Dr Jamie Matu

Background Joint replacement surgery has revolutionised the management of degenerative joint disease. Increasing demand for surgery and post-surgical reviews has overwhelmed orthopaedic services and, consequently, many centres have reduced or stopped follow-up. Such disinvestment is without an evidence base and raises questions regarding the consequences to patients. Objectives To produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Our research question was ‘Is it safe to disinvest in mid- to late-term follow-up of hip and knee replacement?’. Methods The study comprised three complementary evidence synthesis work packages to inform a final consensus process. Work package 1 was a systematic review of the clinical effectiveness and cost-effectiveness literature. Work package 2 used routine national data sets (i.e. the Clinical Practice Research Datalink–Hospital Episode Statistics, Hospital Episode Statistics–National Joint Registry–patient-reported outcome measures) to identify pre, peri and postoperative predictors of mid- to late-term revision, and prospective data from 560 patients to understand how patients present for revision surgery. Work package 3 used a Markov model to simulate the survival, health-related quality of life and NHS costs of patients following hip or knee replacement surgery. Finally, evidence from work packages 1–3 informed a face-to-face consensus panel, which involved 32 stakeholders. Results Our overarching statements are as follows: (1) these recommendations apply to post primary hip and knee replacement follow-up; (2) the 10-year time point in these recommendations is based on a lack of robust evidence beyond 10 years; and (3) in these recommendations, the term ‘complex cases’ refers to individual patient and surgical factors that may increase the risk of replacement failure. Our recommendations are as follows: for Orthopaedic Data Evaluation Panel 10A* (ODEP-10A*) minimum implants, it is safe to disinvest in routine follow-up from 1 to 10 years post non-complex hip and knee replacement provided that there is rapid access to orthopaedic review; (2) for ODEP-10A* minimum implants in complex cases or non-ODEP-10A* minimum implants, periodic follow-up post hip and knee replacement may be required from 1 to 10 years; (3) at 10 years post hip and knee replacement, clinical and radiographic evaluation is recommended; and (4) after 10 years post hip and knee replacement, frequency of further follow-up should be based on the 10-year assessment (note that ongoing rapid access to orthopaedic review is still required) [Stone M, Smith L, Kingsbury S, Czoski-Murray C, Judge A, Pinedo-Villanueva R, et al. Evidence-based follow-up recommendations following primary hip and knee arthroplasty (UK SAFE). Orthop Proc 2020;102–B:13. https://doi.org/10.1302/1358-992X.2020.5.013]. Limitations The current absence of data beyond 10 years restricted the evidence base. Conclusions For ODEP-10A* prostheses, the UK SAFE programme demonstrated that it is safe to disinvest in routine follow-up in the 1- to 10-year period after non-complex hip and knee replacement. At 10 years, clinical and radiographic review is recommended. Complex cases, implants not meeting the 10A* criteria and follow-up after revision surgery are not covered by this recommendation. Future work The evidence base for follow-up after 10 years requires further evaluation. Further work should establish the most clinically effective and cost-effective model of delivering a rapid access service and evaluate alternative models for follow-up services, such as virtual clinics. Finally, the needs and outcomes of patients who are symptomatic but do not have appropriate follow-up should be investigated.

Introduction: Hip and knee arthroplasties have revolutionised the management of degenerative joint diseases and, due to an ageing population, are becoming increasingly common. Follow-up of joint prostheses is to identify problems in symptomatic or asymptomatic patients due to infection, osteolysis, bone loss or potential peri-prosthetic fracture, enabling timely intervention to prevent catastrophic failure at a later date. Early revision is usually more straight-forward surgically and less traumatic for the patient. However, routine long-term follow-up is costly and requires considerable clinical time. Therefore, some centres in the UK have curtailed this aspect of primary hip and knee arthroplasty services, doing so without an evidence-base that such disinvestment is clinically- or cost-effective. Methods: Given the timeline from joint replacement to revision, conducting a randomised controlled trial (RCT) to determine potential consequences of disinvestment in hip and knee arthroplasty follow-up is not feasible. Furthermore the low revision rates of modern prostheses, less than 10% at 10 years, would necessitate thousands of patients to adequately power such a study. The huge variation in follow-up practice across the UK also limits the generalisability of an RCT. This study will therefore use a mixed-methods approach to examine the requirements for arthroplasty follow-up and produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Four interconnected work packages will be completed: 1) a systematic literature review; 2a) analysis of routinely-collected NHS data from five national datasets to understand when and which patients present for revision surgery; 2b) prospective data regarding how patients currently present for revision surgery; 3) economic modelling to simulate long-term costs and quality-adjusted life years associated with different follow-up care models; 4) a Delphi-consensus process, involving all stakeholders, to develop a policy document which includes a stratification algorithm to determine appropriate follow-up care for an individual patient.

Poor oral health can impact an individual’s ability to eat and has been associated with an increased risk of non-communicable diseases. While the benefits of nitrate consumption on oral health were first proposed more than 20 years ago, no systematic review has been published examining effects of dietary nitrate on oral health. This systematic review investigated the effects of dietary nitrate on markers of oral health in vivo in randomized controlled trials (RCTs). Five databases (PubMed, The Cochrane Library, CINAHL, MEDLINE, and SPORTDiscus) were searched from inception until March 2023. Nine articles reporting data on 284 participants were included. Dietary nitrate was provided via beetroot juice in most studies. The duration of the interventions ranged from one day to six weeks. Dietary nitrate supplementation increased the relative abundance of several individual bacterial genera including Neisseria and Rothia. Dietary nitrate supplementation increased salivary pH and decreased salivary acidification following consumption of a sugar-sweetened beverage. Furthermore, dietary nitrate supplementation resulted in a decrease in the gingival inflammation index. The results of this systematic review suggest that dietary nitrate could represent a potential nutritional strategy to positively modify oral health by impacting the oral microbiome, altering salivary pH, and minimizing gingival inflammation.

Isotope-based tracer methods allow the determination of total energy expenditure (TEE), water turnover (rH2O), and total body water (TBW) in free-living conditions. These methods have exciting applications in athletes. However, the limited number of available measurements constrains their applicability. The aim was to describe the application of isotope dilution techniques for measuring TEE, rH2O, and TBW in athletic populations. A comprehensive search (https://doi.org/10.17605/OSF.IO/7932T) was performed in three databases: PubMed, EBSCO (CINAHL, MEDLINE, and SPORTDiscus), and Cochrane Library. A total of 1,540 records were identified (564 excluded) and 174 through other sources. After excluding 53 duplicates, 1,097 articles were screened. A total of 121 studies were included, totaling 3,244 measurements from different types of sports, age range, and tier level, with 1,020 from female athletes and 139 measurements where sex was not reported. For TEE, 75 studies were included with values ranging from 1,939 to 10,070 kcal/day. For rH2O, 15 studies were included with values ranging from 2.7 to 13.4 L/day. For TBW, 77 studies were included with values ranging from 29.8 to 76.8 kg. Variability was observed across the studies among the variables of interest. Overall, males showed higher TEE, rH2O, and TBW values than females, with endurance sports showing the greatest variability in energy and water flux, and TBW values varying most in team and mixed sports. Future research should increase representation of females, athletes with disabilities, and Tier 5 “world-class” athletes to establish normative values across sports, age groups, and sex while applying standardized isotope dilution methodologies.

Objective: Evaluate knowledge and beliefs about dietary nitrate among United Kingdom (UK)-based adults. Design: An online questionnaire was administered to evaluate knowledge and beliefs about dietary nitrate. Overall knowledge of dietary nitrate was quantified using a 21-point Nitrate Knowledge Index. Responses were compared between sociodemographic groups. Setting: UK. Participants: A nationally representative sample of three hundred adults. Results: Only 19% of participants had heard of dietary nitrate prior to completing the questionnaire. Most participants (∼70%) were unsure about the effects of dietary nitrate on health parameters (e.g., blood pressure, cognitive function, cancer risk) or exercise performance. Most participants were unsure of the average population intake (78%) and acceptable daily intake (ADI) (83%) of nitrate. Knowledge of dietary sources of nitrate was generally low, with only ∼30% of participants correctly identifying foods with higher/lower nitrate contents. Almost none of the participants had deliberately purchased, or avoided purchasing, a food based around its nitrate content. Nitrate Knowledge Index scores were generally low (median[IQR]: 5[8]), but were significantly higher in individuals who were currently employed vs. unemployed (median[IQR]: 5[7]vs.4[7]; p<0.001), in those with previous nutrition education vs. no nutrition education (median[IQR]: 6[7]vs.4[8]; p=0.012), and in individuals who had heard of nitrate prior to completing the questionnaire vs. those who had not (median [IQR]: 9[8]vs.4[7]; p<0.001). Conclusions: This study demonstrates low knowledge around dietary nitrate in UK-based adults. Greater education around dietary nitrate may be valuable to help individuals make more informed decisions about their consumption of this compound.

Background: Vascular dementia (VaD) is the second most common cause of dementia globally and is associated with a significant economic and social burden. Diet could represent an important tractable risk factor for VaD. We synthesised current evidence on associations between consumption of specific foods or dietary patterns and VaD risk. Methods: Five databases were searched from inception to January 2024 for prospective cohort studies exploring associations between individual foods or dietary patterns and incident VaD. Results: Sixteen studies were included. Compared with low intake reference groups, higher fruit and vegetable intake, moderate alcoholic drink intake (1–3 drinks/day), higher tea and coffee intake, and following a plant-based dietary pattern were associated with lower VaD risk. Conversely, moderate fried fish intake (0.25–2 servings/week), higher ultra-processed food intake (especially intake of sweetened beverages) and higher processed meat intake (≥ 2 servings/week) were associated with increased VaD risk. Inconsistent findings were observed for other dietary exposures. Discussion: A healthy diet could lower VaD risk. However, evidence is characterised by a limited number of studies for specific dietary exposures. Further research is needed to inform personalised and population-based approaches to lower VaD risk.

