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BACKGROUND: There is a need to determine whether iron absorption from iron amino acid chelates is protected from inhibition by dietary phytate and regulated normally by iron status. OBJECTIVE: The objective of this study was to compare iron absorption from ferrous sulfate, ferrous bisglycinate, and ferric trisglycinate in whole-maize meal; to determine whether iron from ferrous bisglycinate and ferrous sulfate exchanges in the intestinal pool; and to assess iron absorption from ferrous bisglycinate and ferric trisglycinate over a range of iron statuses. DESIGN: In study 1A, 10 iron-sufficient men consumed ferrous sulfate-fortified whole-maize meal porridge equilibrated with (59)Fe-sulfate on day 1 and (55)Fe-bisglycinate on day 2. In study 1B, these volunteers consumed ferrous sulfate-fortified porridge equilibrated with (59)Fe-sulfate and (55)Fe-bisglycinate simultaneously. In studies 2A and 2B, iron absorption from 3 mg Fe as (59)Fe-ascorbate, (55)Fe-bisglycinate, or (59)Fe-trisglycinate in water and in porridge was compared in 23 subjects with a range of iron statuses. Iron absorption was determined from blood radioactivity on day 16. RESULTS: In study 1A, geometric mean iron absorption from ferrous bisglycinate was 6.0% (range: 2.6-13.6%), 4 times higher than that from ferrous sulfate (1. 7%; range: 1.0-3.3%; P < 0.05). In study 1B, absorption from neither source was different from that in study 1A. In studies 2A and 2B, absorption from all sources was strongly inversely related to serum ferritin, with geometric means of 32.5% (iron ascorbate), 9.1% (bisglycinate), and 15.3% (trisglycinate). Iron from ferric trisglycinate was poorly absorbed (2.3%; range: 0.5-9.2%) from maize. CONCLUSION: In whole-maize meal, iron from ferrous bisglycinate is better absorbed than is iron from ferrous sulfate and does not exchange with iron from maize or ferrous sulfate in the intestinal pool. Absorption of iron from bisglycinate and trisglycinate is regulated normally by iron status. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes., Objectives: To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies., Selection Criteria: Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy., Data Collection and Analysis: We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy., Main Results: We included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo.Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women). Although the difference between groups did not reach statistical significance, women who received iron supplements were more likely than controls to report side effects (25.3% versus 9.91%) (RR 2.36; 95% CI 0.96 to 5.82, 11 trials, 4418 women), particularly at doses 60 mg of elemental iron or higher. Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130g/L during pregnancy and at term. Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%., Authors' Conclusions: Prenatal supplementation with daily iron are effective to reduce the risk of low birthweight, and to prevent maternal anaemia and iron deficiency in pregnancy. Associated maternal side effects and particularly high Hb concentrations during pregnancy at currently used doses suggest the need to update recommendations on doses and regimens for routine iron supplementation.

Unlabelled: Universal prenatal daily supplementation with iron (60-120mg iron) plus folic acid (0.4mg), as recommended by INACG/WHO/UNICEF, prevents anemia where iron deficiency is prevalent but may be excessive for non-anemic women. Weekly supplementation with 120mg iron plus various amounts of folic acid similarly prevents significant anemia., Objective: Determine, in non-anemic pregnant women, if oxidative stress is produced by recommended daily or weekly supplementation schemes., Procedure: 100 non-anemic pregnant women, 30% iron-deficient at week 20, were randomly supplemented daily followed by weekly, each for 8 weeks, or in reversed order., Results: With daily supplementation thio-barbituric-acid-reacting-substances (TBARS) increased significantly and high serum ferritin, iron, and excessively elevated hemoglobin occurred near term. During weekly supplementation significant anemia and high iron parameters were prevented, and elevated TBARS declined., Conclusion: In non-anemic pregnant women both schemes prevented significant anemia. Oxidative stress occurred only during daily supplementation periods. Weekly supplementation appears safer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus.Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation., Objectives: To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012)., Selection Criteria: Randomised or quasi-randomised trials., Data Collection and Analysis: We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy., Main Results: This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation.Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD -8.62 g; 95% CI -52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or congenital anomalies.For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women's anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on the results of the review., Authors' Conclusions: The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.

