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Advances in Nutrition (Bethesda, Md.) May 2024A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and β-carotene and type 2... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and β-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and the Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, β-cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random-effects models. The certainty of the evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations framework. Among 6190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was seen at intakes of 70 mg/d of vitamin C (RR: 0.76; CI: 0.61, 0.95), 12 mg/d of vitamin E (RR: 0.72; CI: 0.61, 0.86), and 4 mg/d of β-carotene (RR: 0.78; CI: 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI: 0.93, 1.10) or β-carotene (RR: 0.98; CI: 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI: 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI: -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and β-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and β-carotene may lower risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. This systematic review and meta-analysis was registered in PROSPERO with registration number CRD42022343482.
Topics: Diabetes Mellitus, Type 2; Humans; beta Carotene; Ascorbic Acid; Vitamin E; Antioxidants; Dietary Supplements; Insulin Resistance; Diet; Risk Factors; Male; Female; Middle Aged; Adult; Aged
PubMed: 38493875
DOI: 10.1016/j.advnut.2024.100211 -
Free Radical Research May 2015β-Carotene, the precursor of vitamin A, possesses pronounced radical scavenging properties. This has centered the attention on β-carotene dietary supplementation in... (Review)
Review
β-Carotene, the precursor of vitamin A, possesses pronounced radical scavenging properties. This has centered the attention on β-carotene dietary supplementation in healthcare as well as in the therapy of degenerative disorders and several cancer types. However, two intervention trials with β-carotene have revealed adverse effects on two proband groups, that is, cigarette smokers and asbestos-exposed workers. Beside other causative reasons, the detrimental effects observed have been related to the oxidation products of β-carotene. Their generation originates in the polyene structure of β-carotene that is beneficial for radical scavenging, but is also prone to oxidation. Depending on the dominant degradation mechanism, bond cleavage might occur either randomly or at defined positions of the conjugated electron system, resulting in a diversity of cleavage products (CPs). Due to their instability and hydrophobicity, the handling of standards and real samples containing β-carotene and related CPs requires preventive measures during specimen preparation, analyte extraction, and final analysis, to avoid artificial degradation and to preserve the initial analyte portfolio. This review critically discusses different preparation strategies of standards and treatment solutions, and also addresses their protection from oxidation. Additionally, in vitro oxidation strategies for the generation of oxidative model compounds are surveyed. Extraction methods are discussed for volatile and non-volatile CPs individually. Gas chromatography (GC), (ultra)high performance liquid chromatography (U)HPLC, and capillary electrochromatography (CEC) are reviewed as analytical tools for final analyte analysis. For identity confirmation of analytes, mass spectrometry (MS) is indispensable, and the appropriate ionization principles are comprehensively discussed. The final sections cover analysis of real samples and aspects of quality assurance, namely matrix effects and method validation.
Topics: Animals; Biological Assay; Calibration; Cells, Cultured; Chemistry Techniques, Analytical; Drug Stability; Free Radical Scavengers; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Oxidants; Oxidation-Reduction; Reference Standards; Solubility; Structure-Activity Relationship; beta Carotene
PubMed: 25867077
DOI: 10.3109/10715762.2015.1022539 -
Biochimica Et Biophysica Acta.... May 2022Vitamin A deficiency (VAD) results in intestinal inflammation, increased redox stress and reactive oxygen species (ROS) levels, imbalanced inflammatory and...
Vitamin A deficiency (VAD) results in intestinal inflammation, increased redox stress and reactive oxygen species (ROS) levels, imbalanced inflammatory and immunomodulatory cytokines, compromised barrier function, and perturbations of the gut microbiome. To combat VAD dietary interventions with β-carotene, the most abundant precursor of vitamin A, are recommended. However, the impact of β-carotene on intestinal health during VAD has not been fully clarified, especially regarding the VAD-associated intestinal dysbiosis. Here we addressed this question by using LratRbp (vitamin A deficient) mice deprived of dietary preformed vitamin A and supplemented with β-carotene as the sole source of the vitamin, alongside with WT (vitamin A sufficient) mice. We found that dietary β-carotene impacted intestinal vitamin A status, barrier integrity and inflammation in both WT and LratRbp (vitamin A deficient) mice on the vitamin A-free diet. However, it did so to a greater extent under overt VAD. Dietary β-carotene also modified the taxonomic profile of the fecal microbiome, but only under VAD. Given the similarity of the VAD-associated intestinal phenotypes with those of several other disorders of the gut, collectively known as Inflammatory Bowel Disease (IBD) Syndrome, these findings are broadly relevant to the effort of developing diet-based intervention strategies to ameliorate intestinal pathological conditions.
