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            C Natural Abundance of Serum Retinol is a Novel Biomarker for Evaluating Effectiveness of Provitamin A Biofortified Maize and Carrots in Male Mongolian Gerbils

Plants that undergo C4 photosynthesis, such as maize, are enriched in the stable isotope of carbon (13C) compared with other dietary plants and foods. Consumption of maize that has been biofortified to contain elevated levels of provitamin A carotenoids (orange maize) increased the abundance of 13C in serum retinol of Mongolian gerbils. We evaluated this method in humans to determine if it has potential for further use in intervention effectiveness studies. A random subset of samples from a two-month randomized controlled feeding trial of rural three- to five-year old Zambian children were used to determine the impact of orange maize intake on serum carotenoid concentrations ( n = 88) and 13C-natural abundance in serum retinol ( n = 77). Concentrations of β-cryptoxanthin (a xanthophyll provitamin A carotenoid) and the dihydroxy xanthophylls lutein and zeaxanthin, which do not have vitamin A activity, were elevated in children consuming orange maize compared with those consuming a white maize control ( P < 0.001), while β-carotene was not different ( P > 0.3). Furthermore, 13C natural abundance was higher after two months’ intervention in the orange maize group compared with the white maize group ( P = 0.049). Predictions made from equations developed in the aforementioned gerbil study estimated that maize provided 11% (2–21%, 95% confidence interval) of the recent dietary vitamin A to these children. These results demonstrate that orange maize is efficacious at providing retinol to the vitamin A pool in children through provitamin A carotenoids, as monitored by the change in 13C enrichment, which was not reflected in serum β-carotene concentrations. Further effectiveness studies in countries who have adopted orange maize should consider determining differences in retinol 13C-enrichment among target groups in addition to profiling serum xanthophyll carotenoids with specific emphasis on zeaxanthin. Impact statement Maize biofortified with provitamin A carotenoids (orange) has been released in some African markets. Responsive and sensitive methods to evaluate dissemination effectiveness are needed. This study investigated methods to evaluate effectiveness of orange maize consumption using serum from Zambian children fed orange maize for two months. Many varieties of orange maize contain higher amounts of the xanthophyll carotenoids in addition to β-carotene compared with typical varieties. This study uniquely showed higher concentrations of the maize xanthophylls lutein, zeaxanthin, and β-cryptoxanthin in children who consumed orange maize compared with white. Furthermore, maize is a C4 plant and is therefore naturally enriched with 13C. Higher 13C was detected in the serum retinol of the orange maize consumers with no change in serum β-carotene concentration suggesting preferential bioconversion to retinol. The combined analyses of serum zeaxanthin specifically and 13C-natural abundance of retinol could prove useful in effectiveness studies between orange maize adopters and non-adopters.

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Cassava with enhanced β-carotene maintains adequate vitamin A status in Mongolian gerbils (Meriones unguiculatus) despite substantial cis-isomer content

British Journal Of Nutrition ◽

10.1017/s0007114508184720 ◽

2009 ◽

Vol 102 (3) ◽

pp. 342-349 ◽

Cited By ~ 25

Author(s):

Julie A. Howe ◽

Bussie Maziya-Dixon ◽

Sherry A. Tanumihardjo

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Meriones Unguiculatus ◽

Provitamin A ◽

Carotenoid Content ◽

Mongolian Gerbils ◽

Serum Retinol ◽

Vitamin A Status ◽

Isomer Content ◽

Β Carotene

Efforts to increase β-carotene in cassava have been successful, but the ability of high-β-carotene cassava to prevent vitamin A deficiency has not been determined. Two studies investigated the bioefficacy of provitamin A in cassava and compared the effects of carotenoid content and variety on vitamin A status in vitamin A-depleted Mongolian gerbils (Meriones unguiculatus). Gerbils were fed a vitamin A-free diet 4 weeks prior to treatment. In Expt 1, treatments (ten gerbils per group) included 45 % high-β-carotene cassava, β-carotene and vitamin A supplements (intake matched to high-β-carotene cassava group), and oil control. In Expt 2, gerbils were fed cassava feeds with 1·8 or 4·3 nmol provitamin A/g prepared with two varieties. Gerbils were killed after 4 weeks. For Expt 1, liver vitamin A was higher (P < 0·05) in the vitamin A (1·45 (sd 0·23) μmol/liver), lower in the control (0·43 (sd 0·10) μmol/liver), but did not differ from the β-carotene group (0·77 (sd 0·12) μmol/liver) when compared with the high-β-carotene cassava group (0·69 (sd 0·20) μmol/liver). The bioconversion factor was 3·7 μg β-carotene to 1 μg retinol (2 mol:1 mol), despite 48 % cis-β-carotene [(Z)-β-carotene] composition in cassava. In Expt 2, cassava feed with 4·3 nmol provitamin A/g maintained vitamin A status. No effect of cassava variety was observed. Serum retinol concentrations did not differ. β-Carotene was detected in livers of gerbils receiving cassava and supplements, but the cis-to-trans ratio in liver differed from intake. Biofortified cassava adequately maintained vitamin A status and was as efficacious as β-carotene supplementation in the gerbil model.

