Lilian de Jonge

Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates

BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year. METHODS We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content. RESULTS At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels. CONCLUSIONS Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.)

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 NCT00099151

Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor

Metabolic flexibility of skeletal muscle, that is, the preference for fat oxidation (FOx) during fasting and for carbohydrate oxidation in response to insulin, is decreased during insulin resistance. The aim of this study was to test the hypothesis that the capacity of myotubes to oxidize fat in vitro reflects the donors metabolic characteristics. Insulin sensitivity (IS) and metabolic flexibility of 16 healthy, young male subjects was determined by euglycemic hyperinsulinemic clamp. Muscle samples were obtained from vastus lateralis, cultured, and differentiated into myotubes. In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration). We termed these dynamic changes in FOx metabolic switching. In vivo, metabolic flexibility was positively correlated with IS and maximal oxygen uptake and inversely correlated with percent body fat. In vitro suppressibility was inversely correlated with IS and metabolic flexibility and positively correlated with body fat and fasting FFA levels. Adaptability was negatively associated with percent body fat and fasting insulin and positively correlated with IS and metabolic flexibility. The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.

Effect of calorie restriction on resting metabolic rate and spontaneous physical activity.

Objective: It is unclear if resting metabolic rate (RMR) and spontaneous physical activity (SPA) decrease in weight‐reduced non‐obese participants. Additionally, it is unknown if changes in SPA, measured in a respiratory chamber, reflect changes in free‐living physical activity level (PAL).

Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating: A Randomized Controlled Trial

CONTEXT The role of diet composition in response to overeating and energy dissipation in humans is unclear. OBJECTIVE To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. DESIGN, SETTING, AND PARTICIPANTS A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. INTERVENTION After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d). MAIN OUTCOME MEASURES Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. RESULTS Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets. CONCLUSIONS Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00565149.

Family History of Diabetes Links Impaired Substrate Switching and Reduced Mitochondrial Content in Skeletal Muscle

Insulin resistance is associated with metabolic inflexibility, impaired switching of substrate oxidation from fatty acids to glucose in response to insulin. Impaired switching to fat oxidation in response to a high-fat diet (HFD) is hypothesized to contribute to insulin resistance. The objective of this study was to test the hypothesis that defects in substrate switching in response to insulin and a HFD are linked to reduced mitochondrial biogenesis and occur before the development of diabetes. Metabolic flexibility was measured in young sedentary men with (n = 16) or without (n = 34) a family history of diabetes by euglycemic-hyperinsulinemic clamp. Flexibility correlated with fat oxidation measured in a respiratory chamber after a 3-day HFD. Muscle mitochondrial content was higher in flexible subjects with high fat oxidation after a HFD and contributed 49% of the variance. Subjects with a family history of diabetes were inflexible and had reduced HFD-induced fat oxidation and muscle mitochondrial content but did not differ in the amount of body or visceral fat. Metabolic inflexibility, lower adaptation to a HFD, and reduced muscle mitochondrial mass cluster together in subjects with a family history of diabetes, supporting the role of an intrinsic metabolic defect of skeletal muscle in the pathogenesis of insulin resistance.

Evening Chronotype Is Associated with Changes in Eating Behavior, More Sleep Apnea, and Increased Stress Hormones in Short Sleeping Obese Individuals

Background Short sleep duration and decreased sleep quality are emerging risk factors for obesity and its associated morbidities. Chronotype, an attribute that reflects individual preferences in the timing of sleep and other behaviors, is a continuum from morningness to eveningness. The importance of chronotype in relation to obesity is mostly unknown. Evening types tend to have unhealthy eating habits and suffer from psychological problems more frequently than Morning types, thus we hypothesized that eveningness may affect health parameters in a cohort of obese individuals reporting sleeping less than 6.5 hours per night. Methodology and Principal Findings Baseline data from obese (BMI: 38.5±6.4 kg/m2) and short sleeping (5.8±0.8 h/night by actigraphy) participants (n = 119) of the Sleep Extension Study were analyzed (www.ClinicalTrials.gov, identifier NCT00261898). Assessments included the Horne and Ostberg Morningness-Eveningness questionnaire, a three-day dietary intake diary, a 14-day sleep diary, 14 days of actigraphy, and measurements of sleep apnea. Twenty-four hour urinary free cortisol, 24 h urinary norepinephrine and epinephrine levels, morning plasma ACTH and serum cortisol, fasting glucose and insulin, and lipid parameters were determined. Eveningness was associated with eating later in the day on both working and non-working days. Progression towards eveningness was associated with an increase in BMI, resting heart rate, food portion size, and a decrease in the number of eating occasions and HDL-cholesterol. Evening types had overtly higher 24 h urinary epinephrine and morning plasma ACTH levels, and higher morning resting heart rate than Morning types. In addition, Evening types more often had sleep apnea, independent of BMI or neck circumference. Conclusions Eveningness was associated with eating later and a tendency towards fewer and larger meals and lower HDL-cholesterol levels. In addition, Evening types had more sleep apnea and higher stress hormones. Thus, eveningness in obese, chronically sleep-deprived individuals compounds the cardiovascular risk associated with obesity.

