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Elucidating the inhibitory potential of Vitamin A against fibrillation and amyloid associated cytotoxicity.
Alam, P, Siddiqi, MK, Malik, S, Chaturvedi, SK, Uddin, M, Khan, RH
International journal of biological macromolecules. 2019;:333-338
Abstract
Protein aggregation and amyloid fibrillation are associated with many serious human pathophysiologies like Alzheimer's, Parkinson's diseases, type II diabetes etc. A powerful strategy for controlling and understanding amyloid protein aggregation is the modulation of protein self-assembly. In this study, anti-fibrillation activity of vitamin A (VA) and its effect on the kinetics of amyloid formation of Aβ-42 peptide was investigated by employing various spectroscopic, imaging and computational approaches. The present data of Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), dynamic light scattering assay, transmission electron microscopy and cell cytotoxicity assay demonstrated that vitamin A significantly inhibits fibril formation. Our experimental studies inferred that Vitamin A protects human neuroblastoma cell line (SH-SY5Y) and the neuroprotective effect against amyloid induced cytotoxicity is through modification of the amyloid formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin A interacts with Aβ-42 through hydrophobic interactions as well as hydrogen bonding. Therefore, the study signifies the role of vitamin A as a potential molecule in preventing Aβ-42 aggregation and associated pathophysiology. Hence, Vitamin A and related compounds can thus act as effective inhibitors in the therapeutic development to combat systemic amyloidosis.
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The Role of Vitamin A in Wound Healing.
Polcz, ME, Barbul, A
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(5):695-700
Abstract
Vitamin A is an essential micronutrient that comes in multiple forms, including retinols, retinals, and retinoic acids. Dietary vitamin A is absorbed as retinol from preformed retinoids or as pro-vitamin A carotenoids that are converted into retinol in the enterocyte. These are then delivered to the liver for storage via chylomicrons and later released into the circulation and to its biologically active tissues bound to retinol-binding protein. Vitamin A is a crucial component of many important and diverse biological functions, including reproduction, embryological development, cellular differentiation, growth, immunity, and vision. Vitamin A functions mostly through nuclear retinoic acid receptors, retinoid X receptors, and peroxisome proliferator-activated receptors. Retinoids regulate the growth and differentiation of many cell types within skin, and its deficiency leads to abnormal epithelial keratinization. In wounded tissue, vitamin A stimulates epidermal turnover, increases the rate of re-epithelialization, and restores epithelial structure. Retinoids have the unique ability to reverse the inhibitory effects of anti-inflammatory steroids on wound healing. In addition to its role in the inflammatory phase of wound healing, retinoic acid has been demonstrated to enhance production of extracellular matrix components such as collagen type I and fibronectin, increase proliferation of keratinocytes and fibroblasts, and decrease levels of degrading matrix metalloproteinases.
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Outcome of Combined Neoadjuvant Chemotherapy and Vitamin A in Advanced Cervical Carcinoma: A Randomized Double-Blind Clinical Trial.
Sanusi, RS
Asian Pacific journal of cancer prevention : APJCP. 2019;(7):2213-2218
Abstract
Background: The latest World Health Organization (WHO) inquiry on the epidemiology of cervical cancers indicate there are approximately 528,000 new cases per year, ranking fourth after breast, colorectal and lung cancer. The validity of neoadjuvant chemotherapy (NAC) alone in advanced cervical cancer is still being debated. NAC induces tumor shrinkage prior to pursuing surgery. NAC also has the benefit of sterilizing the lymph nodes and parametria, thereby lowering the need for adjuvant therapy after surgery. This research aims to determine the impact on the treatment of advanced cervical carcinoma with NAC, with the additional provision of Vitamin A during treatment to assess the factors that could affect the outcome of clinical treatment. Methodology: The research methodology and design of this study is a randomized double-blind clinical trial to compare the effects of treatment with NAC and treatment with NAC + Vitamin A, in advanced cervical carcinoma. Both study groups received treatments consisting of a regime of cisplatin and paclitaxel. The study was conducted at the General Hospital of Dr. Mohammad Hoesin. The total number of patients recruited for the trial was 30 with 15 patients per treatment arm. One group received NAC consisting of cisplatin and paclitaxel and the remaining 15 patients received NAC + Vitamin A. Results: The addition of Vitamin A was found to be much better in influencing the clinical response in the treatment of advanced cervical carcinoma, although this was not statistically significant. However, a larger sample size with the reported proportion of higher positive outcome for NAC + Vitamin A may be statistically significant. Conclusion: Based on the results, Vitamin A supplementation in the treatment of advanced cervical carcinoma with neoadjuvant chemotherapy may play a crucial role in the treatment of cervical carcinoma.
