Impact of exercise on markers of B cell-related immunity: A systematic review.

BACKGROUND: B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literature on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE, Web of Science, and Embase were searched on March 8, 2023. Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions, immunoglobulin levels, salivary flow rate, or secretory immunoglobulin A secretion rate were included. Quality and reporting of exercise training studies was assessed using the Tool for the Assessment of Study Quality and reporting in Exercise. Study characteristics, outcome measures, and statistically significant changes were summarized tabularly. RESULTS: Of the 67 eligible studies, 22 applied acute exercise and 45 applied exercise training. All included outcomes revealed significant alterations over time in acute exercise and exercise training context, but only a few investigations showed significant differences compared to control conditions. Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training. CONCLUSION: B cell-related outcomes are altered by acute exercise and exercise training, but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities. Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

Physical activity is related to disease severity and fatigue, but not to relapse rate in persons with relapsing remitting multiple sclerosis - a self-reported questionnaire based study.

Introduction: Based on theoretical models, physical activity has been introduced as a promoting method to mitigate the disease severity, fatigue and relapse rate in multiple sclerosis. The primary objective of the study was to investigate the relation between self-reported physical activity level and disease severity, fatigue and relapse rate in persons with relapsing remitting multiple sclerosis (RRMS). Methods: A survey was offered to persons with RRMS from March 2019 to August 2021 (n = 253). Physical activity level, fatigue and disease severity were determined using the Godin Leisure-Time Questionnaire (GLTEQ), the Patient Determined Disease Steps (PDDS) scale and the Fatigue Scale for Motor and Cognitive Functions (FSMC). Additionally, participants' relapse rate was recorded. Results: Bivariate correlations revealed an inverse relation between physical activity level and PDDS (ρ = -0.279; p < 0.001) as well as between physical activity and FSMC (r = -0.213, p < 0.001), but not between physical activity and relapse rate (r = 0.033, p > 0.05). Multiple linear regression analyses explained 12.6% and 5.2% of the variance of PDDS and FSMC. Conclusion: Our findings confirm a relation between self-reported physical activity, disease severity and fatigue in persons with RRMS. However, self-reported physical activity level does not seem to affect the annualised relapse rate.

Effects of inpatient energy management education and high-intensity interval training on health-related quality of life in persons with multiple sclerosis: A randomized controlled superiority trial with six-month follow-up.

BACKGROUND: Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (pwMS) and impacts health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for the treatment of fatigue in pwMS. However, high-quality evidence exists only for unimodal interventions, such as physical therapies/exercise or energy/fatigue management programmes. The primary objective of the current study was to test the hypothesis that a combination of inpatient energy management education (IEME) and high-intensity interval training (HIIT) is superior to a combination of progressive muscle relaxation (PMR) and moderate continuous training (MCT) for improving HRQoL at 6-month follow-up in fatigued pwMS. METHODS: A randomized (1:1) controlled superiority trial with fatigued pwMS >18 years of age, with Expanded Disability Status Scale (EDSS) score ≤6.5, recruited at the Valens clinic, Switzerland. Participants in the experimental group performed IEME twice and HIIT 3 times per week and those in the usual care group performed PMR twice and MCT 3 times per week, during a 3-week inpatient rehabilitation stay. Primary outcome was HRQoL (Physical and Mental Component Scales of the Medical Outcome Study 36-item Short Form Health Survey (SF-36)), assessed at entry to the clinic (T0), after 3 weeks' rehabilitation (T1) and 4 (T2) and 6 (T3) months after T0. Secondary outcomes included SF-36 subscales, fatigue (Fatigue Scale for Motor and Cognitive Functions (FSMC)), mood (Hospital Anxiety and Depression Scale (HADS)), self-efficacy for performing energy conservation strategies (Self-Efficacy for Performing Energy Conservation Strategies Assessment (SEPECSA)), self-perceived competence in activities of daily living (Occupational Self Assessment (OSA)) and cardiorespiratory fitness (peak oxygen consumption (VÈ®2peak)). Data were analysed using a mixed model for repeated measures approach. RESULTS: A total of 106 pwMS (age (years): 49.75 (9.87), 66% female, EDSS: 4.64 (1.32)) were recruited. There were no significant group × time interaction effects in the primary and secondary outcomes. There were significant between-group differences in the pairwise comparisons of the group × time interaction in favour of the IEME + HIIT group at: (i) T1 in cardiorespiratory fitness (p = 0.011) and SEPECSA (p = 0.032); (ii) T2 in SF-36 mental health subscale (p = 0.022), HADS anxiety subscale (p = 0.014) and SEPECSA (p = 0.040); (iii) T3 in SF-36 physical functioning subscale (p = 0.012) and SEPECSA (p = 0.003). CONCLUSION: IEME + HIIT was not superior to PMR + MCT regarding the effects on HRQoL (SF-36 Physical and Mental Component Scales) at 6-month follow-up in pwMS. However, there were significant between-group differences in favour of IEME + HIIT in physical functioning and mental health (SF-36 subscales), anxiety (HADS), cardiorespiratory fitness (VÈ®2peak) and self-efficacy (SEPECSA) at different measurement time-points that need to be considered in clinical practice.

