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Objective: This study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples., Methods: The model development group included healthy nonexercising adults (n = 897) who had whole-body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26)., Results: A series of SM prediction models were developed in a sample of 415 males and 482 females. Model-predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model-predicted values., Conclusions: Nonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10-kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing., (© 2023 The Obesity Society.)

Lack of efficacy of weight loss(WL) interventions is attributed in-part to low adherence to dietary/physical activity(PA) recommendations. However, some compensation may occur in PA as a response to energy restriction such as a decrease in non-exercise PA(NEPA) or non-exercise activity thermogenesis(NEAT). The current study aim was (1) to investigate whether adaptive thermogenesis(AT) in NEAT occurs after WL, and (2) to understand the associations of these compensations with WL. Ninety-four former athletes [mean±SD, age: 43.0±9.4y, BMI: 31.1±4.3 kg/m 2 , 34.0% female] were recruited and randomly assigned to intervention or control groups (IG, CG). The IG underwent a one-year lifestyle WL-intervention; no treatments were administered to the CG. PA was measured using accelerometery and NEAT was predicted with a model including sample baseline characteristics. AT was calculated as measured NEAT 4mo/12mo (kcal/d) - predicted NEAT 4mo/12mo (kcal/d) - measured NEAT baseline (kcal/d) - predicted No significant differences were found for non-exercise activity thermogenesis (NEAT) or non-exercise physical activity (NEPA) after the weight loss (WL) intervention;Although a large variability was found for NEAT and NEPA, the interindividual variability regarding these outcomes is not relevant. The variability in these outcomes might reflect a large within-subject variability and/or a large degree of random measurement error;Although no energy conservation was observed in NEAT after moderate WL (mean values), further studies are needed to clarify the mechanisms behind the large variability in adaptive thermogenesis observed in NEAT and related changes in NEPA to better implement lifestyle-induced WL interventions. baseline (kcal/d). Dual-energy x-ray absorptiometry was used to assess fat-free mass and fat mass. No differences were found in the IG for NEAT or NEPA after WL. Considering mean values, AT was not found for either group. The SD of individual response (SD IR ) for AT was -2(4-months) and 24(12-months) (smallest worthwhile change = 87kcal/d), suggesting that the interindividual variability regarding AT in NEAT is not relevant and the variability in this outcome might reflect a large within-subject variability and/or a large degree of random measurement error. No associations were found between AT in NEAT and changes in body composition. Further studies are needed to clarify the mechanisms behind the large variability in AT observed in NEAT and related changes in NEPA to better implement lifestyle-induced WL interventions. Highlights No significant differences were found for non-exercise activity thermogenesis (NEAT) or non-exercise physical activity (NEPA) after the weight loss (WL) intervention;Although a large variability was found for NEAT and NEPA, the interindividual variability regarding these outcomes is not relevant. The variability in these outcomes might reflect a large within-subject variability and/or a large degree of random measurement error;Although no energy conservation was observed in NEAT after moderate WL (mean values), further studies are needed to clarify the mechanisms behind the large variability in adaptive thermogenesis observed in NEAT and related changes in NEPA to better implement lifestyle-induced WL interventions. Trial registration: ClinicalTrials.gov identifier: NCT03031951.

Adaptive thermogenesis (AT) is the mass-independent decrease in energy expenditure (EE) in response to caloric restriction and weight loss. AT becomes manifest throughout all periods of weight loss and persists during subsequent weight maintenance. AT occurs in resting and nonresting energy expenditure as AT REE and AT NREE , respectively. AT REE appears in different phases of weight loss, each with likely different mechanisms. By contrast, during weight maintenance after weight loss, AT NREE exceeds AT REE . Some of the mechanisms of AT are known now and others are not. Future studies on AT will need an appropriate conceptual framework within which to design experiments and interpret results., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Adaptive thermogenesis (AT) is currently defined as the fat-free mass (FFM)-independent change in resting energy expenditure (REE) in response to caloric restriction (CR) or overfeeding (OF). So far, the impact of changes in the anatomical and molecular composition of FFM on AT has not been addressed., Objectives: To assess the impact of changes in FFM composition on AT., Methods: FFM was assessed in 32 healthy young men during controlled 21-d CR and 14 d of subsequent OF. Anatomical (i.e., the organ/tissue level) and molecular (i.e., water, mineral, and protein content and thus body density) composition of FFM were characterized. REE was measured by indirect calorimetry., Results: With CR, body weight and REE decreased by 4.2 ± 0.9 kg and 173 ± 107 kcal/d, respectively, with corresponding increases of 3.5 ± 1.2 kg and 194 ± 110 kcal/d during OF (P < 0.001 for all changes). Changes in FFM explained 56.7% and 66.7% of weight loss and weight gain, respectively. Weight changes were associated with changes in various anatomical (i.e., masses of skeletal muscle, liver, kidneys, and brain) and molecular components (total body water, protein, and bone minerals) of FFM. After adjustments for changes in FFM only, AT was 116 ± 127 (P < 0.001) and 27 ± 115 kcal/d (NS) with CR and OF, respectively. Adjustments for FFM and its anatomical and molecular composition reduced AT in response to CR to 83 ± 116 and 122 ± 123 kcal/d (P < 0.05 and P < 0.001) whereas during OF, AT became significant at 87 ± 146 kcal/d (anatomical; P < 0.05) and 86 ± 118 kcal/d (molecular; P < 0.001)., Conclusions: Adjusting changes in REE with under- and overfeeding for the corresponding changes in the anatomical and molecular composition of FFM decreased AT after CR and increased AT after OF, but overall adjusted AT was likely not large enough in magnitude to be able to prevent weight loss or resist weight gain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss., Methods: A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively., Results: Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg)., Conclusions: Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use., (© 2021 The Obesity Society.)

