Effects of Hormonal Contraception and the Menstrual Cycle on Fatigability and Recovery From an Anaerobic Exercise Test.

ABSTRACT: Cabre, HE, Ladan, AN, Moore, SR, Joniak, KE, Blue, MNM, Pietrosimone, BG, Hackney, AC, and Smith-Ryan, AE. Effects of hormonal contraception and the menstrual cycle on fatigability and recovery from an anaerobic exercise test. J Strength Cond Res 38(7): 1256-1265, 2024-This study sought to evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared with a eumenorrheic (EUM) cycle, on fatigability and recovery between hormone the phases. Peak power (PP), average power (AP), fatigue index (FI), blood lactate, vessel diameter, and blood flow (BF) were measured from a repeated sprint cycle test (10 × 6 seconds) in 60, healthy, active women (mean ± SD ; age: 26.5 ± 7.0 years, BMI: 22.5 ± 3.7 kg·m -2 ) who used monophasic OC (≥6 months; n = 21), had a H-IUD (≥6 months; n = 20), or had regular naturally occurring menstrual cycle (≥3 months) or had a nonhormonal IUD (EUM; n = 19). Subjects were randomly assigned to begin in either the low-hormone phase (LHP) or high-hormone phase (HHP) and were tested once in each phase. Separate univariate analyses of covariances assessed the change from HHP to LHP between the groups, covaried for progesterone, with significance set at p ≤ 0.05. All groups demonstrated similar changes in PP, AP, FI, blood lactate, vessel diameter, and BF between the phases ( p > 0.05). Although not significant, AP was higher in LHP for OC (Δ -248.2 ± 1,301.4 W) and EUM (Δ -19.5 ± 977.7 W) and higher in HHP for H-IUD (Δ 369.3 ± 1,123.0 W). Oral contraceptive group exhibited a higher FI (Δ 2.0%) and reduced blood lactate clearance (Δ 2.5%) in HHP. In recreationally active women, hormonal contraception and hormone phases may minimally impact fatigue and recovery. Individual elite female athletes may benefit from understanding hormonal contraception type as performance and recovery may slightly vary across the cycle.

Caffeine Expectancy Does Not Influence the Physical Working Capacity at the Fatigue Threshold.

ABSTRACT: Ambrozy, CA, Hawes, NE, Hayden, OL, Sortzi, I, and Malek, MH. Caffeine expectancy does not influence the physical working capacity at the fatigue threshold. J Strength Cond Res 38(6): 1056-1062, 2024-The placebo effect occurs when a desired outcome is experienced due to the belief that a treatment is effective, even in the absence of an active ingredient. One explanation for this effect is based on a person's expectations of a drug or supplement. Although caffeine's effects on sports performance have been studied, little is known about how expectations of caffeine affect neuromuscular fatigue during continuous muscle action. The physical working capacity at the fatigue threshold (PWCFT) can be used to assess neuromuscular fatigue noninvasively using surface electromyography. Thus, the purpose of this study was to investigate whether caffeine expectancy influences PWCFT. We hypothesized that regardless of expectancy, caffeine consumption would delay neuromuscular fatigue. The study involved 8 healthy college-aged men (mean ± SEM: age, 25.6 ± 1.0 years) who visited the laboratory on 4 occasions, each separated by 7 days. The subjects completed 4 experimental conditions, in random order, where they were told that they were consuming caffeine or placebo and either received caffeine or placebo. After consuming the drink, the subjects remained in the laboratory for an hour and then performed an incremental exercise test. The results showed that the condition where subjects were told that they were consuming caffeine and received caffeine had significantly higher mean values for maximal power output (F(3, 21) = 11.75; p < 0.001), PWCFT (F(3, 21) = 12.28; p < 0.001), PWCFT (%maximal power output; F(3, 21) = 8.75; p < 0.001), and heart rate at end exercise (%predicted; F(3, 21) = 3.83; p = 0.025) compared with the 2 conditions where placebo was received. However, no statistically significant mean differences were found from the condition where subjects were told that they were consuming placebo but consuming caffeine. This suggests that a person's expectancy and potential somatic response may serve as a cue for how an ergogenic aid or placebo could affect subsequent performance.

