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The enhancement of fat oxidation during exercise is an aim for both recreational exercising individuals and endurance athletes. Nutritional status may explain a large part of the variation in maximal rates of fat oxidation during exercise. This review reveals novel insights into nutritional manipulation of substrate selection during exercise, explaining putative mechanisms of action and evaluating the current evidence. Lowering the glycaemic index of the pre-exercise meal can enhance lipid utilisation by up to 100 % through reduced insulin concentrations, although its application may be restricted to specific training sessions rather than competition. Chronic effects of dietary glycaemic index are less clear and warrant future study before firm recommendations can be made. A flurry of recent advances has overthrown the conventional view of l-carnitine supplementation, with skeletal muscle uptake possible under certain dietary conditions and providing a strategy to influence energy metabolism in an exercise intensity-dependent manner. Use of non-carbohydrate nutrients to stimulate muscle l-carnitine uptake may prove more beneficial for optimising lipid utilisation, but this requires more research. Studies investigating fish oil supplementation on fat oxidation during exercise are conflicting. In spite of some strong putative mechanisms, the only crossover trial showed no significant effect on lipid use during exercise. Ca may increase NEFA availability although it is not clear whether these effects occur. Ca and caffeine can increase NEFA availability under certain circumstances which could theoretically enhance fat oxidation, yet strong experimental evidence for this effect during exercise is lacking. Co-administration of nutrients to maximise their effectiveness needs further investigation. [ABSTRACT FROM AUTHOR]

The gut microbiome plays a significant role in physiological functions such as nutrient processing, vitamin production, inflammatory response, and immune modulation, which, in turn, are important contributors to athlete health and performance. To date, the interpretation, discussion, and visualization of microbiome results of athletes are challenging, due to a lack of standard parameters and reference data for collection and comparison. The purpose of this perspective piece is to provide researchers with an easy-to-understand framework for the collection, analysis, and data management related to the gut microbiome with a specific focus on athletic populations. In the absence of a consensus on microbiome research in the sports field, we hope that these considerations serve as foundational "best practice." Adherence to these standard operating procedures will accelerate the path toward improving the quality of data and ultimately our understanding of the influence of the gut microbiome in sport settings., Competing Interests: Declaration of interests R.I. is an employee of the Gatorade Sports Science Institute, a division of PepsiCo, Incorporated. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of PepsiCo, Incorporated., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

There is little evidence that body size alters exogenous glucose oxidation rates during exercise. This study assessed whether larger people oxidize more exogenous glucose during exercise than smaller people. Fifteen cyclists were allocated into two groups based on body mass (SMALL, <70 kg body mass, n = 9, two females) or (LARGE, >70 kg body mass, n = 6) matched for lactate threshold (SMALL: 2.3 ± 0.4 W/kg, LARGE: 2.3 ± 0.3 W/kg). SMALL completed 120 min of cycling at 95% of lactate threshold1. LARGE completed two trials in a random order, one at 95% of lactate threshold1 (thereby exercising at the same relative intensity [RELATIVE]) and one at an absolute intensity matched to SMALL (ABSOLUTE). In all trials, cyclists ingested 90 g/hr of 13C-enriched glucose. Total exogenous glucose oxidation was (mean ± SD) 33 ± 8 g/hr in SMALL versus 45 ± 13 g/hr in LARGE-RELATIVE (mean difference: 13 g/hr, 95% confidence interval [2, 24] g/hr, p = .03). Large positive correlations were observed for measures of exogenous carbohydrate oxidation versus body size (body mass, height, and body surface area; e.g., body surface area vs. peak exogenous glucose oxidation, r = .85, 95% confidence interval [.51, .95], p < .01). When larger athletes reduced the intensity from RELATIVE to ABSOLUTE, total exogenous glucose oxidation was 39 ± 7 g/hr (p = .43 vs. LARGE-RELATIVE). In conclusion, the capacity for exogenous glucose oxidation is, on average, higher in larger athletes than smaller athletes during exercise. The extent to which this is due to higher absolute exercise intensity requires further research, but body size may be a consideration in tailoring sports nutrition guidelines for carbohydrate intake during exercise.

Background: Following consumption of a meal, circulating glucose concentrations can rise and then fall briefly below the basal/fasting concentrations. This phenomenon is known as reactive hypoglycaemia but to date no researcher has explored potential inter-individual differences in response to meal consumption., Objective: We conducted a secondary analysis of existing data to examine inter-individual variability of reactive hypoglycaemia in response to breakfast consumption., Methods: Using a replicate crossover design, 12 healthy, physically active men (age: 18-30 y, body mass index: 22.1 to 28.0 kg⋅m - 2 ) completed two identical control (continued overnight fasting) and two breakfast (444 kcal; 60% carbohydrate, 17% protein, 23% fat) conditions in randomised sequences. Blood glucose and lactate concentrations, serum insulin and non-esterified fatty acid concentrations, whole-body energy expenditure, carbohydrate and fat oxidation rates, and appetite ratings were determined before and 2 h after the interventions. Inter-individual differences were explored using Pearson's product-moment correlations between the first and second replicates of the fasting-adjusted breakfast response. Within-participant covariate-adjusted linear mixed models and a random-effects meta-analytical approach were used to quantify participant-by-condition interactions., Results: Breakfast consumption lowered 2-h blood glucose by 0.44 mmol/L (95%CI: 0.76 to 0.12 mmol/L) and serum NEFA concentrations, whilst increasing blood lactate and serum insulin concentrations (all p < 0.01). Large, positive correlations were observed between the first and second replicates of the fasting-adjusted insulin, lactate, hunger, and satisfaction responses to breakfast consumption (all r > 0.5, 90%CI ranged from 0.03 to 0.91). The participant-by-condition interaction response variability (SD) for serum insulin concentration was 11 pmol/L (95%CI: 5 to 16 pmol/L), which was consistent with the τ-statistic from the random-effects meta-analysis (11.7 pmol/L, 95%CI 7.0 to 22.2 pmol/L) whereas effects were unclear for other outcome variables (e.g., τ-statistic value for glucose: 0 mmol/L, 95%CI 0.0 to 0.5 mmol/L)., Conclusions: Despite observing reactive hypoglycaemia at the group level, we were unable to detect any meaningful inter-individual variability of the reactive hypoglycaemia response to breakfast. There was, however, evidence that 2-h insulin responses to breakfast display meaningful inter-individual variability, which may be explained by relative carbohydrate dose ingested and variation in insulin sensitivity of participants., (© 2024. The Author(s).)

