Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as > 1.0 µmol retinol/g liver. Bone parameters included markers of bone formation (P1NP), bone resorption (CTX), parathyroid hormone, calcium, vitamin A, and vitamin D. Low dietary vitamin A intake increased P1NP. PURPOSE: Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some groups are consuming excessive VA. Bone metabolism and inflammatory parameters were measured in Zambian children who had high prevalence of hypervitaminosis A determined by 13C-retinol isotope dilution. METHODS: Children (n = 143), 5 to 7 years, were recruited into a placebo-controlled biofortified orange maize feeding study for 90 days. Bone turnover (P1NP and CTX) and inflammatory (C-reactive protein (CRP) and alpha-1-acid glycoprotein) biomarkers were measured in fasting blood samples before and/or after intervention with the following: (1) VA at the recommended dietary allowance (400 µg retinol activity equivalents/day (as retinyl palmitate)), (2) maize enhanced with the provitamin A carotenoid ß-carotene (2.86 mg/day), or (3) a placebo. Parathyroid hormone, calcium, and 25(OH)-vitamin D were measured at end line. RESULTS: Bone formation, as measured by P1NP, increased (P < 0.0001) in the placebo group who consumed low preformed VA during the intervention. Bone resorption, measured by CTX, was not affected. P1NP and CTX were negatively associated with inflammation, most strongly with CRP. Serum calcium did not differ among groups and was low (7.29 ± 0.87 µg/dL). Serum 25(OH) D did not differ among groups (54.5 ± 15 nmol/L), with 91% < 75 nmol/L and 38% < 50 nmol/L. CONCLUSIONS: Reduction of dietary preformed VA in Zambian children for 4 months improved bone formation. Chronic consumption of preformed VA caused hypervitaminosis A and may impair bone formation. In children, this could be associated with failure to accrue optimal peak bone mass. TRIAL REGISTRATION: The NIH Clinical Trial registry number is NCT01814891; https://clinicaltrials.gov/ct2/show/NCT01814891 .

Carrot leaves improve color and xanthophyll content of egg yolk in laying hens but are not as effective as commercially available marigold fortificant1.

Yellow and orange egg yolks are good sources of xanthophyll carotenoids, consumption of which is associated with health benefits, such as cancer prevention, eye health, and bone health. Industrial feed fortificants used to improve egg yolk color and carotenoid concentration typically are derived from marigold flowers. Green leafy vegetables are also concentrated sources of the xanthophylls lutein and zeaxanthin (L+Z), but they have not been rigorously evaluated in laying hen feeds as a yolk colorant. The addition of food manufacturing byproducts, including carrot leaves, to animal feed is a promoted method of improving animal nutrition. The ability of dehydrated carrot leaves to improve egg yolk color and L+Z concentration was evaluated by feeding laying hens (n = 40) white maize-based feeds fortified with 2 different dehydrated carrot leaves, marigold as a positive control, or no fortificant as a negative control for 28 D. After a 7-D washout period, the hens were separated into 4 groups, and eggs were collected every other day. Yolks were analyzed by using a portable colorimeter to define the color space and by ultra-performance liquid chromatography to determine the carotenoid profile. Carotenoid concentration rapidly declined from day 0 to 8, confirming adequate washout conditions. The white maize negative control (WM) day 28 lutein concentration (3.59 ± 0.51 nmol/g) was significantly less than orange-carrot leaf-treated (OCL) (5.34 ± 0.36 nmol/g) and red-carrot leaf-treated hens (RCL) (5.92 ± 1.00 nmol/g) in addition to the marigold-treated hens (MG). However, MG was significantly higher than both leaf-treated groups. From day 8 (3.93 ± 0.74 nmol/g) to 28 (9.32 ± 1.66 nmol/g), MG had the largest increase in lutein and was the only treatment to surpass day 0 initial concentrations (8.50 ± 1.64 nmol/g). A similar trend was observed for zeaxanthin and was reflected in the color space.

Hypercarotenodermia in Zambia: which children turned orange during mango season?