The iron endowment at birth depends, in large part, on the newborn's birth weight and gestational age. These are determined by many factors, some of which are maternal characteristics, including the following: maternal iron stores at her own birth and during her own early life, maternal growth and development, maternal age at conception, intergenesic intervals, maternal body characteristics and iron status at conception and during early pregnancy, gestational body weight gain, and iron status throughout gestation, particularly at conception and early pregnancy, and gestational body weight gain. Although less studied, paternal influences on the initiation and progression of pregnancy and on maternal environmental exposures are also important. Even though tools for the quantitative evaluation of women's iron status are very well developed, the quantitative estimation of body iron in the newborn and young infant remains a challenge. This article describes the crucial role played by the placenta in protecting the embryo and the fetus. In addition, neonatal health, particularly early in pregnancy, is briefly addressed, as are some important aspects of antenatal nutritional interventions that include iron., (© 2011 International Life Sciences Institute.)

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population.

This Special Issue summarizes the results of several studies aimed at providing information on a series of questions related to the adequate protein and energy intakes that allow adequate growth and function in children and work performance and productivity in adults. The effect of different sources of protein on nitrogen balance and the requirements of essential amino acids in young children were also explored in fully recovered, previously malnourished children housed in the Metabolic Ward of the Biomedical Division of INCAP. The following are the main results of these investigations: Animal experiments and studies in children recovering from protein-energy malnutrition (PEM) strongly suggest that even when requirements of all nutrients are satisfied, inactivity reduces the rate of linear growth and physical activity improves it as well as lean body mass repletion. The effects of different energy intakes on nitrogen balance demonstrated how energy intake modifies the need to ingest different amounts of protein to satisfy protein requirements. Insensible nitrogen losses in preschool children and their relation to protein intake was demonstrated. The quality of even "good protein sources" modifies the amount needed to satisfy nitrogen requirements, and corn and bean-based diets can satisfy protein needs for health and even growth of young children. Essential amino acid requirements of 2-year-old children was assessed by diverse measurements of nitrogen metabolism and amino acid levels in blood, and were found lower than those recommended by FAO-WHO. In rural adult populations the relationship between energy and protein intake, productivity and body composition, and the impact of environmental hygiene on nitrogen balance was demonstrated and measured.

Anemia is highly prevalent, especially in poorly nourished populations living in unsanitary conditions. Studies of the Central American population showed that iron was the predominant deficient hematopoietic micronutrient and that correction of nutrient deficiencies led to hematological normality as defined by WHO. The bioavailability of diverse iron compounds added to the mostly vegetable diets of such populations showed the superior absorption of chelated iron (NaFeEDTA) and its strong effectiveness in correcting iron deficiency when added to sugar. The consequences on development and mental behavioral functions as well as on work capacity of iron deficiency and anemia in infants, children and adults, and the positive effects of their correction was demonstrated. In protein-energy malnourished (PEM) children, the deficit in active tissue mass (basal oxygen consumption) and in total hemoglobin content were closely related. This relationship persisted as the rates of active tissue mass repletion was modified by levels of protein intake. This demonstrated the strong adaptive nature of hemoglobin content in response to oxygen needs in PEM and during recovery. Gastrointestinal functions in PEM and in populations demonstrated the bacterial invasion of the upper GI tract and how this resulted in secondary bile acids that are toxic to the intestinal mucosal cells impairing their absorptive functions. Environmental hygiene in populations reversed gut bacterial migration and improved GI function.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