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Association of plasma retinol levels with incident cancer risk in Chinese hypertensive adults: a nested case-control study.
Xie, L, Song, Y, Lin, T, Guo, H, Wang, B, Tang, G, Liu, C, Huang, W, Yang, Y, Ling, W, et al
The British journal of nutrition. 2019;(3):293-300
Abstract
We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case-control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2-4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose-response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).
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Plasma retinol and the risk of first stroke in hypertensive adults: a nested case-control study.
Yu, Y, Zhang, H, Song, Y, Lin, T, Zhou, Z, Guo, H, Liu, L, Wang, B, Liu, C, Li, J, et al
The American journal of clinical nutrition. 2019;(2):449-456
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Abstract
BACKGROUND Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited. OBJECTIVES We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. METHODS The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y. RESULTS There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18). CONCLUSIONS Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. This study was registered at clinicaltrials.gov as NCT00794885.
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Reduction of Serum Concentrations and Synergy between Retinol, β-Carotene, and Zinc According to Cancer Staging and Different Treatment Modalities Prior to Radiation Therapy in Women with Breast Cancer.
Rosa, C, Franca, C, Lanes Vieira, S, Carvalho, A, Penna, A, Nogueira, C, Lessa, S, Ramalho, A
Nutrients. 2019;(12)
Abstract
UNLABELLED The procedures used for breast cancer treatment are able to increase the level of oxidative stress and cause depletion of antioxidants. OBJECTIVES To investigate the relationship between serum concentrations of retinol, β-carotene, and zinc, according to breast cancer staging, considering different treatment modalities prior to radiation therapy and the synergistic action between these micronutrients. METHODS This is a cross-sectional observational study comprising a cohort of patients with breast cancer which was carried out prior to radiation therapy. Patients were divided into 3 groups: G1 comprised women who had undergone breast-conserving surgery, G2 comprised those who had undergone chemotherapy, and G3 those who had undergone breast-conserving surgery and chemotherapy. Serum concentrations of retinol, β-carotene, and zinc were quantified. Breast cancer staging was based on the TNM (Tumor, Node, Metastasis) classification of malignant tumors, a type of staging tool for different cancers. RESULTS A total of 230 patients were assessed. A decrease of the serum concentrations of the micronutrients assessed as the staging level of the disease increased was observed. Surgery alone had a greater negative impact on serum concentrations of retinol. Considering the treatments prior to radiotherapy, patients undergoing surgery alone and chemotherapy associated with surgery had higher percentages of deficiency of β-carotene and retinol. There was a positive correlation between the concentrations of zinc, retinol, and β-carotene, showing a synergy between these micronutrients. CONCLUSION A significant reduction in the serum concentrations of the assessed micronutrients was observed, according to the increase in breast cancer staging. The synergy between the micronutrients must be considered in order to maximize the benefits and minimize the adverse effects of irradiation to normal cells.
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Role of vitamin A supplementation in prevention of bronchopulmonary dysplasia in extremely low birth weight neonates: a systematic review of randomized trials.
Garg, BD, Bansal, A, Kabra, NS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(15):2608-2615
Abstract
BACKGROUND Bronchopulmonary dysplasia (BPD) is one of the most common consequence of extreme prematurity (<28 weeks of gestation). BPD affects approximately 55% of extremely low birth weight (ELBW) neonates. AIMS The aim of this systematic review is to evaluate the role of vitamin A supplementation in prevention of BPD in ELBW neonates. METHOD The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ongoing clinical trials. RESULTS This review included two RCTs that fulfilled inclusion criteria. There were statistically significant reduction in the incidence of BPD (oxygen requirement at 36 weeks of postmenstrual age (PMA)) (relative risk (RR) 0.88; 95%CI 0.77-0.99; p = .04; NNTB 14) and borderline significant reduction in combined outcomes of mortality/BPD (oxygen requirement at 36 weeks of PMA) (RR 0.90; 95%CI 0.82-1.00; p = .05). However, oxygen requirement at 28 days of life and combined outcome of mortality/BPD (oxygen requirement at 28 days of life) were not statistically significant. CONCLUSIONS The role of vitamin A supplementation in the prevention of BPD is supported by the current evidences. However, due to limited number of studies, current evidences are not sufficient which can translate into routine clinical practice. We need large high-quality trials, with sufficient power to reliably assess clinically relevant differences in outcomes.
