Intermittent Energy Restriction Improves Weight Lo

Accepted Article Preview: Published ahead of advance online publication
Intermittent energy restriction improves weight loss efficiency in

obese menFThe MATADOR study
N M Byrne, A Sainsbury, N A King, A P Hills, R E Wood
Cite this article as: N M Byrne, A Sainsbury, N A King, A P Hills, R E Wood,

Intermittent energy restriction improves weight loss efficiency in obese menFThe
MATADOR study, International Journal of Obesity accepted article preview 17
August 2017; doi: 10.1038/ijo.2017.206.
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Received 3 March 2017; revised 2 July 2017; accepted 6 August 2017; Accepted
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© 2017 Macmillan Publishers Limited. All rights reserved.

Title: Intermittent energy restriction improves weight loss efficiency in obese men - The
MATADOR study
Authors: Nuala M Byrne1,2, Amanda Sainsbury3, Neil A King2, Andrew P Hills1,2, Rachel E
Wood1,2
1
School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS,
Australia.
2
Queensland University of Technology, School of Exercise and Nutrition Sciences and Institute of
Health and Biomedical Innovation, Brisbane, QLD, Australia.

3
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School,
Charles Perkins Centre, The University of Sydney, Camperdown NSW, Australia.
Corresponding Author:
Professor Nuala M Byrne
School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, Australia.
Telephone: +61 3 6324 3741
Email: [email protected]
1
ABSTRACT
Background/Objectives: The MATADOR (Minimising Adaptive Thermogenesis And
Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER)
improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER
attenuated compensatory responses associated with ER. Subjects/Methods: Fifty-one men with
obesity were randomised to 16 weeks of either: [1] continuous (CON), or [2] intermittent (INT) ER
completed as 8×2-week blocks of ER alternating with 7×2-week blocks of energy balance (30
weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the
intervention (CON: N=23, 39.4 ± 6.8 y, 111.1 ± 9.1 kg, 34.3 ± 3.0 kg.m-2; INT: N=24, 39.8 ± 9.5 y,
110.2 ± 13.8 kg, 34.1 ± 4.0 kg.m-2). During ER, energy intake was equivalent to 67% of weight
maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM), and
resting energy expenditure (REE) were measured throughout the study. Results: For the N=19
CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT
(14.1 ± 5.6 vs 9.1 ± 2.9 kg; P<0.001). INT had greater FM loss (12.3 ± 4.8 vs 8.0 ± 4.2 kg; P<0.01),
but FFM loss was similar (INT: 1.8 ± 1.6 vs CON: 1.2 ± 2.5 kg; P=0.4). Mean weight change
during the 72-week INT energy balance blocks was minimal (0.0 ± 0.3 kg). While reduction in
absolute REE did not differ between groups (INT: -502 ± 481 vs CON: -624 ± 557 kJ/d; P=0.5),
after adjusting for changes in body composition, it was significantly lower in INT (INT: -360 ± 502
vs CON: -749 ± 498 kJ/d; P<0.05).
Conclusions: Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with
energy balance ‗rest periods‘ may reduce compensatory metabolic responses and, in turn, improve
weight loss efficiency.
Trial registration: Australian New Zealand Clinical Trials Registry ref: ACTRN12611001017910
2
Funding: This project and salary for REW was funded by an Australian National Health and
Medical Research Council (NHMRC) project grant (497223). AS was supported by NHMRC
Fellowships (481355 and 1042555).
Key Words: intermittent energy restriction, continuous energy restriction, obesity, weight loss,
diet, energy expenditure
3
BACKGROUND
Part of the difficulty in losing weight and maintaining weight loss by lifestyle changes is that the
body responds to energy restriction (ER) through a series of compensatory changes in biological
and behavioural determinants of body weight (1, 2). A key component of this is a reduction in
resting energy expenditure (REE), which has been observed in lean rodents and humans during
fasting and severe ER (3-5). Paradoxically, it is also seen in people with overweight or obesity after
only modest weight loss (6-8), as we have outlined in a recent review (9).
Given that REE is determined largely by body size and composition, it is expected to decrease with
weight loss. However, during ER, REE has been reported to decrease to a greater extent than that
expected from changes in body composition, a phenomenon termed ‗adaptive thermogenesis‘ (10).
This leads to markedly reduced efficiency of weight loss. For instance, we (11) and others (12, 13)
have shown that, at the onset of prolonged continuous ER interventions, actual weight loss was
almost 100% of that expected from energetic calculations. However, as the period of continuous ER
continues, weight loss per unit energy deficit was substantially reduced, and a large proportion of
the less than expected weight loss could be explained by the reduction in REE (11). Therefore,
finding ways to attenuate this adaptive decrease in REE during ER may improve weight loss and
maintenance.
While some studies of adults with overweight or obesity suggest that compensatory responses to ER
and weight loss persist beyond the ER period (14-19), other research suggests that many of these
responses can be reversed following a 7- to 14-day period of energy balance post-weight loss (1,
20). This raises the possibility that periods of deliberate energy balance could be exploited during
dietary interventions to enhance the efficiency of weight loss. This approach is akin to periodization
in exercise training programs which incorporate stimulus cycles to progressively overload the
physiology and stimulate positive adaptations in functional capacity, and cycles of reduced training
4
volume designed to avoid overtraining and the negative effects on performance that result from
chronically high training loads (21). In a similar way, an intermittent approach to ER, consisting of
cycles of restriction interspersed with periods of energy balance, may attenuate compensatory
responses associated with chronic ER, and thus provide a more effective and sustainable weight loss
strategy than traditional continuous approaches.
We proposed that an optimal intermittent ER cycle might be to combine 2-week blocks of energy
balance (sufficient time for the attenuation of adaptive thermogenesis) with ER blocks of the same
length. The use of 2-week blocks of ER is based on analysis of the seminal Minnesota semi-
starvation studies which revealed that the reduction in REE accompanying ER comprises two
phases; a rapid, early phase (~2 weeks; 22, 23) which is likely attributable to alterations in
processes regulating cellular metabolism in response to an acute change in energy balance (13, 24-
26), and a later phase where the reduction in REE is a function of reduced body tissue (27).
Based on the above considerations, we examined the effect of repeatedly interrupting ER with
deliberate periods of energy balance (intermittent ER), in terms of its effects on body weight, body
composition, and REE. We hypothesised that, compared with continuous ER, intermittent ER,
delivered as alternating 2-week blocks of ER and energy balance, would result in more efficient
weight and fat loss (greater loss per unit ER), and that the compensatory reduction in REE typically
associated with continuous ER, would be attenuated.
METHODS/DESIGN
The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study
was a single-centre, parallel-group, randomised controlled trial. The study was granted ethics
approval through the University Human Research Ethics Committee at the Queensland University
of Technology, Australia. Fifty-one males with obesity were recruited in cohorts and, after
5
screening, were allocated to the continuous (CON) or intermittent (INT) ER interventions.
Participants initially undertook a 4-week baseline (weight stabilisation) phase to determine energy
needs and help them to accommodate to the study diet macronutrient composition, and then
undertook 16 weeks of ER delivered as either: 1) CON: 16 weeks of continuous (daily) ER, or 2)
INT: 16 weeks of ER as 8×2-week blocks of ER interspersed with 7×2-week blocks of energy
balance (30 weeks total; please see study design in Supplementary Item 1). Both groups then
completed an 8-week post-weight loss energy balance phase. Including the 4-week baseline, 16- or
30-week ER, and 8-week post-weight loss energy balance phases, the total length of the
intervention was 28 and 42 weeks for the CON and INT groups, respectively. Food was provided
for each of these three phases (further details in Provision of diet, below). Participants were
followed up after a 6-month free-living period.
Eligibility criteria for participants
Eligible participants were males aged 25-54 years, with a body mass index (BMI) classified as
