is exercise best served on an empty stomach? proceedings ... · the nutrition society scottish...

The Nutrition Society Scottish Section Meeting was held at the Royal College of Physicians and Surgeons, Glasgow on 26–27 March 2018

Conference on ‘Nutrient–nutrient interaction’Symposium 3: The mechanisms of nutrient interactions

Is exercise best served on an empty stomach?

Gareth A. Wallis1* and Javier T. Gonzalez21School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK

2Department for Health, University of Bath, Bath BA2 7AY, UK

The objective of this review paper is to evaluate the impact of undertaking aerobic exercisein the overnight-fasted v. fed-state, in the context of optimising the health benefits of regularphysical activity. Conducting a single bout of aerobic exercise in the overnight-fasted v. fed-state can differentially modulate the aspects of metabolism and energy balance behaviours.This includes, but is not limited to, increased utilisation of fat as a fuel source, improvedplasma lipid profiles, enhanced activation of molecular signalling pathways related to fuelmetabolism in skeletal muscle and adipose tissue, and reductions in energy intake overthe course of a day. The impact of a single bout of overnight-fasted v. fed-state exerciseon short-term glycaemic control is variable, being affected by the experimental conditions,the time frame of measurement and possibly the subject population studied. The healthresponse to undertaking overnight-fasted v. fed-state exercise for a sustained period oftime in the form of exercise training is less clear, due to a limited number of studies.From the extant literature, there is evidence that overnight-fasted exercise in young, healthymen can enhance training-induced adaptations in skeletal muscle metabolic profile, andmitigate against the negative consequences of short-term excess energy intake on glucose tol-erance compared with exercising in the fed-state. Nonetheless, further long-term studies arerequired, particularly in populations at-risk or living with cardio-metabolic disease to eluci-date if feeding status prior to exercise modulates metabolism or energy balance behavioursto an extent that could impact upon the health or therapeutic benefits of exercise.

Physical activity: Nutrient timing: Metabolism: Health

Regular physical activity and exercise has been asso-ciated with a number of health benefits including reducedrisk of developing CHD, stroke, type 2 diabetes andsome forms of cancer. Mechanistically, these effects aremediated through improvements in numerous risk fac-tors for disease such as blood pressure, lipoproteinprofile, inflammation, insulin sensitivity and weight man-agement(1). Regular physical activity and exercise hasalso been increasingly recognised for its therapeuticpotential in many clinical contexts such as obesity, type2 diabetes and CVD(2,3). Indeed, the concept of exerciseas medicine has gained significant traction in recentyears with initiatives such as Exercise is Medicine®

(http://www.exerciseismedicine.org/) managed by theAmerican College of Sports Medicine established to

increase the use of exercise programmes within primaryand other health care settings. A parallel exists betweenthe salutary effects of exercise and the clinical effective-ness of many other medications in that some individualsdisplay a less than expected therapeutic response. Forexample, the HERITAGE Family Study showed thatstructured regular aerobic exercise training led toincreased insulin sensitivity (determined by intravenousglucose tolerance test) on average in previously sedentaryindividuals. However, of the entire cohort, 42 % of parti-cipants displayed no change or decreased insulin sensitiv-ity(4). A further study reported that 12-week structuredaerobic exercise training resulted in weight loss ofabout 4 kg on average, although over 50 % of participantswere identified as losing less weight than predicted(5).

*Corresponding author: Gareth A. Wallis, email [email protected]

Proceedings of the Nutrition Society (2019), 78, 110–117 doi:10.1017/S0029665118002574© The Authors 2018 First published online 18 October 2018

Proceedings

oftheNutritionSo

ciety

https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0029665118002574Downloaded from https://www.cambridge.org/core. IP address: 54.39.106.173, on 16 Jun 2020 at 12:01:16, subject to the Cambridge Core terms of use, available at

http://www.exerciseismedicine.org/

http://www.exerciseismedicine.org/

mailto:[email protected]

https://www.cambridge.org/core/terms

https://doi.org/10.1017/S0029665118002574

https://www.cambridge.org/core

Whether such observations reflect true inter-individualvariability in responsiveness to exercise training isdebated, but the evidence does indicate that some indi-viduals may not be achieving the full potential benefitsof exercise. Physical activity relates to any type of move-ment that requires muscle contraction and raises energyexpenditure, a sub-component of which is structured,volitional exercise. While generic physical activity andexercise guidelines are clearly established, identifyingstrategies to maximise the therapeutic benefit for allindividuals represents an important step in the refine-ment and optimisation of public health physical activityrecommendations.

