Modified Relative Dose Response Research Articles

Adjustments to the Modified Relative Dose Response (MRDR) Test for Assessment of Vitamin A Status Minimize the Blood Volume Used in Piglets

The modified relative dose response (MRDR) test is widely used in public health research to assess vitamin A (VA) status of populations and individuals. However, method adjustments intended to make the test more useful in large field studies and/or less invasive have not been systematically verified. To compare the similarity between modified tests and the standard MRDR test, and validate both modified and standard tests against liver reserves of VA, we used a piglet model. Following the typical MRDR procedure, piglets (n = 10) were dosed with 5.3 micromol 3,4-didehydroretinyl acetate. Method adjustments were made to the postdose blood sample collection time to decrease both the amount of serum analyzed and sample throughput time. We collected 3 blood samples/piglet at 3, 5, and 7 h or 4, 6, and 8 h postdose. Postdose blood samples obtained between 4 and 7 h gave MRDR values that did not differ. Serum volumes as small as 200 microL, half the volume of the standard method, yielded accurate MRDR values. Method adjustments to reduce sample throughput time require further investigation. In conclusion, because 200 microL of serum can be used in the test, only 0.5 mL, as opposed to 1 mL of blood has to be collected from an individual. This adjustment allows for easier application of the test to individuals, especially infants, from whom it is difficult to obtain a large venous blood sample, thus increasing the utility of the test for researchers.

The effect of retinyl palmitate added to iron-fortified maize porridge on erythrocyte incorporation of iron in African children with vitamin A deficiency.

Retinyl palmitate added to Fe-fortified maize bread has been reported to enhance Fe absorption in adult Venezuelan subjects but not in Western Europeans. It is not known to what extent these results were influenced by differences in vitamin A status of the study subjects. The objective of the present study was to evaluate the influence of retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe in children with vitamin A deficiency, before and after vitamin A supplementation. Erythrocyte incorporation of Fe-stable isotopes was measured 14 d after intake of maize porridge (2.0 mg Fe added as ferrous sulfate) with and without added retinyl palmitate (3.5 micromol; 3300 IU). The study was repeated 3 weeks after vitamin A supplementation (intake of a single dose of 210 micromol retinyl palmitate; 'vitamin A capsule'). Vitamin A status was evaluated by the modified relative dose-response (MRDR) technique. Retinyl palmitate added to the test meal reduced the geometric mean erythrocyte incorporation of Fe at baseline from 4.0 to 2.6 % (P=0.008, n 13; paired t test). At 3 weeks after vitamin A supplementation, geometric mean erythrocyte incorporation was 1.9 and 2.3 % respectively from the test meal with and without added retinyl palmitate (P=0.283). Mean dehydroretinol:retinol molar ratios were 0.156 and 0.125 before and after intake of the single dose of 210 micromol retinyl palmitate; 'vitamin A capsule' (P=0.15). In conclusion, retinyl palmitate added to the labelled test meals significantly decreased erythrocyte incorporation of Fe in children with vitamin A deficiency at baseline but had no statistically significant effect 3 weeks after vitamin A supplementation. The difference in response to retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe before and after intake of the vitamin A capsule indicates, indirectly, changes in vitamin A status not measurable by the MRDR technique. The lack of conclusive data on the effect of retinyl palmitate on Fe absorption indicates the complexity of the interactions between vitamin A status, dietary vitamin A and Fe metabolism.

Vitamin A Supplementation of Women Postpartum and of Their Infants at Immunization Alters Breast Milk Retinol and Infant Vitamin A Status

Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus (DPT) and oral polio vaccine (OPV) immunizations have both been suggested as measures to prevent deficiency among infants. This multicenter randomized, double-blind, placebo-controlled trial was conducted in Ghana, India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status. Mothers in the intervention group received 60 mg vitamin A (as retinol palmitate) at 18-42 d postpartum; their infants were given 7.5 mg three times, i.e., at 6, 10 and 14 wk of age with DPT and OPV immunizations. Mothers and infants in the comparison group received a placebo. Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum [difference in means 7.1, 95% confidence interval (CI), 3.4, 10.8 nmol/g fat] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat (15.2 vs. 26.6%, 95% CI of difference -16.6, -4.1%). At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol. Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L (30.4 vs. 37%, 95% CI of difference -13.7, 0.6%) and that with low vitamin A stores as indicated by the modified relative dose response (MRDR) > 0.06 (44.2 vs. 52.9%, 95% CI of difference -16.6, -0.9%) at 6 mo. Supplementation had no effect at 9 mo. The beneficial effect of supplementation on breast milk retinol and infants' vitamin A status varied by site. It was greatest in India followed by Ghana and Peru. At the doses used, maternal supplementation improved breast milk retinol status at 2 mo (P < 0.001) and maternal and infant supplementation modestly increased (P = 0.03) infant vitamin A status at 6 mo of age. Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered.

