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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:290S-293S, January 2004

Supplement: Proceedings of Symposium to Honor the Memory of James Allen Olson

Assessing Vitamin A Status: Past, Present and Future1,2

Sherry A. Tanumihardjo3

Department of Nutritional Sciences, UW-Madison, Madison, WI 53706-1571

3To whom correspondence should be addressed. E-mail: sherry{at}nutrisci.wisc.edu.


   ABSTRACT
TOP
 ABSTRACT
SUMMARY
 LITERATURE CITED
 
Xerophthalmia classification was traditionally used to identify populations with vitamin A deficiency. Currently, night blindness and dark adaptometry have been proposed as population assessment methods. While eye signs and function tests are still used in areas where vitamin A deficiency is severe, a subclinical vitamin A deficiency is more prevalent. Serum and breast milk retinol concentrations are used to identify vitamin A deficiency risk. However, in healthy individuals, serum retinol concentrations are homeostatically controlled and do not begin to decline until liver reserves of vitamin A are dangerously low. Moreover, serum retinol and retinol binding protein (RBP) concentrations fall during times of infection. The RBP:transthyretin ratio may help to determine if serum retinol concentrations are depressed by infection. Other methods better reflect liver reserves of vitamin A, the "gold" standard. The relative dose response and modified relative dose response tests involve giving a small dose of retinyl or dehydroretinyl ester, respectively, and determining a response in the serum at about 5 h. A new response test where retinoyl ß-glucuronide is administered and the degree of hydrolysis to retinoic acid is measured has been investigated. Unlike isotope dilution tests, the dose response tests lack utility in defining the total body reserve of vitamin A. The deuterated retinol isotope dilution test has been used in several different groups. Recently, a new isotope assay was developed using 13C-retinyl acetate and gas chromatography-combustion-isotope ratio mass spectrometry for analysis. Thus, having many choices of vitamin A assessment methods, laboratory sophistication and resources available will usually dictate which methods are chosen.

KEY WORDS: • vitamin A • retinol • vitamin A indicators

Past indicators of vitamin A status

Traditionally, clinical signs and symptoms of xerophthalmia were used to identify populations with vitamin A deficiency (Table 1) and recommended by the International Vitamin A Consultative Group (IVACG)3 in 1976 (1). Liver concentrations of vitamin A have been determined in justifiable instances, but will never be acceptable in field surveys. Livers have been analyzed using biopsy or samples taken at the time of surgery or during autopsy (2–4).


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  		TABLE 1 The traditional xerophthalmia classification system adopted by the International vitamin A consultative group in 1976

 
Present indicators of vitamin A status

The biological, functional and histological indicators of vitamin A status include xerophthalmia, night blindness, conjunctival impression cytology and dark adaptometry (Table 2). Currently, night blindness during pregnancy and dark adaptometry testing have been proposed as population assessment methods by IVACG in 2001 (5). While eye signs and function tests are still used in areas where vitamin A depletion is severe (6–8), a subclinical vitamin A deficiency is more prevalent.


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  		TABLE 2 Current and future methodologies to assess vitamin A status

 
Conjunctival impression cytology (CIC) has been used in field surveys (9) but does seem to be negatively impacted in drier African countries. The equipment necessary for conducting CIC is not expensive. Briefly, a small circle of filter paper is quickly touched to the eye surface using a manual pumping device to hold the paper in position. The filter paper is then placed into fixative and subsequently stained to differentiate the goblet cells from the endothelial cells. The goblet cells are counted under a microscope and the eye classified as normal or abnormal based on the number of goblet cells. In our experience with Indonesian children, many had only one eye abnormal, which correlated to other more sensitive indicators of vitamin A status being abnormal (9).

Biochemical assessment methods available include serum retinol and breast milk retinol concentrations, relative dose response and modified relative dose response tests and the deuterated retinol isotope dilution test (Table 2). Serum retinol concentrations have been used extensively to identify populations at risk of vitamin A deficiency (9). The major drawback of serum retinol is that blood samples are required. Moreover, in healthy individuals, serum retinol concentrations are homeostatically controlled and do not begin to decline until liver reserves of vitamin A are dangerously low. Furthermore, retinol-binding protein (RBP) is a negative acute phase protein; therefore, serum retinol and RBP concentrations will fall during times of infection. Because of the high degree of infection in children at risk of vitamin A deficiency and the homeostatic mechanism, serum retinol does not always respond to vitamin A intervention strategies (10). The status of other nutrients, particularly iron deficiency, may also negatively affect serum retinol concentrations (11). Iron deficiency also may decrease the mobilization of vitamin A from liver storage (12).

