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Effects of aerobic exercise performed in fasted
v.
fed state on fat and
carbohydrate metabolism in adults: a systematic review and meta-analysis
Alexandra Ferreira Vieira
2
*, Rochelle Rocha Costa
1,2
, Rodrigo Cauduro Oliveira Macedo
1,3
,
Leandro Coconcelli
1,2
and Luiz Fernando Martins Kruel
1,2
1
Physical Education, Physiotherapy and Dance School, Federal University of Rio Grande do Sul, 750, Felizardo Street,
90690-200 Porto Alegre, Brazil
2
Research Group on Water and Land Activities, Federal University of Rio Grande do Sul, 750, Felizardo Street,
90690-200 Porto Alegre, Brazil
3
Research Group on Exercise Physiology and Biochemistry, Federal University of Rio Grande do Sul, 750, Felizardo Street,
90690-200 Porto Alegre, Brazil
(Submitted 7 March 2016 –Final revision received 29 July 2016 –Accepted 3 August 2016)
Abstract
This study aimed to verify the effect of aerobic exercise performed in the fasted v. fed states on fat and carbohydrate metabolism in adults.
Searches were conducted in March 2015, and updated in July 2016, using PubMed
®
, Scopus and Cochrane databases (terms: ‘fasting’,
‘exercise’,‘aerobic exercise’,‘substrate’,‘energy metabolism’,‘fat’,‘glucose’,‘insulin’and ‘adult’) and references from selected studies. Trials
that compared the metabolic effects of aerobic exercise (duration ≤120 min) performed in the fasted v. fed states in adults were accepted. The
outcomes evaluated were fat oxidation during exercise and the plasma concentrations of insulin, glucose and NEFA before and immediately
after exercise; two independent reviewers extracted the data (A. F. V. and L. C.). The results were presented as weighted mean differences
between treatments, with 95 % CI. Of 10 405 articles identified, twenty-seven studies –with a total of 273 participants –were included. There
was a significant increase in fat oxidation during exercise performed in the fasted, compared with fed, state (−3·08 g; 95 % CI −5·38, −0·79; I
2
39·1 %). The weighted mean difference of NEFA concentrations was not significantly different between states (0·00 mmol/l; 95 % CI −0·07,
0·08; I
2
72·7 %). However, the weighted mean differences of glucose (0·78 mmol/l; 95 % CI 0·43, 1·14; I
2
90·8 %) and insulin concentrations
(104·5 pmol/l; 95 % CI 70·8, 138·2; I
2
94·5 %) were significantly higher for exercise performed in the fed state. We conclude that aerobic
exercise performed in the fasted state induces higher fat oxidation than exercise performed in the fed state.
Key words: Fasting: Exercise: Energy metabolism: Reviews
Fasting is characterised by the absence of food and/or energy
beverage intake for a period of time, which may last from several
hours to a few weeks
(1,2)
. However, most people fast for 8–12 h
daily –the ‘overnight fasting’period
(2)
. During this period, NEFA,
ketone bodies and glucose derived from liver glycogen and
gluconeogenesis are the predominant energy sources
(3)
.
During exercise, NEFA also make a considerable contribution
to energy metabolism owing to the increased availability of
these substrates in the plasma. This is caused by increased
adrenaline levels and decreased insulin concentrations in the
blood
(4)
. Fasting promotes low levels of insulin and hepatic
glycogen
(2)
. Thus, when aerobic exercise is performed under
these conditions, an increase in the utilisation of fat as an
energy substrate is observed, when compared with exercise
performed in the fed state
(5,6)
. The decrease in fat oxidation
during exercise in the fed state can be mainly attributed to
higher insulin concentrations caused by a meal, which may
inhibit the breakdown of intramuscular TAG (IMTG) and
reduce the availability of NEFA for oxidation
(7,8)
.
Several studies have indicated that regular exercise promotes
beneficial effects in terms of health and body composition
(9–11)
,
including an improvement in insulin sensitivity and main-
tenance and reduction of body weight and body fat. It has been
suggested that exercise enhances fat oxidation and that
this adaptation may be associated with improved insulin
sensitivity
(12)
. Furthermore, higher fat oxidation capacity during
exercise seems to be related to a decrease in the number of
metabolic risk factors
(13)
. Venables & Jeukendrup
(14)
demon-
strated that participating in a training programme for 4 weeks,
with continuous aerobic exercise programmed for the max-
imum contribution of fat as the energy substrate during each
session, can further increase fat oxidation. This higher oxidation
was associated with improvements in insulin sensitivity in
obese men. In healthy, young men, the maximal fat oxidation
Abbreviation: IMTG; intramuscular TAG.
*Corresponding author: A. F. Vieira, fax +55 51 3308 5820, email alexandrafvieira@hotmail.com
British Journal of Nutrition, page 1 of 12 doi:10.1017/S0007114516003160
© The Authors 2016
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during exercise was positively associated with insulin sensitivity
and 24-h fat oxidation
(15)
. Studies have demonstrated that
exercise performed in the fasted state can increase the rate of fat
oxidation at rest from 9
(16)
to 24 h
(17–19)
after exercise when
compared with the same exercise performed after a meal. This
higher utilisation of fat as an energy source at rest may promote
reduction in body fat.
On the basis of these data, aerobic exercise performed in the
fasted state has been considered a strategy to increase fat
oxidation during exercise and, chronically, to promote adapta-
tions that may be beneficial to health. However, although most
studies reported higher fat oxidation under these conditions
compared with a carbohydrate-fed state, it is not clear whether
the stimulation of lipolytic activity and/or decreased
re-esterification of NEFA that occur during the fasted state
(20)
result in a significantly increased use of fat as an energy substrate
during exercise. This systematic review with meta-analysis aimed
to verify the effect of aerobic exercise performed during fasted v.
fed states on fat and carbohydrate metabolism in adults.
Methods
Eligibility criteria
This review considered clinical trials (parallel and randomised
cross-over designs) evaluating the effect of performing an
aerobic exercise intervention of no >120 min duration (or data
at 120 min for those interventions with longer durations) in
a fasted state among adults aged 19–59 years. These interven-
tions had to be compared with the same exercise performed in
the fed state (prior consumption of meals containing at least
25 g of carbohydrates)
(21)
. Included studies evaluated the
following outcome measures: fat oxidation during exercise,
considered the primary end point; and serum concentrations of
NEFA, glucose and insulin immediately before and after the
exercise session; the absolute weighted mean differences of
these concentrations were considered the secondary end
points. Studies that evaluated these acute responses to aerobic
exercise were included; trials that did not present acute
outcome data were excluded. In the case of trials with several
publications (or sub-studies), the study was included only once.
Search strategy
The electronic databases MEDLINE
®
(via PubMed
®
), Scopus
and Cochrane were used. In addition, manual searches were
conducted of references of studies identified for inclusion. The
search was conducted in March 2015 and updated in July 2016.
The terms ‘fasting’,‘exercise’,‘aerobic exercise’,‘substrate’,
‘energy metabolism’,‘fat’,‘glucose’,‘insulin’and ‘adult’as well
as related entry terms were used. The searches were limited
to articles published in English, Portuguese and Spanish
languages. The search strategy used in the PubMed
®
database is
available as the online Supplementary Material. Details of other
strategies may be obtained upon request. This systematic
review and meta-analysis was prepared and is presented in
accordance with ‘Preferred Reporting Items for Systematic
Reviews and Meta-Analyses’guidelines
(22,23)
.
Selection of studies
Selection of studies for review was performed independently and
duplicated, without restriction on the date of publication. First,
the titles and abstracts of all articles identified by the search
strategy were evaluated for inclusion independently by two
researchers (A. F. V. and L. C.), in duplicate form. Whenever the
abstract did not provide sufficient information about inclusion
and exclusion criteria, the full article was evaluated. Second, the
same reviewers independently evaluated the full articles of those
identified as appropriate from the abstract screening process, and
made their selection according to eligibility criteria. Disagree-
ments between reviewers were resolved by consensus, and in
the case of continuing disagreement the evaluation was made by
a third reviewer (R. R. C.). To avoid possible double counting of
participants included in more than one report by the same
authors/working groups, the periods of recruitment of partici-
pants and areas of recruitment were evaluated, and authors were
contacted for clarification where necessary.
