retinol-palmitate and Vitamin-A-Deficiency

To evaluate the effect of vitamin A supplementation in postpartum infants and women on serum retinol levels and breast milk. The databases Medline, PubMed, Lilacs and SciELO were consulted. The descriptors used were vitamin A, dietary supplement, child, postpartum period, infant and nutrition programs policies. Search found 7432 articles. After elimination of duplicity and application of eligibility criteria, 8 studies remained. All evaluated the effect of vitamin A supplementation on immediate postpartum, five studies used retinyl palmitate supplementation, one with retinyl palmitate and two did not specify the form of supplementation. Six studies evaluated colostrum and two included supplementation of children. It was found that supplementation in the puerperium increases the concentrations of serum retinol and breast milk, however, this result was in the short term and was relevant when the previous concentrations of the mother were low. When maternal serum concentrations are adequate, the retinol content in milk does not change, with little relevance for children. Further studies should be performed to evaluate the effect of megadoses supplementation on serum concentrations of children.

Topics: Colostrum; Dietary Supplements; Diterpenes; Female; Humans; Infant, Newborn; Milk, Human; Postpartum Period; Pregnancy; Retinyl Esters; Time Factors; Vitamin A; Vitamin A Deficiency

To report treatment of vitamin A deficiency retinopathy with sublingual vitamin A drops.. Case report with review of the literature.. A 69-year-old Caucasian woman with a history of small bowel resection presented with progressive symptoms of bilateral nyctalopia and decreased visual acuity. Ophthalmic examination revealed bilateral conjunctival xerosis and fine white granular deposits in the midperipheral retina suggestive of vitamin A deficiency. Full-field electroretinogram (ERG), multifocal ERG (mfERG), and two-color dark adaptometry revealed significant impairment of rod and cone photoreceptor function. Kinetic perimetry demonstrated depressed macular sensitivity with constriction of the finer isopters. After 5 months of treatment with sublingual vitamin A drops, the patient's vision, ERG, mfERG, dark adaptometry, and perimetry normalized. A review of the literature summarizing the electrophysiologic testing in vitamin A deficiency is also discussed.. This case highlights novel observations on the effects of sublingual vitamin A supplementation for acquired vitamin A deficiency retinopathy. Sublingual vitamin A may represent a viable and efficacious treatment modality for vitamin A deficiency.

Topics: Administration, Sublingual; Aged; Diterpenes; Electroretinography; Female; Humans; Night Blindness; Retina; Retinyl Esters; Visual Acuity; Visual Field Tests; Visual Fields; Vitamin A; Vitamin A Deficiency

Vitamin A deficiency continues to be an international public health problem with several important health consequences including blindness and overall increased rates of morbidity and mortality. To address this widespread issue, a series of strategies have been put into place from dietary diversification to supplementation and fortification programs. Retinyl palmitate has been used successfully for decades as a supplement as well as a way to fortify numerous foods, including vegetable oil, rice, monosodium glutamate, cereal flours and sugar. Recently, there has been rising interest in using a natural source of carotenoids, β-carotene from red palm oil (RPO), for fortification. Although RPO interventions have also been shown to effectively prevent Vitamin A deficiency, there are numerous challenges in using beta-carotene from RPO as a fortification technique. β-Carotene can induce significant changes in appearance and taste of the fortified product. Moreover, costs of fortifying with beta-carotene are higher than with retinyl palmitate. Therefore, RPO should only be used as a source of Vitamin A if it is produced and used in its crude form and regularly consumed without frying. Furthermore, refined RPO should be fortified with retinyl palmitate, not β-carotene, to ensure that there is adequate Vitamin A content.

Topics: beta Carotene; Diet; Dietary Supplements; Diterpenes; Edible Grain; Feasibility Studies; Food, Fortified; Humans; Palm Oil; Plant Oils; Randomized Controlled Trials as Topic; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Studies in India demonstrate that the beta-carotene in red palm oil is as effective as high-dose retinyl palmitate as a supplement to restore and preserve vitamin A nutriture in schoolchildren and may be an effective food-based strategy to combat hypovitaminosis A.

Topics: Anticarcinogenic Agents; Child; Controlled Clinical Trials as Topic; Diet; Diterpenes; Humans; India; Nutritional Requirements; Palm Oil; Plant Oils; Retinyl Esters; Vitamin A; Vitamin A Deficiency

The availability of synthetic vitamin A and its esters in unlimited quantities, has enabled populations around the world, consuming inadequate amounts of this vital micro-nutrient and hence subject to potential loss of sight or other manifestations of vitamin A deficiency, to have hope for a better future life. A technology exists for the preparation of synthetic vitamin A in various application forms. Many commonly-consumed foods may be used as carriers or vehicles of vitamin A to assure deficient populations of a sufficient intake of this antixerophthalmic and anti-infective vitamin.

Topics: Animals; Dietary Fats; Diterpenes; Edible Grain; Food, Fortified; Global Health; Humans; Margarine; Milk; Palmitates; Retinyl Esters; Sodium Chloride; Sodium Glutamate; Sucrose; Tea; Technology, Pharmaceutical; Vitamin A; Vitamin A Deficiency

Maternal supplementation with vitamin A is one of the strategies for controlling its deficiency in the mother-child dyad, although studies with animals showed that supplementation with high doses of vitamin A reduces the levels of α-tocopherol (vitamin E) in the mother's serum and milk. The objective of the present study was to assess the influence of maternal supplementation with vitamin A on the concentration of retinol and α-tocopherol in human milk.. Healthy puerperal women were randomly distributed into a control group (n = 44) and a supplemented group (n = 44). Blood and colostrum samples were collected after delivery, and mature milk samples were collected 30 days later. The supplemented group received 200 000 IU of retinyl palmitate after the first colostrum collection. The retinol and α-tocopherol levels in the samples were determined by high-performance liquid chromatography.. The mean (SD) retinol and α-tocopherol levels in the maternal serum were considered adequate at 46.4 (15.9) and 1023.6 (380.4) μg dL(-1) , respectively. The colostrum retinol levels of the supplemented group increased significantly 24 h after the intervention (P < 0.001). However, the retinol levels in the mature milk of both groups did not differ (P > 0.05). Moreover, after maternal supplementation with vitamin A, the colostrum α-tocopherol level decreased by 16.4%, which is a significant reduction (P < 0.05). However, vitamin A supplementation did not affect the α-tocopherol level of mature milk (P > 0.05).. Maternal supplementation with high doses of vitamin A increased the colostrum level of this nutrient but reduced the bioavailability of α-tocopherol, which may harm the newborn's health because newborns have limited vitamin E reserves.

Topics: alpha-Tocopherol; Brazil; Colostrum; Developing Countries; Dietary Supplements; Diterpenes; Female; Hospitals, Maternity; Humans; Infant, Newborn; Lactation; Lost to Follow-Up; Male; Maternal Nutritional Physiological Phenomena; Milk, Human; Nutritional Status; Postpartum Period; Retinyl Esters; Risk; Vitamin A; Vitamin A Deficiency; Vitamin E Deficiency

Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants.. We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.. Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.. Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).. Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.

Topics: Adult; Body Mass Index; Diterpenes; Female; Food, Fortified; Hemoglobins; Humans; Lactation; Milk, Human; Nutritional Status; Provitamins; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Young Adult; Zambia; Zea mays

Supplementation of vitamin A in children aged 6-59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months).. We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055.. Between Aug 26, 2010, and March 3, 2013, 31,999 newborn babies were randomly assigned to receive vitamin A (n=15,995) or placebo (n=16,004; 15,428 and 15,464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95-1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90-1·29) and for girls was 1·12 (0·91-1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing.. Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation.. Bill & Melinda Gates Foundation to WHO.

Topics: Administration, Oral; Capsules; Dietary Supplements; Diterpenes; Double-Blind Method; Drug Combinations; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Kaplan-Meier Estimate; Male; Retinyl Esters; Tanzania; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamins

Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age.. We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220.. Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32]).. The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy.. Bill & Melinda Gates Foundation to WHO.

Topics: Administration, Oral; Capsules; Dietary Supplements; Diterpenes; Double-Blind Method; Drug Combinations; Female; Humans; India; Infant; Infant Mortality; Infant, Newborn; Male; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamins

Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana.. This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055.. We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130).. The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana.. Bill & Melinda Gates Foundation grant to the WHO.

Topics: Administration, Oral; Dietary Supplements; Diterpenes; Double-Blind Method; Drug Combinations; Female; Ghana; Humans; Infant; Infant Mortality; Infant, Newborn; Kaplan-Meier Estimate; Male; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamins

Biofortification of cassava with the provitamin A carotenoid β-carotene is a potential mechanism for alleviating vitamin A deficiency. Cassava is a staple food in the African diet, but data regarding the human bioavailability of β-carotene from this food are scarce. The objective of the present study was to evaluate provitamin A-enhanced cassava as a source of β-carotene and vitamin A for healthy adult women. The study was a randomised, cross-over trial of ten American women. The subjects consumed three different porridges separated by 2 week washout periods. Treatment meals (containing 100 g cassava) included: biofortified cassava (2 mg β-carotene) porridge with added oil (15 ml peanut or rapeseed oil, 20 g total fat); biofortified cassava porridge without added oil (6 g total fat); unfortified white cassava porridge with a 0·3 mg retinyl palmitate reference dose and added oil (20 g total fat). Blood was collected six times from - 0·5 to 9·5 h post-feeding. TAG-rich lipoprotein (TRL) plasma was separated by ultracentrifugation and analysed using HPLC with coulometric array electrochemical detection. The AUC for retinyl palmitate increased after the biofortified cassava meals were fed (P< 0·05). Vitamin A conversion was 4·2 (sd 3·1) and 4·5 (sd 3·1) μg β-carotene:1 μg retinol, with and without added oil, respectively. These results show that biofortified cassava increases β-carotene and retinyl palmitate TRL plasma concentrations in healthy well-nourished adult women, suggesting that it is a viable intervention food for preventing vitamin A deficiency.

Topics: Adult; Area Under Curve; beta Carotene; Diterpenes; Female; Food, Fortified; Humans; Lipoproteins; Manihot; Plant Oils; Reference Values; Retinyl Esters; Triglycerides; Vitamin A; Vitamin A Deficiency; Young Adult

Within a neonatal vitamin A supplementation (VAS) trial, we investigated the effect of VAS on TNF-α, IL-10, IL-5 and IL-13 production after lipopolysaccharide, purified protein derivative (PPD) of Mycobacterium tuberculosis and phytohaemagglutinin stimulation using a whole blood culture protocol. We found that VAS recipients had lower unstimulated TNF-α concentrations than placebo recipients. In the present paper, we investigated whether the SNP TNF-α - 308, TNF-α - 238, IL-10 - 592, IL-10 - 1082 and toll-like receptor 4 (TLR4)+896 modified the effect of VAS on cytokine production. DNA and cytokine concentrations were available from 291 children. We found a significant interaction between TNF-α - 308 genotype and VAS for the unstimulated TNF-α production (Pinteraction = 0·04); among G homozygotes, TNF-α concentrations were significantly lower after VAS compared with placebo, whereas for A carriers, VAS did not appear to have any effect. For TNF-α - 238, there was a tendency towards an increase in PPD-stimulated TNF-α production after VAS for the G homozygotes, but the opposite tendency for A allele carriers (Pinteraction = 0·07). Stratification by sex revealed a significant VAS-genotype interaction for boys for TNF-α - 238. There was a borderline-significant three-way interaction (P = 0·05) between sex, VAS and TLR4+896 genotype. Although the present study had very limited representation of the genetic variation with potential for modification of the response to VAS, it adds to the efforts of untangling the diverse effects and impact of VAS.

Topics: Blood Cells; Cells, Cultured; Cytokines; Dietary Supplements; Diterpenes; Double-Blind Method; Female; Genetic Association Studies; Guinea-Bissau; Homozygote; Humans; Immunologic Factors; Infant, Newborn; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Retinyl Esters; Sex Characteristics; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin A Deficiency

Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown.. The efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 μg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 μg/dL).. In this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed.. Twelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (±SD) in serum retinol (3.6 ± 2.8 μg/dL) in those taking 600 μg vitamin A/d was significantly different from the decrease (±SD; -2.8 ± 2.4 μg/dL) in those taking 300 μg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses.. Compared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.

