Influence of Vitamin D on ICU Length of Stay

Greg Martin, MD


April 20, 2015

Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency: The VITdAL Randomized Clinical Trial

Amrein K, Schnedl C, Holl A, et al
JAMA. 2014;312:1520-1530

Study Summary

Vitamin D insufficiency and deficiency are common, particularly among critically ill patients.[1] It remains controversial whether vitamin D deficiency contributes to adverse outcomes in this population.[2,3,4] There are biological reasons why it might: Aside from its effects on bone, muscle, and skin health, it also modulates a variety of immune system functions including the expression of antimicrobial peptides.

The authors sought to determine if high-dose vitamin D replacement (540,000 IU vitamin D3 once and 90,000 IU monthly thereafter) would reduce hospital length of stay as well as other clinically relevant outcomes. The study analyzed 475 patients, and the median length of hospital stay was not different between groups (20.1 days vs 19.3 days; P = .98).

Hospital mortality and 6-month mortality were also not different (hospital mortality: 28.3% vs 35.3%; P = .18 and 6-month mortality: 35.0% vs 42.9%; P = .09). In the severe vitamin D deficiency subgroup (n = 200 with vitamin D levels ≤ 12 ng/mL), length of hospital stay was not different between the 2 study groups (20.1 days vs 19.0 days); hospital mortality was significantly lower (28.6% vs 46.1%, P for interaction = .04) but not different for 6-month mortality (34.7% vs 50.0%, P for interaction = .12).

The authors concluded that among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 does not reduce hospital length of stay, hospital mortality, or 6-month mortality, although lower hospital mortality was observed in the severe vitamin D deficiency subgroup.


Vitamin D continues to grow in popularity as a supplement and as an area of medical investigation. However, as noted above, the literature remains mixed on the subject of how and if vitamin D influences outcomes in critically ill patients.

This study is among the first to test high-dose vitamin D replacement in critically ill patients and importantly demonstrated that these very high doses (540,000 IU) were tolerated without major safety concerns.

However, the study failed to demonstrate clear efficacy. The subgroup of patients with severe deficiency was a prespecified subgroup of interest, and biologically it makes sense to consider the greatest benefits to accrue in the patients with the greater deficiency.

We must still decide whether this is a real benefit or a statistical anomaly from a subgroup analysis. It is possible that vitamin D reduced rates of nosocomial infections, a biologically plausible effect based upon what we know about vitamin D effects, and that may have improved mortality without changing length of hospital stay. Further study is necessary both to examine the mechanisms attributable to any benefits with vitamin D therapy in critically ill patients and to demonstrate if a true clinical benefit may exist.



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