Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss.
ABSTRACT: BACKGROUND:Metabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured. METHODOLOGY AND PRINCIPAL FINDINGS:Forty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m(2)) participants were randomized to four groups for 6-months; CONTROL:energy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were -1.0+/-1.1% (CONTROL), -10.4+/-0.9% (CR), -10.0+/-0.8% (CR+EX) and -13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (-454+/-76 kcal/d) and LCD (-633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (-316+/-118 kcal/d) and LCD (-389+/-124 kcal/d) but reached significance only when CR and LCD were combined (-351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by -431+/-51 and -240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6. CONCLUSIONS:For the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance. TRIAL REGISTRATION:ClinicalTrials.gov NCT00099151.
Project description:Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life.Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months.Mean +/- SE body weight was reduced by -1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and -13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23% +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX, LCD, and control groups.Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health.clinicaltrials.gov Identifier: NCT00099151.
Project description:The energy intake necessary to maintain weight and body composition is called the energy requirement for weight maintenance and can be determined by using the doubly labeled water (DLW) method.The objective was to determine the energy requirements of nonobese men and women in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy 2 study.Energy requirements were determined for 217 healthy, weight-stable men and women [aged >21 to <50 y; 70% female, 77% white; body mass index (BMI; in kg/m(2)) 22 to <28; 52% overweight] over 28 d with 2 consecutive 14-d DLW assessments in addition to serial measures of body weight and fat-free mass and fat mass by dual-energy X-ray absorptiometry. Energy intake and physical activity were also estimated by self-report over ?6 consecutive d in each DLW period.Total daily energy expenditure (TDEE) was consistent between the 2 DLW studies (TDEE1: 2422 ± 404 kcal/d; TDEE2: 2465 ± 408 kcal/d; intraclass correlation coefficient = 0.90) with a mean TDEE of 2443 ± 397 kcal/d that was, on average, 20% (580 kcal/d) higher in men than in women (P < 0.0001). The regression equation relating mean TDEE to demographics and weight was as follows: TDEE (kcal/d) = 1279 + 18.3 (weight, kg) + 2.3 (age, y) - 338 (sex: 1 = female, 0 = male); R(2) = 0.57. When body composition was included, TDEE (kcal/d) = 454 + 38.7 (fat-free mass, kg) - 5.4 (fat mass, kg) + 4.7 (age in y) + 103 (sex: 1 = female, 0 = male); R(2) = 0.65. Individuals significantly underreported energy intake (350 kcal/d; 15%), and underreporting by overweight individuals (~400 kcal/d; 16%) was greater (P < 0.001) than that of normal-weight individuals (~270 kcal/d; 12%). Estimates of TDEE from a 7-d physical activity recall and measured resting metabolic rate also suggested that individuals significantly underreported physical activity (~400 kcal/d; 17%; P < 0.0001).These new equations derived over 1 mo during weight stability can be used to estimate the free-living caloric requirements of nonobese adults. This trial was registered at clinicaltrials.gov as NCT00427193.
Project description:Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age-associated decline in growth hormone (GH), insulin-like growth factor (IGF)-1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty-three young (36.8 +/- 1.0 years), overweight (BMI 27.8 +/- 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00-08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: -1 +/- 1%, CR: -10 +/- 1%, CR + EX: -10 +/- 1%, LCD: -14 +/- 1%), fat mass (control: -2 +/- 3%, CR: -24 +/- 3%, CR + EX: -25 +/- 3%, LCD: -31 +/- 2%) and visceral fat (control: -2 +/- 4%, CR: -28 +/- 4%, CR + EX: -27 +/- 3%, LCD: -36 +/- 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 +/- 13%, LCD: 27 +/- 22%, P < 0.05) and amplitude (CR + EX: 34 +/- 14%, LCD: 30 +/- 20%, P < 0.05) but not to changes in secretory burst frequency or GH half-life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF-1 concentrations were increased only in CR + EX (10 +/- 7%, P < 0.05) and LCD (19 +/- 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF-1 in nonobese men and women.
