{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:09:19Z","timestamp":1787695759744,"version":"build-2784847793"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Vitamin D plays an important role in immune regulation, and vitamin D deficiency has been increasingly associated with susceptibility to infection and adverse outcomes in critically ill patients. Numerous systematic reviews and meta-analyses have examined the relationship between vitamin D status, vitamin D receptor (VDR) gene polymorphisms, and sepsis; however, the evidence remains fragmented. Objective: The aim of this work was to synthesize high-level evidence on the association between vitamin D deficiency, VDR gene polymorphisms, vitamin D supplementation, and sepsis-related outcomes through a PRISMA 2020-compliant umbrella review. Methods: An umbrella review of systematic reviews and meta-analyses published between 2014 and 2025 was conducted using PubMed, PubMed Central, and journal archives. Eligible studies included adult, pediatric, and neonatal populations and evaluated sepsis incidence, mortality, disease severity, secondary outcomes, and genetic associations. Data were synthesized qualitatively due to overlap of primary studies and heterogeneity. Conceptual forest plots and funnel plots were used to summarize evidence direction and potential publication bias. Results: Nineteen systematic reviews and meta-analyses encompassing over 300 primary studies were included. Vitamin D deficiency was consistently associated with an increased risk of sepsis, higher mortality, and greater disease severity across adult and pediatric populations. Stronger associations were observed in children and neonates, including higher PRISM III scores, increased need for mechanical ventilation, and longer hospital stays. VDR gene polymorphisms were modestly but consistently associated with increased sepsis susceptibility. In contrast, vitamin D supplementation did not demonstrate a consistent reduction in sepsis risk or mortality. Conclusions: Vitamin D deficiency is a robust marker of sepsis risk, severity, and poor prognosis, whereas current evidence does not support vitamin D supplementation as an effective treatment for established sepsis.<\/jats:p>","DOI":"10.3390\/nu18050869","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitamin D Status and Sepsis Outcomes: A PRISMA-Compliant Umbrella Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6928-9728","authenticated-orcid":false,"given":"Gracia","family":"Castro-Luna","sequence":"first","affiliation":[{"name":"Department of Nursing, Physiotherapy and Medicine, University of Almeria, 04120 Almeria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henar","family":"G\u00f3mez Galera","sequence":"additional","affiliation":[{"name":"Consultorio de Rioja, UGC Bajo Andarax, 04260 Almeria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"S\u00e1nchez Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Consultorio de Rioja, UGC Bajo Andarax, 04260 Almeria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Gongora-Beltran","sequence":"additional","affiliation":[{"name":"Consultorio de Rioja, UGC Bajo Andarax, 04260 Almeria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.clnu.2019.08.010","article-title":"Association between vitamin D status and sepsis in children: A meta-analysis of observational studies","volume":"39","author":"Xiao","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J. (2023). Infections and autoimmunity\u2014The immune system and vitamin D: A systematic review. Nutrients, 15.","DOI":"10.3390\/nu15173842"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e23827","DOI":"10.1097\/MD.0000000000023827","article-title":"Vitamin D status was associated with sepsis in critically ill children: A PRISMA compliant systematic review and meta-analysis","volume":"100","author":"Yu","year":"2021","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Upala, S., Sanguankeo, A., and Permpalung, N. (2015). Significant association between vitamin D deficiency and sepsis: A systematic review and meta-analysis. BMC Anesthesiol., 15.","DOI":"10.1186\/s12871-015-0063-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e35130","DOI":"10.1097\/MD.0000000000035130","article-title":"Association of vitamin D receptor gene polymorphism with the risk of sepsis: A systematic review and meta-analysis","volume":"102","author":"Li","year":"2023","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.jiph.2024.01.011","article-title":"Association between vitamin D receptor gene variants and neonatal sepsis: A systematic review and meta-analysis","volume":"17","author":"Darnifayanti","year":"2024","journal-title":"J. Infect. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13908","DOI":"10.1111\/ijcp.13908","article-title":"Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children: A meta-analysis","volume":"75","author":"He","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e027666","DOI":"10.1136\/bmjopen-2018-027666","article-title":"Importance of vitamin D in acute and critically ill children with subgroup analyses of sepsis and respiratory tract infections: A systematic review and meta-analysis","volume":"9","author":"Cariolou","year":"2019","journal-title":"BMJ Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/fsn3.2003","article-title":"Effects of vitamin D on neonatal sepsis: A systematic review and meta-analysis","volume":"9","author":"Bitew","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108450","DOI":"10.1016\/j.rmed.2025.108450","article-title":"Impact of vitamin D supplementation on short- and long-term mortality in sepsis: A systematic review and meta-analysis","volume":"249","author":"Zhang","year":"2025","journal-title":"Respir. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1186\/s13054-014-0660-4","article-title":"Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: Systematic review and meta-analysis","volume":"18","author":"Groeneveld","year":"2014","journal-title":"Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhu, H., Li, K., Zhao, Y., Qin, J., and Song, G. (2025). Assessment of the influence of vitamin D in patients with sepsis: A systematic review and meta-analysis. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1670083"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, Y., and Ding, S. (2020). Serum 25-hydroxyvitamin D and the risk of mortality in adult patients with sepsis: A meta-analysis. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4879-1"},{"key":"ref_14","first-page":"275","article-title":"Vitamin D deficiency in the ICU: A systematic review","volume":"39","author":"Zajic","year":"2014","journal-title":"Minerva Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/s41430-018-0249-0","article-title":"Vitamin D deficiency and clinical outcomes related to septic shock in children with critical illness: A systematic review","volume":"73","author":"Wang","year":"2019","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cao, M., He, C., Gong, M., Wu, S., and He, J. (2023). The effects of vitamin D on all-cause mortality in different diseases: An evidence-map and umbrella review of 116 randomized controlled trials. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1132528"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.24171\/j.phrp.2025.0006","article-title":"The role of vitamin D and the VDR gene polymorphism in sepsis risk and mortality: A systematic review and meta-analysis","volume":"16","author":"Jaya","year":"2025","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"bvaf053","DOI":"10.1210\/jendso\/bvaf053","article-title":"Vitamin D deficiency and clinical outcomes in critically ill pediatric patients: A systematic review and meta-analysis","volume":"9","author":"Tan","year":"2025","journal-title":"J. Endocr. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.clnu.2024.03.030","article-title":"Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis","volume":"43","author":"Safabakhsh","year":"2024","journal-title":"Clin. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:59:46Z","timestamp":1773071986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":19,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18050869"],"URL":"https:\/\/doi.org\/10.3390\/nu18050869","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}