Correlation between serum 25-hydroxyvitamin D level and mortality risk in adults with sepsis: a meta-analysis_West China Medical Journal

Authors：

ZHENG Hong ^1,2 , ZHANG Penghui ³ , ZHENG Ying ⁴ , ZHOU Yitong ⁵ , ZHANG Lei ⁵ , BEI Chaoyong ⁵ , MO Zhongcheng ¹ ,  WEI Bing ²

1. Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi 541199, P. R. China;
2. Geriatrics Department, the First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P. R. China;
3. First Clinical Medical College, Gannan Medical University, Ganzhou, Jiangxi 341000, P. R. China;
4. Nutrition Department, Guangdong Provincial People’s Hospital, Guangzhou, Guangdong 510080, P. R. China;
5. Emergency Medicine Department, the First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P. R. China;

Corresponding author：

WEI Bing, Email: 231351289@qq.com

Keywords：

Serum 25-hydroxyvitamin D; mortality risk; adult; sepsis; meta-analysis

DOI：

10.7507/1002-0179.202411299

Video：

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Objective To systematically evaluate the correlation between serum 25-hydroxyvitamin D [25(OH)D] level and mortality risk in adult with sepsis. Methods We searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases for studies on the correlation between serum 25(OH)D and mortality risk in adults with sepsis. The search period was from the establishment of databases to December 2023. Meta-analysis was conducted using RevMan 5.4 software. Results A total of 9 studies were included, with a total of 2267 patients. The meta-analysis results showed that sepsis patients with low serum 25(OH)D levels (<30 ng/mL), insufficient levels (20-30 ng/mL), and deficient levels (<20 ng/mL) had a higher mortality risk compared to those with normal levels (relative risk=1.96, 1.62, 2.21, P<0.05). Subgroup analysis based on different sepsis diagnostic criteria, regions, and research types also showed that sepsis patients with lower serum 25(OH)D levels (<30 ng/mL) had a higher mortality risk compared to those with normal levels (P<0.05). Conclusions Adult sepsis patients with low serum 25(OH)D levels have a higher mortality risk than those with normal levels.

Citation： ZHENG Hong, ZHANG Penghui, ZHENG Ying, ZHOU Yitong, ZHANG Lei, BEI Chaoyong, MO Zhongcheng, WEI Bing. Correlation between serum 25-hydroxyvitamin D level and mortality risk in adults with sepsis: a meta-analysis. West China Medical Journal, 2025, 40(7): 1105-1109. doi: 10.7507/1002-0179.202411299 Copy

