[Prevalence and determinants of anemia in young children in French-speaking Africa. Role of iron deficiency]. / Prévalence et déterminants de l'anémie chez le jeune enfant en Afrique francophone--implication de la carence en fer.

Anemia and iron deficiency are major public health issues worldwide and particularly in Africa. Reliable information about their prevalence and associated factors is required to allow for effective actions. In this study, we used data from recent (2006-2012) large population health surveys, carried out in 11 French-speaking African countries (Benin, Burkina Faso, Cameroon, Congo Brazzaville, Ivory Coast, Gabon, Guinea, Mali, Niger, Democratic Republic of Congo, and Senegal). Hemoglobin (Hb) was assessed and demographic and health-related parameters were obtained from nation-representative samples of children aged 6-59 months. Anemia (Hb<11g/dL) was found in 72.4% of the children (60.2-87.8%), with no gender difference but a slightly lower incidence in older children (62% at age 4-5 years versus 85% at age 9 months), especially for the more severe forms (2.1% versus 8.7%, respectively). Anemia was only slightly but significantly affected by location (75.5% in rural areas versus 67.3% in towns), income (79.8% in lower quintile of income versus 62.3% in higher quintile), or maternal education (74.1% in children from non-educated mothers versus 62.4% in children whose mothers had secondary education). Nearly 50% of women of child-bearing age had anemia. In the countries that report this information, less than 50% (17-65%) of children consumed iron-rich foods regularly and only 12% (7.4-20.5%) received iron supplementation. Infection and parasitism are known to affect some markers of iron status, because of the inflammatory reaction, thereby making the diagnosis of iron deficiency difficult. In the study countries, acute respiratory diseases and diarrhea affected 6.2 and 15.6% of children aged between 6 and 59 months, respectively; their distribution according to age and location is very different from the one of anemia, which is also the case for the distribution of malaria. It is thus likely that a large part of the anemia observed in young children is due to iron deficiency, although further research is needed to confirm this. This fully justifies the nationwide programs of iron fortification of flour, currently undergoing in most countries of French-speaking Africa. Their formal evaluation is still pending but the initial data suggest some efficacy, although far from optimal. It is thus likely that a more holistic approach, including iron fortification, actions against undernutrition and parasitism in children, and actions in favor of improving young women's iron and nutritional status, together with appropriate communication and education objectives, would be more effective.

A multipurpose tool to evaluate the nutritional quality of individual foods: Nutrimap.

BACKGROUND/OBJECTIVES: With obesity and nutrition-related diseases rising, public health authorities have recently insisted nutritional quality be included when advertising and labelling food. The concept of nutritional quality is, however, difficult to define. In this paper we present an innovative, science-based nutrient profiling system, Nutrimap, which quantifies nutritional assets and weaknesses of foods. METHODS: The position of a food is defined according to its nutritional composition, food category, the consumer's nutritional needs, consumption data and major public health objectives for nutrition. Amounts of each of 15 relevant nutrients (in 100 kcal) are scored according to their ability to 'rebalance' or 'unbalance' the supply in the whole diet, compared with current recommendations and intakes. These scores are weighted differently in different food categories according to the measured relevance of the category to a nutrient's supply. Positive (assets) and negative (weaknesses) scores are totalled separately. RESULTS: Nutrimap provides an overall estimate of the nutritional quality of same-category foods, enabling easy comparisons as exemplified for cereals and fruit/vegetables. Results are consistent with major nutritional recommendations and match classifications provided by other systems. Simulations for breakfasts show that Nutrimap can help design meals of controlled nutritional value. CONCLUSIONS: Combining objective scientific bases with pragmatic concerns, Nutrimap appears to be effective in comparing food items. Decision-makers can set their own limits within the Nutrimap-defined assets and weaknesses of foods and reach categorisations consistent with their objectives--from regulatory purposes to consumer information or support for designing meals (catering) or new products (food industry).

Nutrient profiling: comparison and critical analysis of existing systems.

