Exercise in the heat often causes gastrointestinal (GI) disturbances, which can impair performance. Single amino acid supplementation can attenuate gut damage and enhance exercise tolerance; however, the effectiveness of innate amino acid blends from plant-based proteins remains underexplored. In this study, we investigated the effects of a novel fava bean-derived plant protein (ATURA) on thermoregulation, endurance performance and GI disturbances during exercise. Twelve healthy, non-heat-acclimatized participants completed an exercise trial (10 min walk, 40 min run, graded exercise test) in the heat (35°C; 40% relative humidity), before and after 8 days of ATURA (60 g/day) or placebo, in a double-blind, randomized, cross-over design. Whole-body sweat rate, local sweat rate, pulmonary gas exchange, skin and core temperature and perceptual responses were monitored, with pre- and post-trial blood samples. ATURA increased whole-body sweat rate (11%; P = 0.03) and back local sweat rate (11%; P < 0.001) and reduced core temperature (ATURA, 38.7°C ± 0.5°C; placebo, 38.8°C ± 0.5°C; P = 0.04) and thermal sensation (P = 0.05) in comparison to placebo. There were no differences for skin temperature, thermal comfort or graded exercise test time (P > 0.05). ATURA reduced postexercise intestinal fatty-acid binding protein (22%) compared with placebo (P = 0.05), with no difference for soluble CD14 or GI symptoms. Pre-to-post HSP70 was higher after ATURA (12%, P = 0.05), with no difference for interleukin-6 (P > 0.05). Pre-exercise fava bean protein reduced postexercise intestinal fatty-acid binding protein, indicating a potential protective effect on intestinal integrity, and was well tolerated, without increasing GI symptoms. Exploratory outcomes suggest possible thermoregulatory benefits, warranting further investigation.

Background/Objectives: Adenosine monophosphate deaminase deficiency has been implicated in impaired exercise capacity. We examined whether the AMPD1 C34T (rs17602729) genotype was associated with athlete status and performance in distance runners (DRs) and rugby union (RU) athletes. Methods: Participants included 621 elite male RU athletes, 666 elite/sub-elite male and female DRs, and 1029 male and female non-athletes (NA), all of European ancestry. Genotyping was performed using real-time PCR with TaqMan reagents. Genotype and allele frequencies were compared using χ2 tests, while performance data were analysed using Kruskal-Wallis H, Mann-Whitney U, one-way ANOVA, and t-tests, with Benjamini-Hochberg correction applied for multiple comparisons. Results: Genotype and allele frequencies did not differ between athletes and NA or between athlete groups. In all DRs, run times did not differ between genotypes, although participants with the CT genotype in the elite and elite male subgroups were up to 5% faster than CC and TT homozygotes. In RU, participants with the CC genotype played 13% longer per appearance than those with the CT genotype, while forwards and front five participants with the CC genotype played 13% and 26% longer per appearance than T-allele carriers, respectively. Front five T-allele carriers made 75% more clean breaks than the front five with the CC genotype despite playing for a shorter time, although this finding should be interpreted cautiously. Conclusions: In summary, while the AMPD1 C34T genotype was not associated with athlete status, the CC genotype was associated with greater RU playing time per appearance in forwards, and the CT genotype was associated with superior performance in elite DRs.

Dietary supplements are widely used among individuals exposed to hot environments, but whether their consumption confers any thermoregulatory effect is unclear. Therefore, we systematically evaluated the effect of dietary supplementation on key aspects of thermoregulation [core temperature (Tcore) and sweating responses] in the heat. Three databases were searched in April 2024. After screening, 124 peer-reviewed articles were identified for inclusion within three separate meta-analyses: 1) peak Tcore; 2) whole body sweat rate (WBSR); 3) local sweat rate (LSR). The moderating effect of several variables (e.g., training and heat acclimation status), known to influence thermoregulatory function, were assessed via subanalysis and meta-regression. There was no overall effect of the differing supplement types on WBSR (P = 0.405) and LSR (P = 0.769), despite taurine significantly increasing WBSR (n = 3, Hedges' g = 0.79, P = 0.006). Peak Tcore was significantly affected by supplement type (P = 0.011), primarily due to caffeine's "small" significant positive effect (n = 30; Hedges' g = 0.44, P < 0.001) and taurine's (n = 3, Hedges' g = -0.66, P = 0.043) and oligonol's (n = 3; Hedges' g = -0.50, P = 0.014) "medium" significant negative effects. Dietary supplements, such as amino acids (e.g., taurine), some antioxidants and anti-inflammatories (e.g., oligonol) conferred the greatest thermoregulatory benefits during heat exposure. Taurine ingestion in such conditions may lower heat strain, which is likely through its augmentation of thermal sweating. Conversely, caffeine intake may potentially pose the greatest risk in the heat due to its effect on Tcore.NEW & NOTEWORTHY The effects of dietary supplements on core temperature and sweating responses when ingested in the heat varied greatly. Some supplements demonstrated the potential to improve thermoregulatory capacity (e.g., select amino acids, anti-oxidants and anti-inflammatories), while others had no or even deleterious effects on thermal balance (e.g., caffeine). These findings have implications for those ingesting dietary supplements for their health and/or performance effects during exposure to hot environmental conditions. Certain supplements should possibly be avoided in the heat, while others may elicit a thermoregulatory benefit.

