The Effect of Duration on Performance and Perceived Fatigability During Acute High-Intensity Interval Exercise in Young, Healthy Males and Females.

Few studies have explored the kinetics of performance and perceived fatigability during high-intensity interval training, despite its popularity. We aimed to characterize the kinetics of fatigability and recovery during an 8 × 4-min HIIT protocol, hypothesizing that most muscle function impairment would occur during the initial four intervals. Fifteen healthy males and females (mean ± standard deviation; age = 26 ± 5 years, V̇O2max = 46.8 ± 6.1 mL·kg-1·min-1) completed eight, 4-min intervals at 105% of critical power with 3 min of rest. Maximal voluntary knee extension contractions (MVCs) coupled with electrical nerve stimulation were performed at baseline and after the first, fourth, and eighth intervals. MVC, potentiated twitch force (Pt), and Db10:100 ratio all declined throughout HIIT (p < 0.05). MVC sharply declined after interval 1 (-15 ± 9% relative to baseline; p < 0.05) and had only further declined after interval 8 (-26 ± 11%; p < 0.05), but not interval 4 (-19 ± 13%; p > 0.05). Pt and Db10:100 also sharply declined after interval 1 (Pt: -18 ± 13%, Db10:100: -14 ± 20%; p < 0.05) and further declined after interval 4 (Pt: -35 ± 19%, Db10:100: -30 ± 20%; p < 0.05) but not interval 8 (Pt: -41 ± 19%; Db10:100: -32 ± 18%; p > 0.05). Voluntary activation did not significantly change across the HIIT protocol (p > 0.05). Evoked force recovery was significantly blunted as more intervals were completed: after interval 1, Pt recovered by 7 ± 11% compared to -6 ± 7% recovery after interval 8 (p < 0.05). Ratings of perceived effort, fatigue, and leg pain rose throughout the session (p < 0.05 for each) and were greater (effort and fatigue) for females (p < 0.05). Otherwise, males and females exhibited similar performance fatigability kinetics, with contractile function declines blunted in response to additional intervals.

Acute neuromuscular, cardiovascular, and muscle oxygenation responses to low-intensity aerobic interval exercises with blood flow restriction.

We investigated the influence of short- and long-interval cycling exercise with blood flow restriction (BFR) on neuromuscular fatigue, shear stress and muscle oxygenation, potent stimuli to BFR-training adaptations. During separate sessions, eight individuals performed short- (24 × 60 s/30 s; SI) or long-interval (12 × 120 s/60 s; LI) trials on a cycle ergometer, matched for total work. One leg exercised with (BFR-leg) and the other without (CTRL-leg) BFR. Quadriceps fatigue was quantified using pre- to post-interval changes in maximal voluntary contraction (MVC), potentiated twitch force (QT) and voluntary activation (VA). Shear rate was measured by Doppler ultrasound at cuff release post-intervals. Vastus lateralis tissue oxygenation was measured by near-infrared spectroscopy during exercise. Following the initial interval, significant (P < 0.05) declines in MVC and QT were found in both SI and LI, which were more pronounced in the BFR-leg, and accounted for approximately two-thirds of the total reduction at exercise termination. In the BFR-leg, reductions in MVC (-28 ± 15%), QT (-42 ± 17%), and VA (-15 ± 17%) were maximal at exercise termination and persisted up to 8 min post-exercise. Exercise-induced muscle deoxygenation was greater (P < 0.001) in the BFR-leg than CTRL-leg and perceived pain was more in LI than SI (P < 0.014). Cuff release triggered a significant (P < 0.001) shear rate increase which was consistent across trials. Exercise-induced neuromuscular fatigue in the BFR-leg exceeded that in the CTRL-leg and was predominantly of peripheral origin. BFR also resulted in diminished muscle oxygenation and elevated shear stress. Finally, short-interval trials resulted in comparable neuromuscular and haemodynamic responses with reduced perceived pain compared to long-intervals.

Visual light flicker stimulation: enhancing alertness in sleep-deprived rats.

