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Iron Supplementation Influence on the Gut Microbiota and Probiotic Intake Effect in Iron Deficiency-A Literature-Based Review.
Rusu, IG, Suharoschi, R, Vodnar, DC, Pop, CR, Socaci, SA, Vulturar, R, Istrati, M, Moroșan, I, Fărcaș, AC, Kerezsi, AD, et al
Nutrients. 2020;(7)
Abstract
Iron deficiency in the human body is a global issue with an impact on more than two billion individuals worldwide. The most important functions ensured by adequate amounts of iron in the body are related to transport and storage of oxygen, electron transfer, mediation of oxidation-reduction reactions, synthesis of hormones, the replication of DNA, cell cycle restoration and control, fixation of nitrogen, and antioxidant effects. In the case of iron deficiency, even marginal insufficiencies may impair the proper functionality of the human body. On the other hand, an excess in iron concentration has a major impact on the gut microbiota composition. There are several non-genetic causes that lead to iron deficiencies, and thus, several approaches in their treatment. The most common methods are related to food fortifications and supplements. In this review, following a summary of iron metabolism and its health implications, we analyzed the scientific literature for the influence of iron fortification and supplementation on the gut microbiome and the effect of probiotics, prebiotics, and/or synbiotics in iron absorption and availability for the organism.
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Iron Deficiency and Iron Deficiency Anemia: Implications and Impact in Pregnancy, Fetal Development, and Early Childhood Parameters.
Means, RT
Nutrients. 2020;(2)
Abstract
A normal pregnancy consumes 500-800 mg of iron from the mother. Premenopausal women have a high incidence of marginal iron stores or iron deficiency (ID), with or without anemia, particularly in the less developed world. Although pregnancy is associated with a "physiologic" anemia largely related to maternal volume expansion; it is paradoxically associated with an increase in erythrocyte production and erythrocyte mass/kg. ID is a limiting factor for this erythrocyte mass expansion and can contribute to adverse pregnancy outcomes. This review summarizes erythrocyte and iron balance observed in pregnancy; its implications and impact on mother and child; and provides an overview of approaches to the recognition of ID in pregnancy and its management, including clinically relevant questions for further investigation.
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3.
Iron balance and iron supplementation for the female athlete: A practical approach.
Pedlar, CR, Brugnara, C, Bruinvels, G, Burden, R
European journal of sport science. 2018;(2):295-305
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Abstract
Maintaining a positive iron balance is essential for female athletes to avoid the effects of iron deficiency and anaemia and to maintain or improve performance. A major function of iron is in the production of the oxygen and carbon dioxide carrying molecule, haemoglobin, via erythropoiesis. Iron balance is under the control of a number of factors including the peptide hormone hepcidin, dietary iron intake and absorption, environmental stressors (e.g. altitude), exercise, menstrual blood loss and genetics. Menstruating females, particularly those with heavy menstrual bleeding are at an elevated risk of iron deficiency. Haemoglobin concentration [Hb] and serum ferritin (sFer) are traditionally used to identify iron deficiency, however, in isolation these may have limited value in athletes due to: (1) the effects of fluctuations in plasma volume in response to training or the environment on [Hb], (2) the influence of inflammation on sFer and (3) the absence of sport, gender and individually specific normative data. A more detailed and longitudinal examination of haematology, menstrual cycle pattern, biochemistry, exercise physiology, environmental factors and training load can offer a superior characterisation of iron status and help to direct appropriate interventions that will avoid iron deficiency or iron overload. Supplementation is often required in iron deficiency; however, nutritional strategies to increase iron intake, rest and descent from altitude can also be effective and will help to prevent future iron deficient episodes. In severe cases or where there is a time-critical need, such as major championships, iron injections may be appropriate.
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Ironing out the Details: Untangling Dietary Iron and Genetic Background in Diabetes.