Sport and exercise scientists have been studying nutri-ent–exercise interactions for decades in the search fornutritional strategies that may contribute to improvingexercise performance. It is well known that nutrientintake around exercise can interact with, and modulate,metabolic, hormonal and molecular responses that mayultimately influence exercise adaptation in endurance-trained individuals(6). While ensuring a high dietarycarbohydrate intake remains critical for optimisingacute endurance exercise performance and recovery,such a strategy has been proposed to blunt some of thekey skeletal muscle adaptive responses to exercise train-ing(7). Accordingly, endurance athletes are now advisedto consider a periodised dietary approach by alteringnutrient, and particularly carbohydrate intake, as appro-priate to support their training and performance goals(8).This may include undertaking selected training sessionsunder conditions of low carbohydrate availability inorder to maximise the adaptive response to exercise,such as performing exercise in the overnight-fasted v.postprandial state. Much of the nutrient–exercise inter-action research has occurred in the sports performancedomain, but there is an increasing interest in exploringits potential translation into optimising exercise responsesfor health or therapeutic benefit(9,10). It is well known thatthe effectiveness of some medicines may be reduced bythe presence of nutrients in the gastrointestinal tract orthe direct effects of nutrients on drug metabolism(11).An important question in light of maximising the thera-peutic benefit of exercise for all individuals is whetherexercise, such as some medicines, is best taken on anempty stomach? Perhaps the less than expected responseto exercise training observed in some individuals relatesto their feeding status about individual exercise bouts?Accordingly, in this narrative review, we evaluate theimpact of undertaking aerobic exercise in the overnight-fasted v. fed-state in the context of optimising the healthor therapeutic benefits of regular physical activity.

Short-term metabolic responses to overnight-fasted v.fed-state exercise

Energy production during sustained aerobic exercise per-formed in the overnight-fasted state (i.e. 8–12 h) is sup-ported primarily by the oxidation of endogenous fatand carbohydrate stores. Fat oxidation predominatesduring low-intensity exercise (<45 % VO2max), both fat

and carbohydrate oxidation increase to supportmoderate-intensity exercise (45–65 % VO2max), whileunder most conditions carbohydrate oxidation predomi-nates at higher exercise intensities (>65 % VO2max). Arecent systematic review and meta-analysis clearlydemonstrated that as compared with performing exercisein the overnight fasted-state, the consumption of acarbohydrate-containing meal between 0·5 and 3 hbefore exercise reduces fat oxidation (and increasescarbohydrate oxidation) during exercise performed forup to 2 h duration at <70 % VO2max

(12). The suppressionof fat oxidation during fed-state exercise occurred regard-less of exercise duration, participant sex, BMI, exercisetraining status, duration between feeding and exerciseor meal carbohydrate content. Plasma NEFA concentra-tions did not significantly differ between exercise per-formed in the fed v. overnight-fasted state. A cleareffect of fed-state exercise on blood glucose and insulinconcentrations points towards increases in glycolyticflux as the dominant regulator of fuel metabolism inthese conditions(13). Further, previous research has estab-lished that the increased fat oxidation observed duringexercise in the overnight-fasted state appears to be sup-ported by both increased plasma long-chain fatty acidoxidation and type 1 skeletal muscle fibre intramuscularTAG utilisation at least in lean individuals(13,14). Theredoes not appear to be any modulation of liver fat duringexercise regardless of whether this was performed in theovernight-fasted or fed-state(15).

Whether the increased fat oxidation when exercise isperformed in the overnight-fasted state can impact upondaily fat oxidation, which would be more representativeof long-term potential to alter fat balance, is of para-mount importance. Traditionally, despite exercise increas-ing fat oxidation during the exercise bout itself, increasesin fat oxidation and reductions in fat balance over a 24 hperiod measured using whole-room indirect calorimetryhave not been observed when studied under conditionsof energy balance(16). This has been attributed to theeffects of insulin as a consequence of consuming carbohy-drate-containing meals suppressing lipid utilisationthroughout the day. However, it is notable that exercisein these studies was not undertaken in the overnight-fasted state. Iwayama et al. demonstrated recently inlean healthy men that 1 h moderate-intensity exerciseresults in increased 24 h fat oxidation measured usingwhole-room indirect calorimetry when exercise wasperformed before (i.e. in the overnight-fasted state)breakfast, but not after lunch or dinner, even when par-ticipants remained in overall energy balance(17). Thesame group have also shown improved 24 h fat oxidationand fat balance with pre-breakfast exercise in women(18).Exercise performed in the overnight-fasted state wouldappear necessary to alter 24 h fat oxidation. Whilethis area has not received extensive mechanistic inves-tigation, negative correlations between energy balanceor carbohydrate balance with 24 h fat oxidation sug-gests transient energy and/or carbohydrate deficitsmay be driving the response(17).

The study of nutrient–exercise interactions in the con-text of substrate oxidation is important because links

Exercise and timing of food intake 111

Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


between fat oxidation during exercise and daily fat oxida-tion have been made(19), as have associations betweendaily fat oxidation and obesity risk(20). Of potentiallyequal importance is consideration of how timing offood intake around exercise modulates other risk factorsfor cardio-metabolic diseases, such as circulating lipidand glucose concentrations. With regard to blood lipidprofiles, a study by Enevoldsen et al. is insightful(21).This group determined blood metabolite and hormoneresponses across the course of 5·5 h in young healthymen who undertook exercise either before or aftermixed macronutrient meal ingestion. Over the durationof the study period, a more favourable response of cir-culating markers of lipid availability (e.g. lower plasmaTAG and VLDL-TAG concentrations) was observedwhen exercise was performed before as compared toafter meal ingestion. A similar result was observedmore recently in a study of overweight men, wherebyexercise followed by food intake but not food intakefollowed by exercise significantly lowered plasmaTAG concentrations as compared with a non-exercisecontrol trial(22). Collectively, the afore-mentioned stud-ies imply a potentially beneficial impact of overnight-fasted v. fed-state exercise on the aspects of body fatregulation and lipid metabolism at least in the contextof single bouts of exercise.