Introduction: In the evolving field of neurophysiological research, visual light flicker stimulation is recognized as a promising non-invasive intervention for cognitive enhancement, particularly in sleep-deprived conditions. Methods: This study explored the effects of specific flicker frequencies (40 Hz and 20-30 Hz random flicker) on alertness recovery in sleep-deprived rats. We employed a multidisciplinary approach that included behavioral assessments with the Y-maze, in vivo electrophysiological recordings, and molecular analyses such as c-FOS immunohistochemistry and hormone level measurements. Results: Both 40 Hz and 20-30 Hz flicker significantly enhanced behavioral performance in the Y-maze test, suggesting an improvement in alertness. Neurophysiological data indicated activation of neural circuits in key brain areas like the thalamus and hippocampus. Additionally, flicker exposure normalized cortisol and serotonin levels, essential for stress response and mood regulation. Notably, increased c-FOS expression in brain regions related to alertness and cognitive functions suggested heightened neural activity. Discussion: These findings underscore the potential of light flicker stimulation not only to mitigate the effects of sleep deprivation but also to enhance cognitive functions. The results pave the way for future translational research into light-based therapies in human subjects, with possible implications for occupational health and cognitive ergonomics.

Adenosine A2A and dopamine D2 receptor interaction controls fatigue resistance.

Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.

Replicating human characteristics: A promising animal model of central fatigue.

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

Effects of caffeine supplementation on anaerobic power and muscle activity in youth athletes.

This study aimed to investigate the effects of caffeine ingestion on anaerobic performance and muscle activity in young athletes. In this randomized, double-blind, and placebo-controlled study, ten highly trained male post-puberal futsal players aged 15.9 ± 1.2 years conducted two laboratory sessions. Athletes performed the Wingate test 60 min after ingestion of caffeine (CAF, 6 mg/kg body mass) or placebo (PL, dextrose) (blinded administration). Peak power, mean power, and the fatigue index were assessed. During the performance of the Wingate test, electromyographic (EMG) data were recorded from selected lower limbs muscles to determine the root mean square (RMS), mean power frequency (MPF), and median power frequency (MDPF) as frequency domain parameters and wavelet (WT) as time-frequency domain parameters. Caffeine ingestion increased peak (0.80 ± 0.29 W/Kg; p = 0.01; d = 0.42) and mean power (0.39 ± 0.02 W/Kg; p = 0.01; d = 0.26) but did not significantly affect the fatigue index (52.51 ± 9.48%, PL: 49.27 ± 10.39%; p = 0.34). EMG data showed that the MPF and MDPF parameters decreased and the WT increased, but caffeine did not have a significant effect on these changes (p > 0.05). Moreover, caffeine ingestion did not significantly affect RMS changes in the selected muscles (p > 0.05). Here we showed that acute caffeine ingestion improved anaerobic performance without affecting EMG parameters in young male futsal athletes.

Females show less decline in contractile function than males after repeated all-out cycling.

Females demonstrate greater fatigue resistance during a range of exercise modalities; however, this may be confounded by the lower mechanical work completed. Accordingly, this study examined the sex-specific peripheral and central fatigue mechanisms during repeated all-out cycling and whether they are affected by total mechanical work performed. A total of 26 healthy young adults (12 females) performed 10 × 10 s all-out cycling interspersed by 30 s passive recovery. Metabolic responses, peripheral and central fatigue, were quantified via changes in pre- to post-exercise blood lactate, potentiated quadriceps twitch force (and contractile properties) evoked via supramaximal electrical stimulation of the femoral nerve, and voluntary activation of the knee extensors, respectively. During exercise, mechanical work, vastus lateralis muscle activation (via surface electromyography), and deoxygenation (via near-infrared spectroscopy) were recorded. Sex comparison analyses were performed before and after statistically controlling for total mechanical work (via ANCOVA). Mechanical work and muscle activation plateaued at similar sprint repetition (sprint 5) and voluntary activation change (pre vs. post) was similar between the sexes. Females, however, showed lower %work decrement (i.e., fatigability; P = 0.037) and peripheral responses as evident by lower reductions in quadriceps twitch force (P < 0.001) and muscle deoxygenation (P = 0.001). Adjusting for total mechanical work did not change these sex comparison results. We show that females' greater fatigue resistance during repeated all-out cycling may not be attributed to the greater total mechanical work performed but could be mediated by lower peripheral fatigue in the knee extensor muscles.

