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Time-restricted eating research

Time-restricted eating research

The increase in pTregs in the eTRF group Tims-restricted also contribute Gaming power top-up the beneficial effects of eTRF Gaming power top-up fating, because a Time-rfstricted pTreg Time-rstricted is associated resaerch obesity, Time-restricted eating research Gymnastics performance food, and inflammatory responses 49505152 Mitchell SEDelville CKonstantopedos Pet al. Moon S, Kang J, Kim SH, Chung HS, Kim YJ, Yu JM, et al. Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice.

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Time-restricted eating research -

Metrics details. Time-restricted eating TRE is a current popular dietary strategy for noncommunicable diseases. However, studies demonstrated contradictory results for it and in all dietary strategies, diet quality is an the important part of the well-being. Our study aimed to investigate the effect of TRE and energy-restricted diet ERD on the nutritional status and diet quality of individuals.

This pilot study was completed 23 healthy overweight female. Anthropometric and body composition measurements of individuals were taken. The energy expenditure was measured using indirect calorimetry.

Blood pressure and heart rate measurements were made. Biochemical parameters were evaluated and food consumption were taken.

The quality of dietary intake was assessed using the Healthy Eating Index HEI The physical activity levels of the individuals were estimated using the physical activity record. The Statistical Package for the Social Sciences version A p-value of less than 0.

There was a 3. A statistically significant decrease was found in the total cholesterol 3. In addition, a statistically significant increase was found in adiponectin Energy-restricted diet yielded better results in weight loss and improvement of body composition and diet quality compared to TRE.

Also, a decrease in total cholesterol level was found in the ERD group. However, more studies should be done with longer follow-ups and high sample sizes are very important in terms of creating public health-based recommendations.

Peer Review reports. Obesity is a health problem that affects all age groups and has a high prevalence worldwide. The prevalence of obesity worldwide has nearly tripled since When viewed on the basis of gender; in , According to the World Health Organization European Regional Obesity Report , while the prevalence of obesity among adults in Europe is Lifestyle changes are recommended along with diets in which individual-specific energy restriction is applied to ensure body weight loss, improve body composition and metabolic health [ 4 ].

However, with this diet approach, both the goal of body weight loss is achieved in a long time and the compliance of individuals to the diet may decrease [ 5 , 6 , 7 ]. Intermittent fasting, which has become a popular topic recently, is an alternative energy restriction method that has emerged to provide body weight loss with dietary modifications, improve body composition, prevent or treat obesity and chronic diseases [ 8 , 9 , 10 , 11 ].

It is a dietary approach characterized by diurnal nutrition and prolongation of nocturnal fasting. This dietary approach provides individuals with the opportunity to be fed ad libitum without the need to calculate the energy taken outside of the fasting period.

In this dietary approach, there is no intervention to change the amount of food intake of individuals [ 12 , 13 ].

Time-restricted eating is a dietary approach that is based on the reduction of daily eating time and is suitable for human physiology, without night eating.

Therefore, it is associated with the circadian rhythm. The hypothesis that meal timing and increased daily eating time may cause metabolic dysfunction has been put forward in recent years.

Frequent eating ensures the physiology of satiety, causes deterioration of the metabolic state during fasting, and decreases the normal circadian oscillator in metabolic organs, including the liver.

It has been reported that TRE practice compatible with the circadian rhythm can have a positive effect on body composition, metabolic processes and preventing the formation of chronic diseases [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].

In the literature, the number of studies investigating the effect of TRE on diet quality is quite limited [ 23 , 24 ]. This study was planned to investigate the effect of TRE on the nutritional status and diet quality of individuals and to compare the effects of TRE and energy-restricted diet ERD in healthy overweight individuals.

It is thought that the study will fill an important gap in the literature. This experimental study was carried out with 26 healthy overweight female individuals aged between 19 and 32 years, who applied to Gazi University Faculty of Health Sciences Nutrition and Diet Individual Counseling Center between January - May The study was completed by 23 individuals with 10 individuals in the TRE group.

Three individuals were excluded from the study because they did not adhere to the diet. In addition, individuals were asked to maintain their physical activity levels throughout the study. Through an application on the phone, the daily step count of the individuals was determined and their physical activity levels were followed during the study.

For this reason, individuals who wanted to increase their physical activity level in addition to the applied diet were not included in the study. Consent form was signed by the individuals who accepted the study. All procedures were carried out in accordance with the Declaration of Helsinki. The data were collected using a face-to-face interview method via a questionnaire.

All measurements were made on individuals in both groups. They were fed ad libitum between m and fasted between No restrictions were imposed on the type and amount of food consumed during the feeding period.

During the fasting period, individuals consumed water and non-energy drinks tea, coffee, soda, etc. Individuals in the ERD group followed a diet specially prepared for them for 8 weeks.

At the first encounter with individuals, resting energy expenditure REE was measured by the indirect calorimetry method. Physical Activity Level PAL was determined by physical activity record.

Individuals were not given a diet containing energy below the REE. Acceptable macronutrient distribution range were taken as dietary content. Nutritional habits of individuals were taken into consideration while planning the diet. Each individual consumed 3 main meals and the number of snacks was determined individually.

Food exchange lists were given to individuals and nutrient changes were explained in detail. Anthropometric and body composition measurements of individuals were taken by the researcher at the beginning and end of the study in accordance with technique.

Body weight and body composition measurements were taken using an Inbody body analyzer. Inbody is multifrequency and has a bioelectrical impedance analysis system. The height of the individuals was measured with a stadiometer with a sensitivity of 0.

For waist circumference measurement, the midpoint between the lowest rib bone and the cristailiac was found, and the circumference measurement passing through this point was taken.

Neck circumference was measured with a non-flexible tape measure perpendicular to the neck axis, just below the cricoid cartilage, with the head in an upright position [ 29 ]. The degree of visceral adiposity range 1—59 arbitrary units and abdominal adiposity were measured with the Tanita Viscan AB abdominal analyzer.

