Does the Combined Effect of Resistance Training with EPO and Iron Sulfate Improve Iron Metabolism in Older Individuals with End-Stage Renal Disease?

We sought to investigate the effects of resistance training (RT) combined with erythropoietin (EPO) and iron sulfate on the hemoglobin, hepcidin, ferritin, iron status, and inflammatory profile in older individuals with end-stage renal disease (ESRD). ESRD patients (n: 157; age: 66.8 ± 3.6; body mass: 73 ± 15; body mass index: 27 ± 3), were assigned to control (CTL; n: 76) and exercise groups (RT; n: 81). The CTL group was divided according to the iron treatment received: without iron treatment (CTL—none; n = 19), treated only with iron sulfate or EPO (CTL—EPO or IRON; n = 19), and treated with both iron sulfate and EPO (CTL—EPO + IRON; n = 76). The RT group followed the same pattern: (RT—none; n = 20), (RT—EPO or IRON; n = 18), and (RT—EPO + IRON; n = 86). RT consisted of 24 weeks/3 days per week at moderate intensity of full-body resistance exercises prior to the hemodialysis section. The RT group, regardless of the iron treatment, improved iron metabolism in older individuals with ESRD. These results provide some clues on the effects of RT and its combination with EPO and iron sulfate in this population, highlighting RT as an important coadjutant in ESRD-iron deficiency.     

Iron and Parkinson's disease: chelators to the rescue?

The essential metal iron has long been implicated in the neuronal damage associated with Parkinson's disease. Recent findings show that iron chelation may prevent the reductions in dopamine and motor disturbances associated with this disease, and suggest the need to examine the role of dietary iron and the use of metal chelators in neurodegenerative disorders.     

Iron,Zinc and α -Tocopherol Content of Bovine Hemopoietic Marrow

Marrow was obtained from trimmed bovine cervical vertebrae by refrigerated centrifugation so that its moisture, protein, fat, iron, zinc and α -tocopherol content could be determined. Fatty marrow from the shaft of femurs was also analyzed for α -tocopherol which is located in the membrane and bulk oil portions of the adipose cell. Hemopoietic marrow from cervical vertebrae, fatty marrow from femurs and lean from the vertebrae averaged 16%, 86% and 1% ether extract, respectively, but the variability for hemopoietic marrow was high. The high fat variability probably contributed to a range of 10.0–34.0 mg iron/100 g of fresh hemopoietic marrow. However, even the lowest iron value in hemopoietic marrow was much higher than it is in muscle. Hence, part of the increase in iron in mechanically recovered meat, when compared to hand-boned meat, is beneficial nutritionally but it could increase lipid oxidation. Zinc was lower in hemopoietic marrow than it was in muscle but means for α -tocopherol in hemopoietic marrow, fatty marrow and muscle did not differ (P>0.05). In contrast to iron, neither zinc nor α -tocopherol can be used to support the claim that marrow is a rich source of nutrients and neither would be expected to alter the processing characteristics of meat containing marrow.     

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores.Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins.Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status.Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins.Statins, prescribed widely for primary and secondary prevention of cardiovascular disease (CVD),1,2 have been recommended for expanded use in apparently healthy individuals at risk for CVD.3 On February 8, 2010 the US Food and Drug Administration approved rosuvastatin (Crestor) for

reducing the likelihood of a heart attack or stroke or the need for a procedure to treat blocked or narrowed arteries in patients who have never been told they have heart disease but are nevertheless at increased risk of a cardiac event.3

The target population included men older than 50 years and women older than 60 years with elevated levels of high-sensitivity C-reactive protein and an additional CVD risk factor such as smoking, hypertension, a family history of premature CVD, or low levels of high-density lipoprotein (HDL) cholesterol.4Computational studies concluded that a “treat-all” approach to CVD prevention is cost-effective.5–7 However, misgivings over widespread statin use have been expressed on the basis of overall societal impact, including cost and toxicity, especially with the extension of treatment to children.8–10 The wholesale cost of a 40-milligram rosuvastatin tablet at a local pharmacy recently was $4.22. Side effects of statins involve primarily liver11 and muscle12 damage. Statins also have been associated with risk of diabetes,13 nonmelanotic skin cancer,14 and adverse drug interactions.15–17 Although statins are of proven efficacy,1,2 CVD remains a major public health problem beckoning further innovative approaches to prevention and treatment.18The clinical benefits of statins relate to their ability to reduce cholesterol levels by inhibiting the rate-limiting cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-CoA reductase.1,2 However, drugs other than statins that effectively lower lipids have not improved clinical outcomes.19 Statins are effective in individuals with normal lipid levels1,2 exhibiting pleiotropic properties unrelated to lipid reduction.20,21 These properties include stimulation of new blood vessel22 and bone formation23 and the reduction of inflammation and oxidative stress.24–35Mascitelli and Goldstein provided evidence that the beneficial effects of statins may result from their ability to favorably alter iron homeostasis.36 Pathologic cellular iron retention has been implicated in systemic oxidative stress, vascular inflammation, and atherogenesis. Statins reduce ferritin levels in patients with advanced CVD,37–39 renal disease,40 and diabetes.41 Data from a randomized trial of iron (ferritin) reduction (the Iron and Atherosclerosis Study [FeAST]) in participants with advanced peripheral arterial disease (PAD) showed significant improvement in all-cause mortality and combined death plus nonfatal myocardial infarction and stroke with iron reduction.42 There is evidence suggesting that iron reduction may provide an alternative to statins for reducing inflammation associated with atherosclerosis.     

