Atherosclerotic lesions containing lipoproteins form when elevated cholesterol levels lead to the accumulation of lipoproteins in the subendothelial space of arterial walls. β-carotene, a carotenoid that is converted into vitamin A by β-carotene oxygenase 1 (BCO1), causes the yellow color associated with these deposits. The existing literature demonstrates an inverse relationship between plasma concentrations of β-carotene and the incidence of atherosclerotic cardiovascular disease, yet they provide little description of the molecular pathways involved in the inverse association. Amengual and colleagues examined the impact of β-carotene consumption and BCO1 activity on cholesterol metabolism. The results of their study are found in the August 2020 issue of The Journal of Nutrition.
Their first study measured plasma cholesterol in control and BCO1-deficient mice provided diets containing 50 mg/kg of β-carotene for 10 days. Their second study explored the impact of 5 common small nucleotide polymorphisms in the BCO1 gene locus on serum cholesterol in young Mexican adults participating in the UP AMIGOS study.
The BCO1 knockout mice responded to β-carotene consumption by having increased plasma β-carotene, total cholesterol, and non-HDL cholesterol, as compared to the control mice. The results from the human study demonstrated that one polymorphism located upstream of the BCO1 gene coding region resulted in a reduction in total cholesterol concentrations once the data were adjusted for vitamin A and carotenoid intakes. When adjustments were made for vitamin A and either total carotenoids or β-carotene intakes, the concentration of non-HDL cholesterol was also reduced. Collectively, these observations led the authors to conclude that BCO1 activity affects circulating cholesterol levels, which helps to explain the relationship between vitamin A formation and the risk of atherosclerotic cardiovascular disease.
In a commentary on this article, von Lintig argues the results described by Amengual and colleagues could be a “gamechanger” in our understanding of the interaction between β-carotene and cholesterol metabolism. The observations linking BCO1 activity and cholesterol metabolism provide a molecular mechanism that, in part, explain the ability of vitamin A to serve as a modulator of inflammation and lipid metabolism. This led him to conclude that larger clinical studies are needed to continue the exploration of this relationship, and the importance of β-carotene intake in the development of atherosclerotic cardiovascular disease.
Amengual J, Coronel J, Marques C, Aradillas-Garcia C, Morales JMV, Andrade FCD, Erdman Jr JW, Teran-Garcia M. β-carotene oxygenase 1 activity modulates circulating cholesterol concentrations in mice and humans. The Journal of Nutrition, Volume 150, Issue 8, August 2020, Pages 2023–2030, https://doi.org/10.1093/jn/nxaa143.
Commentary provided by:
von Lintig J. Eat your carrots! β-carotene and cholesterol homeostasis. The Journal of Nutrition, Volume 150, Issue 8, August 2020, Pages 2003–2005, https://doi.org/10.1093/jn/nxaa189.