Adherence to Diet and Meal Timing in a Randomized Controlled Feeding Study of Time-Restricted Feeding

Adherence is critical in feeding studies to determine the efficacy of dietary interventions. This time-restricted intake of meals (TRIM) investigation was a controlled feeding study that randomized 41 participants to follow 12 weeks of time-restricted feeding (TRF) or a usual feeding pattern (UFP). Adherence was optimized through careful screening and participant orientation, flexibility in beverages and seasonings, and frequent contact between participants and staff. Adherence was measured daily using a self-administered diary form. We calculated the percentage of participant-days with perfect adherence to meal timing (ate all meals within their designated time window) and to food consumption (ate all study food and no non-study food). Adherence was compared between study arms, days of the week, and weeks of the study period using generalized estimating equations (GEE) regression. There was perfect adherence to meal timing on 87% of participant-days and to food consumption on 94% of participant-days, with no significant difference by arm. In UFP, but not TRF, participants had lower adherence to meal timing over the weekend (p-value = 0.002) and during the first two weeks of intervention (p-value = 0.03). A controlled feeding study randomizing free-living individuals to different meal timings achieved a high degree of adherence to meal timing and food consumption, utilizing multiple strategies.     

Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity

Background: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. Methods: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. Results: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. Conclusions: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.     

Four Weeks of 16/8 Time Restrictive Feeding in Endurance Trained Male Runners Decreases Fat Mass,without Affecting Exercise Performance

Background: Time restricted Feeding (TRF) is a dietary pattern utilized by endurance athletes, but there is insufficient data regarding its effects on performance and metabolism in this population. The purpose of this investigation was to examine the effects of a 16/8 TRF dietary pattern on exercise performance in trained male endurance runners. Methods: A 4-week randomized crossover intervention was used to compare an 8-h TRF to a 12-h normal diet (ND) feeding window. Exercise training and dietary intake were similar across interventions. Runners completed a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, a graded treadmill running test to assess substrate utilization, and ran a 10 km time trial to assess performance. Results: There was a significant decrease in fat mass in the TRF intervention (−0.8 ± 1.3 kg with TRF (p = 0.05), vs. +0.1 ± 4.3 kg with ND), with no significant change in fat-free mass. Exercise carbon dioxide production (VCO₂) and blood lactate concentration were significantly lower with the TRF intervention (p ≤ 0.02). No significant changes were seen in exercise respiratory exchange ratio or 10 km time trial performance (−00:20 ± 3:34 min:s TRF vs. −00:36 ± 2:57 min:s ND). Conclusion: This investigation demonstrated that adherence to a 4-week 16/8 TRF dietary intervention decreased fat mass and maintained fat-free mass, while not affecting running performance, in trained male endurance runners.     

Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag

We used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and Agrp/Npy mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured. Preventing the disruption of the food intake pattern during chronic jetlag using TRF restored the rhythmicity in hypothalamic clock gene mRNA expression of Reverbα but not of Arntl. TRF countered the changes in plasma ghrelin levels and in hypothalamic Npy mRNA expression induced by chronic jetlag, thereby reestablishing the food intake pattern. Increase in body mass induced by chronic jetlag was prevented. Alterations in diurnal fluctuations in fecal SCFAs during chronic jetlag were prevented thereby re-entraining the rhythmic expression of peripheral clock genes. In conclusion, TRF during chronodisruption re-entrains the rhythms in clock gene expression and signals from the gut that regulate food intake to normalize body homeostasis.     

限时进食调节光诱导超重/肥胖大鼠摄食、体温及瘦素昼夜节律的研究

目的 探讨限时进食（time-restricted feeding, TRF）对光诱导超重/肥胖大鼠进食、体温、褪黑素及瘦素昼夜节律的影响。方法 将65只SD雄性大鼠随机分为正常光照LD组（light/dark:12 h/12 h,20只）、24 h光照LL组（light/dark:24 h/0 h,45只）,自由进食普通饲料,34 d后在LL组筛选出高于LD组体重均值10%以上的样本为模型LL组（20只）,再将正常光照LD组随机分为LD+自由进食组（LD+ALF组）、LD+TRF组;LL组随机分为LL+自由进食组（LL+ALF组）、LL+TRF组,TRF进食窗为10 h(ZT 14-ZT 24),每日记录饲料摄入量,隔日记录体重变化。饲养3周后分别时序记录体温、留取尾尖血,于第24 d采集空腹血后处死大鼠,采用ELISA法检测血清褪黑素、瘦素的含量变化,利用Matlab软件进行时序指标余弦拟合。结果 模型组体重增加、褪黑素均值降低,与正常光照组比较差异有统计学意义（P<0.05）。TRF干预3周后,LD+ALF、LD+TRF组大鼠平均饲料累积摄入量均显著低于LL+ALF、LL+...     

