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Purpose: We investigated whether hepcidin and erythroferrone (ERFE) could complement the Athlete Biological Passport (ABP) in indirectly detecting a 130 mL packed red blood cells (RBCs) autologous blood transfusion. Endurance performance was evaluated.Methods: Forty-eight healthy men (n = 24) and women (n = 24) participated. Baseline samples were collected weekly followed by randomization to a blood transfusion (BT, n = 24) or control group (CON, n = 24). Only the BT group donated 450 mL whole blood from which 130 mL RBCs was reinfused four weeks later. Blood samples were collected 3, 7, 14, 21 and 28 days after donation, and 3, 6, and 24 hours and 2, 3, and 6 days following reinfusion. In the CON group samples were collected with the same frequency. Endurance performance was evaluated by a 650-kCal time trial (n = 13) before and one and six days after reinfusion.Results: A time×treatment effect existed (P < 0.05) for hepcidin and ERFE. Hepcidin was increased (P < 0.01) ~110 and 89% six and 24 hours after reinfusion. Using an individual approach (99% specificity, e.g. allowing 1:100 false-positive), sensitivities, i.e. true positives, of 30% and 61% was found for hepcidin and ERFE, respectively. For the ABP, the most sensitive marker was Off-hr score ([Hb] (g·L-1) - 60 × √RET%) (P < 0.05) with a maximal sensitivity of ~58% and ~ 9% following donation and reinfusion, respectively. Combining the findings for hepcidin, ERFE and the ABP yielded a sensitivity across all time-points of 83% following reinfusion in BT. Endurance performance increased 24 hours (+6.4%, P < 0.01) and six days following reinfusion (+5.8%, P < 0.01).Conclusions: Hepcidin and ERFE may serve as biomarkers in an anti-doping context following an ergogenic, small-volume blood transfusion.

PURPOSE: The World Anti-Doping Agency prohibits glucocorticoid administration in competition but not in periods out of competition. Glucocorticoid usage is controversial as it may improve performance, albeit debated. A hitherto undescribed but performance-relevant effect of glucocorticoids in healthy humans is accelerated erythropoiesis. We investigated whether a glucocorticoid injection accelerates erythropoiesis, increases total hemoglobin mass, and improves exercise performance.METHODS: In a counterbalanced, randomized, double-blinded, placebo-controlled crossover design (3 months washout), 10 well-trained males (peak oxygen uptake, 60 ± 3 mL O 2 ·min -1 ·kg -1 ) were injected with 40 mg triamcinolone acetonide (glucocorticoid group) or saline (placebo group) in the gluteal muscles. Venous blood samples collected before and 7-10 h, 1, 3, 7, 14, and 21 d after treatment were analyzed for hemoglobin concentration and reticulocyte percentage. Hemoglobin mass and mean power output in a 450-kcal time trial were measured before as well as 1 and 3 wk after treatment.RESULTS: A higher reticulocyte percentage was evident 3 d (19% ± 30%, P < 0.05) and 7 d (48% ± 38%, P < 0.001) after glucocorticoid administration, compared with placebo, whereas hemoglobin concentration was similar between groups. Additionally, hemoglobin mass was higher ( P < 0.05) 7 d (glucocorticoid, 886 ± 104 g; placebo, 872 ± 103 g) and 21 d (glucocorticoid, 879 ± 111 g; placebo, 866 ± 103 g) after glucocorticoid administration compared with placebo. Mean power output was similar between groups 7 d (glucocorticoid, 278 ± 64 W; placebo, 275 ± 62 W) and 21 d (glucocorticoid, 274 ± 62 W; placebo, 275 ± 60 W) after treatment.CONCLUSIONS: Intramuscular injection of 40 mg triamcinolone acetonide accelerates erythropoiesis and increases hemoglobin mass but does not improve aerobic exercise performance in the present study. The results are important for sport physicians administering glucocorticoids and prompt a reconsideration of glucocorticoid usage in sport.

