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Supplementation of vitamin B12 or folic acid on hemoglobin concentration in children 6-36 months of age: A randomized placebo controlled trial.
Kumar, T, Taneja, S, Sachdev, HPS, Refsum, H, Yajnik, CS, Bhandari, N, Strand, TA, ,
Clinical nutrition (Edinburgh, Scotland). 2017;(4):986-991
Abstract
BACKGROUND & AIMS The main objective of this report is to measure to what extent folate or vitamin B12 given daily for 6 months to young North Indian Children improves hemoglobin (Hb) concentration. METHODS In a randomized placebo controlled trial in low-to-middle income neighborhoods in New Delhi, India, children were randomized into four groups in a 1:1:1:1 ratio and supplemented daily for 6 months with 2 RDAs of vitamin B12, folic acid, both, or placebo. All children with anemia at baseline were given iron supplementation daily for 2 months. We measured the plasma concentrations of soluble transferrin receptor (sTfR), folate, vitamin B12, total homocysteine (tHcy) and Hb in 262 children. RESULTS Mean Hb concentration decreased in all four study groups during the six months of follow up and supplementation of either or both of the vitamins did not improve the Hb concentration. Iron supplements for the initial 2 mo had limited effect on anemia at 6 mo as almost 90% were still anemic at study end. CONCLUSION Supplementation of folic acid and/or vitamin B12 for 6 months does not improve Hb concentration in young children. Our findings do not argue for widespread vitamin B12 or folic acid supplementation to combat anemia. Our results also call for alternative strategies to improve iron status and treat iron deficiency anemia. CLINICAL TRIAL REGISTRY NCT00717730 at www.clinicaltrials.gov, CTRI No.: CTRI/2010/091/001090 at www.ctri.nic.in.
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Late-Pregnancy Salivary Cortisol Concentrations of Ghanaian Women Participating in a Randomized Controlled Trial of Prenatal Lipid-Based Nutrient Supplements.
Oaks, BM, Laugero, KD, Stewart, CP, Adu-Afarwuah, S, Lartey, A, Ashorn, P, Vosti, SA, Dewey, KG
The Journal of nutrition. 2016;(2):343-52
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BACKGROUND High circulating cortisol is associated with miscarriage, preterm birth, and low birth weight. Research in nonpregnant individuals suggests that improved nutrition may lower cortisol concentrations. It is unknown whether nutritional supplementation during pregnancy lowers cortisol. OBJECTIVE Our objective was to determine whether women receiving a lipid-based nutrient supplement (LNS) throughout pregnancy would have lower salivary cortisol at 36 wk gestation compared with women receiving other nutrient supplements. METHODS We conducted a randomized controlled trial in 1320 pregnant Ghanaian women at ≤20 wk gestation who were assigned to receive daily throughout pregnancy: 1) 60 mg iron + 400 μg folic acid (IFA), 2) multiple micronutrients (MMNs), or 3) 20 g LNS (containing 118 kcal, 22 micronutrients, and protein). Morning salivary cortisol was collected from a subsample at baseline and at 28 and 36 wk gestation. RESULTS A total of 758 women had cortisol measurements at 28 or 36 wk gestation. Salivary cortisol at 36 wk gestation did not differ between groups and was (mean ± SE) 7.97 ± 0.199 in the IFA group, 7.84 ± 0.191 in the MMN group, and 7.77 ± 0.199 nmol/L in the LNS group, when adjusted for baseline cortisol, time of waking, and time between waking and saliva collection (P = 0.67). There was an interaction between supplementation group and women's age (continuous variable, P-interaction = 0.03); and when age was dichotomized by the median, significant differences in salivary cortisol concentrations between groups were seen in women ≤26 y of age (IFA = 8.23 ± 0.284 nmol/L, MMN = 8.20 ± 0.274 nmol/L, and LNS = 7.44 ± 0.284 nmol/L; P = 0.03) but not in women >26 y old (IFA = 7.71 ± 0.281 nmol/L, MMN = 7.50 ± 0.274 nmol/L, and LNS = 8.08 ± 0.281 nmol/L; P = 0.13). CONCLUSIONS We conclude that supplementation with LNSs or MMNs during pregnancy did not affect the cortisol concentration in the study population as a whole, in comparison with IFA, but that LNS consumption among younger women may lead to lower cortisol at 36 wk gestation. This trial was registered at clinicaltrials.gov as NCT00970866.
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Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations.
