Relative Dose Response Test Research Articles

The Vitamin A Status of Zambian Children in a Community of Vitamin A Supplementation and Sugar Fortification Strategies as measured by the Modified Relative Dose Response (MRDR) Test

The main objective of the study was to determine the vitamin A status of Zambian children less than five years of age in a community where strategies of vitamin A supplementation and consumption of vitamin A fortified sugar have been introduced. In a cross-sectional study, a total of 537 children were enrolled. Their vitamin A status was measured using the modified relative dose response (MRDR) test. Their vitamin A status was compared to the status measured using a similar method in 1996, before vitamin A supplementation through capsule distribution and fortification of sugar was implemented as strategies to reduce vitamin A deficiency in the country. Results showed that the vitamin A status of children improved markedly as a result of these strategies.

Vitamin A deficiency among Brazilian school-aged children in a healthy child service

Vitamin A deficiency (VAD) is a world public health problem contributing to the increase in childhood morbidity and mortality in developing countries and severe deficiency of vitamin A may lead to xerophthalmia and blindness. The objective of this study was to determine the prevalence of VAD among Brazilian school-aged children attended at a primary health unit and to verify if some considered risk factor was associated with VAD in this group. A descriptive prospective transverse study was conducted on 103 randomly selected children. A total of 54 boys and 49 girls aged 5.5-11 years had the relative dose-response (RDR) test performed on. Possible ocular alterations related to vitamin A and the status of anemia, serum zinc, some acute-phase proteins, and anthropometric situation were determinate by an analytic design. No child presented xerophthalmia. Serum retinol values lower than 1.05 and 0.7 micromol l(-1), respectively were found in 26.2 and 5.8% of the children. The prevalence of hypovitaminosis detected by RDR test was 20.4%. The following variables and their relationship with VAD were evaluated: sex (P=0.33; 95% confidence interval 0.61-4.34), weight and height (P> or =0.5), hemoglobin (P=0.15), C-reactive protein (P=0.56; 95% confidence interval 0.75-18.26), alpha-1-acid-glycoprotein (P=0.56; 95% confidence interval 0.15-15.42) and serum zinc (P=0.31). None of these variables was related to VAD. In this population, the prevalence of VAD detected could be considered a public health problem. School-aged children can be considered at risk for VAD mainly of a subclinical level, even without some associated risk factors.

One-time graded doses of vitamin A to weanling piglets enhance hepatic retinol but do not always prevent vitamin A deficiency

Background: Vitamin A supplements are administered to infants in developing countries at immunization contacts; doses of 50000 IU vitamin A are recommended. Doses of 100000 IU are given to children aged 0.5–1 y. The efficacy of these doses has not been adequately determined.Objective: We aimed to quantify liver vitamin A after the administration of vitamin A doses to piglets. Piglets are a good model for infants because of their similar size, gastrointestinal anatomy, and vitamin A requirements.Design: Castrated male piglets born to sows fed a vitamin A–depleted diet throughout 1 (parity A) or 3 (parity B) pregnancy and lactation cycles were randomly assigned to receive 1 of 4 oral vitamin A doses (ie, 0, 25000, 50000, or 100000 IU) at weaning (days 9–14). A vitamin A–depleted diet was fed until the piglets were killed on day 10. Serum retinol was measured on days 1, 2, 4, 7, and 10. The modified relative dose response was measured before supplementation and at the time of killing, and liver vitamin A concentration was measured.Results: In both parities, 25000 IU did not result in a mean liver retinol reserve > 0.07 μmol/g liver (the deficiency cutoff). The 50000-IU dose increased mean reserves above 0.07 μmol/g only in parity A. Liver vitamin A reserves with the 100000-IU treatment were only 5% above those with the 50000-IU treatment. The modified relative dose-response test reflected differences in liver vitamin A stores in parity B, and the 0-IU group differed significantly from the 100000-IU group (P = 0.011).Conclusion: This piglet model suggests that, for supplementation to infants <6 mo old, a 50000-IU dose is likely to be more efficacious in mitigating deficiency than is a 25000-IU dose.

