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Energy deficit increases hepcidin and exacerbates declines in dietary iron absorption following strenuous physical activity: a randomized-controlled cross-over trial.
Hennigar, SR, McClung, JP, Hatch-McChesney, A, Allen, JT, Wilson, MA, Carrigan, CT, Murphy, NE, Teien, HK, Martini, S, Gwin, JA, et al
The American journal of clinical nutrition. 2021;(2):359-369
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Abstract
BACKGROUND Strenuous physical activity promotes inflammation and depletes muscle glycogen, which may increase the iron regulatory hormone hepcidin. Hepcidin reduces dietary iron absorption and may contribute to declines in iron status frequently observed following strenuous physical activity. OBJECTIVES To determine the effects of strenuous physical activity on hepcidin and dietary iron absorption and whether energy deficit compared with energy balance modifies those effects. METHODS This was a randomized, cross-over, controlled-feeding trial in healthy male subjects (n = 10, mean ± SD age: 22.4 ± 5.4 y, weight: 87.3 ± 10.9 kg) with sufficient iron status (serum ferritin 77.0 ± 36.7 ng/mL). Rest measurements were collected before participants began a 72-h simulated sustained military operation (SUSOPS), designed to elicit high energy expenditure, glycogen depletion, and inflammation, followed by a 7-d recovery period. Two 72-h SUSOPS trials were performed where participants were randomly assigned to consume either energy matched (±10%) to their individual estimated total daily energy expenditure (BAL) or energy at 45% of total daily energy expenditure to induce energy deficit (DEF). On the rest day and at the completion of BAL and DEF, participants consumed a beverage containing 3.8 mg of a stable iron isotope, and plasma isotope appearance was measured over 6 h. RESULTS Muscle glycogen declined during DEF and was preserved during BAL (-188 ± 179 mmol/kg, P-adjusted < 0.01). Despite similar increases in interleukin-6, plasma hepcidin increased during DEF but not BAL, such that hepcidin was 108% greater during DEF compared with BAL (7.8 ± 12.2 ng/mL, P-adjusted < 0.0001). Peak plasma isotope appearance at 120 min was 74% lower with DEF (59 ± 38% change from 0 min) and 49% lower with BAL (117 ± 81%) compared with rest (230 ± 97%, P-adjusted < 0.01 for all comparisons). CONCLUSIONS Strenuous physical activity decreases dietary iron absorption compared with rest. Energy deficit exacerbates both the hepcidin response to physical activity and declines in dietary iron absorption compared with energy balance. This trial was registered at clinicaltrials.gov as NCT03524690.
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Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial.
Hedrick, J, Yeiser, M, Harris, CL, Wampler, JL, London, HE, Patterson, AC, Wu, SS
Nutrients. 2021;(12)
Abstract
Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow's milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow's milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14-120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14-120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow's milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.
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The Effect of Parenteral or Oral Iron Supplementation on Fatigue, Sleep, Quality of Life and Restless Legs Syndrome in Iron-Deficient Blood Donors: A Secondary Analysis of the IronWoMan RCT.
Macher, S, Herster, C, Holter, M, Moritz, M, Matzhold, EM, Stojakovic, T, Pieber, TR, Schlenke, P, Drexler, C, Amrein, K
Nutrients. 2020;(5)
Abstract
UNLABELLED Background: Besides anemia, iron deficiency may cause more subtle symptoms, including the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis of the IronWoMan randomized controlled trial (RCT) was to compare the frequency and severity of symptoms associated with iron deficiency before and after (intravenous or oral) iron supplementation in iron deficient blood donors. METHODS/DESIGN Prospective, randomized, controlled, single-centre trial. (ClinicalTrials.gov: NCT01787526). SETTING Tertiary care center in Graz, Austria. PARTICIPANTS 176 (138 female and 38 male) whole-blood and platelet apheresis donors aged ≥ 18 and ≤ 65 years with iron deficiency (ferritin ≤ 30ng/mL at the time of blood donation). INTERVENTIONS Intravenous iron (1 g ferric carboxymaltose, n = 86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n = 90). MEASUREMENTS Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1), including questions about symptoms of restless legs syndrome (RLS), chronic fatigue syndrome (CFS), sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes in fingernails or hair. RESULTS We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p < 0.001). Furthermore, a significant decrease in headaches, dyspnoea, dizziness and palpitations was reported (p < 0.05). There was no difference between the type of iron supplementation (intravenous versus oral) and clinical outcome data. CONCLUSION Iron supplementation in iron-deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.
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Effect of procyanidin on dietary iron absorption in hereditary hemochromatosis and in dysmetabolic iron overload syndrome: A crossover double-blind randomized controlled trial.