Breast milk retinol concentrations have also been proposed as a population measure of vitamin A status (13,14). Breast milk collection is less invasive and usually easier than blood drawing. Breast milk samples do not have to be further processed at the field station, thus shortening sample preparation. While a unique indicator to lactating women, the status of the mother can usually be predictive of the nursing infant (14). Therefore, if the lactating women of a community have a marginal vitamin A status, chances are high that the children of that community are also at risk of vitamin A depletion (9,14,15). We have simplified the breast milk assay by using 3,4-didehydroretinyl acetate as an internal standard. Even though the extraction efficiency (or degree of saponification) obtained was 23 to 89% by varying the saponification times, the CV of the method was only 4.1 and 1.8% for 250 and 500 µL samples of breast milk, respectively (16).

During the past two decades, other methods to determine vitamin A status have been developed that better reflect liver reserves of vitamin A, the "gold" standard. The relative dose response (RDR) test, which involves giving a small dose of retinyl ester and taking a blood sample at time 0 and 5 h after the dose and calculating a percent increase, has been used in several studies (9). The RDR test is based on the principle that during vitamin A depletion apo-RBP accumulates in the liver. By giving a challenge dose of retinyl ester, the retinol will bind to the excess RBP and be shipped out into the serum as the holo-RBP-retinol complex. A modification of this method was made by using 3,4-didehydroretinyl acetate as the challenge dose and subsequently termed the modified relative dose response (MRDR) test (17). Because circulating concentrations of 3,4-didehydoretinol are very low in human plasma, a single blood sample is all that is required 4 to 6 h after dosing and a ratio of 3,4-didehydoretinol to retinol is calculated. We continue to support the use of the MRDR test by synthesizing 3,4-didehydroretinyl acetate and giving interested researchers technical advice on its use in the field.

In healthy American children and adults from middle to upper income families, the MRDR values (the dehydroretinol to retinol ratio at 5 h postdosing) were always found to be <0.04 (18,19). However, when the test was applied to a group of children (n = 77) from lower socio-economic standing, a broader range of MRDR values, i.e., 0.005 to 0.055, was obtained suggesting that the vitamin A status of this group was not ideal (20). Specifically, 32% of these children tested above 0.030. Moreover, when the MRDR test was applied to pregnant women (n = 57) from a similar background, MRDR values were indicative of very poor liver reserves of vitamin A with 26% testing above 0.030 and 9% testing above 0.060 (21). In fact the women from this study responded very similarly to a group of pregnant Indonesian women from lower to middle economic status (22). The MRDR test has been used extensively throughout the world to diagnose a subclinical vitamin A status. Studies in Indonesia have shown significant differences between groups of children living literally across the street from each other (9). The major dietary difference observed between these two groups of children was that one of the groups was including eggs frequently in the diet, a good source of preformed vitamin A. The MRDR test is also more responsive to intervention with vitamin A supplementation than serum retinol concentrations (10,15,23) when the vitamin A intervention is enough to change overall vitamin A status (24). The poor vitamin A status of pregnant and lactating women in developing countries has been shown by a large percentage of abnormal MRDR values (13–15,22,25).

The dose response tests, however, lack utility in defining the total body reserve of vitamin A. The deuterated retinol isotope dilution (DRD) test has been used successfully in several different population groups (2,3). With improvements in the sensitivity of mass spectrometers, the method has gained some momentum (26). The longer DRD test described by Furr et al. (2) requires the equilibration of an oral dose of deuterated vitamin A with the body pool of vitamin A, a process that takes ~20 d (26,27). This procedure has been validated with liver biopsy samples in adult American (2) and Bangladeshi (3) surgical patients with adequate to low vitamin A status. The calculated values for vitamin A body stores using the DRD test correlated well with values obtained by direct measurement of vitamin A in the liver biopsies, with correlation coefficients of 0.88 (2) and 0.75 (3). A shortened time interval of three days has been suggested with the DRD test (26,28). The 3-d DRD test does not require equilibration of the vitamin A isotope with the body’s vitamin A storage pool. In studies in older adults (26), the ratio of deuterated to nondeuterated retinol in serum at 3 d after an oral dose of deuterated retinyl acetate correlates well with the calculated values for total body stores of vitamin A when the 20-d DRD test and the mathematical formula of Furr et al. (2) are used (r = -0.75). Recent studies by Ribaya-Mercado et al. have shown that the relationship is nonlinear and can be described by the equation: vitamin A body stores = 0.00468 x 10(37) (dose in mmol) (D:H)-retinol at 3 d (29). The ability of the 3-d DRD test to predict total body vitamin A stores without the requirement for isotope dose equilibration with the body’s vitamin A pool is consistent with data obtained in rats (30). Furthermore, in food-intervention studies in Filipino school-aged children (28), it was found that the 3-d DRD test can detect changes in body pool size of vitamin A and that the bioconversion of plant carotenoids to vitamin A varies inversely with total-body stores of vitamin A as measured by the 3-d DRD test but is influenced little or not at all by serum retinol concentrations.

