Vitamin D: beyond bone

Abstract

In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.

Figure 1

Genomic mechanism of vitamin D action. Mechanism of action of 1,25(OH)₂D₃ in target cells. The VDR heterodimerizes with the RXR. After interaction with the VDRE (vitamin D response element), transcription proceeds through the interaction of the VDR with coactivators and with the transcription machinery. The histone acetyltransferase (HAT) activity–containing complex (SRC/p160 and CBP), the DRIP complex, and additional coactivators not shown (including specific methyltransferases) are recruited by liganded VDR. 1,25(OH)₂D₃ is known to maintain calcium homeostasis and to affect numerous other cell types. Effects on other cell systems, including modulation of the immune system and inhibition of proliferation of cancer cells, are discussed. With permission from Christakos.

Figure 2

Body-weight gain in mice fed high-fat diets with increased levels of Ca and vitamin D. Weight matched mice were randomly assigned to the experimental high-fat (HF) diets containing 60% energy as fat (the normal control diet contained 10% energy as fat). The treatment groups on HF diet were high-calcium (Ca diet, 1.2% Ca), high-vitamin D₃ (D diet; vitamin D₃ intake 10 times higher than the recommended level of 1000 IU/kg) and high-Ca plus high-D₃ (Ca + D diet). Data are means for each group and time point; n = 7–8 per group from week 1 to week 10. The insert shows (from left to right) mice from the DIO, control, and Ca + D groups at week 10. Data are unpublished and from work in progress.

Figure 3

Lung function and plasma vitamin D levels in a group of 151 COPD patients. FEV1, forced expiratory volume in 1 s. These data are from an unpublished secondary analysis by Ruttan and colleagues.