Metabolic adaptation is an illusion, only present when participants are in negative energy balance

ABSTRACT

setting The universe of metabolic adaptation, following weight loss, remains a controversial offspring. To our cognition, no study has evaluated the function of department of energy balance ( EB ) in modulating metabolic adaptation. Objectives The purpose of this study was to determine if metabolic adaptation, at the level of resting metabolic rate ( RMR ), is modulated by participants ’ EB status. A secondary aim was to investigate if metabolic adaptation was associated with weight recover.

Methods seventy-one individuals with fleshiness ( BMI : 34.6 ± 3.4 kg/m2 ; age : 45.4 ± 8.2 y ; 33 men ) enrolled in a 1000-kcal/d diet for 8 wk, followed by 4 wk of slant stabilization and a 9-mo weight personnel casualty sustenance broadcast. Body weight/composition and RMR were measured at baseline, workweek 9 ( W9 ), workweek 13 ( W13 ), and 1 y ( 1Y ). metabolic adaptation was defined as a significantly different ( lower or higher ) measured compared with bode RMR. Results Participants lost on median 14 kilogram by W9, followed by weight stabilization at W13, and regained 29 % of their initial weight loss at 1Y. metabolic adaptation was found at W9 ( −92 ± 110 kcal/d, P < 0.001 ) and W13 ( −38 ± 124 kcal/d, P = 0.011 ) but was not correlated with weight find. A significant decrease in metabolic adaptation was seen between W9 and W13 ( −53 ± 101 kcal/d, P < 0.001 ). In a subset of participants who gained burden between W9 and W13 ( nitrogen = 33 ), no metabolic adaptation was seen at W13 ( −26.8 ± 121.5 kcal/d, P = 0.214 ). In a subset of participants with data at all time points ( n = 45 ), metabolic adaptation was give at W9 and W13 ( −107 ± 102 kcal/d, P < 0.001 and −49 ± 128 kcal/d, P = 0.013 ) but not at 1Y ( −7 ± 129, P = 0.701 ). decision After weight loss, metabolic adaptation at the level of RMR is dependent on the EB status of the participants, being reduced to half after a period of system of weights stabilization. furthermore, metabolic adaptation does not predict weight unit find at 1Y follow-up. These trials were registered at clinicaltrials.gov as NCT02944253 and NCT03287726 . See corresponding editorial on page 1157.

Introduction

Weight loss is accompanied by a meaning decrease in total energy outgo due to a decrease in both pillow and nonresting energy outgo ( EE ) ( 1 ). Some have argued that this reduction is greater than predicted, given the measured losses in both fatty batch ( FM ) and nonfat mass ( FFM ) ( 1–6 ), a mechanism known as metabolic adaptation or adaptive thermogenesis. metabolic adaptation would then correspond to an exaggerated reduction in EE, below predicted levels, and could be a barrier to successful weight passing care. however, others have reported no evidence of metabolic adaptation when weight-stable individuals who had fleshiness and lost slant were compared with BMI-matched controls ( 7–12 ), and to our cognition, no one has ever reported metabolic adaptation to be a risk component for weight recover. The being, or lack of, and clinical relevance of metabolic adaptation, in reply to underfeeding and weight loss, has been one of the most controversial issues in the fleshiness field ( 13–19 ). A careful interrogation of the available literature seems to suggest that differences among studies derive from inconsistencies related with the status of energy balance ( EB ) and/or weight stability of the participants when measurements are taken. In fact, there is a course for longitudinal studies to report metabolic adaptation ( 1–5 ), while cross-sectional studies, comparing individuals who lost slant with BMI-matched controls, do not tend to report metabolic adaptation ( 7–9, 20 ). however, cross-sectional studies suffer from interindividual unevenness in resting metabolic rate ( RMR ) and body composition. Comparing individuals with fleshiness who have lost weight unit with lean controls is consequently not as probably to demonstrate metabolic adaptation as carefully controlled longitudinal studies. We have recently shown that when EE measurements are taken under conditions of weight stability, metabolic adaptation, at the level of RMR, is entirely ∼50 kcal/d after a 12-kg slant loss in previously fleshy women ( 21 ). however, in that survey, measurements were not taken immediately after weight unit personnel casualty, and as such, it is not possible to ascertain the role of weight constancy in modulating metabolic adaptation. therefore, the aim of the show junior-grade analysis was to determine if metabolic adaptation, at the degree of RMR, was modulated by weight stability in a population of men and women with fleshiness by measuring RMR immediately after weight personnel casualty and after a 4-wk weight stabilization time period. secondary aims were to investigate the presence of metabolic adaptation at 1-y ( 1Y ) follow-up and to determine if metabolic adaptation after weight loss was correlated with weight recover at 1Y follow-up. We hypothesized that metabolic adaptation would be reduced, or wholly lacking, when measurements were performed after a period of weight stabilization compared with immediately after weight loss ( under conditions of negative EB ). furthermore, we besides hypothesized that metabolic adaptation would not be introduce at 1-y follow-up and that metabolic adaptation after burden loss [ either week 9 ( W9 ) or workweek 13 ( W13 ) ] would not be associated with weight find at 1Y follow-up.

