Vitamin A is an anti-oxidant which has been presumed to act as an anti-infective vitamin in many studies. This study aimed to evaluate the association between vitamin A supplementation and c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) levels in randomized control trials (RCTs) studies on adults. A systematic search was performed on databases including PUBMED, SCOPUS, and the Cochrane library. The studies included were considered for data extraction and subsequently assessed for effect. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were evaluated. Among 13,219 articles 13 studies were included for analysis of CRP and TNF-α, as well as 9 studies included for IL-6 in quality and quantity. The pooled WMD analysis of CRP demonstrated that vitamin A supplementation significantly increased CRP concentration with (WMD: 0.84 mg/L; 95% CI 0.29–1.39, I2 = 0.96.2% and p value < 0.003). However, there was no significant correlation between vitamin A supplementation and lower plasma TNF-α (p < 0.45)). Subgroup analysis by dosage demonstrate significant association between vitamin A supplementation and IL-6 in dosage with 50,000 with (WMD: − 1.53 mg/L; 95% CI − 2.36 to − 0.71, p value < 0.00001) as well as a negative significant association was seen at 44 weeks of supplementation with 50,000 IU/day retinyl palmitate and TNF-a in chronic hepatitis B conditions with (− 0.94 (− 1.19, − 0.69) p < 0.0001). The result of this study demonstrates that supplementation of vitamin A at low and high dosages for short and long durations increases the CRP plasma concentrations on adults and vitamin A supplementation decreases the TNF-α concentrations in chronic hepatitis B on adults. Therefore, there is an inverse association between vitamin A supplementation and plasma and fecal IL-6 concentrations in many infection conditions.

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