Effects of hemp supplementation during resistance training in trained young adults.

PURPOSE: Hemp contains protein with high concentrations of the branched-chain amino acids leucine, isoleucine, and valine and oils that have anti-inflammatory properties. Our purpose was to investigate the effects of hemp supplementation during resistance training in trained young adults. METHODS: Males (n = 22, 29 ± 8y) and females (n = 12, 30 ± 9y) were randomized (double-blind) to receive 60 g/d of hemp (containing 40 g protein and 9 g oil) or 60 g/d of soy (matched for protein and calories) during eight weeks of resistance training (~  4x/week). Before and after the intervention, participants were assessed for whole-body lean tissue and fat mass (dual-energy X-ray absorptiometry), regional muscle hypertrophy (ultrasound), strength (1-repetition maximum leg press, bench press, biceps curl), voluntary activation (interpolated twitch technique), resting twitch properties (single pulse; 0.5 ms) (before and after a fatigue test), markers of inflammation (Interleukin 6 and C-reactive protein), and bone resorption (urinary N-telopeptides). RESULTS: Hemp supplementation increased elbow flexor muscle thickness in females (2.6 ± 0.4-3.1 ± 0.5 cm, p = 0.012) while soy supplementation increased elbow flexor muscle thickness in males (3.7 ± 0.4-4.0 ± 0.5 cm, p < 0.01). Twitch torque and rate of torque development were preserved after a fatigue test in males consuming hemp compared to males on soy (p < 0.001). CONCLUSION: Overall, hemp provides some sex-specific beneficial effects on measures of muscle accretion and torque under fatiguing conditions in resistance trained young adults. CLINICALTRIALS: gov Identifier: NCT02529917, registered August 11, 2015.

Quadriceps fatigue during hypoxic and ischemic knee-extension exercise is similar in males and females.

Hypoxia is known to increase muscle fatigue via both central and peripheral mechanisms. Females are typically less fatigable than males during isometric fatiguing contractions due to greater peripheral blood flow. However, sex differences in fatigue are blunted during dynamic fatiguing tasks. Thus, this study determined the interactions of sex and hypoxia on knee extensor muscle contractile function during a dynamic, ischemic fatiguing contraction. Electrical stimulation was used to determine contractile properties of the knee extensor muscles in eight males and eight females before and after an ischemic, dynamic fatiguing task while inspiring room air or a hypoxic gas mixture (10% O2:90% N2). Fatigue (assessed as time-to-task failure) was ∼10% greater during the hypoxic condition (94.3 ± 33.4 s) compared with normoxic condition (107.0 ± 42.8 s, P = 0.041) and ∼40% greater for females than males (77.1 ± 18.8 vs. 124.2 ± 38.7, P < 0.001). Immediately after the dynamic fatiguing task, there were reductions in maximal voluntary contraction force (P = 0.034) and electrically evoked twitch force (P < 0.001), and these reductions did not differ based on sex or inspirate. Cerebral tissue oxygenation showed a significant interaction of time and inspirate (P = 0.003) whereby it increased during normoxia and remained unchanged in hypoxia. No sex-related differences in the changes of cerebral tissue oxygenation were observed (P = 0.528). These data suggest that acute hypoxia increases central fatigue during ischemic single-leg exercise resulting in earlier exercise termination, but the effect does not differ based on sex.NEW & NOTEWORTHY Hypoxia exacerbates fatigue via central mechanisms after ischemic single-leg exercise. The greater fatigue observed during ischemic dynamic fatiguing exercise with hypoxia inspirate did not differ between the sexes. Hypoxia-induced central limitations are present in acute ischemic exercise and do not appear different in males and females.