Background/Objectives: Osteoarthritis (OA) is one of the most prevalent chronic conditions and significantly contributes to local and global disease burden. Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been developed that can impact OA symptoms without severe side-effects. One such alternative is the Red Algae Lithothamnion species (Litho). However, there is little mechanistic knowledge of its potential to effect OA gene expression, and a human in vitro model using commercially available cell lines to test its effectiveness has yet to be developed. Methods: Human osteoblast (hFOB 1.19. CRL-11372) and chondrocyte (C28/I2) cell lines were co-cultured indirectly using transwells. IL1-β was used to induce an inflammatory state and gene expression profiles following treatment were the primary outcome. Conclusions: Results indicated that the model was physiologically relevant, remained viable over at least seven days, untreated or following induction of an inflammatory state while maintaining hFOB 1.19. and C28/I2 cell phenotypic characteristics. Following treatment, Litho reduced the expression of inflammatory and pain associated genes, most notably IL-1β, IL-6, PTGS2 (COX-2) and C1qTNF2 (CTRP2). Confirmatory analysis with droplet digital PCR (ddPCR) revealed that Il-1β induced a significant reduction in C1qTNF2 at 7 days which was ameliorated with Litho treatment. These data present a novel and replicable co-culture model of inflammatory OA that can be used to investigate bioactive nutraceuticals. For the first time, this model demonstrated a reduction in C1qTNF2 expression that was mitigated by Red Algae Lithothamnion species.

OBJECTIVES:To investigate associations between genetic variants within COLGALT1, COL1A1, COL3A1, COL5A1, KDR, MIR608, MMP3, NID1, TIMP2 and VEGFA and injury history in elite male rugby athletes. DESIGN:A case-control genetic association study was conducted on 184 elite male rugby athletes. METHODS:Participants were genotyped for 13 genetic polymorphisms previously associated with soft tissue injury using standard PCR assays. Injury data were collected via a self-reported injury-history questionnaire. Single-locus association and Total Genotype Score (TGS) analyses were conducted using χ2 tests. In addition, multifactor dimensionality reduction and inferred haplotype analysis were used to identify genetic interactions. RESULTS:The TT genotype of MMP3 rs679620 was underrepresented in the non-injured ligament group compared to the ligament sprain and ligament rupture groups (10 %, 32 %, 25 %; P < 0.04, respectively). The T allele of MMP3 rs679620 was overrepresented in the non-injured tendon group compared to the tendinopathy group (50 %, 38 %; P < 0.02). The proportion of C allele carriers of COL5A1 rs12722 was higher in the tendon rupture group than the non-injured tendon group (96 %, 75 %; P < 0.02). Furthermore, the T-C inferred haplotype frequency of COL5A1 rs12722 and COL5A1 rs3196378 was higher in the tendon rupture, ligament sprain and total injured athlete groups compared to their respective non-injured groups (P < 0.02). CONCLUSIONS:This study is the first to identify associations between MMP3 rs679620 and COL5A1 rs12722 and soft-tissue injury history in elite male rugby athletes. These findings support the growing evidence that soft-tissue injury could be influenced by an athlete's genetic predisposition.

