scholarly journals Serum retinyl esters are positively correlated with analyzed total liver vitamin A reserves collected from US adults at time of death

2018 ◽  
Vol 108 (5) ◽  
pp. 997-1005 ◽  
Author(s):  
Kiersten Olsen ◽  
Devika J Suri ◽  
Christopher Davis ◽  
Jesse Sheftel ◽  
Kohei Nishimoto ◽  
...  
Keyword(s):  
Vitamin A ◽  
Ultra Performance Liquid Chromatography ◽  
Total Serum ◽  
Serum Retinol ◽  
Hypervitaminosis A ◽  
Individual Level ◽  
Total Liver ◽  
Retinyl Esters ◽  
The Individual ◽  
Liver Vitamin

ABSTRACT Background Minimal human data exist on liver vitamin A (VA) compared with serum biomarkers. Cutoffs of 5% and 10% total serum VA as retinyl esters (REs) suggest a VA intoxication diagnosis. Objectives We compared total liver VA reserves (TLRs) with the percentage of total serum VA as REs to evaluate hypervitaminosis with the use of US adult autopsy samples. Secondary objectives evaluated serum retinol sensitivity, TLRs among lobes, and hepatic α-retinol concentrations, an α-carotene cleavage product. Design Matched serum and liver samples were procured from cadavers (n = 27; mean ± SD age: 70.7 ± 14.9 y; range: 49–101 y). TLRs and α-REs were quantified by ultra-performance liquid chromatography. Pearson correlations showed liver and serum associations. Sensitivity and specificity were calculated for >5%, 7.5%, and 10% total serum VA as REs to predict TLRs and for serum retinol <0.7 and 1 μmol/L to predict deficiency. Results Serum RE concentrations were correlated with TLRs (r = 0.497, P < 0.001). Nine subjects (33%) had hypervitaminosis A (≥1.0 μmol VA/g liver), 2 of whom had >7.5% total serum VA as REs; histologic indicators corroborated toxicity at 3 μmol/g liver. No subject had >10% total serum VA as REs. Serum retinol sensitivity to determine deficiency (TLRs <0.1 μmol VA/g) was 83% at 0.7 and 1 μmol/L. Hepatic α-retinol was positively correlated with age (P = 0.047), but removing an outlier nullified significance. Conclusions This study evaluated serum REs as a biomarker of VA status against TLRs (gold standard), and abnormal histology suggested that 7.5% total serum VA as REs is diagnostic for toxicity at the individual level in adults. The long-term impact of VA supplements and fortificants on VA status is currently unknown. Considering the high prevalence of hypervitaminotic TLRs in this cohort, and given that many countries are adding preformed VA to processed products, population biomarkers diagnosing hypervitaminosis before toxicity are urgently needed. This trial was registered at clinicaltrials.govas NCT03305042.

scholarly journals South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study

2019 ◽  
Vol 110 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Martha E van Stuijvenberg ◽  
Muhammad A Dhansay ◽  
Jana Nel ◽  
Devika Suri ◽  
Michael Grahn ◽  
...  
Keyword(s):  
South Africa ◽  
Preschool Children ◽  
Vitamin A ◽  
Total Serum ◽  
High Dose ◽  
Serum Retinol ◽  
Hypervitaminosis A ◽  
Total Liver ◽  
Before And After ◽  
Retinyl Esters

ABSTRACT Background In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. Objective We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. Methods After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 μmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. Results At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 μmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 μmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). Conclusions In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

scholarly journals Effects of food or nutrient restriction on milk vitamin A transfer and neonatal vitamin A stores in the rat

1990 ◽  
Vol 63 (2) ◽  
pp. 351-362 ◽  
Author(s):  
Ana Maria ◽  
G. Pasatiempo ◽  
A. Catharine Ross
Keyword(s):  
Vitamin A ◽  
Maternal Diet ◽  
Control Diet ◽  
Serum Vitamin ◽  
Liver Weight ◽  
Retinol Binding Protein ◽  
Serum Retinol ◽  
Total Food Intake ◽  
Affect Transfer ◽  
Liver Vitamin