Since the first glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) was approved in 2005 (exenatide twice daily) for type 2 diabetes (T2D), the class has developed with newer compounds having more pronounced effects on glycaemic control and body weight. Also, administration regimes have become more convenient with once weekly injections, and recently an oral administration has become available. Large-scale randomized controlled cardiovascular (CV) outcome trials (CVOTs) have shown that GLP-1RA therapy can reduce the risk of CV disease (CVD) in high-risk individuals with T2D. In addition, GLP-1RAs may have renal benefits driven by new-onset macroalbuminuria, although no effect on hard renal endpoints has been found. Subsequently, the place for GLP-1RA therapy has changed over recent years, with most societies endorsing GLP-1RA therapy in patients with established or high risk of CVD independently of glycaemia. Initiation of GLP-1RA therapy can be complex due to differences in efficacy, side effects and safety profiles as well as administration forms within the class. Implementing guideline recommendations into ideal patient selection may be challenging both in specialty and non-specialty settings. To ensure adequate and proactive use of modern glucose-lowering medications in the treatment of T2D, it is essential to recognize patients with high risk or documented CVD. The present review provides an overview of the efficacy and benefits of the currently available GLP-1RA compounds. Furthermore, we review the results from recent large-scale CVOTs in a clinical context and suggest improving the implementation of GLP-1RA therapy across specialties to improve overall patient selection.

Current markers of iron deficiency (ID) such as ferritin and hemoglobin have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n=39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an anti-doping context.Clinical trial registration: Clinical trials identifier, NCT04227665

Some have questioned the evidence for performance-enhancing effects of several substances included on the World Anti-Doping Agency's Prohibited List due to the divergent or inconclusive findings in randomized controlled trials (RCTs). However, inductive statistical inference based on RCTs-only may result in biased conclusions because of the scarcity of studies, inter-study heterogeneity, too few outcome events, or insufficient power. An abductive inference approach, where the body of evidence is evaluated beyond considerations of statistical significance, may serve as a tool to assess the plausibility of performance-enhancing effects of substances by also considering observations and facts not solely obtained from RCTs. Herein, we explored the applicability of an abductive inference approach as a tool to assess the performance-enhancing effects of substances included on the Prohibited List. We applied an abductive inference approach to make inferences on debated issues pertaining to the ergogenic effects of recombinant human erythropoietin (rHuEPO), beta2-agonists and anabolic androgenic steroids (AAS), and extended the approach to more controversial drug classes where RCTs are limited. We report that an abductive inference approach is a useful tool to assess the ergogenic effect of substances included on the Prohibited List - particularly for substances where inductive inference is inconclusive. Specifically, a systematic abductive inference approach can aid researchers in assessing the effects of doping substances, either by leading to suggestions of causal relationships or identifying the need for additional research.

We investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low-dose recombinant human erythropoietin (rhEpo) treatment at sea-level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex-XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty-nine participants completed two interventions, each containing a four-week baseline, a four-week SL or AL (2,230m) exposure and a four-week follow-up. During exposure, rhEpo (20 IU·kg-1) or placebo (PLA) was injected at SL (SLrhEpo n = 25, SLPLA n = 9) and AL (ALrhEpo n = 12, ALPLA n = 27) every second day for three weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC was up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post-treatment, respectively. Compared with ALPLA, IRF and IR/RBC was up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post-treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC was up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post-treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single-fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001), and provided larger or similar changes compared to multi-fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low-dose rhEpo misuse at SL and AL.

Objectives Optimized concurrent training regimes are warranted in physical training of military-, law enforcement- and rescue-personnel. This study investigated if four 15-min endurance training sessions weekly improve aerobic capacity and performance more than one 60-min endurance session weekly during the initial phase of a Basic Military Training program. Design A randomized training intervention study with functional and physiological tests before and after the intervention. Methods Military conscripts (n = 290) were randomly allocated to three groups completing 9 weeks training. Weekly training consisted of four endurance and four strength training sessions lasting 15 min each (‘Micro-training’: MIC); one strength and one endurance session lasting 60 min each (‘Classical-training’: CLA) or two 60 min sessions of standard military training (‘Control-training’: CON). Results Both 12-min (∼7−10%) and shuttle run performance (∼35−42%) improved (P ≤ 0.001) similarly in all groups. Likewise, functional 2-min maximal repetition exercise capacity increased (P ≤ 0.05) similarly in all groups (Lunges ∼17−24 %; PushUp ∼10−20%; AbdominalFlexions∼21−23%). Peak oxygen uptake changes depended on group (P ≤ 0.05) with increases (P ≤ 0.01) in MIC (7 ± 7%, n = 23) and CON (12 ± 18%, n = 17) and no changes in CLA. Maximal m. vastus lateralis citrate synthase activity decreased 14 ± 26% (P ≤ 0.001, n = 18) in CLA. Likewise, maximal m. vastus lateralis 3-hydroxyacyl-CoA dehydrogenase activity decreased 8 ± 17% in MIC (n = 28) and 14 ± 24% in CLA (n = 18). Conclusions Four 15-min endurance training sessions weekly improves running performance and strength-endurance similarly to one 60 min session. Peak oxygen uptake only increases with more than one endurance session weekly and leg muscle oxidative capacity appears reduced after basic military training.

