Total Body Vitamin A Research Articles

Comparison of Total Body Vitamin A Stores Using Individual versus Population 13C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries

BackgroundStable isotope techniques using 13C to assess vitamin A (VA) dietary sources, absorption, and total body VA stores (TBSs) require determination of baseline 13C abundance. 13C-natural abundance is approximately 1.1% total carbon, but varies with foods consumed, supplements taken, and food fortification with synthetic retinyl palmitate. ObjectivesWe determined 13C variation from purified serum retinol and the resulting impact on TBSs using pooled data from preschool children in Burkina Faso, Cameroon, Ethiopia, South Africa, Tanzania, and Zambia and Zambian women. MethodsSeven studies included children (n = 639; 56 ± 25 mo; 48% female) and one in women (n = 138; 29 ± 8.5 y). Serum retinol 13C-natural abundance was determined using GC-C-IRMS. TBSs were available in 7 studies that employed retinol isotope dilution (RID). Serum CRP and α1-acid-glycoprotein (AGP) were available from 6 studies in children. Multivariate mixed models assessed the impact of covariates on retinol 13C. Spearman correlations and Bland–Altman analysis compared serum and milk retinol 13C and evaluated the impact of using study- or global-retinol 13C estimates on calculated TBSs. Results13C-natural abundance (%, median [Q1, Q3]) differed among countries (low: Zambia, 1.0744 [1.0736, 1.0753]; high: South Africa, 1.0773 [1.0769, 1.0779]) and was associated with TBSs, CRP, and AGP in children and with TBSs in women. 13C-enrichment from serum and milk retinol were correlated (r = 0.52; P = 0.0001). RID in children and women using study and global estimates had low mean bias (range, −3.7% to 2.2%), but larger 95% limits of agreement (range, −23% to 37%). Conclusions13C-natural abundance is different among human cohorts in Africa. Collecting this information in subgroups is recommended for surveys using RID. When TBSs are needed on individuals in clinical applications, baseline 13C measures are important and should be measured in all enrolled subjects.

Total Liver Vitamin A Reserves, Determined With 13C2-Retinol Isotope Dilution, are Similar Among Tanzanian Preschool Children in Areas With Low and High Vitamin A Exposure

In Tanzania, some districts have single vitamin A (VA) interventions and others have multiple interventions. There is limited information on total liver VA reserves (TLRs) among preschool children (PSC) in Tanzania. We assessed total body VA stores (TBSs) and TLRs among PSC living in 2 districts with low and high exposures to VA interventions using 13C-retinol isotope dilution. A cross-sectional, health facility-based study was conducted in 2 districts with access to VA supplementation only (low exposure to VA interventions) or multiple interventions (high exposure to VA interventions) to determine TLRs in 120 PSC aged 36-59months. A questionnaire was used to collect data. Height and weight were measured, and the prevalence of undernutrition was based on z-scores. Blood samples were collected for measurement of TBSs, TLRs, retinol, biomarkers of infection and inflammation, and hemoglobin. 13C2-retinyl acetate (1.0μmol) was administered to each child after blood collection, and the second sample was taken 14 days later. Serum was analyzed with HPLC and gas chromatography-combustion-isotope ratio mass spectrometry. Mann-Whitney U test was used to compare medians of nonnormally distributed variables. Pearson χ2 test was used to assess associations between 2 categorical variables. Median TBSs differed between PSC from low-exposure (196 μmol; IQR, 120 μmol) and high-exposure (231 μmol; IQR, 162 μmol) intervention areas (P=0.015). Median TLRs were 0.23 μmol/g liver (IQR, 0.14 μmol/g liver) and 0.26 μmol/g liver (IQR, 0.16 μmol/g liver) from low- and high-exposure areas, respectively, which did not significantly differ (P=0.12). Prevalences of VA deficiency (VAD; ≤0.1μmol/g liver) were 6.3% and 1.7% for PSC from low- and high-exposure areas, respectively. There was no significant difference in VAD (P=0.25). No child had hypervitaminosis A (≥1.0μmol/g liver). TLRs in Tanzanian PSC from 2 districts did not differ between low and high exposures to VA interventions. The majority had adequate VA stores. VAD in the study area presented a mild public health problem.

