Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations.
We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
In this study, the pathway of β-citraurin biosynthesis, carotenoid contents and the expression of genes related to carotenoid metabolism were investigated in two varieties of Satsuma mandarin (Citrus ...unshiu), Yamashitabeni-wase, which accumulates β-citraurin predominantly, and Miyagawa-wase, which does not accumulate β-citraurin. The results suggested that CitCCD4 (for Carotenoid Cleavage Dioxygenase4) was a key gene contributing to the biosynthesis of β-citraurin. In the flavedo of Yamashitabeni-wase, the expression of CitCCD4 increased rapidly from September, which was consistent with the accumulation of β-citraurin. In the flavedo of Miyagawa-wase, the expression of CitCCD4 remained at an extremely low level during the ripening process, which was consistent with the absence of β-citraurin. Functional analysis showed that the CitCCD4 enzyme exhibited substrate specificity. It cleaved β-cryptoxanthin and zeaxanthin at the 7,8 or 7′,8′ position. But other carotenoids tested in this study (lycopene, α-carotene, β-carotene, all-trans-violaxanthin, and 9-cis-violaxanthin) were not cleaved by the CitCCD4 enzyme. The cleavage of β-cryptoxanthin and zeaxanthin by CitCCD4 led to the formation of β-citraurin. Additionally, with ethylene and red light-emitting diode light treatments, the gene expression of CitCCD4 was up-regulated in the flavedo of Yamashitabeni-wase. These increases in the expression of CitCCD4 were consistent with the accumulation of β-citraurin in the two treatments. These results might provide new strategies to improve the carotenoid contents and compositions of citrus fruits.
Enzymology of vertebrate carotenoid oxygenases Harrison, Earl H.; Kopec, Rachel E.
Biochimica et biophysica acta. Molecular and cell biology of lipids,
11/2020, Volume:
1865, Issue:
11
Journal Article
Peer reviewed
Open access
Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that function as carotenoid ...oxygenases. β-Carotene 15,15′-dioxygenase (BCO1) catalyzes the oxidative cleavage of the central 15,15′ carbon-carbon double of β-carotene bond by addition of molecular oxygen. The product of the reaction is retinaldehyde (retinal or β-apo-15-carotenal). Thus, BCO1 is the enzyme responsible for the conversion of provitamin A carotenoids to vitamin A. It also cleaves the 15,15′ bond of β-apocarotenals to yield retinal and of lycopene to yield apo-15-lycopenal. β-Carotene 9′,10′-dioxygenase (BCO2) catalyzes the cleavage of the 9,10 and 9′,10′ double bonds of a wider variety of carotenoids, including both provitamin A and non-provitamin A carotenoids, as well as the xanthophylls, lutein and zeaxanthin. Indeed, the enzyme shows a marked preference for utilization of these xanthophylls and other substrates with hydroxylated terminal rings. Studies of the phenotypes of BCO1 null, BCO2 null, and BCO1/2 double knockout mice and of humans with polymorphisms in the enzymes, has clarified the role of these enzymes in whole body carotenoid and vitamin A homeostasis. These studies also demonstrate the relationship between enzyme expression and whole body lipid and energy metabolism and oxidative stress.
In addition, relationships between BCO1 and BCO2 and the development or risk of metabolic diseases, eye diseases and cancer have been observed. While the precise roles of the enzymes in the pathophysiology of most of these diseases is not presently clear, these gaps in knowledge provide fertile ground for rigorous future investigations.
This article is part of a Special Issue entitled Carotenoids: Recent Advances in Cell and Molecular Biology edited by Johannes von Lintig and Loredana Quadro.
•Vertebrates have two carotenoid cleavage enzymes, a family widespread in other taxa.•BCO1 catalyzes central cleavage of dietary provitamin A carotenoids to retinaldehyde.•BCO2 catalyzes eccentric cleavage of a wider variety of carotenes and xanthophylls.•BCO1/2 function in vitamin A, carotenoid, lipid, energy, and oxidative homeostasis•BCO1/2 SNPs in humans are associated with metabolic, eye, and neoplastic diseases.
