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Background: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system., Objective: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated., Methods: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight., Results: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y., Conclusions: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

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) 0 μg retinol activity equivalents (RAE)/d as boiled white-fleshed sweet potatoes (WFSP) and a corn oil capsule, 2) 600 μg RAE/d as boiled OFSP and a corn oil capsule, 3) fried OFSP and a corn oil 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 plasma retinol concentrations (mean ± SD) 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. Initial and final plasma β-carotene concentrations were 0.10 ± 00 μmol/L and 0.18 ± 0.09 μmol/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.

The estimated average requirement (EAR) for vitamin A (VA) of adult males is based on the amount of dietary VA required to maintain adequate function and provide a modest liver VA reserve (0.07 μmol/g). In the present study, the paired-deuterated retinol dilution technique was used to estimate changes in VA pool size in Bangladeshi men from low-income, urban neighborhoods who had small initial VA pool sizes (0.059 ± 0.032 mmol, or 0.047 ± 0.025 μmol/g liver; n = 16). The men were supplemented for 60 d with 1 of 8 different levels of dietary VA, ranging from 100 to 2300 μg/d (2 men/dietary VA level). VA pool size was estimated before and after the supplementation period. The mean change (plus or minus) in VA pool size in the men was plotted against their corresponding levels of daily VA intake and a regression line was fit to the data. The level of intake at which the regression line crossed the x-axis (where estimates of VA pool size remained unchanged) was used as an estimate of the EAR. A VA intake of 254-400 μg/d was sufficient to maintain a small VA pool size (0.059 ± 0.032 mmol) in the Bangladeshi men, corresponding to a VA intake of 362-571 μg/d for a 70-kg U.S. man, which is lower than their current EAR of 625 μg/d. The data suggest that the paired-deuterated retinol dilution technique could be used for estimating the EAR for VA for population subgroups for which there are currently no direct estimates.

A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children lt 5 y of age. To explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 micromol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 micromol; 5 mg), which was used to estimate VA pool size, in 3- to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of [(14)C(2)]-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify (14)C in stool and urine. Estimates of absorption, retention, and the urinary elimination rate (UER) were 83.8 +/- 7.1%, 76.3 +/- 6.7%, and 1.9 +/- 0.6%/d, respectively, for the HD-VA supplement and 76.5 +/- 9.5%, 71.1 +/- 9.4%, and 1.8 +/- 1.2%/d, respectively, for the SI-labeled VA. Mean estimates of absorption, retention, and the UER did not differ by size of the VA dose administered. Estimated absorption and retention were negatively associated with reported fever (r = minus 0.83; P = 0.011). The HD-VA supplement and SI-labeled VA were adequately absorbed, retained, and utilized in apparently healthy Zambian preschool-age boys; absorption and retention may be affected by recent fever.

Background: It is not known whether daily consumption of vitamin A-containing foods is efficacious for treating nightblindness., Objective: We assessed the effect of supplementation with vitamin A from food or synthetic sources on dark adaptation and plasma retinol concentrations in nightblind pregnant Nepali women., Design: Nightblind pregnant women were randomly assigned to 1 of 6 treatment groups to receive 6 d/wk for 6 wk either 850 microg retinol equivalents/d as retinyl palmitate, vitamin A-fortified rice, goat liver, amaranth leaves, or carrots or 2000 microg retinol equivalents/d as retinyl palmitate. Dark adaptation was assessed weekly by using the pupillary threshold (PT) test; plasma retinol concentrations were measured before and after the intervention. These outcomes were also assessed in a comparison group of nonnightblind pregnant women., Results: In the nightblind women, the mean PT improved significantly (P<0.0001) from -0.71+/-0.04 to -1.42+/-0.02 log cd/m2, and the final mean PT did not differ significantly from that in the nonnightblind women (-1.43+/-0.04; P=0.55). Improvement in dark adaptation was greater in the liver group than in the vitamin A-fortified rice group (P<0.02). Plasma retinol concentrations increased significantly (P<0.0001) from 0.95+/-0.05 to 1.07+/-0.05 micromol/L. The plasma retinol response was greater in the higher-dose capsule and liver groups than in the vegetable groups and significantly greater in the liver group than in the vitamin A-fortified rice group (both: P<0.05)., Conclusion: Improvement in dark adaptation did not differ significantly between women who received vitamin A as liver, amaranth leaves, carrots, or retinyl palmitate.

