title: Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We hypothesized that zinc down-regulates the production of atherosclerosis-related cytokines/molecules in humans.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest that zinc may have a protective effect in atherosclerosis because of its antiinflammatory and antioxidant functions.
authors.affiliation: Department of Internal Medicine, Wayne State University, Detroit, MI, USA. bbao@med.wayne.edu <bbao@med.wayne.edu>
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.forename: Ananda S
authors.initials: AS
authors.lastname: Prasad
authors.forename: Frances W J
authors.initials: FW
authors.lastname: Beck
authors.forename: James T
authors.initials: JT
authors.lastname: Fitzgerald
authors.forename: Diane
authors.initials: D
authors.lastname: Snell
authors.forename: Ginny W
authors.initials: GW
authors.lastname: Bao
authors.forename: Tapinder
authors.initials: T
authors.lastname: Singh
authors.forename: Lavoisier J
authors.initials: LJ
authors.lastname: Cardozo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004268:DNA-Binding Proteins; D019587:Dietary Supplements; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016328:NF-kappa B / Q000097:blood; D009687:Nuclear Proteins / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000097:blood; D054467:Phospholipases A2 / Q000097:blood; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D015032:Zinc / Q000008:administration & dosage* / Q000097:blood
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D008315:Malondialdehyde; D002097:C-Reactive Protein; D054467:Phospholipases A2; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D015032:Zinc