Effects of a Low Dose of Orally Administered Creatine Monohydrate on Post-Fatigue Muscle Power in Young Soccer Players.

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg-1·day-1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Study on Anti-fatigue Effects and Mechanisms of Polysaccharide from Paris polyphylla.

The objectives of this study were to investigate the anti-fatigue effects of Paris polyphylla polysaccharide component 1 (PPPm-1) and explore its mechanisms. A mouse model of exercise-induced fatigue was established by weight-bearing swimming to observe the effects of different concentrations of PPPm-1 on weight-bearing swimming time. The anti-fatigue effect of PPPm-1 was determined by the effects of contraction amplitude, contraction rate, and diastolic rate of the frog gastrocnemius muscle in vivo before and after infiltration with 5 mg/mL PPPm-1. The effects of PPPm-1 on the contents of blood lactate, serum urea nitrogen, hepatic glycogen, muscle glycogen in the exercise fatigue model of mice, and acetylcholine (ACh) content and acetylcholinesterase (AChE) activity at the junction of the frog sciatic nerve-gastrocnemius under normal physiological, and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of the frog gastrocnemius were determined by enzyme-linked immunosorbent assay (ELISA), to investigate the anti-fatigue mechanisms of PPPm-1. The results showed that PPPm-1 could significantly prolong the weight-bearing swimming time in mice (P < 0.01), decrease the contents of blood lactate and serum urea nitrogen, increase the contents of the hepatic glycogen and muscle glycogen of mice after exercise fatigue compared with those of the control group, and there was extremely significant difference in most indicators (P < 0.01). The 5 mg/mL of PPPm-1 could significantly promote the contraction amplitude, contraction rate, and relaxation rate of the gastrocnemius muscle in the frogs, and the content of ACh at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01), but it had obvious inhibitory effetc on the activity of AChE at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01). PPPm-1 could increase the Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of gastrocnemius in the frogs (for Ca2+-Mg2+-ATPase, P < 0.01). The above results suggested that the PPPm-1 had a good anti-fatigue effect, and its main mechanisms were related to improving endurance and glycogen reserve, reducing glycogen consumption, lactate and serum urea nitrogen accumulation, and promoting Ca2+ influx.

A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.

Short term creatine loading improves strength endurance even without changing maximal strength, RPE, fatigue index, blood lactate, and mode state.

Creatine is consumed by athletes to increase strength and gain muscle. The aim of this study was to evaluate the effects of creatine supplementation on maximal strength and strength endurance. Twelve strength-trained men (25.2 ± 3.4 years) supplemented with 20 g Creatina + 10g maltodextrin or placebo (20g starch + 10g maltodextrin) for five days in randomized order. Maximal strength and strength endurance (4 sets 70% 1RM until concentric failure) were determined in the bench press. In addition, blood lactate, rate of perceived effort, fatigue index, and mood state were evaluated. All measurements were performed before and after the supplementation period. There were no significant changing in maximal strength, blood lactate, RPE, fatigue index, and mood state in either treatment. However, the creatine group performed more repetitions after the supplementation (Cr: Δ = +3.4 reps, p = 0.036, g = 0.53; PLA: Δ = +0.3reps, p = 0.414, g = 0.06), and higher total work (Cr: Δ = +199.5au, p = 0.038, g = 0.52; PLA: Δ = +26.7au, p = 0.402, g = 0.07). Creatine loading for five days allowed the subjects to perform more repetitions, resulting in greater total work, but failed to change the maximum strength.

Piperine enhances contractile force in slow- and fast-twitch muscle.