Topics: Anemia, Sickle Cell; Child; Child, Preschool; Dietary Supplements; Diterpenes; Double-Blind Method; Female; Hemoglobin, Sickle; Homozygote; Humans; Male; Nutritional Requirements; Nutritional Status; Pilot Projects; Prevalence; Retinyl Esters; Severity of Illness Index; United States; Vitamin A; Vitamin A Deficiency; Zinc Sulfate

To alleviate vitamin A (VA) deficiency (VAD) in Senegal, understanding the relationship between VA status of lactating women and their 6-mo-old infants is important. This study measured 6-mo-old infants' VA intake from human milk and assessed the VA status of mothers and infants. A comprehensive study was undertaken in 34 mother-infant pairs. Nonpregnant lactating women and their infants were included. None of the infants had received a VA supplement. Mothers were grouped as supplemented with 2 doses of 200,000 iu (60,000 μg; 210 μmol) retinol as retinyl palmitate (n = 13) or nonsupplemented (n = 19) after delivery. Breast milk intake was measured by the deuterium dilution technique. Plasma and breast milk retinol concentrations were measured by HPLC. Infants' VA liver stores were assessed by the modified relative dose-response (MRDR) test. Plasma retinol detected 15% VAD among infants and the MRDR test (≥0.06) indicated 73.5% with low VA liver stores. Infants' milk VA intakes were close to estimated requirements (375 μg/d). No correlation was found between infants' plasma retinol and MRDR value. Infants' MRDR value was lower in the group from supplemented mothers (0.055 ± 0.017 vs. 0.073 ± 0.017; P = 0.009), but no difference was observed between plasma retinol concentrations of both groups of mothers; 8.8% of mothers were VA deficient based on plasma retinol (≤0.7 μmol/L). Low VA liver stores were prevalent among Senegalese infants at the beginning of the complementary feeding period. Postpartum VA-supplemented mothers significantly enhanced their infants' VA liver stores.

Topics: Breast Feeding; Dietary Supplements; Diterpenes; Dose-Response Relationship, Drug; Female; Humans; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Liver; Maternal Nutritional Physiological Phenomena; Milk, Human; Prevalence; Retinyl Esters; Senegal; Vitamin A; Vitamin A Deficiency

Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival.. To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality.. Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007. Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 μg of retinol equivalents as retinyl palmitate, 42 mg of all-trans beta carotene, or placebo. Married women (n = 125,257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies.. All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome.. Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100,000 pregnancies) were 41 and 206 (95% confidence interval [CI], 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 [95% CI, 1.42-1.50] μmol/L vs 1.13 [95% CI, 1.09-1.17] μmol/L and 1.18 [95% CI, 1.14-1.22] μmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene [P < .001 for both]).. Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality.. clinicaltrials.gov Identifier: NCT00198822.

Topics: Adolescent; Adult; beta Carotene; Developing Countries; Dietary Supplements; Diterpenes; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Maternal Mortality; Middle Aged; Night Blindness; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Retinyl Esters; Rural Population; Stillbirth; Vitamin A; Vitamin A Deficiency; Vitamins; Young Adult

The aim of this study was to assess the effect of 2 different megadoses of retinyl palmitate on the level of retinol in the breast milk of healthy women. In total, 199 women were randomly allocated to 3 groups and supplemented in the postpartum period with a single retinyl palmitate dose of 200 000 IU (S1), a double dose of 200 000 IU 24 hours apart (S2), or no supplementation (C). Retinol content of colostrum and mature milk at 4 weeks was determined by high-performance liquid chromatography (HPLC). For colostrum, no significant difference was found between the groups (P = .965). The retinol content in mature milk differed between group C and groups S1 and S2 (P < .05). The double dose of vitamin A did not significantly increase the retinol content of milk at 4 weeks postpartum in comparison to a single dose; however, future research is needed to determine the optimal timing of the second dose of vitamin A.

Topics: Adult; Brazil; Chromatography, High Pressure Liquid; Colostrum; Dietary Supplements; Diterpenes; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Male; Milk, Human; Postpartum Period; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Young Adult

Vitamins A and E are recognisably important in the initial stages of life, and the newborn depends on nutritional adequacy of breast milk to meet their needs. These vitamins share routes of transport to the tissues and antagonistic effects have been observed in animals after supplementation with vitamin A. The present study aimed to determine the effect of maternal supplementation with a megadose of retinyl palmitate in the immediate post-partum on α-tocopherol concentration in the colostrum.. Healthy parturient women at a Brazilian public maternity were recruited for the study and divided into two groups: control (n = 37) and supplemented (n = 36). Blood and colostrum samples were collected up to 16 h post-partum. The supplemented group was administered with a retinyl palmitate capsule and, 24 h after the first collection, the second colostrum sample was obtained in the two groups for analysis of α-tocopherol. The cut-off points for deficiency are <1.05 μmol L(-1) for retinol and <11.6 μmol L(-1) for α-tocopherol.. The mean (SD) serum concentration of 1.77 (0.50) μmol L(-1) for retinol and 30.81 (6.46) μmol L(-1) for α-tocopherol indicates an adequate biochemical status. The supplemented group showed an increase of α-tocopherol in the colostrum 24 h after supplementation (P = 0.04), and this finding was not observed in the control group.. Supplementation with a 200,000 IU megadose of vitamin A did not negatively affect α-tocopherol levels in colostrum.

Topics: Adolescent; Adult; alpha-Tocopherol; Brazil; Breast Feeding; Colostrum; Cross-Sectional Studies; Dietary Supplements; Diterpenes; Female; Humans; Nutritional Status; Postpartum Period; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Vitamin E Deficiency; Young Adult

To assess the effect of maternal supplementation with a single dose of retinyl palmitate during the postpartum period, in order to provide vitamin A for the infant.. A clinical trial was conducted in Natal (Northern Brazil), between March and December 2007, on 85 women distributed randomly into two groups. The postpartum supplements of retinyl palmitate consisted of a single dose of 200,000 IU (experimental group) and zero IU (control group). The retinol levels in milk were quantified using high performance liquid chromatography. Based on the retinol concentrations obtained in breast milk and through simulations, vitamin A consumption among infants 24 hours and 30 days postpartum was calculated.. The daily provision of retinol to newborns through colostrum, 24 hours postpartum, was 1.63 micromol for the controls and 2.9 micromol for the experimental group, taking adequate intake to be 1.40 micromol/day and the milk volume consumed to be 500 ml/day. Thirty days postpartum, these values were 0.64 micromol/day (controls) and 0.89 micromol/day (experimental group), corresponding to a 39% increase in retinol concentration in the experimental group, in relation to the control group, or 64% of the recommendation for infants aged zero to six months.. Maternal supplementation with 200,000 IU of retinyl palmitate during the immediate post-partum period, and promotion of breastfeeding practices, are efficient for increasing the nutritional status of vitamin A for the mother-child pair.

Topics: Brazil; Breast Feeding; Dietary Supplements; Diterpenes; Female; Humans; Infant, Newborn; Milk, Human; Nutritional Status; Postpartum Period; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Young Adult

In Bangladesh, some commonly consumed, indigenous, freshwater small fish species (eaten whole with bone, head and eyes) such as mola (Amblypharyngodon mola) are nutrient-dense, containing preformed vitamin A as retinol and especially 3,4-dehydroretinol. The objective of the present randomised, controlled efficacy study was to evaluate the effects of mola on biochemical indicators of vitamin A status. Children (n 196), aged 3-7 years, with serum retinol 0.36-0.75 micromol/l, were randomly allocated to one of three treatment groups to receive a daily test meal (6 d/week for 9 weeks) of rice and vegetable curry (no vitamin A) ad libitum and 50 g fish curry consisting of: (1) mola, 600 retinol activity equivalents (RAE) (using 40 % biological activity of 3,4-dehydroretinol isomers) (experimental group, n 66); (2) rui (Labeo rohita), a large fish (no vitamin A), with added retinyl palmitate, 600 RAE (positive control group, n 65); or (3) rui, 0 RAE (negative control group, n 65). The nutrient compositions of the dishes were analysed. After 9 weeks, no significant treatment effects were observed for serum retinol (P = 0.52) and retinol-binding protein (P = 0.81) in the experimental group compared with the negative control, whereas the positive control improved significantly (P < 0.001). The present results do not suggest conversion of the large amount of 3,4-dehydroretinol in mola curry to retinol. Further research on the functional effect of mola in humans is needed. Mola is a nutrient-dense animal-source food, rich in haem Fe, Zn and especially Ca, thus consumption of mola in Bangladesh should continue to be encouraged.

Topics: Animals; Anthropometry; Bangladesh; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Developing Countries; Diterpenes; Female; Fishes; Food Analysis; Fresh Water; Humans; Male; Nutritive Value; Patient Compliance; Retinol-Binding Proteins; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency

It is not known whether daily consumption of vitamin A-containing foods is efficacious for treating nightblindness.. We assessed the effect of supplementation with vitamin A from food or synthetic sources on dark adaptation and plasma retinol concentrations in nightblind pregnant Nepali women.. Nightblind pregnant women were randomly assigned to 1 of 6 treatment groups to receive 6 d/wk for 6 wk either 850 microg retinol equivalents/d as retinyl palmitate, vitamin A-fortified rice, goat liver, amaranth leaves, or carrots or 2000 microg retinol equivalents/d as retinyl palmitate. Dark adaptation was assessed weekly by using the pupillary threshold (PT) test; plasma retinol concentrations were measured before and after the intervention. These outcomes were also assessed in a comparison group of nonnightblind pregnant women.. In the nightblind women, the mean PT improved significantly (P<0.0001) from -0.71+/-0.04 to -1.42+/-0.02 log cd/m2, and the final mean PT did not differ significantly from that in the nonnightblind women (-1.43+/-0.04; P=0.55). Improvement in dark adaptation was greater in the liver group than in the vitamin A-fortified rice group (P<0.02). Plasma retinol concentrations increased significantly (P<0.0001) from 0.95+/-0.05 to 1.07+/-0.05 micromol/L. The plasma retinol response was greater in the higher-dose capsule and liver groups than in the vegetable groups and significantly greater in the liver group than in the vitamin A-fortified rice group (both: P<0.05).. Improvement in dark adaptation did not differ significantly between women who received vitamin A as liver, amaranth leaves, carrots, or retinyl palmitate.

Topics: Adolescent; Adult; Animals; Dark Adaptation; Diet; Diterpenes; Female; Food, Fortified; Goats; Humans; Liver; Meat; Nepal; Night Blindness; Pregnancy; Pregnancy Complications; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency

Malabsorption of fat-soluble vitamins is a major complication of chronic cholestatic liver disease. The most accurate way to assess vitamin A status in children who have cholestasis is unknown. The goal of this study was to assess the accuracy of noninvasive tests to detect vitamin A deficiency. Children with chronic cholestatic liver disease (n = 23) and noncholestatic liver disease (n = 10) were studied. Ten cholestatic patients were identified as vitamin A-deficient based on the relative dose response (RDR). Compared with the RDR, the sensitivity and specificity to detect vitamin A deficiency for each test was, respectively: serum retinol, 90% and 78%; retinol-binding protein (RBP), 40% and 91%; retinol/RBP molar ratio, 60% and 74%; conjunctival impression cytology, 44% and 48%; slit-lamp examination, 20% and 66%; tear film break-up time, 40% and 69%; and Schirmer's test, 20% and 78%. We developed a modified oral RDR via oral coadministration of d-alpha tocopheryl polyethylene glycol-1000 succinate and retinyl palmitate. This test had a sensitivity of 80% and a specificity of 100% to detect vitamin A deficiency. In conclusion, vitamin A deficiency is relatively common in children who have chronic cholestatic liver disease. Our data suggest that serum retinol level as an initial screen followed by confirmation with a modified oral RDR test is the most effective means of identifying vitamin A deficiency in these subjects.

Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholestasis; Chronic Disease; Diterpenes; Dry Eye Syndromes; Female; Humans; Infant; Liver Diseases; Male; Polyethylene Glycols; Retinol-Binding Proteins; Retinyl Esters; Sensitivity and Specificity; Vitamin A; Vitamin A Deficiency; Vitamin E

Red palm oil (5 ml and 10 ml), ground nut oil fortified with 400 and 800 retinol equivalent retinol palmitate, and ground nut oil (5 and 10 ml), were administered to six groups of preschool children (four experimental and two control groups) in randomly assigned balwadis of Ramanathapuram District of Tamil Nadu for a period of 7 months, to monitor the difference in the efficacy of the mode of supplementation and the optimum dose for improving vitamin A status. Results show that red palm oil groups recorded more gain in retinol and beta-carotene levels compared to other dosage groups, and that administration of 10 ml did not offer any substantial improvement over the 5-ml daily dose.

