vitamin-a2 and Vitamin-A-Deficiency

Discovered in the late 1920s, 3,4-didehydroretinol (DROL, vitamin A

Topics: Animals; Bangladesh; Biological Availability; Diet; Fishes; Humans; Prevalence; Vitamin A; Vitamin A Deficiency

Dietary α-carotene is present in oranges and purple-orange carrots. Upon the central cleavage of α-carotene in the intestine, α-retinal and retinal are formed and reduced to α-retinol (αR) and retinol. Previous reports have suggested that αR has 2% biopotency of all-trans-retinyl acetate due in part to its inability to bind to the retinol-binding protein. In the present work, we carried out three studies. Study 1 re-determined αR's biopotency compared with retinol and 3,4-didehydroretinol in a growth assay. Weanling rats (n 40) were fed a vitamin A-deficient diet for 8 weeks, divided into four treatment groups (n 10/group) and orally dosed with 50 nmol/d retinyl acetate (14.3 μg retinol), α-retinyl acetate (143 μg αR), 3,4-didehydroretinyl acetate (14.2 μg DR) or cottonseed oil (negative control). Supplementation was continued until the control rats exhibited deficiency signs 5 weeks after the start of supplementation. Body weights and AUC values for growth response revealed that αR and DR had 40-50 and 120-130% bioactivity, respectively, compared with retinol. In study 2, the influence of αR on liver ROH storage was investigated. The rats (n 40) received 70 nmol retinyl acetate and 0, 17.5, 35 or 70 nmol α-retinyl acetate daily for 3 weeks. Although liver retinol concentrations differed among the groups, αR did not appreciably interfere with retinol storage. In study 3, the accumulation and disappearance of αR over time and potential liver pathology were determined. The rats (n 15) were fed 3.5 μmol/d α-retinyl acetate for 21 d and the groups were killed at 1-, 2- and 3-week intervals. No liver toxicity was observed. In conclusion, αR and didehydroretinol are more biopotent than previously reported at sustained equimolar dosing of 50 nmol/d, which is an amount of retinol known to keep rats in vitamin A balance.

Topics: Animals; Area Under Curve; Body Weight; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Growth; Liver; Male; Rats; Rats, Sprague-Dawley; Vitamin A; Vitamin A Deficiency; Weaning

Relationships between increased adiposity and fat-soluble vitamin storage and metabolism are poorly understood. To examine these associations, 6% or 21% dietary fat was fed to rats for 11 weeks and tissue vitamin A storage determined. Two levels of supplemental vitamin A were administered. At the end of the tenth week, 3,4-didehydroretinol (DR) was administered orally, and its kinetics were followed for 1 week in serum and tissues. Model-based compartmental analysis was applied to these data. Kidney total retinol (R) concentrations were elevated in rats fed 6% compared with 21% dietary fat (n = 24/group). The fractional transfer coefficient (FTC) describing the movement of tracer from plasma to extravascular stores was two times higher in the 6% compared with the 21% fat group. Consistent with the elevated renal R in 6% fat fed rats, there was a 2-fold increase in the FTC representing tracer distribution from plasma to kidney in the 6% compared with 21% fat group. Taken together with a fat main effect on renal vitamin A, our data support the evidence that faster turnover of kidney R may help set the mechanism governing vitamin A tissue distribution during deficiency. Rats fed 21% versus 6% dietary fat conserved hepatic R more efficiently.

Topics: Adipose Tissue; Adiposity; Animals; Body Weight; Dietary Fats; Diterpenes; Liver; Male; Models, Biological; Obesity; Rats; Rats, Sprague-Dawley; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency

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.

