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Over the last decades the cellular immune inflammation markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII = NLR × platelets) have emerged in clinical context as markers of disease-related inflammation and are now widely appreciated due to their integrative character. Transferring these clinically established inflammation markers into exercise physiology seems highly beneficial, especially due to the low temporal, financial and infrastructural resources needed for assessment and calculation. Therefore, the aim of this review is to summarize evidence on the value of the integrative inflammation markers NLR, PLR and SII for depiction of exercise-induced inflammation and highlight potential applications in exercise settings. Despite sparse evidence, multiple investigations revealed responsiveness of the markers to acute and chronic exercise, thereby opening promising avenues in the field of exercise physiology. In performance settings, they might help to infer information for exercise programming by reflecting exercise strain and recovery status or periods of overtraining and increased infection risk. In health settings, application involves the depiction of anti-inflammatory effects of chronic exercise in patients exhibiting chronic inflammation. Further research should, therefore, focus on establishing reference values for these integrative markers in athletes at rest, assess the kinetics and reliability in response to different exercise modalities and implement the markers into clinical exercise trials to depict anti-inflammatory effects of chronic exercise in different patient collectives.

Stressful training with insufficient recovery can impair muscle performance. Expression of mitogen-activated protein kinases (MAPK) has been reported at rest following overreaching and overtraining. The acute myocellular exercise response to stressful training with insufficient recovery has not been investigated. We investigated MAPK, androgen, and glucocorticoid receptor phosphorylation following a period of stressful training. Sixteen resistance-trained men were matched on barbell squat 1 repetition maximum strength and randomized into a group that performed normal training or stressful training with insufficient recovery. The control group (CON) performed three speed-squat training sessions on non-consecutive days, while the stressful training group (NFOR) performed 15 training sessions over 7.5 days. Resting and post-exercise skeletal muscle biopsies were obtained prior to (T1) and after the training period (T2). Samples were analyzed for total and phosphorylated androgen receptor (AR), glucocorticoid receptor (GR), and MAPKs (ERK, JNK, and p38). Total AR were down-regulated post-exercise at T2 in NFOR only. Phospho-AR at ser515 increased in both groups post-exercise at T1; however, ser515 only increased at T2 in NFOR. Phosphorylated ERK, JNK, and p38 increased post-exercise in CON and NFOR at T1 and T2. Post-exercise phospho-p38 was blunted in NFOR at T2 compared to T1. After the training intervention, resting phospho-p38 was higher in NFOR compared to T1. At T2, post-exercise phospho-GR at ser226 was lower compared to T1, and resting levels increased in NFOR. Steroid receptors are phosphorylated after acute resistance exercise, and in addition to MAPKs, are differentially regulated after stressful training with insufficient recovery.

Overtraining syndrome (OTS) is reported in endurance sports. Thyroid hormones (TH) regulate metabolism, mood, and energy production, and may play a role in OTS of endurance athletes. The purpose of this study was to investigate relationships in TH and symptoms of OTS in track and field endurance runners (ER). Sixteen female track and field middle distance (MD; n = 9; age: 20.2 ± 1.5 years; ht: 167.86 ± 5.04 cm; body-mass: 57.97 ± 5.05 kg; VO2MAX: 53.62 ± 6.04 ml/kg/min) and long distance (LD; n = 7; age: 20.5 ± 1.5 years; ht: 162.48 ± 6.11 cm; body-mass: 56.15 ± 5.99 kg; VO2MAX: 61.94 ± 3.29 ml/kg/min) ER participated in this descriptive study (15-weeks). Thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4), were collected at pre-(PRE) and post-season (POST). A fatigue scale was administered weekly, and percent change (PΔ) in race time (season best vs. championship performance) was calculated. Wilcoxon-sign ranked tests and Spearman’s rho correlations were used to determine changes and relationships between TH and performance. TSH, T 3 and T 4 did not change from PRE to POST. The percent change (PΔ) in T 3 from PRE to POST was correlated with running performance at the end of the season (ρ = − 0.70, p = 0.036). Fatigue at week 12 correlated with running performance at the end of the season (ρ = − 0.74, p = 0.004). TH may be valuable in assessing the overall training state of ER. TH concentrations change too slowly to be a frequent marker of monitoring OTS, but are related to markers of decreased performance. Monitoring dietary intake, and fatigue may be predictive markers to assess OTS and training status of female ER.

