Plasma alpha1-acid glycoprotein can be used to adjust inflammation-induced hyporetinolemia in vitamin A-sufficient, but not vitamin A-deficient or -supplemented rats

We examined the association between alpha(1)-acid glycoprotein (AGP), all-trans-retinol (retinol), and albumin concentrations in a longitudinal animal model of IL-6-induced inflammation. Vitamin A-sufficient (VAS) male Sprague-Dawley rats were administered recombinant human IL-6 [n = 4, 65 mug/(kg.d)] or PBS (n = 4) continuously for 7 d via osmotic minipumps. Plasma samples were obtained daily and concentrations of retinol, AGP, albumin, and total protein were measured. Compared with both baseline and controls, retinol and albumin decreased (P < 0.05), AGP increased (P < 0.05), and total protein concentrations were unaffected in IL-6-treated rats. In vitamin A-deficient (VAD) rats, AGP concentrations were significantly lower at all time points and increased only to one-third of that in VAS rats. The AGP cut-off value indicative of inflammation was 0.11 g/L (i.e., 95% upper limit of baseline concentrations). After 20.5 h, there was an inverse linear correlation between AGP concentrations and the relative change in retinol to baseline (y = -0.18x + 0.48, r = -0.84, P < 0.001). However, changes in AGP and albumin were not correlated (P = 0.94). The application of this function to retinol concentrations in rats from separate experiments showed that hyporetinolemia cannot be adjusted using plasma AGP in VAD or vitamin A-supplemented rats. In conclusion, correcting inflammation-induced hyporetinolemia using an acute-phase protein requires longitudinally derived data, knowledge of vitamin A status, and a common underlying mechanism of change.     

Carotenoid status among preschool children with vitamin A deficiency in the Republic of the Marshall Islands

Although carotenoids are known to be important dietary sources of vitamin A, there have been few epidemiological studies that have characterized the serum concentrations of major dietary carotenoids among preschool children with vitamin A deficiency. We conducted a population-based, cross-sectional study of serum pro-vitamin A carotenoids (alpha -carotene, beta-carotene, beta-cryptoxanthin), non-provitamin A carotenoids (lutein/zeaxanthin, and lycopene), and retinol among 278 children, aged 1-5 y, in the Republic of the Marshall Islands. Vitamin A deficiency was defined as serum retinol <0.70 micromol/L. Geometric mean serum concentrations of carotenoids among children with and without vitamin A deficiency were 0.003 vs 0.006 micromol/L for alpha-carotene (P = 0.0017), 0.011 vs 0.023 micromol/L for beta-carotene (P <0.0001), 0.023 vs 0.034 micromol/L for beta-cryptoxanthin (P = 0.0075), 0.007 vs 0.012 micromol/L for lycopene (P = 0.037), 0.044 vs 0.052 micromol/L for lutein/zeaxanthin (P = 0.2), and 0.045 vs 0.074 micromol/L for total provitamin A carotenoids (P <0.0001) respectively. In a multivariate analysis adjusting for sex, age (Odds Ratio [O.R.] 1.44, 95% confidence interval [C.I.] 1.16-1.78), and serum provitamin A carotenoids (O.R. 0.49, 95% C.I. 0.34-0.71) were associated with vitamin A deficiency, but serum non-provitamin A carotenoids were not associated with vitamin A deficiency (O.R. 0.93, 95% C.I. 0.67-1.28). Preschool children with vitamin A deficiency in the Republic of the Marshall Islands have extremely low serum concentrations of provitamin A carotenoids and interventions are needed to improve the dietary intake of provitamin A carotenoids among Marshallese children.     

