The concentration of free holo-retinol binding protein is higher in vitamin A-sufficient than in deficient Nepalese women in late pregnancy

Free holo-retinol binding protein (RBP) [i.e., unbound to transthyretin (TTR)] plays a role in transporting vitamin A across the placenta during pregnancy. In a cross-sectional study of clinically healthy urban women, we assessed the association among clinical and biochemical factors on estimated concentrations of free holo-RBP during the last trimester of pregnancy. Serum samples obtained from a subsample of women (n = 259), who had participated in the Night Vision Threshold Test study in Nepal, were analyzed for determinations of retinol by HPLC, and RBP, TTR, and alpha-1 acid glycoprotein by radial immunodiffusion. Free holo-RBP concentrations were calculated using dissociation constants for free holo- and apo-RBP. Among these women, 30% were vitamin A deficient based on either the RBP:TTR index < or = 0.36 or serum retinol < 1.05 micromol/L. Using stepwise regression analyses, the RBP:TTR index explained 75% of the variance in free holo-RBP concentrations, whereas retinol explained only 14%. Women were classified as vitamin A sufficient (n = 185) or deficient (n = 74) using the RBP:TTR index and were stratified into 3 gestational groups (I: 24-28 wk, II: 29-33 wk, III: >33 wk). Concentrations of free holo-RBP were higher in vitamin A-sufficient women than in vitamin A-deficient women (mean +/- SEM, 48.1 +/- 1.2 vs. 27.6 +/- 0.8 nmol/L; P < 0.001), and in a 3 x 2 factorial analysis, the interaction between gestational group and vitamin A status was significant. These results demonstrate that the RBP:TTR index is a useful proxy for free holo-RBP concentration and that vitamin A status affects its distribution.     

Long-term marginal intakes of zinc and retinol affect retinol homeostasis without compromising circulating levels during lactation in rats.

Marginal zinc or vitamin A intake is more common than previously thought in industrialized and developing countries, with pregnant and lactating women believed to be particularly at risk. However, the lack of sensitive indicators of zinc and vitamin A status precludes accurate assessment of marginal nutriture. Concurrent deficiencies in zinc and vitamin A intake often coexist, and the interaction between zinc deficiency and vitamin A metabolism may confound results from epidemiologic or intervention studies. To investigate effects of a maternal diet chronically restricted in zinc or vitamin A intake on indices of vitamin A metabolism, we fed rats a control diet (C) or a diet marginal in zinc (ZD), marginal in vitamin A (AD), marginal in both (DD) or pair-fed to DD (PF), preconception through lactation. Plasma retinol (ROH) was greater and retinol binding protein (RBP) was lower in rats fed ZD, AD and DD compared with those fed C. Hepatic cellular retinol binding protein (CRBP) expression was greater than controls in rats fed ZD and AD and lower in those fed DD, whereas RBP expression was greater in the DD- and PF-fed groups compared with rats C. Mammary gland CRBP and RBP expression were not affected by the diets. Milk ROH was lower in rats fed AD, and milk RBP was lower in those fed ZD and DD compared with rats fed C. In summary, chronic, marginal intake of zinc or vitamin A resulted in alterations in tissue retinol metabolism and milk retinol levels without decreasing plasma zinc, retinol or ROH:RBP during lactation. These observations are of concern because these parameters, which are commonly used to assess zinc and vitamin A status, may lead to misassessment of marginal zinc or vitamin A nutriture in some human populations.     