Impact of 6-month caloric restriction on autonomic nervous system activity in healthy, overweight, individuals.

Caloric restriction (CR) increases maximum lifespan but the mechanisms are unclear. Dominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PNS) has been shown to be a strong risk factor for cardiovascular disease. Obesity and aging are associated with increased SNS activity, and weight loss and/or exercise seem to have positive effects on this balance. We therefore evaluated the effect of different approaches of CR on autonomic function in 28 overweight individuals participating in the Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy (CALERIE) trial. Participants were randomized to either control, CR: 25% decrease in energy intake, CREX: 12.5% CR + 12.5% increase in energy expenditure, or LCD: low‐calorie diet until 15% weight reduction followed by weight maintenance. Autonomic function was assessed by spectral analysis of heart‐rate variability (HRV) while fasting and after a meal. Measurements were performed at baseline and 6 months. HR and SNS index decreased and PNS index increased in all intervention groups but reached significance only in CREX. HR and SNS index increased and PNS index decreased in response to the meal in all intervention groups. The results therefore suggest that weight loss improved SNS/PNS balance especially when CR is combined with exercise.

Neck Circumference Is a Predictor of Metabolic Syndrome and Obstructive Sleep Apnea in Short-Sleeping Obese Men and Women

BACKGROUND The constellation of metabolic syndrome, although controversial with regard to its clinical usefulness, is epidemiologically related to increased diabetes risk and cardiovascular mortality. Our goal was to investigate the associations among neck circumference (NC), obstructive sleep apnea syndromes (OSAS), and metabolic syndrome in obese men and women sleeping less than 6.5 hr per night. METHODS This was a cross-sectional study of obese men and premenopausal obese women sleeping less than 6.5 hr per night. We enrolled 120 individuals (92 women), age 40.5±6.9 years and body mass index (BMI) 38.6±6.5 kg/m(2). Metabolic syndrome severity was assessed by a score and OSAS was defined as a respiratory disturbance index (RDI) ≥5. Metabolic end endocrine parameters were measured, and sleep duration was determined by actigraphy and validated questionnaires. RESULTS Metabolic syndrome was found in 41% and OSAS in 58% (28% had both). Subjects with metabolic syndrome were 3 years older and more often Caucasian; they had higher RDI scores, larger NC, more visceral fat, lower serum adiponectin, higher 24-hr urinary norepinephrine (NE) excretion, and lower growth hormone concentrations. A NC of ≥38 cm had a sensitivity of 54% and 58% and a specificity of 70% and 79% in predicting the presence of metabolic syndrome and OSAS, respectively. RDI, adiponectin, and NC accounted for approximately 30% of the variability in the metabolic syndrome score, as estimated by an age-, gender-, and race-corrected multivariate model (R(2)=0.376, P<0.001). CONCLUSION Greater NC is associated with OSAS and metabolic syndrome in short-sleeping obese men and premenopausal obese women. Addition of NC to the definition of metabolic syndrome should be considered and needs to be validated in future studies.

Effect of diet composition and weight loss on resting energy expenditure in the POUNDS LOST study

Weight loss reduces energy expenditure, but it is unclear whether dietary macronutrient composition affects this reduction. We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet. The Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST study, a prospective, randomized controlled trial in 811 overweight/obese people who were randomized in a 2 × 2 design to diets containing 20en% or 40en% fat and 15en% or 25en% protein (diets with 65%, 55%, 45%, and 35% carbohydrate) provided the data to test this hypothesis. Resting energy expenditure (REE) was measured at baseline, 6, and 24 months using a ventilated hood. REE declined at 6 months by 99.5 ± 8.0 kcal/day in men and 55.2 ± 10.6 kcal/day in women during the first 6 months. This decline was related to the weight loss, and there was no difference between the diets. REE had returned to baseline by 24 months, but body weight was still 60% below baseline. Measured REE at 6 months was significantly lower than the predicted (−18.2 ± 6.7 kcal/day) and was the result of significant reductions from baseline in the low‐fat diets (65% or 55% carbohydrate), but not in the high fat diet groups. By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted (21.8 ± 10.1 kcal/day). In conclusion, we found that REE fell significantly after weight loss but was not related to diet composition. Adaptive thermogenesis was evident at 6 months, but not at 24 months.