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      Skeletal Muscle and the Maintenance of Vitamin D Status

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          Abstract

          Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter.

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          Most cited references59

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          Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

          The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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            Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.

            We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.
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              An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

              Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                26 October 2020
                November 2020
                : 12
                : 11
                : 3270
                Affiliations
                [1 ]Department of Physiology, School of Medical Sciences and Bosch Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; mark.rybchyn@ 123456sydney.edu.au (M.S.R.); Myriam.abboud@ 123456zu.ac.ae (M.A.); dpug9928@ 123456alumni.sydney.edu.au (D.A.P.); clare.gordon-thomson@ 123456sydney.edu.au (C.G.-T.); tara.speranza@ 123456sydney.edu.au (T.C.B.-S.); rebecca.mason@ 123456sydney.edu.au (R.S.M.)
                [2 ]Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Dubai, Abu Dhabi P.O. Box 144534, UAE
                [3 ]School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
                [4 ]Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia
                Author notes
                [* ]Correspondence: david.fraser@ 123456sydney.edu.au ; Tel.: +61-2-93512139
                Author information
                https://orcid.org/0000-0002-4336-6227
                https://orcid.org/0000-0001-8025-7823
                https://orcid.org/0000-0003-1534-9697
                https://orcid.org/0000-0003-2560-0750
                Article
                nutrients-12-03270
                10.3390/nu12113270
                7692087
                33114526
                f7e36b83-b4e0-48d6-b780-af45ce18b083
                © 2020 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 (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2020
                : 21 October 2020
                Categories
                Review

                Nutrition & Dietetics
                vitamin d,muscle,parathyroid hormone,vitamin d-binding protein
                Nutrition & Dietetics
                vitamin d, muscle, parathyroid hormone, vitamin d-binding protein

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