The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans.

Whether cyclooxygenase (COX)/prostaglandin E2 (PGE2) thermoregulatory pathways, observed in rodents, present in humans? Participants (n = 9) were exposed to three environments; cold (20 °C), thermoneutral (30 °C) and hot (40 °C) for 120 min. Core (Tc)/skin temperature and thermal perception were recorded every 15 min, with COX/PGE2 concentrations determined at baseline, 60 and 120 min. Linear mixed models identified differences between and within subjects/conditions. Random coefficient models determined relationships between Tc and COX/PGE2. Tc [mean (range)] increased in hot [+ 0.8 (0.4-1.2) °C; p < 0.0001; effect size (ES): 2.9], decreased in cold [- 0.5 (- 0.8 to - 0.2) °C; p < 0.0001; ES 2.6] and was unchanged in thermoneutral [+ 0.1 (- 0.2 to 0.4) °C; p = 0.3502]. A relationship between COX2/PGE2 in cold (p = 0.0012) and cold/thermoneutral [collapsed, condition and time (p = 0.0243)] was seen, with higher PGE2 associated with higher Tc. A within condition relationship between Tc/PGE2 was observed in thermoneutral (p = 0.0202) and cold/thermoneutral [collapsed, condition and time (p = 0.0079)] but not cold (p = 0.0631). The data suggests a thermogenic response of the COX/PGE2 pathway insufficient to defend Tc in cold. Further human in vivo research which manipulates COX/PGE2 bioavailability and participant acclimation/acclimatization are warranted to elucidate the influence of COX/PGE2 on Tc.

Skeletal Muscle Signaling Following Whole-Body and Localized Heat Exposure in Humans.

This study identified the changes in hypertrophy/atrophy and mitochondrial-related signaling in human skeletal muscle following whole-body (WB) and localized single leg (SL) heat treatment. Nine active male participants were administered either 60 min of passive WB (44-50°C, 50% humidity) or SL (water-perfused suit at 49.5 ± 1.4°C) heat treatment at least 1 week apart in a counterbalanced order. The untreated leg during SL was considered as control (CON). Core, skin, and quadriceps muscle temperature were monitored throughout the experimental trials. Muscle microbiopsy samples were obtained prior to (PRE), and 30 min and 3 h post (POST) following heat treatment. Muscle temperature increased with time (p < 0.0001) in both WB and SL, with no differences between conditions (38.8 ± 0.5°C vs. 38.1 ± 0.6°C, p = 0.065). Core temperature increased only following WB, and was significantly higher compared with SL (39.1 ± 0.3°C vs. 37.1 ± 0.1, p < 0.0001). Compared with PRE, WB up-regulated the phosphorylation status of the majority of the Akt/mTOR pathway (Akt, mTOR, S6K1, rpS6, and p-eIF4E; p ≤ 0.050), with the exception of 4EBP1 (p = 0.139). WB also increased the mRNA of HSPs 72, 90, and 25 (all p < 0.021), and increased or tended to increase the phosphorylation of FOXO1 (p = 0.066) and FOXO3a (p = 0.038). In addition, most (NRF1, NRF2, COX2, and COX4-I2; all p ≤ 0.050), but not all (CS, Cyt c, and COX4-I1; p > 0.441) mRNA content indicative of mitochondrial biogenesis were increased following WB, with no changes evident in these parameters in SL or CON (all p > 0.090). These results indicate that 1 h of WB heat treatment enhanced anabolic (Akt/mTOR), mitochondrial, and cyto-protective signaling (HSP), with a concomitant possible inhibition of FOXO transcription factors.

A novel mixed living high training low intervention and the hematological module of the athlete biological passport.

Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well-trained middle-distance runners participated in a "live high, train low and high" (LHTLH) altitude training camp for 14 days. The participants spent ˜6 hr.d-1 at 3000-5400 m during waking hours and ˜10 h.d-1 overnight at 2400-3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF-score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an "atypical passport finding" (ATPF) due to deviation of the OFF-score. When this sample was evaluated by ABP experts it was considered "normal". In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.

The Effects of a Single Versus Three Consecutive Sessions of Football Training on Postprandial Lipemia: a Randomized, Controlled Trial in Healthy, Recreationally Active Males.