Data extraction
Data extraction was performed by two reviewers (A. F. V. and
L. C.) independently concerning methodological characteristics,
interventions and outcomes of the studies using a standardised
form. As in the selection stage, disagreements were resolved
by consensus or by a third reviewer (R. R. C.). The extracted
data included average age, BMI, sex and training status of
participants; exercise duration and intensity; time between dietary
intake and the start of exercise; amount of carbohydrate
consumed in the pre-exercise meal; and the end points analysed.
Iftherequireddatawerenotfoundinthepublishedreport,the
corresponding author was contactedtoprovidemissingdataand,
in the absence of responses or data extraction alternatives, the
study or missing end point was excluded from the review. Data
presented only graphically, and for which more detail was not
provided despite a request to the corresponding authors, were
extracted using ‘DigitizeIt’software. Where it was not possible to
extract means or standard deviations from graphs at the required
points, the variable was excluded from the analysis.
In this phase, studies that included diabetic participants, or those
in which carbohydrates were provided during exercise as part of
the study protocol, were excluded to avoid possible bias in the
results. The primary end point we assessed was the total absolute
average fat oxidation during exercise. Secondary end points were
theweightedmeandifferenceininsulin,glucoseandNEFAcon-
centrations. Weighted mean differences were calculated from
values taken immediately before and during the last minute of
exercise for studies lasting ≤120 min. For studies of longer dura-
tion, the time ‘120 min’was considered the last minute of exercise.
In studies where the total absolute average fat oxidation during
exercise was not presented in the published article, a request was
submitted to the authors, and if means for VO
2
and carbon
dioxide production values were provided these were applied to
the formula determined by Péronnet & Massicotte
(24)
in order to
determine the fat oxidation rate. The units of measurements
used in this review were grams for fat oxidation, mmol/l for
concentrations of NEFA and glucose, and pmol/l for insulin
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concentrations. Study data not presented in these units were
converted. For instance, where fat oxidation was presented using
an energy value (kJ/kcal), these averages were divided by 40·79 kJ
(9·75 kcal) in order to obtain the value in grams
(25)
.Ifthesedata
were not provided by authors, or if it was not possible to calculate
the total oxidised absolute averageduringexercise,thevariableor
the study was excluded. Studies with two or more comparison
groups with the same population were included with only one
comparator, which was selected according to the time between
dietary intake and exercise and/or the nutritional characteristics of
meals consumed that most closely resembled the other studies
being reviewed, in an effort to standardise results. For studies with
two or more intervention groups, a single group was also inclu-
ded, selected according to characteristics similar to other studies.
Evaluation of risk of bias
The assessment of the methodological quality of included
studies was performed according to criteria proposed by
Cochrane
(26)
: appropriate use of randomisation sequences,
allocation concealment, blinding of participants and/or thera-
pists, blinding of assessors to outcomes, and description of
losses and exclusions. When these processes had been descri-
bed in the published document, it was considered that criteria
had been met and these studies were classified as being at ‘low
risk’of bias and, in opposition, as ‘high risk’. Studies that did not
report these data were classified as ‘unclear risk’. Descriptions
of losses and exclusions were considered ‘low risk’when the
number of participants evaluated were presented in the legends
of charts and graphs. Quality evaluation was performed
independently by two reviewers (A. F. V. and L. C.).
Data analysis
Results are presented as weighted mean differences for absolute
values between treatments with 95 % CI. The standard deviation
of mean difference values not provided by studies was imputed
according to the equation proposed by Higgins et al.
(27)
.
Statistical heterogeneity of treatment effects between studies
was evaluated by Cochran’sQtest and I
2
inconsistency test;
values above 50 % indicated high heterogeneity
(28)
. In case of
low heterogeneity, the fixed effect model was used to pool
study results for the outcomes. When significant heterogeneity
was observed (I
2
>50 %), the random effects model was
applied. Meta-analyses comprised comparisons of fat oxidation
during aerobic exercise performed in the fasted v. fed state and
the changes in concentrations (expressed using weighted mean
differences) of glucose, NEFA and insulin from immediately
before exercise to the last minute of exercise (post-exercise).
Values of α≤0·05 were considered statistically significant.
For variables with high heterogeneity, sensitivity analyses
were performed according to the following criteria: exercise
time, exercise intensity, sex of participants, BMI of participants,
training level of participants, pre-exercise values for each vari-
able, time between dietary intake and the start of exercise, and
amount of carbohydrate consumed in the pre-exercise meal.
Furthermore, publication bias was assessed using funnel plots
for each outcome (of each trial’s effect size against the standard
error). Funnel plot asymmetry was evaluated using Begg and
Egger tests
(29)
,andasignificant publication bias was considered
if P<0·10. The trim-and-fill computation was used to estimate
the effect of publication bias on the interpretation of results.
All analyses were performed using Comprehensive
Meta-Analysis version 2.0, except the risk of bias, which was
performed using Review Manager version 5.3 (Cochrane
Collaboration).
Results
Description of studies
Of the 10 405 studies identified from the database searches,
twenty-three met our inclusion criteria. An additional four studies
were included from a manual search of the reference lists of the
included studies, bringing the total number of articles included to
twenty-seven. Of these, three studies
(30–32)
were included twice
because they had met eligibility criteria for two groups with
different populations, in which each population had a different
intervention group and control group: references ‘Bergman &
Brooks, 1999a’and ‘Montain et al., 1991a’related to populations
comprised of trained men, ‘Bergman & Brooks, 1999b’and
‘Montain et al., 1991b’related to populations comprised of
untrained men, and ‘Isacco et al., 2012a’and ‘Isacco et al., 2012b’
related to populations of women who did not and did use the
contraceptive pill, respectively. Thus, thirty comparisons were
used in this meta-analysis (Fig. 1). In total, 270 and 269 partici-
pants were included in the fasted and fed groups, respectively.
The majority of studies (80 %) analysed men, whereas 13·3%
analysed women, and 6·6 % analysed both sexes. Most samples
comprised physically active individuals (86·7 %), and exercise
sessions lasted an average of 73min. The meals were provided
30–240min before the interventions and were composed of a
maximum of 215g of carbohydrates (Table 1).
In all, four studies were excluded from our analysis: one study
was unaccessible
(33)
, and the other three met all eligibility criteria,
but were not used because of the unavailability of results
(34)
,
or the presentation of averages
(19)
and standard deviations
(35)
graphically, with no clarification received from authors and no
possibility of data extraction using ‘DigitizeIt’software.
From some of the studies included, it was necessary to exclude
certain variables because absolute averages were not given –for
example, the absolute average of fat oxidation during
exercise
(6,7,36–38)
. Other variables were excluded as it was
impossible to extract values for standard deviation of insu-
lin
(39–42)
,glucose
(40,41,43)
and NEFA
(32,40)
concentrations. These
data were all requested from authors but were not provided.
‘DigitizeIt’software was used to extract the average relating to fat
oxidation from one study
(44)
, relating to NEFA concentrations
from fourteen studies
(6,7,37,38, 41–43,45–51)
, relating to glucose con-
centrations from sixteen studies
(6,7,32,36–39,42,45–52)
and relating to
insulin concentrations from thirteen studies
(6,7,37,38 ,43,45–52)
.
Risk of bias
Of the included studies, 80 % showed adequate generation
of randomisation sequence, 6·6 % reported allocation
Exercise in fasted adults and fat oxidation 3
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concealment, 20 % had blinded participants and/or therapists,
6·6 % had blinded the assessors to the outcomes and 66·6%
described losses to follow-up and exclusions (Fig. 2 and 3).
Effects of interventions
Fat oxidation. Data on fat oxidation were available from eleven
studies
(30,31,39–41,43,44,47,50–52)
, with a total of 117 individuals
evaluated (Fig. 4). Aerobic exercise performed in the fasted
state was associated with a significant increase in fat oxidation
during exercise when compared with the fed state (effect size:
−3·53; 95 % CI −4·76, −2·30; I
2
39·1 %). Aerobic exercise
performed in the fasted state led to an increase in fat oxidation
of approximately 3·53 g, compared with execution of the same
exercise after consumption of meals containing carbohydrates.
However, the analysis of publication bias identified a significant
bias (P=0·007), and thus the adjusted value of the effect size,
according to the Duval & Tweedie’s trim and fill test, resulted
in 3·08 g.