Tanita Viscan AB has bioelectrical impedance analysis and the amount of visceral and abdominal fat is estimated by measuring the voltage produced in this location [ 30 ].

Resting energy expenditure was measured at the beginning and end of the study using indirect calorimetry COSMED, FitMatePro, Rome, Italy. Measurements were taken in the early morning hours after at least 8 h of fasting.

The device is automatically calibrated before each measurement. Measurements were taken in a quiet environment with a room temperature of 22—24 °C while the subjects were resting in a still and supine position.

Each measurement took an average of 15 min [ 31 , 32 ]. Blood samples from individuals were taken at the beginning and end of the study, after at least 8 h of fasting, in the morning hours by the Gazi University Medical Faculty Hospital blood collection unit in 10 ml yellow capped tubes and delivered to the researcher.

The blood samples, which were kept for half an hour by the researcher, were then centrifuged at rpm for 15 min to ensure separation of serum and stored as samples at ºC. Total cholesterol, high density lipoprotein cholesterol HDL-C , triglyceride, fasting glucose, insulin, C-reactive protein and interleukin 6 IL-6 were analyzed in Gazi University Medical Faculty Hospital Biochemistry Laboratory.

Total cholesterol, HDL-C, triglyceride and fasting glucose analysis were performed on Beckman Coulter AU biochemistry analyzer. The calculated LDL-C level was taken from the system. Insulin analysis was performed on a Beckman Coulter DxI hormone autoanalyzer operating with the chemiluminescence method.

C-reactive protein analysis was measured on a Beckman Coulter Immage autoanalyzer according to the nephelometric method. Homeostatic Model Assessment of Insulin Resistance HOMA-IR was calculated by the researcher.

The HOMA-IR cut-off point was taken as 2. Leptin and adiponectin analysis were performed in a private laboratory with Sunred ELISA kits [ 35 ]. Total antioxidant status TAS and total oxidant status TOS analysis were performed on Mindray BS autoanalyzer with Relassay ELISA kits.

Oxidative stress index OSI was obtained by multiplying the ratio of total oxidant status to total antioxidant status by The measurement was made 3 times on the left arm after 20 min of rest and the average values were taken. At the beginning of the study, it was explained how the dietary records would be taken by the expert dietitian researcher and a dietary record form was given.

Dietary records of the individuals were taken by the researcher for 3 days 2 days on weekdays, 1 day on weekends before the study, in the first and last week of the study. The energy and nutrient intakes of the individuals during the study were determined by calculating the average of the dietary records taken in the first and last week.

Energy and nutrient intakes of individuals were calculated using the Nutrition Information System BEBIS 8. This program is a software program used in Turkey to calculate the nutritional value of foods [ 38 ].

Diet quality was assessed with the Healthy Eating Index HEI The index consists of 13 components. HEI components are reverse scored based on their consumption of fatty acids, sodium, added sugars, and saturated fats.

The total score is obtained by summing the scores of 13 components. The highest score on the index is and the lowest score is zero. In the study, only the amount of sodium that individuals take with food was questioned, and table salt was not included in the amount of sodium.

The physical activity levels of the individuals were determined at the beginning of the study using the physical activity record.

The type and duration of the activities performed by the individuals were recorded in the form. The activity durations min were multiplied by the energy costs Physical Activity Ratio-PAR values according to the types of physical activities, and the values found were summed.

PAL was calculated by dividing the total sum of PAR x min values by min. Individuals were asked to maintain their physical activity levels throughout the study. The daily step count of individuals during the study was determined through an application on the smartphone Samsung Health.

Individuals with a daily step count of Data were evaluated with descriptive statistics such as mean, standard deviation, median, number, percentage and quartile.

Distribution analysis of the data was performed using the histogram, coefficient of variation ratio, Skewness, Kurtosis and Kolmogorov-Smirnov tests. Mann Whitney U test was used in independent groups and Wilcoxon test was used in dependent groups for comparison of paired groups.

Differences in mean values between groups were evaluated with the Independent t test. The McNemar-Bowker test was used in dependent groups to compare categorical variables. Chi-square analysis was used to compare qualitative data and detect differences between groups.

Twenty-three healthy and overweight female individuals aged between 19 and 32 years participated in the study. The characteristics of the individuals at the beginning of the study are given in Table 1. Age and BMI were similar between groups.

The changes in anthropometric measurement, body composition and energy expenditure of individuals as a result of the eight-week diet intervention are given in Table 2. It was determined that in TRE group there was a decrease of 2. In the ERD group there was a decrease of 4.

The decrease in body weight, waist circumference, BMI, fat mass and body fat percentage was higher in the ERD group. Also, the increase in fat free mass percentage and body water percentage was higher in the ERD group.

Changes in biochemical parameters and blood pressure of individuals are given in Table 3. The amount of energy and nutrients that individuals take in the diet are given in Table 4.

The comparison of diet qualities is given in Table 5. While The consumption amounts of the food groups calculated from the food consumption record of the individuals in the TRE group are given in Fig. The consumption amounts of the food groups calculated from the food consumption record of the individuals in the ERD group are given in Fig.

A statistically significant decrease was determined in the consumption of bread and cereals, oilseeds, solid fats, oils, sugar and confectionery. Comparison of the consumption amounts of the food groups during the study of the individuals in the TRE and ERD groups is given in Fig. In this study, TRE and ERD were compared in terms of nutritional status and diet quality.

According to the results of the study, body weight loss was observed and some biochemical parameters were improved in both ERD and TRE. However, only the individuals in the ERD group had an increase in diet quality and a decrease in body fat percentage.

Time-restricted eating is promising in terms of body weight loss in this study. It was determined that the overweight individuals in the TRE group had a 3.

Consistent with this study, Chow et al. In previous similar studies, body weight loss was observed in individuals [ 43 , 44 , 45 , 46 ], but contrary to this study, most of studies conducted showed a significant decrease in body fat percentages with loss of body weight in individuals [ 43 , 45 , 47 , 48 ].