Lobbes, H, Gladine, C, Mazur, A, Pereira, B, Dualé, C, Cardot, JM, Ruivard, M
Clinical nutrition (Edinburgh, Scotland). 2020;(1):97-103
Abstract
BACKGROUND & AIMS Type I hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) are the two most prevalent iron overload diseases. Although many food components, particularly polyphenols, reduce iron bioavailability, there is no clinically validated nutritional strategy to reduce food-iron absorption in patients with these diseases. We aimed to determine whether supplementation with 100 mg of procyanidins during a meal reduces dietary iron absorption in patients with HH or DIOS. METHODS 20 HH and 20 DIOS patients were enrolled in a double-blind three-period crossover randomized study. Basal serum iron level was measured following an overnight fast. Each patient consumed a standardized test iron-rich meal containing 43 mg of iron with two capsules of placebo or procyanidin supplementation. Each period was separated by a 3-day wash-out period. The primary objective was a reduction of dietary iron absorption, assessed by a reduction of serum-iron area under the curve (AUC) corrected for baseline serum iron. RESULTS All patients completed the study. The meal and the procyanidin supplements were well tolerated. In both HH and DIOS patients, the iron-rich meal induced a significant increase of serum iron compared with baseline at 120, 180, 240 min, from 8 to 9.1% (p = 0.002, 0.001 and 0.003, respectively) in DIOS and from 15.8 to 25.7% (p < 0.001) in HH. Iron absorption was 3.5-fold higher in HH than in DIOS (p < 0.001). Procyanidin supplementation did not significantly modify iron absorption in DIOS (AUC of added iron 332.87 ± 649.55 vs 312.61 ± 678.61 μmol.h/L, p = 0.916) or in HH (1168.62 ± 652.87 vs 1148.54 μmol.h/L ± 1290.05, p = 0.917). CONCLUSIONS An iron-rich test meal led to a marked increase in iron absorption in HH but a mild increase in DIOS. Procyanidin supplementation does not significantly reduce dietary iron absorption in either disease. CLINICAL TRIAL REGISTRY clinicaltrials.gov (NCT03453918).
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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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Anemia management in non-menopausal women in a primary care setting: a prospective evaluation of clinical practice.
Bayen, S, Le Grand, C, Bayen, M, Richard, F, Messaadi, N
BMC family practice. 2020;(1):13
Abstract
BACKGROUND The study aimed to analyze anemia management in non-pregnant, and non-menopausal women aged from 18 to 50 years old, in a French primary care setting. METHODS An observational descriptive prospective study was conducted between November 2018 and February 2019. Inclusion criteria were as followed: anemia diagnosed in women aged from 18 to 50, not pregnant and not menopausal. Quantitative and qualitative data were anonymized and collected through an electronic survey. Investigating general practitioners completed the questionnaire for each newly diagnosed woman. Mean values and medians were calculated for the quantitative data. Answers to the open questions were encoded manually and proportions of the different modalities have been calculated. RESULTS Altogether, 43 women with anemia were ascertained. Moderate microcytic anemia, due to an iron deficiency in a context of menorrhagia, was the most observed anemia profile. The mean value of hemoglobin was 10.5 ± 1 g/dl. Among these women: 32 (74%) presented an iron deficiency, 17 (53%) had inappropriate intakes, and 9 (28%) reported menorrhagia. For 17 (40%) women, unnecessary or inappropriate exams were prescribed. The investigations did not allow to establish a differential diagnosis for 12 women (28%). Even for similar clinical situations, anemia management was variable. Among the women who presented iron deficiency, 15 (47%) were informed about an iron-rich diet and received a daily iron supplementation of ferrous sulfate between 80 mg and 160 mg. CONCLUSIONS Our study highlights that, in the absence of specific national guidelines for anemia management in non-pregnant, non-menopausal women in primary care settings, French GPs undergo various clinical management strategies leading to a heterogeneous, sometimes inappropriate follow-up. Women with iron deficiency were prescribed higher daily iron supplementation than recommended, according to new evidence, suggesting a maximal daily dose of 50 mg of elementary iron in a context of Hepcidin up-regulation in the case of an iron overload. Additional longitudinal studies with a bigger sample size and randomized controlled trials are needed to confirm our results and to elaborate national guidelines.
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Association between Iron Intake and Diabetic Peripheral Neuropathy in Type 2 Diabetes: Significance of Iron Intake and the Ratio between Iron Intake and Polyunsaturated Fatty Acids Intake.
