Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials

Abstract

Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. Pubmed (Medline), Scopus, Web of Science, and Embase databases were searched up to December 10th, 2020. Randomized placebo-controlled trials have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in >15 years’ subjects were included. A pooled meta-analysis was performed using a random-effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. Potential causes of heterogeneity were determined using subgroup analyses. The relationship between effect size and co-variables was explored using meta-regression. In the cases of the presence of publication bias, trim and fill analysis was carried out. Cochrane Collaboration’s tool was used for assessing the quality of the included studies. A total of 12 studies was included in meta-analysis. Zn could decrease IL-6 levels (SMD= -0.76 pg/ml; 95% CI: -1.28, -0.24; P= 0.004). There was no significant change in TNF-α (SMD= 0.42 pg/ml; 95% CI: -0.31, 1.16; P= 0.257) and IL-2 levels (SMD= 1.64 pg/ml; 95% CI: -1.31, 4.59; P= 0.277) following Zn supplementation. However, Zn could increase IL-2 significantly after deletion of one arm in sensitivity analysis (SMD= 2.96 pg/ml; 95% CI: 2.03, 3.88; P< 0.05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.

Development and management of gastrointestinal symptoms in long-term COVID-19

“…Moreover, vitamins D and A, selenium, flavonoids, zinc, and unsaturated fatty acids can alleviate inflammatory response in patients with COVID-19 via inhibiting the activation of nuclear factor kappa-B (NF-κB), hence reducing the production of pro-inflammatory cytokines, such as IL-6 and TNF-α. However, foods with higher glycemic load, carbohydrates, saturated fatty acids, and processed foods are found to disrupt the homeostasis of gut microbiota and are positively related to inflammation conditions in COVID-19 patients ( Faghfouri et al, 2020 , 2021 ; Zabetakis et al, 2020 ). In addition, appropriate intake of specific dietary fiber ( Zhao et al, 2018 ), promote the growth of beneficial bacteria in the intestine, which may reduce the risk of SARS-CoV-2 infection ( Kalantar-Zadeh et al, 2020 ; Merino et al, 2021 ).…”

Investigating the Role of Zinc in Atherosclerosis: A Review

“…IL-6 and IL-1β are the major pro-inflammatory cytokines that innate immune cells secrete [ 124 ]. A meta-analysis conducted by Faghfouri et al [ 129 ] indicated that zinc supplementation can decrease IL-6 levels, and another former study shows that IL-6 induces low zinc ion availability by modulating MT gene expression [ 130 ].…”

“…After the TCR trigger, certain zinc transporters, such as ZIP-6 and ZIP-8, are up-regulated and induce a rise in cellular zinc concentration, which is directly involved in T cell activation [ 137 , 138 ]. On the other hand, the cytokine-mediated signaling pathway is regulated by IL-2, and according to Faghfouri et al, zinc can increase IL-2 levels [ 129 ]. IL-2 stimulation can induce T cell proliferation and development through three different signaling pathways: Janus kinase 1/3 (JAK1/3)- signal transducer and activator of transcription 5 (STAT5), ERK1/2, and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) [ 124 ].…”

The association between inflammatory and immune system biomarkers and the dietary inflammatory index in patients with COVID-19

“…Moreover, some of the nutrients including vitamins D and A, zinc, selenium, flavonoids, and unsaturated fatty acids can reverse inflammatory conditions in these patients, especially by affecting nuclear factor kappa-B (NF-κB), which is the main production regulator of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). However, foods with higher glycemic load, simple carbohydrates, saturated fatty acids, processed foods, and red meats found in Western diets are positively associated with inflammation in COVID-19 (19)(20)(21)(22).…”