Beta-carotene (BC), a red-colored pigment found in plants and animals, is one of the most extensively investigated carotenoids due to its provitamin-A, antioxidant, and anticancer properties. The ...anticancer activity of BC through oral administration is severely affected due to its low bioavailability and oxidative degradation. The present study aimed to formulate and characterize solid lipid nanoparticles (SLNs) of BC for enhanced bioavailability and therapeutic efficacy. Beta-carotene-loaded solid lipid nanoparticles (BC-SLNs) were prepared employing different combinations of glyceryl monostearate and gelucire. The characterization studies were performed for particle size, morphology, release behavior, and stability. BC-SLNs were also studied for
in vitro
cytotoxicity in human breast cancer cell lines (MCF-7) and pharmacokinetic studies in Wistar rats. The cytotoxicity studies confirmed that encapsulation of BC within the lipid bilayers of nanoparticles did not affect its anticancer efficacy. An improved anticancer activity was observed in BC-SLNs as compared to the free BC. BC-SLNs enhanced the bioavailability of BC on oral administration by sustaining its release from the lipid core and prolongation of circulation time in the body. Similarly, area under the curve (AUC
total
) enhanced 1.92-times more when BC was incorporated into SLNs as compared to free BC. In conclusion, solid lipid nanoparticles could be an effective and promising strategy to improve the biopharmaceutical properties of carotenoids for anticancer effects.
ABSTRACT
The key enzyme responsible for β‐carotene conversion into retinal is β‐carotene 15,15′‐monoxygenase (BCMO1). Since it has been reported that the conversion of β‐carotene into vitamin A is ...highly variable in up to 45% of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24%, respectively. In vitro biochemical characterization of the recombinant 267S + 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57% (P<0.001). Assessment of the responsiveness to a pharmacological dose of β‐carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert β‐carotene, as indicated through reduced retinyl palmitate:β‐carotene ratios in the triglyceride‐rich lipoprotein fraction −32% (P=0.005) and −69% (P=0.001), respectively and increased fasting β‐carotene concentrations +160% (P=0.025) and +240% (P=0.041), respectively. Our data show that there is genetic variability in β‐carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population.—Leung, W. C., Hessel, S., Méplan, C., Flint, J., Oberhauser, V., Tourniaire, F., Hesketh, J. E., vonLintig, J., Lietz, G. Two common single nucleotide polymorphisms in the gene encoding β‐carotene 15,15′‐monoxygenase alter β‐carotene metabolism in female volunteers. FASEB J. 23, 1041–1053 (2009)
Reduction of nitrogen application in crop production is desirable for ecological and health-related reasons. Interestingly, nitrogen deficiency can lead to enhanced concentrations of polyphenols in ...plants. The reason for this is still under discussion. The plants' response to low nitrogen concentration can interact with other factors, for example radiation intensity. We cultivated red and green leaf lettuce hydroponically in a Mediterranean greenhouse, supplying three different levels of nitrogen (12 mM, 3 mM, 0.75 mM), either in full or reduced (-50%) radiation intensity. In both red and green lettuce, we found clear effects of the nitrogen treatments on growth characteristics, phenolic and photosynthetic compounds, nitrogen, nitrate and carbon concentration of the plants. Interestingly, the concentrations of all main flavonoid glycosides, caffeic acid derivatives, and sucrose increased with decreasing nitrogen concentration, whereas those of chlorophylls, beta-carotene, neoxanthin, lactucaxanthin, all trans- and cis-violaxanthin decreased. The constitutive concentrations of polyphenols were lower in the green cultivar, but their relative increase was more pronounced than in the red cultivar. The constitutive concentrations of chlorophylls, beta-carotene, neoxanthin, all trans- and cis-violaxanthin were similar in red and green lettuce and with decreasing nitrogen concentration they declined to a similar extent in both cultivars. We only detected little influence of the radiation treatments, e.g. on anthocyanin concentration, and hardly any interaction between radiation and nitrogen concentration. Our results imply a greater physiological plasticity of green compared to the red lettuce regarding its phenolic compounds. They support the photoprotection theory regarding anthocyanins as well as the theory that the deamination activity of phenylalanine ammonia-lyase drives phenylpropanoid synthesis.
In recent years, a number of studies have produced evidence to suggest that consuming carotenoids may provide a variety of health benefits including a reduced incidence of a number of cancers, ...reduced risk of cardiovascular disease, and improved eye health. Evolving evidence on the health benefits of several carotenoids has sparked interest in incorporating more carotenoids into functional food products. Unfortunately, the same structural attributes of carotenoids that are thought to impart health benefits also make these compounds highly susceptible to oxidation. Given the susceptibility of carotenoids to degradation, particularly once they have been extracted from biological tissues, it is important to understand the major mechanisms of oxidation in order to design delivery systems that protect these compounds when they are used as functional food ingredients. This article reviews current understanding of the oxidation mechanisms by which carotenoids are degraded, including pathways induced by heat, light, oxygen, acid, transition metal, or interactions with radical species. In addition, several carotenoid delivery systems are evaluated for their potential to decrease carotenoid degradation in functional food products.