Restricted sugar and ketogenic diets can alter energy balance/metabolism, but decreased energy intake may be compensated by reduced expenditure. In healthy adults, randomization to restricting free sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduces fat mass without changing energy expenditure versus control. Free-sugar restriction minimally affects metabolism or gut microbiome but decreases low-density lipoprotein cholesterol (LDL-C). In contrast, a ketogenic diet decreases glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose and increases apolipoprotein B, C-reactive protein, and postprandial glycerol concentrations. However, despite sustained ketosis, these effects are no longer apparent by week 12, when gut microbial beta diversity is altered, possibly reflective of longer-term adjustments to the ketogenic diet and/or energy balance. These data demonstrate that restricting free sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles, and gut microbiome., Competing Interests: Declaration of interests P.D.C. is a co-founder and CTO of SeqBiome Ltd. J.T.G. has received research funding from BBSRC, MRC, Cancer Research UK, the British Heart Foundation, Clasado Biosciences, Lucozade Ribena Suntory, Arla Foods Ingredients, the Cosun Nutrition Center, and the Fruit Juice Science Center; is a scientific advisory board member to ZOE; and has completed paid consultancy for 6d Sports Nutrition, The Dairy Council, PepsiCo, Violicom Medical, Tour Racing Ltd., and SVGC. J.A.B. is an investigator on research grants funded by BBSRC, MRC, the British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, Arla Foods, Cosun Nutrition Center, American Academy of Sleep Medicine Foundation, and Salus Optima (L3M Technologies Ltd.); has completed paid consultancy for PepsiCo, Kellogg’s, SVGC, and Salus Optima (L3M Technologies Ltd.); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in-Chief of International Journal of Sport Nutrition & Exercise Metabolism., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

High (free) sugar intakes can increase self-reported energy intake and are associated with unfavourable cardiometabolic health. However, sugar source may modulate the effects of sugars due to several mechanisms including the food matrix. The aim of this review was to assess the current state of evidence in relation to food source effects on the physiological responses to dietary sugars in humans relevant to cardiometabolic health. An additional aim was to review potential mechanisms by which food sources may influence such responses. Evidence from meta-analyses of controlled intervention trials was used to establish the balance of evidence relating to the addition of sugars to the diet from sugar-sweetened beverages, fruit juice, honey and whole fruit on cardiometabolic outcomes. Subsequently, studies which have directly compared whole fruit with fruit juices, or variants of fruit juices, were discussed. In summary, the sources of sugars can impact physiological responses, with differences in glycaemic control, blood pressure, inflammation, and acute appetite. Longer-term effects and mechanisms require further work, but initial evidence implicates physical structure, energy density, fibre, potassium and polyphenol content, as explanations for some of the observed responses., (© 2024. The Author(s).)

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

There is evidence across species and across many traits that males display greater between-individual variance. In contrast, (premenopausal) females display large within-individual variance in sex hormone concentrations, which can increase within-individual variance in many other parameters. The latter may contribute to the lower representation of females in metabolic research. This study is a pooled secondary analysis of data from seven crossover studies to investigate the between-individual and the within-individual variance in fasting plasma metabolites, resting metabolic rate (RMR), and body mass. Females demonstrated higher within-individual variability of plasma 17β-estradiol [coefficient of variation (CV): 15 ± 15% for males vs. 38 ± 34% for females, P < 0.001] and progesterone concentrations (CV: 13 ± 11% for males vs. 52 ± 51% for females, P < 0.001) but there were no meaningful differences in the variability of plasma glucose (CV: 4 ± 3% for males vs. 5 ± 5% for females), insulin, lactate, triglycerides (CV: 15 ± 9% for males vs. 15 ± 10% for females), and esterified fatty acid concentrations or in RMR and body mass (CV: 0.43 ± 0.34% for males vs. for 0.42 ± 0.33% females; P > 0.05 for all outcomes). Males displayed higher between-individual variance in RMR compared with females (SD: 224 kcal·day -1 for males vs. 151 kcal·day -1 for females). In conclusion, these data do not provide evidence that females show greater within-individual variability in many fasting metabolic variables, RMR, or body mass compared with males. We conclude that including females in metabolic research is unlikely to introduce greater within-individual variance when using the recruitment and control procedures described in these studies. NEW & NOTEWORTHY To investigate the within-individual variability in metabolic parameters in males and females, we performed a pooled secondary analysis of fasting blood samples, resting metabolic rate, and body mass from seven crossover studies. We found a greater day-to-day variation in 17β-estradiol and progesterone in females compared with males but no meaningful difference in within-individual variability of fasting plasma glucose, insulin, lactate, triglycerides, NEFA, resting metabolic rate, or body mass between females and males.