12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial.

BACKGROUND: Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. RESULTS: The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05). CONCLUSIONS: Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

Cycling in primary progressive multiple sclerosis (CYPRO): study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is the least prevalent multiple sclerosis (MS) phenotype. For persons with PPMS (pwPPMS), pharmacological treatment options are limited. As a complementary non-pharmacological treatment, endurance training improves the health-related quality of life (HRQoL), numerous MS symptoms, and MS-related performance impediments. High-intensity interval training (HIIT) has been shown to induce superior effects compared to moderate-intensity continuous training (MCT). As current evidence is based on MS samples with mixed phenotypes, generalizability to pwPPMS remains unclear. METHODS: CYPRO is a parallel-group, single-center, and single-blind randomized controlled superiority trial evaluating the effects of HIIT compared to MCT in pwPPMS. Sixty-one pwPPMS are randomized (1:1) to perform volume-matched HIIT or MCT sessions on bicycle ergometers two to three times per week in addition to standard rehabilitative care during their three-week inpatient stay at Valens rehabilitation clinic, Switzerland. Standard rehabilitative care comprises endurance and strength training, physiotherapy, and occupational therapy. HIIT sessions include six 90-second intervals at 95% peak heart rate (HRpeak), interspersed by 90-second active breaks with unloaded pedaling, aimed to reach 60%HRpeak. MCT represents the standard treatment at Valens rehabilitation clinic and is performed as continuous cycling at 60%HRpeak for the duration of 26 minutes. The primary outcome is cardiorespiratory fitness, assessed as peak oxygen consumption (V̇O2peak) during cardiopulmonary exercise testing (CPET). Secondary outcomes include peak power output during CPET, walking capacity, cognitive performance, HRQoL, fatigue, anxiety and depressive symptoms, and blood-derived biomarkers (e.g., serum neurofilament light chain, glial fibrillary acidic protein, kynurenine pathway metabolites) related to MS pathophysiology. All outcomes are assessed at baseline and discharge after three weeks. Venous blood sampling is additionally performed immediately and two hours after the first HIIT or MCT session. DISCUSSION: CYPRO will expand current knowledge on symptom management and rehabilitation in MS to the subpopulation of pwPPMS, and will contribute to the exploration of potential disease-modifying effects of endurance training in MS. The superiority design of CYPRO will allow deriving explicit recommendations on endurance training design in pwPPMS that can be readily translated into clinical practice. TRIAL REGISTRATION: CYPRO has been prospectively registered at ClinicalTrials.gov on 8 February 2022 (NCT05229861).

The serum kynurenine pathway metabolic profile is associated with overweight and obesity in multiple sclerosis.

