VitA Deficiency Research Articles

Connecting clinical, environmental, and genetic factors point to an essential role for vitamin A signaling in the pathogenesis of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental disorder that results in incomplete diaphragm formation, pulmonary hypoplasia, and pulmonary hypertension. Although a variety of genes have been linked to its etiology, CDH is not a monogenetic disease, and the cause of the condition is still unclear in the vast majority of clinical cases. By comparing human clinical data and experimental rodent data from the literature, we present clear support demonstrating the importance of vitamin A (vitA) during the early window of pregnancy when the diaphragm and lung are forming. Alteration of vitA signaling via dietary and genetic perturbations can create diaphragmatic defects. Unfortunately, vitA deficiency is chronic among people of child-bearing age, and this early window of diaphragm development occurs before many might be aware of pregnancy. Furthermore, there is an increased demand for vitA during this critical period, which exacerbates the likelihood of deficiency. It would be beneficial for the field to further investigate the connections between maternal vitA and CDH incidence, with the goal of determining vitA status as a CDH risk factor. Regular clinical monitoring of vitA levels in child-bearing years is a tractable method by which CDH outcomes could be prevented or improved.

Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification

Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.

Probing the physicochemical characteristics of carrot sauce during storage.

Globally, the prevalence of vit-A deficiency disorders i.e., xerophthalmia and nyctalopia is increasing especially in teenagers due to lifestyle shifts and undernutrition. This research was designed to develop carrot-supplemented tomato sauce to overcome vit-A deficiency and its related disorders. The carrot sauce was formulated with the addition of 50, 60, and 70% carrot pulp in tomato paste. The prepared sauce samples were tested for physical and biochemical changes in beta carotene (BC), lycopene, viscosity, pH, total soluble solids, titratable acidity, total plate count, and sensory parameters for 12 weeks. A non-significant effect of storage on BC, lycopene, and total soluble solids was observed. The total plate count, acidity, pH, and viscosity were influenced significantly. Sauce containing 60% of the carrot paste showed good sensory characteristics and 42.39 μg/g BC for the whole period of storage. It is concluded that carrot sauce can be used as tomato ketchup replacers to boost the overall quality of life by fighting against vit-A deficiency disorders.

Design and Nutrient Analysis of a Carotenoid-Rich Food Product to Address Vitamin A and Protein Deficiency

Worldwide undernutrition affects over 820 million individuals and is the underlying cause of over 50% of all childhood deaths. Sweet potatoes have been promoted to address vitamin A (vitA) deficiency, with a single, orange-fleshed sweet potato (OFSP) providing enough vitA, as β-carotene, to meet daily needs. However, the bioavailability of β-carotene is dependent on the presence of dietary fat, which is not provided by OFSP, and it lacks some essential amino acids. Therefore, in an attempt to create a food product that meets daily vitA requirements with adequate bioavailability and complete protein, we designed and assessed a sweet potato, peanut paste, and legume product. The final food product formulation, developed through computer modeling, resulted in a 65/5/35 (w/w/w) formulation in a 250 g serving and ~330 kcal. We then confirmed the nutrient content of macronutrients, and essential amino acids, zinc, and iron contents. Total β-carotene was assessed by HPLC and was lower than predicted through computer modeling, likely due to losses through thermal processing and/or degradation from storage. The results of this project indicate that the three ingredients can be combined into a single 250 g food product to provide >300 kcal energy, complete protein, and micronutrients in a more bioavailable form.

Vitamin A levels reflect disease severity and portal hypertension in patients with cirrhosis