The aim of this study was to assess whether adding Ca 2+  to aggregate or native forms of β -lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β -lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca 2+ -rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13 C-acetate and 13 C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1 TOTAL ) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1 TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v . 1550 ± 456 pmol·l -1 ·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v . 1844 ± 550 pmol·l -1 ·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life ( P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v . 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v . AGGREG ( P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca 2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).

Context: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism., Objective: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol., Methods: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression., Results: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity., Conclusion: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Midlobular hepatocytes are proposed to be the most plastic hepatic cell, providing a reservoir for hepatocyte proliferation during homeostasis and regeneration. However, other mechanisms beyond hyperplasia have been little explored and the contribution of other hepatocyte subpopulations to regeneration has been controversial. Thus, re-examining hepatocyte dynamics during regeneration is critical for cell therapy and treatment of liver diseases. Using a mouse model of hepatocyte- and non-hepatocyte- multicolor lineage tracing, we demonstrate that midlobular hepatocytes also undergo hypertrophy in response to chemical, physical, and viral insults. Our study shows that this subpopulation also combats liver impairment after infection with coronavirus. Furthermore, we demonstrate that pericentral hepatocytes also expand in number and size during the repair process and Galectin-9-CD44 pathway may be critical for driving these processes. Notably, we also identified that transdifferentiation and cell fusion during regeneration after severe injury contribute to recover hepatic function., (© 2024. The Author(s).)

Changes in blood glucose concentrations are underpinned by blood glucose kinetics (endogenous and exogenous glucose appearance rates and glucose disappearance rates). Exercise potently alters blood glucose kinetics and can thereby be used as a tool to control blood glucose concentration. However, most studies of exercise-induced changes in glucose kinetics are conducted in a fasted state, and therefore less is known about the effects of exercise on glucose kinetics when exercise is conducted in a postprandial state. Emerging evidence suggests that food intake prior to exercise can increase postprandial blood glucose flux compared with when meals are consumed after exercise, whereby both glucose appearance rates and disappearance rates are increased. The mechanisms underlying the mediating effect of exercise conducted in the fed versus the fasted state are yet to be fully elucidated. Current evidence demonstrates that exercise in the postprandial state increased glucose appearance rates due to both increased exogenous and endogenous appearance and may be due to changes in splanchnic blood flow, intestinal permeability, and/or hepatic glucose extraction. On the other hand, increased glucose disappearance rates after exercise in the fed state have been shown to be associated with increased intramuscular AMPK signaling via a mismatch between carbohydrate utilization and delivery. Due to differences in blood glucose kinetics and other physiological differences, studies conducted in the fasted state cannot be immediately translated to the fed state. Therefore, conducting studies in the fed state could improve the external validity of data pertaining to glucose kinetics and intramuscular signaling in response to nutrition and exercise.

