RESUMEN
Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes, as these interventions may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentration in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intake, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n = 6/30; inflammation-adjusted ferritin <15 µg/L). Multiple linear regression was used to assess the associations of a number of independent explanatory variables with log-transformed serum ferritin (µg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9%-37%) higher mean ferritin concentrations, and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1%-2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Novelty Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, noninvasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.
Asunto(s)
Anemia Ferropénica/sangre , Anemia Ferropénica/epidemiología , Atletas/estadística & datos numéricos , Índice de Masa Corporal , Ferritinas/sangre , Menstruación/fisiología , Adolescente , Adulto , Biomarcadores/sangre , Canadá/epidemiología , Dieta/métodos , Suplementos Dietéticos , Femenino , Humanos , Inflamación/sangre , Inflamación/epidemiología , Hierro/sangre , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. METHODS: Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. RESULTS: After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). CONCLUSIONS: Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.
Asunto(s)
Anemia/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hepcidinas/metabolismo , Inflamación/tratamiento farmacológico , Hierro/metabolismo , HumanosRESUMEN
Iron overload pathophysiology has benefited from significant advances in the knowledge of iron metabolism and in molecular genetics. As a consequence, iron overload nosology has been revisited. The hematologist may be confronted to a number of iron overload syndromes, from genetic or acquired origin. Hemochromatoses, mostly but not exclusively related to the HFE gene, correspond to systemic iron overload of genetic origin in which iron excess is the consequence of hepcidin deficiency, hepcidin being the hormone regulating negatively plasma iron. Iron excess develops following hypersideremia and the formation of non-transferrin-bound iron, which targets preferentially parenchymal cells (hepatocytes). The ferroportin disease has a totally different iron overload mechanism consisting of defective egress of cellular iron into the plasma, iron deposition taking place mostly within the macrophages (spleen). Hereditary aceruloplasminemia is peculiar since systemic iron overload involves the brain. Two main types of acquired iron overload can be seen by the hematologist, one related to dyserythropoiesis (involving hypohepcidinemia ), the other related to multiple transfusions (thalassemias, myelodysplasia, hematopoietic stem cell transplantation). Congenital sideroblastic anemias, either monosyndromic (anemia) or polysyndromic (anemia plus extra-hematological syndromes), develop both compartimental iron excess within the erythroblast mitochondria, and systemic iron overload (through dyserythropoiesis and/or transfusions).
Asunto(s)
Sobrecarga de Hierro/fisiopatología , Hierro/metabolismo , Homeostasis/fisiología , Humanos , Hierro/sangre , Sobrecarga de Hierro/diagnósticoRESUMEN
OBJECTIVE@#To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism.@*METHODS@#Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (=30) and treatment group (=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels.@*RESULTS@#After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all =0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (=0.000).@*CONCLUSIONS@#Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.
RESUMEN
In case of erythropoiesis, body iron needs to increase to enable the production of new red blood cells. In the 1950s, the observation of an increased digestive iron absorption in the case of phlebotomies had led to propose the existence of an "erythroid factor", which regulate the availability of iron for erythropoiesis in this situation. The factor regulating iron stores has been identified in 2000 to be hepcidin. Recently, in 2014, a new factor was discovered, which regulates iron metabolism, independently of iron stores and responds to the increased requirements for iron after stimulation of erythropoiesis by erythropoietin. This factor has been referred to as erythroferrone. Thus, the regulation of iron stores depends on hepcidin, while the adaptation mechanisms of iron availability in case of anemia, are mediated by an erythroid factor that could be erythroferrone. This review summarizes the current knowledge on the role of erythroferrone in iron metabolism, starting from experimental results, obtained mainly on mouse models, and related to iron overload in ß-thalassemia, iron disturbances during anemia of chronic diseases and chronic renal failure. These results will have to be compared with those obtained in humans, as soon as a reliable assay for human erythroferrone is available. From a clinical point of view, erythroferrone could become a useful biological marker of iron metabolism and a therapeutic target.
