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The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.

The Bath Breakfast Project is a series of randomised controlled trials exploring the effects of extended morning fasting on energy balance and health. These trials were categorically not designed to answer whether or not breakfast is the most important meal of the day. However, this review will philosophise about the meaning of that question and about what questions we should be asking to better understand the effects of breakfast, before summarising how individual components of energy balance and health respond to breakfast v. fasting in lean and obese adults. Current evidence does not support a clear effect of regularly consuming or skipping breakfast on body mass/composition, metabolic rate or diet-induced thermogenesis. Findings regarding energy intake are variable, although the balance of evidence indicates some degree of compensatory feeding later in the day such that overall energy intake is either unaffected or slightly lower when breakfast is omitted from the diet. However, even if net energy intake is reduced, extended morning fasting may not result in expected weight loss due to compensatory adjustments in physical activity thermogenesis. Specifically, we report that both lean and obese adults expended less energy during the morning when remaining in the fasted state than when consuming a prescribed breakfast. Further research is required to examine whether particular health markers may be responsive to breakfast-induced responses of individual components of energy balance irrespective of their net effect on energy balance and therefore body mass.

Attenuating blood glucose excursions in the postprandial state have the capacity to reduce the risk for cardiovascular disease, type 2 diabetes, and mortality, even in apparently healthy populations. Nearly a century ago, it was reported that oral glucose tolerance is improved by prior glucose consumption. This was termed the second-meal phenomenon and is also seen with consumption of mixed-macronutrient–containing meals. In this context, a number of mechanisms probably contribute to the attenuation of glycemia, including gastric emptying, early-phase insulin secretion, hepatic glucose output, and muscle glucose uptake. More recently, a paradoxical second-meal phenomenon has been observed in the immediate postexercise period whereby prior meal consumption deteriorated glucose tolerance. The mechanisms regulating the postexercise second-meal phenomenon are less clear, but are likely to involve an increase in intestinal absorption, greater hepatic glucose output, and under circumstances of muscle damage, reductions in muscle glucose uptake. Further work is required to confirm these mediating factors and to characterize the time course of this paradox, which is likely to only exist within the first 4 h following exercise. Critically, this acute postexercise phenomenon should be maintained in the perspective of the benefits of chronic exercise training, which for the majority of individuals improves glycemic control and reduces many health risks including those associated with exaggerated postprandial glycemia.

The present study examined the impact of breakfast and exercise on postprandial metabolism, appetite and macronutrient balance. A sample of twelve (blood variables n 11) physically active males completed four trials in a randomised, crossover design comprising a continued overnight fast followed by: (1) rest without breakfast (FR); (2) exercise without breakfast (FE); (3) breakfast consumption (1859 kJ) followed by rest (BR); (4) breakfast consumption followed by exercise (BE). Exercise was continuous, moderate-intensity running (expending approximately 2·9 MJ of energy). The equivalent time was spent sitting during resting trials. A test drink (1500 kJ) was ingested on all trials followed 90 min later by an ad libitum lunch. The difference between the BR and FR trials in blood glucose time-averaged AUC following test drink consumption approached significance (BR: 4·33 (sem 0·14) v. FR: 4·75 (sem 0·16) mmol/l; P= 0·08); but it was not different between FR and FE (FE: 4·77 (sem 0·14) mmol/l; P= 0·65); and was greater in BE (BE: 4·97 (sem 0·13) mmol/l) v. BR (P= 0·012). Appetite following the test drink was reduced in BR v. FR (P= 0·006) and in BE v. FE (P= 0·029). Following lunch, the most positive energy balance was observed in BR and least positive in FE. Regardless of breakfast, acute exercise produced a less positive energy balance following ad libitum lunch consumption. Energy and fat balance is further reduced with breakfast omission. Breakfast improved the overall appetite responses to foods consumed later in the day, but abrogated the appetite-suppressive effect of exercise.

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.

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.