Circulating levels of retinol, tocopherol and carotenoid in Nepali pregnant and postpartum women following long-term beta-carotene and vitamin A supplementation

OBJECTIVE: To characterize circulating carotenoid and tocopherol levels in Nepali women during pregnancy and post-partum and to determine the effects of beta-carotene and vitamin A supplementation on their concentration in serum. DESIGN: Randomized community supplementation trial. SETTING: The study was carried out from 1994 to 1997 in the Southern, rural plains District of Sarlahi, Nepal. SUBJECTS: A total of 1431 married women had an ascertained pregnancy, of whom 1186 (83%) provided an analyzable serum sample during pregnancy; 1098 (77%) provided an analyzable 3-4 months post-partum serum sample. INTERVENTIONS: Women received a weekly dose of vitamin A (7000 microg RE), beta-carotene (42 mg) or placebo before, during and after pregnancy. Serum was analyzed for retinol, alpha-tocopherol, gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, lutein + zeaxanthin, and beta-cryptoxanthin concentrations during mid-pregnancy and at approximately 3 months post-partum. RESULTS: Compared to placebo, serum retinol, beta-carotene, gamma-tocopherol, beta-cryptoxanthin and lutein + zeaxanthin concentrations were higher among beta-carotene recipients during pregnancy and, except for beta-cryptoxanthin, at postpartum. In the vitamin A group, serum retinol and beta-cryptoxanthin were higher during pregnancy, and retinol and gamma-tocopherol higher at postpartum. Lutein + zeaxanthin was the dominant carotenoid, regardless of treatment group, followed by serum beta-carotene. Serum lycopene level was lowest, and very low compared to the US population. Serum retinol was higher, and carotenoid and alpha-tocopherol lower, at postpartum than during pregnancy in all groups. CONCLUSIONS: Pregnant and lactating Nepali women have lower serum carotenoid and tocopherol levels than well-nourished populations. beta-carotene supplementation appeared to increase levels of tocopherol and other carotenoids in this population.     

Retinol, alpha-tocopherol and carotenoids in diabetes.

OBJECTIVE: A case-control study was conducted to evaluate the effects of diabetes mellitus on serum levels of vitamin A, alpha-carotene, beta-carotene, alpha-tocopherol, serum and urine RBP. SUBJECTS: One hundred and seven patients with Type 2 diabetes mellitus (28-74 y) were recruited from those attending a primary health care clinic in King Khalid University Hospital in Riyadh City (Saudi Arabia). They were matched for age and sex with 143 healthy individuals. METHODS: Fasting blood samples and 10h urine collections were obtained from all subjects. Levels of vitamins and carotenoids in serum measured by high performance liquid chromatography (HPLC), and of retinol binding protein (RBP) in serum and urine by an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum concentrations of retinol, alpha-carotene, and alpha-tocopherol were similar in both groups after correction of lipid soluble vitamins for serum lipids levels. However, serum beta-carotene concentration was significantly higher in control subjects than diabetics (P = 0.002). Serum and urine RBP concentrations were significantly higher in diabetics than in controls (P = 0.0001). In normal subjects (but not diabetics) serum concentrations of retinol and RBP were higher in men than in women (P = 0.02, P = 0.0001 respectively). In both normal and diabetic subjects, serum levels of alpha-tocopherol (P = 0.007) and urine RBP (P = 0.005), were higher in men than women. Urinary excretion of RBP was significantly higher in diabetic patients with renal impairment than other diabetics or controls (P = 0.0001). There was a negative correlation between fasting blood glucose (FBG) concentration and serum beta-carotene (P = 0.008) in the total combined group and a positive correlation between FBG and urinary RBP/creatinine (P = 0.009) in diabetic patients. CONCLUSION: Serum beta-carotene concentration was significantly lower in diabetic patients than controls. Serum retinol concentration in patients with diabetes was normal, yet serum and urine RBP concentrations were significantly higher in diabetics than in controls.     

Regulation of metabolism of retinol-binding protein by vitamin A status in children with biliary atresia

Regulation of retinol-binding protein (RBP) by vitamin A status was studied in 43 children; 25 had biliary atresia and vitamin A deficiency, 15 had biliary atresia treated by vitamin A, and 9 control children had normal liver and vitamin A status. Vitamin A and RBP were assayed and the two forms of RBP, holo-RBP and apo-RBP, were separated in both liver and plasma. No difference in liver RBP concentrations was found between the three groups; apo-RBP was the most abundant form. Plasma RBP concentrations and the ratio of retinol to RBP were lower for vitamin A-deficient than for vitamin A-treated children. Two models could be proposed: 1) a preferential secretion of holo-RBP with variations in RBP catabolism or synthesis in vitamin A-deficient liver and 2) a continuous secretion of RBP by the liver with a rapid clearance of plasma apo-RBP in vitamin A deficiency.     

