The nonskeletal effects of vitamin D: An Endocrine Society scientific statement

Tufts University School of Medicine, Boston, MA 02111, USA.
Endocrine reviews (Impact Factor: 19.36). 05/2012; 33(3):456-92. DOI: 10.1210/er.2012-1000
Source: PubMed

ABSTRACT Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders.

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    • "Further emerging vitamin D health relationships include physiological parameters like improved immune response (Baeke et al., 2010; Schwalfenberg, 2011; Hewison, 2012; White, 2012), improved respiratory health(Berry et al., 2011; Charan et al., 2012; Choi et al., 2013; Hirani, 2013) possibly also relate to reduced tuberculosis incidence (Nnoaham and Clarke, 2008; Martineau et al., 2011; Mitchell et al., 2011; Coussens et al., 2012; Salahuddin et al., 2013; Huaman et al., 2014); and reduced risk to develop autoimmune diseases like multiple sclerosis (Solomon and Whitham, 2010; Cantorna, 2012; Dobson et al., 2013) or type 1 diabetes (Hypponen et al., 2001; Holick, 2003; Ramos-Lopez et al., 2006; Baeke et al., 2010; De Boer et al., 2012; Dong et al., 2013; Van Belle et al., 2013). In chronic, non-communicable diseases, vitamin D deficiency is being discussed to possibly ameliorate the incidence of some neoplastic diseases like colorectal, lung, prostate, and breast cancers (Ng et al., 2008; Rosen et al., 2012; Welsh, 2012; Cheng et al., 2013); cardiovascular diseases (CVDs) including hypertension, myocardial infarction, stroke (Forman et al., 2007; Giovannucci et al., 2008; Gardner et al., 2011; Bischoff-Ferrari et al., 2012; Tamez and Thadhani, 2012; Karakas et al., 2013; Pilz et al., 2013a; Schroten et al., 2013); life-style diseases like obesity and type 2 diabetes (Pittas et al., 2007; González-Molero et al., 2012; Khan et al., 2013; Pilz et al., 2013b; Schottker et al., 2013; Tsur et al., 2013; Van Belle et al., 2013; Bouillon et al., 2014); diseases related to the decline in sight function including age-related macular degeneration (Parekh et al., 2007; Millen et al., 2011; Lee et al., 2012); and neurological disorders including Alzheimer and Parkinson disease (Buell and Dawson-Hughes, 2008; Annweiler et al., 2012; Eyles et al., 2013; Zhao et al., 2013). One may wonder about the width of possible implications being looked at, but considering the more than 1000 genes which vitamin D is regulating through the VDR (Carlberg and Campbell, 2013), this may actually not be a surprise. "
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    ABSTRACT: Vitamin D is a micronutrient that is needed for optimal health throughout the whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human skin upon exposure to the UV light of the sun, or it is obtained from the diet. If the photoconversion in the skin due to reduced sun exposure (e.g., in wintertime) is insufficient, intake of adequate vitamin D from the diet is essential to health. Severe vitamin D deficiency can lead to a multitude of avoidable illnesses; among them are well-known bone diseases like osteoporosis, a number of autoimmune diseases, many different cancers, and some cardiovascular diseases like hypertension are being discussed. Vitamin D is found naturally in only very few foods. Foods containing vitamin D include some fatty fish, fish liver oils, and eggs from hens that have been fed vitamin D and some fortified foods in countries with respective regulations. Based on geographic location or food availability adequate vitamin D intake might not be sufficient on a global scale. The International Osteoporosis Foundation (IOF) has collected the 25-hydroxy-vitamin D plasma levels in populations of different countries using published data and developed a global vitamin D map. This map illustrates the parts of the world, where vitamin D did not reach adequate 25-hydroxyvitamin D plasma levels: 6.7% of the papers report 25-hydroxyvitamin D plasma levels below 25 nmol/L, which indicates vitamin D deficiency, 37.3% are below 50 nmol/Land only 11.9% found 25-hydroxyvitamin D plasma levels above 75 nmol/L target as suggested by vitamin D experts. The vitamin D map is adding further evidence to the vitamin D insufficiency pandemic debate, which is also an issue in the developed world. Besides malnutrition, a condition where the diet does not match to provide the adequate levels of nutrients including micronutrients for growth and maintenance, we