Vitamin A and Iron Status Are Improved by Vitamin A and Iron Supplementation in Pregnant Indonesian Women

In Indonesia, deficiencies of vitamin A and iron are of public health concern during pregnancy. We sought to determine the effects of vitamin A and iron supplementation on the vitamin A and iron status of pregnant Indonesian women. The women (n = 27) were randomly assigned to four groups. The modified relative dose response (MRDR) test for vitamin A status and hemoglobin, hematocrit and ferritin values were determined at baseline. Thereafter, daily supplements were administered: placebo [Pl] (n = 7), 8.4 micromol vitamin A [A] (n = 7), 1.07 mmol iron [Fe] (n = 5), and 8.4 micromol vitamin A plus 1.07 mmol iron [A + Fe] (n = 8). Post-treatment tests were performed after 8 wk. The MRDR value was reduced, i.e., vitamin A status improved, more markedly by the combination of vitamin A and iron than by either nutrient alone (P = 0.034). The decrease in the MRDR relative to baseline was significant in the A + Fe group (P = 0.008). Iron status was also significantly improved in these women (P < 0.05) with both iron and vitamin A supplementation. The mechanism of the enhancing effect of iron on the vitamin A-induced reduction in the MRDR is not known.

Association between vitamin A status and lung function level in children aged 6--9 years in Wukro wereda, Northern Ethiopia.

In developing countries, studies using morbidity recalls to evaluate the benefits of vitamin A on respiratory health in children under 6 years of age have been inconclusive. This relationship has not been examined in older children. Spirometric measurements, an objective means of assessing respiratory health, require the subject's collaboration and have been successfully used in children over 6 years of age. This report describes a cross-sectional analysis of the relationship between lung function and vitamin A status in an area endemic to vitamin A deficiency. The data on which this report is based were gathered prior to the implementation of a prospective trial of the effect of vitamin A supplementation on lung function level in Northern Ethiopia. Vitamin A status was assessed by the Modified Relative Dose Response (MRDR) method and lung function assessed by spirometry in 702 rural children aged 6--9 years. Demographic, personal health, household, environmental and socioeconomic data were gathered by questionnaire. In children with low vitamin A reserve, the unadjusted forced expiratory volume in one second (FEV(1)) was 48.8 ml (P = 0.006) lower than in those with adequate reserve. This difference was 23.1 ml (P = 0.04) when adjusted for age, gender and height and 14.1 ml (P = 0.20) when adjusted for children's demographic, general health, lung function and household-related characteristics. Although these findings suggest that vitamin A plays a relatively minor role in determining FEV(1) level, interpretation is limited by the cross-sectional design. Further clarification of its role requires a trial of vitamin A supplementation.

Vitamin A Requirements of Infants under Six Months of Age

Infants are born with negligible liver stores of vitamin A. to enable some storage of the vitamin, the infant needs to be predominantly breastfed with milk containing at least 30 μg/dl. Where vitamin A in breastmilk is low, maternal supplementation with a single postpartum high dose increases milk vitamin A for three to eight months. the current cutoff levels for serum retinol and the modified relative dose response (MRDR) ratio probably need to be revised for young infants. Kinetic analyses of infants’ retention of vitamin A from breastmilk and supplements indicate that the doses of vitamin A given with immunizations in the World Health Organization (WHO) multicenter trial were inadequate to maintain adequate normal stores for more than a few months. the recommendation to double the doses currently given to mothers and infants in the Expanded Program in Immunization should prevent the depletion of liver vitamin A stores for most of the first year of life.

Efficacy of a vitamin A–fortified wheat-flour bun on the vitamin A status of Filipino schoolchildren

Wheat flour is a possible food vehicle for vitamin A fortification. This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children. This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up. Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05). Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.