Retinol binding protein as a surrogate measure for serum retinol: studies in vitamin A-deficient children from the Republic of the Marshall Islands

BACKGROUND: Serum retinol is transported by retinol binding protein (RBP), which has one high-affinity binding site for retinol; consequently, the molar ratio of retinol to RBP in the circulation is approximately 1 to 1. In vitamin A deficiency (VAD), both serum retinol and RBP decline. However, the retinol-RBP relation has not been well studied in populations with a high incidence of severe VAD. OBJECTIVE: The purpose of this study was to determine whether RBP is a good surrogate for serum retinol at the very low retinol concentrations encountered in VAD. DESIGN: The stoichiometric relation between retinol and RBP was studied in 239 Marshallese children: 65 with severe VAD (< or = 0.35 micromol retinol/L), 94 with moderate VAD (0.36-0.70 micromol retinol/L), and 80 with vitamin A sufficiency (> 0.70 micromol retinol/L). RESULTS: Excellent correlation between retinol and RBP (r = 0.94) was observed across all retinol concentrations. Severe VAD was predicted with 96% sensitivity and 91% specificity on the basis of an RBP cutoff of < or = 0.48 micromol/L, whereas moderate VAD was predicted with 87% sensitivity and 98% specificity on the basis of an RBP cutoff of < or = 0.70 micromol/L. CONCLUSIONS: The use of RBP results in the classification of essentially the same children with VAD as does retinol, and RBP is an excellent surrogate for serum retinol. Considering the relative ease of measuring RBP with immunodiagnostic kits compared with that of serum retinol by HPLC, the use of RBP concentrations to assess VAD may be particularly advantageous in field settings. Consequently, measuring RBP concentrations may be a practical alternative to measuring serum retinol in population surveys assessing the prevalence of VAD.     

The effect of vitamin A on epithelial integrity.

Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-beta-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A.     

Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children.

BACKGROUND: Zinc deficiency limits the bioavailability of vitamin A. Because zinc and vitamin A deficiency often coexist in malnourished children, simultaneous zinc and vitamin A supplementation may improve the vitamin A deficiency in these children. OBJECTIVE: A randomized, double-blind, placebo-controlled intervention trial was conducted to evaluate whether combining zinc and vitamin A supplementation would improve the biochemical indexes of vitamin A nutriture. DESIGN: Children aged 12-35 mo were randomly assigned to 1 of 4 intervention groups: 20 mg Zn/d for 14 d (Z group), 60000 retinol equivalents (200000 IU) vitamin A on day 14 (A group), zinc plus vitamin A (ZA group), or placebo syrup and placebo capsule (placebo group). Venous blood was drawn at enrollment and on day 21. RESULTS: Mean serum retinol concentrations were not significantly different between the A and ZA groups. Among vitamin A-deficient children, the proportion of children who remained vitamin A deficient (serum retinol <0.7 micromol/L) after supplementation was 40.6% in the Z group, 37.5% in the A group, and 47.0% in the placebo group; only 13.3% in the ZA group remained vitamin A deficient (P < 0.05 compared with the placebo group). The proportion of children whose retinol binding protein concentrations remained low was significantly lower in the ZA group than in the other groups (P < 0.05). CONCLUSION: Combined zinc and vitamin A supplementation improves vitamin A nutriture in vitamin A-deficient children.     

Detection of vitamin A deficiency in Brazilian preschool children using the serum 30-day dose-response test

BACKGROUND: Vitamin A deficiency (VAD) is endemic in Brazil and health professionals have difficulty in recognizing its subclinical form. In addition, serum retinol concentrations do not always represent vitamin A status in the organism. OBJECTIVE: To identify VAD in preschool children by the serum 30-day dose-response test (+S30DR) and to examine its potential as a tool for the assessment of vitamin A status in the community. DESIGN: A prospective transverse study in which blood samples were obtained from 188 preschool children for the determination of serum retinol concentrations and the children were submitted to ocular inspection and anthropometric measurements. Information about the presence of diarrhea and/or fever during the 15 days preceding the study was also obtained. The children received an oral dose of 200,000 IU vitamin A immediately after the first blood collection. A second blood sample was obtained 30-45 days after supplementation in order to determine the +S30DR. RESULTS: In all, 74.5% (140/188; 95% confidence interval: 68.3-80.7%) of the children presented +S30DR values indicative of low hepatic reserves. The mean serum retinol concentration was significantly lower before supplementation (0.92 and 1.65 micromol/l, respectively; P < 0.0001). No child presented xerophthalmia; 3.7% (7/188) of the children were malnourished. The presence of fever and/or diarrhea during the 15 days preceding the first blood collection did not affect the +S30DR value. CONCLUSIONS: The prevalence of VAD in the study group was elevated. +S30DR proved to be a good indicator of subclinical VAD in children from an underdeveloped country.     

