Stephanie Mondloch1, Bryan M Gannon1, Christopher R Davis1, Justin Chileshe2, Chisela Kaliwile3, Cassim Masi3, Luisa Rios-Avila4, Jesse F Gregory4, Sherry A Tanumihardjo5. 1. Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI; 2. Tropical Diseases Research Centre, Ndola, Zambia; 3. National Food and Nutrition Commission of Zambia, Lusaka, Zambia; and. 4. University of Florida, Gainesville, FL. 5. Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI; sherry@nutrisci.wisc.edu.
Abstract
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 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.
RCT Entities:
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 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.
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