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Influence of Periodizing Dietary Carbohydrate on Iron Regulation and Immune Function in Elite Triathletes.
McKay, AKA, Heikura, IA, Burke, LM, Peeling, P, Pyne, DB, van Swelm, RPL, Laarakkers, CM, Cox, GR
International journal of sport nutrition and exercise metabolism. 2020;(1):34-41
Abstract
Sleeping with low carbohydrate (CHO) availability is a dietary strategy that may enhance training adaptation. However, the impact on an athlete's health is unclear. This study quantified the effect of a short-term "sleep-low" dietary intervention on markers of iron regulation and immune function in athletes. In a randomized, repeated-measures design, 11 elite triathletes completed two 4-day mixed cycle run training blocks. Key training sessions were structured such that a high-intensity training session was performed in the field on the afternoon of Days 1 and 3, and a low-intensity training (LIT) session was performed on the following morning in the laboratory (Days 2 and 4). The ingestion of CHO was either divided evenly across the day (HIGH) or restricted between the high-intensity training and LIT sessions, so that the LIT session was performed with low CHO availability (LOW). Venous blood and saliva samples were collected prior to and following each LIT session and analyzed for interleukin-6, hepcidin 25, and salivary immunoglobulin-A. Concentrations of interleukin-6 increased acutely after exercise (p < .001), but did not differ between dietary conditions or days. Hepcidin 25 increased 3-hr postexercise (p < .001), with the greatest increase evident after the LOW trial on Day 2 (2.5 ± 0.9 fold increase ±90% confidence limit). The salivary immunoglobulin-A secretion rate did not change in response to exercise; however, it was highest during the LOW condition on Day 4 (p = .046). There appears to be minimal impact to markers of immune function and iron regulation when acute exposure to low CHO availability is undertaken with expert nutrition and coaching input.
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Iron Metabolism at the Interface between Host and Pathogen: From Nutritional Immunity to Antibacterial Development.
Marchetti, M, De Bei, O, Bettati, S, Campanini, B, Kovachka, S, Gianquinto, E, Spyrakis, F, Ronda, L
International journal of molecular sciences. 2020;(6)
Abstract
Nutritional immunity is a form of innate immunity widespread in both vertebrates and invertebrates. The term refers to a rich repertoire of mechanisms set up by the host to inhibit bacterial proliferation by sequestering trace minerals (mainly iron, but also zinc and manganese). This strategy, selected by evolution, represents an effective front-line defense against pathogens and has thus inspired the exploitation of iron restriction in the development of innovative antimicrobials or enhancers of antimicrobial therapy. This review focuses on the mechanisms of nutritional immunity, the strategies adopted by opportunistic human pathogen Staphylococcus aureus to circumvent it, and the impact of deletion mutants on the fitness, infectivity, and persistence inside the host. This information finally converges in an overview of the current development of inhibitors targeting the different stages of iron uptake, an as-yet unexploited target in the field of antistaphylococcal drug discovery.
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Iron Status of Burkinabé Adolescent Girls Predicts Malaria Risk in the Following Rainy Season.
Brabin, L, Roberts, SA, Tinto, H, Gies, S, Diallo, S, Brabin, B
Nutrients. 2020;(5)
Abstract
High levels of storage iron may increase malaria susceptibility. This risk has not been investigated in semi-immune adolescents. We investigated whether baseline iron status of non-pregnant adolescent girls living in a high malaria transmission area in Burkina Faso affected malaria risk during the following rainy season. For this prospective study, we analysed data from an interim safety survey, conducted six months into a randomised iron supplementation trial. We used logistic regression to model the risk of P. falciparum infection prevalence by microscopy, the pre-specified interim safety outcome, in relation to iron status, nutritional indicators and menarche assessed at recruitment. The interim survey was attended by 1223 (82%) of 1486 eligible participants, 1084 (89%) of whom were <20 years at baseline and 242 (22%) were pre-menarcheal. At baseline, prevalence of low body iron stores was 10%. At follow-up, 38% of adolescents had predominantly asymptomatic malaria parasitaemias, with no difference by menarcheal status. Higher body iron stores at baseline predicted an increased malaria risk in the following rainy season (OR 1.18 (95% CI 1.05, 1.34, p = 0.007) after adjusting for bed net use, age, menarche, and body mass index. We conclude that routine iron supplementation should not be recommended without prior effective malaria control.
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Iron Deficiency Anemia at Time of Vaccination Predicts Decreased Vaccine Response and Iron Supplementation at Time of Vaccination Increases Humoral Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants.
Stoffel, NU, Uyoga, MA, Mutuku, FM, Frost, JN, Mwasi, E, Paganini, D, van der Klis, FRM, Malhotra, IJ, LaBeaud, AD, Ricci, C, et al
Frontiers in immunology. 2020;:1313
Abstract
Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y. Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo. Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.
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5.
Global look at nutritional and functional iron deficiency in infancy.