Breast Milk Retinol Concentrations Reflect Total Liver Vitamin A Reserves and Dietary Exposure in Thai Lactating Women from Urban and Rural Areas

Measuring vitamin A (VA) status during lactation is required to inform dietary recommendations. Limited data exist on VA stores in women. Our objective was to assess VA status in lactating Thai women by measuring total body VA stores (TBSs), serum and breast milk retinol concentrations, and dietary intake. Lactating women (n=94), 6-8 wk postpartum, were enrolled from rural (Ayutthaya) and urban (Bangkok) areas. TBSs were measured by the 13C-retinol isotope dilution (RID) technique using 2.0 μmol 13C-retinyl acetate and a single blood sample 14 d post-dose. Natural 13C-enrichment was determined in nonenrolled women (n=11). Estimated total liver VA reserves (TLRs) were determined using assumptions for lactation. Serum, foremilk, and hindmilk samples were analyzed for retinol by HPLC. Dietary VA intake was assessed by FFQ and 24-h dietary recalls for 3 d. Multiple regression and Pearson correlation were used to evaluate relations. Median VA intakes were 51.8% of 2003 Thai daily recommendations for lactating women, with the majority from animal-source foods. Many women in Ayutthaya consumed liver weekly. Considering TLRs as 50% TBS, 20% and 11% of mothers in Ayutthaya and Bangkok, respectively, showed deficient reserves (≤0.10μmol retinol/g). Median (quartile 1, quartile 3) serum [1.58 (1.34, 1.91) and 1.52 (1.30, 1.70) μmol/L] and milk [1.88 (1.29, 2.95) and 1.74 (0.96, 2.26) μmol/L] retinol in Ayutthaya and Bangkok, respectively, were normal. Women with deficient TLRs showed low milk retinol concentrations (≤1.0μmol/L) and consumed less dietary VA, especially from animal-source foods. Breast milk retinol concentrations, especially hindmilk, demonstrated strong correlation with TBSs and TLRs estimated from the RID test. Approximately 15% of Thai lactating women had deficient TLRs. Breast milk retinol concentrations in conjunction with dietary intake records show potential to screen mothers at risk of VA deficiency to guide interventions.The Thai Clinical Trials Registry number is TCTR20160824001 for the work in Thailand.

Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children

Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. Primary outcomes in these children (n=94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5mg/L) and/or α1-acid glycoprotein (AGP; ≥1g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50nmol/L). CRP and AGP were not associated with growth measurements. Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.

Vitamin A–fortified rice increases total body vitamin A stores in lactating Thai women measured by retinol isotope dilution: a double-blind, randomized, controlled trial

Lactating women are at increased risk for vitamin A (VA) deficiency due to demands for breast milk content and limited hepatic stores for women in some countries. Previously, consumption of triple-fortified rice, which included VA, iron, and zinc, successfully improved the VA status of Thai children in whom their total body VA stores (TBSs) were doubled in 2 mo. This study assessed the efficacy of consuming VA-fortified rice, which delivered 500 µg retinol activity equivalents (RAEs)/d, on TBSs and estimated total liver VA reserves (TLRs) in Thai lactating women using the retinol isotope dilution (RID) test. A randomized controlled trial was conducted with 70 lactating women (n=35/group) who received either VA-fortified rice (500 µg RAEs/d) or unfortified rice for 14 wk on weekdays only. Serum retinol concentrations (SRs), C-reactive protein, and TBSs were assessed before and after the intervention. The paired 13C-RID test was used to measure TBSs. After a baseline blood sample, 2.0 µmol [14,15]-13C2-retinyl acetate was administered orally. A follow-up blood sample was drawn 14 d later. The RID test was repeated after the intervention. TBSs increased significantly (P<0.05) in the intervention group from 240 (182, 316) to 331 (251, 447) [geometric means (95% CIs)] µmol retinol, and this change in TBSs was significantly higher (P<0.05) than that in the control group [+52.9 (-74, 453) compared with -4.3 (-106, 275) µmol retinol]. Estimated TLRs indicated a high prevalence of VA deficiency among these lactating women. Initial and final SRs did not differ by group and did not change over the course of the intervention. VA-fortified rice improved the VA status of lactating women by increasing TBSs. A targeted approach to disseminate VA interventions among vulnerable groups should be considered in some contexts. This trial was registered at clinicaltrials.gov as NCT03056625.