The impact of overnight-fasted v. fed-state exercise onthe aspects of glycaemic control has been subject to con-siderable recent debate(23). Provision of carbohydrate-containing meals increases blood glucose and insulinconcentrations, but when this is followed by exerciseglucose uptake into skeletal muscle is enhanced leadingto a lowering effect on blood glucose. This has beenargued to be of particular importance in the contextof diabetes, with the commencement of exercise 30–90min post-prandial suggested to be optimal in accelerat-ing meal-derived glucose disposal thus avoiding hyper-glycaemia but also minimising risk of post-exercisehypoglycaemia(23). This glucose-lowering effect of fed-state exercise in type 2 diabetes does appear to bemost pronounced in those with the highest pre-exerciseblood glucose concentrations(24). Taking subsequentmeals into account can present a different picture. Forexample, feeding prior to exercise in lean, healthy indi-viduals has been observed to increase the post-exercisepostprandial glucose response to mixed macronutrientingestion as compared with fasted-state exercise(25).Furthermore, when glycaemic control was assessed inindividuals with prediabetes over the course of a fullday after overnight-fasted or fed-state exercise usingcontinuous glucose monitoring, interstitial glucose vari-ability but not total interstitial glucose exposure (areaunder the curve) was improved with fed-state exercise(26).It would seem that the reported influence of a single boutof overnight-fasted v. fed-state exercise on short-term gly-caemic control can be affected by the experimental condi-tions (e.g. when assessed over single v. multiple meals),the time frame of measurement and possibly the popula-tions studied. However, as will be discussed in a later sec-tion, it is critically important to consider the differencebetween the acute effects of a single exercise bout and

the adaptive response to chronic exercise training resultingfrom the culmination of those single exercise bouts.

Short-term energy balance behaviour responses toovernight-fasted v. fed-state exercise

Exercising in the overnight-fasted v. fed-state will clearlylead to a longer period of energy deficit, and from anenergy balance perspective, it is important to understandthe extent to which compensation of this energy deficitmay occur during the post-exercise period.

This was initially investigated in a study by Gonzalezet al. who had twelve young physically active men under-take 1 h moderate-intensity treadmill running exerciseperformed in the overnight-fasted state or 2 h afterbreakfast consumption(27). After exercise, all participantsconsumed a standardised mixed-macronutrient drink,followed 90 min later by provision of an ad libitum testlunch, allowing for calculation of energy and macronutri-ent intake. Indirect calorimetry was conducted during theexperiment to calculate energy expenditure and substrateoxidation. This group reported that despite the absenceof breakfast in the overnight-fasted exercise, energyintake during the test lunch was similar when exercisewas performed in the fed-state. Accordingly, energyintake and energy balance across the entire study periodwas significantly less when exercise was performed in theovernight-fasted v. fed-state. Interestingly, the lowerenergy balance with overnight-fasted exercise was attrib-utable to reduced fat but not carbohydrate balance, theimportance of which are 2-fold. First, greater reductionsin fat balance may be more likely to induce favourableeffects on body fat loss if sustained over time.Secondly, it is possible that the maintenance of carbohy-drate balance is more important and tightly regulatedthan fat balance possibly due to finite carbohydrate stor-age capacity as has been previously suggested(28). Insupport of this assertion, it has been reported that indi-viduals who utilise more carbohydrate during exerciseare more likely to compensate for the energy expended dur-ing exercise with greater post-exercise energy intake(29), andmice overexpressing hepatic protein targeted to glycogen(resulting in increased liver glycogen concentrations underfasted and fed conditions) display reduced energy intakeand increased energy expenditure(30). As such, interventionsthatminimise carbohydrate oxidation during exercise (suchas overnight-fasted exercise) may serve to limit subsequentenergy intake.

More recently, the effects of overnight-fasted v. fed-state exercise (i.e. breakfast) on energy intake was exam-ined over the course of an entire day, which may be morereflective of the potential for long-term impact on energybalance(31). The study by Bachman et al. reported that adlibitum food (and energy) intake over a 24 h period waslower when exercise was performed prior to breakfastconsumption. Interestingly, reduced energy intake wasnot simply a function of breakfast omission but foodintake during meals and snacks consumed later in theday suggesting more prolonged effects of overnight-fasted

