Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.

The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglandin-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.

Telemonitoring-Supported Exercise Training in Employees With Metabolic Syndrome Improves Liver Inflammation and Fibrosis.

INTRODUCTION: Metabolic syndrome (MetS) is a major health problem worldwide and the main risk factor for metabolic-associated fatty liver disease (MAFLD). Established treatment options are lifestyle interventions facilitating dietary change and increased physical activity. Here, we tested the effect of a telemonitoring-supported intervention on liver parameter of inflammation and fibrosis in individuals with MetS. METHODS: This was a prospective, randomized, parallel-group, and assessor-blind study performed in workers of the main Volkswagen factory (Wolfsburg, Germany). Volunteers with diagnosed MetS were randomly assigned (1:1) to a 6-month lifestyle intervention focusing on supervised, activity-tracker-guided exercise or to a waiting-list control group. This secondary analysis assessed the effect of the intervention on liver enzymes and MAFLD-related parameters. RESULTS: We screened 543 individuals between October 10, 2017, and February 27, 2018, of whom 314 were randomly assigned to the intervention group (n = 160) or control group (n = 154). Liver transaminases, alkaline phosphatase, and gamma-glutamyl transferase significantly decreased after 6 months in the intervention group compared with the CG. Furthermore, an aspartate aminotransferase-to-platelet ratio index score as a marker for liver fibrosis significantly decreased in the intervention group. These improvements were associated with changes in obesity and exercise capacity. DISCUSSION: A 6-month lifestyle intervention based on exercise training with individualized telemonitoring-based supervision led to improvements of liver inflammation and fibrosis in employees with MetS. Therefore, this intervention shows therapeutic potential for individuals at high risk of MAFLD (ClinicalTrials.gov Identifier: NCT03293264).

Energy Metabolism in Continuous, High-Intensity, and Sprint Interval Training Protocols With Matched Mean Intensity.

ABSTRACT: Eigendorf, J, Maassen, M, Apitius, D, and Maassen, N. Energy metabolism in continuous, high-intensity, and sprint interval training protocols with matched mean intensity. J Strength Cond Res 35(11): 3104-3110, 2021-To evaluate acute physiological reactions and energy metabolism with 3 different training regimes, 7 subjects performed a high-intensity interval training (HIT), a sprint interval training (SIT), and a continuous training (CT) in a cross-over design. All training sessions were matched for relative mean intensity (50% Pmax). Stress-to-pause-ratios were chosen as 6-24 seconds (SIT) and 30-30 seconds (HIT) for interval protocols. No significant differences (significance level p ≤ 0.05) were found for oxygen uptake (V̇o2), respiratory exchange ratio (RER), slope of RER (RERslope), and heart rate between the different training regimes. Lactate concentrations ([Lac]) in CT were significantly lower (p < 0.01) compared with HIT and SIT. No significant differences were found for free fatty acids ([FFA], p = 0.41) and glycerol ([GLY], p = 0.26) levels during all 3 training protocols (CT 0.27 mmol·L-1, SIT 0.22 mmol·L-1, and HIT 0.22 mmol·L-1). Ammonia (NH3, p > 0.05) levels did not show significant differences between the 3 training protocols during exercise phase. The comparable physiological reactions of [FFA], [GLY], and RER show that the activation of fat metabolism is not different between training regimes with different stress-to-pause-ratios. Moreover, mean intensity and time of exercise influence activation of fat metabolism. Increases in [NH3] suggest similar sources between the 3 training protocols and the need for further research concerning amino acid deamination. The better understanding of the acute reactions and changing of the energy metabolism during training sessions will help athletes in planning and executing their training sessions more efficiently and more precisely in the context of periodization.

Employers With Metabolic Syndrome and Increased Depression/Anxiety Severity Profit Most From Structured Exercise Intervention for Work Ability and Quality of Life.