Similar to this study, in different studies, a significant decrease was found in the waist circumference, and it was concluded that TRE has the potential to reduce the risk of abdominal obesity and cardiometabolic disease [ 45 , 49 ].

In all of the studies within our knowledge in the literature, it has been shown that the ERD has positive effects on anthropometric measurements and body composition in parallel with this study [ 50 , 51 , 52 , 53 ].

In the study of Catenacci et al. In the study of Carter et al. In the study of Varady et al. Changes in body weight and composition of individuals may differ depending on the methodology and duration of the studies.

In this study, a decrease was observed in the REE of individuals in both groups, but these changes were not statistically significant. In addition, individuals maintained their physical activity levels during the study, therefore, no significant change was determined in the TEE of the individuals.

Similar to this study, it was concluded that TRE [ 47 , 56 ] and ERD practices [ 53 ] did not provide a significant change in REE of individuals. Eight weeks after the intervention, a significant decrease was found in total cholesterol and LDL-C in the TRE group.

In a study conducted by Wilkinson et al. The results of this study support the improvement in the lipid profile in the fasting state. The results obtained were very important in terms of reducing the risk of cardiovascular disease and improving metabolic health.

The proposed mechanism in this regard is the changes in the expression of peroxisome proliferator activated receptor alpha PPAR-α and peroxisome proliferator activated receptor gamma coactivator 1alpha PGC-1α in the liver during fasting. According to this mechanism; expression of PPAR-α and PGC-1α leads to increased fatty acid oxidation and apolipoprotein A synthesis, and decreased apolipoprotein B synthesis.

Fatty acid oxidation causes a decrease in liver triglyceride level and very low density lipoprotein production. Serum cholesterol and triglyceride concentrations decrease.

Fasting practices can reduce serum LDL-C levels by decreasing liver apolipoprotein B synthesis [ 57 ]. There was a significant decrease in total cholesterol levels of individuals in the ERD group. At the end of eight weeks, a decrease in the total cholesterol was detected.

In the study of Molina-Jiménez et al. Healthy nutrition recommendations are given to individuals with an ERD. It is thought that the change in food consumption of individuals has a positive effect on the total cholesterol level.

It is known that adipokine levels change depending on body weight loss. Circulating concentrations of adipokines produced by adipocyte excluding adiponectin tend to decrease with body weight loss, while adiponectin concentration tends to increase [ 59 , 60 , 61 ].

In the study of Christiansen et al. The results of the studies are similar to this study. In this study, individuals in the ERD group had a decrease in body weight, while an increase was observed in adiponectin levels.

Adiponectin is anti-atherogenic and has an insulin-sensitizing effect [ 64 , 65 ]. It can be said that the increase in the adiponectin levels of the individuals in this study may cause positive effects in terms of health. The antioxidant defense system plays a role against reactive oxygen species and oxidative stress in the body.

Antioxidants prevent or reduce the damage caused by oxidation in body tissues by scavenging free radicals, reactive oxygen and nitrogen species.

The main source of non-enzymatic antioxidants is a balanced diet. The main nutrients that are sources of antioxidants in the diet are vegetables and fruits containing vitamins A, E and C [ 66 , 67 ]. Parallel to this finding, there was a slight increase in the consumption of vegetables and a significant increase in the consumption of fruits.

In this study, it was determined that the mean energy intake of individuals in the TRE group decreased by No change was found in the percentages of energy from macronutrients. Recurrent circadian fasting RCF improves blood pressure, biomarkers of cardiometabolic risk and regulates inflammation in men.

Yasumoto, Y. Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice.

Metabolism 65 , — Gualillo, O. Ghrelin, a widespread hormone: insights into molecular and cellular regulation of its expression and mechanism of action. FEBS Lett. Wehrens, S. Meal timing regulates the human circadian system.

Manoogian, E. Circadian rhythms, time-restricted feeding, and healthy aging. Ageing Res. Jordan, S. Dietary intake regulates the circulating inflammatory monocyte pool. Cell , — Yang, Y. China Food Composition Peking University Medical Press, Masella, A.

PANDAseq: paired-end assembler for illumina sequences. BMC Bioinform. Edgar, R. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26 , — Langille, M.

Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Segata, N.

Metagenomic biomarker discovery and explanation. Genome Biol. Zhou, Z. Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus. Acta , 98— Refinetti, R. Procedures for numerical analysis of circadian rhythms.

Rhythm Res. Download references. This work was supported by grants from the CAMS Innovation Fund for Medical Sciences CIFMS No. and H. The study sponsors played no role in study design, conduct, data acquisition, analysis, manuscript preparation or the decision to submit the manuscript for publication.

We thank Mark Cleasby, PhD from Liwen Bianji Edanz www. cn for editing the language of a draft of this manuscript. Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

You can also search for this author in PubMed Google Scholar. oversaw the design, regulatory compliance, execution, and data analyses in this study. designed the study. Zhang, Z. Zhao, and H. recruited participants, collected data, and monitored participants compliance.

All the authors contributed to data analyses. wrote the manuscript. All the authors contributed to the composition and revision of the manuscript and gave final approval to its content. Correspondence to Huayu Yang or Yilei Mao. Nature Communications thanks Heather Allore, Marta Garaulet and the other anonymous reviewer s for their contribution to the peer review this work.

Peer reviewer reports are available. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Xie, Z. Randomized controlled trial for time-restricted eating in healthy volunteers without obesity. Nat Commun 13 , Download citation. Received : 18 January Accepted : 03 February Published : 22 February Anyone you share the following link with will be able to read this content:.

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Skip to main content Thank you for visiting nature. nature nature communications articles article. Download PDF. Subjects Feeding behaviour Nutrition Obesity Pre-diabetes. Abstract Time-restricted feeding TRF improves metabolic health. Introduction Long-term dietary habits are determinants of metabolic health 1.