G. A. Wallis and J. T. Gonzalez112

Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


exercise on regulation of food intake. At this stage, theinvolvement of metabolic (e.g. carbohydrate status) and/or modulation of appetite hormone regulatory mechan-isms in explaining this lower energy intake withovernight-fasted exercise has not been resolved. The pos-sibility of simply having less time in the day to consumefood should also not be excluded, and while speculative,if this is relevant then aspects of the purported benefitsof time-restricted feeding may be worthy for consider-ation(32). Importantly, the study by Bachman et al. didnot quantify energy expenditure across the entire studyperiod, thus the overall impact of the interventions onenergy balance was not reported. This may be particu-larly important, as in conditions where free-living expend-iture has been quantified, omission of breakfast per se (i.e.without exercise intervention) may transiently lower phys-ical activity energy expenditure which would impact onenergy balance(33). These collective studies suggest thatshort-term studies that encompass and allow for thebehavioural responses to overnight-fasted v. fed-stateexercise to occur may be particularly useful for under-standing the potential for long-term impacts upon metab-olism and health outcomes. However, the impact ofaltering carbohydrate oxidation on all components ofenergy balance (including physical activity) in the post-exercise period currently remains unknown, as do themechanisms that link carbohydrate balance to any behav-ioural responses in human subjects.

Longer term metabolic and health outcomes in responseto overnight-fasted and fed-state exercise

It is clear from the previous sections that overnight-fasted v.fed-state exercise can modulate metabolic and behaviouralresponses to a single bout of exercise. A relevant question isthe extent to which such short-term responses translate intolong-term modifications in biomarkers or risk factors forcardio-metabolic disease. If the feeding status around singleexercise bouts is influential in determining long-term adap-tive responses to exercise, then it may in part explain whysome individuals do not always adapt to exercise trainingas would be predicted. The implication would be that ifall exercise training sessions within a training study wereundertaken with standardisation of pre-exercise nutrition,adaptive responses may be more consistent. However, toour knowledge, there are no studies investigating overnight-fasted v. fed-state exercise training on the consistency orvariability of exercise adaptation. Indeed, with a few excep-tions described below, the vast majority of aerobic exercisetraining intervention studies focus on the exercise compo-nent rather consideration of nutritional control or timingof food intake around exercise bouts.

The effects of overnight-fasted v. fed-state exercise ontotal body mass and indices of body composition havebeen investigated in training studies conducted under dif-fering states of energy balance. Under isoenergetic andhypoenergetic conditions, when the state of energy bal-ance is matched between intervention groups, responsesof total body mass, fat mass or fat-free mass did not differas a function of short-term (i.e. 4–6 weeks) overnight-fasted

v. fed-state exercise training(14,34–36). While the effects ontotal body mass may be predictable, the lack of differ-ence in body fat reduction contrasts what could theoret-ically be expected based on previously observed increasesin daily fat oxidation and less positive (more negative) fatbalance as a result of conducting overnight-fasted exer-cise in acute studies. One of the afore-mentioned studiesutilised a high-intensity interval training programme(34),which may not be favourable for increasing fat oxidationduring exercise. As well, in all studies, the duration oftraining (i.e. 4–6 weeks) may have been insufficient torealise the theoretical advantages of overnight-fastedexercise training on body fat mass. Previous studies ofexercise training per se would indicate that at least 12weeks is necessary to induce measurable reductions inbody fat(37,38). Thus, to date, experimental conditionsmay not have been optimised to conclusively study ifbody composition can be improved with regularovernight-fasted v. fed-state exercise training in iso andhypoenergetic conditions. Indeed it could be that anyshort-term changes in daily substrate oxidation and stor-age are balanced out over periods of days and weeks suchthat body composition remains unaltered over the longterm unless there are clear perturbations to long-termenergy balance(39).

In contrast, a study conducted by Van Proeyen and col-leagues indicated that effects of overnight-fasted exercisetraining on body composition may be revealed duringconditions of hyperenergetic feeding(40). These researcherssubjected three groups of lean, healthy men to 6 weeks of30 % excess of habitual energy intake in the form of afat-rich (50 % dietary energy) diet. Participants either per-formed no exercise (control, Con), overnight-fasted (Fast)or fed-state (Fed) exercise four times per week. In Con andFed, body mass significantly increased as compared withpre-diet values by about 3 and 1·4 kg, respectively, whileno significant changes were observed in Fast. While inter-esting, it should be noted that despite apparentwithin-group differences in body mass gain, no significantbetween-group differences were observed between Fedand Fast. Incidentally, body fat assessed using skinfoldthickness measurements increased in Con, but did notchange significantly in Fed or Fast. Overall, there is apaucity of evidence to support a clear influence ofovernight-fasted v. fed-state exercise training on bodyweight and composition, at least when studied over ashort duration of training and in the state of energy bal-ance is matched between intervention arms. However, aswe discuss later, a more fruitful approach in the contextof body weight and composition may be to not clampenergy balance between interventions and allow naturalalterations in energy balance behaviours to occur out-side of the specific controlled fasted or fed-exerciseprescription.