Vitamin A: overlapping delivery pathways to tissues from the circulation

Although retinol bound to retinol-binding protein (RBP) is the most abundant retinoid form present in the circulations of humans and most mammals, other retinoid and proretinoid forms are also present in the blood. We are interested in understanding to what extent each of these circulating retinoid forms contributes towards retinoid actions within cells and tissues. Here we report two studies focused on this question. First, we examined retinoid transport and storage in RBP-deficient mice that lack circulating RBP. These mice under normal laboratory conditions are phenotypically normal except for a visual impairment early in life that is corrected if the mice are maintained on a vitamin A-sufficient diet throughout life. The RBP-deficient mice take up vitamin A from the diet into most tissues at least as well as wild type mice. Compared to wild type mice, mice lacking RBP accumulate excess vitamin A in the liver, since there is no RBP to facilitate mobilization of stored retinol from hepatic stores. In a second study, we explored in vitro the actions of carotene cleavage enzyme (CCE) in facilitating beta-carotene cleavage to retinoid in the testis. CCE is most highly expressed in the testis. Pull-down experiments coupled with MALDI-MS analysis showed that mouse testis CCE is able to interact with the testis-specific lactate dehydrogenase-C (LDH-C) isoform. This may suggest that CCE and LDH-C act in concert to catalyze beta-carotene cleavage.     

Plasma vitamin A, E, and beta-carotene levels in adult post-partum Algerian women.

Vitamins A and E are essential for foetal growth, reproduction, and lactation. In this article we report the results of a study, lead in three Eastern Algeria cities, that involved 786 post-partum women and 250 control. Plasma levels of vitamins A, E, beta-carotene, and some nutritional indexes were measured in both groups. In control women, plasma retinol and beta-carotene levels were significantly lower in Algeria than in France (retinol: 1.4 +/- 0.42 vs. 1.78 +/- 0.53 mumol/l; beta-carotene: 0.35 +/- 0.261 vs. 0.94 +/- 0.611). These differences could be the consequence of different beta-carotene and retinol intakes. In Algeria, comparisons between post-partum women and controls, showed that plasma vitamin A and beta-carotene levels were significantly lower in post-partum than in control women. This fact, and the lower level of retinol in control women, raises the question of supplementation for pregnant women in Algeria, at least for those with the lowest standard of living whose protein and zinc levels are also very low after delivery. Plasma vitamin E levels and vitamin E/total lipid ratios were not different in Algeria and in France. Vitamin E concentration was higher during pregnancy, but the vitamin E/total lipid ratio was significantly lower, which shows a relative deficiency at the end of pregnancy. Comparisons of plasma vitamin E levels, at delivery, in primiparous and in multiparous women reveal a better tocopherol status in multiparous women. This difference could reflect an adaptive response to oxidative stress in multiparous women.     

Determinants of plasma retinol, beta-carotene, and alpha-tocopherol during adolescence

The relationships of plasma retinol, retinol-binding protein (RBP), beta-carotene, and alpha-tocopherol with their potential determinants, plasma cholesterol and triglyceride, body fat, dietary intake, stages of pubertal development, and drugs, were examined in a French sample of 263 boys and 246 girls aged 10-15 y. By use of multiple-regression analysis, plasma retinol concentration was positively related to plasma cholesterol and triglyceride, sexual-maturation index, body fat, and being male. For plasma RBP the same predictors were identified. Plasma beta-carotene was positively related to plasma cholesterol and beta-carotene nutrient density and negatively related to body fat and plasma triglyceride. Three predictors of plasma alpha-tocopherol were identified: plasma cholesterol and vitamin E nutrient density, which were positively related to its concentration, and sexual-maturation index, which was negatively related. These results confirm that physiological developmental age should be considered in epidemiologic studies of plasma fat-soluble vitamins in adolescents.     