obese (30-45 kg.m-2), weight-stable (±2 kg for 6 months prior to participation), and sedentary (<60
minutes of structured moderate to vigorous intensity physical activity per week). Exclusion criteria
are listed in Supplementary Item 2.
Recruitment and screening strategies
Supplementary Item 3 is a CONSORT diagram providing an overview of the flow of participants
through the study. The three-step screening process to assess eligibility is detailed in
Supplementary Item 4. After providing informed consent, participants were randomly assigned in a
1:1 ratio to either the CON or INT interventions. While it was not possible to blind participants or
research staff to the assigned treatment groups, there was no discussion with the participants
regarding the difference between the two interventions. As shown in the CONSORT diagram, 51
men were randomised and commenced the 4-week baseline weight stabilisation phase, 47
6
completed the baseline phase, 41 completed the ER phase (16 or 30 weeks, in the CON and INT
groups, respectively), and 36 completed the ER phase per protocol, which was defined as
completion of the assigned ER intervention (CON or INT) without weight gain while in restriction,
and meeting assessment requirements up to and including Week16 ER.
Determination of weight maintenance energy requirements
Weight maintenance energy requirements were estimated for each participant by multiplying
measured REE (detailed below) by an appropriate physical activity level (PAL) based on self-
reported work-time and leisure-time physical activity. Participants were prescribed an
individualised diet (detailed below) designed to maintain weight stability, and were provided with
an electronic weighing scale to self-record body weight at home. These weights were used to assess
the adequacy of energy intake for weight maintenance, and to adjust energy intake as required. If
participants gained or lost weight consistently over at least three days, they were provided with
instructions on how to adjust the energy intake of the provided diet to maintain weight stability.
Energy Restriction interventions
The study was designed so that the ER diet for participants in both groups was equivalent to 67% of
individual weight maintenance energy requirements (i.e. 33% reduction in energy intake). The
energy intake prescription was adjusted to account for reductions in REE that were measured after
every 4 weeks of ER, to ensure that participants remained in the same relative energy deficit
throughout the study. Consequently, the absolute deficit (kJ/d) decreased significantly over time (p
< 0.001) in both groups, but did not differ between CON and INT groups (p = 0.49): WK1-4ER:
-4142 ± 442 and -4009 ± 647 kJ/d; WK5-8ER: -3998 ± 464 and -3885 ± 538 kJ/d; WK9-12ER: -
3902 ± 505 and -3790 ± 583 kJ/d; WK13-16ER: -3810 ± 533 and -3740 ± 444 kJ/d. During the
seven energy balance blocks in the INT group, participants were prescribed a diet providing 100%
of weight maintenance energy requirements.
7
Provision of diet
Participants were provided with all main meals and morning and afternoon snacks for the duration
of the study (28 or 42 weeks for the CON and INT interventions, respectively). Meals were
prepared by a commercial kitchen under the direction of a dietitian and delivered to the participants‘
homes each week. This ‗base‘ diet supplied the majority of each participant‘s energy requirements.
The remaining energy intake came from additional, discretionary items, chosen by individual
participants in consultation with a researcher (REW). Inclusion of discretionary items in a long-term
(24-month) dietary intervention has been shown to increase compliance (28). The planned
macronutrient distribution in both ER and energy balance diets was 25–30% of energy as fat, 15-
20% as protein, and 50–60% as carbohydrate. Participants were required to complete daily self-
report food diaries for the duration of the study (28 or 42 weeks for CON and INT groups,
respectively). The completion of these diaries was required for participants to be considered
compliant with the study requirements, but the data have not been analysed as a measure of dietary
adherence.
Overview of data collection
As shown in Supplementary Item 1, weight, body composition, and REE were measured at the start
and end of the 4-week baseline phase, after every 4 weeks of ER, at weeks 1, 2, 4, and 8 of the 8-
week post-ER energy balance phase, and at follow-up 6 months later. REE is not reported for the
post-ER energy balance and 6-month follow-up timepoints due to a large amount of missing data.
During ER, measurements were taken after the same number of weeks of ER for both groups. For
example, the Week 4 measurement was taken 4 weeks after baseline for the CON group, and 6
weeks after baseline for the INT group (i.e. after the first 2×2-week blocks of ER separated by 1×2-
week block of energy balance). As another example, the Week 8 measurement was taken 8 weeks
after baseline for the CON group, and 14 weeks after baseline for the INT group (i.e. after 4×2-
8
week blocks of ER separated by 3×2-week blocks of energy balance). Measurements were included
every 4 weeks during the ER intervention to provide information on the time course of responses, in
addition to pre-post comparisons. All measurements during the ER intervention were taken during
restriction in both groups. For the INT group, measurements were made at the end of a 2-week
block of ER.
Body height, weight, and composition
Height was measured to the nearest 0.1 cm using a Harpenden stadiometer (Holtain Ltd, Crosswell,
UK). At each laboratory visit, body weight was measured to the nearest 0.1 kg using a calibrated
digital scale, and body composition was calculated from body density measured by air displacement
plethysmography (BOD POD, Life Measurement Inc., Concord, CA). In addition to laboratory
measurements of weight, all participants were provided with an electronic weighing scale (Model
WW147A, Conair Australia, Pty Ltd, NSW, Australia), and asked to record body weight at least
weekly during the study. These self-reported body weights were used to track progress throughout
the study, and provide additional information on the time course of changes in weight in the periods
between laboratory visits.
Resting energy expenditure (REE)
REE was measured using a ventilated hood system (TrueOne 2400 Metabolic System, ParvoMedics
Inc, Sandy, UT, USA), which was calibrated before each measurement using standardized gases.
All testing was conducted between 0600-0900 hours after a minimum 10-hour overnight fast.
Participants arrived at the laboratory by car and were instructed to minimise physical activity prior
to arrival. Testing was performed in a thermo-neutral environment with participants lying supine in
a comfortable position, head on a pillow, and a transparent ventilated hood placed over their head.
During the measurement period, participants were asked to remain as relaxed as possible without
falling asleep, and instructed not to talk or fidget. To reduce boredom and prevent sleep,
9
participants listened to quiet music throughout the measurement. VO2 and VCO2 were measured
continuously for 30 minutes. After discarding the first 10 mins of data, REE was calculated as the
lowest consecutive 10-min average value, provided that the coefficient of variation within that 10-
min interval was <5%. REE was calculated using the Weir equation (29).
Calculation of predicted REE, and of changes from baseline
Given the contention regarding the best analytical approach to assess and define adaptive
thermogenesis (30-38), we examined changes in REE using three approaches:
1. Comparing REE over the intervention after adjustment for changes in FM and FFM.
2. Comparing measured REE with REE predicted from the group-specific equations developed
using regression analysis of baseline data (see details below).
3. Comparing measured REE with REE predicted from the reference equation published by
Muller et al. (39).
It has been suggested (32) that the most appropriate analysis uses the study-specific regression
equation derived from baseline data (REE, body composition, age, sex). As such, linear regression
analyses were performed to develop prediction equations for REE from baseline data (group
allocation, age, FM, FFM). Whereas age did not significantly explain any of the variance in REE,
group allocation accounted for a significant proportion of variance in REE. Consequently, a
separate equation was derived for CON and INT:
CON: REE(kJ/d) = 93.60  FFM(kg) + 36.04  FM(kg) + 1184
[R2 = 0.54; P < 0.01; RMSE = 545.4]
INT: REE(kJ/d) = 54.92  FFM(kg) + 46.46  FM(kg) + 2821
[R2 = 0.57; P < 0.01; RMSE = 617.9]
10
Given the relatively small, homogeneous sample in the present study, it could be argued that the
