Special Article Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials Aya Mousa, Negar Naderpoor, Helena Teede, Robert Scragg, and Barbora de Courten Background: Vitamin D has been proposed to have anti-inflammatory properties; however, the effect of vitamin D supplementation on inflammation in type 2 diabe- tes has not been established. Objective: The aim of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on inflam- matory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge. Data sources: MEDLINE, CINAHL, Embase, and EBM Reviews were searched systematically from inception to January 25, 2017. Study selection: Randomized controlled trials (RCTs) investigating the effects of vitamin D supplemen- tation (any form, route, and duration, and with any cosupplementation) compared with placebo or usual care on inflammatory markers in patients with type 2 diabetes were selected. Data extraction: Study and sample characteristics and aggregate outcome data were extracted, risk of bias was determined, and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Twenty-eight RCTs were included, 20 of which had data available for pooling. In meta-analyses of 20 RCTs (n ¼ 1270 partici- pants), vitamin D–supplemented groups had lower levels of C-reactive protein (stan- dardized mean difference [SMD] 0.23; 95%CI, 0.37 to 0.09; P ¼ 0.002) and tumor necrosis factor a (SMD 0.49; 95%CI, 0.84 to 0.15; P ¼ 0.005), a lower erythrocyte sedimentation rate (SMD 0.47; 95%CI, 0.89 to 0.05; P ¼ 0.03), and higher levels of leptin (SMD 0.42; 95%CI, 0.04–0.81; P ¼ 0.03) compared with control groups. No differences were observed for adiponectin, interleukin 6, or E-selectin (all P > 0.05). In meta-regression and subgroup analyses, age, sex, body mass index, duration of diabetes, baseline vitamin D status, and dose and duration of supple- mentation did not alter the results. Conclusions: This meta-analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low-grade inflamma- tion in patients with type 2 diabetes. Systematic Review Registration: PROSPERO CRD42016047755. Available at: https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID¼47755 (9/15/2016). Affiliation: A. Mousa, N. Naderpoor, H. Teede, and B. de Courten are with the Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. R. Scragg is with the School of Population Health, University of Auckland, Auckland, New Zealand. Correspondence: B. de Courten, Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Level 1, 43-51 Kanooka Grove, Clayton, Melbourne, VIC 3168, Australia. Email: barbora.decourten@monash.edu. Key words: inflammation, meta-analysis, randomized controlled trials, type 2 diabetes, vitamin D. V C The Author(s) 2018. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. doi: 10.1093/nutrit/nux077 380 Nutrition Reviews V R Vol. 76(5):380–394 Downloaded from https://academic.oup.com/nutritionreviews/article/76/5/380/4912422 by guest on 23 December 2022