To D or not to D? Social deprivation as a confounder of the association between 25-hydroxyvitamin D and atherosclerosis

Abstract

Vitamin D is traditionally considered as one of the key player in bone metabolism because of its regulatory action on calcium absorption and extracellular matrix mineralization [ 1 Holick M.F. Vitamin D: a d-lightful solution for health. J Investig Med. 2011; 59: 872-880 PubMed Google Scholar , 2 Pettifor J.M. Prentice A. The role of vitamin D in paediatric bone health. Best Pract Res Clin Endocrinol Metab. 2011; 25: 573-584 Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar ]. Besides its primary function for maintaining serum calcium levels within a normal range so as to support cellular activities and neuromuscular function, vitamin D is also involved in the pathogenesis of several inflammatory diseases via its non-calcemic, non-skeletal-related functions [ [3] LoPiccolo M.C. Lim H.W. Vitamin D in health and disease. Photodermatol Photoimmunol Photomed. 2010; 26: 224-229 Crossref PubMed Scopus (39) Google Scholar ]. Two distinct forms of vitamin D have been described: vitamin D2 (ergocalciferol) which is found in plants, and vitamin D3 (cholecalciferol) which is synthesized in the skin upon exposure to sunlight [ [4] van Schoor N.M. Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011; 25: 671-680 Abstract Full Text Full Text PDF PubMed Scopus (434) Google Scholar ]. In human skin, 7-dehydrocholesterol (provitamin D3), which is produced in relatively large quantities, absorbs ultraviolet-B(UVB) radiation (290–315 nm wavelengths) upon exposure to sunlight [ 1 Holick M.F. Vitamin D: a d-lightful solution for health. J Investig Med. 2011; 59: 872-880 PubMed Google Scholar , 5 McGreevy C. Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011; 155: 820-826 Crossref PubMed Scopus (133) Google Scholar ]. Absorption of UVB rays causes transformation of 7-dehydrocholesterol to previtamin D3. Vitamin D3 is then transported mainly by the vitamin D binding protein (DBP) to the liver [ [1] Holick M.F. Vitamin D: a d-lightful solution for health. J Investig Med. 2011; 59: 872-880 PubMed Google Scholar ]. Upon reaching the hepatic parenchyma, vitamin D is hydroxylated by a 25- hydroxylase enzyme, forming 25-hydroxyvitamin D [25(OH)D], which represents the major circulating form of vitamin D. From the liver, 25(OH)D is released back into the bloodstream where it is transported bound to DBP to the kidney and other tissues where it is further hydroxylated by a 1-α-hydroxylase enzyme, producing the active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], which mainly acts in the cells by influencing gene transcription [ 1 Holick M.F. Vitamin D: a d-lightful solution for health. J Investig Med. 2011; 59: 872-880 PubMed Google Scholar , 5 McGreevy C. Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011; 155: 820-826 Crossref PubMed Scopus (133) Google Scholar ]. 25-Hydroxyvitamin D is lower in deprived groups, but is not associated with carotid intima media thickness or plaques: Results from pSoBidAtherosclerosisVol. 223Issue 2PreviewThe association of the circulating serum vitamin D metabolite 25-hydroxyvitamin D (25OHD) with atherosclerotic burden is unclear, with previous studies reporting disparate results. Full-Text PDF