**Abstract**

There has been a progression of investigations of the biology and pharmacology of vitamin D. Original work proved the importance of this axis on bone and skeletal homeostasis. Subsequent knowledge of basic cellular physiology led to studies of the role of vitamin D in other tissues where calcium flux is important to cellular functions. This was the beginning of exploration of vitamin D in extraskeletal health. Next came investigations into extraskeletal diseases which appeared to be more prevalent in vitamin D-deficient individuals. It was surprising that not only was there higher mortality from those diseases associated with low vitamin D levels, but also all-cause mortality was higher as well. Cellular pathophysiology of these findings was explored. Finally, studies have focused on outcomes in seriously ill patients with those diseases when hospitalized in the intensive care unit (ICU). Inverse correlations have been seen of several common ICU outcomes with levels of vitamin D at entry to the ICU, but the current effort is now in clarifying a role for routine measurement of these levels and the possible role of at least vitamin D replacement or even supplementation in the ICU patient with multiple organ pharmacologic or mechanical life support.

**Keywords:** vitamin D, extraskeletal, supplementation

### **1. Introduction**

The important role of vitamin D in calcium homeostasis which in turn is so important to the cellular functions of diverse organs naturally led to interest in studying its role in extraskeletal health [1]. Calcium ions play an important role in signal transduction pathways where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. It was natural for studies to begin to explore the impact of vitamin D on vascular tone, cardiac contractility, neuron function, and hormone release and function. As mentioned in the introductory chapter, my observations led to further studies on the role of vitamin D and calcium on vascular tone, blood pressure, and hypertensive states [2, 3]. It was not surprising when Framingham data and the National Health and Nutrition Examination Survey (NHANES 2001–2004) suggested that individuals with low levels of vitamin D were more likely to have a cardiovascular event, a higher prevalence of angina and myocardial infarction, and higher prevalence of heart failure and peripheral arterial disease [4, 5]. Reports of the consequences of vitamin D on mortality in a variety of serious illnesses and even all-cause mortality were furthering this expanded role for vitamin D [5]. The purpose of this chapter is to review the evidence for and against the impact of deficiency of vitamin D on the most seriously ill patients, those in the intensive care unit (ICU).