Iron overload in Sub-Saharan Africa: to what extent is it a public health problem?

Excessive deposition of Fe in the organs and tissues of Sub-Saharan Africans was first described in South Africa in 1929. Fe overload, or siderosis, was initially attributed to infections and to metallic poisoning (Cu, Sn, Zn), and then to malnutrition. In 1953 it was hypothesized that it was due primarily to excessive Fe intake derived from foods and drinks prepared in Fe vessels. Recently, in 1992 it was advanced that a gene distinct from any HLA-linked locus may also play a role. As to sequelae, in early research on series of hospital patients, the condition was linked to scurvy, osteoporosis, diabetes, cirrhosis, and latterly, to hepatocellular cancer and tuberculosis. Accordingly, many have concluded that Fe overload is responsible for considerable morbidity and mortality, that adventitious Fe intake should be reduced, and that phlebotomy be recommended for those severely affected. However, there are numerous limitations in the evidence. There are also problems in interpretation, since levels of Fe in the serum are affected additionally by a variety of factors: infection, inflammation, certain cancers and alcohol intake. These considerations complicate attempts to assess to what extent the associations described denote causation, and whether Fe overload has significant ramifications for ill in the general African population. While the adverse sequelae of overload may be less of significance than many believe, the precise pathogenicity of the phenomenon will remain uncertain until further investigations, including prospective studies, are undertaken.     

Iron status influences the efficacy of iodine prophylaxis in goitrous children in Côte d'Ivoire

In the developing countries of Africa, many children are at high risk for both goiter and iron-deficiency anemia (IDA). Because iron (Fe) deficiency can have adverse effects on thyroid metabolism, Fe deficiency may influence response to supplemental iodine in areas of endemic goiter. Therefore, our aims were to determine: 1) if goitrous children also suffering from IDA could respond to oral iodine supplementation; and 2) if Fe supplementation in goitrous children with IDA would improve their response to oral iodized oil and iodized salt. First, we compared the efficacy of oral iodized oil in two groups of goitrous children: a nonanaemic group vs. an IDA group. The therapeutic response to iodized oil was impaired in the goitrous children with IDA. Second, an open trial of Fe treatment in goitrous children with IDA improved their response to oral iodized oil. Finally, in a randomized double-blind trial, goitrous, Fe-deficient children consuming iodized salt were given Fe supplementation or placebo. Fe supplementation improved the efficacy of the iodized salt. In these studies, both anatomic (thyroid size) and biochemical (TSH, T4) measures indicated that iodine significantly improved thyroid function in the nonanaemic children compared to the Fe deficient children. Iodine was less efficacious in children with lower Hb at baseline and in those with a poorer response to Fe. The data suggest that a high prevalence of IDA among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis.     

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term

Purpose

An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8–1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term.

Methods

At term age, 3 and 6 months post-term, ferritin (μg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated.

Results

Iron was supplemented to 71.7 % of HM-fed and 83.7 % of IFF-fed infants between term age and 3 months post-term and to 13 % of HM-fed and 0 % of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 μg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8 % and 26.3 vs. 9.5 %, P < 0.02).

Conclusion

This observational study demonstrates that ferritin <12 μg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8–1.0 mg iron/100 ml), as they achieve ferritin ≥12 μg/l without additional iron supplements between 3 and 6 months post-term.     

Reducing Iron Deficiency in 18–36-months-old US Children: Is the Solution Less Calcium?

