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High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

ABSTRACT: BACKGROUND:Biomarkers of micronutrient status are needed to best define deficiencies and excesses of essential nutrients. OBJECTIVE:We evaluated several supporting biomarkers of vitamin A status in Zambian children to determine whether any of the biomarkers were consistent with high liver retinol stores determined by using retinol isotope dilution (RID). DESIGN:A randomized, placebo-controlled, biofortified maize efficacy trial was conducted in 140 rural Zambian children from 4 villages. A series of biomarkers were investigated to better define the vitamin A status of these children. In addition to the assessment of total-body retinol stores (TBSs) by using RID, tests included analyses of serum carotenoids, retinyl esters, and pyridoxal-5'-phosphate (PLP) by using high-pressure liquid chromatography, retinol-binding protein by using ELISA, and alanine aminotransferase (ALT) activity by using a colorimetric assay. RESULTS:Children (n = 133) were analyzed quantitatively for TBSs by using RID. TBSs, retinyl esters, some carotenoids, and PLP differed by village site. Serum carotenoids were elevated above most nonintervened reference values for children. ?-Carotene, ?-carotene, and lutein values were >95th percentile from children in the US NHANES III, and 13% of children had hypercarotenemia (defined as total carotenoid concentration >3.7 ?mol/L). Although only 2% of children had serum retinyl esters >10% of total retinol plus retinyl esters, 16% of children had >5% as esters, which was consistent with high liver retinol stores. Ratios of serum retinol to retinol-binding protein did not deviate from 1.0, which indicated full saturation. ALT activity was low, which was likely due to underlying vitamin B-6 deficiency, which was confirmed by very low serum PLP concentrations. CONCLUSIONS:The finding of hypervitaminosis A in Zambian children was supported by high circulating concentrations of carotenoids and mildly elevated serum retinyl esters. ALT-activity assays may be compromised with co-existing vitamin B-6 deficiency. Nutrition education to improve intakes of whole grains and animal-source foods may enhance vitamin B-6 status in Zambians.

SUBMITTER: Mondloch S

PROVIDER: S-EPMC6546228 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

Mondloch Stephanie S Gannon Bryan M BM Davis Christopher R CR Chileshe Justin J Kaliwile Chisela C Masi Cassim C Rios-Avila Luisa L Gregory Jesse F JF Tanumihardjo Sherry A SA

The American journal of clinical nutrition 20150715 2

<h4>Background</h4>Biomarkers of micronutrient status are needed to best define deficiencies and excesses of essential nutrients.<h4>Objective</h4>We evaluated several supporting biomarkers of vitamin A status in Zambian children to determine whether any of the biomarkers were consistent with high liver retinol stores determined by using retinol isotope dilution (RID).<h4>Design</h4>A randomized, placebo-controlled, biofortified maize efficacy trial was conducted in 140 rural Zambian children fr ...[more]

PMID: 26178727

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Project description:BackgroundVitamin A (VA) deficiency is a public health problem in some countries. Fortification, supplementation, and increased provitamin A consumption through biofortification are efficacious, but monitoring is needed due to risk of excessive VA intake when interventions overlap.ObjectivesTwo studies in 28-36-d-old male Mongolian gerbils simulated exposure to multiple VA interventions to determine the effects of provitamin A carotenoid consumption from biofortified maize and carrots and preformed VA fortificant on status.MethodsStudy 1 was a 2 × 2 × 2 factorial design (n = 85) with high-β-carotene maize, orange carrots, and VA fortification at 50% estimated gerbil needs, compared with white maize and white carrot controls. Study 2 was a 2 × 3 factorial design (n = 66) evaluating orange carrot and VA consumption through fortification at 100% and 200% estimated needs. Both studies utilized 2-wk VA depletion, baseline evaluation, 9-wk treatments, and liver VA stores by HPLC. Intestinal scavenger receptor class B member 1 (Scarb1), β-carotene 15,15'-dioxygenase (Bco1), β-carotene 9',10'-oxygenase (Bco2), intestine-specific homeobox (Isx), and cytochrome P450 26A1 isoform α1 (Cyp26a1) expression was analyzed by qRT-PCR in study 2.ResultsIn study 1, liver VA concentrations were significantly higher in orange carrot (0.69 ± 0.12 μmol/g) and orange maize groups (0.52 ± 0.21 μmol/g) compared with baseline (0.23 ± 0.069 μmol/g) and controls. Liver VA concentrations from VA fortificant alone (0.11 ± 0.053 μmol/g) did not differ from negative control. In study 2, orange carrot significantly enhanced liver VA concentrations (0.85 ± 0.24 μmol/g) relative to baseline (0.43 ± 0.14 μmol/g), but VA fortificant alone (0.42 ± 0.21 μmol/g) did not. Intestinal Scarb1 and Bco1 were negatively correlated with increasing liver VA concentrations (P < 0.01, r2 = 0.25-0.27). Serum retinol concentrations did not differ.ConclusionsBiofortified carrots and maize without fortification prevented VA deficiency in gerbils. During adequate provitamin A dietary intake, preformed VA intake resulted in excessive liver stores in gerbils, despite downregulation of carotenoid absorption and cleavage gene expression.