Findings in 3 clinical trials challenge the accuracy of the Institute of Medicine’s estimated average requirements for vitamin A in children and women

Vitamin A (VA) estimated average requirements (EARs) for women and children are extrapolated from rats and adult males. The retinol isotope dilution (RID) test can sensitively characterize VA status and intake requirements. These studies evaluated current EARs for children 4-8 y and women 19-30 y old. Zambian children (n=133, ages 5-7 y), US women (n=51, ages 19-27 y), and Indonesian women (n=29, ages 19-30 y) were provided diets or supplements containing 30%-155% of VA EARs for 42-90 d. RID was performed before and after the intervention to quantify changes in total body VA stores (TBSs) and total liver VA reserves (TLRs). Linear regression was performed between VA intake and change in TBSs or TLRs. Baseline mean±SD TLRs were hypervitaminotic in Zambian children (1.13±0.41 μmol VA/g liver), optimal in US women (0.46±0.32 μmol/g VA/g liver), and deficient to marginal in Indonesian women (0.10±0.08 μmol VA/g liver). VA intakes, resulting in no change in TBSs or TLRs, were 185 (95% CI: 18, 288) or 257 (95% CI: 124, 411) and 285 or 330 (CIs undefined) μg retinol activity equivalents (RAE)/d in the Zambian and US trials, respectively, but inconclusive in Indonesian women. The regression was not significant in either group of women. Point estimates of VA intakes to maintain stores were below the current EARs of 275 (children) and 500 (women) μg RAE/d despite the TLRs being higher than the EARs were formulated to maintain (i.e., 0.07 μmol VA/g liver). Interventions based on these EARs may need to be scaled back. Lack of change in VA stores in women taking lower doses may result from physiological adaptation resulting in lower VA utilization. Longer, larger, and controlled studies are needed to accurately define EARs for VA.These trials were registered at Clinicaltrials.gov as NCT04123210 and NCT01814891.

Duration of Retinol Isotope Dilution Studies with Compartmental Modeling Affects Model Complexity, Kinetic Parameters, and Calculated Vitamin A Stores in US Women

Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published. We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes. In this longitudinal study, women (mean ± SD age: 22±3 y; n=7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol 13C4-VA, and data were modeled as long as enrichment was above baseline (5 y). Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P=0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P=0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P<0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P=0.0031]. Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover. This study is registered at www.clinicaltrials.gov as NCT03248700.

Effect of regular consumption of provitamin A biofortified staple crops on Vitamin A status in populations in low-income countries

Biofortification of staple crops with provitamin A (PVA) carotenoids is an innovative strategy for controlling vitamin A (VA) deficiency in low-income countries (LIC). Plant breeding programs have been successful in developing biofortified varieties of cassava, maize, and orange-fleshed sweet potatoes that contain amounts of PVA-carotenoids that have the potential to impact VA status in human populations. Nutrition studies indicate that beta-carotene in biofortified staple crops is converted efficiently to VA in the body. Randomized, controlled, community-based efficacy and effectiveness trials have been conducted to assess the effect of regular consumption of PVA-carotenoid biofortified staple crops on VA status. Results indicate that regular consumption of biofortified staple crops increases plasma beta-carotene concentrations consistently, but has a moderate effect, or no effect, on VA status, when assessed by serum retinol concentration, breast milk retinol concentration, or total body VA stores. Studies are currently underway to further investigate whether consumption of biofortified staple crops improves VA status in population subgroups at risk of VA deficiency, and to better understand how to optimize the biological impact of these interventions in resource-poor settings. Keywords: Beta-carotene, Biofortification, Bioavailability, Cassava, Maize, Provitamin A, Sweet potatoes, Vitamin A

Current Capabilities and Limitations of Stable Isotope Techniques and Applied Mathematical Equations in Determining Whole-Body Vitamin A Status.

