Effect of Vitamin E Supplementation on Biomarkers of Endothelial Function in Adults: A GRADE-assessed Systematic Review and Dose-Response Meta-Analysis

Abstract Background and Objective Endothelial dysfunction is a central factor in the development of cardiovascular diseases. Serum adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are important biomarkers of vascular health. Due to its antioxidant properties and the inconsistent findings from previous clinical trials, the potential role of Vitamin E in improving endothelial function remains unclear. This study aims to systematically evaluate the effects of Vitamin E supplementation on endothelial function in adults. Methods A comprehensive systematic search was conducted on databases to find relevant randomized controlled trials (RCTs) published up to October 2025. Following the study selection process, data were extracted from eligible RCTs. The overall effect size was estimated using weighted mean differences (WMDs) with 95% confidence intervals (CIs) via a random-effects model. Heterogeneity was assessed, including sensitivity analysis and assessment of publication bias. Statistical analyses were conducted using STATA. Results The pooled analysis of 12 RCTs revealed that Vitamin E supplementation significantly decreased VCAM-1 levels (WMD: -21.59 ng/ml, 95% CI: [-42.00, -1.19], p = 0.038). However, no significant effect was observed on ICAM-1 levels (WMD: -2.08 ng/ml, 95% CI: [-5.72, 1.55], p = 0.262). Subgroup analysis revealed greater reductions with longer trials, specific isoforms (α-tocopherol for ICAM-1, tocotrienol for VCAM-1), and lower doses (≤ 400 IU/day). Notable effects were observed in overweight individuals and patients with renal disease for ICAM-1 and in individuals with normal BMI for VCAM. Conclusion Vitamin E supplementation appears to exert beneficial effects on biomarkers of endothelial function, with significant reductions in ICAM-1 observed in overweight individuals, low-dose recipients, and those with renal disease. Additionally, reductions in VCAM-1 were seen in longer trials, among normal-weight participants, and with tocotrienol or mixed isoforms. These findings suggest that the efficacy of vitamin E on endothelial markers may depend on dose, isoform, intervention duration, and participant characteristics.