Correcting for inflammation changes estimates of iron deficiency among rural Kenyan preschool children

The assessment of iron status where infections are common is complicated by the effects of inflammation on iron indicators and in this study we compared approaches that adjust for this influence. Blood was collected in 680 children (aged 6-35 mo) and indicators of iron status [(hemoglobin (Hb), zinc protoporphyrin (ZP), ferritin, transferrin receptor (TfR), and TfR/ferritin index)] and subclinical inflammation [(the acute phase proteins (APP) C-reactive protein (CRP), and α-1-acid glycoprotein (AGP)] were determined. Malaria parasitemia was assessed. Subclinical inflammation was defined as CRP >5 mg/L and/or AGP >1 g/L). Four groups were defined based on APP levels: reference (normal CRP and AGP), incubation (raised CRP and normal AGP), early convalescence (raised CRP and AGP), and late convalescence (normal CRP and raised AGP). Correction factors (CF) were estimated as the ratios of geometric means of iron indicators to the reference group of those for each inflammation group. Corrected values of iron indicators within inflammation groups were obtained by multiplying values by their respective group CF. CRP correlated with AGP (r = 0.65; P < 0.001), ferritin (r = 0.38; P < 0.001), Hb (r = -0.27; P < 0.001), and ZP (r = 0.16; P < 0.001); AGP was correlated with ferritin (r = 0.39; P < 0.001), Hb (r = -0.29; P < 0.001), and ZP (r = 0.24; P < 0.001). Use of CF to adjust for inflammation increased the prevalence of ID based on ferritin < 12 μg/L by 34% (from 27 to 41%). Applying the CF strengthened the expected relationship between Hb and ferritin (r = 0.10; P = 0.013 vs. r = 0.20; P < 0.001, before and after adjustment, respectively). Although the use of CF to adjust for inflammation appears indicated, further work is needed to confirm that this approach improves the accuracy of assessment of ID.     

Interpretation of serum ferritin concentrations as indicators of total-body iron stores in survey populations: the role of biomarkers for the acute phase response

BACKGROUND: Nutritional surveys use acute phase protein (APP) biomarkers such as C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) to identify the influence of inflammation on the distribution of iron status biomarkers. Few, however, have examined which biomarker better identifies persons with spurious elevations in iron status markers. OBJECTIVE: We explored the relations of APP biomarkers to iron-status biomarkers in infants and school-age children. DESIGN: In screening surveys, we identified a sample of African American infants (n = 351) and Guatemalan school-age children (n = 375). We used a common set of APP and iron-status biomarkers to examine the association between the 2 sets of markers (laboratory variables). RESULTS: The overall prevalence of either inflammation or iron deficiency was <10% in both samples. The log AGP and CRP values were significantly correlated (r = 0.70), but the unexplained variance still was >50%. Serum ferritin-but not transferrin receptor, transferrin receptor index, or serum iron-was related to APP concentrations, but poor positive predictive value (<72%) and low kappa scores were found. Ferritin concentrations >1 geometric SD above the geometric mean were poorly predicted by either elevated AGP or CRP. Qualitative CRP analysis was not effective in identifying persons who had other indications of mild inflammation. CONCLUSIONS: These analyses show that a low prevalence of inflammation has little influence on the distribution of ferritin, and 2 common indicators of inflammation do not perform equally well in identifying persons who may have elevations in ferritin due to inflammation.     

Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults

Inflammation influences the assessment of nutritional status. For example, inflammation reduces plasma retinol concentrations and vitamin A deficiency is overestimated. Conversely inflammation increases plasma ferritin concentrations and Fe deficiency is underestimated. Blood samples were obtained from 163 free-living HIV-1-infected adults, not on continuous medication, anti-retroviral drugs or micronutrients, not unwell and who had not reached WHO stage IV of HIV/AIDS. We used four markers of inflammation, C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin and erythrocyte sedimentation rate but mainly CRP and AGP were used to separate the subjects into four groups: 'healthy' where both CRP and AGP were normal; 'incubation phase' where CRP was elevated; 'early convalescence' where AGP and CRP were elevated and 'late convalescence' where only AGP was elevated. Correction factors were calculated to remove the influence of inflammation from each biomarker and group where inflammation was present and the data are shown before and after recalculation. The correction increased median plasma retinol concentrations of the whole group from 1.16 to 1.33 micromol/l, comparable with values (mean 1.29 micromol/l) in HIV-negative Kenyan women. Median ferritin concentrations fell by about 50% in both sexes and the number of women with plasma ferritin concentrations < or = 12 microg/l increased from eleven to twenty. The correction also increased plasma carotenoids and Hb but not alpha-tocopherol concentrations. We suggest that the method described to remove the influence of inflammation from nutritional biomarkers should be generally applicable in apparently healthy people and prevents discarding valuable data because of mild inflammation. The method does now need to be tested in other populations.     

Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants

Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), and indicators of micronutrient status were analyzed in 418 infants who completed a 6-mo randomized, double-blind, placebo-controlled, supplementation trial with iron, zinc and/or beta-carotene. The acute phase response, defined by raised CRP (plasma concentration >10 mg/L), raised AGP (>1.2 g/L), or both raised CRP and AGP, significantly affected indicators of iron, vitamin A and zinc status, independently of the effects of supplementation. Plasma ferritin concentrations were higher by 15.7 (raised AGP) to 21.2 (raised CRP and AGP) micro g/L in infants with elevated acute phase proteins compared with infants without acute phase response (P < 0.001). In contrast, plasma concentrations of retinol were lower by 0.07 (P < 0.05, raised AGP) to 0.12 (P < 0.01, raised CRP) micro mol/L, and of zinc lower by 1.49 (P < 0.01, raised AGP) to 1.89 (P < 0.05, raised CRP and AGP) micro mol/L. Hemoglobin concentrations and the modified relative dose response were not affected. Consequently, the prevalence of iron deficiency anemia was underestimated in infants with raised acute phase proteins by >15%, whereas the prevalence of vitamin A deficiency was overestimated by >16% compared with infants without acute phase response. Hence, using indicators of micronutrient status without considering the effects of the acute phase response results in a distorted estimate of micronutrient deficiencies, whose extent depends on the prevalence of infection in the population.     

Impact of acute malaria on plasma concentrations of transferrin receptors

The acute-phase response to infection alters the plasma concentrations of most biochemical measures of iron status, rendering assessment of status difficult. Soluble transferrin receptors (TfR) may be an exception but have not been examined longitudinally during the major metabolic and inflammatory changes which occur during clinical malaria. Blood samples were collected daily during hospitalization, and again at a follow-up 2-6 weeks after discharge, from adult, mainly European, patients (n = 49) who developed uncomplicated Plasmodium falciparum malaria following visits to endemic areas. Parasitaemia and plasma concentrations of ferritin, TfR, C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT) were measured. The concentrations of CRP, AGP and ACT correlated highly (P < 0.001) with each other and with plasma ferritin, and were significantly higher (P < 0.05) at all time points in hospital compared to the follow-up. TfR concentration correlated negatively and significantly (P < 0.05) with AGP and CRP but not with ACT or ferritin, and was significantly lower (around 30%) at all time points in hospital compared to follow-up, although in only 1 subject did it ever fall outside the normal reference range. In areas where both iron deficiency and clinical episodes of malaria are common, plasma TfR values need to be interpreted cautiously as indicators of iron status.     

Iron status and oxidative stress biomarkers in adults: A preliminary study

ObjectiveAlthough essential to many vital processes, iron catalyzes reactions that produce reactive oxygen species, which are associated with the increased risk of non-communicable chronic diseases and precocious aging. This study investigated whether ferritin, hemoglobin concentration, and dietary iron consumption are related to oxidative stress biomarkers in adults.MethodsData were collected from 134 allegedly healthy subjects >18 y of age who were randomly selected to participate in a cross-sectional study as part of the pilot project Prevalence of Risk Factors for Non-communicable Chronic Diseases in the Federal District, Brazil (VIVA Saúde-DF). Serum ferritin, malondialdehyde (MDA) and protein carbonyl concentrations, hemoglobin, and dietary iron consumption were analyzed.ResultsA weak positive correlation (r = 0.189, P = 0.032) and association (P = 0.046) was observed for serum ferritin and MDA. Hemoglobin concentrations were positively associated with serum MDA (P = 0.040). Dietary iron intake and serum protein carbonyl concentrations showed a weak positive correlation (r = 0.173, P = 0.046) for all subjects. Iron intake by women was positively associated with serum protein carbonyl (P = 0.03). A lower serum MDA concentration was found in ferritin-deficient subjects (P = 0.015) and men with anemia (P = 0.011).ConclusionThese results suggest that low levels of iron may reduce oxidative stress.     

Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial

In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n = 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 x 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 +/- 1.8 vs. 3.8 +/- 1.2 g/L, P < 0.001). The serum ferritin concentrations increased by 17.7 +/- 3.9 microgram/L (P < 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P = 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries.     

School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls.

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.     