This study aimed to quantify the relationship between venous and capillary blood sampling methods for the measurement of plasma interleukin-6 (IL-6). A parallel study was conducted to determine the possibility of measuring IL-6 in sweat using an enzyme-linked immunosorbent assay (ELISA) and investigate the relationship between plasma- and sweat-derived measures of IL-6.Twelve male participants were recruited for the measurement of IL-6 at rest and during exercise (study 1). An additional group of five female participants was recruited for the measurement of IL-6 in venous blood versus sweat at rest and following exercise (study 2). In study 1, venous and capillary blood samples were collected at rest and in response to exercise. In study 2, venous and sweat samples were collected following exercise.Mean plasma IL-6 concentration was not different between venous and capillary blood sampling methods either at rest (4.27 ± 5.40 vs. 4.14 ± 4.45 pg ml(-1)), during (5.40 ± 5.17 vs. 5.58 ± 6.34 pg ml(-1)), or in response to exercise (6.95 ± 6.37 vs. 6.99 ± 6.74 pg ml(-1)). There was no IL-6 detectable in sweat either at rest or following exercise.There are no differences in the measurement of plasma IL-6 using either venous or capillary blood sampling methods. Capillary measurement represents a minimally invasive way of measuring IL-6 and detecting changes in IL-6, which are linked to fatigue and overtraining.

Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. The results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

In classic concentric/eccentric exercise, the same absolute load is applied in concentric and eccentric actions, which infers a smaller relative eccentric load. We compared the effects of 6 weeks of classic concentric/eccentric quadriceps strength training (CON/ECC, 11 subjects) to eccentric overload training (CON/ECC+, 14 subjects) in athletes accustomed to regular strength training. The parameters determined included functional tests, quadriceps and fibre cross-sectional area (CSA), fibre type distribution by ATPase staining, localisation of myosin heavy chain (MHC) isoform mRNAs by situ hybridization and the steady-state levels of 48 marker mRNAs (RT-PCR) in vastus lateralis biopsies taken before and after training. Both training forms had anabolic effects with significant increases in quadriceps CSA, maximal strength, ribosomal RNA content and the levels of mRNAs involved in growth and regeneration. Only the CON/ECC+ training led to significantly increased height in a squat jump test. This was accompanied by significant increases in IIX fibre CSA, in the percentage of type IIA fibres expressing MHC IIx mRNA, in the level of mRNAs preferentially expressed in fast, glycolytic fibres, and in post-exercise capillary lactate. The enhanced eccentric load apparently led to a subtly faster gene expression pattern and induced a shift towards a faster muscle phenotype plus associated adaptations that make a muscle better suited for fast, explosive movements.

The aim of this study was to identify indicators of non-functional overreaching (NFOR) in team sport athletes undertaking intensive training loads. Eighteen semi-professional rugby league players were randomly assigned into two pair matched groups. One group completed 6 weeks of normal training (NT) whilst the other group was deliberately overreached through intensified training (IT). Both groups then completed the same 7-day stepwise training load reduction taper. Multistage fitness test (MSFT) performance, $$ \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{{2\max }} $$ , peak aerobic running velocity (V max), maximal heart rate, vertical jump, 10-s cycle sprint performance and body mass were measured pre- and post-training period and following the taper. Hormonal, haematological and immunological parameters were also measured pre-training and following weeks 2, 4 and 6 of training and post-taper. MANOVA for repeated measures with contrast analysis indicated that MSFT performance and $$ \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{{2\max }} $$ were significantly reduced in the IT group over time and condition, indicating that a state of overreaching was attained. However, the only biochemical measure that was significantly different between the IT and NT group was the glutamine to glutamate (Gln/Glu) ratio even though testosterone, testosterone to cortisol (T/C) ratio, plasma glutamate, and CK activity were significantly changed after training in both groups. Positive endurance and power performance changes were observed post-taper in the IT group confirming NFOR. These changes were associated with increases in the T/C ratio and the Gln/Glu ratio and decreases in plasma glutamate and CK activity. These results indicate that although there was no single reliable biochemical marker of NFOR in these athletes, the Gln/Glu ratio and MSFT test may be useful measures for monitoring responses to IT in team sport athletes.