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 microg vitamin A palmitate shortly after delivery, and their infants received 7500 microg at the same time as vaccinations given at approximately 1, 2, and 3 mo of age. In the other group, mothers received a second 60,000-microg dose when their infant was aged 1 mo, and their infants received 15,000 microg at the same time as the routine vaccinations. VAD was defined as a modified relative dose-response test result of >or=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.     

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.     

Moderate maternal vitamin A deficiency affects perinatal organ growth and development in rats

Vitamin A deficiency during pregnancy is associated with detrimental effects in the offspring. We have developed a rat model to examine specific effects of maternal vitamin A status on perinatal growth and development. A total of 54 female rats were fed a vitamin A-free (VAF), -marginal (VAM) or -sufficient (VAS) diet from weaning until mating (at 7 weeks) and throughout pregnancy. Half of the rats in each group were injected with a single large dose of vitamin A on day 10 of pregnancy. Fetal and neonatal samples were taken on day 20 of pregnancy and the day of birth respectively. Maternal plasma retinol concentrations on day 20 and at birth were 50% and 30% lower in the VAF and VAM when compared to the VAS group. Fetal weight and survival did not differ between groups although placental:fetal ratio was higher in the VAF group than in the VAS group (0.195 (SE 0.005) v. 0.175 (SE 0.004), P < 0.05). Rats fed the VAF diet gave birth at 23.5 d, an average of 1 d later than the other groups, and had lower number of live neonates at birth. Fetal liver, heart and lung weights relative to total body weight were lower in the VAF group and had altered growth trajectories. In neonates, only the relative lung weight was reduced. In addition, an increased protein:DNA ratio indicated hypertrophy in fetal kidneys. Vitamin A injection had no additional effect on length of gestation and fetal or neonatal number. However, injection increased relative fetal organ weights in the VAF group but did not alter the effects of vitamin A deficiency in the neonate. These data suggest that chronic vitamin A deficiency during pregnancy compromises liver, heart and kidney and impairs lung growth and development during the last few days of gestation and reduces number of live neonates at birth.     

Nutritional vitamin A status in northeast Brazilian lactating mothers

Background: Vitamin A deficiency is the major cause of morbidity and mortality among children and in women of reproductive age in developing countries. The present study aimed to assess maternal nutritional vitamin A status, as well as analyse the association of preformed vitamin A and pro‐vitamin A consumption on the nutritional status of nursing mothers, based on serum retinol and retinol colostrum concentrations coupled with dietary intake. Methods: Serum and colostrums were collected from 86 healthy parturients, recruited within 16 h postpartum. Blood samples were obtained, the morning after an overnight fast. Retinol was analysed by high‐performance liquid chromatography. Dietary vitamin A was assessed using a food frequency questionnaire and the women were separated into two groups according to the predominant dietary source of vitamin A: group A, >50% preformed vitamin A (n = 37); and group B >50% pro‐vitamin A carotenoids, (n = 49). Results: Serum retinol and total vitamin A ingestion (mean ± SD) were higher in group A than in group B (1.4 ± 0.4 μmol L^?1 and 2072.0 ± 1465.9 μg retinol activity equivalent (RAE) day^?1 versus 1.2 ± 0.6 μmol L^?1 and 1051.6 ± 920.4 μg RAE day^?1, respectively (P < 0.05), but colostrum retinol (3.4 ± 1.7 μmol L^?1 and 3.6 ± 1.9 μmol L^?1) was similar in both groups. In group B, 36.7% (n = 18) of the nursing mothers presented a risk of developing vitamin A deficiency, based on their dietary intake. Conclusions: On the basis of the intake of the pro‐vitamin A carotenoids, some women may be at risk of vitamin A deficiency. However, their status is currently normal, as indicated by serum and milk retinol concentrations.     