Endurance exercise, especially under heat stress, temporarily compromises the integrity of the intestinal barrier in healthy individuals. Consequently, there is growing interest in developing effective dietary strategies to alleviate exercise-induced gastrointestinal symptoms and gut damage. This meta-analysis investigated the effects of dietary supplements on mitigating these challenges. The search was performed in November 2024 following PRISMA guidelines, and 26 peer-reviewed studies were included across three meta-analyses: (1) gastrointestinal symptoms, (2) circulating intestinal fatty acid-binding protein (i-FABP), and (3) exercise performance. The moderating effect of variables was assessed via sub-group analysis and meta-regression. Overall, there was no pooled effect of supplement interventions on gastrointestinal symptoms (Hedges’ g = 0.42, 95% CI −0.17: 1.02, p = 0.15), and probiotics had a moderate significant effect for gastrointestinal symptoms (Hedges’ g = −0.62, 95% CI −1.01; 1.01, p = 0.05). There was a significant increase in i-FABP concentrations pre- to post exercise (∆ 106%; Hedges’ g = 1.01, 95% CI 0.63; 1.38, p = 0.01). There were no pooled or sub-group differences for exercise performance for any supplements (p = 0.53). Moderate-to-large heterogeneity was observed across studies (I2 ≥ 58.6%), and candidate moderators (exercise duration, modality, and environmental temperature) had no significant effect on any outcomes (p > 0.05). A significant increase in circulating i-FABP during exercise was observed. However, when examining the effects of different supplement categories, although significance was observed for a select few supplements, the changes in i-FABP, gastrointestinal symptoms, and exercise performance were outside of clinical relevance. Although probiotics showed a moderate significant effect for gastrointestinal symptoms, the conflicting findings across studies may have been due to inadequate control of confounding variables across studies. Further research is required to assess the alternative dietary supplements’ effects on gastrointestinal health and exercise performance, particularly under varied environmental conditions, where more rigorous control for cofounding factors is implemented.

To determine the effect of taurine supplementation on sweating and core temperature responses, including the transition from compensable to uncompensable heat stress, during prolonged low-intensity exercise of a fixed-heat production ( 200W/m2) in hot conditions (37.5 °C), at both fixed and incremental vapour-pressure. Fifteen females (n = 3) and males (n = 12; 27 ± 5 years, 78 ± 9 kg, V̇ O2max 50.3 ± 7.8 mL/kg/min), completed a treadmill walking protocol ( 200W/m2 heat production [Ḣprod]) in the heat (37.5 ± 0.1 °C) at fixed-(16-mmHg) and ramped-humidity (∆1.5-mmHg/5-min) following 1 week of oral taurine supplementation (50 mg/kg/bm) or placebo, in a double-blind, randomised, cross-over design. Participants were assessed for whole-body sweat loss (WBSL), local sweat rate (LSR), sweat gland activation (SGA), core temperature (Tcore), breakpoint of compensability (Pcrit) and calorimetric heat transfer components. Plasma volume and plasma taurine concentrations were established through pre- and post-trial blood samples. Taurine supplementation increased WBSL by 26.6