Background: Recent evidence suggests that the vitamin A equivalency of beta-carotene from plant sources is lower than previously estimated., Objective: We assessed the effect of 60 d of daily supplementation with 750 microg retinol equivalents (RE) of either cooked, puréed sweet potatoes; cooked, puréed Indian spinach (Basella alba); or synthetic sources of vitamin A or beta-carotene on total-body vitamin A stores in Bangladeshi men., Design: Total-body vitamin A stores in Bangladeshi men (n = 14/group) were estimated by using the deuterated-retinol-dilution technique before and after 60 d of supplementation with either 0 microg RE/d (white vegetables) or 750 microg RE/d as sweet potatoes, Indian spinach, retinyl palmitate, or beta-carotene (RE = 1 microg retinol or 6 microg beta-carotene) in addition to a low-vitamin A diet providing approximately 200 microg RE/d. Mean changes in vitamin A stores in the vegetable and beta-carotene groups were compared with the mean change in the retinyl palmitate group to estimate the relative equivalency of these vitamin A sources., Results: Overall geometric mean (+/-SD) initial vitamin A stores were 0.108 +/- 0.067 mmol. Relative to the low-vitamin A control group, the estimated mean changes in vitamin A stores were 0.029 mmol for sweet potato (P = 0.21), 0.041 mmol for Indian spinach (P = 0.033), 0.065 mmol for retinyl palmitate (P < 0.001), and 0.062 mmol for beta-carotene (P < 0.002). Vitamin A equivalency factors (beta-carotene:retinol, wt:wt) were estimated as approximately 13:1 for sweet potato, approximately 10:1 for Indian spinach, and approximately 6:1 for synthetic beta-carotene., Conclusion: Daily consumption of cooked, puréed green leafy vegetables or sweet potatoes has a positive effect on vitamin A stores in populations at risk of vitamin A deficiency.

Background: 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., Objectives: 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., Design: 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., Results: 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)., Conclusions: 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.

Background Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case. Objectives The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences. Methods Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6–23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures. Results In CS models, geometric mean pF and sTfR concentrations were 8–340% greater, and RBP and pZn 2–18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar. Conclusions The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853. [ABSTRACT FROM AUTHOR]

Describes the plasma retinol kinetics of an oral dose of [2H4] retinyl acetate in four healthy adults using a deuterated retinol dilution (DRD) technique to determine the total amount of vitamin A the body stores, in relation to clinical nutrition. Information on this technique; Administration of [2H4] in the plasma; Details on the DRD technique; What the time needed for plasma to reach a plateau is referred to; Method used to carry out the study.

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 TBVA pool size that occurs in response to consumption of different amounts of vitamin A (mean change in pool size = final pool size minus initial pool size). We used the paired-DRD technique to estimate the level of daily vitamin A intake that is required to maintain a constant TBVA pool size, i.e. the level of daily intake at which TBVA pool size is maintained, in two groups of adult males (n=32/group) with initial mean (± SD) TBVA pool sizes of either 0.059 ± 0.032 mmol or 0.181 ± 0.062 mmol. TBVA pool size was estimated before and 60 d after consumption of a low vitamin A diet, that was supplemented daily with one of 16 levels of vitamin A (100-2300 µg/d). Change in TBVA pool size was plotted against level of daily vitamin A intake, and the point where the regression line crosses the x-axis was used as an estimate of the level of daily vitamin A intake required to maintain a constant vitamin A pool size. Preliminary data indicate that an intake of 368 µg/d (95% CI: 274, 527; n=16) maintained a constant pool size among individuals with lower initial TBVA; and an intake of 763 µg/d (95% CI: not yet defined; n=16) maintained a constant pool size among individuals with larger initial TBVA. [ABSTRACT FROM AUTHOR]