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Tanumihardjo, S.A.

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Tanumihardjo
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S.A.
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Tanumihardjo, S.A.
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0000-0002-7022-1760

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2014 - 20162
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    13C natural abundance of serum retinol is a novel biomarker for evaluating provitamin A carotenoid-biofortified maize consumption in male Mongolian gerbils
    (American Society for Nutrition, 2016) Gannon, B.M.; Pungarcher, I.; Mourao, L.; Davis, C.R.; Simon, P.W.; Pixley, K.V.; Tanumihardjo, S.A.
    Background: Crops such as maize, sorghum, and millet are being biofortified with provitamin A carotenoids to ensure adequate vitamin A (VA) intakes. VA assessment can be challenging because serum retinol concentrations are homeostatically controlled and more sensitive techniques are resource-intensive. Objectives: We investigated changes in serum retinol relative differences of isotope amount ratios of 13C/12C (d13C) caused by natural 13C fractionation in C3 compared with C4 plants as a biomarker to detect provitamin A efficacy from biofortified (orange) maize and high-carotene carrots. Methods: The design was a 2 3 2 3 2 maize (orange compared with white) by carrot (orange compared with white) by a VA fortificant (VA+ compared with VA2) in weanling male Mongolian gerbils (n = 55), which included a 14-d VA depletion period and a 62-d treatment period (1 baseline and 8 treatment groups; n = 527/group). Liver VA and serum retinol were quantified, purified by HPLC, and analyzed by GC combustion isotope ratio mass spectrometry for 13C. Results: Treatments affected liver VA concentrations (0.048 6 0.039 to 0.79 6 0.24 mmol/g; P < 0.0001) but not overall serum retinol concentrations (1.3860.22 mmol/L). Serum retinol and liver VA d13C were significantly correlated (R2 = 0.92; P < 0.0001). Serum retinol d13C differentiated control groups that consumed white maize and white carrots (227.1 6 1.2 d13C&) from treated groups that consumed orange maize and white carrots (221.6 6 1.4 d13C&; P < 0.0001) and white maize and orange carrots (230.6 6 0.7 d13C&; P < 0.0001). A prediction model demonstrated the relative contribution of orange maize to total dietary VA for groups that consumed VA from mixed sources. Conclusions: Provitamin A efficacy and quantitative estimation of the relative contribution to dietary VA were demonstrated with the use of serum retinol d13C. This method could be used for maize efficacy or effectiveness studies and with other C4 crops biofortified with provitamin A carotenoids (e.g., millet, sorghum). Advantages include no extrinsic tracer dose, 1 blood sample, and higher sensitivity than serum retinol concentrations alone.
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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 1–6
    (American Society for Nutrition, 2014) Gannon, B.M.; Kaliwile, C.; Arscott, S.A.; Schmaelzle, S.; Chileshe, J.; Kalungwana, N.; Mosonda, M.; Pixley, K.V.; Masi, C.; Tanumihardjo, S.A.
    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 Awith consumption of biofortified maize. Design: A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired 13C-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 (VA2), orange maize with placebo (orange), and white maize with VA in oil [400 mg retinol activity equivalents (RAEs) in 214 mL 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: VA2, 13 (219, 44) mmol; orange, 84 (21, 146) mmol; and VA+, 98 (24, 171) mmol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA2 (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) mmol/g liver, with 59% .1 mmol/g, the subtoxicity cutoff; none were ,0.1 mmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 mg b-carotene equivalents/1 mg 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 a-1-acid glycoprotein (P = 0.0023) at baseline. Conclusions: b-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. Am J Clin Nutr 2014;100:1541–50.
    Publication