Piperine has been shown to bind to myosin and shift the distribution of conformational states of myosin molecules from the super-relaxed state to the disordered relaxed state. However, little is known about the implications for muscle force production and potential underlying mechanisms. Muscle contractility experiments were performed using isolated muscles and single fibres from rats and mice. The dose-response effect of piperine on muscle force was assessed at several stimulation frequencies. The potentiation of muscle force was also tested in muscles fatigued by eccentric contractions. Potential mechanisms of force potentiation were assessed by measuring Ca2+ levels during stimulation in enzymatically dissociated muscle fibres, while myofibrillar Ca2+ sensitivity was assessed in chemically skinned muscle fibres. Piperine caused a dose-dependent increase in low-frequency force with no effect on high-frequency force in both slow- and fast-twitch muscle, with similar relative increases in twitch force, rate of force development and relaxation rate. The potentiating effect of piperine on low-frequency force was reversible, and piperine partially recovered low-frequency force in fatigued muscle. Piperine had no effect on myoplasmic free [Ca2+] levels in mouse muscle fibres, whereas piperine substantially augmented the force response to submaximal levels of [Ca2+] in rat MyHCII fibres and MyHCI fibres along with a minor increase in maximum Ca2+-activated force. Piperine enhances low-frequency force production in both fast- and slow-twitch muscle. The effects are reversible and can counteract muscle fatigue. The primary underlying mechanism appears to be an increase in Ca2+ sensitivity. KEY POINTS: Piperine is a plant alkaloid derived from black pepper. It is known to bind to skeletal muscle myosin and enhance resting ATP turnover but its effects on contractility are not well known. We showed for the first time a piperine-induced force potentiation that was pronounced during low-frequency electrical stimulation of isolated muscles. The effect of piperine was observed in both slow and fast muscle types, was reversible, and could counteract the force decrements observed after fatiguing muscle contractions. Piperine treatment caused an increase in myofibrillar Ca2+ sensitivity in chemically skinned muscle fibres, while we observed no effect on intracellular Ca2+ concentrations during electrical stimulation in enzymatically dissociated muscle fibres.

Effects of Hormonal Contraception and the Menstrual Cycle on Fatigability and Recovery From an Anaerobic Exercise Test.

ABSTRACT: Cabre, HE, Ladan, AN, Moore, SR, Joniak, KE, Blue, MNM, Pietrosimone, BG, Hackney, AC, and Smith-Ryan, AE. Effects of hormonal contraception and the menstrual cycle on fatigability and recovery from an anaerobic exercise test. J Strength Cond Res 38(7): 1256-1265, 2024-This study sought to evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared with a eumenorrheic (EUM) cycle, on fatigability and recovery between hormone the phases. Peak power (PP), average power (AP), fatigue index (FI), blood lactate, vessel diameter, and blood flow (BF) were measured from a repeated sprint cycle test (10 × 6 seconds) in 60, healthy, active women (mean ± SD ; age: 26.5 ± 7.0 years, BMI: 22.5 ± 3.7 kg·m -2 ) who used monophasic OC (≥6 months; n = 21), had a H-IUD (≥6 months; n = 20), or had regular naturally occurring menstrual cycle (≥3 months) or had a nonhormonal IUD (EUM; n = 19). Subjects were randomly assigned to begin in either the low-hormone phase (LHP) or high-hormone phase (HHP) and were tested once in each phase. Separate univariate analyses of covariances assessed the change from HHP to LHP between the groups, covaried for progesterone, with significance set at p ≤ 0.05. All groups demonstrated similar changes in PP, AP, FI, blood lactate, vessel diameter, and BF between the phases ( p > 0.05). Although not significant, AP was higher in LHP for OC (Δ -248.2 ± 1,301.4 W) and EUM (Δ -19.5 ± 977.7 W) and higher in HHP for H-IUD (Δ 369.3 ± 1,123.0 W). Oral contraceptive group exhibited a higher FI (Δ 2.0%) and reduced blood lactate clearance (Δ 2.5%) in HHP. In recreationally active women, hormonal contraception and hormone phases may minimally impact fatigue and recovery. Individual elite female athletes may benefit from understanding hormonal contraception type as performance and recovery may slightly vary across the cycle.

Study of anti-fatigue activity of polysaccharide from fruiting bodies of Armillaria gallica.