Background: Intake of supplements containing iron or a combination of iron and folic acid by pregnant women may improve maternal health and pregnancy outcomes. Recently, intermittent supplementation regimens have been proposed as alternatives to daily regimens., Objectives: To assess the effectiveness and safety of daily and intermittent use of iron or iron+folic acid supplements by pregnant women., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2009) and contacted relevant organisations for the identification of ongoing and unpublished studies., Selection Criteria: All randomised or quasi-randomised trials evaluating the effect of supplementation with iron or iron+folic acid during pregnancy., Data Collection and Analysis: We assessed the methodological quality of trials using the standard Cochrane criteria. Two authors independently assessed which trials to include in the review and one author extracted data., Main Results: We included 49 trials, involving 23,200 pregnant women. Overall, the results showed significant heterogeneity across most prespecified outcomes and were analysed assuming random-effects. The trials provided limited information related to clinical maternal and infant outcomes.Overall, daily iron supplementation was associated with increased haemoglobin levels in maternal blood both before and after birth and reduced risk of anaemia at term. These effects did not differ significantly between women receiving intermittent or daily iron or iron+folic acid supplementation. Women who received daily prenatal iron supplementation with or without folic acid were less likely to have iron deficiency at term as defined by current cut-off values than those who received no treatment or placebo. Side effects and haemoconcentration (a haemoglobin level greater than 130 g/L) were more common among women who received daily iron or iron+folic acid supplementation than among those who received no treatment or placebo. The risk of haemoconcentration during the second and third trimester was higher among those on a daily regimen of iron supplementation. The clinical significance of haemoconcentration remains uncertain., Authors' Conclusions: Universal prenatal supplementation with iron or iron+folic acid provided either daily or weekly is effective to prevent anaemia and iron deficiency at term. We found no evidence, however, of the significant reduction in substantive maternal and neonatal adverse clinical outcomes (low birthweight, delayed development, preterm birth, infection, postpartum haemorrhage). Associated side effects and particularly haemoconcentration during pregnancy may suggest the need for revising iron doses and schemes of supplementation during pregnancy and adjust preventive iron supplementation recommendations.

This paper presents some of the most commonly utilized indicators to assess food and nutritional status. With respect to the indicators reflecting food access, those addressing poverty as well as food consumption are included. In addition, a variety of serum biochemical measures for the estimation of iron nutritional status and anemia are discussed; it is recommended that some of these be adjusted to account for sex, age, physiological status, and altitude above sea level.

The aim of this study was to determine whether women with low iron stores (plasma ferritin

Background: Lime-treated corn gruel (atole) is a common weaning food in iron-deficient populations, especially in Mexico and Central America, and is a potential vehicle for fortification with iron., Objective: The objective of this study was to screen promising iron compounds for use in the fortification of atole, using in vitro enzymatic digestion-dialysis techniques, while also considering their response to known iron absorption enhancers and inhibitors., Methods: Atole, unaltered or preincubated with phytase, was fortified with iron (10 mg/L) from ferrous sulfate, ferrous bisglycinate, or ferrous fumarate, or with ferric chloride, ferric ammonium citrate, or ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), and submitted to in vitro digestion. Dialysis of calcium, copper, iron, phosphorus, and zinc (analyzed by inductively coupled plasma atomic emission spectrometry) was measured when atole was fortified with iron compounds alone or together with ascorbic acid or disodium ethylenediaminetetraacetic acid (Na2EDTA)., Results: Iron dialyzability was higher with NaFeEDTA (p < .05) than with all other iron compounds, which did not differ among themselves in iron dialyzability. Addition of ascorbic acid had no significant effect on iron dialysis, whereas Na2EDTA enhanced iron dialyzability by 7 to 10 times in unaltered atole and 15 to 20 times in phytase-preincubated atole (p < .05). Addition of Na2EDTA always increased intrinsic zinc dialyzability, and most of the time this increase was significant. Phytase pretreatment generally increased mineral dialysis., Conclusions: Adding EDTA (either as NaFeEDTA or as Na2EDTA) to atole can increase the dialyzability of ferrous and ferric iron compounds and enhance the dialyzability of intrinsic zinc without any negative effects on calcium, phosphorus, or copper dialysis.