Retinol isotope dilution (RID) methodology provides a quantitative estimate of total body vitamin A (VA) stores and is the best method currently available for assessing VA status in adults and children. The methodology has also been used to test the efficacy of VA interventions in a number of low-income countries. Infections, micronutrient deficiencies (eg, iron and zinc), liver disease, physiological age, pregnancy, and lactation are known or hypothesized to influence the accuracy of estimating total body VA stores using the isotope dilution technique. Our objectives were to review the strengths and limitations of RID methods, to discuss what is known about the impact of various factors on results, and to summarize contributions of model-based compartmental analysis to assessing VA status. Relevant published literature is reviewed and discussed. Various equations and compartmental modeling have been used to estimate the total body VA stores using stable isotopes, including a newer 3-day equation that provides an estimate of total body VA stores in healthy adults. At present, there is insufficient information on absorption of the isotope tracer, and there is a need to further investigate how various factors impact the application of RID techniques in field studies. Isotope dilution methodology can provide useful estimates of total body VA stores in apparently healthy populations under controlled study conditions. However, more research is needed to determine whether the method is suitable for use in settings where there is a high prevalence of infection, iron deficiency, and/or liver disease.

Uncertainties of assessing total body vitamin A stores in community settings in low-income countries using the stable-isotope dilution methodology

Uncertainties of assessing total body vitamin A stores in community settings in low-income countries using the stable-isotope dilution methodology

Simplified approaches for estimating vitamin A stores and β‐carotene bioconversion in humans (39.6)

Better methods are needed to assess vitamin A (VA) status and the efficiency of bioconversion of β‐carotene (BC) to retinol (ROH). Data on plasma ROH kinetics from 2 h to 14 d after an oral tracer dose of [13C10]BC and [13C10]retinyl acetate (RAc) to 33 healthy young adults were analyzed using model‐based compartmental analysis (WinSAAM, the Windows version of the Simulation, Analysis and Modeling software). The 6‐compartment model that fit data for all subjects predicted 5.3 pools of plasma ROH were transferred into extravascular stores each day, with ~17%/d recycling back to plasma; 6.5%/day was irreversibly lost and total body VA stores (TBS) were 146 ± 89 μmol (mean ± SD). We derived a simplified isotope dilution (“Olson”) equation for TBS, eliminating several factors and assumptions: TBS = F * (1 / SA), where F (fraction of dose [FD] absorbed and retained) was estimated as 0.61 from the kinetic data and SA (specific activity) is FD 13C10[ROH] in plasma 3 d after dosing / plasma ROH pool (μmol). TBS calculated using the equation was 149 ± 85 μmol, essentially the same as the value predicted by the model. BC bioconversion, calculated as FD 13C5[ROH] (derived from BC) / 13C10[ROH] (derived from RAc) at 2 d, averaged 23 ± 11% and was significantly correlated (R=0.942) with WinSAAM’s estimate based on areas under the curves (26 ± 12%). Our results indicate that both TBS and BC conversion to ROH can be estimated based on blood samples taken 3 and 2 d, respectively, after dosing. With further refinement, one sample at 3 d may suffice.Grant Funding Source: BBSRC, U.K. and DSM, Basel, Switzerland

Vitamin A-Fortified Milk Increases Total Body Vitamin A Stores in Mexican Preschoolers

