Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

BACKGROUND: Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. OBJECTIVE: To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. METHODS: A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. RESULTS: After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 µmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 µmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 µmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 µmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). CONCLUSIONS: In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake. TRIAL REGISTRATION: Clinicaltrials.gov NCT01551238.

Protein diets, body weight loss and weight maintenance.

PURPOSE OF REVIEW: The review addresses briefly the relevance of protein diets for body weight loss and weight maintenance. The addition of recent findings on age-dependent protein requirements, specific effects of protein intake and protein source, the relevance of the other dietary macronutrients, especially of 'low-carb', 'protein leverage', the mechanisms of protein-induced satiety, and food-reward makes the review up-to-date. RECENT FINDINGS: Different effects of protein diets in different age groups result from age-dependent protein requirements that are primarily related to effects on body composition. A protein intake of 0.8 g/kg/day is sufficient to sustain a negative energy balance in adults, irrespective of the protein source. 'Low-carb' diets trace back to the protein-induced effects. Evidence that protein intake drives energy intake as suggested by the 'Protein leverage hypothesis' is scarce and equivocal. Finally, limited protein-induced food reward may affect compliance to a protein diet. SUMMARY: An implication of the findings for clinical practice is that a protein intake of 0.8-1.2 g/kg/day is sufficient to sustain satiety, energy expenditure, and fat-free mass, independent of a dietary 'low-carb' content. Limited protein-induced food reward may affect compliance to a protein diet.

Sleep architecture when sleeping at an unusual circadian time and associations with insulin sensitivity.

UNLABELLED: Circadian misalignment affects total sleep time, but it may also affect sleep architecture. The objectives of this study were to examine intra-individual effects of circadian misalignment on sleep architecture and inter-individual relationships between sleep stages, cortisol levels and insulin sensitivity. Thirteen subjects (7 men, 6 women, age: 24.3±2.5 y; BMI: 23.6±1.7 kg/m²) stayed in a time blinded respiration chamber during three light-entrained circadian cycles (3x21h and 3x27h) resulting in a phase advance and a phase delay. Sleep was polysomnographically recorded. Blood and salivary samples were collected to determine glucose, insulin and cortisol concentrations. Intra-individually, a phase advance decreased rapid eye movement (REM) sleep and slow-wave sleep (SWS), increased time awake, decreased sleep and REM sleep latency compared to the 24h cycle. A phase delay increased REM sleep, decreased stage 2 sleep, increased time awake, decreased sleep and REM sleep latency compared to the 24h cycle. Moreover, circadian misalignment changed REM sleep distribution with a relatively shorter REM sleep during the second part of the night. Inter-individually, REM sleep was inversely associated with cortisol levels and HOMA-IR index. Circadian misalignment, both a phase advance and a phase delay, significantly changed sleep architecture and resulted in a shift in rem sleep. Inter-individually, shorter REM sleep during the second part of the night was associated with dysregulation of the HPA-axis and reduced insulin sensitivity. TRIAL REGISTRATION: International Clinical Trials Registry Platform NTR2926 http://apps.who.int/trialsearch/

Acute effects of capsaicin on energy expenditure and fat oxidation in negative energy balance.

BACKGROUND: Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. AIM: We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. METHODS: Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions '100%CAPS', '100%Control', '75%CAPS' and '75%Control'. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. RESULTS: An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. CONCLUSION: In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. TRIAL REGISTRATION: Nederlands Trial Register; registration number NTR2944.

Disadvantageous shift in energy balance is primarily expressed in high-quality sleepers after a decline in quality sleep because of disturbance.

BACKGROUND: Epidemiologic studies have shown an inverse or U-shaped relation between sleep duration and body mass index (BMI; in kg/m(2)). Moreover, associations between energy balance (EB) and characteristics of quality sleep (QS) have recently been reported. OBJECTIVE: We assessed the relation between total energy expenditure (TEE) as well as substrate oxidation and QS after disturbed compared with nondisturbed sleep in EB. DESIGN: Fifteen healthy men (mean ± SD BMI: 24.1 ± 1.9; age: 23.7 ± 3.5 y) were included in a randomized crossover study. TEE and substrate oxidation were measured twice for 48 h in a respiration chamber, whereas slow-wave sleep (SWS), rapid eye movement (REM)-sleep, total sleeping time (TST), sleep stage 2 (S2), and QS [(SWS + REM) ÷ TST × 100%] were determined by using electroencephalography. During 2 nights, sleep (2330-0730) was either disturbed or nondisturbed (control). RESULTS: Positive correlations were shown for TEE, activity-induced energy expenditure corrected for body mass (AEE/BM), respiratory quotient (RQ), and carbohydrate oxidation with QS and SWS during nondisturbed sleep. Fat oxidation was inversely correlated with QS and SWS. RQ and carbohydrate oxidation were inversely related to REM sleep. During the disturbed condition SWS, REM, TST, and S2 were reduced, and positive correlations were shown between TEE and AEE/BM with QS. The reduction in QS was stronger in high-quality sleepers; QS reduction was positively associated with increases in energy intake, TEE, and EB. CONCLUSION: A disadvantageous shift in energy balance is primarily expressed in high-quality sleepers after a decline in QS because of disturbance, implying that good sleepers are most liable to a positive energy balance because of sleep disturbance. This trial was registered at ISRCTN as NTR1919.

Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass.

Energy-restricted high-protein diets (HPDs) have shown favorable results for body weight (BW) management, yet studies differ in their outcomes depending on the dietary protein content. Our objective was to determine the effects of dietary protein content on BW loss-related variables during a 6-mo energy restriction with the use of diets containing protein at the level of requirement [normal-protein diet (NPD), 0.8 g · kg BW(-1) (.) d(-1)] and above (HPD, 1.2 g · kg BW(-1) (.) d(-1)). In overweight and obese participants (24 men and 48 women), BW, body composition, and metabolic responses were assessed before and after subsequent energy intakes of 100, 33, and 67% of the original individual daily energy requirements. Protein intake was consistent in the NPD (0.8 ± 0.3 g · kg BW(-1) (.) d(-1)) and HPD (1.2 ± 0.3 g · kg BW(-1) (.) d(-1)) groups throughout the study (P < 0.001). BMI and body fat mass similarly decreased in the NPD and HPD groups (P < 0.01). Fat free mass (FFM), resting energy expenditure (REE) compared with predicted REE, and diastolic blood pressure (DBP) changed favorably with the HPD compared with the NPD group after BW loss (P < 0.05). A NPD of 0.8 g · kg BW(-1) (.) d(-1) is sufficient for BW management, whereas a HPD of 1.2 g · kg BW(-1) (.) d(-1) is necessary for preservation of REE and a stronger initial sparing effect of FFM and lowering of DBP.

Effects of sleep fragmentation on appetite and related hormone concentrations over 24 h in healthy men.

In addition to short sleep duration, reduced sleep quality is also associated with appetite control. The present study examined the effect of sleep fragmentation, independent of sleep duration, on appetite profiles and 24 h profiles of hormones involved in energy balance regulation. A total of twelve healthy male subjects (age 23 (sd 4) years, BMI 24·4 (sd 1·9) kg/m²) completed a 24 h randomised crossover study in which sleep (23.30-07.30 hours) was either fragmented or non-fragmented. Polysomnography was used to determine rapid-eye movement (REM) sleep, slow-wave sleep (SWS) and total sleep time (TST). Blood samples were taken at baseline and continued hourly for the 24 h period to measure glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1) and melatonin concentrations. In addition, salivary cortisol levels were measured. Visual analogue scales were used to score appetite-related feelings. Sleep fragmentation resulted in reduced REM sleep (69·4 min compared with 83·5 min; P< 0·05) and preservation of SWS without changes in TST. In fragmented v. non-fragmented sleep, glucose concentrations did not change, while insulin secretion was decreased in the morning, and increased in the afternoon (P< 0·05), and GLP-1 concentrations and fullness scores were lower (P< 0·05). After dinner, desire-to-eat ratings were higher after fragmented sleep (P< 0·05). A single night of fragmented sleep, resulting in reduced REM sleep, induced a shift in insulin concentrations, from being lower in the morning and higher in the afternoon, while GLP-1 concentrations and fullness scores were decreased. These results may lead to increased food intake and snacking, thus contributing to a positive energy balance.

Effect of a phase advance and phase delay of the 24-h cycle on energy metabolism, appetite, and related hormones.

BACKGROUND: The disruption of the circadian system has been associated with the development of obesity. OBJECTIVE: We examined the effects of circadian misalignment on sleep, energy expenditure, substrate oxidation, appetite, and related hormones. DESIGN: Thirteen subjects [aged 24.3 ± 2.5 (mean ± SD) y; BMI (in kg/m²): 23.6 ± 1.7 (mean ± SD)] completed a randomized crossover study. For each condition, subjects stayed time blinded in the respiration chamber during 3 light-entrained circadian cycles that resulted in a phase advance (3 × 21 h) and a phase delay (3 × 27 h) compared with during a 24-h cycle. Sleep, energy expenditure, substrate oxidation, and appetite were quantified. Blood and saliva samples were taken to determine melatonin, glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1), and cortisol concentrations. RESULTS: Circadian misalignment, either phase advanced or phase delayed, did not result in any changes in appetite or energy expenditure, whereas meal-related blood variables (glucose, insulin, ghrelin, leptin, and GLP-1) followed the new meal patterns. However, phase-advanced misalignment caused flattening of the cortisol-secretion pattern (P < 0.001), increased insulin concentrations (P = 0.04), and increased carbohydrate oxidation (P = 0.03) and decreased protein oxidation (P = 0.001). Phase-delayed misalignment increased rapid eye movement sleep (P < 0.001) and the sleeping metabolic rate (P = 0.02), increased glucose (P = 0.02) and decreased GLP-1 (P = 0.02) concentrations, and increased carbohydrate oxidation (P = 0.01) and decreased protein oxidation (P = 0.003). CONCLUSIONS: The main effect of circadian misalignment, either phase advanced or phase delayed, is a concomitant disturbance of the glucose-insulin metabolism and substrate oxidation, whereas the energy balance or sleep is not largely affected. Chronically eating and sleeping at unusual circadian times may create a health risk through a metabolic disturbance. This trial was registered at the International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/) as NTR2926.