Time-Restricted Feeding and Metabolic Outcomes in a Cohort of Italian Adults

Background: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals. Methods: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h. Results: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes. Conclusions: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study.     

Time-Restricted Feeding Restores Obesity-Induced Alteration in Adipose Tissue Immune Cell Phenotype

Studies suggest that time-restricted feeding (TRF) may prevent obesity and its commodities. At present, little is known about how TRF impacts immune cells, and whether such an effect is linked to altered metabolic parameters under condition of a high-fat diet (HFD)-induced obesity. To address these issues, we conducted a study in which we determined whether TRF has therapeutic efficacy against weight gain, adiposity, as well as associated immune cell disturbance found in obese mice. Six-week-old male C57BL/6 mice were fed a low-fat diet (LFD) or HFD ad libitum for six weeks, after which time a subgroup of HFD mice was switched to the 10 h TRF paradigm (HFD-TRF) for additional eight weeks. We found that TRF intervention reduced HFD-induced weight gain. Even with comparable fat mass and mean adipocyte area, the HFD-TRF group had lower mRNA levels of proinflammatory cytokine Tnfα and chemokine Ccl8, along with reduced numbers of adipose tissue macrophages (ATM), CD11c⁺ ATM, and CD8⁺ T cell compared to the HFD group, while maintaining CD8⁺ to CD4⁺ ratio at levels similar to those in the LFD group. Furthermore, TRF intervention was effective in improving glucose tolerance and reducing HOMA-IR. Taken together, our findings suggest that TRF restores the obesity-induced alteration in immune cell composition, and this effect may in part contribute to health benefits (including insulin sensitivity) of practicing TRF.     

Exercising fasting or fed to enhance fat loss? Influence of food intake on respiratory ratio and excess postexercise oxygen consumption after a bout of endurance training

Exercise and nutrition are often used in combination to lose body fat and reduce weight. In this respect, exercise programs are as important as correct nutrition. Several issues are still controversial in this field, and among them there are contrasting reports on whether training in a fasting condition can enhance weight loss by stimulating lipolytic activity. The authors' purpose was to verify differences in fat metabolism during training in fasting or feeding conditions. They compared the effect on oxygen consumption (VO2) and substrate utilization, estimated by the respiratory-exchange ratio (RER), in 8 healthy young men who performed the same moderate-intensity training session (36 min of cardiovascular training on treadmill at 65% maximum heart rate) in the morning in 2 tests in random sequence: FST test (fasting condition) without any food intake or FED test (feeding condition) after breakfast. In both cases, the same total amount and quality of food was assumed in the 24 hr after the training session. The breakfast, per se, increased both VO2 and RER significantly (4.21 vs. 3.74 and 0.96 vs. 0.84, respectively). Twelve hours after the training session, VO2 was still higher in the FED test, whereas RER was significantly lower in the FED test, indicating greater lipid utilization. The difference was still significant 24 hr after exercise. The authors conclude that when moderate endurance exercise is done to lose body fat, fasting before exercise does not enhance lipid utilization; rather, physical activity after a light meal is advisable.     

Signaux anaboliques et optimisation du métabolisme musculaire

Control of muscle mass and function is dependent on biochemical processes for synthesis and protein degradation. Dynamic imbalance of these pathways necessarily causes a gain or loss of muscle. These pathways are also regulated by nutrients, hormones or exercise. Thus, it is of interest to understand their effects and their involvement in physiological and pathological conditions such as aging or chronic diseases. Daily metabolic changes induced by food intake can help fight against muscle loss. New strategies to limit sarcopenia are precisely based on the nutritional characteristics of dietary protein, including feeding pattern and the timing of protein ingestion. Essential amino acids are also interesting to reach these objectives. Finally, multimodal therapeutic approaches to limit muscle loss may combine adequate protein intake, physical exercise, hormonal therapy or selective drugs.     

