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.

Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Human Subjects ◽  
The Body ◽  
Pool Size ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

scholarly journals Cassava with enhanced β-carotene maintains adequate vitamin A status in Mongolian gerbils (Meriones unguiculatus) despite substantial cis-isomer content

2009 ◽  
Vol 102 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Julie A. Howe ◽  
Bussie Maziya-Dixon ◽  
Sherry A. Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Meriones Unguiculatus ◽  
Provitamin A ◽  
Carotenoid Content ◽  
Mongolian Gerbils ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Isomer Content ◽  
Β Carotene

Efforts to increase β-carotene in cassava have been successful, but the ability of high-β-carotene cassava to prevent vitamin A deficiency has not been determined. Two studies investigated the bioefficacy of provitamin A in cassava and compared the effects of carotenoid content and variety on vitamin A status in vitamin A-depleted Mongolian gerbils (Meriones unguiculatus). Gerbils were fed a vitamin A-free diet 4 weeks prior to treatment. In Expt 1, treatments (ten gerbils per group) included 45 % high-β-carotene cassava, β-carotene and vitamin A supplements (intake matched to high-β-carotene cassava group), and oil control. In Expt 2, gerbils were fed cassava feeds with 1·8 or 4·3 nmol provitamin A/g prepared with two varieties. Gerbils were killed after 4 weeks. For Expt 1, liver vitamin A was higher (P < 0·05) in the vitamin A (1·45 (sd 0·23) μmol/liver), lower in the control (0·43 (sd 0·10) μmol/liver), but did not differ from the β-carotene group (0·77 (sd 0·12) μmol/liver) when compared with the high-β-carotene cassava group (0·69 (sd 0·20) μmol/liver). The bioconversion factor was 3·7 μg β-carotene to 1 μg retinol (2 mol:1 mol), despite 48 % cis-β-carotene [(Z)-β-carotene] composition in cassava. In Expt 2, cassava feed with 4·3 nmol provitamin A/g maintained vitamin A status. No effect of cassava variety was observed. Serum retinol concentrations did not differ. β-Carotene was detected in livers of gerbils receiving cassava and supplements, but the cis-to-trans ratio in liver differed from intake. Biofortified cassava adequately maintained vitamin A status and was as efficacious as β-carotene supplementation in the gerbil model.

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

2000 ◽  
Vol 83 (5) ◽  
pp. 513-520 ◽  
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.

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 Maize meal fortification is associated with improved vitamin A and iron status in adolescents and reduced childhood anaemia in a food aid-dependent refugee population

2008 ◽  
Vol 11 (7) ◽  
pp. 720-728 ◽  
Author(s):  
Andrew Seal ◽  
Emmanuel Kafwembe ◽  
Ismail AR Kassim ◽  
Mei Hong ◽  
Annie Wesley ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Iron Status ◽  
Household Survey ◽  
Refugee Camp ◽  
Food Aid ◽  
Serum Retinol ◽  
Post Intervention ◽  
Vitamin A Status ◽  
Maize Meal

AbstractObjectiveTo assess changes in the Fe and vitamin A status of the population of Nangweshi refugee camp associated with the introduction of maize meal fortification.DesignPre- and post-intervention study using a longitudinal cohort.SettingNangweshi refugee camp, Zambia.SubjectsTwo hundred and twelve adolescents (10–19 years), 157 children (6–59 months) and 118 women (20–49 years) were selected at random by household survey in July 2003 and followed up after 12 months.ResultsMaize grain was milled and fortified in two custom-designed mills installed at a central location in the camp and a daily ration of 400 g per person was distributed twice monthly to households as part of the routine food aid ration. During the intervention period mean Hb increased in children (0·87 g/dl;P< 0·001) and adolescents (0·24 g/dl;P= 0·043) but did not increase in women. Anaemia decreased in children by 23·4 % (P< 0·001) but there was no significant change in adolescents or women. Serum transferrin receptor (log10-transformed) decreased by −0·082 μg/ml (P= 0·036) indicating an improvement in the Fe status of adolescents but there was no significant decrease in the prevalence of deficiency (−8·5 %;P= 0·079). In adolescents, serum retinol increased by 0·16 μmol/l (P< 0·001) and vitamin A deficiency decreased by 26·1 % (P< 0·001).ConclusionsThe introduction of fortified maize meal led to a decrease in anaemia in children and a decrease in vitamin A deficiency in adolescents. Centralised, camp-level milling and fortification of maize meal is a feasible and pertinent intervention in food aid operations.

