Circulating Lycopene and β-Carotene Levels Are Inversely Associated with Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis.

Background: Carotid intima-media thickness (IMT) is a well-established surrogate marker of subclinical atherosclerosis and a predictor of cardiovascular risk. Carotenoids, particularly lycopene and β-carotene, have been proposed as protective antioxidants against vascular damage, but evidence from population-based studies is inconsistent. Objective: We aim to perform a systematic review and meta-analysis of the associations between circulating levels of lycopene and β-carotene and carotid IMT in the general adult population, including potential sex-specific effects. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to March 2025, following PRISMA guidelines (PROSPERO registration: CRD420251003810). Observational and experimental studies reporting cross-sectional associations between plasma carotenoids and IMT were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated via random effects models. Subgroup and meta-regression analyses explored potential modifiers, including sex and cardiovascular risk factors. Results: Thirteen studies (n = 9131; mean age 46.4-71.6 years) met the inclusion criteria, eight of which were eligible for meta-analysis. High circulating lycopene levels were significantly associated with low IMT (pooled OR = 0.70; 95% CI: 0.59-0.84; I2 = 65.7%). The association was stronger in men (OR = 0.62; 95% CI: 0.45-0.84) than in women (OR = 0.74; 95% CI: 0.58-0.95). In contrast, β-carotene was only marginally associated with IMT (pooled OR = 0.96; 95% CI: 0.92-0.99; I2 = 72.6%). Meta-regression suggested that systolic blood pressure modified the lycopene-IMT relationship, whereas body mass index and low-density lipoprotein cholesterol influenced the β-carotene-IMT association. No evidence of publication bias was found. Conclusions: Increased serum lycopene concentrations, and to a lesser extent β-carotene concentrations, are inversely associated with carotid IMT, suggesting a protective role of lycopene in vascular health. The effect appears more pronounced in men, highlighting potential sex-specific differences in carotenoid metabolism and cardiovascular risk modulation.