Early versus late time‐restricted feeding in adults at increased risk of developing type 2 diabetes: Is there an optimal time to eat for metabolic health?

Time‐restricted feeding (TRF) is a novel dietary approach where energy intake is limited to a set number of hours in the day (typically ≤12 hours), which leads to an extension of the daily fast that generally occurs overnight. Human pilot studies (based on animal experiments) have demonstrated that TRF has the potential to reduce risk factors for type 2 diabetes (T2DM): mediating weight loss, the reduction of low‐density lipoprotein (LDL) cholesterol and improving insulin sensitivity. However, it remains unclear whether it is better to restrict food intake to earlier in the day (early‐TRF) or later in the day (late‐TRF). The aim of this study is to investigate the effects of TRF on established risk factors for T2DM and its application to wider society. The primary hypothesis is that 10 weeks of daily TRF will reduce food intake, bodyweight and adiposity while improving markers of metabolic disease risk, such as LDL‐cholesterol and insulin sensitivity. The secondary hypothesis is that early‐TRF will induce larger metabolic changes in comparison to late‐TRF. Eligible volunteers will be randomised to either the early‐TRF (7 am to 3 pm), late‐TRF (12 pm to 8 pm) or control group (unrestricted eating window) for 10 weeks. Changes in fasting markers, diet, bodyweight and body composition will be assessed throughout the experiment, as well as the effects on psychological wellbeing and social and family interactions.     

Physiopathological mechanism of sarcopenia

The aetiology of sarcopenia is multifactorial but still poorly understood while the sequelae of this phenomenon, i.e. loss of independence and metabolic complications, represent a major public health. The most evident metabolic explanation for muscle decline in elderly people is an imbalance between protein synthesis abd breakdown rates but other causes like neurodegenerative processes, reduction in anabolic hormone productions or sensitivity such as insulin, growth and sex hormones, dysregulation of cytokine secretions, modification in the response to inflammatory events, inadequate nutritional intakes and sedentarity lifestyle are involved. Consequently, the age-related loss of muscle mass could be counteracted by adequate metabolic interventions including nutritional intakes or exercise training. Recent observations clearly show that changes in quantitative as well as qualitative intakes of dietary protein are able to counteract some pathophysiological processes related to muscle loss progression. Other strategies including changes in daily protein pattern, the speed of protein digestion or specific amino acids supplementation may be beneficial to improve short term muscle anabolic response in elderly people. The beneficial impact of resistance or endurance training on muscle mass and function is highlighted in many studies suggesting that the potential anabolic response to exercise still remains despite a lesser metabolic response to nutrients. Thus a multimodal approach combining nutrition, exercise, hormones, specific anabolic drugs may an innovative treatment for limiting the development of sarcopenia with aging.     

The Health Impact of Nighttime Eating: Old and New Perspectives

Nighttime eating, particularly before bed, has received considerable attention. Limiting and/or avoiding food before nighttime sleep has been proposed as both a weight loss strategy and approach to improve health and body composition. Indeed, negative outcomes have been demonstrated in response to large mixed meals in populations that consume a majority of their daily food intake during the night. However, data is beginning to mount to suggest that negative outcomes may not be consistent when the food choice is small, nutrient-dense, low energy foods and/or single macronutrients rather than large mixed-meals. From this perspective, it appears that a bedtime supply of nutrients can promote positive physiological changes in healthy populations. In addition, when nighttime feeding is combined with exercise training, any adverse effects appear to be eliminated in obese populations. Lastly, in Type I diabetics and those with glycogen storage disease, eating before bed is essential for survival. Nevertheless, nighttime consumption of small (~150 kcals) single nutrients or mixed-meals does not appear to be harmful and may be beneficial for muscle protein synthesis and cardiometabolic health. Future research is warranted to elucidate potential applications of nighttime feeding alone and in combination with exercise in various populations of health and disease.     