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

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) micromol/l, and 33.3% were<0.7 micromol/l. Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group: (0.67 v. 0.60 micromol/l; 0.52 v. 0.44 micromol/l; 0.50 v. 0.44 micromol/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.

Assessment of vitamin A nutritional status in newborn preterm infants

Objective This study assessed the vitamin A nutritional status of preterm infants determined by the vitamin A relative dose-response test (RDR) compared with serum levels of vitamin A, retinol-binding protein (RBP), transthyretin (TTR), and retinol relations with carrier proteins. Methods Serum levels of retinol, RBP, and TTR and retinol/RBP, retinol/TTR, and RBP/TTR molar ratios were determined in 120 infants at 7 d and in 92 at 28 d. For the determination of the performance of the tests, the RDR was considered the reference method. The sensitivity and specificity for all possible cutoff values were determined by constructing receiver operator characteristic curves. The areas under the curves were used to estimate the overall accuracy of the tests. The best cutoff values to be used for the calculation of sensitivity and specificity were determined with 95% confidence intervals. Results RDR indicated vitamin A deficiency in 60% of the infants at 7 d and in 51.1% at 28 d. In the receiver operator characteristic curves, the best area under the curve was 0.710 obtained for serum retinol at 28 d of postnatal age and considered moderately accurate. The least inadequate cutoff level was set at 25 mg/dL, but no value was considered adequate due to low sensitivity and/or low specificity. Conclusion Compared with RDR, the determination of serum levels of retinol, RBP, and TTR and their molar ratios are not adequate to assess nutritional vitamin A status in preterm infants.

Randomized controlled safety and efficacy trial of 2 vitamin A supplementation schedules in Tanzanian infants

Background: Vitamin A supplementation reduces morbidity and mortality in children living in areas endemic for vitamin A deficiency. Routine vitamin A supplementation usually starts only at age 9 mo, but high rates of illness and mortality are seen in the first months of life.Objective: The objective of the study was to evaluate the safety and efficacy of vitamin A supplementation at the same time as routine vaccination in infants aged 1–3 mo.Design: We recruited 780 newborn infants and their mothers to a randomized double-blind controlled trial in Ifakara in southern Tanzania. In one group, mothers received 60 000 μg vitamin A palmitate shortly after delivery, and their infants received 7500 μg at the same time as vaccinations given at ≈1, 2, and 3 mo of age. In the other group, mothers received a second 60 000-μg dose when their infant was aged 1 mo, and their infants received 15 000 μg at the same time as the routine vaccinations. VAD was defined as a modified relative dose-response test result of ≥0.060.Results: High-dose vitamin A supplementation was well tolerated. The relative risk of VAD at 6 mo in the high-dose group compared with the lower dose group was 0.91 (95% CI: 0.76, 1.09; P = 0.32). Serum retinol and incidence of illness did not differ significantly between the 2 groups. Some vitamin A capsules degraded toward the end of the study.Conclusions: Doubling the doses of vitamin A to mothers and their young infants is safe but unlikely to reduce short-term morbidity or to substantially enhance the biochemical vitamin A status of infants at age 6 mo. The stability of vitamin A capsules merits further investigation.

The modified relative dose response (MRDR) test value predicts liver vitamin A reserves in a piglet model

The modified relative dose response (MRDR) test is an indicator of vitamin A (VA) status when defined by hepatic VA. Debate exists as to how accurately the MRDR test reflects hepatic VA or a change in VA status. We examined the MRDR test and serum retinol as indicators of hepatic VA in piglets using the following values to indicate deficient or marginal status: ≥ 0.060, < 0.70 μmol/L, and < 30 retinol equivalents/g, respectively. In piglets (n = 100) with a 78% prevalence of deficiency, the negative predictive value and sensitivity are higher using the MRDR test than serum retinol. The MRDR test more accurately indicated a change in VA status in groups of animals receiving supplementation than serum retinol. Serum retinol remains under homeostatic control throughout a wide range of liver values, but can be depressed due to protein-energy undernutrition, iron and zinc deficiency, and the acute-phase response even if hepatic VA is unaffected. Alternatively, the MRDR test reflects normal through severely depleted hepatic VA and is less affected by the acute-phase response and mild to moderate protein-energy undernutrition. Serum retinol and the MRDR test are correlated when hepatic VA is extremely low and when hepatic VA is ample. However, in groups with marginal status, the indicators are not correlated and the MRDR test gives a better definition of overall VA status. Supported by NIHNIDDK 61973 and USDA NRI 2003-35200-13754.