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Dietary Supplements; Diterpenes; Female; Humans; Infant; Male; Plant Oils; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency

Thirty-four asymptomatic children, ages 5-35 mo, were studied to compare the conjunctival impression cytology technique with the relative dose response test in detection of subclinical vitamin A deficiency. Conjunctival smears were collected from the infero-temporal-bulbar conjunctiva of each eye with a strip of cellulose acetate filter paper and transferred onto a glass slide. Venous blood was drawn at 0 and 5 h after administration of an oral dose of 1000 micrograms of retinol palmitate (relative dose response test). An increase in serum retinol concentration (> or = 20%) in the 5-h value was considered indicative of an inadequate liver store of vitamin A and hence subclinical vitamin A deficiency. Of the 34 children, 26 (76.5%) had moderate to severe protein-energy malnutrition. Only three children (9%) had abnormal conjunctival impression cytology, whereas 23 (68%) had abnormal relative dose response. Even more striking was the finding that only two of the 23 children with abnormal relative dose response had abnormal conjunctival impression cytology. The results suggest that the conjunctival impression cytology test has poor agreement with the relative dose response test results in assessing vitamin A status in young children. If relative dose response is considered an acceptable reference method for assessing vitamin A status, then the conjunctival impression cytology test cannot be considered a valid measure of subclinical vitamin A deficiency in this population.

Topics: Bangladesh; Child, Preschool; Conjunctiva; Cytological Techniques; Diterpenes; Dose-Response Relationship, Drug; Female; Humans; Infant; Liver; Male; Protein-Energy Malnutrition; Retinyl Esters; Vitamin A; Vitamin A Deficiency

To assess vitamin A status in children with pneumonia.. Thirty-four hospitalised patients with pneumonia were randomly allocated into two groups: the study group, besides the routine treatment, received a high dose of aqueous retinyl palmitate oral solution; the control group received only the routine treatment.. The concentrations of plasma vitamin A and carotenoids were determined by colorimetric method. Retinol binding protein (RBP) was determined by the radial immunodiffusion technique.. After 1 week of treatment there was a statistically significant (P < 0.05) increase in the levels (mean +/- s.e.) of vitamin A (study group: 14.1 +/- 1.6 to 26.5 +/- 5.8 micrograms/dl; control group: 16.1 +/- 3.3 to 24.1 +/- 2.3 micrograms/dl) and RBP (study group: 0.8 +/- 0.2 to 2.2 +/- 0.6 mg/dl; control group: 0.6 +/- 0.2 to 3.0 +/- 0.5 mg/dl) in both groups as compared to the baseline. On day 7 of treatment when the average levels of vitamin A (26.5 +/- 5.8 and 24.1 +/- 2.3 micrograms/dl) were compared, there was no statistically significant difference between the groups.. This study suggests that low levels of circulating plasma vitamin A in child with pneumonia may be a consequence of acute phase of infectious disease.

Topics: Acute-Phase Reaction; Administration, Oral; Carotenoids; Child; Child, Preschool; Diterpenes; Dose-Response Relationship, Drug; Female; Humans; Infant; Male; Nutritional Status; Pneumonia; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Retinyl Esters; Vitamin A; Vitamin A Deficiency

To determine whether beta carotene is therapeutically equivalent to retinyl palmitate in the formulation currently recommended by the World Health Organisation.. Randomised blind equivalence trial.. Rural area in Senegal.. Children aged 2-15 years suffering from vitamin A deficiency as defined by abnormal results on eye cytology were randomly allocated treatment with retinyl palmitate (n = 256) and beta carotene (n = 254).. Reversion to normal results on eye cytology as defined by the reappearance of goblet cells and normalisation of the epithelial cells.. Seven weeks after the supplement was given the percentages were 51.2% (124/242) children taking retinyl palmitate and 50.0% (123/246) of those taking beta carotene, who had reverted to normal eye cytology, a difference of 1.2% (95% confidence interval 6.2% to 8.6%) [corrected]. According to an equivalence testing procedure, the two treatments were statistically equivalent; the null hypothesis of non-equivalence was rejected (one tailed p value = 0.03).. beta Carotene supplementation seems to be a promising candidate for the alleviation of vitamin A deficiency. It could be given either as high dose capsule or through increased dietary intake. The challenge now is to improve dietary intake of vitamin A in programmes that are effective and sustainable at the community level.

Topics: Adolescent; beta Carotene; Carotenoids; Child; Child, Preschool; Diterpenes; Female; Humans; Male; Retina; Retinyl Esters; Therapeutic Equivalency; Vitamin A; Vitamin A Deficiency

Topics: Diterpenes; Female; Humans; Male; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Vitamins

To assess oil consumption, vitamin A intake and retinol status before and a year after the fortification of unbranded palm oil with retinyl palmitate.. Pre-post evaluation between two surveys.. Twenty-four villages in West Java.. Poor households were randomly sampled. Serum retinol (adjusted for subclinical infection) was analysed in cross-sectional samples of lactating mothers (baseline n 324/endline n 349), their infants aged 6-11 months (n 318/n 335) and children aged 12-59 months (n 469/477), and cohorts of children aged 5-9 years (n 186) and women aged 15-29 years (n 171), alongside food and oil consumption from dietary recall.. Fortified oil improved vitamin A intakes, contributing on average 26 %, 40 %, 38 %, 29 % and 35 % of the daily Recommended Nutrient Intake for children aged 12-23 months, 24-59 months, 5-9 years, lactating and non-lactating women, respectively. Serum retinol was 2-19 % higher at endline than baseline (P<0·001 in infants aged 6-11 months, children aged 5-9 years, lactating and non-lactating women; non-significant in children aged 12-23 months; P=0·057 in children aged 24-59 months). Retinol in breast milk averaged 20·5 μg/dl at baseline and 32·5 μg/dl at endline (P<0·01). Deficiency prevalence (serum retinol <20 μg/dl) was 6·5-18 % across groups at baseline, and 0·6-6 % at endline (P≤0·011). In multivariate regressions adjusting for socio-economic differences, vitamin A intake from fortified oil predicted improved retinol status for children aged 6-59 months (P=0·003) and 5-9 years (P=0·03).. Although this evaluation without a comparison group cannot prove causality, retinyl contents in oil, Recommended Nutrient Intake contributions and relationships between vitamin intake and serum retinol provide strong plausibility of oil fortification impacting vitamin A status in Indonesian women and children.

Topics: Adolescent; Adult; Child; Child, Preschool; Cooking; Cross-Sectional Studies; Diet; Diterpenes; Female; Food, Fortified; Humans; Indonesia; Infant; Male; Milk, Human; Nutritional Status; Palm Oil; Plant Oils; Poverty; Prevalence; Program Evaluation; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Vitamins; Young Adult

Vitamin A deficiency (VAD) is associated with the progression of chronic liver disease (CLD). The aim in this study was to assess levels of serum retinol and retinol-binding protein (RBP) as well as liver vitamin A stores in the presence of liver cirrhosis and hepatocellular carcinoma.. We ascertained the serum retinol and RBP levels of randomly selected CLD patients divided into two groups, one given 1500 UI (n = 89) and the other receiving 2500 UI (n = 89) doses of retinyl palmitate for the relative dose response test. Blood samples were collected in a fasting state and 5 and 7 h after supplementation.. The prevalence of VAD was 62.4%. There was a progressive drop in serum retinol (P < 0.001) and RBP (P = 0.002) according to the severity of the liver disease, and a greater prevalence of severe VAD was noted in cirrhosis Child & Pugh C (52.8%). Fifty percent of the patients presented a low availability of RBP relative to retinol concentration, and there was no peak in RBP levels regardless of the dose of retinyl palmitate administered.. Our findings suggest serum retinol and RBP are relevant as indicators of vitamin A nutritional status in the presence of CLD. Liver vitamin A store cannot be evaluated using the RDR test because CLD causes a reduction in RBP synthesis and interferes with the mobilization of endogenous vitamin A. Considering how the patients already showed a drop in RBP relative to retinol concentrations, it is reasonable to assume vitamin A supplementation may trigger harmful effects in CLD patients.

Topics: Adult; Aged; Diterpenes; Female; Humans; Liver Diseases; Male; Metabolism, Inborn Errors; Middle Aged; Nutritional Status; Retinol-Binding Proteins; Retinyl Esters; Severity of Illness Index; Treatment Outcome; Vitamin A; Vitamin A Deficiency

Our previous studies showed that intranasal vaccination of vitamin A-deficient (VAD) mice failed to induce normal levels of upper respiratory tract IgA, a first line of defense against respiratory virus infection. Here we demonstrate that the impaired responses in VAD animals are corrected by a single intranasal application of retinyl palmitate with the vaccine. Results encourage the clinical testing of intranasal vitamin A supplements to improve protection against respiratory viral disease in VAD populations.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Diterpenes; Female; Immunity, Mucosal; Immunoglobulin A; Mice, Inbred C57BL; Pregnancy; Respiratory System; Retinyl Esters; Viral Vaccines; Vitamin A; Vitamin A Deficiency

Vitamin A deficiency (VAD) is a leading cause of pediatric morbidity and mortality due to infectious diseases. Recent pre-clinical studies have revealed that VAD impairs mucosal IgA-producing antibody forming cell (AFC) responses toward a paramyxovirus vaccine in the upper respiratory tract (URT), thus impeding a first line of defense at the pathogen's point-of-entry. The studies described here tested the hypothesis that VAD may also impair immune responses after FluMist vaccinations. Results show that (i) IgA-producing antibody forming cells (AFCs) are significantly reduced following FluMist vaccination in VAD mice, and (ii) oral doses of either retinyl palmitate or retinoic acid administered on days 0, 3, and 7 relative to vaccination rescue the response. Data encourage the conduct of clinical studies to determine if there are FluMist vaccine weaknesses in human VAD populations and to test corrective supplementation strategies. Improvements in vaccine efficacy may ultimately reduce the morbidity and mortality caused by influenza virus worldwide.

Topics: Administration, Intranasal; Animals; Antibody-Producing Cells; Diterpenes; Female; Immunity, Mucosal; Immunoglobulin A; Influenza Vaccines; Mice; Mice, Inbred C57BL; Pregnancy; Retinyl Esters; Tretinoin; Vaccination; Vitamin A; Vitamin A Deficiency

The relationship of dietary vitamin A transfer from mother to fetus is not well understood. The difference in swine offspring liver reserves was investigated between single-dose vitamin A provided to the mother post-conception compared with continuous provitamin A carotenoid dietary intake from biofortified (enhanced provitamin A) orange maize (OM) fed during gestation and lactation. Vitamin A-depleted sows were fed OM (n = 5) or white maize (WM) + 1.05 mmol retinyl palmitate administered at the beginning of gestation (n = 6). Piglets (n = 102) were killed at 0, 10, 20, and 28 d after birth. Piglets from sows fed OM had higher liver retinol reserves (P < 0.0001) and a combined mean concentration from d 10 to 28 of 0.11 ± 0.030 μmol/g. Piglets from sows fed WM had higher serum retinol concentrations (0.56 ± 0.25 μmol/L; P = 0.0098) despite lower liver retinol concentrations of 0.068 ± 0.026 μmol/g from d 10 to 28. Milk was collected at 0, 5, 10, 20, and 28 d. Sows fed OM had a higher milk retinol concentration (1.36 ± 1.30 μmol/L; P = 0.038), than those fed WM (0.93 ±1.03 μmol/L). Sow livers were collected at the end of the study (n = 3/group) and had identical retinol concentrations (0.22 ± 0.05 μmol/g). Consumption of daily provitamin A carotenoids by sows during gestation and lactation increased liver retinol status in weanling piglets, illustrating the potential for provitamin A carotenoid consumption from biofortified staple foods to improve vitamin A reserves. Biofortified OM could have a measurable impact on vitamin A status in deficient populations if widely adopted.