Consumption of nitrate-rich vegetables increases nitric oxide bioavailability, lowers blood pressure, and improves endothelial function. These effects could also translate into reduced cardiovascular disease (CVD) risk and mortality. This systematic review aimed to investigate the associations between habitual vegetable nitrate intake and CVD incidence and mortality. A secondary aim was to identify factors that moderate the relationship between vegetable nitrate intake and CVD incidence/mortality. Seven databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, CINAHL, and APA PsycINFO) were searched from inception to 13 February 2023. Observational studies quantifying vegetable nitrate intake in participants aged 18+ years through self-reported dietary exposure and assessing incidence or mortality from CVD overall, or individual CVD subtypes, were eligible. Five studies including a total of 63,155 participants were included. There was an inverse association between vegetable nitrate intake and most reported CVD outcomes. Reported risk reductions tended to plateau at moderate intake, suggesting a possible ceiling effect. The risk of bias across all studies was low. The results of this systematic review suggest a potential role for vegetable nitrate in reducing CVD risk and mortality. Further randomised controlled trials are now required to corroborate these findings.

Purpose Dietary nitrate supplementation increases nitric oxide (NO) bioavailability and reduces blood pressure (BP). Inter-individual differences in these responses are suspected but have not been investigated using robust designs, e.g., replicate crossover, and appropriate statistical models. We examined the within-individual consistency of the effects of dietary nitrate supplementation on NO biomarkers and BP, and quantified inter-individual response differences. Methods Fifteen healthy males visited the laboratory four times. On two visits, participants consumed 140 ml nitrate-rich beetroot juice (~ 14.0mmol nitrate) and, on the other two visits, they consumed 140 ml nitrate-depleted beetroot juice (~ 0.03mmol nitrate). Plasma nitrate and nitrite concentrations were measured 2.5 h post-supplementation. BP was measured pre- and 2.5 h post-supplementation. Between-replicate correlations were quantified for the placebo-adjusted post-supplementation plasma nitrate and nitrite concentrations and pre-to-post changes in BP. Within-participant linear mixed models and a meta-analytic approach estimated participant-by-condition treatment response variability. Results Nitrate-rich beetroot juice supplementation elevated plasma nitrate and nitrite concentrations and reduced systolic (mean:-7mmHg, 95%CI: -3 to -11mmHg) and diastolic (mean:-6mmHg, 95%CI: -2 to -9mmHg) BP versus placebo. The participant-by-condition interaction response variability from the mixed model was ± 7mmHg (95%CI: 3 to 9mmHg) for systolic BP and consistent with the treatment effect heterogeneity t = ± 7mmHg (95%CI: 5 to 12mmHg) derived from the meta-analytic approach. The between-replicate correlations were moderate-to-large for plasma nitrate, nitrite and systolic BP (r = 0.55 to 0.91). Conclusions The effects of dietary nitrate supplementation on NO biomarkers and systolic BP varied significantly from participant to participant. The causes of this inter-individual variation deserve further investigation. Trial registration: https://clinicaltrials.gov/study/NCT05514821.

Background The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. Methods Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer’s disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. Results A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG β: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG β: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic β: -0.24, 95% CI: -0.45, -0.03; diastolic β: -0.16, 95% CI: -0.29, -0.03; BMI β: -0.09, 95% CI: -0.16, -0.01). Conclusions Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Ageing is a multifactorial process associated with reduced function and increased risk of morbidity and mortality. Recently, nine cellular and molecular hallmarks of ageing have been identified, which characterise the ageing process, and collectively, may be key determinants of the ageing trajectory. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Healthier dietary patterns reduce the risk of age-related diseases and increase longevity and may influence positively one or more of these hallmarks. The Mediterranean dietary pattern (MedDiet) is a plant-based eating pattern that was typical of countries such as Greece, Spain, and Italy pre-globalisation of the food system and which is associated with better health during ageing. Here we review the potential effects of a MedDiet on each of the nine hallmarks of ageing, and provide evidence that the MedDiet as a whole, or individual elements of this dietary pattern, may influence each hallmark positively—effects which may contribute to the beneficial effects of this dietary pattern on age-related disease risk and longevity. We also highlight potential avenues for future research.

Penile cancer is a rare but debilitating condition, which often requires aggressive treatment. Partial penectomy is considered as a treatment option when a sufficient portion of the penile shaft can be maintained to preserve functionality. This systematic review, which followed the PRIMSA guidelines, aimed to evaluate the effects of partial penectomy for penile cancer on sexual function-the maintenance of which is often a priority in patient groups-and to identify potential factors which may moderate these effects. A systematic search of PubMed, The Cochrane Library, and Open Grey as well as MEDLINE, CINAHL and Open Dissertations via EBSCOhost was conducted from inception through to 24th March, 2022. Studies were required to include adults aged ≥18 years who had undergone partial penectomy for the treatment of penile cancer, with a quantitative measure of sexual function available pre- and post-surgery. Four eligible articles were identified for inclusion in this review, three of which reported a decrease in sexual function pre- to post-surgery across all domains of the International Index of Erectile Function (IIEF) questionnaire (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction). Conversely, one study reported an increase in sexual function across IIEF domains, except for orgasmic function, which decreased, pre- to post-surgery. Greater penile length was associated with higher post-operative sexual function, whilst increasing age and higher anxiety levels were associated with lower post-operative sexual function levels in one study. Despite the overall drop in sexual function, many patients were still able to maintain satisfactory sex lives following partial penectomy. Given the limited research in this area and small sample sizes across studies, additional well-controlled investigations are warranted to provide further evidence on the effects of partial penectomy for penile cancer on sexual function.

In recent years, a number of studies have explored the potential salutary effects of dietary nitrate, with promising findings emerging. Indeed, numerous investigations have now demonstrated that increasing intake of dietary nitrate can reduce blood pressure, improve endothelial function, decrease platelet aggregation, increase cognitive function and brain perfusion, and enhance exercise performance. Most researchers have explored the health and/or performance effects of dietary nitrate by providing participants with concentrated beetroot juice, which is rich in this compound. Another strategy for increasing/optimising dietary nitrate intake, which could be embraced alongside or instead of nitrate-rich supplements in research and non-research settings, is the consumption of whole nitrate-rich vegetables. In this review, we explore the potential advantages and disadvantages of increasing consumption of various whole nitrate-rich vegetables to augment dietary nitrate intake. We compare the cost, convenience, availability, feasibility/acceptability, and efficacy of consumption of nitrate via whole nitrate-rich vegetables against concentrated beetroot juice ‘shots’ as defined supplements. We also discuss possible strategies that could be used to help individuals maximise their intake of nitrate via whole vegetables, and outline potential avenues for future research.

Background: The Eatwell guide reflects the UK governments recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. Methods: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimers disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. Results: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (1.66) (out of a possible 12 points) and GEWG score of 39.88 (6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG B: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG B: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic B: -0.24, 95% CI: -0.45, -0.03; diastolic B: -0.16, 95% CI: -0.29, -0.03; BMI B: -0.09, 95% CI: -0.16, -0.01). Conclusions: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Nutrition plays a key role in training for, and competing in, competitive sport, and is essential for reducing risk of injury and illness, recovering and adapting between bouts of activity, and enhancing performance. Consumption of a Mediterranean diet (MedDiet) has been demonstrated to reduce risk of various non-communicable diseases and increase longevity. Following the key principles of a MedDiet could also represent a useful framework for good nutrition in competitive athletes under most circumstances, with potential benefits for health and performance parameters. In this review, we discuss the potential effects of a MedDiet, or individual foods and compounds readily available in this dietary pattern, on oxidative stress and inflammation, injury and illness risk, vascular and cognitive function, and exercise performance in competitive athletes. We also highlight potential modifications which could be made to the MedDiet (whilst otherwise adhering to the key principles of this dietary pattern) in accordance with contemporary sports nutrition practices, to maximise health and performance effects. In addition, we discuss potential directions for future research.

Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.

Objective: To conduct a systematic review and meta-analysis investigating effects of MedDiet on blood pressure in randomised controlled trials (RCTs) and associations of MedDiet with risk of hypertension in observational studies. Methods: PubMed, The Cochrane Library and EBSCOhost were searched from inception until January 2020 for studies that met the following criteria: 1) participants aged ≥18 years, 2) RCTs investigating effects of a MedDiet versus control on BP, 3) Observational studies exploring associations between MedDiet adherence and risk of hypertension. Random-effects meta-analyses were conducted. Meta-regression and subgroup analyses were performed for RCTs to identify potential effect moderators. Results: Nineteen RCTs reporting data on 4137 participants and 16 observational studies reporting data on 59,001 participants were included in the meta-analysis. MedDiet interventions reduced systolic and diastolic BP by a mean -1.4 mmHg (95% CI: -2.40 to -0.39 mmHg, p=0.007, I2=53.5%, Q=44.7, τ2=1.65, df=19) and -1.5 mmHg (95% CI: -2.74 to -0.32 mmHg, p=0.013, I2=71.5%, Q=51.6, τ2=4.72, df=19) versus control, respectively. Meta-regression revealed that longer study duration and higher baseline systolic BP was associated with a greater decrease in BP, in response to a MedDiet (p<0.05). In observational studies, odds of developing hypertension were 13% lower with higher versus lower MedDiet adherence (95% CI: 0.78 to 0.98, p=0.017, I2=69.6%, Q=41.1, τ2=0.03, df=17). Conclusions: Data suggest that MedDiet is an effective dietary strategy to aid BP control, which may contribute towards the lower risk of CVD reported with this dietary pattern. This study was registered with PROSPERO: CRD42019125073. KEY WORDS: Mediterranean diet, blood pressure, hypertension, cardiovascular disease

BACKGROUND: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

This report summarises a Forum conducted in June 2023 to explore the current state of the knowledge around the Eatwell Guide, which is the UK government's healthy eating tool, in relation to population and planetary health. The 1.5-day Forum highlighted the limited, albeit promising evidence linking higher adherence to the Eatwell Guide with favourable health outcomes, including reduced overall mortality risk, lower abdominal obesity in post-menopausal women and improved cardiometabolic health markers. Similarly, evidence was presented to suggest that higher adherence to the Eatwell Guide is associated with reduced greenhouse gas emissions. Presentations were given around cultural adaptations of the Eatwell Guide, including African Heritage and South Asian versions, which are designed to increase the acceptability and uptake of the Eatwell Guide in these communities in the United Kingdom. Presentations highlighted ongoing work relevant to the applications of the Eatwell Guide in randomised controlled trials and public health settings, including the development of a screening tool to quantify Eatwell Guide adherence. The Forum ended with a World Café-style event, in which the strengths and limitations of the Eatwell Guide were discussed, and directions for future research were identified. This Forum report serves as a primer on the current state of the knowledge on the Eatwell Guide and population and planetary health and will be of interest to researchers, healthcare professionals and public health officials.

