A Low Molar Ratio of Retinol Binding Protein to Transthyretin Indicates Vitamin A Deficiency during Inflammation: Studies in Rats and A Posteriori Analysis of Vitamin A–Supplemented Children with Measles

1. Changes in total retinol-binding protein (RBP), the holoprotein (holoRBP) and prealbumin (PA) concentrations have been monitored in plasma of thirty protein- and vitamin A-deficient preschool children from within a few hours up to 7 weeks after treatment with retinol and a good-quality protein diet.2. The children were classified into groups according to nutritional status as having either kwashiorkor, marasmus-kwashiorkor or marasmus, and given formula diets whose protein and energy contents increased stepwise from 1 g and 105 kJ/kg body-weight respectively up to 4 g and 733 kJ/kg body-weight after 4 weeks. Retinol was administered in the forms of retinyl palmitate either orally or intramuscularly.3. PA and total RBP were determined by electroimmunoassay procedures and the holoRBP by its fluorescence after separation from other plasma proteins.4. RBP in plasma of the vitamin A-deficient child is largely denatured and incapable of binding administered retinol, which must first be taken up by the liver before native holoRBP is released. An increased pool of native apoprotein accumulates in the liver during vitamin A deficiency which is released into plasma quickly after retinol uptake to form peak concentrations of total and holoRBP approximately 3 h after dosing intramuscularly and 6 h orally.5. The accumulated pool of RBP was highest in livers from the marasmus group and lowest in those from the kwashiorkor group, reflecting their relative capacities to synthesize plasma proteins.6. The mean plasma concentrations of total and holoRBP for the various groups were minimal 24–48 h after dosing with retinol and then improved almost linearly over the following week.7. Mean plasma PA concentrations of the various groups on admission were also in order of the severity of their malnutrition. There was little or no change in this protein concentration over the first 24 h after dosing with retinol, but thereafter the mean values rose almost linearly over 2 weeks. Albumin on the other hand changed little during the first week. The results show that PA is the more sensitive measurement of protein nutritional status.

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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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Biochemical Indicators of Vitamin A Deficiency: Serum Retinol and Serum Retinol Binding Protein

Journal of Nutrition ◽

10.1093/jn/132.9.2895s ◽

2002 ◽

Vol 132 (9) ◽

pp. 2895S-2901S ◽

Cited By ~ 157

Author(s):

Saskia de Pee ◽

Omar Dary

Keyword(s):

Vitamin A ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein ◽

Serum Retinol ◽

Biochemical Indicators

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Rapid diagnostic testing platform for iron and vitamin A deficiency

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1711464114 ◽

2017 ◽

Vol 114 (51) ◽

pp. 13513-13518 ◽

Cited By ~ 19

Author(s):

Zhengda Lu ◽

Dakota O’Dell ◽

Balaji Srinivasan ◽

Elizabeth Rey ◽

Ruisheng Wang ◽

...

Keyword(s):

Vitamin A ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Work Capacity ◽

Diagnostic Methods ◽

Retinol Binding Protein ◽

Micronutrient Deficiencies ◽

C Reactive Protein ◽

Laptop Computer ◽

Reactive Protein

Micronutrient deficiencies such as those of vitamin A and iron affect a third of the world’s population with consequences such as night blindness, higher child mortality, anemia, poor pregnancy outcomes, and reduced work capacity. Many efforts to prevent or treat these deficiencies are hampered by the lack of adequate, accessible, and affordable diagnostic methods that can enable better targeting of interventions. In this work, we demonstrate a rapid diagnostic test and mobile enabled platform for simultaneously quantifying iron (ferritin), vitamin A (retinol-binding protein), and inflammation (C-reactive protein) status. Our approach, enabled by combining multiple florescent markers and immunoassay approaches on a single test, allows us to provide accurate quantification in 15 min even though the physiological range of the markers of interest varies over five orders of magnitude. We report sensitivities of 88%, 100%, and 80% and specificities of 97%, 100%, and 97% for iron deficiency (ferritin <15 ng/mL or 32 pmol/L), vitamin A deficiency (retinol-binding protein <14.7 μg/mL or 0.70 μmol/L) and inflammation status (C-reactive protein >3.0 μg/mL or 120 nmol/L), respectively. This technology is suitable for point-of-care use in both resource-rich and resource-limited settings and can be read either by a standard laptop computer or through our previously developed NutriPhone technology. If implemented as either a population-level screening or clinical diagnostic tool, we believe this platform can transform nutritional status assessment and monitoring globally.

