Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss

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/m²) 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 {"type":"clinical-trial","attrs":{"text":"NCT00099151","term_id":"NCT00099151"}}NCT00099151     

Relationship of Co-Morbidities of Obesity to Weight Loss and Four-Year Weight Maintenance/Rebound

This study examined the effect of weight loss (separate from energy restriction) and weight maintenance/rebound over time on blood pressure, serum lipids, and body composition in 24 obese (mean 137% ideal body weight (IEW)) females with mild to moderate hypertension. Weight loss was induced under tightly controlled General Clinical Research Center conditions until each subject had lost at least 10 kg (mean 13 kg) and attained normal body weight (<120% IBW). After 4 years subjects returned for repeat evaluation. Weight changes were compared with 24 pair-matched normal weight controls who were also followed for 4 years. With weight loss, significant improvements were seen in standing mean arterial pressure (MAP), serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Subjects regained 11 kg (87% of the weight lost) over the 4 year follow-up period while control subjects gained only 2 kg. Subjects who chose self-selected exercise gained less weight than nonexercisers (6 kg vs. 13 kg, P<0.05). With weight regain there were significant increases in standing and supine MAP, total cholesterol, and high-density lipoprotein (HDL) cholesterol. The amount of weight regained was significantly correlated with standing MAP (r=0.73), triglycerides (r=0.43), and HDL cholesterol (r=-0.47). The percentage fat of the weight regained was no greater than that of the weight previously lost. Weight loss, distinct from energy restriction, was associated with improvements in blood pressure and serum lipid levels. The ability to sustain these improvements in the co-morbidities of obesity was directly related to the persistence and magnitude of weight loss maintenance.     

Reductions in Internal Disinhibition During Weight Loss Predict Better Weight Loss Maintenance

The construct of disinhibition, as measured by the Eating Inventory, was recently found to have two factors: internal disinhibition (eating in response to cognitive and emotional cues) and external disinhibition (eating in response to environmental cues). This study examined whether early changes in disinhibition that occurred during a weight loss program predicted later weight loss maintenance. Participants were adults enrolled in a weight loss treatment study (n = 81, 16% men, BMI = 38.4 ± 6.5 kg/m²). Two‐thirds of participants were African Americans. Participants received a uniform, meal‐replacement‐based weight loss program in months 1–3 and one of four nutritionally focused programs for weight loss maintenance in months 4–12. Disinhibition and weight were assessed at clinic visits. Change in internal disinhibition from months 1–3 (i.e., the weight loss period) significantly predicted change in weight from month 4 to 12 (i.e., the weight maintenance period); this remained significant when treatment group, age, gender, ethnicity, baseline weight, baseline depression, baseline internal disinhibition, and initial weight loss were controlled for (P = 0.03). A comparable analysis examining change in external disinhibition found that it was not a significant predictor of weight maintenance (P = 0.43). Participants who experienced the biggest decreases in internal disinhibition during the initial phase of treatment had the most success maintaining their weight loss in the next phase of treatment. Long‐term weight loss outcomes may be improved by spending sufficient treatment time teaching strategies for reducing eating in response to internal cues.     

Mediators of Weight Loss and Weight Loss Maintenance in Middle‐aged Women

Long‐term behavioral self‐regulation is the hallmark of successful weight control. We tested mediators of weight loss and weight loss maintenance in middle‐aged women who participated in a randomized controlled 12‐month weight management intervention. Overweight and obese women (N = 225, BMI = 31.3 ± 4.1 kg/m²) were randomly assigned to a control or a 1‐year group intervention designed to promote autonomous self‐regulation of body weight. Key exercise, eating behavior, and body image variables were assessed before and after the program, and tested as mediators of weight loss (12 months, 86% retention) and weight loss maintenance (24 months, 81% retention). Multiple mediation was employed and an intention‐to‐treat analysis conducted. Treatment effects were observed for all putative mediators (Effect size: 0.32–0.79, P < 0.01 vs. controls). Weight change was ?7.3 ± 5.9% (12‐month) and ?5.5 ± 5.0% (24‐month) in the intervention group and ?1.7 ± 5.0% and ?2.2 ± 7.5% in controls. Change in most psychosocial variables was associated with 12‐month weight change, but only flexible cognitive restraint (P < 0.01), disinhibition (P < 0.05), exercise self‐efficacy (P < 0.001), exercise intrinsic motivation (P < 0.01), and body dissatisfaction (P < 0.05) predicted 24‐month weight change. Lower emotional eating, increased flexible cognitive restraint, and fewer exercise barriers mediated 12‐month weight loss (R² = 0.31, P < 0.001; effect ratio: 0.37), but only flexible restraint and exercise self‐efficacy mediated 24‐month weight loss (R² = 0.17, P < 0.001; effect ratio: 0.89). This is the first study to evaluate self‐regulation mediators of weight loss and 2‐year weight loss maintenance, in a large sample of overweight women. Results show that lowering emotional eating and adopting a flexible dietary restraint pattern are critical for sustained weight loss. For long‐term success, interventions must also be effective in promoting exercise intrinsic motivation and self‐efficacy.     