BACKGROUND: Major depressive disorder and anxiety disorders are associated with less productivity, earlier retirement, and more sick-days at the workplace. These associations also exist for patients with metabolic syndrome. For both, exercise is a generally recommended part of multimodal treatments. However, for individuals with metabolic syndrome, in which depression and anxiety is more prevalent and severe, evidence for the efficacy of exercise interventions is limited. METHODS: Company employees with diagnosed metabolic syndrome (n=314, age: 48 ± 8 yrs) were randomized to a 6-month exercise intervention (150 min per week) or wait-list control. Participants received individual recommendations for exercise activities by personal meetings, telephone, or via a smartphone app. Physical activities were supervised and adapted using activity monitor data transferred to a central database. Work ability (work ability index), depression severity and anxiety severity [hospital anxiety and depression scale (HADS)], and health-related quality of live [short form 36 (SF-36)] were assessed. RESULTS: We included 314 subjects from which 287 finished the intervention. Total work ability, depression- and anxiety severity, and the mental component score of the SF-36 improved after 6 months exercise compared to controls. After baseline stratification for normal (HADS scores 0-7) and increased depression- and anxiety scores (HADS scores 8-21) individuals with increased severity scores had similar age, body composition, blood lipids, and cardiorespiratory fitness compared to those with normal scores, but lower total work ability and component sum scores of health-related quality of life. After 6 months total work ability increased in the exercise group compared to controls with the magnitude of the observed increase being significantly greater for subjects with increased depression- and anxiety severity at baseline compared to those with normal severity scores. CONCLUSIONS: A 6-month exercise intervention for company employees with metabolic syndrome showed strongest effects on self-perceived work ability in individuals with mild to severe depression- and anxiety severity. This suggests exercise programs offered to workers with metabolic syndrome not only reduces individual disease risk but may also reduce healthcare and employers costs arising from metabolic syndrome and mental disease conditions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03293264.

Effects of six month personalized endurance training on work ability in middle-aged sedentary women: a secondary analysis of a randomized controlled trial.

BACKGROUND: To test the effects of guided endurance training on work ability in middle-aged female hospital workers of various occupations. METHODS: We randomized 265 healthy, sedentary, middle-aged women (45-65 years) to an endurance training group (EG 210 min/week) or a wait-list control group (CG). At baseline and at 6-month follow-up, we assessed work ability (Work Ability Index [WAI]), physical activity (Freiburger activity questionnaire) and peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. To examine the influence of baseline work ability, participants were divided into poor-moderate (WAI 1, 7-36 points, n = 83), good (WAI 2, 37-43 points, n = 136) and excellent (WAI 3, 44-49 points, n = 46) WAI subgroups. RESULTS: Cardiorespiratory fitness improved significantly after 6 months in the EG but not in the CG. The WAI total score increased significantly in the EG (38.3 ± 5.0 to 39.8 ± 4.9 points) but not in the CG (39.4 ± 4.7 to 39.3 ± 4.9 points), with a significant difference between groups (p < 0.01). In the EG, only the poor-moderate subgroup (WAI 1, 33.0 ± 2.9 to 36.6 ± 4.8 points, p < 0.05) increased the WAI total score, with this increase being significantly higher compared to the good (WAI 2, 40.2 ± 2.1 to, 40.4 ± 3.7 points) and excellent (WAI 3, 45.6 ± 1.5 to 45.7 ± 1.8 points) subgroup. CONCLUSIONS: A 6-month guided exercise training intervention significantly increases cardiorespiratory fitness with concomitant improvements in work ability in middle-aged previously sedentary hospital employees. Women with low baseline work ability seem to particularly benefit from the intervention, which implies that similar interventions may be particularly beneficial for this group of individuals. TRIAL REGISTRATION: German Clinical Trails Register Identifier: DRKS00005159. Registered 25 September 2013.

Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians.

Keywords: sirtuins; vegetarian; vegan; exercise; endurance athletes; metabolic regulation.

High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT?

BACKGROUND: Adoptive transfer of virus-specific T cells (VSTs) represents a prophylactic and curative approach for opportunistic viral infections and reactivations after transplantation. However, inadequate frequencies of circulating memory VSTs in the T-cell donor's peripheral blood often result in insufficient enrichment efficiency and purity of the final T-cell product, limiting the effectiveness of this approach. METHODS: This pilot study was designed as a cross-over trial and compared the effect of a single bout (30 min) of high-intensity interval training (HIT) with that of 30 min of continuous exercise (CONT) on the frequency and function of circulating donor VSTs. To this end, we used established immunoassays to examine the donors' cellular immune status, in particular, with respect to the frequency and specific characteristics of VSTs restricted against Cytomegalovirus (CMV)-, Epstein-Barr-Virus (EBV)- and Adenovirus (AdV)-derived antigens. T-cell function, phenotype, activation and proliferation were examined at different time points before and after exercise to identify the most suitable time for T-cell donation. The clinical applicability was determined by small-scale T-cell enrichment using interferon- (IFN-) γ cytokine secretion assay and virus-derived overlapping peptide pools. RESULTS: HIT proved to be the most effective exercise program with up to fivefold higher VST response. In general, donors with a moderate fitness level had higher starting and post-exercise frequencies of VSTs than highly fit donors, who showed significantly lower post-exercise increases in VST frequencies. Both exercise programs boosted the number of VSTs against less immunodominant antigens, specifically CMV (IE-1), EBV (EBNA-1) and AdV (Hexon, Penton), compared to VSTs against immunodominant antigens with higher memory T-cell frequencies. CONCLUSION: This study demonstrates that exercise before T-cell donation has a beneficial effect on the donor's cellular immunity with respect to the proportion of circulating functionally active VSTs. We conclude that a single bout of HIT exercise 24 h before T-cell donation can significantly improve manufacturing of clinically applicable VSTs. This simple and economical adjuvant treatment proved to be especially efficient in enhancing virus-specific memory T cells with low precursor frequencies.