Purpose of Review: Validated thermodynamic energy balance models that predict weight change are ever more in use today. Delivery of model predictions using web-based applets and/or smart phones has transformed these models into viable clinical tools. Here, we provide the general framework for thermodynamic energy balance model derivation and highlight differences between thermodynamic energy balance models using four representatives., Recent Findings: Energy balance models have been used to successfully improve dietary adherence, estimate the magnitude of food waste, and predict dropout from clinical weight loss trials. They are also being used to generate hypotheses in nutrition experiments. Applications of thermodynamic energy balance weight change prediction models range from clinical applications to modify behavior to deriving epidemiological conclusions. Novel future applications involve using these models to design experiments and provide support for treatment recommendations.

Background: While many people with overweight or obesity can lose weight temporarily, most have difficulty maintaining weight loss over the long term. Studies of dietary composition typically focus on weight loss, rather than weight-loss maintenance, and rely on nutrition education and dietary counseling, rather than controlled feeding protocols. Variation in initial weight loss and insufficient differentiation among treatments confound interpretation of results and compromise conclusions regarding the weight-independent effects of dietary composition. The aim of the present study was to evaluate three test diets differing in carbohydrate-to-fat ratio during weight-loss maintenance., Design and Dietary Interventions: Following weight loss corresponding to 12±2% of baseline body weight on a standard run-in diet, 164 participants aged 18 to 65years were randomly assigned to one of three test diets for weight-loss maintenance through 20weeks (test phase). We fed them high-carbohydrate (60% of energy from carbohydrate, 20% fat), moderate-carbohydrate (40% carbohydrate, 40% fat), and low-carbohydrate (20% carbohydrate, 60% fat) diets, controlled for protein content (20% of energy). During a 2-week ad libitum feeding phase following the test phase, we assessed the effect of the test diets on body weight., Outcomes: The primary outcome was total energy expenditure, assessed by doubly-labeled water methodology. Secondary outcomes included resting energy expenditure and physical activity, chronic disease risk factors, and variables to inform an understanding of physiological mechanisms by which dietary carbohydrate-to-fat ratio might influence metabolism. Weight change during the ad libitum feeding phase was conceptualized as a proxy measure of hunger., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact of weight loss on bone in reduced overweight/obese women compared with women who regained their weight was examined in this study using a case-control design., Methods: Postmenopausal women (N = 42; mean [SD] body mass index, 28.3 [2.8] kg/m; mean [SD] age, 60.7 [5.5] y) were recruited 2 years after the start of a 6-month weight loss trial; those who maintained their weight (weight loss maintainer [WL-M] group) were matched to a cohort of women who regained their weight (weight loss regainer [WL-R] group). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck, trochanter, spine, radius, and total body, and soft-tissue composition were taken at baseline, 0.5 years, and 2 years., Results: During weight loss, both groups lost 9.3% (3.4%) of body weight, with no significant difference between the groups. After weight loss, weight change was -0.1% (2.7%) and 6.0% (3.3%) in the WL-M (n = 22) and WL-R (n = 20) groups, respectively. After 2 years, both groups lost BMD at the femoral neck and trochanter (P ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (P < 0.001). There was greater BMD loss at the trochanter (-6.8% [5.7%]) and 1/3 radius (-4.5% [3.3%]) in the WL-M group compared with the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (P < 0.05)., Conclusions: After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for those who maintain weight and those who regain weight., Competing Interests: None

Background: Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information., Methods: Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations., Results: We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations., Conclusions: False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.).

Earlier cross-sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24-week CB-1R inverse agonist clinical trial (weight change, -7.7 ± 5.3 kg; SAT change, -5.4 ± 4.9 l, VAT change, -0.8 ± 1.0 l). VAT and SAT volumes at baseline and 24 weeks were derived from whole-body MRI images. The VAT area 5-10 cm above L(4)-L(5) (A(+5-10)) (R(2) = 0.59-0.70, P < 0.001) best predicted changes in VAT volume but the strength of these correlations was significantly lower than those at baseline (R(2) = 0.85-0.90, P < 0.001). Furthermore, the L(4)-L(5) slice poorly predicted VAT volume changes (R(2) = 0.24-0.29, P < 0.001). Studies will require 44-69% more subjects if (A(+5-10)) is used and 243-320% more subjects if the L(4)-L(5) slice is used for equivalent power of multislice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross-sectional SAT (R(2) = 0.31-0.49 vs. R(2) = 0.52-0.68, P < 0.05). Results were the same when examined in men and women separately. A single MRI slice 5-10 cm above L(4)-L(5) is more powerful than the traditionally used L(4)-L(5) slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multislice imaging may be more cost-effective than single slice imaging in detecting changes for VAT and SAT.