resulting prediction equation may not be robust (35). To overcome this potential weakness, REE
was also predicted from the equation developed by Muller et al. (39) on a larger, phenotypically
similar cohort (BMI>30 kg.m-2; N=278); where female=0, male=1:
REE(MJ/d) = 0.05685  FFM(kg) + 0.04022  FM(kg) + 0.808  sex – 0.01402  age(y) + 2.818
[R2=0.70; RMSE=0.87]
These equations were used to predict REE at baseline, and after 4, 8, 12, and 16 weeks of ER for the
CON and INT groups separately. Changes in REE from baseline for measured and predicted values
were then compared.
Statistical analyses
All analyses were performed using the STATA statistical software package Version 14.2 (Statacorp,
Texas, USA). Data are reported as mean ± standard deviation (SD) unless otherwise specified.
Mixed model repeated measures analyses were employed to determine changes in outcome
variables from baseline, and differences between the CON and INT groups accounting for
covariates (fat mass, fat-free mass, age) where appropriate. Linear regression analyses were used to
examine relationships between REE and body composition. Differences were considered significant
where p < 0.05.
Data are reported for all randomized participants via intention-to-treat (ITT) analysis using the Last-
Observation-Carried-Forward (LOCF) method, whereby the last available measurement for each
participant at the time-point prior to withdrawal from the study is retained for each missing time-
point thereafter in the analysis. The ITT analyses include every participant who was randomized
according to randomized treatment assignment, ignoring level of compliance, protocol deviations,
11
and withdrawals (40). Consequently, the estimate of treatment effect from ITT analyses is generally
conservative. As some participants dropped out during the baseline phase without participating in
the ER interventions, analyses are also provided for the sub-samples of all participants who
completed the baseline phase (CON=23; INT=24), and those who completed Week16 of ER
(CON=22; INT=19). In this way, we are able to report on the effect of the interventions with the
maximum sample at the end of each stage of the study as reported in the CONSORT diagram.
To examine the efficacy of the two interventions, analyses were provided for the cohort of
participants who completed Week16 of ER per protocol (CON=19; INT=17). Finally, as not all
participants were available at the 6-month follow-up, analyses are also provided for participants
who completed Week16 of ER per protocol and were available for measurements at the 8-week
post-ER energy balance phase and 6-month follow-up (CON=13; INT=15).
The primary outcome variable for the study was weight loss, and the secondary outcome was REE.
Over 16 weeks of ER, the energy deficit imposed by a 33% energy deficit would result in an
estimated weight loss of ~14 kg for a 110 kg male. However, we and others have found, in well-
controlled medium-length (12-24 weeks) dietary restriction interventions, that weight loss is 60-
70% of what is predicted from the ER imposed (9-11). As such, the expected weight loss during
continuous ER would be ~9 kg. We tested the hypothesis that weight loss would be greater (higher
loss per unit ER) with intermittent versus continuous ER, in part because of attenuation of adaptive
thermogenesis (smaller reduction in REE) in response to intermittent ER.
Accounting for the expected variance in starting weight, we calculated that 34 participants (17 per
group) would be required, at a statistical power of 0.8 (α=0.05), to detect (2-tailed) an ~5 kg greater
weight loss from ER without adaptive thermogenesis (INT: 14 kg) compared with weight loss
during continuous ER inducing thermogenic compensation (CON: 9 kg).
12
It was uncertain a priori the degree to which adaptive thermogenesis could be attenuated using the
model of intermittent ER we employed. Body composition-adjusted REE has been shown to
decrease by ~400 kJ/d within 2 weeks of commencing moderate ER, and larger reductions have
been reported in response to more severe and prolonged ER (11, 13, 18, 26, 41). We, and others,
have shown the decrease in body composition-adjusted REE, even in response to severe ER, is
completely reversed after 10-14 days of reinstating an energy balance diet (11, 20, 41).
Consequently, 18 participants (9 per group) would be required at a statistical power of 0.8 (α=0.05)
to detect (2-tailed) a 400 kJ/d reduction in body composition-adjusted REE compared with no
change. Given that REE was measured during ER for both groups, but the magnitude of adaptive
thermogenesis was predicted to be modified by the 2-week blocks of energy balance in the INT
intervention, we estimated the effect would be potentially halved. To detect a difference of this
magnitude (~200 kJ/d), a cohort of 38 (19 per group) would be required (2-tailed) at a statistical
power of 0.8 (α=0.05). Anticipating a 25% drop-out during the intensive intervention, we planned
to recruit 50 participants (25 per group).
RESULTS
Baseline
The only variable in which the two groups differed at baseline was REE, and only in the subset of
participants who completed the intervention, or who completed the intervention per protocol (Table
1). This difference was largely accounted for by group differences (non-significant) in FFM and FM
in these reduced cohorts (data not reported). As shown in Figure 1A, the change in body weight
over the 4-week baseline for the total group (n=47) was -1.6 ± 1.4 kg (-1.4 ± 1.2%), and did not
differ, on average, between the CON and INT groups. For the 47 participants with measures at the
start and end of baseline, the change in REE was -138 ± 511 kJ/d (-1 ± 6%). This change tended to
be related to weight loss (r = 0.26, p = 0.07). One participant lost 6.1 kg during the baseline phase
because of an error in the calculation of prescribed energy intake. Excluding this participant‘s data,
13
average changes in body weight (-1.5 ± 1.3 kg; -1.3 ± 1.1%) and in REE (-125 ± 511 kJ/d; -1 ± 6%)
were not related (r = 0.22, p = 0.13).
Intervention: pre vs post
Weight loss was significantly greater in the INT than CON group for each analysis approach (Table
2). Specifically, weight loss over the 16-week ER intervention in the INT group was 47% greater
than that in the CON group when considering data for all participants randomized or who
completed baseline, 58% greater for those who completed the intervention, 53% greater for those
who completed the intervention per protocol, and 80% greater for the cohort who were available for
the 6-month follow-up.
There was a significantly greater average loss of FM in the INT compared with CON group for
those who completed the intervention, those who completed the intervention per protocol, and those
who were available for follow-up (p < 0.01 for each analysis), and a tendency towards significance
in the ITT analysis (p = 0.09; Table 2). Changes in FFM were small, and not different between
groups in any analyses. The proportional changes of FM and FFM did not differ between groups;
FM comprised ~87 ± 21% of the weight lost.
The reduction in absolute REE at completion of Wk16 ER did not differ between groups, with
average differences of 6 ± 6% (CON: 7 ± 6%; INT: 6 ± 5%) from end of baseline to Wk16ER.
However, given the marked difference in weight loss between groups, after adjusting for changes in
body composition, the reduction in REE was significantly smaller in INT (4 ± 6%) than in CON (9
± 6%), and this was evident for both ITT and completers analyses (Table 2).
Intervention: time-course of responses
14
The change in weight from the end of baseline was significant throughout ER for both groups, and
cumulative weight loss was significantly greater in INT than CON from Wk8ER onwards (Fig1A).
Importantly, the weight change during the 7×2-week energy balance blocks in the INT group was,
on average, 0.0 ± 0.3 kg (Figure 1B). Supplementary Item 5 shows the magnitude of weight loss
for every 4 weeks of ER. FM was significantly lower than baseline at each time-point during the ER
intervention for the INT group, whereas the reduction plateaued by Wk12ER in the CON group
(Figure 2).
The INT group had a greater initial decrease in absolute REE compared with CON (Figure 3A).
However, the reduction in REE was similar between groups at Wk16ER, despite the greater
reduction in body weight in INT. When adjusted for body composition, REE in CON decreased
progressively across the intervention. In contrast, the initial decrease in REE in INT was partly
reversed during the final four weeks of ER, resulting in a significantly lower reduction in REE than
CON at Wk16ER (Fig3B). Using the prediction equations derived at baseline, measured REE was
