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      Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

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      1 , 1 , 1 , 2 , *
      Nutrients
      MDPI
      zinc, cardiovascular diseases, diabetes, epidemiology

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          Abstract

          Zinc is an essential trace element with proposed therapeutic effects in Type 2 diabetes mellitus (DM), however, the associations between zinc status and the prospective risks of cardiovascular diseases (CVD) and Type 2 DM have not been evaluated. The current systematic review aims to determine the relationships between zinc intake or plasma/serum zinc levels and prospective incidence of CVD and Type 2 DM. Fourteen papers describing prospective cohort studies were included, reporting either CVD ( n = 91,708) and/or Type 2 DM ( n = 334,387) outcomes. Primary analyses from four out of five studies reported no association between zinc intake and CVD events, when adjusted for multiple variables. Higher serum zinc level was associated with lower risk of CVD in three out of five studies; pronounced effects were observed in vulnerable populations, specifically those with Type 2 DM and patients referred to coronary angiography. The limited evidence available suggests no association between zinc status and Type 2 DM risk. Further investigations into the mechanisms of zinc’s action on the pathogenesis of chronic diseases and additional evidence from observational studies are required to establish a recommendation for dietary zinc in relation to the prevention of CVD and Type 2 DM.

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          Genomics, type 2 diabetes, and obesity.

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            Standards of medical care in diabetes.

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              Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent.

              Chronic inflammation and oxidative stress are common risk factors for atherosclerosis. Zinc is an essential micronutrient that can function as an antiinflammatory and antioxidative agent, and as such, it may have atheroprotective properties. We hypothesized that zinc down-regulates the production of atherosclerosis-related cytokines/molecules in humans. To examine these effects, we conducted a randomized, double-blinded, placebo trial of zinc supplementation in elderly subjects. We recruited 40 healthy elderly subjects (aged 56-83 y) and randomly assigned them to 2 groups. One group was given an oral dose of 45 mg zinc/d as a gluconate for 6 mo. The other group was given a placebo. Cell culture models were conducted to study the mechanism of zinc as an atheroprotective agent. After 6 mo of supplementation, the intake of zinc, compared with intake of placebo, increased the concentrations of plasma zinc and decreased the concentrations of plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, and malondialdehyde and hydroxyalkenals (MDA+HAE) in elderly subjects. Regression analysis showed that changes in concentrations of plasma zinc were inversely associated with changes in concentrations of plasma hsCRP, MCP-1, VCAM-1, and MDA+HAE after 6 mo of supplementation. In cell culture studies, we showed that zinc decreased the generation of tumor necrosis factor-alpha, IL-1beta, VCAM-1, and MDA+HAE and the activation of nuclear transcription factor kappaB and increased antiinflammatory proteins A20 and peroxisome proliferator-activated receptor-alpha in human monocytic leukemia THP-1 cells and human aortic endothelial cells compared with zinc-deficient cells. These findings suggest that zinc may have a protective effect in atherosclerosis because of its antiinflammatory and antioxidant functions.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                05 November 2016
                November 2016
                : 8
                : 11
                : 707
                Affiliations
                [1 ]Department of Human Nutrition, University of Otago, Dunedin 9054, New Zealand; anna.chu@ 123456otago.ac.nz (A.C.); meika.foster@ 123456otago.ac.nz (M.F.)
                [2 ]Discipline of Nutrition and Metabolism, School of Life and Environmental Sciences, University of Sydney, Sydney 2006, NSW, Australia
                Author notes
                [* ]Correspondence: samir.samman@ 123456otago.ac.nz ; Tel.: +64-3-479-7954
                Article
                nutrients-08-00707
                10.3390/nu8110707
                5133094
                27827959
                9b5ec432-ec01-42f4-99d1-057e085b061f
                © 2016 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
                : 31 August 2016
                : 26 October 2016
                Categories
                Article

                Nutrition & Dietetics
                zinc,cardiovascular diseases,diabetes,epidemiology
                Nutrition & Dietetics
                zinc, cardiovascular diseases, diabetes, epidemiology

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