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•Red-peeled huyou accumulates β-citraurin in peel while ordinary huyou not.•Transcript level of CCD4b1 is nearly 100 fold higher in red-peeled huyou peel.•β-Citraurin accumulation was ...most favored at 15 °C in red-peeled huyou peel.•Ethylene did not affect β-citraurin accumulation in red-peeled huyou peel.•Expression of CCD4b1 and PSY1 paralleled temperature effects on peel color.
Red-peeled huyou has a distinct red peel color due mainly to the presence of red apocarotenoid β-citraurin as well as the increase in amount of total carotenoids. The expression level of carotenoid cleavage dioxygenase 4b1 (CCD4b1) accounted for 99.0% of total transcript abundance of CCD4s in red-peeled huyou peel and was nearly 100 times higher than that in ordinary huyou. β-Citraurin accumulation and peel coloration was mostly favored at 15 °C but strongly inhibited at moderately high temperatures 20 °C and 25 °C. Exogenous ethylene application for 3 d had no obvious effect on β-citraurin accumulation in red-peeled huyou but holding fruit at moderately higher temperatures (20 °C and 25 °C) for 3 d had a significant adverse effect on β-citraurin accumulation. The expression of phytoene synthase 1 (PSY1) and CCD4b1 was higher at 10 °C and 15 °C and significantly lower at 20 °C and 25 °C. The mechanisms governing the accumulation of β-citraurin are discussed.
The objectives of this research were to study the encapsulation of beta‐carotene (BC) in solid lipid microparticles (SLM) of palm stearin (PS) and stabilized with hydrolyzed soy protein isolate ...(HSPI), and also to investigate the effect of alpha‐tocopherol (TOC) addition to the systems. Through the characterizations of SLM produced with different formulations, it was verified that systems with 5% (w/v) PS, 1.0% (w/v) HSPI, and 0.3% (w/v) xanthan gum (XG) presented the highest stability, with average diameters of approximately 1.2 μm. This formulation was applied for the production of BC‐loaded SLM, with different concentrations of TOC. In SLM containing TOC, nearly 75% of encapsulated BC was preserved after 45 d of storage. The kinetic profiles for degradation of encapsulated BC were fitted to a pseudo‐1st‐order model, and the results showed that the main difference among the systems with different BC:TOC ratios was the residual concentration of BC. The stability of the BC‐loaded SLMs was also studied after stress conditions, and the results showed that the SLMs were able to support thermal treatments over 60 °C but presented low stability after different ionic strength stresses.
Practical Application
An approach to improve the stability and increase bioavailability of the beta‐carotene is to encapsulate this compound in lipid‐based matrices, such as the solid lipid microparticles (SLM). The production method (high shear mixing) applied in this study for the production of the beta‐carotene‐loaded SLM is easy to implement on an industrial scale. A great advantage of using SLM is that they do not require equipment such as high‐pressure homogenizers, thus making the SLM a cheaper ingredient for incorporation into food products than lipid nanoparticles.
Atherosclerosis is a major cause of morbidity and mortality in developed societies, and begins when activated endothelial cells recruit monocytes and T-cells from the bloodstream into the arterial ...wall. Macrophages that accumulate cholesterol and other fatty materials are transformed into foam cells. Several epidemiological studies have demonstrated that a diet rich in carotenoids is associated with a reduced risk of heart disease; while previous work in our laboratory has shown that the 9-cis β-carotene rich alga Dunaliella inhibits atherogenesis in mice. The effect of 9-cis β-carotene on macrophage foam cell formation has not yet been investigated. In the present work, we sought to study whether the 9-cis β-carotene isomer, isolated from the alga Dunaliella, can inhibit macrophage foam cell formation upon its conversion to retinoids. The 9-cis β-carotene and Dunaliella lipid extract inhibited foam cell formation in the RAW264.7 cell line, similar to 9-cis retinoic acid. Furthermore, dietary enrichment with the algal powder in mice resulted in carotenoid accumulation in the peritoneal macrophages and in the inhibition of foam cell formation ex-vivo and in-vivo. We also found that the β-carotene cleavage enzyme β-carotene 15,15'-monooxygenase (BCMO1) is expressed and active in macrophages. Finally, 9-cis β-carotene, as well as the Dunaliella extract, activated the nuclear receptor RXR in hepa1-6 cells. These results indicate that dietary carotenoids, such as 9-cis β-carotene, accumulate in macrophages and can be locally cleaved by endogenous BCMO1 to form 9-cis retinoic acid and other retinoids. Subsequently, these retinoids activate the nuclear receptor RXR that, along with additional nuclear receptors, can affect various metabolic pathways, including those involved in foam cell formation and atherosclerosis.
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