BACKGROUND: Exercise frequency is important for maintaining health; however, its effects on postprandial responses remain largely unknown. Better understanding this during popular sports activities such as football may influence exercise habits. Therefore, the aim of the present study was to examine the effects of playing one single versus three consecutive days of 60-min small-sided football matches on postprandial lipemia. METHODS: Fifteen males performed either one (1FOOT; n = 7) or three 60-min football (3FOOT; n = 8) sessions across an 8-day trial period. On day 1, a blood sample was collected at fasted (0 min) and 0.75, 2, 4, 6 h after a high-fat meal. Participants were then randomly allocated to the 1FOOT (day 7) or 3FOOT (days 5, 6, 7) condition. On day 8, they repeated the high-fat meal and blood sampling for 6 h following the meal. Postprandial total and incremental area under the curve (AUC, iAUC, respectively) were calculated. RESULTS: The postprandial triglyceride iAUC was 41% lower from pre- to post-measures for the 1FOOT (p < 0.05; ES = 1.02) and 15.7% lower for the 3FOOT (ns; ES = 0.41). Total triglyceride AUC was lower (26%) post-football matches in the 3FOOT group only (p < 0.01; ES = 1.23). In 3FOOT, insulin concentration was lower for post- compared to pre-measures at 0.75 and 2 h, respectively (p < 0.001). CONCLUSION: One single 60-min small-sided football match lowered postprandial TG incremental area under the curve while performing three consecutive days of football matches did not result in a greater attenuation. TRIAL REGISTRATION: ISRCTN17934193 , registered 06 April 2019.

Breaking up prolonged sitting with moderate-intensity walking improves attention and executive function in Qatari females.

BACKGROUND: Cultural, environmental and logistical factors promote a sedentary lifestyle within Qatar, particularly for females. Sedentary behaviour is acutely associated with poor cognitive function and fatigue, and chronically may be implicated with cognitive decline (i.e. Alzheimer's disease). PURPOSE: To examine the effects of breaking up sitting with short-duration frequent walking bouts on cognitive function and fatigue in Qatari females. METHOD: Eleven sedentary (sitting ≥7 h/day) females completed three visits; the first being familiarisation. In a cross-over randomised manner, experimental visits two and three were identical, except participants either remained seated for 5-h (SIT) or interrupted their sitting every 30-min with a 3-min moderate-intensity walk (WALK) on a motorised treadmill. The Computerised Mental Performance Assessment System (COMPASS) assessed cognition at baseline (-15-min), and then at 2.5-h and 5-h into the experimental conditions. Specific COMPASS tasks employed were; serial-3 subtractions (2-min), serial-7 subtractions (2-min), simple reaction time (RT; 50 stimuli), rapid visual information processing [RVIP (5-min)], choice reaction time (CRT; 50 stimuli), and Stroop (60 stimuli); and a visual analogue scale for fatigue (VAS-F) was completed at the same time intervals. RESULTS: There was a significant condition effect for CRT (f = 26.7, p = 0.007). On average CRT was 101 s (95% CI = -47 to -156 s) quicker in WALK compared to SIT. There was a significant time effect for CRT (f = 15.5, p = 0.01). On average CRT was 134 s slower at 5-h compared to baseline (p = 0.006; 95% CI = -64 to -203 s), and 114 s slower at 5-h compared to 2.5-h (p = 0.01; 95% CI = -44 to -183 s). There was a significant interaction effect for RT in the Stroop incongruent task (f = 10.0, p = 0.03). On average RT was 210 s quicker at 2.5-h in WALK compared to SIT (p = 0.01; 95% CI = -76 to -346 s). CONCLUSION: Breaking up prolonged sitting with moderate-intensity walking offers an ecologically valid intervention to enhance some aspects of cognitive function, whilst not affecting fatigue in sedentary Qatari females. Whilst these findings are promising, the long-term effects of breaking up sitting on cognitive function requires testing before population level recommendations can be made.

Postprandial Insulin and Triglyceride Concentrations Are Suppressed in Response to Breaking Up Prolonged Sitting in Qatari Females.