Objectives National surveys consistently identify iron deficiency (ID) in US children between 1 and 3 years of age, when the brain is rapidly developing and vulnerable to the effects of ID. However, controversy remains as to how best to recognize and prevent ID in young children, in part because of the multiple potential etiologies. The objective of this project was to assess ID in children and identify potential individual dietary predictors of status. Methods We examined three biomarkers of ID [soluble transferrin receptor (sTfR) and serum ferritin (SF), and body iron (calculated from sTfR and SF)] against parent-provided dietary calcium and iron intake for eight-three 18–36 month old children from middle class families. Results Using literature-based cutoffs, fourteen children (16.9 %) had at least one indicator of ID: low SF(<10 μg/l, 7.2 %), negative body iron (<0 mg/kg, 7.2 %) or elevated sTfR (>8.4 μg/ml, 13.2 %). All children consumed more than the Dietary Reference Intake (DRI) Estimated Average Requirement of 3 mg/d iron. The mean iron intake of children identified with ID approximated the Recommended Dietary Allowance of 7 mg/d. Most children (81 %) consumed above the DRI Adequate Intake of 500 mg/d of calcium. Calcium intakes were generally high and predicted lower body iron (p = 0.0005), lower SF (p = 0.0086) and higher sTfR (p = 0.0176). Conclusions for Practice We found rates of ID similar to US national averages. Dietary calcium intake predicted lower iron status more than deficits in iron intake. Teaching parents to balance calcium and iron intake in toddlers could be a strategy to prevent ID.     

Iron status of one-year-olds and association with breast milk, cow’s milk or formula in late infancy

Purpose

Studies on iron status in infancy and early childhood have shown contradicting results concerning prolonged breast-feeding and cow’s milk intake. The aim of the present study was to investigate associations between iron status among one-year-olds and feeding, with focus on the type of milk.

Methods

Randomly selected healthy infants were prospectively investigated until 1 year of age in two cohorts born 1995–1996 (n = 114) and 2005 (n = 140). Information on birth data, feeding and growth until 12 months and iron status at 12 months was collected. Data from the two cohorts were pooled and the infants categorized into three groups according to their predominant milk consumption at 9 months of age, that is, breast milk, cow’s milk or follow-on formula.

Results

The prevalence of iron deficiency was highest in the cow’s milk group and lowest in the follow-on formula group. According to a linear model, adjusted for gender, birth weight and exclusive breast-feeding duration, cow’s milk consumption was negatively associated with serum ferritin (SF) and formula positively, but breast milk not. Predicted SF (μg/l) = 11.652(intercept) ? 5.362(boy) + 0.005 × birth weight (g) + 2.826(exclusively breastfed ≥ 4 months) + 0.027 × formula (ml) ? 0.022 × cow’s milk (ml) + 0.005 × breast milk (ml). Correction for other dietary factors did not change these results.

Conclusion

In this pooled analysis, cow’s milk intake in late infancy associated negatively, and follow-on formula positively, with iron status. Prolonged partial breast-feeding does not seem to be of importance for iron status. Fortified food seems to improve iron status in late infancy.     

Iron status and neuropsychological consequences in women of reproductive age: what do we know and where are we headed?

Iron deficiency disproportionately affects infants, children, and women of reproductive age. It is more prevalent in developing countries but continues to be a problem in developed countries. Included among the consequences of iron deficiency are changes in cognitive performance, emotions, and behavior. Although the behavioral and developmental sequelae of iron deficiency in young children have received much interest, data on the consequences of iron deficiency in women of reproductive age are just beginning to emerge. Interest in this area increased as a result of the findings that brain iron is much more fluid than previously thought and iron-deficient animals experience nondevelopment-dependent brain alterations. These findings, coupled with the symptoms often reported by iron-deficient women (lethargy, inability to concentrate, difficulty with memory, etc.), have led researchers to begin to explore the relation between iron and neuropsychological outcomes in this population. This paper reviews findings from studies that have examined the brain functional consequences of iron deficiency in women of reproductive age. Additional consideration is given to the fact that detriments to cognition and behavior in a woman of reproductive age may have negative implications beyond the woman's health; specifically, they may negatively influence her children. Therefore, the roles that cognitive and behavioral changes in these women have on their children's development is also reviewed. The paper concludes with a discussion on ways to use technological advances (especially in neuroimaging techniques) to help us elucidate the role of iron in the brains of women of reproductive age.     

