Comment on: Does Zinc Supplementation Affect Inflammatory Markers in Hemodialysis Patients?

Dear Sir

Zinc is a trace element essential for the action of many metallo-enzymes, which has an important role in polymeric organization of macromolecules such as DNA and RNA, protein synthesis, cell division, and gonad functions.^1,2 Moreover, zinc is an essential micronutrient that can function as an anti-inflammatory and antioxidative agent.³ The relationship between antioxidant trace elements measured in the nail and the blood inflammatory markers' concentrations has been studied before.⁴ Therefore, antioxidant intake may be linked to a reduction of the chronic low-grade inflammatory state seen in different metabolic syndromes.⁴ In a recent study, Wang and colleagues⁵ suggested that multivitamin and mineral supplementation, for example, zinc, could have blood pressure lowering effect and could reduce serum C-reactive protein (CRP) in the women studied.

Furthermore, zinc supplementation causing an increase in serum zinc (Zn) concentration in the hemodialysis (HD) patients and the subsequent decrease in serum CRP was studied in a randomized, double-blinded, placebo-controlled clinical trial in our center recently.⁶ Zinc deficiency in the Middle East area and Iran is estimated to be seen in around 30% of healthy persons. It is even more common in chronic medical conditions, for example, renal failure patients on dialysis.^7,8 The rate of zinc deficiency in patients with HD is about 40–78%.^9–11

In a prospective cohort study, the effects of oral zinc sulfate supplementation on serum CRP, erythrocyte sedimentation rate (ESR), and ferritin level in HD patients were studied. From 155 patients with end-stage renal disease on HD in the outpatient HD unit, 41 patients with low Zn level (Zn < 70 µg/mL) and normal serum iron were included in the study. For the purpose of this study, Zn levels were assessed using fasting plasma samples collected in acid-washed tubes. Zn was measured using the atomic absorption method in the same laboratory for all of the patients. We also checked the plasma levels of CRP, ESR, and ferritin. Patients with signs of iron deficiency anemia, hemoglobulin <7 mg/dL, and hypocalcemia (corrected serum calcium level <7) were excluded from the study.¹² The patients received oral zinc supplement [zinc sulfate, (250 mg/day); Alhavi Pharmaceutical, Tehran, Iran] for 6 weeks. Levels of Zn, CRP, ESR, ferritin, and BUN were rechecked after 6 weeks. Parametric data are presented as mean [standard deviation (SD)]. The variables were analyzed using SPSS 15 software.

Mean age of 38 patients who completed the study (three patients with noncompliance) was 53.2 years (SD: 18.5; range: 21–83). Mean duration of dialysis in these patients was 12.1 months (range: 3–51). Mean Zn concentration for the subjects increased from 53.27 µg/mL (SD: 15.27) to 80.38 µg/mL (SD: 20.54) after 42 days of zinc supplementation (p < 0.05). Serum CRP decreased significantly during the same period (p < 0.05) although we did not detect a significant change in serum ESR, ferritin, and BUN levels (Table 1).

Table 1.  Variables before and after intervention

	Before intervention, mean (SD)	After intervention, mean (SD)	p-Value
Plasma zinc level (µg/mL)	53.27 (15.27)	80.38 (20.54)	p < 0.05
Serum ferritin level (mg/dL)	377.2 (181.9)	339.1 (128.6)	p > 0.05
Plasma BUN level (mg/dL)	52.3 (29.1)	55.9 (31.4)	p > 0.05
Erythrocyte sedimentation rate (mm/h)	73.6 (11.4)	70.2 (13.5)	p > 0.05
C-reactive protein level (mg/L)	16.8 (2.2)	12.6 (3.7)	p < 0.05

Oxidative stress and chronic inflammation are important factors in the pathophysiology of many chronic diseases, for example, atherosclerosis, neurological and malignant disorders, autoimmune- and HD-dependant end-stage renal diseases.¹³ Zinc as an anti-inflammatory agent can decrease the oxidative stress and inflammatory cytokine generation.¹³ It has been shown that concurrent zinc deficiency changes the expected clinical picture in many diseases and will affect cell-mediated immunity and the generation of inflammatory cytokines in the patients.¹³ Zinc supplement decreasing CRP, lipid peroxidation, and inflammatory cytokines in the elderly subjects have been reported before.³ Zinc supplementation may also decrease inflammation in HD patients.⁶ In this study although zinc supplement did not have significant effect on plasma levels of ESR and ferritin as inflammatory factors in HD patients, it caused a significant decrease in CRP. Accordingly, administration of zinc supplement in HD patients may decrease chronic inflammation in some but not in all the aspects.

Department of Public Health, School of Health andNutrition, Shiraz University of Medical Sciences,