Editorial
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On adaptive thermogenesis: just another weight-loss tale?
Faidon Magkos
Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark
The most widely told weight-loss story begins with optimism
and rigorous diet adherence but more often than not concludes
with patient disappointment, lack of motivation, and eventually
relapse, leading to weight regain. There are many physiological
(but also behavioral) changes occurring with calorie restriction
that make weight loss progressively more difficult to sustain. The
early weight-loss phase lasts several weeks and is characterized
by relatively rapid loss of body mass consisting mainly of water,
glycogen, and protein; this is followed by a late weight-loss
phase, which extends for several months and is characterized
by slower loss of body mass consisting mainly of body fat (1).
The gradually increasing contribution of fat tissue to weight loss
results in an increase in the energy content of lost weight, from
∼4750 kcal/kg after 1 mo of dieting to ∼7000 kcal/kg after
6 mo (2), when maximum weight loss is typically observed (3).
This effectively translates in a need to increase the magnitude of
dietary calorie restriction by almost 50% during this time frame
to keep losing weight at the same rate. In addition, a number
of physiological adaptations involving hormonal changes (e.g.,
reduced triiodothyronine and leptin concentrations) and neural
changes (e.g., reduced sympathetic nervous system activity)
collectively trigger reductions in total energy expenditure, which
attenuate the magnitude of a given dietary energy deficit (4).
Total energy expenditure consists of 3 main components—
resting metabolic rate (RMR), diet-induced thermogenesis, and
physical activity-induced thermogenesis—all of which decrease
with weight loss. The loss of lean body mass consisting of
metabolically active tissues and organs (e.g., skeletal muscle,
heart, liver, and kidneys) results in decreased RMR; the reduction
in food intake invariably results in decreased diet-induced
thermogenesis; and the reduction in body weight results in
decreased energy cost of movement (i.e., lower mass needs to be
moved for a given activity pattern) and, thus, decreased physical
activity-induced thermogenesis (4, 5). Obligatory energy losses
in feces and urine comprise a very small part of total energy
expenditure (∼2%) and do not typically vary with changes in
body weight (6).
“Metabolic adaptation” or “adaptive thermogenesis” refers to
the decrease in RMR with weight loss beyond what can be
predicted from the loss of body weight and the corresponding
changes in fat and lean tissues. The existence of metabolic
adaptation can mitigate further the effect of dietary calorie
restriction on energy balance, making weight loss even more
difficult to sustain. Two main approaches have been taken
to investigate this phenomenon: cross-sectional comparisons
of “post-obese” patients (i.e., subjects with overweight and
obesity after weight loss) against control subjects who have the
Am J Clin Nutr 2020;00:1–3. Printed in USA. Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.
same body weight but have never undergone weight loss; and
longitudinal evaluations in subjects with overweight and obesity
before and after weight loss, where the difference between
measured and predicted RMR is calculated by using a regression
equation that is constructed from the same subjects at baseline
(and most commonly includes lean mass as a predictor that
explains 60–80% of the interindividual variance in RMR). The
former studies typically do not provide evidence of metabolic
adaptation, but one can assert that small differences in RMR
would be impossible to detect between weight-matched groups of
different individuals, given the variability in the relation between
RMR and lean body mass (7). This “noise” becomes less when
one uses data from the same individuals at baseline to construct a
regression of RMR on lean body mass, inasmuch as longitudinal
studies do indeed find some adaptive thermogenesis after weight
loss in the range of 90–180 kcal/d (4, 6). Still, a few questions
remain unresolved. Is the magnitude of metabolic adaptation
large enough to counter diet-induced energy deficits? Is adaptive
thermogenesis a transient phenomenon or a persistent response
leading to weight regain? And, how prevalent is it among patients
who lose weight?
Martins et al. (8) have recently evaluated RMR and body
weight in 156 overweight women, who were treated with a
800-kcal/d diet until reaching a BMI (kg/m2 ) <25, and demon-
strated an average adaptive thermogenesis of ∼54 kcal/d below
predicted levels (P < 0.05) after ∼16% weight loss (∼12 kg over
∼5 mo), even when the active weight-loss phase was followed by
∼4 wk of weight stabilization; however, no metabolic adaptation
was detectable after 1 and 2 y (<20 kcal/d below predicted;
P = NS), nor did it correlate with the amount of weight
regain (8). In this issue of the Journal, the same investigators
expanded on this work by measuring RMR and body weight in
71 men and women with obesity, immediately after consuming a
1000-kcal/d diet for 2 mo and again after 4 wk of stabilization at
the new lower body weight (9). At the end of the active weight-
loss phase, when subjects had lost ∼14 kg (13% of baseline
weight), metabolic adaptation was ∼92 kcal/d below predicted
levels, but this was more than halved to ∼38 kcal/d after 4 wk of
weight stabilization (both P < 0.05). This finding demonstrates
that the magnitude of adaptive thermogenesis depends on energy
balance, with acute negative energy balance immediately after
weight loss being responsible for about half of the apparent
The author reported no funding received for this work.
Address correspondence to FM (e-mail: fma@nexs.ku.dk).
First published online 0, 2020; doi: https://doi.org/10.1093/ajcn/nqaa262.
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2 Editorial

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FIGURE 1 Individual values for adaptive thermogenesis, calculated as the difference between measured and predicted resting metabolic rate, in 227 men
and women with overweight or obesity who lost weight with dietary calorie restriction and then stabilized for ∼4 wk at the new lower body weight (8, 9).
