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

2020 ◽  
Vol 150 (11) ◽  
pp. 2912-2923 ◽  
Author(s):  
Margaret Sowa ◽  
Luciana Mourao ◽  
Jesse Sheftel ◽  
Mikayla Kaeppler ◽  
Gabrielle Simons ◽  
...  

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.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 110-110
Author(s):  
Mikayla Kaeppler ◽  
Jordan Smith ◽  
Christopher Davis ◽  
Philipp Simon ◽  
Sherry Tanumihardjo

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).


2009 ◽  
Vol 102 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Julie A. Howe ◽  
Bussie Maziya-Dixon ◽  
Sherry A. Tanumihardjo

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.


2017 ◽  
Vol 242 (15) ◽  
pp. 1508-1514 ◽  
Author(s):  
Jesse Sheftel ◽  
Bryan M Gannon ◽  
Christopher R Davis ◽  
Sherry A Tanumihardjo

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.


2006 ◽  
Vol 96 (2) ◽  
pp. 258-267 ◽  
Author(s):  
Mandy Porter Dosti ◽  
Jordan P. Mills ◽  
Philipp W. Simon ◽  
Sherry A. Tanumihardjo

Vitamin A (VA) deficiency is a worldwide public health problem. Biofortifying existing sources of β-carotene (βC) and increasing dietary βC could help combat the issue. Two studies were performed to investigate the relative βC bioavailability of a βC supplement to purple, high-βC orange, and typical orange carrots using Mongolian gerbils (Meriones unguiculatus). In study 1, which used a traditional bioavailability design, gerbils (n32) received a diet containing orange, purple, or white carrot powder, or white carrot powder +a βC supplement. In study 2, which included βC-biofortified carrots, gerbils (n 39) received orange, high-βC orange, purple, or white carrot powder in their diet. Both studies lasted 21 d and the gerbils were killed to determine the effect of carrot type or supplement on serum and liver βC, α-carotene, and VA concentrations. Liver stores of βC or VA in the gerbils did not differ between orange and purple carrot diets when equal amounts of βC from each of the diets were consumed (P>0·05). Both the orange and purple carrot diet resulted in higher liver VA compared with the supplement (P<0·05). High-βC carrots resulted in more than 2-fold higher βC and 1·1 times greater VA liver stores compared with typical orange carrots (P<0·05). These results suggest that high-βC carrots may be an alternative source of VA to typical carrots in areas of VA deficiency. Second, phenolics including anthocyanins and phenolic acids in purple carrot do not interfere with the bioavailability of βC from purple carrots.


2010 ◽  
Vol 13 (11) ◽  
pp. 1863-1869 ◽  
Author(s):  
Nguyen Cong Khan ◽  
Phan Van Huan ◽  
Nguyen Van Nhien ◽  
Le Danh Tuyen ◽  
Saskia de Pee ◽  
...  

AbstractObjectiveTo characterize the relationship between serum carotenoids, retinol and anaemia among pre-school children.DesignA cross-sectional study was conducted in two groups: anaemic and non-anaemic. Serum levels of retinol, α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin were measured in the study subjects.SettingSix rural communes of Dinh Hoa, a rural and mountainous district in Thai Nguyen Province, in the northern mountainous region of Vietnam.SubjectsA total of 682 pre-school children, aged 12–72 months, were recruited.ResultsGeometric mean serum concentrations of carotenoids (μmol/l) were 0·056 for α-carotene, 0·161 for β-carotene, 0·145 for β-cryptoxanthin, 0·078 for lycopene, 0·388 for lutein and 0·075 for zeaxanthin. The mean levels of Hb and serum retinol were 108·8 g/l and 1·02 μmol/l, respectively. The prevalence of anaemia and vitamin A deficiency was 53·7 % and 7·8 %, respectively. After adjusting for sex and stunting, serum retinol concentrations (μmol/l; OR = 2·06, 95 % CI 1·10, 3·86, P = 0·024) and total provitamin A carotenoids (μmol/l; OR = 1·52, 95 % CI 1·01, 2·28, P = 0·046) were independently associated with anaemia, but non-provitamin A carotenoids (μmol/l; OR = 0·93, 95 % CI 0·63, 1·37, P = 0·710) were not associated with anaemia.ConclusionsAmong pre-school children in the northern mountainous region of Vietnam, the prevalences of vitamin A deficiency and anaemia are high, and serum retinol and provitamin A carotenoids are independently associated with anaemia. Further studies are needed to determine if increased consumption of provitamin A carotenoids will reduce anaemia among pre-school children.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1422 ◽  
Author(s):  
Jean Bationo ◽  
Augustin Zeba ◽  
Souheila Abbeddou ◽  
Nadine Coulibaly ◽  
Olivier Sombier ◽  
...  

