No acute hyperglycemia induced impairment in brachial artery flow-mediated dilation before or after aerobic exercise training in young recreationally active males.

There is some evidence that transient endothelial dysfunction induced by acute hyperglycemia may be attenuated by a single bout of aerobic exercise. However, the impact of aerobic exercise training on acute hyperglycemia-induced endothelial dysfunction has not been explored. The purpose of this study was to determine the impact of aerobic exercise training on the endothelial function response to acute hyperglycemia. Brachial artery flow-mediated dilation (FMD) was assessed in 24 healthy males (21 ± 1 years) pre-, 60 and 90 min post ingestion of 75 g of glucose. Participants completed a four-week control (CON; n = 13) or exercise training (EX; n = 11) intervention. The EX group completed four weeks of cycling exercise (30 min, 4×/week at 65% work rate peak). Cardiorespiratory fitness ([Formula: see text]O2peak) increased and resting HR decreased in EX, but not CON post-intervention (p < 0.001). Glucose and insulin increased (p < 0.001) following glucose ingestion, with no significant difference pre- and post-intervention. In contrast to previous research, FMD was unaffected by glucose-ingestion, pre- and post-intervention in both groups. In conclusion, acute hyperglycemia did not impair endothelial function, before or after exercise training. Relatively high baseline fitness ([Formula: see text]O2peak ~ 46 mL/kg/min) and young age may have contributed to the lack of impairment observed. Further research is needed to examine the impact of exercise training on hyperglycemia-induced impairments in endothelial function in sedentary males and females.

The acute effect of a laboratory shame induction protocol on endothelial function in young, healthy adults.

NEW FINDINGS: What is the central question of this study? Shame is a form of social stress that involves internalizing social devaluations imposed by others. The aim of this study was to determine, for the first time, how acutely experienced shame impacts endothelial function. What is the main finding and its importance? Brachial artery flow-mediated dilatation, an index of endothelial function, was impaired after an intervention that acutely increased self-reported shame. This occurred without increases in cortisol or tumor necrosis factor alpha receptor binding. Frequent or prolonged shame-induced endothelial dysfunction could have important cardiovascular consequences. ABSTRACT: The objective of this study was to examine the impact of a shame induction protocol on endothelial function. Fifteen participants (n = 7 men, n = 8 women) completed both a written shame induction protocol and a control protocol on two different experimental days. Pre- and post-protocol we assessed: (1) endothelial function and arterial shear rate via a standard brachial artery reactive hyperaemia flow-mediated dilatation (FMD) test across two post-intervention time points (15 and 35 min post); (2) perceived shame via the experiential shame scale (ESS); and (3) cortisol and soluble tumor necrosis factor alpha receptor (sTNFαRII) through oral fluid analysis. Shame increased after the shame induction protocol (pre, 2.9 ± 0.6 vs. post, 3.7 ± 0.5, P < 0.001) but not the control protocol (pre, 3.0 ± 0.5 vs. post, 2.8 ± 0.5, P = 0.15; protocol by time interaction, P < 0.001). When all three time points were included in the analysis, %FMD did not change over time. Considering only the lowest post time point, %FMD decreased significantly in response to the shame protocol (pre, 4.8 ± 1.9 vs. post, 3.2 ± 1.6, P < 0.001) but not the control protocol (pre, 4.2 ± 1.8 vs. post, 3.8 ± 1.5, P = 0.45; protocol by time interaction, P = 0.035). Covariation of the shear rate stimulus for FMD did not alter the FMD results. When including both the control and shame protocols, but not the shame protocol alone, increased shame was significantly associated with decreased FMD (r = -0.37, P < 0.046). There were no significant time by protocol interaction effects for cortisol or sTNFαRII. In conclusion, temporary increases in shame might cause transient endothelial dysfunction which, if chronically repeated, could manifest as reduced vasoprotection against atherosclerosis.

Directions for Exercise Treatment Response Heterogeneity and Individual Response Research.

Treatment response heterogeneity and individual responses following exercise training are topics of interest for personalized medicine. Proposed methods to determine the contribution of exercise to the magnitude of treatment response heterogeneity and categorizing participants have expanded and evolved. Setting clear research objectives and having a comprehensive understanding of the strengths and weaknesses of the available methods are vital to ensure the correct study design and analytical approach are used. Doing so will ensure contributions to the field are conducted as rigorously as possible. Nonetheless, concerns have emerged regarding the ability to truly isolate the impact of exercise training, and the nature of individual responses in relation to mean group changes. The purpose of this review is threefold. First, the strengths and limitations associated with current methods for quantifying the contribution of exercise to observed treatment response heterogeneity will be discussed. Second, current methods used to categorize participants based on their response to exercise will be outlined, as well as proposed mechanisms for factors that contribute to response variation. Finally, this review will provide an overview of some current issues at the forefront of individual response research.

Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle.

Fasting rapidly (≤ 6 h) activates mitochondrial biogenic pathways in rodent muscle, an effect that is absent in human muscle following prolonged (10-72 h) fasting. We tested the hypotheses that fasting-induced changes in human muscle occur shortly after food withdrawal and are modulated by whole-body energetic stress. Vastus lateralis biopsies were obtained from ten healthy males before, during (4 h), and after (8 h) two supervised fasts performed with (FAST+EX) or without (FAST) 2 h of arm ergometer exercise (~ 400 kcal of added energy expenditure). PGC-1α mRNA (primary outcome measure) was non-significantly reduced (p = 0.065 [ηp2 = 0.14]) whereas PGC-1α protein decreased (main effect of time: p < 0.01) during both FAST and FAST+EX. P53 acetylation increased in both conditions (main effect of time: p < 0.01) whereas ACC and SIRT1 phosphorylation were non-significantly decreased (both p < 0.06 [ηp2 = 0.15]). Fasting-induced increases in NFE2L2 and NRF1 protein were observed (main effects of time: p < 0.03), though TFAM and COXIV protein remained unchanged (p > 0.05). Elevating whole-body energetic stress blunted the increase in p53 mRNA, which was apparent during FAST only (condition × time interaction: p = 0.04). Select autophagy/mitophagy regulators (LC3BI, LC3BII, BNIP3) were non-significantly reduced at the protein level (p ≤ 0.09 [ηp2 > 0.13]) but the LC3II:I ratio was unchanged (p > 0.05). PDK4 mRNA (p < 0.01) and intramuscular triglyceride content in type IIA fibers (p = 0.04) increased similarly during both conditions. Taken together, human skeletal muscle signaling, mRNA/protein expression, and substrate storage appear to be unaffected by whole-body energetic stress during the initial hours of fasting.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Examining interindividual differences in select muscle and whole-body adaptations to continuous endurance training.

NEW FINDINGS: What is the central question of the study? Do interindividual differences in trainability exist for morphological and molecular skeletal muscle responses to aerobic exercise training? What is the main finding and its importance? Interindividual differences in trainability were present for some, but not all, morphological and molecular outcomes included in our study. Our findings suggest that it is inappropriate, and perhaps erroneous, to assume that variability in observed responses reflects interindividual differences in trainability in skeletal muscle responses to aerobic exercise training. ABSTRACT: Studies have interpreted a wide range of morphological and molecular changes in human skeletal muscle as evidence of interindividual differences in trainability. However, these interpretations fail to account for the influence of random measurement error and within-subject variability. The purpose of the present study was to use the standard deviation of individual response (SDIR ) statistic to test the hypothesis that interindividual differences in trainability are present for some but not all skeletal muscle outcomes. Twenty-nine recreationally active males (age: 21 ± 2 years; BMI: 24 ± 3 kg/m2 ; V̇O2peak ; 45 ± 7 ml/kg/min) completed 4 weeks of continuous training (REL; n = 14) or control (n = 15). Maximal enzyme activities (citrate synthase and ß-hydroxyacyl-CoA dehydrogenase), capillary density, fibre type composition, fibre-specific succinate dehydrogenase activity and substrate storage (intramuscular triglycerides and glycogen), and markers of mitophagy (BCL2-interacting protein 3 (BNIP3), BNIP3-like protein, parkin and PTEN-induced kinase 1) were measured in vastus lateralis samples collected before and after the intervention. We also calculated SDIR values for V̇O2peak , peak work rate and the onset of blood lactate accumulation for the REL group and a separate group that exercised at the negative talk test stage. Although positive SDIR values - indicating interindividual differences in trainability - were obtained for aerobic capacity outcomes, maximal enzyme activities, capillary density, all fibre-specific outcomes and BNIP3 protein content, the remaining outcomes produced negative SDIR values indicating a large degree of random measurement error and/or within-subject variability. Our findings question the interpretation of heterogeneity in observed responses as evidence of interindividual differences in trainability and highlight the importance of including control groups when analysing individual skeletal muscle response to exercise training.