Topics: Animals; Disease Models, Animal; Dysbiosis; Inflammation; Intestinal Diseases; Mice; Vitamin A; Vitamin A Deficiency; beta Carotene
PubMed: 35158041
DOI: 10.1016/j.bbalip.2022.159122 -
Nutrients Apr 2019Over the past decades, obesity has become a rising health problem as the accessibility to high calorie, low nutritional value food has increased. Research shows that... (Review)
Review
Over the past decades, obesity has become a rising health problem as the accessibility to high calorie, low nutritional value food has increased. Research shows that some bioactive components in fruits and vegetables, such as carotenoids, could contribute to the prevention and treatment of obesity. Some of these carotenoids are responsible for vitamin A production, a hormone-like vitamin with pleiotropic effects in mammals. Among these effects, vitamin A is a potent regulator of adipose tissue development, and is therefore important for obesity. This review focuses on the role of the provitamin A carotenoid β-carotene in human health, emphasizing the mechanisms by which this compound and its derivatives regulate adipocyte biology. It also discusses the physiological relevance of carotenoid accumulation, the implication of the carotenoid-cleaving enzymes, and the technical difficulties and considerations researchers must take when working with these bioactive molecules. Thanks to the broad spectrum of functions carotenoids have in modern nutrition and health, it is necessary to understand their benefits regarding to metabolic diseases such as obesity in order to evaluate their applicability to the medical and pharmaceutical fields.
Topics: Adipocytes; Animals; Diet; Humans; Obesity; beta Carotene; beta-Carotene 15,15'-Monooxygenase
PubMed: 31013923
DOI: 10.3390/nu11040842 -
ELife Feb 2024β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved...
β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in mice implicate vitamin A production in the effects of β-carotene on atherosclerosis resolution. To explore the direct implication of dietary β-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that β-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of β-carotene on atherosclerosis resolution. Our data highlight the potential of β-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.
Topics: Mice; Humans; Animals; beta Carotene; Vitamin A; Liver; Atherosclerosis; Lipids
PubMed: 38319073
DOI: 10.7554/eLife.87430 -
Human & Experimental Toxicology 2022Beta-carotene (β-carotene, BC) is one of the carotenoids most commonly consumed by humans. BCMO1 is expressed in various human tissues and is considered to be a key...
Beta-carotene (β-carotene, BC) is one of the carotenoids most commonly consumed by humans. BCMO1 is expressed in various human tissues and is considered to be a key enzyme that converts BC into vitamin A. Studies indicated that BC-derived carotenoid signaling molecules affected the physiological functions of fat cells. In order to investigate the role and possible molecular mechanism of BC in mouse adipocytes, we conducted 4-group and 2-group difference analysis based on the data of GSE27271 chip in the Gene Expression Omnibus database. Genes differentially expressed in the inguinal white adipose tissue of mice were screened out and combined with the STRING database to construct protein-protein interaction (PPI) networks. Among them, Alb (albumin), Mug1 (murinoglobulin-1) and Uox (urate oxidase) genes were at relatively key positions and may affect the action of BC. Besides, Ppara (peroxisome proliferator-activated receptor alpha), Acly (ATP-citrate lyase) and Fabp5 (fatty acid-binding protein 5) genes constituted functional partners with many genes in the PPI network, and these genes may be Bcmo1 targeting molecules. Gene Ontology (GO) function and signaling pathways enrichment analysis were performed on the genes with protein interaction relationship in the PPI network. Fatty acid binding, cholesterol metabolic process, and regulation of fatty acid metabolic process were significantly enriched, and PPAR signaling pathway showed the most significant, indicating that BC and Bcmo1 might synergistically affect body metabolic functions such as fat metabolism. In general, BC and Bcmo1 may play a role in fat metabolism in mice, thereby affecting other functions or diseases.