significantly lower than predicted in CON at Wk16ER (Fig3C), but tended to be higher than
predicted at Wk16ER in INT (Fig3D). Compared with REE predicted from the equation of Muller
et al. (37), the measured change in REE in the CON group was similar to predicted REE at Wk4ER
and Wk8ER, but decreased to a greater extent than predicted from Wk12ER onwards (Fig3E). In
contrast, measured change in REE in the INT group was lower than predicted at Wk4ER but similar
to predicted thereafter (Fig3F).
Intervention: 8-week post-weight loss energy balance and 6-month follow-up
A subset of the cohort (CON=13, INT=15) was available for body weight and composition
measures during the 8-week post-weight loss energy balance phase and at the 6-month free-living
follow-up. The weight change from the start of baseline to Wk16ER in this subset (Figure 4A:
CON: -10.1  3.7 kg; INT: -15.4  5.6 kg) was similar to that in the larger cohort who completed
15
the ER intervention (Figure 1). Weight was stable in INT throughout the 8-week post-weight loss
energy balance phase. Weight was also stable in the CON group for the first 2 weeks of this phase,
with subsequent small, but significant, increases of 0.6 ± 1.3 kg at Wk4 and 1.2 ± 2.1 kg at Wk8
(Weeks 20 and 24 on Fig4A).
Weight regain over the 6-month post-intervention phase varied between individuals. On average,
both groups regained weight over the 6-month follow-up (INT: 3.5 ± 5.9 vs CON: 5.9 ± 4.7 kg; P =
0.24), but the total weight lost from the end of baseline remained greater in the INT group at follow-
up (INT: -11.1 ± 7.4 vs CON: -3.0 ± 4.4 kg, P = 0.001). FM at the 6-month follow-up remained
significantly lower than baseline in INT, but was not significantly different from baseline in CON
(Fig4B). The changes in FM were 4.9 ± 3.9 and 2.9 ± 5.6 kg, and in FFM were 1.0 ± 1.9 and 0.6 ±
0.9 kg for CON and INT, respectively.
DISCUSSION
The aim of this investigation was to compare changes in body weight, body composition, and REE
in men with obesity in response to: 1) 16 weeks of continuous ER, or 2) an equivalent duration and
magnitude of ER delivered intermittently as alternating 2-week blocks of ER and energy balance. In
support of the hypotheses, intermittent ER resulted in greater weight loss and greater (or a tendency
for greater) fat loss, without greater loss of FFM, than an equivalent ‗dose‘ of continuous ER. In
addition, despite greater weight loss, there was a significantly smaller reduction in REE (adjusted
for changes in FM and FFM) in the INT than in the CON group, consistent with attenuation of
adaptive thermogenesis. Furthermore, although both groups regained weight post-intervention,
weight loss (reduction from baseline) was, on average, 8.1 kg greater in the INT than CON group at
the 6-month follow-up.
16
The superior weight loss in the INT group in the present study is in contrast with the majority of
studies that have reported no advantage of intermittent over continuous ER. The term ‗intermittent
energy restriction‘ has become almost synonymous with the term ‗intermittent fasting‘, which
consists of alternating 1- to 7-day periods of complete or partial food restriction (true or modified
fasting), and ad libitum food consumption (9). A recent 12-month clinical trial (42) and several
recent reviews (e.g. 9, 43, 44) have concluded that existing models of intermittent ER (largely
versions of intermittent fasting), could be considered equivalent, but not superior, alternatives for
weight loss.
The intermittent approach in the present study differs fundamentally from intermittent fasting. In
intermittent fasting paradigms, weight loss occurs over time if energy intake during ad libitum
feeding periods is not sufficient to compensate for the substantially reduced energy intake on
‗fasting‘ days (e.g. 45). In contrast, energy intake was prescribed in both the ER and energy balance
blocks in the present study, to create distinct periods of weight loss and maintenance. Given that
this is the first application of an intermittent model using 2:2-week blocks of ER and energy
balance, direct comparisons with other studies are not possible. However, previous studies that have
compared continuous ER with intermittent approaches using ratios of ER to energy balance of
5:5-weeks over 25 weeks (46) or 1:1-week over 8 weeks (47) have reported no advantage of
intermittent ER (although the energy deficit in the latter study was not matched between groups). In
addition, weight loss was not different following 14 weeks of continuous ER, and 14 weeks of ER
interrupted by either a single 6-week break or 3×2-week breaks of ad libitum intake (48). Given
these findings, it is interesting to consider possible reasons for the superior weight loss in the INT
vs CON group in the present study, in which both groups were exposed to the same ‗dose‘ of ER.
Importantly, the average weight change (a proxy measure of energy balance) during the seven
energy balance blocks in the INT group was only 0.0 ± 0.3 kg. Therefore, the greater weight loss in
17
the INT group can be attributed to a higher rate of weight loss during the 8×2-week ER blocks, and
not simply continual weight loss over a longer (30-week) intervention period. Indeed, it is possible
that the attainment of energy balance during the ‗breaks‘ from ER may be critical to the success of
this approach. Allowing relatively uncontrolled or ad libitum feeding during the ‗breaks‘ from ER
often results in a hyperphagic response which may compromise weight loss (41, 49). On the other
hand, simply alternating between different levels of energy intake (while still maintaining a degree
of ER) during a dietary intervention appears to be no more effective than using a continuous fixed
level of ER (50, 51). As such, incorporating periods of controlled energy balance, not simply
variations in energy intake, may be necessary to realise the beneficial effects of intermittent ER.
We hypothesized that intermittent ER would attenuate the decrease in REE. In support of this
hypothesis, REE (adjusted for FM and FFM) decreased to a lesser extent in the INT group such that
it was ~377 kJ/d lower in the CON than INT group at Wk16ER. This is consistent with the 2-week
blocks of energy balance functioning as ‗metabolic rest periods‘, attenuating the compensatory
reduction in REE associated with continuous ER. There is scant evidence on changes in REE with
intermittent ER (9) but these findings are broadly consistent with the work of Jebb et al. (41) who
reported no change REE/kgFFM following an 18-week intervention consisting of repeated cycles of
2 weeks of a very low energy diet alternating with 4 weeks of ad libitum intake. However, a
continuous comparison group was not investigated in that study, and participants regained weight
during the ad libitum periods such that the ~10.7 kg lost during ER periods was reduced to 5.9 kg
over the entire intervention. Importantly, in the present study, the preservation of REE during ER in
the INT group was achieved without compromising weight loss.
Weight regain following successful weight loss through dietary intervention is common, and for
decades there has been a concerted effort to find strategies to prevent recidivism (52). Follow-up
data were only available for a subsample in the present study, although these participants did not
18
differ appreciably from the total cohort at baseline, nor in their magnitude of response to the
intervention. While both the CON and INT groups regained weight over the 6-month follow-up, the
smaller (albeit non-significantly smaller) regain in the INT vs CON group resulted in a widening of
the difference in weight loss between groups from ~5 kg at Wk16ER to ~8 kg at the 6-month
follow-up. Indeed, weight at follow-up was not significantly different from weight at the end of
baseline in the CON group (signifying almost complete weight regain), whereas it remained
significantly reduced relative to baseline in the INT group. This suggests that the intermittent
approach employed in this study may have benefits over continuous ER that extend beyond the
period of active ER. Further, the guidelines from the National Health and Medical Research Council
of Australia (53), in line with other health organisations around the world, recommend that adults
with overweight or obesity should aim to lose 5% of initial weight as this can result in significant
health benefits. To achieve this level of weight loss it took, on average, 8 weeks of continuous, but
only 4 weeks of intermitent ER. Furthermore, at the 6-month follow-up, only the INT group had an
average weight loss above this 5% threshold.
A strength of this study was the tight control of dietary prescription and food provision which
ensured that the CON and INT groups received the same ‗dose‘ of ER by: 1) matching energy