Christian, P, Nanayakkara-Bind, A, Schulze, K, Wu, L, LeClerq, SC, Khatry, SK
Maternal & child nutrition. 2016;(1):64-73
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Antenatal iron and multiple micronutrient supplementation has been shown in randomized trials to improve birthweight, although mechanisms are unknown. We examined late pregnancy serum erythropoietin (EPO) and cortisol concentrations in relation to maternal micronutrient supplementation and iron status indicators (haemoglobin, serum ferritin, soluble transferrin receptor) in 737 rural Nepalese women to explore evidence of stress or anaemia-associated hypoxia. A double-masked randomized control trial was conducted from December 1998 to April 2001 in Sarlahi, Nepal, in which women received vitamin A alone (as control), or with folic acid (FA), FA + iron, FA + iron + zinc and a multiple micronutrient supplement. In a substudy, we collected maternal blood in the first and third trimester for biochemical assessments. Generalized estimating equations linear regression analysis was used to examine treatment group differences. EPO was ∼ 14-17 mIU mL(-1) lower (P < 0.0001) in late pregnancy in groups receiving iron vs. the control group, with no difference in the FA-only group. Cortisol was 1.3 μg dL(-1) lower (P = 0.04) only in the micronutrient supplement group compared with the control group. EPO was most strongly associated with iron status indicators in groups that did not receive iron, and in the non-iron groups cortisol was positively correlated with EPO (r = 0.15, P < 0.01) and soluble transferrin receptor (sTfR, r = 0.19, P < 0.001). In adjusted analyses, third trimester EPO was associated with a reduction in low birthweight, whereas cortisol was negatively associated with length of gestation and higher risk of preterm birth. Iron and multiple micronutrient supplementation may enhance birth outcomes by reducing mediators of maternal stress and impaired erythropoiesis.
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Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.
Perelló, MF, Coloma, JL, Masoller, N, Esteve, J, Palacio, M
BJOG : an international journal of obstetrics and gynaecology. 2014;(6):706-13
Abstract
OBJECTIVE The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia. DESIGN A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre. SETTING Hospital Clinic of Barcelona, Barcelona, Spain. POPULATION A cohort of 72 women with severe postpartum anaemia (6.0-8.0 g/dl) treated with oral ferrous sulphate (two tablets of 525 mg). METHODS Women were randomised to receive either intravenous ferrous sucrose (200 mg/24 hours for two consecutive days) or intravenous placebo, in addition to standard iron therapy. Clinical and laboratory data were obtained at 1, 2, and 6 weeks. MAIN OUTCOME MEASURES Haemoglobin and haematocrit at 1, 2, and 6 weeks. Other haematological and clinical parameters, psychological status, and adverse side effects were also evaluated. RESULTS Haemoglobin and haematocrit values were comparable in women receiving intravenous iron or placebo in addition to oral iron therapy at any of the time points. At 6 weeks, haemoglobin level (mean ± SD) was 12.2 ± 1.0 versus 12.2 ± 0.9 g/dl, with a mean difference of -0.03 (95% CI -0.6 to 0.6), in the placebo and in the intravenous iron groups, respectively. No differences were found between clinical symptoms of anaemia, psychological status, and adverse side effects between groups. CONCLUSIONS Intravenous iron added to oral iron therapy did not show significant benefits over placebo, neither in haemoglobin rise nor in symptoms or adverse side effects.
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Effects of different complementary feeding regimens on iron status and enteric microbiota in breastfed infants.
Krebs, NF, Sherlock, LG, Westcott, J, Culbertson, D, Hambidge, KM, Feazel, LM, Robertson, CE, Frank, DN
The Journal of pediatrics. 2013;(2):416-23
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OBJECTIVE To compare iron status in breastfed infants randomized to groups receiving complementary feeding regimens that provided iron from fortified infant cereals or meats, and to examine the development of the enteric microbiota in these groups. STUDY DESIGN Forty-five exclusively breastfed 5-month-old infants were randomized to 1 of 3 feeding groups (FGs)-commercially available pureed meats, iron- and zinc-fortified infant cereals, or iron-only fortified infant cereals-as the first and primary complementary food through 9-10 months of age. Dietary iron was determined by monthly 3-day diet records. Iron status was assessed at the end of the study by measurements of hemoglobin, serum ferritin, and soluble transferrin receptor levels. In a subsample of 14 infants, enteric microbiota were profiled in monthly stool samples (5-9 months) by 16S ribosomal RNA gene pyrosequencing. RESULTS Infants in the 2 cereal FGs had 2- to 3-fold greater daily iron intakes versus the meat FG (P < .0001). More than one-quarter (27%) of the infants had a low serum ferritin level, and 36% were mildly anemic, with no significant differences by FG; more infants in the meat FG had a high soluble transferrin receptor value (P = .03). Sequence analysis identified differences by time and FG in the abundances of several bacterial groups, including significantly more abundant butyrate-producing Clostridium group XIVa in the meat FG (P = .01) CONCLUSION A high percentage of healthy infants who were breastfed-only were iron-deficient, and complementary feeding, including iron exposure, influenced the development of the enteric microbiota. If these findings are confirmed, then reconsideration of strategies to both meet infants' iron requirements and optimize the developing microbiome may be warranted.
