ArticleThe American journal of clinical nutrition2018
Serum retinyl esters are positively correlated with analyzed total liver vitamin A reserves collected from US adults at time of death.
Article in The American journal of clinical nutrition, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 16 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Vitamin A Liver Reserves and Serum Markers of Vitamin A in US Adults at Time of Death
Niveles de Retinol Hepatico y óseo en cadáveres de Adolescentes y Adultos Guatemaltecos (Liver and Bone Retinol Levels in Guatemalan Adolescents and Adults)
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Selected laboratory-based biomarkers for assessing vitamin A deficiency in at-risk individuals.The Cochrane database of systematic reviews · 2025Pooled it
- Systematic Review and Meta-Analysis of the Relative Dose-Response Tests to Assess Vitamin A Status.Advances in nutrition (Bethesda, Md.) · 2021Pooled it
- Modified relative dose response values differ between lactating women in the United States and Indonesia.Experimental biology and medicine (Maywood, N.J.) · 2020Trial
- Determination of Retinol, Cholecalciferol, α-Tocopherol and Phylloquinone Levels in Dogs with Dilated Cardiomyopathy: A Preliminary Study.Animals : an open access journal from MDPI · 2025Article
- Evaluating a novel method for vitamin A analysis in an observational study of the UAE's obese population.Scientific reports · 2024Observational
- Scientific opinion on the tolerable upper intake level for preformed vitamin A and β-carotene.EFSA journal. European Food Safety Authority · 2024Article
- Pet Wellness and Vitamin A: A Narrative Overview.Animals : an open access journal from MDPI · 2024Review
- Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.The Journal of pediatrics · 2024Article
- Understanding health disparities affecting people of West Central African descent in the United States: An evolutionary perspective.Evolutionary applications · 2023Review
- Inflammation Adjustments to Serum Retinol and Retinol-Binding Protein Improve Specificity but Reduce Sensitivity when Estimating Vitamin A Deficiency Compared with the Modified Relative Dose-Response Test in Ghanaian Children.Current developments in nutrition · 2021Article
- Findings in 3 clinical trials challenge the accuracy of the Institute of Medicine's estimated average requirements for vitamin A in children and women.The American journal of clinical nutrition · 2021Article
- Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Overlapping Vitamin A Interventions with Provitamin A Carotenoids and Preformed Vitamin A Cause Excessive Liver Retinol Stores in Male Mongolian Gerbils.The Journal of nutrition · 2020Article
- Dynamics of vitamin A uptake, storage, and utilization in vocal fold mucosa.Molecular metabolism · 2020Article
- Liver retinol estimated byExperimental biology and medicine (Maywood, N.J.) · 2019Article
- Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.Annals of the New York Academy of Sciences · 2019Article
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Authors and funding
9 authors.
Funding
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.
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