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2.	Shapiro NI, Wolfe RE, Moore RB, et al. Mortality in emergency department sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med, 2003, 31(3): 670-675.
3.	Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 801-810.
4.	Perner A, Cecconi M, Cronhjort M, et al. Expert statement for the management of hypovolemia in sepsis. Intensive Care Med, 2018, 44(6): 791-798.
5.	Prescott HC, Angus DC. Postsepsis morbidity. JAMA, 2018, 319(1): 91.
6.	Reinhart K, Daniels R, Kissoon N, et al. Recognizing sepsis as a global health priority - a WHO resolution. N Engl J Med, 2017, 377(5): 414-417.
7.	罗家庆. 连续性血液净化应用于 ICU 重症脓毒血症治疗临床疗效及安全性评价. 中国实用医药, 2016, 11(9): 124-125.
8.	Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med, 2009, 361(21): 2066-2078.
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11.	Christakos S, Veldurthy V, Patel N, et al. Intestinal regulation of calcium: vitamin d and bone physiology. Adv Exp Med Biol, 2017, 1033: 3-12.
12.	Allgrove J. Physiology of calcium, phosphate, magnesium and vitamin D. Endocr Dev, 2015, 28: 7-32.
13.	Christakos S, Dhawan P, Verstuyf A, et al. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev, 2016, 96(1): 365-408.
14.	Bouillon R. Vitamin D and cardiovascular disorders. Osteoporos Int, 2019, 30(11): 2167-2181.
15.	Vanherwegen AS, Gysemans C, Mathieu C. Regulation of immune function by vitamin D and its use in diseases of immunity. Endocrinol Metab Clin North Am, 2017, 46(4): 1061-1094.
16.	Jiménez-Sousa MÁ, Martínez I, Medrano LM, et al. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease. Front Immunol, 2018, 9: 458.
17.	Mangin M, Sinha R, Fincher K. Inflammation and vitamin D: the infection connection. Inflamm Res, 2014, 63(10): 803-819.
18.	de Haan K, Groeneveld AB, de Geus HR, et al. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. Crit Care, 2014, 18(6): 660.
19.	Upala S, Sanguankeo A, Permpalung N. Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis. BMC Anesthesiol, 2015, 15: 84.
20.	Zhou W, Mao S, Wu L, et al. Association between vitamin D status and sepsis. Clin Lab, 2018, 64(4): 451-460.
21.	杜晓敏, 戴科芳, 张瑞英, 等. 血清 25-羟维生素 D 水平对糖尿病合并脓毒症患者预后的影响. 中文科技期刊数据库(文摘版)医药卫生, 2021(2): 97.
22.	孙斐. 急性胰腺炎患者血清 25-羟维生素 D 水平与预后的关系探讨. 中国实用乡村医生杂志, 2022, 29(12): 59-61, 65.
23.	刘瑜, 黄方, 严妤函, 等. 血清 25-羟维生素 D 水平与急性胰腺炎预后的相关性. 医学研究生学报, 2021, 34(7): 706-711.
24.	Trongtrakul K, Feemuchang C. Prevalence and association of vitamin D deficiency and mortality in patients with severe sepsis. Int J Gen Med, 2017, 10: 415-421.
25.	Charoenngam N, Shirvani A, Reddy N, et al. Association of vitamin D status with hospital morbidity and mortality in adult hospitalized patients with COVID-19. Endocr Pract, 2021, 27(4): 271-278.
26.	贾育梅, 赵永祯, 吴彩军. 血清 25-羟维生素 D 水平对急诊脓毒症患者预后的影响//《中华急诊医学杂志》编辑部. 第十三届组稿会暨第六届急诊医学青年论坛论文集. 北京: 2014: 48-51.
27.	Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2000.
28.	Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
29.	Patsopoulos NA, Evangelou E, Ioannidis JP. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol, 2008, 37(5): 1148-1157.
30.	Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2011, 96(7): 1911-1930.
31.	陈朝彦, 罗佐杰, 胡杰妤, 等. 维生素 D 缺乏与脓毒症预后相关性研究. 中国实用内科杂志, 2014, 34(11): 1087-1090.
32.	Zajic P, Schnedl C, Valentin T, et al. Vitamin D status and overall and sepsis mortality in critically ill patients. Critical Care, 2013, 17(Suppl 2): 447.
33.	Amrein K, Zajic P, Schnedl C, et al. Vitamin D status and its association with season, hospital and sepsis mortality in critical illness. Crit Care, 2014, 18(2): R47.
34.	Takeuti FAC, Guimaraes FSF, Guimaraes PSF. Applications of vitamin D in sepsis prevention. Discov Med, 2018, 25(140): 291-297.
35.	Trochoutsou AI, Kloukina V, Samitas K, et al. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem, 2015, 15(11): 953-963.
36.	Wang TJ. Vitamin D and cardiovascular disease. Annu Rev Med, 2016, 67: 261-272.
37.	Parekh D, Thickett DR, Turner AM. Vitamin D deficiency and acute lung injury. Inflamm Allergy Drug Targets, 2013, 12(4): 253-261.
38.	Yang S, Li A, Wang J, et al. Vitamin D receptor: a novel therapeutic target for kidney diseases. Curr Med Chem, 2018, 25(27): 3256-3271.
39.	Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. the ACCP/SCCM consensus conference committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 1992, 101(6): 1644-1655.
40.	Nguyen HB, Eshete B, Lau KH, et al. Serum 1, 25-dihydroxyvitamin D: an outcome prognosticator in human sepsis. PLoS One, 2013, 8(5): e64348.

1. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 762-774.
2. Shapiro NI, Wolfe RE, Moore RB, et al. Mortality in emergency department sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med, 2003, 31(3): 670-675.
3. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 801-810.
4. Perner A, Cecconi M, Cronhjort M, et al. Expert statement for the management of hypovolemia in sepsis. Intensive Care Med, 2018, 44(6): 791-798.
5. Prescott HC, Angus DC. Postsepsis morbidity. JAMA, 2018, 319(1): 91.
6. Reinhart K, Daniels R, Kissoon N, et al. Recognizing sepsis as a global health priority - a WHO resolution. N Engl J Med, 2017, 377(5): 414-417.
7. 罗家庆. 连续性血液净化应用于 ICU 重症脓毒血症治疗临床疗效及安全性评价. 中国实用医药, 2016, 11(9): 124-125.
8. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med, 2009, 361(21): 2066-2078.
9. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med, 2006, 34(1): 15-21.
10. Kahn JM, Le T, Angus DC, et al. The epidemiology of chronic critical illness in the United States. Crit Care Med, 2015, 43(2): 282-287.
11. Christakos S, Veldurthy V, Patel N, et al. Intestinal regulation of calcium: vitamin d and bone physiology. Adv Exp Med Biol, 2017, 1033: 3-12.
12. Allgrove J. Physiology of calcium, phosphate, magnesium and vitamin D. Endocr Dev, 2015, 28: 7-32.
13. Christakos S, Dhawan P, Verstuyf A, et al. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev, 2016, 96(1): 365-408.
14. Bouillon R. Vitamin D and cardiovascular disorders. Osteoporos Int, 2019, 30(11): 2167-2181.
15. Vanherwegen AS, Gysemans C, Mathieu C. Regulation of immune function by vitamin D and its use in diseases of immunity. Endocrinol Metab Clin North Am, 2017, 46(4): 1061-1094.
16. Jiménez-Sousa MÁ, Martínez I, Medrano LM, et al. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease. Front Immunol, 2018, 9: 458.
17. Mangin M, Sinha R, Fincher K. Inflammation and vitamin D: the infection connection. Inflamm Res, 2014, 63(10): 803-819.
18. de Haan K, Groeneveld AB, de Geus HR, et al. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. Crit Care, 2014, 18(6): 660.
19. Upala S, Sanguankeo A, Permpalung N. Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis. BMC Anesthesiol, 2015, 15: 84.
20. Zhou W, Mao S, Wu L, et al. Association between vitamin D status and sepsis. Clin Lab, 2018, 64(4): 451-460.
21. 杜晓敏, 戴科芳, 张瑞英, 等. 血清 25-羟维生素 D 水平对糖尿病合并脓毒症患者预后的影响. 中文科技期刊数据库(文摘版)医药卫生, 2021(2): 97.
22. 孙斐. 急性胰腺炎患者血清 25-羟维生素 D 水平与预后的关系探讨. 中国实用乡村医生杂志, 2022, 29(12): 59-61, 65.
23. 刘瑜, 黄方, 严妤函, 等. 血清 25-羟维生素 D 水平与急性胰腺炎预后的相关性. 医学研究生学报, 2021, 34(7): 706-711.
24. Trongtrakul K, Feemuchang C. Prevalence and association of vitamin D deficiency and mortality in patients with severe sepsis. Int J Gen Med, 2017, 10: 415-421.
25. Charoenngam N, Shirvani A, Reddy N, et al. Association of vitamin D status with hospital morbidity and mortality in adult hospitalized patients with COVID-19. Endocr Pract, 2021, 27(4): 271-278.
26. 贾育梅, 赵永祯, 吴彩军. 血清 25-羟维生素 D 水平对急诊脓毒症患者预后的影响//《中华急诊医学杂志》编辑部. 第十三届组稿会暨第六届急诊医学青年论坛论文集. 北京: 2014: 48-51.
27. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2000.
28. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
29. Patsopoulos NA, Evangelou E, Ioannidis JP. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol, 2008, 37(5): 1148-1157.
30. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2011, 96(7): 1911-1930.
31. 陈朝彦, 罗佐杰, 胡杰妤, 等. 维生素 D 缺乏与脓毒症预后相关性研究. 中国实用内科杂志, 2014, 34(11): 1087-1090.
32. Zajic P, Schnedl C, Valentin T, et al. Vitamin D status and overall and sepsis mortality in critically ill patients. Critical Care, 2013, 17(Suppl 2): 447.
33. Amrein K, Zajic P, Schnedl C, et al. Vitamin D status and its association with season, hospital and sepsis mortality in critical illness. Crit Care, 2014, 18(2): R47.
34. Takeuti FAC, Guimaraes FSF, Guimaraes PSF. Applications of vitamin D in sepsis prevention. Discov Med, 2018, 25(140): 291-297.
35. Trochoutsou AI, Kloukina V, Samitas K, et al. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem, 2015, 15(11): 953-963.
36. Wang TJ. Vitamin D and cardiovascular disease. Annu Rev Med, 2016, 67: 261-272.
37. Parekh D, Thickett DR, Turner AM. Vitamin D deficiency and acute lung injury. Inflamm Allergy Drug Targets, 2013, 12(4): 253-261.
38. Yang S, Li A, Wang J, et al. Vitamin D receptor: a novel therapeutic target for kidney diseases. Curr Med Chem, 2018, 25(27): 3256-3271.
39. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. the ACCP/SCCM consensus conference committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 1992, 101(6): 1644-1655.
40. Nguyen HB, Eshete B, Lau KH, et al. Serum 1, 25-dihydroxyvitamin D: an outcome prognosticator in human sepsis. PLoS One, 2013, 8(5): e64348.

West China Medical Journal

Correlation between serum 25-hydroxyvitamin D level and mortality risk in adults with sepsis: a meta-analysis

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