BACKGROUND: Overweight and obesity increase multiple sclerosis (MS) susceptibility, disease severity, and disability progression. Kynurenine pathway (KP) dysregulation is present in overweight and obesity, and in MS. Since the effect of overweight and obesity on KP dysregulation in persons with MS (pwMS) remains to be established, this study primarily aims to explore the effect of overweight and obesity on the serum KP metabolic profile in pwMS. METHODS: This cross-sectional study represents a secondary analysis of a randomized clinical trial at Valens rehabilitation clinic, Switzerland. Registration was performed on 22 April 2020 at clinicaltrials.gov (NCT04356248, https://clinicaltrials.gov/ct2/show/NCT04356248). The first participant was enrolled on 13 July 2020. Based on body mass index (BMI), 106 MS inpatients (Expanded Disability Status Scale (EDSS) score ≤ 6.5) were dichotomised to a lean group (LG, BMI < 25 kg/m2), and an overweight/obese group (OG, BMI ≥ 25 kg/m2). Targeted metabolomics (LC-MS/MS) was performed to determine serum concentrations of tryptophan (TRP), KP downstream metabolites, and neopterin (Neopt). Correlations between BMI, kynurenine-to-TRP ratio (KTR), and serum concentrations of TRP, KP downstream metabolites, and Neopt were calculated. ANCOVA was used to determine differences in KTR, and serum concentrations of TRP, KP downstream metabolites and Neopt between OG and LG, and across MS phenotypes. RESULTS: Higher BMI correlated with higher KTR (r = 0.425, p <0.001) and serum concentrations of most KP downstream metabolites, but not with EDSS score. Higher KTR (r = 0.470, p < .001) and serum concentrations of most KP downstream metabolites correlated with a higher serum concentration of Neopt. The OG (n = 44, 59% female, 51.68 (9.98) years, EDSS: 4.71 (1.37)) revealed higher KTR (0.026 (0.007) vs. 0.022 (0.006), p=.001) and serum concentrations of most KP downstream metabolites than the LG (n = 62, 71% female, 48.37 (9.63) years, EDSS: 4.60 (1.29)). KP metabolic profiles did not differ between MS phenotypes. CONCLUSION: Overweight and obesity are associated with a systemic elevation of KP metabolic flux and an accumulation of most KP downstream metabolites in pwMS. Further research is needed to clarify if KP involvement serves as a mechanism linking overweight and obesity with symptom expression, disease severity, and disability progression in pwMS.

Tissue-specific effects of exercise as NAD+ -boosting strategy: Current knowledge and future perspectives.

Nicotinamide adenine dinucleotide (NAD+ ) is an evolutionarily highly conserved coenzyme with multi-faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD+ levels are a shared characteristic of various diseases and aging per se, several NAD+ -boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD+ homeostasis through metabolic adaption to chronically recurring states of increased energy demand. In this review we discuss the impact of acute exercise and exercise training on tissue-specific NAD+ metabolism of rodents and humans to highlight the potential value as NAD+ -boosting strategy. By interconnecting results from different investigations, we aim to draw attention to tissue-specific alterations in NAD+ metabolism and the associated implications for whole-body NAD+ homeostasis. Acute exercise led to profound alterations of intracellular NAD+ metabolism in various investigations, with the magnitude and direction of changes being strongly dependent on the applied exercise modality, cell type, and investigated animal model or human population. Exercise training elevated NAD+ levels and NAD+ metabolism enzymes in various tissues. Based on these results, we discuss molecular mechanisms that might connect acute exercise-induced disruptions of NAD+ /NADH homeostasis to chronic exercise adaptions in NAD+ metabolism. Taking this hypothesis-driven approach, we hope to inspire future research on the molecular mechanisms of exercise as NAD+ -modifying lifestyle intervention, thereby elucidating the potential therapeutic value in NAD+ -related pathologies.

Cellular Integrative Immune Markers in Elite Athletes.

The integrative immune markers neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR) and systemic immune inflammation index (SII) are established markers in clinical patient care. Adoption of these markers in elite athletics might prove beneficial for monitoring training and health. Blood samples of 195 healthy national Olympic squad athletes were collected before a graded bicycle-ergometric exercise test until complete exhaustion. Measurements included white blood cells, lymphocytes and platelets, allowing for the calculation of the integrative immune markers. Correlations between athlete characteristics (sex, age, sporting discipline, training experience, training volume) and integrative immune marker-values were assessed. In a subgroup analysis a second blood sample was collected from 25 athletes at 1 minute after exercise test to assess its effect on the immune marker levels.An inverse correlation between peak power output and SII-level (Pearson correlation coefficient=-.270, p<.001) and NLR-level (Pearson correlation coefficient=-.249, p<.001) was found. Athletes with higher aerobic fitness had significantly lower values of SII and PLR compared to athletes with lower aerobic fitness. An elevated SII (p=.003) and a reduced PLR (p=.001) was documented as acute response to the exercise test. The integrative immune markers might be a promising tool for monitoring training and health in elite athletes.

