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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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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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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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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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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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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.
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Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women.
Kabat, GC, Kim, M, Adams-Campbell, LL, Caan, BJ, Chlebowski, RT, Neuhouser, ML, Shikany, JM, Rohan, TE, ,
The American journal of clinical nutrition. 2009;(1):162-9
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BACKGROUND Prospective studies have examined the association of serum and plasma carotenoids and micronutrients and breast cancer; however, to date, studies have only assessed exposure at one point in time. OBJECTIVE This study analyzed baseline and repeated serum measurements of carotenoids, retinol, and tocopherols to assess their associations with postmenopausal breast cancer risk. DESIGN Serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol were measured in a 6% sample of women in the Women's Health Initiative clinical trials at baseline and at years 1, 3, and 6 and in a 1% sample of women in the observational study at baseline and at year 3. The association of baseline compounds and breast cancer risk was estimated by Cox proportional hazards models. In addition, repeated measurements were analyzed as time-dependent covariates. Of 5450 women with baseline measurements, 190 incident cases of breast cancer were ascertained over a median of 8.0 y of follow-up. RESULTS After multivariable adjustment, risk of invasive breast cancer was inversely associated with baseline serum alpha-carotene concentrations (hazard ratio for highest compared with the lowest tertile: 0.55; 95% CI: 0.34, 0.90; P = 0.02) and positively associated with baseline lycopene (hazard ratio: 1.47; 95% CI: 0.98, 2.22; P = 0.06). Analysis of repeated measurements indicated that alpha-carotene and beta-carotene were inversely associated with breast cancer and that gamma-tocopherol was associated with increased risk. CONCLUSIONS The present study, which was the first to assess repeated measurements of serum carotenoids and micronutrients in relation to breast cancer, adds to the evidence of an inverse association of specific carotenoids with breast cancer. The positive associations observed for lycopene and gamma-tocopherol require confirmation. This trial was registered at ClinicalTrials.gov as NCT00000611.
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Benefit of vitamin A supplementation on ascaris reinfection is less evident in stunted children.
Payne, LG, Koski, KG, Ortega-Barria, E, Scott, ME
The Journal of nutrition. 2007;(6):1455-9
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Abstract
Despite the common coexistence of vitamin A deficiency and Ascaris infection in preschool children in developing countries, and despite the widespread use of vitamin A supplements, remarkably little is understood about the impact of vitamin A supplementation on this gastrointestinal nematode. The Ministry of Health of Panama recently initiated a vitamin A supplementation program in rural indigenous populations. We took advantage of this initiative to assess the benefit of 200,000 IU (60 mg retinol) vitamin A on reinfection with Ascaris following deworming. Baseline stool exams, anthropometry, and socio-economic data were collected for 328 preschool children from 12-60 mo of age (106 supplemented within previous 3 mo and 222 unsupplemented within previous 6 mo). All children were dewormed with albendazole, and reinfection levels were monitored 3 and 5 mo later. Baseline prevalence of Ascaris was 79.5%. Stepwise regression showed that Ascaris intensity was lower in Vit A-supplemented children at baseline and 3 mo after deworming, but not after 5 mo. As 61% of the children were stunted, the impact of supplementation on Ascaris reinfection was examined separately for stunted and children of normal height. Prevalence and intensity of Ascaris at baseline and 3 mo after deworming were lower in children of normal height, but in stunted children the benefit was restricted to those who were dewormed within 6 wk of supplementation. Our study provides evidence that combined vitamin A supplementation and deworming reduces Ascaris reinfection in children living in areas of chronic parasitosis, but that the duration of the benefit is less in stunted children.
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Short-term effects of vitamin A and antimalarial treatment on erythropoiesis in severely anemic Zanzibari preschool children.
Cusick, SE, Tielsch, JM, Ramsan, M, Jape, JK, Sazawal, S, Black, RE, Stoltzfus, RJ
The American journal of clinical nutrition. 2005;(2):406-12
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BACKGROUND The pathophysiology of anemia in coastal East Africa is complex. Impaired erythropoietin production is one possible mechanism. Plasmodium falciparum malaria has been found to blunt erythropoietin production, whereas vitamin A stimulates erythropoietin production in vitro. OBJECTIVE We investigated the 72-h effects of vitamin A and the antimalarial drug sulfadoxine pyramethamine (SP) on erythropoietin production in severely anemic (hemoglobin < or = 70 g/L) preschool children in Zanzibar, a region of known vitamin A deficiency. We hypothesized that both treatments would stimulate erythropoietin production directly, within 72 h, before a change in hemoglobin would occur. DESIGN One hundred forty-one severely anemic children were identified during the baseline assessment of a morbidity substudy of a community-based micronutrient supplementation trial. All severely anemic children were randomly assigned to receive either vitamin A (100,000 or 200,000 IU depending on age) or SP at baseline; 72 h later they received the opposite treatment plus daily hematinic syrup for 90 d. Erythropoietic and parasitic indicators were assessed at baseline and again after 72 h. RESULTS After 72 h, SP reduced the malaria parasite density (by 5029 parasites/microL; P < 0.001), CRP concentrations (by 10.6 mg/L; P = 0.001), and the proportion of children infected with malaria (by 32.4%; P < 0.001). Vitamin A reduced CRP (by 9.6 mg/L; P = 0.011), serum ferritin (by 18.1 microg/L; P = 0.042), and erythropoietin (by 194.7 mIU/mL; P = 0.011) concentrations and increased the reticulocyte production index (by 0.40; P = 0.041). CONCLUSIONS Contrary to our hypothesis, vitamin A significantly decreased erythropoietin concentration. The most important effect of both vitamin A and SP was the rapid reduction of inflammation. Vitamin A also mobilized iron from stores and stimulated the production of new erythrocytes.