Three mutations have recently been detected in the hereditary hemochromatosis HFE gene (282C-->Y, 63H-->D, and 65S-->C). To determine their prevalence in a northeastern Spanish Mediterranean population, we studied 812 subjects between 18 and 75 years of age, randomly selected from the electoral roll of three villages. There were no homozygotes for the 282C-->Y or S65D mutations in this sample. For the 63H-->D mutation, 4.8% were homozygotes; 4.3, 32.3, and 2% were heterozygotes for the 282C-->Y, 63H-->D, and 65S-->C mutations, respectively. The prevalence of compound heterozygotes was 2% for 282C-->Y/63H-->D and 0.6% for 63H-->D /65S-->C. We found no significant differences between men and women. In conclusion, 46% of this Mediterranean population of Spain are carriers of at least one of the three mutations that can increase iron absorption.

Background: It has been suggested that routine intake of supplements containing iron or combination of iron and folic acid during pregnancy improves maternal health and pregnancy outcomes., Objectives: To assess the efficacy, effectiveness and safety of routine antenatal daily or intermittent iron supplementation with or without folic acid during pregnancy on the health of mothers and newborns., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2005). Additionally, we contacted relevant organizations for the identification of ongoing and unpublished studies., Selection Criteria: All randomised or quasi-randomised trials evaluating the effect of routine supplementation with iron or combination of iron and folic acid during pregnancy., Data Collection and Analysis: We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion and one author extracted data. We collected information on randomisation method, allocation concealment, blinding and loss to follow up. The primary outcomes included maternal and infant clinical and laboratory outcomes., Main Results: Forty trials, involving 12706 women, were included in the review. Overall, the results showed significant heterogeneity across most prespecified outcomes. Heterogeneity could not be explained by standard sensitivity analyses including quality assessment; therefore, all results were analysed assuming random-effects. Very limited information related to clinical maternal and infant outcomes was available in the included trials. The data suggest that daily antenatal iron supplementation increases haemoglobin levels in maternal blood both antenatally and postnatally. It is difficult to quantify this increase due to significant heterogeneity between the studies. Women who receive daily antenatal iron supplementation are less likely to have iron deficiency and iron-deficiency anaemia at term as defined by current cut-off values. Side-effects and haemoconcentration are more common in women who receive daily iron supplementation. No differences were evident between daily and weekly supplementation with regards to gestational anaemia; haemoconcentration during pregnancy appears less frequent with the weekly regimen. The clinical significance of hemoconcentration defined as haemoglobin greater than 130 g/L remains uncertain., Authors' Conclusions: Further studies are needed to assess the effects of routine antenatal supplementation with iron or a combination of iron and folic acid on clinically important maternal and infant outcomes.

Background: We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20., Methods: Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated., Results: Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74)., Conclusions: In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

Objective: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc., Methods: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study., Results: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively., Conclusion: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.

Background: Little is known about the long-term evolution, nutrition status, growth, and eventual deficiencies of patients with short bowel syndrome (SBS) adapted to oral feeding after parenteral nutrition (PN). Because there are not absolute criteria for weaning from parenteral or enteral nutrition to oral feeding, new nutrient deficiencies may develop. Subtle nutrition deficits could induce subclinical immune deficiencies; therefore, we studied long-term growth, nutrition status, and the state of the immune system in 10 patients with SBS after weaning PN for at least 2 years., Methods: Ten children with SBS (3-12 years old; mean, 7.4 years) who had not received PN for at least 2 years were studied. Anthropometric measurements, hemoglobin values, and indicators of iron, zinc, copper, folate and vitamin B(12) nutrition status were evaluated, along with immunoglobulins, lymphocyte subpopulations, and polymorphonuclear candidicidal activity., Results: Weight-for-height was normal in 8 children; height-for-age was low in 5 children whose SBS was established early in life. Fat body mass was also low in 5 subjects. Four children presented macrocytosis, 2 with anemia. Low serum levels of vitamin B(12) (1 child), folates (4 children), and ferritin (2 children) were observed. Diminished candidicidal activity (4 children) was the only remarkable immunological abnormality., Conclusion: Many biologic and growth deficiencies are frequently seen in patients with SBS, even in children adapted to enteral feeding. This finding and the existence of previously unreported decreased candidicidal activity in some patients with SBS deserve long-term clinical and biologic follow up.