BACKGROUND: Nutrient profiling systems aim at positioning foodstuffs relative to each other according to their contribution to a balanced diet. The accuracy and performance of methodologies are still debated. We present here a critical analysis of the structure and efficiency of the current schemes. METHODS: The literature survey detected only four systems addressing the issue on an 'across the board' approach and with enough detail to enable analysis. The building principles of these systems were compared and their performance was estimated via their classification of a series of 125 foodstuffs on the basis of nutritional composition. These classifications were compared with one another and with an empirical classification by expert nutritionists. RESULTS: All systems gave a similar overview, with fruits and vegetables ranked as the most favourable foods and fatty and sugary foods as the least favourable ones, but numerous discrepancies existed in every system, mainly related to their choice of nutrients and thresholds. The FSA scoring system seemed the most consistent approach, although it still generated some questionable rankings. Expert classification did not clearly validate any scheme, and cannot be considered as a true reference. CONCLUSION: Nutrient profiling systems are confirmed to be powerful tools to translate nutritional information related to the whole diet into the level of individual foods. However, the performance of the existing schemes remains moderate. Alternative approaches, such as considering food categories or introducing more stringent validation steps by a panel of expert nutritionists, could be ways to reach more efficient and consensual tools.

Retinol mobilization from cultured rat hepatic stellate cells does not require retinol binding protein synthesis and secretion.

Retinol mobilization from retinyl esters stores of hepatic stellate cells (HSCs) is a key step in the regulation of mammalian retinol homeostasis, but the precise mechanisms of such a mobilization are still poorly understood. Using primary cultures of HSCs, we first demonstrated that HSCs expressed immunoreactivity against retinol-binding-protein (RBP) when cultured in a medium containing RBP but were unable to synthesize RBP transcripts and proteins. Using pulse and chase-type experiments, we demonstrated that radioactive retinol was released in culture medium without binding proteins. Inhibition of protein secretion by brefeldin A did not modify quantitatively retinol release. This data ruled out, for the first time, the direct involvement of RBP in retinol mobilization from HSCs. Moreover, HSCs co-cultured with primary isolated hepatocytes displayed an increase of retinol transfer from HSCs to hepatocytes when they established direct physical contacts, as compared with co-cultures without contact. Based on this latter data, a mechanism of retinol mobilization from HSCs via the hepatocytes using retinol transfer through cellular membranes is proposed.

Simple method for clinical determination of 13 carotenoids in human plasma using an isocratic high-performance liquid chromatographic method.

We report a reversed-phase high-performance liquid chromatography method which resolves 13 identified carotenoids and nine unknown carotenoids from human plasma. A Nucleosil C18 column and a Vydac C18 column in series are used with an isocratic solvent system of acetonitrile-methanol containing 50 mM acetate ammonium-dichloromethane-water (70:15:10:5, v/v/v/v) as mobile phase at a flow-rate of 2 ml/min. The intra-day (4.5-8.3%) and inter-day (1.3-12.7%) coefficients of variation are suitable for routine clinical determinations.

Processing of vitamin A and E in the human gastrointestinal tract.

We aimed to provide basic data on the processing of vitamin A and E in the human gastrointestinal tract and to assess whether the size of emulsion fat globules affects the bioavailability of these vitamins. Eight healthy men received intragastrically two lipid formulas differing in their fat-globule median diameter (0.7 vs. 10. 1 microm. Formulas provided 28 mg vitamin A as retinyl palmitate and 440 mg vitamin E as all-rac alpha-tocopherol. Vitamins were measured in gastric and duodenal aspirates, as well as in chylomicrons, during the postprandial period. The gastric emptying rate of lipids and vitamin A and E was similar. The free retinol/total vitamin A ratio was not significantly modified in the stomach, whereas it was dramatically increased in the duodenum. The proportion of ingested lipid and vitamins was very similar in the duodenal content. The chylomicron response of lipids and vitamins was not significantly different between the two emulsions. Our main conclusions are as follows: 1) there is no significant metabolism of vitamin A and E in the human stomach, 2) the enzyme(s) present in the duodenal lumen is significantly involved in the hydrolysis of retinyl esters, and 3) the size of emulsion fat globules has no major effect on the overall absorption of vitamin A and E.

Vitamin A, vitamin E and carotenoid status and metabolism during ageing: functional and nutritional consequences (VITAGE PROJECT).

Among the nutritional factors contributing to maintain health during ageing, fat-soluble vitamins (FSV) are crucial to protect against free radical-generated degenerative processes or impaired efficiency of the immune system. However, no sound scientific evidence is able to confirm specific dietary needs in vitamin A, vitamin E and carotenoids for the healthy elderly. VITAGE project aims at providing such evidence by undertaking studies on male volunteers from 3 European countries, aged between 20-75 years. Biomarkers and variables related to status, metabolism and functions will be measured either in steady-state conditions, or during dietary depletion and repletion in FSV. Original, yet already developed, methodologies will provide clear information about the physiological characteristics of vitamin A, vitamin E and carotenoids. Simultaneously, marketing opportunities for FSV-enriched dietetic foods, specifically designed for the elderly will be determined. The scientific and economical evidence obtained in this project will provide the basis to implement a EU nutritional policy towards the elderly and to develop a new sector of dietetic food products.