Topics: Aging; Animals; Blood; Child, Preschool; Cross-Sectional Studies; Dietary Sucrose; Dietary Supplements; Feces; Female; Food, Fortified; Humans; Infant; Male; Nutrition Assessment; Nutrition Policy; Nutritional Status; Plasmodium; Surveys and Questionnaires; Vitamin A; Vitamin A Deficiency; Zambia

The vitamin A status of 87 children, 7-29 months of age, who were randomly selected from attendees at a pediatric clinic in Ndola, Zambia, were evaluated by the modified relative dose response (MRDR) test. By using a MRDR ratio cut-off point of 0.06, 78% of the children had inadequate vitamin A status. Both male and female children were equally affected. Of those with inadequate vitamin A status, 82% were between 7-19 months of age. A significant inverse relationship (p < 0.005) existed between vitamin A inadequacy and Z scores for height for age, weight for age and weight for height. Children with lower Z scores showed a better vitamin A status in comparison to those with a higher Z score. This unexpected relationship is probably due to an increased demand for vitamin A in children with a higher weight and rapid growth rate. Serum vitamin A values correlated poorly with MRDR values except at extreme ends of the distribution. Although clinical vitamin A deficiency is relatively infrequent in Zambia, we conclude that the vitamin A status of our children nonetheless needs to be improved.

Topics: Child, Preschool; Female; Humans; Infant; Male; Nutritional Status; Vitamin A; Vitamin A Deficiency; Zambia

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.

Topics: Adult; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Indonesia; Vitamin A; Vitamin A Deficiency

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.. 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.

Topics: Administration, Oral; Adolescent; Adult; Body Weight; Dose-Response Relationship, Drug; Female; Humans; Indonesia; Lactation; Nutrition Assessment; Reproducibility of Results; Socioeconomic Factors; Suburban Population; Vitamin A; Vitamin A Deficiency

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.

Topics: Administration, Oral; Body Weight; Child; Child, Preschool; Chromatography, High Pressure Liquid; Conjunctiva; Cytological Techniques; Dose-Response Relationship, Drug; Humans; Indonesia; Infant; Nutrition Assessment; Nutritional Status; Reference Standards; Rural Population; Vitamin A; Vitamin A Deficiency

Effect of vitamin A-deficient diet on Heteropneustes fossilis results in anemia, loss of haemoglobin and erythrocyte, leucocyte and thrombocyte number, inhibition of synthesis of erythroblast along with the reduction of cytoplasmic and nuclear size of different blood corpuscles. Granulocytes are also affected, and although there is loss of granules and appearance of vacuolated lymphocytes, yet neutrophil, eosinophil and basophil show an increase in number, as examined after 90-100 days of administration of vitamin A-deficient diet.

Topics: Animals; Catfishes; Diet; Erythrocyte Count; Fish Diseases; Hemoglobins; Leukocyte Count; Vitamin A; Vitamin A Deficiency

The modified relative-dose-response (MRDR) assay has been validated in rats as a function of vitamin A status and tested in a group of American children. In this study the MRDR assay was applied to West Javan children who are at risk of being vitamin A deficient. Of 86 children enrolled, 75 were tested. In a time-course study involving 22 children aged 3.7-5.3 y, blood samples were taken at different times after doses of 0.35 mumol 3,4-didehydroretinyl acetate/kg body wt. Generally, the ratio of dehydroretinol to retinol (DR-R ratio) peaked between 4 and 8 h. Thereafter, in a survey of 53 children aged 0.6-4.8 y, single blood samples were drawn 5 h after the dehydroretinyl acetate dose. The DR-R ratio ranged from 0.0028 to 0.169. With a DR-R ratio of 0.03 as the cutoff value, 62% of the children were judged to be of marginal vitamin A status.

