Carrots are a good source of beta-carotene, which is a precursor of vitamin A. But to get the full health benefits of this superfood, you need an active enzyme to produce this vitamin.
Beta-carotene is the bioactive compound that gives carrots their orange color. Studies with humans and mice show the conversion of beta-carotene to vitamin A reduces “bad” cholesterol in the blood.
Thus, beta-carotene can help protect against atherosclerosis development, which leads to the accumulation of fats and cholesterol in our arteries.
Atherosclerosis cardiovascular disease is the primary cause of death worldwide, says Jaume Amengual, assistant professor of personalized nutrition in the Department of Food Science and Human Nutrition at University of Illinois.
Amengual and his colleagues conducted two studies to further understand the effects of beta-carotene on cardiovascular health. They confirmed its importance, but identified a critical step in the process.
Beta-carotene converts to vitamin A with the help of an enzyme called beta-carotene oxygenase 1 (BCO1). A genetic variation determines if you have a more or less active version of BCO1.
People with a less active enzyme could need other sources for vitamin A in their diet, Amengual says.
The first study, published in the Journal of Nutrition, analyzed blood and DNA samples from 767 healthy young adults aged 18 to 25. As expected the researchers found a correlation between BCO1 activity and bad cholesterol level.
“People who had a genetic variant associated with making the enzyme BCO1 more active had lower cholesterol in their blood. That was our first observation,” Amengual notes.
To follow up on these findings, Amengual and his colleagues conducted a second study, published in the Journal of Lipid Research, using mice.
“In the human study, we saw that cholesterol was higher in people who do not produce much vitamin A. To know if that observation has an effect in the long run, we would have to wait 70 years to see if they develop cardiovascular. In real life, that is not doable. That’s why we use animals for certain studies, so we can speed up the process,” he explains.
“The main findings of the mice study reproduce what we found in humans. We saw that when we give beta-carotene to mice, they have lower cholesterol levels. These mice develop smaller atherosclerosis lesions, or plaques, in their arteries.
This means that mice fed beta-carotene are more protected against atherosclerosis than those fed a diet without this bioactive compound,” Amengual states.
In the second study, the researchers also investigated the biochemical pathways of these processes, determining where in the body the effect occurs.
“We narrow it down to the liver as the organ in charge of producing and secreting lipoproteins to the bloodstream, including those lipoproteins known as bad cholesterol. We observed that in mice with high levels of vitamin A, the secretion of lipids into the bloodstream slows down,” Amengual notes.
Understanding how the BCO1 enzyme relates to cholesterol has important implications. Typically, high beta-carotene levels in the blood are associated with health benefits. But it could also be a sign of a less active BCO1 enzyme that is not converting the beta-carotene we eat into vitamin A.
Up to 50% of the population have the less-active variant of the enzyme, Amengual notes. That means their body is slower at producing vitamin A from a plant source, and they could need to get this nutrient directly from an animal source such as milk, or cheese, for example.
Malnutrition and micronutrient deficiencies contribute to major health problems in developing countries. Looking at vitamin A, an insufficient sustenance is observed in about 250 million pre-school children [1] and 19.1 million pregnant women. Plasma retinol concentrations < 0.7 µmol/L define vitamin A deficiency (VAD), with sub-Saharan Africa and South East Asia showing the highest prevalence [2,3].
The main symptoms of VAD comprise visual impairment (xerophthalmia and night blindness), and increased morbidity and mortality from infectious diseases (e.g., measles and diarrhea) caused by an impaired immune system [4]. During pregnancy, low plasma retinol concentrations have a negative impact on cell differentiation and proliferation, thereby leading to disturbed embryonal development and growth retardation of the child [5,6].
Vitamin A can either be consumed as preformed vitamin A (retinol, retinyl palmitate) from animal-derived products (meat, especially liver, and dairy products) or as carotenoids with provitamin A (proVA) activity (α-carotene, β-carotene, β-cryptoxanthin) from plant-based foods (yellow- and orange-fleshy fruits and vegetables, green leaves) [3,7].
However, African diets are low in the consumption of animal products and proVA mainly contributes to the vitamin A supply [8]. In the enterocytes, 55–75% of the absorbed carotenoids are cleaved centrally into one (α-carotene, β-cryptoxanthin) or two (β-carotene) molecules of (all-trans-) retinal by the cytoplasmatic protein β-carotene 15,15’-oxygenase (BCO1), which is the key cleaving enzyme in the vitamin A metabolism.