Exercising in the overnight-fasted v. fed-state has beenlinked to a number of responses that could plausiblytranslate to long-term improvements in lipid and glucosemetabolism. Adipose tissue plays a critical role in thestorage of ingested dietary fats with relevance for post-prandial lipemia and minimising ectopic lipid storage.Indeed, high turnover of adipose tissue lipid stores has


Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


been associated with improved metabolic health(41,42)

suggesting that frequent oxidation of adipose tissuefatty acids increases the ability of adipose tissue to bufferlipid flux. Feeding status may therefore alter adipose tis-sue physiology with resultant implications for health.Consistent with this line of reasoning, a single bout offed-state exercise blunts the effects typically seen withovernight-fasted exercise on the expression of genesrelated to lipid metabolism, insulin sensitivity and glu-cose uptake in adipose tissue(43). In a similar manner,fed-state exercise tends to blunt acute exercise-relatedresponses in skeletal muscle molecular pathways asso-ciated with the up-regulation of oxidative, lipid andcarbohydrate metabolism (e.g. gene expression of FAT/CD36, CPT1, UCP3, PDK4, GLUT4, AMPKα2)(44,45).As well, in young lean men, overnight-fasted but not fed-state exercise increased utilisation of intramuscular TAGin type 1 skeletal muscle fibres(14); high rates ofintramuscular TAG turnover (i.e. storage and breakdownfor NEFA oxidation) have been implicated in the mainten-ance of muscle insulin sensitivity(46). Finally, while notunequivocal(35,47), greater long-term changes in markersof skeletal muscle training adaptation such as the proteincontents of GLUT4, FAT/CD36 and FABP and the max-imal activities of the mitochondrial enzymes citrate syn-thase and β-hydroxyacyl-coA dehydrogenase have beenobserved with overnight-fasted exercise training(35,40).

In general, the afore-mentioned evidence points to thepotential for overnight-fasted exercise to promote greaterbenefits to metabolic health outcomes than conductingregular exercise in the fed-state, although the numberof investigations in this area is remarkably limited.Summarising the evidence that is available to date,Hansen et al. concluded that there does not appearto be clear impact of short-term fed v. fasted-statedexercise training on overnight-fasted resting bloodmarkers such as glucose, insulin and NEFA; notably stud-ies have generally been performed in young lean indivi-duals(9). Only the study by Van Proeyen and colleaguesdescribed previously, which adopted 6 weeks of hypere-nergetic fat-rich feeding, has addressed the impact ofovernight-fasted v. fed-state exercise training on a dynamicmeasure of metabolic function(40). These authors foundthat the Matsuda Insulin Sensitivity Index (calculatedfrom an oral glucose tolerance test) was higher in thegroup that performed overnight-fasted exercise trainingas compared with the no exercise control trial. No signifi-cant differences were reported between fed-state exerciseand no exercise control, with the implication that fasted-state exercise improves glucose tolerance during a fat-richdiet. The authors rightly acknowledge that body massgain in the control (and fed-exercise) trial but not thefasted-exercise trial could contribute to the observed dif-ferential responses to insulin sensitivity. Nonetheless,these data provide promising proof of concept for a rolefor overnight-fasted training in enhancing benefits of exer-cise on glucose tolerance at least under conditions ofexcess energy intake, which could have relevance withinobesogenic environments.

As stated earlier, there is a clinical view that post-prandial exercise is preferable over fasted-state exercise

for the acute control of blood glucose, at least in patientsliving with type 2 diabetes(23). However, if an individualperforms fasted-state exercise, it is not clear if the subse-quent post-prandial rises in blood glucose are patho-logical. As well, we also highlighted earlier that ascompared with fasted-state exercise, fed-state exercisecan result in a worsening of subsequent post-prandialglucose control(25). Again, the question arises as to whetherthis is potentially pathological or simply reflectingshort-term adaptive physiology. Our recent work exam-ining post-prandial glucose fluxes after no exercise,exercise performed in the overnight-fasted or fed-statewould suggest the latter(48). Specifically, we observedin healthy young men that fed-state exercise increasesglucose appearance rates into the circulation duringsubsequent glucose ingestion, and this was explainedby increases in the appearance of the ingested glucose.However, this was met with increases in whole bodyglucose disposal, such that the increased influx of glu-cose was appropriately cleared. Whether this appliesin other study populations remains to be determined,but it does lend support to the notion that the responsesof blood glucose to single bouts of exercise performed inthe fed or fasted state are part of normal physiology.What is perhaps more important is the adaptive stimu-lus provided by acute bouts of exercise, for example, inskeletal muscle, that when accrued over time results inchronic changes in the capacity to manage postprandialexcursions in blood glucose (and lipids). In this respect,the work from Van Proeyen and colleagues showingthat the aspects of glucose control may be preferentiallyaffected by consistent exercise training in the overnight-fasted v. fed-state (under conditions of excess energyintake) is perhaps most revealing(40), although clearlythere is a need to follow-up this work in patients atrisk of or living with disturbances in glucose control suchas type 2 diabetes.

