Document Type : Original article


1 Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Science, Gonabad, Iran

3 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Metabolic Syndrome Research Center. Mashhad University of Medical Sciences, Mashhad, Iran.

5 5International UNESCO Center for Health Related Basic Sciences and Human Nutrition, Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

6 Department of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, UK.

7 Biochemistry and Nutrition Research Center and Department of clinical biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran


Introduction: The pandemic of COVID-19 created a psychological response. So, the psychological function of COVID-19 patients is an important subject that forces us to follow up with them.
Aim: Assess the correlation between vitamin D serum concentrations and psychological functions such as insomnia, stress, and depression through the COVID-19 pandemic
Methods: In this cross-sectional study, blood samples from 120 COVID-19 patients (61 males and 59 females) who had more than 30 years, were taken. Also, 25(OH)D Serum level of COVID-19 patients was analyzed. The Insomnia Severity Index (ISI), Depression anxiety stress scales (DASS), and the Short Form Health Survey (SF-36) were used to analyze insomnia, anxiety, stress, quality of life, and depression.
Results: The relationship between temperature (p=0.039), PCO2 (p=0.022), and serum vitamin D level was significant. Additionally, there was a significant correlation between stress (p=-0.023, OR=0.389, 95% CI for OR=0.047, 0.843), depression (p=0.012, OR=0.659, 95% CI for OR=0.476, 0.913), and the concentration of serum vitamin D.
Conclusion:This study recommends that vitamin D supplementation improve psychological state in COVID-19 patients.


