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    Decreased thermic effect of food after an irregular compared with a regular meal pattern in healthy lean women. Farshchi H R,Taylor M A,Macdonald I A International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity OBJECTIVES:To investigate the impact of irregular meal frequency on body weight, energy intake, appetite and resting energy expenditure in healthy lean women. DESIGN:Nine healthy lean women aged 18-42 y participated in a randomised crossover trial consisting of three phases over a total of 43 days. Subjects attended the laboratory at the start and end of phases 1 and 3. In Phase 1 (14 days), subjects were asked to consume similar things as normal, but either on 6 occasions per day (regular meal pattern) or follow a variable predetermined meal frequency (between 3 and 9 meals/day) with the same total number of meals over the week. In Phase 2 (14 days), subjects continued their normal diet as a wash-out period. In Phase 3 (14 days), subjects followed the alternative meal pattern to that followed in Phase 1. Subjects recorded their food intake for three predetermined days during the irregular period when they were eating 9, 3 and 6 meals/day. They also recorded their food intake on the corresponding days during the regular meal pattern period. Subjects fasted overnight prior to each laboratory visit, at which fasting resting metabolic rate (RMR) was measured by open-circuit indirect calorimetry. Postprandial metabolic rate was then measured for 3 h after the consumption of a milkshake test meal (50% CHO, 15% protein and 35% fat of energy content). Subjects rated appetite before and after the test meal. RESULTS:There were no significant differences in body weight and 3-day mean energy intake between the regular and irregular meal pattern. In the irregular period, the mean energy intake on the day when 9 meals were eaten was significantly greater than when 6 or 3 meals were consumed (P=0.0001). There was no significant difference between the 3 days of the regular meal pattern. Subjective appetite measurement showed no significant differences before and after the test meal in all visits. Fasting RMR showed no significant differences over the experiment. The overall thermic effect of food (TEF) over the 3 h after the test meal was significantly lower after the irregular meal pattern (P=0.003). CONCLUSION:Irregular meal frequency led to a lower postprandial energy expenditure compared with the regular meal frequency, while the mean energy intake was not significantly different between the two. The reduced TEF with the irregular meal frequency may lead to weight gain in the long term. 10.1038/sj.ijo.0802616
    Acute effects on metabolism and appetite profile of one meal difference in the lower range of meal frequency. Smeets Astrid J,Westerterp-Plantenga Margriet S The British journal of nutrition A gorging pattern of food intake has been shown to enhance lipogenesis and increase body weight, which may be due to large fluctuations in storage and mobilisation of nutrients. In a state of energy balance, increasing meal frequency, and thereby decreasing inter-meal interval, may prevent large metabolic fluctuations. Our aim was to study the effect of the inter-meal interval by dividing energy intake over two or three meals on energy expenditure, substrate oxidation and 24 h satiety, in healthy, normal-weight women in a state of energy balance. The study was a randomised crossover design with two experimental conditions. During the two experimental conditions subjects (fourteen normal-weight women, aged 24.4 (SD 7.1) years, underwent 36 h sessions in energy balance in a respiration chamber for measurements of energy expenditure and substrate oxidation. The subjects were given two (breakfast, dinner) or three (breakfast, lunch, dinner) meals per d. We chose to omit lunch in the two meals condition, because this resulted in a marked difference in inter-meal-interval after breakfast (8.5 h v. 4 h). Eating three meals compared with two meals had no effects on 24 h energy expenditure, diet-induced thermogenesis, activity-induced energy expenditure and sleeping metabolic rate. Eating three meals compared with two meals increased 24 h fat oxidation, but decreased the amount of fat oxidised from the breakfast. The same amount of energy divided over three meals compared with over two meals increased satiety feelings over 24 h. In healthy, normal-weight women, decreasing the inter-meal interval sustains satiety, particularly during the day, and sustains fat oxidation, particularly during the night. 10.1017/S0007114507877646