Individual patterns of response to traditional and modified sprint interval training.

We compared the incidence of response between a traditional sprint interval training (SIT) protocol (30:240: 4-6 x 30-s, 240-s recovery) and 2 modified SIT protocols (15:120: 8-12 x 15-s, 120-s recovery; 5:40: 24-36 x 5-s, 40-s recovery) over 4 weeks of training in 84 recreationally active individuals (n = 23 per SIT group/15 control participants). Pre- and post-testing measures included V. O2max, 5-km time trial, and anaerobic capacity. Responders were classified using 2x typical error and seven other approaches to explore the impact of classification method on response rates. There was no difference in the proportion (2x typical error) of V.O2max responders across groups (30:240: 64%; 15:120: 39%; 5:40: 41%; CTRL: 33%; P= 0.190). The 30:240 group had more responders (P< 0.05) for time trial performance (70%) and peak speed during the 30 s running test (48%) compared to CTRL (21% and 0%, respectively). There were no other between-group differences (P> 0.112). Approaches with the largest response thresholds resulted in the fewest responders highlighting response rates are influenced by the method used. Additionally, we observed intra-individual differences in responsiveness across outcomes. This is the first study to empirically test the difference in the incidence of response and demonstrate individual patterns of response across different SIT protocols.

The impact of acute and chronic exercise on Nrf2 expression in relation to markers of mitochondrial biogenesis in human skeletal muscle.

PURPOSE: To examine the relationship between changes in nuclear factor erythroid 2-related factor 2 (Nrf2) expression and markers of mitochondrial biogenesis in acutely and chronically exercised human skeletal muscle. METHODS: The impact of acute submaximal endurance (END) and supramaximal interval (Tabata) cycling on the upregulation of Nrf2 (and its downstream targets), nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) mRNA expression was examined in healthy young males (n = 10). The relationship between changes in citrate synthase (CS) maximal activity and the protein content of Nrf2, heme oxygenase 1 (HO-1), NRF-1, and TFAM was also investigated following 4 weeks of Tabata in a separate group of males (n = 21). RESULTS: Nrf2, NRF-1, and HO-1 mRNA expression increased after acute exercise (p < 0.05), whereas the increase in superoxide dismutase 2 (SOD2) mRNA expression approached significance (p = 0.08). Four weeks of Tabata increased CS activity and Nrf2, NRF-1, and TFAM protein content (p < 0.05), but decreased HO-1 protein content (p < 0.05). Training-induced changes in Nrf2 protein were strongly correlated with NRF-1 (r = 0.63, p < 0.01). When comparing protein content changes between individuals with the largest (HI: + 23%) and smallest (LO: - 1%) observed changes in CS activity (n = 8 each), increases in Nrf2 and TFAM protein content were apparent in the HI group only (p < 0.02) with medium-to-large effect sizes for between-group differences in changes in Nrf2 (ηp2=0.15) and TFAM (ηp2 = 0.12) protein content. CONCLUSION: Altogether, our findings support a potential role for Nrf2 in exercise-induced mitochondrial biogenesis in human skeletal muscle.

Gene expression variability in human skeletal muscle transcriptome responses to acute resistance exercise.

NEW FINDINGS: What is the central question of this study? Does exercise, independent of random error and within-subject variability, contribute to the variability in gene expression responses to an acute bout of resistance exercise? What is the main finding and its importance? A reanalysis of publicly available microarray data revealed that variability in observed gene expression responses for a subset of genes could be partially attributable to an effect of acute resistance exercise. These finding support the notion that individual responsiveness explains a portion of the variability in observed gene expression responses to acute resistance exercise. ABSTRACT: The purpose of this study was to use publicly available transcriptomic data to determine whether variability in gene expression responses to an acute bout of acute resistance exercise (ARE) can be attributable to an effect of ARE per se. We examined microarray data from a previous study that collected skeletal muscle biopsies before and 24 h after ARE or a no-exercise time-matched control period (CTL). By subtracting the standard deviation in the observed responses to CTL from ARE, we determined that ARE contributed to the variability in the observed gene expression responses for many (∼31,000), but not all, transcripts included on the Affymetrix Human Genome chips. ARE had a large effect on variability in the observed gene expression responses in 1290 genes that was not attributed to any technical/biological variability associated with repeated measurements. Pathway analysis using WebGestalt revealed that several of these 1290 genes are involved in pathways known to regulate skeletal muscle adaptations to chronic resistance training. These results suggest that variability in the observed gene expression responses for a subset of genes could be partially attributable to an effect of ARE.

Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle.

NEW FINDINGS: What is the central question of this study? Are individual changes in exercise-induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)? What is the main finding and its importance? Exercise-induced changes in mRNA expression are not repeatable even under identical experimental conditions, thereby challenging the use of mRNA expression as a biomarker of adaptive potential and/or individual responsiveness to exercise. ABSTRACT: It remains unknown if (1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and (2) the individual responsiveness to exercise is protocol-specific. We examined the repeatability of skeletal muscle PGC-1α, PDK4, NRF-1, VEGF-A, HSP72 and p53 mRNA expression following two identical endurance exercise (END) bouts (END-1, END-2; 30 min of cycling at 65% of peak work rate (WRpeak ), n = 11) and inter-individual variability in PGC-1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20 s cycling intervals at ∼170% WRpeak , n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within-sample fibre-type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICC > 0.71; CV < 10%; r > 0.85, P < 0.01), gene analysis steps (ICC > 0.73; CV < 24%; r > 0.75, P < 0.01), and similar group-level changes in mRNA expression, individual changes in PGC-1α, PDK4, VEGF-A and p53 mRNA expression were not repeatable (ICC < 0.22; CV > 20%; r < 0.21). Fibre-type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, P = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analysing individual responsiveness to exercise.

The application of repeated testing and monoexponential regressions to classify individual cardiorespiratory fitness responses to exercise training.

PURPOSE: We tested the hypothesis that monoexponential regressions will increase the certainty in response estimates and confidence in classification of cardiorespiratory fitness (CRF) responses compared to a recently proposed linear regression approach. METHODS: We used data from a previously published RCT that involved 24 weeks of training at high amount-high intensity (HAHI; N = 28), high amount-low intensity (HALI; N = 48), or low amount-low intensity (LALI; N = 33). CRF was measured at 0, 4, 8, 16, and 24 weeks. We fit the repeated CRF measures with monoexponential and linear regressions, and calculated individual response estimates, the error in these estimates (TEMONOEXP and TESLOPE, respectively), and 95% confidence intervals (CIs). Individuals were classified as responders, uncertain, or non-responders based on where their CI lay relative to a minimum clinically important difference. Additionally, responses were classified using observed pre-post-changes and the typical error of measurement. RESULTS: Comparing the error in response estimates revealed that monoexponential regressions were a better fit than linear regressions for the majority of individual responses (N = 81/109) and mean CRF data (mean TEMONOEXP:TESLOPE; HAHI = 2.00:2.58, HALI = 1.91:2.46, LALI = 1.63:2.18; all p < 0.01). Fewer individuals were confidently classified as responders with linear regressions (N = 29/109) compared to monoexponential (N = 55/109). Additionally, response estimates were highly correlated across all three approaches (all r > 0.92). CONCLUSIONS: Future studies should determine the type of regression that best fits their data prior to classifying responses. The similarity in response estimates and classification from regressions and observed pre-post-changes questions the purported benefit of using repeated measures to characterize CRF responses to training.

Risk of bias and reporting practices in studies comparing VO2max responses to sprint interval vs. continuous training: A systematic review and meta-analysis.

BACKGROUND: It remains unclear whether studies comparing maximal oxygen uptake (VO2max) response to sprint interval training (SIT) vs. moderate-intensity continuous training (MICT) are associated with a high risk of bias and poor reporting quality. The purpose of this study was to evaluate the risk of bias and quality of reporting in studies comparing changes in VO2max between SIT and MICT. METHODS: We conducted a comprehensive literature search of 4 major databases: AMED, CINAHL, EMBASE, and MEDLINE. Studies were excluded if participants were not healthy adult humans or if training protocols were unsupervised, lasted less than 2 weeks, or utilized mixed exercise modalities. We used the Cochrane Collaboration tool and the CONSORT checklist for non-pharmacological trials to evaluate the risk of bias and reporting quality, respectively. RESULTS: Twenty-eight studies with 30 comparisons (3 studies included 2 SIT groups) were included in our meta-analysis (n = 360 SIT participants: body mass index (BMI) = 25.9 ± 3.7 kg/m2, baseline VO2max = 37.9 ± 8.0 mL/kg/min; n = 359 MICT participants: BMI = 25.5 ± 3.8 kg/m2, baseline VO2max = 38.3 ± 8.0 mL/kg/min; all mean ± SD). All studies had an unclear risk of bias and poor reporting quality. CONCLUSION: Although we observed a lack of superiority between SIT and MICT for improving VO2max (weighted Hedge's g = -0.004, 95% confidence interval (95%CI): -0.08 to 0.07), the overall unclear risk of bias calls the validity of this conclusion into question. Future studies using robust study designs are needed to interrogate the possibility that SIT and MICT result in similar changes in VO2max.

