Search

Contains fulltext : 244703.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 208453.pdf (publisher's version ) (Open Access), Antibodies to Streptococcus gallolyticus subspecies gallolyticus (SGG) have been associated with colorectal cancer (CRC). Because SGG may correlate with impaired gut epithelia, we assessed the association of antibodies to bacterial flagellin C (FliC), a measure potentially related to this impairment, with CRC and the CRC-specific interaction with antibodies to SGG proteins. Antibodies to FliC and SGG pilus proteins Gallo2178 and Gallo2179 were measured in two independent studies, a combined study from Nijmegen and Detroit (93 CRC cases, 74 controls) and a replication data set including 576 cases and 576 controls from the Spanish multicenter multicase-control study (MCC-Spain). Logistic regression was applied to assess whether antibodies to FliC were associated with CRC and modified the association of antibodies to SGG proteins with CRC. Antibodies to FliC were associated with those to SGG Gallo2178 among CRC cases, resulting in an interaction in the association of antibodies to Gallo2178 with CRC (p = 0.007). This association was only present among individuals with high antibody responses to FliC (OR: 2.42, 95% CI: 1.45-4.06). In conclusion, our findings suggest that colorectal tumorigenesis could be accompanied by an impaired integrity of the epithelium that could result in associated increased antibody responses to bacterial proteins.

Contains fulltext : 167947.pdf (publisher's version ) (Open Access)

Item does not contain fulltext

Item does not contain fulltext, BACKGROUND: In sub-Saharan Africa, parasitic diseases and low bioavailable iron intake are major causes of anemia. Anemia results from inflammation, preventing iron recycling and decreasing dietary iron absorption. Hookworm, Plasmodium, and Schistosoma infections contribute to anemia, but their influence on dietary iron absorption and recycling is unknown. OBJECTIVE: The objective was to measure inflammation biomarkers, hepcidin, iron absorption, and utilization pre- and posttreatment in children with afebrile malaria, hookworm, and Schistosoma haematobium infection. DESIGN: Ivorian children aged 11-17 y with afebrile Plasmodium falciparum (n = 17), hookworm (n = 16), or S. haematobium infection (n = 8) consumed a syrup containing 3 mg (57)Fe as ferrous sulfate and received an intravenous infusion of 50 mug (58)Fe as ferrous citrate. Children were treated for their respective infection, and the iron studies were repeated 4 wk later. Iron and inflammation biomarkers and hepcidin were measured. RESULTS: Geometric mean iron absorptions in the afebrile malaria and hookworm groups were 12.9% and 32.2% (P < 0.001) before treatment and 23.6% and 30.0% (P = 0.113) after treatment, respectively. Treatment of afebrile malaria reduced inflammation (P < 0.001) and serum hepcidin (P = 0.004) and improved iron absorption (P = 0.003). Treatment of hookworm infection neither affected inflammation biomarkers nor altered iron absorption. Similarly, there was a lack of treatment effects in the S. haematobium-infected group; however, the small sample size limits conclusions. Geometric mean iron utilization ranged between 79.1% and 88.0% in the afebrile malaria and hookworm groups with no significant differences pre- and posttreatment. CONCLUSIONS: In school-age children, hookworm infection does not produce inflammation or increase serum hepcidin, and it does not influence iron absorption or utilization. In contrast, afebrile malaria causes inflammation, increases hepcidin, and reduces

Item does not contain fulltext, OBJECTIVES: The post-exercise interleukin-6 (IL-6) and hepcidin response was investigated during the hormone-deplete and hormone-replete phases of an estradiol and progestogen regulated oral contraceptive cycle (OCC). DESIGN: Counterbalanced, repeated measures cross-over study. METHODS: Ten active female monophasic oral contraceptive pill (OCP) users completed two 40 min treadmill running trials at 75% of their pre-determined peak oxygen uptake velocity (vVO2peak). These trials were randomly performed in two specific phases of the OCC: (a) Day 2-4, representing a hormone-free withdrawal period (D-0); (b) Day 12-14, representing the end of the first week of active hormone therapy (D+7). Venous blood samples were drawn pre-, post- and 3h post-exercise. RESULTS: In both trials, serum IL-6 was significantly elevated (p<0.05) immediately post-exercise, while serum hepcidin was significantly elevated (p<0.05) 3h post-exercise, with no significant differences recorded between trials. CONCLUSIONS: These findings suggest that exercise performed during the different phases (D-0 vs. D+7) of a monophasic OCP regulated cycle does not alter exercise induced IL-6 or hepcidin production. As such, future studies looking to investigate similar variables post-exercise, may not need to 'control' for different phases of the OCC, provided participants are current monophasic OCP users.

