Cod Liver Oil,but Not Retinoic Acid,Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.     

Priming with Retinoic Acid,an Active Metabolite of Vitamin A,Increases Vitamin A Uptake in the Small Intestine of Neonatal Rats

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of ³H-labeled VA, pups were euthanized at selected times (n = 4–6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of ³H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.     

维生素A缺乏对雌性大鼠生长发育及胚胎影响

目的建立维生素A（VA）完全及边缘缺乏的雌性大鼠模型,观察维生素A缺乏（VAD）对雌性大鼠及胚胎的影响。方法将初断乳SD雌性大鼠60只,随机分为VA缺乏组（AD）、VA边缘缺乏组（AM）、正常对照组（AN）,喂饲VA含量不同的饲料,耗竭性喂养后交配。将交配后的雌鼠在各组内随机分为VA缺乏组（A）、VA缺乏妊娠0d补充组（B）、VA边缘缺乏组（C）、VA边缘缺乏妊娠0d补充组（D）。B、D组于妊娠第0d喂饲补充饲料。于妊娠第19.5d将所有孕鼠处死并观察胚胎发育情况。结果发生AD组雌鼠出现明显的生长发育抑制。A组胚胎全为吸收胎,C组胚胎生长发育明显低于AN及B、C组,而畸胎死胎出现率明显高于AN及B、C组。结论VAD可明显影响雌性大鼠及其胚胎的生长发育,孕期补充VA可有效降低VAD对胚胎的发育毒性。     

Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review

Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.     

边缘VA缺乏对大鼠胚胎骨骼发育及视黄酸受体表达的影响

目的研究边缘性维生素A(VA)缺乏及补充对大鼠胚胎骨骼发育的影响,及其与视黄酸受体(RARs)基因表达的关联性。方法初断乳SD雌性大鼠30只,按体重随机分为边缘性VA缺乏组(AM),边缘性VA缺乏妊娠0d(E0d)补充组(AS)和正常对照组(AN)。AM和AS组喂饲边缘性VA缺乏饲料(含VA0.4IU/gdiet),AN组喂饲VA充足饲料(含VA4IU/gdiet)。60d后与正常雄鼠交配。AS组自E0起改喂VA补充饲料(含VA10IU/gdiet)。于E12.5d和E19.5d将孕鼠处死,取胚胎。观测E19.5d胚胎骨骼发育指标;用荧光定量PCR及Westernblot检测E12.5d胚胎组织视黄酸受体的表达。结果AM组97.2%的E19.5d胚胎骨骼发育明显迟缓并出现多种骨骼畸形;E12.5d胚胎RARβ、RARγ表达水平明显下降。AS组胚胎各指标较AN组无异。结论视黄酸受体参与介导边缘性VA缺乏导致的大鼠胚胎骨骼发育异常,孕早期补充VA可有效预防骨骼畸形的发生。     

Plasma Vitamin A Homeostasis: The Relative Dose Response As A Measure Of Liver Vitamin A Reserves

Retinol levels in plasma of rats are constant and independent of dietary intake or liver stores above 10 μg per gram. If tissue needs of retinol are decreased by limiting protein intake or by feeding retinoic acid, plasma levels correspondingly decline. A single dose of newly supplied vitamin A leads to a short-term surge in plasma retinol level which may be a measure of liver reserves and vitamin A status.     

Vitamin A supplementation modifies the antioxidant system in rats

BACKGROUND/OBJECTIVESIt has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats.MATERIALS/METHODSForty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope.RESULTSLipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation.CONCLUSIONSThese results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.     

Turnover And Recycling Of Vitamin A In Vitamin A-Deficient And Sufficient Rats

The turnover rate and uptake of labeled retinol was found to be greater in the vitamin A-sufficient than in the vitamin A-deficient rats, though fractional turnover rates were about equal.     

Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01–30.26]; p = 0.048) and mortality (OR 5.21 [1.06–25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.     

VITAMIN A AND RETINOL-BINDING PROTEIN IN FETAL GROWTH AND DEVELOPMENT OF THE RAT

Studies on the transport of retinol and retinol-binding protein through the placenta and concentrations in the rat fetus at different stages of development tell much about their role in fetal growth and development.     