Project description:OBJECTIVE:The objective of this study was to compare physical activity energy expenditure (PAEE) and total daily energy expenditure (TDEE) in successful weight loss maintainers (WLM) with normal weight controls (NC) and controls with overweight/obesity (OC). METHODS:Participants were recruited in three groups: WLM (n?=?25, BMI 24.1?±?2.3 kg/m2 ; maintaining ??13.6-kg weight loss for ??1 year), NC (n?=?27, BMI 23.0?±?2.0 kg/m2 ; similar to current BMI of WLM), and OC (n?=?28, BMI 34.3?±?4.8 kg/m2 ; similar to pre-weight loss BMI of WLM). TDEE was measured using the doubly labeled water method. Resting energy expenditure (REE) was measured using indirect calorimetry. PAEE was calculated as (TDEE?-?[0.1?×?TDEE]?-?REE). RESULTS:PAEE in WLM (812?±?268 kcal/d, mean?±?SD) was significantly higher compared with that in both NC (621?±?285 kcal/d, P?<?0.01) and OC (637?±?271 kcal/d, P?=?0.02). As a result, TDEE in WLM (2,495?±?366 kcal/d) was higher compared with that in NC (2,195?±?521 kcal/d, P?=?0.01) but was not significantly different from that in OC (2,573?±?391 kcal/d). CONCLUSIONS:The high levels of PAEE and TDEE observed in individuals maintaining a substantial weight loss (-26.2?±?9.8 kg maintained for 9.0?±?10.2 years) suggest that this group relies on high levels of energy expended in physical activity to remain in energy balance (and avoid weight regain) at a reduced body weight.
Project description:Context:Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Objective:Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Design:Cross-sectional study. Setting:Academic research center. Participants:Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Main Outcome:Total daily energy expenditure (TDEE) determined by DLW. Results:TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Conclusions:Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation.
Project description:The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5-29.9 kg/m² adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE - RMR - 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity.
Project description:BACKGROUND/OBJECTIVES:Circadian physiology has been linked to body weight regulation and obesity. To date, few studies have assessed the association between exercise timing and weight related outcomes. The aim of this secondary analysis was to explore the impact of exercise timing (i.e., 24?h clock time of exercise session) on weight loss and components of energy balance. SUBJECTS/METHODS:Overweight/obese (BMI 25.0-39.9?kg/m2), physically inactive, young adults (~51% female) completed a 10-month supervised exercise program (400 or 600?kcal/session for 5 days/week) or served as non-exercise controls (CON). Participants were categorized based on the time of day in which they completed exercise sessions (Early-Ex:?>50% of sessions completed between 7:00 and 11:59?am; (n?=?21), Late-Ex:?>50% of sessions completed between 3:00 and 7:00?pm; (n?=?25), Sporadic-Ex:?<50% of sessions completed in any time category; (n?=?24), and CON; (n?=?18)). Body weight, energy intake (EI; digital photography), and non-exercise physical activity (NEPA; accelerometer) were assessed at baseline, 3.5, 7, and 10 months. Total daily energy expenditure (TDEE; doubly labeled water), was assessed at baseline and 10 months. RESULTS:At month 10, weight loss was significantly greater in both Early-EX (-7.2?±?1.2%; p?<?0.001) and Sporadic-EX (-?5.5?±?1.2%; p?=?0.01) vs CON (+0.5?±?1.0%), and Early-EX vs Late-EX (-2.1?±?1.0%; p?<?0.001). There were no between group differences for change in TDEE, EI, and non-exercise energy expenditure (P?>?0.05). A significant group?×?time interaction (p?=?0.02) was observed for NEPA (counts/min), however, after adjusting for multiple comparisons, group effects were no longer significant. CONCLUSIONS:Despite minimal differences in components of energy balance, Early-EX lost significantly more weight compared with Late-Ex. Although the mechanisms are unclear, the timing of exercise may be important for body weight regulation.