Methods

Participants

Participants in this analysis are separate of a large burden loss report ( ASKED—Ketosis and Appetite Suppression ) that was then followed by a weight personnel casualty maintenance cogitation. The elementary bearing of the studies was to identify the maximum carbohydrate ( CHO ) intake that is silent associated with appetite inhibition in a low-energy diet ( LED ) and to investigate the impression of probiotics ( compared with placebo ) on weight loss sustenance, respectively. The master learn included adult ( aged 18–65 y ) healthy volunteers, men and women, with fleshiness [ BMI ≥30 ( in kg/m2 ) ], weight static ( < 2-kg magnetic declination in system of weights within the past 3 missouri ), not presently dieting to lose weight, and not using any medications known to affect body weight, appetite, or metamorphosis. Given that both the RMR and appetite of normally ovulating women have been shown to vary across the menstrual bicycle ( 22, 23 ) but not in those who take oral contraception ( 24 ), we included in this learn postmenopausal women and premenopausal women taking oral contraceptives or with a normal menstrual cycle ( 28 ± 2 five hundred ) ( but not those with an irregular menstrual cycle ). This was done to make indisputable that measurements were taken in the same phase of the menstrual cycle. The studies were both approved by the local anesthetic ethical committee and were registered at clinicaltrials.gov as NCT02944253 and NCT03287726, respectively. All participants provided informed accept before participating in the discipline.

Study design

The weight loss survey was a randomized controlled trial with repeat measurements conducted at the Regional Center for Obesity Research and Innovation ( ObeCe ) in Trondheim, Norway. All participants, both men and women, were randomly allocated to 3 isocaloric 1000-kcal/d LEDs for 8 wk containing varying amounts of CHO ( 70, 100, and 130 guanine in each group ) and a fix come of protein ( 75 g/d ), with fat counterbalancing the calories from CHO. This was followed by a 4-wk see time period of weight stabilization. At W9, participants were gradually reintroduced to consume convention foods while reducing the inhalation of LED products. An individualized dietary plan, aiming at weight stabilization, was prescribed to each participant following the Nordic Nutrition Recommendations consisting of 15–20 % protein, 20–30 % fatten, and 50–60 % CHO ( 25 ). Energy needs were estimated by multiplying RMR values at W9 by physical activeness flat ( PAL ) extracted from physical activity monitors ( SenseWear ). The consumption of LED products was discontinued by the end of week 10. At W13, participants were randomly allocated ( duplicate blinded, placebo controlled ) to take a multistrain probiotic ( 8 strains of lactobacillus and bifidobacteria ) ( Nycopro Ferie ; Nycomed ) or placebo twice daily ( 1 with lunch and 1 with dinner ) over a period of 9 missouri. Energy needs were recalculated at W13 by using RMR at W13 and PAL at workweek 12 ( W12 ) and a raw dietary plan prescribed to each participant, with the same macronutrient composing as for the 4-wk weight stabilization period. Participants had to attend follow-up meetings at ObeCe every month with a research nurse for weighing, discussion of likely side effects, and collection of probiotics dose for the follow calendar month. A flow chart of the discipline can be seen in Figure 1.
FIGURE 1Open in new tabDownload slide Flowchart for the study. FIGURE 1Open in new tabDownload slide Flowchart for the study. Participants were asked not to change their physical natural process ( PA ) levels during the beginning 12 wk of the study and to increase it subsequently during the 9-mo burden care phase.

Data collection

The follow measurements were conducted at baseline, immediately after system of weights loss ( day after the 8 wk of the 1000-kcal/d diet ) ( W9 ), after 4 wk of slant stabilization ( W13 ), and at 1Y follow-up while the participants were in the fast express and immediately after they had voided in the dawn.

Body weight and composition

body weight and composition were determined by whole-body breeze shift plethysmography ( ADP ) ( BOD POD ; COSMED ). intracellular water ( ICW ), as an indirect measure of glycogen storage ( 26 ), was measured by bioimpedance analysis ( BIA ) ( InBody 720 ; Biospace ).

Resting metabolic rate

RMR was measured by collateral calorimetry ( Vmax Encore 29N ; Care Fusion ) using a canopy system and standard operational procedures ( 27 ).

Physical activity levels

Participants were asked to wear armbands ( SenseWear ) for a 7-d menstruation at service line ; weeks 4, 8, and 12 ; and 12-mo follow-up. Data were considered valid if the participants wore the device for a minimal of 4 d, including at least 1 weekend day and > 95 % of the time ( 28 ). The follow variables were analyzed : number of steps per day ; time spent on sedentary [ < 1.5 metabolic equivalent of tasks ( METs ) ], light ( 1.5–3 METs ), mince ( 3–6 METs ), and vigorous to very vigorous ( > 6 METs ) PA ; and total PA ( > 1.5 METs ) per day.