Abstract

ABSTRACT

The Eatwell Guide depicts the UK Government’s healthy eating recommendations and is widely used in clinical practice and public health settings. There is limited evidence on whether adherence to the Eatwell Guide differs by socio-demographic characteristics. This study aimed to explore patterns of Eatwell Guide adherence across socio-demographic groups in the UK Biobank cohort. Eatwell Guide adherence scores were derived for 192,825 individuals from 24-hour dietary recall data (Oxford WebQ), and quantified using a graded, food-based scoring system. Eatwell Guide scores were compared between different age, sex, BMI, ethnicity, socioeconomic status and education groups. Data were analysed using independent sample t-tests, and one-way ANOVA with Tukey post-hoc tests. Eatwell Guide adherence was higher for older than younger, and female compared with male participants (both p <0.001). There was a main effect of BMI on total adherence ( p <0.001), with the highest scores achieved by those with a healthy BMI. Eatwell Guide adherence was higher in white vs non-white participants ( p <0.001), and differed significantly by education level ( p <0.001), with the highest score achieved by participants with a higher education level. Total adherence scores differed by socio-economic status (all p <0.001), with the highest score achieved by the least deprived participants and the lowest score achieved by the most deprived participants. These data demonstrate that Eatwell Guide adherence differs significantly between socio-demographic groups in the UK Biobank. Exploring the consistency of these findings in other cohorts and developing strategies to increase adherence to the Eatwell Guide in groups with low adherence, are future research priorities.

A learning game has been developed which allows learners to study and learn about the significance of three important variables in human physiology (lactate, glycogen, and hydration) and their influence on sports performance during running. The player can control the speed of the runner, and as a consequence the resulting physiological processes are simulated in real-time. The performance degradation of the runner due to these processes requires that different strategies for pacing the running speed are applied by the player, depending on the total length of the run. The game has been positively evaluated in a real learning context of academic physiology teaching.

Carbohydrate mouth rinsing can improve endurance exercise performance and is most ergogenic when exercise is completed in the fasted state. This strategy may also be beneficial to increase exercise capacity and the energy deficit achieved during moderate intensity exercise relevant to weight control when performed after an overnight fast. Eighteen healthy men (mean(SD); age 23(4)years, body mass index 23.1(2.4)kg.m-2 ) completed a familiarisation trial and three experimental trials. After an overnight fast, participants performed 60-minutes of treadmill walking at a speed that equated to a rating of perceived exertion of 13 (“fairly hard”). Participants manually adjusted the treadmill speed to maintain this exertion. Mouth rinses for the experimental trials contained either a 6.4% maltodextrin solution with sweetener (CHO), a taste-matched placebo (PLA) or water (WAT). Appetite ratings were collected using visual analogue scales and exercise energy expenditure and substrate oxidation were calculated from online gas analysis. Increased walking distance during CHO and PLA induced greater energy expenditure compared with WAT (mean difference (90% CI); 79(60)kJ; P=0.035; d=0.24 and 90(63)kJ; P=0.024; d=0.27, respectively). Appetite area under the curve was lower in CHO and PLA than WAT (8(6)mm; P=0.042; d=0.43 and 6(8)mm; P=0.201; d=0.32, respectively). Carbohydrate oxidation was higher in CHO than PLA and WAT (7.3(6.7)g; P=0.078; d=0.47 and 10.1(6.5)g; P=0.015; d=0.81, respectively). This study provides novel evidence that mouth rinsing with a sweetened solution may promote a greater energy deficit during moderate exertion walking exercise by increasing energy expenditure and decreasing appetite. A placebo effect may have contributed to these benefits.

ABSTRACT

Abstract

Cross-sectional studies in younger adults have demonstrated a positive association between energy intake (EI) and fat-free mass (FFM), with this relationship seemingly mediated by resting metabolic rate (RMR). Establishing a causal effect longitudinally would be prudent in older adults suffering from loss of appetite. We investigated the effects of FFM on RMR, appetite and EI in 39 healthy older adults (age: 66 ± 4 years, BMI: 25.1 ± 3.5 kg·m2) assigned to either 12-week resistance training + protein supplementation group (RT + PRO) or control group (CON). Body composition, subjective appetite, leptin, insulin, RMR and laboratory-measured ad libitum EI were measured at baseline, weeks 6 and 12 of the intervention, while daily EI at baseline and week 12. FFM (+1.2 kg; p = 0.002), postprandial subjective appetite (+8 mm; p = 0.027), ad libitum EI (+119 kcal; p = 0.012) and daily EI (+133 kcal; p = 0.010) increased from baseline to week 12 in the RT + PRO. RMR, fasted subjective appetite, leptin and insulin concentrations remained unchanged (all p > 0.05). The increases ad libitum EI correlated with increases in FFM (r = 0.527, p = 0.001), with 54% of the change in EI attributed to FFM changes. In conclusion, FFM increases were associated with an increased ad libitum EI and postprandial appetite in older adults.

Background: A recent commentary has been published on our meta-analysis, which investigated substrate oxidation during exercise matched for relative intensities in hypoxia compared with normoxia. Within this commentary, the authors proposed that exercise matched for absolute intensities in hypoxia compared with normoxia, should have been included within the analysis, as this model provides a more suitable experimental design when considering nutritional interventions in hypoxia. Main body: Within this response, we provide a rationale for the use of exercise matched for relative intensities in hypoxia compared with normoxia. Specifically, we argue that this model provides a physiological stimulus replicable of real world situations, by reducing the absolute workload undertaken in hypoxia. Further, the use of exercise matched for relative intensities isolates the metabolic response to hypoxia, rather than the increased relative exercise intensity experienced in hypoxia when utilising exercise matched for absolute intensities. In addition, we also report previously unpublished data analysed at the time of the original meta-analysis, assessing substrate oxidation during exercise matched for absolute intensities in hypoxia compared with normoxia. Conclusion: An increased reliance on carbohydrate oxidation was observed during exercise matched for absolute intensities in hypoxia compared with normoxia. These data now provide a comparable dataset for the use of researchers and practitioners alike in the design of nutritional interventions for relevant populations.

The marketing of unhealthy foods has been implicated in poor diet and rising levels of obesity. Rapid developments in the digital food marketing ecosystem and associated research mean that contemporary review of the evidence is warranted. This preregistered (CRD420212337091)1 systematic review and meta-analysis aimed to provide an updated synthesis of the evidence for behavioural and health impacts of food marketing on both children and adults, using the 4Ps framework (Promotion, Product, Price, Place). Ten databases were searched from 2014 to 2021 for primary data articles of quantitative or mixed design, reporting on one or more outcome of interest following food marketing exposure compared with a relevant control. Reviews, abstracts, letters/editorials and qualitative studies were excluded. Eighty-two studies were included in the narrative review and twenty-three in the meta-analyses. Study quality (RoB2/Newcastle–Ottawa scale) was mixed. Studies examined ‘promotion’ (n 55), ‘product’ (n 17), ‘price’ (n 15) and ‘place’ (n 2) (some > 1 category). There is evidence of impacts of food marketing in multiple media and settings on outcomes, including increased purchase intention, purchase requests, purchase, preference, choice, and consumption in children and adults. Meta-analysis demonstrated a significant impact of food marketing on increased choice of unhealthy foods (OR = 2·45 (95 % CI 1·41, 4·27), Z = 3·18, P = 0·002, I2 = 93·1 %) and increased food consumption (standardised mean difference = 0·311 (95 % CI 0·185, 0·437), Z = 4·83, P < 0·001, I2 = 53·0 %). Evidence gaps were identified for the impact of brand-only and outdoor streetscape food marketing, and for data on the extent to which food marketing may contribute to health inequalities which, if available, would support UK and international public health policy development.

Nitrate supplementation appears to be most ergogenic when oxygen availability is restricted and subsequently may be particularly beneficial for swimming performance due to the breath-hold element of this sport. This represents the first investigation of nitrate supplementation and swimming time-trial (TT) performance. In a randomised double-blind repeated-measures crossover study, ten (5male, 5female) trained swimmers ingested 140ml nitrate-rich (~12.5mmol nitrate) or nitrate-depleted (~0.01mmol nitrate) beetroot juice. Three hours later, subjects completed a maximal effort swim TT comprising 168m (8 x 21m lengths) backstroke. Pre-exercise fractional exhaled nitric oxide concentration was significantly elevated with nitrate compared to placebo (17±9 vs. 7±3p.p.b., p=0.008). Nitrate supplementation had a likely trivial effect on overall swim TT performance (mean difference 1.22s; 90% CI -0.18– 2.6s; 0.93%; p=0.144; d=0.13; unlikely beneficial (22.6%), likely trivial (77.2%), most unlikely negative (0.2%)). The effects of nitrate supplementation during the first half of the TT were trivial (mean difference 0.29s; 90% CI -0.94–1.5s; 0.46%; p=0.678; d=0.05), but there was a possible beneficial effect of nitrate supplementation during the second half of the TT (mean difference 0.93s; 90% CI 0.13–1.70s; 1.36%; p=0.062; d=0.24; possibly beneficial (63.5%), possibly trivial (36.3%), most unlikely negative (0.2%)). The duration and speed of underwater swimming within the performance did not differ between nitrate and placebo (both p>0.30). Nitrate supplementation increased nitric oxide bioavailability but did not benefit short-distance swimming performance or the underwater phases of the TT. Further investigation into the effects of nitrate supplementation during the second half of performance tests may be warranted.

Importance: The effectiveness of anti-obesity medications for children and adolescents is unclear. Objective: To update the evidence on the benefits and harms of anti-obesity medication. Data sources: Cochrane CENTRAL, MEDLINE, ClinicalTrials.gov, WHO ICTRP (1/1/16-17/3/23). Study selection: Randomized controlled trials ≥6-months in people <19years living with obesity. Data extraction and Synthesis: Screening, data extraction, quality assessment conducted in duplicate, independently. Main Outcomes and Measures: Body Mass Index (BMI): 95th percentile BMI, adverse events, quality of life. Results: Thirty-five trials (N=4,331), follow-up: 6-24 months; age: 8.8-16.3 years; BMI: 26.2-41.7kg/m2. Moderate certainty evidence demonstrated a -1.71 (95% confidence interval [CI]: -2.27 to -1.14)-unit BMI reduction, ranging from -0.8 to -5.9 units between individual drugs with Semaglutide producing the largest reduction of -5.88 kg/m2 (95% CI: -6.99 to -4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: -11.88 percentage points (95% CI: -18.43 to -5.30, N = 668). Serious adverse events and study discontinuation due to adverse events, did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I2 = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities, and weight loss maintenance. Conclusions and Relevance: Anti-obesity medications in addition to behaviour-change, improves BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event.