The classic rule stating that restricting intake by 3500 kcal/wk will lead to a 1-lb/wk rate of weight loss has come under intense scrutiny. Generally not a component of most weight loss prediction models, the "early" rapid weight loss phase may represent a period during which the energy content of weight change (ΔEC/ΔW) is low and thus does not follow the classic "rule." The current study tested this hypothesis. Dynamic ΔEC/ΔW changes were examined in 23 Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Study overweight men and women evaluated by dual-energy x-ray absorptiometry during weight loss at treatment weeks 4 to 24. Changes from baseline in body energy content were estimated from fat and fat-free mass. Repeated-measures analysis of variance was used to determine if ΔEC/ΔW changed significantly over time. The evaluation was expanded with addition of the Kiel 13-week weight loss study of 75 obese men and women to test with adequate power if there are sex differences in ΔEC/ΔW. The analysis of variance CALERIE time effect was significant (P < .001), with post hoc tests indicating that ΔEC/ΔW (kilocalories per kilogram) increased significantly from week 4 (X ± SEM; 4, 858 ± 388) to 6 (6, 041 ± 376, P < .01) and changed insignificantly thereafter; ΔEC/ΔW was significantly larger for Kiel women (6, 804 ± 226) vs men (6, 119 ± 240, P < .05). Sex-specific dynamic relative changes in body composition and related ΔEC/ΔW occur with weight loss initiation that extend for 1 month or more. These observations provide new information for developing energy balance models and further define limitations of the 3500-kcal energy deficit → 1-lb weight loss rule., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pharmacologic inhibition of the cannabinoid-1 receptor (CB1R) in rodent models leads to weight loss and time-dependent changes in energy balance. This study evaluated the effects of CB1R inhibition on weight loss, energy expenditure (EE), and food intake (FI) in an obese canine model following 4 weeks of treatment. Eighteen maintenance-fed obese beagles were evenly and randomly allocated to a CB1R inverse agonist (AM251) (2 mg/kg), a 70% food-restricted (FR) diet, or a control group (C). Evaluations included body weight and composition (dual-energy x-ray absorptiometry scan), EE (doubly labeled water), and FI. Change in body mass at week 4 was significantly greater (P < .050) in the AM251 (-1476.7 g) and FR groups (-1100.0 g) than in the C group (-228.3 g). Food intake was decreased from week 2 onward in the FR and AM251 groups (P < .05). Absolute and lean mass-adjusted EEs were decreased only in the FR group (P < .01); EE in the AM251 group was greater (P < .05) than that in the FR group. Pharmacologic inhibition of CB1R in a canine model led to sustained effects on FI and EE. Weight loss was greater with AM251 than could be accounted for by food restriction (∼25%), an effect likely mediated by the EE response to CB1R inhibition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although dietary weight-loss counseling usually employs a 500 to 1,000 kcal/day energy deficit to induce weight loss of 0.5 to 1 kg/week, this rate of weight loss is rarely achieved in research settings. Biological factors, such as changes in metabolic rate, are partly responsible, but would only account for a small deviation from expected weight loss. There must be other factors, behavioral or related to study design and implementation, that affect the rate of weight loss observed., Objective: To examine factors that influence the rate of weight loss obtained in clinical studies., Design: Thirty-five weight-loss studies published between 1995 and 2009 were identified that used dietary counseling to induce weight loss in healthy subjects. Studies were included if they had a duration of at least 6 weeks, used a strategy to counsel subjects to reduce free-living energy intakes, and reported weight-loss data based on a completers analysis. Variables that were associated with the rate of weight loss among age, sex (percent female subjects), initial body weight, frequency of dietary counseling, placebo use, exercise level, study length, and prescribed energy deficit were examined using linear regression analysis., Results: Study length was negatively related to the rate of weight loss (P<0.0001), whereas subject age (P<0.002), subject age squared (P=0.0073), initial body weight (P=0.0003), frequency of dietary counseling (P=0.0197), and prescribed energy deficit (P<0.0001) were positively related to the rate of weight loss observed in clinical studies., Conclusions: These findings provide a tool for investigators and clinical dietitians to predict the rate of weight loss that can be expected within a population given the age, initial body weight, frequency of dietary counseling, and energy deficit prescription. These data from clinical studies suggest that the rate of weight loss is greater in older and heavier subjects and with higher contact frequency and caloric restriction., (Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Improving the maintenance of weight loss remains a critical challenge for obesity researchers. The present 1-year, randomized, placebo-controlled trial evaluated the safety and efficacy of weight maintenance counseling combined with either placebo or the cannabinoid-1 receptor inverse agonist, taranabant, for sustaining prior weight loss achieved on a low-calorie diet (LCD). Seven hundred eighty-four individuals who had lost ≥ 6% of body weight during six initial weeks of treatment with an 800 kcal/day liquid LCD were randomly assigned to placebo or once-daily taranabant in doses of 0.5, 1, or 2 mg. All participants were provided monthly, on-site behavioral weight maintenance counseling, as well as monthly phone calls. The primary end point was change in body weight from randomization to week 52. The randomized participants lost an average of 9.6 kg (9.5% of initial weight) during the 6-week LCD. The model-adjusted mean change in body weight during the subsequent 1 year was +1.7 kg for placebo, compared with -0.1, -0.6, and -1.2 kg for the taranabant 0.5, 1, and 2 mg doses, respectively (all P values ≤ 0.007 vs. placebo). The incidences of psychiatric-related adverse events, including irritability, were higher for taranabant 1 and 2 mg vs. placebo (P ≤ 0.038). In addition to reporting data on the safety and efficacy of taranabant, this study provides a method for studying the combination of lifestyle modification and pharmacotherapy for weight maintenance after diet-induced weight loss.