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Fortification of staple foods with vitamin A for vitamin A deficiency.
Hombali, AS, Solon, JA, Venkatesh, BT, Nair, NS, Peña-Rosas, JP
The Cochrane database of systematic reviews. 2019;(5):CD010068
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Abstract
BACKGROUND Vitamin A deficiency is a significant public health problem in many low- and middle-income countries, especially affecting young children, women of reproductive age, and pregnant women. Fortification of staple foods with vitamin A has been used to increase vitamin A consumption among these groups. OBJECTIVES To assess the effects of fortifying staple foods with vitamin A for reducing vitamin A deficiency and improving health-related outcomes in the general population older than two years of age. SEARCH METHODS We searched the following international databases with no language or date restrictions: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE and MEDLINE In Process OVID; Embase OVID; CINAHL Ebsco; Web of Science (ISI) SCI, SSCI, CPCI-exp and CPCI-SSH; BIOSIS (ISI); POPLINE; Bibliomap; TRoPHI; ASSIA (Proquest); IBECS; SCIELO; Global Index Medicus - AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched clinicaltrials.gov and the International Clinical Trials Registry Platform to identify ongoing and unpublished studies. The date of the last search was 19 July 2018. SELECTION CRITERIA We included individually or cluster-randomised controlled trials (RCTs) in this review. The intervention included fortification of staple foods (sugar, edible oils, edible fats, maize flour or corn meal, wheat flour, milk and dairy products, and condiments and seasonings) with vitamin A alone or in combination with other vitamins and minerals. We included the general population older than two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS Two authors independently screened and assessed eligibility of studies for inclusion, extracted data from included studies and assessed their risk of bias. We used standard Cochrane methodology to carry out the review. MAIN RESULTS We included 10 randomised controlled trials involving 4455 participants. All the studies were conducted in low- and upper-middle income countries where vitamin A deficiency was a public health issue. One of the included trials did not contribute data to the outcomes of interest.Three trials compared provision of staple foods fortified with vitamin A versus unfortified staple food, five trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus unfortified staple foods, and two trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus no intervention. No studies compared staple foods fortified with vitamin A alone versus no intervention.The duration of interventions ranged from three to nine months. We assessed six studies at high risk of bias overall. Government organisations, non-governmental organisations, the private sector, and academic institutions funded the included studies; funding source does not appear to have distorted the results.Staple food fortified with vitamin A versus unfortified staple food We are uncertain whether fortifying staple foods with vitamin A alone makes little or no difference for serum retinol concentration (mean difference (MD) 0.03 μmol/L, 95% CI -0.06 to 0.12; 3 studies, 1829 participants; I² = 90%, very low-certainty evidence). It is uncertain whether vitamin A alone reduces the risk of subclinical vitamin A deficiency (risk ratio (RR) 0.45, 95% CI 0.19 to 1.05; 2 studies; 993 participants; I² = 33%, very low-certainty evidence). The certainty of the evidence was mainly affected by risk of bias, imprecision and inconsistency.It is uncertain whether vitamin A fortification reduces clinical vitamin A deficiency, defined as night blindness (RR 0.11, 95% CI 0.01 to 1.98; 1 study, 581 participants, very low-certainty evidence). The certainty of the evidence was mainly affected by imprecision, inconsistency, and risk of bias.Staple foods fortified with vitamin A versus no intervention No studies provided data for this comparison.Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods Fortifying staple foods with vitamin A plus other micronutrients may not increase the serum retinol concentration (MD 0.08 μmol/L, 95% CI -0.06 to 0.22; 4 studies; 1009 participants; I² = 95%, low-certainty evidence). The certainty of the evidence was mainly affected by serious inconsistency and risk of bias.In comparison to unfortified staple foods, fortification with vitamin A plus other micronutrients probably reduces the risk of subclinical vitamin A deficiency (RR 0.27, 95% CI 0.16 to 0.49; 3 studies; 923 participants; I² = 0%; moderate-certainty evidence). The certainty of the evidence was mainly affected by serious risk of bias.Staple foods fortified with vitamin A plus other micronutrients versus no interventionFortification of staple foods with vitamin A plus other micronutrients may increase serum retinol concentration (MD 0.22 μmol/L, 95% CI 0.15 to 0.30; 2 studies; 318 participants; I² = 0%; low-certainty evidence). When compared to no intervention, it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency (RR 0.71, 95% CI 0.52 to 0.98; 2 studies; 318 participants; I² = 0%; very low-certainty evidence) . The certainty of the evidence was affected mainly by serious imprecision and risk of bias.No trials reported on the outcomes of all-cause morbidity, all-cause mortality, adverse effects, food intake, congenital anomalies (for pregnant women), or breast milk concentration (for lactating women). AUTHORS' CONCLUSIONS Fortifying staple foods with vitamin A alone may make little or no difference to serum retinol concentrations or the risk of subclinical vitamin A deficiency. In comparison with provision of unfortified foods, provision of staple foods fortified with vitamin A plus other micronutrients may not increase serum retinol concentration but probably reduces the risk of subclinical vitamin A deficiency.Compared to no intervention, staple foods fortified with vitamin A plus other micronutrients may increase serum retinol concentration, although it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency as the certainty of the evidence has been assessed as very low.It was not possible to estimate the effect of staple food fortification on outcomes such as mortality, morbidity, adverse effects, congenital anomalies, or breast milk vitamin A, as no trials included these outcomes.The type of funding source for the studies did not appear to distort the results from the analysis.