Given the influence of exercise intensity on fat oxidation,
sensitivity analyses were performed to identify whether there
was an effect difference when stratified by two different
intensity ratings –VO
2max
<70 % and VO
2max
≥70 %. Thus, even
though the meta-analysis did not demonstrate significant het-
erogeneity (P=0·07), sensitivity analyses were performed:
<70 % VO
2max
(3·45 g; 95 % CI 2·19, 4·71; P<0·001; I
2
50 %) and
≥70 % VO
2max
(5·38 g; 95 % CI −0·45, 11·21; P=0·07; I
2
0 %).
Aerobic exercise of low-to-moderate intensity performed in the
fasted state induced a higher fat oxidation compared with a fed
state. On the other hand, there was no significant difference
between fasted and fed states in relation to fat oxidation during
aerobic exercise of moderate-to-high intensity.
Sensitivity analyses were also performed for fat oxidation
taking the following into account: exercise time (≤60 min:
3·35 g; 95 % CI 2·07, 4·62; P<0·001; I
2
54 %; >60 min: 6·13 g;
95 % CI 1·37, 10·88; P=0·01; I
2
9 %); sex of participants (male:
6·39 g; 95 % CI 3·84, 8·94; P<0·001; I
2
0 %; female: 2·60 g;
95 % CI 1·19, 4·01; P=0·0003; I
2
0 %); BMI of participants
(<25 kg/m
2
:2·79 g; 95 % CI 1·42, 4·17; P<0·001; I
2
30 %);
training level of participants (physically active: 3·74 g; 95 % CI
1·97, 5·52; P<0·001; I
2
49 %; sedentary: 3·34 g; 95 % CI 1·62,
5·05; P=0·0001; I
2
23 %); time between consumption of meal
and the beginning of exercise (<100 min: 3·41 g; 95 % CI 1·68,
5·14; P=0·0001; I
2
57 %; >100 min: 3·66 g; 95 % CI 1·91, 5·41;
P<0·001; I
2
37 %); and quantity of carbohydrate consumed in
the pre-exercise meal (<100 g: 3·51 g; 95 % CI 1·84, 5·17;
P<0·001; I
2
34 %; ≥100 g: 3·56 g; 95 % CI 1·73, 5·39; P=0·0001;
I
2
53 %). Thereby, these results demonstrated no change in
the pattern already presented, of higher fat oxidation when
the exercise is performed in the fasted state, regardless of the
adopted criteria for the sensitivity analyses.
NEFA. Data on NEFA concentrations were available from
sixteen studies
(6,7,31,37,38,41–43,45–52)
, with a total of 144 indivi-
duals evaluated (Fig. 5). All but one of these studies used
the same sample populations for both interventions
(37)
. The
weighted mean difference of NEFA before and after exercise
10 405 articles identified through
database search
Identification
9857 articles after the removal of
duplicates
69 full-text articles assessed
for eligibility
27 articles included 3 studies with two different populations
4 studies selected based on analysis of the
references of included studies
46 exclusions after reading the full-text
4 did not study the target population
3 did not evaluate the interest variables
23 did not perform the intervention
10 did not have the adequate comparator
2 studies with multiple publications
4 studies without access to the results
9788 exclusions based on the title and/or
summary review
2073 did not study the target population
5020 did not perform the intervention
40 did not have the adequate comparator
56 did not evaluate the interest variables
2599 did not have the appropriate design
SelectionEligibilityInclusion
Fig. 1. Flow chart of the included studies.
4 A. F. Vieira et al.
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Tab le 1 . Characteristics of included studies
(Mean values and standard deviations)*
Age (years)
Exercise duration Time between meal Amount of carbohydrate
Studies Mean SD Sex/nTraining status (min) Exercise intensity and exercise (min) pre exercise meal (g)
Aziz et al.
(53)
27·37·2 Male/10 Physically active 60 65·0% VO
2max
180 to 240 126·7
Bergman & Brooks
(30)
25·14·8 Male/7 Physically active 90 60·0% VO
2peak
180 119·6
Bergman & Brooks
(30)
22·13·4 Male/7 Sedentary 120 40·0% VO
2peak
180 119·6
Bouhlel et al.
(54)
19·02·0 Male/9 Physically active 30 20·0, 30·0, 40·0, 50·0, 60·0% W
max
Does not mention Does not mention
Coyle et al.
(45)
25·05·0 Male/7 Physically active 105 70·0% VO
2max
240 141·8
Coyle et al.
(7)
22·04·9 Male/6 Physically active 40 50·0% VO
2max
60 and 10 96·6
Dohm et al.
(46)
28·73·9 Male/9 Physically active 90 or until exhaustion
(about 80)
70·0–75·0% VO
2max
120 to 240 47·0
Farah & Gill
(39)
28·110·7 Male/10 Sedentary 60 50·0% VO
2max
30 56·5
Gonzalez et al.
(47)
23·24·3 Male/12 Physically active 59 61·1% VO
2peak
120 66·6
Guéye et al.
(55)
22·51·7 Male/12 Physically active 60 75·0% HR
max
Does not mention Does not mention
Horowitz et al.
(6)
26·59·3 Male/6 Physically active 60 44·0% VO
2peak
60 60·0
Isacco et al.
(31)
22·93·6 Female/10 Sedentary 45 65·0% VO
2max
180 72·2
Isacco et al.
(31)
21·21·9 Female/11 Sedentary 45 65·0% VO
2max
180 73·4
Kirwan et al.
(48)
22·02·4 Male/6 Physically active Until exhaustion (120) 60·0% VO
2peak
45 75·0
Kirwan et al.
(49)
24·04·9 Female/6 Physically active Until exhaustion (120) 60·0% VO
2peak
45 75·0
Little et al.
(36)
23·33·8 Male/7 Physically active 90 (45) V
max
180 86·0
Little et al.
(50)
22·83·2 Male/13 Physically active 105 V
max
120 Does not mention (1·5 g/kg)
Massicotte et al.
(52)
24·8(SD 6·9) (fast)
22·1(
SD 5·8) (fed)
Male/5 Physically active 120 (60) 52·0% VO
2max
180 50·0
Maughan &
Gleeson
(40)
34·08·9 Male/5 Physically active Until exhaustion (90) 70·0% VO
2max
45 69·8
Montain et al.
(32)
Does not mention Male/9 Physically active 30 70·0% VO
2peak
120 131·6
Montain et al.
(32)
Does not mention Male/8 Physically active 30 70·0% VO
2peak
120 154·6
Paul et al.
(41)
24·93·4 Mixed/12 Physically active 90 60·0% VO
2peak
90 32·4
Ramos-Jiménez
et al.
(56)
22·53·7 Mixed/30 Physically active 8 to 15 98·0% HR
max
70 Does not mention
(60 % ETV meal)
Satabin et al.
(42)
25·217·7 Male/9 Physically active 110 60·0% VO
2max
60 100·0
Schabort et al.
(37)
26·07·9 Male/7 Physically active 105 70·0% VO
2max
180 100·0
Shin et al.
(38)
23·32·5 Male/8 Physically active 60 50·0% VO
2max
30 66·4
Whitley et al.
(43)
21·010·8 Male/8 Physically active 90 70·0% VO
2max
240 215·0
Willcutts et al.
(44)
23·72·4 Female/8 Physically active 30 (23) 62·0% VO
2max
90 109·3
Wu et al.
(51)
26·83·3 Male/9 Physically active 60 65·0% VO
2max
180 141·0
Ziogas & Thomas
(57)
27·43·8 Male/7 Physically active 60 60·0% VO
2max
180 111·5
VO
2peak
, peak VO
2
;W
max
, maximum power; HR
max
, maximum heart rate; V
max
, maximum velocity; ETV, energy total value.
* Exercise duration: total time of exercise duration evaluated in the study (time post exercise extracted).
Exercise in fasted adults and fat oxidation 5
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was not demonstrated to be significantly different between
exercise performed in the fasted or fed states (effect size: 0·00;
95 % CI −0·07, 0·08; I
2
72·7 %). The analysis of publication bias
for this outcome showed no significant bias (P=0·124).
Owing to the high heterogeneity (P<0·001) found in the
analysis of this variable, sensitivity analyses were performed.