Vitamin A (VA) deficiency is a public health problem in many countries. The World Health Organization recommends high-dose VA supplements to children aged 6-59 months based on unequivocal evidence that supplements decreased mortality risk. VA supplements were meant as a temporary intervention until more sustainable approaches could be implemented. Fortification of processed foods with preformed VA is a means to improve VA status. The most recent addition of retinyl palmitate to cooking oil in countries that may also fortify margarine and milk will undoubtedly have a positive impact on VA status. However, quantitative measures have not been used to assess the underlying VA status of the groups who have adopted widespread fortification. The addition of preformed VA to otherwise adequate diets in VA may cause excessive total body stores. Monitoring population status will require accurate VA assessment to ensure that hypervitaminosis does not prevail. This perspective describes a cohort of rural Zambian children who have adequate diets in VA, mostly as provitamin A carotenoids; who were given high-dose VA supplements till the age of 5 years; who have access to VA-fortified sugar; and whose mothers had access to VA-fortified sugar throughout pregnancy and lactation. Many of these children turned orange during mango season, and this phenomenon occurred at estimated liver reserve concentrations >1 µmol retinol equivalents/g liver. It will be necessary to continue to monitor VA status, including all sectors of the population that have access to successful interventions, to optimize health with the intent to lower retinol content of fortified foods or better target VA supplementation to areas of most need.

ß-Cryptoxanthin biofortified maize (Zea mays) increases ß-cryptoxanthin concentration and enhances the color of chicken egg yolk.

The laying hen has a natural ability to deposit carotenoids into its egg yolks, especially the xanthophyll carotenoid lutein that is used commercially as an egg colorant. Can this ability to deposit carotenoids be used to enrich egg yolk provitamin A value? After a 10-d carotenoid depletion period in hens (n = 24), the effects of a 20-d intervention with high-ß-cryptoxanthin, high-ß-carotene, or typical yellow maize on color and carotenoid profile were compared with the effects of a white maize diet (n = 6/treatment). Eggs were collected every other day and yolks were analyzed by using a portable colorimeter to define the color space and by using an HPLC to determine the carotenoid profile. The high-ß-cryptoxanthin and yellow maize increased ß-cryptoxanthin in the yolk (0.55 ± 0.08 to 4.20 ± 0.56 nmol/g and 0.55 ± 0.08 to 1.06 ± 0.12 nmol/g, respectively; P < 0.001). Provitamin A equivalents increased in eggs from hens fed high-ß-cryptoxanthin maize (P < 0.001) but not the high-ß-carotene maize. The color (L*, a*, and b*) assessment of the yolks showed an increase in the high-ß-cryptoxanthin treatment for the red-green a* scale (P < 0.001) and a decrease for the light-dark L* scale (P < 0.001). No appreciable change was noted in the yellow-blue b* scale for the high-ß-cryptoxanthin treatment; but significant changes were noted for the yellow (P = 0.002) and high-ß-carotene maize (P = 0.005) treatments, which were most evident at the end of the washout period with white maize. ß-Cryptoxanthin-biofortified maize is a potential vehicle to elevate provitamin A equivalents and to enhance the color of yolks. This could lead to a human health benefit if widely adopted.

Increased vegetable and fruit consumption during weight loss effort correlates with increased weight and fat loss.

BACKGROUND: Individuals who focused on calorie counting lost more weight than those who focused on increasing vegetable and fruit (V&F) intake in a weight loss program. We now present serum carotenoid data (biomarkers of V&F intake) from both groups and test whether these biomarkers correlate with changes in weight and body fat. DESIGN: Sixty obese volunteers were randomized to one of the following weight loss programs: 500 kcal per day reduction (Reduction) or a focus on consuming eight vegetables per day and 2-3 fruits per day (HiVeg). Volunteers in the Reduction group were 36.8±10.3 years with a body mass index of 33.5; 83% were white, 17% chose not to report race; 70% were not Hispanic or Latino, 13% were Hispanic or Latino and 17% chose not to report ethnicity. Volunteers in the HiVeg group were 30.4±6.6 years with a body mass index of 33.2: 74% white, 11% Asian, 5% black or African American, 5% multiracial and 5% chose not to report race; 89% were not Hispanic or Latino, 5% were Hispanic or Latino and 5% chose not to report ethnicity. Subjects were taught basic nutrition principles, received breakfast and lunch 5 days per week for 3 months, meals 2 days per week during month 4, then regular phone calls to month 12. RESULTS: Total serum carotenoid concentrations increased from baseline to 3 months and remained elevated at 12 months, but there was no difference between groups. Changes in weight, fat and % fat correlated negatively with serum carotenoid concentrations. CONCLUSION: Increased serum carotenoids (a biomarker for V&F intake) correlated with improved weight and fat loss indicating that increased V&F consumption is an appropriate strategy for weight loss. However, in light of the fact that the Reduction group lost more weight, the consumption of increased V&F for the purpose of weight loss should happen within the context of reducing total caloric intake.