2,3,7,8-tetrachlorodibenzo-p-dioxin increases serum and kidney retinoic acid levels and kidney retinol esterification in the rat.

Halogenatedorganic environmental contaminants such as dioxins are well-known to affect tissue levels of retinoids. To further investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid homeostasis, adult male Sprague-Dawley rats were killed 1-112 days after a single oral dose of 10 microg TCDD/kg body wt. Additional groups of rats were killed three days after a single oral dose of 0.1, 1, 10, or 100 microg TCDD/kg body wt. Serum and renal retinoic acid levels were measured, as were levels of serum retinol-binding protein (RBP) in liver, kidneys, and serum. Hepatic and renal formation as well as hepatic hydrolysis of retinyl esters were determined, together with hepatic and renal retinoid levels. In addition, one of the retinyl ester hydrolase (REH) activities was investigated in isolated hepatocytes and hepatic stellate cells from rats killed 7 days after a single oral dose of 10 microg TCDD/kg body wt. No increased hepatic REH activity that could explain the decreased hepatic retinyl ester levels following TCDD treatment was found. In the liver, TCDD increased protein levels, but not mRNA levels, of RBP. A causal relationship is suggested for the increased renal lecithin:retinol acyltransferase (LRAT) activity and increased renal retinyl ester levels in TCDD-treated rats. Importantly, TCDD was shown to substantially increase serum and renal levels of retinoic acid. The ability of TCDD to cause increased tissue retinoic acid levels suggests that TCDD may alter the transcription of retinoic acid-responsive genes.

Esterification of vitamin A by the human placenta involves villous mesenchymal fibroblasts.

Vitamin A (retinol) and its active derivatives (retinoic acids) are essential for growth and development of the mammalian fetus. Maternally derived retinol must pass the placenta to reach the developing fetus. Despite its apparent importance, little is known concerning placental transfer and metabolism of retinol, and particularly of placental production and storage of retinyl esters. To elucidate this metabolic pathway, we incubated, in the presence of retinol, 1) human full-term placental explants and 2) primary cultures of major cells types contributing to placental function: trophoblasts and villous mesenchymal fibroblasts. We used HPLC to determine the types and concentrations of retinyl esters produced by these explants and cells. About 14% of total cellular retinol in placental explants was esterified. The most abundant esters were myristate and palmitate. Primary cell cultures showed that fibroblasts efficiently produced retinyl esters, but trophoblasts did not. In both types of experiments, no retinyl esters were detected in the culture medium, suggesting that retinyl esters were produced for storage purpose. These results suggest that villous mesenchymal fibroblasts are primary sites of retinol esterification and storage in the placenta.

Vitamin A in pregnancy: requirements and safety limits.

Most of the functions of vitamin A are mediated through the binding of retinoic acid to specific nuclear receptors that regulate genomic expression. Recent experimental work in transgenic mice showed clearly that normal embryonic development depends on the correct spatial and temporal expression of the receptors in the differentiating cells and on the binding of specific forms of retinoic acid. This implies that the parent compound, vitamin A, is available in adequate forms and quantities. Excessive dietary intake of vitamin A has been associated with teratogenicity in humans in <20 reported cases over 30 y. However, caution must be exercised to avoid unnecessary supplementation of women of childbearing age. Hypovitaminosis A affects millions of women and children worldwide. The main consequence of a poor vitamin A supply during pregnancy is a low vitamin A status at birth and in the next few months. Vitamin A deficiency is strongly associated with depressed immune function and higher morbidity and mortality due to infectious diseases such as diarrhea, measles, and respiratory infections. Vitamin A deficiency is often associated with an increased mother-to-child transmission of HIV-1. The initiation of vitamin A supplementation should be carefully examined in each case according to the risk-to-benefit ratio. The final decision should take into account the estimated vitamin A status of the woman, the availability of vitamin A-rich foods in her diet, and whether supplementation can be supervised.

Effect of vitamin A status at the end of term pregnancy on the saturation of retinol binding protein with retinol.