Effect of ferroportin Q248H polymorphism on iron status in African children

BACKGROUND: Iron deficiency is common in African children, but genetic variations affecting susceptibility have not been identified. The Q248H mutation in ferroportin, a cellular iron exporter regulated by iron status and inflammation, may be associated with high iron stores in African adults. OBJECTIVE: The study examined the prevalence of iron deficiency in African children in an area where malaria transmission is low to absent and investigated whether ferroportin Q248H provides protection from iron deficiency. DESIGN: Complete blood counts, serum markers of iron status and inflammation, and ferroportin Q247H were measured in 208 preschool children in Harare, Zimbabwe. Iron deficiency was defined by serum ferritin and C-reactive protein (CRP) concentrations (definition 1) or by ferritin and the ratio of transferrin receptor to log10 ferritin (definition 2). RESULTS: Q248H was present in 40 children (38 heterozygotes, 2 homozygotes), elevated CRP was present in 26 (12.5%), and iron deficiency was present in 50 (24.0%) (definition 1) or 55 (26.4%) (definition 2). The interaction between ferroportin Q248H and CRP was significant for ferritin concentrations (P = 0.027) in a 2-factor analysis of variance model. With elevated CRP, the estimated geometric mean (SE range) ferritin concentration was 74 (52-106) microg/L for Q248H heterozygotes but 24 (20-30) microg/L for wild-type subjects (P = 0.016). With normal CRP, the ferritin concentration was 16 (14-19) microg/L whether or not the mutation was present. After adjustment for age and weight-for-height z score, the odds ratio (OR) for iron deficiency in Q248H heterozygotes was not significant according to definition 1 (OR: 0.53; 95% CI: 0.18, 1.40; P = 0.222) or definition 2 (OR: 0.39; 95% CI: 0.14, 1.07; P = 0.068). CONCLUSIONS: Any effect of Q248H in protecting against iron deficiency may be observable in children exposed to repeated inflammatory conditions. Further studies of iron status and ferroportin Q248H in African children are needed.     

Iron nutrition does not account for the hemoglobin differences between blacks and whites.

Many researchers have reported lower hemoglobin concentrations in blacks than in whites, but the reason for this difference is unknown. Data for 2515 persons (in 3-12 y and 18-45 y age groups) from the Second National Health and Nutrition Examination Survey (NHANES II) were evaluated to investigate the roles of iron intake and biochemical iron status indicators in explaining black and white differences in hemoglobin concentration. Dietary iron intake was estimated from one 24-h food recall, and hemoglobin, serum ferritin, transferrin saturation and erythrocyte protoporphyrin were measured by standard laboratory methods. Hemoglobin levels were substantially lower in black children (120.3 g/L) than in white children (126.8 g/L). Hemoglobin concentrations were also lower in black women (128.4 g/L) than in white women (133.9 g/L), and in black men (144.8 g/L) than in white men (153.2 g/L). Blacks had lower hemoglobin concentration than whites at most levels of dietary iron intake, serum ferritin, transferrin saturation and erythrocyte protoporphyrin. Despite their lower hemoglobin levels, blacks had higher serum ferritin levels than whites. These results suggest that the difference in hemoglobin concentrations between blacks and whites in the United States is the result of factors other than iron intake and iron status. More specific investigations of both the genetic and environmental determinants of iron utilization in blacks are needed.     

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status,Anemia, and Dietary Intake in South African Schoolchildren

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03–5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4–5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6–27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B₁₂, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT03572010","term_id":"NCT03572010"}}NCT03572010.     

Influence of inflammation on laboratory indicators of iron deficiency in the elderly

Hemoglobin, serum iron, transferrin, erythrocyte protoporphyrin and serum ferritin concentrations were measured in 151 elderly institutionalized women. One hundred-fifteen subjects presented an inflammatory process identified by at least one abnormal value for serum concentration of orosomucoid, C-reactive Protein and sedimentation rate. Thirty-six subjects did not present any biological evidence of inflammatory process. Anemia (according to WHO references) was present in 4 (11%) women without and in 37 (32%) women with inflammation. Hemoglobin and serum iron were negatively correlated with the different markers of inflammation, while erythrocyte protoporphyrin and serum ferritin were positively correlated with them. Total iron-binding capacity may be considered as the iron parameter the least affected by the inflammatory process. In women without inflammation, iron deficiency was defined as a combination of low transferrin saturation and a high erythrocyte protoporphyrin concentration. In women with inflammation, iron deficiency was defined as the same association combined with a high total iron-binding capacity. According to these definitions, iron deficiency was present in 11% of elderly women without inflammation and in 16% with biochemical evidence of an inflammatory process, respectively.     

