Effect of Cyclodextrins on Cardiometabolic Indices: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Publisher

Summary: Could cyclodextrins improve blood sugar control? A meta-analysis suggests modest post-meal benefits, but no consistent long-term cardiometabolic gains. #Glucose #Nutrition

Talebi S ; Bagherniya M ; Hassanizadeh S ; Santos R D ; Kesharwani P ; Sahebkar A
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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 Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.