Effects of Zinc Supplementation on Nutritional Status in Children with Chronic Kidney Disease: A Randomized Trial

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Abstract

Background: Zinc is an essential micronutrient for human beings and its deficiency affects their normal growth and development. Objective: The main aim was to evaluate the effect of two doses of zinc supplementation (ZS) on the nutritional status in chronic kidney disease (CKD) children. Methods: A randomized-trial multicentric study was conducted in 48 CKD (23 females) patients under 18-years-old, for a year. At random, participants took 30 or 15 mg/day of ZS, respectively. Anthropometric measurements and biochemical analysis were performed. Hypozincemia was determined by serum zinc concentration (SZC) using atomic absorption spectrophotometry. The positive or negative change in patients’ body mass index (BMI) Z-score, serum albumin, zinc and C-reactive protein (CRP) levels were used to evaluate the effect of ZS. Results: Mean SZC was normal before and after ZS. Despite ZS, there were no significant changes in serum albumin, zinc and CRP levels. A positive and significant association was observed between SZC and serum albumin before ( p = 0.000) and after ( p = 0.007) ZS. In both groups of ZS, there was a small but positive and significant change in body mass and normalization in BMI Z-score, hypoalbuminemia, hypozincemia and high CRP, especially with 30 mg/day of ZS. Conclusions: Zinc supplementation may be beneficial for nutritional status in children and adolescents with CKD.

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Most cited references 77

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Zinc requirements and the risks and benefits of zinc supplementation.

Wolfgang Maret, Harold Sandstead (2006)

The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.

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The role of zinc in growth and cell proliferation.

Ruth MacDonald (2000)

The inhibition of growth is a cardinal symptom of zinc deficiency. In animals fed a zinc-inadequate diet, both food intake and growth are reduced within 4-5 d. Despite the concomitant reduction in food intake and growth, reduced energy intake is not the limiting factor in growth, because force-feeding a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, although well coordinated, mechanisms. Despite the long-term study of zinc metabolism, the first limiting role of zinc in cell proliferation remains undefined. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Removing zinc from the extracellular milieu results in decreased activity of deoxythymidine kinase and reduced levels of adenosine(5')tetraphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis through these systems. Zinc also influences hormonal regulation of cell division. Specifically, the pituitary growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis is responsive to zinc status. Both increased and decreased circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling. Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Overall, the evidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferation in response to IGF-I.

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Biomarkers of Nutrition for Development (BOND)-Zinc Review.

Janet King, Kenneth Brown, Rosalind Gibson … (2016)

Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or DNA damage.

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Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 05 November 2019

Publication date Collection: November 2019

Volume: 11

Issue: 11

Electronic Location Identifier: 2671

Affiliations

[1 ]Faculty of Medicine, National University of San Marcos, Cangallo 818, 15001 Cercado de Lima, Peru

[2 ]National Institute of Child Health, Paediatric Nephrology Service, Avenida Brasil 600, 15083 Breña, Peru; chela_sakihara@ 123456yahoo.com

[3 ]Faculty of Medicine, Valladolid University, Avenida Ramón y Cajal, 7, 47005 Valladolid, Spain

[4 ]Faculty of Food Science and Technology, National Agrarian University, Avenida la Molina, s/n, 15024 La Molina, Lima, Peru; silviacesi@ 123456yahoo.com

[5 ]Department of Public Health and Preventive Medicine, Faculty of Medicine, Valladolid University, 47005 Valladolid, Spain; aalmaraz@ 123456med.uva.es

[6 ]Department of Analytical Chemistry, Science Faculty, University of Valladolid, Campus Miguel Delibes, Calle Paseo de Belén, 7, 47011 Valladolid, Spain; ebarrado@ 123456qa.uva.es

[7 ]Department of Paediatrics of the Faculty of Medicine, Valladolid University, Section of Gastroenterology and Pediatric Nutrition, University Clinical Hospital of Valladolid, 47005 Valladolid, Spain; jmmarugan@ 123456telefonica.net

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[* ]Correspondence: amescobedo@ 123456msn.com ; Tel.: +34-639-590-467

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Marlene Fabiola Escobedo-Monge https://orcid.org/0000-0002-1295-3752

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Publisher ID: nutrients-11-02671

DOI: 10.3390/nu11112671

PMC ID: 6893698

PubMed ID: 31694220

SO-VID: c80af46d-9d55-4bef-9356-4fef27071b21

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Effects of Zinc Supplementation on Nutritional Status in Children with Chronic Kidney Disease: A Randomized Trial

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Karger: Nutrition and Dietetics

Most cited references 77

Zinc requirements and the risks and benefits of zinc supplementation.

The role of zinc in growth and cell proliferation.

Biomarkers of Nutrition for Development (BOND)-Zinc Review.

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