Miranda, MA, Lawson, HA
Nutrients. 2018;(10)
Abstract
The search for genetic risk factors in type-II diabetes has been hindered by a failure to consider dietary variables. Dietary nutrients impact metabolic disease risk and severity and are essential to maintaining metabolic health. Genetic variation between individuals confers differences in metabolism, which directly impacts response to diet. Most studies attempting to identify genetic risk factors in disease fail to incorporate dietary components, and thus are ill-equipped to capture the breadth of the genome's impact on metabolism. Understanding how genetic background interacts with nutrients holds the key to predicting and preventing metabolic diseases through the implementation of personalized nutrition. Dysregulation of iron homeostasis is associated with type-II diabetes, but the link between dietary iron and metabolic dysfunction is poorly defined. High iron burden in adipose tissue induces insulin resistance, but the mechanisms underlying adipose iron accumulation remain unknown. Hepcidin controls dietary iron absorption and distribution in metabolic tissues, but it is unknown whether genetic variation influencing hepcidin expression modifies susceptibility to dietary iron-induced insulin resistance. This review highlights discoveries concerning the axis of iron homeostasis and adipose function and suggests that genetic variation underlying dietary iron metabolism is an understudied component of metabolic disease.
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The Role of Iron in Type 1 Diabetes Etiology: A Systematic Review of New Evidence on a Long-Standing Mystery.
Søgaard, KL, Ellervik, C, Svensson, J, Thorsen, SU
The review of diabetic studies : RDS. 2017;(2-3):269-278
Abstract
BACKGROUND The incidence of type 1 diabetes (T1D) is rising, which might be due to the influence of environmental factors. Biological and epidemiological evidence has shown that excess iron is associated with beta-cell damage and impaired insulin secretion. AIM: In this review, our aim was to assess the association between iron and the risk of T1D. METHODS A systematic literature search was performed in PubMed and EMBASE in July 2016. Studies investigating the effect of iron status/intake on the risk of developing T1D later were included, and study quality was evaluated. The results have been summarized in narrative form. RESULTS From a total of 931 studies screened, we included 4 observational studies evaluating iron intake from drinking water or food during early life and the risk of T1D. The quality of the studies was moderate to high assessed via the nine-star Newcastle Ottawa Scale. One out of the four studies included in this review found estimates of dietary iron intake to be associated with risk of T1D development, whereas three studies found no such relationship for estimates of iron in drinking water. CONCLUSIONS The limited number of studies included found dietary iron, but not iron in drinking water, to be associated with risk of T1D. Further studies are needed to clarify the association between iron and risk of T1D, especially studies including measurements of body iron status.
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The Relationship Between Body Iron Status, Iron Intake And Gestational Diabetes: A Systematic Review and Meta-Analysis.
Fu, S, Li, F, Zhou, J, Liu, Z
Medicine. 2016;(2):e2383
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Abstract
Biological and epidemiological evidence have found that gestational diabetes mellitus (GDM) may be correlated with body iron status and dietary iron intake. Therefore, we investigated the relationship between dietary iron intake and body iron status and GDM risk.We conducted a systematic search in Embase, PubMed, Web of Science, and Cochrane Library up to April 2015. Prospective cohort studies or case-control studies which appraised the relationship between body iron status, dietary iron intake, and GDM risk were included. Relative risks (RRs), standard mean difference (SMD), and 95% confidence intervals [CIs] were used to measure the pooled data.A total of 8 prospective cohort studies and 7 case-control studies were in accordance with inclusive criteria, and 14 studies were included in meta-analysis. The overall RR comparing the highest and lowest levels of serum ferritin was 3.22 (95% CI: 1.73-6.00) for prospective cohort studies. Serum ferritin of GDM group is markedly higher than that of control (0.88 ng/mL; 95% CI: 0.40-1.35 ng/mL) for case-control studies. The comparison between the highest and the lowest serum ferritin levels and dietary total iron levels revealed pooled RRs of 1.53 (95% CI: 1.17-2.00) and 1.01 (95% CI: 1.00-1.01) for prospective cohort studies, respectively. The combined SMD comparing serum transferrin levels of cases and controls was -0.02 μmol/L (95% CI: -0.22 to 0.19 μmol/L) for case-control studies.Increased higher ferritin levels were significantly correlated with higher risk of GDM, and higher heme iron levels may be correlated with higher risk of GDM; however, the present conclusion did not constitute definitive proof that dietary total iron or serum transferrin have relation to GDM.