Previous work has found adverse mental health symptomology in women living with obesity, compared with those of healthy weight, around the time of pregnancy. This meta-analysis aimed to explore the association between anxiety, depression, and weight status in women living with obesity before, during, and after pregnancy. Bibliographic databases were systematically searched, and 14 studies were included, which aimed to assess the association between excess weight and anxiety or depression outcomes in women before, during, or after pregnancy. Data were analyzed via narrative synthesis and random effects multi-level meta-analyses. Scores on mental health indices were significantly greater (indicative of worse anxiety/depression) in women with obesity compared to women of a healthy weight, around the time of pregnancy (SMD = 0.21 [95% CI: 0.11–0.31; 95% prediction intervals: 0.13–0.56], I2 = 73%, p < 0.01). Depressive symptoms were greater during and after pregnancy (SMD = 0.23 [95% CI: 0.13–0.34; 95% prediction intervals: −0.12 to 0.59], I2 = 75.0%, p < 0.01), and trait anxiety symptoms were greater during pregnancy (SMD = 0.24 [95% CI: 0.01–0.47; 95% prediction intervals: −0.25 to 0.72], I2 = 83.7%, p = 0.039) in women living with obesity, compared to those of healthy weight. Narrative evidence suggests that socioeconomic status and ethnicity may modify the relationship between obesity and mental health symptomology. The findings indicate that maternal obesity is associated with greater anxiety and depression symptoms. These findings may inform the design of maternal weight management interventions.

Background: Emotional eating (EE) is a barrier to long-term success of weight loss interventions. Psychological interventions targeting EE have been shown to reduce EE scores and weight (kg), though the mechanisms remain unclear. This review and meta-analysis aimed to identify the specific behaviour change techniques (BCTs) associated with improved outcomes. Methods: This is a review update and extension, with new studies extracted from searches of CINAHL, PsycINFO, MEDLINE, and EMBASE 01/01/22- 31/04/23. EE interventions for adults with BMI >25kg/m2, were considered for inclusion. Paper screening, extraction, BCT-coding and risk of bias were completed using the Template for Intervention Description and Replication (TIDieR) checklist, Behaviour Change Taxonomy v1 (BCTTv1) and Risk of Bias2 (RoB2)/ Risk of Bias In Non-randomised Studies (ROBINS-I) tool. Narrative syntheses and random effects multi-level meta-analyses were conducted. Results: 6,729 participants were included across 47 studies (13 identified in the update). Forty-two studies contributed to the pooled estimate for the impact of interventions on EE (SMD = -0.99 [95% CI: -0.73 to -1.25], p < .001). Thirty-two studies contributed to the pooled estimate for the impact of interventions on weight (-4.09 kg [95% CI: -2.76 to -5.43 kgs], p < .001). Five BCTs related to identity, values and self-regulation, were associated with notable improvements to both weight and EE (‘incompatible beliefs’, ‘goal setting outcome’. ‘review outcome goals’, ‘feedback on behaviour’ and ‘pros/ cons’). Conclusion: Implementation and evaluation of the highlighted BCTs are required. Weight management services should consider screening patients for EE to tailor interventions to individual need.

Acute exposure to high altitude (>3500m) is associated with marked changes in appetite regulation and substrate oxidation but the effects of lower altitudes are unclear. This study examined appetite, gut hormone, energy intake and substrate oxidation responses to breakfast ingestion and exercise at simulated moderate and severe altitudes compared with sea-level. Twelve healthy males (mean±SD; age 30±9years, body mass index 24.4±2.7kg.m-2) completed in a randomised crossover order three, 305 minute experimental trials at a simulated altitude of 0m, 2150m (~15.8% O2) and 4300m (~11.7% O2) in a normobaric chamber. Participants entered the chamber at 8am following a 12h fast. A standardised breakfast was consumed inside the chamber at 1h. One hour after breakfast, participants performed a 60 minute treadmill walk at 50% of relative V̇O2max. An ad-libitum buffet meal was consumed 1.5h after exercise. Blood samples were collected prior to altitude exposure and at 60, 135, 195, 240 and 285 minutes. No trial based differences were observed in any appetite related measure before exercise. Post-exercise area under the curve values for acylated ghrelin, pancreatic polypeptide and composite appetite score were lower (all P<0.05) at 4300m compared with sea-level and 2150m. There were no differences in glucagon-like peptide-1 between conditions (P=0.895). Mean energy intake was lower at 4300m (3728±3179kJ) compared with sea-level (7358±1789kJ; P=0.007) and 2150m (7390±1226kJ; P=0.004). Proportional reliance on carbohydrate as a fuel was higher (P=0.01) before breakfast but lower during (P=0.02) and after exercise (P=0.01) at 4300m compared with sea-level. This study suggests that altitude-induced anorexia and a subsequent reduction in energy intake occurs after exercise during exposure to severe but not moderate simulated altitude. Acylated ghrelin concentrations may contribute to this effect.

Introduction Acute exposure to very high altitude (>3500m) is associated with a significant suppression of appetite and energy intake, which may contribute to losses of lean mass and functional capacity. The reasons for this appetite suppression are unclear and it is unknown whether this will occur during acute exposure to moderate altitudes. This study examined the effects of exercise on appetite, appetite hormones and energy intake at moderate and very high altitudes. Methods Twelve healthy males (mean±SD; age 30±9years, body mass index 24±3kg.m-2) completed three, 305-minute experimental trials at a simulated altitude of 0m (sea level: SL), 2150m (~15.8% O2) and 4300m (~11.7% O2) in a normobaric chamber. The trials were randomised using a counterbalanced Latin Square design. Participants arrived at the laboratory after a 12h fast, entering the chamber at 8am. A standardised breakfast was consumed inside the chamber at 1h. One hour after breakfast, participants performed a 60-minute treadmill walk at 50% of altitude specific VO2max. An ad-libitum buffet meal was consumed 1.5h after exercise. Composite appetite score (CAS) ([hunger+prospective food consumption+(100–fullness)+(100–satisfaction)]/4), acylated ghrelin (AG), glucagon like peptide-1 (GLP1) and insulin were measured throughout. Results During the resting period prior to exercise there were no significant differences in any variables between conditions. During exercise, area under the curve (AUC) for CAS was significantly lower at 4,300m (33±5mm.h-1) compared with 2150m (44±5mm.h-1; p=0.024) but not compared with SL (42±4mm.h-1; p>0.05). In the post-exercise period, AUC for CAS was significantly lower at 4300m (40±19mm.h-1) compared with SL (55±15mm.h-1; p=0.004) and 2150m (60±14mm.h-1; p<0.001). During exercise, AUC for AG was significantly lower at 4300m (48±23pg.mL-1.h-1) compared with SL (69±27pg.mL-1.h-1; p=0.005) and 2150m (67±31pg.mL-1.h-1; p=0.01). During the post exercise period AUC for AG was significantly lower at 4,300m (49±31pg.mL-1.h-1) compared with SL (116±49pg.mL-1.h-1; p<0.001) and 2150m (111±62pg.mL-1.h-1; p=0.002). There were no differences in GLP1 or insulin between conditions. Mean energy intake was significantly lower at 4300m (3728±3179kJ) compared with SL (7358±1789kJ; p=0.007) and 2150m (7390±1226kJ; p=0.004). There was no difference in CAS, AG or energy intake between SL and 2150m. Discussion This study suggests that altitude-induced anorexia and a subsequent reduction in energy intake occurs with acute exposure to very high but not moderate altitudes. This effect may be explained by reduced concentrations of AG at very high altitudes. Further research should aim to identify methods of reducing appetite suppression at altitude.

Exposure to hypoxia appears to depress appetite and energy intake, however the mechanisms are not fully understood. The aim of this review was to determine the magnitude of changes in hunger and energy intake in hypoxic compared with normoxic environments, and establish any alterations in appetite-related hormone concentrations. PubMed and The Cochrane Library as well as MEDLINE, SPORTDiscus, PsycINFO and CINAHL, via EBSCOhost, were searched through 1st April 2017 for studies that evaluated hunger, energy intake and/or appetite-related hormones in normoxia and during hypoxic exposure in a within-measures design. A total of 28 studies (comprising 54 fasted and 22 postprandial comparisons) were included. A random-effects meta-analysis was performed to establish standardised mean difference (SMD) with 95% confidence intervals. Hypoxic exposure resulted in a trivial but significant decrease in postprandial hunger scores (SMD: -0.15, 95% CI: -0.29 to -0.01; n = 14; p = 0.043) and a moderate decrease in energy intake (SMD: -0.50, 95% CI: -0.85 to -0.15; n = 8; p = 0.006). Hypoxic exposure resulted in a decrease (albeit trivial) in postprandial acylated ghrelin concentrations (SMD: -0.16, 95% CI: -0.25 to -0.08; n = 7; p < 0.0005), and a moderate increase in fasted insulin concentrations (SMD: 0.41, 95% CI: 0.17 to 0.65; n = 34; p = 0.001). Meta-regression revealed a decrease in postprandial acylated ghrelin concentrations (p = 0.010) and an increase in fasted insulin concentrations (p = 0.020) as hypoxic severity increased. Hypoxic exposure reduces hunger and energy intake, which may be mediated by decreased circulating concentrations of acylated ghrelin and elevated insulin concentrations. PROSPERO registration number: CRD42015017231.

Nutrition strategies and supplements may have a role to play in diminishing exercise associated gastrointestinal cell damage and permeability. The aim of this systematic review was to determine the influence of dietary supplements on markers of exercise-induced gut endothelial cell damage and/or permeability. Five databases were searched through to February 2021. Studies were selected that evaluated indirect markers of gut endothelial cell damage and permeability in response to exercise with and without a specified supplement, including with and without water. Acute and chronic supplementation protocols were included. Twenty-seven studies were included. The studies investigated a wide range of supplements including bovine colostrum, glutamine, probiotics, supplemental carbohydrate and protein, nitrate or nitrate precursors and water across a variety of endurance exercise protocols. The majority of studies using bovine colostrum and glutamine demonstrated a reduction in selected markers of gut cell damage and permeability compared to placebo conditions. Carbohydrate intake before and during exercise and maintaining euhydration may partially mitigate gut damage and permeability but coincide with other performance nutrition strategies. Single strain probiotic strains showed some positive findings, but the results are likely strain, dosage and duration specific. Bovine colostrum, glutamine, carbohydrate supplementation and maintaining euhydration may reduce exercise-associated endothelial damage and improve gut permeability. In spite of a large heterogeneity across the selected studies, appropriate inclusion of different nutrition strategies could mitigate the initial phases of gastrointestinal cell disturbances in athletes associated with exercise. However, research is needed to clarify if this will contribute to improved athlete gastrointestinal and performance outcomes.

