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.

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/

Overnight energy expenditure determined by whole-body indirect calorimetry does not differ during different sleep stages.

BACKGROUND: Sleep has been associated with the regulation of energy balance, yet the relation between sleep stages and energy expenditure remains unclear. OBJECTIVE: The objective was to investigate the relation between sleep stages and energy expenditure, with sleep stage and overnight energy expenditure patterns taken into account. DESIGN: Thirteen subjects aged (mean ± SD) 24.3 ± 2.5 y with a BMI (in kg/m(2)) of 23.6 ± 1.7 slept in a respiration chamber while sleep was polysomnographically recorded to determine wake after sleep onset (WASO), slow-wave sleep (SWS), and rapid eye movement (REM) sleep. Energy expenditure was calculated during each sleep stage for the whole night and separately for sleeping metabolic rate (SMR; ie, 3-h period during the night with the lowest mean energy expenditure) and non-SMR. RESULTS: Energy expenditure and sleep stages showed characteristic patterns during the night, independently of each other. Sleep stages exerted no effect on energy expenditure during the whole night, except for WASO compared with SWS (P < 0.05) and WASO compared with REM sleep (P < 0.05). During the SMR and non-SMR periods of the night, no overall effect of sleep stage on energy expenditure, except for WASO compared with SWS (P < 0.05) and WASO compared with REM sleep (P < 0.01) during the non-SMR period of the night, was found. Energy expenditure and activity counts during the night were positively correlated (r = 0.927, P < 0.001). CONCLUSIONS: Energy expenditure does not vary according to sleep stage overnight, except for higher energy expenditure during wake episodes than during SWS and REM sleep. Coincidence of the sleep stage pattern and the overnight energy expenditure pattern may have caused accidental relations in previous observations. This trial was registered at http://apps.who.int/trialsearch as NTR2926.

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.

Sleep duration, sleep quality and body weight: parallel developments.

The increase in obesity, including childhood obesity, has developed over the same time period as the progressive decrease in self-reported sleep duration. Since epidemiological studies showed an inverse relationship between short or disturbed sleep and obesity, the question arose, how sleep duration and sleep quality are associated with the development of obesity. In this review, the current literature on these topics has been evaluated. During puberty, changes in body mass index (BMI) are inversely correlated to changes in sleep duration. During adulthood, this relationship remains and at the same time unfavorable metabolic and neuro-endocrinological changes develop, that promote a positive energy balance, coinciding with sleep disturbance. Furthermore, during excessive weight loss BMI and fat mass decrease, in parallel, and related with an increase in sleep duration. In order to shed light on the association between sleep duration, sleep quality and obesity, until now it only has been shown that diet-induced body-weight loss and successive body-weight maintenance contribute to sleep improvement. It remains to be demonstrated whether body-weight management and body composition improve during an intervention concomitantly with spontaneous sleep improvement compared with the same intervention without spontaneous sleep improvement.

Concomitant changes in sleep duration and body weight and body composition during weight loss and 3-mo weight maintenance.

BACKGROUND: An inverse relation between sleep duration and body mass index (BMI) has been shown. OBJECTIVE: We assessed the relation between changes in sleep duration and changes in body weight and body composition during weight loss. DESIGN: A total of 98 healthy subjects (25 men), aged 20-50 y and with BMI (in kg/m(2)) from 28 to 35, followed a 2-mo very-low-energy diet that was followed by a 10-mo period of weight maintenance. Body weight, body composition (measured by using deuterium dilution and air-displacement plethysmography), eating behavior (measured by using a 3-factor eating questionnaire), physical activity (measured by using the validated Baecke's questionnaire), and sleep (estimated by using a questionnaire with the Epworth Sleepiness Scale) were assessed before and immediately after weight loss and 3- and 10-mo follow-ups. RESULTS: The average weight loss was 10% after 2 mo of dieting and 9% and 6% after 3- and 10-mo follow-ups, respectively. Daytime sleepiness and time to fall asleep decreased during weight loss. Short (≤7 h) and average (>7 to <9 h) sleepers increased their sleep duration, whereas sleep duration in long sleepers (≥9 h) did not change significantly during weight loss. This change in sleep duration was concomitantly negatively correlated with the change in BMI during weight loss and after the 3-mo follow-up and with the change in fat mass after the 3-mo follow-up. CONCLUSIONS: Sleep duration benefits from weight loss or vice versa. Successful weight loss, loss of body fat, and 3-mo weight maintenance in short and average sleepers are underscored by an increase in sleep duration or vice versa. This trial was registered at clinicaltrials.gov as NCT01015508.

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.

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.