Background Osteoarthritis (OA) is characterised by the failure of normal biological processes to repair following damage. Traditionally, OA was considered a "wear and tear" disorder; however, it is now a recognised inflammatory condition, preceded by molecular modifications. The aim of this study was to evaluate inflammatory markers among individuals with early knee OA (eKOA) and well-matched asymptomatic controls. Methods Twenty six eKOA (females, n = 13; age = 60.2 +/- 5.4 yrs, height = 1.73 +/- 0.11 m, body mass = 77.8 +/- 12.8 kg, body fat = 33.9 +/- 8.5%) and twenty-three asymptomatic individuals (females, n = 14; age = 59.9 +/- 5.5yrs, height = 1.71 +/- 0.09 m, body mass = 72.6 +/- 11.3 kg, body fat = 30.4 +/- 8.2%) were recruited. The Timed Up and Go, and the 6 Minute Walk Tests evaluated physical function in addition to pain specific questionnaires (KOOS and ICOAP). Serum levels of IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-8(CXCL8), IL-10, hsCRP and TNF-alpha were quantified using a multiplex assay via V-plex (R) Sector Imager 2400. Results As hypothesised, only KOOS and EQ-5D-5L metrics differed between the groups for non-blood derived measures (p < 0.04). Only IL-6 was higher in eKOA (P = 0.02; 95% CI = 0.202; by 0.197 pg/mL; 34.5%). Among eKOA, IL-6 did not relate to severity of KOOS pain (P = 0.696, r = -0.088), but had a positive relationship with ICOAP consistent (r = 0.469, P = 0.045) rather than intermittent pain. There was a moderate correlation between 6MWD and IL-8 (r = 0.471, P = 0.012). Conclusion Our results illustrate the potential for IL-6 as a biomarker for eKOA, and introduce the proposition for particular consideration in those with consistent pain. Further, for the first time the present data showed greater walking distance in eKOA with lower circulating IL-8. Future work should seek to verify these results and further investigate IL-6 and IL-8 related molecular pathways in eKOA, and their potential relationships with consistent knee pain and physical function.(c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Fucoidan has attracted considerable attention from scientists and pharmaceutical companies due to its antioxidant, anticoagulant, anti-inflammatory, anti-tumor, and health-enhancing properties. However, the extraction of fucoidan from seaweeds often involves the use of harsh chemicals, which necessitates the search for alternative solvents. Additionally, the high viscosity and low cell permeability of high molecular weight (Mw) fucoidan can limit its effectiveness in drug action, while lower Mw fractions exhibit increased biological activity and are also utilized as dietary supplements. The study aimed to (1) extract fucoidan from the seaweed Fucus vesiculosus (FV) using an environmentally friendly solvent and compare it with the most commonly used extraction solvent, hydrochloric acid, and (2) assess the impact of ultrasound-assisted depolymerization on reducing the molecular weight of the fucoidan extracts and examine the cytotoxic effect of different molecular weight fractions. The findings indicated that the green depolymerization solvent, in conjunction with a brief ultrasound treatment, effectively reduced the molecular weight. Moreover, a significant decrease in cell viability was observed in selected samples, indicating potential anticancer properties. As a result, ultrasound was determined to be an effective method for depolymerizing crude fucoidan from Fucus Vesiculosus seaweed.

Caffeine is a commonly used ergogenic aid for endurance events; however, its efficacy and safety have been questioned in hot environmental conditions. The aim of this study was to investigate the effects of acute caffeine supplementation on cycling time to exhaustion and thermoregulation in the heat. In a double-blind, randomised, cross-over trial, 12 healthy caffeine-habituated and unacclimatised males cycled to exhaustion in the heat (35 °C, 40

Post-exercise passive heating has been reported to augment adaptations associated with endurance training. The current study evaluated the effect of a 4-week remotely administered, post-exercise passive leg heating protocol, using an electrically heated layering ensemble, on determinants of endurance performance. Thirty recreationally trained participants were randomly allocated to either a post-exercise passive leg heating (PAH, n = 16) or unsupervised training only control group (CON, n = 14). The PAH group wore the passive heating ensemble for 90–120 min/day, completing a total of 20 (16 post-exercise and 4 stand-alone leg heating) sessions across 4 weeks. Whole-body (peak oxygen uptake, gas exchange threshold, gross efficiency and pulmonary oxygen uptake kinetics), single-leg exercise (critical torque and NIRS-derived muscle oxygenation), resting vascular characteristics (flow-mediated dilation) and angiogenic blood measures (nitrate, vascular endothelial growth factor and hypoxia inducible factor 1−α) were recorded to characterize the endurance phenotype. All measures were assessed before (PRE), at 2 weeks (MID) and after (POST) the intervention. There was no effect of the intervention on test of whole-body endurance capacity, vascular function or blood markers (p > 0.05). However, oxygen kinetics were adversely affected by PAH, denoted by a slowing of the phase II time constant; τ (p = 0.02). Furthermore, critical torque–deoxygenation ratio was improved in CON relative to PAH (p = 0.03). We have demonstrated that PAH had no ergogenic benefit but instead elicited some unfavourable effects on sub-maximal exercise characteristics in recreationally trained individuals.