Angiotensin-converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well-controlled studies in humans without confounding conditions are lacking. Thus, the purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double-blind, placebo-controlled trial. Eight weeks of exercise training combined with placebo (PLA, n = 25) or ACE inhibitor (ACEi, n = 23) treatment was carried out. Before and after the intervention, cardiovascular characteristics were investigated. Mean arterial blood pressure was reduced (p i , whereas the 0.7 [-2.0; 3.5] mmHg fluctuation in PLA was non-significant. Maximal oxygen uptake increased (p i and 13 [9; 17] % in PLA. In addition, skeletal muscle endurance increased (p i and 74 [48; 105] % in PLA. In contrast, left atrial volume decreased (p i , but increased (p p i , while a non-significant numeric increase of 2 [-0.4; 4] % existed in PLA. The lean mass remained constant in ACEi but increased (p

Dried blood spot (DBS) testing allows fast, easy, and minimally invasive collection of microvolumes of blood. In an anti-doping context, DBS testing has particular relevance for substances prohibited in-competition only such as ephedrine, which is currently detected by urine analysis, since DBS can add information about the blood drug concentrations during the in-competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper-arm DBS, fingerprick DBS and venous plasma samples from 8 healthy, male subjects in an 8-hour period following oral administrations of 20 mg ('low dose') and 60 mg ('high dose') of ephedrine. We show that the use of alternative sampling sites and matrices are feasible possibilities for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.

The SHFT device is a novel running wearable consisting of two pods connected to your smartphone issuing several running metrics based on accelerometer and gyroscope technology. The purpose of this study was to investigate the reliability and validity of the power output (PO) metric produced by the SHFT device. To assess reliability, 12 men ran on an outdoor track at 10.5 km·h-1 and 12 km·h-1 on two consecutive days. To assess validity, oxygen uptake (VO2) and SHFT data from eight men and seven women were collected during incremental submaximal running tests on an indoor treadmill on one to four separate days (34 tests in total). SHFT reliability on the outdoor track was strong with coefficients of variance (CV) of 1.8% and 2.4% for 10.5 and 12 km·h-1, respectively. We observed a very strong linear relationship between PO and VO2 (r2 = 0.54) within subjects, and a very strong linear relationship within each subject within each treadmill test (r2 = 0.80). We conclude that SHFT provides a reliable running power estimate and that a very strong relationship between SHFT-Power and metabolic rate exists, which places SHFT as one of the leading commercially available running power meters.

Oral semaglutide (Rybelsus®) is a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) with 94% homology to human GLP-1. It is the first GLP-1RA developed for oral administration, and it comprises a co-formulation of the peptide semaglutide with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, which overcomes the challenges of peptide absorption in the acidic conditions of the stomach. Oral semaglutide is indicated for use as an add-on combination therapy (with other glucose-lowering agents, including insulin) or as a monotherapy (in patients who are intolerant to metformin) for type 2 diabetes when diet and exercise do not provide adequate glycemic control. In an extensive phase III clinical program including patients from across the disease spectrum, treatment with oral semaglutide resulted in effective glycemic control, reductions in body weight, and decreases in systolic blood pressure when used as monotherapy or in combination with other glucose-lowering therapies. Studies showed that oral semaglutide was well tolerated, with a safety profile consistent with the GLP-1RA drug class. The risk of hypoglycemia was low, and the most common adverse events were gastrointestinal, with nausea and diarrhea generally being the most frequently reported manifestations. Cardiovascular (CV) safety was shown to be noninferior to placebo and observations suggest that the CV profile of oral semaglutide is likely to be similar to that of subcutaneous semaglutide. The evolution of the GLP-1RA class to include an oral agent could facilitate the use of these agents earlier in the diabetes treatment cascade owing to wider acceptance from patients and healthcare professionals. Video abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01499-w.

