Marginal Vitamin A Deficiency Research Articles

Effects of early intervention on learning and memory in young rats of marginal vitamin A deficiency and it's mechanism

In recent years, some experiments on vitamin A-deprived animals reveal a progressive and ultimately profound impairment of hippocampal CA1 area's long-term potentiation and these losses are fully reversible by dietary vitamin A replenishment in vivo. Our previous study revealed that marginal vitamin A deficiency (MVAD) beginning from embryonic period impairs learning, memory and long-term potentiation (LTP) in young rats. But the losses might not be reversible if the vitamin A supplementation is late, especially when the critical period of hippocampus development is missed. The present study aimed to observe the recovery of learning and memory in vitamin A marginally deficient young rats after early intervention with vitamin A supplementation and begin to study the mechanism. Rats were divided into control, MVAD, vitamin A intervention 1 (VAI1) and VAI2 groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 U/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 U/kg). In VAI1 group (10 young rats) the dams were fed with MVAD diet till day 14 of pregnancy, then were fed with normal diet and the pups were fed with normal diet. In VAI2 group (13 young rats) the dams were fed with MVAD diet till delivery, then were fed with normal diet and the pups were fed with normal diet too. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique. The expression of RAR-alpha, RAR-beta, RXR-beta, RXR-gamma, RC3 and tTG mRNA was detected by using semi-quantified RT-PCR in hippocampus. (1) The times to reach the learning standard in MVAD group (45.6 +/- 12.1) were more than those in control group (17.1 +/- 4.4) (P < 0.01), in both VAI1 group (20.8 +/- 3.1) and VAI2 group (22.1 +/- 4.0) were more than those in group MVAD (P < 0.01), and there were no significant differences among groups VAI1, VAI2 and control (P > 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group [(22.9 +/- 9.4)%] and VAI2 group [(39.1 +/- 4.33)%] were less than that of control group [(57.5 +/- 27.3)%], respectively (P < 0.05). No significant difference was found between VAI1 and control group (P > 0.05). (3) The expression of RAR-beta and RXR-beta mRNA decreased by 48.72% and 37.84% respectively (P < 0.05) compared with control, but the expression of RAR-beta mRNA in group VAI1 was higher than that in group MVAD (P = 0.065). The expression of RC3 mRNA in MVAD group was lower than that in control (P = 0.061) and RAR-alpha mRNA in MVAD group was higher than that in control (P = 0.061). The expression of RXR-gamma and tTG mRNA had no significant difference among different groups as determined with semi-quantified RT-PCR in hippocampus. Early vitamin A intervention may make the impaired learning and memory behavior due to marginal vitamin A deficiency recover to the normal level in young rats, but lip losses in group VAI2 might not be reversible. Vitamin A may modulate the expression of RC3 mRNA by affecting RAR-alpha, RAR-beta and RXR-beta to influence the LTP, learning and memory.

Vitamin A Supplementation of Vitamin A Deficient Measles Patients Lowers the Risk of Measles-Related Pneumonia in Zambian Children

This is an a posteriori analysis of previously published data to assess whether improving vitamin A (VA) status resolves measles-related pneumonia (MP). Nonhospitalized acute measles patients (2 d of rash onset) had their VA status determined based on the molar ratio of retinol-binding protein to transthyretin (RBP/TTR). Using a cutoff value of </=0.36, indicative of marginal VA deficiency, 82 children were diagnosed as marginally VA deficient and 114 were diagnosed as VA sufficient. At baseline, marginally VA-deficient patients had significantly lower serum retinol and higher serum C-reactive protein concentrations than VA-sufficient children. At the 2-wk follow-up visit, serum retinol and the RBP/TTR ratio were significantly greater in marginally VA-deficient measles patients receiving VA supplements than in those receiving placebo; whereas in VA-sufficient measles patients, retinol increased in those receiving VA supplements or placebo. Concomitantly the odds ratio of unresolved pneumonia in marginally VA-deficient measles patients receiving VA supplements compared with those receiving placebo was 0.20 (95% confidence interval, 0.05-0.71). In conclusion, VA supplements during measles infection improved VA status of VA-deficient children and helped resolve MP, demonstrating the importance of determining VA status when assessing the efficacy of VA supplements.

Iron Deficiency and Marginal Vitamin A Deficiency Affect Growth, Hematological Indices and the Regulation of Iron Metabolism Genes in Rats

Iron deficiency and marginal vitamin A (VA) deficiency frequently coexist and affect billions of people, mostly children and women, worldwide. The effects of these micronutrient deficiencies alone and in combination on hematologic, biochemical and molecular indices of iron and VA status were investigated in a 2 x 2 randomized blocked study conducted in growing male Sprague-Dawley rats. From 3-8 wk of age, rats were fed one of four purified diets that were either adequate or restricted in iron (Fe) and adequate or marginal in VA: (+)Fe(+)VA, 20.3 and 0.367 micro g/g, respectively, denoted control diet; (-)Fe(+)VA, 3.34 and 0.405 micro g/g; (+)FeVA(m), 22.2 and 0.051 micro g/g; or (-)FeVA(m), 3.03 and 0.055 micro g/g. Weight-matched rats fed adequate micronutrients were included to control for possible confounding effects of Fe deficiency on growth and feed efficiency. Iron restriction reduced (P < 0.05) weight gain, feed efficiency, blood hemoglobin and hematocrit. Plasma and liver iron and plasma transferrin saturation were reduced by approximately 50%, whereas liver transferrin mRNA and protein and transferrin receptor mRNA were elevated, as was liver ferritin light-chain protein and light-chain mRNA. Liver heavy-chain ferritin mRNA, hemopexin, ceruloplasmin and cellular retinol-binding protein mRNA were not affected by iron or VA restriction. Although marginal VA deficiency did not exacerbate indices of poor iron status during iron deficiency, iron deficiency was associated with lower plasma retinol and elevated liver VA concentrations. These results are consistent with an impaired mobilization of liver retinol during iron deficiency as well as multiple alterations in iron metabolism.