Neonatal-age treatment with vitamin A delays postweaning vitamin A deficiency and increases the antibody response to T-cell dependent antigens in young adult rats fed a vitamin A-deficient diet

Vitamin A supplementation for infants and young children is recommended by WHO/UNICEF for countries with a high prevalence of vitamin A deficiency, and vitamin A is often administered at immunization contacts. Using a rat model, we tested whether supplementation with vitamin A or other retinoids at the time of neonatal immunization has prospective benefit in terms of preventing postweaning vitamin A deficiency and promoting antibody responses to T-cell dependent (TD) antigens administered at the neonatal stage and at the young adult stage. Rats were treated orally on postnatal d 6-8 with oil (placebo control), vitamin A, retinoic acid, or a combination of both (VARA) (n > or = 12/group), and immunized with tetanus toxoid (TT) on d 7. The primary anti-TT response was measured on d 21, after which weanling rats were fed the vitamin A-deficient diet until approximately 10 wk. At 8 wk, rats were immunized again with TT to determine the recall response, and with a novel TD antigen, keyhole limpet hemocyanin (KLH), to assess the adult primary response. None of the supplements affected the plasma titer of anti-TT immunoglobulin G (IgG) on d 21 (P = 0.25). However, neonatal-age supplementation with vitamin A or VARA at the young adult stage resulted in: >5 times higher anti-TT IgG recall response (P < 0.01); 5- and 9-times higher anti-KLH primary IgM and IgG responses, respectively (P < 0.05), and plasma retinol in the normal range (approximately 1.0 micromol/L vs. approximately 0.35 micromol/L in retinoic acid-treated and control groups, P < 0.0001). We conclude that early-life supplementation with vitamin A or VARA can prospectively benefit the primary and recall antibody responses to TD antigens administered at the young adult stage, which may involve the maintenance of normal plasma retinol levels.     

A theoretical increase in infants' hepatic vitamin a is realized using a supplemented lactating sow model

Vitamin A deficiency (VAD) is a public health problem affecting millions in developing nations. Supplementation for lactating women, whose needs are high, involves large oral doses of the preformed vitamin. The safety and efficacy of these doses has been inadequately studied. Lactating women typically receive 210 micro mol of retinyl ester during early lactation, but 420 micro mol has also been administered. If larger doses of vitamin A are not significantly more effective in preventing VAD in mothers and infants, then smaller doses would be recommended. We therefore examined the vitamin A concentration of milk from lactating sows (n = 15) that were provided two different doses of vitamin A (i.e., 1050 or 2100 micro mol, n = 6/group) or corn oil (n = 3), corresponding to doses given women on the basis of body weight. Compared with controls, an overall significant treatment effect was found (P = 0.0019), but there was no difference in milk concentration between treatment groups. Theoretically, applying the mean milk vitamin A concentrations of the groups through 12 h and values to 48 h from 4 sows, we estimate that an infant of a supplemented mother could realize an increase of +0.08 or 0.16 micro mol/g liver from the low or high dose, respectively.     