Future indicators of vitamin A status

Methods that are in development include dried blood spot retinol determination (31), retinol binding protein concentrations and retinol binding protein to transthyretin ratios (RBP:TTR) (32), retinoyl ß-glucuronide (RAG) hydrolysis test (33,34) and the 13C-retinol isotope dilution assay using gas chromatography-combustion-isotope ratio mass spectrometry (GCCIRMS) detection (35,36) (Table 2). The new response test in which retinoyl ß-glucuronide is administered and the degree of hydrolysis to retinoic acid is measured has been applied to rats and to some humans. In vitamin A sufficient rats very little hydrolysis to retinoic acid occurs. On the other hand, in deficient animals hydrolysis to retinoic acid occurs and more hydrolysis is associated with the length of time on a vitamin A depletion regimen (33,34).

Recently, 13C4-retinyl acetate was synthesized (35) using modifications of the procedure used for the synthesis of the deuterated retinyl acetate analogs (37). The compound was purified and characterized using GCMS, HPLC and UV-VIS spectroscopy. Thereafter, a physiological dose was fed to rats of varying vitamin A status (36). After extraction from the serum and purification by HPLC, the analysis of the 13C to 12C ratio was performed by GCCIRMS. The sensitivity of the assay was so great that we have subsequently synthesized retinyl acetate with only 2 of the carbons labeled. This new isotope method distinguished the three dietary groups of rats with amazing accuracy. The change in atom % excess [(Fpostdose - Fbaseline) x 100] with time in the three dietary groups of rats studied was distinctly different between groups (P < 0.0001). Regardless of the day, the difference between the groups was always significant (P < 0.0001). The physiological dose reached equilibrium between 4 and 10 d in rats.

The relationship across the dietary groups was not different from unity with a slope of 1.0 and correlation coefficient of 0.98 (P < 0.0001) for the calculated versus measured assessment. On the other hand, serum retinol concentrations did not show a difference in the dietary groups even though there was a 2- to 10-fold difference in the total body reserves of the rats. This new isotope dilution method holds considerable promise in accurately determining total body reserves of vitamin A in humans. The method has been applied to a female volunteer (38) by giving a single oral dose of 17.5 µmol of 13C4-retinyl acetate. After a fasting baseline blood, samples were obtained at 2, 4, 8, 16, 24, 32, 64, 128 and 256 d. Based on assumptions used in the deuterated retinol assay, the calculated liver reserve at 24 d was 0.3 µmol/g, which is a reasonable amount for a woman not taking supplements. The 13C/12C began to plateau in as little as 8 d. We hope to refine this test so that small doses of isotope (3.5–7 µmol) can be administered and as little as 0.5 mL of serum will be required for analysis.