Sex differences in HPA axis activity in response to a meal.

BACKGROUND: Sex may influence the relationship between HPA axis functioning and obesity. This has been suggested to be due to sex-specific differences in body composition, body fat distribution and psychological variables. Age and the use of oral contraceptives may also influence the relationship between HPA axis functioning and obesity. OBJECTIVE: To systematically investigate whether body composition, body fat distribution, psychological variables, age, or possible oral contraceptive use contribute to sex differences in HPA axis activity in response to a meal. METHODS: Subjects were men (n=19) and women (n=19) between 18 and 51 years old with BMI between 20.3 and 33.2 kg/m(2). HPA axis activity was measured by salivary free cortisol levels before consuming a meal, and at 45, 75 and 125 min postprandial on four repeated test days. Anthropometric and body composition measurements were performed. Questionnaires were used to assess cognitive eating behavior and trait anxiety level. RESULTS: No differences between the test days in postprandial cortisol responses appeared. Responses were significantly higher in men compared with women (p<.05). No significant correlations were found between cortisol concentrations and sex-specific body composition or body fat distribution. Psychological variables did not contribute to differences in cortisol responses after a meal between men and women. In women, baseline cortisol concentrations correlated inversely with age (p=.024). CONCLUSION: Higher HPA axis activity following a meal in men vs. women remained irrespective of sex-specific differences in body composition, body fat distribution, psychological variables, or in age. In women baseline cortisol concentrations were age-dependent.

Effects of sleep fragmentation in healthy men on energy expenditure, substrate oxidation, physical activity, and exhaustion measured over 48 h in a respiratory chamber.

BACKGROUND: Epidemiologic studies show an inverse or U-shaped relation between sleep duration and BMI. Decreases in total energy expenditure (TEE) and physical activity have been suggested to be contributing factors. OBJECTIVE: The objective was to assess the effect of sleep fragmentation on energy metabolism and energy balance in healthy men. DESIGN: Fifteen healthy male subjects [mean ± SD BMI (in kg/m(2)): 24.1 ± 1.9; age: 23.7 ± 3.5 y] were included in a randomized crossover study in which energy expenditure, substrate oxidation, and physical activity (by radar) were measured twice for 48 h in a respiration chamber while subjects were monitored by electroencephalography to determine slow-wave sleep (SWS), rapid eye movement (REM) sleep, and total sleeping time (TST). During 2 nights, sleep (2330-0730 h) was either fragmented or nonfragmented. RESULTS: Fragmented sleep led to reductions in TST, SWS, and REM sleep (P < 0.001). TEE did not differ (9.96 ± 0.17 compared with 9.83 ± 0.13 MJ/d, NS) between the sleep groups, nor did the components of energy expenditure, with the exception of activity-induced energy expenditure (AEE; 1.63 ± 0.15 compared with 1.42 ± 0.13 MJ/d for fragmented and nonfragmented sleep, respectively; P < 0.05). Physical activity, exhaustion, sleepiness, respiratory quotient (RQ), and carbohydrate oxidation were elevated in comparison with nonfragmented sleep [physical activity counts: 2371 ± 118 compared with 2204 ± 124 counts/d, P < 0.02; exhaustion: 40.1 ± 3.8 compared with 21.8 ± 2.4 mm (by using a visual analog scale; VAS), P < 0.001; sleepiness: 47.4 ± 4.2 compared with 33.9 ± 4.6 mm (VAS), P < 0.001; RQ: 0.94 ± 0.04 compared with 0.91 ± 0.03, P < 0.05; and carbohydrate oxidation: 346.3 ± 23.8 compared with 323.7 ± 22.5 g/d, P < 0.05], whereas fat oxidation was reduced (29.1 ± 9.1 compared with 61.0 ± 6.6 g/d, P < 0.01). CONCLUSIONS: Fragmented compared with nonfragmented sleep induced reductions in the most important sleep phases, which coincided with elevated AEE, physical activity, exhaustion, and sleepiness. RQ and carbohydrate oxidation increased and fat oxidation decreased, which may predispose to overweight. This trial is registered at www.who.int/ictrp and www.trialregister.nl as NTR1919.