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The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta‐analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C‐reactive protein [CRP], tumor necrosis factor‐α [TNF‐α], and interleukin‐6 [IL‐6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF‐α, and IL‐6 were included. For each outcome, mean differences and SDs were pooled using a random‐effects model. Overall, eight RCTs were included in this meta‐analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: −0.43 mg/L; 95% confidence interval [CI]: −1.04 to 0.17; p = .16), serum TNF‐α (WMD: −1.29 pg/mL; 95% CI: −4.13 to 1.55; p = .37), and IL‐6 concentrations (WMD: 0.11 pg/mL; 95% CI: −0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF‐α in studies that recruited non‐diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non‐linear effect of saffron dosage on serum CRP concentrations (pnon‐linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high‐quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

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