   SUMMARY
TOP
 ABSTRACT
 SUMMARY
LITERATURE CITED
 
Figure 1 summarizes vitamin A indicators and the estimated range of vitamin A status that the indicator is useful in determining. Not all indicators have been compared with direct measurement of liver reserves of vitamin A, the "gold" standard. Specifically, isotope ratio and dose response tests have been validated against liver reserves in either animals or humans. If individuals are suffering from xerophthalmia, X1, X2 and X3 (Table 1), they are already vitamin A deficient. If a population group has a high incidence of night blindness (XN), liver stores of vitamin A are already seriously depleted. If dark adaptometry and CIC are abnormal, vitamin A stores are depleted to a point that normal function is not maintained but overt clinical signs are absent. If homeostatic serum retinol concentrations are interrupted, liver stores are depleted. While the RAG-hydrolysis test has not been field tested, as a response test one assumes that it will work in the subclinical range of vitamin A status. The RBP:TTR is a static measure which helps to interpret depressed serum retinol concentration due to infection. Breast milk retinol concentrations are useful in determining the vitamin A status of groups of lactating women and seem to respond to vitamin A supplementation. The dose response tests, RDR and MRDR, are probably more sensitive than the latter indicators of vitamin A status. However, they are not useful in determining total body reserves and do not differentiate between different degrees of adequate and toxic levels of vitamin A. Due to the fact that negative values have been reported with the RDR test, the MRDR test may well respond better in times of infection (10,39). Isotope dilution testing, although not completely user friendly, will accurately determine total body reserves of vitamin A; however, there probably will be accuracy issues when the individual is in the toxic range of vitamin A status. Direct measurement of liver reserves of vitamin A status, the "gold" standard, through biopsy will never be a field friendly indicator and therefore has limited utility in the real world.



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  		FIGURE 1 The estimated relationship of vitamin A status indicator to liver reserves of vitamin A. [CIC, conjunctival impression cytology; RAG, retinoyl ß-glucuronide; RBP:TTR, retinol binding protein to transthyretin ratio; RDR, relative dose response; MRDR, modified relative dose response.]

 
Thus, researchers have many choices of vitamin A assessment methods. The degree of sophistication of the laboratory and resources available will usually dictate which methods are chosen for population assessment and intervention evaluation. In the short term, it is important for developing countries to incorporate vitamin A supplementation programs into health programs for children who are at risk of vitamin A deficiency. Of course, in the long term, fortification of staple foods and promotion of eggs and vegetables and fruits high in ß-carotene are the most sustainable methods to improve the vitamin A status of communities.


   FOOTNOTES
 
1 Presented as part of the James Allen Olson Memorial Symposium, "Functions and Actions of Retinoids and Carotenoids" held at Iowa State University, June 21–24, 2001 to honor the memory of James Allen Olson. This conference was supported by the U.S. Department of Agriculture; National Institutes of Health; Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University (ISU); Department of Food Science and Human Nutrition, ISU; College of Liberal Arts and Sciences, ISU; F. Hoffmann-La Roche; Kemin Foods, L.C., Procter & Gamble Company; Lipton; Best Foods; BASF; SmithKline Beecham; Cognis Corporation; Allergen and INEXA. Guest editor for this symposium was Norman I. Krinsky, Department of Biochemistry, School of Medicine, and the Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111-1837. Back

2 Funded in part by Hatch-Wisconsin Agricultural Experiment Station number WIS0438 and the UW-Madison Graduate School. The research presented in this paper had multiple sources of funding and included the Thrasher Research Fund, the National Institutes of Health and the United States Department of Agriculture. Back

4 Abbreviations used: CIC, conjunctival impression cytology; DRD, deuterated retinol isotope dilution; GCCIRMS, gas chromatography-combustion-isotope ratio mass spectrometry; IVACG, International Vitamin A Consultative Group; MRDR, modified relative dose response; RDR, relative dose response; RBP, retinol-binding protein; RBP:TTR, retinol binding protein to transthyretin; RAG, retinoyl ß-glucuronide. Back


   LITERATURE CITED
TOP
 ABSTRACT
 SUMMARY
 LITERATURE CITED
 

1. Sommer, A., McLaren, D. S. & Olson, J. A. (1976) Assessment of vitamin A status: IVACG Task Force on Assessment. Guidelines for the Eradication of Vitamin A Deficiency and Xerophthalmia. A Report of the International Vitamin A Consultative Group (IVACG) 1976:I-1-I-7.

2. Furr, H. C., Amedee-Manesme, O., Clifford, A. J., Bergen, H. R., III, Jones, A. D. & Olson, J. A. (1989) Vitamin A concentrations in liver determined by isotope dilution assay with tetra-deuterated vitamin A and by biopsy in generally healthy adult humans. Am. J. Clin. Nutr. 49:713-716.[Abstract/Free Full Text]

3. Haskell, M. J., Handelman, G. J., Peerson, J. M., Jones, A. D., Rabbi, M. A., Awal, M. A., Wahed, M. A., Mahalanabis, D. & Brown, K. H. (1997) Assessment of vitamin A status by the deuterated-retinol-dilution technique and comparison with hepatic vitamin A concentration in Bangladeshi surgical patients. Am. J. Clin. Nutr. 66(1):67-74.[Abstract/Free Full Text]

4. Tanumihardjo, S. A., Furr, H. C., Amedee-Manesme, O. & Olson, J. A. (1990) Composition of retinyl esters (vitamin A esters) and carotenoids in human liver. Int. J. Vitam. Nutr. Res. 60:307-313.[Medline]

5. XX International vitamin A consultative group (IVACG) meeting. (2001) 25 Years of Progress in Controlling Vitamin A Deficiency: Looking to the Future 2001:12 IVACG meeting program .

