Long-term persistence of hormonal adaptations to weight loss.

BACKGROUND: After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss. METHODS: We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. RESULTS: Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). CONCLUSIONS: One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

The effect of rate of weight loss on long-term weight management: a randomised controlled trial.

BACKGROUND: Guidelines recommend gradual weight loss for the treatment of obesity, indicative of a widely held opinion that weight lost rapidly is more quickly regained. We aimed to investigate the effect of the rate of weight loss on the rate of regain in obese people. METHODS: For this two phase, randomised, non-masked, dietary intervention trial in a Melbourne metropolitan hospital, we enrolled 204 participants (51 men and 153 women) aged 18­70 years with a BMI between 30 and 45 kg/m2. During phase 1, we randomly assigned (1:1) participants with a block design (block sizes of 2, 4, and 6) to account for sex, age, and BMI, to either a 12-week rapid weight loss or a 36-week gradual programme, both aimed at 15% weight loss. We placed participants who lost 12·5% or more weight during phase 1 on a weight maintenance diet for 144 weeks (phase 2). The primary outcome was mean weight loss maintained at week 144 of phase 2. We investigated the primary outcome by both completers only and intention-to-treat analyses. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000190909. FINDINGS: 200 participants were randomly assigned to the gradual weight loss (n=103) or rapid weight loss (n=97) programme between Aug 8, 2008, and March 9, 2010. After phase 1, 51 (50%) participants in the gradual weight loss group and 76 (81%) in the rapid weight loss group achieved 12·5% or more weight loss in the allocated time and started phase 2. At the end of phase 2, both gradual weight loss and rapid weight loss participants who completed the study (n=43 in gradual weight loss and n=61 in rapid weight loss) had regained most of their lost weight (gradual weight loss 71·2% regain, 95% CI 58·1­84·3 vs rapid weight loss 70·5%, 57·8­83·2). Intention-to-treat analysis showed similar results (gradual weight loss 76·3% regain, 95% CI 65·2­87·4 vs rapid weight loss 76·3%, 65·8­86·8). In phase 1, one participant in the rapid weight loss group developed cholecystitis, requiring cholecystectomy. In phase 2, two participants in the rapid weight loss group developed cancer. INTERPRETATION: The rate of weight loss does not affect the proportion of weight regained within 144 weeks. These findings are not consistent with present dietary guidelines which recommend gradual over rapid weight loss, based on the belief that rapid weight loss is more quickly regained. FUNDING: The Australian National Health and Medical Research Council and the Sir Edward Dunlop Medical Research Foundation.

One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: does diet composition matter?

BACKGROUND: For many people, maintenance of weight loss is elusive. Whereas high-protein (HP) diets have been found to be superior to high-carbohydrate (HC) diets for weight loss in the short term, their benefits long term are unclear, particularly for weight maintenance. Furthermore, the literature lacks consensus on the long-term effects of an HP diet on cardiovascular disease risk factors. OBJECTIVE: The objective was to investigate whether macronutrient dietary composition plays a role in weight maintenance and in improvement of cardiovascular disease risk factors. DESIGN: The study comprised 2 phases. Phase 1 featured a very-low-energy diet for 3 mo. In phase 2, the subjects were randomly assigned to an HP or an HC diet for 12 mo. The diets were isocaloric, tightly controlled, and individually prescribed for weight maintenance. The subjects were overweight or obese but otherwise healthy men and women. RESULTS: The subjects lost an average of 16.5 kg during phase 1 and maintained a mean (+/-SEM) weight loss of 14.5 +/- 1.2 kg (P < 0.001) during phase 2; no significant differences between groups were observed. By the end of the study, reductions in systolic blood pressure were 14.3 +/- 2.4 mm Hg for the HP group and 7.7 +/- 2.2 mm Hg for the HC group (P < 0.045). Forty-seven percent of the 180 subjects who began the study completed both phases. CONCLUSIONS: The results indicate that the protein or carbohydrate content of the diet has no effect on successful weight-loss maintenance. A general linear model analysis indicated that dietary treatment (HP or HC) was a significant factor in systolic blood pressure change and in favor of the HP diet. This trial was registered at www.clinicaltrials.gov as NCT 00625236.

Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations.

BACKGROUND: Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior. OBJECTIVE: The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain. DESIGN: The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance. RESULTS: Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60). CONCLUSION: Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.

State of the science: VLED (Very Low Energy Diet) for obesity.

It is often stated, "the faster you lose weight, the faster it is regained ". A review of existing literature does not support such a statement--indeed if anything the reverse is true. The origins of this erroneous view are the misconceptions that weight regain is a simple matter of bad dietary and social habits and that it takes time to change these, that physiological adaptations to rapid weight loss are different to those of gradual weight loss and that weight regain is simply due to a return to old habits. Indeed there are many advantages to rapid weight loss achieved with the use of a modern very low energy diet, including the fact that rapid weight loss is a motivating factor, that the mild ketosis that occurs not only suppresses hunger, but also slows protein loss and that adherence is easier with a structured dietary regime. VLEDs are dietary preparations that provide all nutritional requirements together with between 1845 and 3280 KJ (450 and 800 Kcal) per day. An individual takes this meal replacement three times daily as a substitute for breakfast, lunch and dinner. In addition, a bowl of non-starchy vegetables once daily provides some fibre and helps to satisfy the social aspect of eating. A teaspoon of oil on the vegetables contracts the gall bladder to minimise the risk of gall stone formation. Since weight loss, at whatever rate, results in physiological adaptations leading to weight regain, careful attention must be paid to the period after the VLED regime is completed. Lifestyle modification, diet and exercise are instituted optimally with behaviour modification. If, despite the subject's best efforts, weight regain occurs, an appetite suppressant is advisable to help control the drive to eat.