This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with chronic hypoxia provided an additive erythropoietic response and whether the Athlete Biological Passport (ABP) sensitivity improved with hypoxia. Two interventions were completed, each containing four weeks baseline, four weeks exposure at sea-level or 2,320m of altitude and four weeks follow-up. Participants were randomly assigned to 20 IU·kg bw-1 rhEpo or placebo injections every second day for three weeks during the exposure period at sea-level (rhEpo n=25, placebo n=9) or at altitude (rhEpo n=12, placebo n=27). Venous blood was analyzed weekly. Combining rhEpo and hypoxia induced larger changes compared with rhEpo or hypoxia alone for [Hb] (p < 0.001, p > 0.05, respectively), reticulocyte percentage (p < 0.001) and OFF-hr score (p < 0.01, p < 0.001, respectively). The most pronounced effect was observed for reticulocyte percentage with up to ~35% (p < 0.001) and ~45% (p < 0.001) higher levels compared with rhEpo or hypoxia only, respectively. The ABP sensitivity for the combined treatment was 54 and 35 percentage points higher for [Hb] (p < 0.05) and reticulocyte percentage (p < 0.05), respectively, but similar for OFF-hr score, compared with rhEpo at sea-level. Across any time point, [Hb] and OFF-hr score combined identified 14 unique true-positive participants (56%) at sea-level and 12 unique true-positive participants (100%) at altitude. However, a concurrent reduction in specificity existed at altitude. In conclusion, rhEpo treatment combined with hypoxic exposure provided an additive erythropoietic response compared to rhEpo or hypoxic exposure alone. Correspondingly, ABP was more sensitive to rhEpo at altitude than at sea-level, but a compromised specificity existed with hypoxic exposure.

Physical inactivity alters glucose homeostasis in skeletal muscle, potentially developing into overt metabolic disease. The present study sought to investigate the role of skeletal muscle capillarization in glucose tolerance and insulin sensitivity (IS) using a classic human model of physical inactivity. Thirteen healthy males (age = 23 ± 2 years) underwent 4 days of full-time supervised and diet-controlled bed rest. Oral glucose tolerance test, indices of IS (quantitative insulin sensitivity check index (QUICKI), Matsuda index), as well as skeletal muscle biopsies with measurement of fiber type distribution, fiber cross-sectional area (FCSA), capillary-to-fiber ratio (C/F ratio), and capillary density (CD) were assessed prior to and after bed rest. Body weight and composition were unaltered by bed rest. Fasting glucose/insulin ratio (G0/I0ratio) (−25%, P = 0.016), QUICKI (−7%, P = 0.023), and Matsuda index (−24%, P = 0.003) diminished with bed rest. Skeletal muscle FCSA decreased (−737.4 ± 763.2 μm−2(−12%), P = 0.005) while C/F ratio was preserved, resulting in augmented CD (+93.9 ± 91.5 capillaries·mm−2(+37%), P = 0.003) with bed rest. No association was detected between changes in skeletal muscle variables and metabolic outcomes. Independently of bed rest-induced effects, a positive linear relationship was detected between C/F ratio and G0/I0ratio (β = 17.09, P = 0.021). In conclusion, impaired glucose homeostasis with bed rest is not prevented nor associated with enhanced skeletal muscle capillarization in healthy individuals.

BACKGROUND Whether arterial stiffness (AS) can be improved by regular exercise in healthy individuals remains equivocal according to cross-sectional and longitudinal studies assessing arterial properties at discrete time points. The purpose of the present study was to pinpoint the time course of training-induced adaptations in central AS. METHODS Aorta characteristic impedance (Zc) and carotid distensibility (CD) were determined with ultrasonography prior to (week 0) and across 8 weeks (weeks 2, 4, and 8) of supervised endurance training (ET) (3 × 60 minutes cycle ergometry sessions per week), in 9 previously untrained healthy normotensive adults (27 ± 4 years) with no history of cardiovascular disease. Exercise capacity was assessed by maximal oxygen consumption (VO2max) elicited by incremental ergometry. RESULTS VO2max increased throughout the ET intervention (+12% from week 0 to week 8, P < 0.001, P for linear trend