Background: In 2020, the National Health Service Low-Calorie Diet Programme (NHS-LCD) was launched, piloting a total diet (TDR) replacement intervention with behaviour change support for people living with Type 2 Diabetes (T2D) and excess weight. Four independent service providers were commissioned to design and deliver theoretically grounded programmes in localities across England. Aims: 1) to develop a logic model detailing how the NHS-LCD programme is expected to produce changes in health behaviour, and (2) to analyse and evaluate the use of behaviour change theory in providers’ NHS-LCD Programme designs. Methods: A documentary review was conducted. Information was extracted from the NHS-LCD service specification documents on how the programme expected to produce outcomes. The Theory Coding Scheme (TCS) was used to analyse theory use in providers’ programme design documents. Results: The NHS-LCD logic model included techniques aimed at enhancing positive outcome expectations of programme participation and beliefs about social approval of behaviour change, to facilitate programme uptake and behaviour change intentions. This was followed by techniques aimed at shaping knowledge and enhancing the ability of participants to self-regulate their health behaviours, alongside a supportive social environment and person-centred approach. Application and type of behaviour change theory within service providers’ programme designs varied. One provider explicitly linked theory to programme content; two providers linked 63% and 70% of intervention techniques to theory; and there was limited underpinning theory identified in the programme design documents for one of the providers. Conclusion: The nature and extent of theory use underpinning the NHS-LCD varied greatly amongst service providers, with some but not all intervention techniques explicitly linked to theory. How this relates to outcomes across providers should be evaluated. It is recommended that explicit theory use in programme design and evidence of its implementation becomes a requirement of future NHS commissioning processes.

Purpose: Reported substrate oxidation responses in hypoxia are divergent, and may be due to differences in methodological design, such as pre-exercise nutritional status and exercise intensity. This study investigated the effect of breakfast consumption versus omission on substrate oxidation at varying exercise intensities in normobaric hypoxia compared with normoxia. Methods: Twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. Exercise consisted of walking for 20-minutes at 40%, 50% and 60% of altitude-specific V̇O2max at 10-15% gradient with a 10 kg backpack. Indirect calorimetry was used to calculate carbohydrate and fat oxidation. Results: The relative contribution of carbohydrate oxidation to energy expenditure was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission at 40% (22.4 ± 17.5% vs. 38.5±15.5%, p = 0.03) and 60% V̇O2max (35.4±12.4 vs. 50.1±17.6%, p = 0.03), with a trend observed at 50% V̇O2max (23.6±17.9% vs. 38.1± 17.0%, p = 0.07). The relative contribution of carbohydrate oxidation to energy expenditure was not significantly different in hypoxia compared with normoxia during exercise after breakfast consumption at 40% (42.4±15.7% vs. 48.5±13.3%, p = 0.99), 50% (43.1±11.7% vs. 47.1±14.0%, p = 0.99) and 60% V̇O2max (54.6±17.8% vs. 55.1±15.0%, p = 0.99). Conclusions: Relative carbohydrate oxidation was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission but not during exercise after breakfast consumption. This response remained consistent with increasing exercise intensities. These findings may explain some of the disparity in the literature

BACKGROUND: A recent commentary has been published on our meta-analysis, which investigated substrate oxidation during exercise matched for relative intensities in hypoxia compared with normoxia. Within this commentary, the authors proposed that exercise matched for absolute intensities in hypoxia compared with normoxia, should have been included within the analysis, as this model provides a more suitable experimental design when considering nutritional interventions in hypoxia. MAIN BODY: Within this response, we provide a rationale for the use of exercise matched for relative intensities in hypoxia compared with normoxia. Specifically, we argue that this model provides a physiological stimulus replicable of real world situations, by reducing the absolute workload undertaken in hypoxia. Further, the use of exercise matched for relative intensities isolates the metabolic response to hypoxia, rather than the increased relative exercise intensity experienced in hypoxia when utilising exercise matched for absolute intensities. In addition, we also report previously unpublished data analysed at the time of the original meta-analysis, assessing substrate oxidation during exercise matched for absolute intensities in hypoxia compared with normoxia. CONCLUSION: An increased reliance on carbohydrate oxidation was observed during exercise matched for absolute intensities in hypoxia compared with normoxia. These data now provide a comparable dataset for the use of researchers and practitioners alike in the design of nutritional interventions for relevant populations.

Introduction The hypoxic exposure experienced at altitude is known to impair endurance performance, which may in part be related to changes in substrate utilisation. However, equivocal findings have been reported regarding the contribution of carbohydrate and fat to the total energy yield in hypoxia. These divergent findings may be due to differences in methodological design, such as the nutritional status of participants prior to exercise. As such, this study was the first to investigate the effect of the fasted and fed state on substrate utilisation during exercise in normoxia and normobaric hypoxia. Methods Twelve men rested and performed exercise twice in sea level (SL) conditions (~20.93% O2) and twice at normobaric hypoxia (NH) equivalent to 4300m (Fi02~11.7%) in a randomised, crossover design. Participants entered the chamber after an overnight fast. After 1 hour, one trial within each experimental condition remained fasted, while the other included consumption of a high carbohydrate breakfast (567 kcal, 68% carbohydrate, 12% fat, 20% protein). One hour after consumption of breakfast (fed trials) or no breakfast (fasted trials), participants walked for one hour at intensities of 40%, 50% and 60% of altitude specific VO2max. Walking was performed on a treadmill at 10-15% gradient whilst carrying a 10kg backpack to simulate altitude trekking. Expired gas was measured throughout, using online gas analysis for the quantification of carbohydrate and fat oxidation. Results Relative carbohydrate oxidation was significantly reduced in NH fasted conditions compared with SL fasted conditions at 40% (SL fasted: 38.5±15.5%; NH fasted: 22.4±17.5%; p = 0.03) and 60% VO2max (SL fasted: 50.1±17.6%; NH fasted: 35.4±12.4%; p = 0.03), with a trend observed at 50% VO2max (SL fasted: 38.0±17.0%; NH fasted: 23.6±17.9%; p = 0.07). Relative fat oxidation in the fasted state was reciprocal to the fasted relative carbohydrate findings at all intensities. No significant differences in relative carbohydrate oxidation were observed in NH fed conditions compared with SL fed conditions at 40% (SL fed: 48.5±13.3%; NH fed: 44.1±20.6%; p = 0.99), 50% (SL fed: 47.1±14.0%; NH fed: 43.1±11.7%; p = 0.99) and 60% VO2max (SL fed: 55.1±15.0%; NH fed: 54.6±17.8%; p = 0.99). Relative fat oxidation in the fed state was reciprocal to the fed relative carbohydrate findings at all intensities. Conclusion This study is the first to establish that relative carbohydrate contributions to energy expenditure decrease, while relative fat contributions increase, during exercise matched for relative intensities in NH compared with SL when in the fasted, but not fed state. These findings suggest that the feeding state of participants may explain some of the divergence within the current literature regarding the effects of hypoxia on substrate utilisation. Further, these findings should be considered when prescribing nutritional support for mountaineers and military personnel trekking at high altitude.

Purpose: The purpose of experiment one was to determine the appetite, acylated ghrelin and energy intake response to breakfast consumption and omission in hypoxia and normoxia. Experiment two aimed to determine the appetite, acylated ghrelin and energy intake response to carbohydrate supplementation after both breakfast consumption and omission in hypoxia. Methods: In experiment one, twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. In experiment two, eleven participants rested and exercised in normobaric hypoxia (4300 m: FiO2 ~11.7%), twice after consuming a high carbohydrate breakfast and twice after breakfast omission. Participants consumed both a carbohydrate (1.2g·min

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Introduction It is well established that acute exposure to very high altitude (>3500m) is associated with a suppression of appetite, acylated ghrelin and energy intake. Ghrelin is post-translationally modified with a medium chain fatty acid and this acylation is necessary for ghrelin to exert its orexigenic effects. This novel study investigated the effects of a high-fat (HF) breakfast rich in medium chain fatty acids versus a high-carbohydrate (HC) breakfast on appetite, ghrelin constituents and energy intake at 4300m simulated altitude. Methods Twelve healthy males (mean (SD); age 26 (8) years, body mass index 23.9 (2.7) kg·m-2) completed two, 305-minute experimental trials at a simulated altitude of 4300m (~11.7% O2) in a normobaric chamber. Trials were conducted in a randomised, single blind, counter-balanced fashion. After an overnight fast, participants entered the chamber and rested until receiving breakfast at 1h. Participants consumed either an isocaloric HF (60% fat, 25% carbohydrate and 15% protein) or HC (60% carbohydrate, 25% fat and 15% protein) breakfast. One hour after breakfast, participants performed a 60-minute treadmill walk at 50% of relative V̇O2max. An ad-libitum buffet meal was consumed 1.5h after exercise. Composite appetite score (CAS) as well as acylated (AG) and de-acylated ghrelin (DG) were measured throughout. Results At baseline and during the resting period prior to exercise there were no significant differences in any variables between conditions (all P≥0.137). During exercise, area under the curve (AUC) for CAS was significantly higher following the HF breakfast (39 (12) mm·h-1) compared with the HC breakfast (30 (17) mm·h-1, P=0.036). Similarly, AUC for AG was significantly higher during exercise following the HF breakfast (152 (180) pg·mL-1·h-1) compared with the HC breakfast (101 (106) pg·mL-1·h-1, P=0.048). During the post-exercise period there was no significant difference in CAS (P=0.356) or AG (P=0.229) between conditions. No differences were observed during any time period in DG (all P≥0.207). Energy intake at the buffet did not significantly differ between conditions (P=0.384). Discussion This study suggests that, in comparison with a HC breakfast, a HF breakfast rich in medium chain fatty acids can attenuate appetite suppression during exercise at 4300m simulated altitude. However, this did not translate into increased ad-libitum energy intake when food was provided 90 minutes after exercise. It would be beneficial for further research to establish whether a prolonged HF diet can promote a positive energy balance at altitude.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