Statistical analysis

merely participants with RMR data available at baseline, W9, and W13 were included in this analysis. As no significant differences were seen in metabolic adaptation among randomly allocated groups, either at W9 or W13 ( P = 0.921 and P = 0.952, respectively, from a one-factor ANOVA ), all participants were analyzed in concert. statistical analysis was performed with SPSS adaptation 22 ( SPSS, Inc. ), data were presented as mean ± SD ( except for PA data, which were presented as mean ± SEM ), and statistical significance was set at P < 0.05. Changes in body weight/composition and RMR over time were assessed with a repeated-measures ANOVA, using Bonferroni discipline for multiple comparisons. The presence of metabolic adaptation was tested by paired thyroxine tests, comparing measured RMR ( RMRm ) and predicted RMR ( RMRp ) at the lapp fourth dimension points. An equation to predict RMR was derived from baseline data of all participants that were part of this analysis and included old age, sex, FM, and FFM as predictors. $ $ \begin { eqnarray* } { R^2 } = 0.79 ; P \lt 0.001 \end { eqnarray* } $ $ ( 1 ) RMRp ( kcal/d ) = 505.945 + [ 110.894 × sex ( 1 for females and 2 for males ) ] + [ 0.402 × Age ( years ) ] + [ 5.616 × FM ( kilogram ) ] + [ 15.213 × FFM ( kilogram ) ]. This equation, derived from baseline data, was then used to predict RMR at W9, W13, and 1Y, by using FM and FFM at each specific time point. Differences between metabolic adaptation at weeks 9 and 13 were evaluated by paired samples metric ton test. correlation coefficient analysis was performed between metabolic adaptation after burden loss ( W9 and W13 ) and weight unit find at 1Y ( as a share of the initial system of weights lost ) using Pearson or Spearman correlation coefficients, when allow. Changes in PA over time were analyzed using a analogue shuffle model with perennial measures, with a restricted maximum likelihood appraisal and specify effects for time. A Bonferroni correction was applied for post hoc pairwise comparisons.

Results

Baseline characteristics of the study participants are shown in table 1. Seventy-one adult participants ( 33 men ) with fleshiness were included in the present analysis, with an average age of 45.4 ± 8.2 y and an average BMI of 34.6 ± 3.4.

TABLE 1

Characteristic .	Value .
Age, y	45.4 ± 8.2
Males, n (%)	33 (47)
Anthropometrics
BMI, kg/m2	34.6 ± 3.4
Weight, kg	104.0 ± 14.6
Height, cm	173.1 ± 8.9
Fat mass, kg	43.3 ± 9.1
Fat mass, %	41.7 ± 6.4
Fat free mass, kg	60.9 ± 10.9
Fat free mass, %	58.4 ± 6.4

Characteristic .	Value .
Age, y	45.4 ± 8.2
Males, n (%)	33 (47)
Anthropometrics
BMI, kg/m2	34.6 ± 3.4
Weight, kg	104.0 ± 14.6
Height, cm	173.1 ± 8.9
Fat mass, kg	43.3 ± 9.1
Fat mass, %	41.7 ± 6.4
Fat free mass, kg	60.9 ± 10.9
Fat free mass, %	58.4 ± 6.4

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TABLE 1

Characteristic .	Value .
Age, y	45.4 ± 8.2
Males, n (%)	33 (47)
Anthropometrics
BMI, kg/m2	34.6 ± 3.4
Weight, kg	104.0 ± 14.6
Height, cm	173.1 ± 8.9
Fat mass, kg	43.3 ± 9.1
Fat mass, %	41.7 ± 6.4
Fat free mass, kg	60.9 ± 10.9
Fat free mass, %	58.4 ± 6.4

Characteristic .	Value .
Age, y	45.4 ± 8.2
Males, n (%)	33 (47)
Anthropometrics
BMI, kg/m2	34.6 ± 3.4
Weight, kg	104.0 ± 14.6
Height, cm	173.1 ± 8.9
Fat mass, kg	43.3 ± 9.1
Fat mass, %	41.7 ± 6.4
Fat free mass, kg	60.9 ± 10.9
Fat free mass, %	58.4 ± 6.4

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Anthropometrics and RMR data, at baseline, W9, and W13, in all participants can be seen in table 2. average weight loss at W9 was 14.1 ± 0.4 kilogram ( 13.2 % ± 2.8 % ), followed by sustenance between W9 and W13 ( 0.09 ± 0.22kg, P = 0.999 ). FM and FFM ( kilogram ) were significantly reduced at W9 and W13, compared with service line ( P < 0.001 for all comparisons ), but a significant decrease in FM and a significant increase in FFM ( kilogram ) was seen between W9 and W13 ( P < 0.001 for both ). BIA data showed a significant decrease in ICW from baseline to W9 ( P < 0.001 ), which returned to baseline at W13 ( P = 0.126 ). RMRm was significantly lower than RMRp at both W9 and W13, resulting in a metabolic adaptation of −92 ± 110 ( P < 0.001 ) and −38 ± 124 kcal/d ( P = 0.011 ), respectively. A significant reduction in metabolic adaptation was seen from W9 to W13 ( −53 ± 101 kcal/d, P < 0.001 ). In a subset of participants who gained weight between W9 and W13 ( newton = 33 ), RMRm−RMRp was −3.3 ± 119 kcal/d ( P = 0.874 ) at service line, −90.0 ± 94.5 kcal/d ( P < 0.001 ) at W9, −26.8 ± 121.5 kcal/d ( P = 0.214 ) at W13, and 6.4 ± 97.8 kcal/d ( P = 0.769 ) at 1Y.