Exercise-Induced Oxidative Stress, Nitric Oxide and Plasma Amino Acid Profile in Recreational Runners with Vegetarian and Non-Vegetarian Dietary Patterns.

This study investigated the exercise-induced changes in oxidative stress, nitric oxide (NO) metabolism and amino acid profile in plasma of omnivorous (OMN, n = 25), lacto-ovo-vegetarian (LOV, n = 25) and vegan (VEG, n = 23) recreational runners. Oxidative stress was measured as malondialdehyde (MDA), NO as nitrite and nitrate, and various amino acids, including homoarginine and guanidinoacetate, the precursor of creatine. All analytes were measured by validated stable-isotope dilution gas chromatographic-mass spectrometric methods. Pre-exercise, VEG had the highest MDA and nitrate concentrations, whereas nitrite concentration was highest in LOV. Amino acid profiles differed between the groups, with guanidinoacetate being highest in OMN. Upon acute exercise, MDA increased in the LOV and VEG group, whereas nitrate, nitrite and creatinine did not change. Amino acid profiles changed post-exercise in all groups, with the greatest changes being observed for alanine (+28% in OMN, +21% in LOV and +28% in VEG). Pre-exercise, OMN, LOV and VEG recreational runners differ with respect to oxidative stress, NO metabolism and amino acid profiles, in part due to their different dietary pattern. Exercise elicited different changes in oxidative stress with no changes in NO metabolism and closely comparable elevations in alanine. Guanidinoacetate seems to be differently utilized in OMN, LOV and VEG, pre- and post-exercise.

Exercise capacity of vegan, lacto-ovo-vegetarian and omnivorous recreational runners.

BACKGROUND: In search of the right nutrition for the athlete, numerous nutritional strategies and diets were discussed over time. However, the influence of plant-based diets, especially veganism, on exercise capacity has not been clarified. METHODS: We conducted a cross-sectional study to compare the exercise capacity of vegan (VEG, n = 24), lacto-ovo-vegetarian (LOV, n = 26) and omnivorous (OMN, n = 26) recreational runners. To determine maximal exercise capacity, participants performed an incremental exercise test on a bicycle ergometer until voluntary exhaustion. During the test capillary blood samples were taken at several time points for the measurement of arterial lactate [lac] and glucose [glc] concentrations. To determine nutrient intake, a 24 h dietary recall was conducted. RESULTS: The groups showed comparable training habits in terms of training frequency (mean 3.08 ± 0.90 time/wk., p = 0.735), time (mean 2.93 ± 1.34 h/wk., p = 0.079) and running distance (mean 29.5 ± 14.3 km/wk., p = 0.054). Moreover, similar maximum power output (PmaxBW) was observed in all three groups (OMN: 4.15 ± 0.48 W/kg, LOV: 4.20 ± 0.47 W/kg, VEG: 4.16 ± 0.55 W/kg; p = 0.917) and no differences regarding [lac] throughout the exercise test and maximum lactate could be observed between the groups (OMN: 11.3 ± 2.19 mmol/l, LOV: 11.0 ± 2.59 mmol/l, VEG: 11.9 ± 1.98 mmol/l; p = 0.648). CONCLUSION: The data indicate that each examined diet has neither advantages nor disadvantages with regard to exercise capacity. These results suggest that a vegan diet can be a suitable alternative for ambitious recreational runners. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00012377 ). Registered on 28 April 2017.

Micronutrient Status of Recreational Runners with Vegetarian or Non-Vegetarian Dietary Patterns.

Vegetarian diets have gained popularity in sports. However, few data exist on the status of micronutrients and related biomarkers for vegetarian and vegan athletes. The aim of this cross-sectional study was to compare the micronutrient status of omnivorous (OMN, n = 27), lacto-ovo-vegetarian (LOV, n = 26), and vegan (VEG, n = 28) recreational runners. Biomarkers of vitamin B12, folate, vitamin D, and iron were assessed. Additionally, serum levels of calcium, magnesium, and zinc were examined. Lifestyle factors and supplement intake were recorded via questionnaires. About 80% of each group showed vitamin B12 adequacy with higher levels in supplement users. Mean red blood cell folate exceeded the reference range (>340 nmol/L) in all three groups (OMN: 2213 ± 444, LOV: 2236 ± 596, and VEG: 2354 ± 639 nmol/L; not significant, n.s.). Furthermore, vitamin D levels were comparable (OMN: 90.6 ± 32.1, LOV: 76.8 ± 33.7, and VEG: 86.2 ± 39.5 nmol/L; n.s.), and we found low prevalence (<20%) of vitamin D inadequacy in all three groups. Less than 30% of each group had depleted iron stores, however, iron deficiency anemia was not found in any subject. Our findings suggest that a well-planned, health-conscious lacto-ovo-vegetarian and vegan diet, including supplements, can meet the athlete's requirements of vitamin B12, vitamin D and iron.

