Abstract ED02-02: Vitamin D status as a measure of chronic disease risk

A great deal of attention has recently been focused on vitamin D and its metabolites, 25-hydroxycalciferol [25(OH)D] and 1, 25-dihydroxycalciferol [1, 25(OH)₂D], and many chronic disease outcomes. Vitamin D insufficiency has been demonstrated to be common in all regions of the United States, with those having highly pigmented skin at particular risk. This is an important public health challenge as vitamin D insufficiency has been implicated in a wide range of chronic diseases for which disparities have repeatedly been observed, including cancer, cardiovascular disease, and diabetes. Vitamin D is part of a complicated pathway for a multitude of reasons, and studies of vitamin D need to account for several factors. The most abundant circulating vitamin D metabolite is 25(OH)D, an indicator of both vitamin D intake and endogenous synthesis, which can be used as a marker for vitamin D status. Concentrations of 25(OH)D have been established as being lower in African Americans and Hispanics as compared to whites in all regions of the United States. This has been hypothesized to occur due to the sequestration of UV light in skin pigment, thus inhibiting the synthesis of 25(OH)D. In the kidney, 25(OH)D is hydroxylated at the 1 carbon position to form 1, 25(OH)₂D. This potent hormonal metabolite of vitamin D can exert transcriptional effects on target genes after binding with the nuclear vitamin D receptor (VDR), a member of the steroid and nuclear receptor superfamily. In epidemiological studies, low circulating concentrations of the biomarker for vitamin D status, 25(OH)D, have been associated with higher risk for several chronic diseases; however, this vitamin D metabolite is also related to several other characteristics which themselves are related to disease risk. For example, lower circulating 25(OH)D concentrations are associated with higher body mass index, less physical activity, lower dietary and supplemental intake of vitamin D, African American or Hispanic race or ethnicity, and genetic variation in key vitamin D metabolic pathway enzymes. When studying associations between 25(OH)D and disease it may be difficult to separate the contribution of each of these characteristics from 25(OH)D itself. In addition, there is a paradox in vitamin D research in that epidemiological studies primarily employ 25(OH)D as a biomarker for vitamin D status, as is appropriate; while the majority of laboratory experiments are conducted with the hormonal form of vitamin D, 1, 25(OH)₂D, which may have biological effects on up to 1000 genes. Unlike its precursor 25(OH)D, circulating 1, 25(OH)₂D is under tight homeostatic control and does not usually exhibit marked variation in humans except in the case

of extreme vitamin D deficiency or in some genetic disorders. Therefore, the mechanism through which higher 25(OH)D levels can manifest as protection against chronic disease is an intensely studied area. Several randomized clinical trials are currently underway to assess the effect of vitamin D supplementation on outcomes such as cancer and cardiovascular disease, though the best strategy for improving vitamin D status is still being debated, and the optimal concentration of serum 25(OH)D remains somewhat controversial. Further, due to the lower capacity for endogenous vitamin D synthesis depending on a number of potential factors including race/ethnicity, latitude of residence, and genetic background, overall strategies and recommendations for vitamin D supplementation may vary for different populations. This presentation will therefore cover several aspects of the use of vitamin D status as a measure of chronic disease risk and its use in investigations of disparate study populations. It will include a discussion of some of the common epidemiological risk factors across several disease pathways and how vitamin D might act as a marker for these traits and as a marker of overall health risks. The challenges with the interpretation of epidemiological data will also be addressed, as will the results of a pilot trial of over-the-counter supplementation with vitamin D on blood levels of 25(OH)D and its implications for public health recommendations that effectively address disparities in several chronic diseases.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):ED02-02.