Topics: Anthropometry; Child, Preschool; Dose-Response Relationship, Drug; Humans; Indonesia; Infant; Nutritional Status; Time Factors; Tretinoin; Vitamin A; Vitamin A Deficiency

3,4-Didehydroretinol (vitamin A2, DR, dehydroretinol), a naturally occurring analogue of retinol (vitamin A1, R), is active in vision, growth and cellular differentiation but is converted to retinol in very small amounts, if at all. When vitamin A-depleted rats were given 500 micrograms of R acetate, a naturally occurring mixture of 480 micrograms DR ester and 20 micrograms R ester or 500 micrograms DR acetate orally in corn oil, serum levels of all administered retinoids peaked between 3.5 and 5 h and then declined. When an oral dose of 600 micrograms DR/kg body wt was administered to rats with various liver reserves of vitamin A, the serum ratio of DR to R at 3.5 h was inversely related to the liver reserves of vitamin A below approximately 2 micrograms/g liver. Because the administration of DR does not affect serum R values, a single blood sample taken at 3.5 h might provide information analogous to that obtained from two blood samples in the conventional relative dose-response method.

Topics: Animals; Chromatography, High Pressure Liquid; Female; Liver; Rats; Rats, Inbred Strains; Tretinoin; Vitamin A; Vitamin A Deficiency

The acetate and palmitate esters of 3,4-didehydroretinol (DR; vitamin A2 alcohol) have been synthesized and characterized. When administered orally in corn oil to female rats, DR was present in the serum as the alcohol, but primarily as esters in the liver. As total stores of retinol (R; vitamin A1 alcohol) decrease, the ratio of DR to R in the serum markedly increases. The ratio of DR to R in serum was greater than 0.27 at liver vitamin A1 palmitate values of less than 3 micrograms/g, 0.05-0.14 at 3-19 micrograms/g, and less than 0.04 at greater than or equal to 20 micrograms/g. Thus, the ratio of DR to R in the serum at a suitable interval after the administration of dehydroretinyl acetate may aid in assessing marginal vitamin A status. DR was not demonstrably converted to R in these studies.

Topics: Animals; Diterpenes; Female; Liver; Rats; Rats, Inbred Strains; Retinyl Esters; Vitamin A; Vitamin A Deficiency

1. The metabolism of dehydroretinyl ester has been studied in vitamin-A-deficient white leghorn chicks. Dehydroretinyl ester was metabolized to 3-hydroxyretinol diester, 3-hydroxyanhydroretinol and rehydrovitamin A2 which were isolated from the intestines and livers of chicks. 2. The metabolism of 3-hydroxyretinol diester and 3-hydroxyanhydroretinol, which were immediate metabolites of dehydroretinol, was studied in chicks. 3. Retinol was not detected in these experiments.

Topics: Absorption; Animals; Animals, Newborn; Chickens; Esters; Liver; Reference Values; Vitamin A; Vitamin A Deficiency

In search of other provitamins A, the metabolism of cryptoxanthin was studied in several species of freshwater fish, i.e. Channa gachua, Labeo boga (retinol-rich) and Heteropneustes fossilis (dehydroretinol-rich). The fish were either allowed to starve for 20-25 d to make their intestines free from carotenoids and vitamin A or kept on a vitamin-A-deficient diet for 140-150 d to deplete the initial reserve of vitamin A in the livers. Retinol-rich freshwater fish such as C. gachua and L. boga converted cryptoxanthin into retinol and no 3-dehydroretinol or 3-hydroxyretinol could be isolated from those fish that received cryptoxanthin. 3-Hydroxyretinol and 3-dehydroretinol were isolated from the vitamin-A-deficient H. fossilis, a 3-dehydroretinol-rich freshwater siluroid, after the administration of cryptoxanthin.

Topics: Animals; beta Carotene; Carotenoids; Cryptoxanthins; Fishes; Intestinal Mucosa; Liver; Vitamin A; Vitamin A Deficiency; Xanthophylls

Topics: Animals; Biotransformation; Fishes; Liver; Vitamin A; Vitamin A Deficiency

Topics: Animals; Larva; Photoreceptor Cells; Retinal Pigments; Spectrophotometry; Vitamin A; Vitamin A Deficiency; Xenopus laevis