Results Participants Ninety volunteers who met the eligibility criteria participated in the trial and were randomized at a ratio of to eTRF, mTRF, and control groups Fig. Full size image. Table 1 Baseline Characteristics.

Full size table. Discussion The present study has shown that 5 weeks of eTRF, but not mTRF, improves insulin sensitivity, reduces fasting plasma glucose, reduces body mass and adiposity, ameliorates inflammation, and increases gut microbial diversity.

Randomization procedure For the pilot RCT, participants were randomly assigned to either the eTRF, mTRF, or control group in a ratio, using a computer-based random-number generator by designated researchers. Inclusion and exclusion criteria The inclusion criteria were: 1 18—64 years old; 2 ability to attend the hospital at regular intervals; 3 ability to independently provide informed consent; 4 BMI between Anthropometric measurements Body mass and percentage body fat were measured using an HBF Bioelectrical impedance analyzer Omron Healthcare Co.

Blood sampling and storage Blood sampling was performed at the beginning and the end of the trial. Flow cytometric analysis PBMCs were separated from blood samples using Ficoll GE Healthcare, Chicago, IL and centrifugation. Fecal sample collection and storage Fecal samples were collected during the 3 days before the start of the trial and during the same period of time before the end of the trial.

Biochemical measurements The plasma activities of AST, ALT, ALP, GGT, and lactate dehydrogenase; and the concentrations of LDL-C, HDL-C, total cholesterol, triglyceride, and glucose were measured using an automated analyzer Beckmann-Coulter AU , Brea, CA. Real-time quantitative PCR RNA was pooled from PBMCs and used for cDNA synthesis.

Subjective sleep quality and eating habits The participants were required to maintain their normal sleeping habits throughout the trial and to avoid undergoing testing after a night shift. Statistical analysis For the sample size calculation, we estimated that the eTRF group would show a Data availability The individual de-identified participant microbiota metagenomic sequencing data can be accessed from the BioProject Database of National Centre for Biotechnology Information with the dataset accession number PRJNA Code availability No code was involved in this manuscript.

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Article CAS PubMed Google Scholar Refinetti, R. Acknowledgements This work was supported by grants from the CAMS Innovation Fund for Medical Sciences CIFMS No. Author information Author notes These authors contributed equally: Zhibo Xie, Yuning Sun, Yuqian Ye.

View author publications. Ethics declarations Competing interests The authors declare no competing interests. Peer review Peer review information Nature Communications thanks Heather Allore, Marta Garaulet and the other anonymous reviewer s for their contribution to the peer review this work.

Supplementary information. Supplementary Information. Peer Review File. Reporting Summary. Source data Source Data. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4. About this article. Cite this article Xie, Z.

Copy to clipboard. McHill Kenneth P. Wright Nature Reviews Endocrinology Time-restricted eating with calorie restriction on weight loss and cardiometabolic risk: a systematic review and meta-analysis Jing-Chao Sun Zhen-Tao Tan Gang Qian European Journal of Clinical Nutrition Circadian alignment of food intake and glycaemic control by time-restricted eating: A systematic review and meta-analysis Susana Rovira-Llopis Clara Luna-Marco Victor M.

Victor Reviews in Endocrine and Metabolic Disorders Intermittent fasting and Alzheimer's disease—Targeting ketone bodies as a potential strategy for brain energy rescue Yu- Cai Ye Shi-Fan Chai Zhao-Jun Wang Metabolic Brain Disease Comments By submitting a comment you agree to abide by our Terms and Community Guidelines.

After 7 weeks, tissue samples were taken from multiple organs and examined for any changes in gene expression. Genes code for the production of proteins, so basically the researchers measured whether the production of various proteins increased or decreased.

Genes that code for proteins responsible for inflammation were found to be less active, while genes that produce proteins that repair damage to DNA and ones that inhibit cancer cell survival geared up. But, of course, mice are not men or women.

So, what about men or women? One interesting study examined changes in a number of proteins produced as a result of eating only during a hour period and fasting for 14 hours. The subjects, 8 men and 6 women, were all observers of the Muslim religious month of Ramadan during which no food or drink is consumed between dawn and sunset.

These parameters are easily monitored and can provide information about the health effects of fasting in addition to changes in gene expression. All of the markers of metabolic syndrome shifted in the right direction during the month of the hour fast, as did proteins involved in destroying cancer cells, repairing DNA, and improving immune function.

All very interesting, but the experimental group was small and the study period of a month was short. Also, the subjects all had metabolic syndrome, and calorie intake was not considered. Basically, not much can be inferred as far as the general population goes.

That though is not the case for a study that compared the effects of eating an early or late dinner on glucose levels, insulin production, triglyceride levels and fatty acid oxidation which is a measure of ketosis. Subjects ate their dinner either at 6 or 10 PM, and then had their blood chemistry monitored every hour through an intravenous line.

The late dinner resulted in greater glucose intolerance and reduced fatty acid oxidation, both of which can promote obesity.

Why should this happen? During sleep, metabolism normally winds down since the body needs less energy. Therefore, ingested glucose and fats are not burned for energy, but rather end up being stored as fat. If dinner is eaten earlier, metabolism remains active until sleep time and less fat ends up being stored.

This study would seem to corroborate the benefits of the daily time-restricted fast since if no food is eaten after late afternoon, the reduced metabolism associated with sleep is less of an issue because most of the food will have been metabolized in the 5 or 6 hours between the last meal and sleep.

Now, just as I was ready to wrap things up with a final praise of intermittent fasting schemes, I learned of two recently published papers in respected journals. One found that in adults over the age of 40, a time interval of fewer than 4. The second study asked participants to use an app to record the timing of their meals and then went on to relate this to their body weight as documented in their medical records over a ten-year period.

Weight changes were not associated with the time between the first and last meals, which would seem to argue against trying to lose weight by time-restricted eating. Where does all this leave us? As is the case with almost every aspect of nutrition there is controversy, and studies can be found to back up each side.

Separating the wheat from the chaff is challenging and requires an extensive review of studies to try to get a handle on the preponderance of evidence.