Background: Typical breakfast foods are rich in carbohydrate, so they not only elevate blood glucose during the morning, but also elicit a second-meal effect that can attenuate blood glucose responses in the afternoon., Objectives: To determine whether a reduced-carbohydrate protein-enriched breakfast can elicit similar effects on glucose control later in the day but without hyperglycemia in the morning., Methods: In a randomized crossover design, 12 healthy men and women (age 22 ± 2 y, BMI 24.1 ± 3.6 kg·m -2 ; Mean ± SD) completed 3 experimental conditions. In all conditions, participants consumed an ad libitum lunch at 1200 ± 1 h but differed in terms of whether they had fasted all morning (control) or had consumed a standardized porridge breakfast at 0900 ± 1 h (320 ± 50 kcal; prescribed relative to resting metabolic rate) that was either carbohydrate-rich (50 ± 10 g CHO) or protein-enriched (that is, isoenergetic substitution of carbohydrate for 15 g whey protein isolate)., Results: The protein-enriched breakfast reduced the morning glycemic response (iAUC 87 ± 36 mmol·L -1 ·180 min) relative to the carbohydrate-rich breakfast (119 ± 37 mmol·L -1 ·180 min; P = 0.03). Despite similar energy intake at lunch in all 3 conditions (protein-enriched 769 ± 278 kcal; carbohydrate-rich 753 ± 223 kcal; fasting 790 ± 227 kcal), postlunch insulinemic responses were markedly attenuated when breakfasts had been consumed that were either protein-enriched (18.0 ± 8.0 nmol·L -1 ·120 min; P = 0.05) or carbohydrate-rich (16.0 ± 7.7 nmol·L -1 ·120 min; P = 0.005), relative to when lunch was consumed in an overnight fasted state (26.9 ± 13.5 nmol·L -1 ·120 min)., Conclusions: Breakfast consumption attenuates insulinemic responses to a subsequent meal, achieved with consumption of energy-matched breakfasts typically high in carbohydrates or enriched with whey protein isolate relative to extended morning fasting., Trial Registration Number: NCT03866720 (clinicaltrials.gov)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Polymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation., Objectives: To assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia., Methods: Fifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m 2 ): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide)., Results: Serum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition-time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions., Conclusions: PP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations. This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The idea that increasing physical activity directly adds to TEE in humans (additive model) has been challenged by the energy constrained hypothesis (constrained model). This model proposes that increased physical activity decreases other components of metabolism to constrain TEE. There is a logical evolutionary argument for trade-offs in metabolism, but, to date, evidence supporting constraint is subject to several limitations, including cross-sectional and correlational studies with potential methodological issues from extreme differences in body size/composition and lifestyle, potential statistical issues such as regression dilution and spurious correlations, and conclusions drawn from deductive inference rather than direct observation of compensation. Addressing these limitations in future studies, ideally, randomized controlled trials should improve the accuracy of models of human energy expenditure. The available evidence indicates that in many scenarios, the effect of increasing physical activity on TEE will be mostly additive although some energy appears to "go missing" and is currently unaccounted for. The degree of energy balance could moderate this effect even further., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims/hypothesis: The aim of this systematic review was to synthesise the study findings on whether GLP-1 secretion in response to a meal tolerance test is affected by the presence of type 2 diabetes (T2D). The influence of putative moderators such as age, sex, meal type, meal form, and assay type were also explored., Methods: A literature search identified 32 relevant studies. The sample mean and SD for fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC were extracted and used to calculate between-group standardised mean differences (SMD), which were meta-analysed using a random-effects model to derive pooled estimates of Hedges' g and 95 % prediction intervals (PI)., Results: Pooled across 18 studies, the overall SMD in GLP-1 TOTAL iAUC between individuals with T2D (n = 270, 1047 ± 930 pmol·L -1 ·min) and individuals without T2D (n = 402, 1204 ± 937 pmol·L -1 ·min) was very small, not statistically significant and heterogenous across studies (g = -0.15, p = 0.43, PI: -1.53, 1.23). Subgroup analyses demonstrated an effect of assay type whereby Hedges' g for GLP-1 iAUC was greater in individuals with, versus those without T2D when using ELISA or Mesoscale (g = 0.67 [moderate], p = 0.009), but not when using RIA (g = -0.30 [small], p = 0.10). Pooled across 30 studies, the SMD in fasting GLP-1 TOTAL between individuals with T2D (n = 580, 16.2 ± 6.9 pmol·L -1 ) versus individuals without T2D (n = 1363, 12.4 ± 5.7 pmol·L -1 ) was small and heterogenous between studies (g = 0.24, p = 0.21, PI: -1.55, 2.02)., Conclusions: Differences in fasting GLP-1 TOTAL and GLP-1 TOTAL iAUC between individuals with, versus those without T2D were generally small and inconsistent between studies. Factors influencing study heterogeneity such as small sample sizes and poor matching of groups may help to explain the wide prediction intervals observed. Considerations to improve comparisons of GLP-1 secretion in T2D and potential mediating factors more important than T2D diagnosis per se are outlined., Prospero Id: CRD42020195612., Competing Interests: Declaration of competing interest JW has received research funding as part of their PhD studentship from Arla Foods Ingredients (DK). SC, and GA have no conflicts of interest. JJH is a member of the advisory board to Novo Nordisk. FK is supported by MRC (UK) funding (MR/P002927/1). JAB is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, ARLA foods, Kennis Centrum Suiker and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg's, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in Chief of International Journal of Sport Nutrition & Exercise Metabolism. J.T.G. is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, The Rank Prize Funds, The European Society for Clinical Nutrition and Metabolism (ESPEN), Lucozade Ribena Suntory, ARLA Foods Ingredients, Kenniscentrum Suiker and Voeding and Clasado Biosciences; and has completed paid consultancy for PepsiCo and SVGC., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h., Methods: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning., Results: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d -1 ; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d -1 ; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01)., Conclusion: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes., Clinical Trials Registration Id: NCT03509610, https://clinicaltrials.gov/show/NCT03509610., (© 2022. The Author(s).)

Intravenous ketone body infusion can increase erythropoietin (EPO) concentrations, but responses to ketone monoester ingestion postexercise are currently unknown. The purpose of this study was to assess the effect of ketone monoester ingestion on postexercise erythropoietin (EPO) concentrations. Nine healthy men completed two trials in a randomized, crossover design (1-wk washout). During trials, participants performed 1 h of cycling (initially alternating between 50% and 90% of maximal aerobic capacity for 2 min each interval, and then 50% and 80%, and 50% and 70% when the higher intensity was unsustainable). Participants ingested 0.8 g·kg -1 sucrose with 0.4 g·kg -1 protein immediately after exercise, and at 1, 2, and 3 h postexercise. During the control trial (CONTROL), no further nutrition was provided, whereas on the ketone monoester trial (KETONE), participants also ingested 0.29 g·kg -1 of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate immediately postexercise and at 1 and 2 h postexercise. Blood was sampled immediately postexercise, every 15 min in the first hour and hourly thereafter for 4 h. Serum EPO concentrations increased to a greater extent in KETONE than in CONTROL (time × condition interaction: P = 0.046). Peak serum EPO concentrations were higher with KETONE (means ± SD: 9.0 ± 2.3 IU·L -1 ) compared with CONTROL (7.5 ± 1.5 IU·L -1 , P < 0.01). Serum β-hydroxybutyrate concentrations were also higher, and glucose concentrations lower, with KETONE versus CONTROL (both P < 0.01). In conclusion, ketone monoester ingestion increases postexercise erythropoietin concentrations, revealing a new avenue for orally ingestible ketone monoesters to potentially alter hemoglobin mass. NEW & NOTEWORTHY To our knowledge, this study was the first to assess the effects of ketone monoester ingestion on erythropoietin concentrations after exercise. We demonstrated that ingestion of a ketone monoester postexercise increased serum erythropoietin concentrations and reduced serum glucose concentrations in healthy men. These data reveal the possibility for ketone monoesters to alter hemoglobin mass.