obviously have a situation where enough nutrients were consumed, but lacked to reach sufficient vitamin D micronutrient levels. The latter situation is known as hidden hunger. The inadequate vitamin D status impacts on health care costs, which in turn could result in significant savings, if corrected. Since little is known about the effects on the molecular level that accompany the pandemic like epigenetic imprinting, the insufficiency-triggered gene regulations or the genetic background influence on the body to maintain metabolic resilience, future research will be needed. The nutrition community is highly interested in the molecular mechanism that underlies the vitamin D insufficiency caused effect. In recent years, novel large scale technologies have become available that allow the simultaneous acquisition of transcriptome, epigenome, proteome, or metabolome data in cells of organs. These important methods are now used for nutritional approaches summarized in emerging scientific fields of nutrigenomics, nutrigenetics, or nutriepigenetics. It is believed that with the help of these novel concepts further understanding can be generated to develop future sustainable nutrition solutions to safeguard nutrition security.
    Frontiers in Physiology 07/2014; 5:248. DOI:10.3389/fphys.2014.00248 · 3.50 Impact Factor
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    • "Vitamin D is related to bone metabolism, being a secosteroid synthesized in the skin by the action of ultraviolet irradiation from the sun. The extraskeletal effects of vitamin D are currently the focus of research efforts [Rosen et al. 2012]. The relationship of vitamin D with the immune system is being intensely discussed. "
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    ABSTRACT: The extraskeletal effects of vitamin D have attracted considerable interest. Vitamin D deficiency appears to be related to the development of diabetes mellitus type 2 and the metabolic syndrome. Vitamin D may affect glucose homeostasis, vitamin D levels having been found to be inversely related to glycosylated hemoglobin levels in gestational diabetes mellitus. In addition, vitamin D appears to protect from the development of gestational diabetes mellitus. The aim was to study levels of 25-hydroxy vitamin D3 [25(OH)D3] and the relationship between 25(OH)D3 levels and glycemic control in patients with diabetes mellitus type 2. Glycosylated hemoglobin (HbA1c) and 25(OH)D3 levels were measured in a group of 120 diabetes mellitus type 2 patients. The same measurements were performed in a group of 120 control subjects of the same age and sex. 25(OH)D3 was measured by radioimmunoassay and glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography. 25(OH)D3 levels were lower in the diabetes mellitus type 2 patients than in the control group, being 19.26 ± 0.95 ng/ml and 25.49 ± 1.02 ng/ml, in the patient and control groups, respectively (p < 0.001, Student's t-test). 25(OH)D3 levels were found to be inversely associated with HbA1c levels in the diabetic patients (p = 0.008, r (2) = 0.058, linear regression). 25(OH)D3 levels were found to be inversely associated with HbA1c when the patient and control groups were analysed together (p < 0.001, r (2) = 0.086). Vitamin D levels appeared to be lower in diabetes mellitus type 2 patients than in the control group, vitamin D levels being related to glycemic control in diabetes mellitus type 2. These findings may have therapeutic implications as cautious vitamin D supplementation may improve glycemic control in diabetes mellitus type 2.
    Therapeutic advances in endocrinology and metabolism 08/2013; 4(4):122-8. DOI:10.1177/2042018813501189
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    • "Vitamin D is a pleiotropic hormone that affects classical and nonclassical tissues. Its primary sites of action are still considered to be the intestine, bone, and kidneys [10]. A "
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    ABSTRACT: Introduction. Acute kidney injury (AKI) pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im) daily; Genta group, gentamicin 100 mg/kg/day (im); Genta + vitamin D, gentamicin 100 mg/kg/day (im) in addition to 1 α , 25 (OH)2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.
    International Journal of Endocrinology 06/2013; 2013:313528. DOI:10.1155/2013/313528 · 1.52 Impact Factor
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