Metabolic syndrome consists of Gaming power top-up constellation Time-restricted eating research clinical factors eatinb with Time-restrictes increased risk of cardiovascular disease, type 2 diabetes, and cancer. Preclinical studies demonstrate that restricting Effective metabolism support time during etaing hour Gaming power top-up when Tjme-restricted obese Gaming power top-up eats time-restricted feeding Time-restricted eating research to metabolic benefits. These benefits, which may or may not be reesarch with eatimg loss, often lead Balanced diet for performance improvements eesearch glucose researcj and insulin sensitivity. Studies seeking to determine whether similar benefits result when humans restrict daily eating time time-restricted eating are less mature and less consistent in their findings. In this commentary, we outline some of the exciting preclinical findings, the challenges that preliminary studies in humans present, and efforts of the US National Institutes of Health and specifically the National Cancer Institute to address the role of time-restricted eating in cancer. Although some individuals with obesity are metabolically fit, with a metabolic profile like nonobese individuals 1obesity is an important risk factor for the development of metabolic syndrome 2. Time-restricted feeding [TRF] in animals or time-restricted eating [TRE] in humans is a type of intermittent fasting IF that can potentially improve metabolic health.

Time-restricted eating research -

Findings were published April 21, , in The New England Journal of Medicine. Researchers in China randomly apportioned obese men and women into two groups. One group was told to limit daily calorie intake 1, to 1, calories or men, and 1, to 1, calories for women.

The other group was told to follow the same calorie limits but to eat only between 8 a. Daily rhythm variations have been suggested to be associated with the differing effects of TRFs during different periods of the day in animal studies 24 , 25 , and in humans We also evaluated the daily rhythms of plasma adipokine concentrations and clock gene expression in peripheral blood mononuclear cells PBMCs.

We found that eTRF was associated with a larger improvement in insulin sensitivity than mTRF, and eTRF, but not mTRF, was associated with lower fasting plasma glucose, body mass, adiposity, and inflammation; and a more diverse gut microbiota than the control group. In addition, the two types of TRF had differing effects on the daily rhythms of plasma adipokines and PBMC clock gene expression.

Taken together, these findings suggest that TRF with a window for food consumption early in the day is better for metabolic health than a window later in the day, and that the mechanism may involve changes to daily rhythms.

Ninety volunteers who met the eligibility criteria participated in the trial and were randomized at a ratio of to eTRF, mTRF, and control groups Fig. Eighty-two participants Self-reported compliance with the regimens was out of person-days Comparisons of the groups with respect to age, sex distribution, body mass, and body mass index BMI at baseline are shown in Table 1.

A total of individuals were assessed for eligibility and were excluded as they did not meet inclusion criteria, and 17 were excluded as they declined to participate. Ninety participants were randomized into one of three groups: eTRF, mTRF, or control, and baseline measures were assessed after randomization.

Remaining 82 participants completed the trial and were included in the present analysis. Energy intake was estimated using pictures of the meals consumed.

Data is visualized as Tukey box plots line at mean, top of the box at the 75th percentile, bottom of the box at the 25th percentile, whiskers at the highest and lowest values, outliers shown as triangles beyond the whiskers.

Tumor necrosis factor-α TNF-α , interleukin-8 IL-8 , and high sensitivity C-reactive protein hsCRP are important circulating markers of inflammation 28 , 29 , However, the activities of alanine aminotransferase ALT , alkaline phosphatase ALP , and gamma-glutamyltransferase GGT did not differ among the three groups Table S1.

There were no differences in the changes in white blood cell WBC count among the three groups. LEfSe analysis was used to identify bacterial taxa that differed in abundance between the beginning and end of the study in each group.

No significant differences were found in the relative abundances of taxa between these time points. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States PICRUSt was used to analyze the representation of gene functions in the microbial communities in each group.

We predicted function using clusters of orthologous group COG analysis, and found 29, 26, and 1 significantly different functional COGs between baseline and follow-up testing in the eTRF group, mTRF group, and control group, respectively Fig.

The Pittsburgh Sleep Quality Index PSQI was used to evaluate the sleep quality of the participants; a higher PSQI score is indicative of worse sleep quality The Council of Nutrition Assessment Questionnaire CNAQ is used to evaluate the appetite of individuals The fasting plasma concentrations of resistin, leptin, and ghrelin were measured, and no significant changes were found in any of the three groups with respect to the concentrations of these substances.

Furthermore, blood samples were collected at four times of day , , , and at both the beginning and end of the interventions from 19 participants five, eight, and six from the eTRF, mTRF, and control groups, respectively. Two-way ANOVA showed that the plasma ghrelin concentration at was significantly increased by eTRF 0.

No changes in the concentrations of any of these substances were identified in the mTRF group Fig. Plasma adipokine concentrations resistin, leptin, and ghrelin were measured at four time points.

Two-way repeated-measures ANOVA with time of day and feeding regimens as the two independent variables. BL baseline, FU follow up. The expression of the clock genes BMAL1 ARNTL , SIRT1, PER1, PER2, PER3, CRY1 , and CRY2 was measured in PBMCs of the same 19 participants, and the amplitudes, midline-estimating statistics of rhythm MESORs , and acrophases of the expression levels of these genes were calculated using Cosinor analysis.

Because not all the expression levels of the clock genes could be fitted using Cosinor curves, the parameters were calculated for exploratory purposes only plots for each participant are shown in Fig. S5 and the corresponding r 2 values in Table S2. In the eTRF group, the SIRT1 mRNA expression of all the participants increased in amplitude during the trial Fig.

Although participants in the mTRF group all showed increases in the amplitude of PER2 mRNA expression, they also showed decreases in the amplitude of PER1 mRNA expression Fig.

In addition, all the participants in the eTRF group showed increases in the MESORs for BMAL1, PER2 , and SIRT1 mRNA expression during the trial Fig. All the participants in the mTRF group also showed an increase in the MESOR for PER2 mRNA expression, but the decreases in the MESOR for PER1 mRNA expression were quite consistent in this group Fig.