Daily iron supplementation programs for pregnant women recommend amounts of iron that are considered by some to be excessive, and either lower-dose or less frequent iron supplementation regimens have been proposed. A randomized, placebo-controlled study was performed to assess and compare the relative effectiveness of a weekly (WS) or twice weekly (TW) iron supplementation schedule in maintaining or achieving hemoglobin (Hb) levels at term considered to carry minimal maternal and fetal risk (90-130 g/L). Pregnant women (n = 116) at wk 10-30 of gestation (63 WS and 53 TW) were enrolled in the study (52 in WS and 44 TW completed the study). Women were randomly allocated to receive a 120-mg oral dose of iron as ferrous sulfate and 0.5 mg of folic acid weekly (n = 52) or 60 mg iron and 0.25 mg folic acid and a placebo twice weekly (n = 44). Hb, hematocrit, serum ferritin, and transferrin saturation were estimated at baseline and at 36-39 wk of gestation. Baseline dietary data and the presence and intensity of intestinal helminthic infections were assessed. The duration of supplementation was 14 +/- 4 wk and the median level of adherence was 60.5%. Hb concentrations improved in women following the TW regimen and in women following WS who had low baseline Hb levels. About 89% of WS women and 95% of TW women maintained Hb levels at term (between 90 g/L and 130 g/L), a range associated with optimal pregnancy outcomes. One woman in the TW group exhibited higher Hb levels that potentially carried perinatal risk (>130 g/L). Intermittent iron and folic acid supplementation may be a valid strategy when used as a preventive intervention in prenatal care settings.

Extrinsic and intrinsic iron and zinc labels were used to test iron and zinc absorption from two bean (Phaseolus vulgaris) genotypes, containing normal (common beans, CB) or higher (HFeZnB) iron and zinc concentrations, fed in single meals to young women with low iron reserves. The women were divided into two groups, with one receiving a CB test meal (n = 12) and the other, an HFeZnB test meal (n = 11). The beans were intrinsically labeled hydroponically with (55)Fe (CB and HFeZnB) and with (70)Zn (HFeZnB). Concentrations of zinc and iron were 98 and 65% higher, respectively, in HFeZnB as compared to CB, but phytic acid contents were similar. Extrinsic labels were (59)Fe (CB and HFeZnB), (67)Zn (CB), and (68)Zn (HFeZnB). Iron and zinc percent absorption levels were calculated from radio-iron activity in red blood cells and from urinary excretion of zinc isotopes. Intrinsic and extrinsic iron absorption measures were highly correlated (R (2) = 0.986) (average extrinsic/intrinsic ratio was 1.00). Iron absorption was low (geometric mean < 2%) in both bean types, and total iron absorbed was not different between types. Intrinsic zinc absorption from the HFeZn beans was higher than extrinsic absorption (15.2% vs 13.4%, p < 0.05) (average extrinsic/intrinsic was 0.90). The correlation between intrinsic and extrinsic zinc measures was not as high as that for iron (R (2) = 0.719). Percent zinc absorption levels were similar in both bean types, but total extrinsic zinc absorbed was 90% higher (p < 0.05) from the HFeZnB meal. Thus, the less expensive and time-consuming extrinsic labeling may be used to screen various varieties of beans for iron bioavailability in humans, but it underestimates zinc absorption by approximately 10%. Selective breeding for high-zinc bean genotypes may improve zinc status. However, high-iron genotypes appear to have little effect on iron status when fed alone in single meals to women with low iron reserves.

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.