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

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 alpha 1-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 mumol/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.

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

Conflicting results have been reported regarding the relative performance of serum retinol, the modified-relative-dose-response (MRDR) ratio, and breast-milk vitamin A concentrations in detecting changes in maternal vitamin A status. We used receiver operating characteristic analyses and standardized differences to compare the ability of these indicators to detect a response to postpartum vitamin A supplementation in lactating Bangladeshi women. At 2 wk postpartum, women were randomly assigned to receive either a single dose of vitamin A [200000 IU (60000 retinol equivalents); n = 74] or placebo (n = 73). Data from maternal serum and breast milk collected 3 mo postpartum and from infant serum collected 6 mo postpartum were used to examine the ability of serum retinol, the MRDR ratio, and breast-milk vitamin A to discriminate between individuals in the supplemented and unsupplemented groups. Breast milk was collected by expressing the entire contents of one breast that had not been used to feed an infant for > or =2 h (full samples) or without controlling the time since the last breast-feeding episode (casual samples). Casual breast-milk samples performed better than full breast-milk samples in detecting a response to maternal supplementation. The MRDR ratio performed better than serum retinol in both the women and their infants. Overall, the most responsive indicator was the measurement of breast-milk vitamin A per gram of fat in casual breast-milk samples. Breast-milk vitamin A and the MRDR ratio are responsive indicators of vitamin A status, especially in women with mild vitamin A deficiency.

Maternal Vitamin A or β-Carotene Supplementation in Lactating Bangladeshi Women Benefits Mothers and Infants but Does Not Prevent Subclinical Deficiency

The effects of maternal postpartum vitamin A or β-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1–3 wk postpartum, women were randomly assigned to receive either (1) a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of β-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The β-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (≤1.05 μmol/L or ≤0.28 μmol/g fat) throughout the study. Overall, mean maternal serum retinol concentrations were not affected by supplementation. Compared to the placebo group, the mean MRDR ratio of 6-mo-old infants was higher in the vitamin A group. Infants (33%) had serum retinol concentrations <0.70 μmol/L and 88% had MRDR ratios ≥0.06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status.

A community based study of vitamin A and vitamin E status of adolescent girls living in the Shire Valley, Southern Malawi.

To assess vitamin A and E status and anaemia in non-pregnant Malawian adolescent girls. A cross-sectional study in rural village communities in the Shire Valley, Southern Malawi. Adolescent girls, n = 118, aged between 10 and 19 y, 112 of whom were unmarried. Socio-demographic information was collected by questionnaire, heights and weights were measured. Vitamin A was assessed by the Modified Relative Dose Response (MRDR) test, in addition to serum retinol values. Blood samples were collected 4-5 h after administration of 3,4-didehydroretinyl acetate. Retinol and alpha-tocopherol levels were measured by HPLC. Serum retinol results for non-pregnant girls were compared with values for 43 adolescent pregnant girls which were available from a previous study. 26.6% of non-pregnant girls had serum retinol values < 0.70 micromol/L; 40.2% had an MRDR ratio > 0.060. In 59.3%, serum tocopherol levels were < 11.5 micromol/L and the tocopherol/cholesterol ratio was < 2.2 in 23.9%. 11.3% had a haemoglobin > or = 12 g/dl. Vitamin A levels were significantly related to age, and younger girls were more likely to be deficient. Significant correlations were found between serum retinol, MRDR values and serum tocopherol. Girls with a low body mass index for age had tocopherol cholesterol ratios < 2.2. Low serum retinol values occurred significantly more often in stunted girls (P=0.01). Serum retinol values of adolescent pregnant girls were significantly lower than those of non-pregnant adolescents (P=0.002). Vitamin A and E deficiency and anaemia were common in adolescent non-pregnant girls, and thought to partly result from increased growth requirements. Girls who become pregnant at an early age are at risk of depletion of their nutritional reserves. Measures to reduce nutritional deficiencies before the first pregnancy are needed.

Vitamin A status does not influence neopterin production during illness or health in South African children.