Psychomotor Performance after 30 h of Sleep Deprivation Combined with Exercise.

Sleep deprivation (SD) usually impairs psychomotor performance, but most experiments are usually focused on sedentary conditions. The purpose of this study was to evaluate the influence of 30 h of complete SD combined with prolonged, moderate exercise (SDE) on human psychomotor performance. Eleven endurance-trained men accustomed to overnight exertion were tested twice: in well-slept and non-fatigued conditions (Control) and immediately after 30 h of SDE. They performed a multiple-choice reaction time test (MCRT) at rest and during each workload of the graded exercise test to volitional exhaustion. At rest, the MCRT was shorter after SDE than in the Control (300 ± 13 ms vs. 339 ± 11 ms, respectively, p < 0.05). During graded exercise, there were no significant differences in MCRT between groups, but the fastest reaction was observed at lower workloads after SDE (158 ± 7 W vs. 187 ± 11 W in Control, p < 0.05). The total number of missed reactions tended to be higher after SDE (8.4 ± 0.7 vs. 6.3 ± 0.8 in Control, p = 0.06). In conclusion, SDE is different from SD alone; however, well-trained men, accustomed to overnight exertion can maintain psychomotor abilities independently of the extent of central fatigue. Exercise can be used to enhance psychomotor performance in sleep-deprived subjects in whom special caution is required in order to avoid overload.

Different ramp-incremental slopes elicit similar V̇o2max and fatigability profiles in females and males despite differences in peak power output.

The aim of this article is to investigate the effects of different ramp-incremental (RI) slopes on fatigability and its recovery in females and males. Ten females and 11 males performed RI tests with distinct slopes, in separated and randomized sessions, 15 (RI15), 30 (RI30), and 45 (RI45) W·min-1. Performance fatigability was assessed by femoral nerve electrical stimuli evoked during and after isometric maximal voluntary contraction (IMVC) of knee extensors at baseline and after task failure at min 0.5, 1.5, 2.5, 5, and 10. Maximal oxygen uptake (V̇o2max) and peak power output (POpeak) were also measured. There were significant and similar declines from pre- to post-RI test in RI15, RI30, and RI45 for IMVC (-23%; -25%; -25%, respectively; P < 0.05) and potentiated single twitch (-46%; -47%; -49%; P < 0.05), whereas voluntary activation did not change (-1%; -1%; 0%; P > 0.05). There were no RI condition effects, nor time × condition interaction for IMVC, potentiated single twitch and voluntary activation (all P > 0.05). V̇o2max was not different among RI15, RI30, and RI45 conditions (3.30, 3.29, and 3.26 L·min-1, respectively; P = 0.717), but POpeak was (272, 304, and 337 W, respectively; P < 0.001). Overall, performance fatigability profiles were similar between sexes after the RI tests and during recovery. In addition, during recovery, high-frequency doublets and single twitch recovered faster after RI30 and RI45 compared with RI15, regardless of sex (all P > 0.05 for sex differences). In conclusion, RI tests of different slopes that elicited similar V̇o2max but different POpeak did not affect the profile of performance fatigability at task failure in females and males.NEW & NOTEWORTHY It was unknown whether performance fatigability and its recovery are affected by different slopes in a ramp incremental (RI) test. It was also uncertain if females and males would respond differently. Performance fatigability was the same regardless of the RI slope adopted and the sex of the population, which was accompanied by similar maximal oxygen uptake but different power output achieved. The recovery of contractile function was similar between sexes but delayed after slower RI slopes.

Complete recovery of quadriceps muscle peripheral fatigue after running in Olympic, but not Sprint, triathlon.