Effect of sleep and fatigue on cardiovascular performance in young, healthy subjects.

Physical performance could be negatively affected by sleep deficiency and fatigue. The present study assesses the role of sleep quality, fatigue and motivation on cardiovascular performance (VO2peak, Wmax, and HRmax) in a sample of active young subjects. The current study is a cross-sectional design. Ninety-six university students (males 54.2%; 21.5 ± 2.9 yrs) completed an incremental exercise test on a bicycle ergometer. Sleep, fatigue, and motivation were assessed with the Pittsburgh Sleep Quality Index and two visual analogue scales, respectively. Differences in VO2peak, Wmax, HRmax, self-perceived fatigue and motivation were compared between good and bad sleepers and sleep duration >/<7.5 h, while regression analysis defined the predictors of VO2peak, Wmax, and HRmax. In the male sample, good and bad sleepers' differences were significant only for self-perceived fatigue (p = 0.04). The female sample showed no statistically significant differences between good and bad sleepers and different sleep durations. In the male sample, linear regression analysis showed a significant inverse correlation between Wmax and the PSQI score (-0.4, p = 0.004). The stepwise regression model indicated that sleep (ß = -0.3, p = 0.02) was a significant predictor of VO2peak in males accounting for 20% of the variance, whereas physical performance seems more affected by fatigue (ß = -0.4, p = 0.03) in females. In conclusion, chronic inadequate and self-reported sleep quality seems to be one of the factors compromising cardiovascular performance in males.

Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression.

BACKGROUND: A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking. OBJECTIVE: The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.e., EDSS, relapse rate, lesion load, brain volume, MSFC) and (ii) how the physical activity and fitness level interact with these measures. METHODS: Literature search was conducted in MEDLINE, EMBASE, CINAHL, and SPORTDiscus. Evaluation of evidence quality was done based on standards published by The American Academy of Neurology. RESULTS: It is likely that exercise improves the MSFC score, whereas the EDSS score, lesion load, and brain volume are likely to remain unchanged over the intervention period. It is possible that exercise decreases the relapse rate. Results from cross-sectional studies indicate beneficial effects of a high physical activity or fitness level on clinical measures which, however, is not corroborated by high evidence quality. CONCLUSIONS: A (supportive) disease-modifying effect of exercise in pwMS cannot be concluded. The rather low evidence quality of existing RCTs underlines the need to conduct more well-designed studies assessing different measures of disease activity or progression as primary end points. A major limitation is the short intervention duration of existing studies which limits meaningful exercise-induced effects on most disability measures. Findings from cross-sectional studies are difficult to contextualize regarding clinical importance due to their solely associative character and low evidence quality. PROSPERO REGISTRATION NUMBER: CRD42020188774.

The aerobic capacity - fatigue relationship in persons with Multiple Sclerosis is not reproducible in a pooled analysis of two randomized controlled trials.

