Maintaining normal vascular endothelial function is important for preventing arteriosclerosis. Flow-mediated dilatation (FMD) is widely used to evaluate vascular endothelial function. Lycopene, a carotenoid abundant in tomatoes, has been reported to improve FMD, but its effect after 4 weeks of intake remains unclear. We conducted a randomized, placebo-controlled, double-blind, parallel-group trial to assess the effects of lycopene. Seventy-five healthy adults with borderline FMD (4–7%) were randomly assigned to placebo juice (0.7 mg lycopene), tomato juice (TJ, 15.0 mg), or high-lycopene tomato juice (HLTJ, 26.7 mg) groups. FMD, serum lycopene, oxidative stress markers (malondialdehyde, 8-hydroxy-2′-deoxyguanosine, 8-iso-prostaglandin F2α), and nitrogen oxide concentrations were measured every 4 weeks over a 12-week intervention. The participants analyzed included 23 (placebo), 25 (TJ), and 24 (HLTJ). Data were analyzed using a linear mixed effects model adjusting for baseline covariates and a post hoc Dunnett's test with Bonferroni correction for intergroup comparisons. At week 12, FMD was significantly higher in the TJ (6.1 ± 0.5%, p < 0.001) and HLTJ groups (7.0 ± 0.7%, p < 0.001) than in the placebo group (5.4 ± 0.6%). In the HLTJ group, FMD at weeks 4 (6.2 ± 1.0%, p < 0.001) and 8 (6.7 ± 0.7%, p < 0.001) was significantly higher than in the placebo group (5.4 ± 0.9% and 5.3 ± 0.6%, respectively). Serum lycopene concentrations were significantly increased in TJ and HLTJ groups than in the placebo group. No significant differences were observed in oxidative stress or nitrogen oxide levels. These findings suggest that lycopene intake improves vascular endothelial function, though the mechanism remains unclear. Trial registration: UMIN000051176.

Background/Objectives: Vascular endothelial dysfunction is an early marker of cardiovascular disease. Lycopene, a naturally red carotenoid with strong antioxidant activity, may improve vascular endothelial function. This systematic review and meta-analysis examined lycopene’s effects on vascular endothelial function in healthy adults in the context of cardiovascular risk assessment. Methods: In June 2026, we searched four literature databases (Ichushi-Web, PubMed, Cochrane Central Register of Controlled Trials, and Global Index Medicus), three clinical trial registries (International Clinical Trial Registry Platform, ClinicalTrials.gov, and University Hospital Medical Information Network Clinical Trials Registry), and notification information for Foods with Function Claims, using peer-reviewed search strategies. We extracted human intervention studies assessing oral lycopene intake and vascular endothelial function. Two authors independently selected eligible studies and assessed the risk of bias. Data were pooled as mean differences (MDs) and analyzed using a random-effects model. The protocol was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000058348). Results: Six studies were included in this systematic review. A meta-analysis of four continuous (≥7 days) lycopene-containing product intake studies measuring flow-mediated dilation (FMD) (n = 182) revealed a significant increase in FMD (MD = 1.36, 95% confidence interval: 0.20, 2.51, p = 0.02). The certainty of the evidence across the four studies was limited and moderate. One study not included in the meta-analysis showed that 15 mg of lycopene intake for 8 weeks significantly increased the reactive hyperemia peripheral arterial tonometry index. Conclusions: This systematic review/meta-analysis with limited and moderate certainty evidence suggests that the continuous intake of lycopene-containing products may have beneficial effects on vascular endothelial function in healthy adults. However, the findings were derived from a small-scale meta-analysis in which the result was no longer statistically significant after the exclusion of one study.