Effect of cyclodextrins on cardiometabolic indices: a systematic review and meta-analysis of randomized controlled...

Cyclodextrins (CDs) are cyclic oligosaccharides with potential cardiometabolic and glucometabolic benefits; however, evidence from randomized controlled trials (RCTs) remains inconsistent. This systematic review and meta-analysis evaluated the effects of oral CD supplementation on cardiometabolic outcomes in adults.

PubMed, Scopus, Web of Science, and Google Scholar were searched from inception to January 2026 according to PRISMA 2020 guidelines. RCTs investigating oral CD supplementation and reporting cardiometabolic outcomes were included. Random-effects meta-analyses were performed to calculate pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane tool, and the certainty of evidence was evaluated according to the GRADE approach.

Thirteen RCTs involving 742 participants were included, with intervention durations ranging from acute postprandial studies lasting several hours to long-term interventions of up to six months. Narrative findings suggested that CD consumption may improve postprandial glucose and insulin responses, with some long-term studies also reporting beneficial effects on glycemic control, lipid profile, adiponectin levels, and body weight, particularly in individuals with obesity, prediabetes, or type 2 diabetes. However, pooled meta-analyses showed no significant overall effects of CD supplementation on long-term triglyceride (TG) levels (WMD: 0.03 mmol/L; 95% CI: -0.11 to 0.17; p = 0.68), blood glucose (BG) levels (WMD: -0.05 mmol/L; 95% CI: -0.15 to 0.04; p = 0.25), or HbA1c concentrations (WMD: -0.06%; 95% CI: -0.30 to 0.17; p = 0.59). Subgroup analyses demonstrated that studies with a 24-week intervention duration showed a significant increase in TG levels (WMD: 0.29 mmol/L; 95% CI: 0.02 to 0.55; p = 0.03), whereas no significant effect was observed in studies lasting 12 weeks. Significant reductions in long-term BG and HbA1c levels were observed in food-enrichment interventions (BG: WMD: -0.16 mmol/L; 95% CI: -0.21 to -0.10; p < 0.001; HbA1c: WMD: -0.30%; 95% CI: -0.40 to -0.19; p < 0.001). However, these significant subgroup findings were generally based on single-study estimates and further studies are needed to confirm these results. For postprandial outcomes, CD supplementation did not significantly affect TG levels overall (WMD: -0.002 mmol/L; 95% CI: -0.20 to 0.20; p=0.98) or insulin concentrations (WMD: -2.22 µU/ml; 95% CI: -5.43 to 0.99; p=0.17). However, after subgroup analysis, postprandial BG levels showed significant reductions with α-CD supplementation (WMD: -0.19 mmol/L; 95% CI: -0.38 to -0.007; p=0.04) and food-enrichment interventions (WMD: -0.12 mmol/L; 95% CI: -0.23 to -0.02; p=0.01). Pure supplement formulations also showed a borderline reduction in postprandial TG levels (WMD: -0.16 mmol/L; 95% CI: -0.33 to 0.01; p=0.06). Considerable heterogeneity was observed across several outcomes, whereas sensitivity analyses confirmed the robustness of the pooled estimates. Funnel plot assessment, Begg's and Egger's tests, and trim-and-fill analyses suggested no substantial publication bias. According to the GRADE framework, the certainty of evidence ranged from low to moderate.

CD supplementation, particularly α-CD and food-enrichment formulations, may modestly improve postprandial glycemic responses. However, overall evidence does not consistently support significant benefits for long-term cardiometabolic outcomes, and several subgroup findings were based on limited data. Further large-scale, long-duration randomized controlled trials are needed to confirm these effects.

The online version contains supplementary material available at 10.1007/s40200-026-01976-7.