TABLE 2

.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	Baseline vs. week 9 .	Baseline vs. week 13 .	Week 9 vs. week 13 .
Weight, kg	104.0 ± 14.6	90.1 ± 11.6	90.0 ± 11.8	<0.001	<0.001	0.999
FM, kg	43.3 ± 9.1	32.4 ± 8.6	31.4 ± 8.4	<0.001	<0.001	<0.001
FFM, kg	60.0 ± 10.9	57.6 ± 9.9	58.3 ± 10.1	<0.001	<0.001	<0.001
ICW, L	28.4 ± 5.9	27.2 ± 5.2	27.9 ± 9	<0.001	0.791	0.126
RMRm, kcal/d	1856 ± 249	1654 ± 204	1715 ± 238	<0.001	<0.001	<0.001
RMRp, kcal/d	1856 ± 221	1746 ± 193	1754 ± 197	<0.001	<0.001	0.005
RMRm−p, kcal/d	−0.01 ± 113	−92 ± 110***	−38 ± 124*

.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	Baseline vs. week 9 .	Baseline vs. week 13 .	Week 9 vs. week 13 .
Weight, kg	104.0 ± 14.6	90.1 ± 11.6	90.0 ± 11.8	<0.001	<0.001	0.999
FM, kg	43.3 ± 9.1	32.4 ± 8.6	31.4 ± 8.4	<0.001	<0.001	<0.001
FFM, kg	60.0 ± 10.9	57.6 ± 9.9	58.3 ± 10.1	<0.001	<0.001	<0.001
ICW, L	28.4 ± 5.9	27.2 ± 5.2	27.9 ± 9	<0.001	0.791	0.126
RMRm, kcal/d	1856 ± 249	1654 ± 204	1715 ± 238	<0.001	<0.001	<0.001
RMRp, kcal/d	1856 ± 221	1746 ± 193	1754 ± 197	<0.001	<0.001	0.005
RMRm−p, kcal/d	−0.01 ± 113	−92 ± 110***	−38 ± 124*

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TABLE 2

.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	Baseline vs. week 9 .	Baseline vs. week 13 .	Week 9 vs. week 13 .
Weight, kg	104.0 ± 14.6	90.1 ± 11.6	90.0 ± 11.8	<0.001	<0.001	0.999
FM, kg	43.3 ± 9.1	32.4 ± 8.6	31.4 ± 8.4	<0.001	<0.001	<0.001
FFM, kg	60.0 ± 10.9	57.6 ± 9.9	58.3 ± 10.1	<0.001	<0.001	<0.001
ICW, L	28.4 ± 5.9	27.2 ± 5.2	27.9 ± 9	<0.001	0.791	0.126
RMRm, kcal/d	1856 ± 249	1654 ± 204	1715 ± 238	<0.001	<0.001	<0.001
RMRp, kcal/d	1856 ± 221	1746 ± 193	1754 ± 197	<0.001	<0.001	0.005
RMRm−p, kcal/d	−0.01 ± 113	−92 ± 110***	−38 ± 124*

.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	Baseline vs. week 9 .	Baseline vs. week 13 .	Week 9 vs. week 13 .
Weight, kg	104.0 ± 14.6	90.1 ± 11.6	90.0 ± 11.8	<0.001	<0.001	0.999
FM, kg	43.3 ± 9.1	32.4 ± 8.6	31.4 ± 8.4	<0.001	<0.001	<0.001
FFM, kg	60.0 ± 10.9	57.6 ± 9.9	58.3 ± 10.1	<0.001	<0.001	<0.001
ICW, L	28.4 ± 5.9	27.2 ± 5.2	27.9 ± 9	<0.001	0.791	0.126
RMRm, kcal/d	1856 ± 249	1654 ± 204	1715 ± 238	<0.001	<0.001	<0.001
RMRp, kcal/d	1856 ± 221	1746 ± 193	1754 ± 197	<0.001	<0.001	0.005
RMRm−p, kcal/d	−0.01 ± 113	−92 ± 110***	−38 ± 124*

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Anthropometrics and RMR data over time in a subgroup with data at all points ( including 1Y ) ( north = 45, 33 males ) can be seen in table 3. average weight personnel casualty in this subsample at W9 was 14.4 ± 0.6 kilogram ( P < 0.001 ), followed by sustenance between W9 and W13 ( −0.01 ± 0.3 kilogram, P = 0.999 ) and regain between W13 and 1Y ( 4.1 ± 1.2 kg, P < 0.001 ). average slant find at 1Y was 29.1 % ± 52.1 %. There was a significant metabolic adaptation at both W9 ( −107 ± 102 kcal/d, P < 0.001 ) and W13 ( −49 ± 128 kcal/d, P = 0.013 ), despite a significant decrease in metabolic adaptation between W9 and W13 ( −57 ± 93 kcal/d, P < 0.001 ). No metabolic adaptation was seen at 1Y follow-up. Despite no significant differences in body system of weights between W9 and W13, at group charge, there was a very large interindividual variation ( range : −4.0 to +4.4 kilogram ).

