β-Carotene Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

beta-carotene is widely available in plant-based foods, while the efficacy of beta-carotene supplementation on cardiovascular disease (CVD) risk remains controversial. Hence, we performed a systematic review and meta-analysis on randomized controlled trials to investigate the associations between beta-carotene supplementation and CVD risk as well as mortality. We conducted literature searches across eight databases and screened the publications from January 1900 to March 2022 on the topic of beta-carotene treatments and cardiovascular outcomes. There were 10 trials and 16 reports included in the meta-analysis with a total of 182,788 individuals enrolled in the study. Results from the random-effects models indicated that beta-carotene supplementation slightly increased overall cardiovascular incidence (RR: 1.04; 95% CI: 1.00, 1.08) and was constantly associated with increased cardiovascular mortality (RR: 1.12; 95% CI: 1.04, 1.19). Subgroup analyses suggested that, when beta-carotene treatments were given singly, a higher risk of cardiovascular outcomes was observed (RR: 1.06; 95% CI: 1.01, 1.12). In addition, cigarettes smoking was shown to be a risk behavior associated with increased cardiovascular incidence and mortality in the beta-carotene intervention group. In sum, the evidence of this study demonstrated that beta-carotene supplementation had no beneficial effects on CVD incidence and potential harmful effects on CVD mortality. Further studies on understanding the efficacy of multivitamin supplementation in nutrient-deficient or sub-optimal populations are important for developing the tolerable upper intake level for beta-carotene of different age and sex groups.