Item does not contain fulltext

Item does not contain fulltext, BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, incr

Item does not contain fulltext, Anemia is a frequent sign in patients with diffuse large B-cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin and interleukin-6 (IL-6) in plasma samples of 53 patients with DLBCL. The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in particular when anemia was present (p = 0.01). Hepcidin plasma levels were significantly higher in patients compared to controls (p = 0.006), particularly in those with characteristics associated with a more active disease, including elevated lactate dehydrogenase (LDH) (p = 0.0004), B-symptoms (p = 0.07) and an age-adjusted international prognostic index (IPI) score > 1 (p = 0.01). Hepcidin levels correlated strongly to ferritin (r = 0.77, p < 0.0001) and weakly to IL-6 concentrations (r = 0.30, p = 0.03), but not to hemoglobin values. IL-6 inversely correlated to hemoglobin values in both univariate and multivariate analysis (p = 0.04), including hepcidin and erythropoietin as variables. Our findings suggest that elevated hepcidin levels and inadequate erythropoietin response are frequent in DLBCL, but elevated IL-6 plays the major role for the development of anemia.

Item does not contain fulltext, The association of colorectal neoplasia (CRN) with Streptococcus bovis biotype I (SBI) infection is well recognized. However, this is not the case for Streptococcus bovis biotype II (SBII). We conducted this study in order to analyze the relationship between SBII and CRN. We analyzed all cases of bacteremia due to SBI (n = 99) and SBII (n = 36) diagnosed in our hospital (during the period 1988-2011) that were followed up with colonoscopy. In addition, we reviewed the literature (during the period 1982-2011) to select all cases of infection of SB that had undergone colonoscopy or other adequate form of colorectal examination. A multivariate analysis was performed to detect CRN risk factors in patients infected with SB. From the 223 cases of SB infection included in the analysis (135 from our institution and 88 from the literature review), 159 were due to SBI and 64 were caused by SBII. As compared with SBI, the SBII cases had a lower frequency of CRN (27 % vs. 67 %, p <0.001), advanced adenomas (8 % vs. 29 %, p <0.01), and carcinomas (6 % vs. 21 %, p <0.01). In a multivariate analysis, and after adjusting for age, sex, type of infection, and biotype, SBII infection was not associated with CRN: odds ratio (OR) = 0.17; 95 % confidence interval (CI) = 0.09 to 0.33. The only factor independently associated with CRN was SBI infection: OR = 5.7; 95 % CI = 3.0 to 10.9. The prevalence of CRN in patients infected with SBII is significantly lower than patients with SBI and does not appear to be higher than the CRN prevalence among the general population.

Item does not contain fulltext, AIM: Iron deficiency is an important child health problem. Its diagnosis in areas of high infection exposure remains complicated as inflammation may interfere with the accuracy of peripheral iron markers. With this study, we aimed to validate the conventional iron markers and two novel iron markers, hepcidin and Red blood cell Size Factor (RSf), against the reference standard of iron status, bone marrow iron, in children living in an infectious setting. METHODS: We compared ferritin, soluble transferrin receptor, Soluble Transferrin Log-Ferritin Index (sTfR-F), mean cellular volume, mean cellular haemoglobin concentration, hepcidin and RSf, against bone marrow iron in 87 healthy Malawian children (6-66 months) scheduled for elective surgery. RESULTS: Of all children, 44.8% had depleted bone marrow iron stores. Using optimised cut-offs, ferritin (<18 microg/L) and sTfR-F (>1.85) best predicted depleted iron stores with a sensitivity/specificity of 73.7%/77.1% and 72.5%/75.0%, respectively. Hepcidin (<1.4 nmol/L) was a moderate sensitive marker (73.0%) although specificity was 54.2%; RSf poorly predicted depleted iron stores. CONCLUSIONS: We provide the first bone marrow-validated data on peripheral iron markers in African children, and showed ferritin and sTfR-F best predicted iron status. Using appropriately defined cut-offs, these indicators can be applied in surveillance and research. As their accuracy is limited for clinical purposes, more reliable iron biomarkers are still required in African children.