No consistent shifts in the acrophases of the expression of clock genes were identified in any of the groups Fig. After Cosinor analysis, the amplitudes of clock gene expression in each individual were calculated. a The change in amplitude of clock genes after analyzed with Cosinor analysis in eTRF group.

All participants in eTRF group showed an increase in the amplitude of SIRT1 after the trial. b The change in amplitude of clock genes after analyzed with Cosinor analysis in mTRF group. All participants in mTRF group showed an increase in the amplitude of PER2, but a decrease in that of PER1 after the trial.

c The change in amplitude of clock genes after analyzed with Cosinor analysis in control group. The present study has shown that 5 weeks of eTRF, but not mTRF, improves insulin sensitivity, reduces fasting plasma glucose, reduces body mass and adiposity, ameliorates inflammation, and increases gut microbial diversity.

However, there were no significant differences among the three groups with respect to blood pressure, circulating lipid concentrations, HbA1c, hsCRP, sleep quality, or appetite.

The good compliance with the two TRF protocols in the present study implies that TRF is an easy-to-execute fasting regimen, and the similar compliance with each suggests that they are similarly feasible.

However, there were reductions in energy intake in both of the TRF groups, which implies that energy intake can be limited just by shortening the daily duration of food consumption.

Furthermore, the lack of a significant difference in the change in energy intake between the two TRF groups suggests that the differences in the improvements in metabolic health were not caused by differences in energy intake. The benefits of improving insulin sensitivity are numerous Consistent with the results of previous studies 3 , 14 , 35 , we found that eTRF, but not mTRF, improved insulin sensitivity.

Remarkably, this is the first trial to show that eTRF is superior to mTRF with respect to its ability to improve insulin sensitivity by directly comparing these two TRF regimens.

Although similar changes in energy intake occurred in both TRF groups, only the eTRF group showed a reduction in body mass versus the control group, which was accompanied by reductions in both the percentage body fat and fat mass. These may indicate an improvement in fat deposition, which requires further visceral fat measuring parameters in future trials.

Besides, the weight loss in eTRF group was relatively modest compared with prior eTRF studies 3 , 36 , which may be the result of different inclusion criteria of participants, with normal weight humans included in this trial, while mostly overweight participants or individuals with obesity were included in prior eTRF studies 3 , Only one trial by Courtney Peterson et al.

has previously reported the effect of eTRF on blood pressure, with participants showing markedly reduced blood pressure after eTRF 3.

In contrast, no significant changes in blood pressure were noticed in the eTRF group in the present trial. The baseline blood pressure levels might be the reason for the different effects of eTRF between these two trials, because the trial by Courtney Peterson et al.

was carried on those with a mean blood pressure within prehypertensive range 3 , while the present trial on healthy participants. In addition, there was no effect of either TRF regimen on circulating lipid concentrations, but this was not unexpected, because the blood concentrations of most of the participants were within the normal range.

Excess nutrient intake usually induces an inflammatory response, which has been causally linked to the dysregulation of glucose and lipid metabolism Previous studies have shown beneficial effects of TRF to reduce inflammation in individuals with obesity or metabolic diseases 3 , 22 , 38 , and we have shown that eTRF reduces inflammation in individuals without obesity, in the form of reductions in the plasma concentrations of TNF-α and IL A high plasma AST activity is a feature of obesity-induced hepatic steatosis 39 , 40 , and we have also shown a potential protective effect of eTRF against high liver enzyme activity, which is consistent with the results of most previous studies of animal models of liver steatosis, non-alcoholic fatty liver disease 4 , 6 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , or hepatic ischemia-reperfusion 5 ; only one previous study showed that TRF does not affect the activities of the liver enzymes ALT, ALP, and GGT The increase in pTregs in the eTRF group may also contribute to the beneficial effects of eTRF on metabolism, because a low pTreg count is associated with obesity, insulin resistance, and inflammatory responses 49 , 50 , 51 , 52 , Although the mechanism of the effect of TRF on pTregs is still under investigation, intermittent fasting has been shown to increase the number of pTregs in rodent intestines, where they have an immunoregulatory effect We also found that the α-diversity of the gut microbiota increased in the eTRF group, and this has been reported to be associated with a healthier gut microbiota 55 , whereas low gut microbial diversity is associated with metabolic diseases Our finding that eTRF has superior effects to mTRF may be the results of different effects on mediators of the peripheral daily rhythm.

Disturbances in the daily rhythms of secreted substances are associated with obesity and metabolic health 57 , 58 , 59 , and diet influences these 60 , 61 , 62 , A previous study conducted in rodents showed that food restriction within an active period influences the daily rhythm of these substances and improves metabolic health Although in the present study TRFs seemed to have no effects on the fasting plasma concentrations of these substances, eTRF influenced the daily rhythms of ghrelin and resistin.

Although the daily variations in the circulating concentration of resistin has been reported to be related to feeding rhythm in rats 65 , and TRF has been reported to influence the circulating concentration of resistin in men 66 , the effect of a change in the feeding window on the daily rhythm of resistin had not been previously reported.

This change might merely be a reaction to the change in feeding rhythm. The daily rhythm in circulating ghrelin concentration has been reported to synchronize with TRF in mice, with the concentration increasing before the feeding period 67 , and it should be noted that ghrelin has an important role in the feeling of hunger Therefore, the higher concentration of ghrelin that was identified at in the eTRF group might be at least in part the results of a longer period of fasting in this group at that time point.

Cosinor analysis has been reported to accurately reflect the rhythmic changes in clock gene expression 69 ; therefore, we used this to compare clock gene expression among the groups. Because not all the expression data for every participant fitted Cosinor curves, the parameters were calculated just for exploratory purposes, to provide clues for future investigations.