Innovative approaches to vitamin A assessment

The health and sight of millions of children are compromised each year as a consequence of vitamin A (VA) deficiency. Serum retinol is the most commonly used indicator of VA status. Unfortunately, its use is impractical for national surveys because it involves collection of venous blood, centrifugation and frozen storage before analysis. To make VA assessment more practical, we have developed approaches incorporating dried blood spots (DBS) or portable instrumentation. DBS have been used as a sample matrix to screen neonates for many biochemical compounds. Until recently, it was not thought that VA was stable in DBS. However, we demonstrated that the measure of DBS retinol correlates well with serum retinol in both healthy adults (r(2) = 0.88-0.90) and compromised populations (r(2) = 0.73-0.84). Compared with serum retinol, the sensitivity and specificity of detecting VA deficiency by DBS retinol range from 73 to 93% and from 90 to 100%, respectively. Although few data are available, retinol binding protein (RBP) can also be measured in DBS. RBP has been used as a surrogate marker for serum retinol. Correlations coefficients (r(2)) between serum RBP and serum retinol range from 0.4 to 0.8. In addition, work has been done to develop portable instrumentation to measure VA status in the field. A fluorometer has been optimized for VA fluorescence and is linear into the deficient range for the direct fluorimetric measurement of serum holo-RBP. Progress is being made to use the instrument to directly measure holo-RBP in a drop of whole blood.     

Biochemical but not clinical vitamin A deficiency results from mutations in the gene for retinol binding protein

BACKGROUND: Two German sisters aged 14 and 17 y were admitted to the Tübingen eye hospital with a history of night blindness. In both siblings, plasma retinol binding protein (RBP) concentrations were below the limit of detection (<0.6 micromol/L) and plasma retinol concentrations were extremely low (0.19 micromol/L). Interestingly, intestinal absorption of retinyl esters was normal. In addition, other factors associated with low retinol concentrations (eg, low plasma transthyretin or zinc concentrations or mutations in the transthyretin gene) were not present. Neither sibling had a history of systemic disease. OBJECTIVE: Our aim was to investigate the cause of the retinol deficiency in these 2 siblings. DESIGN: The 2 siblings and their mother were examined clinically, including administration of the relative-dose-response test, DNA sequencing of the RBP gene, and routine laboratory testing. RESULTS: Genomic DNA sequence analysis revealed 2 point mutations in the RBP gene: a T-to-A substitution at nucleotide 1282 of exon 3 and a G-to-A substitution at nucleotide 1549 of exon 4. These mutations resulted in amino acid substitutions of asparagine for isoleucine at position 41 (Ile41-->Asn) and of aspartate for glycine at position 74 (Gly74-->Asp). Sequence analysis of cloned polymerase chain reaction products spanning exons 3 and 4 showed that these mutations were localized on different alleles. The genetic defect induced severe biochemical vitamin A deficiency but only mild clinical symptoms (night blindness and a modest retinal dystrophy without effects on growth). CONCLUSIONS: We conclude that the cellular supply of vitamin A to target tissues might be bypassed in these siblings via circulating retinyl esters, beta-carotene, or retinoic acid, thereby maintaining the health of peripheral tissues.     

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.     

Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin A status in both mothers and infants

BACKGROUND: Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant. OBJECTIVE: We examined whether supplementation during pregnancy with iron and folic acid plus beta-carotene or zinc or both improves the micronutrient status of mothers and infants postpartum. DESIGN: Pregnant women (n = 170) were supplemented daily only during pregnancy with beta-carotene (4.5 mg), zinc (30 mg), or both or placebo plus iron (30 mg) and folic acid (0.4 mg) in a randomized, double-blind, placebo-controlled trial. Micronutrient status was assessed 1 and 6 mo postpartum. RESULTS: Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not. Infants born to mothers supplemented with beta-carotene + zinc had higher plasma retinol concentrations, with the frequency of vitamin A deficiency reduced by >30% compared with the other 3 groups. Breast-milk beta-carotene concentrations were higher in all women supplemented with beta-carotene, but breast-milk retinol concentrations were higher only in women who received beta-carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants. CONCLUSIONS: Zinc supplementation during pregnancy improved the vitamin A status of mothers and infants postpartum, which indicates a specific role of zinc in vitamin A metabolism. Addition of both beta-carotene and zinc to iron supplements during pregnancy could be effective in improving the vitamin A status of mothers and infants.     

Retinol analysis in dried blood spots by HPLC

There are many advantages to measuring vitamin A in dried blood spots (DBS) from a finger prick as compared to plasma collected by venipuncture. The advantages include easier collection, transport and storage; accessibility to younger and more remote populations; and decreased risk of disease transmission. We describe a method for the extraction of retinol from DBS for analysis by HPLC and initial comparison to plasma retinol. The effects of various buffers, detergents, antioxidants and chelators were evaluated to establish the most effective approach to elute the retinol: retinol binding protein (holo-RBP) complex from the blood collection cards. The process involves ultrasonic agitation to elute holo-RBP into a phosphate buffer containing an antioxidant and metal chelator. The holo-RBP complex was denatured by the addition of ethanol containing additional antioxidants permitting the extraction of free retinol into hexane. Following solvent evaporation, the extract was dissolved in methanol for HPLC analysis. The initial measured retinol levels in freshly collected DBS declined for 6-10 d whether stored at 25, 4 or -20 degrees C, but remained consistent thereafter (homeostatic). By incorporating a "recovery/volume adjustment" factor, measured retinol values in homeostatic DBS were adjusted to the equivalent of plasma retinol. For 17 normal adults, the correlation coefficient was 0.90 between plasma retinol and adjusted DBS retinol in samples that had been stored at -70 degrees C for < 9 mo. The use of this new sample matrix for vitamin A assessment will allow access to previously unavailable populations.     

Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal

BACKGROUND: Impaired dark adaptation occurs commonly in vitamin A deficiency. OBJECTIVE: We sought to examine the responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in Nepali women. DESIGN: The dark-adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were also tested at 3 mo postpartum. Results were compared with those for 100 nonpregnant US women of similar age. The amount of light required for pupillary constriction was recorded after bleaching and dark adaptation. RESULTS: Pregnant women receiving vitamin A had better dark-adaptation thresholds (-1.24 log cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta-carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction). Dark-adaptation threshold was associated with serum retinol concentration in pregnant women receiving placebo (P: = 0.001) and in those receiving beta-carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving placebo, mean dark-adaptation thresholds were better during the first trimester (-1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2); P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all 3 groups). CONCLUSIONS: During pregnancy, pupillary dark adaptation was strongly associated with serum retinol concentration and improved significantly in response to vitamin A supplementation. This noninvasive testing technique is a valid indicator of population vitamin A status in women of reproductive age.     

Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease

Retinol binding protein 4 (RBP4) is the specific transport protein of the lipophilic vitamin A, retinol, in blood. Circulating RBP4 originates from the liver. It is secreted by hepatocytes after it has been loaded with retinol and binding to transthyretin (TTR). TTR association prevents renal filtration due to the formation of a higher molecular weight complex. In the circulation, RBP4 binds to specific membrane receptors, thereby delivering retinol to target cells, rendering liver-secreted RBP4 the major mechanism to distribute hepatic vitamin A stores to extrahepatic tissues. In particular, binding of RBP4 to ‘stimulated by retinoic acid 6’ (STRA6) is required to balance tissue retinoid responses in a highly homeostatic manner. Consequently, defects/mutations in RBP4 can cause a variety of conditions and diseases due to dysregulated retinoid homeostasis and cover embryonic development, vision, metabolism, and cardiovascular diseases. Aside from the effects related to retinol transport, non-canonical functions of RBP4 have also been reported. In this review, we summarize the current knowledge on the regulation and function of RBP4 in health and disease derived from murine models and human mutations.     

