An intensified training schedule in recreational male runners is associated with increases in erythropoiesis and inflammation and a net reduction in plasma hepcidin

ABSTRACT Background Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. Objective We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. Design In a prospective intervention, nonanemic, iron-sufficient men (n = 10) completed a 34-d study consisting of a 16-d control phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Results Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P < 0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P < 0.05). Training tended to increase geometric mean iron absorption by 24% (P = 0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P < 0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P < 0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. Conclusions In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.

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Iron bioavailability of a casein-based iron fortificant compared with that of ferrous sulfate in whole milk: a randomized trial with a crossover design in adult women

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz237 ◽

2019 ◽

Vol 110 (6) ◽

pp. 1362-1369 ◽

Cited By ~ 2

Author(s):

Sharon J Henare ◽

Nadia Nur Singh ◽

Ashling M Ellis ◽

Paul J Moughan ◽

Abby K Thompson ◽

...

Keyword(s):

Young Women ◽

Ferrous Sulfate ◽

Iron Absorption ◽

Iron Status ◽

Controlled Trial ◽

Geometric Mean ◽

Crossover Design ◽

Iron Bioavailability ◽

Adult Women ◽

Whole Milk

ABSTRACT Background A highly soluble iron–casein complex has been developed for food fortification purposes with the aim to provide high iron bioavailability. Objective We aimed to determine the iron bioavailability of the iron–casein complex relative to that of ferrous sulfate (control) when given with whole milk in healthy young women. Methods A randomized comparator-controlled trial with a crossover design was conducted using the erythrocyte incorporation dual stable isotope (57Fe, 58Fe) technique. Iron absorption from the iron–casein complex was compared with that from ferrous sulfate in 21 healthy women aged 20–38 y with normal iron status. Results Fractional iron absorption (geometric mean; −SD, +SD) from the iron–casein complex (3.4%; 1.4%, 5.4%) and from ferrous sulfate (3.9%; 1.7%, 6.1%) were not statistically different (P > 0.05). The relative bioavailability value of the iron–casein complex to ferrous sulfate was determined to be 0.87 (−1 SD, +1 SD: −0.90, +2.64). Conclusions The iron–casein complex has iron bioavailability comparable to that of ferrous sulfate in healthy young women. This trial was registered at www.anzctr.org.au as ACTRN12615000690550.

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The effect of iron dosing schedules on plasma hepcidin and iron absorption in Kenyan infants

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa174 ◽

2020 ◽

Vol 112 (4) ◽

pp. 1132-1141 ◽

Cited By ~ 1

Author(s):

Mary A Uyoga ◽

Nadja Mikulic ◽

Daniela Paganini ◽

Edith Mwasi ◽

Nicole U Stoffel ◽

...

Keyword(s):