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota.

Anti-fatigue effects of enzyme-hydrolyzed okara in C2C12 myotubes and Sprague-Dawley rats.

Okara is a by-product of tofu or soymilk production processes. The disposal of huge quantities of okara is a significant issue. Based on previous reports, protein hydrolysis can release excess free amino acids and small peptides from okara and exhibit anti-fatigue function. We aimed to investigate the anti-fatigue effect of okara protein hydrolysate (OPH) in vitro and in vivo. In the first phase, we treated C2C12 myotubes with different processed OPHs to detect mitochondrial functions. The results revealed that OPH hydrolyzed with alcalase containing 2% E/S for 2 h increased the mitochondrial mRNA level (cytochrome b and cytochrome c oxidase I) and enzyme activity (citrate synthase and cytochrome c oxidase) most efficiently. In the second phase, we conducted animal studies to assess the anti-fatigue function of OPH. After acclimatization, 8 week-old male Sprague-Dawley (SD) rats were randomly classified into four groups: (1) control group, (2) 1X-OPH, (3) 2X-OPH, and (4) 5X-OPH (8 rats per group, treated for 28 days). The results indicated that the intake of OPH for 28 days increased the exhaustive swimming time of rats and lowered the increment of the lactate ratio, as well as the activity of lactate dehydrogenase and creatine kinase. These results indicated that OPH improves exercise performance and anti-fatigue function in male SD rats. Therefore, OPH could be a potential health supplement for anti-fatigue function.

Effectiveness of Nitrate Intake on Recovery from Exercise-Related Fatigue: A Systematic Review.

BACKGROUND: Recovery between efforts is critical to achieving optimal physical and sports performance. In this sense, many nutritional supplements that have been proven to improve recovery and physical and physiological performance are widely used. Supplements such as nitrates (NO3-), including organic foods such as beets, promote muscle recovery and relieve fatigue. This study aimed to comprehensively summarise the available literature on the effect of NO3- consumption on exercise-related fatigue and muscle damage. METHODS: A systematic search was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) using electronic databases (e.g., PubMed, Scopus, and Web of Science). From a total of 1634 studies identified, 15 studies were included in this review. RESULTS: Based on the review, NO3- intake provokes physiological and metabolic responses that could potentially boost exercise-related recovery. NO3- could improve recovery indicators related to strength, pain, inflammation, and muscle damage. CONCLUSIONS: Despite the relative proven effectiveness of NO3- on recovery after aerobic and anaerobic efforts, based on the heterogeneity of the procedures (e.g., dosage, chronic vs. acute intake, participants' characteristics, variables and outcomes), it could be premature to suggest its extended use in sports.

Capsaicin and Its Effect on Exercise Performance, Fatigue and Inflammation after Exercise.

Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: -52 ± 6 vs. CAP: -42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: -47 ± 33 vs. CAP: -29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.

The anti-fatigue effect of the Auxis thazard oligopeptide via modulation of the AMPK/PGC-1α pathway in mice.

The Auxis thazard oligopeptide (ATO) was obtained by papain digestion and ultrafiltration membrane separation, and its anti-fatigue effects and mechanisms were evaluated using animal experiments on Kunming mice. Compared with the negative control group, the ATO extended the time to exhaustion in mice in a forced swim test by 0.81-1.62 times. Liver glycogen levels were significantly increased by 0.6-1.63 times and muscle glycogen levels were increased by 9.52-10.02%; the levels of lactic acid (16.46-17.21%) and urea nitrogen (34.88-41.91%) decreased. The ATO also increased antioxidant activity, reduced malondialdehyde levels (18.00-35.79%) in the liver and myocardium, and increased the gene and protein expression of AMPK and PGC-1α in fatigued mice. These results indicate that the ATO exerts an anti-fatigue effect via improving energy metabolism and decreasing oxidative stress.

Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue.

