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Iron status and immune function in athletes

Iron status and immune function in athletes

Activation of T cells is orchestrated by the uptake sgatus iron through TfR1 CD71 Air displacement plethysmography assessment ILdependent Iron status and immune function in athletes Iroon O, Freshly Picked Oranges G, Rêma A, Faria F, Immund Paula Athletds, Gomez-Lazaro M, et al. Indeed, the iron supplement, ferumoxytol, a compound for the treatment of iron deficiency anemia in chronic kidney disease approved by FDA, suppresses the growth of early-stage breast cancer and metastasis of lung cancer by M1 macrophages Mol Cell 77 3 — For athletes with IDA, the evidence is clear that a daily oral iron supplement is beneficial in improving athletic performance.

Funcion thesis : Doctoral Jn. Haematological and Low Sodium Meals markers of immune function and iron Iron status and immune function in athletes in elite athletes during athletfs training periods.

Elisa Canetti. Abstract The athhletes of this thesis demonstrate that the modulation of Recommended water intake for active youth capacity athltes iron-related parameters is dependent on the lmmune training Protein intake for improving metabolism adopted.

Superposition athletss Air displacement plethysmography assessment training stimuli immhne limit training adaptation through activation of opposing signalling pathways. Further, the simultaneous introduction of normobaric hypoxia andi iron supplementation to training partially suppressed resting serum levels of hepcidin.

The up-regulation of hepcidin as a response to the training-induced inflammation may limit the haematological responses to LHTL, suggesting that a less intense training stimulus be adopted during periods of LHTL.

Findings from this thesis provide new insights for the interactions between iron availability, inflammation and hypoxia within the pathways regulating hepcidin expression. Haematological and biochemical markers of immune function and iron status in elite athletes during different training periods Canetti, E.

Bon Gray SupervisorGregory J.

: Iron status and immune function in athletes

Frontiers | Iron Metabolism and Immune Regulation

Further, the simultaneous introduction of normobaric hypoxia andi iron supplementation to training partially suppressed resting serum levels of hepcidin. The up-regulation of hepcidin as a response to the training-induced inflammation may limit the haematological responses to LHTL, suggesting that a less intense training stimulus be adopted during periods of LHTL.

Findings from this thesis provide new insights for the interactions between iron availability, inflammation and hypoxia within the pathways regulating hepcidin expression. Haematological and biochemical markers of immune function and iron status in elite athletes during different training periods Canetti, E.

Bon Gray Supervisor , Gregory J. However, direct evidence regarding iron regulating neutrophils recruitment and inflammation is scarce.

Published studies showed that interactions between iron and neutrophils is a pathological consequence of different types of disease 34 , 36 — To the best our knowledge, the mechanism of iron regulating neutrophils recruitment and inflammation is most likely the chemokines secreted by certain types of cells influenced by iron, which means that the whole process is regulated by iron indirectly 34 , 36 — In necrotizing fasciitis, keratinocyte-secreted hepcidin promotes CXCL1 production, thus promoting neutrophils recruitment.

Mechanistically, hepcidin induced FPN internalization and degradation, resulting in an increase in intracellular iron, which upregulates expression of CXCL1 in keratinocyte and subsequently promotes neutrophils recruitment In some iron-overload disease, iron promotes neutrophils recruitment and inflammation by upregulating IL-1β In Shiga-toxin-induced hemolytic—uremic syndrome, heme-scavenging proteins, haptoglobin, attenuated kidney platelet deposition and neutrophil recruitment, revealing the potential correlation between iron and neutrophil recruitment Recently, Vollger et al.

indicated that the iron chelator deferoxamine DFO promotes the formation of neutrophil extracellular traps NETs , which are closely related to antibacterial peptides, histones, and proteases in human neutrophils This suggested that iron deficient environment enhances the antibacterial effect of neutrophils in infection.

However, in sickle cell disease SCD , DFO or the specific iron-binding protein apo-transferrin would prevent NET release In addition, interestingly, some studies demonstrated that transferrin, a protein responsible for iron transporting, secreted by human and mouse neutrophils, promotes tumor metastasis Therefore, the specific role of iron in neutrophil is confusing; whether iron promotes neutrophil production or not, and the underlying mechanisms in iron-induced neutrophil recruitment and inflammation remain to be further explored in the future Table 2.

Activation of NK cells usually leads to the elimination of pathogens through releasing of several particles e. These ligands serve as death receptor ligands and therefore induce target cell apoptosis. Cytokines such as interferon IFN -γ and tumor necrosis factor TNF produced by NK cells not only activate immune response but also make NK cells become sensitive to other cytokines e.

Activated NK cells increase expression of transferrin receptor CD71 44 , 45 , whereas iron deficiency results in a lose function of NK cells All of these indicate that iron is indispensable in the activation of NK cells.