To determine the prevalence of anemia, and iron (ID) and vitamin A deficiencies aiming at their prevention, 414 children between 6 and 24 months of age, were randomly selected from the whole province of Chaco. A sociodemographic survey was implemented, and hemoglobin (Hb), plasma ferritin and retinol were measured. Anemia prevalence (Hb < 110 g/L) was 66.4%, without differences between age groups, and included 18% with Hb < 90 g/L. These cases were significantly less in children 6-8 month of age (5.1%) than in the others (approximately equal to 20%) (P: 0.007). Mean Hb was also higher in 6-8 months old children and was associated with lower prevalence of ID (ferritin < 12 micrograms/L) (p < 0.000) but not with age (p = 0.8865). ID already present, however, in 36.6% of children in this age group, reached a prevalence of 72.9% in children older than 18 months. Anemia prevalence was significantly higher in males, in children whose birth weight was < 3000 g, in those who had never taken iron supplements and among the poor, both structural and by income. Retinol values < 20 micrograms/dl occurred only in 5.1% of children. Iron nutrition prior to, during pregnancy and in children during the first 2 years of life must be improved by joining strategies based on community empowerment aimed at improving dietary iron, assuring effective preventive supplementation and promoting the opportune umbilical cord ligation.

Tracer methodology using radioisotopes in human nutrition research has been the object of unjustified limitations in its use. These limitations have encumbered research studies where micronutrient and macronutrient deficiencies are prevalent. Stable isotope methodologies are expensive, including the cost of the isotopes, equipment and its maintenance, and are often fraught with serious pitfalls. We have been developing safe radioisotopic methods to study the metabolism of micronutrients, especially iron and zinc in the developing world. These should allow scientists everywhere to conduct their own research without having to depend on facilities and laboratories in the industrial world, and thus enhance productive collaborative research. All radioisotopic research must be subjected to strict safety criteria, based on scientific evidence of risk, but should not be hampered by unscientific fears. Examples on the use of radio and stable isotopes to study iron and zinc absorptions are given including the radiation exposure and risk calculations.

Aiming at their prevention, to determine the prevalence of gestational iron deficiency and anemia, considering access to health care and associations with social and biological variables in the Province of el Chaco, Argentina. Three hundred and sixty four, randomly selected pregnant women from the whole province participated. Mean Hemoglobin (Hb) +/- SD dropped progressively from 118.4 +/- 11.0 to 112.1 +/- 11.5 g/L (p = 0.015) between the 1st and the 3rd gestational trimesters. Anemia prevalence (Hb < 110 g/L) was 17.4, 26.5 and 35.8%. From the 1st to the 3rd trimesters. Second trimester prevalence was 14.1% using Hb < 105 g/L as recently suggested. The ferritin geometric mean during the progressive gestational trimesters were 28.9; 16.0 and 11.1 micrograms/L. 21.7, 40.5 and 60.5% had ferritins < 12 micrograms/L, and 39.1, 58.9 and 83.2% had ferritins < 20 micrograms/L in these respective trimesters (p < 0.004 between trimesters in both cases). Both iron deficiency and anemia were significantly greater in women with unfinished primary education and with interpregnancy interval < 1 year. Seventy five percent of women had adequate number of antenatal visits but only 23% were taking iron supplements and 10% had stopped taking them. The prevention and correction of gestational iron deficiency and anemia must focus on the preconceptional period (inter-pregnancy spacing and increasing iron intake using all available means) as well as during pregnancy improving adherence to iron supplements by means of motivation of health workers and community.

Tracer methodology using radioisotopes in human nutrition and metabolism research has been very productive but its use has been the object of unjustified limitations because of modeling decisions without adequate consideration of new data. These limitations have encumbered research studies in the metabolism of micro- and macronutrients particularly where nutritional deficiencies are prevalent. Even though stable isotope methodologies in human research are very useful in specific applications they are expensive and are often fraught with serious pitfalls, when compared to studies for the same purposes using radioisotopes. We have been developing safe radioisotopic methods to study the absorption and metabolism of micronutrients, especially iron and zinc, that can be applied to populations in the developing world. These and other applications of radioisotopes should allow scientists to conduct research diminishing the dependence on stable isotopes and on facilities and laboratories existing only in selected sites in the industrial world, and thus should enhance productive local and collaborative research. All radioisotopic research must be subjected to strict safety criteria, based on scientific evidence of risk, but should not be hampered by exaggerated fears of unfounded risk. Examples on the use of radio and stable isotopes to study iron and zinc absorptions are given including the radiation exposure and risk calculations.