BACKGROUND: Fatigue is one of the most frequent symptoms of persons with Multiple Sclerosis (pwMS) but has limited treatment options. Aerobic capacity and endurance training have been discussed as relevant factors to improve fatigue. However, over the last decades, results have been equivocal. This secondary analysis of two pooled parallel group RCTs of three weeks of endurance training (high intensity interval training (HIIT) and moderate continuous training (MCT)) for pwMS aimed to (I) reproduce reported associations between aerobic capacity and fatigue on a cross-sectional and interventional level. The analysis further aimed to (II) investigate intervention effects on fatigue in a severely fatigued subgroup and (III) analyze differences in changes of fatigue between peak oxygen uptake (VO2peak) responders and non-responders. METHODS: Both RCTs were conducted in the same inpatient rehabilitation clinic in Valens, Switzerland. Original primary outcomes were cognitive function (RCT1) and change in proportion of circulating regulatory T-cells (RCT2). PwMS (n = 131) with a relapsing-remitting or secondary progressive MS phenotype and Expanded Disability Status Scale score between 1 - 6.5 were eligible. Over the two studies participants exercised 3 - 5 times per week on cycle ergometers at intensities of 65 - 70% of maximum heart rate (HRmax) for 30 min (MCT groups) or three times per week with five 90 - 180 s intervals at intensities of 85% - 100% of HRmax and 90 s rest intervals (HIIT groups). Main outcome measures for the present secondary analysis were VO2peak measured during a cardiopulmonary exercise test and the Fatigue Scale for Motor and Cognitive Functions (FSMC), both assessed at the start and end of inpatient rehabilitation. RESULTS: Baseline correlations did not reveal a significant association between VO2peak and FSMC. There were no significant improvements in fatigue after the HIIT and MCT in the overall sample or the subsample of severely fatigued pwMS and no significant differences in fatigue changes between VO2peak-responders and non-responders. CONCLUSIONS: Our analysis did not confirm the aerobic capacity - fatigue relationship on a cross-sectional and experimental level, even when analyzing subgroups that should benefit the most according to proposed hypotheses.

Is high-intensity interval training harmful to health?

High-intensity interval training (HIIT) is a common method to increase performance and promote health in elite sports, rehabilitation, and disease prevention. Flockhart et al. suggest a limit of HIIT above which detrimental effects on metabolic health emerge. We put these findings into context and assess the evidence that HIIT might be harmful.

Sleep problems and their interaction with physical activity and fatigue in hematological cancer patients during onset of high dose chemotherapy.

PURPOSE: Sleep problems reported by hematological cancer patients are usually linked to higher levels of cancer-related fatigue. Although the awareness of sleep problems in solid cancer patients is rising, there has been less attention to the issue in hematological cancer patients. The present study assesses the differences in sleep by comparing physical activity and fatigue levels among hematological cancer patients during the onset of chemotherapy. Furthermore, it investigates the relationship between sleep, physical activity, and fatigue through mediation analysis. METHODS: The recruited sample consists of 58 newly diagnosed hematological cancer patients (47.1 ± 15.4 yrs; 51.7% males). Subjects completed questionnaires assessing sleep (PSQI), physical activity (visual analogue scale), fatigue (MFI-20), anxiety, depression (HADS), and quality of life (EORTC QLQ-C30) within two weeks from starting treatment. RESULTS: The sample reported more sleep problems in comparison to the German population norm. The classification as good (ca 25%) or bad sleepers (ca 75%) showed less frequent physical activity (p = .04), higher fatigue (p = .032), anxiety (p = .003), depression (p = .011) and pain (p = .011) in bad sleepers. The mediation analysis revealed significant indirect effects of sleep on fatigue through physical activity habits. CONCLUSIONS: This study highlights the combined action of sleep problems and physical activity on fatigue during the onset of induction chemotherapy. These two parameters could represent meaningful intervention targets to improve a patient's status during chemotherapy. TRIAL REGISTRATION: The study was registered on the WHO trial register (DRKS00007824).

Exercise reduces systemic immune inflammation index (SII) in childhood cancer patients.

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a randomized-controlled trial. Results show associations between inflammation markers and patient-reported outcomes. Compared to the control group, SII was significantly reduced following exercise (p=0.036). Anti-inflammatory effects of exercise are also present in CCPs and may underlie exercise-induced benefits on symptoms. Clinical Trial Registration Number: NCT02612025.

How acute physical and psychological stress differentially influence the kynurenine pathway: A randomized cross-over trial.

