Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users

Vitamins are essential compounds obtained through diet that are necessary for normal development and function in an organism. One of the most important vitamins for human physiology is vitamin A, a group of retinoid compounds and carotenoids, which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in the vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids such as β-carotene from plants or preformed vitamin A such as retinyl esters from animal sources are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carotenoid cleavage oxygenases (CCOs), such as Beta-carotene 15,15’-monooxygenase (BCO1), to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein 4 receptor 2 (RBPR2) in systemic tissues (e.g., in the retina and the liver, respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature regarding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

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Use of the retinol-binding protein : transthyretin ratio for assessment of vitamin A status during the acute-phase response

British Journal Of Nutrition ◽

10.1017/s0007114500000659 ◽

2000 ◽

Vol 83 (5) ◽

pp. 513-520 ◽

Cited By ~ 21

Author(s):

Suzanne M. Filteau ◽

Juana F. Willumsen ◽

Keith Sullivan ◽

Karin Simmank ◽

Mary Gamble

Keyword(s):

Vitamin A ◽

Sensitivity And Specificity ◽

Assessment Tool ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein ◽

Serum Retinol ◽

Vitamin A Status ◽

Plasma Retinol

The ratio plasma retinol-binding protein (RBP) : transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma α1-acid glycoprotein (AGP) level. The RBP : TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP : TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP : TTR ratio against established measures of vitamin A status using a cut-off value of 0·3 for RBP : TTR and standard cut-off values for MRDR (0·06) and plasma retinol (0·7 μmol/l). Compared with MRDR, RBP : TTR had sensitivities of 76 % and 43 % and specificities of 22 % and 81 % to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88 % and 44 % and specificities were 55 % and 64 % in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62 % and 100 % against MRDR and plasma retinol respectively) and specificity (100 % and 60 % against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP : TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.

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Vitamin A and retinol-binding protein metabolism during fetal development in the rat.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1977.233.4.e263 ◽

1977 ◽

Vol 233 (4) ◽

pp. E263 ◽

Cited By ~ 5

Author(s):

Y I Takahashi ◽

J E Smith ◽

D S Goodman

Keyword(s):

Vitamin A ◽

Fetal Development ◽

Early Phase ◽

Fetal Liver ◽

Binding Protein ◽

Retinol Binding Protein ◽

Second Phase ◽

Organ Differentiation ◽

Third Phase ◽

Plasma Retinol

Studies were conducted on the metabolism and placental transport of vitamin A and plasma retinol-binding protein (RBP) during fetal development in the rat. Vitamin A accumulated in the conceptus in three phases: an early phase (days 7-9 of gestation) characterized by a high vitamin A concentration; a second phase (days 11-14) where vitamin A and RBP accumulated in parallel; and a third phase of continued vitamin A and RBP accumulation (days 16-20) in which vitamin A was stored in the fetal liver. The early phase of vitamin A accumulation may reflect a mechanism that exists to prepare the conceptus to meet the presumably higher vitamin A requirements of the critical period (days 10-14) of organ differentiation. Fetuses and placentas from retinol-deficient dams showed low levels of RBP through days 16-18 of gestation. A retinol-repletion study suggested, moreover, that the maternal retinol-RBP complex crossed the placenta. The various studies all suggest that vitamin A is transported from dam to fetus, from and after day 11, mainly by transplacental transport of maternal retinol-RBP. Finally, evidence was obtained indicating that the fetal liver begins to synthesize RBP around the 16th day of gestation and that by the 20th day, the fetal liver has a considerable capacity for RBP synthesis.