Significant heterogeneity was found for most of the variables
analysed: exercise time (≤60 min: I
2
93 %; P<0·001; >60 min:
I
2
83 %; P<0·001); exercise intensity (<70 % VO
2max
:I
2
92 %;
P<0·001; ≥70 % VO
2max
:I
2
74 %; P=0·004); sex of participants
(male: I
2
90 %; P<0·001; female: I
2
90 %; P<0·001); BMI of
participants (<25 kg/m
2
:I
2
90 %; P<0·001; >25 kg/m
2
:I
2
0%;
P=0·76); training level of participants (physically active:
I
2
90 %; P<0·001; sedentary: I
2
0%; P=0·65); pre-exercise
values for fasting (<1 mmol/l: I
2
90 %; P<0·001); time between
consumption of meal and the beginning of exercise (<100 min:
I
2
85 %; P<0·001; >100 min: I
2
82 %; P<0·001); and quantity of
carbohydrate consumed in the pre-exercise meal (<100 g:
I
2
87 %; P<0·001; ≥100 g: I
2
90 %; P<0·001). Sensitivity ana-
lyses for the criterion ‘pre-exercise values in fasting >1 mmol/l’
were not performed because only one study presented this
characteristic. The criteria ‘BMI >25 kg/m
2
’and ‘sedentary’
showed no significant heterogeneity, although sensitivity ana-
lyses were performed with only two studies for each. Owing to
the maintenance of high heterogeneity and/or low number
of studies, the data presented graphically (Fig. 5) refer to the
general analysis (disregarding the sensitivity analysis).
Glucose. Data on glucose concentrations were available from
twenty-two studies
(6,7,31,32,36–39,42,45–57)
, with a total of 226
individuals evaluated (Fig. 6). All but one of these studies used
the same sample populations for both interventions
(37)
. Sig-
nificantly lower variation was reported for glucose concentra-
tions from before to after exercise in the fasted v. fed states
(effect size: 0·60; 95 % CI 0·25, 0·94; I
2
90·8 %). Nevertheless, the
analysis of publication bias identified a significant bias
(P=0·057), and thus the adjusted value of the effect size,
according to the Duval & Tweedie’s trim-and-fill test, resulted in
0·78 mmol/l.
Because of the high heterogeneity (P=0·001) found for this
variable, sensitivity analyses were performed and, again, sig-
nificant heterogeneity was found in most analyses. These vari-
ables were as follows: exercise time (≤60 min: I
2
95 %;
P<0·001; >60 min: I
2
99 %; P<0·001); exercise intensity
(<70 % VO
2max
:I
2
98 %; P<0·001; ≥70 % VO
2max
:I
2
80 %;
P<0·001); sex of participants (male: I
2
95 %; P<0·001; female:
I
2
99 %; P<0·001); BMI of participants (<25 kg/m
2
:I
2
99 %;
P<0·001; >25 kg/m
2
:I
2
82 %; P=0·001); training level of
participants (physically active: I
2
97 %; P<0·001; sedentary:
I
2
16 %; P=0·30); pre-exercise values in fasting (<5 mmol/l:
I
2
95 %; P<0·001; >5 mmol/l: I
2
99 %; P<0·001); time between
consumption of meal and the beginning of exercise (<100 min:
I
2
98 %; P<0·001; >100 min: I
2
69 %; P<0·001); and quantity of
carbohydrate consumed in the pre-exercise meal (<100 g:
I
2
98 %; P<0·001; ≥100 g: I
2
44 %; P=0·08). Again, the criterion
‘sedentary’showed no significant heterogeneity, although the
sensitivity analysis was performed with only two studies. The
criterion ‘quantity of carbohydrate consumed in the pre-
exercise meal ≥100 g’was analysed with eight interventions
(n66), and did not show significant heterogeneity. Therefore, in
this case, the weighted mean difference of relative glucose
concentrations did not appear to differ significantly when
exercise was performed in a fasted v. fed state (P=0·91).
Because of the high heterogeneity and/or low number of stu-
dies, the data presented graphically (Fig. 6) refer to the general
analysis (disregarding the sensitivity analysis). More detailed
results of the sensitivity analysis performed for this variable
relating to the criterion ‘quantity of carbohydrate consumed in
the pre-exercise meal ≥100 g’can be provided on request.
Insulin. Data on insulin concentrations were available from
fifteen studies
(6,7,31,32,37,38,43,45–52)
, with a total of 140 individuals
evaluated (Fig. 7). Again, all but one of these studies used the
same sample populations for both interventions
(37)
. Sig-
nificantly lower variation was reported for insulin concentra-
tions from before to after exercise in the fasted v. fed states
(effect size: 104·5; 95 % CI 70·8, 138·2; I
2
92·5 %). However, the
analysis of publication bias identified a significant bias
(P<0·001), and thus the adjusted value of the effect size,
according to the Duval & Tweedie’s trim and fill test, resulted in
104·5 pmol/l.
As with the other blood variables, high heterogeneity was
found (P<0·001) and sensitivity analyses were consequently
performed. Once again, significant heterogeneity was found for
most comparisons: exercise time (≤60 min: I
2
82 %; P<0·001;
>60 min: I
2
95 %; P<0·001); exercise intensity (<70 % VO
2max
:
I
2
91 %; P<0·001; ≥70 % VO
2max
:I
2
89 %; P<0·001); sex of
participants (male: I
2
93 %; P<0·001; female: I
2
96 %;
P<0·001); BMI of participants (<25 kg/m
2
:I
2
90 %; P<0·001;
>25 kg/m
2
:I
2
98 %; P<0·001); training level of participants
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
0 255075100
%
Fig. 2. Risk of bias in the included studies. , Low risk of bias; , unclear risk of bias; , high risk of bias.
6 A. F. Vieira et al.
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(physically active: I
2
95 %; P<0·001; sedentary: I
2
0%;
P=0·39); pre-exercise values in the fed state (<200 pmol/l:
I
2
92 %; P<0·001; >200 pmol/l: I
2
83 %; P<0·001); time between
consumption of meal and the beginning of exercise (<100 min:
I
2
95 %; P<0·001; >100 min: I
2
91 %; P<0·001); and quantity of
carbohydrate consumed in the pre-exercise meal (<100 g:
I
2
91 %; P<0·001; ≥100 g: I
2
92 %; P<0·001). Once again, the
variable ‘sedentary’showed no significant heterogeneity,
although the sensitivity analysis was performed with only two
interventions. Owing to the high heterogeneity and/or low
number of studies, the data presented graphically (Fig. 7) refer to
the general analysis (disregarding the sensitivity analysis).
Discussion
The major finding of this systematic review with meta-analysis is
that performing aerobic exercise at low-to-moderate intensity in
the fasted state induces a significant increase (3·08 g) in fat
oxidation while exercise is being performed. No difference was
seen in the variation of NEFA concentrations between exercise
performed in the fasted v. fed states. However, greater varia-
tions in glucose and insulin concentrations were seen when
exercise was performed in a fed state.
Carbohydrates and fats are the most important sources of fuel
during rest and exercise
(4)
. In general, the lipolytic activity of
adipose tissue is regulated by the balance between stimulating
hormones such as catecholamines and those that inhibit the
enzyme responsible for lipolysis (lipase sensitive hormone),
especially insulin
(58)
. Because of higher muscular energy
exigency and increased availability of NEFA
(58)
, mediated by
increased adrenergic stimulation
(59)
, exercise alone can
increase fat oxidation compared with rest
(39)
.
Among the primary responses to fasting are the partial mobi-
lisation of TAG reserves contained in the adipose tissue and the
decreased re-esterification of NEFA. This leads to an increase in
the concentration of circulating NEFA in plasma and, conse-
quently, greater availability of this fuel source for the muscles
(2,20)
.
These fundamental principles can explain the findings of the
present study, suggesting that when exercise is performed in the
fasted state, lipolytic activity is increased further because of the
action of lipolysis-stimulating hormones and limited action of
insulin. However, increased plasma concentrations of NEFA
during exercise are attenuated by carbohydrate intake before
exercise, due to the inhibition of lipolysis mediated by insulin
(6)
.It
has also been suggested that increases in insulin concentrations
can directly inhibit the transfer of fat through the muscle cell
membrane and/or mitochondrial membranes
(8)
. Therefore, as a
consequence of lower availability of NEFA and the inhibition of
oxidation of IMTG, exercise performed in the fed state shows
reduced fat oxidation
(7)
.