TABLE 3

.	.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	1 y .	Baseline vs. week 9 .	Baseline vs. week 13 .	Baseline vs. 1 y .	Week 9 vs. week 13 .	Week 13 vs. 1 y .
Weight, kg	105.1 ± 14.0	90.7 ± 11.4	90.7 ± 11.5	94.8 ± 15.5	<0.001	<0.001	<0.001	0.999	0.005
FM, kg	42.6 ± 9.1	31.4 ± 8.6	30.6 ± 8.3	35.4 ± 10.6	<0.001	<0.001	<0.001	0.006	<0.001
FFM, kg	62.7 ± 10.8	59.2 ± 9.8	60.1 ± 10.1	59.4 ± 11.5	<0.001	<0.001	<0.001	0.001	0.999
RMRm, kcal/d	1884 ± 253	1665 ± 211	1732 ± 242	1790 ± 228	<0.001	<0.001	<0.001	<0.001	0.037
RMRp, kcal/d	1888 ± 216	1773 ± 190	1781 ± 195	1798 ± 224	<0.001	<0.001	<0.001	0.088	0.999
RMRm−p, kcal/d	−4 ± 122	−107 ± 102***	−49 ± 128*	−7 ± 129

.	.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	1 y .	Baseline vs. week 9 .	Baseline vs. week 13 .	Baseline vs. 1 y .	Week 9 vs. week 13 .	Week 13 vs. 1 y .
Weight, kg	105.1 ± 14.0	90.7 ± 11.4	90.7 ± 11.5	94.8 ± 15.5	<0.001	<0.001	<0.001	0.999	0.005
FM, kg	42.6 ± 9.1	31.4 ± 8.6	30.6 ± 8.3	35.4 ± 10.6	<0.001	<0.001	<0.001	0.006	<0.001
FFM, kg	62.7 ± 10.8	59.2 ± 9.8	60.1 ± 10.1	59.4 ± 11.5	<0.001	<0.001	<0.001	0.001	0.999
RMRm, kcal/d	1884 ± 253	1665 ± 211	1732 ± 242	1790 ± 228	<0.001	<0.001	<0.001	<0.001	0.037
RMRp, kcal/d	1888 ± 216	1773 ± 190	1781 ± 195	1798 ± 224	<0.001	<0.001	<0.001	0.088	0.999
RMRm−p, kcal/d	−4 ± 122	−107 ± 102***	−49 ± 128*	−7 ± 129

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TABLE 3

.	.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	1 y .	Baseline vs. week 9 .	Baseline vs. week 13 .	Baseline vs. 1 y .	Week 9 vs. week 13 .	Week 13 vs. 1 y .
Weight, kg	105.1 ± 14.0	90.7 ± 11.4	90.7 ± 11.5	94.8 ± 15.5	<0.001	<0.001	<0.001	0.999	0.005
FM, kg	42.6 ± 9.1	31.4 ± 8.6	30.6 ± 8.3	35.4 ± 10.6	<0.001	<0.001	<0.001	0.006	<0.001
FFM, kg	62.7 ± 10.8	59.2 ± 9.8	60.1 ± 10.1	59.4 ± 11.5	<0.001	<0.001	<0.001	0.001	0.999
RMRm, kcal/d	1884 ± 253	1665 ± 211	1732 ± 242	1790 ± 228	<0.001	<0.001	<0.001	<0.001	0.037
RMRp, kcal/d	1888 ± 216	1773 ± 190	1781 ± 195	1798 ± 224	<0.001	<0.001	<0.001	0.088	0.999
RMRm−p, kcal/d	−4 ± 122	−107 ± 102***	−49 ± 128*	−7 ± 129

.	.	.	.	.	P value .
Characteristic .	Baseline .	Week 9 .	Week 13 .	1 y .	Baseline vs. week 9 .	Baseline vs. week 13 .	Baseline vs. 1 y .	Week 9 vs. week 13 .	Week 13 vs. 1 y .
Weight, kg	105.1 ± 14.0	90.7 ± 11.4	90.7 ± 11.5	94.8 ± 15.5	<0.001	<0.001	<0.001	0.999	0.005
FM, kg	42.6 ± 9.1	31.4 ± 8.6	30.6 ± 8.3	35.4 ± 10.6	<0.001	<0.001	<0.001	0.006	<0.001
FFM, kg	62.7 ± 10.8	59.2 ± 9.8	60.1 ± 10.1	59.4 ± 11.5	<0.001	<0.001	<0.001	0.001	0.999
RMRm, kcal/d	1884 ± 253	1665 ± 211	1732 ± 242	1790 ± 228	<0.001	<0.001	<0.001	<0.001	0.037
RMRp, kcal/d	1888 ± 216	1773 ± 190	1781 ± 195	1798 ± 224	<0.001	<0.001	<0.001	0.088	0.999
RMRm−p, kcal/d	−4 ± 122	−107 ± 102***	−49 ± 128*	−7 ± 129