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Iron deficiency in sports - definition, influence on performance and therapy.
Clénin, G, Cordes, M, Huber, A, Schumacher, YO, Noack, P, Scales, J, Kriemler, S
Swiss medical weekly. 2015;:w14196
Abstract
Iron deficiency is frequent among athletes. All types of iron deficiency may affect physical performance and should be treated. The main mechanisms by which sport leads to iron deficiency are increased iron demand, elevated iron loss and blockage of iron absorption due to hepcidin bursts. As a baseline set of blood tests, haemoglobin, haematocrit, mean cellular volume, mean cellular haemoglobin and serum ferritin levels help monitor iron deficiency. In healthy male and female athletes >15 years, ferritin values <15 mcg are equivalent to empty, values from 15 to 30 mcg/l to low iron stores. Therefore a cut-off of 30 mcg/l is appropriate. For children aged from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 mcg/l, respectively, are recommended. As an exception in adult elite sports, a ferritin value of 50 mcg/l should be attained in athletes prior to altitude training, as iron demands in these situations are increased. Treatment of iron deficiency consists of nutritional counselling, oral iron supplementation or, in specific cases, by intravenous injection. Athletes with repeatedly low ferritin values benefit from intermittent oral substitution. It is important to follow up the athletes on an individual basis, repeating the baseline blood tests listed above twice a year. A long-term daily oral iron intake or i.v. supplementation in the presence of normal or even high ferritin values does not make sense and may be harmful.
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Postdischarge Iron Requirements of the Preterm Infant.
Domellöf, M, Georgieff, MK
The Journal of pediatrics. 2015;(4 Suppl):S31-5
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Intermittent oral iron supplementation during pregnancy.
Peña-Rosas, JP, De-Regil, LM, Gomez Malave, H, Flores-Urrutia, MC, Dowswell, T
The Cochrane database of systematic reviews. 2015;(10):CD009997
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Abstract
BACKGROUND Anaemia is a frequent condition during pregnancy, particularly among women in low- and middle-income countries. Traditionally, gestational anaemia has been prevented with daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. two or three times a week on non-consecutive days) supplementation has been proposed as an alternative to daily supplementation. OBJECTIVES To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015), the WHO International Clinical Trials Registry Platform (ICTRP) (31 July 2015) and contacted relevant organisations for the identification of ongoing and unpublished studies (31 July 2015). SELECTION CRITERIA Randomised or quasi-randomised trials. DATA COLLECTION AND ANALYSIS We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. MAIN RESULTS This review includes 27 trials from 15 countries, but only 21 trials (with 5490 women) contributed data to the review. All studies compared daily versus intermittent iron supplementation. The methodological quality of included studies was mixed and most had high levels of attrition.The overall assessment of the quality of the evidence for primary infant outcomes was low and for maternal outcomes very low.Of the 21 trials contributing data, three studies provided intermittent iron alone, 14 intermittent iron + folic acid and four intermittent iron plus multiple vitamins and minerals in comparison with the same composition of supplements provided in a daily regimen.Overall, for women receiving any intermittent iron regimen (with or without other vitamins and minerals) compared with a daily regimen there was no clear evidence of differences between groups for any infant primary outcomes: low birthweight (average risk ratio (RR) 0.82; 95% confidence interval (CI) 0.55 to 1.22; participants = 1898; studies = eight; low quality evidence), infant birthweight (mean difference (MD) 5.13 g; 95% CI -29.46 to 39.72; participants = 1939; studies = nine; low quality evidence), premature birth (average RR 1.03; 95% CI 0.76 to 1.39; participants = 1177; studies = five; low quality evidence), or neonatal death (average RR 0.49; 95% CI 0.04 to 5.42; participants = 795; studies = one; very low quality). None of the studies reported congenital anomalies.For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80; participants = 676; studies = four; I² = 10%; very low quality). Women receiving intermittent supplementation had fewer side effects (average RR 0.56; 95% CI 0.37 to 0.84; participants = 1777; studies = 11; I² = 87%; very low quality) and were at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.53; 95% CI 0.38 to 0.74; participants = 2616; studies = 15; I² = 52%; (this was not a primary outcome)) compared with women receiving daily supplements. There were no significant differences in iron-deficiency anaemia at term between women receiving intermittent or daily iron + folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63; participants = 156; studies = one). