Community mobilization during biofortified orange maize feeding trials in Zambia.

In some societies, studies involving blood draws, oral vaccinations, or supplementation are surrounded by myths and disbeliefs. If not clarified, they may affect study implementation and negatively impact the outcome of well-intended studies from inadequate participation. Through participatory action research, this paper suggests how future trials could be enhanced with reference to community mobilization, drawing from the experience of two interventions in Zambian children with nutritionally enhanced, biofortified orange maize conducted by the National Food and Nutrition Commission and Tropical Diseases Research Center (Zambia), and University of Wisconsin-Madison (USA). The preparatory phase included site visits, signing of a Memorandum of Understanding, equipment inventory, hiring staff, and community meetings. Prior results were shared before the second intervention. After Institutional Review Boards' approval of procedures, written informed consent was obtained from caregivers. There was overwhelming community participation attributed to the demystification that the project was run by satanists prior to and during the study. Participation led to excellent compliance with 92.8 and 96.4% of subjects completing the final blood draw in 2010 and 2012, respectively. The results of the trials were successfully shared with the district officials and communities from where the study participants were drawn. The positive response by partners and communities, including information sharing, suggests that community mobilization, with the use of varied methods, is effective for full participation of the target groups in feeding trials and would be the case in similar trials if effectively carried out. Community participation in research studies may result in long-term adoption of biofortified foods.

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.

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, ß-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 µmol/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.

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.

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 µg retinol activity equivalents (RAEs) in 214 µL 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) µmol; orange, 84 (21, 146) µmol; and VA+, 98 (24, 171) µmol. 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) µmol/g liver, with 59% >1 µmol/g, the subtoxicity cutoff; none were <0.1 µmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 µg ß-carotene equivalents/1 µg 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 α-1-acid glycoprotein (P = 0.0023) at baseline. CONCLUSIONS: ß-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.

Nutrient and nontraditional food intakes by Zambian children in a controlled feeding trial.

BACKGROUND: Many programs aim to alleviate vitamin A deficiency. Biofortification is an approach to improve provitamin A carotenoid concentrations of staple crops in some developing countries. In rural Zambia, maize accounts for the majority of energy intake. Provitamin A-biofortified (orange) maize has been released in Zambia. OBJECTIVE: This study quantified food intake of Zambian children from records collected in a feeding trial in 2012 in order to compare adoption of orange maize and a new vegetable (green beans) with white maize and traditional foods. METHODS: One hundred thirty-six children with a mean age of 71.5 +/- 6.9 months were fed three meals a day for 6 days a week for 15 weeks at four feeding centers. Breakfast consisted of maize porridge, and lunch and dinner were stiff porridge (nshima) with various side dishes (relishes). There were three treatment groups, which received orange maize and placebo oil, white maize and placebo oil, or white maize and a daily vitamin A supplement. Food was weighed before and after consumption. Nutritionists were trained to interview the children's caregivers about the previous day's intake using dietary recalls. Nine dietary recalls for each child were recorded and analyzed. RESULTS: Total food intake did not differ among the groups (p = .31) and energy intakes on Sundays (< or = 880 kcal) were below recommendations. Nshima intake was lower in the orange-maize group (p = .008), largely due to a genotype effect. Intakes of relish, green bean, and porridge did not differ among the groups (p > .19). Dietary recalls revealed that children living in sites closer to the main road consumed more on Sundays than children living about 8 km from the main road, but less in the evenings when children were off site. CONCLUSIONS: The intakes of energy of these Zambian children were low. Implementation and adoption of new and biofortified foods is possible with promotion.

The acute phase response affected traditional measures of micronutrient status in rural Zambian children during a randomized, controlled feeding trial.

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 α1-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.