Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study.

BACKGROUND: Weight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined. OBJECTIVE: This study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings. METHODS: This was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m2; age: 47±1 y; 26 males) underwent an 8 wk low-energy diet, followed by 4 wk of refeeding and weight stabilization. The RMR, respiratory quotient (RQ), body composition, plasma concentrations of ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, insulin, and appetite ratings in the fasting and postprandial states were measured at baseline, Wk9 and 13. Metabolic adaptation was defined as significantly lower when measured versus the predicted RMR (pRMR) (from own regression model using baseline data). RESULTS: A 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ. CONCLUSION: A larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.

Association between ß-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition.

BACKGROUND: Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), whereas preserving fat-free mass (FFM). Additionally, animal data support the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge, a potential association between ß-hydroxybutyrate (ßHB) plasma concentrations and changes in body composition has never been explored. OBJECTIVES: The main aim of this analysis was to determine if ßHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity. METHODS: Data from 199 individuals (BMI = 36.6 ± 4.3 kg/m2; age = 43.6 ± 9.8 y; 82 men) were collated from 3 weight loss studies employing common measures of body composition (air displacement plethysmography) and ßHB plasma concentration (ELISA). The association between ßHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multivariable linear regression was used to determine if ßHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors. RESULTS: ßHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r = 0.182, P = 0.01, n = 199) and a trend with weight loss (r = 0.128, P = 0.072, n = 199). ßHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study. CONCLUSIONS: The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved. This trial was registered at clinicaltrials.gov identifier as NCT01834859, NCT04051190, NCT02944253.

Association between ketosis and metabolic adaptation at the level of resting metabolic rate.

BACKGROUND: The ketone body ß-hydroxybutyrate (ßHB) has been shown to act as a signaling molecule that regulates metabolism and energy homeostasis during starvation in animal models. A potential association between ßHB and metabolic adaptation (a reduction in energy expenditure below predicted levels) in humans has never been explored. OBJECTIVE: To determine if metabolic adaptation at the level of resting metabolic rate (RMR) was associated with the magnitude of ketosis induced by a very-low energy diet (VLED). A secondary aim was to investigate if the association was modulated by sex. METHODS: Sixty-four individuals with obesity (BMI: 34.5 ± 3.4 kg/m2; age: 45.7 ± 8.0 years; 31 males) enrolled in a 1000 kcal/day diet for 8 weeks. Body weight/composition, RMR and ßHB (as a measure of ketosis) were determined at baseline and week 9 (W9). Metabolic adaptation was defined as a significantly lower measured versus predicted RMR (from own regression model). RESULTS: Participants lost on average 14.0 ± 3.9 kg and were ketotic (ßHB: 0.76 ± 0.51 mM) at W9. A significant metabolic adaptation was seen (-84 ± 106 kcal/day, P < 0.001), with no significant differences between sexes. [ßHB] was positively correlated with the magnitude of metabolic adaptation in females (r = 0.432, P = 0.012, n = 33), but not in males (r = 0.089, P = 0.634, n = 31). CONCLUSION: In females with obesity, but not males, the larger the [ßHB] under VLED, the greater the metabolic adaptation at the level of RMR. More studies are needed to confirm these findings and to explore the mechanisms behind the sex difference in the association between ketosis and metabolic adaptation. TRIAL REGISTRATION NAME: Clinicaltrials.gov. STUDY REGISTRATION ID: NCT02944253. URL: https://clinicaltrials.gov/ct2/show/NCT02944253.

Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets.

BACKGROUND: The practical relevance of metabolic adaptation remains a controversial issue. To the best of our knowledge, no study has properly evaluated the role of metabolic adaptation in modulating weight loss outcomes. Therefore, the aim of this study was to determine the association between metabolic adaptation, at the level of resting metabolic rate (RMR), and weight and fat mass (FM) loss after low-energy diets (LED), after adjusting for dietary adherence and other confounders. METHODS: 71 individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 years; 33 males) were randomized to one of three 1000 kcal/day diets for 8 weeks. Body weight, FM and fat-free mass (FFM) (air displacement plethysmography), RMR (indirect calorimetry) and physical activity level (PAL) (armbands) were measured at baseline and at week 9. Metabolic adaptation at week 9 was defined as measured RMR minus predicted RMR at week 9. An equation to predict RMR was derived from baseline data of all participants that were part of this analysis and included age, sex, FM and FFM as predictors. Dietary adherence was calculated from RMR, PAL and body composition changes. Linear regression was used to assess the potential role of metabolic adaptation in predicting weight and FM loss after adjusting for dietary adherence, average PAL, sex, baseline FM and FFM and randomization group. RESULTS: Participants lost on average 14 ± 4 kg of body weight (13 ± 3%) and presented with metabolic adaptation (-92 ± 110 kcal/day, P < 0.001). Metabolic adaptation was a significant predictor of both weight (ß = -0.009, P < 0.001) and FM loss (ß = -0.008, P < 0.001), even after adjusting for confounders (R2 = 0.88, 0.93, respectively, P < 0.001 for both). On average, an increase in metabolic adaptation of 50 kcal/day was associated with a 0.5 kg lower weight and FM loss in response to the LED. CONCLUSION: In individuals with obesity, metabolic adaptation at the level of RMR is associated with less weight and FM loss in response to LED. Trial registration ID: NCT02944253.

Ketogenic diets and appetite regulation.

