Journal of Trace Elements in Medicine and Biology 27 (2013) 137–142 Contents lists available at SciVerse ScienceDirect Journal of Trace Elements in Medicine and Biology j ourna l homepage: www.elsevier.de/jtemb Nutrition Zinc and glycemic control: A meta-analysis of randomised placebo controlled supplementation trials in humans Jasmine Capdor a , Meika Foster a , Peter Petocz b , Samir Samman a,∗ a Discipline of Nutrition & Metabolism, School of Molecular Bioscience, University of Sydney, NSW 2006, Australia b Department of Statistics, Macquarie University, NSW 2109, Australia a r t i c l e i n f o Article history: Received 23 March 2012 Accepted 27 August 2012 Keywords: Zinc Glucose HbA1c Insulin a b s t r a c t Background: Impaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus. Methods: A systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011. Results: Fourteen reports (n = 3978 subjects) were included in the meta-analysis. In the overall anal- ysis, a small but statistically significant reduction in fasting glucose concentrations was observed (−0.19 ± 0.08 mmol/L, P = 0.013) after zinc supplementation. HbA1c tended to decrease in zinc- supplemented individuals (−0.64 ± 0.36%, P = 0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03 ± 0.81 mol/L, P = 0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (−0.49 ± 0.11 mmol/L, P = 0.001) compared to the effect that was observed in healthy participants. Conclusion: The significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyper- glycemia in individuals with chronic metabolic disease. © 2012 Elsevier GmbH. All rights reserved. Introduction Zinc is a component of numerous enzymes that function in a wide range of biological processes, including growth and development, intermediary metabolism and immunity [1,2]. Zinc deficiency is associated with a multitude of clinical manifestations [1,2], and may play a role in chronic diseases such as cardiovascular disease (CVD) [3] and type 2 diabetes mellitus (DM) [4]. Zinc is implicated in glucose metabolism through its par- ticipation in insulin crystallisation and signalling [5,6]. Under physiological conditions zinc is abundant throughout the pancreas, but is concentrated in the secretory vesicles of the -cells where ∗ Corresponding author at: Discipline of Nutrition & Metabolism, School of Molec- ular Bioscience, Building G08, The University of Sydney, NSW 2006, Australia. Tel.: +61 2 9351 2476; fax: +61 2 9351 5858. E-mail address: samir.samman@sydney.edu.au (S. Samman). it forms an integral component of the insulin structure [7], serving to stabilise it and minimise its susceptibility to oxidative damage [8,9]. Recent evidence has demonstrated a role for zinc in insulin sensitivity via the induction of the PI3K/Akt cascade that mediates insulin signalling and subsequent glucose disposal [6]. A defect in zinc homeostasis is reported in DM patients, including higher uri- nary zinc excretion in some studies [10], and lower serum zinc concentrations [11] as compared to healthy controls. Low zinc sta- tus in DM is associated with a decrease in insulin sensitivity [12] and impaired glucose utilisation [13]. Zinc supplementation has been investigated as a potential adjunct therapy in the management of DM, however the outcomes of such interventions are conflicting [14]. The aims of the present study are to systematically evaluate the effects of zinc supplemen- tation on markers of glycemic control (glucose, insulin and HbA1c) in humans and to conduct a meta-analysis of eligible controlled trials to quantify the magnitude of the response to zinc supple- mentation. 0946-672X/$ – see front matter © 2012 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.jtemb.2012.08.001