Vitamin D as the essential immunonutrient – the evidence base update: A review

Cover Page

Cite item

Full Text

Abstract

The micronutrient status plays a key role for adequate immune response, including in diseases caused by respiratory viruses. Numerous studies conducted since the beginning of the COVID-19 pandemic, examining the impact of micronutrient availability, have shown their importance in the prevention of this disease. The largest number of publications is devoted to vitamin D. As a result, in less than two years, 17 meta-analyses and analytical reviews were published on the role of vitamin D and the availability of this micronutrient in various population groups in reducing the incidence, incidence of severe forms of COVID-19 and mortality. This review summarizes the results of published meta-analyses and systematic reviews. The analysis of literature data confirms that vitamin D has the highest evidence base as a micronutrient that reduces the risk of disease and the occurrence of severe forms of COVID-19. It also provides up-to-date recommendations on vitamin D supplementation for adult and pediatric patients.

About the authors

Svetlana G. Makarova

National Medical Research Center for Children's Health; Lomonosov Moscow State University

Author for correspondence.
Email: sm27@yandex.ru
ORCID iD: 0000-0002-3056-403X

D. Sci. (Med.), National Medical Research Center for Children's Health, Lomonosov Moscow State University

Russian Federation, Moscow; Moscow

Evgeny E. Emelyashenkov

National Medical Research Center for Children's Health

Email: dkswdsman@mail.ru
ORCID iD: 0000-0002-0995-4260

Graduate Student, National Medical Research Center for Children's Health

Russian Federation, Moscow

Dmitry S. Yasakov

National Medical Research Center for Children's Health

Email: dmyasakov@mail.ru
ORCID iD: 0000-0003-1330-2828

Cand. Sci. (Med.), National Medical Research Center for Children's Health

Russian Federation, Moscow

Irina Yu. Pronina

National Medical Research Center for Children's Health; Endocrinology Research Centre

Email: krapchatovaiv@yandex.ru
ORCID iD: 0000-0003-3306-6869

Res. Assist., National Medical Research Center for Children's Health, Endocrinology Research Centre

Russian Federation, Moscow; Moscow

Oksana A. Ereshko

National Medical Research Center for Children's Health

Email: sm27@yandex.ru
ORCID iD: 0000-0002-1650-652X

Cand. Sci. (Med.), National Medical Research Center for Children's Health

Russian Federation, Moscow

Irina G. Gordeeva

National Medical Research Center for Children's Health

Email: sm27@yandex.ru
ORCID iD: 0000-0001-6658-0624

Res. Assist., National Medical Research Center for Children's Health

Russian Federation, Moscow

Albina A. Galimova

National Medical Research Center for Children's Health

Email: albina86@yandex.ru
ORCID iD: 0000-0002-6701-3872

Res. Assist., National Medical Research Center for Children's Health

Russian Federation, Moscow

Tamara R. Chumbadze

National Medical Research Center for Children's Health

Email: tamararob@rambler.ru
ORCID iD: 0000-0002-8172-5710
Scopus Author ID: 57193925434

Cand. Sci. (Med.), National Medical Research Center for Children's Health

Russian Federation, Moscow

Ayina M. Lebedeva

National Medical Research Center for Children's Health; Federal Research Center of Nutrition, Biotechnology and Food Safety

Email: sm27@yandex.ru
ORCID iD: 0000-0001-6469-0766

laboratory assistant, National Medical Research Center for Children's Health, Federal Research Center of Nutrition, Biotechnology and Food Safety