Many physiological maladaptations persist after overreaching and overtraining resistance exercise (RE). However, no studies have investigated changes in mitogen-activated protein kinases (MAPK) after overtraining in humans, despite their critical role regulating exercise-induced muscular adaptations. The purpose of this study was to describe the changes in total and resting phosphorylation status of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38-MAPK following a period of RE overreaching or overtraining. Following 2–4 weeks of normal training (low volume/low intensity), two groups of males performed either a high-power overreaching protocol (HPOR n = 6, mean ± SD, age 23 ± 3.4 years, mass 86.5 ± 17.7 kg, height 1.77 ± 0.06 m) or high-intensity overtraining protocol (HIOT n = 8, age 19.8 ± 1.8 years, mass 76.8 ± 6.7 kg, height 1.8 ± 0.06 m). Resting muscle biopsies were obtained at baseline (BL; end of normal training period) and 24 h after the final session of stressful training (i.e., HPOR or HIOT programs). Total MAPK and ratio of phosphorylated/total (p-MAPK)- ERK1/2, JNK, and p38-MAPK were analyzed via western blotting. 2 × 2 (group × time) ANOVA determined differences in MAPK between BL and post-training protocols. Compared to BL, total-ERK increased after HPOR, but decreased after HIOT (p ≤ 0.05). p-ERK1/2/total-ERK increased after HIOT (p ≤ 0.05). The ratio of p-JNK/total-JNK and p-ERK1/2/total-ERK decreased after HPOR (p ≤ 0.05); however, this result was primarily due to increased total MAPK content. p-p38-MAPK decreased after HPOR (p ≤ 0.05). Total and p-MAPK are differentially expressed after HPOR and HIOT RE. These changes are likely involved in the maladaptation reported in overreaching and overtraining exercise. This is the first study describing altered MAPK in RE overtrained and overreached humans.

To determine the effects of creatine supplementation during short-term resistance training overreaching on performance, body composition, and resting hormone concentrations, 17 men were randomly assigned to supplement with 0.3 g/kg per day of creatine monohydrate (CrM: n=9) or placebo (P: n=8) while performing resistance exercise (5 days/week for 4 weeks) followed by a 2-week taper phase. Maximal squat and bench press and explosive power in the bench press were reduced during the initial weeks of training in P but not CrM. Explosive power in the bench press, body mass, and lean body mass (LBM) in the legs were augmented to a greater extent in CrM ( P

This study investigated the impact of intensified training (IT) and carbohydrate (CHO) supplementation on resting and exercise-induced oxidative stress. Male cyclists (n = 13, mean ± SD: age 25 ± 6 years; $$\dot{V}{\text{O}}_{2\hbox{max} }$$ 72 ± 5 ml/kg/min) undertook two 9 day periods of endurance-based IT. In a counter-balanced, crossover and double-blinded study design, participants completed IT whilst ingesting high (H-CHO) or moderate (M-CHO) CHO beverages before (H-CHO: 24 g vs. M-CHO: 2 g), during (H-CHO: 60 g/h vs. M-CHO: 20 g/h) and after training sessions (H-CHO: 44 g vs. M-CHO: 10 g). Participants completed fasted performance trials without CHO on days 2, 6 and 10. Blood samples were taken before and immediately after exercise to assess plasma oxidative stress. Resting thiol (-SH) and catalase (CAT) activities decreased following 6 days of IT, independent of CHO condition [-SH (μM oxidised NADPH): H-CHO—14.0 ± 18.8, M-CHO—20.4 ± 20.3 and CAT (nmol/min/ml): H-CHO 12.5 ± 12.5, M-CHO 6.0 ± 4.5; all p

Mood, as measured by the profile of mood states questionnaire (POMS), salivary cortisol (F) and testosterone (T) levels, and performance were examined in 17 male soccer players 4 times during a season. Soccer players provided three saliva samples when getting up (resting values, 8 a.m.), before breakfast (11.30 a.m.), and between 4.00 p.m. and 6.00 p.m. The initial measures were performed 1 day following the start of season training (T1). They were then performed before and after a high-intensity training programme (T2 and T3, respectively) and 16 weeks after T3 (T4). Iceberg profiles of POMS were observed during T1, T2 and T3, which coincided with successful performance. Subsequent decreased performance between T3 and T4 coincided with a decrease in vigor and an increase in tension and depression. Indeed, when the normal nycthemeral rhythm for F was observed (i.e. a decrease from morning until evening at all times; T1-T4), there was seemingly a non-statistical elevation of F on the morning of T3, which only became statistically significant at 11.30 a.m. on T3. In spite of a post-high-intensity training programme (T3) increase in catabolism, the soccer players presented iceberg profiles together with a high percentage of winning. Our results could suggest that in team soccer, a decreased T:F ratio does not automatically lead to a decrease in team performance or a state of team overtraining. It appears that combined psychological and physiological changes during high-intensity training are primarily of interest when monitoring training stress in relation to performance.

