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.

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 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.

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.

scholarly journals Vitamin A status of neonatal foals assessed by serum retinol concentration and a relative dose response test

1996 ◽  
Vol 12 (3) ◽  
pp. 181-183 ◽  
Author(s):  
K M Greiwe-Crandell ◽  
D S Kronfeld ◽  
L S Gay ◽  
D Sklan ◽  
P A Harris
Keyword(s):  
Vitamin A ◽  
Dose Response ◽  
Serum Retinol ◽  
Response Test ◽  
Vitamin A Status ◽  
Serum Retinol Concentration ◽  
Retinol Concentration

scholarly journals Proxy Markers of Serum Retinol Concentration, Used Alone and in Combination, to Assess Population Vitamin A Status in Kenyan Children

2015 ◽  
Vol 5 (5) ◽  
pp. 615-616
Author(s):  
Elise Talsma ◽  
Hans Verhoef ◽  
Inge Brouwer ◽  
Anne Mburu-deWagt ◽  
Paul Hulshof ◽  
...  
Keyword(s):  
Vitamin A ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Serum Retinol Concentration ◽  
Retinol Concentration

scholarly journals Stable isotope dilution techniques for assessing vitamin A status and bioefficacy of provitamin A carotenoids in humans

2005 ◽  
Vol 8 (6) ◽  
pp. 596-607 ◽  
Author(s):  
Harold C Furr ◽  
Michael H Green ◽  
Marjorie Haskell ◽  
Najat Mokhtar ◽  
Penelope Nestel ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Vitamin A ◽  
Isotope Dilution ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
Provitamin A ◽  
Global Public Health ◽  
Nutritional Values ◽  
Stable Isotope Dilution ◽  
Vitamin A Status

AbstractVitamin A deficiency is a major global public health problem. Among the variety of techniques that are available for assessing human vitamin A status, evaluating the provitamin A nutritional values of foodstuffs and estimating human vitamin A requirements, isotope dilution provides the most accurate estimates. Although the relative expense of isotope dilution restricts its applications, it has an important function as the standard of reference for other techniques. Mathematical modelling plays an indispensable role in the interpretation of isotope dilution data. This review summarises recent applications of stable isotope methodology to determine human vitamin A status, estimate human vitamin A requirements, and calculate the bioconversion and bioefficacy of food carotenoids.

scholarly journals The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya

2007 ◽  
Vol 98 (2) ◽  
pp. 422-430 ◽  
Author(s):  
R. A. Ayah ◽  
D. L. Mwaniki ◽  
P. Magnussen ◽  
A. E. Tedstone ◽  
T. Marshall ◽  
...  
Keyword(s):  
Vitamin A ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Maternal Serum ◽  
High Dose ◽  
Serum Retinol ◽  
Double Blind ◽  
Vitamin A Supplementation ◽  
Factors Affecting ◽  
Vitamin A Status

Postpartum vitamin A supplementation of mothers and infants is recommended, but the efficacy has been questioned. In this double-blind, placebo-controlled trial, Kenyan mother–infant pairs were randomised to maternal vitamin A (400 000 IU) or placebo < 24 h postpartum, and infant vitamin A (100 000 IU) or placebo at 14 weeks. Milk retinol was determined at weeks 4, 14 and 26, and maternal and infant serum retinol at weeks 14 and 26. Infant retinol stores were assessed at week 26, using a modified relative dose response (MRDR) test. Among 564 women, serum retinol at 36 weeks gestation was 0·81 (sd 0·21) μmol/l, and 33·3 % were < 0·7 μmol/l. Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group: (0·67 v. 0·60 μmol/l; 0·52 v. 0·44 μmol/l; 0·50 v. 0·44 μmol/l at 4, 14 and 26 weeks, respectively). When expressed per gram fat, milk retinol was higher in the vitamin A group only at 4 weeks. Infant serum retinol was not different between groups. However, although most infants had deficient vitamin A stores (MRDR>0·06 %) at 26 weeks, vitamin A to infants, but not mothers, resulted in a lower proportion of infants with deficient vitamin A stores (69 v. 78 %). High-dose postpartum vitamin A supplementation failed to increase serum retinol and infant stores, despite modest effects on milk retinol. Infant supplementation, however, increased stores. There is a need for a better understanding of factors affecting absorption and metabolism of vitamin A.

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