Values are ranked from the smallest (left) to the largest (right), with negative values (69% of subjects) indicating lower metabolic rates after weight loss than
predicted (more negative values indicate greater metabolic adaptation) and positive values (31% of subjects) indicating greater metabolic rates after weight loss
than predicted.

adaptation. In fact, in a subset of 33 participants who gained a
small amount of weight during the stabilization period (reflecting
a positive energy balance), metabolic adaptation was no longer
evident (9). This is consistent with the earlier observation by
Leibel et al. (6) who measured RMR immediately after weight
loss and again after 2 wk of weight stabilization, and reported
a significant increase of 150–350 kcal/d. Even though the
difference from predicted RMR was not reported in that study,
one can presume that predicted RMR would not change much
during weight stability; thus, the observed increase in measured
RMR would have led to attenuated adaptive thermogenesis (i.e.,
smaller negative difference from predicted RMR), as persuasively
shown by Martins et al. (9), or even a positive difference from
predicted RMR (which is not uncommon; see later). Furthermore,
and consistent with their earlier observation (8), Martins et al.
found that metabolic adaptation after active weight loss or after
weight stabilization did not predict weight regain at 1 y (9).
Results from these studies, which are among the largest and
longest longitudinal studies to date on metabolic adaptation, cast
doubt on adaptive thermogenesis as being a key mechanism
of body-weight regulation in response to weight loss. One
can reasonably argue that an adaptation of ∼50 kcal/d below
predicted for the new body weight and body composition is not
negligible for long-term body-weight homeostasis, particularly
if one considers that most prospective studies around the world
report average annual weight gains—responsible for the current
epidemic of obesity—within 0.1 and 0.6 kg/y, corresponding
to an excess of just 9 kcal/d (10)! Albeit small, this energy
imbalance would have to be sustained chronically, in fact
for several years, in order to affect body weight and explain
the high rate of weight-loss recidivism. There is a report
from the CALERIE (Comprehensive Assessment of the Long-
Term Effects of Reducing Intake of Energy) randomized trial
of significant metabolic adaptation at the levels of sleeping
metabolic rate and total energy expenditure after 2 y of calorie
restriction (weight loss of ∼8.7 kg), but these results are puzzling
in light of 1) the same metabolic adaptation in total (but not
sleeping) energy expenditure observed in control subjects who
actually gained ∼1.8 kg of weight, 2) the absence of differences
between groups in spontaneous physical activity, and 3) the
lack of weight stabilization before measurements of energy
metabolism were made (11). The results of Martins et al. (8,
9) demonstrate the complete absence of adaptive thermogenesis
after 1 and 2 y and the lack of correlation with weight regain.
If metabolic adaptation were a critical physiological response
preventing further weight loss and favoring weight regain, it
would have to be a rather persistent phenomenon, but the
significant reduction in adaptive thermogenesis after just 2–
4 wk of weight stabilization (6, 9) further challenges this notion.
What is more, as metabolic adaptation is not an immediate
response to calorie restriction but instead takes ≥2 wk to develop
(4), accordingly it may take >2–4 wk of weight stabilization
at net energy balance to completely dissipate. This would be
accentuated by most patients coming out of an active weight-
loss phase of considerable negative energy balance (low-calorie
or very-low-calorie diet regimens)—and thus out of some degree
of ketosis—and entering a period of weight stabilization that
likely involves considerable glycogen and water replenishment
 Editorial
rather than reflecting true stability of body weight (and hence,
true net energy balance). Last, but certainly not least, adaptive
thermogenesis is not an ubiquitous response; only 25–50% of
patients exhibit reductions in excess of 40 kcal/d after various
weight-loss regimens (4), which is far fewer than all those who
experience relapse. Data from Martins et al. (8, 9) demonstrate
a large interindividual variability in this adaptive response
(Figure 1). Overall, metabolic adaptation among their 227
subjects ranged from −337 to +352 kcal/d, with only ∼55% of
patients exhibiting reductions in excess of 40 kcal/d, and 1 out
of 3 actually having a positive difference between measured and
predicted RMR (Figure 1).
Before fully dismissing the importance of metabolic adapta-
tion as a barrier to weight loss and a driver of weight regain,
however, one needs to remember that the full adaptive response
to weight loss refers to changes in total energy expenditure, and
thus, not only to adaptations in RMR but also those in diet- and
physical activity-induced thermogenesis, or even cold-induced
thermogenesis. The decrease in RMR is responsible for only
∼30–50% of the decrease in total energy expenditure with weight
loss (5, 6). Leibel et al. (6) reported that differences between
measured and predicted total energy expenditure after weight loss
were, in fact, almost exclusively because of differences between
measured and predicted non-resting energy expenditure, whereas
the differences between measured and predicted RMR were not
always significantly different from zero and contributed little to
the total metabolic adaptation (6). Apparently, therefore, a few
more pages are still missing from this weight-loss story and I, for
one, am excited about reading on!
The author thanks Catia Martins, PhD, from the Department of Clinical
and Molecular Medicine, Norwegian University of Science and Technology
(NTNU), Norway, for supplying the raw data shown in Figure 1.
3
FM is a member of the Journal’s Editorial Board. He reports no other
conflicts of interest.
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