    The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting. Paoli Antonio,Tinsley Grant,Bianco Antonino,Moro Tatiana Nutrients The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective research has demonstrated a significant increase in disease risk with a high meal frequency (≥6 meals/day) as compared to a low meal frequency (1⁻2 meals/day). Apart from meal frequency and timing we also have to consider breakfast consumption and the distribution of daily energy intake, caloric restriction, and night-time eating. A central role in this complex scenario is played by the fasting period length between two meals. The physiological underpinning of these interconnected variables may be through internal circadian clocks, and food consumption that is asynchronous with natural circadian rhythms may exert adverse health effects and increase disease risk. Additionally, alterations in meal frequency and meal timing have the potential to influence energy and macronutrient intake.A regular meal pattern including breakfast consumption, consuming a higher proportion of energy early in the day, reduced meal frequency (i.e., 2⁻3 meals/day), and regular fasting periods may provide physiological benefits such as reduced inflammation, improved circadian rhythmicity, increased autophagy and stress resistance, and modulation of the gut microbiota. 10.3390/nu11040719
    Energy depletion by 24-h fast leads to compensatory appetite responses compared with matched energy depletion by exercise in healthy young males. Thivel David,Finlayson Graham,Miguet Maud,Pereira Bruno,Duclos Martine,Boirie Yves,Doucet Eric,Blundell John E,Metz Lore The British journal of nutrition Although there is a growing interest for the effects of intermittent fasting on energy balance, this study aimed to compare appetite, energy intake and food reward responses with an energy depletion induced either by 24-h food restriction or an equivalent deficit with exercise in healthy males. In all, twelve healthy lean males (21·5 (sd 0·5) years old; BMI: 22·5 (sd 1·7) kg/m2) participated in this study. Body composition, aerobic capacity, food preferences and energy intake were assessed. They randomly completed three conditions: (i) no depletion (CON); (ii) full 24-h energy restrictions (Def-EI); and (iii) exercise condition (Def-EX). Ad libitum energy intake and food reward were assessed at the end of each session. Appetite feelings were assessed regularly. Ad libitum energy intake was higher on Def-EI (7330 (sd 2975) kJ (1752 (sd 711) kcal) compared with that on CON (5301 (sd 1205) kJ (1267 (sd 288) kcal)) (P<0·05), with no difference between CON and Def-EX (6238 (sd 1741) kJ (1491 (sd 416) kcal) (P=0·38) and between Def-EX and Def-EI (P=0·22). There was no difference in the percent energy ingested from macronutrients. Hunger was lower on CON and Def-EX compared with Def-EI (P<0·001). Satiety was higher on CON and Def-EI compared with that on Def-EX (P<0·001). There was a significant interaction condition × time for food choice fat bias (P=0·04), showing a greater preference for high-fat v. low-fat food during Def-EI and Def-EX. Although 24-h fasting leads to increased energy intake at the following test meal (without total daily energy intake difference), increased hunger profile and decreased post-meal food choice fat bias, such nutritional responses are not observed after a similar deficit induced by exercise. 10.1017/S0007114518001873
    Metabolic impacts of altering meal frequency and timing - Does when we eat matter? Hutchison Amy T,Heilbronn Leonie K Biochimie Obesity prevalence continues to rise throughout the developed world, as a result of positive energy balance and reduced physical activity. At present, there is still a perception within the general community, and amongst some nutritionists, that eating multiple small meals spaced throughout the day is beneficial for weight control and metabolic health. However, intervention trials do not generally support the epidemiological evidence, and data is emerging to suggest that increasing the fasting period between meals may beneficially impact body weight and metabolic health. To date, this evidence is of short term duration, and it is becoming increasingly apparent that meal timing must also be considered if we are to ensure optimal health benefits in response to this dietary pattern. The purpose of this review is to summate the existing human literature on modifying meal frequency and timing on body weight control, appetite regulation, energy expenditure, and metabolic health under conditions of energy balance, restriction and surplus. 10.1016/j.biochi.2015.07.025