Anaemia and vitamin A deficiency in poor urban pregnant women of Bangladesh

This cross-sectional study investigated the prevalence of anaemia and vitamin A deficiency (VAD) among pregnant women in a poor urban population of Bangladesh. It also examined the association of various socio-economic and dietary factors with anaemia and vitamin A status. A maternal and child health clinic in Dhaka city, Bangladesh was used to obtain the sample. Three hundred and eighty three pregnant women, aged 20-30 years, of 20-30 weeks gestation were randomly selected from women on their first presentation for antenatal care. Socio-economic, pregnancy related information, usual dietary pattern and anthropometric data were collected. Blood haemoglobin and serum retinol (vitamin A) concentrations were determined. About 40% of the pregnant women were anaemic (haemoglobin <11.0 g/dl) and 45% had low serum vitamin A levels (<30 microg/dl); with 8.6% having sub-clinical VAD (serum retinol <20 microg/dl). The women with low serum vitamin A levels had 1.8 times greater risk of being anaemic than did the women with normal vitamin A status. Food frequency data revealed that a large proportion of these women did not consume egg (49%), milk (25%), meat (31%), liver (83%), large fish (32%), small fish (39%) and sweet pumpkin (52%) at all; while about 25% of the women reported consuming dark green leafy vegetables (DGLV) and 64% reported an intake of fruit at least four servings a week. The pregnant women who were either illiterate or received only informal education (up to grade ten) had significantly lower haemoglobin and serum vitamin A levels compared to those who completed at least a secondary school certificate. The women whose husbands were illiterate or received only informal education had significantly (P= 0.01) lower serum vitamin A levels than those whose husbands had received at least a secondary school certificate. The women who came from families with a per-capita income below the poverty line had significantly lower haemoglobin and serum vitamin A levels compared to those who came from families with a per-capita income above the poverty line. The women who consumed three servings or less of DGLV and fruit per week had significantly lower haemoglobin and serum vitamin A levels than those who consumed four or more servings a week. The women who never consumed large fish had significantly lower haemoglobin compared to those who reported at least one serving a week. Furthermore, the women who never consumed sweet pumpkin had significantly lower serum vitamin A than the women who ate at least one serving a week. By multiple regression analysis, intake of meat, DGLV and fruit, and serum vitamin A levels were found to have a significant independent relationship with haemoglobin. The overall F-ratio (9.9) was highly significant (P=0.000), the adjusted R-square was 0.086 (multiple R=0.309). Multiple regression analysis for serum vitamin A also revealed a significant independent relationship with per capita income, haemoglobin levels, intakes of DGLV and sweet pumpkin. The overall F-ratio (10.2) was highly significant (P=0.000), the adjusted R-square was 0.10 (multiple R=0.312). In conclusion, anaemia and vitamin A deficiency were highly prevalent among poor urban pregnant women in Bangladesh. Various socio-economic and dietary factors may influence the anaemia and vitamin A status of these women. The present study emphasizes the need for a comprehensive intervention strategy, which include both nutritional and environmental factors, to improve the nutritional status of this population.     

Vitamin A deficiency is prevalent in children less than 5 y of age in Nigeria

Vitamin A deficiency (VAD) is a serious and widespread public health problem in developing countries. We conducted a nationwide food consumption and nutrition survey in Nigeria to help fomulate strategies to address VAD, among other deficiencies. One objectives was to assess the vitamin A status of children <5 y old. A total of 6480 households with a mother and child <5 y old were randomly sampled. Blood samples were collected by venipuncture and processed to obtain serum for measurement of retinol concentration by HPLC. Nationwide, 29.5% of children <5 y old were vitamin A deficient (serum retinol <0.70 micromol/L). The proportions of children with VAD differed among the agroecological zones; incidences were 31.3% in the dry savanna, 24.0% in the moist savanna, and 29.9% in the humid forest (P < 0.001). More children (P < 0.05) with severe deficiency (serum retinol < 0.35 micromol/L) lived in the humid forest (7.1%) than in the dry (3.1%) or moist savanna (2.4%). The distribution of VA in children <5 y old was 25.6% in the rural sector, 32.6% in the medium, and 25.9% in the urban sector (P < 0.05). In conclusion, VAD is a severe public health problem in Nigeria. Although the proportion of children with low serum vitamin A levels varies agroecologically and across sectors, it is an important public health problem in all zones and sectors.     

Discovery and biological relevance of 3,4-didehydroretinol (vitamin A2) in small indigenous fish species and its potential as a dietary source for addressing vitamin A deficiency

Discovered in the late 1920s, 3,4-didehydroretinol (DROL, vitamin A₂) plays a significant biological role in freshwater fish. The functions of this vitamin have been investigated but to a far lesser extent than those of retinol (ROL, vitamin A₁). A recent study indicating all-trans DROL has 119–127% vitamin A biological activity compared to that of all-trans ROL suggests the significance of DROL for addressing vitamin A deficiency (VAD) in comparison to ROL may be currently overlooked. Freshwater fish such as small indigenous fish species (SIS), with high DROL content can be a promising dietary source for reducing VAD in areas where SIS are readily available and consumed. In this paper, the discovery and biological relevance of DROL are reviewed and furthermore, the vast potential of production and consumption of DROL-rich SIS in food-based strategies to combat VAD in Bangladesh and other developing countries with high prevalence of VAD is highlighted.     