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Anthocyanin and Lycopene Content Do Not Affect Beta-Carotene Bioefficacy from Multicolored Carrots in Male Mongolian Gerbils

Current Developments in Nutrition ◽

10.1093/cdn/nzaa041_014 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 110-110

Author(s):

Mikayla Kaeppler ◽

Jordan Smith ◽

Christopher Davis ◽

Philipp Simon ◽

Sherry Tanumihardjo

Keyword(s):

Vitamin A ◽

Public Health Problem ◽

Negative Control Group ◽

Negative Control ◽

Provitamin A ◽

Control Group ◽

Anthocyanin Content ◽

Mongolian Gerbils ◽

Serum Retinol ◽

Freeze Dried

Abstract Objectives Increasing provitamin A carotenoid consumption is one way to combat vitamin A (VA) deficiency, which is a public health problem in various countries. Multicolored carrots contain provitamin A carotenoids as well as other bioactive phytochemicals, such as anthocyanins and lycopene. Two studies in male Mongolian gerbils were conducted to assess the bioefficacy of β-carotene (BC) with simultaneous consumption of anthocyanins and lycopene from multicolored carrots. Methods In Study 1 (n = 65), BC bioefficacy was compared in gerbils fed diets with a range of lycopene concentrations, sourced from freeze-dried red carrots. Study 2 (n = 66) utilized purple red carrots to create diets with varying anthocyanin content. Each study included positive and negative control groups (n = 10/group) fed white carrot VA-free feeds. Each study included 3-wk VA-depletion, baseline evaluation in 5 or 6 gerbils, and 4-wk treatment periods with 10 gerbils/treatment. HPLC analysis of liver VA stores and serum VA were performed. Results In Study 1, there were no differences among groups. These results may have been influenced by an unanticipated high variation in gerbil starting weight, which was correlated to their final hepatic VA stores. In Study 2, vitamin A liver stores (0.21 ± 0.08 μmol/g) of the treatment groups did not differ from baseline (0.23 ± 0.06 μmol/g) or the positive control group (0.22 ± 0.08 μmol/g), but all groups significantly differed from the negative control group (0.11 ± 0.07μmol/g). Serum retinol concentrations did not correlate with the hepatic VA stores in either study. Conclusions These results confirm previous studies that BC is bioavailable from purple red carrots. The results from Study 2, suggest that simultaneous consumption of carotenoids and anthocyanins do not impact the relative bioavailability of BC. These results add more evidence that serum VA concentrations do not accurately represent hepatic VA stores at deficient to normal concentrations. Funding Sources California Fresh Carrot Advisory Board and the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2016–51,181-25,400 (PWS).

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Overlapping Vitamin A Interventions with Provitamin A Carotenoids and Preformed Vitamin A Cause Excessive Liver Retinol Stores in Male Mongolian Gerbils

Journal of Nutrition ◽

10.1093/jn/nxaa142 ◽

2020 ◽

Vol 150 (11) ◽

pp. 2912-2923 ◽

Cited By ~ 1

Author(s):

Margaret Sowa ◽

Luciana Mourao ◽

Jesse Sheftel ◽

Mikayla Kaeppler ◽

Gabrielle Simons ◽

...

Keyword(s):

Vitamin A ◽

Factorial Design ◽

Scavenger Receptor ◽

Public Health Problem ◽

Negative Control ◽

Provitamin A ◽

Mongolian Gerbils ◽

Serum Retinol ◽

Class B ◽

Β Carotene

ABSTRACT Background Vitamin A (VA) deficiency is a public health problem in some countries. Fortification, supplementation, and increased provitamin A consumption through biofortification are efficacious, but monitoring is needed due to risk of excessive VA intake when interventions overlap. Objectives Two studies in 28–36-d-old male Mongolian gerbils simulated exposure to multiple VA interventions to determine the effects of provitamin A carotenoid consumption from biofortified maize and carrots and preformed VA fortificant on status. Methods Study 1 was a 2 × 2 × 2 factorial design (n = 85) with high-β-carotene maize, orange carrots, and VA fortification at 50% estimated gerbil needs, compared with white maize and white carrot controls. Study 2 was a 2 × 3 factorial design (n = 66) evaluating orange carrot and VA consumption through fortification at 100% and 200% estimated needs. Both studies utilized 2-wk VA depletion, baseline evaluation, 9-wk treatments, and liver VA stores by HPLC. Intestinal scavenger receptor class B member 1 (Scarb1), β-carotene 15,15′-dioxygenase (Bco1), β-carotene 9′,10′-oxygenase (Bco2), intestine-specific homeobox (Isx), and cytochrome P450 26A1 isoform α1 (Cyp26a1) expression was analyzed by qRT-PCR in study 2. Results In study 1, liver VA concentrations were significantly higher in orange carrot (0.69 ± 0.12 μmol/g) and orange maize groups (0.52 ± 0.21 μmol/g) compared with baseline (0.23 ± 0.069 μmol/g) and controls. Liver VA concentrations from VA fortificant alone (0.11 ± 0.053 μmol/g) did not differ from negative control. In study 2, orange carrot significantly enhanced liver VA concentrations (0.85 ± 0.24 μmol/g) relative to baseline (0.43 ± 0.14 μmol/g), but VA fortificant alone (0.42 ± 0.21 μmol/g) did not. Intestinal Scarb1 and Bco1 were negatively correlated with increasing liver VA concentrations (P < 0.01, r2 = 0.25–0.27). Serum retinol concentrations did not differ. Conclusions Biofortified carrots and maize without fortification prevented VA deficiency in gerbils. During adequate provitamin A dietary intake, preformed VA intake resulted in excessive liver stores in gerbils, despite downregulation of carotenoid absorption and cleavage gene expression.

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