Alterations of vitamin D metabolism and requirements in clinical conditions with impaired gastro-intestinal and renal function and in critical illness.
The Journal of steroid biochemistry and molecular biology 2025
DOI : 10.1016/j.jsbmb.2025.106909
PubMed ID : 41344558
PMCID :
URL : https://linkinghub.elsevier.com/retrieve/pii/S0960076025002377
Abstract
Many studies show inverse relationships between the prevalence and severity of clinical conditions and vitamin D status. This may be partly due to reverse causality because of altered organ function, influencing vitamin D metabolism and bioavailability. Here we provide a narrative review of the impact of clinical conditions on vitamin D metabolism reviewing intestinal absorption, vitamin D binding protein (DBP) function and renal metabolism. Dietary vitamin D absorption is dependent on its incorporation in fat droplets in chylomicrons. Gastrointestinal inflammation and impaired fat digestion and absorption lead to decreased vitamin D bioavailability, whereas the hydroxylated form, 25-hydroxyvitamin D (25(OH)D), is less dependent on these factors. Vitamin D metabolites circulate predominantly bound to DBP which facilitates transportation, cellular uptake and regulates hydroxylation into 1,25-dihydroxy vitamin D (1,25(OH)D) and catabolic products. DBP also plays a key role in scavenging of actin upon cellular damage and inflammation and activation of the innate immune response. A decline in DBP due to actin-scavenging leads to alterations in vitamin D binding, bioavailability and metabolism. The kidney has several roles in vitamin D metabolism: internalisation and hydroxylation of 25(OH)D into 1,25(OH)D and catabolites and reabsorption of DBP-vitamin D metabolite complex from the glomerular filtrate. Renal damage leads to impairment of these functions. Specific guidance on vitamin D requirements accounting for alterations in vitamin D physiology with many clinical conditions is lacking, except for chronic kidney disease. Understanding how clinical conditions alter organ function and vitamin D metabolism is essential for management of vitamin D status and function.