scholarly journals Vitamin A deficiency in Bangladesh: a review and recommendations for improvement

1999 ◽  
Vol 2 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Faruk Ahmed
Keyword(s):  
Vitamin A ◽  
Nutrition Education ◽  
Night Blindness ◽  
Vitamin A Deficiency ◽  
School Age Children ◽  
Serum Retinol ◽  
Population Groups ◽  
Vitamin A Status ◽  
Subclinical Vitamin

AbstractObjective:This article provides a comprehensive review of the change in vitamin A status and the extent of vitamin A deficiency among different population groups in Bangladesh up to the present time. The result of experience with different strategies and interventions designed to improve vitamin A status are then reviewed, leading to a discussion of key options for action, as well as important areas for research and evaluation.Design and setting:All the available data have been examined in detail, including data from nationally representative samples and nationwide surveys, as well as small studies in different population groups. Reports on the effectiveness of different intervention programmes have been used.Results:Over the past three decades a number of studies, which include national nutrition surveys, have been carried out to investigate the prevalence of vitamin A deficiency among different population groups in Bangladesh, and they have demonstrated a significant public health problem. Studies have shown that the prevalence of severe deficiency, based on the prevalence of night blindness in preschool children, decreased from 3.6% in 1982–83 to 1.78% in 1989 and 0.6% in 1996. However, there is still a high prevalence of subclinical vitamin A deficiency, based on the biochemical assessment of serum retinol levels in preschool children, estimated mainly from hospital-based groups. Night blindness and Bitot's spot are also found to exist among school-age children and adolescents. Recent reports indicate that night blindness among rural mothers is as high as 1.4%. Only a limited number of studies, with small sample sizes, are available where serum retinol has been reported for school-age children, adolescents and pregnant women. Nevertheless, these studies confirm the presence of low levels of serum retinol and hence, the existence of subclinical vitamin A deficiency. Furthermore, the dietary intake of vitamin A in each population group has been found to be less than the Recommended Daily Allowance (RDA), indicating a significant risk of deficient intakes of vitamin A.To address the problem of vitamin A deficiency, the government of Bangladesh started the Nutritional Blindness Programme in 1973. The main activities of the programme include vitamin A capsule (VAC) supplementation to children of 6 months to 6 years old, nutrition education to increase the production and consumption of vitamin A rich foods, and training of primary health-care workers on the clinical diagnosis and treatment of vitamin A deficiency, VAC distribution and nutrition education. Since 1988, as a long-term strategy, Helen Keller International has been implementing community home gardening promotion projects. To date, the possibility that foods may be fortified with vitamin A, has not been explored as a possible approach in Bangladesh.Conclusion:Although short- to long-term prevention and control programmes are to some extent in place, to improve the situation of vitamin A deficiency, Bangladesh needs a more appropriate mix of interventions for the entire population. More operational research and evaluation are needed if a fully effective programme to alleviate the problem of vitamin A deficiency is to be developed. Finally, to achieve the goal of virtual elimination of vitamin A deficiency will require an integrated approach which brings together appropriate actions at every level, within and across the many sectors of society.

scholarly journals International Experiences in Assessing Vitamin A Status and Applying the Vitamin A-Labeled Isotope Dilution Method

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 40-51 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Justin Chileshe ◽  
Nicole Idohou-Dossou ◽  
Tetra Fajarwati ◽  
Gabriel Medoua Nama ◽  
...  
Keyword(s):  
Vitamin A ◽  
Dose Response ◽  
Isotope Dilution ◽  
Qualitative Assessment ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Serum Retinol ◽  
Retinyl Acetate ◽  
Positive Effects ◽  
Vitamin A Status

Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the “gold standard” for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a population’s dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.