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Effect of trypsin and mucin on heme iron bioavailability in humans.
Cediel, G, Olivares, M, Gaitán, D, Flores, S, Brito, A, Pizarro, F
Biological trace element research. 2012;(1-3):37-41
Abstract
UNLABELLED In the human gastrointestinal tract, trypsin and mucin may affect the absorption of heme iron. However, these interactions have not been well-established. We determined the effect of trypsin and mucin on heme iron absorption in humans. DESIGN Twenty-eight apparently healthy females participated in two studies (14 per study). Study A evaluated the effect of trypsin on iron bioavailability. Subjects ingested 100 mg trypsin and 1.7 g mucin on 5 mg heme iron bioavailability on days 1, 2, 14, and 15, respectively. In study B, which assessed the effect of mucin on heme iron bioavailability, the subjects ingested hemin, hemin plus mucin, hemoglobin (Hb), and Hb plus mucin, on days 1, 2, 14, and 15, respectively. RESULTS In study A, the geometric means ± 1 SD of heme iron absorption were 5.1 % (3.1-8.3), 2.9 % (1.6-5.1), 7.3 % (4.1-13.1), and 6 % (2.7-13) for hemin, hemin plus trypsin, Hb plus trypsin, and Hb plus mucin plus trypsin, respectively. In study B, the geometric means ± 1 SD of heme iron absorption were 16.4 % (10.5-25.7), 13.1 % (9.0-18.9), 13.7 % (9.0-20.7), and 11.8 % (7.6-18.3) for hemin, hemin plus mucin, Hb, and Hb plus mucin, respectively. The ratio increased when Hb plus trypsin was ingested and decreased when hemin plus trypsin was ingested. There were no differences in other ratios with respect to the ratio on day 1 (P < 0.05). CONCLUSION Trypsin is the only human gastrointestinal protein that evaluated the affects of heme iron absorption. However, this effect depends on how heme iron is ingested.
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Altered plasma response to zinc and iron tolerance test after Roux-en-Y gastric bypass.
Rosa, FT, de Oliveira-Penaforte, FR, de Arruda Leme, I, Padovan, GJ, Ceneviva, R, Marchini, JS
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2011;(3):309-14
Abstract
BACKGROUND The duodenum and proximal jejunum are excluded after Roux-en-Y gastric bypass but these intestinal sites are where iron and zinc are most absorbed. Therefore, they are among the nutrients whose digestive and absorptive process can be impaired after surgery. The aim of the present study was to investigate the iron and zinc plasma response to a tolerance test before and after bariatric surgery. The study was performed at São Paulo University School of Medicine of Ribeirão Preto, Brazil. METHODS In a longitudinal paired study, 9 morbidly obese women (body mass index ≥40 kg/m(2)) underwent an iron and zinc tolerance test before and 3 months after surgery. The iron and zinc levels were determined at 0, 1, 2, 3, and 4 hours after a physiologic unique oral dose. The mineral concentrations in the plasma and 24-hour urine sample were assayed using an atomic absorption spectrophotometer. The anthropometric measurements and 3-day food record were also evaluated. A linear mixed model was used to compare the plasma concentration versus interval after the oral dose, before and after surgery. RESULTS The pre- and postoperative test results revealed a significantly lower plasma zinc response (P <.01) and a delayed response to iron intake after surgery. The total plasma iron concentration area, during the 4 hours, was not different after surgery (P >.05). The 24-hour urinary iron and zinc excretion did not differ between the pre- and postoperative phases. CONCLUSION The present data showed a compromised response to the zinc tolerance test after gastric bypass surgery, suggesting an impaired absorption of zinc. More attention must be devoted to zinc nutritional status after surgery.