Asunto(s)
Hierro/metabolismo , Hormonas Peptídicas/fisiología , Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Animales , Modelos Animales de Enfermedad , Eritropoyesis/fisiología , Hepcidinas/fisiología , Humanos , Inflamación/metabolismo , Inflamación/patología , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/patología , Ratones , Talasemia beta/metabolismo , Talasemia beta/patologíaRESUMEN
We determined the effects of repeated sprint exercise under normoxic and hypoxic conditions on serum hepcidin levels. Ten male athletes (age: 20.9 ± 0.3 years; height: 175.7 ± 6.0 cm; weight: 67.3 ± 6.3 kg) performed 2 exercise trials under normoxic (NOR; fraction of inspiratory oxygen (FiO2): 20.9%) or hypoxic conditions (HYPO; FiO2: 14.5%). The exercise consisted of 3 sets of 5 × 6 s of maximal pedaling (30-s rest periods between sprints, 10-min rest periods between sets). Blood samples were collected before exercise, immediately after exercise, and 1 and 3 h after exercise. Serum hepcidin levels were significantly elevated after exercise in both trials (both P < 0.01), with no significant difference between the trials. The postexercise blood lactate levels were significantly higher in the HYPO than the NOR (P < 0.05). Both trials caused similar increases in plasma interleukin-6 and serum iron levels (P < 0.001), with no significant difference between the trials. A significant interaction (trial × time) was apparent in terms of serum erythropoietin (EPO) levels (P = 0.003). The EPO level was significantly higher in the HYPO than the NOR at 3 h after exercise (P < 0.05). In conclusion, repeated sprint exercise significantly increased serum hepcidin levels to similar extent in 2 trials, despite differences in the inspired oxygen concentrations during both the exercise and the 3-h postexercise period.
Asunto(s)
Ejercicio Físico , Hepcidinas/metabolismo , Hipoxia , Carrera/fisiología , Atletas , Hepcidinas/sangre , Humanos , Masculino , Oxígeno , Adulto JovenRESUMEN
Alcohol consumption during pregnancy places the fetus at risk for permanent physical, cognitive, and behavioral impairments, collectively termed fetal alcohol spectrum disorder (FASD). However, prenatal alcohol exposure (PAE) outcomes vary widely, and growing evidence suggests that maternal nutrition is a modifying factor. Certain nutrients, such as iron, may modulate FASD outcomes. Untreated gestational iron deficiency (ID) causes persistent neurodevelopmental deficits in the offspring that affect many of the same domains damaged by PAE. Although chronic alcohol consumption enhances iron uptake and elevates liver iron stores in adult alcoholics, alcohol-abusing premenopausal women often have low iron reserves due to menstruation, childbirth, and poor diet. Recent investigations show that low iron reserves during pregnancy are strongly associated with a worsening of several hallmark features in FASD including reduced growth and impaired associative learning. This review discusses recent clinical and animal model findings that maternal ID worsens fetal outcomes in response to PAE. It also discusses underlying mechanisms by which PAE disrupts maternal and fetal iron homeostasis. We suggest that alcohol-exposed ID pregnancies contribute to the severe end of the FASD spectrum.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Trastornos del Espectro Alcohólico Fetal/metabolismo , Hierro , Micronutrientes/uso terapéutico , Neurogénesis , Animales , Modelos Animales de Enfermedad , Femenino , Trastornos del Espectro Alcohólico Fetal/patología , Humanos , Hierro/sangre , Hierro/uso terapéutico , Deficiencias de Hierro , Hígado/metabolismo , Hígado/patología , EmbarazoRESUMEN
