Analytical measurement and clinical relevance of vitamin D3 C3-epimer

With an ever-increasing clinical interest in vitamin D insufficiency, numerous automated immunoassays, protein binding assays, and in-house LC-MS/MS methods are being developed for the quantification of 25-hydroxyvitamin D3 (25(OH)D3). Recently, LC-MS/MS methods have identified an epimeric form of 25(OH)D3 that has been shown to contribute significantly to 25(OH)D3 concentration, particularly in infant populations. This review describes the metabolic pathway and physiological functions of 3-epi-vitamin D, compares the capability of various 25(OH)D3 methods to detect the epimer, and highlights recent publications quantifying 3-epi-25(OH)D3 in infant, pediatric, and adult populations. In total, this review summarizes the information necessary for clinicians and laboratorians to decide whether or not to report/consider the C3-epimer in the analysis and clinical assessment of vitamin D status.

► All major vitamin D metabolites can be epimerized at the C-3 position.
► 3-epi-1α,25(OH)2D3 has reduced calcemic and non-calcemic effects versus calcitriol.
► LC-MS/MS methods often fail to differentiate epi-vitamin D from vitamin D.
► 3-epi-25(OH)D3 is present in all individuals, with higher amounts in infants.
► 3-epi-25(OH)D3 should be distinguished from 25(OH)D3 in pediatric populations.