We have investigated the effects of maternal diets low in fat or protein, or restricted in total food intake on vitamin A transfer from the dam to her pups. When animals were fed on diets moderately restricted in fat or protein, minimal differences in milk, serum, and liver vitamin A concentrations were observed compared with animals fed on a control diet. In a second study, dams were fed on diets more severely restricted in protein, or fat, or both, or were fed on a control diet equal to 50% of the intake of control rats but containing an equal amount of vitamin A. The quantity of milk obtained from these more severely restricted dams' nipples or the pups' stomachs was greatly reduced; however, there were no differences in milk vitamin A concentration. Body-weight, liver weight, and total liver vitamin A stores of undernourished pups were just half those measured for control pups, although serum vitamin A and serum retinol-binding protein were nearly normal in concentration. We conclude that (a) moderate restrictions in fat or protein in the maternal diet are insufficient to affect transfer of vitamin A to the suckling pup; (b) further dietary restrictions could cause decreased milk production with little change in milk vitamin A concentration and, hence, (c) the neonates' hepatic retinol accumulation during the suckling period is markedly reduced when maternal diets are severely deficient in fat or protein or of normal composition but restricted in amount.

Simultaneous determination of retinol and retinyl esters in serum or plasma by reversed-phase high-performance liquid chromatography.

1978 ◽  
Vol 24 (11) ◽  
pp. 1920-1923 ◽  
Author(s):  
M G DeRuyter ◽  
A P De Leenheer
Keyword(s):  
Vitamin A ◽  
High Performance ◽  
Chromatographic Determination ◽  
Reversed Phase ◽  
Retinyl Palmitate ◽  
Serum Retinol ◽  
Liquid Chromatographic Determination ◽  
Retinyl Esters ◽  
Liquid Chromatographic

Abstract We propose a single-run liquid-chromatographic determination, with ultraviolet detection at 330 nm, for serum retinol and retinyl esters. The vitamin A derivatives are extracted according to the Bligh-Dyer procedure. With 200 microliter or serum, the lower detection limit is 50 microgram/liter for retinol and about 100 microgram/liter for retinyl esters. Within-run precision (CV) was 2.3% for retinol, 4.3% for retinyl palmitate. Day-to-day percision (CV, n = 20) for retinol was 4.9% during a month. The method can be used for the assessment of vitamin A absorption tests and for the determination of serum retinol (normal, subnormal, and above-normal concentrations). Serum retinyl esters can only be measured in conditions where concentrations exceed 100 microgram/liter.

scholarly journals Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows

2019 ◽  
Vol 244 (7) ◽  
pp. 579-587 ◽  
Author(s):  
Jesse Sheftel ◽  
Rebecca L Surles ◽  
Sherry A Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Isotope Dilution ◽  
Equilibration Time ◽  
Serum Retinol ◽  
Retinyl Acetate ◽  
Hypervitaminosis A ◽  
Post Dose ◽  
Human Infants ◽  
Lactating Women ◽  
Lactating Sows

Retinol isotope dilution (RID) is used to estimate total body vitamin A (VA) stores in groups to assess VA status. Metabolic differences during lactation may affect RID calculations as currently applied. We evaluated the time required for isotopic equilibration between serum and liver retinol in piglets, and the utility of milk retinol isotopic enrichment as a proxy for serum in lactating sows. Piglets ( n = 24) and sows ( n = 6) were fed 1.75 or 20 µmol 13 C2-retinyl acetate, respectively. Piglets ( n = 5 or 7) were killed on d 0, 4, 7, or 14. Blood and milk were collected at d 0, 0.5, 1, 2, 4, 7, 10, 14, and 21 before the sows were killed to collect liver. Retinol 13 C-enrichment was determined by gas chromatography-combustion-isotope ratio mass spectrometry. Equilibration time and RID-predicted liver VA reserves were calculated. In piglets, serum and liver retinol 13 C-enrichment differed significantly in individuals at d 4 and 7 ( P = 0.008, 0.03) but not d 14 ( P = 0.06); however, mean values were not different by d 4 ( P = 0.62). Current RID equations accurately predicted VA deficiency (means ≤0.027 µmol/g liver) in the piglets. In sows, milk and serum retinol 13 C-enrichment reached equilibrium between 2 and 7 d post-dose. After correcting for dose lost to milk, RID equations predicted higher liver stores than measured values even though the serum to liver atom % was 1.00 ± 0.01 at kill. In VA deficient infants, a shorter period may be accurate in population-level RID studies when using appropriate assumptions. In lactating women, the RID may have decreased accuracy due to variable losses of tracer in milk. Furthermore, assumptions about storage and loss of the dose in milk must be evaluated in lactating women considering the observed discrepancy between predicted and measured stores. Impact statement Vitamin A (VA) deficiency and hypervitaminosis A have been reported in groups of people worldwide. Conventional biomarkers of VA deficiency (e.g. serum retinol concentration, dose response tests) are not able to distinguish between sufficiency and hypervitaminosis A. Retinol isotope dilution (RID) predictions of VA status have been validated in humans and animal models from deficiency through toxicity; however, RID during life stages with unique issues related to isotopic tracing, such as infancy and lactation, requires further evaluation. This study investigated RID in piglets and lactating sows as models for human infants and women. In piglets, RID successfully determined VA deficiency (confirmed with liver analysis), and that the tracer mixes quickly. Conversely, in lactating sows, although serum and milk enrichments were similar, traditional RID equations overestimated VA stores, likely due to losses of tracer and higher extrahepatic VA storage than predictions. These data inform researchers about the challenges of using RID during lactation.