BACKGROUND: Vitamin A (retinol), which is required for normal fetal development and successful gestation, circulates in the blood bound to a specific protein, the retinol binding protein (RBP). Little is known about the transport and metabolism of this complex protein or about retinol status during normal human pregnancy. OBJECTIVE: The aim of this study was to assess retinol status and transport modalities of retinol in well-nourished women with normal pregnancies, a population poorly investigated compared with pathologic and malnourished pregnant women. DESIGN: The maternal blood and cord blood concentrations of retinol, vitamin E, beta-carotene, RBP, and transthyretin of pregnant French women at term (n = 27) were measured and compared with values from a nonpregnant control group (n = 27). In addition, holo-RBP (retinol bound), apo-RBP (retinol free), and total protein were assessed in both groups to enable the hemodilution occurring during pregnancy to be taken into consideration and to evaluate the extent of saturation of RBP with retinol. RESULTS: Healthy pregnant women at term had normal serum circulatory amounts of retinol, vitamin E, binding proteins, and beta-carotene. However, they had less binding of retinol to RBP (holo-RBP: 49.9% in pregnant women, 54.0% in cord blood, and 77.5% in the control group). CONCLUSION: The results of this study suggest that retinol homeostasis and transport are modified during normal human pregnancy.

Age-related changes in plasma lycopene concentrations, but not in vitamin E, are associated with fat mass.

The aim of the present study was to assess the influence of age on plasma concentration of alpha-tocopherol, retinol and carotenoids with a special attention paid to natural differences in body composition. Forty healthy subjects were recruited: twenty were less than 35 years old and twenty above 60 years old. Males and females were equally represented in each age group. Subjects were kept in energy balance and received controlled diets for 36 h. Fat mass and fat-free mass were determined with the (18)0-enriched water dilution technique. Plasma vitamins A and E, and carotenoid levels were determined after 12 h fasting and were shown to be similar in women and men. Plasma alpha-tocopherol concentration increased with age (+44 % elderly v. young), and correlated with % fat mass and plasma cholesterol. After adjustment for plasma cholesterol, the effect of age and % fat mass disappeared. In contrast, plasma lycopene level was 2-fold lower in the elderly than in the young group, and was inversely correlated with fat mass. When lycopene values were adjusted for fat mass, the effect of age disappeared. These results suggest that plasma levels of vitamin E and lycopene differed in the two age groups and that differences in plasma cholesterol and fat mass might participate in such an effect. Short-term vitamin intake did not appear to influence plasma vitamin concentrations.

Dietary restriction alters retinol and retinol-binding protein metabolism in aging rats.

Recent studies reported that retinoid metabolism was influenced by long-term dietary restriction (DR) in rats. Because plasma retinol was decreased in rats subjected to DR, it was thought that this dietary manipulation may have an effect on retinol-binding protein (RBP) metabolism. Thus, the aim of this study was to assess retinoids, RBP, and transthyretin (TTR) levels in plasma and liver of young (3 months), adult (12 months), and old (22 months) female Sprague-Dawley rats fed ad libitum (AL) or subjected to a 40% DR, enriched (DR+), or not (DR), with vitamins and minerals. Results indicate that hepatic total retinoid concentrations and content increased with age in all the groups. DR+ rats showed higher hepatic retinoid concentrations than age-matched AL and DR rats. Adult and old DR and DR+ rats exhibited significantly lower plasma RBP-retinol and higher total retinoic acid levels than corresponding controls, although these parameters were not influenced by aging. Liver RBP levels were also decreased in DR and DR+ rats when compared to respective AL controls. There was a slight age-related decline in plasma TTR levels in DR and DR+ rats which was not associated with modifications in liver TTR levels. Hepatic gene expression of RBP and TTR, as evaluated by Northern blot hybridization, did not change with age or diet, suggesting that the lower levels of plasma RBP-retinol and liver RBP in vitamin A-sufficient rats subjected to DR may reflect post-transcriptional alterations and/or accelerated degradation of hepatic RBP. The elevated plasma levels of retinoic acid may represent an adaptive mechanism developed by DR rats to maintain retinoid-dependent functions.

Cellular retinol-binding protein I is essential for vitamin A homeostasis.

The gene encoding cellular retinol (ROL, vitA)-binding protein type I (CRBPI) has been inactivated. Mutant mice fed a vitA-enriched diet are healthy and fertile. They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensable for RA synthesis. However, CRBPI deficiency results in an approximately 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells. This reduction is due to a decreased synthesis and a 6-fold faster turnover, which are not related to changes in the levels of RE metabolizing enzymes, but probably reflect an impaired delivery of ROL to lecithin:retinol acyltransferase. CRBPI-null mice fed a vitA-deficient diet for 5 months fully exhaust their RE stores. Thus, CRBPI is indispensable for efficient RE synthesis and storage, and its absence results in a waste of ROL that is asymptomatic in vitA-sufficient animals, but leads to a severe syndrome of vitA deficiency in animals fed a vitA-deficient diet.