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.Most of the studies included in the review (14/21 contributing data) compared intermittent oral iron + folic acid supplementation compared with daily oral iron + folic acid supplementation (4653 women) and findings for this comparison broadly reflect findings for the main comparison (any intermittent versus any daily regimen).Three studies with 464 women examined supplementation with intermittent oral iron alone compared with daily oral iron alone. There were no clear differences between groups for mean birthweight, preterm birth, maternal anaemia or maternal side effects. Other primary outcomes were not reported.Four studies with a combined sample size of 412 women compared intermittent oral iron + vitamins and minerals supplementation with daily oral iron + vitamins and minerals supplementation. Results were not reported for any of the review's infant primary outcomes. One study reported fewer maternal side effects in the intermittent iron group, and two studies that more women were anaemic at term compared with those receiving daily supplementation.Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women's anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on results. AUTHORS' CONCLUSIONS This review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation in pregnant women on haematological and pregnancy outcomes. Findings suggest that intermittent regimens produced similar maternal and infant outcomes as daily supplementation but were associated with fewer side effects and reduced the risk of high levels of Hb in mid and late pregnancy, although the risk of mild anaemia near term was increased. While the quality of the evidence was assessed as low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.
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Efficacy of oral iron therapy in improving the developmental outcome of pre-school children with non-anaemic iron deficiency: a systematic review.
Abdullah, K, Kendzerska, T, Shah, P, Uleryk, E, Parkin, PC
Public health nutrition. 2013;(8):1497-506
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Abstract
OBJECTIVE To systematically review the efficacy and safety of oral Fe therapy in pre-school children (1–5 years) with non-anaemic Fe deficiency, determined by children’s developmental and haematological status and the incidence of reported side-effects. DESIGN A random-effects model was used to show mean differences with 95% confidence intervals of developmental and haematological scores between Fe-treated and non-treated groups. SETTING MEDLINE, EMBASE, Cochrane library and bibliographies of identified articles were searched up to September 2011. Randomized and observational studies were assessed by two reviewers independently. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment and completeness of follow-up. SUBJECTS From the titles of 743 articles, full text review was completed on forty-six and two randomized trials of acceptable quality met the inclusion criteria. The two trials included a total of sixty-nine children. RESULTS One study showed a statistically significant difference in the post-treatment Mental Developmental Index score among children who received oral Fe therapy v. no therapy (mean difference56?3, 95% CI 1?5, 11?0, P value not provided). Both studies showed significant improvement in serum ferritin level (mg/l: mean difference551? 1, 95% CI 33?6, 68?6, P,0?01 and mean difference517?1, 95% CI 7?5, 26?6, P value not provided, respectively) in children who received Fe therapy. CONCLUSIONS Evidence is insufficient to recommend oral Fe therapy to children with non-anaemic Fe deficiency. There is urgent need of conducting adequately powered, randomized trials examining the efficacy of oral Fe therapy in pre-school children with non-anaemic Fe deficiency.