scholarly journals Metabolomics Identifies Serum Metabolites Different in Zambian Women with Adequate versus Deficient Total Liver Vitamin A Reserves Despite Adequate Serum Retinol Levels

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 73-73
Author(s):  
Catherine Johnson ◽  
Sophia Brown ◽  
Chandler Phelps ◽  
Chisela Kaliwile ◽  
Jesse Sheftel ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Future Research ◽  
Serum Retinol ◽  
Serum Samples ◽  
Metabolomics Data ◽  
Total Liver ◽  
Funding Sources ◽  
University Of Wisconsin ◽  
Deficient Group

Abstract Objectives Vitamin A deficiency (VAD) has remained a leading cause of morbidity and mortality throughout the world for decades, however there are still challenges defining VA status because the most common biomarker, serum retinol, is regulated homeostatically except in extreme deficiency and affected by inflammation; therefore, more accurate biomarkers to define VAD are needed. Furthermore, the effects of VAD on metabolism are still being uncovered. The objective was to investigate whether serum metabolomics profiles differed between Zambian women with adequate versus deficient VA status measured by the gold-standard biomarker total liver VA reserves (TLR) whose serum retinol concentrations did not differ. Methods Retinol isotope dilution (RID) was used to estimate TLR in Zambian women in the Rufunsa district; serum aliquots were selected for metabolomics based on adequate (TLR &gt; 0.1–1 μmol VA/g liver) or deficient (TLR &lt; 0.1 μmol/g) VA status (n = 10/group). Serum retinol levels were indicative of adequacy (&gt;0.7 μmol/L) and were not different between groups. Serum samples were analyzed by LC-MS using four metabolomics assays. Metabolomics data were covariate-adjusted for age and BMI. Results Ten metabolites were different between the adequate and deficient vitamin A groups (P &lt; 0.05). Metabolites lower in the deficient group included multiple phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), as well as lipoxygenase (LOX)-derived oxylipins (9-HODE and 17-HDoHE), choline, and anthranilic acid. One cholestryl ester was elevated in the deficient group. Conclusions The study revealed numerous metabolites altered by RID-measured VAD and adequacy despite similarly adequate serum retinol levels in both groups. Future research is required to investigate the mechanisms by which phospholipids such as PCs and PEs, as well as LOX-derived oxylipins, are altered by VA status and the potential use of these metabolites as biomarkers of VAD. Funding Sources University of Wisconsin-Madison Global Health Institute visiting scholar fellowship (CK and SAT).

scholarly journals Comparisons among Equations Used for Retinol Isotope Dilution in the Assessment of Total Body Stores and Total Liver Reserves

2015 ◽  
Vol 145 (5) ◽  
pp. 847-854 ◽  
Author(s):  
Bryan M Gannon ◽  
Sherry A Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Isotope Dilution ◽  
Vitamin A Deficiency ◽  
Storage Site ◽  
Serum Retinol ◽  
Negative Effects ◽  
Hypervitaminosis A ◽  
Major Drawback ◽  
Vitamin A Status ◽  
Wide Range