Contains fulltext : 137963.pdf (publisher's version ) (Open Access), BACKGROUND: This investigation compared the effects of an extended period of weight-bearing (running) vs. non-weight-bearing (cycling) exercise on hepcidin production and its implications for iron status. METHODS: Ten active males performed two separate exercise training blocks with either running (RTB) or cycling (CTB) as the exercise mode. Each block consisted of five training sessions (Day 1, 2, 4, 5, 6) performed over a seven day period that were matched for exercise intensity. Basal venous blood samples were obtained on Day 1 (D1), and on Recovery Days 3 (R3) and 7 (R7) to assess iron status, while basal and 3 h post-exercise urinary hepcidin levels were measured on D1, D2, D6, as well as R3 and R7 (basal levels only) for each condition. RESULTS: Basal urinary hepcidin levels were significantly elevated (p

Item does not contain fulltext, PURPOSE: To assess the influence of a simulated altitude exposure (~2,900 m above sea level) for a 3 h recovery period following intense interval running on post-exercise inflammation, serum iron, ferritin, erythropoietin, and hepcidin response. METHODS: In a cross-over design, ten well-trained male endurance athletes completed two 8 x 3 min interval running sessions at 85 % of their maximal aerobic velocity on a motorized treadmill, before being randomly assigned to either a hypoxic (HYP: F IO2 ~0.1513) or a normoxic (NORM: F IO2 0.2093) 3 h recovery period. Venous blood was collected pre- and immediately post-exercise, and after 3 and 24 h of recovery. Blood was analyzed for interleukin-6, serum iron, ferritin, erythropoietin, and hepcidin. RESULTS: Interleukin-6 was significantly elevated (p < 0.01) immediately post-exercise compared to baseline (NORM: 1.08 +/- 0.061 to 3.12 +/- 1.80) (HYP: 1.32 +/- 0.86 to 2.99 +/- 2.02), but was not different between conditions. Hepcidin levels were significantly elevated (p < 0.01) at 3 h post-exercise for both conditions when compared to baseline (NORM: 3.25 +/- 1.23 to 7.40 +/- 4.00) (HYP: 3.24 +/- 1.94 to 5.42 +/- 3.20), but were significantly lower (p < 0.05) in the HYP trial compared to NORM. No significant differences existed between HYP and NORM for erythropoietin, serum iron, or ferritin. CONCLUSION: Simulated altitude exposure (~2,900 m) for 3 h following intense interval running attenuates the peak hepcidin levels recorded at 3 h post-exercise. Consequently, a hypoxic recovery after exercise may be useful for athletes with compromised iron status to potentially increase acute dietary iron absorption.

Item does not contain fulltext, BACKGROUND: The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation. METHODS: We included 400 healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.

Item does not contain fulltext

Radboud Universiteit Nijmegen, 16 december 2014, Promotor : Swinkels, D.W. Co-promotor : Tjalsma, H., Contains fulltext : 132635.pdf (publisher's version ) (Open Access), Iron is a highly abundant metal on earth and is vital for virtually all organisms, including most bacterial species. Nonetheless, iron deficiency is the most prevalent human nutrition disorder worldwide, which can generally be treated by oral iron administration. However, oral iron administration in infection endemic regions is associated with an increased susceptibility of children to infections. The aim of this thesis was to investigate the impact of oral iron administration at the intestinal epithelial interface on i) the pathogenicity of intestinal pathogens, ii) the gut microbiota composition, iii) gut microbial metabolism, and iv) host responses. This thesis exemplifies that oral administration can increase the abundance of intestinal pathogens and may increase their pathogenicity, while it can decrease the abundance of beneficial gut microbes. Furthermore, it may also decrease host intestinal defenses (i.e. via: iron-induced oxidative damage to the gut wall, increased production of toxic microbial metabolites affecting the gut wall, or a decreased host innate defense) at the same time. This undesired combination may provide intestinal pathogens with increased opportunities to evade the host defense during oral iron therapy. Together this strengthens the idea that oral iron administration programs in developing countries with high infection pressure need to be set up with the highest amount of care, and should be accompanied with close health monitoring until the remaining questions about the actual effect of iron at the intestinal host-microbiota interface have been unraveled. Future research should also be directed at finding iron formulations that minimize the negative impact on the gut microbiome. This thesis exposes health problems and potential threats with regarding to oral iron administration and it increases the understanding of iron-driven alterations of host-pathogen interactions, which is indispensible in the design of safe iron formulations.