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Changes in body composition ( FM and FFM ) over time using data from BIA were of similar magnitude and meaning as the changes previously reported based on ADP ( data not shown ). metabolic adaptation at W9 or W13 was not correlated with weight find at 1Y follow-up ( gas constant = 0.034, P = 0.824, n = 45 and r = 0.106, P = 0.488, newton = 45, respectively ). Changes in PA over meter can be seen in table 4. A significant overall effect of time was seen for steps/d ( P = 0.006 ) ; sedentary ( P < 0.001 ), light ( P < 0.001 ), moderate ( P = 0.13 ), and vigorous to very vigorous ( P = 0.001 ) PA ; and full PA duration ( P = 0.001 ). A significant increase in steps/d was seen at 1Y compared with baseline ( P = 0.03 ). Time spent on sedentary PA was significantly lower than baseline at workweek 8 ( W8 ) ( P < 0.001 ). Time spent on fall PA was importantly higher than service line at W8, week 12 ( W12 ), and 1Y ( P < 0.001 for all ). No significant changes from baseline were seen for meter spent on mince PA. A meaning increase in time spent on vigorous to very vigorous PA was seen at 1Y compared with service line ( P = 0.025 ). Time spent on sum PA was significantly higher than baseline at W8, W12, and 1Y ( P = 0.007, P < 0.001, and P < 0.001, respectively ).

TABLE 4

Characteristic .	Baseline .	Week 4 .	Week 8 .	Week 12 .	1 y .	P value .
Steps/d	6556 ± 285	6548 ± 286	6627 ± 287	7156 ± 295	7519 ± 340*	0.006
Sedentary time, min/d	1184 ± 19	1177 ± 19	1071 ± 19***	1130 ± 20	1127 ± 24	<0.001
Light PA, min/d	188 ± 7	202 ± 8	221 ± 7***	227 ± 8***	229 ± 9***	<0.001
Moderate PA, min/d	55 ± 5	46 ± 5	54 ± 5	60 ± 5	59 ± 6	0.013
Vigorous to very vigorous PA, min/d	0.9 ± 0.4	0.5 ± 0.4	1.0 ± 0.4	1.8 ± 0.4	2.7 ± 0.5*	0.001
Total PA, min/d	244 ± 10	249 ± 10	276 ± 10**	289 ± 10***	290 ± 11***	0.001

Characteristic .	Baseline .	Week 4 .	Week 8 .	Week 12 .	1 y .	P value .
Steps/d	6556 ± 285	6548 ± 286	6627 ± 287	7156 ± 295	7519 ± 340*	0.006
Sedentary time, min/d	1184 ± 19	1177 ± 19	1071 ± 19***	1130 ± 20	1127 ± 24	<0.001
Light PA, min/d	188 ± 7	202 ± 8	221 ± 7***	227 ± 8***	229 ± 9***	<0.001
Moderate PA, min/d	55 ± 5	46 ± 5	54 ± 5	60 ± 5	59 ± 6	0.013
Vigorous to very vigorous PA, min/d	0.9 ± 0.4	0.5 ± 0.4	1.0 ± 0.4	1.8 ± 0.4	2.7 ± 0.5*	0.001
Total PA, min/d	244 ± 10	249 ± 10	276 ± 10**	289 ± 10***	290 ± 11***	0.001

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TABLE 4

Characteristic .	Baseline .	Week 4 .	Week 8 .	Week 12 .	1 y .	P value .
Steps/d	6556 ± 285	6548 ± 286	6627 ± 287	7156 ± 295	7519 ± 340*	0.006
Sedentary time, min/d	1184 ± 19	1177 ± 19	1071 ± 19***	1130 ± 20	1127 ± 24	<0.001
Light PA, min/d	188 ± 7	202 ± 8	221 ± 7***	227 ± 8***	229 ± 9***	<0.001
Moderate PA, min/d	55 ± 5	46 ± 5	54 ± 5	60 ± 5	59 ± 6	0.013
Vigorous to very vigorous PA, min/d	0.9 ± 0.4	0.5 ± 0.4	1.0 ± 0.4	1.8 ± 0.4	2.7 ± 0.5*	0.001
Total PA, min/d	244 ± 10	249 ± 10	276 ± 10**	289 ± 10***	290 ± 11***	0.001

Characteristic .	Baseline .	Week 4 .	Week 8 .	Week 12 .	1 y .	P value .
Steps/d	6556 ± 285	6548 ± 286	6627 ± 287	7156 ± 295	7519 ± 340*	0.006
Sedentary time, min/d	1184 ± 19	1177 ± 19	1071 ± 19***	1130 ± 20	1127 ± 24	<0.001
Light PA, min/d	188 ± 7	202 ± 8	221 ± 7***	227 ± 8***	229 ± 9***	<0.001
Moderate PA, min/d	55 ± 5	46 ± 5	54 ± 5	60 ± 5	59 ± 6	0.013
Vigorous to very vigorous PA, min/d	0.9 ± 0.4	0.5 ± 0.4	1.0 ± 0.4	1.8 ± 0.4	2.7 ± 0.5*	0.001
Total PA, min/d	244 ± 10	249 ± 10	276 ± 10**	289 ± 10***	290 ± 11***	0.001