6. Christian, P., West, K. P., Jr, Khatry, S. K., LeClerq, S. C., Kimbrough-Pradhan, E., Katz, J. & Shrestha, S. R. (2001) Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal. J. Nutr. 131(5):1510-1512.[Abstract/Free Full Text]

7. Christian, P., West, K. P., Jr, Khatry, S. K., Katz, J., LeClerq, S. C., Pradhan, E. K. & Shrestha, S. R. (1998) Vitamin A or beta-carotene supplementation reduces but does not eliminate maternal night blindness in Nepal. J. Nutr. 128(9):1458-1463.[Abstract/Free Full Text]

8. Congdon, N. G., Dreyfuss, M. L., Christian, P., Navitsky, R. C., Sanchez, A. M., Wu, L. S., Khatry, S. K., Thapa, M. D., Humphrey, J., Hazelwood, D. & West, K. P., Jr (2000) Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal. Am. J. Clin. Nutr. 72(4):1004-1009.[Abstract/Free Full Text]

9. Tanumihardjo, S. A., Permaesih, D., Dahro, A. M., Rustan, E., Muhilal, , Karyadi, D. & Olson, J. A. (1994) Comparison of vitamin A assessment techniques in children from two Indonesian villages. Am. J. Clin. Nutr. 60:136-141.[Abstract/Free Full Text]

10. Tanumihardjo, S. A., Permaesih, D., Muherdiyantiningsih, , Rustan, E., Rusmil, K., Fatah, A. C., Wilbur, S., Muhilal, , Karyadi, D. & Olson, J. A. (1996) Vitamin A status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin A supplements and albendazole. J. Nutr. 126:451-457.

11. Rosales, F. J., Jang, J. T., Pinero, D. J., Erikson, K. M., Beard, J. L. & Ross, A. C. (1999) Iron deficiency in young rats alters the distribution of vitamin A between plasma and liver and between hepatic retinol and retinyl esters. J. Nutr. 129:1223-1228.[Abstract/Free Full Text]

12. Jang, J. T., Green, J. B., Beard, J. L. & Green, M. H. (2000) Kinetic analysis shows that iron deficiency decreases liver vitamin A mobilization in rats. J. Nutr. 130:1291-1296.[Abstract/Free Full Text]

13. Rice, A. L., Stoltzfus, R. J., de Francisco, A. & Kjolhede, C. L. (2000) Evaluation of serum retinol, the modified-relative-dose-response ratio, and breast-milk vitamin A as indicators of response to postpartum maternal vitamin A supplementation. Am. J. Clin. Nutr. 71:799-806.[Abstract/Free Full Text]

14. Rice, A. L., Stoltzfus, R. J., de Francisco, A., Chakraborty, J., Kjolhede, C. L. & Wahed, M. A. (1999) Maternal vitamin A or beta-carotene supplementation in lactating Bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency. J. Nutr. 129:356-365.[Abstract/Free Full Text]

15. Tanumihardjo, S. A., Muherdiyantiningsih, , Permaesih, D., Komala, , Muhilal, , Karyadi, D. & Olson, J. A. (1996) Daily supplements of vitamin A (8.4 µmol; 8000 IU) improve the vitamin A status of lactating Indonesian women. Am. J. Clin. Nutr. 63:32-35.[Abstract/Free Full Text]

16. Tanumihardjo, S. A. & Penniston, K. L. (2002) Simplified methodology to determine breast milk retinol concentrations. J. Lipid. Research 43:350-355.[Abstract/Free Full Text]

17. Tanumihardjo, S. A., Cheng, J. C., Permaesih, D., Muherdiyantiningsih, , Rustan, E., Muhilal, , Karyadi, D. & Olson, J. A. (1996) Refinement of the modified-relative-dose-response test as a method for assessing vitamin A status in a field setting: experience with Indonesian children. Am. J. Clin. Nutr. 64:966-971.[Abstract/Free Full Text]

