Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients

Transl Res. 2008 Aug;152(2):67-80. doi: 10.1016/j.trsl.2008.06.001. Epub 2008 Jul 11.


Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / drug therapy*
  • Anemia, Sickle Cell / physiopathology
  • Cell Adhesion Molecules / metabolism
  • Cytokines / biosynthesis*
  • DNA / metabolism
  • Dietary Supplements
  • Gene Expression Regulation / drug effects
  • Hemodynamics / drug effects
  • Humans
  • Incidence
  • Infections / complications*
  • Infections / drug therapy
  • Infections / epidemiology*
  • Infections / physiopathology
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Michigan / epidemiology
  • Middle Aged
  • NF-kappa B / metabolism
  • Oxidative Stress* / drug effects
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Zinc / administration & dosage
  • Zinc / blood
  • Zinc / pharmacology
  • Zinc / therapeutic use*


  • Cell Adhesion Molecules
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • DNA
  • Zinc