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Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.
Collings, R, Fairweather-Tait, SJ, Dainty, JR, Roe, MA
The Journal of nutrition. 2011;(5):805-8
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Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.
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Iron intake and iron status in breastfed infants during the first year of life.
Dube, K, Schwartz, J, Mueller, MJ, Kalhoff, H, Kersting, M
Clinical nutrition (Edinburgh, Scotland). 2010;(6):773-8
Abstract
BACKGROUND & AIMS Breastfed infants may be at particular risk for iron deficiency because breast milk is low in iron. In a secondary analysis of data from a complementary feeding trial, indicators of iron status were examined, with particular focus on the development of iron status in those infants who were fully breastfed during the first 4 months of life. METHODS In this retrospective analysis of data from a randomized controlled trial infants were stratified according to their predominant milk diet during the first 4 months of life, a subgroup of breastfed infants (group BM, n=53) were compared with a subgroup of infants fed (iron-fortified) formula (group F, n=23). Dietary iron intake and indicators of iron status were analysed at 4 months of age (during the full milk feeding period), and during the complementary feeding period at 7 and 10 months of age. RESULTS Iron intake was low in the BM group, ranging below the Dietary Reference Intakes throughout the complementary feeding period, with the (estimated) bioavailable iron intake only just achieving the reference requirements. At 4 months, iron deficiency (ID, Ferritin <12.0 ng/mL) was observed in 3 infants in the BM group and in 1 infant in the F group; no infant developed iron deficiency anaemia (IDA, ID and Hb <10.5 g/dl). At 7 and at 10 months of age, iron status was adequate in all infants of the F group. In the BM group, at 7 (10) months of age, ID was diagnosed in 10 (11) infants and IDA was found in 2 (1) infants. CONCLUSIONS Healthy infants, fully breastfed at 4 months of age, demonstrated ID in about 21% and IDA in up to 6% during the second half of infancy while fed according to the paediatric dietary guidelines. This finding supports the recommendation that supplementation with bioavailable iron via complementary foods should be started early (4-6 months of age) in order to prevent iron deficiency during infancy.
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Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children.
Sarker, SA, Mahmud, H, Davidsson, L, Alam, NH, Ahmed, T, Alam, N, Salam, MA, Beglinger, C, Gyr, N, Fuchs, GJ
Gastroenterology. 2008;(5):1534-42
Abstract
BACKGROUND & AIMS We investigated Helicobacter pylori (H pylori)-infection as a cause of iron deficiency (ID) and iron-deficiency anemia (IDA) or treatment failure of iron supplementation. METHODS We randomized 200 Hp-infected children (positive urea breath test) 2-5 years of age with IDA (hemoglobin level <110 g/L; serum ferritin level <12 microg/L; and soluble transferrin receptor >8.3 mg/L) or ID (serum ferritin level <12 microg/L or soluble transferrin receptor level >8.3 mg/L) to 1 of 4 regimens: 2-week anti-Hp therapy (amoxicillin, clarithromycin, and omeprazole) plus 90-day oral ferrous sulfate (anti-Hp plus iron), 2-week anti-Hp therapy alone, 90-day oral iron alone, or placebo. Sixty noninfected children with IDA received iron treatment as negative control. RESULTS Hp-infected children receiving iron had significantly less frequent treatment failure compared with those with no iron in correcting IDA (11% [95% confidence interval (CI), 2%-20%] for anti-Hp plus iron, 0% for iron alone vs 33% [95% CI, 26%-46%] for anti-Hp and 45% [95% CI, 31%-59%] for placebo; chi(2) = 127; P < .0001), ID (19% [95% CI, 8%-30%] for anti-Hp plus iron, 7% [95% CI, 0%-14%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone, and 78% [95% CI, 66%-90%] for placebo; chi(2) = 124; P < .0001), or anemia (34% [95% CI, 20%-40%] for anti-Hp plus iron, 27% [95% CI, 14%-40%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone and 78% [95% CI, 66%-90%] for placebo; chi(2) = 46; P < .0001). Cure rates of IDA, ID, or anemia with iron were comparable with that of the negative control group. Improvements in iron status also were significantly greater in groups with iron. CONCLUSIONS H pylori is neither a cause of IDA/ID nor a reason for treatment failure of iron supplementation in young Bangladeshi children.