Effects of a longitudinal training program on responses to exercise in overweight men

OBJECTIVE: The aim of this study was to determine how training modifies metabolic responses and lipid oxidation in overweight young male subjects. RESEARCH METHODS AND PROCEDURES: Eleven overweight subjects were selected for a 4-month endurance training program. Before and after the training period, they cycled for 60 minutes at 50% of their VO(2)max after an overnight fast or 3 hours after eating a standardized meal. Various metabolic and endocrine parameters, and respiratory exchange ratio values were evaluated. RESULTS: Exercise-induced plasma norepinephrine concentration increases were similar before and after training in fasted or fed conditions. After food intake, exercise promoted a decrease in plasma glucose and a higher increase in epinephrine than in fasting conditions. The increase in epinephrine after the meal was more marked after training (264 +/- 32 vs. 195 +/- 35 pg/mL). Training lowered the resting plasma nonesterified fatty acids. During exercise, changes in glycerol were similar to those found before training. Lipid oxidation during exercise was higher in fasting than in fed conditions (15.5 +/- 1.4 vs. 22.3 +/- 1.7 g/h). Training did not significantly increase fat oxidation when exercise was performed in fed conditions, but it did in fasting conditions (18.6 +/- 1.4 vs. 27.2 +/- 1.8 g/h). DISCUSSION: Endurance training decreased plasma nonesterified fatty acids, cholesterol, and insulin concentrations. Training increased lipid oxidation during exercise, in fasting conditions, and not when exercise was performed after the meal. During exercise in overweight subjects, the fasting condition seems more suited to oxidizing fat and maintaining glucose homeostasis than a 3-hour wait after a standard meal.     

Can Fasting Curb the Metabolic Syndrome Epidemic?

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia. Due to the high prevalence (around 1/3 of the world population) economic burden of MetS, there is a need for new dietary, lifestyle, and therapeutic options. Recently, fasting emerged as a dietary method proposed for controlling metabolic risk factors. Intermittent fasting (IF), or time-restricted feeding (TRF), describes an array of feeding patterns in which calorie intake is restricted to a specific time period. Hence, this review aimed to elucidate the latest data on MetS and explore the viability of simple management options, such as IF and TRF. Preclinical studies have shown how IF/TRF exerts beneficial effects on the gut microbiota, glucose and insulin metabolism, weight and visceral fat, and lipid metabolism. However, the results obtained from human studies are somewhat conflicting, as weight loss was achieved in all studies, whereas in some studies, there was no significant effect on insulin resistance, cholesterol/lipid metabolism, or blood pressure. Nevertheless, as only very few human studies were performed, there is a need for more randomized control trials on larger cohorts of patients with MetS to gather higher-yield evidence to clarify whether IF/TRF are suitable dietary patterns for this population.     

Pre-Exercise Nutrition: The Role of Macronutrients,Modified Starches and Supplements on Metabolism and Endurance Performance

Endurance athletes rarely compete in the fasted state, as this may compromise fuel stores. Thus, the timing and composition of the pre-exercise meal is a significant consideration for optimizing metabolism and subsequent endurance performance. Carbohydrate feedings prior to endurance exercise are common and have generally been shown to enhance performance, despite increasing insulin levels and reducing fat oxidation. These metabolic effects may be attenuated by consuming low glycemic index carbohydrates and/or modified starches before exercise. High fat meals seem to have beneficial metabolic effects (e.g., increasing fat oxidation and possibly sparing muscle glycogen). However, these effects do not necessarily translate into enhanced performance. Relatively little research has examined the effects of a pre-exercise high protein meal on subsequent performance, but there is some evidence to suggest enhanced pre-exercise glycogen synthesis and benefits to metabolism during exercise. Finally, various supplements (i.e., caffeine and beetroot juice) also warrant possible inclusion into pre-race nutrition for endurance athletes. Ultimately, further research is needed to optimize pre-exercise nutritional strategies for endurance performance.     