Usefulness of Vitamin A Isotope Methods for Status Assessment: From Deficiency through Excess

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 16-24 ◽  
Author(s):  
Sherry A. Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Isotope Dilution ◽  
Clinical Signs ◽  
Provitamin A ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Indirect Indicator ◽  
Staple Foods ◽  
Retinol Concentration

A variety of methods exist to assess vitamin A status of groups and populations. Vitamin A status is usually defined by the liver retinol concentration. Most indicators of status do not measure or estimate liver stores of retinol. Clinical signs only have utility when liver reserves are almost exhausted, and serum retinol concentrations have utility in the zone of overt deficiency. Dose response tests offer more coverage, but cannot distinguish among liver vitamin A stores in the adequate through toxic range. Different countries continue, or are beginning, to add preformed vitamin A to a variety of staple foods through fortification, and vitamin A supplements are still being distributed in many countries, especially to preschool children. Further, provitamin A biofortified crops are currently being released in several countries. Assessing population vitamin A status in response to these interventions needs to move beyond serum retinol concentrations. Indicators that work in the excessive to toxic range of liver reserves are needed. To date, the only indirect indicator that has been validated in this range of liver reserves in animals and humans is the retinol isotope dilution test using deuterium or 13C, which spans the entire liver reserve continuum from deficiency through excess.

scholarly journals A Comparison of Vitamin A Status Among Elderly Chinese Population Between 2002 and 2012: A Cross-Sectional Analysis of the China National Nutrition and Health Survey

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1851-1851
Author(s):  
Rui Wang ◽  
Chen Jing ◽  
Yichun Hu ◽  
Xiaoguang Yang ◽  
Lichen Yang
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Health Survey ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
The Elderly ◽  
Serum Retinol ◽  
Nutrition And Health ◽  
Chinese Elderly ◽  
Vitamin A Status

Abstract Objectives Vitamin A deficiency is recognized as a major public health nutrition issue in developing countries including China. It is one of the most common micronutrient deficiencies, yet vitamin A status of the elderly in China paucity of data since 2002. We sought to evaluate Chinese elderly aged 60 years and above in vitamin A status, and to compare vitamin A insufficiency between year 2002 and 2012. Methods We compared serum retinol concentrations from the China National Nutrition and Health Survey 2002 (CNNHS 2002), with CNNHS data collected during 2010 through 2012 (CNNHS 2010–2012). Complete data were available for 4933 elderly participants in CNNHS 2002 and 5613 elderly participants in CNNHS 2010–2012. Results The mean serum retinol concentration was 1.69 (95% confidence interval (CI): 1.68–1.71) μmol/L during CNNHS 2002 and increase to 1.98 (1.96–2.00) μmol/L during CNNHS 2010–2012. Compared with 2002, the vitamin A levels in the elderly across all region, gender and age groups showed an upward trend, with the difference being statistically significant (all P &lt; 0.05). In 2012, the incidence of VAD in the elderly participants was higher than in 2002 (3.39vs1.46) (P &lt; 0.001). However, the incidence of marginal VAD was lower than in 2002 (7.38vs8.62) (P = 0.019). VAD in those being large cities, small and medium-sized cities, rural area, male and female, aged 60–69 or 70–79 were higher than in 2002 (all P &lt; 0.05), poor rural areas was significantly lower than in 2002 (P &lt; 0.001). The prevalence of marginal VAD among the urban elderly in 2012 was higher than in 2002 (P &lt; 0.05), whereas the prevalence was lower than that in 2002 among the rural elderly (P &lt; 0.001). The prevalence of marginal VAD in the male elderly (P &lt; 0.001) and in the 60–69 age group (P = 0.014) were lower than in 2002. Conclusions Our findings showed that vitamin A status among elderly was greatly improved by 10 years, but VAD remains a public health problem in the Chinese elderly population. Therefore, reducing the incidence of VAD is crucial to the health of the elderly in China. In particular, attention needs to be paid to the nutrition and health status of urban and ≥80 year elderly. Funding Sources This research was supported by the Special Fund for Health-scientific Research in the Public Interest (No. 20,120,212) from the National Health and Family Planning Commission of the People's Republic of China.

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