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High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.
Ahmad, SM, Raqib, R, Huda, MN, Alam, MJ, Monirujjaman, M, Akhter, T, Wagatsuma, Y, Qadri, F, Zerofsky, MS, Stephensen, CB
The Journal of nutrition. 2020;(1):176-183
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Abstract
BACKGROUND Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function. OBJECTIVE Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median). METHODS Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight. RESULTS VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively. CONCLUSION In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
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Effect of High-dose Vitamin A Supplementation in Children With Sickle Cell Disease: A Randomized, Double-blind, Dose-finding Pilot Study.
Brownell, JN, Schall, JI, Mcanlis, CR, Smith-Whitley, K, Norris, CF, Stallings, VA
Journal of pediatric hematology/oncology. 2020;(2):83-91
Abstract
Suboptimal vitamin A status (serum retinol <30 µg/dL) is associated with poor clinical outcomes in children with the hemoglobin-SS disease (HbSS), and supplementation with the recommended daily allowance of retinol is ineffective in improving vitamin A status. In a single-center randomized blinded dose-finding pilot study, we compared vitamin A and nutritional status in children with HbSS to healthy children and explored the impact of high-dose supplementation on the primary outcome serum vitamin A status. Exploratory outcomes included hematologic, nutritional, immunologic, and muscle function status in children with HbSS. A mixed-effects linear regression model evaluated associations between vitamin A dose, serum retinol, and exploratory outcomes. Twenty healthy children participated, and 22 subjects with HbSS were randomized to oral 3000 or 6000 IU/d retinol for 8 weeks; 21 subjects completed all evaluations. Serum retinol, growth, and nutritional status were all suboptimal in HbSS subjects at baseline, and supplementation did not change vitamin A status. Fetal hemoglobin (Δ=2.5, 95% confidence interval [CI], 0.5-4.3), mean corpuscular volume (Δ=2.7, 95% CI, 0.7-4.7), mean corpuscular hemoglobin (Δ=1.4, 95% CI, 0.5-2.3), and mean corpuscular hemoglobin concentration (Δ=0.5, 95% CI, 0.1-0.9) all improved with supplementation. Mild improvements in erythrocyte indices, growth status, and muscle function occurred independent of hydroxyurea use.
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High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age.
Ahmad, SM, Huda, MN, Raqib, R, Qadri, F, Alam, MJ, Afsar, MNA, Peerson, JM, Tanumihardjo, SA, Stephensen, CB
The Journal of nutrition. 2020;(11):3005-3012
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Abstract
BACKGROUND Vitamin A (VA) stores are low in early infancy and may impair development of the immune system. OBJECTIVE This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated. METHODS In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight. RESULTS VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y. CONCLUSIONS Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
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Effects of liposomal nasal spray with vitamins A and E on allergic rhinitis.
Lauriello, M, di Marco, GP, Necozione, S, Tucci, C, Pasqua, M, Rizzo, G, Eibenstein, A
Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale. 2020;(3):217-223
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The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function.
Herz, CT, Kiefer, FW
Frontiers in endocrinology. 2020;:608
Abstract
In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning." Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms.
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Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.
Kangas, ST, Salpéteur, C, Nikièma, V, Talley, L, Briend, A, Ritz, C, Friis, H, Kaestel, P
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3512-3519
Abstract
BACKGROUND & AIMS Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 μmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 μg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 μmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 μg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.
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Observation for clinical effect of acupuncture combined with conventional therapy in the treatment of acne vulgaris.
Kou, L, Yu, N, Ren, J, Yang, B, Tao, Y
Medicine. 2020;(18):e19764
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Abstract
INTRODUCTION Acne vulgaris is a chronic inflammatory disease of the sebaceous glands that occurs in adolescent men and women. In recent years, the incidence of acne has increased year by year, so it is of great significance to find a precise and effective treatment and further explore its possible mechanism of action. The purpose of this study will be to explore a treatment method that has both traditional Chinese medicine characteristics and significant effects, and provides a higher level of evidence for acupuncture for acne vulgaris. It also provides patients with more treatment options. METHODS/DESIGN The study will be a randomized controlled trial divided into 2 parallel groups. This pragmatic randomized controlled trial will recruit 66 patients who are diagnosed with acne vulgaris. 30-minutes acupuncture sessions will be provided to patients assigned to the intervention group. All participants will continue to receive conventional treatment. The selection of outcomes will be evaluated by the skin lesions score scale. DISCUSSION This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with acne vulgaris. TRIAL REGISTRATION NUMBER CTR2000030427.
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Drugs to Prevent Bronchopulmonary Dysplasia: Effect of Baseline Risk on the Number Needed to Treat.
Jensen, EA, Roberts, RS, Schmidt, B
The Journal of pediatrics. 2020;:244-247
Abstract
Infants born very preterm have a variable baseline risk of bronchopulmonary dysplasia (BPD). Using the example of evidence-based drug therapies to prevent BPD, we designed a visual aid that displays the "number needed to treat" with CIs for caffeine, vitamin A, and hydrocortisone over a range of baseline risks.
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Vitamin A: its many roles-from vision and synaptic plasticity to infant mortality.
Dowling, JE
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology. 2020;(3):389-399
Abstract
The recognition that a dietary factor is essential to maintain good and sensitive vision as well as overall health goes back over 3,000 years to the ancient Egyptians. With the discovery of the vitamins at the turn of the twentieth century, fat-soluble vitamin A was soon shown to be the essential factor. In the first half of the twentieth century, the role vitamin A plays in vision, as precursor to the light-sensitive visual pigment molecules in the photoreceptors was elegantly worked out, especially by George Wald and his colleagues. Beginning in the 1960s, with the recognition of the active metabolite of vitamin A, its acid form now called retinoic acid, the roles of vitamin A in maintaining overall health of an organism began to be explored, and this research continues to this day. Receptors activated by retinoic acid, the RARs and RXRs have been shown to regulate gene transcription in a surprisingly wide variety of biological processes from early growth and development to the maintenance of epithelial tissues in many organs, the regulation of the immune system, and even the modulation of synaptic function in the brain involved in mechanisms underlying memory and learning. Therapeutic uses for retinoic acid have been developed, including one for a specific form of leukemia. The story is by no means complete and it is likely more surprises await with regard to this remarkable molecule.
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Retinoids in health and disease: A role for hepatic stellate cells in affecting retinoid levels.
Haaker, MW, Vaandrager, AB, Helms, JB
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020;(6):158674
Abstract
Vitamin A (retinol) is important for normal growth, vision and reproduction. It has a role in the immune response and the development of metabolic syndrome. Most of the retinol present in the body is stored as retinyl esters within lipid droplets in hepatic stellate cells (HSCs). In case of liver damage, HSCs release large amounts of stored retinol, which is partially converted to retinoic acid (RA). This surge of RA can mediate the immune response and enhance the regeneration of the liver. If the damage persists activated HSCs change into myofibroblast-like cells producing extracellular matrix, which increases the chance of tumorigenesis to occur. RA has been shown to decrease proliferation and metastasis of hepatocellular carcinoma. The levels of RA and RA signaling are influenced by the possibility to esterify retinol towards retinyl esters. This suggests a complex regulation between different retinoids, with an important regulatory role for HSCs.