The health benefits of fruits and vegetables are well-documented. Those rich in provitamin A carotenoids are good sources of vitamin A. This cross-sectional study indirectly assessed fruit and vegetable intakes using serum carotenoids in 193 schoolchildren aged 7 to 12 years in the Western part of Burkina Faso. The mean total serum carotenoid concentration was 0.23 ± 0.29 µmol/L, which included α- and β-carotene, lutein, and β-cryptoxanthin, and determined with serum retinol concentrations in a single analysis with high performance liquid chromatography. Serum retinol concentration was 0.80 ± 0.35 µmol/L with 46% of children (n = 88) having low values <0.7 µmol/L. Total serum carotene (the sum of α- and β-carotene) concentration was 0.13 ± 0.24 µmol/L, well below the reference range of 0.9–3.7 µmol carotene/L used to assess habitual intake of fruits and vegetables. Individual carotenoid concentrations were determined for α-carotene (0.01 ± 0.05 µmol/L), β-carotene (0.17 ± 0.24 µmol/L), β-cryptoxanthin (0.07 ± 0.06 µmol/L), and lutein (0.06 ± 0.05 µmol/L). These results confirm the previously measured high prevalence of low serum vitamin A concentrations and adds information about low serum carotenoids among schoolchildren suggesting that they have low intakes of provitamin A-rich fruits and vegetables.


2007 ◽  
Vol 177 (2) ◽  
pp. 305-316 ◽  
Author(s):  
Tao Wang ◽  
Yuchen Jiao ◽  
Craig Montell

Dietary carotenoids are precursors for the production of retinoids, which participate in many essential processes, including the formation of the photopigment rhodopsin. Despite the importance of conversion of carotenoids to vitamin A (all-trans-retinol), many questions remain concerning the mechanisms that promote this process, including the uptake of carotenoids. We use the Drosophila visual system as a genetic model to study retinoid formation from β-carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina. The protein is coexpressed and functionally coupled with the β, β-carotene-15, 15′-monooxygenase, NINAB, which converts β-carotene to all-trans-retinal. Another class B scavenger receptor, NINAD, functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to propose a pathway involving multiple extraretinal cell types and proteins essential for the formation of rhodopsin.


2010 ◽  
Vol 103 (11) ◽  
pp. 1594-1601 ◽  
Author(s):  
Richard A. Ejoh ◽  
Joseph T. Dever ◽  
Jordan P. Mills ◽  
Sherry A. Tanumihardjo