BCO1 is mainly expressed in the small intestine, but also in other organs like the liver, kidney, reproductive tissues, skin, and eyes, indicating a need of vitamin A in these tissues [9,10]. The synthesized retinal can further be metabolized to (all-trans-) retinol if required, or to transcriptionally active retinoic acid [11].
To avoid the accumulation of toxic amounts of retinol in the body, the cleavage of proVA is regulated by a negative feedback loop. Synthesized retinoic acid binds to retinoic acid receptors (RARs), which induces the expression of intestinal transcription factor intestine specific homeobox (ISX). The induction of ISX inhibits the expression of scavenger receptor class B member 1 (SR-BI) and BCO1, and hence leads to a reduction in the uptake and cleavage of dietary carotenoids [12].
Alicke et al. previously analyzed data of 188 adolescents from the Agogo 2000 birth cohort study to characterize “the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors” in rural Ghana. In this population, more than one-third (36%) had VAD, and the median plasma retinol concentration was 0.77 (IQR: 0.49–1.05) µmol/L [13]. However, the total plasma carotenoid concentrations (median: 2.8 (2.2–3.8) µmol/L) and β-carotene concentrations (1.49 (1.12–2.22) µmol/L) were three times higher than the reference values [14,15].
This was also seen among Nigerian mother–child pairs, who showed lower retinol and higher plasma carotenoid concentrations than mother–child pairs in the United States [16].
Many genetic variants in enzymes associated with the vitamin A metabolism were identified and associated with altered functionality [17–21]. As the conversion of β-carotene is mediated by BCO1, we focused on five genetic variants in this enzyme to explain the observed low retinol but high carotenoid concentrations in the adolescents in the Agogo 2000 birth cohort study.
The BCO1 variant rs6564851 is the best described candidate in the literature, showing higher β-carotene and α-carotene concentrations in carriers of the G allele, caused by a decreased conversion efficiency of the BCO1 enzyme [17,18,21,22]. Further, the single nucleotide polymorphisms (SNPs) rs7500996 and rs10048138 have an impact on lutein and zeaxanthin concentrations [18,21].
The A allele of SNP rs10048138 is associated with higher concentrations of these carotenoids [18]. SNPs rs6420424 and rs8044334 have been reported by Ferrucci et al. and Lietz et al., with carriers of the A and G allele showing higher plasma β-carotene concentrations, due to a decrease of the BCO1 conversion efficiency [17,22].
Thus, genetic variants in the proVA cleaving enzyme can influence the vitamin A production in the human body.
Food fortification and vitamin A supplementation have reduced VAD prevalence in many affected
countries, with the exception of sub-Saharan Africa [2]. The reasons for this still remain to be uncovered. Potential determinants comprise food-related (matrix, composition) and host-related
factors (socio-demographic factors, health and nutritional status, genetics). While ethnic background has already been coined as a predictor of carotenoid and retinol concentrations, the underlying mechanisms are poorly understood [23,24].
Owing to the previously observed conflicts between retinol and carotenoid concentrations, and due to the lack of data on BCO1-relevance in this study population, the aim of this secondary, cross-sectional analysis was to identify the relationships between relevant genetic variants in the BCO1 gene and plasma carotenoid concentrations among Ghanaian adolescents in the Agogo 2000 birth cohort study. The primary aim of the study was to establish the impact of gestational malaria on health outcomes in later life.
Conclusions
To date, food fortification is established in affected countries to improve the vitamin A status of populations at risk. Regarding the presence of genetic variant encoding in the cleaving enzyme BCO1, preformed vitamin A should be considered as the main component to be added to foods.
Further, introducing biofortification of plants high in β-carotene might have a reduced benefit on retinol concentrations in the body when the conversion efficiency of the BCO1 gene product is impaired. Therefore, it is warranted to investigate the role of BCO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in sub-Saharan Africa.
REFERENCE : doi:10.3390/nu12061786
More information: Jaume Amengual et al. β-Carotene Oxygenase 1 Activity Modulates Circulating Cholesterol Concentrations in Mice and Humans, The Journal of Nutrition (2020). DOI: 10.1093/jn/nxaa143
