**4. Contradictory recent major studies**

In the past few decades, there appeared to be a crescendo of possible multisystem benefits from vitamin D supplementation reported throughout the world medical literature. However, the crescendo has been halted by several recent negative studies. In a long-awaiting randomized, double-blinded, controlled trial, Manson studied vitamin D dosing of 2000 units of D3 daily in 25,000 adults with a mean age of 67 followed for a mean of 5.3 years [11]. He did not show difference in the occurrence of cardiovascular diseases or outcome of patients with invasive cancer or incidence of death from cancer, cardiovascular disease, or any cause which did not differ from those treated with placebo.

However, another recent prospective placebo-controlled report by Witte et al. [12] still suggests usefulness of vitamin D supplementation in patients with heart failure which likely contributes to morbidity in many if not most ICU patients. This is the vitamin D treating patients with chron*ic* he*a*r*t* failur**e** trial (VINDICATE). In this trial, there was no improvement in a 6-min walk but had beneficial effects on left ventricular structure and function in 229 patients with vitamin D levels <50 nmol/L or which is <20 ng/mL treated with 4000 units daily who had already been on contemporary optimal medical therapy for their heart failure with optimal medical therapy. Left ventricular structure was assessed by changes in stroke volume, and remodeling was assessed from improved left ventricular systolic diameter and end-diastolic diameter. One of the most recent issues of JAMA reported that high-dose vitamin D vs. standard-dose vitamin D when added to standard chemotherapy had no benefit for the outcome of median progression-free survival but did reduce the hazard ratio for progression or death. [13].

Just when the pendulum in the world's literature seems to swing in one direction, new publications are reported for the opposite conclusions about vitamin D and extraskeletal health. The pendulum right now has swung against routine screening or supplementation in the treatment or prevention of extraskeletal organ dysfunction. But then Witte and the recent studies in dialysis patients suggest that the patients with heart and kidney dysfunction do benefit not only in organ function but also overall survival.

### **5. Conclusions and recommendations**

There is some evidence that deficiency of vitamin D at the time of entry to the ICU is associated with worse outcomes. There are weak correlations between vitamin D levels and outcomes during the course of the ICU stay. Vitamin D is not recommended at this time to be routinely checked in ICU patients unless part of several large studies is ongoing worldwide such as the VINDICATE trial described above. Supplementation with vitamin D is routine in patients with renal failure and does improve outcomes in that group of patients commonly hospitalized in the ICU. There appears some benefit to supplementation of vitamin D in patients with heart failure, another group commonly hospitalized in the ICU. Studies are ongoing in this subgroup of patients. There appears no evidence for measurement or supplementation of vitamin D to patients with COPD exacerbations, asthma, and pneumonia or to assist with liberation from the ventilator. More large-scaled, multicenter, prospective, randomized, and controlled trials are needed. Dosing duration and correction of deficiency vs. creation of elevated levels by low- or highdose treatments are all variables which need systematic study.

**99**

**Author details**

Edward T. Zawada

Medicine, USA

Department of Internal Medicine, University of South Dakota, Sanford School of

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: ezawada@sio.midco.net

provided the original work is properly cited.

*Extraskeletal Effects of Vitamin D Deficiency in Intensive Care Patients*

*DOI: http://dx.doi.org/10.5772/intechopen.89317*

*Extraskeletal Effects of Vitamin D Deficiency in Intensive Care Patients DOI: http://dx.doi.org/10.5772/intechopen.89317*

*Fads and Facts about Vitamin D*

but also overall survival.

medical literature. However, the crescendo has been halted by several recent negative studies. In a long-awaiting randomized, double-blinded, controlled trial, Manson studied vitamin D dosing of 2000 units of D3 daily in 25,000 adults with a mean age of 67 followed for a mean of 5.3 years [11]. He did not show difference in the occurrence of cardiovascular diseases or outcome of patients with invasive cancer or incidence of death from cancer, cardiovascular disease, or any cause

However, another recent prospective placebo-controlled report by Witte et al. [12] still suggests usefulness of vitamin D supplementation in patients with heart failure which likely contributes to morbidity in many if not most ICU patients. This is the vitamin D treating patients with chron*ic* he*a*r*t* failur**e** trial (VINDICATE). In this trial, there was no improvement in a 6-min walk but had beneficial effects on left ventricular structure and function in 229 patients with vitamin D levels <50 nmol/L or which is <20 ng/mL treated with 4000 units daily who had already been on contemporary optimal medical therapy for their heart failure with optimal medical therapy. Left ventricular structure was assessed by changes in stroke volume, and remodeling was assessed from improved left ventricular systolic diameter and end-diastolic diameter. One of the most recent issues of JAMA reported that high-dose vitamin D vs. standard-dose vitamin D when added to standard chemotherapy had no benefit for the outcome of median progression-free survival but did

Just when the pendulum in the world's literature seems to swing in one direction, new publications are reported for the opposite conclusions about vitamin D and extraskeletal health. The pendulum right now has swung against routine screening or supplementation in the treatment or prevention of extraskeletal organ dysfunction. But then Witte and the recent studies in dialysis patients suggest that the patients with heart and kidney dysfunction do benefit not only in organ function

There is some evidence that deficiency of vitamin D at the time of entry to the ICU is associated with worse outcomes. There are weak correlations between vitamin D levels and outcomes during the course of the ICU stay. Vitamin D is not recommended at this time to be routinely checked in ICU patients unless part of several large studies is ongoing worldwide such as the VINDICATE trial described above. Supplementation with vitamin D is routine in patients with renal failure and does improve outcomes in that group of patients commonly hospitalized in the ICU. There appears some benefit to supplementation of vitamin D in patients with heart failure, another group commonly hospitalized in the ICU. Studies are ongoing in this subgroup of patients. There appears no evidence for measurement or supplementation of vitamin D to patients with COPD exacerbations, asthma, and pneumonia or to assist with liberation from the ventilator. More large-scaled, multicenter, prospective, randomized, and controlled trials are needed. Dosing duration and correction of deficiency vs. creation of elevated levels by low- or high-

dose treatments are all variables which need systematic study.

which did not differ from those treated with placebo.

reduce the hazard ratio for progression or death. [13].

**5. Conclusions and recommendations**

**98**