Isotopic tracers can reveal insights into the temporal nature of metabolism and track the fate of ingested substrates. A common use of tracers is to assess aspects of human carbohydrate metabolism during exercise under various established models. The dilution model is used alongside intravenous infusion of tracers to assess carbohydrate appearance and disappearance rates in the circulation, which can be further delineated into exogenous and endogenous sources. The incorporation model can be used to estimate exogenous carbohydrate oxidation rates. Combining methods can provide insight into key factors regulating health and performance, such as muscle and liver glycogen utilization, and the underlying regulation of blood glucose homeostasis before, during, and after exercise. Obtaining accurate, quantifiable data from tracers, however, requires careful consideration of key methodological principles. These include appropriate standardization of pretrial diet, specific tracer choice, whether a background trial is necessary to correct expired breath CO2 enrichments, and if so, what the appropriate background trial should consist of. Researchers must also consider the intensity and pattern of exercise, and the type, amount, and frequency of feeding (if any). The rationale for these considerations is discussed, along with an experimental design checklist and equation list which aims to assist researchers in performing high-quality research on carbohydrate metabolism during exercise using isotopic tracer methods.

Introduction: Dietary inorganic nitrate is a popular nutritional supplement, which increases nitric oxide bioavailability and may improve exercise performance. Despite over a decade of research into the effects of dietary nitrate supplementation during exercise there is currently no expert consensus on how, when and for whom this compound could be recommended as an ergogenic aid. Moreover, there is no consensus on the safe administration of dietary nitrate as an ergogenic aid. This study aimed to address these research gaps., Methods: The modified Delphi technique was used to establish the views of 12 expert panel members on the use of dietary nitrate as an ergogenic aid. Over three iterative rounds (two via questionnaire and one via videoconferencing), the expert panel members voted on 222 statements relating to dietary nitrate as an ergogenic aid. Consensus was reached when > 80% of the panel provided the same answer (i.e. yes or no). Statements for which > 80% of the panel cast a vote of insufficient evidence were categorised as such and removed from further voting. These statements were subsequently used to identify directions for future research., Results: The 12 panel members contributed to voting in all three rounds. A total of 39 statements (17.6%) reached consensus across the three rounds (20 yes, 19 no). In round one, 21 statements reached consensus (11 yes, 10 no). In round two, seven further statements reached consensus (4 yes, 3 no). In round three, an additional 11 statements reached consensus (5 yes, 6 no). The panel agreed that there was insufficient evidence for 134 (60.4%) of the statements, and were unable to agree on the outcome of the remaining statements., Conclusions: This study provides information on the current expert consensus on dietary nitrate, which may be of value to athletes, coaches, practitioners and researchers. The effects of dietary nitrate appear to be diminished in individuals with a higher aerobic fitness (peak oxygen consumption [V̇O 2peak ] > 60 ml/kg/min), and therefore, aerobic fitness should be taken into account when considering use of dietary nitrate as an ergogenic aid. It is recommended that athletes looking to benefit from dietary nitrate supplementation should consume 8-16 mmol nitrate acutely or 4-16 mmol/day nitrate chronically (with the final dose ingested 2-4 h pre-exercise) to maximise ergogenic effects, taking into consideration that, from a safety perspective, athletes may be best advised to increase their intake of nitrate via vegetables and vegetable juices. Acute nitrate supplementation up to ~ 16 mmol is believed to be safe, although the safety of chronic nitrate supplementation requires further investigation. The expert panel agreed that there was insufficient evidence for most of the appraised statements, highlighting the need for future research in this area., (© 2022. The Author(s).)

It was previously demonstrated that postexercise ingestion of fructose-glucose mixtures can lead to superior liver and equal muscle glycogen synthesis as compared with glucose-based carbohydrates (CHOs) only. After an overnight fast, liver glycogen stores are reduced, and based on this we hypothesized that addition of fructose to a glucose-based breakfast would lead to improved subsequent endurance exercise capacity. In this double-blind cross-over randomized study (eight males, peak oxygen uptake: 62.2 ± 5.4 ml·kg-1·min-1), participants completed two experimental trials consisting of two exercise bouts. In the afternoon of Day 1, they completed a cycling interval training session to normalize glycogen stores after which a standardized high-CHO diet was provided for 4 hr. On Day 2, in the morning, participants received 2 g/kg of CHOs in the form of glucose and rice or fructose and rice, both in a CHO ratio of 1:2. Two hours later they commenced cycling exercise session at the intensity of the first ventilatory threshold until task failure. Exercise capacity was higher in fructose and rice (137.0 ± 22.7 min) as compared with glucose and rice (130.06 ± 19.87 min; p = .046). Blood glucose and blood lactate did not differ between the trials (p > .05) and neither did CHO and fat oxidation rates (p > .05). However, due to the duration of exercise, total CHO oxidation was higher in fructose and rice (326 ± 60 g vs. 298 ± 61 g, p = .009). Present data demonstrate that addition of fructose to a glucose-based CHO source at breakfast improves endurance exercise capacity. Further studies are required to determine the mechanisms and optimal dose and ratio.