Background: Energy intake (EI) during weight loss is difficult and costly to measure accurately., Objective: The objective was to develop and validate a computational energy balance differential equation model to determine individual EI during weight loss., Design: An algorithm was developed to quantify EI during weight loss based on a validated one-dimensional model for weight change. By using data from a 24-wk calorie-restriction study, we tested the validity of the EI model against 2 criterion measures: 1) EI quantified through food provision from weeks 0-4 and 4-12 and 2) EI quantified through changes in body energy stores [measured with dual-energy X-ray absorptiometry (DXA)] and energy expenditure [measured with doubly labeled water (DLW)] from weeks 4-12 and 12-24., Results: Compared with food provision, the mean (±SD) model errors were 41 ± 118 kcal/d and -22 ± 230 kcal/d from weeks 0-4 and 4-12, respectively. Compared with EI measured with DXA and DLW, the model errors were -71 ± 272 kcal/d and -48 ± 226 kcal/d from weeks 4-12 and 12-24, respectively. In every comparison, the mean error was never significantly different from zero (P values > 0.10). Furthermore, Bland and Altman analysis indicated that error variance did not differ significantly over amounts of EI (P values > 0.26). Almost all individual participants' values were within CI limits., Conclusion: The validity of the newly developed EI model was supported by experimental observations and can be used to determine an individual participant's EI during weight loss.

Background: Weight loss leads to reduced resting energy expenditure (REE) independent of fat-free mass (FFM) and fat mass (FM) loss, but the effect of changes in FFM composition is unclear., Objective: We hypothesized that a decrease in REE adjusted for FFM with weight loss would be partly explained by a disproportionate loss in the high metabolic activity component of FFM., Design: Forty-five overweight and obese women [body mass index (in kg/m(2)): 28.7-46.8] aged 22-46 y followed a low-calorie diet for 12.7 +/- 2.2 wk. Body composition was measured by magnetic resonance imaging, dual-energy X-ray absorptiometry, and a 4-compartment model. REE measured by indirect calorimetry (REEm) was compared with REE calculated from detailed body-composition analysis (REEc) by using specific organ metabolic rates (ie, organ REE/mass)., Results: Weight loss was 9.5 +/- 3.4 kg (8.0 +/- 2.9 kg FM and 1.5 +/- 3.1 kg FFM). Decreases in REE (-8%), free triiodothyronine concentrations (-8%), muscle (-3%), heart (-5%), liver (-4%), and kidney mass (-6%) were observed (all P < 0.05). Relative loss in organ mass was significantly higher (P < 0.01) than was the change in low metabolically active FFM components (muscle, bone, and residual mass). After weight loss, REEm - REEc decreased from 0.24 +/- 0.58 to 0.01 +/- 0.44 MJ/d (P = 0.01) and correlated with the decrease in free triiodothyronine concentrations (r = 0.33, P < 0.05). Women with high adaptive thermogenesis (defined as REEm - REEc < -0.17 MJ/d) had less weight loss and conserved FFM, liver, and kidney mass., Conclusions: After weight loss, almost 50% of the decrease in REEm was explained by losses in FFM and FM. The variability in REEm explained by body composition increased to 60% by also considering the weight of individual organs.

Background: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods., Methodology/principal Findings: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive., Conclusion/significance: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.

Attrition is a common problem in weight loss trials. The present analysis examined several baseline and early-treatment process variables, as predictors of attrition and outcome in a clinical trial that combined pharmacotherapy and behavior therapy for weight loss. Participants were 224 obese adults who were treated with sibutramine alone, lifestyle modification alone, combined therapy, or sibutramine plus brief lifestyle modification. Predictors included baseline characteristics (e.g., demographic, weight-related, psychological, and consumption-related variables), plus attendance, adherence, and weight loss in the early weeks of treatment. Outcomes were attrition and weight loss success (i.e., >or=5% reduction in body weight) at 1 year. Multivariable models, adjusting for other relevant variables, found that younger age and greater baseline depressive symptoms were related to increased odds of attrition (ps

