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Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12-23 months and their non-pregnant caregivers.
Whitehead, RD, Ford, ND, Mapango, C, Ruth, LJ, Zhang, M, Schleicher, RL, Ngalombi, S, Halati, S, Ahimbisibwe, M, Lubowa, A, et al
Experimental biology and medicine (Maywood, N.J.). 2021;(8):906-915
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Abstract
Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12-23 months and 28 non-pregnant mothers aged 15-49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were -0.19 µmol/L (95% limits of agreement [LOA] 0.62, -0.99) for children and -0.01 µmol/L (95% LOA -1.11, -1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA -0.37, 1.03) for children, and 0.29 µmol/L (95% LOA -0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA -0.23, 0.49) for children and 0.18 µmol/L (95% LOA -0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.
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Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.
Rysavy, MA, Li, L, Tyson, JE, Jensen, EA, Das, A, Ambalavanan, N, Laughon, MM, Greenberg, RG, Patel, RM, Pedroza, C, et al
The Journal of pediatrics. 2021;:78-85.e5
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Abstract
OBJECTIVE To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION ClinicalTrials.gov NCT01203488.
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Serum Metabolomics Analysis of Asthma in Different Inflammatory Phenotypes: A Cross-Sectional Study in Northeast China.
Pang, Z, Wang, G, Wang, C, Zhang, W, Liu, J, Wang, F
BioMed research international. 2018;:2860521
Abstract
BACKGROUND AND OBJECTIVE Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them. METHODS Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography-Mass Spectrometry technique. RESULTS Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log(P) > 4) between the phenotypes. CONCLUSIONS We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.
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Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.
Pettinelli, P, Arendt, BM, Teterina, A, McGilvray, I, Comelli, EM, Fung, SK, Fischer, SE, Allard, JP
PloS one. 2018;(10):e0205747
Abstract
Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 μmol/L) and NASH (1.51 ± 0.56 μmol/L) compared to LD (1.21 ± 0.38 μmol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH.
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Effect of vitamin A administration on free radicals and lactate levels in individuals exercised to exhaustion.
Patlar, S, Baltaci, AK, Mogulkoc, R
Pakistan journal of pharmaceutical sciences. 2016;(5):1531-1534
Abstract
This study was performed to explore the effect of vitamin A administration on Free Radicals production and antioxidant system activity and lactate levels in individuals exercised to exhaustion The study registered 10 healthy sedentary males their mean age was 22,85±0,26 years. The subjects were orally administrated with 300 mg vitamin A (retinol) for 4 weeks and engaged in strenuous exercise (using the Bruce protocol) once a week. Blood samples were collected from the subjects at four different times, before and after the supplementation and before and after exercise to analyze Malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), Glutathione peroxidase (GSH-Px), Catalase (CAT), Superoxide dismutase (SOD) levels using colorimetric ELISA test kits and plasma lactate levels using an autoanalyzer. Exhaustion exercise leaded to an increase in both MDA, NO, and lactate, and GSH, GSH-Px, CAT and SOD levels compared to resting levels both before and after supplementation (p<0.05). Increased NO levels found in pre-supplementation exhaustion showed a significant decrease after the supplementation of vitamin A (p<0.05), but the other parameters were not changed after vitamin A administration. The results of our study demonstrate that the increase caused by 4-week strenuous exercise in the levels of the free radical NO was offset by vitamin A supplementation. It can be suggested that supplementation of vitamin A at physiological doses has a limited effect on lipid peroxidation caused by strenuous exercise.
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Supplementation with red palm oil increases β-carotene and vitamin A blood levels in patients with cystic fibrosis.
Sommerburg, O, De Spirt, S, Mattern, A, Joachim, C, Langhans, CD, Nesaretnam, K, Siems, W, Stahl, W, Mall, MA
Mediators of inflammation. 2015;:817127
Abstract
Patients with cystic fibrosis (CF) show decreased plasma concentrations of antioxidants due to malabsorption of lipid soluble vitamins and consumption by chronic pulmonary inflammation. β-Carotene is a major source of retinol and therefore is of particular significance in CF. The aim of this study was to investigate the effect of daily intake of red palm oil (RPO) containing high amounts of β-carotene on the antioxidant levels in CF patients. Sixteen subjects were recruited and instructed to enrich their food with 2 to 3 tablespoons of RPO (~1.5 mg of β-carotene) daily over 8 weeks. Carotenoids, retinol, and α-tocopherol were measured in plasma at baseline and after intervention. In addition β-carotene, lycopene, α-tocopherol, and vitamin C were measured in buccal mucosa cells (BMC) to determine the influence of RPO on antioxidant tissue levels. Eleven subjects completed the study properly. Plasma β-carotene, retinol, and α-carotene of these patients increased, but plasma concentrations of other carotenoids and α-tocopherol as well as concentrations of β-carotene, lycopene, α-tocopherol, and vitamin C in BMC remained unchanged. Since RPO on a daily basis did not show negative side effects the data suggest that RPO may be used to elevate plasma β-carotene in CF.
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[The state of the antioxidant status of children of different ages].