Introduction: Continuous exercise can increase postprandial gut hormone such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) responses, but it is unknown whether interrupting prolonged sitting with intermittent walking elicits this effect., Method: Ten participants with central overweight/obesity (7 men and 3 postmenopausal women, 51 ± 5 yr; mean ± SD) completed a randomized crossover study in which they consumed breakfast and lunch in the laboratory while either sitting continuously for the entire 5.5-h period (SIT) or the prolonged sitting interrupted every 20 min by walking briskly (6.4 km·h-1) for 2 min (BREAKS). Blood samples were collected at regular intervals to examine postprandial plasma GLP-1, PYY, and glucose-dependent insulinotropic polypeptide concentrations. Adipose tissue samples were collected at baseline and at the end of the trials to examine changes in net dipeptidyl peptidase 4 secretion from primary explants., Results: Mean (95% confidence interval) postprandial GLP-1 and PYY incremental area under curve values were elevated by 26% and 31% in the BREAKS trial versus SIT (8.4 [0.7, 16.1] vs 6.7 [-0.8, 14.2], P = 0.001, and 26.9 [8.1, 45.6] vs 20.4 [5.1, 35.8] nmol·330 min·L-1, P = 0.024, respectively) but without any such effect on glucose-dependent insulinotropic polypeptide (P = 0.076) or net adipose tissue dipeptidyl peptidase 4 secretion (P > 0.05)., Conclusions: Interrupting prolonged sitting with regular short bouts of brisk walking increases postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity., (Copyright © 2022 by the American College of Sports Medicine.)

We examined the effects of carbohydrate (CHO) delivery form on exogenous CHO oxidation, gastrointestinal discomfort, and exercise capacity. In a randomized repeated-measures design [after 24 h of high CHO intake (8 g·kg -1 ) and preexercise meal (2 g·kg -1 )], nine trained males ingested 120 g CHO·h -1 from fluid (DRINK), semisolid gel (GEL), solid jelly chew (CHEW), or a coingestion approach (MIX). Participants cycled for 180 min at 95% lactate threshold, followed by an exercise capacity test (150% lactate threshold). Peak rates of exogenous CHO oxidation (DRINK 1.56 ± 0.16, GEL 1.58 ± 0.13, CHEW 1.59 ± 0.08, MIX 1.66 ± 0.02 g·min -1 ) and oxidation efficiency (DRINK 72 ± 8%, GEL 72 ± 5%, CHEW 75 ± 5%, MIX, 75 ± 6%) were not different between trials (all P > 0.05). Despite ingesting 120 g·h -1 , participants reported minimal symptoms of gastrointestinal distress across all trials. Exercise capacity was also not significantly different (all P > 0.05) between conditions (DRINK 446 ± 350, GEL 529 ± 396, CHEW 596 ± 416, MIX 469 ± 395 s). Data represent the first time that rates of exogenous CHO oxidation (via stable isotope methodology) have been simultaneously assessed with feeding strategies (i.e., preexercise CHO feeding and the different forms and combinations of CHO during exercise) commonly adopted by elite endurance athletes. We conclude that 120 g·h -1 CHO (in a 1:0.8 ratio of maltodextrin or glucose to fructose) is a practically tolerable strategy to promote high CHO availability and oxidation during exercise. NEW & NOTEWORTHY We demonstrate comparable rates of exogenous CHO oxidation from fluid, semisolid, solid, or a combination of sources. Considering the sustained high rates of total and exogenous CHO oxidation and relative lack of gastrointestinal symptoms, consuming 120 g CHO·h -1 appears to be a well-tolerated strategy to promote high CHO availability during exercise. Additionally, this is the first time that rates of exogenous CHO oxidation have been assessed with feeding strategies (e.g., coingestion of multiple CHO forms) typically reported by endurance athletes.

Ketone ingestion can alter metabolism but effects on exercise performance are unclear, particularly with regard to the impact on intermittent-intensity exercise and team-sport performance. Nine professional male rugby union players each completed two trials in a double-blind, randomized, crossover design. Participants ingested either 90 ± 9 g carbohydrate (CHO; 9% solution) or an energy matched solution containing 20 ± 2 g CHO (3% solution) and 590 mg/kg body mass β-hydroxybutyrate monoester (CHO + BHB-ME) before and during a simulated rugby union-specific match-play protocol, including repeated high-intensity, sprint and power-based performance tests. Mean time to complete the sustained high-intensity performance tests was reduced by 0.33 ± 0.41 s (2.1%) with CHO + BHB-ME (15.53 ± 0.52 s) compared with CHO (15.86 ± 0.80 s) placebo (p = .04). Mean time to complete the sprint and power-based performance tests were not different between trials. CHO + BHB-ME resulted in blood BHB concentrations that remained >2 mmol/L during exercise (p < .001). Serum lactate and glycerol concentrations were lower after CHO + BHB-ME than CHO (p < .05). Coingestion of a BHB-ME with CHO can alter fuel metabolism (attenuate circulating lactate and glycerol concentrations) and may improve high-intensity running performance during a simulated rugby match-play protocol, without improving shorter duration sprint and power-based efforts.