Project description:BackgroundThe WHO estimates that 190 million preschool children have vitamin A deficiency (VAD). Serum retinol (SR) concentration is a common indicator of vitamin A (VA) status, but SR is homeostatically controlled and suppressed during inflammation, which may lead to misdiagnosis.ObjectiveThe sensitivity and specificity of SR compared with VA total liver reserves (TLRs) were evaluated for VAD in children from Thailand (n = 37) and Zambia (n = 128). SR was adjusted for inflammation in the Zambian children.DesignEach child was classified as VA-deficient or not based on cutoffs of <0.1 μmol VA/g liver with the use of retinol isotope dilution and <0.7 μmol/L for SR concentrations. Four categories of infection status in the Zambian children were based on elevated C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Sensitivity and specificity were calculated with the use of unadjusted and inflammation marker-adjusted SR cutoffs.ResultsVAD was 65% and 0% according to TLRs and SR, respectively, in Thai children and 0% and 17%, respectively, in Zambian children. No true positive VAD cases occurred; thus, sensitivity was 0% and indeterminable, respectively; specificity was 100% and 82.8%, respectively. CRP was elevated in 26.6% of Zambian children, whereas 97.7% had elevated AGP, categorizing them as having no infection (2.3%) or in early (26.6%) or late (58.6%) convalescence. With the use of marker-adjusted SR cutoffs of 0.6 μmol/L for late convalescence and 0.5 μmol/L for early convalescence, the adjusted prevalence of SR deficiency was 2.3%, increasing specificity to 97.3%.ConclusionsNo cases of VAD were identified by both TLRs and SR (true positives) in Thai or Zambian children. Specificity of SR to evaluate VAD was high, but additional research is needed to investigate sensitivity. Adjusting SR cutoffs for inflammation improved specificity by reducing false positives. SR as a VAD indicator may depend on infection rates, which should be taken into consideration. These studies were registered at clinicaltrials.gov as NCT01061307 (for Thailand) and NCT01814891 (for Zambia).

Project description:This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as >?1.0 ?mol retinol/g liver. Bone parameters included markers of bone formation (P1NP), bone resorption (CTX), parathyroid hormone, calcium, vitamin A, and vitamin D. Low dietary vitamin A intake increased P1NP. PURPOSE:Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some groups are consuming excessive VA. Bone metabolism and inflammatory parameters were measured in Zambian children who had high prevalence of hypervitaminosis A determined by 13C-retinol isotope dilution. METHODS:Children (n?=?143), 5 to 7 years, were recruited into a placebo-controlled biofortified orange maize feeding study for 90 days. Bone turnover (P1NP and CTX) and inflammatory (C-reactive protein (CRP) and alpha-1-acid glycoprotein) biomarkers were measured in fasting blood samples before and/or after intervention with the following: (1) VA at the recommended dietary allowance (400 ?g retinol activity equivalents/day (as retinyl palmitate)), (2) maize enhanced with the provitamin A carotenoid ?-carotene (2.86 mg/day), or (3) a placebo. Parathyroid hormone, calcium, and 25(OH)-vitamin D were measured at end line. RESULTS:Bone formation, as measured by P1NP, increased (P?<?0.0001) in the placebo group who consumed low preformed VA during the intervention. Bone resorption, measured by CTX, was not affected. P1NP and CTX were negatively associated with inflammation, most strongly with CRP. Serum calcium did not differ among groups and was low (7.29?±?0.87 ?g/dL). Serum 25(OH) D did not differ among groups (54.5?±?15 nmol/L), with 91% <?75 nmol/L and 38% <?50 nmol/L. CONCLUSIONS:Reduction of dietary preformed VA in Zambian children for 4 months improved bone formation. Chronic consumption of preformed VA caused hypervitaminosis A and may impair bone formation. In children, this could be associated with failure to accrue optimal peak bone mass. TRIAL REGISTRATION:The NIH Clinical Trial registry number is NCT01814891; https://clinicaltrials.gov/ct2/show/NCT01814891 .

Dataset Information

High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

Publications

High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

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