Biofortified Orange Maize is as Efficacious as a Vitamin A Supplement in Zambian Children Even on the Background of High Liver Reserves of Vitamin A.

Objectives: The main objective of this study was to determine the vitamin A (VA) bioefficacy of high β-carotene, biofortified (orange) maize in Zambian preschool children. Methods: A randomized, placebo-controlled orange maize efficacy trial was conducted in rural Zambian children (n = 140, 71.5±6.9 months). The paired 13C-retinol isotope dilution test, the most sensitive indirect marker of VA status, was used to measure total body reserves (TBR) of VA before and after a 90-d intervention. Treatment arms were white maize with placebo oil (VA-), white maize with 400 μg (VA+), and orange maize with placebo oil (orange). Results: TBR of VA increased in the VA+ and orange groups (203±386 and 109±341 μmol, respectively) (P = 0.0034), and were different from the VA- group (-4.5±208 μmol) using nonparametric analysis. Medians were VA- 12.6, VA+ 97.8, orange 83.7 μmol. Baseline estimates of liver concentration were 1.13±0.41 μmol/g, with 59% >1 μmol/g, the current sub-toxicity cutoff; none were <0.1 μmol/g, the proposed cutoff for deficiency. The bioconversion factor was 10.4 μg β-carotene: 1 μg retinol using the middle three quintiles of change in TBR from each treatment group. Serum retinol concentrations did not respond (P = 0.16). Conclusions: Biofortified maize is a very effective VA source when consumed as a staple food and could avoid potential toxicity issues with preformed VA from supplementation or fortification programs as observed in this population. Stable isotope methodology should be used to elucidate VA status of various populations, and serum retinol should be used with caution in setting global health policy.

Impact of Provitamin a Biofortified Maize Flour Consumption on Dark Adaptation in Zambian Children.

Objectives: Approximately one third of children in developing countries are deficient in vitamin A (VA). Of these, 5.2 million are affected by night blindness—a severe impairment in dark adaptation. ProVA biofortified “orange” maize has been introduced in Africa as a potential intervention to address VA deficiency. We tested the impact of regular orange maize flour consumption on dark adaptation in preschool-aged children. Methods: This was a cluster-randomized trial of children aged 4-8 years (n=1,024; 50 clusters) in Mkushi, Zambia comparing orange maize to conventional white maize. A random subsample (n=542) was assessed pre- and post-intervention using a portable field dark adaptometer to record pupillary response to varying light stimuli (-2.9 to 0.1 c/m2). We measured pre- and post-stimuli pupil diameter using Tracker video analysis software and calculated the % change (i.e., “responsiveness”). Pupillary threshold was defined as the lowest stimulus causing a ≥20% reduction in pupil diameter. Results: At baseline, children assigned to orange maize were less responsive than those in the white group to all light stimuli. After the six-month intervention, pupillary responsiveness in the orange group improved across all stimuli. No consistent changes in responsiveness were observed in the white group. Pupillary threshold scores improved in 47% of orange group children versus 35% in the control arm. Improvements were more pronounced among children who consumed >75% of the maize meal provided, compared to those with lower compliance. Conclusions: Regular consumption of proVA biofortified maize flour improved dark adaptation in a marginally VA deficient population.

Malaria Exacerbates Inflammation-induced Bias in Ferritin and Soluble Transferrin Receptor Values.

Objectives: In the context of malaria and inflammation, the utility of ferritin and soluble transferring receptor (sTfR), as indicators of iron status may be compromised. In this study, we evaluated the effects of correcting for malaria and inflammation on the prevalence of iron deficiency (ID) as estimated by a) ferritin and b) sTfR. Methods: The analyses used baseline data from 1085 children, 4-8 y, who participated in a carotenoid biofortified maize flour trial in rural Zambia. For each biomarker, we compared the prevalence of ID with the prevalence corrected for a) CRP and AGP only; and b) CRP, AGP and concurrent malaria. Inflammation was defined as CRP>5mg/L and/or AGP>1g/L. Malaria was defined by microscopy. Children were first stratified into groups defined by inflammation and malaria status. Correction factors were then generated by dividing the group geometric means by that of the reference group (those free of both malaria and inflammation). Correction factors were applied to each individual concentration to generated corrected concentrations. Results: For ferritin, the unadjusted prevalence of ID (WHO age-specific cut-offs) increased from 7.3% to 9.5% (p<0.01) and 10.3 %( p<0.01), respectively, after correcting for CRP/AGP only, and CRP, AGP and concurrent malaria combined. For sTfR, the unadjusted ID prevalence (cutoff >8.3 mg/l) decreased from 28% to 21% (p<0.01) after correcting CRP/AGP only, and 19% (p<0.01) after correcting for CRP, AGP and concurrent malaria. Conclusions: Our findings highlight the need to account for both malaria and inflammation when interpreting ferritin and sTfr concentrations in malaria endemic regions.