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      Vitamin D Supplementation and Non-Alcoholic Fatty Liver Disease: Present and Future

      review-article
      , , *
      Nutrients
      MDPI
      vitamin D, NAFLD, therapy, nutraceuticals

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          Abstract

          Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease throughout the Western world and is recognized as the main cause of cryptogenic cirrhosis; however, the identification of an effective therapy for NAFLD is still a major challenge. Vitamin D deficiency is a wide-spread condition which reaches epidemic proportions in industrialized countries, mainly in relation to current lifestyle and limited dietary sources. Epidemiological studies point towards an association between hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH), independently of confounders such as obesity and insulin resistance. Furthermore, several pieces of experimental data have shown the anti-fibrotic, anti-inflammatory and insulin-sensitizing properties exerted by vitamin D on hepatic cells. However, results from trials evaluating the effects of oral vitamin D supplementation on liver damage in NAFLD and NASH are controversial. The aim of this review is to give an overview of the evidence currently available from clinical trials and to discuss possible shortcomings and new strategies to be considered in future investigations.

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          Most cited references48

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          Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

          Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.
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            A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response.

            Liver fibrosis is a reversible wound-healing response involving TGFβ1/SMAD activation of hepatic stellate cells (HSCs). It results from excessive deposition of extracellular matrix components and can lead to impairment of liver function. Here, we show that vitamin D receptor (VDR) ligands inhibit HSC activation by TGFβ1 and abrogate liver fibrosis, whereas Vdr knockout mice spontaneously develop hepatic fibrosis. Mechanistically, we show that TGFβ1 signaling causes a redistribution of genome-wide VDR-binding sites (VDR cistrome) in HSCs and facilitates VDR binding at SMAD3 profibrotic target genes via TGFβ1-dependent chromatin remodeling. In the presence of VDR ligands, VDR binding to the coregulated genes reduces SMAD3 occupancy at these sites, inhibiting fibrosis. These results reveal an intersecting VDR/SMAD genomic circuit that regulates hepatic fibrogenesis and define a role for VDR as an endocrine checkpoint to modulate the wound-healing response in liver. Furthermore, the findings suggest VDR ligands as a potential therapy for liver fibrosis. Copyright © 2013 Elsevier Inc. All rights reserved.
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              EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease.

              (2016)
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                14 September 2017
                September 2017
                : 9
                : 9
                : 1015
                Affiliations
                Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy; ilaria.barchetta@ 123456uniroma1.it (I.B.); flaviaagata.cimini@ 123456uniroma1.it (F.A.C.)
                Author notes
                [* ]Correspondence: gisella.cavallo@ 123456uniroma1.it ; Tel.: +39-064-997-4692; Fax: +39-064-997-4698
                Article
                nutrients-09-01015
                10.3390/nu9091015
                5622775
                28906453
                a9e25f77-c5ca-4041-b17e-affea8f6b666
                © 2017 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
                : 20 August 2017
                : 11 September 2017
                Categories
                Review

                Nutrition & Dietetics
                vitamin d,nafld,therapy,nutraceuticals
                Nutrition & Dietetics
                vitamin d, nafld, therapy, nutraceuticals

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