Topics: Animal Feed; Animals; Animals, Suckling; Diet; Diterpenes; Female; Lactation; Liver; Male; Milk; Retinyl Esters; Swine; Vitamin A; Vitamin A Deficiency; Zea mays

Iron bioavailability seems to be regulated by vitamin A (VA) but the molecular events involved in this mechanism are not well understood. It is also known that retinoids mediate most of their function via interaction with retinoid receptors, which act as ligand-activated transcription factors controlling the expression of a number of target genes. Here, we evaluated the VA effects on the modulation of the levels of mRNA encoding proteins involved in the iron bioavailability, whether in the intestinal absorption process or in the liver iron metabolism. The expression of genes involved in iron intestinal absorption (divalent metal transporter 1, duodenal cytochrome B, ferroportin 1 FPN1, and ferritin) were evaluated in vitro by treating Caco-2 cells with retinoic acid or in vivo by observing the effects of vitamin A deficiency (VAD) in BALB/C mice. Liver hepcidin and ferritin mRNA levels were upregulated by VAD; however, this condition did not promote any change on the expression of those genes that participate in the iron absorption. Moreover, data from the in vitro analysis showed that VA induced FPN1 gene expression by a hepcidin-independent manner. Therefore, the in vivo results support the idea that VAD may not affect iron absorption but would rather affect iron mobilization mechanisms. On the other hand, our results using Caco-2 cells raises the possibility that VA addition to intestinal epithelium may improve iron absorption through the induction of FPN1 gene expression.

Topics: Animals; Antimicrobial Cationic Peptides; Blotting, Western; Caco-2 Cells; Cation Transport Proteins; Dietary Supplements; Diterpenes; Drug Evaluation, Preclinical; Duodenum; Ferritins; Gene Expression Regulation; Hepcidins; Humans; Intestinal Absorption; Intestinal Mucosa; Iron; Liver; Male; Mice; Mice, Inbred BALB C; Retinyl Esters; RNA, Messenger; Tretinoin; Vitamin A; Vitamin A Deficiency

Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A.. This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month.. Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05).. Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

Topics: Adult; Case-Control Studies; Dark Adaptation; Diterpenes; Female; Humans; Injections, Intramuscular; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Transplantation; Male; Middle Aged; Prospective Studies; Retinyl Esters; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Vitamins; Zinc

Vitamin A (VA) deficiency is still a major health problem in the developing world. It affects various cellular functions and causes hypolipidemic effects in the body. β-Carotene (BC)-rich foods are promising sources of VA. Phospholipids are reported to improve BC bioefficacy in normal rats, but whether they show similar effects during VA deficiency is unknown.. To compare the BC metabolism and plasma lipid responses in VA-sufficient (+VA) and VA-deficient (-VA) rats after a single oral dose of micellar BC containing phospholipids.. Groups of rats were fed with a VA-free diet and when they attained the weight-plateau stage of deficiency, both +VA and -VA rats were divided into 2 groups (phosphatidylcholine, PC and lysophosphatidylcholine, LPC). Each group was further divided into 4 subgroups (1, 2, 3, and 6 h; n = 5 rats/time point) and determined the BC metabolism and plasma lipid responses to a post-dose of micellar BC with phospholipids.. Maximal plasma BC (pmol/mL) levels were observed at 2 h in PC (1330 ± 124) and at 1 h in LPC (1576 ± 144) groups of +VA rats, and at 3 h in the PC (1621 ± 158) and LPC (2248 ± 675) groups of -VA rats. Liver BC (pmol/g) was maximum at 1 h in the PC (218 ± 32) and LPC (249 ± 24) groups of +VA rats, and at 2 h in PC (228 ± 23) and at 3 h in LPC (277 ± 18) groups of -VA rats. Plasma and liver BC levels were significantly (P < 0.05) higher in -VA rats than +VA rats. Plasma retinyl palmitate (pmol/mL) was maximum at 3 h in PC (97 ± 18) and at 2 h in LPC (126 ± 14) groups of +VA rats, and at 2 h in the PC (92 ± 13) and LPC (134 ± 27) groups of -VA rats. The higher (P < 0.05) BC monoxygenase activity in -VA rats compared to +VA rats supports the BC bioefficacy. Plasma retinol level was improved in the PC and LPC groups, but the effect of LPC was higher (P < 0.05) than PC. Micellar phospholipids mitigate the VA deficiency-induced hypolipidemic effects.. Micellar phospholipids improved BC metabolism and reinstated the hypolipidemic effects, perhaps by modifying the fat-metabolizing enzymes and repairing the altered intestinal membrane structure.

Topics: Animals; beta Carotene; Diet; Diterpenes; Dose-Response Relationship, Drug; Lipid Metabolism; Liver; Lysophosphatidylcholines; Male; Micelles; Phosphatidylcholines; Rats; Rats, Wistar; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Topics: Alcoholism; Conjunctival Diseases; Corneal Diseases; Diterpenes; Humans; Injections, Intramuscular; Liver Function Tests; Malabsorption Syndromes; Male; Middle Aged; Retinyl Esters; Tomography, X-Ray Computed; Vitamin A; Vitamin A Deficiency

Vitamin A deficiency in Central America was first identified as a public health problem in the 1950s. It affected primarily children. The main underlying cause was a deficient intake of pre-formed vitamin A, but infection and intestinal parasitism also played important roles. INCAP focused its efforts on overcoming this problem and developed, as a short-term solution, the technology to fortify sugar with vitamin A. Fortification programs were implemented in several Central American countries. Evaluation of these programs revealed a significant impact-not only on vitamin A status, but also on iron nutrition and hematological condition. Longer-term solutions, like increasing the availability and consumption of vitamin A-rich foods, were later suggested and operational tools were developed to assist the countries in the region in the implementation, evaluation and monitoring of their own fortification programs.

Topics: Academies and Institutes; Anemia, Iron-Deficiency; Carotenoids; Central America; Diet; Dietary Sucrose; Diterpenes; Food Analysis; Food Supply; Food, Fortified; History, 20th Century; Humans; Nutrition Policy; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Several clinical trials have revealed that individuals who were given beta-carotene and vitamin A did not have a reduced risk of cancer compared to those given placebo; rather, vitamin A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S. & Hammar, S. N. Engl. J. Med (1996) 334, 1150-1155; Hennekens, C.H., Buring, J.E., Manson, J.E., Stampfer, M., Rosner, B., Cook, N.R., Belanger, C., LaMotte, F., Gaziano, J.M., Ridker, P.M., Willet, W. & Peto, R. (1996) N. Engl. J. Med. 334, 1145-1149]. Using differential display techniques, an initial survey using rats showed that liver RNA expression of c-H-Ras was decreased and p53 increased in rats with chronic vitamin A deficiency. These findings prompted us to evaluate the expression of c-Jun, p53 and p21WAF1/CIF1 (by RT-PCR) in liver and lung of rats. This study showed that c-Jun levels were lower and that p53 and p21WAF1/CIF1 levels were higher in chronic vitamin A deficiency. Vitamin A supplementation increased expression of c-Jun, while decreasing the expression of p53 and p21WAF1/CIF1. Western-blot analysis demonstrated that c-Jun and p53 showed a similar pattern to that found in the RT-PCR analyses. Binding of retinoic acid receptors (RAR) to the c-Jun promoter was decreased in chronic vitamin A deficiency when compared to control hepatocytes, but contrasting results were found with acute vitamin A supplementated cells. DNA fragmentation and cytochrome c release from mitochondria were analyzed and no changes were found. In lung, an increase in the expression of c-Jun produced a significant increase in cyclin D1 expression. These results may explain, at least in part, the conflicting results found in patients supplemented with vitamin A and illustrate that the changes are not restricted to lung. Furthermore, these results suggest that pharmacological vitamin A supplementation may increase the risk of adverse effects including the risk of oncogenesis.

Topics: Animals; Blotting, Western; Cell Division; Chronic Disease; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Diterpenes; DNA; Gene Expression Profiling; Gene Expression Regulation; Hypervitaminosis A; Liver; Lung; Macromolecular Substances; Precipitin Tests; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Receptors, Retinoic Acid; Retinyl Esters; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Suppressor Protein p53; Vitamin A; Vitamin A Deficiency

Recent studies have revealed that retinoids play an important role in the adult central nervous system and cognitive functions. Previous investigations in mice have shown that vitamin A deficiency (VAD) generates a hypo-expression of retinoic acid (RA, the active metabolite of vitamin A) receptors and of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) and a concomitant selective behavioural impairment. Knowing that RC3 is both a triiodothyronine (T3) and a RA target gene, and in consideration of the relationships between the signalling pathways of retinoids and thyroid hormones, the involvement of T3 on RA signalling functionality in VAD was investigated. Thus, the effects of vitamin A depletion and subsequent administration with RA and/or T3 on the expression of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and on RC3 in the brain were examined. Rats fed a vitamin A-deficient diet for 10 weeks exhibited a decreased expression of RAR, RXR and TR mRNA and of RC3 mRNA and proteins. RA administration to these vitamin A-deficient rats reversed only the RA hypo-signalling in the brain. Interestingly, T3 is able to restore its own brain signalling simultaneously with that of vitamin A and the hypo-expression of RC3. These results obtained in vivo revealed that one of the consequences of VAD is a dysfunction in the thyroid signalling pathway in the brain. This seems of crucial importance since the down regulation of RC3 observed in the depleted rats was corrected only by T3.

Topics: Animals; Blotting, Western; Brain Chemistry; Calmodulin-Binding Proteins; Diterpenes; GTP-Binding Proteins; Liver; Male; Nerve Tissue Proteins; Neurogranin; Protein Glutamine gamma Glutamyltransferase 2; Rats; Rats, Wistar; Receptors, Retinoic Acid; Receptors, Thyroid Hormone; Retinoid X Receptors; Retinyl Esters; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription Factors; Transglutaminases; Tretinoin; Triiodothyronine; Vitamin A; Vitamin A Deficiency

Retinyl palmitate added to Fe-fortified maize bread has been reported to enhance Fe absorption in adult Venezuelan subjects but not in Western Europeans. It is not known to what extent these results were influenced by differences in vitamin A status of the study subjects. The objective of the present study was to evaluate the influence of retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe in children with vitamin A deficiency, before and after vitamin A supplementation. Erythrocyte incorporation of Fe-stable isotopes was measured 14 d after intake of maize porridge (2.0 mg Fe added as ferrous sulfate) with and without added retinyl palmitate (3.5 micromol; 3300 IU). The study was repeated 3 weeks after vitamin A supplementation (intake of a single dose of 210 micromol retinyl palmitate; 'vitamin A capsule'). Vitamin A status was evaluated by the modified relative dose-response (MRDR) technique. Retinyl palmitate added to the test meal reduced the geometric mean erythrocyte incorporation of Fe at baseline from 4.0 to 2.6 % (P=0.008, n 13; paired t test). At 3 weeks after vitamin A supplementation, geometric mean erythrocyte incorporation was 1.9 and 2.3 % respectively from the test meal with and without added retinyl palmitate (P=0.283). Mean dehydroretinol:retinol molar ratios were 0.156 and 0.125 before and after intake of the single dose of 210 micromol retinyl palmitate; 'vitamin A capsule' (P=0.15). In conclusion, retinyl palmitate added to the labelled test meals significantly decreased erythrocyte incorporation of Fe in children with vitamin A deficiency at baseline but had no statistically significant effect 3 weeks after vitamin A supplementation. The difference in response to retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe before and after intake of the vitamin A capsule indicates, indirectly, changes in vitamin A status not measurable by the MRDR technique. The lack of conclusive data on the effect of retinyl palmitate on Fe absorption indicates the complexity of the interactions between vitamin A status, dietary vitamin A and Fe metabolism.

Topics: Adolescent; Antioxidants; Capsules; Child; Diterpenes; Dose-Response Relationship, Drug; Erythrocytes; Female; Food, Fortified; Humans; Iron; Male; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Zea mays

Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.

