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Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.

ABSTRACT: 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.

SUBMITTER: Gannon B

PROVIDER: S-EPMC4232019 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.

Gannon Bryan B Kaliwile Chisela C Arscott Sara A SA Schmaelzle Samantha S Chileshe Justin J Kalungwana Ngándwe N Mosonda Mofu M Pixley Kevin K Masi Cassim C Tanumihardjo Sherry A SA

The American journal of clinical nutrition 20141008 6

<h4>Background</h4>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.<h4>Objective</h4>The study sought to determine changes in total body reserves (TBRs) of vitamin A with consumption of biofortified maize.<h4>Design</h4>A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired (13)C-ret ...[more]

PMID: 25411289

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Project description:BackgroundBiofortification of staple crops with β-carotene is a strategy to reduce vitamin A deficiency, and several varieties are available in some African countries. β-Cryptoxanthin (BCX)-enhanced maize is currently in field trials. To our knowledge, maize BCX bioavailability has not been assessed in humans. Serum retinol 13C content and xanthophyll concentrations are proposed effectiveness biomarkers for biofortified maize adoption.ObjectiveWe determined the relative difference in BCX and zeaxanthin bioavailability from whole-grain and refined BCX-biofortified maize during chronic feeding compared with white maize and evaluated short-term changes in 13C-abundance in serum retinol.DesignAfter a 7-d washout, 9 adults (mean ± SD age: 23.4 ± 2.3 y; 5 men) were provided with muffins made from BCX-enhanced whole-grain orange maize (WGOM), refined orange maize (ROM), or refined white maize (RWM) for 12 d in a randomized, blinded, crossover study followed by a 7-d washout. Blood was drawn on days 0, 3, 6, 9, 12, 15, and 19. Carotenoid areas under the curve (AUCs) were compared by using a fixed-effects model. 13C-Abundance in serum retinol was determined by using gas chromatography/combustion/isotope-ratio mass spectrometry on days 0, 12, and 19. Vitamin A status was determined by 13C-retinol isotope dilution postintervention.ResultsThe serum BCX AUC was significantly higher for WGOM (1.70 ± 0.63 μmol ⋅ L-1 ⋅ d) and ROM (1.66 ± 1.08 μmol ⋅ L-1 ⋅ d) than for RWM (-0.06 ± 0.13 μmol ⋅ L-1 ⋅ d; P < 0.003). A greater increase occurred in serum BCX from WGOM muffins (131%) than from ROM muffins (108%) (P ≤ 0.003). Zeaxanthin AUCs were higher for WGOM (0.94 ± 0.33) and ROM (0.96 ± 0.47) than for RWM (0.05 ± 0.12 μmol ⋅ L-1 ⋅ d; P < 0.003). The intervention did not affect predose serum retinol 13C-abundance. Vitamin A status was within an optimal range (defined as 0.1-0.7 μmol/g liver).ConclusionsBCX and zeaxanthin were highly bioavailable from BCX-biofortified maize. The adoption of BCX maize could positively affect consumers' BCX and zeaxanthin intakes and associated health benefits. This trial is registered at www.clinicaltrials.gov as NCT02800408.

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 .

Project description:Purpose: This study is designed to identify genes and processes that are differentially regulated in corn when it is grown with or without weeds through the entire critical weed free period (to V8) or when weeds were removed early in the critical weed free period (at V4) and the plants were allowed to recover until V8. Methods: Corn was grown as described above in field plots near Brookings SD in 2007 and 2008 and RNA was extracted from the top-most leaf tips from four plants per treatment plot. Unidirectional cDNA illumina sequencing libraries were constructed for each sample (pooled leaf tips from the given plot), and were sequenced (some samples were paired end sequenced and some were single end sequenced - all 100 bases for PE and SE reads), quality trimmed, and analyzed using the Tuxedo suite of programs for SE reads of the forward read libraries for each sample. Results: We identified a small number of genes that were differentially expressed in both years. More importantly, gene set enrichment analysis of the data determined that weeds, when present through the critical weed free period impacted phytochrome signaling, defense responses, photosynthetic processes, oxidative stress responses, and various hormone signaling processes. When weeds were removed at V4 and the plants allowed to recover until V8, the weeds still imprinted impacts on phytochrome signaling, oxidative stress, and defense responses. Thus, it appears that weeds presence through the early portion of the critical weed free period, even after removal, induced processes that reduce corn growth and yield that lasted at least through V8. Conclusions: This study represents the first investigation of the impact of the lasting effects of weeds during the early critical weed free period on the transcriptome of corn, and provides additional data on the impact of weeds through the critical weed free period that augments and confirms much of what was observed in similar microarray studies.

Dataset Information

Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.

Publications

Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.

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