Previous studies identified a positive relationship between the amplitude of oscillation of rhythmic components and metabolic health We found that eTRF might enhance the daily rhythms in human clock genes, on the basis of the findings that all the participants in the eTRF group showed increases in the amplitude of SIRT1 expression and the MESORs of BMAL1 , PER2 , and SIRT1 expressions in PBMCs.

In contrast, mTRF had diverse effects on the daily rhythms of expression of several clock genes: it increased the amplitude and MESOR of PER2 expression, but reduced the amplitude and MESOR of PER1 expression in all the participants. This suggests that mTRF has relatively complex effects on daily rhythms, which will be further investigated in the future.

However, it is worth noting that the timing of food intake on the test day might influence the results of the analyses of daily rhythm-related parameters. Although it has been shown in rodent models that peripheral concentrations of secreted substances and PBMC gene expression can be influenced by changes in feeding rhythm, rather than just by recent food intake 65 , 71 , it is unclear at present which of these has a greater effect on the daily rhythms of secreted substances and PBMC clock gene expression in humans.

The present study had several limitations. Firstly, although it was a randomized trial, the participants could not be blinded to the intervention. Secondly, the people who applied to join the trial might already have been interested in TRF or wished to improve their health through making a dietary change, and most were women.

Thirdly, the number of participants in the trial was relatively small and they may not have been representative of the wider population. Fourthly, the potential barriers to TRF were not analyzed. The influence of the duration of food consumption on the effects of TRF requires further investigation.

Sixthly, the changes in the eating periods that were made in the TRF groups may have caused changes in the duration of fasting prior to testing, which might have influenced the results. Lastly, daily rhythm-related parameters were measured in limited numbers of participants and few time points were assessed.

To better assess the effects of TRFs on daily rhythms, further, larger studies should be conducted that include shorter intervals between measurements and more than one diurnal cycle.

Participants in the eTRF and mTRF groups were only allowed to consume water, flavored carbonated water, unsweetened tea, and coffee during the fasting period. The primary outcome was the change in HOMA-IR, an index of insulin resistance that is calculated using the fasting glucose and insulin concentrations.

The secondary outcomes were changes in energy intake, fasting glucose, body mass, body composition, blood pressure, blood lipid concentrations, inflammatory markers, liver enzymes, immune cells, gut microbiota, sleep quality, and appetite.

Change in daily rhythms of plasma adipokine concentrations and PBMC clock gene expression were measured as exploratory analyses. Prior to enrolling participants, the study was registered at chictr.

cn ChiCTR Participants were recruited from the Beijing area from Feb. The participants maintained their habitual alcohol intake during the trial, which was no more than twice a week, as required in the eligibility criteria.

Alcohol intake was forbidden on the test days and the preceding days. To ensure compliance, participants were required to take photos of their food as they began to eat and as they finished and to send them privately to the investigators using a WeChat-supported web message-sending applet.

All participants wrote a consent form and guaranteed to supply real data about food intake at the beginning of the trial. The energy content of each meal was estimated using China Food Composition Database One designated researcher who had got a good clinical practice certificate was trained to estimate the number of different types of food using the posted photos, which would be double-checked by another researcher.

Standardized measurement guides were used to assess portion sizes. The records for all the meals of every participant were included in the analysis, except for non-compliant days.

To estimate compliance, the number of person-days for each group was defined as 35 days the length of the trial multiplied by the number of participants who finished the trial.

The compliance rate was calculated as the number of self-reported compliant days divided by the total number of person-days for each group. Because 28, 26, and 28 participants in the eTRF, mTRF, and control groups, respectively, completed the trial, the compliance levels were calculated to be 35 × 28 for the eTRF group and 35 × 26 for the mTRF group.

Because participants were instructed to take either TRF regimen or normal diet regimen, they were not blinded to the assignment of the groups. Investigators who checked posted photos and estimated energy contents from photos were not blinded to the assignment of the group.

Other investigators and statisticians were blinded during the study procedure, and were unblinded after all the data had been analyzed. For the pilot RCT, participants were randomly assigned to either the eTRF, mTRF, or control group in a ratio, using a computer-based random-number generator by designated researchers.

The inclusion criteria were: 1 18—64 years old; 2 ability to attend the hospital at regular intervals; 3 ability to independently provide informed consent; 4 BMI between The exclusion criteria were: 1 night-shift work more than once a week; 2 fasting during the preceding 8 weeks; 3 alcohol consumption more than twice a week; 4 pregnancy, gastrointestinal abnormalities or eating disorders, history of gastrointestinal surgery or systemic disease; 5 use of corticosteroid drugs, β-receptor blockers, or other drugs that might affect the findings; 6 a diagnosis of hypertension, diabetes, or other metabolic disease; and 7 a diagnosis of insomnia.

Body mass and percentage body fat were measured using an HBF Bioelectrical impedance analyzer Omron Healthcare Co. Height was measured using a metric tape, with the participant standing up straight against a wall. BMI was calculated using the body mass in kilograms divided by the height in meters, squared.

Blood sampling was performed at the beginning and the end of the trial. For those who participated in the analysis of daily rhythms, blood sampling was performed at , after an overnight fast, and at , , and PBMCs were separated from blood samples using Ficoll GE Healthcare, Chicago, IL and centrifugation.

Flow cytometric data were analyzed using FlowJo Version Fecal samples were collected during the 3 days before the start of the trial and during the same period of time before the end of the trial.

Detailed instructions regarding sample collection and transportation were provided by the study personnel and the participants were provided with containers with feces-preserving fluid. The plasma activities of AST, ALT, ALP, GGT, and lactate dehydrogenase; and the concentrations of LDL-C, HDL-C, total cholesterol, triglyceride, and glucose were measured using an automated analyzer Beckmann-Coulter AU , Brea, CA.

Insulin was measured using an ADVIA Centaur XP Siemens, Munich, Germany. The IL-8 and TNF-α concentrations were measured using an Immulite Siemens. The concentrations of resistin AdipoGen Life Science, Liestal, Switzerland , leptin Phoenix Pharmaceuticals, Burlingame, CA , and ghrelin Thermo Fisher, Waltham, MA were measured using ELISA kits on a microplate reader Bio-Rad Laboratories.