Topics: Animals; Case-Control Studies; Diterpenes; Dog Diseases; Dogs; Female; Male; Mucoproteins; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Retinyl Esters; Urinary Calculi; Uromodulin; Vitamin A; Vitamin A Deficiency

Chronic ethanol intake results in decreased hepatic vitamin A levels through both enhanced degradation of vitamin A via a cytochrome P450 enzyme (CYP)-dependent process and increased mobilization of vitamin A from the liver into the circulation. This study investigated whether treatment with chlormethiazole, a CYP inhibitor, restores vitamin A in the livers of ethanol-fed rats.. Ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole (10 and 100 mg/kg body weight) for 1 month. Liver and plasma levels of retinol and retinyl palmitate were analyzed by high-performance liquid chromatography. Expressions of hepatic lecithin:retinol acyltransferase (LRAT) and cellular retinol-binding protein were analyzed with reverse transcription-polymerase chain reaction. Hepatic retinol esterification by LRAT was examined by using incubations of the microsomal fractions of livers with exogenous sources of retinol.. Ethanol-feeding in rats for a month resulted in lower hepatic levels of retinol and retinyl palmitate than those found in controls and the occurrence of several polar retinoid metabolites. In contrast, treatment with chlormethiazole at two different doses in ethanol-fed rats completely blocked the formation of hepatic retinoid polar metabolites and restored hepatic levels of retinol and hepatic retinyl palmitate in a dose-dependent manner. Furthermore, increased plasma concentrations of retinyl palmitate in rats fed with ethanol, which indicate increased mobilization of vitamin A, were partially inhibited by chlormethiazole treatment. However, neither ethanol nor chlormethiazole treatment altered the expression and activity of LRAT in the liver of rats. Hepatic expression of cellular retinol-binding protein increased significantly in ethanol-fed rats with or without chlormethiazole treatment compared with control rats.. These data suggest that chlormethiazole can restore both hepatic retinol and retinyl ester concentrations to normal levels in ethanol-fed rats through blocking enhanced both degradation of vitamin A and mobilization of vitamin A from the liver into the circulation.

Topics: Alcohol Drinking; Animals; Chlormethiazole; Diterpenes; Dose-Response Relationship, Drug; Ethanol; Liver; Male; Rats; Rats, Sprague-Dawley; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Vitamin A (VA) and insulin-like growth factors (IGF) are important regulators of a wide range of physiological processes. To investigate the IGF system's involvement in the physiological actions of VA, we examined the effects of VA status on components of the IGF system in rats. Male rats (3-wk-old) fed a VA-deficient diet for 11 wk developed VA deficiency, as confirmed by the depletion of serum retinol and hepatic retinyl palmitate. Rats fed the VA-deficient diet had significantly lower body weight (p < 0.05) and lower serum IGF-I concentrations than the rats fed the control diet. The decreases in serum IGF-I levels were accompanied by approximately 40% lower levels of the IGF-I mRNA in the liver and lungs. With respect to the gene expression of other IGF system components, VA deficiency caused a twofold induction of IGF-I receptor (IGF-IR) mRNA in the heart and a twofold reduction in IGFBP-6 mRNA in the lungs, but did not alter the expression of IGF-II, IGFBP-1, IGFBP-3, IGFBP-4 or IGFBP-5 in all tissues examined. When VA-deficient rats received a single injection of retinoic acid (2 mg/rat), tissue IGF-I and IGF-IR gene expression did not change after 4 or 8 h, while the expression of IGF-II, IGFBP-4, and IGFBP-6 mRNAs in some tissues increased rapidly. These results suggest a possible involvement of the IGF system in mediating the physiological actions of VA, including VA-supported growth, in the rat.

Topics: Animals; Blotting, Northern; Diterpenes; Gene Expression Regulation; Insulin-Like Growth Factor Binding Proteins; Male; Random Allocation; Rats; Rats, Wistar; Retinyl Esters; RNA, Messenger; Somatomedins; Tissue Distribution; Tretinoin; Vitamin A; Vitamin A Deficiency

To examine the role of retinoids in hematopoietic cell growth in vivo, we studied female SENCAR mice made vitamin A deficient by dietary restriction. Deficient mice exhibited a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. The abnormal expansion of myeloid cells was detected from an early stage of vitamin A deficiency and contrasted with essentially normal profiles of T and B lymphocytes. This abnormality was reversed on addition of retinoic acid to the vitamin A-deficient diet, indicating that the myeloid cell expansion is a direct result of retinoic acid deficiency. TUNEL analysis indicated that spontaneous apoptosis, a normal process in the life cycle of myeloid cells, was impaired in vitamin A-deficient mice, which may play a role in the increased myeloid cell population. Quantitative reverse transcriptase-polymerase chain reaction analysis of purified granulocytes showed that expression of not only RAR, but RXRs, 2 nuclear receptors that mediate biologic activities of retinoids, was significantly reduced in cells of deficient mice. This work shows that retinoids critically control the homeostasis of myeloid cell population in vivo and suggests that deficiency in this signaling pathway may contribute to various myeloproliferative disorders.

Topics: Animals; Apoptosis; B-Lymphocytes; Bone Marrow; Colony-Forming Units Assay; Cytokines; Diet; Diterpenes; Female; Granulocytes; Hematopoietic Stem Cells; In Situ Nick-End Labeling; Liver; Mice; Mice, Inbred SENCAR; Retinyl Esters; Reverse Transcriptase Polymerase Chain Reaction; Spleen; T-Lymphocytes; Vitamin A; Vitamin A Deficiency

Normal embryonic development and survival in utero is dependent on an adequate supply of vitamin A. Embryos from vitamin A-deficient (VAD) pregnant rats fed an inadequate amount of all-trans retinoic acid (atRA; 12 microg per g of diet or approximately 230 microg per rat per day) exhibit severe developmental abnormalities of the anterior cardinal vein and hindbrain by embryonic day (E) 12.5 and die shortly thereafter.. In the present study, we sought to determine whether supplementation of VAD-RA supported (12 microg per g of diet) pregnant rats with retinol (ROL) at the late-gastrula (presomite or rat E9.5) or early somite stages (E10.5), or provision of higher levels of atRA throughout this period could prevent abnormalities in the developing cardiovascular and nervous systems.. A newly described defect in the sinuatrial venus valve along with enlarged anterior cardinal veins and nervous system abnormalities and the later death of embryos are prevented by supplementing pregnant animals with ROL on the morning of E9.5. If ROL supplementation is delayed by 1 day (E10.5), most embryos are abnormal and die by E18.5. Supplementation of VAD rats with atRA (250 microg per g of diet) between E8.5 and E10.5 also prevents the cardiovascular and nervous system abnormalities and a significant number of these embryos survive to parturition. Thus, high levels of atRA can obviate the need for ROL between E9.5 and E10.5.. These results support an essential role for retinoid signaling between the late gastrula and early somite stages in the rat embryo for normal morphogenesis of the primitive heart tube and the posterior hindbrain. Further, these results suggest that embryonic death occurring at midgestation in the VAD rat may be linked to the abnormal development of one or both of these embryonic structures.

Topics: Abnormalities, Multiple; Animal Feed; Animals; Cranial Nerves; Diterpenes; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Female; Fetal Death; Fetal Heart; Fetal Resorption; Gastrula; Genes, Homeobox; Gestational Age; Morphogenesis; Pregnancy; Pregnancy Complications; Rats; Retinyl Esters; Rhombencephalon; Transcription Factors; Tretinoin; Veins; Vitamin A; Vitamin A Deficiency

Two German sisters aged 14 and 17 y were admitted to the Tübingen eye hospital with a history of night blindness. In both siblings, plasma retinol binding protein (RBP) concentrations were below the limit of detection (<0.6 micromol/L) and plasma retinol concentrations were extremely low (0.19 micromol/L). Interestingly, intestinal absorption of retinyl esters was normal. In addition, other factors associated with low retinol concentrations (eg, low plasma transthyretin or zinc concentrations or mutations in the transthyretin gene) were not present. Neither sibling had a history of systemic disease.. Our aim was to investigate the cause of the retinol deficiency in these 2 siblings.. The 2 siblings and their mother were examined clinically, including administration of the relative-dose-response test, DNA sequencing of the RBP gene, and routine laboratory testing.. Genomic DNA sequence analysis revealed 2 point mutations in the RBP gene: a T-to-A substitution at nucleotide 1282 of exon 3 and a G-to-A substitution at nucleotide 1549 of exon 4. These mutations resulted in amino acid substitutions of asparagine for isoleucine at position 41 (Ile41-->Asn) and of aspartate for glycine at position 74 (Gly74-->Asp). Sequence analysis of cloned polymerase chain reaction products spanning exons 3 and 4 showed that these mutations were localized on different alleles. The genetic defect induced severe biochemical vitamin A deficiency but only mild clinical symptoms (night blindness and a modest retinal dystrophy without effects on growth).. We conclude that the cellular supply of vitamin A to target tissues might be bypassed in these siblings via circulating retinyl esters, beta-carotene, or retinoic acid, thereby maintaining the health of peripheral tissues.

Topics: Adolescent; Base Sequence; Diterpenes; Exons; Female; Humans; Molecular Sequence Data; Nuclear Family; Point Mutation; Prealbumin; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Zinc

During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, precipitates respiratory distress syndrome (RDS) of the neonate. Although vitamin A (retinol) and retinoic acid have been shown to enhance the synthesis of phospholipid surfactant components, their effect on surfactant-specific proteins is unclear. No attempt has been made to evaluate the consequences of vitamin A restriction on surfactant phospholipid storage or on the expression of the life-essential surfactant protein-B (SP-B). We induced in rats a partial vitamin A deficiency leading to a 30-60% reduction in blood retinol, a status compatible with maintenance of gestation and absence of gross abnormalities in offspring. At term, lung surfactant phospholipids were reduced by 21%, and the major surfactant phospholipid, disaturated phosphatidylcholine (DSPC), was reduced by 27% in vitamin A-deficient (VAD) fetuses. The decrease in surfactant phospholipids and DSPC correlated linearly with plasma retinol, and reached about 50% in fetuses with the lowest retinol concentrations; it was accompanied by reduced expression of the gene for fatty acid synthase, a key enzyme in the synthetic pathway for surfactant-phospholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consistently, amounts of SP-A and SP-B proteins were diminished as assessed by Western blotting. The proportion of type II cells determined after SP-B labeling was unchanged in VAD as compared with control lungs. Vitamin A deficiency is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk for RDS and an aggravating factor for prematurity.

Topics: Animals; Choline-Phosphate Cytidylyltransferase; Diterpenes; Female; Lung; Phospholipids; Pregnancy; Pregnancy Complications; Pregnancy, Animal; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Retinyl Esters; Vitamin A; Vitamin A Deficiency

We examined the effects of vitamin A palmitate (VA pal) eyedrops on the symptoms caused by vitamin A-deficiency in rabbits.. Three-week-old rabbits were raised on a vitamin A-deficient diet, and were examined for the quantity of retinol in the serum and the condition of the anterior segment of the eye. The vitamin A-deficient animals were treated with VA pal eyedrops.. The retinol in the serum began to decrease seven months after the animals were placed on the vitamin A-deficient diet. After ten months, superficial punctate keratitis and the loss of conjunctival goblet cells were observed. Treatment of the disease in the anterior segment of the eyes with VA pal eyedrops resulted in restoration of normal condition within 3 weeks. The treatment increased the goblet cells in the ocular conjunctiva and the retinol in the serum.. These results show the efficacy of topical VA pal treatment for vitamin A-deficient rabbits.

Topics: Animals; Anterior Eye Segment; Diterpenes; Male; Ophthalmic Solutions; Rabbits; Retinyl Esters; Vitamin A; Vitamin A Deficiency

The effect of vitamin A supplementation on stearoyl-CoA desaturase gene 1 expression in mouse liver was characterized. Normal BALB/c mice were fed 0.01% and 0.1% retinol palmitate as components of nonpurified diets. This treatment resulted in a 3-fold and a 7-fold induction of SCD1 mRNA levels, respectively, as determined by RNase protection analysis. Vitamin A-deficient animals were also fed diets containing 0.01% and 0.1% retinol palmitate, resulting in a similar pattern of SCD1 mRNA induction. Fatty acid synthase and beta-actin mRNA levels did not respond consistently or significantly to retinoic acid treatment. Dietary and hormonal studies were carried out to investigate the role of the retinoid X receptor in the regulation of SCD1 by type II steroid hormones. A receptor-saturating dose of thyroid hormone, triiodothyronine, repressed vitamin A-elevated SCD1 mRNA levels in vivo. Peroxisome proliferator-elevated SCD1 mRNA levels were unaffected by administration of thyroid hormone. This suggests that the retinoic acid receptor transcriptionally regulates SCD1 through a traditional mechanism of heterodimerization with the retinoid X receptor.

