An investigation of potential variables affecting the physiological adaptations to weight loss: weight loss rate, nature of energy restriction, and ketosis
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Various reviews published over the last decades have shown that several compensatory responses on both sides of the energy balance (EB) equation are activated with weight loss (WL), which oppose the maintenance of a reduced body weight. Overall, and despite a significantly reduced total energy expenditure (EE), an increased drive to eat is seen in the reduced obese state. The aim of this PhD was to explore dietary strategies that could modulate the physiological adaptations to WL (in particular changes in EE variables and appetite), namely WL rate, nature of energy restriction (intermittent vs continuous), and ketosis during progressive WL. Therefore, three independent studies were performed. In the first study, 33 (♂: 9; ♀: 24) adults (39.3±9.7 years of age) with obesity (BMI: 33.4±2.8 kg/m2) were randomized to lose a similar weight either rapidly (4 weeks of a very low caloric diet (VLCD); ♂: 660 kcal/day; ♀: 550 kcal/day) or gradually (8 weeks of a low caloric diet (LCD); ♂: 1500 kcal/day; ♀: 1200 kcal/day), followed by 4 weeks of an individualized diet plan aiming at weight stabilization. Both groups had a similar change in body weight (≈9.0% WL) and composition. Resting energy expenditure (REE) decreased and exercise efficiency (ExEff) at 10 watts increased in the rapid WL group only at the end of the WL phase. However, fasting hunger increased with gradual WL only, while postprandial prospective food consumption (PFC) and postprandial hunger decreased (and postprandial fullness increased) with rapid WL only. Postprandial insulin decreased similarly in both groups. After weight stabilization, and no ketosis, no differences between groups were found. In the second study, 28 (♂: 6; ♀: 22) adults (39.3±9.9 years of age) with obesity (BMI: 35.3±3.7 kg/m2) were randomized to lose a similar weight either with intermittent energy restriction (IER) or continuous energy restriction (CER) diets, over a 12 week period. The IER diet consisted of 3 non-consecutive days of VLCD (♂: 660 kcal/day; ♀: 550 kcal/day), interspaced with feeding days (diet matching energy needs using conventional food). The CER diet was a LCD daily using conventional food. Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting respiratory quotient (RQ) and ExEff at 10 watts increased in both groups. REE decreased, and ExEff at 25 and 50 watts increased in IER group only. No significant changes in subjective appetite ratings were seen in either groups. Basal and postprandial active ghrelin (AG) increased in IER group only. Postprandial cholecystokinin (CCK) decreased in both groups. However, no differences between groups were significant for any of the outcome variables. In the third and final study, a longitudinal design with repeated measures was used. A total of 31 (♂: 18; ♀: 13) adults (43.1±10.2 years of age) with obesity (BMI: 36.7±4.5 kg/m2) underwent 8 weeks of VLCD (♂: 660 kcal/day; ♀: 550 kcal/day) followed by 4 weeks of refeeding and weight stabilization. The main findings were that, a significant increase in fasting hunger was observed by day 3 (2±1% WL), 5% WL (12±8 days), and week 13 (17±2% WL). Increased in fasting desire to eat was observed by day 3 and 5% WL. Postprandial PFC was significantly reduced at week 9 (16±2% WL). Postprandial active GLP-1 was increased at 5% WL, and CCK reduced at 5 and 10% WL, and week 9. Basal and postprandial AG were significantly increased at week 13. In conclusion, despite differences while under negative EB, WL rate does not seem to have a significant impact on body composition or on the compensatory mechanisms activated with WL, once EB is reestablished. Moreover, the nature of energy restriction (intermittent vs continuous) also does not seem to influence significantly the compensatory responses to weight reduction. However, being in ketosis was not associated with an increase in appetite, even though it may take up to 3 weeks for this effect to be apparent. Thus, the findings of this PhD work suggest that losing weight rapidly and with IER diets are valid options in the management of obesity, and that ketogenic VLCD may offer some benefits by preventing the anticipated increase in the drive to eat. However, once the participants are in EB and out of ketosis an increase in appetite should be expected. This knowledge should be taken into consideration when discussing treatment options for WL in individuals with obesity.