Vitamin A (VA) deficiency (VAD) continues to be a major nutritional problem in developing countries, including Central America. In Mexico, milk is a well-accepted vehicle for the administration of micronutrients, including VA, to preschoolers. Thus, we conducted a randomized, controlled, clinical trial to investigate the efficacy of daily consumption of 250 mL of VA-fortified milk (which provided 196 retinol equivalents/d) for 3 mo on VA stores in mildly to moderately VAD (serum retinol concentration 0.35–0.7 μmol/L) preschoolers who were not enrolled in a food assistance program. Twenty-seven mildly to moderately VAD children were randomly assigned based on screening measurements to either the intervention (n = 14) or control group (n = 13) (children in the control group did not receive placebo). All children in the control group and 79% (n = 11) of the children in the intervention group completed the study. The total body VA (TBVA) pool size was estimated using the deuterated retinol dilution technique before and after the intervention. After 3 mo, median changes in the serum retinol concentration for the intervention and control groups were 0.13 and −0.21 μmol/L, respectively (P = 0.009). Median changes in the TBVA stores were 0.06 and 0.01 mmol, respectively (P = 0.006) and estimated median changes in the liver VA concentration were 0.09 and 0.01 μmol/g, respectively (P = 0.002). The VA-fortified milk was well accepted among preschoolers and significantly increased TBVA stores, liver VA stores, and serum retinol concentration, indicating that it may be an effective means to ameliorate VAD in young Mexican children.

Daily Consumption of Orange-Fleshed Sweet Potato for 60 Days Increased Plasma β-Carotene Concentration but Did Not Increase Total Body Vitamin A Pool Size in Bangladeshi Women1–3

We assessed the effect of daily consumption of orange-fleshed sweet potatoes (OFSP), with or without added fat, on the vitamin A (VA) status of Bangladeshi women with low initial VA status. Women (n= 30/group) received one of the following for 6 d/wk over 10 wk:1) 0μg retinol activity equivalents (RAE)/d as boiled white-fleshed sweet potatoes (WFSP) and a corn oil capsule,2) 600μg RAE/d as boiled OFSP and a corn oil capsule,3) fried OFSP and a corn oil capsule, or4) boiled WFSP and a retinyl palmitate capsule in addition to their home diets. Plasma concentrations of retinol and β-carotene and total body VA pool size were assessed before and after the 60-d intervention. Initial and final plasma retinol concentrations (mean ± SD) were 0.75 ± 0.18μmol/L and 0.84 ± 0.19μmol/L, respectively (P= 0.31); final means did not differ by group. Initial and final plasma β-carotene concentrations were 0.10 ± 00μmol/L and 0.18 ± 0.09μmol/L, respectively (P< 0.0001); final mean plasma β-carotene concentrations were higher in groups that received OFSP (P< 0.0001), and final mean plasma β-carotene was marginally higher in the group that received fried OFSP compared with boiled OFSP (P= 0.07). Initial and final total body VA pool sizes were 0.060 ± 0.047 mmol and 0.091 ± 0.070 mmol, respectively (P= 0.05,n= 110) and did not differ by group. Despite an increase in plasma β-carotene concentration, the impact of OFSP on VA status appears to be limited in Bangladeshi women residing in a resource-poor community.

Effect of Vitamin A Fortified Milk Intake on Total Body Vitamin A Stores in Mexican Preschoolers

In Mexico, vitamin A deficiency (VAD) is a public health problem for preschool children. Vitamin A (VA) fortified milk (Liconsa) is distributed nationally to fight VAD, nevertheless its effect has yet not been assessed. The aim of this study was to assess the effect of daily intake of VA fortified milk on the total body VA (TBVA) stores of preschoolers.We conducted a randomized controlled clinical trial in Mexico to assess the effect of daily intake of 250 mL of VA fortified Liconsa milk for 12 weeks on VA status of 24 VA‐deficient preschoolers. Subjects were randomly allocated to treatment (n=11) or control (n=13) groups respectively. TBVA stores were calculated using the Olson equation at baseline and three months after daily intake of VA fortified “Liconsa” milk.TBVA stores of the treatment group had a significant increase compared to their baseline value (P&lt;0.05) and stores had a significant difference of 0.75 mmol in treatment vs control groups (P=0.01). Serum retinol concentration was significantly reduced compared to its baseline value in the control group (P&lt;0.05) and serum retinol was 0.291μmol/L greater in the treatment vs control group (P=0.01).Daily intake of vitamin A fortified “Liconsa” milk during 12 weeks, significantly increased TBVA stores and serum retinol levels of Mexican preschoolers.Study supported by the IAEA. LTV received a fellowship from CONACyT.Grant Funding Source : IAEA‐CONACyT