Topics: Actins; Animals; Clofibrate; Diterpenes; Dose-Response Relationship, Drug; Fatty Acid Synthases; Gene Expression Regulation, Enzymologic; Liver; Male; Mice; Mice, Inbred BALB C; Microbodies; Receptors, Retinoic Acid; Retinoid X Receptors; Retinyl Esters; RNA, Messenger; Stearoyl-CoA Desaturase; Transcription Factors; Triiodothyronine; Vitamin A; Vitamin A Deficiency

Vitamin A-deficient humans and animals are more susceptible to infections than are healthy humans and animals. This study compares the early corneal response (within 24 hours) to an experimental Pseudomonas aeruginosa infection between vitamin A deficient and control rats.. Male WAG/Rij/MCW rats were fed either a vitamin A- deficient diet (A-) or the same diet with retinyl palmitate added back in a nonrestricted manner (N) or under pair-fed conditions (A+) to yield weight-matched rats. Some A-rats were repleted wih retinyl palmitate 16 days before being killed and then given free access to the retinyl palmitate-supplemented diet (R). Twenty-four hours before being killed, the corneas of anesthetized rats were scratched and P. aeruginosa organisms were applied to the corneal surface. The rats were killed using an overdose of sodium pentobarbital. Corneas were either processed for light and electron microscopic examination or extracted for proteinase and myeloperoxidase determination. Corneal myeloperoxidase concentrations relative to neutrophil myeloperoxidase concentrations were used to determine the number of neutrophils in the cornea. Zymography was used to study caseinases, gelatinases, and plasminogen activators. Reverse zymography was used to detect proteinase inhibitors. Similar results were noted at early, mid, and late weight plateau stages of vitamin A deficiency.. Ulceration occurred within 24 hours when low numbers of P. aeruginosa (10(4) cpu) were applied topically onto scratched A- corneas, whereas no ulceration was observed in the A+, R, and N corneas. When higher numbers of P. aeruginosa (10(7)-10(8)) were applied to the scratched corneas, all corneas became ulcerated within 24 hours. The extent of ulceration in the control corneas was greater than that in A- corneas by a factor of two. Only the A- corneas contained inflammatory cells with unusual striated deposits in phagolysosomes. The total number of neutrophils in the cornea and the concentrations of caseinases, plasminogen activators, and gelatinases in the infected corneal extracts were similar; however, the concentrations of cysteine proteinase inhibitors were elevated under A- conditions.. Vitamin A deficiency alters the response of the cornea to a P. aeruginosa infection during the first 24 hours. The alterations observed are probably due to multiple factors: an insufficient tear film for bacterial clearance and migration of neutrophils, epithelial keratinization, alterations in corneal wound healing, and changes in polymorphonuclear function.

Topics: Animals; Anticarcinogenic Agents; Blotting, Western; Cornea; Corneal Ulcer; Disease Models, Animal; Disease Susceptibility; Diterpenes; Electrophoresis, Polyacrylamide Gel; Endopeptidases; Eye Infections, Bacterial; Female; Liver; Male; Neutrophils; Peroxidase; Pseudomonas Infections; Rats; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Vitamin A status can influence a number of enzymes and coenzymes involved in folate-dependent one-carbon metabolism as well as subsequent methyl group metabolism. Tracer kinetic techniques were used in the present study to assess the physiological importance of vitamin A deficiency on the de novo synthesis of methionine via the hepatic folate-dependent one-carbon pool. Vitamin A-deficient (0 retinol equivalents (RE) retinyl palmitate/g diet) rats were fed their respective diet for 11 wk, whereas control rats (1.2 RE retinyl palmitate/g diet) were food restricted to match the growth rate exhibited by the vitamin A-deficient group. After the dietary treatment period, duodenal cannulated rats were continuously infused with L-[3-(14)C] serine and L-[methyl-(3)H] methionine until a plateau specific radioactivity was exhibited with respect to the hepatic serine and methionine pools, indicating a steady state had been achieved. The hepatic concentration of both S-adenosylmethionine a S-adenosylhomocysteine were elevated in vitamin A-deficient rats. However, Vitamin A-deficient rats exhibited similar kinetic values compared with control rats fed a vitamin A-sufficient diet. The irreversible loss rate of hepatic serine and methionine, the transfer quotient from serine to methionine and the folate-dependent flow of carbon to methionine from serine were unaffected by vitamin A status. These studies demonstrate that vitamin A deficiency does not affect the reductive carbon flow from serine to methionine because the ability to generate methionine via remethylation of homocysteine with the carbon group originating from serine was not altered in vitamin A-deficient rats. Furthermore, the data illustrate the importance of using tracer kinetic techniques to quantify metabolic flux under steady-state conditions in vivo, thereby evaluating the consequences of an abnormal condition on a physiological and functional basis.

Topics: Animals; Carbon; Carbon Radioisotopes; Diterpenes; Folic Acid; Liver; Male; Methionine; Random Allocation; Rats; Rats, Sprague-Dawley; Retinyl Esters; S-Adenosylhomocysteine; S-Adenosylmethionine; Serine; Tritium; Vitamin A; Vitamin A Deficiency

The present study determined the effects of vitamin A (vA) deficiency on the responses to ozone (O3) challenges in two inbred strains of mice that are differentially susceptible to O3-induced lung inflammation. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) dams at 2 wk gestation were fed test diets containing either 0 or 10 micrograms retinol/g diet. In mice that were maintained on vA-sufficient (vA+) diet, lung and liver tissue concentrations of vA and retinyl palmitate (RP) were significantly (P<0.05) lower in the B6 strain compared with C3, as measured by high-performance liquid chromatography techniques. vA and RP levels were significantly (P<0.05) reduced in lung and liver tissues of 8-wk old B6 and C3 mice that were maintained on a vA deficient (vA-) diet. vA+ and vA- mice of both strains were exposed to air or 0.3 ppm O3/72 h, and lung injury was assessed by differential cell count and total protein concentration in bronchoalveolar lavage (BAL) returns. O3 exposure caused significantly (P<0.05) greater increases in inflammatory cells and a total protein in BAL returns of vA+ B6 mice than vA+ C3 mice. vA deficiency significantly (P<0.05) enhanced O3-induced increases in polymorphonuclear leukocytes in C3 mice and epithelial cells loss in both strains. Compared with vA+ mice, lung permeability was also significantly (P<0.05) enhanced in vA- mice of both strains exposed to O3. vA replacement partially reversed the O3-induced lung injury that was enhanced by vA- diet. Results indicate that vA may have an important role in the pathogenesis of O3-induced lung injury in differentially susceptible inbred strains of mice.

Topics: Analysis of Variance; Animals; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Diterpenes; Epithelial Cells; Epithelium; Female; Inflammation; Liver; Lung; Lung Injury; Lymphocytes; Macrophages, Alveolar; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Ozone; Retinyl Esters; Species Specificity; Vitamin A; Vitamin A Deficiency

In hairless mice, a moderate vitamin-A deficiency, without any clinical signs or weight changes, reduces the activity of soluble cytoplasmic hepatic transglutaminase without affecting the membrane form of the enzyme. This attack of soluble transglutaminase appears to be a biological marker of early deficiency. The relations between this disturbance and the hepatocyte sensitivity to aggressors at this stage are discussed.

Topics: Animals; Body Weight; Cytoplasm; Diet; Diterpenes; Female; Least-Squares Analysis; Liver; Mice; Mice, Hairless; Retinyl Esters; Time Factors; Transglutaminases; Vitamin A; Vitamin A Deficiency; Vitamin E

Different cell culture and organ systems are used to evaluate the physiological responses of the airways to the effects of carcinogenic [e.g., benzo(a)pyrene] and anticarcinogenic (e.g., retinoids) compounds on cellular growth and differentiation. However, in contrast to in vivo conditions dissociated epithelial cells or tracheal ring cultures are covered with medium. Therefore, we developed an ex vivo perfusion model enabling evaluation of morphology and metabolism of different compounds under near-physiological conditions. The trachea was surrounded with culture medium and perfused with air by means of a small animal respirator. To test the viability of the system under various experimental conditions tracheal probes were incubated with either retinoids (retinol 10(-5) mol/l; retinyl palmitate 10(-5) mol/l) or benzo(a)pyrene (10(-7) mol/l) for up to 7 days. At the end of the incubation period metabolites in the trachea and in the medium were measured by means of high-performance liquid chromatography. Samples were examined by light microscopy, and by scanning and transmission electron microscopy for cell morphology. Glycoconjugate expression was assessed by lectin histochemistry. Specimens incubated in a retinoid-supplemented medium revealed no alterations in the distribution of cell types and characteristics of the epithelial layer compared with tracheal biopsies assessed immediately after removal from the animals. Glycoconjugate patterns especially remained intact. Histological changes after incubation with benzo(a)pyrene resembled in vivo morphology of vitamin A-deficient rats. An important advantage of this in vitro model compared with common cell or organ cultures is the preservation of the original phenotype and environment of the tracheobronchial surface. In addition, carcinogenic substances, such as benzo(a)pyrene, can easily be applied by airway or through the medium.

Topics: Animals; Benzopyrenes; Diterpenes; Lectins; Microscopy, Electron; Oligosaccharides; Organ Culture Techniques; Protein Binding; Rats; Rats, Wistar; Retinyl Esters; Trachea; Vitamin A; Vitamin A Deficiency; Xenobiotics

Topics: Administration, Oral; Animals; Antibody-Producing Cells; Bile; Cholera Toxin; Cholera Vaccines; Diterpenes; Immune Tolerance; Immunity, Mucosal; Immunization; Immunoglobulin A; Immunoglobulin A, Secretory; Male; Rats; Rats, Wistar; Retinyl Esters; Vitamin A; Vitamin A Deficiency

We investigated the effect of retinoids on fetal lung development in the rat. The concentration of retinyl palmitate increased rapidly to a peak on day 17 of gestation and decreased to a minimum on day 21 of gestation; there was a slight increase after birth. Retinoid acid receptor (RAR)-alpha and -beta mRNA were detected in all samples obtained from perinatal and adult rat lung, and only a trace of RAR-gamma mRNA was detected in the fetuses on days 15, 17 and 19 of gestation and in the adults by reverse transcriptase-polymerase chain reaction. After a maternal retinol deficiency of 28 days' duration, fetal body and lung weights were significantly lower than those of controls; the concentrations of retinyl palmitate and phosphatidylcholine (PC) in the lung after a maternal retinol deficiency of 14, 21, or 28 days were significantly lower than those of controls. Expression of RAR-beta mRNA in the group with 28-day retinol deficiency was lower than in controls, that of RAR-alpha mRNA was increased and that of RAR-gamma mRNA was not influenced by retinol deficiency. The rate of choline incorporation into PC in fetal lung explants was significantly higher in the group treated with retinoic acid (RA) than in controls. RA enhanced the effect of epidermal growth factor on choline incorporation and prevented that of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Choline; Diterpenes; Fetal Organ Maturity; Gene Expression; Lung; Phosphatidylcholines; Polymerase Chain Reaction; Rats; Rats, Wistar; Receptors, Retinoic Acid; Retinoids; Retinyl Esters; RNA-Directed DNA Polymerase; RNA, Messenger; Vitamin A; Vitamin A Deficiency

Vitamin A status of wild male mallards (Anas platyrhynchos) overwintering in Saskatchewan, Canada was determined. Vitamin A levels < 0.2 micrograms hepatic retinyl palmitate/g liver, occurred in 6% and 25% of male mallards sampled in 1991 to 1992 and 1992 to 1993, respectively. There was no temporal trend in vitamin A levels over either winter. Squamous metaplastic lesions, commonly associated with vitamin A deficiency in domestic animals, were not observed in any bird; hence, they were not a good indicator of vitamin A status in wild mallards. Serum retinol was not a good indicator of vitamin A status in wild mallards. Many mallards in good body condition had low vitamin A levels; thus, we propose that good body condition and ample fat stores are not indicative of overall health of the bird.