Apart from diet, use of energy substrates during exercise
depends on factors such as intensity, duration and level of
training
(4)
. It has been shown that fat oxidation, rather than the
use of carbohydrate as a substrate, tends to be higher at low-
to-moderate intensities of exercise, no >60–65 % VO
2max
, but is
likely to decrease at an intensity >75 % VO
2max(60,61)
. These data
corroborate the findings of the present study, in which most of
the interventions relating to fat oxidation during exercise
Aziz et al., 2010
Bergman & Brooks, 1999a
Bergman & Brooks, 1999b
Bouhlel et al., 2006
Coyle et al., 1985
Coyle et al., 1997
Dohm et al., 1986
Farah & Gill., 2013
Gonalez et al., 2013
Guéye et al., 2003
Horowitz et al., 1997
Isacco et al., 2012a
Isacco et al., 2012b
Kirwan et al., 2001a
Kirwan et al., 2001b
Little et al., 2009
Little et al., 2010
Massicotte et al., 1990
Maughan & Gleeson, 1988
Montain et al., 1991a
Montain et al., 1991b
Paul et al., 1996
Ramos-Jiménez et al., 2014
Satabin et al., 1987
Schabort et al., 1999
Shin et al., 2013
Whitley et al., 1998
Willcutts et al., 1988
Wu et al., 2003
Ziogas & Thomas, 1998
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Fig. 3. Summary of risk of bias in the included studies.
Exercise in fasted adults and fat oxidation 7
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included in the meta-analysis were performed with intensities
between 40 and 65 % VO
2max(30,31,39,41,44,47,51,52)
. Studies that
used greater intensities, and where exact values were given
in the published report, did not surpass 70 % VO
2max(40,43)
.
Concerning the duration of exercise, the studies included were
evaluated up to 120 min. It is suggested that after 2 h of exer-
cising, the substrate utilisation patterns become similar between
fasted and fed states
(45)
. That is, an increase in fat oxidation may
also occur in ‘fed state’individuals after a certain interval, and
may be caused by a reduction in muscle glycogen that occurs in
the advanced stages of prolonged exercise
(4)
. Furthermore, the
majority of included studies were conducted with physically
active individuals
(30,40,41,43,44,47,50–52)
, and the literature
indicates that fat oxidation during sub-maximal exercise is
improved with aerobic physical training
(14,60)
.
As exercise intensity can influence the utilisation of
energy substrates during exercise, sensitivity analyses were
performed according to this criterion. It is well established in
the literature that the contribution of carbohydrate to energy
supply increases incrementally with exercise intensity (>65 %
VO
2max
), whereas the fat oxidation peak occurs at lower
intensities (45–65 % VO
2max
), which may be influenced by sex,
training status, VO
2max
and diet
(60)
. The present analysis
showed that during exercises at intensities <70 % VO
2max
, fat
oxidation was higher in the fasted state (approximately 3·45 g),
but that there was no difference in this variable between
Bergman & Brooks, 1999a
Bergman & Brooks, 1999b
Farah & Gill, 2013
Gonzalez et al., 2013
Isacco et al., 2012a
Isacco et al., 2012b
Little et al., 2010
Massicotte et al., 1990
Maughan & Gleeson, 1988
Paul et al., 1996
Whitley et al., 1998
Willcutts et al., 1988
Wu et al., 2003
Difference
in means SE Variance
Lower
limit
Upper
limit Z-value P
Favours fasted Favours fed
–7.87
–4.49 5.24
–5.70
–6.00
–4.59
–1.74
–5.15
–5.00
–0.90
–41.40
–14.38
–2.62
–18.10
7.65
1.84
4.46
1.86
1.20
3.43
4.99
7.63
17.54
9.67
1.02
5.16
58.57
27.46
3.38
19.86
3.48
1.45
11.74
24.99
58.27
307.60
93.52
1.04
26.65
–22.87
–14.76
–9.30
–14.74
–8.24
–4.10
–11.87
–14.80
–15.86
–75.78
–33.33
–4.62
–28.22
7.13
5.78
–2.10
2.74
–0.94
0.62
1.57
4.80
14.06
–7.03
4.57
–0.62
–7.98
–35.00 –17.50 0.00 17.50 35.00
–1.03
–0.86
–3.10
–1.35
–2.46
–1.45
–1.50
–1.00
–0.12
–2.36
–1.49
–2.57
–3.51
0.304
0.391
0.002
0.178
0.014
0.148
0.133
0.317
0.906
0.018
0.137
0.010
0.000
–3.53 0.63 0.40 –4.76 –2.30 –5.62 0.000
Difference in means and 95 % CIStatistics for each studyStudy name
Fig. 4. Fat oxidation (g) during exercise performed in the fasted state v. fed state. , Study-specific estimates: , pooled estimates of fixed-effects meta-analyses.
Favours fasted Favours fed
Coyle et aI., 1985
Coyle et aI., 1997
Dohm et aI., 1986
Gonzalez et aI., 2013
Horowitz et aI., 1997
Isacco et aI., 2012a
Isacco et aI., 2012b
Kirwan et aI., 2001a
Kirwan et aI., 2001b
Little et aI., 2010
Massicotte et aI., 1990
Paul et aI., 1996
Satabin et aI., 1987
Schabort et aI., 1999
Shin et aI., 2013
Whitley et aI., 1998
Wu et aI., 2003
–1.00 –0.50 0.00 0.50 1.00
Difference
in means SE Variance
Lower
limit
Upper
limit Z-value P
0.09
0.10
–0.40
–0.26
0.05
–0.06
–0.10
0.24
0.20
0.01
0.00
–0.14
0.07
0.03
0.17
0.11
0.05
0.09
0.09
0.10
0.09
0.09
0.35
0.08
0.00
0.00
0.03
0.01
0.00
0.01
0.01
0.01
0.01
0.01
0.12
0.01
–0.04
0.04
–0.72
–0.47
–0.04
–0.23
–0.28
0.05
0.03
–0.16
–0.68
–0.30 0.02 –1.68
0.68
0.18
0.37
0.43
0.08
0.11
0.14
–0.05
–0.08
0.17
0.22 1.39
3.01
–2.42
–2.47
1.12
–0.70
–1.11
2.53
2.34
0.12
0.00
0.165
0.003
0.015
0.013
0.264
0.484
0.265
0.011
0.019
0.908
1.000
0.093
0.31
0.16
0.12
–0.03
–0.28
0.00
0.21
0.30
0.03
0.15
0.08
0.04
0.04
0.09
0.00
0.02
0.01
0.00
–0.09
–0.44
0.05
–0.33
–0.44
–0.07 0.08 0.05
–0.12 –3.48
0.27 –0.20
0.19 3.52
0.76 0.53
0.71 1.50 0.133
0.598
0.000
0.844
0.001
0.957
Difference in means and 95 % CIStatistics for each studyStudy name
Fig. 5. Weighted mean difference of NEFA concentrations (mmol/l) relative to exercise performed in the fasted state v. fed state. , Study-specific estimates: ,
pooled estimates of random-effects meta-analyses.
8 A. F. Vieira et al.
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fasted and fed states during exercises at intensities ≥70 %
VO
2max
. These findings confirm the results reported by
Bergman & Brooks
(30)
, in which the effect of intensity and
previous feeding on energy substrate used during exercise
was verified. Higher fat oxidation was observed in the fasted
state, compared with the fed state, during exercises with
intensities up to 59 % VO
2peak
, but not at the intensity of
75 % VO
2peak
.