deficit over the 16 weeks of restriction, and 2) achieving weight stability in the intervening energy
balance blocks in the INT group. A further strength of this study is that it used the 2:2-week
intermittent model, which was designed based on empirical evidence of the timecourse of
adaptation to changes in energy intake, as a framework to investigate the mechanisms underlying
any differences in weight loss between groups. In contrast, most studies comparing intermittent and
continuous ER have been designed only to determine whether various forms of intermittent ER
produce superior weight loss. This study also has several limitations. Firstly, as a very demanding
study for participants, there was some attrition (Supplementary Item 3). However, it did not differ
appreciably between groups, and was comparable to other studies using intermittent ER (e.g. 47, 52,
19
54). Furthermore, although higher retention would have increased statistical power, we have shown
from completers and ITT analyses that the main findings remained significant despite attrition. A
second limitation was the small weight loss in the 4-week baseline phase. We can only speculate
that the small weight loss was an acute response to changes in diet composition. Despite this, we are
confident that our determination of energy requirements was robust for three reasons: 1) weight
stability was achieved in the INT group during the seven energy balance blocks; 2) weight change
over the 4-week baseline phase in the combined cohort was lower than has been reported in other
free-living studies where energy requirements were calculated from published REE equations (55);
and 3) weight change in the last 2 weeks of baseline was comparable to that reported in a recent
study in which participants were admitted to a metabolic ward with energy requirements determined
from metabolic chamber measurements (56). A third limitation was that we did not measure REE
and body composition during energy balance blocks in the INT group. We are currently undertaking
a follow-up study (Australian New Zealand Clinical Trials Registry ref: ACTRN12615000116527)
including these measurements in both ER and energy balance blocks to provide more detailed
information about the effects of repeated cycles of ER and energy balance. While not a limitation, it
is also important to acknowledge that we cannot determine from the present data whether 2 weeks is
the optimal duration for ER and energy balance blocks, only that this intervention resulted in more
effective weight loss than continuous ER. Indeed, it may be useful to investigate different durations
and ratios of ER to energy balance, given the recent findings of Muller et al. (26), suggesting
adaptive thermogenesis may be completely manifest within just one week of ER.
In conclusion, intermittent ER, delivered as alternating 2-week blocks of ER and energy balance,
resulted in greater weight loss (fat loss) without greater loss of FFM, attenuation of the reduction in
REE, and superior weight loss retention after 6 months, compared with an equivalent ‗dose‘ of
continuous ER. While adaptive reductions in REE were attenuated using this 2:2 intermittent ER
approach, it is possible that greater weight loss in the INT group may also be due to reduced
20
compensation in other energetic functions such as the thermic effect of food and activity energy
expenditure. Additionally, there is the need to investigate the effectiveness of this dietary approach
when individuals are not provided meals in a tightly controlled metabolic study. Therefore, while
additional work is needed to further investigate the mechanistic bases for this novel intermittent
approach, these findings provide preliminary support for the model as a superior alternative to
continuous ER.
Authors’ contributions
NMB led the drafting of the manuscript. NMB, AS, APH, NK conceived of the study and obtained
funding. REW coordinated the study, and with NMB and APH arranged study protocols. All
authors participated in the design of the study protocols, helped to draft the manuscript, read and
approved the final manuscript.
Possible conflicts of interest
Amanda Sainsbury has received payment from Eli Lilly, the Pharmacy Guild of Australia,
Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, and the
Pharmaceutical Society of Australia for seminar presentation at conferences, and has served on the
Nestlé Health Science Optifast®VLCD™ Advisory Board since 2016. She is also the author of The
Don‘t go Hungry Diet (Bantam, Australia and New Zealand, 2007) and Don‘t go Hungry for Life
(Bantam, Australia and New Zealand, 2011).
Supplementary information is available at the International Journal of Obesity‘s website.
21
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27
Figures
Figure 1 Changes in body weight (kg; mean ± SEM) during baseline and 16 weeks of energy
restriction (ER) in the continuous (CON; N=19) and intermittent (INT; N=17) groups.
A. Cumulative weight change (kg) over baseline (-4, -2, 0 weeks) and after 4, 8, 12 and 16 weeks
of ER for the CON and INT groups. *Significant difference between groups; P < 0.05.
#
Significant difference from baseline within-group; P < 0.01.
B. Weight change (kg; mean ± SE) in the intermittent energy restriction (INT) group during each
of the 8 × 2-week energy restriction (ER) and 7 × 2-week energy balance (EB) blocks that
comprised the 30-week intervention. Data are from participant-reported weights measured at
home (N=20 except N=19 for ER5, EB5, EB6, ER7, and EB7, and N=17 for ER8). Weight
change is calculated as the difference in weight measured from Day 1 of one block (e.g. ER1) to
Day 1 of the subsequent block (e.g. EB1). Participants were instructed to record weight daily
throughout the study. The majority (80% or 256/312) of measurements were taken on Day 1 of
the block (as instructed), and 93% (299/312) of measurements were taken within ±1 day of Day
1.
Figure 2 Fat-free mass (FFM) and fat mass (FM) at baseline and during 16 weeks of energy
restriction (ER) for the continuous (CON; N=19) and intermittent (INT; N=17) groups.
A. Fat-free mass (kg; mean ± SD). * Differs significantly (P < 0.05) from all other time-points for
the same intervention group.
B. Fat mass (kg; mean ± SD). *All time-points differ significantly (P < 0.001) from each other
within the same intervention group except those indicated (NS) in CON; these time-points do
not differ significantly (P > 0.05).
Figure 3 Change from baseline in resting energy expenditure (REE; kJ/d) for the continuous
(CON; N=19) and intermittent (INT; N=17) groups. Data are mean ± SEM.
A. Change in absolute (unadjusted) REE after each 4 weeks of ER for the CON and INT groups.
*Significant difference between groups; P < 0.05.
B. Change in REE adjusted for FFM and FM after each 4 weeks of ER in CON and INT groups.
*Significant difference between groups; P < 0.05.
C. Change in predicted REE (from baseline regression equation) and measured REE at 4, 8, 12 and
16 weeks of ER for the CON group. *Significant difference between predicted and measured; P
< 0.05.
D. Change in predicted REE (from baseline regression equation) and measured REE at 4, 8, 12 and
16 weeks of ER for the INT group. *Significant difference between predicted and measured; P
< 0.05.
E. Change in predicted REE (from Muller et al. (37) equation) and measured REE at 4, 8, 12 and
16 weeks of ER for the CON group. *Significant difference between predicted and measured; P
< 0.05.
28
F. Change in predicted REE (from Muller et al. (37) equation) and measured REE at 4, 8, 12 and
16 weeks of ER for the INT group. *Significant difference between predicted and measured; P
< 0.05.
Figure 4 Weight and body composition in the subsample (CON: N=13, INT: N=15) of
participants with data at all the following time points: baseline, during and end of energy restriction
(ER), during and after 8 weeks of energy balance immediately post-ER-intervention, and follow-up
6 months later.
A. Weight loss (kg; mean ± SEM). Significant difference between groups * P < 0.05, ** P < 0.01,
*** P<0.001. Different letters indicate significant differences between time points within each
group (P < 0.05; CON: a,b,c,d,e).
B. Changes in FFM and FM (kg; mean ± SEM). # FM significantly different from baseline in
CON; * FM significantly different from baseline in INT (P < 0.05).
Note: N = 13 for CON, except N=12 for Wk1 and Wk2 of EB (Week 17 and 18) and N = 15 for
INT, except N=14 for Wk1, 2, 4, and 8 of EB (Week 17, 18, 20, and 24).
29
Table 1 Baseline characteristics presented with participants as randomized, completed
baseline, completed intervention, completed intervention per protocol, and completed intervention
per protocol and available for 6-month follow-up.
Continuous Intermittent Difference