PURPOSE OF REVIEW: The popularity of ketogenic diets in the treatment of obesity has increased dramatically over the last years, namely due to their potential appetite suppressant effect. The purpose of this review was to examine the latest evidence regarding the impact of ketogenic diets on appetite. RECENT FINDINGS: The majority of the studies published over the last 2 years adds to previous evidence and shows that ketogenic diets suppress the increase in the secretion of the hunger hormone ghrelin and in feelings of hunger, otherwise see when weight loss is induced by non-ketogenic diets. Research done using exogenous ketones point out in the same direction. Even though the exact mechanisms by which ketogenic diets suppress appetite remain to be fully determined, studies show that the more ketotic participants are (measured as ß-hydroxybutyrate plasma concentration), the smaller is the increase in ghrelin and hunger and the larger is the increase in the release of satiety peptides. Further evidence for a direct effect of ketones on appetite comes from studies using exogenous ketones. SUMMARY: The appetite suppressant effect of ketogenic diets may be an important asset for improving adherence to energy restricted diets and weight loss outcomes.

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

BACKGROUND: The existence of metabolic adaptation, following weight loss, remains a controversial issue. To our knowledge, no study has evaluated the role of energy balance (EB) in modulating metabolic adaptation. OBJECTIVES: The aim of this study was to determine if metabolic adaptation, at the level of resting metabolic rate (RMR), is modulated by participants' EB status. A secondary aim was to investigate if metabolic adaptation was associated with weight regain. METHODS: Seventy-one individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 y; 33 men) enrolled in a 1000-kcal/d diet for 8 wk, followed by 4 wk of weight stabilization and a 9-mo weight loss maintenance program. Body weight/composition and RMR were measured at baseline, week 9 (W9), week 13 (W13), and 1 y (1Y). Metabolic adaptation was defined as a significantly different (lower or higher) measured compared with predicted RMR. RESULTS: Participants lost on average 14 kg by W9, followed by weight stabilization at W13, and regained 29% of their initial weight loss at 1Y. Metabolic adaptation was found at W9 (-92 ± 110 kcal/d, P < 0.001) and W13 (-38 ± 124 kcal/d, P = 0.011) but was not correlated with weight regain. A significant reduction in metabolic adaptation was seen between W9 and W13 (-53 ± 101 kcal/d, P < 0.001). In a subset of participants who gained weight between W9 and W13 (n = 33), no metabolic adaptation was seen at W13 (-26.8 ± 121.5 kcal/d, P = 0.214). In a subset of participants with data at all time points (n = 45), metabolic adaptation was present at W9 and W13 (-107 ± 102 kcal/d, P < 0.001 and -49 ± 128 kcal/d, P = 0.013) but not at 1Y (-7 ± 129, P = 0.701). CONCLUSION: After weight loss, metabolic adaptation at the level of RMR is dependent on the EB status of the participants, being reduced to half after a period of weight stabilization. Moreover, metabolic adaptation does not predict weight regain at 1Y follow-up. These trials were registered at clinicaltrials.gov as NCT02944253 and NCT03287726.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status.

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants-53 with morbid obesity and 58 of normal weight-were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight.

The Impact of Feet Callosities, Arm Posture, and Usage of Electrolyte Wipes on Body Composition by Bioelectrical Impedance Analysis in Morbidly Obese Adults.

OBJECTIVE: This study evaluated the impact of feet callosities, arm posture, and use of electrolyte wipes on body composition measurements by bioelectrical impedance analysis (BIA) in morbidly obese adults. METHODS: 36 morbidly obese patients (13 males, aged 28-70 years, BMI 41.6 ± 4.3 kg/m2) with moderate/severe feet callosities participated in this study. Body composition (percent body fat (%BF)) was measured while fasting using multi-frequency BIA (InBody 720®), before and after removal of callosities, with and without InBody® electrolyte wipes and custom-built auxiliary pads (to assess arm posture impact). Results from BIA were compared to air displacement plethysmography (ADP, BodPod®). RESULTS: Median %BF was significantly higher with auxiliary pads than without (50.1 (interquartile range 8.2) vs. 49.3 (interquartile range 9.1); p < 0.001), while no differences were found with callosity removal (49.3 (interquartile range 9.1) vs. 50.0 (interquartile range 7.9); NS) or use of wipes (49.6 (interquartile range 8.5) vs. 49.3 (interquartile range 9.1); NS). No differences in %BF were found between BIA and ADP (49.1 (IQR: 8.9) vs. 49.3 (IQR: 9.1); NS). CONCLUSION: Arm posture has a significant impact on %BF assessed by BIA, contrary to the presence of feet callosities and use of electrolyte wipes. Arm posture standardization during BIA for body composition assessment is, therefore, recommended.

Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials.

Energy restriction induces physiological effects that hinder further weight loss. Thus, deliberate periods of energy balance during weight loss interventions may attenuate these adaptive responses to energy restriction and thereby increase the efficiency of weight loss (i.e. the amount of weight or fat lost per unit of energy deficit). To address this possibility, we systematically searched MEDLINE, PreMEDLINE, PubMed and Cinahl and reviewed adaptive responses to energy restriction in 40 publications involving humans of any age or body mass index that had undergone a diet involving intermittent energy restriction, 12 with direct comparison to continuous energy restriction. Included publications needed to measure one or more of body weight, body mass index, or body composition before and at the end of energy restriction. 31 of the 40 publications involved 'intermittent fasting' of 1-7-day periods of severe energy restriction. While intermittent fasting appears to produce similar effects to continuous energy restriction to reduce body weight, fat mass, fat-free mass and improve glucose homeostasis, and may reduce appetite, it does not appear to attenuate other adaptive responses to energy restriction or improve weight loss efficiency, albeit most of the reviewed publications were not powered to assess these outcomes. Intermittent fasting thus represents a valid--albeit apparently not superior--option to continuous energy restriction for weight loss.