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A Case of Human Vitamin A Deficiency Caused by an Inherited Defect in Retinol-Binding Protein Without Clinical Symptoms Except Night Blindness

Nutrition Reviews ◽

10.1111/j.1753-4887.1999.tb06955.x ◽

2009 ◽

Vol 57 (8) ◽

pp. 258-260 ◽

Cited By ~ 2

Keyword(s):

Vitamin A ◽

Night Blindness ◽

Clinical Symptoms ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein

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Comparison of Serum Retinol and Retinol-Binding Protein with the Modified Relative Dose-Response Test in Estimating Vitamin A Deficiency Among Ghanaian Women and Children

Current Developments in Nutrition ◽

10.1093/cdn/nzaa053_118 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 913-913

Author(s):

Devika Suri ◽

James Wirth ◽

Nicolai Petry ◽

Fabian Rohner ◽

Seth Adu-Afarwuah ◽

...

Keyword(s):

Vitamin A ◽

Sensitivity And Specificity ◽

Dose Response ◽

Roc Curve ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein ◽

Serum Retinol ◽

Women And Children ◽

Modified Relative Dose Response

Abstract Objectives To evaluate the sensitivity and specificity of serum retinol (SR) and retinol-binding protein (RBP) in determining vitamin A deficiency (VAD) using the modified relative dose-response (MRDR) test as the reference. Methods Subjects included a subset of women and children participating in the Ghana Micronutrient Survey 2017. VAD was determined by the following cut-offs: SR or RBP < 0.7 mmol/L; MRDR ratio of 3,4-didehydroretinol to SR ³0.060. Sensitivity, specificity and the area-under-the-receiver operating characteristic (ROC) curve were calculated for unadjusted and inflammation-adjusted VAD cut-offs (based on C-reactive protein (CRP) and a1-acid-glycoprotein (AGP) for SR and RBP using the MRDR test as the reference. Results In 167 children and 178 women, inflammation (elevated CRP and/or elevated AGP) was present in 41% and 16%, respectively. Prevalence of VAD ranged, depending on the indicator used, from 7% (MRDR) to 40% (unadjusted SR) in children and 1% (RBP) to 4% (SR and MRDR) in women. Among children, sensitivity and specificity of unadjusted and adjusted SR and RBP were highly variable among the children. Highest sensitivity was achieved by unadjusted SR (80% of children with VAD correctly identified), while highest specificity was achieved by adjusted RBP (86% of children without VAD correctly identified). The best predictor of VAD in children compared with MRDR was adjusted SR, with a sensitivity of 78%, specificity of 73%, and an area under the ROC curve of 0.76. Among women, specificity was 97% for unadjusted and adjusted SR with an area under the ROC curve of 0.48; additional values could not be calculated due to lack of VAD cases. Conclusions SR and RBP were only moderately sensitive and specific for identifying VAD in children in Ghana. Low specificity—falsely identifying VAD—is especially problematic when populations are covered by one or more vitamin A interventions. Overlapping sources of preformed vitamin A can lead to hypervitaminosis, which may affect bone metabolism and growth. More accurate measures should be used in conjunction with SR and RBP for evaluating VAD especially in vulnerable populations. Funding Sources UNICEF, Canada's Ministry of Foreign Affairs, Trade and Development.

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