Background: The literature on changes in health-related quality of life (HRQOL) in weight loss studies is inconsistent, and few studies use more than one type of measure. The purpose of the current study was to compare one-year changes in HRQOL as a function of weight change using three different measures: a weight-related measure (Impact of Weight on Quality of Life-Lite [IWQOL-Lite)]) and two generic measures (SF-36; EQ-5D)., Methods: Data were obtained from 926 participants (mean Body Mass Index (BMI) (kg/m(2)) = 35.4; 84% female; mean age = 49.5 years) in a placebo-controlled randomized trial for weight loss. At baseline and one-year, participants completed all three HRQOL measures. HRQOL was compared across weight change categories (> or = 5% and 0-4.9% gain, 0-4.9%, 5.0-9.9% and > or = 10% loss), using effect sizes., Results: The weight-related measure of HRQOL exhibited greater improvements with one-year weight loss than either of the generic instruments, with effect sizes ranging from 0.24 to 0.62 for 5-9.9% weight reductions and 0.44 to 0.95 for > or = 10% reductions. IWQOL-Lite Self-Esteem also showed a small improvement with weight gain. Changes in the two generic measures of HRQOL were inconsistent with each other, and in the case of the SF-36, variable across domains. For participants gaining > or = 5% of weight, the greatest reductions in HRQOL occurred with respect to SF-36 Mental Health, MCS, and Vitality, with effect sizes of -0.82, -0.70, and -0.63 respectively., Conclusion: This study found differences between weight-related and generic measures of health-related quality of life in a one-year weight loss trial, reflecting the potential value of using more than one measure in a trial. Although weight loss was generally associated with improved IWQOL-Lite, physical SF-36 subscale and EQ-5D scores, a small amount of weight gain was associated with a slight improvement on weight-specific HRQOL and almost no change on the EQ-5D, suggesting the need for further research to more fully study these relationships. We believe our findings have relevance for weight loss patients and obesity clinicians/researchers in informing them of likely HRQOL outcomes associated with varying amounts of weight loss or gain.

Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [(18)F]MK-9470 confirmed central nervous system receptor occupancy levels ( approximately 10%-40%) associated with energy balance/weight-loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.

The objective of this study was to determine whether a weight-loss diet high in soy-protein-rich foods leads to greater weight loss and reductions in waist circumference, fat mass, and cardiovascular disease risk factors than a control diet. Groups of overweight women (body mass index [calculated as kg/m(2)] of 28 to 33, aged 25 to 49 years) were counseled to decrease their caloric intake by 500 kcal/day for a period of 12 weeks; in addition, the soy-protein-rich group was counseled to consume 15 g soy protein/1,000 kcal daily. Soy-protein-rich foods were provided to subjects. Body weight, waist circumference, percent body fat, fat-free mass, lipids, glucose, and insulin were measured at repeated intervals. Forty-seven women completed the study. Both groups lost a similar amount of weight both when a completers only (-3.18%+/-0.63% vs -4.04%+/-0.95% for soy-protein-rich and control diets, respectively) and a last-observation-carried-forward analysis (-1.93%+/-0.50% vs -2.50%+/-0.67%, for soy-protein-rich and control diets, respectively) were performed. There was no difference between groups in change in percent fat mass (-5.31%+/-1.50% for soy-protein-rich diet vs -3.94%+/-1.68% for control diet), percent fat-free mass, and waist circumference. There was no dietary assignment-by-group interaction on lipid, glucose, and insulin concentrations when analyses were done on completers only or on all subjects using a last-observation-carried-forward approach. Percent change in any of the biochemical parameters studied over the 12-week period was not significantly different between groups. Our results do not lend support to the emerging notion that soy-protein-rich foods could be considered potential functional foods for weight management, in the quantities consumed in this study.

Maximal weight loss observed in low-calorie diet (LCD) studies tends to be small, and the mechanisms leading to this low treatment efficacy have not been clarified. Less-than-expected weight loss with LCDs can arise from an increase in fractional energy absorption (FEA), adaptations in energy expenditure, or incomplete patient diet adherence. We systematically reviewed studies of FEA and total energy expenditure (TEE) in obese patients undergoing weight loss with LCDs and in patients with reduced obesity (RO), respectively. This information was used to support an energy balance model that was then applied to examine patient adherence to prescribed LCD treatment programs. In the limited available literature, FEA was unchanged from baseline in short-term (<12 wk) treatment studies with LCDs; no long-term (>or=26 wk) studies were found. Review of doubly labeled water and respiratory chamber studies identified 10 reports of TEE in RO patients (n = 150) with long-term weight loss. These patients, who were weight stable, had a TEE almost identical to measured or predicted values in never-obese subjects (weighted mean difference: 1.3%; range: -1.7-8.5%). Modeling of energy balance, as supported by reviewed FEA and TEE studies, suggests that obese subjects participating in LCD programs have a weight loss less than half of that predicted. The small maximal weight loss observed with LCD treatments thus is likely not due to gastrointestinal adaptations but may be attributed, by deduction, to difficulties with patient adherence or, to a lesser degree, to metabolic adaptations induced by negative energy balance that are not captured by the current models.