Russian Federation, Moscow; Moscow

References

  1. Hidden Hunger: Malnutrition and the First 1,000 Days of Life: Causes, Consequences and Solutions. Hardback World Review of Nutrition and Dietetics. Ed. by B Koletzko, HK Biesalski, RE Black, 2016.
  2. Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020;12(4):1181. doi: 10.3390/nu12041181
  3. Фисенко А.П., Макарова С.Г. Обеспеченность микронутриентами, иммунный ответ, COVID-19. Российский педиатрический журнал. 2020;23(3):183-90 [Fisenko AP, Makarova SG. Micronutrients availability, immune response, and COVID-19. Russian Pediatric Journal. 2020;23(3):183-90 (in Russian)]. doi: 10.18821/1560-9561-2020-23-3-183-190
  4. Calder P. Conferenceon ‘Transforming the nutrition landscape in Africa’. Plenary Session 1: Feeding the immune system. Proc Nutr Soc. 2013;72:299-309.
  5. Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020;12:236. doi: 10.3390/nu12010236
  6. Wishart K. Increased micronutrient requirements during physiologically demanding situations: Review of the current evidence. Vitamin Miner. 2017;6:1-16.
  7. Carr AC, Shaw GM, Fowler AA., Natarajan R. Ascorbate-dependent vasopressor synthesis: а rationale for vitamin C administration in severe sepsis and septic shock? Crit Care. 2015;19:418.
  8. Gröber U, Holick MF. The coronavirus disease (COVID-19) – а supportive approach with selected micronutrients. Int J Vitam Nutr Res. 2022;92(1):13-34. doi: 10.1024/0300-9831/a000693
  9. Kumar P, Kumar M, Bedi O, et al. Role of vitamins and minerals as immunity boosters in COVID-19. Inflammopharmacology. 2021;29(4):1001-16. doi: 10.1007/s10787-021-00826-7
  10. Singh V. Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease? Curr Nutr Rep. 2020;9(3):202-9. doi: 10.1007/s13668-020-00330-4
  11. Pedrosa LFC, Barros ANAB, Leite-Lais L. Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review. Clin Nutr ESPEN. 2022;47:9-27. doi: 10.1016/j.clnesp.2021.11.003
  12. Torshin IY, Gromova OA, Chuchalin AG. Computational systematics of nutritional support of vaccination against viral and bacterial pathogens as prolegomena to vaccinations against COVID-19. medRxiv. 2021. doi: 10.1101/2021.09.10.21263398
  13. Khajavi A, Amirhakimi GH. The rachitic lung. Pulmonary findings in 30 infants and children with malnutritional rickets. Clin Pediatr (Phila). 1977;16(1):36-8 doi: 10.1177/000992287701600106
  14. Grant WB, Lahore H, McDonnell ShL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020;12(4):988. doi: 10.3390/nu12040988
  15. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169:384-90. doi: 10.1001/archinternmed.2008.560
  16. Laaksi I, Ruohola JP, Tuohimaa P, et al. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86:714-7.
  17. Sabetta JR, DePetrillo P, Cipriani RJ, et al. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults. PLoS ONE. 2010;5:e11088. doi: 10.1371/journal.pone.0011088
  18. Science M, Maguire JL, Russell ML, et al. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013;57:392-7. doi: 10.1093/cid/cit289
  19. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5:986-1004.
  20. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
  21. Rejnmark L, Bislev LS, Cashman KD, et al. Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data. PLoS ONE. 2017;12:e0180512.
  22. Bergman P, Lindh Å, Björkhem-Bergman L, Lindh J. Vitamin D and respiratory tract infections: A systematic review and meta-analysis of randomized controlled trials. PLoS ONE. 2013;8:e65835.
  23. Charan J, Goyal J, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. J Pharmacol Pharmacother. 2012;3:300-3.
  24. Vuichard Gysin D, Dao D, Gysin CM, et al. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE. 2016;11:e0162996. doi: 10.1371/journal.pone.0162996
  25. Dancer RC, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax. 2015;70:617-24.
  26. Han JE, Jones JL, Tangpricha V, et al. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. J Clin Transl Endocrinol. 2016;4:59-65.
  27. Xiao L, Xing C, Yang Z, et al. Vitamin D supplementation for the prevention of childhood acute respiratory infections: A systematic review of randomised controlled trials. Br J Nutr. 2015;114:1026-34.
  28. Yakoob MY, Salam RA, Khan FR, Bhutta ZA. Vitamin D supplementation for preventing infections in children under five years of age. Cochrane Database Syst Rev. 2016;11:CD008824.
  29. Das RR, Singh M, Naik SS. Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia. Cochrane Database Syst Rev. 2018;7:CD011597.
  30. Yamshchikov AV, Desai NS, Blumberg HM, et al. Vitamin D for treatment and prevention of infectious diseases: A systematic review of randomized controlled trials. Endocr Pract. 2009;15:438-49.
  31. Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021;9(5):276-92. doi: 10.1016/S2213-8587(21)00051-6
  32. Slominski AT, Slominski RM, Goepfert PA, et al. Reply to Jakovac and to Rocha et al.: Can vitamin D prevent or manage COVID-19 illness? Am J Physiol Endocrinol Metab. 2020;319(2):E455-7. doi: 10.1152/ajpendo.00348.2020
  33. Wimalawansa SJ. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019;8(2):30. doi: 10.3390/biology8020030