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.

The adverse effects of micronutrient deficiencies and excesses in children up to reproductive age are presented. A summary of risks and adverse functional and health outcomes associated with deficient and excessive intakes and nutrition status of iron, iodine, zinc, vitamins A and D, folate, vitamin B12, and riboflavin is presented. Nutrient-nutrient interactions of micronutrients, age, gender, and other host and environmental conditions, such as pregnancy, genetic conditions, overall nutrition, force of infection, and social conditions are considered as covariates in trying to define causation and outcomes due to specific micronutrients. The outcomes analyzed focus on growth and development, mental and neuromotor performance, immunocompetence, physical working capacity, morbidity, and in the case of pregnancy, overall reproductive performance. The results presented include responses to specific and multiple "experimental" interventions. A brief analysis of possible public health programs is presented, with emphasis on prevention.

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (< or =5 microg/day) and iron-normal (800 microg/day) rats and in both groups after daily high-iron supplementation (8,000 microg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 microg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 x nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

The absorption of a commercial brand of small-particle reduced iron was evaluated in 10 normal subjects. For each subject, the hemoglobin incorporation method was used to measure the true absorption of 60 mg of iron from either ferrous sulfate or ferric ammonium citrate. The iron tolerance test (ITT) was also studied for these two compounds and for reduced iron. This procedure consisted of measuring the area under the curve of plasma iron elevations at specified times for 6 hours, or the peak plasma iron, corrected by the plasma iron disappearance rate obtained from measuring plasma iron at specified times for 4 hours after the slow intravenous injection of 0.4 mg of iron as ferric citrate. Only the ITT was used to measure the absorption of 60 mg of reduced iron. Reference dose iron ascorbate absorption was measured in each subject. The absorption of ferric ammonium citrate and reduced iron was expressed as percent of dose and also as absorption percent of that of ferrous sulfate. Mean % geometric "true absorptions" were 39.0 for reference dose, 10.4 for FeSO4 and 2.4 for ferric ammonium citrate. The later was 23% that of FeSO4. By ITT the mean geometric % absorptions were 7.9, 3.7 and 3.2 for FeSO4, ferric ammonium citrate and reduced iron respectively, or 47 and 41% of that of FeSO4. We propose that the true absorption of the commercial brand of reduced iron tested was 20% that of FeSO4 based on the relation between the ITT results of reduced iron and the ITT and true absorption values of ferric ammonium citrate in relation to FeSO4. The use of this method for measuring absorption of unlabeled iron compounds is discussed.

Background: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%., Objective: We assessed iron absorption from porridges prepared from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA., Design: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets., Results: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P<0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron., Conclusion: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.

Numerous studies have shown that iron-loaded diets increase markers of lipid peroxidation in rats, but few have addressed the effects of oral iron supplements on these markers. We investigated the effects of daily and intermittent iron supplements on iron and vitamin E status, and lipid peroxidation. Iron supplements were administered in doses equivalent to those often given to pregnant women in the developing world. In Study 1, iron-deficient (D) and iron-normal (N) rats were fed either 0 or 8000 microgram of supplemental iron daily for 21 d. In Study 2, D rats were fed either the same supplements daily or once every 3 d (8 supplements total). Lipid peroxidation was assessed by breath ethane and pentane and by malondialdehyde (MDA) (using GC-MS). In Study 1, daily supplemented N and D rats had liver nonheme iron concentrations that were 1.8- and 2.7-fold higher, respectively, than those in unsupplemented N rats. Breath ethane levels were also higher in supplemented rats (P < 0.05), but MDA (in plasma, liver, kidney) and liver vitamin E did not differ. Unexpectedly, severely D, anemic rats had significant elevations in the levels of breath ethane, liver MDA and kidney MDA. In Study 2, liver iron and breath ethane decreased progressively (P < 0.05) from 1 d to 3 d after the last iron dose in intermittently supplemented rats. We conclude that iron deficiency results in lipid peroxidation, but that its correction with daily iron supplements results in abnormal iron accumulation and increased lipid peroxidation in rats. These effects are mitigated by intermittent iron supplementation.