Kolesnikova, LI, Darenskaia, MA, Grebenkina, LA, Osipova, EV, Dolgikh, MI, Natiaganova, LV
Voprosy pitaniia. 2013;(4):27-33
Abstract
The parameters of lipid peroxidation (blood plasma content of primary products of lipid peroxidation and the end of TBA-active products) and indexes of antioxidant protection (total antioxidant activity, the content of fat-soluble vitamins A and E in blood plasma and riboflavin in blood) has been evaluated in 75 healthy children living in Irkutsk. All respondents were divided into three age periods: preschool age (3-6 years old, mean 4.7 +/- 1.0 - 21 children), primary school age (7-8 years, 7.6 +/- 0.4, - 28 children) and middle-school age (9-11 years, 9.9 +/- 0.7, 26 children). We used spectrophotometric and fluorometric methods. Identified the distinctive features of the metabolic reactions in children at different ages. The increase of the content of the primary products of lipid peroxidation in the early school years and of the end of TBA-active products for children of secondary school age in comparison with the preschool children has been determined. At the same time an increase in the level of total antioxidant activity and fat-soluble vitamins and riboflavin content in young and middle-school aged children in comparison with the pre-school children has been observed. The measurement of vitamins status demonstrated the insufficiency of alpha-tocopherol in half of pre-school children, in 36% of primary school children and 38% of children of secondary school age. Retinol and riboflavin deficiency has been detected in a small proportion of children of all ages. In this regard, the additional supply with vitamins of children in pre-school and middle-school period is essential.
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Yellow maize with high β-carotene is an effective source of vitamin A in healthy Zimbabwean men.
Muzhingi, T, Gadaga, TH, Siwela, AH, Grusak, MA, Russell, RM, Tang, G
The American journal of clinical nutrition. 2011;(2):510-9
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Abstract
BACKGROUND The bioconversion efficiency of yellow maize β-carotene to retinol in humans is unknown. OBJECTIVE The objective of this study was to determine the vitamin A value of yellow maize β-carotene in humans. DESIGN High β-carotene-containing yellow maize was grown in a hydroponic medium with 23 atom% (2)H(2)O during grain development. Yellow maize β-carotene showed the highest abundance of enrichment as [(2)H(9)]β-carotene. Eight healthy Zimbabwean men volunteered for the study. On day 1 after a fasting blood draw, subjects consumed 300 g yellow maize porridge containing 1.2 mg β-carotene, 20 g butter, and a 0.5-g corn oil capsule. On day 8, fasting blood was drawn, and subjects consumed 1 mg [(13)C(10)]retinyl acetate in a 0.5-g corn oil capsule and 300 g white maize porridge with 20 g butter. Thirty-six blood samples were collected from each subject over 36 d. Concentrations and enrichments of retinol and β-carotene in labeled doses and serum were determined with the use of HPLC, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry. RESULTS The area under the curve (AUC) of retinol from 1.2 mg yellow maize β-carotene was 72.9 nmol · d, and the AUC of retinol from 1 mg retinyl acetate (13)C(10) was 161.1 nmol · d. The conversion factor of yellow maize β-carotene to retinol by weight was 3.2 ± 1.5 to 1. CONCLUSION In 8 healthy Zimbabwean men, 300 g cooked yellow maize containing 1.2 mg β-carotene that was consumed with 20.5 g fat showed the same vitamin A activity as 0.38 mg retinol and provided 40-50% of the adult vitamin A Recommended Dietary Allowance. This trial was registered at clinicaltrials.gov as NCT00636038.
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Serum levels of folate, lycopene, β-carotene, retinol and vitamin E and prostate cancer risk.
Beilby, J, Ambrosini, GL, Rossi, E, de Klerk, NH, Musk, AW
European journal of clinical nutrition. 2010;(10):1235-8
Abstract
Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer. Prospective studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer. Similarly, serum β-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk. Using a prospective nested case-control study design, which minimized the possibility of disease effects on serum-vitamin concentrations, we report null associations for serum concentrations of folate, lycopene, β-carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.
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Intestinal permeability, vitamin A absorption and serum alpha-tocopherol in gastrointestinal stromal tumor patients treated with imatinib.
Melichar, B, Kašparová, M, Kalábová, H, Dvorák, J, Hyšpler, R, Tichá, A, Krcmová, L, Plíšek, J, Holecková, P, Solichová, D
Journal of nutritional science and vitaminology. 2010;(6):347-52
Abstract
Administration of imatinib is the therapy of choice in patients with advanced (inoperable) or metastatic gastrointestinal stromal tumors (GIST). Gastrointestinal toxicity is one of the most common side effects of anticancer therapy, including imatinib. Measurement of intestinal permeability represents a method of noninvasive laboratory assessment of gastrointestinal toxicity. We have measured intestinal permeability (by determining absorption of lactulose, mannitol and xylose), vitamin A absorption and serum alpha-tocopherol in 16 patients with advanced/metastatic GIST treated with imatinib. Lactulose/mannitol and lactulose/xylose ratios as well as parameters of vitamin A absorption did not change significantly during the treatment, but a significant decrease of alpha-tocopherol was observed. We conclude that, in contrast to most other anticancer agents studied so far, imatinib does not have an effect on intestinal permeability. No effect on vitamin A absorption was observed, but serum alpha-tocopherol decreased significantly during the treatment.