Many physiological markers vary similarly during training and overtraining. This is the case for the blood lactate concentration ([La-]b), since a right shift of the lactate curve is to be expected in both conditions. We examined the possibility of separating the changes in training from those of overtraining by dividing [La-]b by the rating of perceived exertion ([La-]b/RPE) or by converting [La-]b into a percentage of the peak blood lactate concentration ([La-]b,peak). Ten experienced endurance athletes increased their usual amount of training by 100% within 4 weeks. An incremental test and a time trial were performed before (baseline) and after this period of overtraining, and after 2 weeks of recovery (REC). The [La-]b and RPE were measured during the recovery of each stage of the incremental test. We diagnosed overtraining in seven athletes, using both physiological and psychological criteria. We found a decrease in mean [La-]b,peak from baseline to REC [9.64 (SD 1.17), 8.16 (SD 1.31) and 7.69 (SD 1.84) mmol.l-1, for the three tests, respectively; P < 0.05] and a right shift of the lactate curve. Above 90% of maximal aerobic speed (MAS) there was a decrease of mean [La-]b/RPE from baseline to REC [at 100% of MAS of 105.41 (SD 17.48), 84.61 (SD 12.56) and 81.03 (SD 22.64) arbitrary units, in the three tests, respectively; P < 0.05), but no difference in RPE, its variability accounting for less than 25% of the variability of [La-]b/RPE (r = 0.49). Consequently, [La-]b/RPE provides little additional information compared to [La-]b alone. Expressing [La-]b as a %[La-]b,peak resulted in a suppression of the right shift of the lactate curve, suggesting it was primarily the consequence of a decreased production of lactate by the muscle. Since the right shift of the curve induced by optimal training is a result of improved lactate utilization, the main difference between the two conditions is the decrease of [La-]b,peak during overtraining. We propose retaining it as a marker of overtraining for long duration events, and repeating its measurement after a sufficient period of rest to make the distinction with overreaching.

The purpose of the study was to characterize the changes in purine metabolism in long-distance runners in the main phases of their 1-year training cycle. Nine male athletes competing in distances 5 and 10 km at national/regional level, mean age 22.9 +/- 0.6 years, practising sport for 8.6 +/- 0.3 years, participated in the study. The changes in plasma concentrations of hypoxanthine (Hx), xanthine (X) and uric acid (UA) and the activity of the enzyme HGPRT in red blood cells haemolysate were followed in four characteristic points of the annual training cycle: preparatory phase (specific subphase), competition period, transition period and preparatory phase (intermediate subphase). Resting and postexercise plasma concentrations of X and, Hx and HGPRT activity changed significantly during 1-year training cycle. Significant changes in postexercise Hx values between training phases were found, from 9.3 micromol l(-1) in competition period to 22.9 micromol l(-1) in transition period (Friedmann's ANOVA, P0.01). Postexercise UA values ranged from 371 to 399 micromol l(-1) and did not change significantly between training phases. An increase in resting (from 52.0 to 58.4 IMP mg(-1) Hb min(-1), P0.05) and postexercise (from 70.7 to 76.2 IMP mg(-1) Hb min(-1), not significant) HGPRT activity between the specific preparation and competition period was observed. In the transition period, Hx postexercise concentration increased (22.9 micromol l(-1), P0.01) and HGPRT postexercise activity decreased (58.8 IMP mg(-1) Hb min(-1), P0.01) significantly. The results indicate that the level of plasma Hx at rest and after standard exercise may be a useful tool for monitoring the adaptation of energetic processes in different training phases and support the overload/overtraining diagnosis.

Fifteen healthy men performed a 5-week training program comprising four sets of seven unilateral, coupled concentric-eccentric knee extensions 2-3 times weekly. While eight men were assigned to training using a weight stack (WS) machine, seven men trained using a flywheel (FW) device, which inherently provides variable resistance and allows for eccentric overload. The design of these apparatuses ensured similar knee extensor muscle use and range of motion. Before and after training, maximal isometric force (MVC) was measured in tasks non-specific to the training modes. Volume of all individual quadriceps muscles was determined by magnetic resonance imaging. Performance across the 12 exercise sessions was measured using the inherent features of the devices. Whereas MVC increased (P < 0.05) at all angles measured in FW, such a change was less consistent in WS. There was a marked increase (P < 0.05) in task-specific performance (i.e., load lifted) in WS. Average work showed a non-significant 8.7% increase in FW. Quadriceps muscle volume increased (P < 0.025) in both groups after training. Although the more than twofold greater hypertrophy evident in FW (6.2%) was not statistically greater than that shown in WS (3.0%), all four individual quadriceps muscles of FW showed increased (P < 0.025) volume whereas in WS only m. rectus femoris was increased (P < 0.025). Collectively the results of this study suggest more robust muscular adaptations following flywheel than weight stack resistance exercise supporting the idea that eccentric overload offers a potent stimuli essential to optimize the benefits of resistance exercise.

