Vitamin D Status: Measurement, Interpretation, and Clinical Application

Abstract

Vitamin D, the sunshine vitamin, is now recognized not only for its importance of bone health in children and adults, but also for other health benefits including reducing risk of chronic diseases including autoimmune diseases, common cancer and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires two successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH) 2 D]. With the identification of 25(OH)D and 1,25(OH) 2 D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH) 2 D provides no information about vitamin D status and is often normal or even elevated due to secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of < 20 ng/ml is considered to be vitamin D deficiency whereas a 25(OH)D of 21-29 ng/ml is considered to be insufficient. The goal should be to maintain both children and adults at a level > 30 ng/ml to take full advantage of all the health benefits that vitamin D provides. Historical PerspectiveThe association of sunlight and vitamin D for bone health began with the industrialization of northern Europe. The lack of adequate sun exposure resulted in an epidemic of children with severe growth retardation and bony deformities that was commonly known as rickets. 1 In 1919, Huldschinsky et al 2 reported that exposure to ultraviolet radiation cured rickets. This was followed by Hess and Unger in 1921 3 who observed that exposure to sunlight cured rickets.In the 1930's, it was appreciated that ultraviolet irradiation of yeast extract was effective in producing an antirachitic substance known as vitamin D. This vitamin D was structurally identified and called vitamin D 2 . Vitamin D 3 was identified by the irradiation of 7-dehydocholesterol. Because vitamin D 2 was inexpensive to produce, vitamin D 2 was used widely for the fortification of foods including milk and bread in the United States and Europe. When 7-dehydrocholesterol was easily extracted from lanolin from sheep's wool, vitamin D 3 was inexpensively made and was used in food fortification and for supplements.In the early 1950's, there was an outbreak of hypercalcemia thought due to the over fortification of milk with vitamin D, and as a result, most European countries forbid the fortification of milk Corresponding author: Michael F. Holick, Boston University School of Medicine, 715 Albany Street, M-1013, Tel: 617-638-4545, Fax: 617-638-8882, E-mail: mfholick@bu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its fin...

Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia

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Determinants of vitamin D status in young children: results from the Belgian arm of the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) Study

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Anaemia, lead poisoning and vitamin D deficiency in low-income children: do current screening recommendations match the burden of illness?

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