Background and AimsThe liver plays a key role in the storage, metabolism and homeostasis of fat-soluble vitamins. We investigated the relation of Vitamin(Vit)A/D/E serum levels with severity of liver disease and portal hypertension (PHT).MethodsVitA/D/E serum levels were assessed in 234 patients with advanced chronic liver disease (ACLD, i.e. hepatic venous pressure gradient [HVPG] ≥ 6 mmHg). Patients with hepatocellular carcinoma, pre-/post-hepatic PHT, TIPS or liver transplantation were excluded.ResultsMost patients were male (n = 153; 65%) with a median age of 57.6 (49.7–64.5) years. Thirty-two (14%) patients had HVPG 6–9 mmHg, 66 (28%) 10-15 mmHg, and 136 (58%) ≥ 16 mmHg, respectively. VitD deficiency (25-OH-vitamin-D <50 nmol/L) was found in 133 (57%) with higher prevalence in Child-Turcotte-Pugh (CTP)-C: 85% vs. B: 66% vs. A: 47% (p < 0.001). VitD levels displayed significant but weak correlations with hepatic dysfunction and PHT. VitE levels were normal in 227 (97%) patients and displayed no relevant association with hepatic dysfunction or PHT. Only 63 (27%) patients had normal (>1.05 µmol/L) VitA levels, while 58 (25%) had mild (0.70–1.04 µmol/L), 71 (30%) moderate (0.35–0.69 µmol/L), and 42(18%) severe(<0.35 µmol/L) VitA deficiency. VitA correlated with HVPG (Rho = −0.409), CTP score (Rho = −0.646), and serum bile acid levels (Rho = −0.531; all p < 0.001). The prevalence of decompensated ACLD (dACLD) continuously increased with severity of VitA deficiency (no: 40% vs. mild: 51% vs. moderate: 67% vs. severe: 91% had dACLD; p < 0.001). CTP score (per point; OR 2.46; 95%CI 1.80–3.37; p <0.001), age (per year; OR 0.95; 95%CI 0.92–0.98; p = 0.001) and elevated bile acid levels(>10 µmol/L; OR 3.62; 95%CI 1.61–8.14; p = 0.002) were independently associated with VitA deficiency.ConclusionVitA and VitD but not VitE deficiencies are highly prevalent in ACLD. VitA deficiency strongly correlates with hepatic dysfunction, PHT and bile acid levels and is associated with decompensated ACLD.Trial registration numberNCT03267615.

Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester

To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester. A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 μmol/L), marginal deficiency (0.70-<1.05 μmol/L), and sufficiency (≥1.05 μmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 μmol/L), marginal deficiency (0.35-<0.70 μmol/L), and sufficiency (≥0.70 μmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio. The average retinol concentration of the pregnant women was (1.15±0.30) μmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) μmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (pm=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (pm= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001). There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

Vitamin A deficiency impacts acquisition, but not expression, of autoimmunity to the neuroretina

Abstract Vitamin A (VitA) and its derivative retinoic acid (RA) are essential for immunological responses. Acquisition of effector responses is impeded in VitA-deficient (VAD) mice, but little is known about maintenance and expression of previously acquired effector function in the VAD environment, or its impact on progression of autoimmune diseases. We examined this using two models of uveitis: experimental autoimmune uveitis (EAU) induced by active immunization and spontaneous uveitis in retina-specific T cell receptor transgenic (R161H) mice, and in the model of experimental autoimmune encephalomyelitis (EAE). VAD was induced by dietary lack of VitA from before birth, or by daily injections of a pan-RA receptor inhibitor BMS493 in adult mice fed with standard diet. VAD mice were essentially resistant to induction of EAU or EAE and displayed impaired effector T cell responses. Defective priming/acquisition of effector function by VAD T cells was also evident in vitro. Interestingly, however, effector T cells primed in a VitA-sufficient environment were able to function in VAD recipients and induced EAU. Furthermore, spontaneously uveitic R161H mice fed with VAD diet, in which priming of pathogenic T cells occurs before onset of full VitA deficiency, appeared to develop unreduced or even exacerbated spontaneous uveitis compared to VitA-sufficient R161H mice. We conclude that although priming of naïve T cells in the VAD environment is defective, effector function acquired under VitA-sufficient conditions is maintained and can be expressed under VAD conditions. Because dietary lack of VitA is rarely profound and may be seasonal, our findings may shed light on immunity and autoimmunity in geographical regions where dietary VitA is limiting.

Phasing out of the Universal Mega Dose of Vitamin-A Prophylaxis to Avoid Toxicity.

