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Recommendations Summary

CKD: Micronutrients: Trace Mineral Supplementation, Selenium and Zinc (2020)

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.


  • Recommendation(s)

    CKD: Selenium and Zinc Supplementation

    In adults with CKD 1-5D, we suggest to not routinely supplementing selenium or zinc since there is little evidence that it improves nutritional, inflammatory or micronutrient status (2C).

    Rating: Weak
    Imperative

    • Risks/Harms of Implementing This Recommendation

      There are no obvious risks or harms associated with this recommendation. 

    • Conditions of Application

      Medical Nutrition Therapy requires individualization of nutrition care based on patient’s CKD stage, comorbidities, diet and lifestyle as well as patient preferences. Recommendations are specific to CKD stage described.

      Suggested intake should be based on recommendations for the general population (ex: Recommended Dietary Allowance) unless there are specific considerations requiring modification.

    • Potential Costs Associated with Application

      There are no obvious costs associated with this recommendation. 

    • Recommendation Narrative

      Selenium is a trace element that has known anti-oxidant properties and plays a role in enzymatic activities inside the body. It acts as a cofactor for the reduction in important antioxidant enzymes like glutathione peroxidase and thus protects against oxidation. Several studies have suggested that maintenance hemodialysis (MHD) patients have low levels of selenium compared with healthy controls, and deficiency of this trace element may contribute to increased oxidative stress and inflammation (Marti et al 2011,  Chen et al 2009,  Chen et al 2013,  Fujishima et al 2011). There is also some preliminary suggestion that low selenium levels may be associated with increased death risk in MHD patients, especially death due to infections (Fujishima et al 2011).

      Zinc is an essential micronutrient and forms a component of bio-membranes. It functions not only as an antioxidant but also has anti-inflammatory effects and prevents free radicals-induced injury during inflammation. There is some suggestion that marginal zinc intake may be associated with an increased risk of cardiovascular disease in general population (Prasad et al 2008) and zinc has been shown to protect against atherosclerosis by inhibiting the oxidation of low-density lipoprotein cholesterol in animal studies (diSilvestro et al 1997). Zinc deficiency has been shown to increase oxidative stress and NF-κB DNA-binding activity and induce inflammation in experimental models (Foster et al 2012,  Prasad et al 2014,  Shen et al 2008). Zinc is also essential for insulin synthesis and release and glucose homeostasis (Cooper-Capetini et al 2017) and zinc deficiency has been suggested to impair insulin secretion and decrease leptin levels (Ott et al 2001).  Studies have reported a high prevalence of zinc deficiency in hemodialysis patients (Bozalioglu et al 2005,  Hsieh et al 2006,  Kiziltas et al 2008).

      The current Recommended Dietary Allowance (RDA) for zinc is 8 mg/d for women and 11/d mg for men in the general population and for selenium is 55mcg/d for women and men. Whether similar amount of intake is recommended in various CKD stages and maintenance dialysis population is currently not known.

      Selenium
      In adults with chronic kidney disease (CKD), seven studies have examined the effect of selenium intake on biomarkers and other surrogate health outcomes. Most of the studies utilized oral selenium supplementation and all studies were performed in MHD patients. Koenig et al examined the effect of intravenous selenium supplementation and Stockler-Pinto examined the effect of selenium supplementation in the form of a Brazil nut. Selenium dosages generally ranged from 175-1400 µg per week. The selenium dosage in Stockler-Pinto et al was not described (1 Brazil nut/day) and in Koenig et al, the parenteral dose of selenium used was much higher (400 mg 3 times a week) compared to other studies. Study duration ranged from 14 days to 6 months. In Temple et al, participants’ selenium status at baseline was normal.In study by Tonelli et al, 28% of treatment group versus 15% of placebo group had low selenium levels after supplementation. Around 20% of participants were selenium deficient in Stockler-Pinto et al, and the remaining studies did not report selenium status at baseline.

      Nutritional Status
      Only one very short-term (12 weeks) randomized placebo-controlled study examined the effect of oral selenium supplementation of 200µg per day on nutritional status in 80 MHD patients (Salehi et al 2013). The study reported a significantly greater reduction in SGA and malnutrition-inflammation score in the selenium group compared to the placebo group. However, no significant difference was observed in serum albumin concentrations between the two groups (Salehi et al 2013). The same study by Salehi et al did not observe any difference in the median changes of CRP levels between selenium and placebo groups. Although a smaller increase in interleukin-6 levels was observed in selenium group compared to placebo group (Selehi et al 2013), this is the only study that examined inflammation as an outcome.  Thus, there is not enough evidence to make recommendation of selenium supplementation for malnutrition-inflammation syndrome in MHD patients.