Topics: Animal Nutritional Physiological Phenomena; Animals; Bird Diseases; Body Constitution; Diterpenes; Ducks; Liver; Male; Nutritional Status; Retinyl Esters; Saskatchewan; Seasons; Vitamin A; Vitamin A Deficiency

Captive mallards (Anas platyrhynchos), fed an all-grain diet for up to 5 months during the winters of 1991 to 1992 and 1992 to 1993, developed lesions of squamous metaplasia; some had no detectable hepatic vitamin A. Vitamin A deficiency in mallards was defined as hepatic levels of retinyl palmitate < 2 micrograms/g liver. Lesions were found only in ducks with low levels of hepatic vitamin A, but not all ducks with these low levels of hepatic vitamin A had histological lesions. The prevalence of lesions in the esophagus was greatest cranially and caudally and less common in the central region. Palatine salivary glands rarely were affected. Mallards with liver stores > 600 micrograms of hepatic retinyl palmitate per g liver, fed a diet deficient in vitamin A were unlikely to become deficient over a 5 month period. Birds fed an all-grain diet had significantly lower vitamin A concentrations in their liver compared to those fed an all-grain diet with vitamin A added. Liver weight, when corrected for body size, did not affect vitamin A concentration. Serum retinol levels were conserved over a large range of hepatic vitamin A levels but levels below 300 micrograms retinol/l were useful in detecting vitamin A deficiency in captive mallards. Based on the findings, the presence of lesions provides a conservative measure of vitamin A status in ducks and tissue levels should be measured in instances when mallards have questionable vitamin A status.

Topics: Animals; Bird Diseases; Body Weight; Diet; Diterpenes; Ducks; Esophagus; Female; Kidney; Liver; Male; Metaplasia; Organ Size; Random Allocation; Retinyl Esters; Salivary Glands; Vitamin A; Vitamin A Deficiency

To determine whether vitamin A is involved in pancreatic alpha cell function, we tested for (a) effects of vitamin A deficiency on glucagon release from perifused islets and perfused pancreases, and (b) the presence of cytosolic retinol-binding proteins (CRBP) and retinoic acid-binding proteins (CRABP), in the glucagon-secreting alpha cell line, ln-R1-G9. Arginine 19 mM plus glucose 2.8 mM-stimulated glucagon secretion was markedly impaired in islets and pancreases of vitamin A-deficient rats or rats that had at some time been cycled through vitamin A deficiency (ever A-def) despite repletion with retinoids for 2-4 weeks. Insulin secretion was impaired likewise. Repletion starting early in the development of vitamin A deficiency and for a longer period of time (18 or 60 days) did not restore glucagon secretion, but did normalize insulin secretion. CRBP and CRABP were present in ln-R1-G9 cells. We conclude that (a) vitamin A deficiency is associated with a defect in glucagon secretion; (b) The defect in secretion occurs early in the course of vitamin A deficiency; (c) The defect persists despite repletion; and (d) The requirement of vitamin A for secretion and the presence of CRBP and CRABP in glucagon-secreting cells support a physiologic role for vitamin A at the alpha cell level.

Topics: Animals; Arginine; Cell Line; Diterpenes; Female; Glucagon; Glucose; Insulin; Insulin Secretion; Islets of Langerhans; Pregnancy; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Retinoids; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Retinyl Esters; Tretinoin; Vitamin A; Vitamin A Deficiency

Ten crossbred wether lambs were fed once daily an oat diet that contained 3102 micrograms of retinyl palmitate (control) and were supplemented with 55,000 micrograms of retinyl palmitate orally once every two weeks. Twenty lambs were fed the same oat diet without retinyl palmitate supplements (A-depleted). After being fed the A-depleted diet for 28 weeks, 10 A-depleted lambs were repleted by feeding the control diet and oral supplementation of retinyl palmitate for eight weeks. The A-depleted lambs had serum vitamin A concentrations indicative of vitamin A deficiency, which was supported by very low liver vitamin A concentrations. Light microscopic and ultrastructural examinations revealed that alterations occurred at 50% and 75% of the small intestine length in A-depleted lambs only. Sawtooth configuration of the intestinal epithelium was a distinctive histologic feature. Consistent ultrastructural alterations were vesicular microvillar degeneration and disruption of the capillary endothelium. These results suggests that A-depleted diets have a detrimental effect on the small intestinal epithelium of lambs. Vitamin A repletion appears to minimize the detrimental effects.

Topics: Analysis of Variance; Animals; Diet; Diterpenes; Epithelium; Intestine, Small; Least-Squares Analysis; Microscopy, Electron; Retinyl Esters; Sheep; Sheep Diseases; Time Factors; Vitamin A; Vitamin A Deficiency

Administration of large oral doses of retinyl palmitate has become the most widely practised vitamin A deficiency prevention strategy in developing countries. We conducted a follow-up study among 220 Senegalese children aged 2-7 years suffering from moderate undernutrition to determine the efficacy of vitamin A treatment on their vitamin A status assessed by biochemical and cytological (impression cytology with transfer) methods. The first examination (T = 0 m[onth]) was carried out during April 1989, before the mango (Mangifera indica L,) harvest. The second examination (T = 2 m) was carried out 2 months after vitamin A treatment during June 1989 when ripe mangoes become widely available. Conjunctival cells of the eyes of the children with or without ocular inflammation were responsive to vitamin A administration (P < 0.01). There was a significant increase (P < 0.001) in mean serum retinol and beta-carotene levels between T = 0 m and T = 2 m. Mean serum retinol-binding protein (RBP) and transthyretin (TTR) levels did not differ significantly (P > 0.05) at T = 0 m and T = 2 m. Despite the intake of vitamin A, 54% of the children who had abnormal cytology at T = 0 m remained abnormal at T = 2 m. This was due to inadequate levels of TTR and RBP, presumably due to the cereal diet eaten by the Senegalese population. children with abnormal eye cytology had lower serum retinol levels than those with normal eyes at T = 0 m, and beta-carotene values did not correlate with eye cytological abnormalities at T = 0 m. Children with normal cytology had higher serum retinol and also beta-carotene levels than those with abnormal cytology after massive oral doses of vitamin A and consumption of mangoes at T = 2 m. Retinyl palmitate may, therefore, only lead to partial cytological improvement due to a lack of retinol-carrier proteins but dietary beta-carotene may also be involved.

Topics: beta Carotene; Carotenoids; Child; Child, Preschool; Conjunctiva; Diterpenes; Drug Administration Schedule; Eye Diseases; Follow-Up Studies; Fruit; Humans; Retinyl Esters; Senegal; Vitamin A; Vitamin A Deficiency

Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334-2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 micrograms), followed by 20 applications of TPA (2 micrograms), or by 20 applications of DMBA (25 micrograms for 2 weeks and 51 micrograms thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 micrograms/g of diet) or retinyl palmitate (RP, 6 micrograms/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non-purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Diet; Diterpenes; Female; Mice; Mice, Inbred Strains; Papilloma; Retinyl Esters; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors; Vitamin A; Vitamin A Deficiency

Neonatal vitamin A stores are limited even in well-nourished full-term infants and are yet smaller in the premature infant. The object of this experiment was to determine whether vitamin A deficiency could be induced in pregnant guinea pigs and, if so, whether it would affect vitamin A status of the neonate. Adult (600 g) guinea pigs were fed a casein-agar diet that was vitamin A deficient (AD). Controls (vitamin A adequate) were orally dosed weekly with 2 mg of retinyl palmitate. Weight gains of dams and birth weights of neonates did not differ. No external signs of deficiency were observed. Six of eight AD and seven of eight vitamin A-adequate dams carried pregnancy to term (greater than or equal to Day 64). One AD dam died during delivery. Liver retinol concentrations were below the detection limit (less than 3 micrograms/g) for all AD neonates and dams and in postpartum serum of AD dams. Of neonates born greater than or equal to Day 64, 15 of 18 AD were dead or moribund compared with 4 of 22 vitamin A adequate. The unexpectedly severe effect on the neonate indicates that the guinea pig will be a sensitive model for investigating the affect of poor maternal vitamin A status on neonatal vitamin A-dependent functions. However, a less severe maternal deprivation should be used for such studies.

Topics: Animals; Animals, Newborn; Body Weight; Diterpenes; Female; Guinea Pigs; Litter Size; Liver; Pregnancy; Pregnancy Complications; Reference Values; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Regulation by vitamin A of cell proliferation and differentiation of epithelial tissues is well-established. Deficiency of vitamin A in experimental animals leads to the development of hyperplasia and squamous metaplasia. The objective of the present study was to examine, for young hamsters, the effects of variable levels of the vitamin in the liver and trachea, on cell proliferation and morphology of tracheal epithelium and on body weights. Newly born litters were maintained on vitamin A-supplemented and vitamin A-deficient diets, and various parameters were examined at different ages. Retinol and retinyl palmitate levels were determined by high performance liquid chromatography. For animals on the supplemented diet, concentrations of liver retinyl palmitate and retinol increased progressively with age, reaching highest levels of approximately 84 and 1.9 micrograms g liver, respectively, at 28 d. In contrast, in animals on the vitamin A-deficient diet, the retinyl palmitate and retinol levels decreased progressively, reaching the lowest levels of approximately 0.32 and 0.09 micrograms/g, respectively. No significant reduction in retinol was observed in the trachea of animals maintained on the deficient diet for at least 20 d: their tracheas were depleted of retinol at 28 d. No vitamin A-associated differences were, however, observed in the labelling indices, growth fraction or in the morphology of the tracheal epithelium. Both the control and vitamin A-deficient animals gained weight progressively until 36 d of age, although the weight of animals in the latter group remained below those in the former group. These results show that mild-to-severe deficiency of vitamin A had no effects on cell proliferation or tracheal morphology of the hamster. The hyperplasia and squamous metaplasia in the trachea occurs only at an extreme vitamin A-deficiency when the tissue levels of the vitamin are depleted.

Topics: Animals; Body Weight; Cell Division; Cricetinae; Diterpenes; Liver; Mesocricetus; Retinyl Esters; Thymidine; Trachea; Tritium; Vitamin A; Vitamin A Deficiency

We treated two infants with failure to thrive who presented with clinical evidence of conjunctival and corneal xerosis. One patient was referred with possible infectious corneal ulcer thought to exist because there were deep peripheral ulcerations of the cornea and associated hypopyon. The other patient was initially thought to have a nasolacrimal duct obstruction because of excessive tearing. Xerophthalmia secondary to vitamin A deficiency was suspected and led to the diagnosis and treatment of cystic fibrosis in each case. Therapy with vitamin A promptly resolved the xerosis, but it also caused a transient rise in intracerebral pressure. Xerophthalmia can still be a problem in developed countries when underlying disorders, such as cystic fibrosis, lead to vitamin A malabsorption.

Topics: Cystic Fibrosis; Diterpenes; Female; Humans; Infant; Malabsorption Syndromes; Male; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Xerophthalmia

By use of sensitivity and specificity analysis, conjunctival impression cytology (CIC) was compared with fasting serum vitamin A levels and relative dose response (RDR) of Guatemalan children. One impression was taken from the temporal bulbar aspect of each eye, fasting serum vitamin A levels were then drawn, 480 RE of oil-based retinyl palmitate was given, and a 5-h postdosing vitamin A level was drawn (RDR procedure). For a 20% RDR cutoff, the sensitivity of CIC was 23% with a specificity of 80% and a positive predictive value of 9% (n = 213 children). Compared with fasting vitamin A levels alone (with 0.70 mumol/L as abnormal), the sensitivity of CIC was 26%, specificity was 81%, and positive predictive value was 22% (n = 221 children). There was no significant difference in the mean serum retinol level between those with abnormal and normal CIC. In this study population CIC does not identify the same group of children with marginal vitamin A as identified biochemically.

Topics: Adolescent; Child; Child, Preschool; Conjunctiva; Developing Countries; Diterpenes; Fasting; Female; Guatemala; Humans; Infant; Male; Retinyl Esters; Sensitivity and Specificity; Vitamin A; Vitamin A Deficiency

In vitamin A-deficient rats, liver glutathione peroxidase activity was decreased, alpha-tocopherol content was strongly enhanced, but microsomal liquid peroxidation remained unchanged.

Topics: Animals; Diterpenes; Glutathione Peroxidase; Lipid Peroxidation; Liver; Male; Microsomes, Liver; Rats; Rats, Inbred Strains; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Vitamin E

Many tissues which require vitamin A store the vitamin as long-chain fatty acyl esters of retinol. As part of a study designed to characterize vitamin A metabolism in the lacrimal gland, which transports retinol from blood to lacrimal gland fluid, extracts from lacrimal glands of rabbits and rats were analyzed by non-aqueous high performance liquid chromatography. Retinyl linoleate, retinyl palmitate, and retinyl stearate were identified in these extracts by their co-elution with standards, their retention time relative to retinyl palmitate, and their susceptibility to hydrolysis by saponification. Retinyl palmitate was present in rabbit lacrimal gland at 51.0 +/- 10.1 ng/g tissue. After treatment of vitamin A-deficient rabbits with orally administered [11,12-3H] retinyl acetate, the radiolabeled esters retinyl linoleate, palmitate, and stearate were extracted from the lacrimal glands. These data show that the lacrimal gland stores vitamin A as fatty acyl esters of retinol.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Lacrimal Apparatus; Rabbits; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Post-mortem concentrations of hepatic retinol and retinyl esters were determined in 40 subjects aged over 65 years to assess the effects of disease and malnutrition on vitamin A reserves. Three groups of patients (mean age 79.6 years) were studied: (1) previously healthy, (2) chronically ill, (3) chronically ill and wasted. There was no significant difference in height or age between the groups, but group 3 was lighter than both group 1 (P less than 0.001) and group 2 (P less than 0.05). Free retinol and retinyl esters were measured by high pressure liquid chromatography, and the total hepatic retinol calculated. Analysis of variance showed that the three groups differed significantly (P less than 0.02) with regard to total retinol, retinyl palmitate and total retinyl ester content.