Arterial distensibility, an independent predictor of cardiovascular events, is transiently increased with acute hyperglycemia (AHG) in healthy individuals. Whether this response interacts with physical inactivity remains unknown. We examined the effects of short-term bed rest (BR) on the response of carotid artery distensibility (CD) to AHG, and the influence of underlying changes in insulin resistance and blood volume. CD was assessed with ultrasonography before as well as 30 and 120 minutes following ingestion of 75 g of glucose prior to and after 3 days of BR in 15 healthy male volunteers. Plasma insulin/glucose concentrations and blood volumes were concomitantly determined. On day 4 of BR, blood volume was re-established to pre-BR levels by albumin infusion and CD and insulin/glucose concentrations were determined as in the previous experimental days. Basal CD was not affected by BR. AHG increased CD before and after BR but reached a higher peak increment after BR (12% vs 60% at 30 min OGTT, p=0.028). BR also increased the plasma insulin concentration during AHG ( p=0.007). In regression analyses, plasma insulin and glucose concentrations were positively correlated to CD, particularly after BR ( r=0.31, p

Sprint-interval training (SIT) is efficient at improving maximal aerobic capacity and anaerobic fitness at sea-level and may be a feasible training strategy at altitude. Here, it was evaluated if SIT intensity can be maintained in mild to moderate hypoxia. It was hypothesized that 6 x 30 s Wingate sprint performance with 2 min active rest between sprints can be performed in hypoxic conditions corresponding to ~3,000 m of altitude without reducing mean power output (MPO). In a single-blinded, randomized crossover design, ten highly-trained male endurance athletes with a maximal oxygen uptake (V˙O2max) of 68 ± 5 mL O2× min-1× kg-1completed 6 x 30 s all-out Wingate cycling sprints separated by two-minute active recovery on four separate days in a hypobaric chamber. The ambient pressure within the chamber on each experimental day was 772 mmHg (~0 m), 679 mmHg (~915 m), 585 mmHg (~ 2,150 m), and 522 mmHg (~3,050 m), respectively. MPO was not different at sea-level and up to ~2,150 m (~1% and ~3% non-significant decrements at ~915 and ~2,150 m, respectively), whereas MPO was ~5% lower (P

Purpose: To investigate the hypothesis that a therapeutic oral dose of Tramadol improves cycling time trial performance and compromises motor-cognitive performance in highly trained cyclists.Methods: Following two familiarization trials, 16 highly trained cyclists completed a preloaded time trial (1 hour at 60 % of peak power followed by a 15 km time trial) after ingestion of 100 mg Tramadol or placebo in a double-blind placebo-controlled counterbalanced cross-over design separated by at least 4 days wash-out. Visuo-motor tracking and math tasks were completed during the preload (n=10) to evaluate effects on cognition and fine motor performance.Results: Time trial mean power output (298±42 W vs. 294±44 W) and performance (1474±77 s vs. 1483±85 s) were similar with Tramadol and placebo treatment, respectively. In addition, there were no differences in perceived exertion, reported pain, blood pH, lactate or HCO3 concentrations across trials. Heart rate was higher (PPConclusion: In highly trained cyclists, ingestion of 100 mg Tramadol does not improve performance in a 15 km cycling time trial that was completed after a one hour preload at 60 % peak power. Additionally, a therapeutic dose of Tramadol does not compromise complex motor-cognitive or simple fine motor performances.