Comparison of Indices of Vitamin A Status in Children With Chronic Liver Disease *

Malabsorption of fat-soluble vitamins is a major complication of chronic cholestatic liver disease. The most accurate way to assess vitamin A status in children who have cholestasis is unknown. The goal of this study was to assess the accuracy of noninvasive tests to detect vitamin A deficiency. Children with chronic cholestatic liver disease (n = 23) and noncholestatic liver disease (n = 10) were studied. Ten cholestatic patients were identified as vitamin A-deficient based on the relative dose response (RDR). Compared with the RDR, the sensitivity and specificity to detect vitamin A deficiency for each test was, respectively: serum retinol, 90% and 78%; retinol-binding protein (RBP), 40% and 91%; retinol/RBP molar ratio, 60% and 74%; conjunctival impression cytology, 44% and 48%; slit-lamp examination, 20% and 66%; tear film break-up time, 40% and 69%; and Schirmer's test, 20% and 78%. We developed a modified oral RDR via oral coadministration of d-alpha tocopheryl polyethylene glycol-1000 succinate and retinyl palmitate. This test had a sensitivity of 80% and a specificity of 100% to detect vitamin A deficiency. In conclusion, vitamin A deficiency is relatively common in children who have chronic cholestatic liver disease. Our data suggest that serum retinol level as an initial screen followed by confirmation with a modified oral RDR test is the most effective means of identifying vitamin A deficiency in these subjects.

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.

Assessing Vitamin A Status: Past, Present and Future

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 beta-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.

Assessment of vitamin A status with the relative-dose-response test in Peruvian children recovering from pneumonia

The relative-dose-response (RDR) test is used to identify subjects with marginal liver vitamin A stores, but its use has not been evaluated during episodes of infection. The objective was to assess, with the RDR test, the vitamin A status of children recovering from pneumonia. As part of a double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima, Peru, we examined the association of treatment group, nutritional status, severity of disease, and induction of the acute phase response [on the basis of serum C-reactive protein (CRP)] on serum retinol and the RDR test. Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery. Serum CRP had a significant, inverse association with retinol at both admission and discharge. Serum retinol and CRP concentrations never differed significantly between the treatment groups. Among subjects with CRP > or =10 mg/L, 21% in the vitamin A group and 20% in the placebo groups (P = 0.83) had a positive RDR test result. Among subjects with CRP <10 mg/L, 56% in the placebo group but only 6% in the vitamin A group had positive RDR test results (P = 0.002). The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were <10 mg/L but not when CRP concentrations were higher.

Prevalence of Undernutrition and Vitamin A Deficiency in the Dogon Region, Mali

Objectives: A representative sample of 1510 preschool children living in the Bandiagra circle (Mopti Region, Mali) was examined between March and April 1997 to determine the level of vitamin A deficiency.Methods: Using a randomized two level cluster sampling, 20 clusters of 75 children aged six months to six years were selected for evaluating xerophthalmia (XN night blindness and/or X1B Bitot spot). Concurrently stature and weight were determined. A semiquantitative seven-day dietary questionnaire was applied to the mothers of 484 infants to assess consumption of vitamin A rich foodstuffs. The prevalence of biochemical deficiency was attested using the Modified Relative Dose Response test (MRDR) on a sub-sample of 192.Results: Of the studied children, 4.3% (95% Confidence interval [CI]: 3.2–5.3) reported night blindness and 2% (95% CI: 1.3–2.7) had Bitot spots. Prevalence of xerophthalmia attested by at least one of these signs was 5.4% (95% CI: 4.2–6.5). The prevalence reached 10.5% at three years of age. The MRDR test proved abnormal in 77.1% of the subjects (95% CI: 70.3–82.7). Serum retinol was lower than 0.35 μmol/L in 43.8% (95.6% CI: 36.9–51.3) and less than 0.70 μmol/L in 92.7% of the children (95% CI: 87.8–95.8). Weekly consumption of vitamin A rich food was rare: 75.8% had not eaten any animal vitamin A rich food, and 22.1% had consumed less than seven times a vitamin A rich food of either vegetable or animal origin.Conclusions: These data define vitamin A deficiency as a severe public health problem in the Bandiagara area of Mali.