Excessive interferon-gamma (IFN-gamma) production appears to be a primary immunological lesion in vitamin A-deficient experimental animals but comparable data from humans is lacking. We investigated IFN-gamma production in South African children by measurement of urinary excretion of neopterin, a product of IFN-gamma-activated monocytes or macrophages. Preschool children were examined during an acute inflammatory illness resulting from accidental ingestion of kerosene and they and a neighbourhood control child were examined 3 months later when well. Vitamin A status was assessed by the modified relative dose response (MRDR) test at 3 months and serum retinol and acute phase proteins were measured at both time points. Urinary neopterin was measured for forty cases in hospital, forty-six cases after recovery, and forty-one controls. Significantly increased neopterin excretion was seen following kerosene ingestion and in association with raised serum acute phase protein concentrations. There was no relationship between neopterin excretion at either time point and vitamin A status as assessed by MRDR test. Urinary neopterin was negatively correlated with serum retinol but no significant relationship was observed when acute phase protein concentrations were included in a multiple regression, suggesting the correlation was secondary to illness-induced changes in serum retinol. The results indicate that, contrary to what is observed in rodents under experimental conditions, poor vitamin A status is not associated with altered regulation of IFN-gamma production in children.

Vitamin A and vitamin E statuses of preschool children of socioeconomically disadvantaged families living in the midwestern United States.

To determine the vitamin A and vitamin E statuses of socioeconomically disadvantaged preschool American children. Cross-sectional study of preschool children from socioeconomically disadvantaged families. Central Iowa, USA. A group of 77 apparently healthy children was studied with the following characteristics: 5 mo-6 y; 37 males, 40 females, 56 non-Hispanic Caucasians, 3 Hispanics, 18 Afro-Americans. Modified relative dose response (MRDR) test for vitamin A status assessment; serum retinol, alpha-tocopherol, cholesterol, and carotenoids; weight for age. Although the mean weight for age was the 53rd percentile of the NCHS standard, a significant number of children (P = 0.006, chi(2)) were either markedly underweight or overweight. Ratios of 3,4-didehydroretinol to retinol (DR/R) were > 0.030, in 32% of the children. Mean serum retinol, alpha-tocopherol and cholesterol (+/- s.d.) were 1.09 +/- 0.23 microM/L, 16.8 +/- 6.3 microM/L and 4.01 +/- 0.8 microM/L. Three children (3.9%) showed a serum retinol value < 0.7 microM/L. One child with a serum retinol value < 0.7 microM/L and one additional child showed a ratio of alpha-tocopherol to cholesterol < 1.44 mumol/mmol. The mean alpha-tocopherol to cholesterol ratio for the group (4.31 +/- 1.71 mumol/mmol), however, was satisfactory. The only significant (P < or = 0.05) age-related changes were an increase in the serum cholesterol (P = 0.005) and decrease in the alpha-tocopherol to cholesterol ratio (P < 0.005) between the 0-2 y and the 2-4 y groups. Serum cholesterol (P = 0.0165, two-tailed) and lycopene (P = 0.004) concentrations of Afro-Americans were significantly higher than those of Caucasians. Median serum concentrations of alpha-carotene and beta-carotene were lower and, of lycopene higher than those found in children studied in a national survey. Serum carotenoid concentrations generally increased with age. Larger percentages of underweight and overweight children and a significant degree (32%) of inadequate vitamin A status were found in this group of socioeconomically disadvantaged children. Afro-Americans showed higher serum cholesterol and lycopene concentrations than did Caucasians, but otherwise were nutritionally similar. Age-related changes were small. Of nutritional parameters considered, the vitamin A status of socioeconomically disadvantaged segments of our population clearly needs attention.

Evaluation of biochemical indicators of vitamin A status in breast-feeding and non-breast-feeding Indonesian women

Indicators of vitamin A status were evaluated in nonpregnant breast-feeding (n = 265) and nonpregnant non-breast-feeding (n = 49) Indonesian women. The concentration of vitamin A (not including provitamin A carotenoids) and fat in breast milk was 30% and 20% higher, respectively, for women with a breast-fed child 7-18 mo old than for women with an infant 3-6 mo old. The vitamin A content of milk fat was constant throughout lactation. Breast-milk vitamin A was most sensitive to changes in vitamin A status when expressed per volume. Sensitivity and specificity for detecting serum retinol concentrations < 0.70 mumol/L were < 75% for the concentration of breast-milk vitamin A and serum retinol binding protein (RBP). The modified-relative-dose-response (MRDR) method suffers from a relatively large intraindividual variation in the ratio of dehydroretinol to retinol because of vulnerability of the dehydroretinol concentration to laboratory errors and to variation in dosing and absorption. Within categories of dehydroretinol:retinol, serum retinol concentration was lower in breast-feeding women than in non-breast-feeding women. Thus, it may be necessary to use different cutoff values for the ratio and for serum retinol concentration. Serum retinol concentration, which was just above marginal (0.85 mumol/L), had the smallest within-person variation and was also the most sensitive indicator for detecting a difference between groups in change in vitamin A status postintervention, requiring only 19 subjects per group. Serum RBP concentration, breast-milk vitamin A expressed per volume or per gram milk fat, and the MRDR method required groups of 35, 36, 139, and 53 subjects, respectively.

