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

Abstract

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.

Reducing dietary intake of added sugars could affect the nutritional adequacy of vitamin A in adolescents: the Costa Rica case

“…It has been pointed out that the effect of these factors on retinol levels does not necessarily reflect a good vit-A status, but merely that the body's retinol stores have been redistributed from the liver into circulation [ 37 ]. Meanwhile, an inadequate intake of vit-A for four months can lead to the depletion of retinol stores in the liver [ 38 ] and generate a deficiency in serum levels, as evidenced in adolescents in Brazil [ 39 ], China [ 40 ], the Philippines [ 41 ], Iran [ 42 ], and India [ 43 ]. Although it has been suggested that vit-A deficiency is manifested primarily as a subclinical disease in the Americas [ 44 ], it could generate deleterious effects on the health of adolescents through different pathways, such as those mentioned in the introduction [ 33 , 34 ].…”

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation

“…In addition, our results show that model-predicted TBS for the young people with SCD-HbSS (428 μmol) was not significantly different from TBS predicted by RID at 3 d postdosing (389 μmol; Table 2 ); agreement between TBS predicted by population-based modeling and RID is not surprising [ 18 ], but it increases confidence in both approaches for estimating stores. Further, although mean plasma retinol concentration was lower in the subjects with SCD-HbSS than in healthy peers ( Table 1 ), mean TBS predicted by RID at 3 d postdosing was not significantly different in the 2 groups (389 and 406 μmol, respectively; Table 2 ), and mean estimated liver vitamin A concentrations were adequate in both groups (0.302 μmol/g and 0.277 μmol/g, respectively) compared with the currently used cutoff for adequate (>0.1 μmol/g) [ 46 ] and assuming that 80% of TBS is in the liver [ 40 ]. Also of interest, among the 11 subjects with SCD-HbSS for whom data were available on both day 3 and day 28 postdosing, RID predictions of TBS were not significantly different.…”

Scientific opinion on the tolerable upper intake level for preformed vitamin A and β‐carotene

“…Liver concentrations of retinol of 0.07 μmol/g (as free retinol and retinyl esters) have been proposed as a criterium to define vitamin A adequacy and were used as a reference point to derive vitamin A requirements by different bodies (EFSA NDA Panel, 2015 ). More recently, the cut‐off for vitamin A deficiency has been revised to 0.1 μmol/g liver based on the fact that long‐term storage and biliary excretion do not occur below this liver retinol concentration (Tanumihardjo, 2021 ; Tanumihardjo et al., 2016 ).…”