An integrated approach to evaluate food antioxidant capacity.

Many methods are available for determining food antioxidant capacity, which is an important topic in food and nutrition research and marketing. However, the results and inferences from different methods may vary substantially because each complex chemical reaction generates unique values. To get a complete and dynamic picture of the ranking of food antioxidant capacity, relative antioxidant capacity index (RACI), a hypothetical concept, is created from the perspective of statistics by integrating the antioxidant capacity values generated from different in vitro methods. RACI is the mean value of standard scores transformed from the initial data generated with different methods for each food item. By comparing the antioxidant capacity of 20 commonly consumed vegetables in the U.S. market that were measured with 7 chemical methods, we demonstrated that the RACI correlated strongly with each method. The significant correlation of RACI with an independent data set further confirmed that RACI is a valid tool to assess food antioxidant capacity. The key advantage of this integrated approach is that RACI is in a numerical scale with no units and has consistent agreement with chemical methods. Although it is a relative index and may not represent a specific antioxidant property of different food items, RACI provides a reasonably accurate rank of antioxidant capacity among foods. Therefore, it can be used as an integrated approach to evaluate food antioxidant capacity.

Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.

OBJECTIVE: To assess the effects of vitamin A supplementation in women with anaemia during pregnancy. DESIGN: Single-centre randomised controlled trial. SETTING: Rural community in southern Malawi, central Africa. POPULATION: Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis. METHODS: Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo. MAIN OUTCOME MEASURES: Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection. RESULTS: Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups. CONCLUSIONS: Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality.

Lycopene and beta-carotene are bioavailable from lycopene 'red' carrots in humans.

OBJECTIVE: The purpose of this study was to determine if lycopene and beta-carotene are bioavailable from lycopene red carrots and if lycopene absorption is affected by carrot fiber. DESIGN: Two crossover studies in humans attempted to compare the relative bioavailability of lycopene and beta-carotene from tomato paste to a genetically selected lycopene red carrot during chronic feeding. Each study contained three treatment groups. The vehicle of administration was muffins. INTERVENTION AND METHODS: Study 1 (n=9) used white carrots (0 mg lycopene/day), red carrots (5 mg/day), and tomato paste (20 mg/day). Study 2 (n=10) used red carrots (2.6 mg/day), tomato paste (5 mg/day), and tomato paste plus white carrots (5 mg/day). Each intervention lasted 11 days with a 10-day washout period between treatments. Serum lycopene and beta-carotene were measured by HPLC. RESULTS: Statistical analysis indicated a significant effect of muffin type in study 1 (P<0.001), and a significant treatment by sequence interaction in study 2 (P=0.04). The response to increasing amounts of lycopene is linear at the levels fed in these studies (r=0.94). The data suggest that maintenance of serum lycopene concentrations at 0.3 micromol/l occurs at about 2 mg/day of lycopene from mixed dietary sources and a serum plateau occurs at >/=20 mg/day. CONCLUSIONS: These results show that lycopene and beta-carotene are bioavailable from red carrots and lycopene absorption seems to be affected by carrot fiber. Making inferences from both studies, the lycopene in the red carrot is about 44% as bioavailable as that from tomato paste. Red carrots provide an alternative to tomato paste as a good dietary source of lycopene and also provide bioavailable beta-carotene.

Vitamin A status and hemoglobin concentrations are improved in Indonesian children with vitamin A and deworming interventions.

OBJECTIVE: Anemia is a major public health problem caused by multiple factors. Vitamin A (VA) depletion can affect hemoglobin concentration (Hb). This study investigated the improvement in Hb and VA status in preschool Indonesian children following supplementation with 210 micromol VA and deworming with 400 mg albendazole. SUBJECTS AND DESIGN: Indonesian children (n = 131) infected with Ascaris lumbricoides and/or Trichuris trichiura were enrolled. The children were grouped by length of time since receiving 210 micromol VA through the local health system. Group 1 (VA administered > or = 4 month before baseline) included 51 children with Ascaris and 29 children with Trichuris. Group 2 had received VA < or = 1 month of baseline from the local health post and included 51 children. INTERVENTION AND METHODS: Immediately following baseline Hb and VA status assessment (modified relative dose response (MRDR) test), Group 1 children were given 210 micromol VA and 400 mg albendazole. Group 2 were randomized to be dewormed either 1 week before, at the same time or 1 week after baseline MRDR and Hb measures. Follow-up assessment was 3-4 weeks after baseline. RESULTS: VA status in Group 1 significantly improved in children with either Ascaris (P < 0.0001) or Trichuris (P = 0.028). Although the prevalence of anemia declined, the improvement in Hb was not significant (P = 0.08). In Group 2, improvement in VA status from the VA delivered through the public health system was maintained for more than 1 month. Hb improved (P = 0.0037) and this improvement appeared to be associated with the length of time between deworming and follow-up assessments. CONCLUSION: Public health supplementation programs to improve VA status may also increase Hb concentrations and decrease anemia prevalence, especially when linked to deworming. SPONSORSHIP: These studies were supported by the Thrasher Research Fund, SmithKline Beecham and Hatch-Wisconsin Agricultural Experiment Station number WIS04533.