Daily consumption of orange‐fleshed sweet potato increased plasma beta‐carotene concentration but did not increase total body vitamin A pool size in Bangladeshi women

We assessed the effect of daily consumption of orange‐fleshed sweet potato (OFSP), with or without added fat, on the total body vitamin A (VA) pool size of Bangladeshi women with low initial VA status. Women (n=120) received for 60d either 1) 0 μg RAE/d as boiled white‐fleshed sweet potatoes (WFSP) and a corn oil (CO) capsule; or 600 μg RAE/d as either 2) boiled OFSP and a CO capsule, 3) fried OFSP and a CO capsule, or 4) boiled WFSP and a retinyl palmitate capsule, in addition to their home diets. Plasma concentrations of retinol and β‐carotene, and total body VA pool size were assessed before and after the 60‐d intervention. Initial and final mean plasma retinol concentrations were 0.75 ± 0.18 μmol/L and 0.84 ± 0.19 μmol/L, respectively (p=0.31); final means did not differ by group (p=0.11). Initial and final mean plasma β‐carotene concentrations were 0.10 ± 00 μmol/L and 0.18 ± 0.09 μmol/L, respectively (p&lt;0.0001); final mean plasma β‐carotene concentrations were higher in groups that received OFSP (p&lt;0.0001). Initial and final mean total body VA pool sizes were 17.2 ± 13.3 mg and 26.0 ± 20.1 mg, respectively (p=0.048; n=110). Final mean VA pool sizes did not differ by group (p≥0.12). The 60‐d OFSP intervention increased plasma β‐carotene concentrations but did not increase total body VA pool size. Supported by the HarvestPlus Program and the Int'l Atomic Energy Agency.

Estimated level of daily vitamin A intake required to maintain a constant total body vitamin A pool size in adult males with either small or large initial total body vitamin A pool sizes

The deuterated retinol dilution (DRD) technique provides a quantitative estimate of total body vitamin A (TBVA) pool size. The paired-DRD technique permits calculation of the change (+ or −) in TBV...

Population-based plasma kinetics of an oral dose of [2H4]retinyl acetate among preschool-aged, Peruvian children

The deuterated-retinol-dilution technique provides a quantitative estimate of total-body vitamin A (TBVA) stores in adults. To apply the technique to children, information on plasma retinol kinetics in this age group is needed. We described the plasma retinol kinetics of an oral dose of [(2)H(4)]retinyl acetate in a population of Peruvian children (12-24 mo of age) in order to examine the relation between TBVA stores and individual plasma isotopic ratios 3 d after the dose and to estimate 1) the time required for the isotope dose to mix with endogenous vitamin A, 2) the fractional catabolic rate for retinol, and 3) TBVA stores. An oral dose of [(2)H(4)]retinyl acetate (14 micromol retinol equivalents) was administered to children (n = 107) to construct a population-level kinetic curve of the plasma ratio of [(2)H(4)]retinol to retinol to estimate equilibration time and the fractional catabolic rate. TBVA stores were estimated by using a modification of the isotope dilution equation for adults. The dose of [(2)H(4)]retinyl acetate fully mixed with endogenous vitamin A 8 d after the dose. The fractional catabolic rate was 0.022/d (95% CI: 0.014, 0.030/d). Mean (+/- SD) TBVA stores were estimated as 0.097 +/- 0.081 mmol (range: 0.016-0.392 mmol). Plasma ratios of [(2)H(4)]retinol to retinol 3 d after the dose were correlated with the inverse of estimated TBVA stores (r = -0.74, P < 0.0001). Compared with previous results in adults, the equilibration time occurred earlier and the estimated system fractional catabolic rate was higher in this population of children. The modified isotope dilution equation provided estimates of hepatic vitamin A concentration that are similar to values reported in US children at autopsy.