This study compared central and peripheral fatigue development between the Sprint and Olympic distance triathlon. Fifteen male triathletes performed Sprint and Olympic triathlon simulations in a randomized and counterbalanced order. Central and peripheral fatigue was evaluated from changes in voluntary activation level (VAL) and twitch responses of quadriceps muscle (Qtw,pot), respectively. Qtw,pot reduced from baseline to post-swimming similarly between triathlon simulations (Sprint,-17±11%; Olympic, -13±9%). In post-cycling, Qtw,pot further declined to a similar extent between triathlon distances (Sprint, -31±15%; Olympic, -28±11%). In post-running, Qtw,pot was fully recovered in the Olympic triathlon (-4±10%), whereas there was only a partial recovery of Qtw,pot in the Sprint triathlon (-20±11%). VAL was not reduced in post-swimming, but reduction was similar between triathlon distances in post-cycling (Sprint, -10±9%; Olympic, -8±8%) and post-running (Sprint, -15±14%; Olympic, -16±8%). In the Sprint triathlon, the swimming speed (1.07±0.13m.s-1) was above (p <.001) critical speed (1.01±0.14m.s-1), the cycling power (179.7±27.2W) was below the respiratory compensation point (216.3±27.8W, p <.001) and running speed (13.7±1.05km.h-1) similar to the respiratory compensation point (13.2±0.70km.h-1, p =.124). In the Olympic triathlon, swimming speed (1.03±0.13m.s-1) was similar to critical speed (p =.392), and cycling power (165.3±27.3W) and running speed (12.6±1.05km.h-1) were below the respiratory compensation point (p ≤.007). In conclusion, peripheral fatigue progressed until post-cycling regardless of triathlon distances. However, peripheral fatigue was fully recovered after running in Olympic but not in Sprint triathlon. The central fatigue started in post-cycling and progressed until post-running regardless of triathlon distances.HighlightsThe quadriceps muscle peripheral fatigue progresses similarly in Sprint and Olympic triathlons until post-cycling.The quadriceps muscle peripheral fatigue is completely recovered after running in the Olympic triathlon, whereas it is partially recovered in the Sprint triathlon.The central fatigue starts in post-cycling and progresses similarly until post-running in Sprint and Olympic triathlons, regardless of triathlon distances.

Blood flow restriction during self-paced aerobic intervals reduces mechanical and cardiovascular demands without modifying neuromuscular fatigue.

This study examined cardiovascular, perceptual and neuromuscular fatigue characteristics during and after cycling intervals with and without blood flow restriction (BFR). Fourteen endurance cyclists/triathletes completed four 4-minute self-paced aerobic cycling intervals at the highest sustainable intensity, with and without intermittent BFR (60% of arterial occlusion pressure). Rest interval durations were six, four and four minutes, respectively. Power output, cardiovascular demands and ratings of perceived exertion (RPE) were averaged over each interval. Knee extension torque and vastus lateralis electromyography responses following electrical stimulation of the femoral nerve were recorded pre-exercise, post-interval one (+1, 2 and 4-minutes) and post-interval four (+1, 2, 4, 6 and 8-minutes). Power output during BFR intervals was lower than non-BFR (233 ± 54 vs 282 ± 60 W, p < 0.001). Oxygen uptake and heart rate during BFR intervals were lower compared to non-BFR (38.7 ± 4.5 vs 44.7 ± 6.44 mL kg-1 min-1, p < 0.001; 160 ± 14 vs 166 ± 10 bpm, p < 0.001), while RPE was not different between conditions. Compared to pre-exercise, maximal voluntary contraction torque and peak twitch torque were reduced after the first interval with further reductions following the fourth interval (p < 0.001) independent of condition (p = 0.992). Voluntary activation (twitch interpolation) did not change between timepoints (p = 0.375). Overall, intermittent BFR reduced the mechanical and cardiovascular demands of self-paced intervals without modifying RPE or knee-extensor neuromuscular characteristics. Therefore, BFR reduced the cardiovascular demands while maintaining the muscular demands associated with self-paced intervals. Self-paced BFR intervals could be used to prevent cardiovascular and perceptual demands being the limiting factor of exercise intensity, thus allowing greater physiological muscular demands compared to intervals without BFR.HighlightsThe use of blood flow restriction (BFR) during self-paced intervals (at the highest perceived sustainable intensity) causes a reduction in power output, pulmonary oxygen uptake and heart rate compared with non-restricted self-paced intervals.Despite lower mechanical and physiological demands during BFR cycling, the magnitude and aetiology of neuromuscular fatigue were not different to intervals without BFR, indicating the internal muscular load during BFR was elevated and potentially equivalent compared to without BFR.Self-paced intervals could be a suitable model to prescribe aerobic BFR exercise as an adjunct training stimulus for endurance cyclists.