Childhood blindness due to corneal ulceration was prevalent among poor Indian children. To tackle this situation, the National Institute of Nutrition (NIN), Hyderabad, India, Vitamin-A (Vit-A) prophylaxis programme was launched nationally in 1970 after field testing. Research of Indian Council for Medical Research (ICMR) documented that prevalence of Vit-A deficiency signs such as Bitot's spot decreased among children, over a period of time. However, this decrease cannot be ascertained is due to mass Vit-A prophylaxis programme. This is because coverage was low and patchy. Improved nutrition status, wider vaccination coverage, increased rate in breast feeding and improvement of healthcare services played a crucial role. Rather many studies revealed that (mass prophylaxis to the child who is having adequate Vit-A level) it may be harmful to certain group of children as a result of acute toxic symptoms. High dose of Vit-A is capable of loss of bone density-hence retarded growth may be observed in susceptible individuals. To tackle this issue food based approach should be promoted (which includes breast feeding) along with timely measles vaccination. The children who have signs of Vit-A deficiency (e.g. night blindness, xeropthalmia, Bitot's spot) or post measles children should receive Vit-A in age specific daily doses for two weeks along with Vit-A rich food, like green leafy vegetables, red palm oil, liver etc. Public spirited citizens, together with scientific community in India, should discourage this “one size fit to all” approach. It will not only avoid the ill effects of high dose of Vit-A but also it will help us optimal utilization of health resources in a resource poor country like India.

Vitamin A affects haematology, growth and immune response of Nile tilapia (Oreochromis niloticus, L.), but has no protective effect against bacterial challenge or cold-induced stress

Vitamin A (vitA) is an essential nutrient that acts as an endocrine regulator of several metabolic pathways, modulating normal growth and health status of animals. Although the importance of vitA for normal haematology and immune response is well documented for higher vertebrates, there is limited information on the physiological effects of vitA on fish. Therefore, we designed a 130-day feeding trial to evaluate the effect of vitA supplementation on growth, haematology, immune function and resistance to experimental infection with Aeromonas hydrophila and cold-induced stress. A group of 320 Nile tilapia fingerlings 7.49 ± 0.19 g weight (mean ± SD) were randomly stocked into 40 250 L-aquaria and fed practical diets containing graded levels of vitA (0, 0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 3.84 mg retinol (ROH) kg−1 diet. Growth, haematology, plasma protein profile and immune response were significantly affected by vitA supplementation; however, no clear protective effect of vitA supplementation on disease and cold stress resistance were observed in this study. Clinical signs of vitA deficiency were: resting and abnormal swimming behaviour, exophthalmia, haemorrhages at the base of fins and on skin, serous fluids in abdominal cavity, neutropenia, reduction in red blood cell count, haematocrit and haemoglobin evolving to high mortality rates in a short period of time. A dietary level of vitA around 1.2 mg ROH kg−1 may be required to prevent gross deficiency signs and promote proper growth and health status of Nile tilapia. VitA does not seem to have a pronounced effect on leucocyte differentiation, but clearly plays an important role on maintaining normal erythropoiesis.

Effects of vitamin A on growth, serum anti-bacterial activity and transaminase activities in the juvenile Japanese flounder, Paralichthys olivaceus

The present study examined the effects of dietary vitamin A (vitA) deficiency and excess on growth, serum anti-bacterial activity and serum enzyme activities of juvenile Japanese flounder, Paralichthys olivaceus. Three semi-purified diets containing 0, 10,000 and 25,000 International Units of vitA per kg of diet (IU vitA/kg) were fed to juvenile Japanese flounder (initial weight 1.59 g) for 120 days. At the end of the feeding trial, blood samples were taken from the fish for haematocrit, serum biochemical analysis and serum anti-bacterial activity. Growth performance, in terms of weight gain and specific growth rate, was improved significantly ( P < 0.05) with the addition of vitA to the diet. Total retinol contents in the liver increased with increasing dietary vitA levels. Haematocrit values did not show significant difference among the groups, but the values tended to increase with increasing dietary vitA levels. Serum total protein and albumin contents, and glutamyl oxaloacetic transaminase (GOT) activity tended to be lower in fish fed with 10,000 IU vitA/kg but significant difference was not observed among the groups. Serum total bilirubin content was significantly higher in treatment with no vitA than the other treatments. Glutamyl pyruvic transaminase (GPT) activity was significantly higher in the fish fed 25,000 IU vitA/kg than the other two groups. Serum anti-bacterial activity was significantly higher in the groups fed with 10,000 and 25,000 IU vitA/kg than that of the fish fed with 0 IU vitA/kg. These data suggest that dietary vitA significantly improved the growth performance and anti-bacterial activity of juvenile Japanese flounder. The tendency observed of high values in the blood serum parameters of the fish the diets of 0 and 25,000 IU vitA/kg after 120 days, suggests some negative effect on the liver (the main vitA storage site).