Skeletal muscle echo intensity (EI) is affected by ageing and physical activity; however, the effects of nutrition are less understood. The aim of this study was to explore whether habitual nutrient intake may be associated with ultrasound-derived EI. Partial least squares regression (PLSR) models were trained on an initial sample (n = 100, M = 45; F = 55; 38 ± 15 years) to predict EI of two quadriceps muscles from 19 variables, using the "jack-knife" function within the "pls" package (RStudio), which was then tested in an additional dataset (n = 30, M = 13; F = 17; 38 ± 16 years). EI was determined using B-mode ultrasonography of the rectus femoris (RF) and vastus lateralis (VL) and nutritional intake determined via 3-day weighed food diaries. Mean daily intake of specific nutrients were included as predictor variables with age, sex, and self-reported physical activity. PLSR training model 1 explained ∼52% and model 2 ∼46% of the variance in RF and VL EI, respectively. Model 1 also explained ∼35% and model 2 ∼30% of the variance in RF and VL EI in the additional testing dataset. Age and biological sex were associated with EI in both models (P < 0.025). Dietary protein (RF: β = -7.617, VL: β = -7.480), and selenium (RF: β = -7.144, VL: β = -4.775) were associated with EI in both muscles (P < 0.05), whereas fibre intake (RF: β = -5.215) was associated with RF EI only and omega-3 fatty acids (n-3/ω-3 FAs, RF: β = 3.145) with VL EI only (P < 0.05). Therefore, absolute protein, selenium, fibre, and n-3 FAs may be associated with skeletal muscle EI, although further mechanistic work is required before claiming causal inference.

There has been limited empirical study allowing athletes to voice their opinions on transgender participation in elite sport. This study surveyed 175 national, elite and world class athletes eligible to compete in the female category regarding transgender inclusion and eligibility. The study compared current Olympic versus current Olympic Recognised sports, elite versus world class, and current versus retired Olympic sport athletes. Most athletes favoured biological sex categorisation (58%) and considered it unfair for trans women to compete in the female category, except for precision sports. This view was held most strongly by world class athletes regarding their own sport (77% unfair, 15% fair). For trans men inclusion in the male category, most athletes considered it fair, except for Olympic sport athletes regarding contact sports (49% unfair, 27% fair) and sports heavily reliant on physical capacity (53% unfair, 29% fair). Notwithstanding those views, athletes (81%) believed sporting bodies should improve inclusivity for transgender athletes. Opinion varied somewhat according to career stage, competitive level and sport type. Nevertheless, athletes in the present study favoured categorisation by biological sex and did not support trans women eligibility for the female category in sports reliant on performance-related biological factors that differ between sexes.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.

Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study's definition of "elite"). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes (p = 0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance.

EDITORIAL article Front. Cell Dev. Biol., 21 November 2023Sec. Molecular and Cellular Pathology Volume 11 - 2023 | https://doi.org/10.3389/fcell.2023.1333011

We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat. Ten participants cycled at 70% maximal power output until exhaustion in 35°C and 20% relative humidity after application of (i) 5% isolated menthol, (ii) 5% menthol and 0.025% capsaicin co-application or (iii) placebo cream. Thermo-physiological responses were measured during exercise, with attentional focus and pain determined post-exercise on a 0-to-10 scale. Across the three conditions, time to exhaustion was 13.4 ± 4.8 min, mean ± SD infrared tympanic and skin temperature was 37.2 ± 0.6°C and 35.1 ± 1.2°C, respectively, and heart rate was 152 ± 47 bpm, with no changes between conditions (p > 0.05). Perceived exertion was lower in the isolated menthol vs. all other conditions (p < 0.05, ηp2 = 0.44). Thermal sensation was higher in menthol-capsaicin co-application vs. isolated menthol (p < 0.05, d = 1.1), while sweat rate was higher for capsaicin and menthol co-application compared to menthol (p < 0.05, d = 0.85). The median and interquartile range scores for pain were lower (p < 0.05) in the menthol condition (8, 7-8) compared to both menthol and capsaicin (10, 9-10) and placebo (9, 9-10), which was coupled with a greater distraction (p < 0.05) in the menthol condition (9, 7-10) compared to placebo (6, 5-7). Despite no performance effects for any topical cream application condition, these data reiterate the advantageous perceptual and analgesic role of menthol application and demonstrate no advantage of co-application with capsaicin.HighlightsTopical application of isolated menthol cream to cold-sensitive areas of the body during exhaustive exercise in the heat, elicited reduced perception of pain and enhanced sensation of cooling.While this reduction in generally unpleasant feelings (i.e. pain and heat) were coupled with lower RPE scores in the menthol condition and could be considered beneficial, there was no apparent ergogenic effect in an exercise tolerance test.Co-application of capsaicin and menthol appeared to inhibit the positive sensory effects elicited by menthol.Isolated menthol can induce changes in cognitive processes related to pain and exertion, while also reducing thermal sensation; however, the decision to use menthol creams must be balanced with the limited performance or thermoregulatory effects reported herein during exercise in hot environments.