Kim, K, Song, Y, Oh, TJ, Choi, SH, Jang, HC
Nutrients. 2020;(11)
Abstract
We aimed to investigate the association of iron and polyunsaturated fatty acid (PUFA) intake with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes. This cross-sectional study included 147 individuals with type 2 diabetes. Dietary intake was assessed using three-day food records. DPN was diagnosed on the basis of a Michigan Neuropathy Screening Instrument-Physical Examination score ≥2.5. Adjusted for total energy intake, iron intake was significantly higher in individuals with DPN than in those without DPN (10.9 ± 4.0 mg vs. 9.9 ± 3.6 mg, p = 0.041). In addition, the iron/PUFA ratio was significantly higher in individuals with DPN (1.4 ± 0.8 vs. 1.1 ± 0.4, p = 0.005). Logistic regression analyses showed that iron intake (odds ratio (OR): 1.152; 95% confidence interval (CI): 1.012, 1.311) and iron/PUFA ratio (OR: 2.283; 95% CI: 1.066, 4.887) were associated with DPN after adjustment for total energy intake, sex, age, body mass index, systolic blood pressure, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, low-density lipoprotein cholesterol, and smoking. In conclusion, high dietary iron intake and an elevated iron/PUFA ratio were associated with the presence of DPN. The present study suggests the importance of the dietary pattern of iron and PUFA intake in individuals with type 2 diabetes.
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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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Pattern of urine iodine excretion with low iodine diet during preparation for radioactive iodine ablation in patients with thyroid cancer.
Kang, SW, Yap, ZZ, Lee, CR, Lee, J, Jeong, JJ, Nam, KH, Yun, MJ, Lee, EJ, Chung, WY, Park, CS
Head & neck. 2019;(2):381-387
Abstract
BACKGROUND The optimal period of low iodine diet during preparation for radioactive iodine (RAI) ablation in an area with iodine-rich diet was investigated. METHODS Ninety-four patients with thyroid cancer who underwent low iodine diet and RAI were prospectively allocated into 2 groups-thyroxine withdrawal or using recombinant human thyroid stimulating hormone (rhTSH) for TSH stimulation. Their urinary iodine excretion (UIE) patterns were analyzed. RESULTS There was no clinicopathological difference between the 2 groups except for tumor size and lymph node status. The UIE (median iodine to creatinine ratio, I/Cr) in the withdrawal group on the 7th and 14th day were 18.3 and 17.9 μg/gCr, respectively, with adequate preparation rate of 93.3% on both days (cutoff value 100 μg/gCr). In the rhTSH group, the median I/Cr on the 7th and 14th day were 48.0 and 45.7 μg/gCr (adequate preparation rates 91.8% and 93.8%), respectively. CONCLUSION One week of low iodine diet is sufficient preparation for RAI regardless of method of TSH stimulation.
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Iron supplementation in preterm and low-birth-weight infants: a systematic review of intervention studies.
McCarthy, EK, Dempsey, EM, Kiely, ME
Nutrition reviews. 2019;(12):865-877
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CONTEXT Enteral iron supplementation in preterm infants is recommended to supply sufficient iron for growth and development without increasing the risk of iron overload. However, the current recommendations date from 2010 and are based on limited evidence. OBJECTIVE This systematic review aimed to investigate the effects of enteral iron supplementation on iron status, growth, neurological development, and adverse clinical outcomes in preterm (<37 weeks' gestation) and low-birth-weight (LBW, <2500 g) infants. DATA SOURCES The PubMed/Medline and Cochrane Library databases were searched to 31 October 2018. DATA EXTRACTION Of the 684 records identified, 27 articles, describing 18 randomized controlled trials (RCTs) plus 4 nonrandomized interventions, were included. Using the Cochrane Collaboration's criteria, study quality was found to be poor to fair overall. RESULTS Most articles (23/27) reported iron status indices; supplementation for ≥8 weeks resulted in increased hemoglobin and ferritin concentrations and a reduction in iron deficiency and anemia. No article reported on iron overload. Growth-related parameters reported in 12 articles were not affected by supplementation. Among the 7 articles on neurological development, a positive effect on behavior at 3.5 and 7 years was observed in one Swedish RCT. No association was found between supplementation and adverse clinical outcomes in the 9 articles reporting on studies in which such data was collected. CONCLUSIONS Long-term iron supplementation appears to result in improved iron status and a reduction in iron deficiency and anemia in preterm and LBW infants. However, high-quality evidence regarding the long-term effects of supplementation on functional health outcomes is lacking. Iron overload has largely been ignored. Well-designed, long-term, dose-response RCTs are required to ascertain the optimal dose and delivery method for the provision of dietary iron in preterm infants, with consideration of short- and long-term health effects. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018085214.