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.

Subtoxic hepatic vitamin A concentrations in captive rhesus monkeys (Macaca mulatta).

Although the rhesus monkey (Macaca mulatta) is a widely used experimental animal, its exact vitamin A requirement is unknown. An amount of 430-3600 IU/d [129-1080 retinol equivalents (RE)] is recommended, largely on the basis of depletion studies. Normal hepatic vitamin A appears to be 1 micromol/g liver. Our goal was to determine hepatic vitamin A concentrations of captive monkeys. Liver autopsy samples from rhesus and marmoset (Callithrix jacchus) monkeys were obtained from the Wisconsin Regional Primate Research Center. The rhesus monkeys consumed a diet with 40 IU (12 RE) retinyl acetate/g. Male and female monkeys consumed an estimated 250 and 175 g diet/d, respectively. Marmosets were fed a powder-based diet consisting of 20 IU (6 RE) retinyl acetate/g. The marmosets consumed an estimated 25 g of the diet/d. Liver samples were extracted and analyzed by HPLC. The vitamin A concentration of the rhesus monkey livers was very high at 17.0 +/- 6.3 micromol/g. The hepatic vitamin A of the marmosets was 1.25 +/- 0.58 micromol/g liver. Histologic examination of the livers revealed Ito cell hypertrophy and hyperplasia in the rhesus monkeys compared with the marmosets. Considering that the natural diet of the rhesus monkey (fruits, seeds, roots and insects) is not high in preformed vitamin A, the vitamin A content of the diet appears excessive, supplying four times the NRC recommendation and resulting in high liver stores.

Vitamin A status assessment in rats with (13)C(4)-retinyl acetate and gas chromatography/combustion/isotope ratio mass spectrometry.

Vitamin A assessment methods that indirectly determine liver reserves are still in development. The deuterated vitamin A assay has been successfully applied in several population groups, but large doses of vitamin A must be used and the gas chromatography/mass spectrometry analysis is not very sensitive. Therefore, 10,11,14,15-(13)C(4)-retinyl acetate was synthesized using a modified Wittig-Horner procedure. Thereafter, female Sprague-Dawley rats (n = 47) were fed a vitamin A-deficient diet and divided into three groups: low (L), moderate (M) and high (H) vitamin A. Groups L, M and H were supplemented with 35, 70 and 350 nmol of unlabeled retinyl acetate/d for 17 d. On d 18, three rats from each group were killed to determine baseline (13)C levels. Serum was prepared, and livers were collected and stored at -70 degrees C until analyzed with HPLC and gas chromatography/combustion/isotope ratio mass spectrometry. The remaining rats were supplemented with 52 nmol of (13)C(4)-retinyl acetate. Rats were killed on d 1, 2, 4 and 10. The calculated and measured values of total body reserves (TBR) of vitamin A were within 7% of each other overall, and the relationship was linear (r = 0.98, P < 0.0001). The calculated mean TBR were 0.49 +/- 0.03, 0.82 +/- 0.007 and 3.72 +/- 0.40 micromol, and the measured mean TBR were 0.50 +/- 0.045, 0.69 +/- 0.10 and 3.6 +/- 0.29 micromol for groups L, M and H, respectively. In contrast, serum retinol concentrations did not show a difference among the dietary groups: 1.32 +/- 0.14, 1.35 +/- 0.17 and 1.28 +/- 0.15 micromol/L for groups L, M and H, respectively (P = 0.25). In conclusion, this method offers more sensitivity than traditional methods and may be applicable to human vitamin A status assessment when TBR estimations are desired.

