed in line with the principles of the Declaration of Helsinki.

Consent to Participate

All participants have provided written informed consent.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hui, Y., Guo, G., Mao, L. et al. Associations of Multiple Serum Trace Elements with Abnormal Sleep Duration Patterns in Hospitalized Patient with Cirrhosis. Biol Trace Elem Res 201, 3202–3209 (2023). https://doi.org/10.1007/s12011-022-03425-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03425-x

Keywords

Search

Navigation