Nutrition and exercise metabolism are vibrant physiological fields, yet at times it feels as if greater progress could be made by better integrating these disciplines. Exercise is advocated for improving metabolic health, in part by increasing peripheral insulin sensitivity and glycaemic control. However, when a modest-to-high carbohydrate load is consumed before and/or during each exercise bout within a training programme, increases in oral glucose insulin sensitivity can be blunted in both men of a healthy weight and those with overweight/obesity. Exercise training-induced adaptation in the energy sensing AMP-activated protein kinase (AMPK) and the insulin-sensitive glucose transporter GLUT4 protein levels are sensitive to pre-exercise feeding status in both healthy individuals and individuals classified as overweight or obese. Increased lipid oxidation may, in part, explain the enhanced adaptive responses to exercise training performed before (i.e. fasted-state exercise) versus after nutrient ingestion. Evidence in individuals with type 2 diabetes currently shows no effect of altering nutrient-exercise timing for measured markers of metabolic health, or greater reductions in glycated haemoglobin (HbA1c) concentrations with exercise performed after versus before nutrient provision. Since the metabolic inflexibility associated with type 2 diabetes diminishes differences in lipid oxidation between the fasted and fed states, it is plausible that pre-exercise feeding status does not alter adaptations to exercise when metabolic flexibility is already compromised. Current evidence suggests restricting carbohydrate intake before and during exercise can enhance some health benefits of exercise, but in order to establish clinical guidelines, further research is needed with hard outcomes and different populations., (© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

CD8 + T cell responses are the foundation of the recent clinical success of immunotherapy in oncologic indications. Although checkpoint inhibitors have enhanced the activity of existing CD8 + T cell responses, therapeutic approaches to generate Ag-specific CD8 + T cell responses have had limited success. Here, we demonstrate that cytosolic delivery of Ag through microfluidic squeezing enables MHC class I presentation to CD8 + T cells by diverse cell types. In murine dendritic cells (DCs), squeezed DCs were ∼1000-fold more potent at eliciting CD8 + T cell responses than DCs cross-presenting the same amount of protein Ag. The approach also enabled engineering of less conventional APCs, such as T cells, for effective priming of CD8 + T cells in vitro and in vivo. Mixtures of immune cells, such as murine splenocytes, also elicited CD8 + T cell responses in vivo when squeezed with Ag. We demonstrate that squeezing enables effective MHC class I presentation by human DCs, T cells, B cells, and PBMCs and that, in clinical scale formats, the system can squeeze up to 2 billion cells per minute. Using the human papillomavirus 16 (HPV16) murine model, TC-1, we demonstrate that squeezed B cells, T cells, and unfractionated splenocytes elicit antitumor immunity and correlate with an influx of HPV-specific CD8 + T cells such that >80% of CD8s in the tumor were HPV specific. Together, these findings demonstrate the potential of cytosolic Ag delivery to drive robust CD8 + T cell responses and illustrate the potential for an autologous cell-based vaccine with minimal turnaround time for patients., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Objective: To determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release., Methods: CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies., Results: 17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: -489 kJ; 95% CI, -898 to -80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: -1326 kJ; 95% CI, -2102 to -550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: -2095 kJ; 95% CI, -3910 kJ to -280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: -0.67 kJ/min; 95% CI, -1.10 to -0.23 kJ/min; P = 0.003). Subjective hunger was significantly higher during FastEx + Meal (MD: 13 mm; 95% CI, 5-21 mm; P = 0.001) and FastEx + NoMeal (MD: 23 mm; 95% CI, 16-30 mm; P < 0.001) compared to FedEx + NoMeal., Conclusion: FastEx + NoMeal appears to be the most effective strategy to produce a short-term decrease in energy intake, but also results in increased hunger and lowered energy expenditure. Concerns regarding experimental design however lower the confidence in these findings, necessitating future research to rectify these issues when investigating exercise meal timing and energy balance., Prospero Registration Number: CRD42020208041., Key Points: Fed exercise with a standardised post-exercise meal resulted in the lowest energy intake at the ad libitum meal served following exercise completion. Fasted exercise without a standardised post-exercise meal resulted in the lowest within-lab and 24-h energy intake, but also produced the lowest energy expenditure and highest hunger. Methodological issues lower the confidence in these findings and necessitate future work to address identified problems., (© 2021. The Author(s).)

Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in the intestine that is secreted in response to nutrient exposure. GLP-1 potentiates glucose-dependent insulin secretion from the pancreatic β cells and promotes satiety. These important actions on glucose metabolism and appetite have led to widespread interest in GLP-1 receptor agonism. Typically, this involves pharmacological GLP-1 mimetics or targeted inhibition of dipeptidyl peptidase-IV, the enzyme responsible for GLP-1 degradation. However, nutritional strategies provide a widely available, cost-effective alternative to pharmacological strategies for enhancing hormone release. Recent advances in nutritional research have implicated the combined ingestion of protein and calcium with enhanced endogenous GLP-1 release, which is likely due to activation of receptors with high affinity and/or sensitivity for amino acids and calcium. Specifically targeting these receptors could enhance gut hormone secretion, thus providing a new therapeutic option. This narrative review provides an overview of the latest research on protein- and calcium-mediated GLP-1 release with an emphasis on human data, and a perspective on potential mechanisms that link potent GLP-1 release to the co-ingestion of protein and calcium. In light of these recent findings, potential future research directions are also presented., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