Numerous studies in animals and humans provide evidence that ethane and pentane in expired air are useful markers of in vivo lipid peroxidation. The measurement of breath hydrocarbons, being noninvasive, is well suited for routine use in research and clinical settings. However, the lack of standardized methods for collecting, processing, and analyzing expired air has resulted in the use of a wide variety of different methods that have yielded highly disparate results among investigators. This review outlines the methods that we have developed and validated for measuring ethane and pentane in expired air from rats and humans. We describe the advantages of these methods, their performance, as well as potential errors that can be introduced during sample collection, concentration, and analysis. A main source of error involves contamination with ambient-air ethane and pentane, the concentrations of which are usually much greater and more variable than those in expired air. Thus, it appears that the effective removal of ambient-air hydrocarbons from the subject's lungs before collection is an important step in standardizing the collection procedure. Also discussed is whether ethane or pentane is a better marker of in vivo lipid peroxidation.

This 7-mo double-blind study compared the efficacy of two iron supplementation schemes in improving iron nutrition among 116 healthy fertile-age women. They were randomly distributed in three groups, receiving: Group 1, iron + folate (60 mg and 250 microg, respectively) daily for 3 mo (currently recommended scheme), and folate (250 microg) weekly the subsequent 4 mo. Group 2, folate daily, and 60 mg iron only once weekly for 3 mo, and then weekly iron + folate for 4 mo. Group 3, folate daily for 3 mo and then weekly for 4 mo. At baseline, 16% had depleted stores (plasma ferritin <15 microg/L) and 16% had hemoglobin levels <125 g/L. Eight percent had hemoglobin levels <120 g/L. In Group 1 hemoglobin and ferritin increased at 3 mo but returned to near basal conditions after 4 mo of weekly folate. In Group 2, hemoglobin and ferritin increased progressively throughout the 7 mo but mostly after 3 mo. Group 3 did not change. Side effects were highest with daily iron. Weekly iron supplementation over 7 mo (30 doses) improved and sustained iron nutrition at least as effectively and was better tolerated than 90 daily iron supplements consumed during 3 mo.

We describe a method for the collection of expired air and further document the performance of our analytical technique that is used to measure ethane and pentane simultaneously. Four minutes of breathing hydrocarbon-free air before collection effectively removed high concentrations of residual ambient ethane and pentane from the lungs, with washout times up to 30 min resulting in no further reductions in breath hydrocarbons. Mean (+/-SE) exhalation rates (pmol/kg b.wt./min) in 11 subjects were 2.4 +/- 0.6 for ethane and 1.5 +/- 1.3 for pentane. Total intraindividual variability in exhalation rates (as percent coefficient of variation, %CV), measured from 4 subjects on at least 6 different days, was greater for pentane (44% CV) than for ethane (29% CV). Analytical variability contributed 6% to the total %CV. Advantages of the method are described, and reasons for the large variability in values reported in the literature are discussed.

Iron supplementation is a public health strategy designed for the prevention of iron deficiency and its consecutive anemia. It should be targeted, safe, flexible, long term and ideally, community based under the supervision of the health sector. It must be differentiated from iron therapy, even though, in the intermediate and long term it corrects mild-moderate deficiency of iron and ferropenic anemia. It should complement other measures for the control of iron deficiency. A summary of results comparing daily and intermittent iron supplementation (every 3-days in rats, and weekly in humans) is presented, including studies in an animal model, human supplementary-iron absorption studies, clinical research and field studies. It is concluded that intermittent iron supplementation is efficacious and, that in the long term it achieves an increase in iron reserves while avoiding sustained oxidative stress caused by current practices of excess daily iron supplementation, particularly in the developing world. The stage is set for long-term weekly iron supplementation programs in large population groups to determine its sustainability and effectiveness.