  34. Ahmed A, Siman-Tov G, Hall G, et al. Human Antimicrobial Peptides as Therapeutics for Viral Infections. Viruses. 2019;11(8):704. doi: 10.3390/v11080704
  35. Slominski RM, Stefan J, Athar M, et al. COVID-19 and Vitamin D: A lesson from the skin. Exp Dermatol. 2020;29(2):885-90. doi: 10.1111/exd.14170
  36. Rhodes JM, Subramanian S, Laird E, Kenny RA. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Aliment Pharmacol Ther. 2020;51(12):1434-7. doi: 10.1111/apt.15777
  37. Rao Z, Chen X, Wu J, et al. Vitamin D receptor inhibits NLRP3 activation by impeding Its BRCC3-mediated deubiquitination. Front Immunol. 2019;10:2783. doi: 10.3389/fimmu.2019.02783
  38. Xu J, Yang J, Chen J, et al. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017;16(5):7432-8. doi: 10.3892/mmr.2017.7546
  39. Kaharan S, Katkat F. Impact of serum 25(OH) vitamin D level on mortality in patients with COVID-19 in Turkey. J Nutr Health Aging. 2020;5:1-8. doi: 10.1007/s12603-020-1479-0
  40. Chiu S-K, Tsai K-W, Wu C-C, et al. Putative Role of Vitamin D for COVID-19 Vaccination. Int J Mol Sci. 2021;22:8988. doi: 10.3390/ijms22168988
  41. Maghbooli Z, Ali Sahraian M, Ebrahimi M, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS ONE. 2020;15(9):e0239799.
  42. Kaufman HW, Niles JK, Kroll MH, et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020;15(9):e0239252.
  43. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13(10):1373-80. doi: 10.1016/j.jiph.2020.06.021
  44. Panfili FM, Roversi M, D'Argenio P, et al. Possible role of vitamin D in Covid-19 infection in pediatric population. J Endocrinol Invest. 2021;44(1):27-35. doi: 10.1007/s40618-020-01327-0
  45. Bassatne A, Basbous M, Chakhtoura M, et al. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism. 2021;119:154753. doi: 10.1016/j.metabol.2021.154753
  46. Teshome A, Adane A, Girma B, Mekonnen ZA. The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis. Front Public Health. 2021;9:624559. doi: 10.3389/fpubh.2021.624559
  47. Shah K, Saxena D, Mavalankar D. Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis. QJM. 2021;114(3):175-81. doi: 10.1093/qjmed/hcab009
  48. Borsche L, Glauner B, von Mendel J. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients. 2021;13(10):3596. doi: 10.3390/nu13103596
  49. Szarpak L, Rafique Z, Gasecka A, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J. 2021;28(5):647-54. doi: 10.5603/CJ.a2021.0072
  50. Ghasemian R, Shamshirian A, Heydari K, et al. The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis. Int J Clin Pract. 2021;75(11):e14675. doi: 10.1111/ijcp.14675
  51. Petrelli F, Luciani A, Perego G, et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol. 2021;211:105883. doi: 10.1016/j.jsbmb.2021.105883
  52. Kaya MO, Pamukçu E, Yakar B. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies. Epidemiol Health. 2021;43:e2021074. doi: 10.4178/epih.e2021074
  53. Crafa A, Cannarella R, Condorelli RA, et al. Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis. EClinicalMedicine. 2021;37:100967. doi: 10.1016/j.eclinm.2021.100967
  54. Akbar MR, Wibowo A, Pranata R, Setiabudiawan B. Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis. Front Nutr. 2021;8:660420. doi: 10.3389/fnut.2021.660420
  55. Corrao S, Mallaci Bocchio R, Lo Monaco M, et al. Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc. Nutrients. 2021;13(4):1261. doi: 10.3390/nu13041261
  56. Liu N, Sun J, Wang X, et al. Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis. Int J Infect Dis. 2021;104:58-64. doi: 10.1016/j.ijid.2020.12.077
  57. Ebrahimzadeh A, Mohseni S, Narimani B, et al. Association between vitamin D status and risk of covid-19 in-hospital mortality: A systematic review and meta-analysis of observational studies. Crit Rev Food Sci Nutr. 2021;9:1-11. doi: 10.1080/10408398.2021.2012419
  58. Pereira M, Dantas Damascena A, Galvão Azevedo LM, et al. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022;62(5):1308-16. doi: 10.1080/10408398.2020.1841090
  59. Wang Z, Joshi A, Leopold K, et al. Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis. Clin Endocrinol (Oxf). 2022;96(3):281-7. doi: 10.1111/cen.14540
  60. Pal R, Banerjee M, Bhadada SK, et al. Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest. 2022;45(1):53-68. doi: 10.1007/s40618-021-01614-4
  61. Varikasuvu SR, Thangappazham B, Vykunta A, et al. COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther. 2022;3:1-7. doi: 10.1080/14787210.2022.2035217
  62. Feketea G, Vlacha V, Bocsan IC, et al. Vitamin D in Corona Virus Disease 2019 (COVID-19) Related Multisystem Inflammatory Syndrome in Children (MIS-C). Front Immunol. 2021;12:648546. doi: 10.3389/fimmu.2021.648546
  63. Национальная программа «Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции». Союз педиатров России. М.: ПедиатрЪ, 2021 [Natsional'naia programma “Nedostatochnost' vitamina D u detei i podrostkov Rossiiskoi Federatsii: sovremennye podkhody k korrektsii”. Soiuz pediatrov Rossii. Moscow: Pediatr, 2021 (in Russian)].

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2022 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».