Effects of Zinc Supplementation on Serum Lipids

A Systematic Review and Meta-Analysis

Priyanga Ranasinghe; WS Wathurapatha; MH Ishara; R. Jayawardana; P. Galappatthy; P. Katulanda; GR Constantine

Disclosures

Nutr Metab. 2015;12(26) 

In This Article

Abstract and Introduction

Abstract

Zinc is a mineral that plays a vital role in many biological processes and plays an important role in insulin action and carbohydrate metabolism. It may also have a protective role in the prevention of atherogenesis. Numerous studies have evaluated the effects of Zinc supplementation on serum lipids in humans and have demonstrated varying results. We systematically evaluated the literature and performed a meta-analysis on the effects of Zinc supplementation on serum lipids. A five staged comprehensive search of the literature was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus for studies published before 31st December 2014. All controlled clinical trial in humans, that included a Zinc supplement intervention, either alone or in combination with other micronutrients and evaluated effects on serum lipids (total cholesterol [TC], triglycerides [TG], LDL cholesterol [LDL-c] and HDL cholesterol [HDL-c]). A meta-analysis of selected studies was performed using RevMan v5.3. The Jaded scale was used to assess the methodological quality of the trials included in the systematic review. A total of 24 studies were included in Meta analysis, which included a total of 33 Zinc interventions, in a total of 14,515 participants in the Zinc intervention or control group. The duration of Zinc supplementation ranged from 1 month to 7.5 years. The dose of elemental Zinc supplemented ranged from 15–240 mg/day. The pooled mean difference for TC between Zinc supplemented and placebo groups from random effects analysis was −10.92 mg/dl (95 % CI: −15.33, −6.52; p < 0.0001, I 2 = 83 %), while for HDL cholesterol it was 2.12 mg/dl (95 % CI: −0.74, 4.98; p = 0.15, I 2 = 83 %). The pooled mean difference for LDL-c between Zinc supplemented and placebo group from random effect analysis was −6.87 mg/dl (95 % CI: −11.16,-2.58; p < 0.001, I 2 = 31) and for TG it was −10.92 mg/dl (95 % CI: −18.56, − 3.28; p < 0.01, I 2 = 69 %). In conclusion, Zinc supplementation has favourable effects on plasma lipid parameters. Zinc supplementation significantly reduced total cholesterol, LDL cholesterol and triglycerides. Therefore it may have the potential to reduce the incidence of atherosclerosis related morbidity and mortality.

Introduction

Zinc is a mineral that plays a vital role in many biological processes, such as enzyme action, cell membrane stabilization, gene expression and cell signaling.[1] It is required for structural and functional integrity of more than 2000 transcription factors and 300 enzymes; hence, almost all metabolic pathways are in some ways reliant on at least one Zinc requiring protein.[2,3] Zinc also plays an important role in insulin action and carbohydrate metabolism.[4] Studies have shown that diabetes is accompanied by hypozincemia and hyperzincuria.[5,6] In addition Zinc is also an integral part of key anti-oxidant enzymes and Zinc deficiency impairs their synthesis, resulting in increased oxidative stress.[7]

Zinc deficiency is known to affect 1/3 rd of the world's population.[8] It is estimated that Zinc deficiency is a major factor contributing to 1.4 % of deaths worldwide.[8] Zinc deficiency is more common in developing countries, and although severe deficiency is rare in developed countries, marginal deficiency is thought to be relatively common.[9,10] Zinc deficiency is associated with many diseases, including malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes and malignancy.[11] Animal studies have shown that Zinc deficiency has profound effects on the cell structure of the aorta, fatty acid metabolism and carbohydrate metabolism, being disadvantageous for maintaining vascular health.[12] Zinc deficiency renders vascular endothelial cells more susceptible to the effects of oxidative stress.[13,14] Furthermore, in LDL receptor knock-out mice acute Zinc deficiency elicits changes in key transcription factors and adhesion molecules that are pro-atherogenic.[15] In human studies a strong negative association was observed between the dietary intake of Zinc and the incidence of diabetes and heart disease, as well as several of their associated risk factors including hypertension and hyper-triglyceridemia.[16] Hence Zinc may have a protective role in the prevention of atherogenesis.[12]

Several human studies have demonstrated that Zinc supplementation reduces total cholesterol, LDL cholesterol and triglycerides, in addition to increasing the HDL cholesterol levels.[17–20] However, these results have been contradicted by other studies.[21–23] Even under the most rigorous study design conditions, a single well-planned study rarely provides definitive results.[24] Hence, changing clinical practices relying on a single high-profile clinical trial can be harmful to patients' health. Systematic reviews and meta-analyses on the other hand often have increased power and decreased bias as compared with the individual studies they include, and the careful pooling of treatment effects can provide the most accurate overall assessment of an intervention.[24] In 2008 Foster et al. performed a meta-analysis of controlled clinical trials to determine the effect of Zinc supplementation on serum lipids in humans.[25] They did not observe any beneficial effect of Zinc supplementation on plasma lipoproteins in the overall analysis, whilst in sub group analysis of healthy subjects Zinc supplementation was associated with a reduction in HDL cholesterol concentrations.[25] However, since then several recent studies have evaluated the effects of Zinc supplementation on serum lipids in humans and have demonstrated varying results.[17,21–23,25–28] Hence the present study aims to re-explore the area under discussion, by systematically evaluating the literature and performing an up to date meta-analysis on the effects of Zinc supplementation on serum lipids: total cholesterol (TC); LDL cholesterol (LDL-c); HDL cholesterol (HDL-c); and triglycerides (TG) in humans.

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