Vitamin D Status and Potential Therapeutic Options in Critically Ill Patients: A Narrative Review of the Clinical Evidence

Abstract

Vitamin D covers roles of paramount importance in the regulation of multiple physiological pathways of the organism. The metabolism of vitamin D involves kidney–liver crosstalk and requires an adequate function of these organs, where vitamin D is progressively turned into active forms. Vitamin D deficiency has been widely reported in patients living in the community, being prevalent among the most vulnerable subjects. It has been also documented in many critically ill patients upon admission to the intensive care unit. In this context, vitamin D deficiency may represent a risk factor for the development of life-threatening clinical conditions (e.g., infection and sepsis) and worse clinical outcomes. Several researchers have investigated the impact of vitamin D supplementation showing its feasibility, safety, and effectiveness, although conflicting results have put into question its real benefit in critically ill patients. The existing studies included heterogeneous critically ill populations and used slightly different protocols of vitamin D supplementation. For these reasons, pooling up the results is difficult and not conclusive. In this narrative review, we described vitamin D physiology and the pathophysiology of vitamin D depletion with a specific focus on critically ill patients with liver dysfunction, acute kidney injury, acute respiratory failure, and sepsis.

Update on vitamin D role in severe infections and sepsis

“…Vitamin D is characterised by several pleiotropic activities beyond the calcium/phosphate balance (classical metabolic pathway), which include microbial clearance, immunomodulation of innate and adaptive responses [ 47 ], anti-tumour and cardiovascular homeostasis [ 15 ]. Over the last decades, an increasing amount of evidence has reported an association between vitamin D status alterations and inflammatory diseases [ 16 , 48 ].…”

“…A comprehensive analysis of risk factors for vitamin D deficiency was presented elsewhere [ 15 ]. Critically ill patients represent a subgroup of the population particularly vulnerable to vitamin D deficiency, which has been reported in 40–70% of patients at the admission to the ICU [ 19 ].…”

“…In this context, an increasing amount of research revealed the theoretic role of vitamin D to restore the immune system homeostasis and potentially limiting the consequences of inflammatory dysregulation [ 14 – 16 ]. Vitamin D is a secosteroid hormone, whose metabolism relies on diet, sun exposure, and liver and kidney functions, being altered by acute or chronic diseases affecting these organs [ 15 ]. Epidemiologic reports highlighted the wide diffusion of vitamin D deficiency in the community [ 17 , 18 ] and its large prevalence (about 70%) among critically ill patients admitted to the intensive care unit (ICU) [ 19 ], for whom it represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes [ 20 – 23 ].…”

Vitamin D and Wound Recovery: Illuminating the Path to Enhanced Healing in Diabetic Patients

“…This process occurs successively, resulting in the conversion of vitamin D into 1.25-dihydroxyvitamin D (1.25(OH)2D) in the kidney and 25-hydroxyvitamin D (25(OH)D) in the liver. Although 25-hydroxyvitamin D (25(OH)D) is the principal form circulating in the body and is a reliable indicator of overall vitamin D levels, 1.25-dihydroxy vitamin D (1.25(OH)2D) functions as the metabolically active form of vitamin D. 12 Through both genomic and nongenomic mechanisms, Vitamin D demonstrates its effects. In the genomic pathway, 1.25(OH)2D, serving as a ligand, attaches to the vitamin D receptor (VDR), a liganddependent nuclear receptor.…”