This study investigated whether carbohydrate-energy replacement immediately after prolonged endurance exercise attenuates insulin sensitivity the following morning, and whether exercise improves insulin sensitivity the following morning independent of an exercise-induced carbohydrate deficit. Oral glucose tolerance and whole-body insulin sensitivity were compared the morning after 3 evening conditions, involving (1) treadmill exercise followed by a carbohydrate replacement drink (200 or 150 g maltodextrin for males and females, respectively; CHO-replace ); (2) treadmill exercise followed by a non-caloric, taste-matched placebo ( CHO-deficit ); or (3) seated rest with no drink provided ( Rest ). Treadmill exercise involved 90 minutes at ∼80% age-predicted maximum heart rate. Seven males and 2 females (aged 23 ± 1 years; body mass index 24.0 ± 2.7 kg·m -2 ) completed all conditions in a randomised order. Matsuda index improved by 22% (2.2 [0.3, 4.0] au, p  = 0.03) and HOMA2-IR improved by 10% (-0.04 [-0.08, 0.00] au, p  = 0.04) in CHO-deficit versus CHO-replace , without corresponding changes in postprandial glycaemia. Outcomes were similar between Rest and other conditions. These data suggest that improvements to insulin sensitivity in healthy populations following acute moderate/vigorous intensity endurance exercise may be dependent on the presence of a carbohydrate-energy deficit. Novelty: Restoration of carbohydrate balance following acute endurance exercise attenuated whole-body insulin sensitivity. Exercise per se failed to enhance whole-body insulin sensitivity. Maximising or prolonging the post-exercise carbohydrate deficit may enhance acute benefits to insulin sensitivity.

A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm-2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17-36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time-averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l-1·min-1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).

The benefits of high exogenous glucose availability for endurance exercise performance are well-established. Exogenous glucose oxidation rates are thought to be limited by intestinal glucose transport. Extracellular calcium in rodent intestine increases the translocation of the intestinal glucose transporter GLUT2 which, if translated to humans, could increase the capacity for exogenous glucose availability during exercise. Therefore, this pilot study aimed to explore the effect of calcium co-ingestion during endurance exercise on exogenous glucose oxidation in healthy men. Eight healthy men cycled for 2 h at 50% peak power output, ingesting either 1.2 g min -1 dextrose alone (GLU) or with the addition of 2000 mg calcium (GLU + CAL), in a randomised crossover design. Expired breath samples were collected to determine whole-body and exogenous glucose oxidation. Peak exogenous glucose oxidation during GLU was 0.83 ± 0.15 g min -1 , and was not enhanced during GLU + CAL (0.88 ± 0.11 g min -1 , p  = 0.541). The relative contributions of exogenous carbohydrate (19 ± 3% vs. 20 ± 2%, p  = 0.434), endogenous carbohydrate (65 ± 3% vs. 65 ± 3%, p  = 0.822) and fat (16 ± 3% vs. 15 ± 3%, p  = 0.677) to total substrate utilisation did not differ between trials. These results suggest the addition of calcium to glucose ingestion, at saturating glucose ingestion rates, does not appear to alter exogenous glucose oxidation during endurance exercise in healthy men.

Purpose of Review: To consider emerging research into the physiological effects of excessive dietary carbohydrate intake, with a particular focus on interactions with physical activity., Recent Findings: A single episode of massive carbohydrate overload initiates physiological responses to stimulate additional peptide hormone secretion by the gut and the conversion of carbohydrate into lipid by the intestine, liver and adipose tissue. These acute responses maintain glycaemic control both via increased oxidation of carbohydrate (rather than lipid) and via nonoxidative disposal of surplus carbohydrate into endogenous glycogen and lipid storage depots. Sustained carbohydrate overfeeding therefore results in a chronic accumulation of lipid in the liver, skeletal muscle and adipose tissue, which can impair insulin sensitivity and cardiometabolic health in general. Beyond any direct effect of such lipid deposition on body mass/composition, there is not yet clear evidence of physiologically meaningful metabolic or behavioural adaptations to carbohydrate overfeeding in terms of other components of energy balance. However, regular physical exercise can mitigate the negative health effects of carbohydrate overfeeding, independent of any effect on the net carbohydrate surplus., Summary: Research in this area has advanced understanding regarding the mechanisms of weight gain and associated health outcomes within the modern context of an abundant supply of dietary carbohydrate., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The present review summarized evidence on the role of carbohydrates in recovery from exercise within the context of acute and chronic effects on metabolism and performance., Recent Findings: Recent studies demonstrate that, in contrast to recovery of muscle glycogen stores, the recovery of liver glycogen stores can be accelerated by the co-ingestion of fructose with glucose-based carbohydrates. Three recent studies suggest this can extend time-to-exhaustion during endurance exercise tests. However, periodically restricting carbohydrate intakes during recovery from some training sessions to slow the recovery of liver and muscle glycogen stores may, over time, result in a modest increase in the ability to oxidize fat during exercise in a fasted state. Whether this periodized strategy translates into a performance advantage in the fed state remains to be clearly demonstrated., Summary: To maximize recovery of glycogen stores and the capacity to perform in subsequent endurance exercise, athletes should consider ingesting at least 1.2 g carbohydrate per kilogram body mass per hour - for the first few hours of recovery - as a mixture of fructose and glucose-based carbohydrates. However, if a goal is increased capacity for fat oxidation, athletes should consider restricting carbohydrate intakes during recovery from some key training sessions., Video Abstract: http://links.lww.com/COCN/A15., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (-1.91 ± 0.99 kilograms) almost entirely due to fat loss (-1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (-1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (-0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (-0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (-0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups ( P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)