Physical Activity and Long-Term Maintenance of Weight Loss

To examine the effect of exercise on the long-term maintenance of weight loss, two types of literature were reviewed - correlational studies of predictors of long-term weight loss, and randomized trials comparing diet, exercise, and the combination of diet plus exercise. Both literatures were striking in the consistency with which activity emerged as a determinant of long-term maintenance of weight loss. The benefits of exercise for long-term weight maintenance were observed with different types of populations, diets, and exercise interventions. Several possible explanations for these positive effects of diet plus exercise are presented, and suggestions made for future research on ways to maximize the benefit of this approach to weight control. Since adherence to exercise may ultimately prove to be the cornerstone for long-term weight maintenance, studying ways to improve exercise adherence is recommended.     

Maintenance of Weight Loss: A Needs Assessment

This study identified facilitators and obstacles to maintenance of weight loss following a very-low-calorie-diet and behavior modification program. A survey was mailed to a random sample of 178 program completers and received a 61% response rate; the most frequent follow-up period was more than 2 years. Twenty-nine percent reported weighing the same (within 10 lbs) or less than the end of their participation in the treatment program (maintainers), while 71% reported their present weight was a mean of 65% higher than their initial weight loss (regainers). Maintainers were significantly more likely to report engaging in regular aerobic exercise, attending a maintenance support group, and confidence in their ability to manage their weight in the future, while regainers were more likely to report stress and motivation as frequent weight management obstacles. Respondents consistently identified the need for low/no cost ongoing support. Maintainers and relapsers reported similar challenges in managing their weight, yet with different results, suggesting the need to identify subgroups for which different post-treatment support options could be applied.     

Body Weight Loss and Weight Maintenance in Relation to Habitual Caffeine Intake and Green Tea Supplementation

Objective: Investigation of the effect of a green tea‐caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake. Research Methods and Procedures: A randomized placebo‐controlled double blind parallel trial in 76 overweight and moderately obese subjects, (BMI, 27.5 ± 2.7 kg/m²) matched for sex, age, BMI, height, body mass, and habitual caffeine intake was conducted. A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance (WM); during the WM period, the subjects received a green tea‐caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine per day) or placebo. Results: Subjects lost 5.9 ±1.8 (SD) kg (7.0 ± 2.1%) of body weight (p < 0.001). At baseline, satiety was positively, and in women, leptin was inversely, related to subjects’ habitual caffeine consumption (p < 0.01). High caffeine consumers reduced weight, fat mass, and waist circumference more than low caffeine consumers; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss (p < 0.01). In the low caffeine consumers, during WM, green tea still reduced body weight, waist, respiratory quotient and body fat, whereas resting energy expenditure was increased compared with a restoration of these variables with placebo (p < 0.01). In the high caffeine consumers, no effects of the green tea‐caffeine mixture were observed during WM. Discussion: High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women. In habitual low caffeine consumers, the green tea‐caffeine mixture improved WM, partly through thermogenesis and fat oxidation.     

Brain Response to Food Stimulation in Obese,Normal Weight,and Successful Weight Loss Maintainers

As many people struggle with maintenance of weight loss, the study of successful weight loss maintainers (SWLM) can yield important insights into factors contributing to weight loss maintenance. However, little research has examined how SWLM differ from people who are obese or normal weight (NW) in brain response to orosensory stimulation. The goal of this study was to determine if SWLM exhibit different brain responses to orosensory stimulation. Brain response to 1‐min orosensory stimulation with a lemon lollipop was assessed using functional magnetic resonance imaging among 49 participants, including SWLM (n = 17), NW (n = 18), and obese (n = 14) controls. Significant brain responses were observed in nine brain regions, including the bilateral insula, left inferior frontal gyrus, left putamen, and other sensory regions. All regions also exhibited significant attenuation of this response over 1 min. The SWLM exhibited greater response compared with the other groups in all brain regions. Findings suggest that the response to orosensory stimulation peaks within 40 s and attenuates significantly between 40 and 60 s in regions associated with sensation, reward, and inhibitory control. Greater reactivity among the SWLM suggests that greater sensory reactivity to orosensory stimulation, increased anticipated reward, and subsequently greater inhibitory processing are associated with weight loss maintenance.     