Objective: Partitioning of body energy content in the aleptinemic ob/ob mouse differs from that in wild-type mice, but it is not known whether parallel differences exist between humans with leptin (Lep) gene mutations and healthy adults. The objective of this study was to evaluate body composition in three leptin-treated Turkish adults homozygous for a missense mutation (C-->T substitution at codon 105 resulting in Arg-->Trp) of Lep., Research Methods and Procedures: Subjects, one male and two female Turkish family members, were evaluated at baseline and treated for 18 months with r-MetHuLeptin. Patient data (fat mass, energy content) were compared with adult sex-specific predicted values (adjusted for weight, height, and age) derived in healthy control subjects., Results: Weight loss with leptin treatment was substantial, ranging from 43.9% to 52.1%. At baseline and with leptin treatment, the two women had a fat mass and energy content similar (+/-12%) to predicted values. Baseline fat and energy content in the male patient was high compared with predicted values (e.g., fat +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months of leptin therapy., Discussion: Adult women with Lep mutations had body composition similar to normal women at baseline and with leptin treatment. In contrast, the man with a Lep mutation had high body fat in the untreated state but a normal male phenotype with leptin administration, possibly secondary to androgenic fat partitioning effects. Fat and energy partitioning can, thus, be quantitatively assessed and linked with potential hormonal mechanisms in humans with inherited disturbances in energy regulation.

Objective: We used a rodent model of dietary obesity to evaluate effects of caloric restriction-induced weight loss on mortality rate. Research Measures and Procedures: In a randomized parallel-groups design, 312 outbred Sprague-Dawley rats (one-half males) were assigned at age 10 weeks to one of three diets: low fat (LF; 18.7% calories as fat) with caloric intake adjusted to maintain body weight 10% below that for ad libitum (AL)-fed rat food, high fat (HF; 45% calories as fat) fed at the same level, or HF fed AL. At age 46 weeks, the lightest one-third of the AL group was discarded to ensure a more obese group; the remaining animals were randomly assigned to one of three diets: HF-AL, HF with energy restricted to produce body weights of animals restricted on the HF diet throughout life, or LF with energy restricted to produce the body weights of animals restricted on the LF diet throughout life. Life span, body weight, and leptin levels were measured., Results: Animals restricted throughout life lived the longest (p < 0.001). Life span was not different among animals that had been obese and then lost weight and animals that had been nonobese throughout life (p = 0.18). Animals that were obese and lost weight lived substantially longer than animals that remained obese throughout life (p = 0.002). Diet composition had no effect on life span (p = 0.52)., Discussion: Weight loss after the onset of obesity during adulthood leads to a substantial increase in longevity in rats.

Data suggest that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance loss. Our aim was to determine whether calcium supplementation during a weight loss intervention affects body fat or weight loss. Data were combined from three separate 25-wk randomized, double blind, placebo-controlled trials of 1000 mg/d calcium supplementation in 100 premenopausal and postmenopausal women. The primary outcome measures were change in body weight and fat mass adjusted for baseline values. There were no significant differences in body weight or fat mass change between the placebo and the calcium-supplemented groups in the pooled analysis (adjusted mean +/- SE; body weight, placebo -6.2 +/- 0.7 vs. Ca -7.0 +/- 0.7 kg; fat mass, placebo -4.5 +/- 0.6 vs. Ca -5.5 +/- 0.6 kg), and no significant interactions of calcium supplementation with menopausal/diet status. Analysis as separate trials also found no significant differences between the placebo and the calcium groups. Calcium supplementation did not significantly affect amount of weight or fat lost by women counseled to follow a moderately restricted diet for 25 wk. Nevertheless, the magnitude and direction of the differences for group means are consistent with a hypothesized small effect.

Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.

BackgroundNew recommendations for the assessment of malnutrition and sarcopenia include body composition, specifically reduced muscle mass. Three-dimensional optical imaging (3DO) is a validated, accessible, and affordable alternative to dual X-ray absorptiometry (DXA).ObjectiveIdentify strengths and weaknesses of 3DO for identification of malnutrition in participants with low body mass index (BMI) and eating disorders.DesignParticipants were enrolled in the cross-sectional Shape Up! Adults and Kids studies of body shape, metabolic risk, and functional assessment and had BMI of

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body-resulting from the hormonal responses to a high-glycemic-load diet-drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.

Background: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. Methods: A GLIM‐constituted working group with 36 participants developed consensus‐based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. Results: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C‐reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. Conclusion: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP. [ABSTRACT FROM AUTHOR]

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus‐based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual‐energy x‐ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic‐ and sex‐specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was (1) to assess AT through 13 different mathematical approaches and to compare their results; and (2) to understand if AT occurs after moderate WL. Methods: Ninety-four participants [mean (SD); BMI, 31.1 (4.3) kg/m2; age, 43.0 (9.4) years; 34% females] underwent a 1-year lifestyle intervention (clinicaltrials.gov ID: NCT03031951) and were randomized to intervention (IG, n = 49) or control groups (CG, n = 45), and all measurements were made at baseline and after 4 months. Fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and REE by indirect calorimetry. AT was assessed through 13 different approaches, varying in how REE was predicted and/or how AT was assessed. Results: IG underwent a mean negative energy balance (EB) of 270 (289) kcal/day, p < 0.001), resulting in a WL of − 4.8 (4.9)% and an FM loss of − 11.3 (10.8)%. Regardless of approach, AT occurred in the IG, ranging from ~ − 65 to ~ − 230 kcal/day and three approaches showed significant AT in the CG. Conclusions: Regardless of approach, AT occurred after moderate WL in the IG. AT assessment should be standardized and comparisons among studies with different methodologies to assess AT must be avoided. [ABSTRACT FROM AUTHOR]