Determination of a Cut-Off Value for the Molar Ratio of Retinol-Binding Protein to Transthyretin (RBP:TTR) in Bangladeshi Patients with Low Hepatic Vitamin A Stores

The purpose of this study was to determine a cut-off value of the molar ratio of retinol-binding protein to transthyretin (RBP:TTR) to indicate marginal vitamin A (VA) deficiency. Plasma RBP and TTR were measured by radial immunodiffusion in two groups of patients, i.e., surgical patients with known hepatic VA stores, and a cohort of children residing in a malaria-endemic area of Papua New Guinea who had received placebo or 210 micro mol of VA every 3 mo for 9 mo. A RBP:TTR ratio < or =0.36 selectively detected five of seven patients (71% sensitivity) with hepatic VA stores < or =69.9 nmol/g of tissue (i.e., < or =20 micro g/g), indicative of marginal VA deficiency. Using this cut-off value, 28% (n = 245) of children from Papua New Guinea had marginal VA deficiency before supplementation. After 7 mo, a low ratio persisted in 29% (n = 92) of placebo-treated children but in only 11% (n = 83) of those receiving VA supplements (chi(2), P < 0.01). At the end of the study, 13 mo after initiation or 4 mo after the last dose of VA, the percentage of children with a low ratio was still lower (chi(2), P < 0.02) in the VA group, 42.5% (n = 113) than in the placebo group, 58.6% (n = 118). These results demonstrate that a cut-off value < or =0.36 is indicative of marginal VA deficiency and can be used as an indirect method of VA assessment.

A Low Molar Ratio of Retinol Binding Protein to Transthyretin Indicates Vitamin A Deficiency during Inflammation: Studies in Rats and A Posteriori Analysis of Vitamin A–Supplemented Children with Measles

To assess whether the molar ratio of retinol-binding protein (RBP) to transthyretin (TTR) is of utility in detecting vitamin A (VA) deficiency during inflammation, we analyzed data from a rat model of endotoxin-induced inflammation and from a previously reported randomized, placebo-controlled trial of VA supplementation in children with acute measles. In rats, both marginal VA deficiency and inflammation were independent causes of low plasma RBP (two-way ANOVA, P < 0.001), whereas plasma TTR concentration was reduced only by inflammation (P < 0.001). The molar ratio of plasma RBP to TTR was reduced (by ∼50%) only in rats with marginal VA deficiency and inflammation (two-way ANOVA interaction, P < 0.01). Serum retinol concentration, C-reactive protein (CRP, an indicator of inflammation) and the RBP:TTR molar ratio were determined in children with acute measles at baseline and 2 wk after subgroups received a placebo or a 210 μmol VA supplement. The ratio of RBP:TTR was selectively reduced in children in the placebo group with low plasma retinol (<0.35 μmol/L) and elevated CRP (>40 mg/L). In children with a low RBP:TTR molar ratio (<0.30) at baseline, the RBP:TTR ratio increased significantly 2 wk later only in the VA-treated subgroup. These analyses provide evidence that, because RBP is differentially reduced in comparison to TTR during VA deficiency, the combined determination of the concentrations of serum RBP and TTR may provide a promising means of detecting VA deficiency during inflammation.

Acute Inflammation Induces Hyporetinemia and Modifies the Plasma and Tissue Response to Vitamin A Supplementation in Marginally Vitamin A–Deficient Rats

Plasma retinol is reduced during numerous infections, and inflammation alters the hepatic synthesis of retinol-binding protein (RBP). In this study, we have investigated the effects of endotoxin-induced inflammation on vitamin A (VA) supplementation in a rat model of marginal VA deficiency. Marginally VA-deficient rats received an intraperitoneal dose of lipopolysaccharide (LPS, n = 14) or saline (n = 10); 6 h later, six LPS + VA and six saline + VA rats received 7.1 μmol VA orally. Twenty-four hours after endotoxin administration, rats with inflammation (LPS) had lower plasma retinol, RBP, and hepatic RBP than saline rats (37, 31 and 44%, respectively, P < 0.05). Inflammation did not affect VA concentrations in liver and perirenal adipose tissue, although kidney VA was reduced relative to saline rats. However, urinary VA was not detected. Eighteen hours after VA supplementation, inflammation reduced the plasma unesterified retinol response (P < 0.05) in LPS + VA relative to saline + VA rats, although total VA increased as a result of the presence of retinyl esters in LPS + VA rats. Hepatic esterified retinol concentration was reduced (P < 0.01) in LPS + VA compared with saline + VA rats; however, hepatic unesterified retinol did not differ. Renal total retinol increased in VA-supplemented rats, but urinary retinol excretion, when observed, was low, independently of inflammation. These findings indicate that inflammation-induced hyporetinemia does not necessarily imply a loss of VA, but rather represents a redistribution of tissue VA brought about by a reduced hepatic synthesis of RBP. Practical implications from these collective results are to recommend the determination of both unesterified and esterified retinol to fully assess the plasma response to VA supplementation and to caution the use of VA assessment methodologies that depend on the hepatic synthesis of RBP during acute inflammation.