Zimmermann, MB
Hematology. American Society of Hematology. Education Program. 2020;(1):471-477
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Abstract
Iron-deficiency anemia (IDA) affects many infants in low- and middle-income countries (LMICs) and may impair cognitive development and adaptive immunity. Effective interventions to improve iron intakes for infants in LMICs are urgently needed. However, absorption of oral iron fortificants and supplements is low, usually <10%, and most of the iron passes into the colon unabsorbed. In randomized controlled trials, provision of iron to infants in LMICs adversely affects their gut microbiome and increases pathogenic Escherichia coli, gut inflammation, and diarrhea. To minimize these detrimental effects of iron, it is important to provide the lowest effective dosage and maximize fractional iron absorption. Prebiotic galacto-oligosaccharides and apo-lactoferrin may prove useful in iron formulations in LMICs because they increase absorption of fortificant iron and at the same time may mitigate the adverse effects of unabsorbed iron on the infant gut. Providing well-absorbed iron early in infancy may improve immune function. Recent data from a Kenyan birth cohort suggest IDA at the time of infant vaccination impairs the response to diphtheria, pertussis, and pneumococcus vaccines. A randomized trial follow-up study reported that providing iron to Kenyan infants at the time of measles vaccination increased antimeasles immunoglobulin G (IgG), seroconversion, and IgG avidity. Because IDA is so common among infants in LMICs and because the vaccine-preventable disease burden is so high, even if IDA only modestly reduces immunogenicity of vaccines, its prevention could have major benefits.
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Plants in the real world: An introduction to the JBC Reviews thematic series.
Jez, JM
The Journal of biological chemistry. 2020;(45):15376-15377
Abstract
The deep relationship between plants and humans predates civilization, and our reliance on plants as sources of food, feed, fiber, fuels, and pharmaceuticals continues to increase. Understanding how plants grow and overcome challenges to their survival is critical for using these organisms to meet current and future demands for food and other plant-derived materials. This thematic review series on "plants in the real world" presents a set of eight reviews that highlight advances in understanding plant health, including the role of thiamine (vitamin B1), iron, and the plant immune system; how plants use ethylene and ubiquitin systems to control growth and development; and how new gene-editing approaches, the redesign of plant cell walls, and deciphering herbicide resistance evolution can lead to the next generation of crops.
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How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children.
Abuga, KM, Muriuki, JM, Williams, TN, Atkinson, SH
International journal of molecular sciences. 2020;(18)
Abstract
Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.
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Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.
Bolondi, G, Russo, E, Gamberini, E, Circelli, A, Meca, MCC, Brogi, E, Viola, L, Bissoni, L, Poletti, V, Agnoletti, V
World journal of emergency surgery : WJES. 2020;(1):41
Abstract
BACKGROUND Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. METHODS We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. RESULTS Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. CONCLUSIONS The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.
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Mechanism of colorectal carcinogenesis triggered by heme iron from red meat.
Seiwert, N, Heylmann, D, Hasselwander, S, Fahrer, J
Biochimica et biophysica acta. Reviews on cancer. 2020;(1):188334
Abstract
Colorectal cancer (CRC) is one of the major tumor entities worldwide, with an increasing incidence in younger people. CRC formation is causally linked to various genetic, life-style and dietary risk factors. Among the ladder, the consumption of red meat has emerged as important risk factor contributing to CRC. A large body of evidence shows that heme iron is the critical component of red meat, which promotes colorectal carcinogenesis. In this review, we describe the uptake and cellular fate of both heme and inorganic iron in intestinal epithelial cells. Next, an overview on the DNA damaging properties of heme iron is provided, highlighting the DNA adducts relevant for CRC etiology. Moreover, heme triggered mechanisms leading to colonic hyperproliferation are presented, which are intimately linked to changes in the intestinal microbiota induced by heme. A special focus was set on the impact of heme iron on innate and adaptive immune cells, which could be relevant in the context of CRC. Finally, we recapitulate in vivo studies providing evidence for the tumor-promoting potential of dietary heme iron. Altogether, heme iron affects numerous key pathways involved in the pathogenesis of CRC.
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Smoking-induced iron dysregulation in the lung.
Zhang, WZ, Butler, JJ, Cloonan, SM
Free radical biology & medicine. 2019;:238-247
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Abstract
Iron is one of the most abundant transition elements and is indispensable for almost all organisms. While the ability of iron to participate in redox chemistry is an essential requirement for participation in a range of vital enzymatic reactions, this same feature of iron also makes it dangerous in the generation of hydroxyl radicals and superoxide anions. Given the high local oxygen tensions in the lung, the regulation of iron acquisition, utilization, and storage therefore becomes vitally important, perhaps more so than in any other biological system. Iron plays a critical role in the biology of essentially every cell type in the lung, and in particular, changes in iron levels have important ramifications on immune function and the local lung microenvironment. There is substantial evidence that cigarette smoke causes iron dysregulation, with the implication that iron may be the link between smoking and smoking-related lung diseases. A better understanding of the connection between cigarette smoke, iron, and respiratory diseases will help to elucidate pathogenic mechanisms and aid in the identification of novel therapeutic targets.