scholarly journals A Compartmental Model Describing the Kinetics of β-Carotene and β-Carotene-Derived Retinol in Healthy Older Adults

2020 ◽  
Author(s):  
Michael H Green ◽  
Jennifer Lynn Ford ◽  
Joanne Balmer Green

ABSTRACT Background Descriptive and quantitative information on β-carotene whole-body kinetics in humans is limited. Objectives Our objective was to advance the development of a physiologically based, working hypothesis compartmental model describing the metabolism of β-carotene and β-carotene-derived retinol. Methods We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to analyze previously published data on plasma kinetics of [2H8]β-carotene, [2H4]β-carotene-derived retinol, and [2H8]retinyl acetate-derived retinol in healthy, older US adults (3 female, 2 male; 50–68 y); subjects were studied for 56 d after consuming doses of 11 μmol [2H8]β-carotene and, 3 d later, 9 μmol [2H8]retinyl acetate in oil. Results We developed a complex model for labeled β-carotene and β-carotene-derived retinol, as well as preformed vitamin A, using simulations to augment observed data during model calibration. The model predicts that mean (range) β-carotene absorption (bioavailability) was 9.5% (5.2–14%) and bioefficacy was 7.3% (3.6–14%). Of the absorbed β-carotene, 41% (25–58%) was packaged intact in chylomicrons and the balance was converted to retinol, with 58% (42–75%) transported as retinyl esters in chylomicrons and 0–2% by retinol-binding protein. Most (95%) chylomicron β-carotene was cleared by the liver. Later data revealed differences in the metabolism of retinyl acetate- versus β-carotene-derived retinol; data required that both β-carotene and derived retinol be recycled from extrahepatic tissues (e.g. adipose) in HDL. Of total bioconversion [73% (47–99%)], 82% occurred in the intestine, 17% in the liver, and 0.83% in other tissues. Conclusions Our model advances knowledge about whole-body β-carotene metabolism in healthy adults, including the kinetics of transport in all lipoprotein species, and suggests hypotheses to be tested in future studies, such as the possibility that retinol derived from hepatic conversion over a long period of time might contribute to plasma retinol homeostasis and total body vitamin A stores.

2020 ◽  
Vol 150 (6) ◽  
pp. 1644-1651 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Jennifer L Ford ◽  
Michael H Green ◽  
Brianda Monreal-Barraza ◽  
Lilian García-Miranda ◽  
...  

ABSTRACT Background Retinol isotope dilution (RID) and model-based compartmental analysis are recognized techniques for assessing vitamin A (VA) status. Recent studies have shown that RID predictions of VA total body stores (TBS) can be improved by using modeling and that VA kinetics and TBS in children can be effectively studied by applying population modeling (“super-child” approach) to a composite data set. Objectives The objectives were to model whole-body retinol kinetics and predict VA TBS in a group of Mexican preschoolers using the super-child approach and to use model predictions of RID coefficients to estimate TBS by RID in individuals. Methods Twenty-four healthy Mexican children (aged 3–6 y) received an oral dose (2.96 μmol) of [13C10]retinyl acetate in corn oil. Blood samples were collected from 8 h to 21 d after dosing, with each child sampled at 4 d and at 1 other time. Composite data for plasma labeled retinol compared with time were analyzed using a 6-component model to obtain group retinol kinetic parameters and pool sizes. Model-predicted TBS was compared with mean RID predictions at 4 d; RID estimates at 4 d were compared with those calculated at 7–21 d. Results Model-predicted TBS was 1097 μmol, equivalent to ∼2.4 y-worth of VA; using model-derived coefficients, group mean RID-predicted TBS was 1096 μmol (IQR: 836–1492 μmol). TBS at 4 d compared with a later time was similar (P = 0.33). The model predicted that retinol spent 1.5 h in plasma during each transit and recycled to plasma 13 times before utilization. Conclusions The super-child modeling approach provides information on whole-body VA kinetics and can be used with RID to estimate TBS at any time between 4 and 21 d postdose. The high TBS predicted for these children suggests positive VA balance, likely due to large-dose VA supplements, and warrants further investigation.


2019 ◽  
Vol 149 (6) ◽  
pp. 951-958 ◽  
Author(s):  
Tyler J Titcomb ◽  
Mikayla S Kaeppler ◽  
Sofía Beatriz Sandoval Cates ◽  
Jamie M Shannon ◽  
Philipp W Simon ◽  
...  