High-altitude exposure induces a negative energy balance by increasing resting energy expenditure and decreasing energy intake. This diminished energy intake is likely caused by altitude-induced anorexia and can have detrimental effects for those travelling to high-altitude. We aimed to investigate whether altering the macronutrient composition of breakfast could attenuate altitude-induced anorexia and augment energy intake at high-altitude. Twelve healthy men (aged 26 (8) years, body mass index 23.9 (2.7) kg·m(-2)) completed two, 305min experimental trials at 4300m simulated altitude (~11.7% O2). After an overnight fast, participants entered a normobaric hypoxic chamber and rested for one hour, before receiving either a high fat (HF; 60% fat, 25% carbohydrate) or an isocaloric high carbohydrate (HC; 60% carbohydrate, 25% fat) breakfast. One hour after breakfast, participants performed 60min of treadmill walking at 50% of relative V̇O2max. An ad-libitum buffet meal was consumed 1h 30min after exercise. Appetite perceptions, blood samples and substrate oxidation rates were measured throughout. A significantly higher area under the curve for composite appetite score was observed during exercise in HF (40 (12) mm·h(-1)) compared with HC (30 (17) mm·h(-1), P=0.036). During exercise, lower insulin concentrations (P=0.013) and elevated acylated ghrelin concentrations (P=0.048) were observed in HF compared with HC. After exercise there was no significant difference in composite appetite score (P=0.356), acylated ghrelin (P=0.229) or insulin (P=0.513) between conditions. Energy intake at the buffet did not significantly differ between conditions (P=0.384). A HF breakfast attenuated appetite suppression during exercise at 4300m simulated altitude, however ad-libitum energy intake did not increase.

Abstract

Discrete episodes of overconsumption may induce a positive energy balance and impair metabolic control. However, the effects of an ecologically relevant, single day of balanced macronutrient overfeeding are unknown. Twelve healthy men (of age 22 (sd 2) years, BMI 26·1 (sd 4·2) kg/m2) completed two 28 h, single-blind experimental trials. In a counterbalanced repeated measures design, participants either consumed their calculated daily energy requirements (energy balance trial (EB): 10 755 (sd 593) kJ) or were overfed by 50 % (overfeed trial (OF): 16 132 (sd 889) kJ) under laboratory supervision. Participants returned to the laboratory the next day, after an overnight fast, to complete a mixed-meal tolerance test (MTT). Appetite was not different between trials during day 1 (P>0·211) or during the MTT in the fasted or postprandial state (P>0·507). Accordingly, plasma acylated ghrelin, total glucagon-like peptide-1 and total peptide YY concentrations did not differ between trials during the MTT (all P>0·335). Ad libitum energy intake, assessed upon completion of the MTT, did not differ between trials (EB 6081 (sd 2260) kJ; OF 6182 (sd 1960) kJ; P=0·781). Plasma glucose and insulin concentrations were not different between trials (P>0·715). Fasted NEFA concentrations were lower in OF compared with EB (P=0·005), and TAG concentrations increased to a greater extent on OF than on EB during the MTT (P=0·009). The absence of compensatory changes in appetite-related variables after 1 d of mixed macronutrient overfeeding highlights the limited physiological response to defend against excess energy intake. This supports the concept that repeated discrete episodes of overconsumption may promote weight gain, while elevations in postprandial lipaemia may increase CVD risk.

Ageing is associated with reductions in appetite and food intake (1) resulting in unintentional weight loss (2). Such weight loss, particularly through muscle mass reduction is associated with muscle weakness and functional decline, which represent significant predictors of poor health outcomes (3) and are contributing factors to frailty in older people. Resistance exercise is crucial in attenuating age-induced muscle loss, whilst muscle mass gains have been proposed as a means of increasing appetite and energy intake (EI) through changes in metabolic demand (4). Exercise intensities > 60% of maximal oxygen uptake have consistently been shown to acutely supress appetite in younger adults in a variety of exercise modes (5), yet little is known about the acute effects of resistance exercise on appetite and energy intake particularly in older adults. Understanding these effects may aid exercise prescription and provide post-exercise feeding strategies to reduce age-related anorexia and ultimately attenuate age-associated reductions in muscle mass. Therefore, we investigated the effect of an acute bout of resistance exercise on appetite and EI. Twenty healthy, older adults (13 females and 7 males; 68 ± 5 years old, body mass index of 26.2 ± 4.5 kg.m-2) undertook two 5-h experimental trials. On arrival at the laboratory, participants rested for a 0.5-h period before they were given a standardised breakfast. They then rested for a 1-h period before they completed in a randomised crossover design: 1) a 1-h resistance exercise workout followed by 2-h of rest and 2) a control condition where participants rested for a subsequent 3-h period. On cessation of the trials, participants were administered an ad libitum pasta meal for the assessment of EI. Composite appetite scores (CAS) were measured throughout using visual analogue scales. A paired samples t-test revealed no difference in EI between conditions. Two-way ANOVA revealed a significant effect of condition (p = 0.007) and time (p <0.001) but no significant interaction effect (p = 0.153) for CAS, which were lower in the resistance exercise condition. Similarly, area under the curve for the entire trial was significantly different (p = 0.007) between conditions and was associated with a small effect size (Cohen’s d = 0.27). Our findings suggest that an acute resistance exercise bout does not result in EI reductions during an ad libitum meal given 2 h post-exercise, in spite of significant main condition effects in CAS. This significance can be attributed to the temporary suppression of appetite during the resistance exercise bout. Given that appetite profiles remained similar between conditions for the rest of the trial, and that feeding is likely to take place post-exercise, this mode of exercise is an appropriate means for optimising muscle mass adaptations by maintaining subsequent EI of older adults.

Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = –0.34; 95% CI: –0.52, –0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

Purpose: Exposure to high altitude has been shown to enhance both glucose and lipid utilization depending on experimental protocol. In addition, high and low blood glucose levels have been reported at high altitude. We hypothesized that gradual ascent to high altitude results in changes in glucose levels in healthy young adults. Methods: 25 adult volunteers, split into two teams, took part in the British Services Dhaulagiri Medical Research Expedition completing 14 days of trekking around the Dhaulagiri circuit in Nepal reaching a peak altitude of 5300m on Day 11 of the trek. Participants wore blinded continuous glucose monitors (CGM) throughout. Blood samples for c-peptide, pro-insulin and triacylglycerides were taken at sea level (UK) and in acclimatisation camps at 3600m, 4650m and 5120m. Energy intake was determined from food diaries. Results: There was no difference in time spent in hypoglycemia stratified by altitude. Nocturnal CGM readings (22.00-06.00 hrs) were chosen to reduce the short-term impact of physical activity and food intake and showed a significant (p<0.0001) increase at 3600m (5.53±0.22mmol/L), 4650m (4.77±0.30mmol/L) and 5120m (4.78±0.24mmol/L) compared to baseline altitude 1100m (vs 4.61±0.25mmol/L). Energy intake did not differ by altitude. Insulin resistance and B-cell function, calculated by homeostatic model assessment, was reduced at 3600m compared to sea level. Conclusions: We observed a significant increase in nocturnal CGM glucose at 3600m and above despite gradual ascent from 1100m. Taken with the changes in insulin resistance and B-cell function, it is possible that the stress response to high altitude dominates exercise enhanced insulin sensitivity, resulting in relative hyperglycemia.

There is evidence to suggest that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. HRV (5-minute single lead ECG) was measured in 63 healthy adults (41 men and 22 women) aged 18-56 years at sea level (SL) and during a HA trek at 3619m, 4600m and 5140m respectively. The main effects of altitude (SL, 3619, 4600 and 5140m) and sex (men vs women) and their potential interaction were assessed using a Factorial Repeated Measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. Men and women were of similar age (31.2 ±9.3 vs 31.7±7.5 years), ethnicity, body and mass index. There was main effect for altitude on heart rate, SDNN (standard deviation [SD] of normal-to-normal [NN] intervals), RMSSD (Root mean square of successive differences), NN50 (number of pairs of successive NNs differing by >50 ms), pNN50 (NN50 / total number of NNs), very low frequency (VLF), low frequency (LF), high frequency (HF) and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF, HF and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS.

Summary Background There is limited evidence and clinical guidelines on the behavior change support required for low‐calorie diet programs. This systematic review aimed to establish the behavior change technique(s) (BCT) implemented in weight loss interventions (≤1200 kcal/d) and how these contribute to effectiveness. Methods Databases were searched from inception to April 2022. Screening, data extraction, BCT coding, and quality appraisal were conducted in duplicate using the Template for Intervention Description and Replication framework, Behavior Change Technique Taxonomy, and Cochrane Risk of Bias 2 tool. Data were analyzed via narrative synthesis and random effects multi‐level meta‐analyses. Results Thirty‐two papers reporting on 27 studies were included. Twenty‐four BCTs were identified across studies. Eight BCTs were significantly associated with a larger reduction in weight at the end‐of‐diet time‐point; one BCT was statistically significant at the end of weight maintenance. Physical activity, Type 2 Diabetes, and BMI category moderated intervention effects. Conclusions and implications This is the first meta‐analysis to examine how specific BCTs contribute to the effectiveness of low‐calorie diets. It is recommended that a) these findings are used to develop clinical guidelines specific to behavioral support in low‐calorie diet programs, and b) program commissioners stipulate the use of these BCTs in their service specifications.

A learning game has been developed which allows learners to study and learn about the significance of three important variables in human physiology (lactate, glycogen, and hydration) and their influence on sports performance during running. The player can control the speed of the runner, and as a consequence the resulting physiological processes are simulated in real-time. The performance degradation of the runner due to these processes requires that different strategies for pacing the running speed are applied by the player, depending on the total length of the run. The game has been positively evaluated in a real learning context of academic physiology teaching.