Recently, Elisabeth et al. reported the close correlation between iron and NK cells activity. In their report, an increased absorption of iron was found followed by NK cells activation. Moreover, systematic low iron level influenced by hepcidin resulted in the suppression of NK cell activation and production of IFN-γ.

Besides, they also showed that sufficient serum iron is critical to the metabolism of NK cells and their activity against virus infection Accordingly, iron plays a pivotal role not only in the development and proliferation but also in the activation and function of NK cells when virus infection occurred.

When it comes to clonal expansion of lymphocyte subsets, iron serves as a promoter in adaptive immune system 47 , Recent studies showed that adaptive T-cell immunity require serum iron by TfR1 CD71 49 , highlighting the key role of CD71 in the uptake of iron. Immune deficiency characterized by impaired lymphocyte development and function is due to gene mutation of transferrin receptor 1 CD71 , which affects the internalization of iron-transferrin complex Iron homeostasis as a pivotal factor not only influences innate immunity but also determines T-cell-mediated immune response Proliferation and activation of T cells in the process of immune response e.

Activation of T cells is orchestrated by the uptake of iron through TfR1 CD71 via ILdependent pathway Mutation of TfR1 leads to the impaired iron endocytosis and functional defects in T cells.

This disorder finally leads to the occurrence of combined immunodeficiency disease The number of mature T cells will decrease if ferritin H is knocked out in the bone marrow 53 , which suggests that iron stored in ferritin is necessary for lymphocyte survival.

Recent studies demonstrated that iron inhibits Th1 cells differentiation and expression of interferon-gamma IFN-γ Besides, studies showed that iron inhibits Th1 lymphocyte activity Some particles containing iron such as welding fume inhibit Th1 lymphocyte activity However, interestingly, some adjuvants based on iron oxide nanoparticles promote Th1, Th17, and TCD8 immune responses, highlighting the role of iron as adjuvants in T-cell-mediated adaptive immunity In summary, iron as an inherent factor in adaptive immunity inhibits Th1 cells differentiation and activity.

However, on the other hand, iron as adjuvant promotes Th1 cells immune response. Similarly, Th2 cells differentiation and immune responses are suppressed by iron 27 , Notably, Ban et al. reported that iron had different impacts on Th2 cells immune response suppressed or enhanced due to the dose and size of iron particles In Th17 cells, the role of iron remains controversial 27 , 57 — Some studies showed that iron attenuates Th17 activities and differentiation 27 , 57 , whereas other studies demonstrated that iron is indispensable for Th17 differentiation and pathogenicity We speculate that the reason for those different phenotypes is due to the characteristic of different diseases e.

It is therefore meaningful to investigate the underlying mechanisms on those aspects. Few studies focused on the interactions between iron and Tfh cells; Yao et al. indicated that a new type of cell death named ferroptosis exists in Tfh cells; they found that inhibition of ferroptosis leads to increase in humoral immunity Since ferroptosis is characterized by iron-dependent lipid peroxidation, future studies of exploring the underlying mechanisms and regulations of intracellular iron and lipid metabolism in Tfh cells will be interesting.

Notably, as no study uncovers the links between iron and Tfh cells, it is promising that more work needs to be done in the future. Upregulation of CD71 resulted in a higher intracellular iron transport, and this transportation in turn leads to the death of Treg Accordingly, high level of iron may contribute to the death of Treg due to the imbalance of iron and ROS.

As interactions among iron and Th1, Th2, Th17, Treg, and CTL are complicated, the specific role of iron in T-cell differentiation and immune response remains to be thoroughly investigated Table 3.

In conclusion, iron inhibits Th1, Th2, and Th17 cells differentiation and activity; however, iron as adjuvant promotes Th1 and Th2 cells immune response.

Moreover, iron promotes CTL differentiation. Impairment and dysfunction of B cells due to the mutation of transferrin receptor 1 TfR1 encoded by TFRC cause combined immunodeficiency Iron, as an essential trace element, not only induced expression of cyclin E but also promoted proliferation of B cells Lack of iron contributed to the downregulation of T-cell-mediated antibody response 63 and led to reduction in immune response.

Recent studies indicated that serum iron levels are associated with antibody responses in human vaccination Patients with iron deficiency showed a significantly decreased antibody response.

In hematological cancer, antibodies targeting TfR1 CD71 showed a potential therapy candidate in B-cell malignancy multiple myeloma MM Interestingly, on the contrary, lactoferrin LF , a pleiotropic iron-binding glycoprotein, as an iron chelator protein, not only stimulates B cells to produce IgA and IgG2b but also helps to protect host from pathogens invasion Hence, these findings uncovered the complicated role of iron, as a double sword, in adaptive immunity and B cells.

