Chienhsiu Huang
Journal: Frontiers in nutrition 2026;13():1796272
PMID: 42440428
Vitamin D deficiency is extremely common in patients admitted to intensive care units (ICU), and low vitamin D levels have been linked to worse outcomes in this group. This systematic review and meta-analysis examined the impact of vitamin D supplementation on mortality among critically ill adults. The review included 21 randomised controlled trials comparing vitamin D supplementation to placebo in critically ill adults.
The overall analysis showed that vitamin D supplementation significantly reduced the risk of death in critically ill adults, a roughly 14% lower risk of dying compared to placebo. However, the benefit was not seen equally across all patients. When the results were broken down into specific subgroups, three groups showed the clearest benefit: (1) patients with very low vitamin D levels at the time of ICU admission showed a trend toward reduced mortality; (2) patients who received lower total doses of vitamin D had a significantly lower risk of death; and (3) patients who received vitamin D by injection into a muscle or directly into the bloodstream (rather than by mouth or via a feeding tube) had a 41% lower risk of death compared to controls. High-dose vitamin D did not significantly reduce mortality when a large outlier study (the VIOLET trial) was removed from the analysis. After the VIOLET study was removed, patients receiving vitamin D by mouth or feeding tube did show a significant reduction in mortality.
In conclusion, vitamin D supplementation can reduce the risk of death in critically ill adults, but the benefit depends on who receives it, how much they receive, and how it is delivered. This study could be used by healthcare professionals to understand the relationship between vitamin D supplementation and mortality in critically ill adults. It may aid a more targeted use of vitamin D in intensive care, particularly in patients who are severely deficient at admission, who receive moderate rather than very high doses, and for whom an injectable form may be preferable to oral or enteral delivery. These findings support a personalised approach to vitamin D supplementation in the ICU setting.
BACKGROUND
Randomized controlled trials have failed to demonstrate the effects of vitamin D supplementation on reducing the mortality rate in critically ill adults. A post hoc study revealed that vitamin D administration was linked to a lower 28-day mortality rate. The purpose of this meta-analysis was to investigate how vitamin D supplementation affects mortality in critically ill adults. The effects of vitamin D supplementation, such as baseline 25-hydroxyvitamin D level, vitamin D supplementation dosage, and vitamin D delivery route, were given special attention in relevant subgroups.
METHODS
The inclusion criteria for eligible studies were as follows: (1) randomized controlled trials; (2) critically ill adults; (3) the intervention group was given vitamin D or a vitamin D metabolite without any restrictions on type, dosage, duration, or route of administration; and (4). the outcome of mortality in critically ill adults.
RESULTS
Subgroup analysis revealed the following findings: (1) there was a trend toward reduced mortality in critically ill adults whose baseline 25-hydroxyvitamin D level was less than 20 ng/mL (RR = 0.87, p = 0.05, 95% CI = 0.76-1.00, I 2 = 31%). Meta-analysis revealed a relative risk of mortality of 0.87, indicating that patients with baseline 25-hydroxyvitamin D level less than 20 ng/mL receiving vitamin D supplementation had a 13% lower risk of death than controls; (2) mortality was significantly reduced in patients who received ≤300,000 IU of vitamin D compared with those who received the placebo, (RR = 0.56, p < 0.0001, 95% CI = 0.42-0.74, I 2 = 0%); (3) administration by intramuscular injection or intravenous injection significantly reduced the risk of mortality (RR = 0.59, p = 0.0006, 95% CI = 0.44-0.80, I 2 = 0%).
CONCLUSION
This meta-analysis revealed that vitamin D supplementation significantly reduced mortality in critically ill adult patients, but not all patients benefited. The benefit was observed in three subgroups of patients as below: (1) critically ill adults with baseline 25-hydroxyvitamin D levels below 20 ng/mL; (2) critically ill adults receiving ≤300,000 IU of vitamin D supplementation; (3) critically ill adults receiving the supplement via intramuscular or intravenous injection.
SYSTEMATIC REVIEW REGISTRATION
CRD420251152462.
Copyright © 2026 Huang.
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© Copyright 2026, Nutrition Evidence
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