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Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants.
Church, JA, Rukobo, S, Govha, M, Carmolli, MP, Diehl, SA, Chasekwa, B, Ntozini, R, Mutasa, K, Humphrey, JH, Kirkpatrick, BD, et al
Transactions of the Royal Society of Tropical Medicine and Hygiene. 2019;(3):110-115
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BACKGROUND Micronutrient deficiencies may contribute to reduced oral vaccine immunogenicity in developing countries. We hypothesised that neonatal vitamin A supplementation (NVAS) would improve oral vaccine responses. METHODS We performed a cross-sectional study of infants recruited at birth to the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial, a randomised controlled trial of single, high-dose NVAS vs placebo conducted in Zimbabwe between 1997-2001. We measured poliovirus-specific IgA to type 1-3 polio strains by semiquantitative capture ELISA in cryopreserved plasma samples collected at 6 months of age. RESULTS A total of 181 infants fulfilled inclusion criteria, of whom 80 were randomised to NVAS and 101 to placebo. There were no significant differences in baseline characteristics between groups. At 6 months of age, median (IQR) vaccine titres for infants randomised to NVAS vs placebo were 932 (421-3001) vs 1774 (711-5431) for Sabin-1 (p=0.04); 1361 (705-3402) vs 2309 (1081-4283) for Sabin-2 (p=0.15); and 1584 (796-4216) vs 2260 (996-5723) for Sabin-3 (p=0.14), respectively. After adjusting for breast feeding status, birth weight, season and infant sex in a linear regression model, there was only weak evidence of difference in log mean titres between vitamin A and placebo groups for Sabin-1 (p=0.08) and no evidence of difference in log mean titres for Sabin-2 and Sabin-3. CONCLUSIONS NVAS did not augment oral polio vaccine responses in Zimbabwean infants. Further research is required to understand the impact of NVAS on responses to other oral vaccines.The trial is registered with clinicaltrials.gov identifier: NCT00198718.
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Carotenoids retention in biofortified yellow cassava processed with traditional African methods.
Taleon, V, Sumbu, D, Muzhingi, T, Bidiaka, S
Journal of the science of food and agriculture. 2019;(3):1434-1441
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BACKGROUND Biofortified yellow cassava is being cultivated in countries with high cassava consumption to improve its population's vitamin A status. The carotenoid retention in biofortified cassava when processed as boiled, fufu, and chikwangue was evaluated in this study. Commercial biofortified varieties Kindisa and Vuvu and the experimental genotypes MVZ2011B/360 and MVZ2012/044 were used. Fresh cassava roots were processed as boiled, fufu, and chikwangue. Provitamin A carotenoids (pVACs) content of fresh and processed cassava was measured by high-performance liquid chromatography, and total carotenoids was measured by spectrophotometer. RESULTS pVACs content of fresh peeled cassava was 1.79-6.65 µg g-1 on a fresh weight basis, whereas in boiled cassava, fufu, and chikwangue the pVACs content was 1.71-6.91 µg g-1 , 0.04-0.37 µg g-1 , and 0.52-1.75 µg g-1 respectively. True retention of carotenoids after cooking was 93.2-96.8%, 0.8-3.1%, and 4.0-18.1% for boiled cassava, fufu, and chikwangue respectively. Significant total carotenoids loss was observed during storage. CONCLUSION The results indicated that biofortified boiled cassava could be an effective food product to improve pVACs intake in areas where vitamin A deficiency exists, and processing of chikwangue and fufu should be improved before promoting biofortified cassava in vitamin-A-deficient areas with high cassava consumption. © 2018 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.