Topics: Adipose Tissue; Animals; Databases, Genetic; Female; Gene Expression Regulation; Mice; Oligonucleotide Array Sequence Analysis; Protein Interaction Maps; beta Carotene; beta-Carotene 15,15'-Monooxygenase
PubMed: 35306905
DOI: 10.1177/09603271211072871 -
Molecules (Basel, Switzerland) Dec 2022Carotenoid compounds are ubiquitous in nature, providing the characteristic colouring of many algae, bacteria, fruits and vegetables. They are a critical component of... (Review)
Review
Carotenoid compounds are ubiquitous in nature, providing the characteristic colouring of many algae, bacteria, fruits and vegetables. They are a critical component of the human diet and play a key role in human nutrition, health and disease. Therefore, the clinical importance of qualitative and quantitative carotene content analysis is increasingly recognised. In this review, the structural and optical properties of carotenoid compounds are reviewed, differentiating between those of carotenes and xanthophylls. The strong non-resonant and resonant Raman spectroscopic signatures of carotenoids are described, and advances in the use of Raman spectroscopy to identify carotenoids in biological environments are reviewed. Focus is drawn to applications in nutritional analysis, optometry and serology, based on in vitro and ex vivo measurements in skin, retina and blood, and progress towards establishing the technique in a clinical environment, as well as challenges and future perspectives, are explored.
Topics: Humans; Lutein; Spectrum Analysis, Raman; beta Carotene; Carotenoids; Xanthophylls; Zeaxanthins
PubMed: 36558154
DOI: 10.3390/molecules27249017 -
Food & Function Apr 2017The bioavailability of many carotenoids has been assessed, but little attention has been given to the metabolism of these antioxidant compounds during digestion. The...
The bioavailability of many carotenoids has been assessed, but little attention has been given to the metabolism of these antioxidant compounds during digestion. The isomerization and loss of lutein, lycopene, and β-carotene incorporated into a lipid-rich liquid meal was determined in vitro through the gastric, duodenal, and jejunal phases in the presence and absence of digestive enzymes, and in the presence and absence of known oxidizing agents often found in mixed meals (metmyoglobin in red meat and ferrous sulfate in supplemental iron). Carotenoids were quantitated using HPLC-PDA. In the absence of enzymes, lutein and lycopene were lost during earlier phases of the digestive process. In the presence of enzymes, lutein and lycopene were robust through the gastric and duodenal phases, with statistically significant losses of 40% and 20%, respectively, observed only during the jejunal phase. Regardless of the presence or absence of enzymes, an initial 25% of β-carotene was lost during the gastric phase, but no further loss was observed. Ferrous sulfate had no significant impact on any carotenoid level. Metmyoglobin had no impact on lutein, but significantly reduced lycopene and β-carotene levels by 30% and 80%, respectively, by the end of the jejunal phase. No significant isomerization was observed between the initial and jejunal phases for any of the carotenoids.
Topics: Carotenoids; Dietary Supplements; Digestion; Duodenum; Gastric Mucosa; Humans; Isomerism; Lutein; Lycopene; beta Carotene
PubMed: 28350027
DOI: 10.1039/c7fo00021a -
β-Carotene Oxygenase 1 Activity Modulates Circulating Cholesterol Concentrations in Mice and Humans.The Journal of Nutrition Aug 2020Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction....
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.
Topics: Adolescent; Animals; Cholesterol; Dioxygenases; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; beta Carotene; beta-Carotene 15,15'-Monooxygenase
PubMed: 32433733
DOI: 10.1093/jn/nxaa143 -
International Journal of Cancer Jul 2010The effect of beta-carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of... (Meta-Analysis)
Meta-Analysis Review
The effect of beta-carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta-carotene supplementation on cancer incidence in randomized trials by cancer site, beta-carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta-carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98-1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73-1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85-1.09), prostate cancer (RR, 0.99; 95% CI, 0.91-1.07), breast cancer (RR, 0.96; 95% CI, 0.85-1.10), melanoma (RR, 0.98; 95% CI, 0.65-1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93-1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta-carotene at 20-30 mg day(-1) (RR, 1.16; 95% CI, 1.06-1.27 and RR, 1.34; 95% CI, 1.06-1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07-1.34 and RR, 1.54; 95% CI, 1.08-2.19) compared to the placebo group. Beta-carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20-30 mg day(-1), in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta-carotene supplementation should not be recommended.
Topics: Humans; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; beta Carotene
PubMed: 19876916
DOI: 10.1002/ijc.25008