The literature reports that physical training is able to reduce
insulin resistance
(14)
related to excessive accumulation of IMTG
in sedentary individuals
(62)
. This effect seems to be due to
increased fat oxidation
(15)
, mainly coming from fatty acids
Difference
in means SE Variance
Lower
limit
Upper
limit Z-value P
Favours fasted Favours fed
Difference in means and 95 % CI
Statistics for each study
Study name
–4.00 –2.00 0.00 2.00 4.00
Aziz et al., 2010
Bouhlel et al., 2006
Coyle et al., 1985
Coyle et al., 1997
Dohm et al., 1986
Farah & Gill, 2013
Gonzalez et al., 2013
Guéye et al., 2003
Horowitz et al., 1997
Isacco et al., 2012a
Isacco et al., 2012b
Kirwan et al., 2001a
Kirwan et al., 2001b
Little et al., 2009
Little et al., 2010
Massicotte et al., 1990
Montain et al., 1991a
Montain et al., 1991b
Ramos-Jiménez et al., 2014
Satabin et al., 1987
Schabort et al., 1999
Shin et al., 2013
Wu et al., 2003
Ziogas & Thomas, 1998
1.30
0.20
–0.06
0.93
0.94
0.21
–0.04
1.39
2.23
0.55
0.39
1.26
3.26
–0.27
–0.32
0.15
0.06
0.47
0.41
–0.11
–0.33
2.49
0.00
0.07
0.59
0.028
0.460
0.698
0.063
0.288
0.321
0.767
0.000
0.000
0.012
0.062
0.001
0.000
0.424
0.177
0.838
0.762
0.143
0.457
0.568
0.360
0.000
1.000
0.729
0.001
0.59
0.27
0.16
0.50
0.88
0.21
0.14
0.29
0.52
0.22
0.21
0.38
0.26
0.34
0.24
0.74
0.20
0.32
0.55
0.19
0.36
0.32
0.19
0.20
0.18 0.03
0.04
0.04
0.10
0.13
0.04
0.30
0.10
0.04
0.54
0.06
0.11
0.15
0.07
0.04
0.05
0.27
0.09
0.02
0.05
0.78
0.25
0.02
0.07
0.35 0.14
–0.33
–0.36
–0.05
–0.79
–0.20
–0.31
0.82
0.12
–0.02
0.51
2.75
–0.93
–0.78
–0.33
–0.16
–0.67
–0.49
–1.04
1.87
–0.36
–0.33
0.250
2.46
0.73
0.24
1.91
2.67
0.62
0.23
1.96
3.24
0.98
0.80
2.01
3.77
0.39
0.14
1.58
0.45
1.10
1.49
0.27
0.38
3.11
0.36
0.47
0.95 3.36
0.35
0.00
7.86
–0.92
–0.57
0.75
1.47
0.30
0.21
–1.35
–0.80
12.46
3.31
1.87
2.52
4.33
4.77
–0.29
0.99
1.86
–0.39
0.74
2.20
1.22
1.06
–1.28
Fig. 6. Weighted mean difference of glucose concentrations (mmol/l) relative to exercise performed in the fasted state v. fed state. , Study-specific estimates:
, pooled estimates of random-effects meta-analyses.
Study name Statistics for each study Difference in means and 95 % CI
SE
Lower Upper
in means
Difference
Variance limit limit Z-value P
Coyle et al., 1985
Coyle et al., 1997
Dohm et al., 1986
Gonzalez et al., 2013
Horowitz et al., 1997
Isacco et al., 2012a
Isacco et al., 2012b
Kirwan et al., 2001a
Kirwan et al., 2001b
Little et al., 2010
Massicotte et al., 1990
Montain et al., 1991a
Montain et al., 1991b
Schabort et al., 1999
Shin et al., 2013
Whitley et al., 1998
Wu et al., 2003
32.619
.7
47.2
72.2
35.4
45.7
37.0
18.2
9.9
125.6
13.0
17.3
23.6
49.6
4.4
40.1
18.7
42.8
17.2
200.4
165.5
107.5
192.5
103.1
923.7
15.6
45.1
82.6
188.2
–6.9
196.4
34.2
188.9
104.5
68.7
61.2
386.6
2232.1
1254.6
5218.9
2087.7
1372.0
330.9
97.9
15773.6
170.1
300.9
555.6
2458.4
19.3
1610.5
349.5
1833.2
295.2
–5.9
107.8
23.9
38.1
102.9
30.5
33.0
41.8
677.6
–9.9
11.1
36.4
91.0
–15.5
117.7
–2.5
104.9
70.8
71.1
293.0
307.1
176.9
282.0
175.7
104.3
80.6
1169.9
41.2
79.1
128.8
285.4
1.7
275.1
70.8
272.8
138.2
1.7
4.2
2.3
3.0
4.2
2.8
3.8
6.2
7.4
1.2
2.6
3.5
3.8
4.9
1.8
4.4
6.1
–1.6
0.098
0.000
0.022
0.002
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
–1200.00
0.005
0.231
0.117
0.068
0.009
–600.00 0.00 600.00 1200.00
Favours fasted Favours fed
Fig. 7. Weighted mean difference of insulin concentrations (pmol/l) relative to exercise performed in the fasted state v. fed state. , Study-specific estimates:
, pooled estimates of random-effects meta-analyses.
Exercise in fasted adults and fat oxidation 9
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derived from IMTG
(63)
. The acute effects of exercise in the
fasted state are able to reduce the content of IMTG by
approximately 60 %
(5,64)
, which does not seem to occur in the
fed state
(5)
and, in the long term, seems to be more effective in
improving insulin sensitivity
(65)
.
Venables & Jeukendrup
(14)
demonstrated that an increase in
fat oxidation of approximately 3 g during 30 min of aerobic
exercise was able to enhance insulin sensitivity in obese and
sedentary men. The present meta-analysis indicates that aerobic
exercise performed in the fasted state provides an increase in fat
oxidation of about 3·08 g during the session compared with the
fed state. Therefore, it is suggested that exercising in the fasted
state can be an alternative to increase the use of fat as the
energy source and the increase of oxidised fats by 3·08 g during
an exercise session may be sufficient to induce improvements
in insulin sensitivity.
As previously described, it is well established that plasma
concentrations of NEFA are higher in the fasted states compared
with fed states
(4,66,67)
. However, our results indicate that the
magnitude of variation, from before to after exercise, does not
appear to differ between fasted v. fed states. In general, during the
first 15 min of exercise, plasma NEFA concentrations decrease, as
the utilisation rate in the muscles exceeds the lipolysis-driven
release rate. After this period, the release rate exceeds use in the
muscles and the fatty acid concentrations in the plasma rise
(4)
.On
the basis of the results provided in this meta-analysis, this event
seems to occur in similar ways in both fasted and fed states.
Although the weighted mean difference of NEFA showed no
significant differences, the present study demonstrates that varia-
tion in glucose and insulin concentrations before and after exer-
cise was significantly higher during exercise performed in the fed
state. One possible explanation for this finding in relation to
insulin is that carbohydrate ingestion before exercise can result in
a considerable increase in insulin concentrations
(68)
,whichmay
remain high for about 3 h after consuming a meal
(51)
,andtendto
return to basal values when exercise is performed
(45,47)
.Inthis
case, it is noteworthy that the majority of studies included in the
meta-analysis offered meals up to 180 min before exercis-
ing
(6,7,31,32,37,38,47–52)
. Hence, it is probable that insulin concentra-
tions remained high at the beginning of exercise and decreased
over the course of the exercise for ‘fed state’participants.
Regarding glucose concentrations, the highest variation
generated by exercise performed in the fed state is attributed to
increased glucose concentrations in plasma, due to the intake of
carbohydrates before exercise, and subsequent fall in glucose
concentration due to the combined effects of hyperinsulinaemia
and glucose uptake for use as an energy substrate in muscle
contractile activity
(6,69)
. On the other hand, fasting causes
increases in glycerol release through hydrolysis of TAG
molecules from fat cells; this is a valuable precursor for
hepatic gluconeogenesis, thus contributing to the availability of
glucose
(2)
. These principles can be used to explain the greater
variations in plasma glucose concentration in the fed state
relative to the fasted state. When sensitivity analyses were
performed for this variable according to the criterion
‘quantity of carbohydrate consumed in the pre-exercise meal
≥100 g’, meta-analysis did not demonstrate a significant differ-
ence in the variation of glucose between fasted v. fed states.
A possible hypothesis for this is that the intake of carbohydrate-
rich meals increases the availability of glucose during
exercise
(68)
.
Although this systematic review with meta-analysis was per-
formed with the maximum methodological rigour possible, some
limitations should be highlighted. First was the inclusion of dif-
ferent intensities and durations of exercise, sex, times between
meals and exercise, types of meals and quality and quantity of
carbohydrates: in spite of methodological differences between the
studies under review, we sought to maximise standardisation in
the data examined. Second, as many relatively old publications
were included in this study, certain methodological limitations
and flaws were noted in the presentation of data. We would like
to emphasise in particular that the large number of trials with
results presented exclusively in graphs, and the lack of provision
of these data (means and standard deviations) from authors,
limited the accuracy of data extraction. Third, most of the studies
included in the analyses of glucose concentrations assessed glu-
cose levels using venous blood sampling. Previous studies have
reported
(70,71)
that the arterial sampling would be more recom-
mended to assess glucose levels; however, venous blood sam-
pling is the most commonly used method and it is widely
accepted. In addition, high heterogeneity was identified in meta-
analyses related to blood molecular concentrations, necessitating
caution in interpreting these data.
