Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients

Int J Med Sci. 2013;10(1):79-89. doi: 10.7150/ijms.5291. Epub 2012 Dec 22.


Background: Patients undergoing hemodialysis (HD) have low plasma levels of zinc (Zn), high plasma levels of copper (Cu), and exhibit increased oxidative stress, inflammation, and immune abnormalities. We evaluated the effects of Zn supplementation on abnormal plasma Cu/Zn ratios and clinical outcomes in HD patients.

Design and methods: Patients on long-term HD with lower than normal plasma concentrations of Zn (< 80 mg/dL) were randomized to receive daily oral Zn supplements (n = 40) or no supplements (n = 25) for eight weeks. Age- and sex-matched healthy individuals served as a control group (n = 38). A number of clinical parameters were measured before and after the supplementation period.

Results: Compared with healthy subjects, patients had significantly elevated plasma Cu concentrations and Cu/Zn ratios, as well as higher levels of oxidative stress and pro-inflammatory cytokines. Patients who received Zn supplements for eight weeks had higher plasma concentrations of Zn and lower concentrations of Cu, along with reduced Cu/Zn ratios, oxidative stress status, and inflammatory responses compared to patients who did not receive Zn. Patients receiving Zn also showed significantly higher percentages of CD4 and CD19 lymphocytes, and elevated CD4/CD8 ratios.

Conclusions: Zn supplementation ameliorates abnormally high plasma Cu/Zn ratios and may reduce oxidative stress, improve inflammatory status, and maintain immune function in patients undergoing long-term HD.

Keywords: copper/zinc ratios; hemodialysis patients.; immune function; inflammation; oxidative stress; zinc supplement.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD4-Positive T-Lymphocytes / drug effects
  • Copper / blood*
  • Dietary Supplements
  • Female
  • Humans
  • Inflammation* / diet therapy
  • Inflammation* / immunology
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Oxidative Stress / immunology
  • Renal Dialysis / adverse effects*
  • Superoxide Dismutase / blood
  • Treatment Outcome
  • Zinc* / administration & dosage
  • Zinc* / blood


  • Copper
  • Superoxide Dismutase
  • Zinc