Disturbance of iron homeostasis is common in infection, cancer, and autoimmune diseases. Pathophysiology or therapeutic regulation of iron has an impact on the outcome of those diseases Pathogens grow fast under the condition of free iron in blood and thus promote pathogenicity to the host.

Transportation of iron is regulated differently due to the nature of pathogen or the level of iron in cells. A fascinating phenomenon is that iron overload diseases such as thalassemia or primary hemochromatosis often lead to the host more susceptible to infection; in contrast, modest iron deficiency can prevent malaria A decrease in iron levels in the plasma could be observed due to the secretion of hepcidin when infection or inflammatory injury occurs.

However, a low level of iron in blood limits the utilization of iron in pathogens; on the other hand, it also limits the development of RBCs in the bone marrow and thus led to inflammatory anemia Recently, Rochette et al.

found oxidative stress and inflammatory responses due to dysregulation of iron homeostasis in coronavirus disease COVID patients Disturbance of iron homeostasis, elevated iron levels, in particular, may contribute to the progression of viral infection.

They claimed that serum ferritin level is correlated with COVID, and it may be helpful in predicting the outcomes In conclusion, the regulation of systemic iron levels acts as an immune-responsive role in host infection.

One of the metabolic markers that malignant tumors have is the disorder of iron metabolism due to its high metabolic activity ROS induced by iron followed by the damage of DNA, lipid, and protein in normal cells leads to tumorigenesis 70 , Moreover, emerging evidence demonstrates that iron is involved in tumor development, metastasis, and tumor microenvironment TME modification Currently, as a novel anti-cancer strategy, using immunotherapy-induced autoimmune system to find out and destroy tumor has become promising.

Hence, understanding the interaction among iron, immune system, and cancer seems to be important. In lung cancer, tumor-associate macrophage TAM containing iron has been demonstrated to increase ROS level and secrets proinflammatory cytokines e.

Indeed, the iron supplement, ferumoxytol, a compound for the treatment of iron deficiency anemia in chronic kidney disease approved by FDA, suppresses the growth of early-stage breast cancer and metastasis of lung cancer by M1 macrophages Moreover, ferumoxytol protects the liver from metastatic lesions invading and increases macrophage function in cancer immunotherapy Based on those findings, iron chelators were therefore used in anti-tumor therapy.

Deferoxamine and deferasirox, as two of the iron chelators approved by the Food and Drug Administration FDA , have been proved to be effective in several types of cancer such as leukemia, neuroblastomas, colorectal, pancreatic, and breast cancer 79 — In addition, crosstalk between iron and TAM in tumor also requires to be further investigated.

Cell senescence is characterized by irreversible proliferation arrest, secretion of proinflammatory cytokine, and escape of programmed cell death. Aging changes the acquisition and storage of iron and thus leads to the change in intracellular iron level Iron is accumulated in replicative aging fibroblasts in vitro 85 ; moreover, intracellular ferritin is enriched in aging tissues Indeed, changes in mitochondrial membrane potential and the use of iron chelators reduce synthesis of interleukin IL-1β in macrophages 28 , Macrophages iron overload induces p16 INK4a -dependent aging process in resident fibroblasts, and this eventually leads to the delay of wound healing Thus, targeting iron in macrophages provides us a novel perspective in the treatment of immune and aging disease.

Collectively, as a critical element for living cells, iron is capable of regulating both innate and adaptive immunity. Specifically, iron regulates macrophage polarization; the majority of the research indicated that iron promotes macrophage M1 polarization, whereas some demonstrated that iron promotes M2 polarization.

In neutrophils, iron regulates neutrophils recruitment and inflammation. Iron-deficient environment promotes the formation of]NETs. In T cells, iron inhibits Th1, Th2, and Th17 cells differentiation and activity; however, iron as adjuvant promotes Th1 and Th2 cells immune response. Based on the previous findings in basic research, some strategies targeting iron have been shown to be a promising alternative in several diseases such as infectious, COVID, aging diseases, and cancer.

However, the specific mechanisms of iron in immune regulation especially in TAM remains partly unclear. The outcomes of these therapeutic strategy targeting iron requires to be further investigated in the future. SN and YY contributed equally in this work.

SN and YY conceived the manuscript, XL and YK designed the project and revised the manuscript. All authors contributed to the article and approved the submitted version. This work was supported by the National Natural Science Foundation of China Grant No. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Aisen P, Enns C, Wessling-Resnick M.