Lipid peroxidation and antioxidant status in experimental diabetes.

Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate the oxidative stress related parameters in streptozotocin-induced diabetes in rats using different complementary approaches: susceptibility to in vitro oxidation (lipid peroxidation induction in liver homogenate, red blood cells hemolysis), blood antioxidant status (total antioxidant capacity by two approaches), and plasma isoprostane measurement, a new marker of lipid peroxidation in vivo. We have shown that induced liver thiobarbituric acid reactive substances increased after 4 weeks of diabetes, in spite of increased liver vitamin E content. Red blood cells hemolysis was significantly delayed after 4 weeks of diabetes. Plasma antioxidant capacity (AOC) tended to increase after 4 weeks of diabetes and was correlated with plasma vitamin E levels. Total antioxidant activity (TAA) significantly decreased after 1 week and a significant correlation was observed with plasma albumin levels. Plasma isoprostane (8-epiprostaglandinF2alpha) concentrations were not modified significantly 1 week or 4 weeks after the induction of diabetes. Levels of vitamin E in the diet and changes in its distribution among the body seems to play an important role in the development of oxidative stress during diabetes and its consequences.

Low and high responders to pharmacological doses of beta-carotene: proportion in the population, mechanisms involved and consequences on beta-carotene metabolism.

The aim of this study was to assess the interindividual variability of chylomicron beta-carotene response to a pharmacological load of beta-carotene in the population, to identify the mechanisms responsible for this variability, and to evaluate its consequences on beta-carotene status and metabolism. The variability, as estimated by the 3-h chylomicron beta-carotene response to 120 mg beta-carotene in 79 healthy male volunteers, was high (CV = 61%), but it was unimodal and all the subjects had detectable chylomicron beta-carotene. In 16 subjects randomly selected among the 79, the interindividual variability of the triglyceride-adjusted chylomicron (beta-carotene + retinyl palmitate) response (0-12.5 h area under the curve) was high (CV = 54%), suggesting that there is a high interindividual variability in the efficiency of intestinal absorption of beta-carotene. The chylomicron beta-carotene response was correlated (r = 0.50, P < 0.05) with the chylomicron triglyceride response. The beta-carotene status, as assessed by beta-carotene concentration in buccal mucosal cells, was correlated (r = 0.73, P < 0.05) with the triglyceride-adjusted chylomicron beta-carotene response, i.e., with the ability to respond to beta-carotene. The triglyceride-adjusted chylomicron retinyl-palmitate response was correlated (r = 0.55, P < 0.05) with the triglyceride-adjusted chylomicron beta-carotene response. Plasma all-trans retinoic acid slightly, but significantly, increased (+40%) 3 h after the beta-carotene load, but this increase was not related to the triglyceride-adjusted beta-carotene response. In conclusion, the ability to respond to beta-carotene is highly variable, but there is probably a very small proportion of true non-responders to pharmacological doses of beta-carotene in the healthy population. This variability is apparently mainly due to interindividual differences in the efficiency of intestinal absorption of beta-carotene and in chylomicron metabolism. The ability to respond to beta-carotene can affect the beta-carotene status and the provitamin A activity of beta-carotene, but it has apparently no effect on the amount of retinoic acid appearing in the plasma after the ingestion of a pharmacological dose of beta-carotene.

The bioavailability of alpha- and beta-carotene is affected by gut microflora in the rat.

The present study examined whether the intestinal microflora could affect the bioavailability and vitamin A activity of dietary alpha- and beta-carotene in the rat. In the first set of experiments, we used conventional, germ-free (axenic), and human-flora-associated (heteroxenic) rats. In a second series, conventional rats were treated with either an antibiotic mixture or a potent inhibitor of gastric secretion (Omeprazole). All animals were first depleted of vitamin A over 4 weeks and then were fed on a sterilized diet supplemented with 14 mg beta-carotene and 3 mg alpha-carotene/kg for 2 weeks. In both experiments, a reduction in the intestinal microflora resulted in an increased storage of beta-carotene, alpha-carotene and vitamin A in the liver. Neither the nature of the metabolism of the intestinal microflora (aerobic or anaerobic) nor treatment with omeprazole, to modify intestinal pH, induced a significant effect on the measured variables. When incubated with 15 mumol beta-carotene/l for 72 h, neither the anaerobic nor the aerobic sub-fractions obtained from rat or human faeces contributed to beta-carotene degradation or to vitamin A synthesis. These findings suggest that reduction in gut microflora results in a better utilization of alpha- and beta-carotene by rats, although bacteria do not have a direct effect on the bioavailability of these pigments.