Serum levels of vitamin A and retinol binding protein in chronic renal patients treated by continuous ambulatorial peritoneal dialysis.

The possible causes and consequences of hypervitaminosis A and retinol binding protein (RBP) levels were investigated in patients with chronic renal disease submitted or not to dialysis treatment. The study was conducted on 20 patients divided into two groups: 10 patients with chronic renal failure (CRF) treated by continuous ambulatorial peritoneal dialysis (CAPD), and 10 CRF patients with no dialysis treatment. Ten normal subjects formed the control group. Retinol levels were determined by HPLC, and RBP levels by immunoassay in plasma and in post-dialysis fluid at different periods of time. Laboratory tests were carried out on all subjects, and dietary history was taken. Patients on dialysis had higher retinol levels than untreated patients. Retinol levels were found to be correlated with RBP levels. Serum retinol and RBP levels did not vary with diet, age or time of disease, dialysis group or time of dialysis, nor were they correlated with the levels measured in the dialysis fluid (CAPD). There was no significant correlation in retinol levels between chronic patients and controls. It is suggested that vitamin A and RBP clearances during dialysis do not accompany urea or creatinine clearance. Hypervitaminosis A did not show any toxic effect.     

Use of serum retinol-binding protein for prediction of vitamin A deficiency: effects of HIV-1 infection, protein malnutrition, and the acute phase response

BACKGROUND: Serum retinol is the most commonly used indicator of vitamin A status. Retinol is transported in a 1-to-1 complex with retinol-binding protein (RBP). RBP is easy and inexpensive to measure, and studies have shown a high correlation between concentrations of RBP and concentrations of retinol. The performance of RBP in the context of infection or protein malnutrition, however, has not been evaluated. OBJECTIVE: Our aim was to determine whether RBP is a good surrogate measure for retinol in the context of HIV-1 infection, protein malnutrition, and the acute phase response. DESIGN: The relation between RBP and retinol was examined in a cross-sectional study of 600 Kenyan women. RESULTS: There was a high correlation between concentrations of RBP and those of retinol (r = 0.88). When equimolar cutoffs were used, RBP predicted marginal vitamin A status (retinol < 1.05 micro mol/L) with 93% sensitivity and 75% specificity and vitamin A deficiency (retinol < 0.70 micro mol/L) with 91% sensitivity and 94% specificity. Similarly high sensitivities and specificities were found among subgroups with HIV-1 infection, a positive acute phase response, and protein malnutrition. Protein malnutrition and a positive acute phase response were common, especially among HIV-1-infected women, and were independently and synergistically associated with lower RBP concentrations. CONCLUSIONS: Equimolar RBP cutoffs predict vitamin A deficiency with high sensitivity and specificity, even in the context of infection and protein malnutrition. Like retinol, RBP may not accurately identify true vitamin A status under all conditions, because the acute phase response and protein malnutrition depress RBP concentrations. However, RBP may be a simple, inexpensive tool for assessment of vitamin A deficiency in population studies.     