Item does not contain fulltext

Item does not contain fulltext

Contains fulltext : 138357.pdf (publisher's version ) (Open Access), Oral iron therapy can increase the abundance of bacterial pathogens, e.g., Salmonella spp., in the large intestine of African children. Carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent Salmonella enterica serovar Typhimurium. This study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial pathogenicity during high iron availability. S. Typhimurium was cultured with increasing concentrations of iron and carvacrol to study the effects of these combined interventions on growth, adhesion to intestinal epithelial cells, and iron uptake/influx in both bacterial and epithelial cells. In addition, the ability of carvacrol to remove iron from the high-affinity ligand transferrin and an Fe-dye complex was examined. Carvacrol retarded growth of S. Typhimurium at all iron conditions. Furthermore, iron-induced epithelial adhesion was effectively reduced by carvacrol at high iron concentrations. The reduction of growth and virulence by carvacrol was not paralleled by a change in iron uptake or influx into S. Typhimurium. In contrast, bioavailability of iron for epithelial cells was moderately decreased under these conditions. Further, carvacrol was shown to lack the properties of an iron binding molecule; however, it was able to weaken iron-ligand interactions by which it may possibly interfere with bacterial virulence. In conclusion, our in vitro data suggest that carvacrol has the potential to serve as a novel dietary supplement to prevent pathogenic overgrowth and colonization in the large intestine during oral iron therapy.

Anemia is a frequent sign in patients with diffuse large B-cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin and interleukin-6 (IL-6) in plasma samples of 53 patients with DLBCL. The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in particular when anemia was present (p = 0.01). Hepcidin plasma levels were significantly higher in patients compared to controls (p = 0.006), particularly in those with characteristics associated with a more active disease, including elevated lactate dehydrogenase (LDH) (p = 0.0004), B-symptoms (p = 0.07) and an age-adjusted international prognostic index (IPI) score > 1 (p = 0.01). Hepcidin levels correlated strongly to ferritin (r = 0.77, p < 0.0001) and weakly to IL-6 concentrations (r = 0.30, p = 0.03), but not to hemoglobin values. IL-6 inversely correlated to hemoglobin values in both univariate and multivariate analysis (p = 0.04), including hepcidin and erythropoietin as variables. Our findings suggest that elevated hepcidin levels and inadequate erythropoietin response are frequent in DLBCL, but elevated IL-6 plays the major role for the development of anemia.

Item does not contain fulltext, Bacteria constitute about 90% of all cells in the human body. The densest and most complex bacterial community is in the large intestine. This population is quite stable in healthy intestines, but intestinal disease distorts the ecological balance and induces dysbiosis. Results of studies have indicated that the epithelial and metabolic changes that occur with colorectal cancer provide a competitive advantage to a subset of intestinal bacteria. Strikingly, however, Streptococcus gallolyticus gallolyticus (previously known as Streptococcus bovis biotype I) is one of the very few opportunistic pathogens that has been clinically linked to colonic malignant diseases. In this Personal View we describe how S. gallolyticus gallolyticus exploits its unique range of virulence features to cause infections in patients with colorectal cancer. We postulate that distinct virulence factors on one hand enable this bacterium to establish a symptomatic infection in susceptible individuals, and on the other hand make its ability to do this dependent on pre-existing colonic abnormalities. We believe that our current reconstruction of this route of infection aids understanding of how S. gallolyticus gallolyticus infections can be best exploited for early detection of colorectal cancer.

Item does not contain fulltext, BACKGROUND: The iron-regulating hormone hepcidin is a promising biomarker in the diagnosis of iron disorders. Concentrations of hepcidin have been shown to increase during the day in individuals who are following a regular diet. It is currently unknown whether these increases are determined by an innate rhythm or by other factors. We aimed to assess the effect of dietary iron on hepcidin concentrations during the day. METHODS: Within a 7-day interval, 32 volunteers received an iron-deficient diet on 1 day and the same diet supplemented with 65 mg ferrous fumarate at 0815 and 1145 on another day. Blood was drawn to assess ferritin, hepcidin-25, and transferrin saturation (TS) throughout both days at 4 time points between 0800 (fasted) and 1600. A linear mixed model for repeated data was used to analyze the effect of iron intake on TS and hepcidin concentrations. RESULTS: Baseline values of hepcidin at 0800 correlated significantly with ferritin (r = 0.61). During the day of an iron-deficient diet the mean TS was similar both in men and in women, whereas hepcidin increased. During the day with iron supplementation the mean TS was significantly higher both in men and in women, and the mean hepcidin was moderately but significantly higher in women (1.0 nmol/L, 95% CI, 0.2-1.8) but not in men (0.0 nmol/L, 95% CI, -0.8 to 0.8). CONCLUSIONS: Our data demonstrate that ferritin sets the basal hepcidin concentrations and suggest that innate diurnal rhythm rather than dietary iron mediates the daily hepcidin variations. These findings will be useful for optimizing sampling protocols and will facilitate the interpretation of hepcidin as an iron biomarker.