Interindividual Differences in Trainability and Moderators of Cardiorespiratory Fitness, Waist Circumference, and Body Mass Responses: A Large-Scale Individual Participant Data Meta-analysis.

Although many studies have assumed variability reflects variance caused by exercise training, few studies have examined whether interindividual differences in trainability are present following exercise training. The present individual participant data (IPD) meta-analysis sought to: (1) investigate the presence of interindividual differences in trainability for cardiorespiratory fitness (CRF), waist circumference, and body mass; and (2) examine the influence of exercise training and potential moderators on the probability that an individual will experience clinically important differences. The IPD meta-analysis combined data from 1879 participants from eight previously published randomized controlled trials. We implemented a Bayesian framework to: (1) test the hypothesis of interindividual differences in trainability by comparing variability in change scores between exercise and control using Bayes factors; and (2) compare posterior predictions of control and exercise across a range of moderators (baseline body mass index (BMI) and exercise duration, intensity, amount, mode, and adherence) to estimate the proportions of participants expected to exceed minimum clinically important differences (MCIDs) for all three outcomes. Bayes factors demonstrated a lack of evidence supporting a high degree of variance attributable to interindividual differences in trainability across all three outcomes. These findings indicate that interindividual variability in observed changes are likely due to measurement error and external behavioural factors, not interindividual differences in trainability. Additionally, we found that a larger proportion of exercise participants were expected to exceed MCIDs compared with controls for all three outcomes. Moderator analyses identified that larger proportions were associated with a range of factors consistent with standard exercise theory and were driven by mean changes. Practitioners should prescribe exercise interventions known to elicit large mean changes to increase the probability that individuals will experience beneficial changes in CRF, waist circumference and body mass.

A Systematic Review Examining the Approaches Used to Estimate Interindividual Differences in Trainability and Classify Individual Responses to Exercise Training.

Background: Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as "responders" or "non-responders." The extent to which studies in the exercise training literature have adopted these statistical approaches remains unclear. Objectives: This systematic review primarily sought to determine the extent to which studies in the exercise training literature have adopted sound statistical approaches for examining individual responses to exercise training. We also (1) investigated the existence of interindividual differences in trainability, and (2) tested the hypothesis that less conservative thresholds inflate response rates compared with thresholds that consider error and a smallest worthwhile change (SWC)/minimum clinically important difference (MCID). Methods: We searched six databases: AMED, CINAHL, EMBASE, Medline, PubMed, and SportDiscus. Our search spanned the aerobic, resistance, and clinical or rehabilitation training literature. Studies were included if they used human participants, employed standardized and supervised exercise training, and either: (1) stated that their exercise training intervention resulted in heterogenous responses, (2) statistically estimated interindividual differences in trainability, and/or (3) classified individual responses. We calculated effect sizes (ESIR) to examine the presence of interindividual differences in trainability. We also compared response rates (n = 614) across classification approaches that considered neither, one of, or both errors and an SWC or MCID. We then sorted response rates from studies that also reported mean changes and response thresholds (n = 435 response rates) into four quartiles to confirm our ancillary hypothesis that larger mean changes produce larger response rates. Results: Our search revealed 3,404 studies, and 149 were included in our systematic review. Few studies (n = 9) statistically estimated interindividual differences in trainability. The results from these few studies present a mixture of evidence for the presence of interindividual differences in trainability because several ESIR values lay above, below, or crossed zero. Zero-based thresholds and larger mean changes significantly (both p < 0.01) inflated response rates. Conclusion: Our findings provide evidence demonstrating why future studies should statistically estimate interindividual differences in trainability and consider error and an SWC or MCID when classifying individual responses to exercise training. Systematic Review Registration: [website], identifier [registration number].

Repeatability of training-induced skeletal muscle adaptations in active young males.

