The Effects of Vitamin D Supplementation on Biomarkers of Inflammation and Oxidative Stress in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

In this systematic review and meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients are summarized. The following databases were searched up to December 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI). Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I). Overall, 33 studies were included in the meta-analyses. Vitamin D supplementation were found to significantly reduce serum high-sensitivity C-reactive protein (hs-CRP) (WMD 0.27; 95% CI, - 0.35, - 0.20; p<0.001) and malondialdehyde (MDA) levels (WMD - 0.43, 95% CI - 0.62, - 0.25, p<0.001) in diabetic patients. In addition, vitamin D supplementation were found to increase markers of nitric oxide (NO) release (WMD 4.33, 95% CI 0.96, 7.70), total serum antioxidant capacity (TAC) (WMD 57.34, 95% CI 33.48, 81.20, p<0.001) and total glutathione (GSH) levels (WMD 82.59, 95% CI 44.37, 120.81, p<0.001). Overall, this meta-analysis shows that in diabetic patients, taking vitamin D had significant effects on hs-CRP and MDA levels, and significantly increased NO, TAC and GSH levels.

Mitochondrial Alterations and Enhanced Human Leukocyte/Endothelial Cell Interactions in Type 1 Diabetes

“…Physiologically, ROS are released by inflammatory cells and the endothelium, and an exacerbated ROS production can damage cells and lead to mitochondrial dysfunction and oxidative stress in β-cells, which are related to type 1 diabetes [18,27]. For these reasons, restoring mitochondrial ROS homeostasis could be essential for preventing diabetic complications and improving endothelial function in CVDs, as demonstrated by several meta-analysis studies on antioxidant supplementation in diabetic patients [30][31][32]. Furthermore, we should remember that type 1 diabetes is an autoimmune disease; it has been shown that mitochondrial function is essential for T cell activation and function and antigen presentation (as naive and memory cells depend on efficient mitochondrial oxidative phosphorylation) [33][34][35].…”

Inflammation and Premature Ageing in Chronic Kidney Disease

“…Human ex vivo studies indicate that vitamin D exerts anti-inflammatory effects on uremic lymphocytes under renal replacement therapy (RRT) [96]. Meta-analyses demonstrating reduced circulating markers of inflammation in mostly non-CKD subjects on vitamin D supplementation [97,98], further supporting a significant role of vitamin D on the hallmarks of ageing. However, these associations were not seen in CKD patients on vitamin D supplementation [99].…”

Regulation of Vascular Function and Inflammation via Cross Talk of Reactive Oxygen and Nitrogen Species from Mitochondria or NADPH Oxidase—Implications for Diabetes Progression

“…The contribution of oxidative stress to the cardiovascular complications in diabetes is widely accepted [102,103]. A meta-analysis of 33 studies revealed that administration of vitamin D significantly reduced the serum levels of high-sensitivity C-reactive protein (hs-CRP) and MDA levels in diabetic patients, whereas vitamin D treatment increased • NO bioavailability and the levels of reduced glutathione [104]. Although vitamin D is not a classical low-molecular-weight antioxidant compound, its beneficial effects on oxidative stress are more and more recognized [105][106][107][108].…”