title: 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.
  
  
  METHODS
  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 β-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
  β-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.
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Bryan
authors.initials: B
authors.lastname: Gannon
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Chisela
authors.initials: C
authors.lastname: Kaliwile
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Sara A
authors.initials: SA
authors.lastname: Arscott
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Samantha
authors.initials: S
authors.lastname: Schmaelzle
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Justin
authors.initials: J
authors.lastname: Chileshe
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Ngándwe
authors.initials: N
authors.lastname: Kalungwana
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Mofu
authors.initials: M
authors.lastname: Mosonda
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Kevin
authors.initials: K
authors.lastname: Pixley
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Cassim
authors.initials: C
authors.lastname: Masi
authors.affiliation: From the Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI (BG, SAA, SS, and SAT); National Food and Nutrition Commission of Zambia, Lusaka, Zambia (CK, MM, and CM); Tropical Diseases Research Centre, Ndola, Zambia (JC and NK); and International Maize and Wheat Improvement Center, Texcoco, Mexico (KP).
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Tanumihardjo
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D004032:Diet; D005260:Female; D005527:Food, Fortified / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D014801:Vitamin A / Q000008:administration & dosage* / Q000097:blood; D014802:Vitamin A Deficiency / Q000097:blood* / Q000178:diet therapy / Q000453:epidemiology*; D015024:Zambia / Q000453:epidemiology; D003313:Zea mays / Q000737:chemistry*; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: D019207:beta Carotene; D014801:Vitamin A; D002097:C-Reactive Protein
keywords: 13C-retinol dilution; Zambia; biofortified maize; plant carotenoids; retinol