      Selenium and Lipid Levels
      Although two short-term small randomized controlled studies provided some evidence that selenium supplementation may be useful in increasing plasma and erythrocyte selenium levels (Temple et al 2000,  Adamowicz et al 2002) it is not known if selenium supplementation may impact on any patient health-related or hard clinical outcomes. Only one short-term randomized study by Salehi et al examined the effects of oral selenium supplementation on lipid levels. The results showed no difference between selenium group and control group in any of the lipid parameters including triglyceride, total cholesterol, low density lipoprotein- and high density lipoprotein-cholesterol.

      Zinc

      Nutritional Status
      Three small short-term RCTs examined the effects of zinc supplementation on nutrition status in MHD patients. The study duration ranged from 8 weeks to 90 days. The dose of zinc supplementation ranged from a daily dose of 11mg, 50mg to 100mg elemental zinc (Argani et al 2014,  Guo et al 2013,  Jern et al 2000). In the study by Argani et al, serum albumin levels increased in the zinc supplemented group but there was no change in the placebo group. Guo et al examined zinc supplementation of 11mg daily for 8 weeks in a cohort of 65 MHD patients with low baseline zinc level (<80mg/dL). Descriptive quantitative data was not provided but the authors concluded that protein nitrogen appearance and albumin levels significantly increased in zinc supplemented group but not in control group. Jern et al showed that protein catabolic rate increased with 50mg zinc supplementation for 90 days but no change in placebo group. Between group differences were not provided in these studies. The data from these three small low-quality trials were regarded as inconclusive and not enough to make recommendation.

      Lipid Profile, Homocysteine Levels
      Four short-term RCTs examined the effect of oral zinc supplementation on lipid levels (Argani et al 2014,  Roozbeh et al 2009,  Chevalier et al 2002,  Rahimi-Ardabili et al 2012). The studies by Argani et al and Rahimi-Ardabili et al administered 100 mg oral zinc daily to MHD patients for two months. Argani et al showed no changes in cholesterol and triglyceride levels with zinc supplementation. Rahimi-Ardabili et al showed that cholesterol levels increased significantly in the placebo group but no change in the treatment group and total cholesterol levels were not different between the two groups after 2 months’ study . In the other two studies, Roozbeh et al and Chevalier et al  both supplemented MHD patients with 50 mg zinc daily for six weeks and 90 days, respectively. All patients in both these two studies were zinc deficient at baseline (<80ug/dL). Both studies showed that total cholesterol, LDL-C, HDL-C and serum triglyceride levels increased in zinc supplemented group but no change in the control group. The conclusions by the authors in these studies suggested that this increase in lipid parameters was desirable. Pakfetrat et al examined the effect of 50 mg oral zinc per day for 6 weeks in MHD patients, and found that significantly decreased homocysteine levels decreased in the zinc supplemented group compared to the placebo group.  Two studies examined the effects of zinc supplementation on inflammatory parameters but results were inconclusive (Guo, et al. and Rashidi, et al).  Data on the effects of zinc supplementation on body weight and BMI were mixed and limited (Argani et al 2014,  Mazani et al 2013).

      Zinc Levels
      Six RCTs examined zinc supplementation in relation to serum zinc levels in MHD patients (Argani et al 2014,  Guo et al 2013,  Roozbeh et al 2009,  Chevalier et al 2002,  Tonelli et al 2015,  Zachara et al 2001). All except Tonelli’s study described zinc deficiency at baseline. The dosage of zinc supplementation used ranged from 11mg to 110mg. Study duration ranged from 5 weeks up to 6 months. In the study by Tonelli and co-workers, zinc levels in the medium dose (50mg per day) but not the low dose (25mg per day) group were significantly higher than the non-supplemented group at 90 days and 180 days after supplementation. A pooled analysis of these 6 studies showed a mean (95% confidence intervals) increase of 30.97 (17.45, 44.59) ug/dL of serum zinc levels after supplementation compared to control group. However, heterogeneity was high. Furthermore, it is not known if zinc supplementation in deficient patients may impact on any health-related outcomes or clinical hard outcomes in CKD and dialysis patients. The long-term effects or any toxicity of zinc supplementation are also unclear at this stage.

      There were no identified studies examining the effect of zinc supplementation on dysgeusia in patients with CKD, though this topic has been explored in other populations. .

    • Recommendation Strength Rationale

      The evidence supporting the recommendation on zinc and selenium supplementation is based on Grade III /Grade C evidence.

    • Minority Opinions

      Consensus reached.