The relationship between iron and glucose metabolism has been evidenced strongly, but the molecular mediation of this connection is just being revealed. The discovery of hepcidin as the prime controller of iron metabolism has paved the way for understanding the main actors behind this mediation. Recent data suggest that insulin therapy and probably other diabetes drugs can influence hepcidin production, thus influencing the iron load in cells. Correcting iron load through hepcidin expression could be a novel and important mechanism of action of antidiabetes drugs. This effect would further establish the protective role of antidiabetes therapy and might even affect prevention strategies in diabetes. In this review, we summarize the recent data about iron-glucose links through hepcidin expression, the molecular mediation of this interplay and the clinical implications of these findings.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Glucosa/metabolismo , Hepcidinas/metabolismo , Insulina/metabolismo , Animales , HumanosRESUMEN
Genetic medicine applied to the study of hemochromatosis has identified the systemic loop controlling iron homeostasis, centered on hepcidin-ferroportin interaction. Current challenges are to dissect the molecular pathways underlying liver hepcidin synthesis in response to circulatory iron, HFE, TFR2, HJV, TMPRSS6 and BMP6 functions, and to define the major structural elements of hepcidin-ferroportin interaction. We built a first 3D model of human ferroportin structure, using the crystal structure of EmrD, a bacterial drug efflux transporter of the Major Facilitator Superfamily, as template. The model enabled study of disease-associated mutations, and guided mutagenesis experiments to determine the role of conserved residues in protein stability and iron transport. Results revealed novel amino acids that are critical for the iron export function and the hepcidin-mediated inhibition mechanism: for example, tryptophan 42, localized in the extracellular end of the ferroportin pore and involved in both biological functions. Here, we propose a strategy that is not limited to structure analysis, but integrates information from different sources, including human disease-associated mutations and functional in vitro assays. The first major hypothesis of this PhD thesis is that ferroportin resistance to hepcidin relies on different molecular mechanisms that are critical for ferroportin endocytosis, and include at least three fundamental steps: (i) hepcidin binding to ferroportin, (ii) structural reorganization of the N- and C-ter ferroportin lobes, and (iii) ferroportin ubiquitination.
Asunto(s)
Proteínas de Transporte de Catión/deficiencia , Hemocromatosis/genética , Hepcidinas/farmacología , Mutación Missense , Mutación Puntual , Aminoácidos/fisiología , Transporte Biológico , Proteínas de Transporte de Catión/química , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/fisiología , Proteínas de Escherichia coli/química , Mutación con Ganancia de Función , Humanos , Hierro/sangre , Lisosomas/metabolismo , Proteínas de Transporte de Membrana/química , Modelos Moleculares , Conformación Proteica , Procesamiento Proteico-Postraduccional , Estabilidad Proteica , UbiquitinaciónRESUMEN
Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1. A defect of hepcidin expression leading to the appearance of a parenchymal iron overload may be genetic or secondary to dyserythropoiesis. The exploration of genetic hemochromatosis has revealed the involvement of several genes, including the recently described BMP6. Non-transfusional secondary hemochromatosis is due to hepcidin repression by cytokines, in particular the erythroferone factor that is produced directly by the erythroid precursors. Iron overload is correlated with the appearance of a free form of iron called NTBI. The influx of NTBI seems to be mediated by ZIP14 transporter in the liver and by calcium channels in the cardiomyocytes. Beside the liver, hepcidin is expressed at lesser extent in several extrahepatic tissues where it plays its ancestral role of antimicrobial peptide. In the kidney, hepcidin modulates defense barriers against urinary tract infections. In the heart, hepcidin maintains tissue iron homeostasis by an autocrine regulation of ferroprotine expression on the surface of cardiomyocytes. In conclusion, hepcidin remains a promising therapeutic tool in various iron pathologies.