Implementation and impact of the National Iron Supplementation Program in the city of Viçosa, State of Minas Gerais

The scope of this work was to evaluate the implementation of the National Iron Supplementation Program (NISP) in Vi?osa in the State of Minas Gerais and its impact on 6- to 18-month-old non-anemic infants assisted by the Family Health Teams. Interviews were conducted with the professionals and with the children's mothers/guardians. The non-anemic children who didn't receive the earlier supplementation (n=133) were given ferrous sulphate syrup for six months. Hemoglobin dosage, anthropometric evaluation and a socioeconomic survey were conducted before and after the six-month period. Children who ingested 75% or more of the prescribed dosage were classified as high adhesion, while the others were classified as low adhesion, according to the mothers' testimonials. With respect to the implementation in the city, the distribution system was not always available to the priority group and there was a lack of training and motivation on the part of most Community Health Agents. The lack of promotion of NISP among the priority group was detected, apart from a mothers' awareness drive. Regarding diet supplementation, children showed low adhesion and the dosage wasn't effective in preventing anemia. Therefore, important operational barriers to implementation were observed.     

Are Biofortified Staple Food Crops Improving Vitamin A and Iron Status in Women and Children? New Evidence from Efficacy Trials

Biofortification is the breeding of crops to increase their nutritional value, including increased contents of micronutrients or their precursors. Biofortification aims to increase nutrient levels in crops during plant growth rather than during processing of the crops into foods. Emerging research from 8 human trials conducted in the past decade with staple food crops that have been biofortified by traditional plant breeding methods were presented in this symposium. Specifically, data from 6 efficacy and 2 effectiveness trials were discussed to assess the effects of regular consumption of these enhanced staple crops on improving population vitamin A and iron status and reducing the burden of micronutrient deficiencies in targeted populations living in South Asia, Sub-Saharan Africa, and Latin America. Biofortified food crops appear to have a positive impact on nutritional and functional health outcomes, as the results from the trials suggest. Additional implementation research will be needed to ensure maximization of the beneficial impact of this intervention and a smooth scaling up to make biofortification a sustainable intervention in public health. The challenge for the global health community remains how to take this efficacious intervention and implement at large scale in the real world.     

Iron retention in young women fed chickpea (Cicer Arietinum) and milk‐supplemented wheat diets at two levels of energy

Nine young adult women were fed diets containing wheat, wheat and chickpea or wheat and milk at each of the two energy levels of 1900 and 1600 Kcal/day. Iron was estimated in food, feces and urine. From a balance study, iron intake, iron excretion, iron absorption and iron retention were calculated. The results indicated that utilization of iron was better at higher energy level. The iron absorption and retention was highest in chickpea supplemented diets followed by milk and wheat supplemented diets. The absorption decreased practically in all the subjects when shifted from high to low level of energy. The fecal iron excretion was affected significantly (P ≤ 0.01) as the level of energy is changed from 1900 Kcal to 1600 Kcal. Protein source also affect fecal iron excretion significantly (P ≤ 0.01). Neither the protein source nor the level of energy had any significant effect on urinary iron excretion.     

Is There a Causal Relationship between Iron Deficiency or Iron-Deficiency Anemia and Weight at Birth, Length of Gestation and Perinatal Mortality?

An extensive literature review was conducted to identify whether iron deficiency, iron-deficiency anemia and anemia from any cause are causally related to low birth weight, preterm birth or perinatal mortality. Strong evidence exists for an association between maternal hemoglobin concentration and birth weight as well as between maternal hemoglobin concentration and preterm birth. It was not possible to determine how much of this association is attributable to iron-deficiency anemia in particular. Minimal values for both low birth weight and preterm birth occurred at maternal hemoglobin concentrations below the current cut-off value for anemia during pregnancy (110 g/L) in a number of studies, particularly those in which maternal hemoglobin values were not controlled for the duration of gestation. Supplementation of anemic or nonanemic pregnant women with iron, folic acid or both does not appear to increase either birth weight or the duration of gestation. However, these studies must be interpreted cautiously because most are subject to a bias toward false-negative findings. Thus, although there may be other reasons to offer women supplemental iron during pregnancy, the currently available evidence from studies with designs appropriate to establish a causal relationship is insufficient to support or reject this practice for the specific purposes of raising birth weight or lowering the rate of preterm birth.     

Calcium,Magnesium, Iron,Zinc and Copper,Compositions of Human Milk from Populations with Cereal and ‘Enset’ Based Diets

Background

As breast milk is normally the only source of food in the early stages of life, the dietary levels of the essential elements in the milk of lactating mothers are significantly important. Ethiopia is a country of many nations and nationalities with distinct dietary habits. This variation in food habit may result in the variation of the nutritional quality of milk of lactating mothers who live in different part of the country, which in turn may affect the intake of nutrients by breast-fed infants. Therefore, a cross-sectional study of the levels of Ca, Mg, Fe, Zn and Cu in milk of mothers from societies with cereal and ‘enset’ based dietary habits was carried out to assess the influence of maternal diet on the levels of the elements in human milk.

