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Background: Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction. Human studies suggest that elevated plasma β-carotene is associated with reductions in circulating cholesterol and the risk of myocardial infarction. The molecular mechanisms underlying these observations are unknown.Objective: The objective of this study was to determine the impact of dietary β-carotene and the activity of β-carotene oxygenase 1 (BCO1), which is the enzyme responsible for the conversion of β-carotene to vitamin A, on circulating cholesterol concentration.Methods: In our preclinical study, we compared the effects of a 10-d intervention with a diet containing 50 mg/kg of β-carotene on plasma cholesterol in 5-wk-old male and female C57 Black 6 wild-type and congenic BCO1-deficient mice. In our clinical study, we aimed to determine whether 5 common small nucleotide polymorphisms located in the BCO1 locus affected serum cholesterol concentrations in a population of young Mexican adults from the Universities of San Luis Potosí and Illinois: A Multidisciplinary Investigation on Genetics, Obesity, and Social-Environment (UP AMIGOS) cohort.Results: Upon β-carotene feeding, Bco1-/- mice accumulated >20-fold greater plasma β-carotene and had ∼30 mg/dL increased circulating total cholesterol (P < 0.01) and non-HDL cholesterol (P < 0.01) than wild-type congenic mice. Our results in the UP AMIGOS cohort show that the rs6564851 allele of BCO1, which has been linked to BCO1 enzymatic activity, was associated with a reduction in 10 mg/dL total cholesterol concentrations (P = 0.009) when adjusted for vitamin A and carotenoid intakes. Non-HDL-cholesterol concentration was also reduced by 10 mg/dL when the data were adjusted for vitamin A and total carotenoid intakes (P = 0.002), or vitamin A and β-carotene intakes (P = 0.002).Conclusions: Overall, our results in mice and young adults show that BCO1 activity impacts circulating cholesterol concentration, linking vitamin A formation with the risk of developing ASCVD. [ABSTRACT FROM AUTHOR]

The relations of dietary antioxidants vitamin C and beta-carotene to 30-year risk of stroke incidence and mortality were investigated prospectively in the Chicago Western Electric Study among 1,843 middle-aged men who remained free of cardiovascular disease through their second examination. Stroke mortality was ascertained from death certificates, and nonfatal stroke from records of the Health Care Financing Administration. During 46, 102 person-years of follow-up, 222 strokes occurred; 76 of them were fatal. After adjustment for age, systolic blood pressure, cigarette smoking, body mass index, serum cholesterol, total energy intake, alcohol consumption, and diabetes, relative risks (and 95% confidence intervals) for nonfatal and fatal strokes (n = 222) in highest versus lowest quartiles of dietary beta-carotene and vitamin C intake were 0.84 (0.57-1.24) and 0.71 (0.47-1.05), respectively. Generally similar results were observed for fatal strokes (n = 76). Although there was a modest decrease in risk of stroke with higher intake of beta-carotene and vitamin-C intake, these data do not provide definitive evidence that high intake of antioxidant vitamins decreases risk of stroke.