Abstract Vitamin A plays an essential role in animal biology and has negative effects associated with both hypo- and hypervitaminosis A. Many notable interventions are being done globally to eliminate vitamin A deficiency, including supplementation, fortification, and biofortification. At the same time, it is important to monitor vitamin A status in nations where preformed vitamin A intake is high because of consumption of animal source foods (e.g., liver, dairy, eggs), fortified foods (e.g., milk, cereals, oil, sugar, margarine), or vitamin supplements (e.g., one-a-day multivitamins) to ensure the population does not reach hypervitaminosis A. To accurately assess population status and evaluate interventions aimed at improving vitamin A status, accurate assessment methods are needed. The primary storage site of vitamin A is the liver; however, routinely obtaining liver samples from humans is impractical and unethical. Isotope dilution using deuterium- or 13C-labeled retinol is currently the most sensitive indirect biomarker of vitamin A status across a wide range of liver reserves. The major drawback to its application is the increased technicality in sample analysis and data calculations when compared to less sensitive methodology, such as serum retinol concentrations and dose response tests. Two main equations have emerged for calculating vitamin A body pool size or liver concentrations from isotope dilution data: the “Olson equation” and the “mass balance equation.” Different applications of these equations can lead to confusion and lack of consistency if the underlying principles and assumptions used are not clarified. The purpose of this focused review is to describe the evolution of the equations used in retinol stable-isotope work and the assumptions appropriate to different applications of the test. Ultimately, the 2 main equations are shown to be fundamentally the same and differ only in assumptions made for each specific research application.

Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves

2021 ◽  
pp. 153537022199273
Author(s):  
Sherry A Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Biological Response ◽  
Population Based ◽  
Total Liver ◽  
Long Term Storage ◽  
Micronutrient Status ◽  
Term Storage ◽  
Liver Vitamin

Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs) for North Americans suggested that a minimally acceptable total liver vitamin A reserve (TLR) is 0.07 µmol/g, which is not explicitly expressed as a vitamin A deficiency cutoff. The Biomarkers of Nutrition for Development panel set the TLR cutoff for vitamin A deficiency at 0.1 µmol/g based on changes in biological response of several physiological parameters at or above this cutoff. The criteria used to formulate the DRIs include clinical ophthalmic signs of vitamin A deficiency, circulating plasma retinol concentrations, excretion of vitamin A metabolites in the bile, and long-term storage of vitamin A as protection against vitamin A deficiency during times of low dietary intake. This review examines the biological responses that occur as TLRs are depleted. In consideration of all of the DRI criteria, the review concludes that induced biliary excretion and long-term vitamin A storage do not occur until TLRs are >0.10 µmol/g. If long-term storage is to continue to be part of the DRI criteria, vitamin A deficiency should be set at a minimum cutoff of 0.10 µmol/g and should be set higher during times of enhanced requirements where TLRs can be rapidly depleted, such as during lactation or in areas with high infection burden. In population-based surveys, cutoffs are important when using biomarkers of micronutrient status to define the prevalence of deficiency and sufficiency to inform public health interventions. Considering the increasing use of quantitative biomarkers of vitamin A status that indirectly assess TLRs, i.e. the modified-relative-dose response and retinol-isotope dilution tests, setting a TLR as a vitamin A deficiency cutoff is important for users of these techniques to estimate vitamin A deficiency prevalence. Future researchers and policymakers may suggest that DRIs should be set with regard to optimal health and not merely to prevent a micronutrient deficiency.

scholarly journals Gestational diabetes: a risk of puerperal hypovitaminosis A?

2015 ◽  
Vol 87 (1) ◽  
pp. 463-470 ◽  
Author(s):  
FERNANDA B.S. RESENDE ◽  
LARISSA Q. DE LIRA ◽  
EVELLYN C. GRILO ◽  
MAYARA S.R. LIMA ◽  
ROBERTO DIMENSTEIN
Keyword(s):  
Gestational Diabetes ◽  
Vitamin A ◽  
High Performance ◽  
Vitamin A Deficiency ◽  
Test Group ◽  
Control Group ◽  
Serum Retinol ◽  
Cross Sectional ◽  
The Individual ◽  
Retinol Concentration

The influence of gestational diabetes on vitamin A deficiency in lactating women and, consequently, in their newborn has been verified through a cross-sectional case-control study conducted with volunteer puerperal women. The control group consisted of healthy women and the test group was composed of women with gestational diabetes. One hundred and seven women were recruited, corresponding to 71 controls and 36 cases. Personal, gestational and newborn data were collected directly from medical records during hospitalization. The retinol was determined in maternal colostrum and serum by High Performance Liquid Chromatography. Postpartum women with gestational diabetes were older, had more children and a higher prevalence of cesarean delivery. No difference was found in retinol concentration in maternal milk and serum between the groups. However, it was observed that 16.7% had vitamin A deficiency in the group of patients with diabetes and only 4.1% had such deficiency in the control group. Although no difference was found in colostrum and serum retinol concentration between women with and without gestational diabetes, the individual analysis shows that those with diabetes are at higher risk of being vitamin A deficient.

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