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

OBJECTIVE: To determine the vitamin A and vitamin E statuses of socioeconomically disadvantaged preschool American children. DESIGN: Cross-sectional study of preschool children from socioeconomically disadvantaged families. SETTING: Central Iowa, USA. SUBJECTS: 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. METHODS: Modified relative dose response (MRDR) test for vitamin A status assessment; serum retinol, alpha-tocopherol, cholesterol, and carotenoids; weight for age. RESULTS: 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. CONCLUSIONS: 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.

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 mumol 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.

Application of the modified relative dose response test to pregnant Indonesian women for assessing vitamin A status.

OBJECTIVE: To determine the prevalence of subclinical vitamin A deficiency (vitamin A inadequacy) in Indonesian pregnant women as assessed by the modified relative dose response test. DESIGN: Cross-sectional study of the vitamin A statuses of pregnant (second trimester) women randomly selected from ten different villages. SETTING: West Java, Indonesia. SUBJECTS: A group of 144 pregnant women recruited from the local health posts. INTERVENTIONS: Modified relative dose response (MRDR) test, serum retinol determination and gynecological examinations. RESULTS: The mean (s.d.) MRDR ratio was 0.039 +/- 0.031. Of the women tested, the vitamin A status of 17% was provisionally classified as being marginal (subclinically deficient) (MRDR ratio > or = 0.060), of 35% as being uncertain (MRDR ratio between 0.030 and 0.060) and of 48% as being satisfactory (MRDR ratio < or = 0.030). CONCLUSION: If the vitamin A statuses of the 'uncertain' group are also deemed to be unsatisfactory, approximately half of the pregnant Indonesian women tested could benefit from an increased intake of vitamin A.

Assessment of the vitamin A status in lactating and nonlactating, nonpregnant Indonesian women by use of the modified-relative-dose-response (MRDR) test.

The vitamin A statuses of two groups of Indonesian women were compared by using the modified-relative-dose-response (MRDR) test: 1) lactating, nonpregnant women of lower socioeconomic status (n = 64) and 2) better-educated, premenopausal, nonpregnant, nonlactating women (n = 14). At times from 3 to 6 h after dosing, the mean ratio of dehydroretinol to retinol (DR/R) in the serum was approximately threefold higher in the lactating women than in the control group, eg, 0.109 +/- 0.073 and 0.034 +/- 0.015, respectively, at 5 h. At a provisional DR/R cutoff of 0.06, the vitamin A statuses of 70% of the lactating women and of 7% of the control women were judged to be inadequate. Only 7% of the variability in abnormal MRDR ratios could be attributed to body weight. Both abnormal and normal responses were highly reproducible when performed 0.5-3.25 mo after the first test.

PIP: The vitamin A statuses of two groups of Indonesian women recruited from the suburban areas surrounding Bogor in West Java, Indonesia, were compared by using the modified-relative-dose-response (MRDR) test: 1) 64 lactating nonpregnant women of lower socioeconomic status aged 17-37 years with 1-10 children; and 2) better-educated, pre-menopausal, nonpregnant, nonlactating women, 29-41 years old, with 0-4 children (n = 14) recruited from the staff at the Nutrition Research and Development Center in Bogor. The two groups differed significantly in weight (P 0.001) and age (P 0.001). At times from 3 to 6 hours after dosing, the mean ratio of dehydroretinol to retinol (DR/R) in the serum was approximately threefold higher in the lactating women than in the control group, e.g., 0.109 + or - 0.073 and 0.034 + or - 0.015, respectively, at 5 hours. The slopes of the response means between the groups showed a highly significant difference (P 0.001). The mean DR/Rs obtained by combining 5-hours and 5-hours-predicted values for lactating and control groups were 0.109 + or - 0.073 and 0.034 + or - 0.015, respectively. These two values also showed a highly significant difference (p 0.001). At a provisional DR/R cutoff of 0.06, the vitamin A statuses of 70% of the lactating women and of 7% of the control women were judged to be inadequate. The MRDR values of the control group also show a significant negative correlation with body weight (P 0.01). The slopes [(change in DR/R)/kg body wt] were -0.0055/kg (-0.0036/kg for n - 1) and -0.0015/kg for the lactating and control groups, respectively. Only 7% of the variability in abnormal MRDR ratios could be attributed to body weight. Both abnormal and normal responses were highly reproducible when performed 0.5 -3.25 months after the first test. Thus, safe, low-dose oral supplements of vitamin A ( 8000 IU) should be made available to lactating and pregnant mothers in at-risk populations. Nontoxic provitamin A carotenoids might be preferable as supplements.

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.