Co-existence of anemia, vitamin A deficiency and growth retardation among children 24-84 months old in Maracaibo, Venezuela

Iron deficiency anemia has been associated with alterations in child development and psychomotor function, being myelination and dopaminergic functioning especially vulnerable. Iron deficiency, at different ages, has different reversible and irreversible effects on CNS. Anemia has also been related to vitamin A deficiency (VAD) and growth retardation. The aim of the present paper was to determine the coexistence of micronutrient deficiency, iron and vitamin A, and macronutrient deficiency (growth retardation). The sample consisted of 202 Venezuelan children, aged 24-84 month old, (104 girls, 98 boys); Anemia, VAD and growth retardation was evaluated by means of blood hemoglobin concentration analysis, HPLC serum retinol (values <20 microg/dl reveal VAD) and height/age and weight/age Z scores (< or = - 2 SD express stunting and underweight). Prevalence of anemia was 38.11%; VAD, 21.78%; stunting, 14.36% and underweight, 9.40%. Anemia and VAD clustered in 7.92%; anemia + stunting or + underweight coexisted in 5.94% and 2.97%, respectively. Stunting and underweight clustered with VAD in 2.97% and 1.48%. The three-way combination with anemia was only seen with stunting in 0.99% of the sample. The prevalence of micronutrient deficiencies remain as significant public health problems which should be simultaneously treated as virtually independent, giving priority to infant, toddler and preschool age groups.     

The effectiveness of relative dose response to retinol intake as an evaluation of vitamin A status of cirrhotic patients

Background: The liver is the main organ involved in homeostasis, metabolism and the storage of retinol. During the fibrotic process, hepatic stellate cells lose their lipid drops, and retinol reserves may deplete. Thus, the present study aimed to evaluate serum retinol levels (RL), hepatic retinol storage and dietary vitamin A intake in cirrhotic patients. Methods: RL were measured by high‐performance liquid chromatography in fifty‐eight cirrhotic patients. Fasting RL <1.05 μmol L⁻¹ indicates vitamin A deficiency (VAD). A relative dose response (RDR) to oral retinol ≥20% indicates an inadequate hepatic retinol reserve (positive test). Severe malnutrition was defined as a mid‐arm muscle circumference (MAMC) and/or triceps skinfold thickness (TSF) below the 5th percentile and moderate malnutrition as MAMC and/or TSF below the 10th percentile. Vitamin A daily intake was estimated by a specific questionnaire. The Child‐Pugh classification of liver disease severity and the Model for End‐Stage Liver Disease were used. Results: Low RL were found in 60% of the patients. Twenty‐three cirrhotic patients had adequate fasting RL (RL = 1.34; 1.05–2.12 μmol L⁻¹) and negative RDR, indicating efficient liver stores. Among thirty‐five cirrhotic patients with low RL, 43% had negative RDR (RL = 0.42; 0.06–0.82 μmol L⁻¹) and 57% had positive RDR (RL = 0.45; 0.09–0.93 μmol L⁻¹). Malnutrition (36%) and inadequate vitamin A intake (55%) were not associated with fasting RL or RDR. Conclusions: VAD was highly prevalent in cirrhotic patients. However, in those with low serum RL and negative RDR, factors other than inadequate vitamin A intake, such as impaired hepatic vitamin A mobilization and intestinal vitamin A malabsorption, which were not examined in the present study, could have influenced the negative results obtained by the RDR method.     

Disproportionate Vitamin A Deficiency in Women of Specific Ethnicities Linked to Differences in Allele Frequencies of Vitamin A-Related Polymorphisms