Is worth mentioning that, although our results have shown
increased fat oxidation during exercise performed in the fasted
state, it is necessary to take care when prescribing this strategy
in practice, as this meta-analysis was performed using only data
assessing the acute effects of exercise during fasting v. fed
states. The findings should not be extrapolated as long-term
effects, especially with the aim of reducing body fat, as there is
insufficient evidence of effectiveness and safety.
Conclusion
This systematic review with meta-analysis suggests that aerobic
exercise at low-to-moderate intensity, performed in the fasted
state, induces an increase in fat oxidation, when compared with
exercise performed following consumption of a carbohydrate-
containing meal. Despite high heterogeneity of the data, no
difference appears to exist between exercising in the fasted or
fed states in relation to variations in NEFA concentrations before
and after exercise. In contrast, variation in relation to glucose
and insulin concentrations appears to be higher in the fed
states. Future meta-analyses and randomised clinical trials,
inclusive of an evaluation of the long-term effects of aerobic
exercise on fat and carbohydrate metabolism in the fasted and
fed states, will be necessary to confirm the findings of the
present review, as well as to identify their real benefits or
consequences for long-term health.
Acknowledgements
The authors thank François Péronnet, Jonathan Little, John
Kirwan, Laurie Isacco, Nathalie Boisseau, Bryan Bergman,
10 A. F. Vieira et al.
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Karen Soo, Donald Chisholm and Katarina Borer, all of whom
answered our questions by email.
The present study was supported by the following organi-
sations: CAPES, CNPq and FAURGS.
The authors’contributions are as follows: A. F. V., R. C. O. M.
andR.R.C.formulatedtheresearchquestions;A.F.V.,R.C.O.M.,
R.R.C.andL.F.M.K.designedthestudyandA.F.V.,R.R.C.and
L. C. performed the study; A. F. V. and R. R. C. analysed the data;
A.F.V.,R.R.C.andR.C.O.M.wrotethepaper.Alltheauthors
critically reviewed and improved the manuscript.
The authors declare that there are no conflicts of interest.
Supplementary material
For supplementary material/s referred to in this article, please
visit http://dx.doi.org/doi:10.1017/S0007114516003160
References
1. Longo VD & Mattson MP (2014) Fasting: molecular mechan-
isms and clinical applications. Cell Metab 19, 181–192.
2. Maughan RJ, Fallah J & Coyle EF (2010) The effects of
fasting on metabolism and performance. Br J Sports Med 44,
490–494.
3. Cahill GF Jr (2006) Fuel metabolism in starvation. Annu Rev
Nutr 26,1–22.
4. Jeukendrup AE (2003) Modulation of carbohydrate and fat
utilization by diet, exercise and environment. Biochem Soc
Trans 31, 1270–1273.
5. De Bock K, Richter EA, Russell AP, et al. (2005) Exercise in the
fasted state facilitates fibre type-specific intramyocellular lipid
breakdown and stimulates glycogen resynthesis in humans.
J Physiol 564, 649–660.
6. Horowitz JF, Mora-Rodriguez R, Byerley LO, et al. (1997)
Lipolytic suppression following carbohydrate ingestion limits
fat oxidation during exercise. Am J Physiol 273, E768–E775.
7. Coyle EF, Jeukendrup AE, Wagenmakers AJ, et al. (1997) Fatty
acid oxidation is directly regulated by carbohydrate metabo-
lism during exercise. Am J Physiol 273, E268–E275.
8. Spriet LL (2014) New insights into the interaction of carbo-
hydrate and fat metabolism during exercise. Sports Med 44,
S87–S96.
9. Bassuk SS & Manson JE (2005) Epidemiological evidence for
the role of physical activity in reducing risk of type 2 diabetes
and cardiovascular disease. J Appl Physiol 99, 1193–1204.
10. Donnelly JE, Blair SN, Jakicic JM, et al. (2009) American Col-
lege of Sports Medicine Position Stand. Appropriate physical
activity intervention strategies for weight loss and prevention
of weight regain for adults. Med Sci Sports Exerc 41, 459–471.
11. Slentz CA, Duscha BD, Johnson JL, et al. (2004) Effects of the
amount of exercise on body weight, body composition, and
measures of central obesity. Arch Intern Med 164,31–39.
12. Goodpaster BH, Katsiaras A & Kelley DE (2003) Enhanced fat
oxidation through physical activity is associated with
improvements in insulin sensitivity in obesity. Diabetes 52,
2191–2197.
13. Rosenkilde M, Nordby P, Nielsen LB, et al. (2010) Fat oxidation
at rest predicts peak fat oxidation during exercise and meta-
bolic phenotype in overweight men. Int J Obes 34,871–877.
14. Venables MC & Jeukendrup AE (2008) Endurance training and
obesity: effect on substrate metabolism and insulin sensitivity.
Med Sci Sports Exerc 40, 495–502.
15. Robinson SL, Hattersley J, Frost GS, et al. (2015) Maximal fat
oxidation during exercise is positively associated with 24-hour
fat oxidation and insulin sensitivity in young, healthy men.
J Appl Physiol 118, 1415–1422.
16. Burton FL, Malkova D, Caslake MJ, et al. (2010) Substrate
metabolism, appetite and feeding behavior under low and
high energy turnover conditions in overweight women.
Br J Nutr 104, 1249–1259.
17. Iwayama K, Kawabuchi R, Park I, et al. (2015a) Transient
energy deficit induced by exercise increases 24-h fat oxidation
in young trained men. J Appl Physiol 118,80–85.
18. Iwayama K, Kurihara R, Nabekura Y, et al. (2015b) Exercise
increases 24-h fat oxidation only when it is performed before
breakfast. EBioMedicine 2, 2003–2009.
19. Shimada K, Yamamoto Y, Iwayama K, et al. (2013) Effects of
post-absorptive and postprandial exercise on 24 h fat oxida-
tion. Metabolism 62, 793–800.
20. Enevoldsen LH, Simonsen L, Macdonald IA, et al. (2004) The
combined effects of exercise and food intake on adipose
tissue and splanchnic metabolism. J Physiol 561, 871–882.
21. Lee BM & Wolever TMS (1998) Effect of glucose, sucrose and
fructose on plasma glucose and insulin responses in normal
humans: comparison with white bread. Eur J Clin Nutr 52,
924–928.
22. Liberati A, Altman DG, Tetzlaff J, et al. (2009) The PRISMA
statement for reporting systematic reviews and meta-analyses
of studies that evaluate health care interventions: explanation
and elaboration. Ann Intern Med 151, W-65–W-94.
23. Shamseer L, Moher D, Clarke M, et al. (2015) Preferred
Reporting Items for Systematic Review and Meta-Analysis
Protocols (PRISMA-P) 2015: elaboration and explanation.
BMJ 349,1–25.
24. Péronnet F & Massicotte D (1991) Table of nonprotein
respiratory quotient: an update. Can J Sport Sci 16,23–29.
25. Jeukendrup AE & Wallis GA (2005) Measurement of substrate
oxidation during exercise by means of gas exchange
measurements. Int J Sports Med 26, S28–S37.
26. Deeks JJ, Higgins JPT & Altman DG (editors) (2011) Chapter 9:
Analysing data and undertaking meta-analysis. In Cochrane
Handbook for Systematic Reviews of Interventions, Version
5.1.0 (updated March 2011) [JPT Higgins and S Green, editors].
The Cochrane Collaboration. http://handbook.cochrane.org/
CCAa (accessed September 2015).
27. Higgins JPT, Deeks JJ & Altman DG (editors) (2008) Chapter 16:
Special topics in statistics. In Cochrane Handbook for Systematic
Reviews of Interventions, Version 5.0.1 (updated September
2008) [JPT Higgins and S Green, editors]. The Cochrane
Collaboration. http://www.cochrane-handbook.org (accessed
July 2015).
28. Higgins JPT, Thompson SG, Deeks JJ, et al. (2003) Measuring
inconsistency in meta-analyses. BMJ 327, 557–560.
29. Egger M, Davey Smith G, Schneider M, et al. (1997) Bias in
meta-analysis detected by a simple, graphical test. BMJ 315,
629–634.
30. Bergman BC & Brooks GA (1999a, b) Respiratory gas-
exchange ratios during graded exercise in fed and fasted
trained and untrained men. J Appl Physiol 86, 479–487.
31. Isacco L, Thivel D, Pelle AM, et al. (2012a, b) Oral contraception
and energy intake in women: impact on substrate oxidation
during exercise. Appl Physiol Nutr Metab 37,646–656.