Characterization, dietary habits and nutritional intake of omnivorous, lacto-ovo vegetarian and vegan runners - a pilot study.

BACKGROUND: The number of people preferring plant-based nutrition is growing continuously in the western world. Vegetarianism and veganism are also becoming increasingly popular among individuals participating in sport. However, whether recreationally active vegetarian and vegan populations can meet their nutritional needs is not clear. METHODS: The purpose of this cross-sectional study was to compare the nutrient intake of omnivorous (OMN, n = 27), lacto-ovo vegetarian (LOV, n = 25) and vegan (VEG, n = 27) recreational runners (two to five training sessions per week) with intake recommendations of the German, Austrian and Swiss Nutrition Societies (Deutsche, Österreichische und Schweizerische Gesellschaften für Ernährung, D-A-CH) for the general population. Lifestyle factors and supplement intake were examined via questionnaires; dietary habits and nutrient intake were determined based on 3-day dietary records. RESULTS: More than half of each group did not reach the recommended energy intake (OMN: 10.4, 8.70-12.1; LOV: 9.67, 8.55-10.8; VEG: 10.2, 9.12-11.3 MJ). Carbohydrate intake was slightly below the recommendations of > 50 EN% in OMN (46.7, 43.6-49.8 EN%), while LOV (49.4, 45.5-53.3 EN%) and VEG (55.2, 51.4-59.0 EN%) consumed adequate amounts (p = 0.003). The recommended protein intake of 0.8 g/kg body weight (D-A-CH) was exceeded in all three groups (OMN: 1.50, 1.27-1.66; LOV: 1.34, 1.09-1.56; VEG: 1.25; 1.07-1.42 g/kg BW; p = 0.047). Only VEG (26.3, 22.7-29.8 EN%) did not achieve the recommended fat intake of 30 EN%. The supply of micronutrients, such as vitamin D and cobalamin, was dependent on supplement intake. Additionally, female OMN and LOV achieved the recommended daily intake of 15 mg iron only after supplementation, while VEG consumed adequate amounts solely via food. CONCLUSION: All three groups were sufficiently supplied with most nutrients despite the exceptions mentioned above. The VEG group even showed advantages in nutrient intake (e.g. carbohydrates, fiber and iron) in comparison to the other groups. However, the demand for energy and several macro- and micronutrients might be higher for athletes. Thus, it is also necessary to analyze the endogenous status of nutrients to evaluate the influence of a vegetarian and vegan diet on the nutrient supply of athletes. TRIAL REGISTRATION: German Clinical Trial Register (DRKS00012377), registered on April 28, 2017.

High Intensity High Volume Interval Training Improves Endurance Performance and Induces a Nearly Complete Slow-to-Fast Fiber Transformation on the mRNA Level.

We present here a longitudinal study determining the effects of two 3 week-periods of high intensity high volume interval training (HIHVT) (90 intervals of 6 s cycling at 250% maximum power, Pmax/24 s) on a cycle ergometer. HIHVT was evaluated by comparing performance tests before and after the entire training (baseline, BSL, and endpoint, END) and between the two training sets (intermediate, INT). The mRNA expression levels of myosin heavy chain (MHC) isoforms and markers of energy metabolism were analyzed in M. vastus lateralis biopsies by quantitative real-time PCR. In incremental tests peak power (Ppeak) was increased, whereas V˙ O2peak was unaltered. Prolonged time-to-exhaustion was found in endurance tests with 65 and 80% Pmax at INT and END. No changes in blood levels of lipid metabolites were detected. Training-induced decreases of hematocrit indicate hypervolemia. A shift from slow MHCI/ß to fast MHCIIa mRNA expression occurred after the first and second training set. The mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a master regulator of oxidative energy metabolism, decreased after the second training set. In agreement, a significant decrease was also found for citrate synthase mRNA after the second training set, indicating reduced oxidative capacity. However, mRNA expression levels of glycolytic marker enzyme glyceraldehyde-3-phosphate dehydrogenase did not change after the first and second training set. HIHVT induced a nearly complete slow-to-fast fiber type transformation on the mRNA level, which, however, cannot account for the improvements of performance parameters. The latter might be explained by the well-known effects of hypervolemia on exercise performance.