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Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

ABSTRACT: 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?

SUBMITTER: Tanumihardjo SA

PROVIDER: S-EPMC7189610 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

Tanumihardjo S A SA Gannon B M BM Kaliwile C C Chileshe J J Binkley N C NC

Archives of osteoporosis 20190628 1

This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as > 1.0 μmol 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.<h4>Purpose</h4>Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some grou ...[more]

PMID: 31254130

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Project description: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.

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:Background: Neonatal vitamin A (VA) supplementation is being evaluated as a public health policy for preventing infant mortality, but inconsistencies in mortality trials demand mechanistic work to determine biological plausibility.Objectives: We investigated the absorption, distribution, and storage of single large oral VA doses administered shortly after birth.Methods: Fifty pregnant sows (Sus scrofas domesticas) were fed a VA-free diet. Male and female newborn piglets (n = 313) were orally administered 0, 25,000, 50,000, or 200,000 IU VA in oil within 12 h of birth when mean ± SD weight was 1.56 ± 0.25 kg. Blood was drawn to determine absorption and storage 0.5-240 h after administration. Metabolic and postnatal dose-timing substudies were performed. Liver, lung, kidney, spleen, and adrenal VA concentrations were determined 7-240 h after administration.Results: Serum retinol and retinyl ester concentrations responded to treatment (P < 0.0001); however, differences between groups disappeared by 96 h. Liver VA concentrations responded to treatment (P < 0.0001), which persisted for 240 h. Liver VA for control piglets at 10 d (mean ± SD: 0.05 ± 0.02 ?mol/g) was ?0.1 ?mol/g (deficiency), whereas groups that received VA maintained concentrations >0.1 ?mol/g. Extrahepatic tissue VA concentrations displayed treatment effects (P ? 0.0077); groups that received treatments had higher VA concentrations than controls at early time points. Lung, kidney, and spleen VA did not differ between groups by 96 h, whereas adrenal glands did not differ by 240 h. Body weight was affected by treatment (P = 0.0002); VA-deficient piglets weighed 23-29% more than all treated groups 240 h after administration.Conclusions: A high dose of VA administered to newborn piglets was well absorbed, appeared in serum primarily as retinyl esters, and was taken up dose-dependently in all tissues studied; however, enhancement did not persist in sera, lungs, kidneys, spleens, or adrenal glands. Short-term impacts of retinoid signaling on weight gain remain to be elucidated, and longer follow-up studies are needed.

Project description:BACKGROUND:Biofortification is a strategy to relieve vitamin A (VA) deficiency. Biofortified maize contains enhanced provitamin A concentrations and has been bioefficacious in animal and small human studies. OBJECTIVE:The study sought to determine changes in total body reserves (TBRs) of vitamin A with consumption of biofortified maize. DESIGN:A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired (13)C-retinol isotope dilution test, a sensitive biomarker for VA status, was used to measure TBRs before and after a 90-d intervention. Treatments were white maize with placebo oil (VA-), orange maize with placebo (orange), and white maize with VA in oil [400 ?g retinol activity equivalents (RAEs) in 214 ?L daily] (VA+). RESULTS:In total, 133 children completed the trial and were analyzed for TBRs (n = 44 or 45/group). Change in TBR residuals were not normally distributed (P < 0.0001); median changes (95% CI) were as follows: VA-, 13 (-19, 44) ?mol; orange, 84 (21, 146) ?mol; and VA+, 98 (24, 171) ?mol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA- (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) ?mol/g liver, with 59% >1 ?mol/g, the subtoxicity cutoff; none were <0.1 ?mol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 ?g ?-carotene equivalents/1 ?g retinol by using the middle 3 quintiles of change in TBRs from each group. Serum retinol did not change in response to intervention (P = 0.16) but was reduced with elevated C-reactive protein (P = 0.0029) and ?-1-acid glycoprotein (P = 0.0023) at baseline. CONCLUSIONS:?-Carotene from maize was efficacious when consumed as a staple food in this population and could avoid the potential for hypervitaminosis A that was observed with the use of preformed VA from supplementation and fortification. Use of more sensitive methods other than serum retinol alone, such as isotope dilution, is required to accurately assess VA status, evaluate interventions, and investigate the interaction of VA status and infection. This trial was registered at clinicaltrials.gov as NCT01814891.

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:BackgroundRestricting fluids and foods during labour is common practice across many birth settings with some women only being allowed sips of water or ice chips. Restriction of oral intake may be unpleasant for some women, and may adversely influence their experience of labour.ObjectivesTo determine the benefits and harms of oral fluid or food restriction during labour.Search methodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013) and reference lists of retrieved studies.Selection criteriaRandomised controlled trials (RCTs) and quasi-RCTs of restricting fluids and food for women in labour compared with women free to eat and drink.Data collection and analysisTwo review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction.Main resultsWe identified 19 studies of which we included five, involving 3130 women. We excluded eight studies, one awaits classification and five are ongoing studies. All the included studies looked at women in active labour and at low risk of potentially requiring a general anaesthetic. One study looked at complete restriction versus giving women the freedom to eat and drink at will; two studies looked at water only versus giving women specific fluids and foods and two studies looked at water only versus giving women carbohydrate drinks.When comparing any restriction of fluids and food versus women given some nutrition in labour, the meta-analysis was dominated by one study undertaken in a highly medicalised environment. There were no statistically significant differences identified in: caesarean section (average risk ratio (RR) 0.89, 95% confidence interval (CI) 0.63 to 1.25, five studies, 3103 women), operative vaginal births (average RR 0.98, 95% CI 0.88 to 1.10, five studies, 3103 women) and Apgar scores less than seven at five minutes (average RR 1.43, 95% CI 0.77 to 2.68, four studies, 2902 infants), nor in any of the other outcomes assessed. Women's views were not assessed. The pooled data were insufficient to assess the incidence of Mendelson's syndrome, an extremely rare outcome. Other comparisons showed similar findings, except one study did report a significant increase in caesarean sections for women taking carbohydrate drinks in labour compared with water only, but these results should be interpreted with caution as the sample size was small.Authors' conclusionsSince the evidence shows no benefits or harms, there is no justification for the restriction of fluids and food in labour for women at low risk of complications. No studies looked specifically at women at increased risk of complications, hence there is no evidence to support restrictions in this group of women. Conflicting evidence on carbohydrate solutions means further studies are needed and it is critical in any future studies to assess women's views.

Dataset Information

Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

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Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

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