Nutritional and haematological status of Chinese farmers: the influence of 13.5 months treatment with riboflavin, retinol and zinc

A retinol (15 mg), riboflavin (200 mg) and zinc (50 mg) supplement or a placebo (D-mannitol) was given to 610 Chinese farmers weekly for 13.5 months. Riboflavin, retinol, beta-carotene, tocopherol and zinc status were measured in all subjects at the start and end of the intervention and in a subsample at 2 months. Plasma vitamin C, haemoglobin and haematocrits were measured on other subsamples at the end of the supplementation period. At the start vitamin A, zinc and riboflavin status were poor. Plasma retinol and zinc concentrations were higher in men than women but the opposite was observed with respect to beta-carotene. There was no difference between the sexes for tocopherol and riboflavin. Tocopherol:cholesterol ratios suggested vitamin E status was good and vitamin C status also appeared adequate. The supplement increased plasma retinol throughout the whole period but riboflavin status improved only over the first 2 months and then remained constant. Plasma zinc increased in both treatment and placebo groups by approximately 15 to 20 per cent in men and women. Mean concentrations of retinol and tocopherol and beta-carotene (in women only) increased by approximately 20 per cent in the placebo group. It is argued that seasonal factors and/or the placebo may have been responsible for the increase in retinol and beta-carotene in the placebo group. The lack of an increase in beta-carotene in the men may have been due to their higher retinol requirements. Lastly, the increase in retinol may have been responsible for the increase in tocopherol and zinc in plasma since these nutrients increased in those whose plasma retinol increased, irrespective of treatment.     

Plasma levels of retinol, carotenoids, and tocopherols in relation to dietary pattern among pregnant Tanzanian women

In Tanzania, as in other developing countries, dietary intake of nutrients in pregnant women is marginal or lower than the recommended intakes and therefore these women are at high risk for deficiencies. Our aim was to evaluate the relationship between diet and plasma levels of retinol, carotenoids, and alpha-tocopherol in the third trimester of pregnancy. Ninety pregnant women aged between 18 and 45 years were equally recruited from three villages. Seven-day food frequency data was collected by questionnaire. Plasma levels of retinol, carotenoids, and tocopherols were assessed by high-performance liquid chromatography (HPLC). Results indicated that cooked green leafy vegetables constituted the major source of provitamin A carotenoids, with low intake of yellow/orange fruits and preformed vitamin A. Lutein, lycopene, and beta-carotene were the predominant carotenoids in the plasma with mean values of 1.61, 0.84, and 0.63 mumol/L, respectively. There was no significant correlation between frequencies of vegetable consumption and either plasma retinol or carotenoids. However, increased consumption of green leafy vegetables with oil, which increases bioavailability, was correlated with high plasma retinol levels (p = 0.03). Low retinol levels (< or = 0.70 mumol/L) were present in 26% of women. The mean plasma retinol concentration was 0.89 mumol/L and 63% of the women had values below 1.05 mumol/L. The mean plasma alpha-tocopherol concentration was 15.4 mumol/L and women with plasma retinol concentration > 1.05 mumol/L had significantly higher mean alpha-tocopherol than women with plasma retinol concentration < or = 0.70 mumol/L (p < or = 0.01). Twenty-four percent of the women were anemic (hemoglobin: Hb < 110 g/L) and the mean Hb value was 116.3 g/L.     

Vitamin A, vitamin E, retinol binding protein (RBP), and prealbumin in digestive cancers

The existence of a relation between vitamin A and vitamin E and human cancers is supported by epidemiologic investigations. The aim of this study is to link the level of these vitamins to those of plasmatic protein carriers like retinol binding protein (RBP) and prealbumin (TTR), in three groups of subjects: healthy patients (n = 78), polyp (n = 34) and digestive cancer patients (n = 70). A paired t-test did not reveal any significant variation in any parameter between the polyp group and controls, but did evidence a significant decrease in serum levels of retinol (p less than 2.10(-4], RBP (p less than 2.10(-4), TTR (p less than 10(-5), and alpha-tocopherol (p less than 2.10(-3), in cancer cases as against control subjects. Comparison of RBP renal clearance and retinol tissue clearance in cancer and healthy patients indicates that the decrease in circulating retinol levels cannot be attributed to an increase in peripheral consumption. The simultaneous reduction of RBP and TTR serum levels is to be considered as a sign of protein denutrition. Thus our results suggest that the decrease serum levels of vitamins A and E observed in digestive cancers are a consequence of this nutritional deficiency.