Knee position sense and knee flexor neuromuscular function are similarly altered after two submaximal eccentric bouts.

PURPOSE: This study examined eccentric-induced fatigue effects on knee flexor (KF) neuromuscular function and on knee position sense. This design was repeated across two experimental sessions performed 1 week apart to investigate potential repeated bout effects. METHODS: Sixteen participants performed two submaximal bouts of KF unilateral eccentric contractions until reaching a 20% decrease in maximal voluntary isometric contraction force. Knee position sense was evaluated with position-matching tasks in seated and prone positions at 40° and 70° of knee flexion so that KF were either antagonistic or agonistic during the positioning movement. The twitch interpolation technique was used to assess KF neuromuscular fatigue. Perceived muscle soreness was also assessed. Measurements were performed before, immediately (POST) and 24 h after (POST24) each eccentric bout. RESULTS: No repeated bout effect on neuromuscular function and proprioceptive parameters was observed. At POST, central and peripheral factors contributed to the force decrement as shown by significant decreases in voluntary activation level (- 3.8 ± 4.8%, p < 0.01) and potentiated doublet torque at 100 Hz (- 10 ± 15.8%, p < 0.01). At this time point, position-matching errors significantly increased by 1.7 ± 1.9° in seated position at 40° (p < 0.01). At POST24, in presence of muscle soreness (p < 0.05), although KF neuromuscular function had recovered, position-matching errors increased by 0.6 ± 2.6° in prone position at 40° (p < 0.01). CONCLUSION: These results provide evidence that eccentric-induced position sense alterations may arise from central and/or peripheral mechanisms depending on the testing position.

Effects of α-lactalbumin on strength, fatigue and psychological parameters: a randomised double-blind cross-over study.

PURPOSE: The neurotransmitter serotonin has a strong effect on behaviour and motor control. Regarding motor control, serotonin contributes to the development of fatigue and is also involved in the ability of motor neurones to operate across a large range of forces (gain control). The consumption of tryptophan-rich supplements (such as α-lactalbumin) is of interest because this amino acid is the only precursor for brain serotonin synthesis. Therefore, the purpose of this study was to determine the effects of α-lactalbumin supplementation on neuromuscular performance. METHODS: Using a randomised double-blind cross-over design, 16 healthy participants performed plantar flexor and handgrip maximal voluntary contractions, a 30-s submaximal handgrip contraction, and a plantar flexor fatigue protocol before and 90 min after consuming either 40 g of α-lactalbumin, an isonitrogenous beverage (Zein) or an isocaloric beverage (corn-starch). Sleepiness, mood, and cognition were assessed to evaluate any psychological effects. RESULTS: α-Lactalbumin decreased force steadiness by 25% during the sustained submaximal handgrip contraction (p < 0.01) and induced greater fatigue (15% reduction in total torque-time integral, p = 0.01) during the fatigue protocol. These effects were not observed for the other control beverages. No effects were found for maximal or explosive strength, or psychological measurements. CONCLUSIONS: 40 g of α-lactalbumin increased handgrip force variability and reduced performance during fatiguing muscle contractions but did not influence brief maximal contractions or psychological parameters in healthy individuals. These findings support the hypothesis that the consumption of α-lactalbumin can increase motor neurone input-output gain and exacerbate central fatigue during sustained maximal exercise.

Antifatigue Effects of the Aqueous Extracts of Myrtle Berries, Apple and Clove: An Animal Study.

Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: Sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: Sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1ß, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.

Performance fatigability during isometric vs. concentric quadriceps fatiguing tasks in men and women.

In the present study, we aimed to provide a robust comparison of the fatigability of the knee extensors following isometric (ISO) and concentric (CON) tasks. Twenty young adults (25 ± 4 yr, 10 women) randomly performed the ISO and CON quadriceps intermittent fatigue test, consisting of ten (5 s on/5-s off, ISO) or one-hundred (0.5-s on/0.5-s off, CON) contractions with 10 % increments per stage until exhaustion. Performance fatigability was quantified as maximal isometric (MVIC) and concentric (MVCC) torque loss. Voluntary activation and contractile function (peak-twitch) were investigated using peripheral nerve stimulation. Number of stages (6.2 ± 0.7 vs. 4.9 ± 0.8; P < 0.001) and torque-time integral (20,166 ± 7,821 vs. 11,285 ± 4,933 Nm.s; P < 0.001) were greater for ISO than CON. MVIC, MVCC and voluntary activation decreased similarly between sessions (P > 0.05) whereas peak-twitch amplitude decreased more for CON (P < 0.001). The number of contractions was similar across sexes (ISO: men = 62 ± 8, women = 61 ± 5; CON: men = 521 ± 67, women = 458 ± 76, P > 0.05). MVCC was more reduced in women for both sessions (all P < 0.05), while MVIC loss was similar between sexes. We concluded that, despite greater torque-time integral and duration for ISO, both sessions induced a similar performance fatigability at exhaustion. Contractile function was more altered in CON. Finally, sex-related difference in fatigability depends on the contraction mode used during testing.

KangPiLao decoction modulates cognitive and emotional disorders in rats with central fatigue through the GABA/Glu pathway.

Background: Central fatigue (CF) is a subjective sense of tiredness associated with cognitive and memory disorders, accompanied by reduced physical endurance and negative emotions, such as anxiety and depression. Disease progression and prognosis with regards to CF have been unfavorable and possibly contribute to dementia, schizophrenia, and other diseases. Additionally, effective treatments for CF are lacking. KangPiLao decoction (KPLD) has been widely applied in clinical treatment and is composed of six Chinese herbal medicines, some of which have confirmed anti-fatigue effects. While glutamic acid (Glu) is the main excitatory transmitter in the central nervous system (CNS), gamma-aminobutyric acid (GABA) is the major inhibitory transmitter. Both are involved in emotional, cognitive, and memory functions. This research was designed to explore how KPLD regulates cognitive and emotional disorders in rats with CF and to identify the relationship between the regulatory effect and the GABA/Glu pathway. Methods: The compounds comprising KPLD were analyzed using high-performance liquid chromatography-mass spectrometry. Sixty Wistar rats were randomly divided into six groups. The modified multiple platform method was used to induce CF. Cognitive, emotional, and fatigue states were evaluated by performing behavioral tests (Morris water maze [MWM], open-field test [OFT], and grip strength test). Histomorphology, western blotting, immunohistochemistry, and RT-qPCR were performed to investigate protein and mRNA expression levels in the hippocampus and prefrontal cortexes involved in the GABA/Glu pathway. Results: Rats with CF exhibited impaired spatial cognition and increased negative emotions in the MWM and OFT. KPLD enabled the improvement of these symptoms, especially in the high-concentration group. Western blotting and RT-qPCR demonstrated that the expression of GABAARα1, GABAARγ2, GABABR1, and GAD67 in rats with CF was higher, whereas GAT-1 and NMDAR2B were lower in the hippocampus and prefrontal cortex. KPLD decreased the expression of GABAARα1, GABABR1, GABAARγ2, and GAD67 in the hippocampus and prefrontal cortex and enhanced the expression of NR2B in the prefrontal cortex. Conclusion: KPLD significantly improved cognitive and emotional disorders in rats with CF by regulating the GABA/Glu pathway. Overall, KPLD may be a promising candidate for developing a drug for treating CF.

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives.

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.