18. Tanumihardjo, S. A., Koellner, P. G. & Olson, J. A. (1990) The modified relative dose response (MRDR) assay as an indicator of vitamin A status in a population of well-nourished American children. Am. J. Clin. Nutr. 52:1064-1067.[Abstract/Free Full Text]

19. Tanumihardjo, S. A. & Olson, J. A. (1991) The reproducibility of the modified relative dose response (MRDR) assay in healthy individuals over time and its comparison with conjunctival impression cytology (CIC). Eur. J. Clin. Nutr. 45:407-411.[Medline]

20. Spannaus-Martin, D. J., Cook, L. R., Tanumihardjo, S. A., Duitsman, P. K. & Olson, J. A. (1997) Vitamin A and vitamin E statuses of preschool children of socioeconomically disadvantaged families living in the midwestern United States. Eur. J. Clin. Nutr. 51:864-869.[Medline]

21. Duitsman, P. K., Cook, L. R., Tanumihardjo, S. A. & Olson, J. A. (1995) The vitamin A statuses of pregnant women from disadvantaged socioeconomic backgrounds in urban Iowa. Nutr. Res. 15(9):1263-1276.

22. Tanumihardjo, S. A., Suharno, D., Permaesih, D., Muherdiyantiningsih, , Dahro, A. M., Muhilal, , Karyadi, D. & Olson, J. A. (1995) Application of the modified relative dose response test to pregnant Indonesian women for assessing vitamin A status. Eur. J. Clin. Nutr. 49(12):897-903.[Medline]

23. Tanumihardjo, S. A. (2002) Vitamin A and iron status are improved with vitamin A and iron supplementation in pregnant Indonesian women. J. Nutr. 132:1909-1912.[Abstract/Free Full Text]

24. Tanumihardjo, S. A. (2001) Can lack of improvement in vitamin A status indicators be explained by little or no overall change in vitamin A status of humans?. J. Nutr. 131:3316-3318.[Abstract/Free Full Text]

25. Tanumihardjo, S. A., Muherdiyantiningsih, , Permaesih, D., Dahro, A. M., Muhilal, , Karyadi, D. & Olson, J. A. (1994) Assessment of the vitamin A status in lactating and in nonlactating, nonpregnant Indonesian women by use of the modified relative dose response (MRDR) assay. Am. J. Clin. Nutr. 60:142-147.[Abstract/Free Full Text]

26. Ribaya-Mercado, J. D., Mazariegos, M., Tang, G., Romero-Abal, M. E., Mena, I., Solomons, N. W. & Russell, R. M. (1999) Assessment of total body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilution method. Am. J. Clin. Nutr. 69:278-284.[Abstract/Free Full Text]

27. Haskell, M. J., Islam, M. A., Handelman, G. J., Peerson, J. M., Jones, A. D., Wahed, M. A., Mahalanabis, D. & Brown, K. H. (1998) Plasma kinetics of an oral dose of [2H4]retinyl acetate in human subjects with estimated low or high total body stores of vitamin A. Am. J. Clin. Nutr. 68:90-95.[Abstract]

28. Ribaya-Mercado, J. D., Solon, F. S., Solon, M. A., Cabal-Barza, M. A., Perfecto, C. S., Tang, G., Solon, J.A.A., Fjeld, C. R. & Russell, R. M. (2000) Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status. Am. J. Clin. Nutr. 72:455-465.[Abstract/Free Full Text]

29. Ribaya-Mercado, J. D., Solon, F. S., Dallal, G. E., Solomons, N. W., Fermin, L. S., Mazariegos, M., Dolnikowski, G. G. & Russell, R. M. (2002) A predictive equation for quantitative assessment of vitamin a body stores in humans by a three-day deuterated-retinol-dilution (3-d DRD) procedure. FASEB J. 16:A745 (abstract 566.7).

30. Adams, W. R. & Green, M. H. (1994) Prediction of liver vitamin A in rats by an oral isotope dilution technique. J. Nutr. 124:1265-1270.

31. Craft, N. E. (2001) Innovative approaches to vitamin A assessment. J. Nutr. 131:1626S-1630S.[Abstract/Free Full Text]

32. Rosales, F. J. & Ross, A. C. (1998) A low molar ratio of retinol binding protein to transthyretin indicates vitamin A deficiency during inflammation: studies in rats and a posterior analysis of vitamin A-supplemented children with measles. J. Nutr. 128(10):1681-1687.[Abstract/Free Full Text]

33. Barua, A. B., Tanumihardjo, S. A. & Olson, J. A. (1998) The retinoyl ß-glucuronide (RAG) hydrolysis test: Elevation of the serum retinoic acid (RA) concentration after an oral dose of retinyl ß-glucuronide in vitamin A-depleted rats. FASEB J. 12:A841 (abstract 4871).