Psychological stress is associated with the pathogenesis of several neuropsychiatric disorders. In contrast, physical stress, as provoked by exercise, counteracts symptoms and potentially also disease progression. The kynurenine pathway, which is imbalanced in neuropsychiatric disorders, responds to both psychological and physical stress. Here, we compared the acute effects of psychological versus physical stress on the kynurenine pathway and inflammatory mediators. Thirty-five healthy males (mean age: 24.09±3.39 years) underwent both the Trier Social Stress Test (psychological stressor) and the Wingate-Test (physical stressor). The kinetics of tryptophan and its metabolites as well as cytokines IL-6, IFN-γ, TNF-α, and IL-10 were measured before and after the two stress conditions. After both stressors, there was a significant change over time for the kinetics of tryptophan metabolites and for cytokines. Furthermore, the reactivity of kynurenine pathway metabolite ratios and cytokines was statistically greater after physical stress than after psychological stress. The increased metabolic flux towards kynurenic acid following acute physical stress suggests an exercise-induced neuroprotective mechanism. Despite the paradoxical influence of both stressors on neuropsychiatric diseases, the acute kynurenine pathway reactivity appears to be similar, although effects were more pronounced in response to physical stress.

Systematic Review of Exercise Studies in Persons with Multiple Sclerosis: Exploring the Quality of Interventions According to the Principles of Exercise Training.

INTRODUCTION: The objective of this systematic review is to explore the application and reporting of (i) the principles of exercise training in exercise trials, (ii) the components of exercise prescription, and (iii) the adherence towards the prescribed programmes in randomised controlled trials (RCTs) in persons with multiple sclerosis (pwMS). METHODS: The MEDLINE, CINAHL, SPORTDiscus, PubMed and Embase electronic databases were searched from 1 January 2000 to 16 October 2020. RCTs comprising at least 3 weeks of aerobic and/or resistance exercise intervention in pwMS that reported at least one physiological outcome and were published in peer-reviewed journals were eligible for inclusion. RESULTS: Out of 52 RCTs included in this review, 58 intervention arms were examined. None applied more than four principles of exercise training. Specificity was addressed by 85%, progression by 33%, overload by 59%, initial values by 26%, reversibility by 0% and diminishing returns by 2% of trials. Fifty-two percent of trials reported all components of exercise prescription, and 3% of trials reported the level of adherence to the prescribed exercise. CONCLUSION: This systematic review reveals that exercise training principles were not respected in the majority of included RCTs. The weak quality of reported exercise interventions limits the interpretation of the studies' results and potentially leads to an underestimation of 'exercise as medicine' in pwMS. Also, the vague descriptions of exercise prescription and adherence impede the reproducibility of results. Future studies must attend to all principles of exercise training and provide transparent information on the prescribed and performed programmes to develop specific and valid exercise recommendations for pwMS. SYSTEMATIC REVIEW REGISTRATION: CRD42020162671, 28/04/2020, PROSPERO.

Acute aerobic exercise to recover from mental exhaustion - a randomized controlled trial.

PURPOSE: Prolonged periods of intense cognitive activity lead to a state of mental exhaustion. While widespread strategies to recover from mental exhaustion (i.e., watching TV) are non-effective, aerobic exercise seems to be a promising approach. This can be explained by the acute and chronic aerobic exercise-induced benefits on the central nervous system. METHODS: This study investigated the potential of a single bout of moderate aerobic exercise (65-75% of each participants' individual V˙O2peak) to recover from experimentally induced mental exhaustion. A randomized controlled trial on healthy adults (N = 99) was conducted. They performed 60 min of a cognitively demanding test battery, in order to induce mental exhaustion. Subsequently, they were randomized to one of three treatments: 30 min of moderate aerobic exercise on a cycle ergometer, 30 min of a simple lower body stretching routine (= active control treatment) or watching a popular sitcom (= passive control treatment). Cognitive flexibility performance, mood, tiredness, restlessness, self-perceived cognitive capacity, and motivation were assessed before and after treatment. RESULTS: The empirical results showed that moderate aerobic exercise led to a better recovery for cognitive flexibility (mean difference divided by pooled standard deviation, Cohen's d= 0.737), mood (d= 0.405), tiredness (d= 0.480), self-perceived cognitive capacity (d= 0.214), and motivation (d= 0.524) compared to active control treatment. Moderate aerobic exercise was also more effective than passive control treatment (d= 0.102 - 0.286) with the exemption of tiredness (d= 0.015) and restlessness (d = -0.473). CONCLUSION: In conclusion, this study suggests that a single bout of acute aerobic exercise supports regeneration of cognitive flexibility performance and of subjective well-being. This holds true not just compared to artificial active control treatment but also compared to widespread leisure time activity, namely watching TV.