Prospective Studies ◽

Iron Absorption ◽

Geometric Mean ◽

Oral Iron ◽

Iron Isotopes ◽

Iron Supplement ◽

Micronutrient Powder

ABSTRACT Background In adults, oral iron doses increase plasma hepcidin (PHep) for 24 h, but not for 48 h, and there is a circadian increase in PHep over the day. Because high PHep decreases fractional iron absorption (FIA), alternate day iron dosing in the morning may be preferable to consecutive day dosing. Whether these effects occur in infants is uncertain. Objective Using stable iron isotopes in Kenyan infants, we compared FIA from morning and afternoon doses and from consecutive, alternate (every second day) and every third day iron doses. Methods In prospective studies, we measured and compared FIA and the PHep response from 1) meals fortified with a 12-mg iron micronutrient powder given in the morning or afternoon (n = 22); 2) the same given on consecutive or alternate days (n = 21); and 3) a 12-mg iron supplement given on alternate days or every third day (n = 24). Results In total, 65.7% of infants were anemic. In study 1, PHep did not differ between morning and afternoon (P = 0.072), and geometric mean FIA[−SD, +SD](%) did not differ between the morning and afternoon doses [15.9 (8.9, 28.6) and 16.1 (8.7, 29.8), P = 0.877]. In study 2, PHep was increased 24 h after oral iron (P = 0.014), and mean FIA [±SD](%) from the baseline dose [23.3 (10.9)] was greater than that from the consecutive day dose (at 24 h) [20.1 (10.4); P = 0.042] but did not differ from the alternate day dose (at 48 h) [20.9 (13.4); P = 0.145]. In study 3, PHep was not increased 48 and 72 h after oral iron (P = 0.384), and the geometric mean FIA[−SD, +SD](%) from doses given at baseline, alternate days, and every third day did not differ [12.7 (7.3, 21.9), 13.8 (7.8, 24.2), and 14.8 (8.8, 24.8), respectively; P = 0.080]. Conclusions In Kenyan infants given 12 mg oral iron, morning and afternoon doses are comparably absorbed, dosing on consecutive days increases PHep and modestly decreases iron absorption compared with alternate day dosing, and dosing on alternate days or every third day does not increase PHep or decrease absorption. This trial was registered at clinicaltrials.gov as NCT02989311 and NCT03617575.

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Iron absorption during pregnancy is underestimated when iron utilization by the placenta and fetus is ignored

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa155 ◽

2020 ◽

Vol 112 (3) ◽

pp. 576-585

Author(s):

Katherine M Delaney ◽

Ronnie Guillet ◽

Eva K Pressman ◽

Laura E Caulfield ◽

Nelly Zavaleta ◽

...

Keyword(s):

Iron Absorption ◽

Placental Transfer ◽

Iron Status ◽

Placental Tissue ◽

Iron Isotope ◽

Body Iron ◽

Factors Associated ◽

Maternal Iron ◽

Iron Utilization ◽

Net Transfer

ABSTRACT Background Maternal iron absorption during pregnancy can be evaluated using RBC incorporation of orally administered stable iron isotope. This approach underestimates true maternal absorption of iron as it does not account for absorbed iron that is transferred to the fetus or retained within the placenta. Objective Our objective was to re-evaluate maternal iron absorption after factoring in these losses and identify factors associated with iron partitioning between the maternal, neonatal, and placental compartments. Methods This study utilized data from stable iron isotope studies carried out in 68 women during the third trimester of pregnancy. Iron status indicators and stable iron isotopic enrichment were measured in maternal blood, umbilical cord blood, and placental tissue when available. Factors associated with iron isotope partitioning between the maternal, neonatal, and placental compartments were identified. Results On average, true maternal absorption of iron increased by 10% (from 19% to 21%) after accounting for absorbed iron present in the newborn (P < 0.001), and further increased by 7%, (from 39% to 42%, P < 0.001) after accounting for iron retained within the placenta. On average, 2% of recovered tracer was present in the placenta and 6% was found in the newborn. Net transfer of iron to the neonate was higher in women with lower total body iron (standardized β = −0.48, P < 0.01) and lower maternal hepcidin (standardized β = −0.66, P < 0.01). In women carrying multiple fetuses, neonatal hepcidin explained a significant amount of observed variance in net placental transfer of absorbed iron (R = 0.95, P = 0.03). Conclusions Maternal RBC iron incorporation of an orally ingested tracer underestimated true maternal iron absorption. The degree of underestimation was greatest in women with low body iron. Maternal hepcidin was inversely associated with maternal RBC iron utilization, whereas neonatal hepcidin explained variance in net transfer of iron to the neonatal compartment. These trials were registered at clinicaltrials.gov as NCT01019096 and NCT01582802.

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Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children

Science Advances ◽

10.1126/sciadv.aav9020 ◽

2019 ◽

Vol 5 (3) ◽

pp. eaav9020 ◽

Cited By ~ 11

Author(s):

Andrew M. Prentice ◽

Amat Bah ◽

Momodou W. Jallow ◽

Amadou T. Jallow ◽

Saikou Sanyang ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Respiratory Infections ◽

Fecal Calprotectin ◽

Deficiency Anemia ◽

Low Grade ◽

Reactive Protein ◽

African Children ◽

Low Grade Inflammation

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children.