Refinement of the modified-relative-dose-response test as a method for assessing vitamin A status in a field setting: experience with Indonesian children

The modified-relative-dose-response (MRDR) test, which has been used extensively throughout the world for assessing vitamin A status, has been simplified. The major methodologic change resulting from the current studies in Indonesia is the use of graded standard doses of 3,4-didehydroretinyl acetate (DRA) based on the age range of the population of interest. Instead of a dose of 0.35 mumol/kg body wt, standard doses of 5.3 mumol for children younger than 6 y, 7.0 mumol for children between 6 and 12 y of age, and 8.8 mumol for adults and children > 12 y of age are suggested for field use. The acceptable time between administering the oral dose and obtaining a blood sample was validated as being 4-7 h in a group of children (n = 84) by taking two blood samples per child between 3 and 7 h after dosing with DRA. Furthermore, DRA in vitamin E-containing corn oil, with or without the addition of 4.6 mmol all-rac-alpha-tocopheryl acetate/L, was found to be stable for > or = 18 mo at 2 degrees C and at -20 degrees C, but not at 22 degrees C or at 37 degrees C. When DRA was stored in amber glass vials, stability was affected more by temperature than by exposure to room light. In keeping with earlier studies in adults, the ratio of 3,4-didehydro-retinol to retino tends to be independent of body weight. Indeed, slower growing children (ie, those with lower weight-for-age) may have a somewhat better vitamin A status than their heavier counterparts.

Vitamin A Status of Indonesian Children Infected with Ascaris lumbricoides after Dosing with Vitamin A Supplements and Albendazole

In developing countries, both marginal vitamin A status and intestinal helminths are common among children. Indonesian children (n = 309, 0.6–6.6 y), known to be infected with Ascaris lumbricoides, were randomized into six different treatment groups (A-F). The treatments included 210 µmol vitamin A supplement and a dose of 400 mg albendazole (5-propylthio-1H-benzimidazol-2-yl carbamic acid methyl ester) administered orally either at the same health visit (Groups B and F) or at different contact times during a 1-mo period (groups A, C, D and E). Vitamin A status was assessed both before and 3–4 wk after the treatments by the modified relative dose response (MRDR) test. Vitamin A supplementation was most important in improving the vitamin A status (P < 0.0001) of these children, whereas treatment for ascariasis alone (P = 0.370) and the statistical interaction between treatment for ascariasis and vitamin A (P = 0.752) were not. Serum retinol concentrations marginally improved (P = 0.051) in two of the groups that received vitamin A and albendazole but not in the third group that received vitamin A only. The MRDR test proved a better discriminator of the effects of these treatments on vitamin A status than changes in serum retinol concentrations.

Daily supplements of vitamin A (8.4 mumol, 8000 IU) improve the vitamin A status of lactating Indonesian women