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Discussion

The present article examined if metabolic adaptation, at the level of RMR, was modulated by the energy balance condition of the participants by measuring EE immediately after weight loss ( under negative EB ) and after 4 wk of weight constancy. After a 14-kg ( 13 % ) weight loss, a metabolic adaptation of ∼90 kcal/d below predicted levels was found at W9, when participants were in negative EB, which then was significantly reduced to less than half ( −38 kcal/d ) after 4 wk of weight stabilization. exchangeable results were found when a subset of participants with data at all time points was analyzed, with a metabolic adaptation of ∼110 kcal/d immediately after weight loss at W9, which was then halved after 4 wk of weight stabilization at W13 ( −49 kcal/d ) and disappeared at 1Y follow-up. We confirmed our guess that metabolic adaptation is significantly reduced ( in fact halved ) when measurements are performed after system of weights stabilization, in comparison with immediately after weight loss ( under minus EB ). This reinforces previous research by our group showing a metabolic adaptation of ∼50 kcal/d after a 16 % slant passing in women with corpulence when measurements were done after a 4-wk slant stabilization phase ( 21 ). Two reasons may explain why metabolic adaptation was still present after 4 wk of slant constancy. The first is that 4 wk of slant stabilization may not be enough for metabolic adaptation to disappear. The second gear, and likely more plausible explanation, is that our participants, despite being weight stable, were probably in minus EB when measurements were performed at W13. Weight passing in the give discipline was induced by 1000-kcal/d diets with a CHO contented of 70, 100, or 130 g/d. psychoanalysis of β-hydroxybutyric acid plasma concentrations ( a marker of ketonemia ) at W9 showed that participants were ketotic at W9 ( 0.76 ± 0.51 mmol/L ), careless of the diet, but not at W13 ( 0.11 ± 0.1 mmol/L ). Ketosis is accompanied by glycogen depletion and with it water loss, while refeeding is followed by glycogen refilling and with it increased water content. It has been estimated that glycogen stores are on average 400–500 gigabyte ( 29, 30 ), with 3–4 g of water system constipate to each gram of glycogen ( 29 ). This means that an increase in consistency system of weights between 1.6 and 2.5 kilogram, due to increase water content, should be expected when participants came out of ketonemia ( 30 ). even though we were unable to directly quantify changes in glycogen storage over time in the present study, data from BIA showed a significant reduction in ICW at W9 ( P < 0.001 ), which returned to baseline values at W13. It has previously been shown that changes in ICW derived from BIA can be used as a proxy of changes in glycogen subject due to CHO loading ( 26 ). This powerfully suggests that our participants were in negative EB at W13, which may explain why despite a halve in metabolic adaptation from W9 to W13, metabolic adaptation was still introduce at W13. The fact that RMRm−RMRp was not meaning in a subgroup of participants who gained weight between W9 and W13 adds far evidence to the fact that the remainder metabolic adaptation seen at W13 in all participants is ascribable to the fact that the participants were in veto EB at that time point and that if participants are in EB, no metabolic adaptation should be expected after slant loss. Leibel et alabama. ( 1 ) reported in their 1995 landmark newspaper that the alimony of a 10 % system of weights personnel casualty ( 8 wk of a 800-kcal/d diet, followed by 2 wk of weight stabilization ), in individuals with fleshiness, was followed by a reduction in RMR below predicted levels ( metabolic adaptation ) of 137 ± 305 kcal/d. This prize is much higher ( about 3 times larger ) than the metabolic adaptation reported in the present analysis after a 13 % system of weights loss followed by 4 wk of weight stabilization. A likely reason for this discrepancy could be related to the duration of the stabilization time period, which was only 2 wk in Leibel et alabama. ( 1 ), while in the present analysis, it was 4 wk. Leibel et alabama. ( 1 ) besides measured RMR immediately after weight loss and reported values to be importantly lower than after the 2-wk weight unit stabilization menstruation ( 1598 ± 385 compared with 1747 ± 416 kcal/d, respectively, P = 0.043 ), but the difference between measured and predicted RMR was not reported. even though predicted RMR can be presumed not to have changed importantly during weight stability, there was an modal 1.6-kg weight profit over the 2-wk stabilization period. furthermore, it needs to be emphasized that the data from Leibel et alabama. ( 1 ) previously reported are derived from only 9 individuals with fleshiness, while the confront analysis reflects changes in RMR in 71 individuals. The findings of this study add to previous evidence from cross-section studies showing no metabolic adaptation at the level of RMR when weight-stable individuals with fleshiness who have lost weight are compared with never-obese BMI-matched controls ( 7–10 ) and reinforce the controversy that metabolic adaptation in longitudinal studies ( 1, 4–6 ) is probable a result of measurements taken under negative EB. Importantly, and adding to previous tell ( 4, 21 ), metabolic adaptation after weight loss ( either at W9 or W13 ) was not correlated with system of weights find at 1Y. If metabolic adaptation was part of a compensatory reaction that tries to bring body weight binding to its original state and, therefore, a driver of weight unit find, it would be expected that metabolic adaptation would be present after weight passing, careless of the EB status of the participants, and that a larger metabolic adaptation would be associated with more weight recover in the retentive term. The present analysis refutes both of those premises. It needs to be acknowledged that RMR contributes to only ∼60 % of sum energy expending in individuals with fleshiness ( 12 ). Metabolic adaptation could, therefore, besides be portray at the level of nonresting department of energy consumption ( NREE ) due, purportedly, to increased exercise efficiency. even though Leibel et aluminum. ( 1 ) have reported that metabolic adaptation after a 10 % weight loss, followed by 2 wk of weight constancy, was associated with set metabolic adaptation, peculiarly at the level of NREE ( 1 ), the study suffers from several methodologic limitations, some of them already previously highlighted. This includes a very little sample size and weight unit amplification during the slant stabilization period. In cable with the evidence previously discussed for RMR, it seems that the universe of metabolic adaptation at the grade of NREE after weight unit loss is besides likely to be modulated by the EB condition of the individuals being measured. As such, in corpulence premenopausal women who had lost 10–12 kilogram, no metabolic adaptation was found in NREE when measurements were done in control conditions of weight stability ( 31–34 ). More important, we could not identify a single discipline report increased exercise efficiency after burden passing to be associated with long-run weight recover. In reality, the antonym might be truthful, as better locomotion economy/efficiency following drill prepare has been shown to be associated with increased comfort of locomotion ( 35–38 ), which in plow has been found to be associated with increased engagement in free living physical activity and deoxidize weight recover ( 39–43 ). Despite the potential minor function of metabolic adaptation as a driver of weight recover, the deliver findings have authoritative clinical relevance and might explain why some individuals with fleshiness might experience resistor to further weight loss. If a larger than expected reduction in RMR offsets the positive energy restriction, no farther weight loss will occur. In fact, there is a far-flung dogma among dietitians that individuals with fleshiness who report not being able to lose far system of weights on a LED might continue losing slant under the same dietary prescription after a short period of overfeeding used to “ switch off ” metabolic adaptation. This fits well with the results described in the present article, by which metabolic adaptation was halved after 4 wk of weight stabilization and absent in those who did not lose weight unit between W9 and W13. Our sketch has both strengths and limitations. The independent force is its purpose, with data collected immediately after weight passing, equally well as after a 4-wk slant stabilization period. This allowed us to determine the function of weight constancy and EB in modulating metabolic adaptation. second, gold-standard methods were used for the measurements of RMR ( indirect calorimetry ) and body composition ( BodPod ). Third, it includes a heterogenous sample of both males and females with fleshiness, with a wide range of BMI ( 30–43 ) and long time ( 26–62 y ), which is important for abstraction purposes. however, we did not directly measure changes in glycogen storage over time and, as such, were not able to identify with certainty which participants were or were not in EB at W13. Nevertheless, ICW from BIA provided us with an indirect meter of glycogen and, as such, of EB status of the participants at W13. In conclusion, metabolic adaptation at the level of RMR is reduced ( halved ) to ∼50 kcal/d when measurements are taken under conditions of burden stability compared with immediately after weight loss and is not sustained in the long term with system of weights find. furthermore, metabolic adaptation does not predict backsliding in the retentive term. Further inquiry needs to address option mechanistic pathways that might contribute to relapse in fleshiness treatment.