Background: The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals.Objectives: The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss.Methods: Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12-18% weight loss in ∼14 wk or 10-14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post-weight loss. Associations were analyzed using general linear models with adjustment for covariates.Results: In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 μIU/mL increment in baseline insulin-30; P = 0.005; -1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (-0.465 kg per 100 μIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (-3.37% per 100 μIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude.Conclusions: Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885. [ABSTRACT FROM AUTHOR]

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence. [ABSTRACT FROM AUTHOR]

In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims. [ABSTRACT FROM AUTHOR]

Diurnal variation in glucose tolerance: cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects. Booth ([1]) evidently questions whether insulin secretion affects body composition or body composition affects insulin secretion. High insulin secretion may exist with low or high levels of insulin resistance. [Extracted from the article]

Background: Currently, early weight-loss predictions of long-term weight-loss success rely on fixed percent-weight-loss thresholds. Objective: The objective was to develop thresholds during the first 3 mo of intervention that include the influence of age, sex, baseline weight, percent weight loss, and deviations from expected weight to predict whether a participant is likely to lose 5% or more body weight by year 1. Design: Data consisting of month 1, 2, 3, and 12 treatment weights were obtained from the 2-y Preventing Obesity Using Novel Dietary Strategies (POUNDS Lost) intervention. Logistic regression models that included covariates of age, height, sex, baseline weight, target energy intake, percent weight loss, and deviation of actual weight from expected were developed for months 1, 2, and 3 that predicted the probability of losing <5% of body weight in 1 y. Receiver operating characteristic (ROC) curves, area under the curve (AUC), and thresholds were calculated for each model. The AUC statistic quantified the ROC curve's capacity to classify participants likely to lose <5% of their body weight at the end of 1 y. The models yielding the highest AUC were retained as optimal. For comparison with current practice, ROC curves relying solely on percent weight loss were also calculated. Results: Optimal models for months 1, 2, and 3 yielded ROC curves with AUCs of 0.68 (95% CI: 0.63, 0.74), 0.75 (95% CI: 0.71, 0.81), and 0.79 (95% CI: 0.74, 0.84), respectively. Percent weight loss alone was not better at identifying true positives than random chance (AUC ≤0.50). Conclusions: The newly derived models provide a personalized prediction of long-term success from early weight-loss variables. The predictions improve on existing fixed percent-weight-loss thresholds. Future research is needed to explore model application for informing treatment approaches during early intervention. The POUNDS Lost study was registered at clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]

Background: Clinical weight loss in individuals typically stabilizes at 6 mo. However, validated models of dynamic energy balance have consistently shown weight plateaus between 1 and 2 y. The cause for this discrepancy is unclear. Objective: We developed 2 mathematical models on the basis of the first law of thermodynamics to investigate plausible explanations for reaching an early weight plateau at 6 mo. Design: The first model was an energy-expenditure adaptation model and was applied to determine the degree of metabolic adaptation required to generate this plateau. The second model was an intermittent lack-of-adherence model formulated by using a randomly fluctuating energy intake term accounting for intermittent noncompliance in dietary intake to reach this plateau. To set model variables, validate models, and compare free-living weight-loss patterns to in-residence supervised programs, we applied the following 4 different studies: The US NHANES 1999-2004, Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CAL ERIE) weight-loss study, the Bouchard Twin overfeeding study, and the Minnesota Starvation Experiment. Results: The metabolic adaptation model increased final weight but did not affect the predicted plateau time point. The intermittent lack-of-adherence model generated oscillating weight graphs that have been frequently observed in weight-loss studies. The model showed that a 6-mo weight-loss plateau can be attained despite what can be considered as high diet adherence. The model was programmed as a downloadable application. Conclusions: An intermittent lack of diet adherence, not metabolic adaptation, is a major contributor to the frequently observed early weight-loss plateau. The new weight-loss prediction software, which incorporates an intermittent lack of adherence, can be used to guide and inform patients on realistic levels of adherence on the basis of patient lifestyle. [ABSTRACT FROM AUTHOR]

The article discusses a Consensus Conference entitled "The Role of Energy Balance in Health and 'Wellness" which took place in 2012 and was organized and funded by the American Society for Nutrition and the North American branch of the International Life Sciences Institute. A consensus statement on energy balance and its components and its implications for body weight which resulted from the conference is presented and examined.