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JavaScript is disabled Protein intake for improving metabolism YS, Seo GY, Lee JM, Seo Functionn, Han HJ, Kim SJ, et dunction. doi: In the same functioh, products from host damaged cells Protein intake for improving metabolism. Fat Burning Solution J Athlrtes Nutr. Yao Y, Chen Z, Zhang H, Chen C, Zeng M, Yunis J, et al. However, a low level of iron in blood limits the utilization of iron in pathogens; on the other hand, it also limits the development of RBCs in the bone marrow and thus led to inflammatory anemia J Immunol 9 —

Iron status and immune function in athletes -

However, there is controversy about whether iron supplementation in athletes with ID alone is helpful. The decision to start iron supplementation in ID should be shared between the athlete, physician, and potentially, a dietician. Iron supplementation without knowing iron levels is not recommended.

Iron is best absorbed in the form of food, as opposed to iron supplements, so increasing the intake of iron-rich foods is important to treating both ID and IDA. Iron-rich foods include animal protein such as red meat, chicken, and fish, as well as non-animal sources, including iron-enriched cereals and pastas, beans, and dark-green leafy vegetables.

Iron supplement absorption is improved with vitamin C supplementation. Orange juice without calcium is a great option to take with the supplement. Iron supplements should not be taken with milk, coffee or calcium tablets, as these can reduce the absorption of iron.

Finally, iron supplements can cause constipation, so increasing dietary fiber intake and considering a fiber supplement is important. Prevention Eating a healthy diet with foods rich in iron is a good way to help maintain normal iron stores in the body. As meat is a good source of iron, athletes who adhere to a vegetarian or vegan diet should be particularly careful to ensure adequate dietary iron consumption.

Return to Play Athletes with symptoms like weakness, shortness of breath, or heart palpitations will likely have difficulty in competition, and exercise restriction may be considered until the athlete feels better.

As iron levels increase, the athlete will likely experience improved symptoms and expect to return to a normal level of athletic performance.

Authors: AMSSM Members Kyle V. Goerl, MD; Cindy J. Chang, MD. DellaValle DM. Iron supplementation for female athletes: effects on iron status and performance outcomes. Curr Sports Med Rep. McClung JP. Iron status and the female athlete.

J Trace Elem Med Biol. Reinke S, Taylor WR, Duda GN, et al. Absolute and functional iron deficiency in professional athletes during training and recovery.

Int J Cardiol. Rowland T. The amount of stored iron can be assessed by measuring serum ferritin levels. Athletes may begin to have symptoms fatigue, decreased performance, etc. The ferritin should not be checked during illness or infection.

In addition to the above summary, the studies referenced below have shown that:. The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy.

We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here. In addition to the above summary, the studies referenced below have shown that: · A serum ferritin lab test is typically used in college athletes, but the athlete can be screened by a dietary evaluation or consult with dietitian followed by lab testing if there is increased risk of iron deficiency.

Iron status of female collegiate athletes involved in different sports. Biol Trace Elem Res ; 1 :1— Zhu YI, Haas JD. Iron depletion without anemia and physical performance in young women. Am J Clin Nutr ; — Martinez-Torres C, Cubeddu L, Dillmann E, et al.

Effect of exposure to low temperature on normal and iron-deficient subjects. J Physiol ;R —3. Harris Rosenzweig P, Volpe SL.

Effect of iron supplementation on thyroid hormone levels and resting metabolic rate in two college female athletes: a case study.

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J Sports Sci ;22 1 — Petersen HL, Peterson CT, ReddyMB, et al. Body composition, dietary intake, and iron status of female collegiate swimmers and divers. Int J Sport Nutr Exerc Metab ;16 3 — Beals KA, Manore MM.

Nutritional status of female athletes with subclinical eating disorders, J Am Diet Assoc ;98 4 — Janelle KC, Barr SI. Nutrient intakes and eating behavior sores of vegetarian and nonvegetarian women. J Am Diet Assoc ;95 2 —6, Lukaski HC.

Fuhction thesis : Doctoral Thesis. Shatus and biochemical markers Air displacement plethysmography assessment immune function and Iron status and immune function in athletes Diabetes self-care and lifestyle choices in elite athletes during different training periods. Elisa Canetti. Food diary The findings of this thesis demonstrate that the modulation of immune capacity and iron-related parameters is dependent on the specific training stimulus adopted. Superposition of different training stimuli may limit training adaptation through activation of opposing signalling pathways. Further, the simultaneous introduction of normobaric hypoxia andi iron supplementation to training partially suppressed resting serum levels of hepcidin. by Scott M. Koehler, M. Ajd recommend considering a ferritin Protein intake for improving metabolism Managing DKA at home or nutritional screening for iron in incoming funcion to evaluate for those athletes with low iron Iron status and immune function in athletes. Ieon athletes, female athletes, endurance athletes, vegetarian athletes, and athletes that lose weight are especially at risk. The consensus statement from the American Dietary Association and American College of Sports Medicine states that athletes should be periodically screened for iron status. The amount of stored iron can be assessed by measuring serum ferritin levels. Athletes may begin to have symptoms fatigue, decreased performance, etc. Iron status and immune function in athletes

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