  1. WHO/Europe. WHO announces COVID-19 outbreak a pandemic [Available from: health-topics/health-emergencies/coronavirus-covid-19/ news/news/2020/3/who-announces-covid-19-outbreak apandemic.
  2. Worldometer. COVID-19 CORONAVIRUS PANDEMIC [Available from: coronavirus/.
  3. Ceolin G, Mano GPR, Hames NS, et al. Vitamin D, Depressive Symptoms, and Covid-19 Pandemic. Front Neurosci. 2021;15:670879-.
  4. Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. Journal of affective disorders. 2020.
  5. Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. Brain, behavior, and immunity. 2020;89:531-542.
  6. Ettman CK, Abdalla SM, Cohen GH,et al. Prevalence of depression symptoms in US adults before and during the COVID-19 pandemic. JAMA network open. 2020;3:e2019686-e.
  7. Bhuiyan AI, Sakib N, Pakpour AH, et al. COVID-19-related suicides in Bangladesh due to lockdown and economic factors: case study evidence from media reports. International Journal of Mental Health and Addiction. 2020:1-6.
  8. Thakur V, Jain A. COVID 2019-suicides: A global psychological pandemic. Brain, behavior, and immunity. 2020;88:952.
  9. Smith BJ, Lim MH. How the COVID-19 pandemic is focusing attention on loneliness and social isolation. Public Health Res Pract. 2020;30:3022008.
  10. Luo M, Guo L, Yu M, et al. The psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public–A systematic review and metaanalysis. Psychiatry research. 2020;291:113190.
  11. Sani G, Janiri D, Di Nicola M,et al. Mental health during and after the COVID-19 emergency in Italy. Psychiatry and clinical neurosciences. 2020;74:372-.
  12. Yao H, Chen J-H, Xu Y-F. Patients with mental health disorders in the COVID-19 epidemic. 2020.
  13. Kontoangelos K, Economou M, Papageorgiou C. Mental health effects of COVID-19 pandemia: a review of clinical and psychological traits. Psychiatry investigation. 2020;17:491.
  14. Anglin RE, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and metaanalysis. The British journal of psychiatry. 2013;202:100-107.
  15. Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. The FASEB Journal. 2015;29:2207 2222.
  16. Groves NJ, McGrath JJ, Burne TH. Vitamin D as a neurosteroid affecting the developing and adult brain. Annual review of nutrition. 2014;34:117-141.
  17. Kiraly SJ, Kiraly MA, Hawe RD, et al. Vitamin D as a Neuroactive Substance: Review. TheScientificWorldJOURNAL. 2006;6:281350.
  18. Huiberts LM, Smolders KC. Effects of vitamin D on mood and sleep in the healthy population: Interpretations from the serotonergic pathway. Sleep Medicine Reviews. 2021;55:101379.
  19. Rai V, Agrawal DK. Role of vitamin D in cardiovascular diseases. Endocrinology and Metabolism Clinics. 2017;46:1039-1059.
  20. Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: what comes first? Annals of the New York Academy of Sciences. 2019;1437:57-67.
  21. Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC medicine. 2013;11:1-16.
  22. Lee KM, Ward MH, Han S, Ahn HS, Kang HJ, Choi HS, et al. Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk. Leuk Res. 2009;33(2):250-8.
  23. Di Nicola M, Dattoli L, Moccia L, Pepe M, Janiri D, Fiorillo A, et al. Serum 25-hydroxyvitamin D levels and psychological distress symptoms in patients with affective disorders during the COVID-19 pandemic. Psychoneuroendocrinology. 2020;122:104869-.
  24. Parker GB, Brotchie H, Graham RK. Vitamin D and depression. Journal of Affective Disorders. 2017;208:56-61.
  25. Vellekkatt F, Menon V. Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials. J Postgrad Med. 2019;65:74-80.
  26. Bertone-Johnson ER. Vitamin D and the occurrence of depression: causal association or circumstantial evidence? Nutrition Reviews. 2009;67:481-492.
  27. Shaffer JA, Edmondson D, Wasson LT, et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosomatic medicine. 2014;76:190-196.
  28. Gowda U, Mutowo MP, Smith BJ, et al. Vitamin D supplementation to reduce depression in adults: metaanalysis of randomized controlled trials. Nutrition (Burbank, Los Angeles County, Calif). 2015;31:421-429.
  29. Holick MF. Vitamin D deficiency. The New England journal of medicine. 2007;357:266-281.
  30. Khorasanchi Z, Jafazadeh Esfehani A, Sharifan P, et al. The effects of high dose vitamin D supplementation as a nutritional intervention strategy on biochemical and inflammatory factors in adults with COVID-19: Study protocol for a randomized controlled trial. Nutrition and Health. 2022;28:311-317.
  31. Henry JD, Crawford JR. The short-form version of the Depression Anxiety Stress Scales (DASS-21): Construct validity and normative data in a large non-clinical sample. British journal of clinical psychology. 2005;44:227-239.
  32. Sahebi A, Asghari MJ, Salari RS. Validation of depression anxiety and stress scale (DASS-21) for an Iranian population. 2005.
  33. Morin CM, Belleville G, Bélanger L, et al. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34:601- 608.
  34. Yazdi Z, Sadeghniiat-Haghighi K, Zohal MA, et al. Validity and reliability of the Iranian version of the insomnia severity index. The Malaysian journal of medical sciences: MJMS. 2012;19:31.
  35. Sotodehasl N, Malek F, Tamadon MR. Vitamin D deficiency and depression: a short review article. Middle East Journal of Rehabilitation and Health. 2015;2.
  36. Sotodeh-Asl N, Tamadon M-R, Malek F, et al. Vitamin D deficiency and psychological disorders. Journal of Parathyroid Disease. 2014;2:21-25.
  37. Saharkhiz M, Khorasanchi Z, Karbasi S, et al. The association between adherence to a dietary approaches to stop hypertension (DASH) diet and neuro-psychological function in young women. BMC nutrition. 2021;7:21.
  38. Hoogendijk WJG, Lips P, Dik MG, et al. Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults. Archives of General Psychiatry. 2008;65:508-512.
  39. Pu D, Luo J, Wang Y, et al. Prevalence of depression and anxiety in rheumatoid arthritis patients and their associations with serum vitamin D level. Clinical rheumatology. 2018;37:179- 184.
  40. Murphy PK, Mueller M, Hulsey TC, et al. An exploratory study of postpartum depression and vitamin D. Journal of the American Psychiatric Nurses Association. 2010;16:170-177.
  41. Anglin RES, Samaan Z, Walter SD, et al. Vitamin D deficiency and depression in adults: systematic review and metaanalysis. British Journal of Psychiatry. 2013;202:100-107.
  42. Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Frontiers in neuroendocrinology. 2013;34:47-64.
  43. Cui X, Pertile R, Liu P, Eyles D. Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator. Neuroscience. 2015;304:90-100.
  44. Trinko JR, Land BB, Solecki WB, et al. Vitamin D3: a role in dopamine circuit regulation, diet-induced obesity, and drug consumption. Eneuro. 2016;3.
  45. Kajta M, Makarewicz D, Ziemińska E, et al. Neuroprotection by co-treatment and post-treating with calcitriol following the ischemic and excitotoxic insult in vivo and in vitro. Neurochemistry international. 2009;55:265-274.
  46. Kalueff A, Eremin K, Tuohimaa P. Mechanisms of neuroprotective action of vitamin D 3. Biochemistry (Moscow). 2004;69:738-741.
  47. Langub M, Herman J, Malluche H, et al. Evidence of functional vitamin D receptors in rat hippocampus. Neuroscience. 2001;104:49-56.
  48. Latimer CS, Brewer LD, Searcy JL, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proceedings of the National Academy of Sciences. 2014;111:E4359-E4366.
  49. Obradovic D, Gronemeyer H, Lutz B, Rein T. Cross-talk of vitamin D and glucocorticoids in hippocampal cells. Journal of neurochemistry. 2006;96:500-509.
  50. Bakhtiari-Dovvombaygi H, Izadi S, Moghaddam MZ, et al. Beneficial effects of vitamin D on anxiety and depression like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2021;394:655-667.
  51. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013;246:199-229.
  52. Sedaghat K, Naderian R, Pakdel R, et al. Regulatory effect of vitamin D on pro-inflammatory cytokines and anti oxidative enzymes dysregulations due to chronic mild stress in the rat hippocampus and prefrontal cortical area. Molecular Biology Reports. 2021:1-9.
  53. Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164-175.
  54. Lei G-S, Zhang C, Cheng B-H, Lee C-H. Mechanisms of action of vitamin D as supplemental therapy for Pneumocystis pneumonia. Antimicrobial agents and chemotherapy. 2017;61:e01226-17.
  55. Erren TC, Lewis P. SARS-CoV-2/COVID-19 and physical distancing: risk for circadian rhythm dysregulation, advice to alleviate it, and natural experiment research opportunities. Chronobiology international. 2020;37:1106-1109.
  56. Neshatbini Tehrani A, Farhadnejad H, Salehpour A, Hekmatdoost A. Vitamin D intake and risk of psychological disorders among female adolescents. Nutrition & Food Science. 2021;51:633-642.
  57. Dias CJ, Barroso R, Dias-Filho CAA, et al. Possible influences of vitamin D levels on sleep quality, depression, anxiety and physiological stress in patients with chronic obstructive pulmonary disease: a case control study. Sleep Sci. 2022;15:369-374.
  58. Trovato B, Godos J, Varrasi S, Roggio F, Castellano S, Musumeci G. Physical Activity, Sun Exposure, Vitamin D Intake and Perceived Stress in Italian Adults. Nutrients. 2023;15:2301.
  59. Black LJ, Jacoby P, Allen KL, et al. Low vitamin D levels are associated with symptoms of depression in young adult males. Australian & New Zealand Journal of Psychiatry. 2014;48:464-471.