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Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0443 ◽

2013 ◽

Vol 38 (7) ◽

pp. 779-788 ◽

Cited By ~ 27

Author(s):

Cheyne E. Donges ◽

Rob Duffield ◽

Kym J. Guelfi ◽

Greg C. Smith ◽

David R. Adams ◽

...

Keyword(s):

Body Composition ◽

Exercise Training ◽

Single Mode ◽

Glucose Regulation ◽

Low Grade ◽

Middle Aged ◽

Concurrent Exercise ◽

Low Grade Inflammation

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The Effectiveness of Transdermal Iron Patches in Athletes With Suboptimal Iron Status (Part 1)

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.2019-0309 ◽

2020 ◽

Vol 30 (3) ◽

pp. 185-190 ◽

Cited By ~ 1

Author(s):

Rachel McCormick ◽

Brian Dawson ◽

Marc Sim ◽

Leanne Lester ◽

Carmel Goodman ◽

...

Keyword(s):

Serum Ferritin ◽

Repeated Measures ◽

Iron Status ◽

Maximal Oxygen Consumption ◽

Oral Iron ◽

Iron Stores ◽

Beneficial Effects ◽

Parallel Group ◽

Gastrointestinal Side Effects ◽

Hemoglobin Mass

The authors compared the effectiveness of two modes of daily iron supplementation in athletes with suboptimal iron stores: oral iron (PILL) versus transdermal iron (PATCH). Endurance-trained runners (nine males and 20 females), with serum ferritin concentrations <50 μg/L, supplemented with oral iron or iron patches for 8 weeks, in a parallel group study design. Serum ferritin was measured at baseline and fortnightly intervals. Hemoglobin mass and maximal oxygen consumption () were measured preintervention and postintervention in PATCH. A linear mixed effects model was used to assess the effectiveness of each mode of supplementation on sFer. A repeated-measures analysis of variance was used to assess hemoglobin mass and outcomes in PATCH. There was a significant time effect (p < .001), sex effect (p = .013), and Time × Group interaction (p = .009) for sFer. At Week 6, PILL had significantly greater sFer compared with PATCH (15.27 μg/L greater in PILL; p = .019). Serum ferritin was 15.53 μg/L greater overall in males compared with females (p = .013). There were no significant differences in hemoglobin mass (p = .727) or (p = .929) preintervention to postintervention in PATCH. Finally, there were six complaints of severe gastrointestinal side effects in PILL and none in PATCH. Therefore, this study concluded that PILL effectively increased sFer in athletes with suboptimal iron stores, whereas PATCH showed no beneficial effects.

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The Role of Exercise Training on Low-Grade Systemic Inflammation in Adults with Overweight and Obesity: A Systematic Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182413258 ◽

2021 ◽

Vol 18 (24) ◽

pp. 13258

Author(s):

Paola Gonzalo-Encabo ◽

Gonzalo Maldonado ◽

David Valadés ◽

Carmen Ferragut ◽

Alberto Pérez-López

Keyword(s):