Objectives Military-, rescue- and law-enforcement personnel require a high physical capacity including muscular strength. The present study hypothesized that 9 weeks of volume matched concurrent short frequent training sessions increases strength more efficiently than less frequent longer training sessions. Design A randomized training intervention study with functional and physiological tests before and after the intervention. Methods Military conscripts (n = 290) were assigned to micro-training (four 15-min strength and four 15-min endurance bouts weekly); classical-training (one 60-min strength and one 60-min endurance training session weekly) or a control-group (two 60-min standard military physical training sessions weekly). Results There were no group difference between micro-training and classical-training in measures of strength. Standing long jump remained similar while shotput performance was reduced (P ≤ 0.001) in all three groups. Pull-up performance increased (P ≤ 0.001) in micro-training (7.4 ± 4.6 vs. 8.5 ± 4.0 repetitions, n = 59) and classical-training (5.7 ± 4.1 vs. 7.1 ± 4.2 repetitions, n = 50). Knee extensor MVC increased (P ≤ 0.01) in all groups (micro-training, n = 30, 11.5 ± 8.9%; classical-training, n = 24, 8.3 ± 11.5% and control, n = 19, 7.5 ± 11.8%) while elbow flexor and hand grip MVC remained similar. Micro-training increased (P ≤ 0.05) type IIa percentage from 32.5 ± 11.0% to 37.6 ± 12.3% (n = 20) and control-group increased (P ≤ 0.01) type IIax from 4.4 ± 3.0% to 11.6 ± 7.9% (n = 8). In control-group type I, fiber size increased (P ≤ 0.05) from 5121 ± 959 μm to 6481 ± 2084 μm (n = 5). Satellite cell content remained similar in all groups. Conclusions Weekly distribution of low-volume concurrent training completed as either eight 15-min bouts or two 60-min sessions of which 50% was strength training did not impact strength gains in a real-world setting.

The time course of plasma volume (PV) reduction following an increased training load period is unknown and was investigated. The accompanying fluctuations in [Hb] and OFF-hr score were analyzed in the Athlete Biological Passport. Further, whether fluctuations in plasma albumin, soluble transferrin receptors (sTfR), and pro-atrial natriuretic peptide (proANP) concentrations correlate with PV fluctuations was investigated. Eleven high-level competitive cyclists were investigated for 3 weeks. After initial measurements in week 1, training load was increased ~250% in week 2 followed by a reversion to baseline training load in week 3. PV and hematological variables were determined frequently during all weeks. The higher training load in week 2 increased (P

Bed rest leads to rapid impairments in glucose tolerance. Plasma volume and thus dilution space for glucose are also reduced with bed rest, but the potential influence on glucose tolerance has not been investigated. Accordingly, the aim was to investigate whether bed rest-induced impairments in glucose tolerance are related to a concomitant reduction in plasma volume. This hypothesis was tested mechanistically by restoring plasma volume with albumin infusion after bed rest and parallel determination of glucose tolerance. Fifteen healthy volunteers (age 24 ± 3 yr, body mass index 23 ± 2 kg/m2, maximal oxygen uptake 44 ± 8 ml·min−1·kg−1; means ± SD) completed 4 days of strict bed rest. Glucose tolerance [oral glucose tolerance test (OGTT)] and plasma and blood volumes (carbon monoxide rebreathing) were assessed before and after 3 days of bed rest. On the fourth day of bed rest, plasma volume was restored by means of an albumin infusion prior to an OGTT. Plasma volume was reduced by 9.9 ± 3.0% on bed rest day 3 and area under the curve for OGTT was augmented by 55 ± 67%. However, no association ( R2= 0.09, P = 0.33) between these simultaneously occurring responses was found. While normalization of plasma volume by matched albumin administration (408 ± 104 ml) transiently decreased ( P < 0.05) resting plasma glucose concentration (5.0 ± 0.4 to 4.8 ± 0.3 mmol/l), this did not restore glucose tolerance. Bed rest-induced alterations in dilution space may influence resting glucose values but do not affect area under the curve for OGTT.

Purpose: This study tested the hypothesis that autologous blood transfusion (ABT) of ~50% of the red blood cells (RBCs) from a standard 450 ml phlebotomy would increase mean power in a cycling time trial. Additionally, the study investigated whether further ABT of RBCs obtained from another 450 ml phlebotomy would increase repeated cycling sprint ability.Methods: In a randomized, double-blind, placebo-controlled crossover design (3-month wash-out), nine highly trained male subjects donated two 450 ml blood bags each (BT-trial) or were sham phlebotomized (PLA-trial). Four weeks later, a 650 kcal time trial (n=7) was performed three days before and 2 h after receiving either ~50% (135 ml) of the RBCs or a sham transfusion. On the following day, transfusion of RBCs (235 ml) from the second donation or sham transfusion was completed. A 4×30 s all-out cycling sprint interspersed by 4 min of recovery was performed six days before and three days after the second ABT (n=9).Results: The mean power was increased in time trials from before to after transfusion (PConclusion: ABT of only ~135 ml of RBCs is sufficient to increase mean power in a 650 kcal cycling time trial by ~5% in highly trained men. In contrast, a combined high-volume transfusion of ~135 and ~235 ml of RBCs does not alter 4×30 s all-out cycling performance interspersed with 4 min of recovery.