Contains fulltext : 125929.pdf (publisher's version ) (Open Access), Mass spectrometry (MS)-based assays for the quantification of the iron regulatory hormone hepcidin are pivotal to discriminate between the bioactive 25-amino acid form that can effectively block the sole iron transporter ferroportin and other naturally occurring smaller isoforms without a known role in iron metabolism. Here we describe the design, validation and use of a novel stable hepcidin-25(+40) isotope as internal standard for quantification. Importantly, the relative large mass shift of 40 Da makes this isotope also suitable for easy-to-use medium resolution linear time-of-flight (TOF) platforms. As expected, implementation of hepcidin-25(+40) as internal standard in our weak cation exchange (WCX) TOF MS method yielded very low inter/intra run coefficients of variation. Surprisingly, however, in samples from kidney disease patients, we detected a novel peak (m/z 2673.9) with low intensity that could be identified as hepcidin-24 and had previously remained unnoticed due to peak interference with the formerly used internal standard. Using a cell-based bioassay it was shown that synthetic hepcidin-24 was, like the -22 and -20 isoforms, a significantly less potent inducer of ferroportin degradation than hepcidin-25. During prolonged storage of plasma at room temperature, we observed that a decrease in plasma hepcidin-25 was paralleled by an increase in the levels of the hepcidin-24, -22 and -20 isoforms. This provides first evidence that all determinants for the conversion of hepcidin-25 to smaller inactive isoforms are present in the circulation, which may contribute to the functional suppression of hepcidin-25, that is significantly elevated in patients with renal impairment. The present update of our hepcidin TOF MS assay together with improved insights in the source and preparation of the internal standard, and sample stability will further improve our understanding of circulating hepcidin and pave the way towards further optimization and standardization of p

Item does not contain fulltext, The colonic mucosa is in constant physical interaction with a dense and complex bacterial community that comprises health-promoting and pathogenic microbes. Here, we highlight important clinical studies and experimental models that have linked the intestinal microbiota to the development of colorectal cancer (CRC). Moreover, we use recently published metatranscriptome sequencing data to test whether potentially carcinogenic toxin genes exhibit higher expression levels in human CRC tissue compared to adjacent non-malignant mucosa. Our analyses show a large variation in expression of toxin(-related) genes from different species. Surprisingly, Enterobacterial toxins were among the highest expressed, while Enterobacteria were not among the most abundant species in these samples. Although we can differentiate on- and off-tumour sites based on toxin reads, the read depth profiles are quite similar and show only limited coverage of the toxin genes. Thus, extended metagenomic studies are needed to obtain a high-resolution picture of host-pathogen interactions during human CRC.

Item does not contain fulltext, The effect of exercise modality and intensity on Interleukin-6 (IL-6), iron status, and hepcidin levels was investigated. Ten trained male triathletes performed 4 exercise trials including low-intensity continuous running (L-R), low-intensity continuous cycling (L-C), high-intensity interval running (H-R), and high-intensity interval cycling (H-C). Both L-R and L-C consisted of 40 min continuous exercise performed at 65% of peak running velocity (vVO2peak) and cycling power output (pVO2peak), while H-R and H-C consisted of 8 x 3-min intervals performed at 85% vVO2peak and pVO2peak. Venous blood samples were drawn pre-, post-, and 3 hr postexercise. Significant increases in postexercise IL-6 were seen within each trial (p < .05) and were significantly greater in H-R than L-R (p < .05). Hepcidin levels were significantly elevated at 3 hr postexercise within each trial (p < .05). Serum iron levels were significantly elevated (p < .05) immediately postexercise in all trials except L-C. These results suggest that, regardless of exercise mode or intensity, postexercise increases in IL-6 may be expected, likely influencing a subsequent elevation in hepcidin. Regardless, the lack of change in postexercise serum iron levels in L-C may indicate that reduced hemolysis occurs during weight-supported, low-intensity activity.

Item does not contain fulltext, BACKGROUND: Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption. OBJECTIVE: We investigated whether weight status predicts response to oral iron supplementation in ID South African children. DESIGN: A placebo-controlled trial of oral iron supplementation (50 mg, 4 x weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio. RESULTS: At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (beta=0.232, P<0.001) and lower body iron (beta=-0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin x BAZ interaction (P=0.058). CONCLUSION: South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.