Background: While the current national prevalence rate of vitamin A deficiency (VAD) is estimated to be less than 1%, it is suggested that it varies between different ethnic groups and races within the U.S. We assessed the prevalence of VAD in pregnant women of different ethnic groups and tested these prevalence rates for associations with the vitamin A-related single nucleotide polymorphism (SNP) allele frequencies in each ethnic group. Methods: We analyzed two independent datasets of serum retinol levels with self-reported ethnicities and the differences of allele frequencies of the SNPs associated with vitamin A metabolism between groups in publicly available datasets. Results: Non-Hispanic Black and Hispanic pregnant women showed high VAD prevalence in both datasets. Interestingly, the VAD prevalence for Hispanic pregnant women significantly differed between datasets (p = 1.973 × 10⁻¹⁰, 95%CI 0.04–0.22). Alleles known to confer the risk of low serum retinol (rs10882272 C and rs738409 G) showed higher frequencies in the race/ethnicity groups with more VAD. Moreover, minor allele frequencies of a set of 39 previously reported SNPs associated with vitamin A metabolism were significantly different between the populations of different ancestries than those of randomly selected SNPs (p = 0.030). Conclusions: Our analysis confirmed that VAD prevalence varies between different ethnic groups/races and may be causally associated with genetic variants conferring risk for low retinol levels. Assessing genetic variant information prior to performing an effective nutrient supplementation program will help us plan more effective food-based interventions.     

Biofortified carrot intake enhances liver antioxidant capacity and vitamin a status in mongolian gerbils

Biofortification efforts have increased concentrations of bioactive compounds in carrots. We measured the antioxidant potential and vitamin A bioefficacy of 4 biofortified carrot varieties [purple/orange, purple/orange/red, orange/red, and orange] in Mongolian gerbils (n = 73). Following a 4-wk vitamin A depletion period and baseline kill (n = 7), freeze-dried carrot powders were mixed into purified feeds and fed to 6 groups (n = 11/group) for 4 wk. White carrot-fed control and vitamin A-supplemented groups were used to calculate carrot provitamin A bioefficacy. Antioxidant capacities of carrot powders, sera, and livers were determined using the 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assay and carotenoid and retinol concentrations were determined by HPLC. Antioxidant capacity of liver extracts from the 4 colored carrot-fed groups [10.1 +/- 1.2 mumol Trolox equivalent antioxidant capacity (TEAC)/g] was significantly higher than the white carrot-fed control group (9.3 +/- 0.9 mumol TEAC/g) and vitamin A-supplemented group (8.8 +/- 1.4 mumol TEAC/g) (P < 0.05). Liver retinol stores in the colored carrot-fed groups (0.62 +/- 0.13 to 0.67 +/- 0.08 mumol retinol/liver) did not differ and were higher than the white carrot-fed control group (0.32 +/- 0.08 mumol retinol/g) (P < 0.0001). Serum antioxidant capacity and retinol did not differ among treatment groups. Liver antioxidant capacity and vitamin A stores were higher in gerbils fed colored carrots than in those fed white carrots. Antioxidant activity is one of several proposed mechanisms by which plant foods, like biofortified carrots, may provide additional health benefits beyond maintenance of vitamin A status.     

Weekly vitamin A and iron supplementation during pregnancy increases vitamin A concentration of breast milk but not iron status in Indonesian lactating women

Studies on the effect of vitamin A and iron supplementation during pregnancy on maternal iron and vitamin A status postpartum are scarce. We investigated whether retinol and iron variables in breast milk and in serum postpartum were enhanced more with weekly vitamin A and iron supplementation during pregnancy than with weekly iron supplementation. During pregnancy, subjects were randomly allocated to two groups and received either (n = 88) a weekly supplement of iron (120 mg Fe as FeSO(4)) and folic acid (500 microg) or (n = 82) the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. Transitional milk (4-7 d postpartum) had higher (P < 0.001) concentrations of retinol and iron than mature milk (3 mo postpartum). Compared with the weekly iron group, the weekly vitamin A and iron group had a greater (P < 0.05) concentration of retinol in transitional milk (as micromol/L) and in mature milk (as micromol/g fat). Although serum retinol concentrations approximately 4 mo postpartum did not differ significantly, the weekly vitamin A and iron group had significantly fewer (P < 0.01) subjects with serum retinol concentrations < or = 0.70 micromol/L than the weekly iron group. Iron status and concentrations of iron in transitional and mature milk did not differ between groups. We have shown that weekly vitamin A and iron supplementation during pregnancy enhanced concentrations of retinol in breast milk although not in serum by approximately 4 mo postpartum. However, no positive effects were observed on iron status and iron concentration in breast milk.