Bed rest leads to impaired glucose tolerance. Whether this is linked to maladaptation's in skeletal muscle mitochondrial function and in particular to the level of reactive oxygen species (ROS) is at present unknown. The aim of this longitudinal study was to quantify skeletal muscle mitochondrial function (respiratory capacity and ROS production) together with glucose tolerance after 4 days of strict bed rest in healthy young male subjects (n = 14). Mitochondrial function was determined in permeabilized muscle fibers using high-resolution respirometry and fluorometry, mitochondrial content (citrate synthase [CS] activity) and antioxidant protein expression levels were assessed in parallel to this. Glucose tolerance was determined by means of oral glucose tolerance tests. Intrinsic mitochondrial respiratory capacity was augmented after the bed rest period (CI + IIP : 0.43 ± 0.12 vs. 0.55 ± 0.14 [pmol/sec/mg]/CS activity), due to a decreased CS activity (158 ± 39 vs. 129 ± 25 mU/mg dw.). No differences were observed in ROS production (per mg of tissue or when normalized to CS activity). Furthermore, the protein content for catalase was increased while superoxide dismutase and glutathione peroxidase remained unaffected. These findings were accompanied by an impaired glucose tolerance after the bed rest period (Matsuda index: 12 ± 6 vs. 9 ± 5). The change in intrinsic mitochondrial respiratory capacity could be an early indication in the development of impaired glucose tolerance. The increased catalase protein content might explain that no change was seen in ROS production after 4 days of bed rest. Whether these findings can be extrapolated to lifestyle-dependent decrements in physical activity and the development of type-2-diabetes remains unknown.

Elite endurance athletes possess a high capacity for whole-body maximal fat oxidation (MFO). The aim was to investigate the determinants of a high MFO in endurance athletes. The hypotheses were that augmented MFO in endurance athletes is related to concomitantly increments of skeletal muscle mitochondrial volume density (MitoVD ) and mitochondrial fatty acid oxidation (FAOp ), that is, quantitative mitochondrial adaptations as well as intrinsic FAOp per mitochondria, that is, qualitative adaptations. Eight competitive male cross-country skiers and eight untrained controls were compared in the study. A graded exercise test was performed to determine MFO, the intensity where MFO occurs (FatMax ), and V˙O2Max . Skeletal muscle biopsies were obtained to determine MitoVD (electron microscopy), FAOp , and OXPHOSp (high-resolution respirometry). The following were higher (P

INTRODUCTION The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invasive CO pulse oximeter (Rad-57). METHOD With simultaneous determination of CO in the circulation by ABL800 (%HbCO) and Rad-57 (SpCO), Hbmass and blood volume (BV) were determined in duplicates in 24 volunteers. Percentage of typical errors (%TE) within methods and linear correlations between the two procedures were computed. RESULTS Hbmass (Rad-57 = 798 ± 230 g; ABL800 = 781 ± 192 g) and BV (Rad-57 = 5700 ± 1373 ml; ABL800 = 5581 ± 1096 ml) were similar between methods. However, the %TE for Hbmass was higher (P 905 g and BV > 6193 ml. CONCLUSION Assessment of SpCO by Rad-57 resulted in considerably less precise determinations of Hbmass and BV, especially for high values. Thus, non-invasive assessment of Hbmass and BV cannot be recommended for scientific purposes, but may nonetheless be useful in clinical settings.

The purpose of the present study was to characterize the progression of red blood cell volume (RBCV) expansion and potential volumetric and endocrine regulators of erythropoiesis during endurance training (ET). Nine healthy, untrained volunteers (age = 27 +/- 4 yr) underwent supervised ET consisting of 3-4 x 60 min cycle ergometry sessions per week for 8 wk. Plasma volume (PV), RBCV, and overnight fasting hematological markers were determined before and at weeks 2, 4, and 8 of ET. In addition, plasma erythropoietin (EPO), cortisol, copeptin, and proatrial natriuretic peptide concentrations were measured during a 3-h morning period at baseline and postexercise at weeks 1 and 8. PV increased from baseline (2,405 +/- 335 ml) at weeks 2, 4, and 8 (+/- 374 +/- 194, +505 +/- 156, and + 341 +/- 160 ml, respectively, P