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

β-carotene is widely available in plant-based foods, while the efficacy of β-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 β-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 β-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 β-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 β-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 β-carotene intervention group. In sum, the evidence of this study demonstrated that β-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 β-carotene of different age and sex groups.