Asunto(s)
Hierro/metabolismo , Animales , Transporte Biológico , Proteínas de Transporte de Catión/fisiología , Eritropoyesis/fisiología , Hemocromatosis/genética , Hemocromatosis/metabolismo , Hepcidinas/fisiología , Homeostasis , Humanos , Absorción Intestinal , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Hierro de la Dieta/farmacocinética , Riñón/metabolismo , Hígado/metabolismo , Macrófagos/metabolismoRESUMEN
Iron deficiency anemia is prevalent in subgroups of the Canadian population. The objective of this study was to examine iron status and anemia in preschool-age children. Healthy children (n = 430, 2-5 years old, Montreal, Quebec, Canada) were sampled from randomly selected daycares. Anthropometry, demographics, and diet were assessed. Biochemistry included hemoglobin, ferritin, soluble transferrin receptors (sTfR), ferritin index, markers of inflammation (C-reactive protein, interleukin 6 (IL-6), and tumour necrosis factor alpha (TNFα)), and hepcidin. Iron deficiency and anemia cutoffs conformed to the World Health Organization criteria. Differences among categories were tested using mixed-model ANOVA or χ(2) tests. Children were 3.8 ± 1.0 years of age, with a body mass index z score of 0.48 ± 0.97, and 51% were white. Adjusted intakes of iron indicated <1% were at risk for deficiency. Hemoglobin was higher in white children, whereas ferritin was higher with greater age and female sex. Inflammatory markers and hepcidin did not vary with any demographic variable. The prevalence of iron deficiency was 16.5% (95% confidence interval (CI), 13.0-20.0). Three percent (95% CI, 1.4-4.6) of children had iron deficiency anemia and 12.8% (95% CI, 9.6-16.0) had unexplained anemia. Children with iron deficiency, with and without anemia, had lower plasma ferritin and hepcidin but higher sTfR, ferritin index, and IL-6, whereas those with unexplained anemia had elevated TNFα. We conclude that iron deficiency anemia is not very common in young children in Montreal. While iron deficiency without anemia is more common than iron deficiency with anemia, the correspondingly reduced circulating hepcidin would have enabled heightened absorption of dietary iron in support of erythropoiesis.
Asunto(s)
Anemia Ferropénica/sangre , Ferritinas/sangre , Hierro/sangre , Receptores de Transferrina/sangre , Factores de Edad , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etnología , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Preescolar , Estudios Transversales , Femenino , Humanos , Mediadores de Inflamación/sangre , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Quebec/epidemiología , Factores de Riesgo , Población BlancaRESUMEN
Gaucher disease induces some metabolic abnormalities so increased serum ferritin appears in more than 60% at diagnosis. The storage of glucosylceramide in macrophages produces an inflammatory response with iron recycling deregulation and release of cytokines. Iron homeostasis is controlled by the circulating peptide hepcidin and its production is influenced by inflammatory cytokines. Iron damages cells by excess of catalyzing reactive oxygen species, removal of the excess iron has a positive influence on the response to treatment and survival in patients with iron overload. We have analyzed some inflammatory biomarkers of macrophage activation and related to the iron profile, including hepcidin and liver iron deposits determined by MRI, in 8 type 1 GD patients with hyperferritinemia. We have explored the changes in this profile after 4 months under therapy with two different iron chelators, deferoxamine or deferasirox, by evaluating response, adverse events and quality of life. We observed a significant reduction in serum ferritin and hepcidin levels and in liver iron deposits. No differences were observed in chitotriosidase activity, CCL18/PARC concentration and IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1ß,TNF-α cytokine levels. After two years on follow-up, clinical and analytical data were improved and stable ferritin levels maintained less than 700 ng/dL.
Asunto(s)
Benzoatos/uso terapéutico , Deferoxamina/uso terapéutico , Enfermedad de Gaucher/tratamiento farmacológico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Hierro/sangre , Triazoles/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Citocinas/sangre , Deferasirox , Femenino , Ferritinas/sangre , Estudios de Seguimiento , Enfermedad de Gaucher/sangre , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/patología , Hepcidinas/sangre , Hexosaminidasas/sangre , Homeostasis , Humanos , Inflamación/sangre , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Inflamación/patología , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/patología , Activación de Macrófagos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Calidad de VidaRESUMEN
Iron is a trace mineral that is highly significant to endurance athletes. Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid-base balance. Endurance athletes are at increased risk for suboptimal iron status, with potential negative consequences on performance, because of the combination of increased iron needs and inadequate dietary intake. This review paper summarizes the role of iron in maximal and submaximal exercise and describes the effects of iron deficiency on exercise performance. Mechanisms that explain the increased risk of iron deficiency in endurance athletes, including exercise-associated inflammation and hepcidin release on iron sequestration, are described. Information on screening athletes for iron deficiency is presented, and suggestions to increase iron intake through diet modification or supplemental iron are provided.