Hepcidin and iron status among pregnant women in Bangladesh

Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.     

Calcium supplementation and plasma ferritin concentrations in premenopausal women.

The effect of calcium supplement use on iron stores was examined in a randomized controlled study in free-living, healthy, premenopausal women. Of 109 women who completed the study, 52 were in the control group and 57 took two tablets containing 250 mg Ca as the carbonate with each of two meals daily for 12 wk. In all subjects at baseline, plasma ferritin concentrations were positively correlated with heme-iron intake (r = 0.21, P = 0.04), serum iron concentration (r = 0.19, P = 0.04), transferrin saturation (r = 0.31, P = 0.001), and hemoglobin concentration (r = 0.22, P = 0.02), and negatively correlated with total iron-binding capacity (TIBC, r = -0.42, P < 0.001). No significant differences in absolute or percent changes in plasma ferritin concentrations, serum iron concentrations, TIBC, transferrin saturation, hemoglobin concentrations, or hematocrit were observed between the treatment and control groups. Thus, over a 12-wk period, use of 1000 mg Ca as the carbonate daily with meals does not appear to be detrimental to iron stores in healthy, free-living, premenopausal women.     

Iron status in exercising women: the effect of oral iron therapy vs increased consumption of muscle foods.

Forty-seven previously sedentary women participating in a 12-wk moderate aerobic-exercise program were randomly assigned to one of four dietary groups: 50-mg/d iron supplement and a low food-iron diet (50 FE + EX), 10-mg/d iron supplement and a low food-iron diet (10 FE + EX), placebo and unrestricted diet (P + EX), and meat supplement and high food-iron diet (M + EX). A sedentary control group (n = 13) received no dietary interventions. Hematocrit, total iron-binding capacity, and hemoglobin, serum iron, serum ferritin, and serum albumin concentrations were measured every 4 wk. Hemoglobin values decreased at the end of 4 wk in all exercising groups compared with the control group. Iron status in the 50 FE + EX and M + EX groups improved after week 4 as indicated by an increase in serum ferritin, serum iron, and hemoglobin concentrations, and a decline in total iron-binding capacity. Thus, short-term, moderate aerobic exercise resulted in compromised iron status that was offset to varying degrees by ingesting iron or meat supplements. However, meat supplements were more effective in protecting hemoglobin and ferritin status than were iron supplements.     

Multivitamin-mineral supplementation is not as efficacious as is iron supplementation in improving hemoglobin concentrations in nonpregnant anemic women living in Mexico

BACKGROUND: Iron supplements improve hemoglobin status and reduce anemia due to iron deficiency. It is not known whether multiple micronutrient (MM) supplements are as efficacious as are iron supplements alone in improving hemoglobin concentrations. OBJECTIVE: We conducted a randomized, double-blind community trial in Mexico to compare the efficacy of MM supplements containing iron with that of iron alone in improving hemoglobin concentrations in nonpregnant women. DESIGN: Nonpregnant women (n = 158) were recruited from a semirural community in Mexico and were randomly assigned to receive iron alone (60 mg; Fe group) or MM supplements (vitamins A, B complex, C, D, E, and K and iron, zinc, and magnesium; MM group) 6 d/wk in their home for 12 wk. Hemoglobin concentrations were measured in capillary blood samples at baseline and follow-up. RESULTS: The treatment groups (MM: n = 75; Fe: n = 77) did not differ significantly at recruitment in age, schooling, literacy, or socioeconomic status. There were no significant differences between groups in compliance (median: 97.5%), baseline hemoglobin concentrations, or prevalence of anemia (20%). Losses to follow-up (4%) and mean (+/-SD) changes in hemoglobin (MM group: 6.7 +/- 10.6 g/L; Fe group: 7.1 +/- 13.6 g/L) were not significantly different between groups. However, the change in hemoglobin in anemic subjects was greater in the Fe group than in the MM group (P < 0.05 for interaction), and there was no significant difference in nonanemic subjects. CONCLUSIONS: MM supplements may not be as efficacious as is iron alone in improving the hemoglobin status of anemic women.     