Although there is evidence that 5-HT acts as an excitatory neuromodulator to enhance maximal force generation, it is largely unknown how 5-HT activity influences the ability to sustain a constant force during steady-state contractions. A total of 22 healthy individuals participated in the study, where elbow flexion force was assessed during brief isometric contractions at 10% maximal voluntary contraction (MVC), 60% MVC, MVC, and during a sustained MVC. The selective serotonin reuptake inhibitor, paroxetine, suppressed physiological tremor and increased force steadiness when performing the isometric contractions. In particular, a main effect of drug was detected for peak power of force within the 8-12 Hz range (P = 0.004) and the coefficient of variation (CV) of force (P < 0.001). A second experiment was performed where intermittent isometric elbow flexions (20% MVC sustained for 2 min) were repeatedly performed so that serotonergic effects on physiological tremor and force steadiness could be assessed during the development of fatigue. Main effects of drug were once again detected for peak power of force in the 8-12 Hz range (P = 0.002) and CV of force (P = 0.003), where paroxetine suppressed physiological tremor and increased force steadiness when the elbow flexors were fatigued. The findings of this study suggest that enhanced availability of 5-HT in humans has a profound influence of maintaining constant force during steady-state contractions. The action of 5-HT appears to suppress fluctuations in force regardless of the fatigue state of the muscle.NEW & NOTEWORTHY Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.

Anti-fatigue effect of phlorizin on exhaustive exercise-induced oxidative injury mediated by Nrf2/ARE signaling pathway in mice.

Oxidative stress plays a crucial role in fatigue, thus it is of significance to develop safe and efficient antioxidant to prevent fatigue. Phlorizin (PHZ) is a major active ingredient of dihydrochalcone from Lithocarpus polystachyus Rehd., which has already been approved as a new food material in China since 2017. The current study was designed to investigate the effect of PHZ on fatigue, and further to elucidate its possible underlying mechanism. Our results revealed that PHZ exerted beneficial effect on exhaustive exercise-induced fatigue in mice, as reflected by rotarod test and exhaustive swimming test. Moreover, PHZ also effectively decreased the levels of blood urea nitrogen, creatine kinase and plasma lactic acid, increased the liver glycogen and skeletal muscle glycogen of fatigued mice, as evidenced by enzyme linked immunosorbent assay. PHZ balanced the redox status through reducing generation of reactive oxygen species, enhancing the activities of antioxidative enzymes. Furthermore, PHZ not only increased the ratio of Bcl2/Bax, but also decreased the level of cleaved-caspase 3. Notably, PHZ facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) translocated from cytoplasm to nucleus, and up-regulated its downstream antioxidant response element including heme oxygenase-1 and NADPH quinone oxidoreductase-1. Intriguingly, PHZ directly bound to Nrf2, as evidenced by molecular docking, and the anti-fatigue effects of PHZ were almost abolished in Nrf2 deficient mice. In summary, our findings suggest that PHZ might be a natural occurring antioxidant with safety profile to relieve fatigue via targeting Nrf2 to inhibit apoptosis.

Blockade of 5-HT2 receptors suppresses rate of torque development and motor unit discharge rate during rapid contractions.

Serotonin (5-HT) is a neuromodulator that is critical for regulating the excitability of spinal motoneurons and the generation of muscle torque. However, the role of 5-HT in modulating human motor unit activity during rapid contractions has yet to be assessed. Nine healthy participants (23.7 ± 2.2 yr) ingested 8 mg of the competitive 5-HT2 antagonist cyproheptadine in a double-blinded, placebo-controlled, repeated-measures experiment. Rapid dorsiflexion contractions were performed at 30%, 50%, and 70% of maximal voluntary contraction (MVC), where motor unit activity was assessed by high-density surface electromyographic decomposition. A second protocol was performed where a sustained, fatigue-inducing dorsiflexion contraction was completed before undertaking the same 30%, 50%, and 70% MVC rapid contractions and motor unit analysis. Motor unit discharge rate (P < 0.001) and rate of torque development (RTD; P = 0.019) for the unfatigued muscle were both significantly lower for the cyproheptadine condition. Following the fatigue inducing contraction, cyproheptadine reduced motor unit discharge rate (P < 0.001) and RTD (P = 0.024), whereas the effects of cyproheptadine on motor unit discharge rate and RTD increased with increasing contraction intensity. Overall, these results support the viewpoint that serotonergic effects in the central nervous system occur fast enough to regulate motor unit discharge rate during rapid powerful contractions.NEW & NOTEWORTHY We have shown that serotonin activity in the central nervous system plays a role in regulating human motor unit discharge rate during rapid contractions. Our findings support the viewpoint that serotonergic effects in the central nervous system are fast and are most prominent during contractions that are characterized by high motor unit discharge rates and large amounts of torque development.

