Vitamin C reduces interleukin-6 plasma concentration: a systematic review and meta-analysis of randomized clinical trials

Background Interleukin 6 is an important biomarker for distinguishing high-risk and low-risk patients, and is a constituent of the Nutrition Risk in the Critically III (NUTRIC) Score. Studies have indicated the beneficial effects of vitamin C on lowering IL-6 levels and reducing cytokine storm. However, there is still controversy about the exact effect, appropriate route, and dose of vitamin C usage. This meta-analysis was conducted to evaluate the current evidence base relating to vitamin C intervention on decreasing IL-6 levels. Methods A systematic search was performed in PubMed, Scopus, Google Scholar, and Cochran databases, from database inception to July 3rd 2021, to obtain any possible randomized clinical trial for inclusion. After screening and removing unrelated and duplicate articles, 24 eligible articles remained for statistical analysis. Results We found a significant lowering effect of vitamin C supplementation on IL-6 levels via peroral (PO) (WMD = -0.29 pg/l, 95% CI [-0.42, -0.16], P<0.0001) and intravenous (IV) routes with (WMD = -7.99 pg/l, 95% CI [-8.36, -7.62], P<0.0001). Conclusions Vitamin C, at doses of 250–1000 mg/day and for less than one week of treatment, regardless of the route of administration, reduces IL-6 levels in participants.