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Retinol homeostasis in lambs given low and high intakes of vitamin A

British Journal Of Nutrition ◽

10.1079/bjn19830093 ◽

1983 ◽

Vol 50 (2) ◽

pp. 235-248 ◽

Cited By ~ 17

Author(s):

Susan Donoghue ◽

David S. Kronfeld ◽

David Sklan

Keyword(s):

Vitamin A ◽

Plasma Clearance ◽

Basal Diet ◽

Retinol Binding Protein ◽

Faecal Excretion ◽

Several Variables ◽

Supplemental Vitamin ◽

Retinyl Esters ◽

Plasma Retinol ◽

Retinol Concentration

1. Four groups of lambs were fed on a low-carotene basal diet. One group received no supplemental vitamin A (mildly deficient). Remaining groups were supplemented daily with vitamin A acetate equivalent to 100 (control) 9000 (mildly intoxicated) and 18000 (severely intoxicated) μg retinol/kg body-weight. After 16 weeks lambs received a bolus of[15−3H]retinol intravenously; blood, urine and faeces were sampled for 48 h.2. Plasma retinol was complexed to a protein of 20000 molecular weight (MW), which in turn was complexed to a protein of 65000 MW; these proteins correspond respectively to retinol-binding protein and prealbumin. Plasma retinol concentration reached plateau values in intoxicated lambs, but plasma retinyl ester concentrations increased rapidly when liver contents of both retinol and retinyl esters exceeded approximately 10 and 100 mg respectively and kidney contents of both retinol and retinyl esters exceeded 30 μg. Labelled compounds, more polar than retinol, were found in plasma; their concentration increased tenfold in intoxicated lambs within 48 h.3. Plasma retinol transport rates were 0·1, 10·5 and 11·8 times control values, and clearance rates were 0·3, 14·1 and 14·3 times control values in mildly-deficient, and mildly- or severely-intoxicated lambs respectively. Turnover of retinol increased rapidly when liver contents of retinol and retinyl esters exceeded approximately 10 and 100 mg respectively and kidney contents of both retinol and retinyl esters exceeded approximately 30 μg. Plasma clearance of retinyl esters was unchanged with intake. Faecal excretion of tracer increased linearly with plasma retinol clearance.4. Our findings identify, several variables that appear to be involved in retinol homeostasis, including plasma retinol clearance and excretion.

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Vitamin A Transport and the Transmembrane Pore in the Cell-Surface Receptor for Plasma Retinol Binding Protein

PLoS ONE ◽

10.1371/journal.pone.0073838 ◽

2013 ◽

Vol 8 (11) ◽

pp. e73838 ◽

Cited By ~ 14

Author(s):

Ming Zhong ◽

Riki Kawaguchi ◽

Mariam Ter-Stepanian ◽

Miki Kassai ◽

Hui Sun

Keyword(s):

Vitamin A ◽

Cell Surface ◽

Binding Protein ◽

Retinol Binding Protein ◽

Cell Surface Receptor ◽

Surface Receptor ◽

Plasma Retinol ◽

Vitamin A Transport

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Assessment of Vitamin A Status of Preschool Children in Indonesia Using Plasma Retinol-binding Protein

Journal of Tropical Pediatrics ◽

10.1093/tropej/48.2.84 ◽

2002 ◽

Vol 48 (2) ◽

pp. 84-87 ◽

Cited By ~ 16

Author(s):

R. D. Semba

Keyword(s):

Preschool Children ◽

Vitamin A ◽

Binding Protein ◽

Retinol Binding Protein ◽

Vitamin A Status ◽

Plasma Retinol

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Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12–23 months and their non-pregnant caregivers

Experimental Biology and Medicine ◽

10.1177/1535370220985473 ◽

2021 ◽

pp. 153537022098547

Author(s):

Ralph D Whitehead ◽

Nicole D Ford ◽

Carine Mapango ◽

Laird J Ruth ◽

Ming Zhang ◽

...

Keyword(s):

Vitamin A ◽

Dose Response ◽

High Performance ◽

Binding Protein ◽

Retinol Binding Protein ◽

Enzyme Linked Immunosorbent Assay ◽

Vitamin A Status ◽

Plasma Retinol ◽

Commercial Enzyme Immunoassay ◽

Modified Relative Dose Response

Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12–23 months and 28 non-pregnant mothers aged 15–49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were −0.19 µmol/L (95% limits of agreement [LOA] 0.62, −0.99) for children and −0.01 µmol/L (95% LOA −1.11, −1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA −0.37, 1.03) for children, and 0.29 µmol/L (95% LOA −0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA −0.23, 0.49) for children and 0.18 µmol/L (95% LOA −0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.

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