Effect of vitamin A deficiency on host intestinal immune response to Eimeria acervulina in broiler chickens

The effects of vitamin A (VitA) deficiency on the host intestinal immune response and disease susceptibility to coccidiosis were investigated in broiler chickens following oral infection with Eimeria acervulina (EA). Day-old male broilers were fed milo-soybean meal diets either with 8,000 IU VitA/kg feed (CONT) or without added VitA (A-DEF). At 25 d, a group of randomly selected birds from each treatment was inoculated orally with EA-sporulated oocysts. Intestinal immune response was assessed by the changes in the duodenum intraepithelial lymphocyte (IEL) subpopulations using flow cytometry at 35 d in in fected and noninfected birds. Concanavalin A (ConA)-induced spleen lymphocyte proliferation was tested using dimethylthiazol diphenyltetrazolium bromide colorimetric assay. Whether challenged or not with EA, A-DEF birds had fewer IEL expressing the surface markers CD3, CD4, CD8, alphabetaTCR, and gammabetaTCR. Without EA challenge, A-DEF birds had more surface IgA-expressing cells than CONT birds. Upon challenge, A-DEF chickens showed lower CD4+ IEL than CONT chickens. Following EA infection, CD8+ IEL increased in the CONT group, whereas no change was found in CD8+ IEL of A-DEF birds. A higher number of EA oocysts was recovered from A-DEF birds than from CONT birds (9.2 × 10(8) vs 5.4 × 10(8), respectively; P < or = 0.05). Serum samples taken 10 d post challenge showed higher antibody level against a recombinant coccidial antigen in A-DEF birds than in CONT birds. The A-DEF birds showed depressed ConA-induced lymphoproliferation response and produced lower serum interferon-gamma than CONT birds. These data show that VitA deficiency compromised local immune defenses of challenged birds, as reflected in lymphocyte profiles, oocyst shedding, and interferon-gamma levels in A-DEF birds.

The Effect of Hypovitaminosis A on the Pathogenesis of Pasteurella multocida in Turkeys

It has been proposed that Pasteurella multocida can invade the host tissues via the mucous membrane. Vitamin A (VitA) deficiency has been associated with mucous membrane damage, such as squamous metaplasia. The objective of this study was to determine the early stages in the pathogenesis of P. multocida in VitA-deficient turkeys and clinically healthy turkeys. Fifteen-week-old VitA-deficient and clinically healthy turkeys were inoculated with P. multocida P-1059, a virulent strain, and the portal of entry, invasion, and localization of P. multocida were studied by microbial examination of the trachea, liver, and lung and histologic examinations of internal organs. Higher mortality was found in VitA-deficient turkeys. Pasteurella multocida was first reisolated from the trachea, secondarily from the liver and blood, and finally from the lung in both groups. Invasion of P. multocida into tissues occurred between 3 hr and 24 hr postinoculation in both groups. Our findings suggest that altered membrane integrity in VitA-deficient birds did not appear to change the time course of the systemic spread of P. multocida infection in turkeys and that the increased mortality seen in the VitA-deficient turkeys may be associated with immune system impairment.