    The rate of weight loss does not affect resting energy expenditure and appetite sensations differently in women living with overweight and obesity. Hintze Luzia Jaeger,Goldfield Gary,Seguin Ryan,Damphousse Aleck,Riopel Alexandre,Doucet Éric Physiology & behavior BACKGROUND:Evidence of metabolic adaptations following weight loss is available in the literature. However, the impact of different degrees of caloric restriction on a comprehensive panel including energy expenditure (EE) and intake (EI), appetite, palatability and olfactory performance remains to be investigated. Accordingly, the purpose of the study was to investigate the changes in resting energy expenditure (REE), appetite, olfaction, palatability and EI in women who were engaged in either a slow (-500 kcal/day, 20-week) or in a rapid (-1000 kcal/ day, 10 weeks) weight loss program. METHODS:Thirty-six women with obesity were randomized to a slow or to a rapid weight loss group. Body composition (DXA), REE (indirect calorimetry), olfactory performance (Sniffin' Sticks), appetite (Visual Analogue Scale) were assessed at multiple time points during the intervention. RESULTS:A total of 30 participants completed the study (slow group n = 14; rapid group n = 16). Body weight decreased by -4.46 (3.99) % (P < .001) and - 6.23 (3.06) % (P = .001) in the slow and rapid groups, respectively. No differences in % weight loss were noted between groups (P = .175). Significant decreases in fat mass (P < .001), REE (P = .035), total EI (P = .001) were observed over time from both groups. However, no significant differences emerged between groups for any of the outcomes. The satiety quotient (SQ) at time 180 min significantly increased for desire to eat (P = .01), hunger (P = .011) and PFC (P = .002), while the area under the curve for postprandial appetite rates were not changed. No differences in palatability and olfactory performance were noted after the intervention. CONCLUSIONS:Our results suggest that different rates of weight loss exert similar effects on REE, appetite, satiety, and EI when weight loss are comparable. 10.1016/j.physbeh.2018.11.032
    Time-restricted feeding for prevention and treatment of cardiometabolic disorders. Melkani Girish C,Panda Satchidananda The Journal of physiology The soaring prevalence of obesity and diabetes is associated with an increase in comorbidities, including elevated risk for cardiovascular diseases (CVDs). CVDs continue to be among the leading causes of death and disability in the United States. While increased nutritional intake from an energy-dense diet is known to disrupt metabolic homeostasis and contributes to the disease risk, circadian rhythm disruption is emerging as a new risk factor for CVD. Circadian rhythms coordinate cardiovascular health via temporal control of organismal metabolism and physiology. Thus, interventions that improve circadian rhythms are prospective entry points to mitigate cardiometabolic disease risk. Although light is a strong modulator of the neural circadian clock, time of food intake is emerging as a dominant agent that affects circadian clocks in metabolic organs. We discovered that imposing a time-restricted feeding (TRF) regimen in which all caloric intakes occur consistently within ≤ 12 h every day exerts many cardiometabolic benefits. TRF prevents excessive body weight gain, improves sleep, and attenuates age- and diet-induced deterioration in cardiac performance. Using an integrative approach that combines Drosophila melanogaster (fruit fly) genetics with transcriptome analyses it was found that the beneficial effects of TRF are mediated by circadian clock, ATP-dependent TCP/TRiC/CCT chaperonin and mitochondrial electron transport chain components. Parallel studies in rodents have shown TRF reduces metabolic disease risks by maintaining metabolic homeostasis. As modern humans continue to live under extended periods of wakefulness and ingestion events, daily eating pattern offers a new potential target for lifestyle intervention to reduce CVD risk. 10.1113/JP273094