Prevalence of Undernutrition and Vitamin A Deficiency in the Dogon Region,Mali

Objectives: A representative sample of 1510 preschool children living in the Bandiagra circle (Mopti Region, Mali) was examined between March and April 1997 to determine the level of vitamin A deficiency.

Methods: Using a randomized two level cluster sampling, 20 clusters of 75 children aged six months to six years were selected for evaluating xerophthalmia (XN night blindness and/or X1B Bitot spot). Concurrently stature and weight were determined. A semiquantitative seven-day dietary questionnaire was applied to the mothers of 484 infants to assess consumption of vitamin A rich foodstuffs. The prevalence of biochemical deficiency was attested using the Modified Relative Dose Response test (MRDR) on a sub-sample of 192.

Results: Of the studied children, 4.3% (95% Confidence interval [CI]: 3.2–5.3) reported night blindness and 2% (95% CI: 1.3–2.7) had Bitot spots. Prevalence of xerophthalmia attested by at least one of these signs was 5.4% (95% CI: 4.2–6.5). The prevalence reached 10.5% at three years of age. The MRDR test proved abnormal in 77.1% of the subjects (95% CI: 70.3–82.7). Serum retinol was lower than 0.35 μmol/L in 43.8% (95.6% CI: 36.9–51.3) and less than 0.70 μmol/L in 92.7% of the children (95% CI: 87.8–95.8). Weekly consumption of vitamin A rich food was rare: 75.8% had not eaten any animal vitamin A rich food, and 22.1% had consumed less than seven times a vitamin A rich food of either vegetable or animal origin.

Conclusions: These data define vitamin A deficiency as a severe public health problem in the Bandiagara area of Mali.     

Vitamin A5/X,a New Food to Lipid Hormone Concept for a Nutritional Ligand to Control RXR-Mediated Signaling

Vitamin A is a family of derivatives synthesized from carotenoids acquired from the diet and can be converted in animals to bioactive forms essential for life. Vitamin A1 (all-trans-retinol/ATROL) and provitamin A1 (all-trans-β,β-carotene/ATBC) are precursors of all-trans-retinoic acid acting as a ligand for the retinoic acid receptors. The contribution of ATROL and ATBC to formation of 9-cis-13,14-dihydroretinoic acid (9CDHRA), the only endogenous retinoid acting as retinoid X receptor (RXR) ligand, remains unknown. To address this point novel and already known retinoids and carotenoids were stereoselectively synthesized and administered in vitro to oligodendrocyte cell culture and supplemented in vivo (orally) to mice with a following high-performance liquid chromatography-mass spectrometry (HPLC-MS)/UV-Vis based metabolic profiling. In this study, we show that ATROL and ATBC are at best only weak and non-selective precursors of 9CDHRA. Instead, we identify 9-cis-13,14-dihydroretinol (9CDHROL) and 9-cis-13,14-dihydro-β,β-carotene (9CDHBC) as novel direct nutritional precursors of 9CDHRA, which are present endogenously in humans and the human food chain matrix. Furthermore, 9CDHROL displayed RXR-dependent promnemonic activity in working memory test similar to that reported for 9CDHRA. We also propose that the endogenous carotenoid 9-cis-β,β-carotene (9CBC) can act as weak, indirect precursor of 9CDHRA via hydrogenation to 9CDHBC and further metabolism to 9CDHROL and/or 9CDHRA. In summary, since classical vitamin A1 is not an efficient 9CDHRA precursor, we conclude that this group of molecules constitutes a new class of vitamin or a new independent member of the vitamin A family, named “Vitamin A5/X”.     

