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Gannon B.,University of Wisconsin - Madison | Kaliwile C.,National Food and Nutrition Commission of Zambia | Arscott S.A.,University of Wisconsin - Madison | Arscott S.A.,Standard Process Inc. | And 7 more authors.
American Journal of Clinical Nutrition | Year: 2014

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 Awith consumption of biofortified maize.Design: A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired 13C-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 (VA2), orange maize with placebo (orange), and white maize with VA in oil [400 mg retinol activity equivalents (RAEs) in 214 mL 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: VA2, 13 (219, 44) mmol; orange, 84 (21, 146) mmol; and VA+, 98 (24, 171) mmol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA2 (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) mmol/g liver, with 59% .1 mmol/g, the subtoxicity cutoff; none were ,0.1 mmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 mg b-carotene equivalents/1 mg 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 a-1-acid glycoprotein (P = 0.0023) at baseline.Conclusions: b-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. © 2014 American Society for Nutrition. Source


Bresnahan K.A.,University of Wisconsin - Madison | Chileshe J.,Tropical Diseases Research Center | Arscott S.,University of Wisconsin - Madison | Arscott S.,Standard Process Inc. | And 5 more authors.
Journal of Nutrition | Year: 2014

The acute phase response (APR) to infection can alter blood-based indicators of micronutrient status. Data from a 3-mo randomized, controlled feeding trial in rural Zambian children (n = 181, aged 3-5 y) were used to determine the impact of the APR on indicators of vitamin A and iron status using baseline and final blood samples. Concentrations of acute phase proteins were categorized as raised C-reactive protein (CRP; <5 and <10 mg/L) only, both raised CRP and a1-acid glycoprotein (AGP; <1.2 g/L), raised AGP only, and neither CRP nor AGP raised to identify the respective stages of infection: incubation, early convalescence, convalescence, and healthy state. Data were insufficient to examine the incubation stage of infection. A CRP concentration of <5 mg/L was an effective elevation cutoff point in this population to show impact on micronutrient markers. Time did not affect hemoglobin, serum ferritin, or serum retinol concentrations (P < 0.05). During early convalescence, hemoglobin decreased (14-16%; P ≤ 0.05), serum ferritin increased (279-356%; P ≤ 0.05), and serum retinol decreased (20-30%; P ≤ 0.05). Serum retinol concentrations did not change during convalescence; however, hemoglobin remained depressed (4-9%) and serum ferritin was elevated (67-132%) (both P ≤ 0.05). Modified relative dose response values were unaffected by the APR (P < 0.05) but increased between time points (16%; P ≤ 0.05), indicating a decrease in liver vitamin A reserves on the background of a semiannual vitamin A supplementation program. The observed prevalence of anemia and vitamin A deficiency assessed by serum retinol concentration was higher during the APR (P ≤ 0.05). It is important to consider the impact of infection on dietary interventions and to adjust for acute phase proteins when assessing iron status or vitamin A status by serum retinol concentration alone in children. © 2014 American Society for Nutrition. Source


Mondloch S.,University of Wisconsin - Madison | Gannon B.M.,University of Wisconsin - Madison | Davis C.R.,University of Wisconsin - Madison | Chileshe J.,Tropical Diseases Research Center | And 5 more authors.
American Journal of Clinical Nutrition | Year: 2015

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. α-Carotene, β-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 mmol/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 animalsource foods may enhance vitamin B-6 status in Zambians. Source

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