34. Barua, A. B., Duitsman, P. K. & Olson, J. A. (1998) The role of vitamin A status in the conversion of all-trans retinoyl ß-glucuronide to retinoic acid in male Sprague-Dawley rats. Nutr. Biochem. 9:8-16.

35. Tanumihardjo, S. A. (2001) Synthesis of 10,11,14,15-13C4- and 14,15-13C2-retinyl acetate. J. Labelled. Cpd. Radiopharm. 44:365-372.

36. Tanumihardjo, S. A. (2000) Vitamin A status assessment in rats using 13C4-retinyl acetate and gas chromatography-combustion isotope ratio mass spectrometry (GCCIRMS). J. Nutr. 130:2844-2849.[Abstract/Free Full Text]

37. Bergen, H. R., Furr, H. C. & Olson, J. A. (1988) Synthesis of tri-, tetra-, and penta-deuterated forms of vitamin A. J. Labelled Cpd. Radiopharm. 25:11-21.

38. Tanumihardjo, S. A. (2001) Application of 13C4-retinyl acetate and gas chromatography-combustion isotope ratio mass spectrometry to vitamin A assessment in the human. FASEB J. 15(4):A256 (abstract 228.5).

39. Wieringa, F. T., Dijkhuizen, M. A., West, C. E., Northrop-Clewes, C. A. & Muhilal, (2002) Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J. Nutr. 132:3061-3066.[Abstract/Free Full Text]




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{beta}-Carotene from Red Carrot Maintains Vitamin A Status, but Lycopene Bioavailability Is Lower Relative to Tomato Paste in Mongolian Gerbils
J. Nutr., June 1, 2007; 137(6): 1395 - 1400.
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 Am. J. Clin. Nutr.Home page
S. K Tchum, S. A Tanumihardjo, S. Newton, B. de Benoist, S. Owusu-Agyei, F. K. Arthur, and A. Tetteh
Evaluation of vitamin A supplementation regimens in Ghanaian postpartum mothers with the use of the modified-relative-dose-response test
Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1344 - 1349.
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J. M. Baeten, M. H. Wener, D. D. Bankson, L. Lavreys, B. A. Richardson, K. Mandaliya, J. J. Bwayo, and R. S. McClelland
HIV-1 Infection Alters the Retinol-Binding Protein:Transthyretin Ratio Even in the Absence of the Acute Phase Response
J. Nutr., June 1, 2006; 136(6): 1624 - 1629.
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R. L. Surles, J. Li, and S. A. Tanumihardjo
The Modified-Relative-Dose-Response Values in Serum and Milk Are Positively Correlated over Time in Lactating Sows with Adequate Vitamin A Status
J. Nutr., April 1, 2006; 136(4): 939 - 945.
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K. L Penniston and S. A Tanumihardjo
The acute and chronic toxic effects of vitamin A
Am. J. Clinical Nutrition, February 1, 2006; 83(2): 191 - 201.
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F. T Wieringa and M. A Dijkhuizen
Validity of the dose-response tests for the determination of vitamin A status
Am. J. Clinical Nutrition, November 1, 2005; 82(5): 1138 - 1139.
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P. J van Jaarsveld, M. Faber, S. A Tanumihardjo, P. Nestel, C. J Lombard, and A. J S. Benade
{beta}-Carotene-rich orange-fleshed sweet potato improves the vitamin A status of primary school children assessed with the modified-relative-dose-response test
Am. J. Clinical Nutrition, May 1, 2005; 81(5): 1080 - 1087.
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A. R Valentine and S. A Tanumihardjo
One-time vitamin A supplementation of lactating sows enhances hepatic retinol in their offspring independent of dose size
Am. J. Clinical Nutrition, February 1, 2005; 81(2): 427 - 433.
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A. R. Valentine and S. A. Tanumihardjo
Adjustments to the Modified Relative Dose Response (MRDR) Test for Assessment of Vitamin A Status Minimize the Blood Volume Used in Piglets
J. Nutr., May 1, 2004; 134(5): 1186 - 1192.
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