维生素A与支气管哮喘的关系

研究发现哮喘患者体内维生素A水平显著低于健康人群，维生素A对哮喘的气道炎症、自主神经受体及免疫功能等方面产生有利影响；维生素A维护上皮细胞和抗氧化的功能也共同参与了调节哮喘发病的过程。本文主要综述维生素A与支气管哮喘的关系。     

The Influence of Vitamin A Supplementation on Iron Status

Vitamin A (VA) and iron deficiencies are important nutritional problems, affecting particularly preschool children, as well as pregnant and lactating women. A PubMed (National Library of Medicine, National Institutes of Health, Bethesda, MD, USA) literature review was carried out to search for clinical trials published from 1992 to 2013 that assessed the influence of vitamin A supplementation on iron status. Simultaneous use of iron and vitamin A supplements seemed to be more effective to prevent iron deficiency anemia than the use of these micronutrients alone. Some studies did not include a placebo group and only a few of them assessed vitamin A status of the individuals at baseline. Moreover, the studies did not consider any inflammatory marker and a reasonable number of iron parameters. Another important limitation was the lack of assessment of hemoglobin variants, especially in regions with a high prevalence of anemia. Assessment of hemoglobin variants, inflammatory markers and anemia of chronic inflammation would be important to the studies investigated. Studies involving different populations are necessary to elucidate the interaction between the two micronutrients, especially regarding iron absorption and modulation of erythropoiesis.     

Disproportionate Vitamin A Deficiency in Women of Specific Ethnicities Linked to Differences in Allele Frequencies of Vitamin A-Related Polymorphisms

Background: While the current national prevalence rate of vitamin A deficiency (VAD) is estimated to be less than 1%, it is suggested that it varies between different ethnic groups and races within the U.S. We assessed the prevalence of VAD in pregnant women of different ethnic groups and tested these prevalence rates for associations with the vitamin A-related single nucleotide polymorphism (SNP) allele frequencies in each ethnic group. Methods: We analyzed two independent datasets of serum retinol levels with self-reported ethnicities and the differences of allele frequencies of the SNPs associated with vitamin A metabolism between groups in publicly available datasets. Results: Non-Hispanic Black and Hispanic pregnant women showed high VAD prevalence in both datasets. Interestingly, the VAD prevalence for Hispanic pregnant women significantly differed between datasets (p = 1.973 × 10⁻¹⁰, 95%CI 0.04–0.22). Alleles known to confer the risk of low serum retinol (rs10882272 C and rs738409 G) showed higher frequencies in the race/ethnicity groups with more VAD. Moreover, minor allele frequencies of a set of 39 previously reported SNPs associated with vitamin A metabolism were significantly different between the populations of different ancestries than those of randomly selected SNPs (p = 0.030). Conclusions: Our analysis confirmed that VAD prevalence varies between different ethnic groups/races and may be causally associated with genetic variants conferring risk for low retinol levels. Assessing genetic variant information prior to performing an effective nutrient supplementation program will help us plan more effective food-based interventions.     

维生素A强化牛乳预防婴儿维生素A不足的效果观察

本文观察了出生至15个月食用维生素A强化牛乳(维生素A2000IU/L)629例,和食用普通牛乳或母乳834例小儿一年四季血清中维生素A浓度。结果表明,日食维生素A强化牛乳500ml或以上,不另加维生素A制剂,可预防维生素A不足与过量,并可治疗维生素A的缺乏。     

Mobilization Of Hepatic Vitamin A By Zinc Supplementation In Zinc Deficiency Associated With Protein-Energy Malnutrition

Short-term supplementation with oral zinc increased circulating vitamin A and retinol-binding protein levels in children with protein-energy malnutrition and presumed zinc deficiency, but not in children with a predominantly dietary vitamin A deficiency.     

海南省琼中县中小学学生血清维生素A水平分析

目的了解海南省琼中县中小学学生血清维生素A水平,为该县相应人群维生素A缺乏的防治提供实验依据。方法采用分层整群随机抽样法,抽取琼中县2所小学和2所初中学校,每个学校各年级一个班的学生为研究对象,采用高效液相色谱法检测其血清视黄醇含量。结果 1)共检测561例,琼中县中小学学生血清视黄醇平均水平为(360.36±91.39)ng/mL,且血清视黄醇平均水平在男、女生间差异无统计学意义(P0.05),但其随年龄的增长而升高(P0.05)。2)维生素A缺乏率(≤200ng/mL)为2.0%,边缘缺乏率(200~300ng/mL)为22.3%,两者性别差异均无统计学意义(P0.05),但边缘缺乏率随着年龄的增长总体呈下降趋势(P0.05)。结论琼中县中小学学生维生素A缺乏率较低,但边缘缺乏率较高,应注意监测,且该地区维生素A缺乏重点防治对象为6~7岁的学生。