OBJECTIVES: Measurements of protein content, enzymatic activity, and/or capillarization are frequently utilized as markers of skeletal muscle adaptation following exercise training. Whether changes in these markers of muscle adaptation are repeatable when individuals are repeatedly exposed to the same training stimulus is unknown. The purpose of this study was to test the repeatability of skeletal muscle adaptations to two identical training periods. METHODS: Ten active young males (age: 22 ±â€¯2 years; VO2max: 57 ±â€¯7 ml/kg/min) were exposed to two identical four-week periods of supervised high-intensity interval running (4 × 4 min at 90-95% of HRmax interspersed with 3-min at 70-75% HRmax) separated by a 3-month wash-out period. Vastus lateralis biopsies were obtained before and after each training period for the measurement of protein content, enzyme activity, and capillary density. RESULTS: Training-induced changes in citrate synthase (CS) maximal activity, protein content (PGC-1α, OXPHOS, and LDH-A), and capillary density were not repeatable within individuals (r = -0.52-0.15; ICCs: -0.42-0.04; CVs: 11-67%). Several OXPHOS complex subunits also demonstrated dissimilar group-level adaptations (period × time interaction effects, p < 0.05) with large differences (ηp2 > 0.4) between training periods. A large (ηp2 = 0.65) increase in capillary density was apparent irrespective of training period (main effect of time, p = 0.05). CONCLUSIONS: An individual (or a group of individuals) may exhibit dissimilar skeletal muscle adaptations when re-exposed to the same training stimulus. Our findings challenge the utility of classifying of individuals as high/low responders using measurements of mitochondrial protein content, CS activity and/or capillary density following a single training period.

Exploring Differences in Cardiorespiratory Fitness Response Rates Across Varying Doses of Exercise Training: A Retrospective Analysis of Eight Randomized Controlled Trials.

OBJECTIVE: This study tested the hypothesis that greater mean changes in cardiorespiratory fitness (CRF), in either the absence or presence of reduced interindividual variability, explain larger CRF response rates following higher doses of exercise training. METHODS: We retrospectively analyzed CRF data from eight randomized controlled trials (RCT; n = 1590 participants) that compared at least two doses of exercise training. CRF response rates were calculated as the proportion of participants with individual confidence intervals (CIs) placed around their observed response that lay above 0.5 metabolic equivalents (MET). CIs were calculated using no-exercise control group-derived typical errors and were placed around each individual's observed CRF response (post minus pre-training CRF). CRF response rates, mean changes, and interindividual variability were compared across exercise groups within each RCT. RESULTS: Compared with lower doses, higher doses of exercise training yielded larger CRF response rates in eight comparisons. For most of these comparisons (7/8), the higher dose of exercise training had a larger mean change in CRF but similar interindividual variability. Exercise groups with similar CRF response rates also had similar mean changes. CONCLUSION: Our findings demonstrate that larger CRF response rates following higher doses of exercise training are attributable to larger mean changes rather than reduced interindividual variability. Following a given dose of exercise training, the proportion of individuals expected to improve their CRF beyond 0.5 METs is unrelated to the heterogeneity of individual responses.

Investigating the reproducibility of maximal oxygen uptake responses to high-intensity interval training.

OBJECTIVES: To test the hypothesis that observed maximal oxygen uptake (VO2max) and time to fatigue (TTF) responses to two identical periods of standardized high-intensity interval training are reproducible. DESIGN: Fourteen recreationally active and healthy young males completed two identical four-week periods of high-intensity interval training (4×4-min intervals at 90-95% maximum heart rate [HRmax] separated by 3-min periods of active recovery at 70-75% HRmax). Training periods were separated by a three-month washout period. METHODS: VO2max and TTF were assessed via incremental tests with supramaximal verification before and after each training period. Pearson correlation coefficients (r), intraclass correlation coefficients (ICC), and within-subjects coefficients of variation (CV) were used to assess reproducibility of observed VO2max and TTF responses. RESULTS: VO2max and TTF values before the second training period were not significantly higher than baseline values and there were no significant (p>0.05) interaction effects (period 1: VO2max: +4.04±2.29mL/kg/min, TTF: +70.75±35.87s; period 2: VO2max: +2.83±2.74mL/kg/min, TTF: +83.46±34.55s). We found very weak-to-moderate correlations and poor reproducibility for observed VO2max (mL/kg/min: r=0.40, ICC=0.369, CV=74.4) and TTF (r=0.11. ICC=0.048, CV=45.6) responses to training periods 1 and 2. CONCLUSIONS: Our ANOVA results confirmed that the three-month washout period returned VO2max and TTF levels to baseline and prevented carryover effects. Contrary to our hypothesis, our results suggest that individual observed VO2max and TTF responses to identical training stimuli are not reproducible.