This study was designed to investigate physical education (PE) students the link between mood disturbances, caused by psychological or physical stressors associated with studying, and the autonomic nervous system modifications. PE students completed the profile of mood state (POMS) questionnaire at the end of the university year. Heart rate variability (HRV) was then measured during a head-up tilt test (HUT) in those with the highest and lowest total mood disturbance (TMD) scores on three successive POMS. Among the 218 students who completed the POMS (85 female and 137 male), 65 had high TMD scores, suggesting mood disturbances and fatigue. The final sample included 12 subjects in the potentially overtrained (POT) group and 16 subjects in the control (CTL) group. A greater decrease of two indices of the autonomic system (SD1 and RMSSD) was observed during the HUT in the POT than in the CTL group (P < 0.05). The depression (Dep) and vigor (Vig) subscales of POMS were correlated with several HRV indices. More specifically, in the POT group, the Vig score was correlated with autonomous activity in the supine position, and the Dep score with percentages of change of sympatho-vagal activity during the HUT. This suggests that (1) POT students could present a weaker autonomic response to HUT, (2) Dep and Vig subscales of the POMS questionnaire may indicate autonomic dysregulations.

Exercise training is associated with peripheral-cellular and central-cerebral processes, hormonal-neuronal regulation and transmission mechanisms. During the acute training response, peripheral cellular mechanisms are mainly metabolostatic to achieve energy supply and involve associated cytokine and hormonal reactions. Glycogen deficiency is associated with increased expression of local cytokines (interleukin-6, IL-6), decreased expression of glucose transporters, increased cortisol and decreased insulin secretion and beta-adrenergic stimulation. A nutrient-sensing signal of adipose tissue may be represented by leptin which, as for insulin, IL-6 and insulin-like growth-factor I (IGF-I), has profound effects on the hypothalamus and is involved in the metabolic hormonal regulation of exercise and training. Muscle damage and repair processes may involve the expression of inflammatory cytokines (e.g. tumour necrosis factor-alpha, TNF-alpha) and of stress proteins (e.g. heat shock protein 72). During overreaching and overtraining, a myopathy-like state is observed in skeletal muscle with depressed turnover of contractile proteins (e.g. in fast-type glycolytic fibres with a concomitant increase in slow type myosins). These alterations are influenced by exercise-induced hypercortisolism, and by decreased somatotropic hormones (e.g. IGF-I). The hypothalamus integrates various error signals (metabolic, hormonal, sensory afferents and central stimuli) and therefore pituitary releasing hormones represent the functional status of an athlete and long-term hypothalamic hormonal and sympathoadrenal downregulation are some of the prominent hormonal signs of prolonged overtraining and performance incompetence syndrome.

To examine neuromuscular and hormone changes during 2 weeks of heavy strength training, 18 weight-trained male students were recruited either into a heavy training group (HT, n = 11) or into a control group (Ctr, n = 7). The heavy training protocol consisted of leg-extensor workouts performed daily, while workouts were performed twice a week in the Ctr group. A test of one repetition maximum (1 RM) was performed before heavy training and on the 2nd day after heavy training. Isokinetic knee extensions, electrical stimulation, and squat jumps were performed before, on the 8th day of heavy training, and on the 4th day after heavy training. Morning blood samples (0800 hours) were drawn before, on the 8th day of heavy training, and on the 4th day after heavy training. Before, and on the 5th day after heavy training, 24 h urine samples were collected. The 1 RM leg press increased by 6 (SEM 2)% in the HT group. Testosterone and insulin-like growth factor-1 concentrations were respectively 12 (SEM 5)% and 11 (SEM 3)% lower than baseline on the 8th day of heavy training; however, hormone levels were back to baseline on the 4th day after heavy training. A significant correlation between individual changes in 1 RM leg press and changes in testosterone concentrations was observed in the HT group (r = 0.69). In the HT group, 24 h urinary catecholamine excretion increased by 26 (SEM 12)%, 3-methylhistidine excretion increased by 21 (SEM 6)% and creatinine excretion increased by 11 (SEM 5)%. There were no significant changes in the Ctr group. This work addresses the role of changes in basal hormone status (morning samples) for skeletal muscle adaptation to heavy strength training.