    Sleep duration, nightshift work, and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women. Nagata Chisato,Tamura Takashi,Wada Keiko,Konishi Kie,Goto Yuko,Nagao Yasuko,Ishihara Kazuhiro,Yamamoto Satoru Chronobiology international It has been hypothesized that disruption of circadian rhythms affects human health. Shift work and sleep deprivation are thought to disrupt the normal light-dark cycle, although the disruption due to shiftwork may be dependent on sleep deprivation. Both conditions have been suggested to be associated with an increased risk of cardiometabolic disorders. Non-photic environmental factors, such as the timing of eating, are also thought to regulate circadian rhythm and thus, may have effects on health, but the evidence from human studies is scarce. Oxidative stress is a risk factor of cardiometabolic disorders. Some laboratory studies suggest an involvement of circadian clock genes in the regulation of the redox system. The present study aimed to examine the association of sleeping habits, nightshift work, and the timing of meals with urinary levels of 8-isoprostane, a marker of oxidative stress, and 6-sulfatoxymelatonin, the principal metabolite of melatonin. Study subjects were 542 women who had previously attended a breast cancer mass screening in a community in Japan. Information on bedtimes and wake-up times, history of nightshift work, and the timing of meals was obtained by a self-administered questionnaire. The 8-isoprostane and 6-sulfatoxymelatonin were measured using the first morning void of urine and expressed per mg of creatinine. The geometric mean of 8-isoprostane levels was 12.1% higher in women with ≤6 hours of sleep than that in those with >8 hours of sleep on weekdays, and longer sleep duration on weekdays was significantly associated with lower urinary levels of 8-isoprostane after controlling for covariates (p for trend = 0.04). Women who were currently working the nightshift had a 33.3% higher geometric mean of 8-isoprostane levels than those who were not working nightshift (p = 0.03). Urinary 6-sulfatoxymelatonin levels were unrelated to sleep habits or nightshift work. Women who ate breakfast at irregular times had a 19.8% higher geometric mean of 8-isoprostane levels than those who ate breakfast at a regular time or who did not eat (p = 0.02). Women who ate nighttime snacks at irregular times had a 16.2% higher geometric mean of 8-isoprostane levels than those who did not eat nighttime snacks or who ate nighttime snacks at a regular time (p = 0.003). Among women who ate dinner at a regular time, earlier times for dinner were associated with higher 8-isoprostane and 6-sulfatoxymelatonin levels (p values for trends were 0.01 and 0.02, respectively). However, the times of dinner and nighttime snack are overlapping, and the time of last meal of the day was not associated with 8-isoprostane and 6-sulfatoxymelatonin levels. The time of breakfast or lunch was not associated with these biomarkers among women who ate the meal at regular times. Disturbing the rhythmicity of daily life may be associated with oxidative stress. 10.1080/07420528.2017.1355313
    Two weeks of early time-restricted feeding (eTRF) improves skeletal muscle insulin and anabolic sensitivity in healthy men. Jones Robert,Pabla Pardeep,Mallinson Joanne,Nixon Aline,Taylor Tariq,Bennett Andrew,Tsintzas Kostas The American journal of clinical nutrition BACKGROUND:Altering the temporal distribution of energy intake (EI) and introducing periods of intermittent fasting (IF) exert important metabolic effects. Restricting EI to earlier in the day [early time-restricted feeding (eTRF)] is a novel type of IF. OBJECTIVES:We assessed the chronic effects of eTRF compared with an energy-matched control on whole-body and skeletal muscle insulin and anabolic sensitivity. METHODS:Sixteen healthy males (aged 23 ± 1 y; BMI 24.0 ± 0.6 kg·m-2) were assigned to 2 groups that underwent either 2 wk of eTRF (n = 8) or control/caloric restriction (CON:CR; n = 8) diet. The eTRF diet was consumed ad libitum and the intervention was conducted before the CON:CR, in which the diet was provided to match the reduction in EI and body weight observed in eTRF. During eTRF, daily EI was restricted to between 08:00 and 16:00, which prolonged the overnight fast by ∼5 h. The metabolic responses to a carbohydrate/protein drink were assessed pre- and post-interventions following a 12-h overnight fast. RESULTS:When compared with CON:CR, eTRF improved whole-body insulin sensitivity [between-group difference (95% CI): 1.89 (0.18, 3.60); P = 0.03; η2p = 0.29] and skeletal muscle uptake of glucose [between-group difference (95% CI): 4266 (261, 8270) μmol·min-1·kg-1·180 min; P = 0.04; η2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455) nmol·min-1·kg-1·180 min; P = 0.01; η2p = 0.44]. eTRF caused a reduction in EI (∼400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01) that was matched in CON:CR (-1.24 ± 0.35 kg; P = 0.01). CONCLUSIONS:Under free-living conditions, eTRF improves whole-body insulin sensitivity and increases skeletal muscle glucose and BCAA uptake. The metabolic benefits of eTRF are independent of its effects on weight loss and represent chronic adaptations rather than the effect of the last bout of overnight fast. This trial was registered at clinicaltrials.gov as NCT03969745. 10.1093/ajcn/nqaa192
    Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Jamshed Humaira,Beyl Robbie A,Della Manna Deborah L,Yang Eddy S,Ravussin Eric,Peterson Courtney M Nutrients Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl ( = 0.0003) and glycemic excursions by 12 ± 3 mg/dl ( = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene and the autophagy gene (all < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; = 0.10) and also increased the expression of ( = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes ( < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans. 10.3390/nu11061234
    Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans. Ravussin Eric,Beyl Robbie A,Poggiogalle Eleonora,Hsia Daniel S,Peterson Courtney M Obesity (Silver Spring, Md.) OBJECTIVE:Eating earlier in the daytime to align with circadian rhythms in metabolism enhances weight loss. However, it is unknown whether these benefits are mediated through increased energy expenditure or decreased food intake. Therefore, this study performed the first randomized trial to determine how meal timing affects 24-hour energy metabolism when food intake and meal frequency are matched. METHODS:Eleven adults with overweight practiced both early time-restricted feeding (eTRF) (eating from 8 am to 2 pm) and a control schedule (eating from 8 am to 8 pm) for 4 days each. On the fourth day, 24-hour energy expenditure and substrate oxidation were measured by whole-room indirect calorimetry, in conjunction with appetite and metabolic hormones. RESULTS:eTRF did not affect 24-hour energy expenditure (Δ = 10 ± 16 kcal/d; P = 0.55). Despite the longer daily fast (intermittent fasting), eTRF decreased mean ghrelin levels by 32 ± 10 pg/mL (P = 0.006), made hunger more even-keeled (P = 0.006), and tended to increase fullness (P = 0.06-0.10) and decrease the desire to eat (P = 0.08). eTRF also increased metabolic flexibility (P = 0.0006) and decreased the 24-hour nonprotein respiratory quotient (Δ = -0.021 ± 0.010; P = 0.05). CONCLUSIONS:Meal-timing interventions facilitate weight loss primarily by decreasing appetite rather than by increasing energy expenditure. eTRF may also increase fat loss by increasing fat oxidation. 10.1002/oby.22518
    Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial. Jakubowicz Daniela,Landau Zohar,Tsameret Shani,Wainstein Julio,Raz Itamar,Ahren Bo,Chapnik Nava,Barnea Maayan,Ganz Tali,Menaged Miriam,Mor Naomi,Bar-Dayan Yosefa,Froy Oren Diabetes care OBJECTIVE:In type 2 diabetes, insulin resistance and progressive β-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss and better glycemic control compared with an isocaloric six-meal diet (6Mdiet). RESEARCH DESIGN AND METHODS:Twenty-eight volunteers with diabetes (BMI 32.4 ± 5.2 kg/m and HbA 8.1 ± 1.1% [64.5 ± 11.9 mmol/mol]) were randomly assigned to 3Mdiet or 6Mdiet. Body weight, glycemic control, continuous glucose monitoring (CGM), appetite, and clock gene expression were assessed at baseline, after 2 weeks, and after 12 weeks. RESULTS:3Mdiet, but not 6Mdiet, led to a significant weight loss (-5.4 ± 0.9 kg) ( < 0.01) and decreased HbA (-12 mmol/mol [-1.2%]) ( < 0.0001) after 12 weeks. Fasting glucose and daily and nocturnal glucose levels were significantly lower on the 3Mdiet. CGM showed a significant decrease in the time spent in hyperglycemia only on the 3Mdiet. Total daily insulin dose was significantly reduced by 26 ± 7 units only on the 3Mdiet. There was a significant decrease in the hunger and cravings only in the 3Mdiet group. Clock genes exhibited oscillation, increased expression, and higher amplitude on the 3Mdiet compared with the 6Mdiet. CONCLUSIONS:A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss and significant reduction in HbA, appetite, and overall glycemia, with a decrease in daily insulin. Upregulation of clock genes seen in this diet intervention could contribute to the improved glucose metabolism. 10.2337/dc19-1142
    Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Sutton Elizabeth F,Beyl Robbie,Early Kate S,Cefalu William T,Ravussin Eric,Peterson Courtney M Cell metabolism Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss. 10.1016/j.cmet.2018.04.010