Precision and accuracy of the quantitative magnetic resonance (QMR) system for measuring fat in phantoms and total body fat (TBF) in humans were investigated. Measurements were made using phantoms: oil, beef with water, beef with oil, and humans with oil and water. TBFQMR in humans was compared with TBF by a four-compartment model (TBF4C). The coefficient of variation (CV) for replicate TBFQMR was 0.437%. QMR fat was lower at 23 °C vs. 37 °C. The fat increase in QMR phantom studies was consistent with the oil increase. When oil was added with humans, the increase in TBFQMR was >250 g for the initial 250 g of oil. With additional oil increments, the increase in TBFQMR was consistent with the amount of oil added. When water was added with humans, the TBFQMR increased independent of the amount of water added. TBFQMR was significantly less (mean ± s.e.) than TBF4C (females: −0.68 ± 0.27 kg, males: −4.66 ± 0.62 kg; P = 0.0001), TBFBV (females: −1.90 ± 0.40 kg; males: −5.68 ± 0.75 kg; P = 0.0001), and TBFD2O for males, but greater for females (1.19 ± 0.43 kg vs. −3.69 ± 0.81 kg for males; P = 0.0003). TBFQMR was lower than TBFiDXA with the difference greater in males (P = 0.001) and decreased with age (P = 0.011). The strong linear relationships between TBFQMR and TBF4C, TBFBV, and TBFD2O with slopes consistent with unity suggest that modifications are required to improve the accuracy. Should the latter be accomplished, QMR holds promise as a highly precise, rapid, and safe, noninvasive method for estimating the amount of and changes in TBF in overweight and severely obese persons. [ABSTRACT FROM AUTHOR]

Abstract: Induction and maintenance of a period of negative energy balance are required for overweight and obese subjects to lose weight. Meal replacements, particularly in beverage form, have now evolved as part of the "toolbox" used by researchers and clinicians to achieve negative energy balance. This overview traces the historical development of beverage meal replacements, reviews key studies supporting their clinical efficacy, and examines concerns related to their safe use. This collective information supports the view that meal replacements, particularly in beverage form, are now an effective and safe component for use in the clinical setting. Further studies are needed to identify those subjects most likely to benefit from use of meal replacements as part of their comprehensive weight control program. [Copyright &y& Elsevier]

Objective: To evaluate whether MK-0557, a highly selective, orally administered neuropeptide Y Y5 receptor antagonist, could limit weight regain after very-low-calorie diet (VLCD)-induced weight loss.Research Methods and Procedures: We enrolled 502 patients 18 to 65 years of age with a BMI of 30 to 43 kg/m2. Patients were placed on a VLCD (800 kcal/d liquid diet) for 6 weeks. Patients who lost>or=6% of initial body weight (n=359) were randomized to 52 weeks of 1 mg/d MK-0557 or placebo and maintained on a hypocaloric diet (300 kcal below weight maintenance requirements).Results: In randomized patients, the VLCD was associated with an average weight loss of 9.1 kg. After 12 weeks of double-blind treatment, weight began to gradually increase for both placebo- and MK-0557-treated patients. The mean weight change (95% confidence interval) from baseline at the end of the VLCD to Week 52 was +3.1 (2.1, 4.0) and +1.5 (0.5, 2.4) kg for patients treated with placebo and MK-0557, respectively. The difference of 1.6 kg between the two groups was significant (p=0.014). Secondary endpoints, such as blood pressure, lipid profile, insulin, and leptin, as well as waist circumference and quality-of-life measurements, did not show significant differences between MK-0557 and placebo treatments.Discussion: Although the difference in weight regain between placebo- and MK-0557-treated patients was statistically significant, the magnitude of the effect was small and not clinically meaningful. Antagonism of the neuropeptide Y Y5 receptor is not an efficacious treatment strategy for reducing weight regain after VLCD. [ABSTRACT FROM AUTHOR]

Context: Obese individuals tend to resist the weight-regulating effects of exogenously administered leptin. A genetically engineered recombinant human variant ciliary neurotrophic factor (rhvCNTF) that signals through leptinlike pathways in the hypothalamus has been shown to bypass leptin resistance in animal models of obesity. Objective: To identify a safe and well-tolerated dose of rhvCNTF that causes weight loss in obese adults. Design, Setting, and Patients: Twelve-week, double-blind, randomized, parallel-group, dose-ranging, multicenter clinical trial conducted at 2 university obesity clinics and at 5 independent clinical research clinics from March 2000 to August 2001, and including 173 nondiabetic obese adults, 82.6% of whom were women, with a mean (SD) body mass index of 41.1 (4.1). Interventions: Patients were randomly assigned to receive daily for 12 weeks subcutaneous injections of placebo (n = 32) or 0.3 µg/kg (n = 32), 1.0 µg/kg (n = 38), or 2.0 µg/kg (n = 33) of rhvCNTF. Another group received 1.0 µg/kg for 8 weeks and placebo for 4 weeks (n = 38), but they were not included in the primary analysis. All participants received instructions for a reduced-calorie diet (World Health Organization formula minus 500 kcal/d). Main Outcome Measures: Change in weight during the 12-week double-blind treatment period and proportion of patients who achieved a weight loss of at least 5%. Results: Of the 173 randomized patients, 123 (71%) completed the double-blind dosing period. Mean (SEM) changes in kilograms from baseline body weights were 0.1 (0.6) for placebo and -1.5 (0.6) for the 0.3, -4.1 (0.6) for the 1.0, and –3.4 (0.7) for the 2.0 µg/kg of rhvCNTF dosage groups (P<.001, test for trend). Two patients (8.7%) in the placebo and 2 (8.3%) in the 0.3-µg/kg, 8 (29.6%) in the 1.0-µg/kg, and 5 (26%) in the 2.0-µg/kg treatment groups achieved a weight loss of at least 5%. Recombinant human variant CNTF was generally... [ABSTRACT FROM AUTHOR]