Background: Cultural, environmental and logistical factors challenge the Qatari population, particularly females, to engage in physical activity, and there is a high prevalence of diabetes in this population. Sedentary behavior is associated with increased cardiometabolic disease risk and early mortality and breaking up sitting can attenuate postprandial cardiometabolic risk markers. However, no studies have evaluated the cardiometabolic response to breaking up sitting in a Qatari population. Purpose: To examine the effects of breaking up sitting with moderate-intensity walking breaks on cardiometabolic disease markers in Qatari females. Methods: Eleven sedentary (sitting ≥ 7 h/day) females completed two experimental conditions in a cross-over randomized design. The two conditions were identical, except participants either remained seated for 5-h (SIT), or interrupted their sitting every 30-min with a 3-min walk (WALK) on a motorized treadmill (rating of perceived exertion 12-14). A fasting venous blood sample was obtained at baseline (-10-min) followed by samples at 0.5-, 1-, 2-, 3-, 3.5-, 4-, and 5-h. Postprandial cardiometabolic variables (insulin, glucose, triglycerides) were calculated as derivatives of total area under the curve [AUC; total (tAUC), net incremental (iAUC) and positive AUC]. Results: Data is reported as effect size; ±90% confidence limit. There was a most likely "moderate" lower tAUC (-0.92 ± 0.26), iAUC (-0.96 ± 0.33), and positive AUC (-0.96 ± 0.33) for insulin in WALK compared to SIT. Additionally, there was a most likely "moderate" lower tAUC (-0.63 ± 0.37), iAUC (-0.91 ± 0.49), and positive AUC (-0.91 ± 0.49) for triglycerides in WALK compared to SIT. Glucose did not differ between conditions. Conclusion: Breaking up prolonged sitting with moderate-intensity walking offers a culturally compatible intervention to acutely improve cardiometabolic risk markers in sedentary Qatari females. Whilst the data offers promise, the long-term chronic effects of breaking up sitting in Qatari adults requires investigation before population level and/or policy recommendations can be made.

Exploring possible relationships between 25(OH)D deficiency and variables related to inflammation, endothelial function, and enzymatic antioxidants in adolescent athletes: a prospective study.

Although the role of vitamin D in calcium and bone metabolism is well documented, there is little clarity regarding the implications of low vitamin D status for inflammation, endothelial function, and antioxidant status in adolescent athletes. A prospective cohort study was conducted, and 44 male adolescent athletes, training at a sports academy in the Middle East, were assigned to either the intervention group (VitDs), consisting of vitamin D deficient athletes [twenty-five hydroxyvitamin D (25(OH)D) <20 ng/ml; n = 22], or the comparison group, consisting of vitamin D sufficient athletes [25(OH)D >30 ng/ml; n = 22]. Vitamin D status, inflammatory cytokines, endothelium-related variables, and antioxidant enzymes were measured twice during a nine-week training period. At the baseline, the athletes in the VitDs group had significantly lower concentrations of 25(OH)D, vascular endothelial growth factor (VEGF), and glutathione peroxidase (GPx), and higher levels of parathyroid hormone (PTH), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and nitrite (NO2) (p < 0.05), in comparison to the athletes in the sufficient group. After vitamin D supplementation for the VitDs group, the two cohorts differed considerably in vitamin D binding protein (VDBP) and PTH concentrations (p < 0.05). Our data suggest that the low levels of vitamin D possibly induced alterations in the investigated biochemical parameters of athletes in the VitDs group at the beginning of the monitoring period. Furthermore, while the vitamin D supplementation was effective in increasing 25(OH)D status, it may have concurrently positively influenced variables that are related to inflammation, endothelial function, and enzymatic antioxidants.

Repeated-sprints exercise in daylight fasting: carbohydrate mouth rinsing does not affect sprint and reaction time performance.

To determine the effect of carbohydrate mouth rinsing (CHO-MR) on physical and cognitive performance during repeated-sprints (RS) after 3 days of intermittent fasting (abstaining from food and fluid 14 h per day). In a randomized and counter-balanced manner 15 active healthy males in a fasted state performed a RS-protocol [RSP; 2 sets (SET1 and SET2) of 5×5 s maximal sprints, with each sprint interspersed with 25 s rest and 3 min of recovery between SET1 and SET2] on an instrumented non-motorized treadmill with embedded force sensors under three conditions: i) Control (CON; no-MR), ii) Placebo-MR (PLA-MR; 0% maltodextrin) and iii) CHO-MR (10% maltodextrin). Participants rinsed their mouth with either 10 mL of PLA-MR or CHO-MR solution for 5 s before each sprint. Sprint kinetics were measured for each sprint and reaction time (RTI) tasks (simple and complex) were assessed pre-, during- and post-RSP. There was no statistical main effect of CHO-MR on mean power, mean speed, and vertical stiffness during the sprints between the PLA-MR and CON condition. Additionally, no statistical main effect for CHO-MR on accuracy, movement time and reaction time during the RTI tasks was seen. CHO-MR did not affect physical (RSP) or cognitive (RTI) performance in participants who had observed 3 days of intermittent fasting (abstaining from food and fluid 14 h per day).