P
Mean  SD Mean  SD Mean  SE
Randomized N=25 N=26
Age (y) 39.3  6.6 39.9  9.2 0.6  2.2 0.79
Height (cm) 180.6  5.9 178.4  7.0 2.2  1.8 0.24
Weight (kg) 111.6  10.0 109.8  14.1 1.8  3.4 0.61
BMI (kg/m2) 34.4  3.3 34.6  4.2 0. 2  1.1 0.87
Body fat (%) 38.9  5.2 39.7  6.8 0.8  1.7 0.63
Fat mass (kg) 43.6  8.5 44.1  11.5 0.5  2.9 0.87
Fat-free mass (kg) 68.0  6.1 65.7  7.4 2.2  1.9 0.25
Resting energy expenditure (kJ/d) 9038  737* 8619  963 419  247 0.1
Completed Baseline N=23 N=24

Age (y) 39.4  6.8 39.8  9.5 0.3  2.4 0.89
Height (cm) 180.2  6.0 178.7  7.2 1.5  1.9 0.44
Weight (kg) 110.7  9.1 110.1  13.8 0.6  3.4 0.86
BMI (kg/m2) 34.3  3.0 34.5  4.0 0.3  1.0 0.81
Body fat (%) 39.2  5.3 39.8  6.4 0.7  1.7 0.7
Fat mass (kg) 43.6  8.6 44.2  10.9 0.6  2.9 0.83
Fat-free mass (kg) 67.1  5.2 65.9  7.7 1.2  1.9 0.53
Resting energy expenditure (kJ/d) 9038  737 8585  941 452  247 0.07
Completed Intervention (Wk16) N=22 N=19