Lifestyle Intervention Favorably Affects Weight Loss and Maintenance Following Obesity Surgery

The present study was designed to evaluate the 3 year effects of a lifestyle intervention on weight loss and maintenance, dietary, and physical activity habits and eating behavior of patients following vertical banded gastroplasty (VBG). Thirty severely obese female volunteers were included in the study and they were randomly assigned to one of two intervention groups: usual care (UC) or lifestyle intervention (LS) group. Patients were followed for 3 years postoperatively. Outcome measures included weight loss, dietary habits, physical activity level (PAL), and eating behavior changes. Weight was significantly lower in the LS group after 12 months (84.4 ± 3.9 kg vs. 98.4 ± 4.4 kg, P < 0.05), 24 months (83.0 ± 3.3 vs. 101.9 ± 5.3 kg, P < 0.05), and 36 months following surgery (84.2 ± 3.3 vs. 102.5 ± 3.5 kg, P < 0.05). Repeated measures ANOVA revealed significant differences between the two groups overall and at specific time points for the PAL and TV viewing. With regard to eating behavior, the LS group scored significantly better in total Dutch Eating Behavior Questionnaire (DEBQ), Restraint Eating and External Eating scales at all postoperative time points. Similarly, significant differences were found between the two groups in dietary intake. These findings outline the importance of lifestyle intervention on weight loss and maintenance following bariatric surgery. The favorable effects of lifestyle intervention may be through adoption of healthier eating behaviors and increased physical activity.     

Physical Activity in Relation to Long‐term Weight Maintenance After Intentional Weight Loss in Premenopausal Women

The type and amount of physical activity (PA) needed for prevention of weight regain are not well understood. We prospectively examined the associations between patterns of discretionary PA and 6‐year maintenance of intentional weight loss among 4,558 healthy premenopausal women who were 26–45 years old in 1991 and had lost >5% of their body weight in the previous 2 years. Participants reported their PA and weight in 1991 and 1997. The outcome was weight regain, defined as regaining in 1997 >30% of the lost weight between 1989 and 1991. Between 1991 and 1997, 80% of women regained >30% of their previous intentional weight loss. An increase of 30 min/day in total discretionary activity between 1991 and 1997 was associated with less weight regain (?1.36 kg, 95% confidence interval (CI) = ?1.61, ?1.12), particularly among overweight women (BMI ≥25) (?2.45 kg, ?3.12 to ?1.78). Increased jogging or running was associated with less weight regain (?3.26 kg; ?4.41 to ?2.10) than increased brisk walking (?1.69 kg; ?2.15 to ?1.22) or other activities (?1.26 kg; ?1.65 to ?0.87). Compared to women who remained sedentary, women were less likely to regain >30% of the lost weight if they maintained 30+ min/day of discretionary PA (odds ratio (OR) = 0.69, 0.53 to 0.89) or increased to this activity level (OR = 0.48, 0.39 to 0.60). Conversely, risk was elevated in women who decreased their activity. Increased PA, particularly high intensity activities, is associated with better maintenance of weight loss. The benefits of activity were greater among overweight/obese than normal weight women.     

Relationship of Psychiatric Diagnosis and Weight Loss Maintenance in Obese Breast Cancer Survivors

Objective: Obese breast cancer survivors are a unique population for weight loss counseling because both obesity and a diagnosis of breast cancer can increase the risk of depression. In this pilot study, weight loss maintenance was examined in obese breast cancer survivors with relationship to psychiatric diagnosis. Research Methods and Procedures: Forty‐eight subjects were enrolled. The intervention, which used individualized counseling for diet and exercise, lasted 24 months. After a 6‐month period of no contact with study subjects, a follow‐up body weight was obtained at 30 months. Results: The nine subjects who dropped out of the study before 12 months all failed to complete a structured psychiatric interview. Of the remaining 39 subjects, 9 had major depressive disorder, and 10 had a definable psychiatric disorder of lesser severity such as adjustment disorder. Subjects with any type of psychiatric diagnosis displayed significantly less weight loss at the 12‐month time‐point than those with no diagnosis (6.3% vs. 12.6% loss of baseline weight, respectively). At the 30‐month follow‐up visit, subjects with any psychiatric disorder had a mean weight loss of 1.2% of baseline weight compared with 7.8% weight loss in subjects with no diagnosis. Discussion: These results suggest that the presence of psychiatric disorders can interfere with weight loss. Therefore, recognition and treatment of psychiatric disorders may be important in attempts at weight reduction, and this will be especially important in populations such as cancer survivors, who seem to have higher rates of depression and other disorders than the general population.     

Effects of Diet Composition on Postprandial Energy Availability during Weight Loss Maintenance

Background

The major circulating metabolic fuels regulate hunger, and each is affected by dietary composition. An integrated measure of postprandial energy availability from circulating metabolic fuels may help inform dietary recommendations for weight maintenance after weight loss.

