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      Vitamin D—Effects on Skeletal and Extraskeletal Health and the Need for Supplementation

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          Abstract

          Vitamin D, the sunshine vitamin, has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, cardiovascular disease and infectious diseases. Vitamin D deficiency is now recognized as a global pandemic. The major cause for vitamin D deficiency is the lack of appreciation that sun exposure has been and continues to be the major source of vitamin D for children and adults of all ages. Vitamin D plays a crucial role in the development and maintenance of a healthy skeleton throughout life. There remains some controversy regarding what blood level of 25-hydroxyvitamin D should be attained for both bone health and reducing risk for vitamin D deficiency associated acute and chronic diseases and how much vitamin D should be supplemented.

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          Most cited references196

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          Resurrection of vitamin D deficiency and rickets.

          The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.
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            Overweight and obesity as determinants of cardiovascular risk: the Framingham experience.

            To our knowledge, no single investigation concerning the long-term effects of overweight status on the risk for hypertension, hypercholesterolemia, diabetes mellitus, and cardiovascular sequelae has been reported. Relations between categories of body mass index (BMI), cardiovascular disease risk factors, and vascular disease end points were examined prospectively in Framingham Heart Study participants aged 35 to 75 years, who were followed up to 44 years. The primary outcome was new cardiovascular disease, which included angina pectoris, myocardial infarction, coronary heart disease, or stroke. Analyses compared overweight (BMI [calculated as weight in kilograms divided by the square of height in meters], 25.0-29.9) and obese persons (BMI > or =30) to a referent group of normal-weight persons (BMI, 18.5-24.9). The age-adjusted relative risk (RR) for new hypertension was highly associated with overweight status (men: RR, 1.46; women: RR, 1.75). New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity. The age-adjusted RR (confidence interval [CI]) for cardiovascular disease was increased among those who were overweight (men: 1.21 [1.05-1.40]; women: 1.20 [1.03-1.41]) and the obese (men: 1.46 [1.20-1.77]; women: 1.64 [1.37-1.98]). High population attributable risks were related to excess weight (BMI > or =25) for the outcomes hypertension (26% men; 28% women), angina pectoris (26% men; 22% women), and coronary heart disease (23% men; 15% women). The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae. Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level.
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              Vitamin D3 and calcium to prevent hip fractures in the elderly women.

              Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 January 2013
                January 2013
                : 5
                : 1
                : 111-148
                Affiliations
                Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Nutrition, and Diabetes, Department of Medicine, Boston University Medical Center, 85 East Newton Street, M-1013, Boston, MA 02118, USA; E-Mail: mwacker@ 123456bu.edu
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: mfholick@ 123456bu.edu ; Tel.: +1-617-638-4546; Fax: +1-617-638-8882.
                Article
                nutrients-05-00111
                10.3390/nu5010111
                3571641
                23306192
                0fe7395e-ba2e-4203-b1ea-a5677889cb5b
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 15 October 2012
                : 21 November 2012
                : 13 December 2012
                Categories
                Review

                Nutrition & Dietetics
                vitamin d,25-hydroxyvitamin d,vitamin d deficiency,osteoporosis,fractures,cancer,type 2 diabetes mellitus,cardiovascular diseases,autoimmune diseases,infectious diseases

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