ACKNOWLEDGEMENTS

The authors ’ responsibilities were as follows––CM, JR, and SS : conceived and designed the study ; JR and SS : collected the data ; CM : performed the statistical psychoanalysis ; CM, JR, SS, BAG, and GRH : wrote the manuscript ; CM : had primary responsibility for final content ; and all authors : assisted with data rendition and understand and approved the final manuscript. The authors report no conflicts of interest.

Notes

fund : This study was funded by the norwegian University of Science and Technology ( NTNU ) ( doctoral accord ) and the Liaison Committee for Education, Research, and Innovation in Central Norway in partnership with NTNU ( running costs ). CM was supported by a sabbatical award by the Liaison Committee for Education, Research, and Innovation in Central Norway and the NTNU. Data sharing : Data described in the manuscript will be made available upon request pending approval by the local ethics committee. Abbreviations used : ADP, air shift plethysmography ; BIA, bioelectric electric resistance psychoanalysis ; CHO, carbohydrate ; EB, energy libra ; EE, energy expending ; FM, fat mass ; FFM, nonfat mass ; ICW, intracellular water ; LED, low-energy diet ; MET, metabolic equivalent of tax ; NREE, nonresting energy consumption ; PA, physical action ; PA, physical activity charge ; RMR, resting metabolic rate ; RMRm, resting metabolic rate measured ; RMRp, resting metabolic rate predicted ; W, week ; Y, year.

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