Why don't serum vitamin D concentrations associate with BMD by DXA? A case of being 'bound' to the wrong assay? Implications for vitamin D screening.

BACKGROUND: The association between bone mineral density (BMD) and serum25-hydroxyvitamin D (25(OH)D) concentration is weak, particularly in certain races (eg, BlackAfrican vs Caucasian) and in athletic populations. We aimed to examine if bioavailable vitamin D rather than serum 25(OH)D was related to markers of bone health within a racially diverse athletic population. METHODS: In 604 male athletes (Arab (n=327), Asian (n=48), Black (n=108), Caucasian (n=53) and Hispanic (n=68)), we measured total 25(OH)D, vitamin D-binding protein and BMD by DXA. Bioavailable vitamin D was calculated using the free hormone hypothesis. RESULTS: From 604 athletes, 21.5% (n=130) demonstrated severe 25(OH)D deficiency, 37.1% (n=224) deficiency, 26% (n=157) insufficiency and 15.4% (n=93) sufficiency. Serum 25(OH)D concentrations were not associated with BMD at any site. After adjusting for age and race, bioavailable vitamin D was associated with BMD (spine, neck and hip). Mean serum vitamin D binding protein concentrations were not associated with 25(OH)D concentrations (p=0.392). CONCLUSION: Regardless of age or race, bioavailable vitamin D and not serum 25(OH)D was associated with BMD in a racially diverse athletic population. If vitamin D screening is warranted, clinicians should use appropriate assays to calculate vitamin D binding protein and bioavailable vitamin D levels concentrations than serum 25(OH)D. In turn, prophylactic vitamin D supplementation to 'correct' insufficient athletes should not be based on serum 25(OH)D measures.

Repeated Sprints in Fasted State Impair Reaction Time Performance.

OBJECTIVE: The aim of this study was to assess the effects of 3-day Islamic intermittent fasting (3d-IF) on cognitive performance and serum levels of neurotrophic factors (brain-derived neurotrophic factor [BDNF] and vascular endothelial growth factor [VEGF]) before and after repeated sprints. METHODS: Twenty-one physically active male Muslims (29.8 ± 5.9 years, exercising 4 ± 1.5 times/week) were randomly assigned to one of 2 experimental sessions: the control or nonfasting session (CS) or the fasting session (FS). These 2 sessions occurred 7 days apart in a counterbalanced crossover design. In both conditions, the test was performed at the same time of day, approximately 1 hour before sunset. In the FS, the test occurred on the third day of the 3d-IF and involved the participants' performance of the following: (a) two series of 5 maximal 5-second sprints and (b) 2 cognitive tasks: One Touch Stockings (OTS) and reaction time (simple and complex RTI). RESULTS: In both conditions, the participants' reaction times during the RTI test were similar at the pre- and mid-exercise points, but postexercise, simple and complex reaction times were higher in FS compared to CS (p = 0.045, effect size [ES] = 0.21 and p = 0.006, ES = 0.41, respectively). However, OTS performance and serum levels of neurotrophic factors were not influenced by the 3d-IF. CONCLUSION: Simple and complex reaction times during the RTI test were negatively affected by the 3d-IF after 2 bouts of intensive repeated sprints.

Three Days of Intermittent Fasting: Repeated-Sprint Performance Decreased by Vertical-Stiffness Impairment.