Aim

We examined the effect of low-fat (LF, 60% of energy from carbohydrate, 20% fat, 20% protein), low-glycemic index (LGI, 40%–40%-20%), and very low-carbohydrate (VLC, 10%–60%-30%) diets on total postprandial metabolic fuel energy availability (EA) during weight loss maintenance.

Methods

Eight obese young adults were fed a standard hypocaloric diet to produce 10–15% weight loss. They were then provided isocaloric LF, LGI, and VLC diets in a randomized crossover design, each for a 4-week period of weight loss maintenance. At the end of each dietary period, a test meal representing the respective diet was provided, and blood samples were obtained every 30 minutes for 5 hours. The primary outcome was EA, defined as the combined energy density (circulating level×relative energy content) of glucose, free fatty acids, and β-hydroxybutyrate. Secondary outcomes were individual metabolic fuels, metabolic rate, insulin, glucagon, cortisol, epinephrine, and hunger ratings. Respiratory quotient was a process measure. Data were analyzed by repeated-measures analysis of variance, with outcomes compared in the early (30 to 150 min) and late (180 to 300 min) postprandial periods.

Results

EA did not differ between the test meals during the early postprandial period (p = 0.99). However, EA in the late postprandial period was significantly lower after the LF test meal than the LGI (p<0.0001) and VLC (p<0.0001) test meals. Metabolic rate also differed in the late postprandial period (p = 0.0074), with higher values on the VLC than LF (p = 0.0064) and LGI (p = 0.0066) diets.

Conclusion

These findings suggest that an LF diet may adversely affect postprandial EA and risk for weight regain during weight loss maintenance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00315354","term_id":"NCT00315354"}}NCT00315354     

Fluoxetine: A Randomized Clinical Trial in the Maintenance of Weight Loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost ≤3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean ± standard deviation [SD] weight loss, 6.8 ± 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean ± SD weight loss, 7.2 ± 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (>10% incidence), only asthenia was reported statistically significantly (p< 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Effects of Obesity Phenotype on Coronary Heart Disease Risk Factors in Response to Weight Loss

Objective: To determine whether there is a difference in risk‐factor improvement for coronary heart disease (CHD) between the intra‐abdominal fat (IF) and subcutaneous fat (SF) obesity phenotypes after weight loss. Research Methods and Procedures: Subjects included 55 mildly obese women (body mass index, 25 to 36 kg/m²; age range, 34 to 63 years) who had at least two of three CHD risk factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220 mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity was classified as ≥110 cm² of the IF area measured; subjects with <110 cm² were classified as having SF obesity. The IF and SF obesity groups were divided into diet‐only and diet‐plus‐exercise groups. Assays and measurements were performed before and after a 14‐week (98‐day) intervention. Results: Weight was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic blood pressure, TC, and low‐density lipoprotein‐cholesterol were significantly reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity than in SF obesity, whereas no differences were observed in the improvement of CHD risk factors. Sample sizes needed for observing a significant difference for SBP, TC, triglycerides, and fasting plasma glucose were greater than the number of subjects in this study. Discussion: Our results suggest that the influence of the obesity phenotype on improving CHD risk factors is not apparent. A larger study is needed to prove the validity of this finding.     

Personality as a Predictor of Weight Loss Maintenance after Surgery for Morbid Obesity

Objective: Personality characteristics are assumed to underlie health behaviors and, thus, a variety of health outcomes. Our aim was to examine prospectively whether personality traits predict short‐ and long‐term weight loss after laparoscopic adjustable gastric banding. Research Methods and Procedures: Of patients undergoing laparoscopic adjustable gastric banding, 168 (143 women, 25 men, 18 to 58 years old, mean 37 years, preoperative BMI 45.9 ± 5.6 kg/m²) completed the Dutch Personality Questionnaire on average 1.5 years before the operation. The relationship between preoperative personality and short‐ and long‐term postoperative weight loss was determined using multilevel regression analysis. Results: The average weight loss of patients progressively increased to 10 BMI points until 18 months after surgery and stabilized thereafter. A lower baseline BMI, being a man, and a higher educational level were associated with a lower weight loss. None of the personality variables was associated with weight outcome at short‐term follow‐up. Six of seven personality variables did not predict long‐term weight outcome. Egoism was associated with less weight loss in the long‐term postoperative period. The effect sizes of the significant predictions were small. Discussion: None of the personality variables predicted short‐term weight outcome, and only one variable showed a small and unexpected association with long‐term weight outcome that needs confirmation. This suggests that personality assessment as intake psychological screening is of little use for the prediction of a poor or successful weight outcome after bariatric surgery.     

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss

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