Conclusions

There is little doubt that the investigation of how nutrientintake in and around exercise might modulate the meta-bolic, molecular and adaptive responses to exercise train-ing is of major current interest(9,10,23,49–51). However,there is a need for further research in order to fully eluci-date if overnight-fasted exercise could be a means to opti-mise the health benefits of physical activity. For example,the influence of a single bout of overnight-fasted v. fed-state exercise on the aspects of lipid metabolism andthe molecular signals underpinning training adaptationshould be studied further in populations at risk forcardio-metabolic disease. Characterising 24 h profiles ofcirculating metabolite and hormones related to glucoseand lipid metabolism in participant populations acrossthe health continuum would help to clarify their modula-tion of overnight-fasted or fed-state exercise. As well,there is a need to characterise the influence of overnight-fasted or fed-state exercise on short-term energy balancebehaviours in a range of study populations, as this couldmore adequately reflect responses in real-world settings.


Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


Generation of these data could provide clearer insightsinto which populations and outcome measures mayyield greater benefits from long-term exercise trainingin overnight-fasted conditions.

There is also a need to extend exercise training studiesperformed in the overnight-fasted state v. fed-state forlonger durations (i.e. ≥12 weeks) and into populationgroups with or at risk for cardio-metabolic disease. Indoing this, it would be important to integrate importantclinical outcomes such as body mass and composition,glucose tolerance, glycated Hb and lipid profiles withmeasures of whole-body and tissue-specific metabolicfunction in order to gain further mechanistic insights(e.g. hepatic, adipose and skeletal muscle adaptation).Given that daily variations in glycaemic and lipid profilescould impact upon the aspects of vascular function (e.g. endothelial function, microvascular perfusion), thiswould also be an important area to explore. In con-ducting exercise training studies, an important consid-eration is whether or not to match the state of energybalance between intervention groups. As there appearsto be little compensation of energy intake to acutebouts of overnight-fasted exercise, this approachappears most likely to produce more consistent reduc-tions in energy balance, which over the long term mayprovide complementary benefits to many outcomemeasures relevant to metabolic health. Mechanistically,it is always appealing to tease out intervention effectsindependent from changes in body mass(52). However,if additional health benefits are to be gained fromovernight-fasted v. fed-state exercise, it is probably a mootpoint as to whether the effects arise through direct orindirect mechanisms related to the intervention. Finally,while the focus of the present review was on aerobic

exercise, future work investigating the health impact ofperforming other forms of exercise such as resistancetraining(53) or combined resistance and aerobic training(concurrent exercise) in the overnight-fasted v. fed-statewould be worthwhile.

In conclusion, conducting aerobic exercise in theovernight-fasted v. fed-sate can differentially modulatethe aspects of metabolism (Fig. 1) and it is possiblethat this could influence the overall adaptive responseto exercise training for health benefits. If this is thecase, advice on when to exercise with respect to foodintake could be considered for incorporation into phys-ical activity guidelines in general or for specific sub-populations seeking to optimise the health or therapeuticbenefits of exercise. However, further research, some ofwhich is highlighted in this review, is needed before wecan answer the question as to whether exercise is bestserved on an empty stomach.

Financial Support

G. A. W. has received research funding from theEngineering and Physical Sciences Research Council(UK), the Biotechnology and Biological SciencesResearch Council (UK), GlaxoSmithKline Ltd, SugarNutrition UK, Lucozade Ribena Suntory Ltd, VolacInternational Ltd and the Allen Foundation (USA).J. T. G. has received research funding from TheEuropean Society of Clinical Nutrition and Metabolism,The Rank Prize Funds, The Physiological Society (UK),The Biotechnology and Biological Sciences ResearchCouncil (UK), The Medical Research Council (UK),Arla Foods Ingredients, Lucozade Ribena Suntory and

Fig. 1. (Colour online) Major metabolic and behavioural factors influenced by aerobic exerciseperformed in the overnight-fasted v. fed-state. Acute response refers to a single bout of exercise.Chronic adaptation refers to the culmination of single bouts of exercise over a period of weeks tomonths as a result of undertaking an exercise training programme. The figure includes resultsfrom studies that used a range of study populations and different experimental designs and assuch should be regarded as conceptual rather than definitive. Superscript refers to the appropriatesupporting reference.


Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


Kenniscentrum Suiker and Voeding, and has acted asa consultant to PepsiCo. This research received nospecific grant from any funding agency, commercial ornot-for-profit sectors.

Conflict of Interest

None.

Authorship

The authors had joint responsibility for all aspects ofpreparation of this paper.

References

1. Garber CE, Blissmer B, Deschenes MR, et al. (2011)Quantity and quality of exercise for developing and main-taining cardiorespiratory, musculoskeletal, and neuromotorfitness in apparently healthy adults: guidance for prescribingexercise. Med Sci Sports Exercise 43, 1334–1359.

2. Colberg SR, Sigal RJ, Yardley JE et al. (2016) Physicalactivity/exercise and diabetes: a position statement of theAmerican Diabetes Association. Diabetes Care 39, 2065–2079.

3. Ross R, Blair SN, Arena R et al. (2016) Importance ofassessing cardiorespiratory fitness in clinical practice: acase for fitness as a clinical vital sign: a scientific statementfrom the American Heart Association. Circulation 134,e653–e699.

4. Boulé NG, Weisnagel SJ, Lakka TA et al. (2005) Effects ofexercise training on glucose homeostasis. The HERITAGEFamily Study. Diabetes Care 28, 108–114.