Topics: Aged; Aged, 80 and over; Animals; Autopsy; Chromatography, High Pressure Liquid; Chronic Disease; Diterpenes; Female; Humans; Liver; Male; Nutrition Disorders; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency

These studies were performed to follow a spectrum of relevant parameters in male Syrian golden hamsters fed either a vitamin A-deficient diet or the same diet supplemented with retinoic acid at 3 micrograms/g diet. Body weight and life span were not affected by the vitamin A-deficient diet until after 6-7 wk. Squamous metaplastic lesions of the Formalin-fixed tracheas were not generally observed in the hamsters fed the deficient diet until 6-7 wk, at which time blood retinol and liver retinyl palmitate levels had also decreased. Blood glucose levels remained normal (90 mg/dl) until about 7 wk but declined to about 40% of normal at 9 and 10 wk. Dietary retinoic acid supplementation of the vitamin-deficient diet (3 micrograms/g diet) inhibited the loss of retinol from blood and of retinyl palmitate from the liver so that these compounds were still present at 10 wk, but were not detectable in hamsters fed the vitamin A-deficient diet without retinoic acid.

Topics: Animals; Blood Glucose; Cricetinae; Diet; Diterpenes; Epithelium; Growth; Life Expectancy; Liver; Male; Mesocricetus; Metaplasia; Retinyl Esters; Trachea; Tretinoin; Vitamin A; Vitamin A Deficiency

The relative dose response (RDR) test has been proposed as a tool for estimation of total body stores of vitamin A. In this study we have validated a variation of this test in children with or without liver disease. Administration of vitamin A was done by intravenous injection of 1000 micrograms of retinyl palmitate. We conclude that the RDR test by intravenous injection performed after 5 h is a reliable and sensitive indicator of vitamin A status. Values found were greater than 20% when liver vitamin A concentration is less than 20 micrograms/g liver and less than 10% when liver vitamin A concentration is greater than 20 micrograms/g liver. We also conclude that the RDR test can be applied to evaluate the efficiency of vitamin A therapy and we confirm that plasma retinol levels should not be used to screen vitamin A status.

Topics: Biliary Atresia; Biopsy; Child, Preschool; Diterpenes; Dose-Response Relationship, Drug; Humans; Infant; Liver; Liver Diseases; Retinyl Esters; Time Factors; Vitamin A; Vitamin A Deficiency

A variety of evidence suggests that autoxidation of cellular components probably plays a significant role in the age-related accumulation of lipofuscin, or age-pigment, in the mammalian retinal pigment epithelium (RPE). Among the likely candidates for conversion into RPE lipofuscin fluorophores via autoxidative mechanisms are vitamin A compounds, which are present in the retina and RPE in high concentrations. Vitamin E, an important lipid antioxidant, is likely to inhibit vitamin A autoxidation. Experiments were conducted to evaluate the significance of vitamin A autoxidation in the deposition of lipofuscin in the RPE. Albino rats were fed diets either supplemented with or lacking vitamin E. Each of these two groups of animals was further subdivided into three groups which were fed different levels of vitamin A palmitate: none, 14.0 mumol/kg diet, and 80.5 mumol/kg diet. After 26 weeks, the animals were killed and the RPE lipofuscin contents were determined by both fluorescence measurements and quantitative ultrastructural morphometry. Vitamin A palmitate deficiency led to significant reductions in RPE lipofuscin deposition, relative to the amounts of this pigment present in the groups receiving vitamin A palmitate in their diets. The relative magnitude of the vitamin A effect was greater in the vitamin E-supplemented groups than in the groups fed the diets deficient in vitamin E. This finding suggests that vitamin E interacts with vitamin A ester metabolites in vivo in a more complex manner than simply acting as an antioxidant protectant. Rats fed the diets containing the higher level of vitamin A palmitate failed to display elevated RPE lipofuscin contents relative to those in the rats fed 14.0 mumol of vitamin A palmitate/kg diet. Failure of high vitamin A intake to enhance RPE lipofuscin deposition may have been due to the fact that intake of vitamin A above normal levels did not lead to an elevation in vitamin A content of the retinal tissue. Establishing an effect of vitamin A deficiency on RPE lipofuscin deposition and characterization of the interactions between vitamins E and A are important steps toward defining precisely the molecular and cellular mechanisms underlying age-pigment accumulation in the RPE.

Topics: Animals; Diet; Diterpenes; Drug Interactions; Lipofuscin; Male; Oxidation-Reduction; Photoreceptor Cells; Pigment Epithelium of Eye; Pigments, Biological; Rats; Rats, Inbred F344; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

The temporal effects of retinoic acid supplementation on hepatic cytochrome P-450-dependent enzymes were studied on the rat. Four groups of male weanling rats were fed semi synthetic diets: two groups containing 0 or 4.4 mg retinol equivalents per kg diet as retinyl palmitate (A- RA- and A+ RA- groups) and two similar groups supplemented with all trans retinoic acid (12 mg/kg diet) (A- RA+ and A+ RA+ groups). After five or ten weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for aniline hydroxylase, aminopyrine N demethylase activities and cytochrome P-450 levels. Whereas no change was observed between the four groups after 5 weeks, the following modifications appeared after 10 weeks: Vitamin A deficiency decreased hepatic drug metabolism by phase I enzymes (hydroxylase and N demethylase) but only when liver storage pool was not detectable. Vitamin A concentration as low as 4 micrograms/g is sufficient to avoid any perturbation of these enzymes. Parallel to a sparing effect on liver reserves of vitamin A, retinoic acid maintained a normal activity of enzymes of xenobiotic metabolism. However, retinoic acid treatment produced an alteration of phase I enzymes in vitamin A supplemented group (A+ RA+). As this was accompanied by a doubling of vitamin A liver reserves, compared to A+ RA- group, it is suggested that this might result from a liver vitamin A overloading, leading to membrane damage perturbing microsomal enzymes. These results indicate the need for a more careful use of retinoids as a therapeutic agent.

Topics: Aminopyrine N-Demethylase; Aniline Hydroxylase; Animals; Cytochrome P-450 Enzyme System; Diterpenes; Liver; Male; Rats; Rats, Inbred Strains; Retinyl Esters; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Animals; Antibody-Producing Cells; Diterpenes; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Rats; Retinyl Esters; Tretinoin; Vitamin A; Vitamin A Deficiency

Rats were fed vitamin A deficient diets (-A) or supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet), either without (-RA) or with retinoic acid (+RA) (12 mg/kg diet) supplementation for up to six weeks. Plasma and liver levels as well as the subcellular localization of vitamin A were determined. In rats reared on the vitamin A rich diet the localization of retinyl palmitate (principal reserve form) is shown to be dependent on age. Two pools exist, i.e. one consisting of the nuclear and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. A rapid replenishment of mitochondrial-lysosomal fractions occurs in the first weeks after the weaning. During six weeks of deficient diet an identical mobilization was seen from the different subcellular fractions. Supplementation with RA caused an immediate and sustained reduction of serum vitamin A levels but did not disturb the subcellular localization of retinyl palmitate. A relationship between these phenomena and the subcellular distribution of the retinyl palmitate hydrolase (RPH) and the cellular vitamin A binding proteins (CRBP) is likely to exist.

Topics: Animals; Cell Nucleus; Cytosol; Diet; Diterpenes; Growth; Kinetics; Liver; Lysosomes; Male; Microsomes, Liver; Mitochondria, Liver; Rats; Rats, Inbred Strains; Retinyl Esters; Subcellular Fractions; Vitamin A; Vitamin A Deficiency

It has been shown that in rats with alimentary hypovitaminosis A, with a sufficiently pronounced decrease in the content of free retinol in blood serum (below 140 ng/ml) and in the liver tissue (below 360 ng/g), there is a complete regression of Pliss's lymphosarcoma. Under the conditions indicated, retinoic acid, in contradistinction to retinol, does not promote the tumor growth. A relative and absolute reduction in blood plasma of the essential amino acids, arginine, methionine and lysine, might be one of the reasons for tumor regression under hypovitaminosis A.

Topics: Animals; Diterpenes; Liver; Lymphoma, Non-Hodgkin; Male; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Retinyl Esters; Vitamin A; Vitamin A Deficiency

The total parenteral nutrition (TPN) rat and its sham-operated control were used as a model to compare the metabolism and storage of vitamins A and E when they are administered intravenously or orally. Male Fisher rats were depleted of both vitamins for several months with a diet free of vitamins A or E, but containing retinoic acid for growth. TPN solutions containing aqueous dispersions of retinol, retinyl palmitate and dl-alpha-tocopheryl acetate were infused at 2.3 ml/h into the jugular veins of 10 TPN rats. Eight sham-operated control rats drank similar volumes from food cups. TPN rats received 115.3 +/- 4.5 (mean +/- SEM) micrograms of retinol equivalents and 2.2 +/- 0.2 mg of alpha-tocopherol equivalents per day; controls received 146.4 +/- 16.5 micrograms and 2.1 +/- 0.3 mg, respectively. After 7 days the animals were fasted overnight and killed. Plasma levels of retinol were 27.8 +/- 1.5 micrograms/dl for TPN rats, and 27.4 +/- 1.2 for controls. Plasma alpha-tocopherol was 1909 +/- 183 micrograms/dl for TPN rats and 1063 +/- 77 for controls. The only forms of the vitamins found in plasma after overnight fasting were unesterified retinol and unesterified alpha-tocopherol. Sham-operated control rats stored amounts of vitamins A and E similar to values reported in the literature for fed animals. TPN rats stored more of both vitamins than controls in liver, heart, and spleen, but not in testes. The enhanced liver vitamin storage by TPN rats did not appear to be due to a slight increase in lipid content. The results indicate that both vitamins A and E infused in TPN solutions maintain blood levels and are stored in tissues.

Topics: alpha-Tocopherol; Animals; Diterpenes; Enteral Nutrition; Male; Parenteral Nutrition; Parenteral Nutrition, Total; Rats; Retinyl Esters; Tissue Distribution; Tocopherols; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

The rise in serum vitamin A 5 h after a 450 microgram oral dose of the vitamin (retinyl palmitate) was used to assess vitamin A nutriture in patients with alcoholic cirrhosis. The test was carried out on 21 hospitalized male patients and 12 normal age and sex-matched control subjects. The relative dose response (RDR), expressed as percentage, was calculated as A5 - A0/A5 X 100 where A0 = the fasting serum retinol level and A5 = the serum retinol 5 h postdosing. Vitamin A-deficient patients (those with serum retinol levels less than 30 microgram/dl and an abnormal dark adaptation test or RDR greater than or equal to 14%) were treated with 4 wk of oral vitamin A (10,000 microgram/day), then repeat RDR and dark adaptation tests were carried out. Among eight cirrhotics with abnormal dark adaptation, the mean +/- SEM RDR was 21 +/- 9 versus 3 +/- 3% in patients with normal dark adaptation (p less than 0.01). RDR tests of patients with normal dark adaptation did not differ from those of 12 normal age and sex-matched control subjects (normal RDR response 0 to 14%). Among patients found to be vitamin A-deficient, treatment with vitamin A resulted in the mean +/- SEM RDR declining from 21 +/- 9 to 5 +/- 2%. However, this fall failed to reach statistical significance (p = 0.06). The RDR test appears to be useful as a predictor of vitamin A deficiency, even among patients with far advanced hepatic disease.

Topics: Dark Adaptation; Diterpenes; Dose-Response Relationship, Drug; Humans; Liver Cirrhosis, Alcoholic; Palmitates; Prothrombin Time; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Zinc