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      Intake of 25-hydroxyvitamin D3 reduces duration and severity of upper respiratory tract infection: A randomized, double-blind, placebo-controlled, parallel group comparison study

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          Abstract

          Objectives

          This study aimed to assess the effect of 25-hydroxyvitamin D3 (25OHD) which is a hydroxide of vitamin D3 ingestion on upper respiratory tract infection (URTI).

          Design and Setting

          A prospective, randomized, double-blind, placebo-controlled study was performed from December 2015 to September 2016 in the Nihonbashi Egawa Clinic, Kei Medical Office TOC Building Medical Clinic, and Medical Corporation Kaiseikai Kita-Shinyokohama Medical Clinic, in Japan.

          Participants

          Four hundred twenty eight participants aged 45-74 years were screened by their serum 25-hydoroxyvitamin D concentration.

          Intervention

          The participants were randomized to either 25OHD (10 μg/day) or placebo capsule, daily, for 16 consecutive weeks.

          Measurements

          The primary outcome measure was the incidence proportion of URTI, and the secondary outcome measures were the physical severity score, the quality-of-life (QOL) score, the duration of URTI, and the incidence proportion of new URTI events every four weeks. Data were collected using cold diary Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) during the intervention.

          Results

          Of 428 participants screened, 252 with serum 25-hydroxyvitamn D levels were deficient or insufficient (75 nmol/L or less) were enrolled in this study. Of these, 105 placebo and 110 25OHD group subjects completed the study. For the incidence proportion of URTI, no effect of 25OHD intake was observed. On the other hand, the duration of URTI was shorter in the 25OHD (P = 0.061) compared to placebo. For the incidence proportion of URTI every four weeks, the incidence of new URTI was decreased in both groups over the time of intake. However, when the 25OHD and the placebo were compared, a decrease in the incidence proportion of URTI was seen earlier in the 25OHD. When the total physical severity score and the total QOL score during the study were assessed, they both were significantly improved in the 25OHD compared to placebo.

          Conclusions

          The intake of 25OHD may reduce the duration of URTI, the physical severity, and the QOL when suffering from URTI.

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          Most cited references28

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          Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3.

          Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species. (Blood. 2001;97:3951-3959)
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            Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited.

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              Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

              Background Low levels of 25-OH vitamin D are associated with respiratory tract infection (RTI). However, results from randomized controlled trials are inconclusive. Therefore, we performed a systematic review and meta-analysis to assess the preventive effect of vitamin D supplementation on RTI. Methods Randomized, controlled trials of vitamin D for prevention of RTI were used for the analysis. The risks of within-trial and publication bias were assessed. Odds ratios of RTI were pooled using a random-effects model. Heterogeneity was assessed using Cochran's Q and I2. Meta-regressions and subgroup analyses were used to assess the influence of various factors on trial outcome. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013003530. Findings Of 1137 citations retrieved, 11 placebo-controlled studies of 5660 patients were included in the meta-analysis. Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cohran's Q p<0.0001, I2 = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias. Interpretation Results indicate that vitamin D has a protective effect against RTI, and dosing once-daily seems most effective. Due to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution.
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                Author and article information

                Contributors
                +81-45-820-3755 , +81-45-820-3526 , shimizu_yoshiki@fancl.co.jp
                Journal
                J Nutr Health Aging
                J Nutr Health Aging
                The Journal of Nutrition, Health & Aging
                Springer Paris (Paris )
                1279-7707
                1760-4788
                21 July 2017
                21 July 2017
                2018
                : 22
                : 4
                : 491-500
                Affiliations
                [1 ]FANCL Research Institute, FANCL Corporation, 12-13 Kamishinano, Totsuka-ku, Yokohama, Kanagawa, 244-0806 Japan
                [2 ]Nihonbashi Egawa Clinic, Tokyo, Japan
                [3 ]Japan Osteoporosis Foundation, Tokyo, Japan
                Article
                952
                10.1007/s12603-017-0952-x
                5866826
                29582888
                c067e046-6b15-474a-bea9-3e1c7a614867
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

                The original article was corrected.

                History
                : 17 March 2017
                : 12 June 2017
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                © Serdi and Springer-Verlag France SAS, part of Springer Nature 2018

                25-hydroxyvitamin d3,25-hydroxycholecalciferol,calcifediol,vitamin d3,upper respiratory tract infection,common cold

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