Methods

Milk samples were collected from 27 voluntary mothers in Jimma and in 18 rural areas of Welkite. Breast milk samples were collected within four days postpartum and the concentrations of the elements were determined by using FAAS.

Results

Average concentrations (mg/L) of the elements determined in the milk of mothers from Jimma and rural Welkite respectively were: Ca (758 ± 107, 579 ± 168); Mg (22.6 ± 7.87, 30.5 ± 13.4); Fe (0.50 ± 0.08, 0.41 ± 0.17); Zn (2.3 ± 1.2, 2.49 ± 0.88) and Cu (0.28 ± 0.14, 0.16 ± 0.08).

Conclusions

Milk samples from Jimma were found to have significantly higher levels of Ca and Cu than those of rural Welkite (P < 0.05). Breast milk Ca and Cu levels were thus found to be influenced by dietary intake.     

Dietary Non-heme Iron Bioavailability Among Children (Ages 5–8) in a Rural,High-Anemia-Prevalent Area in North India: Comparison of Algorithms

Non-heme iron bioavailability of diet consumed by children (ages 5 to 8) in rural area of India was estimated by comparison of algorithms. A cross-sectional observational study was conducted among 232 children and consisted of a 24-hour recall on 2 nonconsecutive days. Four algorithms were chosen to estimate the non-heme iron bioavailability. Daily average non-heme iron bioavailability as calculated by different algorithms was low (between 3.2% and 4.6%). Correlations of bioavailable non-heme iron among different algorithms were strong, ranging from rs = 0.67 to rs = 0.85 (p ≤ .01).     

Stability of Vitamin A,Iron and Zinc in Fortified Rice during Storage and Its Impact on Future National Standards and Programs—Case Study in Cambodia

Fortified rice holds great potential for bringing essential micronutrients to a large part of the world population. The present study quantified the losses of three different micronutrients (vitamin A, iron, zinc) in fortified rice that were produced using three different techniques (hot extrusion, cold extrusion, and coating) and stored at two different environments (25 ± 5 °C at a humidity of 60% and 40 ± 5 °C at a humidity of 75%) for up to one year. Fortified rice premix from the different techniques was mixed with normal rice in a 1:100 ratio. Each sample was analyzed in triplicate. The study confirmed the high stability of iron and zinc during storage while the retention of vitamin A was significantly affected by storage and the type of techniques used to make rice premix. Losses for iron and zinc were typically <10% for any type of rice premix. After 12 months at mild conditions (25 °C and humidity of 60%), losses for vitamin A ranged from 20% for cold extrusion, 30% for hot extruded rice 77% for coated rice premix. At higher temperatures and humidity, losses of vitamin A were 40%–50% for extruded premix and 93% for coated premix after 6 months. We conclude that storage does lead to a major loss of vitamin A and question whether rice is a suitable food vehicle to fortify with vitamin A. For Cambodia, fortification of rice with iron and zinc could be an effective strategy to improve the micronutrient status of the population if no other food vehicles are available.     

Determination of Mercury,Cadmium, Lead,Zinc, Selenium and Iron by ICP-OES in Mushroom Samples from Around Thermal Power Plant in Muğla,Turkey

Scleroderma verrucosum, Stropharia coronilla, Lactarius deterrimus, Chroogomphus rutilus, Russula delica, Laccaria laccata, Clitocybe odora var. alba, Lyophyllum decastes, Coprinus comatus, Helvella leucomelaena, Melanoleuca cognata, Melanoleuca cognata, Paxina acetabulum, Clitocybe vermicularis, Sarcosphaera crassa, Rhizopogon roseolu and Thelephora caryophyllea were collected from different localities in Muğla-Yatağan region of Turkey. Their trace metals concentrations were determined by ICPOES after microwave digestion. The results were 0.37 ± 0.01–5.28 ± 0.21 for cadmium, 467 ± 19–3,280 ± 131 for iron, 0.69 ± 0.03–9.15 ± 0.37 for lead, 18.70 ± 0.75–67.10 ± 2.68 for selenium, 75 ± 3–213 ± 8 for zinc and 0.15 ± 0.01–0.55 ± 0.01 for mercury (as μg/g). The detection limits for ICPOES were found as 0.25 for Cadmium, 0.2 for iron, 0.1 for lead, 0.5 for selenium, 0.2 for zinc and 0.03 for mercury (as mg L⁻¹). The Relatively Standard Deviations (R.S.D.) were found below 4.0%. The accuracy of procedure was confirmed by certified reference material.