Age (y) 39.5  6.9 39.5  9.1 0.02  2.5 0.99
Height (cm) 180.6  5.7 178.0  7.4 2.7  2.0 0.2
Weight (kg) 110.9  9.3 108.0  12.7 2.9  3.4 0.41
BMI (kg/m2) 34.1  3.0 34.1  3.7 0.02  1.1 0.99
Body fat (%) 39.0  5.4 39.9  6.8 0.9  1.9 0.64
Fat mass (kg) 43.5  8.8 43.5  10.7 0.1  3.0 0.98
Fat-free mass (kg) 67.3  5.2 64.5  7.8 2.8  2.0 0.18
Completed per protocol (Wk16) N=19 N=17

Age (y) 41.2  5.5 39.5  8.4 1.7  2.3 0.46
Height (cm) 180.3  6.1 177.8  7.7 2.5  2.3 0.28
Weight (kg) 110.9  9.6 107.7  13.3 3.3  3.8 0.39
BMI (kg/m2) 34.3  3.0 34.1  4.0 0.2  1.2 0.86
Body fat (%) 39.4  5.0 39.7  7.1 0.3  2.0 0.89
Fat mass (kg) 43.9  8.4 43.1  11.3 0.9  3.3 0.79

Fat-free mass (kg) 67.0  5.3 64.5  8.1 2.4  2.2 0.29
Completed per protocol (Wk16)

N=13 N=15
and 6 months Follow up
Age (y) 40.0  5.2 40.3  7.6 0.3  0.8 0.72

Height (cm) 180.4  5.6 178.9  6.9 1.6  0.7 0.02
Weight (kg) 110.2  9.3 108.6  13.5 1.6  4.5 0.72
BMI (kg/m2) 34.0  3.6 34.0  4.3 0.0  1.5 0.98
Body fat (%) 38.3  5.4 40.4  6.9 2.2  2.4 0.36
Fat mass (kg) 42.5  8.9 44.2  11.0 1.7  3.8 0.66
Fat-free mass (kg) 67.7  4.8 64.4  8.6 3.3  2.7 0.23
*
N=23 Continuous; REE unavailable for 2 participants (1 due to undiagnosed sleep apnea and
unable to remain awake during measurement; 1 did not adhere to pre-test instructions).

Table 2 Changes in weight, body composition, and resting energy expenditure over the16-
week intervention (from end of baseline to Week 16 of Energy Restriction) based on intention-to-
treat (ITT) and completers analyses.
Continuous Intermittent Difference

P
Mean  SD Mean  SD Mean  SE
Randomized N=25 N=26
Weight (kg) -7.4  4.7 -10.9  7.2 3.5  1.7 0.03
Weight (%) -6.8  4.2 -9.9  5.9 3.2  1.4 0.03
Fat mass (kg) -6.5  4.8 -9.2  6.3 2.7  1.6 0.09
Fat-free mass (kg) -1.0  2.2 -1.7  1.8 0.7  0.6 0.21
Resting energy expenditure (kJ/d) -498  565 -356 ± 644 142  172 0.41
Resting energy expenditure (kJ/d;
-607  506 -251  506 356  142 0.01
adjusted for FFM and FM)
Completed Baseline N=23 N=24

Weight (kg) -8.1  4.2 -11.9  6.4 3.8  1.6 0.02
Weight (%) -7.4  3.8 -10.8  5.4 3.4  1.4 0.02
Fat mass (kg) -7.0  4.6 -10.0  5.9 2.9  1.6 0.06
Fat-free mass (kg) -1.1  2.3 -1.9  1.8 0.8  0.6 0.2
Resting energy expenditure (kJ/d) -540  569 -385  665 155  180 0.4
-669  531 -264  527 406  159 0.01
Completed Intervention (Wk16) N=22 N=19

Weight (kg) -8.5  4.2 -13.4  5.7 5.1  1.5 0.002
Weight (%) -7.6  3.8 -12.3  4.5 4.8  1.3 0.0007
Fat mass (kg) -7.2  4.6 -11.7  4.9 4.4  1.5 0.005
Fat-free mass (kg) -1.1  2.3 -1.8  1.5 0.7  0.6 0.29
-686  485 -314  490 372  163 0.02
Completed per protocol (Wk16) N=19 N=17