ABSTRACT Background Carrots are an important horticultural crop that contain provitamin A carotenoids (PACs). Orange carrots have high concentrations of α-carotene, which upon central cleavage yields 1 retinal and 1 α-retinal molecule. The leaves of carrot plants are a source of PACs when consumed. Objective Male Mongolian gerbils aged 27–30 d were used to assess the bioefficacy of carrot leaves to maintain vitamin A (VA) status and investigate whether the ratio of α- to β-carotene (α:β-carotene) affected bioefficacy. Methods After 3 wk depletion, baseline gerbils were killed (n = 6) and the remaining gerbils (n = 60) were divided into 6 groups to receive 4 VA-deficient, carrot leaf–fortified feeds (1:1.4, 1:2.5, 1:5.0, and 1:80 α:β-carotene ratio) equalized to 4.8 nmol/g β-carotene equivalents (βCEs), or VA-deficient feed with (VA+) or without (VA−) retinyl acetate supplements. Carrot-leaf powder from 4 carrot plants with differing α:β-carotene ratios was used. After 4 wk, gerbils were killed and tissues were collected and analyzed for retinoids by HPLC. Results VA+ had higher total liver VA (means ± SD 0.91 ± 0.29 μmol) than all other groups (range: 0.40–0.62) (P ≤ 0.03), and the carrot leaf treatments did not differ from baseline (0.55 ± 0.09 μmol). VA− (0.40 ± 0.23 μmol VA/liver) did not differ from the leaf-fed groups, but 30% became VA deficient (defined as <0.1 μmol VA/g liver). α-Retinol accumulated in livers and lungs and was correlated to total α-carotene consumption (R2 = 0.83 and 0.88, respectively; P < 0.0001). Bioefficacy factors ranged from 4.2 to 6.2 μg βCE to 1 μg retinol. Conclusions Carrot leaves maintain VA status and prevent deficiency in gerbils regardless of the α:β-carotene ratio. The bioconversion of PACs from carrot leaves to retinol is similar to what has been reported for other green leafy vegetables, making the consumption of carrot leaves a viable method to improve dietary PAC intake.


1992 ◽  
Vol 68 (2) ◽  
pp. 529-540 ◽  
Author(s):  
Cécile Carlier ◽  
Michel Etchepare ◽  
Jean-François Ceccon ◽  
Marie-Sophie Mourey ◽  
Olivier Amédée-Manesme

Administration of large oral doses of retinyl palmitate has become the most widely practised vitamin A deficiency prevention strategy in developing countries. We conducted a follow-up study among 220 Senegalese children aged 2–7 years suffering from moderate undernutrition to determine the efficacy of vitamin A treatment on their vitamin A status assessed by biochemical and cytological (impression cytology with transfer) methods. The first examination (T = 0 m[onth]) was carried out during April 1989, before the mango (Mangifera indica L,) harvest. The second examination (T = 2 m) was carried out 2 months after vitamin A treatment during June 1989 when ripe mangoes become widely available. Conjunctival cells of the eyes of the children with or without ocular inflammation were responsive to vitamin A administration (P < 0.01). There was a significant increase (P < 0.001) in mean serum retinol and β-carotene levels between T = 0 m and T = 2 m. Mean serum retinol-binding protein (RBP) and transthyretin (TTR) levels did not differ significantly (P > 0.05) at T = 0 m and T = 2 m. Despite the intake of vitamin A, 54% of the children who had abnormal cytology at T = 0 m remained abnormal at T = 2 m. This was due to inadequate levels of TTR and RBP, presumably due to the cereal diet eaten by the Senegalese population. Children with abnormal eye cytology had lower serum retinol levels than those with normal eyes at T = 0 m, and β-carotene values did not correlate with eye cytological abnormalities at T = 0 m. Children with normal cytology had higher serum retinol and also β-carotene levels than those with abnormal cytology after massive oral doses of vitamin A and consumption of mangoes at T = 2 m. Retinyl palmitate may, therefore, only lead to partial cytological improvement due to a lack of retinol-carrier proteins but dietary β-carotene may also be involved


1996 ◽  
Vol 76 (6) ◽  
pp. 809-820 ◽  
Author(s):  
Guangya Wang ◽  
Thierry A. Brun ◽  
Catherine A. Geissler ◽  
Banoo Parpia ◽  
Martin Root ◽  
...  