Leafy vegetables are important sources of provitamin A carotenoids. Information on their ability to provide vitamin A is often misleading because of the methodology used to assess bioefficacy. Mongolian gerbils were used to evaluate the bioefficacy of provitamin A carotenoids in tropical leafy vegetables (i.e. Solanum nigrum, Moringa oleifera, Vernonia calvoana and Hibiscus cannabinus) that are indigenous to Africa. Gerbils (n 67) were vitamin A-depleted for 5 weeks. After a baseline kill (n 7), the gerbils were weight-matched and assigned to six treatment groups (n 10; four vegetable groups; negative and positive controls). For 4 weeks, the treatments included 35 nmol vitamin A (theoretical concentrations based on 100 % bioefficacy) in the form of vegetables or retinyl acetate. In addition to their diets, the control and vegetable groups received daily doses of oil, while the vitamin A group received retinyl acetate in oil matched to prior day intake. Serum and livers were analysed for vitamin A using HPLC. Serum retinol concentrations did not differ among groups, but total liver vitamin A of the vitamin A and vegetable groups were higher than that of the negative control group (P < 0·0001). Liver β-carotene 15,15′-monooxygenase-1 expression levels were determined for two vegetable groups and were similar to the positive and negative controls. Conversion factors for the different leafy vegetables were between 1·9 and 2·3 μg β-carotene equivalents to 1 μg retinol. Small quantities of these vegetables maintained vitamin A status in gerbils through efficient bioconversion of β-carotene to retinol.


2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 25-29 ◽  
Author(s):  
Guangwen Tang

Humans need vitamin A and obtain essential vitamin A by conversion of plant foods rich in provitamin A and/or absorption of preformed vitamin A from foods of animal origin. The determination of the vitamin A value of plant foods rich in provitamin A is important but has challenges. The aim of this paper is to review the progress over last 80 years following the discovery on the conversion of β-carotene to vitamin A and the various techniques including stable isotope technologies that have been developed to determine vitamin A values of plant provitamin A (mainly β-carotene). These include applications from using radioactive β-carotene and vitamin A, depletion-repletion with vitamin A and β-carotene, and measuring postprandial chylomicron fractions after feeding a β-carotene rich diet, to using stable isotopes as tracers to follow the absorption and conversion of plant food provitamin A carotenoids (mainly β-carotene) in humans. These approaches have greatly promoted our understanding of the absorption and conversion of β-carotene to vitamin A. Stable isotope labeled plant foods are useful for determining the overall bioavailability of provitamin A carotenoids from specific foods. Locally obtained plant foods can provide vitamin A and prevent deficiency of vitamin A, a remaining worldwide concern.


2013 ◽  
Vol 110 (S3) ◽  
pp. S36-S44 ◽  
Author(s):  
Nipa Rojroongwasinkul ◽  
Kallaya Kijboonchoo ◽  
Wanphen Wimonpeerapattana ◽  
Sasiumphai Purttiponthanee ◽  
Uruwan Yamborisut ◽  
...  

In the present study, we investigated nutritional status and health-related factors in a multistage cluster sample of 3119 Thai urban and rural children aged 0·5–12·9 years. In a subsample, blood samples were collected for the measurement of Hb, transferrin receptor, vitamin A and vitamin D concentrations. The prevalence of stunting and underweight was higher in rural children than in urban children, whereas the wasting rate was similar in both rural and urban areas. Among children aged 3·0–5·9 years, the prevalence of overweight was significantly higher in urban areas than in rural areas and so was the obesity rate in children aged 6·0–12·9 years. Protein intakes of all age groups were relatively high in both the areas. Intakes of Ca, Fe, Zn and vitamin C were significantly higher in urban areas than in rural areas. The prevalence of anaemia in rural areas was twice as high as that in urban areas, particularly in infants and young children. However, the prevalence of Fe-deficiency anaemia was similar in both urban and rural areas. While the prevalence of vitamin A deficiency (by serum retinol cut-off < 0·7 μmol/l) seemed to be very low, vitamin A insufficiency (by serum retinol cut-off < 1·05 μmol/l) was more prevalent (29·4–31·7 %) in both the areas. The prevalence of vitamin D insufficiency ranged between 27·7 and 45·6 % among the children. The present study indicates that the double burden of malnutrition is still a major public health problem in Thailand. Further studies need to explore the associated risk factors for these nutrient deficiencies. Effective strategies and actions are needed to tackle the nutritional problems in Thai children.


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