PURPOSE: To examine the effects of 3 d of intermittent fasting (3d-IF: abstaining from eating/drinking from dawn to sunset) on physical performance and metabolic responses to repeated sprints (RSs). METHODS: Twenty-one active males performed an RS test (2 sets: 5 × 5-s maximal sprints with 25 s of recovery between and 3 min of recovery between sets on an instrumented treadmill) in 2 conditions: counterbalanced fed/control session (CS) and fasting session (FS). Biomechanical and biochemical markers were assessed preexercise and postexercise. RESULTS: Significant main effects of IF were observed for sprints: maximal speed (P = .016), mean speed (P = .015), maximal power (P = .035), mean power (P = .049), vertical stiffness (P = .032), and vertical center-of-mass displacement (P = .047). Sprint speed and vertical stiffness decreased during the 1st (P = .003 and P = .005) and 2nd sprints (P = .046 and P = .048) of set 2, respectively. Postexercise insulin decreased in CS (P = .023) but not in FS (P = .230). Free-fatty-acid levels were higher in FS than in CS at preexercise (P < .001) and at postexercise (P = .009). High-density lipoprotein cholesterol (HDL-C) was higher at postexercise in FS (1.32 ± 0.22 mmol/L) than in CS (1.26 ± 0.21 mmol/L, P = .039). The triglyceride (TG) concentration was decreased in FS (P < .05) compared with CS. CONCLUSIONS: 3d-IF impaired speed and power through a decrease in vertical stiffness during the initial runs of the 2nd set of RS. The findings of the current study confirmed the benefits of 3d-IF: improved HDL-C and TG profiles while maintaining total cholesterol and low-density lipoprotein cholesterol levels. Moreover, improving muscle power might be a key factor to retain a higher vertical stiffness and to partly counteract the negative effects of intermittent fasting.

Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults.

The aim of this review was to highlight the potent effects of intermittent fasting on the cognitive performance of athletes at rest and during exercise. Exercise interacts with dietary factors and has a positive effect on brain functioning. Furthermore, physical activity and exercise can favorably influence brain plasticity. Mounting evidence indicates that exercise, in combination with diet, affects the management of energy metabolism and synaptic plasticity by affecting molecular mechanisms through brain-derived neurotrophic factor, an essential neurotrophin that acts at the interface of metabolism and plasticity. The literature has also shown that certain aspects of physical performance and mental health, such as coping and decision-making strategies, can be negatively affected by daylight fasting. However, there are several types of intermittent fasting. These include caloric restriction, which is distinct from fasting and allows subjects to drink water ad libitum while consuming a very low-calorie food intake. Another type is Ramadan intermittent fasting, which is a religious practice of Islam, where healthy adult Muslims do not eat or drink during daylight hours for 1 month. Other religious practices in Islam (Sunna) also encourage Muslims to practice intermittent fasting outside the month of Ramadan. Several cross-sectional and longitudinal studies have shown that intermittent fasting has crucial effects on physical and intellectual performance by affecting various aspects of bodily physiology and biochemistry that could be important for athletic success. Moreover, recent findings revealed that immunological variables are also involved in cognitive functioning and that intermittent fasting might impact the relationship between cytokine expression in the brain and cognitive deficits, including memory deficits.

Anti-tumoral effect of native and immobilized bovine serum amine oxidase in a mouse melanoma model.

Bovine serum amine oxidase (BSAO) oxidatively deaminates polyamines containing primary amine groups, spermidine and spermine, to form the cytotoxic products hydrogen peroxide and aldehyde(s). Polyamines are present at elevated levels in many tumor tissues. The aims of the study were to evaluate the anti-tumoral activities of native and immobilized BSAO in mouse melanoma and also to determine the mechanism of tumor cell death. C57BL mice received a subcutaneous injection of B16 melanoma cells to induce formation of tumors, prior to antitumor treatments with native and immobilized BSAO. The enzyme was immobilized in a poly(ethylene glycol) (PEG) biocompatible matrix. Antitumor treatments consisted of a single injection of enzyme into the tumor. When immobilized BSAO (2.5mU) was injected into the tumor, there was a marked decrease of 70% of the tumor growth. This was compared with a decrease of only 32% of tumor size when the same amount of native BSAO was administered. The type of cell death was analysed in tumors that were treated with native or immobilized BSAO. When tumors were treated with immobilized BSAO, there was induction of a high level of apoptosis (around 70%), compared to less than 10% with the native enzyme. Apoptotic cell death was assessed by nuclear chromatin condensation using Hoechst staining and labelling of externalized phosphatidylserine using Annexin V. However, native BSAO, probably due to a burst of cytotoxic products, induced a high level of necrosis of about 40%, compared to less than 10% with immobilized BSAO. In conclusion, the advantage is that immobilized BSAO can act by allowing the slow release of cytotoxic products, which induces tumor cell death by apoptosis rather than necrosis.