Vitamin A status of 260 groups of twenty-five males or twenty-five females, aged 35–64 years, surveyed in twenty-four provinces of the People's Republic of China, was assessed by measuring plasma retinol, retinol-binding protein and β-carotene concentrations. Direct measurements of food intake over a 3 d period and questionnaire data on the frequency of consumption of vegetables, fruit, animal products and other dietary items were also used. Vitamin A status appeared to be low only in specific counties but in general was satisfactory or only marginally deficient. Plasma harotene levels were strikingly low in comparison with Western levels despite generous vegetable consumption suggwg that intake of vitamin A precursors may have been adequate but not abundant enough to maintain high circulating plasma levels of β-carotene. Plasma β-carotene, for both males and females, was significantly correlated with the frequency of consumption of green vegetables. Plasma retinol, for males, was highly correlated with meat, fish, oil and alcohol consumption expresPed both in quantity or frequency of consumption. Higher levels of plasma retinol, together with lower levels of plasma β-carotene in males compared with females, suggest that men consume more animal products or may have higher retinol requirements and therefore a higher rate of conversion of β-carotene to retinol.


1998 ◽  
Vol 68 (1) ◽  
pp. 90-95 ◽  
Author(s):  
M J Haskell ◽  
M A Islam ◽  
G J Handelman ◽  
J M Peerson ◽  
A D Jones ◽  
...  

2008 ◽  
Vol 100 (4) ◽  
pp. 786-793 ◽  
Author(s):  
Christopher Davis ◽  
Hua Jing ◽  
Julie A. Howe ◽  
Torbert Rocheford ◽  
Sherry A. Tanumihardjo

Maize with enhanced provitamin A carotenoids (biofortified), accomplished through conventional plant breeding, maintains vitamin A (VA) status in Mongolian gerbils (Meriones unguiculatus). Two studies in gerbils compared the VA value of β-cryptoxanthin with β-carotene. Study 1 (n 47) examined oil supplements and study 2 (n 46) used maize with enhanced β-cryptoxanthin and β-carotene. After 4 weeks' depletion, seven or six gerbils were killed; remaining gerbils were placed into weight-matched groups of 10. In study 1, daily supplements were cottonseed oil, and 35, 35 or 17·5 nmol VA (retinyl acetate), β-cryptoxanthin or β-carotene, respectively, for 3 weeks. In study 2, one group of gerbils was fed a 50 % biofortified maize diet which contained 2·9 nmol β-cryptoxanthin and 3·2 nmol β-carotene/g feed. Other groups were given equivalent β-carotene or VA supplements based on prior-day intake from the biofortified maize or oil only for 4 weeks. In study 1, liver retinol was higher in the VA (0·74 (sd 0·11) μmol) and β-cryptoxanthin (0·65 (sd 0·10) μmol) groups than in the β-carotene (0·49 (sd 0·13) μmol) and control (0·41 (sd 0·16) μmol) groups (P < 0·05). In study 2, the VA (1·17 (sd 0·19) μmol) and maize (0·71 (sd 0·18) μmol) groups had higher liver retinol than the control (0·42 (sd 0·16) μmol) group (P < 0·05), whereas the β-carotene (0·57 (sd 0·21) μmol) group did not. Bioconversion factors (i.e. 2·74 μg β-cryptoxanthin and 2·4 μg β-carotene equivalents in maize to 1 μg retinol) were lower than the Institute of Medicine values.


2012 ◽  
Vol 1 ◽  
Author(s):  
Lei Li ◽  
Xianfeng Zhao ◽  
Jie Wang ◽  
Tawanda Muzhingi ◽  
Paolo M. Suter ◽  
...  

