Vitamin D nutritional policy needs a vision for the future. Exp. Biol. Med. (Maywood)

Department of Biochemistry and Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Experimental Biology and Medicine (Impact Factor: 2.17). 09/2010; 235(9):1034-45. DOI: 10.1258/ebm.2010.010014
Source: PubMed


Historically vitamin D is known to be essential for normal bone growth and quality, and thus appropriate dietary vitamin D supplementation can eliminate vitamin D deficiency childhood rickets and adult osteomalacia. In spite of many government and medical associations' worldwide guidelines for the reference daily intake (RDI) of vitamin D, scientists and nutritionists from many countries agree that at present about half of elderly North Americans and Western Europeans and probably also of the rest of the world are not receiving enough vitamin D to maintain healthy bone. In addition, over the past decade there has been a dramatic increase in our understanding of the many biological actions that result from vitamin D acting through its daughter steroid hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] in collaboration with its cognate vitamin D receptor (VDR). Consequently, evidence has accumulated that beside intestine and bone, there are five additional physiological systems where the VDR with 1alpha,25(OH)(2)D generates biological responses. These include the immune system (both the innate and adaptive), pancreas and metabolic homeostasis, heart-cardiovascular, muscle and brain systems as well as the control of the cell cycle, and thus of the disease process of cancer. Acting through the VDR, 1alpha,25(OH)(2)D(3) can produce a wide array of favorable biological effects that collectively are projected to contribute to the improvement of human health. Responsible medicine demands that worldwide vitamin D nutritional guidelines reflect current scientific knowledge about vitamin D's spectrum of activities. Thus, worldwide vitamin D nutritional policy is now at a crossroads. This paper presents several proposed policy changes with regard to the amount of vitamin D daily intake that if implemented will maximize vitamin D's contribution to reducing the frequency of many diseases, which would then increase the quality and longevity of life and significantly reduce the cost of medical care worldwide.

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Available from: Anthony W Norman
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    • "The VDR is a nuclear receptor mediating 1,25-D3 signaling. It is expressed by at least 38 cell types in the human body (Norman and Bouillon, 2010). In the absence of its ligand 1,25-D3, VDR is mainly found in the cytoplasm (Nagpal et al., 2005). "
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    ABSTRACT: Epigenetic mechanisms play a crucial role in regulating gene expression. The main mechanisms involve methylation of DNA and covalent modifications of histones by methylation, acetylation, phosphorylation, or ubiquitination. The complex interplay of different epigenetic mechanisms is mediated by enzymes acting in the nucleus. Modifications in DNA methylation are performed mainly by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, while a plethora of enzymes, such as histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs) regulate covalent histone modifications. In many diseases, such as cancer, the epigenetic regulatory system is often disturbed. Vitamin D interacts with the epigenome on multiple levels. Firstly, critical genes in the vitamin D signaling system, such as those coding for vitamin D receptor (VDR) and the enzymes 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) have large CpG islands in their promoter regions and therefore can be silenced by DNA methylation. Secondly, VDR protein physically interacts with coactivator and corepressor proteins, which in turn are in contact with chromatin modifiers, such as HATs, HDACs, HMTs, and with chromatin remodelers. Thirdly, a number of genes encoding for chromatin modifiers and remodelers, such as HDMs of the Jumonji C (JmjC)-domain containing proteins and lysine-specific demethylase (LSD) families are primary targets of VDR and its ligands. Finally, there is evidence that certain VDR ligands have DNA demethylating effects. In this review we will discuss regulation of the vitamin D system by epigenetic modifications and how vitamin D contributes to the maintenance of the epigenome, and evaluate its impact in health and disease.
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    • "The efficiency of vitamin D synthesis in the body depends on factors such as pigmentation of the skin, the geographic latitude where an individual lives, the amount of sunlight present, sunlight exposure, and the age of the individual [109]. The primary cause of vitamin D deficiency has been suggested to be geographical conditions, seasons, cultural features, and nutrition. "
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    • "In addition to high educational level, enriched social network and active engagement in mental, social and physical activities (Qiu et al., 2009; Coley et al., 2008), epidemiological data suggest that some nutrients may also have a protective role (Gillette Guyonnet et al., 2007). Some evidence exists that macronutrients have influence on cognitive decline, such as glycemic load, which has an impact on insulin resistance and glucose handling in brain (Hsu et al., 2011), omega-3 fatty acids that would promote neuronal plasticity and improve learning capacities and cognitive functions (Sinclair et al., 2007) and Vitamin D3 that could in case of deficiency to alters adult behavior and brain function by increasing risk of obesity and cardiovascular diseases, impairing insulin secretion and increasing insulin resistance (Norman and Bouillon, 2010). Other micronutrients (vitamins B6, B12 and folate) play a protective role against cognitive decline (Ortega et al., 1997; Murakami et al., 2010; Lee et al., 2009). "
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