Dr Alex Griffiths

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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

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.

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.

Purpose: This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after pre-exercise breakfast consumption and omission. Methods: Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90-min at 50% of hypoxic V̇O2max. Participants were supplemented with a carbohydrate beverage (1.2g·min-1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous (muscle and liver)) and fat oxidation. Results: In the first 60-min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both p = 0.99). In the last 30-min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs. 28.0 ± 12.3, p < 0.01) but not consumption (51.7 ± 12.3 vs. 44.2 ± 10.4, p = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver: 7.7 ± 1.6% vs. 14.8 ± 2.3%, p < 0.01; muscle: 25.4 ± 9.4% vs. 29.4 ± 11.1%, p = 0.99) and omission (liver: 3.8 ± 0.8% vs. 8.7 ± 2.8%, p < 0.01; muscle: 19.4 ± 7.5% vs. 19.2 ± 12.2%, p = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (p = 0.14). Conclusion: In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (> 60 min) after breakfast omission, but not consumption.

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.

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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.

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.

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.

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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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: 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: 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

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.

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.

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).

PURPOSE: To assess indirect markers of intestinal endothelial cell damage and permeability in academy rugby players in response to rugby training at the beginning and end of preseason. METHODS: Blood and urinary measures (intestinal fatty acid binding protein and lactulose:rhamnose) as measures of gastrointestinal cell damage and permeability were taken at rest and after a standardised collision-based rugby training session in 19 elite male academy rugby players (age: 20 ± 1 years, backs: 89.3 ± 8.4 kg; forwards: 111.8 ± 7.6 kg) at the start of preseason. A subsample (n = 5) repeated the protocol after six weeks of preseason training. Gastrointestinal symptoms (GIS; range of thirteen standard symptoms), aerobic capacity (30-15 intermittent fitness test), and strength (1 repetition maximum) were also measured. RESULTS: Following the rugby training session at the start of preseason, there was an increase (median; interquartile range) in intestinal fatty acid binding protein (2140; 1260-2730 to 3245; 1985-5143 pg/ml, p = 0.003) and lactulose:rhamnose (0.31; 0.26-0.34 to 0.97; 0.82-1.07, p < 0.001). After six weeks of preseason training players physical qualities improved, and the same trends in blood and urinary measures were observed within the subsample. Overall, the frequency and severity of GIS were low and not correlated to markers of endothelial damage. CONCLUSIONS: Rugby training resulted in increased intestinal endothelial cell damage and permeability compared to rest. A similar magnitude of effect was observed after six weeks of pre-season training. This was not related to the experience of GIS.

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

The purpose of this study was to assess the reliability of a pre-loaded 1500 m treadmill time-trial, conducted in moderate normobaric hypoxia. Eight trained runners/ triathletes (24 ± 3 years, 73.2 ± 8.1 kg, 182.5 ± 6.5 cm, altitude specific V̇O2max: 52.9 ± 5.5 ml·kg-1·min-1) completed three trials (the first as a familiarisation), involving two, 15 minute running bouts at 45 % and 65 % V̇O2max, respectively, and a 1500 m time-trial in moderate normobaric hypoxia equivalent to a simulated altitude of 2500 m (FiO2 ~ 15 %). Heart rate, arterial oxygen saturation, skeletal muscle and cerebral tissue oxygenation (StO2), expired gas (V̇O2 and V̇CO2), and ratings of perceived exertion were monitored. Running performance (Trial 1: 352.7 ± 40; Trial 2: 353.9 ± 38.2 s) demonstrated a low CV (0.9 %) and high ICC (1). All physiological variables demonstrated a global CV ≤ 4.2 %, and ICC ≥ 0.87, with the exception of muscle (CV 10.4 %; ICC 0.70) and cerebral (CV 4.1 %; ICC 0.82) StO2. These data demonstrate good reliability of the majority of physiological variables, and indicate that a pre-loaded 1500 m time-trial conducted in moderate normobaric hypoxia is a highly reliable test of performance.

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.