IntroductionOver half of patients who spend >48 hours in the intensive care unit (ICU) are fed via a nasogastric (NG) tube. Current guidance recommends continuous delivery of feed throughout the day and night. Emerging evidence from healthy human studies shows that NG feeding in an intermittent pattern (rather than continuous) promotes phasic hormonal, digestive and metabolic responses that are important for effective nutrition. It is not yet known whether this will translate to the critically ill population. Here, we present the protocol for a proof-of-concept study comparing diurnal intermittent vs continuous feeding on hormonal and metabolic outcomes for patients in the ICU.Methods and analysisThe study is a single-centre, prospective, randomised, open-label trial comparing intermittent enteral nutrition with the current standard practice of continuous enteral feeding. It aims to recruit participants (n=30) needing enteral nutrition via an NG tube for >24 hours who will be randomised to a diurnal intermittent or a continuous feeding regimen with equivalent nutritional value. The primary outcome is peak plasma insulin/c-peptide within 3 hours of delivering the morning intermittent feed on the second study day, compared with that seen in the continuous feed delivery group at the same time point. Secondary outcomes include feasibility, tolerability, efficacy and metabolic/hormonal profiles.Ethics and disseminationWe obtained ethical approval from the Wales Research Ethics Committee 3 prior to data collection (reference 23/WA/0297). We will publish the results of this study in an open-access peer-reviewed journal.Trial registration number NCT06115044.

More recent studies using free-living designs over periods of weeks and months [5-8], combined with evidence from more tightly-controlled laboratory studies conducted within a single day [9-11] are beginning to address the causality of breakfast consumption, body weight regulation, and health, whilst providing mechanistic insight into any causal effects. [14] add to this growing body of literature by examining the subjective appetite, metabolic, and hormonal responses to breakfast consumption compared to extended overnight fasting, with the particularly novel component being an exercise bout performed in the afternoon (as opposed to the morning), between a standardized lunch and dinner. Using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence, Am J Clin Nutr, Vol. 98, 2013, 1298-1308 5 J.A. Betts, J.D. Richardson, E.A. Chowdhury, G.D. Holman, K. Tsintzas, D. Thompson, The causal role of breakfast in energy balance and health: A randomized controlled trial in...

Obesity remains a major public health concern and intermittent fasting is a popular strategy for weight loss, which may present independent health benefits. However, the number of diet books advising how fasting can be incorporated into our daily lives is several orders of magnitude greater than the number of trials examining whether fasting should be encouraged at all. This review will consider the state of current understanding regarding various forms of intermittent fasting (e.g. 5:2, time-restricted feeding and alternate-day fasting). The efficacy of these temporally defined approaches appears broadly equivalent to that of standard daily energy restriction, although many of these models of intermittent fasting do not involve fed-fasted cycles every other 24 h sleep–wake cycle and/or permit some limited energy intake outside of prescribed feeding times. Accordingly, the intervention period therefore may not regularly alternate, may not span all or even most of any given day, and may not even involve absolute fasting. This is important because potentially advantageous physiological mechanisms may only be initiated if a post-absorptive state is sustained by uninterrupted fasting for a more prolonged duration than applied in many trials. Indeed, promising effects on fat mass and insulin sensitivity have been reported when fasting duration is routinely extended beyond sixteen consecutive hours. Further progress will require such models to be tested with appropriate controls to isolate whether any possible health effects of intermittent fasting are primarily attributable to regularly protracted post-absorptive periods, or simply to the net negative energy balance indirectly elicited by any form of dietary restriction.

Many adults become vitamin D deficient or insufficient during winter at northerly latitudes when cutaneous vitamin D synthesis does not occur. Vitamin D accumulates in adipose tissue and people with overweight or obesity are more likely to have low systemic vitamin D. This randomized controlled trial demonstrates that regular exercise completely maintains serum concentrations of the active vitamin D metabolite 1,25(OH)2D3 over winter and may ameliorate the decline in 25(OH)D status in overweight men and women, even without weight loss. The binding of 1,25(OH)2D3 to the vitamin D receptor mediates the crucial role for vitamin D in the healthy function of multiple organ systems and vitamin D supplementation does not impact circulating 1,25(OH)2D3. Thus, the VitaDEx study provides causal evidence that exercise plays an important role in vitamin D metabolism that is distinct from the effects of oral supplementation. In people with overweight or obesity, regular exercise even without weight loss or vitamin D supplementation completely prevents the usual winter decline in the vitamin D metabolite that maintains health at a cellular level, 1,25(OH)2D3, and ameliorates the decline in the vitamin D status marker 25(OH)D.