AbstractSpirulina is an alga rich in high-quality protein and carotenoids. It is unclear whether spirulina can improve the total-body vitamin A stores of school-age children in China with a high prevalence of vitamin A malnutrition. We aimed to evaluate the efficacy of spirulina in improving the total-body vitamin A stores of school-age children in rural areas of China when they consumed spirulina in their daily meals. A total of 228 children (6–11 years) were recruited and randomly divided into three groups supplemented with 4 g (containing 4·18 µg β-carotene), 2 g (containing 2·54 µg β-carotene) or 0 g spirulina 5 d/week for 10 weeks, respectively. Before and after the intervention period, each child was given 0·5 mg [2H4]retinyl acetate and [2H8]retinyl acetate, respectively. To assess vitamin A stores, blood samples (3 ml) were collected on the third and the twenty-first day after each labelled retinyl acetate dose for a retinol enrichment analysis using a GC mass spectrometer. The concentrations of retinol and β-carotene in serum samples were also determined by using HPLC. After the 10-week intervention, serum β-carotene concentrations of children with 2 or 4 g spirulina supplement increased by 0·160 and 0·389 µmmol/l, respectively. Total-body vitamin A stores increased significantly, with a median increase of 0·160 mmol in children taking 2 g spirulina and of 0·279 mmol in children taking 4 g spirulina. Spirulina is a good dietary source of β-carotene, which may effectively increase the total-body vitamin A stores of Chinese school-age children.


2004 ◽  
Vol 91 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Zhixu Wang ◽  
Shian Yin ◽  
Xianfeng Zhao ◽  
Robert M. Russell ◽  
Guangwen Tang

The present study was carried out to determine the conversion factor of synthetic2H-labelled β-carotene to vitamin A in Chinese adults by using a stable-isotope dilution technique. Fifteen healthy volunteers aged 50–60 years were recruited for a 55 d experiment. The volunteers (nine males and six females) were each given a physiological dose of [2H8]β-carotene (6 mg) in oil on the first day of the experiment, and a reference dose of [2H8]retinyl acetate (3 mg) in oil was given on the fourth day. Serum samples were collected at 0, 3, 5, 7, 9, 11, and 13 h on the first and the fourth days of the study, daily for 10 d, and then weekly from days 14 to 56. β-Carotene and retinol were extracted from serum and isolated by HPLC, and their enrichments were respectively determined by using GC–electron capture negative chemical ionisation-MS and LC–atmospheric pressure chemical ionisation interface-MS. Four of the subjects exhibited β-carotene to vitamin A conversion factors of >29·0:1 on a molar basis and were termed ‘poor converters’. In the eleven normal converters (seven males and four females), the calculated conversion factors of β-carotene to retinol ranged from 2·0:1 to 12·2:1 with an average of 4·8 (sd 2·8):1 on a molar basis, and from 3·8:1 to 22·8:1 with an average of 9·1 (sd 5·3):1 on a weight basis. The 52 d post-intestinal absorption conversion was estimated to be about 30 % of the total converted retinol.


2019 ◽  
Vol 2 (3) ◽  
pp. 108-119
Author(s):  
Krisna Malau ◽  
◽  
Nuri Andarwulan ◽  
Drajat Martianto ◽  
Desty Gitapratiwi ◽  
...  

2011 ◽  
Vol 107 (9) ◽  
pp. 1350-1366 ◽  
Author(s):  
Abdollah Ghavami ◽  
W. Andy Coward ◽  
Les J. C. Bluck

A strategy to reduce the incidence of vitamin A deficiency is to improve precursor bioavailability from meals. Since vitamin A precursors are fat-soluble, we noted that carotenoids are more easily absorbed from food if prepared in such a way that the food matrix containing provitamin A (β-carotene) is sufficiently fat rich. To quantify this effect, we have developed a stable isotope methodology. By regular watering with2H-labelled water, we were able to produce several kg of intrinsically labelled carrots, with carotenoids labelled to 0·63 % excess2H. These were divided into 100 g portions and fed to a small group of healthy subjects both raw and stir-fried. To normalise for inter-individual variation in absorption and subsequent metabolism, small quantities of extrinsically13C-labelled β-carotene and2H-labelled retinol acetate were also incorporated into the meal. After ingestion of the carrots, blood lipids were monitored for a period of 3 d in order to determine the kinetics of β-carotene and retinol. From kinetic data, it was estimated that the bioavailability of carrot-derived β-carotene compared with pure β-carotene was about 11 % for raw carrots, but 75 % when the carrots were stir-fried. Conversely, there was a slight reduction in the bioconversion to retinol from β-carotene when the latter was derived from the stir-fried meal compared with that from raw carrots. When these two factors are combined, the yield of retinol from the carotene in carrots was found to be enhanced by a factor of 6·5 by stir-frying.


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