32. Montain SJ, Hopper MK, Coggan AR, et al. (1991a, b) Exercise
metabolism at different time intervals after a meal. J Appl
Physiol 70, 882–888.
33. Drenick EJ, Fisler JS, Johnson DG, et al. (1977) The effect of
exercise on substrates and hormones during prolonged
fasting. Int J Obes 1,49–61.
Exercise in fasted adults and fat oxidation 11
http:/www.cambridge.org/core/terms. http://dx.doi.org/10.1017/S0007114516003160
Downloaded from http:/www.cambridge.org/core. Universidade Federal do Rio Grande do Sul, on 12 Sep 2016 at 20:27:50, subject to the Cambridge Core terms of use, available at
34. Borer KT, Wuorinen E, Chao C, et al. (2005) Exercise energy
expenditure is not consciously detected due to oro-gastric, not
metabolic, basis of hunger sensation. Appetite 45, 177–181.
35. Erdmann J, Tholl S & Schusdziarra V (2010) Effect of carbohy-
drate- and protein-rich meals on exercise-induced activation of
lipolysis in obese subjects. Horm Metab Res 42,290–294.
36. Little JP, Chilibeck PD, Ciona D, et al. (2009) The effects of
low- and high-glycemic index foods on high-intensity inter-
mittent exercise. Int J Sports Physiol Perform 4, 367–380.
37. Schabort EJ, Bosch AN, Weltan SM, et al. (1999) The effect of a
preexercise meal on time to fatigue during prolonged cycling
exercise. Med Sci Sports Exerc 31, 464–471.
38. Shin YH, Jung HL, Ryu JW, et al. (2013) Effects of a pre-
exercise meal on plasma growth hormone response and fat
oxidation during walking. Prev Nutr Food Sci 18, 175–180.
39. Farah NMF & Gill JMR (2013) Effects of exercise before or after
meal ingestion on fat balance and postprandial metabolism in
overweight men. Br J Nutr 109, 2297–2307.
40. Maughan RJ & Gleeson M (1988) Influence of a 36h fast
followed by refeeding with glucose, glycerol or placebo on
metabolism and performance during prolonged exercise in
man. Eur J Appl Physiol 57, 570–576.
41. Paul GL, Rokusek JT, Dykstra GL, et al. (1996) Oat, wheat or
corn cereal ingestion before exercise alters metabolism
in humans. J Nutr 126, 1372–1381.
42. Satabin P, Portero P, Defer G, et al. (1987) Metabolic and
hormonal responses to lipid and carbohydrate diets during
exercise in man. Med Sci Sports Exerc 19, 218–223.
43. Whitley HA, Humphreys SM, Campbell IT, et al. (1998)
Metabolic and performance responses during endurance
exercise after high-fat and high-carbohydrate meals. J Appl
Physiol 85, 418–424.
44. Willcutts KF, Wilcox AR & Grunewald KK (1988) Energy
metabolism during exercise at different time intervals
following a meal. Int J Sports Med 9, 240–243.
45. Coyle EF, Coggan AR, Hemmert MK, et al. (1985) Substrate
usage during prolonged exercise following a preexercise
meal. J Appl Physiol 59, 429–433.
46. Dohm GL, Beeker RT, Israel RG, et al. (1986) Metabolic responses
to exercise after fasting. J Appl Physiol 61, 1363–1368.
47. Gonzalez JT, Veasey RC, Rumbold PLS, et al. (2013) Breakfast and
exercise contingently affect postprandial metabolism and energy
balance in physically active males. Br J Nutr 110, 721–732.
48. Kirwan JP, Cyr-Campbell D, Campbell WW, et al. (2001a)
Effects of moderate and high glycemic index meals on meta-
bolism and exercise performance. Metabolism 50, 849–855.
49. Kirwan JP, O’Gorman DJ, Cyr-Campbell D, et al. (2001b)
Effects of a moderate glycemic meal on exercise duration and
substrate utilization. Med Sci Sports Exerc 33, 1517–1523.
50. Little JP, Chilibeck PD, Ciona D, et al. (2010) Effect of low and
high glycemic-index meals on metabolism and performance
during high-intensity, intermittent exercise. Int J Sport Nutr
Exerc Metab 20, 447–456.
51. Wu CL, Nicholas C, Williams C, et al. (2003) The influence of
high-carbohydrate meals with different glycaemic indices on
substrate utilisation during subsequent exercise. Br J Nutr 90,
1049–1056.
52. Massicotte D, Péronnet F, Brisson G, et al. (1990) Oxidation of
exogenous carbohydrate during prolonged exercise in fed
and fasted conditions. Int J Sports Med 11, 253–258.
53. Aziz AR, Wahid MF, Png W, et al. (2010) Effects of
Ramadan fasting on 60 min of endurance running perfor-
mance in moderately trained men. Br J Sports Med 44,
516–521.
54. Bouhlel E, Salhi Z, Bouhlel H, et al. (2006) Effect of Ramadan
fasting on fuel oxidation during exercise in trained male rugby
players. Diabetes Metab 32, 617–624.
55. Guéye L, Seck D, Samb A, et al. (2003) Physiological adap-
tations to exercise during a short-term fasting. Scr Med (Brno)
76, 291–296.
56. Ramos-Jiménez A, Anguiano-Juarez J, Sifuentes-Juarez A, et al.
(2014) Fasting and postprandial glycemia in response to a
strenuous workout in healthy subjects with family history of
diabetes and borderline insulin resistance. Exp Clin Cardiol
20, 139–161.
57. Ziogas G & Thomas TR (1998) Dietary preparation before rest
and exercise testing. Nutrition 14,11–16.
58. Horowitz JF & Klein S (2000) Lipid metabolism during
endurance exercise. Am J Clin Nutr 72, 558S–563S.
59. Arner P, Kriegholm E, Engfeldt P, et al. (1990) Adrenergic
regulation of lipolysis in situ at rest and during exercise. J Clin
Invest 85, 893–898.
60. Achten J & Jeukendrup AE (2004) Optimizing fat oxidation
through exercise and diet. Nutr 20, 716–727.
61. van Loon LJ, Greenhaff PL, Constantin-Teodosiu D, et al.
(2001) The effects of increasing exercise intensity on muscle
fuel utilization in humans. J Physiol 536, 295–304.
62. Kelley DE & Goodpaster BH (2001) Skeletal muscle trigly-
ceride. An aspect of regional adiposity and insulin resistance.
Diabetes Care 24, 933–941.
63. Schrauwen P, van Aggel-Leijssen DP, Hul G, et al. (2002) The
effect of a 3-month low-intensity endurance training program
on fat oxidation and acetyl-CoA carboxylase-2 expression.
Diabetes 51, 2220–2226.
64. van Loon LJC, Koopman R, Stegen JHCH, et al. (2003) Intra-
myocellular lipids form an important substrate source during
moderate intensity exercise in endurance-trained males in a
fasted state. J Physiol 553, 611–625.
65. Van Proeyen K, Szlufcik K, Nielens H, et al. (2010) Training in
the fasted state improves glucose tolerance during fat-
rich diet. J Physiol 588, 4289–4302.
66. Sahlin K & Harris RC (2008) Control of lipid oxidation during
exercise: role of energy state and mitochondrial factors.
Acta Physiol (Oxf) 194, 283–291.
67. Spriet LL & Watt MJ (2003) Regulatory mechanisms in the
interaction between carbohydrate and lipid oxidation during
exercise. Acta Physiol Scand 178, 443–452.
68. Hargreaves M, Hawley JA & Jeukendrup A (2004) Pre-exercise
carbohydrate and fat ingestion: effects on metabolism and
performance. J Sports Sci 22,31–38.
69. Marmy-Conus N, Fabris S, Proietto J, et al. (1996) Pre-exercise
glucose ingestion and glucose kinetics during exercise. J Appl
Physiol 81, 853–857.
70. Liu D, Moberg E, Kollind M, et al. (1992) Arterial,
arterialized venous, venous and capillary blood glucose
measurements in normal man during hyperinsulinaemic
euglycaemia and hypoglycaemia. Diabetologia 35,
287–290.
71. Brouns F, Bjorck I, Frayn KN, et al. (2005) Glycaemic index
methodology. Nutr Res Rev 18, 145–171.
12 A. F. Vieira et al.
http:/www.cambridge.org/core/terms. http://dx.doi.org/10.1017/S0007114516003160
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