Molecular Mechanisms of Muscle Fatigue.

Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support. Although the origin of chronic fatigue is multifactorial, the MF in illness conditions is intrinsically linked to the occurrence of muscle loss. The sequence of events leading to chronic fatigue can be schematically denoted as: trigger (genetic or pathological) -> molecular outcome within the muscle cell -> muscle wasting -> loss of muscle function -> occurrence of chronic muscle fatigue. The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting, thereby helping us understand how we could prevent or treat this debilitating condition.

Antifatigue effects of Hechong (Tylorrhynchus heterochaetus) through modulation of Nrf2/ARE- mediated antioxidant signaling pathway.

This study was to evaluate the antifatigue effect of T. heterochaetus and explore the underlying mechanism of action. T. heterochaetus extract was treated to mice for 28 days. On the 28th day, after weight loaded swimming test. The levels of antioxidant enzymes and levels of pro- and anti-inflammatory cytokines in the liver and muscles of exercised mice were evaluated. mRNA and protein expression levels of Nrf2, SOD, HO-1, and Keap-1 were evaluated using RT-PCR and western blot analysis. The low (2.70 mg/0.5 ml/20 g) and medium (5.41 mg/0.5 ml/20 g) dose enhanced the activities of antioxidant enzymes like SOD, CAT and GPx in the liver and skeletal muscle thereby enhancing the antifatigue effect. The low and medium doses showed good anti-inflammatory effects by evaluating the levels of pro and anti-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-10 both in the liver and skeletal muscle. Furthermore, RT-PCR and western blot analysis showed increased expression of HO-1, SOD, Nrf2, and decreased expression of Keap-1 gene and proteins in liver and skeletal muscle of T. heterochaetus treated group mice. The current results indicate that T. heterochaetus exert the antifatigue effect through attenuating oxidative stress injury and inflammatory responses through the Nrf2/ARE-mediated signaling pathway.

Mitochondria and Antibiotics: For Good or for Evil?

The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.

The Effect of a Multi-Ingredient Pre-Workout Supplement on Time to Fatigue in NCAA Division I Cross-Country Athletes.

This investigation aimed to determine the effect of a multi-ingredient pre-workout supplement (MIPS) on heart rate (HR), perceived exertion (RPE), lactate concentration, and time to fatigue (TTF) during a running task to volitional exhaustion. Eleven NCAA Division I cross-country runners (20 ± 2 year; height: 171 ± 14 cm; weight: 63.5 ± 9.1 kg) participated in this randomized, double-blind, placebo-controlled cross-over study. Bayesian statistical methods were utilized, and parameter estimates were interpreted as statistically significant if the 95% highest-density intervals (HDIs) did not include zero. TTF was increased in the MIPS condition with a posterior Meandiff = 154 ± 4.2 s (95% HDI: -167, 465) and a 0.84 posterior probability that the supplement would increase TTF relative to PL. Blood lactate concentration immediately post-exercise was also higher in the MIPS condition compared to PL with an estimated posterior Meandiff = 3.99 ± 2.1 mmol (95% HDI: -0.16, 7.68). There were no differences in HR or RPE between trials. These findings suggest that a MIPS ingested prior to sustained running at lactate threshold has an 84% chance of increasing TTF in highly trained runners and may allow athletes to handle a higher level of circulating lactate before reaching exhaustion.