Abstract

Due to the unique energetic demands of professional young collision sport athletes, accurate assessment of energy balance is required. Consequently, this is the first study to simultaneously investigate the energy intake, expenditure and balance of professional young rugby league players across a pre-season period. The total energy expenditure of six professional young male rugby league players was measured via doubly labelled water over a fourteen-day assessment period. Resting metabolic rate was measured and physical activity level calculated. Dietary intake was reported via Snap-N-Send over a non-consecutive ten-day assessment period, alongside changes in fasted body mass and hydration status. Accordingly, energy balance was inferred. The mean (standard deviation) difference between total energy intake (16.73 (1.32) MJ.day-1) and total energy expenditure (18.36 (3.05) MJ.day-1) measured over the non-consecutive ten-day period was unclear (-1.63 (1.73) MJ.day-1; ES = 0.91 ±1.28; p = 0.221). This corresponded in a most likely trivial decrease in body mass (-0.65 (0.78) kg; ES = 0.04 ±0.03; p = 0.097). Resting metabolic rate and physical activity level across the fourteen-day pre-season period was 11.20 (2.16) MJ.day-1 and 1.7 (0.2), respectively. For the first time, this study utilises gold standard assessment techniques to elucidate the distinctly large energy expenditures of professional young rugby league players across a pre-season period, emphasising a requirement for equally large energy intakes to achieve targeted body mass and composition adaptations. Accordingly, it is imperative that practitioners regularly assess the energy balance of professional young collision-sport athletes to ensure their unique energetic requirements are achieved.

Aim Exercise appears to cause damage to the endothelial lining of the human gastrointestinal tract and elicit a significant increase in gut permeability. Objective The aim of this review was to determine the effect of an acute bout of exercise on gut damage and permeability outcomes in healthy populations using a meta-analysis. Methods PubMed, The Cochrane Library as well as MEDLINE, SPORTDiscus and CINHAL, via EBSCOhost were searched through February 2019. Studies were selected that evaluated urinary (ratio of disaccharide/monosaccharide excretion) or plasma markers [intestinal Fatty Acid Binding Protein (i-FABP)] of gut permeability and gut cell damage in response to a single bout of exercise. Results A total of 34 studies were included. A random-effects meta-analysis was performed, and showed a large and moderate effect size for markers of gut damage (i-FABP) (ES 0.81; 95% CI 0.63–0.98; n = 26; p < 0.001) and gut permeability (Disaccharide Sugar/Monosaccharide Sugar) (ES 0.70; 95% CI 0.29–1.11; n = 17; p < 0.001), respectively. Exercise performed in hot conditions (> 23 °C) further increased markers of gut damage compared with thermoneutral conditions [ES 1.06 (95% CI 0.88–1.23) vs. 0.66 (95% CI 0.43–0.89); p < 0.001]. Exercise duration did not have any significant effect on gut damage or permeability outcomes. Conclusions These findings demonstrate that a single bout of exercise increases gut damage and gut permeability in healthy participants, with gut damage being exacerbated in hot environments. Further investigation into nutritional strategies to minimise gut damage and permeability after exercise is required. PROSPERO database number (CRD42018086339).

Summary This umbrella review assessed the association between excess weight and COVID‐19 outcomes. MEDLINE, PsycINFO, and CINAHL were systematically searched for reviews that assessed the association between excess weight and COVID‐19 outcomes. A second‐order meta‐analysis was conducted on the available data for intensive care unit admission, invasive mechanical ventilation administration, disease severity, hospitalization, and mortality. The quality of included reviews was assessed using the AMSTAR‐2 appraisal tool. In total, 52 systematic reviews were included, 49 of which included meta‐analyses. The risk of severe outcomes (OR = 1.86; 95% CI: 1.70 to 2.05), intensive care unit admission (OR = 1.58; 95% CI: 1.45 to 1.72), invasive mechanical ventilation administration (OR = 1.70; 95% CI: 1.57 to 1.83), hospitalization (OR = 1.82; 95% CI: 1.61 to 2.05), and mortality (OR = 1.35; 95% CI: 1.24 to 1.48) following COVID‐19 infection was significantly higher in individuals living with excess weight compared with those with a healthy weight. There was limited evidence available in the included reviews regarding the influence of moderating factors such as ethnicity, and the majority of included reviews were of poor quality. Obesity appears to represent an important modifiable pre‐infection risk factor for severe COVID‐19 outcomes, including death.

OBJECTIVES: Full-contact football-code team sports offer a unique environment for illness risk. During training and match-play, players are exposed to high-intensity collisions which may result in skin-on-skin abrasions and transfer of bodily fluids. Understanding the incidence of all illnesses and infections and what impact they cause to time-loss from training and competition is important to improve athlete care within these sports. This review aimed to systematically report, quantify and compare the type, incidence, prevalence and count of illnesses across full-contact football-code team sports. DESIGN/METHODS: A systematic search of Cochrane Library, MEDLINE, SPORTDiscus, PsycINFO and CINAHL electronic databases was performed from inception to October 2019; keywords relating to illness, athletes and epidemiology were used. Studies were excluded if they did not quantify illness or infection, involve elite athletes, investigate full-contact football-code sports or were review articles. RESULTS: Twenty-eight studies met the eligibility criteria. Five different football-codes were reported: American football (n=10), Australian rules football (n=3), rugby league (n=2), rugby sevens (n=3) and rugby union (n=9). One multi-sport study included both American football and rugby union. Full-contact football-code athletes are most commonly affected by respiratory system illnesses. There is a distinct lack of consensus of illness monitoring methodology. CONCLUSIONS: Full-contact football-code team sport athletes are most commonly affected by respiratory system illnesses. Due to various monitoring methodologies, illness incidence could only be compared between studies that used matching incidence exposure measures. High-quality illness surveillance data collection is an essential component to undertake effective and targeted illness prevention in athletes.

Allied Health Professionals (AHPs) have the capacity to promote healthy behaviours in young children through routine ‘contact points’, as well as structured weight management programmes. This scoping review aims to evaluate the impact of AHPs in the prevention of obesity in young children. Databases were searched for relevant evidence between 1st January 2000 and 17th January 2022. Eligibility criteria included primary evidence (including, but not limited to; randomized controlled trials, observational studies, service evaluations) evaluating the impact of AHPs on the primary and secondary prevention of obesity in young children (mean age under 5 years old). AHP-related interventions typically demonstrated improvements in outcomes such as nutritional behaviour (e.g. lower sweetened drink intake), with some reductions in screen time. However, changes in weight outcomes (e.g. body mass index (BMI) z-score, BMI) in response to an AHP intervention were inconsistent. There was insufficient data to determine moderating effects, however tentative evidence suggests that those with a lower socioeconomic status or living in an underprivileged area may be more likely to lose weight following an AHP intervention. There was no evidence identified evaluating how AHPs use routine ‘contact points’ in the prevention of obesity in young children. AHP interventions could be effective in optimizing weight and nutritional outcomes in young children. However, more research is required to determine how routine AHP contact points, across the range of professional groups may be used in the prevention of obesity in young children.

BACKGROUND: NHS England commissioned four independent service providers to pilot low-calorie diet programmes to drive weight loss, improve glycaemia and potentially achieve remission of Type 2 Diabetes across 10 localities. Intervention fidelity might contribute to programme success. Previous research has illustrated a drift in fidelity in the design and delivery of other national diabetes programmes. AIMS: (1) To describe and compare the programme designs across the four service providers; (2) To assess the fidelity of programme designs to the NHS England service specification. METHODS: The NHS England service specification documents and each provider's programme design documents were double-coded for key intervention content using the Template for Intervention Description and Replication Framework and the Behaviour Change Technique (BCT) Taxonomy. RESULTS: The four providers demonstrated fidelity to most but not all of the service parameters stipulated in the NHS England service specification. Providers included between 74% and 87% of the 23 BCTs identified in the NHS specification. Twelve of these BCTs were included by all four providers; two BCTs were consistently absent. An additional seven to 24 BCTs were included across providers. CONCLUSIONS: A loss of fidelity for some service parameters and BCTs was identified across the provider's designs; this may have important consequences for programme delivery and thus programme outcomes. Furthermore, there was a large degree of variation between providers in the presence and dosage of additional BCTs. How these findings relate to the fidelity of programme delivery and variation in programme outcomes and experiences across providers will be examined.

Aims: This study presents data gathered as part of the Re:Mission evaluation of the NHS low-calorie diet programme pilot for Type 2 Diabetes, to address two research questions: 1) What is the presence and severity of emotional and binge eating within this population? 2) Are demographic and health factors associated with the presence of binge eating or the severity of emotional eating? Methods: An online survey gathered data from n = 580 individuals who were enrolled on the programme but had not yet begun total diet replacement. The survey assessed emotional eating (TFEQ-R21), potential Binge Eating Disorder diagnosis (BEDS-7), wellbeing (Short Warwick-Edinburgh Mental Wellbeing Scale), quality of life (EQ-5D-5L), frequency of weight cycling and demographic factors (collected via NHS England programme monitoring). Descriptive statistics and regression analyses were used to address the research questions. Results: The mean emotional eating score from the TFEQ-R21 was 2.58 (0.96), and the presence of potential Binge Eating Disorder diagnosis was demonstrated in 26.0% of the sample. Regression analyses suggested that being female and engaging in more frequent weight cycling was associated with higher emotional eating and greater likelihood of binge eating. Lower wellbeing and lower quality of life were associated with emotional and binge eating, respectively. Conclusions: Rates of emotional and binge eating in the NHS low-calorie diet pilot sample are higher than in the general public, and in other similar samples. Consideration should be given to screening for emotional and disordered eating, and for additional tailored support and monitoring for such individuals.