Hookworms, malaria and vitamin A deficiency contribute to anemia and iron deficiency among pregnant women in the plains of Nepal

Anemia and iron deficiency during pregnancy are prevalent in developing countries, but their causes are not always known. We assessed the prevalence and severity of anemia and iron deficiency and their association with helminths, malaria and vitamin A deficiency in a community-based sample of 336 pregnant women in the plains of Nepal. Hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin were assessed in venous blood samples. Overall, 72.6% of women were anemic (hemoglobin < 110 g/L), 19.9% had moderate to severe anemia (hemoglobin < 90 g/L) and 80.6% had iron deficiency (EP > 70 micromol/mol heme or serum ferritin < 10 microg/L). Eighty-eight percent of cases of anemia were associated with iron deficiency. More than half of the women (54.2%) had a low serum retinol concentration (<1.05 micromol/L), 74.2% were infected with hookworms and 19.8% had Plasmodium vivax malaria parasitemia. Hemoglobin, EP and serum ferritin concentrations were significantly worse and the prevalence of anemia, elevated EP and low serum ferritin was increased with increasing intensity of hookworm infection. Hookworm infection intensity was the strongest predictor of iron status, especially of depleted iron stores. Low serum retinol was most strongly associated with mild anemia, whereas P. vivax malaria and hookworm infection intensity were stronger predictors of moderate to severe anemia. These findings reinforce the need for programs to consider reducing the prevalence of hookworm, malaria infection and vitamin A deficiency where indicated, in addition to providing iron supplements to effectively control anemia.     

Effect of meals with milk on body iron stores and improvement of dietary habit during weight loss in female rhythmic gymnasts

This study investigated the effect of different timings of milk intake on body iron stores and improvement in the dietary habit of female collegiate rhythmic gymnasts. Subjects took iron tablets at both breakfast and dinner times during a weight-loss period. In addition, subjects ingested low-fat milk twice a day either at breakfast or dinner (group I; n = 7), or between meals (group II; n = 6) for 3 mo. Blood was collected four times. Red blood cell count, hemoglobin, serum iron, ferritin and erythropoietin concentrations were measured. Subjects completed a dietary survey for three consecutive days before each blood sampling. The mean body fat in both groups I and II was significantly lower after 3 mo than at the start of the study (p < 0.01). Red blood cell count and hemoglobin of group I were significantly higher as compared to those of group II (p < 0.05). Serum iron concentrations and transferrin saturation values remained unchanged in both groups. Serum ferritin concentrations in group I were significantly higher 3 mo after the start of the study, but this was not observed in group II. Energy and carbohydrate intake in group II, but not in group I, were significantly lower after 3 mo as compared to those after 1 and 2 mo as a result of missing meals. In conclusion, iron-supplemented meals via milk ingestion did not decrease body iron stores and maintained higher body iron stores compared to a diet that included milk intake between meals. Further, milk intake with meals is related to keeping regular meal times and frequency.     

Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria.

BACKGROUND: Serum transferrin receptor concentrations indicate both erythropoietic activity and the deficit of functional iron in the erythron. In contrast with serum ferritin concentrations, serum transferrin receptor concentrations are not or are only marginally influenced by the inflammatory response to infection. OBJECTIVE: We assessed iron status and examined the relation between serum transferrin receptor concentrations and malaria in children aged 2-36 mo who were asymptomatic for malaria. DESIGN: This was a community-based cluster survey (n = 318). RESULTS: Prevalences of malaria, anemia (hemoglobin concentration <110 g/L), iron deficiency (serum ferritin concentration <12 microg/L), and iron deficiency anemia were 18%, 69%, 53%, and 46%, respectively. Malaria was associated with lower mean hemoglobin concentrations (92.7 compared with 104.1 g/L; P = 0.0001) and higher geometric mean serum concentrations of transferrin receptor (11.4 compared with 7.8 mg/L; P = 0.005), ferritin (21.6 compared with 11.9 microg/L; P = 0.05), and C-reactive protein (12.5 compared with 6.8 mg/L; P = 0.004). There was no evidence for an association between serum concentrations of C-reactive protein and transferrin receptor. Children with malaria had higher serum transferrin receptor concentrations than expected for the degree of anemia, even after adjustment for inflammation indicated by serum C-reactive protein concentration quartiles (P = 0.02). CONCLUSIONS: Our findings are consistent with the notion that malaria-induced hemolysis is accompanied by increased erythropoiesis. Serum transferrin receptor concentration is not useful for detecting iron deficiency in individuals with malaria. Individuals with high concentrations of serum C-reactive protein or similar acute phase reactants should be excluded from analysis if serum ferritin concentrations <12 microg/L are to be used to measure iron deficiency in malaria-endemic areas.     

α1-Acid Glycoprotein and Dietary Intake in End-Stage Renal Disease Patients

Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition–inflammation–atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein—α₁-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days—two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate–calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = −0.27) and TIBC (R = −0.30). AGP correlated negatively with the dietary intake of plant protein (R = −0.40), potassium (R = −0.27), copper (R = −0.30), vitamin B₆ (R = −0.27), and folates (R = −0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.