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.

Can Lack of Improvement in Vitamin A Status Indicators Be Explained by Little or No Overall Change in Vitamin A Status of Humans?

Changes in vitamin A status using conventional indicators, i.e., serum and breast milk retinol concentrations and the modified relative dose response test, following a vitamin A intervention have not always been shown. A simplified model to predict calculated changes in vitamin A status after intervention is described. The model shows that changes in indicator values cannot be expected if the change in vitamin A status is only marginal. A critical review of several papers using vitamin A status assessment indicators was undertaken. Assumptions that included current knowledge concerning vitamin A absorption and metabolism were made and applied to the data. Based on current recommended daily allowances for women and children, one cannot necessarily expect a change in indicators if an overall change in vitamin A status was not achieved. Thus, when designing vitamin A intervention studies, the following parameters should be considered if applicable to the population to be enrolled in the study: average body weight, estimated liver weight, amount of vitamin A administered, estimated loss in breast milk and study duration.

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.

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 relative dose response test in undernourished children

The relative dose response (RDR) has been proposed as a method for the estimation of body vitamin A stores and has been tested in children suffering from various grades of malnutrition. RDR was tested before and after 4–6 days of vitamin A administration either as a single massive oral dose of 200,000 i.u. or four smaller doses of 50,000 i.u. each. The results of the study indicated a positive RDR (> 14%) reflecting liver stores depletion in children whose serum levels of vitamin A were less than 0.35 μmol/l. Normal RDR (< 14%) was observed in children whose serum levels of vitamin A were above 0.7 μmol/l indicating normal liver vitamin A reserves. However, the RDR showed variable results in children whose serum vitamin A levels were between 0.35–0.70 μmol. Eleven out of 49 children continued to show positive RDR even after vitamin A supplementation. Associated malnutrition might be responsible for the variation in the response. These results suggest that RDR test may be of a limited value in populations where malnutrition is prevalent.

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.

Toxic Damage to the Respiratory Epithelium Induces Acute Phase Changes in Vitamin A Metabolism without Depleting Retinol Stores of South African Children , ,

Whereas there is much information concerning the effects of vitamin A status on response to infectious challenge, the effects of infection or trauma on vitamin A metabolism and status are less well documented. These relationships need to be understood to optimize clinical and public health programs to improve vitamin A status and health of children in less-developed countries. We measured acute changes in retinol and retinol-binding protein in 57 young South African children hospitalized following respiratory epithelial damage resulting from accidental ingestion of kerosene. In addition, vitamin A status, as measured by the modified relative dose response test, of these children 3 mo later was compared with that of neighborhood control children to determine whether their illness had depleted retinol stores. Plasma retinol was already significantly below control levels when children were admitted [geometric mean (95% CI): 0.57 μmol/L (0.48–0.67) compared with 1.15 μmol/L (1.02–1.30) for controls] and decreased further the following morning [0.38 μmol/L (0.31–0.46)]. Significant differences in retinol-binding protein were not detected until the next morning [5.99 mg/L (4.70–7.63) compared with 14.0 mg/L (11.8–16.6) for controls] and were not as large as the relative differences in retinol. This dissociation between changes in retinol and its binding protein suggests that there may be increased retinol uptake by certain tissues during the acute phase response. The proportion of case children (37/46, 80%) with inadequate liver retinol stores 3 mo after the illness was slightly, but not significantly (χ2 = 2.16, P = 0.14), greater than the proportion of control children (28/42, 67%). Acute respiratory illness therefore did not further deplete retinol stores in this population in which stores were already frequently inadequate.