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

• Published in: The American journal of clinical nutrition Vol. 91; no. 6; pp. 1634 - 1641
• Main Authors: Bao, Bin, Prasad, Ananda S, Beck, Frances WJ, Fitzgerald, James T, Snell, Diane, Bao, Ginny W, Singh, Tapinder, Cardozo, Lavoisier J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.06.2010; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: administration & dosage; Aged; Aged, 80 and over; anti-inflammatory activity; antioxidant activity; atheroprotective activity; atherosclerosis; Atherosclerosis - blood; Atherosclerosis - immunology; Atherosclerosis - prevention & control; Biological and medical sciences; blood; C-reactive protein; C-Reactive Protein - metabolism; Chemokine CCL2; Chemokine CCL2 - blood; Cytokines; Cytokines - blood; dietary mineral supplements; dietary minerals; Dietary Supplements; DNA-Binding Proteins; Double-Blind Method; drug effects; elderly; elderly nutrition; Endothelial Cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; HL-60 Cells; Humans; immunology; inflammation; Interleukin-6; Interleukin-6 - blood; Intracellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins - blood; lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Malondialdehyde; Malondialdehyde - blood; metabolism; Middle Aged; NF-kappa B; NF-kappa B - blood; Nuclear Proteins; Nuclear Proteins - blood; Nutrition; Older people; Original Research Communications; oxidative stress; Oxidative Stress - drug effects; Phospholipases A2; Phospholipases A2 - blood; Plasma; PPAR alpha; PPAR alpha - blood; prevention & control; protective effect; Proteins; Risk factors; Tumor Necrosis Factor alpha-Induced Protein 3; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - blood; Vascular Cell Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1 - blood; Veins & arteries; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamins, Minerals, and Phytochemicals; Zinc; Zinc - administration & dosage; Zinc - blood; Human; Decrease; Cytokine; Lipids; Inflammation; C reactive protein; Elderly; Zinc; Peroxidation
• DOI: 10.3945/ajcn.2009.28836
• ISSN: 0002-9165; 1938-3207

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. DESIGN: 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-α, IL-1β, VCAM-1, and MDA+HAE and the activation of nuclear transcription factor κB and increased antiinflammatory proteins A20 and peroxisome proliferator-activated receptor-α in human monocytic leukemia THP-1 cells and human aortic endothelial cells compared with zinc-deficient cells. CONCLUSION: These findings suggest that zinc may have a protective effect in atherosclerosis because of its antiinflammatory and antioxidant functions.