Exercise Training ◽

Systemic Inflammation ◽

Fat Mass ◽

Overweight And Obesity ◽

Concurrent Training ◽

Low Grade ◽

Mass Reduction ◽

Tnf Α ◽

Exercise Induced ◽

Low Grade Inflammation

Low-grade systemic inflammation leads to critical alterations of several tissues and organs that can promote the appearance of non-communicable diseases, a risk that is increased in adults with obesity. Exercise training may counteract low-grade systemic inflammation, but there is a lack of consensus on how cytokines are modulated by training in adults with obesity. This study aimed of examining the effects of exercise training on circulating pro- and anti-inflammatory cytokines in adults with overweight and obesity, and whether exercise-induced fat mass reduction could mediate that effect. The search was conducted on Medline (Pubmed), SPORTDiscus and Web of Science databases from January 1998 to August 2021, using keywords pertaining to inflammation, exercise, and obesity. A total of 27 studies were selected, in which the circulating concentration levels of cytokines were analyzed. Endurance training (ET) decreased circulating CRP, IL-6 and TNF-α levels. TNF-α was reduced after resistance and concurrent training (CT), while IL-10 increased after resistance training (RT). Changes in IL-10 and CRP coincided with fat mass reduction, while decreased TNF-α levels were concomitant with changes in IL-6 and IL-10. Exercise training may reduce systemic low-grade inflammation profile in adults with overweight and obesity.

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Algorithms for Iron and Zinc Bioavailability: Are they Accurate?

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000032 ◽

2010 ◽

Vol 80 (45) ◽

pp. 257-262 ◽

Cited By ~ 8

Author(s):

Janet R. Hunt

Keyword(s):

Iron Absorption ◽

Iron Status ◽

Large Data ◽

Iron Bioavailability ◽

Dietary Factors ◽

Current Evidence ◽

Zinc Absorption ◽

Data Set ◽

Zinc Bioavailability ◽

Iron And Zinc

Several bioavailability algorithms have been proposed for iron and zinc, confirming the need for these tools while emphasizing the challenge of deriving algorithms with accepted accuracy. This manuscript briefly reviews current evidence on the accuracy of proposed algorithms. Iron absorption is strongly influenced by both body iron status and dietary availability, and most evidence suggests that these do not interact. There is considerable evidence of a logarithmic relationship between percent iron absorption and serum ferritin that allows a simple and accurate computation of how human iron status affects absorption (in the absence of inflammation). Computing the effect of dietary variation on nonheme iron absorption has been challenging because of multiple influential dietary factors and incomplete knowledge of their chemical characteristics, food composition, interactions, and dose-response relationships. At present there is no fully validated algorithm for dietary iron bioavailability. Predicting zinc absorption is less complex. Fractional zinc absorption is substantially influenced by the amount of zinc consumed, and this factor, together with ingested phytic acid, account for a considerable degree of the variance. A multivariate saturation model based on these two variables has been derived using data from multiple studies and independently validated with a single large data set.

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Resistance Exercise Training-Induced Muscle Hypertrophy Was Associated with Reduction of Inflammatory Markers in Elderly Women

Mediators of Inflammation ◽

10.1155/2010/171023 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 65

Author(s):

Kishiko Ogawa ◽

Kiyoshi Sanada ◽

Shuichi Machida ◽

Mitsuharu Okutsu ◽

Katsuhiko Suzuki

Keyword(s):

Exercise Training ◽

Resistance Exercise ◽

Elderly Women ◽

Muscle Thickness ◽

The Elderly ◽

Low Grade ◽

Resistance Exercise Training ◽

Tnf Α ◽

Low Grade Inflammation ◽

Circulating Levels

Aging is associated with low-grade inflammation. The benefits of regular exercise for the elderly are well established, whereas less is known about the impact of low-intensity resistance exercise on low-grade inflammation in the elderly. Twenty-one elderly women (mean age ± SD, 85.0 ± 4.5 years) participated in 12 weeks of resistance exercise training. Muscle thickness and circulating levels of C-reactive protein (CRP), serum amyloid A (SAA), heat shock protein (HSP)70, tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP-1), insulin, insulin-like growth factor (IGF)-I, and vascular endothelial growth factor (VEGF) were measured before and after the exercise training. Training reduced the circulating levels of CRP, SAA (P<.05), HSP70, IGF-I, and insulin (P<.01). The training-induced reductions in CRP and TNF-α were significantly (P<.01,P<.05) associated with increased muscle thickness (r=−0.61,r=−0.54), respectively. None of the results were significant after applying a Bonferroni correction. Resistance training may assist in maintaining or improving muscle volume and reducing low-grade inflammation.

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