Weight (kg) -9.2  3.7 -14.1  5.6 4.8  1.6 0.004
Weight (%) -8.4  3.3 -12.9  4.4 4.5  1.3 0.001
Fat mass (kg) -8.0  4.4 -12.3  4.8 4.3  1.5 0.009
Fat-free mass (kg) -1.2  2.4 -1.8  1.6 0.6  0.7 0.42
-749  498 -360  502 389  176 0.03
Completed per protocol (Wk16) and

N=13 N=15
6 months Follow up
Weight (kg) -7.7  3.1 -13.9  5.5 6.2  1.7 0.001
Weight (%) -7.2  2.9 -12.6  4.2 5.6  1.4 0.0004

Fat mass (kg) -6.6  3.4 -12.3  4.8 5.7  1.6 0.001
Fat-free mass (kg) -1.1  2.4 -1.6  1.4 0.5  0.7 0.49
-770  523 -255  515 515  213 0.02

Figure 1
CON ER
A INT
B
EB
0 1.0
Weight change during each block (kg)

-2 0.5
-4 # 0.0
Weight Loss (kg)
*#
-6 -0.5
*#
-8 # * -1.0
#
-10 -1.5
-12 # -2.0
-14 -2.5
#
-16 -3.0
-18 #
-3.5
EB2
ER1
EB1
ER2
ER3
EB3
ER4
EB4
ER5
EB5
ER6
EB6
ER7
EB7
ER8
-4 -2 0 2 4 6 8 10 12 14 16
Baseline Energy restriction
Week

Figure 2
CON CON
A INT B INT
80 60
*
75 * 55
70 * 50
NS
Fat Free Mass (kg)
Fat Mass (kg)

65 45
60 40
55 35
50 30
45 25
0
40 0
20
BL ER Wk4 ER Wk8 ER Wk12 ER Wk16 BL ER Wk4 ER Wk8 ER Wk12 ER Wk16

Figure 3
CON CON
200 A INT 200 B INT
Change in REE adj for FFM & FM (kJ/d)

0 * 0
*
Change in REE (kJ/d)
-200 -200
-400 -400
-600 -600
-800 -800
Predicted (Baseline equation) Predicted (Baseline equation)

200 C Measured 200 D Measured
CON INT
0 Change in REE (kJ/d) 0
-200 -200
-400 * -400
-600 -600
-800 -800
Predicted (Muller) Predicted (Muller)

200 E Measured 200 F Measured
CON INT
0 0
-200 -200
*
-400 * -400
-600 -600
-800 -800
BL ©
ER Wk4 2017
ER Wk8Macmillan
ER Wk12 Publishers
ER Wk16 Limited. All
BL rights reserved.
ER Wk4 ER Wk8 ER Wk12 ER Wk16
Figure 4 CON
INT
A
0
a
a
-2
-4 a

-6 

**

Weight Loss (kg)
-8 
b
-10 * **
-12
c
**
**
***
**
**
-14 c
d
-16
-18
e
-20
-4 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Baseline Energy restriction Energy balance Follow-up
CON-FM INT-FM
B CON-FFM INT-FFM
2
0
-2
Change in FM and FFM (kg)
-4
-6 **
-8
-10
-12
-14
#
-16
*
-18
-4 0 4 © 20 2017
8 12 16 24 28Macmillan
32 36 40 44Publishers
48 52 Limited. All rights reserved.
BL ER EB Follow-up

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Intermittent energy restriction improves weight loss efﬁciency in

N M Byrne, A Sainsbury, N A King, A P Hills, R E Wood

Cite this article as: N M Byrne, A Sainsbury, N A King, A P Hills, R E Wood,

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs

© 2017 Macmillan Publishers Limited. All rights reserved.

Health and Biomedical Innovation, Brisbane, QLD, Australia.

Charles Perkins Centre, The University of Sydney, Camperdown NSW, Australia.

Professor Nuala M Byrne

School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, Australia.

Telephone: +61 3 6324 3741

Background/Objectives: The MATADOR (Minimising Adaptive Thermogenesis And

vs CON: -749 ± 498 kJ/d; P<0.05).

weight loss efficiency.

Fellowships (481355 and 1042555).

diet, energy expenditure

strategy than traditional continuous approaches.

associated with continuous ER, would be attenuated.

undertook 16 weeks of ER delivered as either: 1) CON: 16 weeks of continuous (daily) ER, or 2)

INT: 16 weeks of ER as 8×2-week blocks of ER interspersed with 7×2-week blocks of energy

followed up after a 6-month free-living period.

Eligibility criteria for participants

are listed in Supplementary Item 2.

Recruitment and screening strategies

Supplementary Item 3 is a CONSORT diagram providing an overview of the flow of participants

and meeting assessment requirements up to and including Week16 ER.

Determination of weight maintenance energy requirements

reported work-time and leisure-time physical activity. Participants were prescribed an

Energy Restriction interventions

of weight maintenance energy requirements.

participants in consultation with a researcher (REW). Inclusion of discretionary items in a long-term

Overview of data collection

Body height, weight, and composition

between laboratory visits.

Resting energy expenditure (REE)

Calculation of predicted REE, and of changes from baseline

thermogenesis (30-38), we examined changes in REE using three approaches:

using regression analysis of baseline data (see details below).

Muller et al. (39).

group allocation accounted for a significant proportion of variance in REE. Consequently, a

separate equation was derived for CON and INT:

CON: REE(kJ/d) = 93.60  FFM(kg) + 36.04  FM(kg) + 1184

[R2 = 0.54; P < 0.01; RMSE = 545.4]

INT: REE(kJ/d) = 54.92  FFM(kg) + 46.46  FM(kg) + 2821

[R2 = 0.57; P < 0.01; RMSE = 617.9]

similar cohort (BMI>30 kg.m-2; N=278); where female=0, male=1:

were then compared.

where p < 0.05.

according to randomized treatment assignment, ignoring level of compliance, protocol deviations,

post-ER energy balance phase and 6-month follow-up (CON=13; INT=15).

thermogenesis (smaller reduction in REE) in response to intermittent ER.

during continuous ER inducing thermogenic compensation (CON: 9 kg).

model of intermittent ER we employed. Body composition-adjusted REE has been shown to

to recruit 50 participants (25 per group).

were not related (r = 0.22, p = 0.13).

Intervention: pre vs post

the 6-month follow-up.

FM comprised ~87 ± 21% of the weight lost.

Intervention: time-course of responses

to predicted thereafter (Fig3F).