Induction of Vitamin A Deficiency in Turkeys

The objective of this study was to determine the relationship between the hepatic vitamin A (VitA) level and the pathologic changes in the oropharynx and esophagus of VitA-deficient turkeys. Study turkeys were provided with a diet sufficient (11,000 IU/kg) or deficient (2750 IU/kg) in VitA from 4 to 17 wk of age. Body weight, bacterial culture, and tissues from internal organs were collected at weekly intervals. VitA deficiency causes epithelial tissue damage in poultry. This epithelial damage was seen grossly as white plaques in the oropharynx and esophagus and histologically as squamous metaplasia of mucosal glands and keratinization of epithelium. No significant difference in body weights was seen among the groups. Moreover, no pathogenic bacteria was isolated during sampling periods. Liver VitA levels declined significantly after consumption of low VitA diet for 3 wk and were depleted after 5 wk. Squamous metaplasia due to VitA deficiency developed in the esophagus after 3 wk and in the oropharynx after 4 wk of consuming a VitA-deficient diet.

Cellular retinol-binding protein I is essential for vitamin A homeostasis.

The gene encoding cellular retinol (ROL, vitA)-binding protein type I (CRBPI) has been inactivated. Mutant mice fed a vitA-enriched diet are healthy and fertile. They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensable for RA synthesis. However, CRBPI deficiency results in an approximately 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells. This reduction is due to a decreased synthesis and a 6-fold faster turnover, which are not related to changes in the levels of RE metabolizing enzymes, but probably reflect an impaired delivery of ROL to lecithin:retinol acyltransferase. CRBPI-null mice fed a vitA-deficient diet for 5 months fully exhaust their RE stores. Thus, CRBPI is indispensable for efficient RE synthesis and storage, and its absence results in a waste of ROL that is asymptomatic in vitA-sufficient animals, but leads to a severe syndrome of vitA deficiency in animals fed a vitA-deficient diet.

Nutritional Status, Hypertension, Proteinuria and Glycosuria amongst the Women of Rural Bangladesh

Methods and materials - A rural community was purposively selected in Sreepur thana of which four villages were selected randomly. The total population of all age groups was 14,165 and the eligible reproductive aged females were 3,820 based on age between 15 and 45 years. Sample size was estimated at 573 (15%) of the eligible participants depending on the availability of time and logistic support. The study design was to use a questionnaire related to age, education, family income, housing and sanitation. Height (ht), weight (wt) and blood pressure (BP) were measured. Urine protein was estimated. Clinical examinations noted the presence of anemia, jaundice, edema, ring-worm, scabies, goiter, xerophthalmia and gum bleeding. Body mass index (BMI) was calculated to determine their obesity or wasting. Results - Overall, 501 volunteered and the response rate was 87.4%. Of these participants, 30.3% were illiterate. Almost all of them had supply of tube-well water and 68% had sanitary latrines. Their mean (±SD) age was 30.2 (±2.9)y, wt was 46 (±8.5)kg, ht was 149 (±5)cm and BMI was 20.5 (±3.5). The poor women had significantly lower BMI than the rich [20.0 (2.93) vs. 21.2 (4.1), (p&lt;0.05)]. Their mean (±SD) systolic and diastolic blood pressure were 116 (±17) and 73 (±12) mmHg, respectively. The prevalence of hypertension, proteinuria and glycosuria were 16.6, 10.4 and 2.6%, respectively. The frequencies of proteinuria and ring-worm were significantly higher among the poor than among the rich social class (both cases p&lt;0.05). Regarding nutritional deficiency, about half of the rural women (52%) had some form of signs relating to Vit-A deficiency and 65% had signs of Vit-B complex deficiency either in the form of glossitis or of angular stomatitis or both. Conclusions - Despite time and logistic constraint, the study revealed that most of the rural women had a poor nutritional status (80% had BMI&lt;23.0). The prevalence of hypertension and glycosuria were also not negligible. Vitamin deficiency disorders (xerophthalmia), gum-bleeding, angular stomatitis were also very high among them. The study also revealed that the poor social class had a significantly lower BMI, higher proteinuria and higher skin problems than their rich counterparts. Ibrahim Med. Coll. J. 2008; 2(1): 21-24 Key Words: doi: 10.3329/imcj.v2i1.2927