Nutrition Research Reviews

Review Article

Epidemiology of vitamin D in health and disease

Sihe Wanga1 c1

a1 Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA


Results from ecological, case–control and cohort studies have shown that vitamin D reduces the risk of bone fracture, falls, autoimmune diseases, type 2 diabetes, CVD and cancer. However, there is still epidemic vitamin D insufficiency especially among individuals living at high latitudes or with dark skin. Serum levels of 25-hydroxyvitamin D (25(OH)D) are considered the best biomarker of vitamin D nutritional status. Appropriate sunshine exposure or oral supplementation is necessary to maintain sufficient vitamin D status, which is generally accepted as serum 25(OH)D>75 nmol/l. Immunoassays, especially RIA, have been primarily used to measure serum 25(OH)D while liquid chromatography–MS (LC–MS) is considered the ‘gold standard’. There is significant disparity among the immunoassays, and all immunoassays have considerable bias compared with LC–MS methods. Because of the variations among the results from these different assays, it is necessary that assay-specific reference ranges be established or standardisation of the assays take place. The present review focuses on ecological, case–control, and cohort studies that investigated the role of vitamin D in health and disease. In addition, analytical techniques used in laboratory evaluation of vitamin D nutritional status are also critically reviewed. The majority of the literature included in the present review is selected from that searchable in PubMed up to the end of September 2008.


c1 Corresponding author: Dr Sihe Wang, fax +1 216 444 4414, email


Abbreviations: DBP, vitamin D binding protein; LC–MS, liquid chromatography–MS; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)2D, 1,25-dihydroxyvitamin D; RR, relative risk