5. King NA, Hopkins M, Caudwell P et al. (2007) Individualvariability following 12 weeks of supervised exercise: iden-tification and characterization of compensation forexercise-induced weight loss. Int J Obes 32, 177.

6. Hawley John A, Maughan Ronald J & Hargreaves M(2015) Exercise metabolism: historical perspective. CellMetab 22, 12–17.

7. Bartlett JD, Hawley JA & Morton JP (2015) Carbohydrateavailability and exercise training adaptation: too much of agood thing? Eur J Sport Sci 15, 3–12.

8. Burke LM, Hawley JA, Wong SHS et al. (2011)Carbohydrates for training and competition. J Sports Sci29, S17–S27.

9. Hansen D, De Strijcker D & Calders P (2017) Impact ofendurance exercise training in the fasted state on musclebiochemistry and metabolism in healthy subjects: canthese effects be of particular clinical benefit to type 2 dia-betes mellitus and insulin-resistant patients? Sports Med47, 415–428.

10. Haxhi J, Scotto di Palumbo A & Sacchetti M (2013)Exercising for metabolic control: is timing important?Ann Nutr Metab 62, 14–25.

11. Genser D (2008) Food and drug interaction: consequencesfor the nutrition/health status. Ann Nutr Metab 52(suppl 1),29–32.

12. Vieira AF, Costa RR, Macedo RCO et al. (2016) Effects ofaerobic exercise performed in fasted v. fed state on fat andcarbohydrate metabolism in adults: a systematic review andmeta-analysis. Br J Nutr 116, 1153–1164.

13. Coyle EF, Jeukendrup AE, Wagenmakers AJ et al. (1997)Fatty acid oxidation is directly regulated by carbohydratemetabolism during exercise. Am J Physiol EndocrinolMetab 273, E268–E275.

14. De Bock K, Richter Erik A, Russell Aaron P et al. (2005)Exercise in the fasted state facilitates fibre type-specificintramyocellular lipid breakdown and stimulates glycogenresynthesis in humans. J Physiol 564, 649–660.

15. Bilet L, Brouwers B, van Ewijk PA et al. (2015) Acute exer-cise does not decrease liver fat in men with overweight orNAFLD. Sci Rep 5, 9709.

16. Melanson EL, Gozansky WS, Barry DW et al. (2009)When energy balance is maintained, exercise does notinduce negative fat balance in lean sedentary, obese seden-tary, or lean endurance-trained individuals. J Appl Physiol107, 1847–1856.

17. Iwayama K, Kurihara R, Nabekura Y et al. (2015)Exercise increases 24-h fat oxidation only when it is per-formed before breakfast. EBioMedicine 2, 2003–2009.

18. Iwayama K, Kawabuchi R, Nabekura Y et al. (2017)Exercise before breakfast increases 24-h fat oxidation infemale subjects. PLoS ONE 12, e0180472.

19. Robinson SL, Hattersley J, Frost GS et al. (2015) Maximalfat oxidation during exercise is positively associated with24-hour fat oxidation and insulin sensitivity in young,healthy men. J Appl Physiol 118, 1415–1422.

20. Zurlo F, Lillioja S, Puente AE-D et al. (1990) Low ratio of fatto carbohydrateoxidationaspredictorofweight gain: studyof24-h RQ. Am J Physiol Endocrinol Metab 259, E650–E657.

21. Enevoldsen LH, Simonsen L, Macdonald IA et al. (2004)The combined effects of exercise and food intake on adiposetissue and splanchnic metabolism. J Physiol 561, 871–882.

22. Farah NMF & Gill JMR (2012) Effects of exercise beforeor after meal ingestion on fat balance and postprandialmetabolism in overweight men. Br J Nutr 109, 2297–2307.

23. Chacko E (2017) A time for exercise: the exercise window. JAppl Physiol 122, 206–209.

24. Poirier P, Tremblay A, Catellier C et al. (2000) Impact oftime interval from the last meal on glucose response toexercise in subjects with type 2 diabetes 1. J ClinEndocrinol Metab 85, 2860–2864.

25. Gonzalez JT (2014) Paradoxical second-meal phenomenonin the acute postexercise period. Nutrition 30, 961–967.

26. Nygaard H, Rønnestad BR, Hammarström D et al. (2017)Effects of exercise in the fasted and postprandial state oninterstitial glucose in hyperglycemic individuals. J SportsSci Med 16, 254–263.

27. Gonzalez JT, Veasey RC, Rumbold PLS et al. (2013)Breakfast and exercise contingently affect postprandialmetabolism and energy balance in physically activemales. Br J Nutr 110, 721–732.

28. Jean-Pierre F (2001) Macronutrient composition and foodselection. Obes Res 9, 256S–262S.

29. Hopkins M, Blundell JE & King NA (2014) Individual vari-ability in compensatory eating following acute exercise in over-weight and obese women. Br J Sports Med 48, 1472–1476.