Project description:Background:African-American (AA) women have poorer pregnancy outcomes, and studies in nonpregnant women suggest a different etiology of weight gain in AA compared with white women. We hypothesized that physiologic factors such as low energy expenditure and physical activity would be present in AA compared with white women in pregnancy. Objective:We aimed to identify physiologic risk factors for disordered energy balance in AA and white women early in pregnancy. Design:This was a cross-sectional study in 66 pregnant women with obesity, between 14 and 16 wk of gestation. Energy intake was calculated using the intake-balance method. Energy expenditure was measured in free-living conditions [total daily energy expenditure (TDEE)] over 7 d with the use of doubly labelled water and during sleep [sleeping EE (SleepEE)] in a room calorimeter. Body composition was measured by air displacement plethysmography and physical activity by accelerometers. Markers of metabolic health were obtained from fasting blood and urine. Results:AA (n = 34) and white (n = 32) women were comparable in age (mean ± SEM: 27.7 ± 0.6 y), enrollment body mass index [mean ± SEM (in kg/m2): 36.9 ± 0.7], and body fat (mean ± SEM: 45.0% ± 0.6%). AA women had more fat-free mass (P = 0.01) and tended to be more insulin-resistant (homeostasis model assessment of insulin resistance, P = 0.06). Energy intake was significantly lower in AA than in white women (2499 ± 76 compared with 2769 ± 58 kcal/d, P = 0.001), although absolute TDEE was comparable (AA: 2590 ± 77 kcal/d; white: 2711 ± 56 kcal/d; P = 0.21). After adjusting for body composition, TDEE was significantly lower in AA women (-231 ± 74 kcal/d, P = 0.003), as was SleepEE (-81 ± 37 kcal/d, P = 0.03). Physical activity, substrate oxidation, and metabolic biomarkers (triiodothyronine and thyroxine concentrations, catecholamine excretion) were not significantly different between groups. Conclusions:Body mass-adjusted energy expenditure is significantly lower in AA than in white pregnant women. Energy intake recommendations for pregnancy do not consider this difference and may therefore overestimate energy requirements in AA women. This may lead to unintentional overeating and contribute to the disparity of excess gestational weight gain and postpartum weight retention that is more prevalent in AA women. This trial was registered at clinicaltrials.gov as NCT01954342.
Project description:CONTEXT:It is not known whether the magnitude of metabolic adaptation, a greater than expected drop in energy expenditure, depends on the type of bariatric surgery and is associated with cardiometabolic improvements. OBJECTIVE:To compare changes in energy expenditure (metabolic chamber) and circulating cardiometabolic markers 8 weeks and 1 year after Roux-en-y bypass (RYGB), sleeve gastrectomy (SG), laparoscopic adjustable gastric band (LAGB), or a low-calorie diet (LCD). Design, Setting, Participants, and Intervention: This was a parallel-arm, prospective observational study of 30 individuals (27 females; mean age, 46 ± 2 years; body mass index, 47.2 ± 1.5 kg/m2) either self-selecting bariatric surgery (five RYGB, nine SG, seven LAGB) or on a LCD (n = 9) intervention (800 kcal/d for 8 weeks, followed by weight maintenance). RESULTS:After 1 year, the RYGB and SG groups had similar degrees of body weight loss (33-36%), whereas the LAGB and LCD groups had 16 and 4% weight loss, respectively. After adjusting for changes in body composition, 24-hour energy expenditure was significantly decreased in all treatment groups at 8 weeks (-254 to -82 kcal/d), a drop that only persisted in RYGB (-124 ± 42 kcal/d; P = .002) and SG (-155 ± 118 kcal/d; P = .02) groups at 1 year. The degree of metabolic adaptation (24-hour and sleeping energy expenditure) was not significantly different between the treatment groups at either time-point. Plasma high-density lipoprotein and total and high molecular weight adiponectin were increased, and triglycerides and high-sensitivity C-reactive protein levels were reduced 1 year after RYGB or SG. CONCLUSIONS:Metabolic adaptation of approximately 150 kcal/d occurs after RYGB and SG surgery. Future studies are required to examine whether these effects remain beyond 1 year.
Project description:To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)).Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test.Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P?=?0.02; CR-6 month P?=?0.002; CR+EX-3 month P?=?0.09; CR+EX-6 month P?=?0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P?=?0.07; CR-3 month P?=?0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both).Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I).ClinicalTrials.gov NCT00099151.