Background: A better understanding of hypoxia-induced changes in substrate utilisation can facilitate the development of nutritional strategies for mountaineers, military personnel and athletes during exposure to altitude. However, reported metabolic responses are currently divergent. As such, this systematic review and meta-analysis aims to determine the changes in substrate utilisation during exercise in hypoxia compared with normoxia and identify study characteristics responsible for the heterogeneity in findings. Methods: A total of six databases (PubMed, the Cochrane Library, MEDLINE, SPORTDiscus, PsychINFO, and CINAHL via EBSCOhost) were searched for published original studies, conference proceedings, abstracts, dissertations and theses. Studies were included if they evaluated respiratory exchange ratio (RER) and/or carbohydrate or fat oxidation during steady state exercise matched for relative intensities in normoxia and hypoxia (normobaric or hypobaric). A random-effects meta-analysis was performed on outcome variables. Meta-regression analysis was performed to investigate potential sources of heterogeneity. Results: In total, 18 studies were included in the meta-analysis. There was no significant change in RER during exercise matched for relative exercise intensities in hypoxia, compared with normoxia (mean difference: 0.01, 95% CI: -0.02 to 0.05; n = 31, p = 0.45). Meta-regression analysis suggests that consumption of a pre-exercise meal (p < 0.01) and a higher exercise intensity (p = 0.04) when exposed to hypoxia may increase carbohydrate oxidation compared with normoxia. Conclusions: Exposure to hypoxia did not induce a consistent change in the relative contribution of carbohydrate or fat to the total energy yield during exercise matched for relative intensities, compared with normoxia. The direction of these responses appears to be mediated by the consumption of a pre-exercise meal and exercise intensity. Key words: Altitude, exercise, substrate, carbohydrate, fat, oxidation, systematic review

Background Previous research has illustrated a drift in the fidelity of behaviour change techniques (BCTs) during the design of the pilot NHS England Low-Calorie Diet (NHS-LCD) Programme. This study evaluated a subsequent domain of fidelity, intervention delivery. Two research questions were addressed: 1) To what extent were BCTs delivered with fidelity to providers programme plans? 2) What were the observed barriers and facilitators to delivery? Methods A mixed-methods sequential explanatory design was employed. Remote delivery of one-to-one and group-based programmes were observed. A BCT checklist was developed using the BCT Taxonomy v1; BCTs were coded as present, partially delivered, or absent during live sessions. Relational content analysis of field notes identified observed barriers and facilitators to fidelity. Results Observations of 122 sessions across eight samples and two service providers were completed. Delivery of the complete NHS-LCD was observed for five samples. Fidelity ranged from 33%-70% across samples and was higher for group-based delivery models (64%) compared with one-to-one models (46%). Barriers and facilitators included alignment with the programme's target behaviours and outcomes, session content, time availability and management, group-based remote delivery, and deviation from the session plan. Conclusions Overall, BCTs were delivered with low-to-moderate fidelity. Findings indicate a dilution in fidelity during the delivery of the NHS-LCD and variation in the fidelity of programmes delivered across England. Staff training could provide opportunities to practice the delivery of BCTs. Programme-level changes such as structured activities supported by participant materials and with sufficient allocated time, might improve the delivery of BCTs targeting self-regulation.

Introduction Acute exposure to very high altitude (>3500m) is associated with a suppression of appetite, acylated ghrelin (AG) and energy intake. Appetite suppression at altitude is likely caused by the reduction in arterial oxygen saturation (SpO2), consequent to the low oxygen tensions present at altitude. Beetroot juice (BRJ) has shown to minimise the altitude-related reductions in SpO2 and may therefore provide relief of altitude-induced suppression of AG and appetite. The present study investigated the effects of BRJ supplementation on appetite, AG and energy intake at 4300m simulated altitude. Methods Ten healthy males (mean(SD); age 24(7) years, body mass index 25(3)kg·m-2) completed two 6h 30mins experimental trials in normobaric hypoxia, simulating an altitude of 4300m (~11.7% FiO2). Trials were conducted in a randomised, double blind, counter-balanced fashion. After an overnight fast, participants arrived at the laboratory and completed baseline measures. Following cannulation, participants consumed a porridge breakfast accompanied by 140ml concentrated BRJ (Beet It, James White Ltd., UK) or placebo. Participants entered the hypoxic chamber 90mins after breakfast, where they rested for 2h 30mins. Participants then completed a 60min treadmill walk at 10% gradient and 50% of relative V̇O2max, whilst carrying a 10kg rucksack. After exercise, participants consumed a snack and 70ml concentrated BRJ or placebo. Participants then rested inside the chamber until 6h 30mins. After leaving the chamber, the participants were given an ad-libitum homogenous pasta meal. Fractional exhaled nitric oxide (FeNO) provided a marker of nitric oxide bioavailability. Composite appetite score (CAS) and AG were measured throughout; results are presented for four area under the curve (AUC) periods: pre-hypoxic, hypoxic rest, exercise and post-exercise. Results At baseline there were no differences in any variables between conditions (P≥0.382). There was no significant difference in FeNO between conditions upon entry to the chamber (P=0.110), however FeNO was significantly elevated in BRJ immediately prior to exercise, compared with placebo (P=0.034). There were no differences between conditions during any of the AUC periods for SpO2 (P≥0.746), AG (P≥0.231), or CAS (P≥0.730). Energy intake at the ad-libitum buffet meal did not differ between BRJ (3542±1306kJ) and placebo (3980±1342kJ; P=0.270). Discussion This study suggests that acute BRJ supplementation has no effect on appetite, AG, or energy intake at 4300m simulated altitude. However, other methodological approaches which may elevate SpO2, such as chronic BRJ loading, require further investigation.

The British Service Dhaulagiri Research Expedition took place in March-May 2016. A total of 129 personnel took part in the expedition and were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of altitude illness. The study took place in a remote and inhospitable environment at altitudes up to 7500m. This paper gives an overview of the challenges involved, the research protocols investigated and the execution of the expedition in Nepal.

Purpose: Collision sports are characterised by frequent high intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. Methods: Using a randomised crossover design, six professional young male rugby league players completed two different five-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly seven days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. Results: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ±0.07; p=0.0021) total energy expenditure across the five-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ±0.74; p=0.007) session rating of perceived exertion and a very likely greater (-14.6 ± 3.3%; ES = -1.60 ±0.51; p=0.002) decrease in wellbeing 24h later. Conclusions: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused” alongside the kinematic “work required”. Key words: Nutrition, Recovery, Contact, Rugby

Purpose Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. Methods Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m−2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). Results Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). Conclusions Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes.

Purpose: Nitric oxide (NO) bioavailability is reduced during acute altitude exposure, contributing towards the decline in physiological and cognitive function in this environment. This study evaluated the effects of nitrate (NO3-) supplementation on NO bioavailability, physiological and cognitive function, and exercise performance at moderate and very-high simulated altitude. Methods: Ten males (mean (SD): V̇O2max: 60.9 (10.1) ml·kg-1·min-1) rested and performed exercise twice at moderate (~14.0 % O2; ~3000 m) and twice at very-high (~11.7% O2; ~4300 m) simulated altitude. Participants ingested either 140 ml concentrated NO3--rich (BRJ; ~12.5 mmol NO3-) or NO3--deplete (PLA; 0.01 mmol NO3-) beetroot juice 2 hours before each trial. Participants rested for 45 minutes in normobaric hypoxia prior to completing an exercise task. Exercise comprised a 45 minute walk at 30 % V̇O2max and a 3 km time-trial (TT), both conducted on a treadmill at a 10 % gradient whilst carrying a 10 kg backpack to simulate altitude hiking. Plasma nitrite concentration ([NO2-]), peripheral oxygen saturation (SpO2), pulmonary oxygen uptake (V̇O2), muscle and cerebral oxygenation, and cognitive function were measured throughout. Results: Pre-exercise plasma [NO2-] was significantly elevated in BRJ compared with PLA (p = 0.001). Pulmonary V̇O2 was reduced (p = 0.020), and SpO2 was elevated (p = 0.005) during steady-state exercise in BRJ compared with PLA, with similar effects at both altitudes. BRJ supplementation enhanced 3 km TT performance relative to PLA by 3.8 % (1653.9 (261.3) vs. 1718.7 (213.0) s) and 4.2 % (1809.8 (262.0) vs. 1889.1 (203.9) s) at 3000 m and 4300 m, respectively (p = 0.019). Oxygenation of the gastrocnemius was elevated during the TT consequent to BRJ (p = 0.011). The number of false alarms during the Rapid Visual Information Processing Task tended to be lower with BRJ compared with PLA prior to altitude exposure (p = 0.056). Performance in all other cognitive tasks did not differ significantly between BRJ and PLA at any measurement point (p ≥ 0.141). Conclusion: This study suggests that BRJ improves physiological function and exercise performance, but not cognitive function, at simulated moderate and very-high altitude

Background National Health Service England piloted a low-calorie diet programme, delivered through total diet replacement and behaviour change support via 1 : 1, group or digital delivery, to improve type 2 diabetes in adults with excess weight. Aim To coproduce a qualitative and economic evaluation of the National Health Service low-calorie diet pilot, integrated with National Health Service data to provide an enhanced understanding of the long-term cost-effectiveness, implementation, equity and transferability across broad and diverse populations. Research questions What are the theoretical principles, behaviour change components, content and mode of delivery of the programme, and is it delivered with fidelity to National Health Service specifications? What are the service provider, user and National Health Service staff experiences of the programme? Do sociodemographics influence programme access, uptake, compliance and success? What aspects of the service work and what do not work, for whom, in what context and why? Can the programme be improved to enhance patient experience and address inequities? What are the programme delivery costs, and policy implications for wide-spread adoption? Methods A mixed-methods study underpinned by a realist-informed approach was delivered across five work packages, involving: semistructured interviews with service users (n = 67), National Health Service staff (n = 55), service providers (n = 9); 13 service provider focus groups; and service user surveys (n = 719). Findings were triangulated with clinical data from the National Health Service England’s first cohort analysis (n = 7540). Results Fifty-five per cent of service users who started total diet replacement completed the programme and lost an average of 10.3 kg; 32% of those with data available to measure remission achieved it. Examination of programme mobilisation identified barriers around referral equality and the impact of COVID-19, while effective cross-stakeholder working and communication were key facilitators. Service delivery and fidelity assessments identified a drift in implementation fidelity, alongside variation in the behaviour change content across providers. Perceived barriers to programme uptake and engagement aligned across service providers and users, resulting in key learning on: the importance of person-centred care, service user support needs, improvements to total diet replacement and the social and cultural impact of the programme. Early National Health Service quantitative analyses suggest some socioeconomic variation in programme uptake, completion and outcomes. Insights from the evaluation and National Health Service data were combined to develop the programme theory and underpinning context, mechanisms and outcomes. These were used to develop a list of recommendations to improve the cultural competency of programme delivery, total diet replacement delivery, peer support and address psychological support needs. Cost-effectiveness analyses using short-term follow-up data indicated there is potential for the programme to be cost-effective, but not cost saving. Conclusions The National Health Service low-calorie diet can provide a clinically effective and potentially cost-effective programme to support weight loss and glycaemic control in adults with type 2 diabetes. However, this evaluation identified areas for improvement in referral equity, uptake and completion, and fidelity of delivery, which have informed the development of the programme, which has now been rolled out nationally. Ongoing programme monitoring and long-term follow-up are now required. Future work and limitations The real-world setting limited some data collection and analysis. Future work will focus on the analysis of long-term clinical and cost-effectiveness, and addressing inequalities. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132075.