30. López-Soldado I, Fuentes-Romero R, Duran J et al. (2017)Effects of hepatic glycogen on food intake and glucosehomeostasis are mediated by the vagus nerve in mice.Diabetologia 60, 1076–1083.

31. Bachman JL, Deitrick RW & Hillman AR (2016)Exercising in the fasted state reduced 24-hour energy intakein active male adults. J Nutr Metab 2016, 1984198.

32. Hutchison A, Wittert G & Heilbronn L (2017) Matchingmeals to body clocks – impact on weight and glucosemetabolism. Nutrients 9, 222.


Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


33. Betts JA, Chowdhury EA, Gonzalez JT et al. (2016) Isbreakfast the most important meal of the day? Proc NutrSoc 75, 464–474.

34. Gillen JB, Percival, Alison L et al. (2013) Interval trainingin the fed or fasted state improves body composition andmuscle oxidative capacity in overweight women. Obesity21, 2249–2255.

35. Proeyen KV, Szlufcik K, Nielens H et al. (2011) Beneficialmetabolic adaptations due to endurance exercise training inthe fasted state. J Appl Physiol 110, 236–245.

36. Schoenfeld BJ, Aragon AA, Wilborn CD et al. (2014) Bodycomposition changes associated with fasted versus non-fasted aerobic exercise. J Int Soc Sports Nutr 11, 54.

37. Ross R, Dagnone D, Jones PH et al. (2000) Reduction inobesity and related comorbid conditions after diet-inducedweight loss or exercise-induced weight loss in men: a rando-mized, controlled trial. Ann Intern Med 133, 92–103.

38. Ross R, Janssen I, Dawson J et al. (2004) Exercise-inducedreduction in obesity and insulin resistance in women: a ran-domized controlled trial. Obes Res 12, 789–798.

39. Hall KD & Guo J (2017) Obesity energetics: body weightregulation and the effects of diet composition.Gastroenterology 152, 1718–1727. e1713.

40. Karen VP, Karolina S, Henri N et al. (2010) Training in thefasted state improves glucose tolerance during fat-rich diet.J Physiol 588, 4289–4302.

41. Arner P, Bernard S, Salehpour M et al. (2011) Dynamics ofhuman adipose lipid turnover in health and metabolic dis-ease. Nature 478, 110–113.

42. Frayn K, Bernard S, Spalding K et al. (2012) Adipocytetriglyceride turnover is independently associated withatherogenic dyslipidemia. J Am Heart Assoc CardiovascCerebrovasc Dis 1, e003467.

43. Chen Y-C, Travers RL, Walhin J-P et al. (2017)Feeding influences adipose tissue responses to exercise inoverweight men. Am J Physiol Endocrinol Metab 313,E84–E93.

44. Civitarese AE, Hesselink MKC, Russell AP et al. (2005)Glucose ingestion during exercise blunts exercise-inducedgene expression of skeletal muscle fat oxidative genes. AmJ Physiol Endocrinol Metab 289, E1023–E1029.

45. Cluberton LJ, McGee SL, Murphy RM et al. (2005) Effectof carbohydrate ingestion on exercise-induced alterations inmetabolic gene expression. J Appl Physiol 99, 1359–1363.

46. Shaw CS, Clark J & Wagenmakers AJM (2010) The effectof exercise and nutrition on intramuscular fat metabolismand insulin sensitivity. Annu Rev Nutr 30, 13–34.

47. Bock KD, Derave W, Eijnde BO et al. (2008) Effect of train-ing in the fasted state on metabolic responses during exercisewith carbohydrate intake. J Appl Physiol 104, 1045–1055.

48. Edinburgh RM, Hengist A, Smith HA et al. (2018)Pre-exercise breakfast ingestion versus extended overnightfasting increases postprandial glucose flux after exercise inhealthy men: pre-exercise feeding and postprandial glucoseflux. Am J Physiol Endocrinol Metab (In the Press).

49. Hawley JA, Lundby C, Cotter JD et al. (2018) Maximizingcellular adaptation to endurance exercise in skeletal muscle.Cell Metab 27, 962–976.

50. Aird TP, Davies RW & Carson BP (2018) Effects of fastedvs fed-state exercise on performance and post-exercisemetabolism: a systematic review and meta-analysis. ScandJ Med Sci Sports 28, 1476–1493.

51. Solomon TPJ, Eves FF & Laye MJ (2018) Targeting post-prandial hyperglycemia with physical activity may reducecardiovascular disease risk. But what should we do, andwhen is the right time to move? Front Cardiovasc Med 5[Epublication ahead of print version].

52. Zarins ZA, Wallis GA, Faghihnia N et al. (2009) Effects ofendurance training on cardiorespiratory fitness and sub-strate partitioning in postmenopausal women. Metab ClinExp 58, 1338–1346.

53. Frawley K, Greenwald G, Rogers RR et al. (2018) Effectsof prior fasting on fat oxidation during resistance exercise.Int J Exerc Sci 11, 827–833.


Proceedings

oftheNutritionSo

ciety



https://doi.org/10.1017/S0029665118002574


is exercise best served on an empty stomach? proceedings ... · the nutrition society scottish...

Documents