A Low-Glucose Eating Pattern Improves Biomarkers of Postmenopausal Breast Cancer Risk: An Exploratory Secondary Analysis of a Randomized Feasibility Trial

Postmenopausal breast cancer is the most common obesity-related cancer death among women in the U.S. Insulin resistance, which worsens in the setting of obesity, is associated with higher breast cancer incidence and mortality. Maladaptive eating patterns driving insulin resistance represent a key modifiable risk factor for breast cancer. Emerging evidence suggests that time-restricted feeding paradigms (TRF) improve cancer-related metabolic risk factors; however, more flexible approaches could be more feasible and effective. In this exploratory, secondary analysis, we identified participants following a low-glucose eating pattern (LGEP), defined as consuming energy when glucose levels are at or below average fasting levels, as an alternative to TRF. Results show that following an LGEP regimen for at least 40% of reported eating events improves insulin resistance (HOMA-IR) and other cancer-related serum biomarkers. The magnitude of serum biomarkers changes observed here has previously been shown to favorably modulate benign breast tissue in women with overweight and obesity who are at risk for postmenopausal breast cancer. By comparison, the observed effects of LGEP were similar to results from previously published TRF studies in similar populations. These preliminary findings support further testing of LGEP as an alternative to TRF and a postmenopausal breast cancer prevention strategy. However, results should be interpreted with caution, given the exploratory nature of analyses.     

Complementary Feeding and Overweight in European Preschoolers: The ToyBox-Study

Complementary feeding (CF) should start between 4–6 months of age to ensure infants’ growth but is also linked to childhood obesity. This study aimed to investigate the association of the timing of CF, breastfeeding and overweight in preschool children. Infant-feeding practices were self-reported in 2012 via a validated questionnaire by >7500 parents from six European countries participating in the ToyBox-study. The proportion of children who received breast milk and CF at 4–6 months was 51.2%. There was a positive association between timing of solid food (SF) introduction and duration of breastfeeding, as well as socioeconomic status and a negative association with smoking throughout pregnancy (p < 0.005). No significant risk to become overweight was observed among preschoolers who were introduced to SF at 1–3 months of age compared to those introduced at 4–6 months regardless of the type of milk feeding. Similarly, no significant association was observed between the early introduction of SF and risk for overweight in preschoolers who were breastfed for ≥4 months or were formula-fed. The study did not identify any significant association between the timing of introducing SF and obesity in childhood. It is likely that other factors than timing of SF introduction may have impact on childhood obesity.     

Eat the meat or feed the meat: protein turnover in remodeling muscle

PURPOSE OF REVIEW: The present review outlines the role of muscle protein turnover in muscle remodeling, with emphasis on the effects of nutrition and exercise. RECENT FINDINGS: Progress in our understanding of the pathways signaling and regulating protein synthesis and degradation, and thus protein turnover, in skeletal muscle has been substantial over the past decade. Protein synthesis and degradation jointly allow the active remodeling of skeletal muscle to adapt to changes in mechanical and metabolic demand. Nutrition and exercise are potent ways to stimulate protein turnover. This occurs in an amino acid and exercise-type (resistance versus endurance) and mode (lengthening and shortening)-specific manner. SUMMARY: For optimal muscle remodeling, the timing and type of feeding and exercise appear to be crucial.     

Interactions of iron deficiency and exercise training relative to tissue norepinephrine turnover, triiodothyronine production and metabolic rate in rats

The interactions of iron deficiency and exercise training relative to resting metabolic rate (RMR), tissue norepinephrine (NE) turnover and triiodothyronine (T3) production were examined in male Sprague-Dawley rats. Animals were assigned to iron-deficient (ID) or control (CN) diets and to sedentary (SD) or treadmill-exercise (EX) groups for 6 or 12 wk. Iron-deficient animals (hemoglobin 7.2 +/- 0.2 g 100 mL-1) had a 17% higher RMR and had slower growth rates than CN animals. Exercise training affected growth but not RMR in iron deficiency. Oxygen consumption (Vo2) following pharmacologic injection of norepinephrine was similar in both iron-deficient and exercised groups despite a 35% lower maximal exercise Vo2 in trained iron-deficient rats. NE turnover was lower in heart (55%) and liver (80%) of iron-deficient animals relative to controls. Trained iron-deficient animals had lower NE turnover in interscapular brown adipose tissue (IBAT) than sedentary iron-deficient animals; however, training did not alter NE turnover in control animals. In vitro liver and IBAT T3 production was similar in all groups except for lower activities (40%) in 6-wk iron-deficient, exercised animals. The significant effect of exercise on the growth attenuation of iron-deficient, exercised animals is thus not explained by increased IBAT metabolic activity or a generalized sympathetic nervous system activation. Decreased T3 production during periods of rapid growth and lean body mass development, however, may be important in exercised, iron-deficient animals.