Flow diagram of study selection is shown in Fig. 1. In total, 431 publications were found through the initial search; among them, 213 were entered in the second screening stage. Two researchers (MR and MV) independently evaluated the articles in the second screening stage and 185 studies that were not relevant were eliminated. Finally 13 studies with 14 effect sizes met the inclusion criteria and were included in the final analysis [17, 18, 20, 26,27,28,29,30,31,32,33,34,35].

Fig. 1 Flow diagram of literature search according to the PRISMA statement Full size image

Study characteristics

The publications included in the meta-analysis are described in Table 2. Out of 13 articles that included in the final analysis, three study had cross-over [32, 33, 35] design and others had parallel design. Trials were conducted in Iran [18, 20, 26, 29, 31, 34], USA [17, 35], Canada [27], China [28], Denmark [33], France [32] and Brazil [30]. These studies were published between 2011 to 2019. Sample size of these studies ranged from 15 to 75 and intervention duration ranged from 4 to 14 weeks. In total, 672 participants (329 in the intervention group and 343 in the control group) included in the final analysis.

Table 2 Characteristics of included studies in the systematic-review1 Full size table

Quality assessment

Findings from assessing the quality of RCTs are shown in Supplementary Table 1. According to the JADAD core, eight studies had high quality [17, 20, 26,27,28, 31, 32, 34] and five trials had low quality [18, 29, 30, 33, 35]. For a more accurate evaluation, we used the Downs and Black assessment tool as well, based on which seven trials had good quality (score > 19) [17, 20, 26, 27, 31, 32, 34], while six studies were deemed as low quality [18, 28,29,30, 33, 35], mostly due to lack of explanation of confounders and insufficient blinding.

Findings from the meta-analysis of the effect of resistant starch on CRP levels

In total, the effect of resistant starch supplementation on CRP levels was examined in 8 clinical trials with 9 effect size [18, 20, 26, 27, 30,31,32, 35], with a total 325 participants. Summarizing these effect sizes, we found that resistant starch consumption caused a non-significant reduction in the CRP concentration (weighed mean difference (WMD) = − 0.21 mg/L; 95% CI: − 1.06, 0.63 mg/L; P = 0.61), with a significant between-study heterogeneity (I2 = 87.7, P < 0.001) (Fig. 2). The subgroup analysis did not identify study quality (high or low) and intervention duration (> 12 weeks or lower) as sources of heterogeneity (Table 3). The sensitivity analysis did not provide any further information.

Fig. 2 Forest plot summarizing the association between intake resistant starches on circulating CRP concentrations Full size image

Table 3 Results of subgroup-analysis for effect of resistant starch on CRP and TNF-α and IL-6 levels Full size table

Findings from the meta-analysis of the effect of resist ant starch on TNF-α levels

Seven RCTs with eight effect sizes had reported the effect of resistant starch intake on TNF-α levels [17, 26,27,28,29, 31, 32]. Overall, we found that consumption of resistant starch could decrease serum TNF-α concentrations in comparison with the control group (WMD = − 2.19 pg/mL; 95% CI: − 3.49, − 0.9 pg/mL; P = 0.001) (Fig. 3). However, a significant between-study heterogeneity was found (I2 = 94.9, P < 0.001). Due to the high between-study heterogeneity, we stratified studies based on study quality (> 19 vs. ≤19) and duration of follow up (> 8 weeks vs. ≤8 weeks). The subgroup analysis did not provide additional information. Sensitivity analysis revealed that no individual study had a great effect on the overall results.

Fig. 3 Forest plot summarizing the association between intake resistant starches on circulating TNF-α concentrations Full size image

Findings from the meta-analysis of the effect of resistant starch on IL-6 levels

Pooling effect sizes from seven studies [26, 28,29,30,31,32,33], the effect of resistant starch supplementation on serum IL-6 concentrations was significant (WMD = − 1.11 pg/mL; 95% CI: − 1.72, − 0.5 pg/mL; P = < 0.001) with a significant heterogeneity (I2 = 93.9, P < 0.001) (Fig. 4). Subgroup analysis based on study quality (> 19 vs. ≤19) and duration of follow up (> 8 weeks vs. ≤8 weeks) revealed a significant change in serum IL-6 concentrations in the high quality studies (WMD = − 0.97 pg/mL; 95% CI: − 1.81, − 0.13 pg/mL; P = 0.024) and that duration of follow up ≤8 weeks (WMD = − 1.40 pg/mL; 95% CI: − 2.22, − 0.58 pg/mL; P = 0.001). Sensitivity analysis revealed that no individual study had a great effect on the overall results.

Fig. 4 Forest plot summarizing the association between intake resistant starches on circulating IL-6 concentrations Full size image

Publication bias

Visual inspection of the funnel plots demonstrated no publication bias of the trials in investigating the effect of resistant starch intake on the IL-6 (Egger’s test P = 0.115; Begg’s test P = 0.24) (Fig. 5a) and CRP (Egger’s test P = 0.84; Begg’s test P = 0.91) (Fig. 5b) concentration. However, the funnel plot, Egger’s and Begg’s test showed a publication bias of the trials in investigating the effect of resistant starch supplementation on TNF-α concentration (Egger’s test P = 0.009; Begg’s test P = 0.013) (Fig. 5c).