The vitamin A statuses of lactating Indonesian women (n = 23) starting at 1-3 mo after delivery were determined at three monthly intervals (times 1, 2, and 3) during lactation and then again (time 4) after they had ingested vitamin A capsules (8.4 mumol, 8000 IU) daily for 35 d. Vitamin A status was determined by using the modified-relative-dose-response (MRDR) test and serum retinol concentrations. The mean MRDR ratio in these women rose from 0.084 +/- 0.047 (time 1) to 0.099 +/- 0.045 (time 2) and then to 0.100 +/- 0.054 (time 3). After supplementation the mean MRDR ratio fell to 0.040 +/- 0.021 (time 4) (P < 0.0001). Mean serum retinol concentrations at the first three times were 0.94 +/- 0.23, 0.87 +/- 0.20, and 0.80 +/- 0.20 mumol/L, but then rose to 1.10 +/- 0.31 mumol/L at time 4 (P < 0.04). After supplementation mean MRDR values and mean serum retinol concentrations were 60% lower and 38% higher, respectively, than those just before supplementation, MRDR values better distinguished the vitamin A statuses of the women than did serum retinol concentrations. Mean hemoglobin values increased during the study from 118 +/- 9 g/L at time 1 to 122 +/- 6 g/L at time 4 (P = 0.0187). The mean hematocrit also rose from 0.35 +/- 0.03 at time 1 to 0.361 +/- 0.17 at time 4 (P = 0.0478). Thus, iron status may also have improved marginally from time 1 to time 4, but most of the increase appeared before the vitamin A intervention.

Vitamin A inadequacy in socioeconomically disadvantaged pregnant Iowan women as assessed by the modified relative dose response (MRDR) test

The vitamin A status of low-income women (n = 57) during the third trimester of pregnancy was assessed by use of the modified relative dose response (MRDR) test. Non-Hispanic White (45), Hispanic (6), Afro-American (5), and Asian (1) women were recruited from public health programs in central Iowa. Serum retinol, β-carotene, α-carotene, lycopene, α-tocopherol, and cholesterol concentrations were also measured. Twenty six percent of the study population were found to be in a marginal vitamin A status with MRDR values ≥0.03, whereas 9% had values ≥0.06. The Hispanic and Afro-American groups seemed to be most at risk, with 50% and 40% (respectively) of the MRDR values ≥0.03 and 33% and 20% (respectively) ≥0.06. Carotenoid values were similar to those found in women in other like studies, except for the Afro-American group, which had mean values less than half those of the other groups. α-Tocopherol concentrations and α-tocopherol/cholesterol ratios of all ethnic groups fell in the normal range. The somewhat elevated cholesterol levels found in all groups can largely be attributed to pregnancy. Clearly, this study identifies a portion of the U.S. population at high risk of vitamin A inadequacy.

Comparison of the modified relative dose response (MRDR) and the relative dose response (RDR) in the assessment of vitamin A status in malnourished children

The modified-relative-dose-response (MRDR) test and the relative-dose-response (RDR) test were compared in 49 mildly to moderately malnourished Bangladeshi children. The MRDR test had a significantly lower sensitivity, detecting only 71% of children with very low serum retinol (< or = 0.35 mumol/L) and 33% of children with low serum retinol (0.355-0.70 mumol/L) compared with 100% and 80% for the RDR test, respectively. The MRDR test showed a very strong dependency on retinol-binding protein (RBP) saturation (ie, percent saturation of RBP with retinol) compared with the RDR test. Only 3 (23%) of 13 children with RBP saturation > or = 55% but low vitamin A stores were diagnosed as abnormal by the MRDR test. This suggests that when apo-RBP concentration is limiting, as it is in malnourished children, didehydroretinol, the analog used in the MRDR test cannot effectively compete with retinol for binding to apo-RBP. Under these circumstances, the MRDR test is rendered ineffective. The possibility of increasing the sensitivity of the test by using a high dose of didehydroretinol needs to be investigated.

Comparison of vitamin A status assessment techniques in children from two Indonesian villages

The vitamin A statuses of preschool-aged children without clinical eye signs of vitamin A deficiency in two villages near Bogor, West Java, Indonesia, were studied by the modified-relative-dose-response (MRDR) test and the conjunctival impression cytology (CIC) method. In the second village the relative-dose-response (RDR) test was also applied. Of the children examined, 71% in the first village (group 1, n = 75) and 36% in the second village (group 2, n = 83) fell below the third percentile of the WHO reference standard of weight-for-age. The following provisional cutoff values for inadequate vitamin A status in Indonesia were used: MRDR (> or = 0.06), RDR (> or = 20%), CIC (an abnormal impression in one eye). The percent abnormal values were as follows: group 1--MRDR 48%, CIC 51%; group 2--MRDR 12%, RDR 11%, CIC 5%. Thus, the indicators gave concordant results for the two populations but did not necessarily identify the same individuals at risk. The consistency of the RDR test was much improved by increasing the oral dose of 3.5 mumol and by retesting only after a 3-wk interval.