RNA was pooled from PBMCs and used for cDNA synthesis. Transcript levels were then quantified by qPCR using SYBR qPCR mix ABI-Invitrogen. The primer sequences are listed in Table S3.

The participants were required to maintain their normal sleeping habits throughout the trial and to avoid undergoing testing after a night shift. Sleep was analyzed using the PSQI questionnaire and eating habits were analyzed using the CNAQ. To generate the 16S rDNA library, PCR analysis was performed using a 16S V3—V4 hypervariable region general primer set and a KAPA HiFi Hotstart ReadyMix PCR Kit KAPA , and the PCR products were collected using an AxyPrep DNA gel extraction kit Axygen.

The 16S rDNA amplicon sequence results were analyzed using the Hiseq PE platform. The sequencing results were first assembled using PANDAseq 2. An operational taxonomic units table was constructed using Usearch Alpha diversity, assessed using chao1, was analyzed using QIIME 2 Analyses of the changes in the gut microbial profiles were performed using LEfSe 1.

PICRUSt 1. For the sample size calculation, we estimated that the eTRF group would show a The reported mean and standard deviation are 1.

Therefore, to detect a Taking into consideration potential drop-outs during the trial, 30 participants were recruited for each group. The energy that was consumed on non-compliant days was not included in the calculation of the mean daily energy consumption and the data for the eight participants who did not complete the trial were excluded from the analyses.

Data are shown as Tukey box plots, with the mean value indicated by a line, unless otherwise stated. Data was collected using Microsoft Excel Microsoft MSO version Statistical calculations were performed using GraphPad Prism 7.

To compare the three groups, one-way repeated-measures ANOVA was used, followed by the Holm-Sidak multiple comparisons test. To analyze the daily rhythms of circulating substance concentrations, the data at each time point were first collated as percentages of the mean of the values at all the time points, then analyzed using two-way repeated-measures ANOVA, with time of day and feeding regimen as the two independent variables.

Cosinor analysis was applied to the clock gene expression data. Cosinor model curves were plotted using the clock gene expression data for each participant on each test day using the following function and the amplitude, MESOR, phase shift and acrophase peak time for each curve 78 :.

Further information on research design is available in the Nature Research Reporting Summary linked to this article. The individual de-identified participant microbiota metagenomic sequencing data can be accessed from the BioProject Database of National Centre for Biotechnology Information with the dataset accession number PRJNA The daily rhythms-related source data underlying Fig.

The other individual de-identified participant data are not openly available due to participant confidentiality and will be shared by the corresponding author upon reasonable request for academic use. The study protocol is available as a supplementary file. China Food Composition Database was used in this manuscript Source data are provided with this paper.

Seconda, L. et al. Assessment of the sustainability of the mediterranean diet combined with organic food consumption: an individual behaviour approach.

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The researchers combed through dozens of animal and human studies to explain how simple fasting improves metabolism, lowers blood sugar levels; lessens inflammation, which improves a range of health issues from arthritic pain to asthma; and even helps clear out toxins and damaged cells, which lowers risk for cancer and enhances brain function.

According to metabolic expert Dr. Deborah Wexler, Director of the Massachusetts General Hospital Diabetes Center and associate professor at Harvard Medical School, says "there is evidence to suggest that the circadian rhythm fasting approach, where meals are restricted to an eight to hour period of the daytime, is effective.

So, here's the deal. There is some good scientific evidence suggesting that circadian rhythm fasting, when combined with a healthy diet and lifestyle, can be a particularly effective approach to weight loss, especially for people at risk for diabetes.

However, people with advanced diabetes or who are on medications for diabetes, people with a history of eating disorders like anorexia and bulimia, and pregnant or breastfeeding women should not attempt intermittent fasting unless under the close supervision of a physician who can monitor them.

Adapted from a Harvard Health Blog post by Monique Tello, MD, MPH. Effects of intermittent fasting on health, aging, and disease. de Cabo R, Mattonson MP. New England Journal of Medicine , December Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

JAMA Internal Medicine , May Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

American Journal of Clinical Nutrition , January Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis.

JBI Database of Systematic Reviews and Implementation Reports, February Metabolic Effects of Intermittent Fasting. Annual Review of Nutrition , August Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.

Cell Metabolism , May As a service to our readers, Harvard Health Publishing provides access to our library of archived content.

Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

You have tremendous latitude in what goes into your daily diet—and the choices you make can have profound consequences for your health. But what diet should you choose? The range is truly dizzying.

Just some of the diets you might encounter are vegan, pegan, and portfolio. Raw food, whole foods, and Whole Keto, carnivore, and paleo. Clean eating and intermittent fasting.

DASH, MIND, and Volumetrics. Mediterranean, Nordic, and Okinawan. What does it all mean? And how can you begin to make sense of it? This Special Health Report is here to help. Thanks for visiting. Don't miss your FREE gift. The Best Diets for Cognitive Fitness , is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School.

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New research Tume-restricted little Time-rextricted of Time-restrixted from prostate biopsies. Gaming power top-up at redearch Time-restricted eating research linked to high blood pressure. Icy fingers and toes: Poor Vitamin C benefits or Raynaud's phenomenon? Gaming power top-up a ton of incredibly promising intermittent fasting IF research done on fat rats. They lose weight, their blood pressure, cholesterol, and blood sugars improve… but they're rats. Studies in humans, almost across the board, have shown that IF is safe and effective, but really no more effective than any other diet. In addition, many people find it difficult to fast. Time-restricted eating research Data were Time-restrifted Gaming power top-up 75 participants; means were estimated using an Powerful antioxidant supplements Time-restricted eating research using a linear mixed model. CR indicates calorie restriction; TRE, gesearch eating. eFigure 3. Difficulty in Adhering to the Time-Restricted Eating vs Calorie Restriction Intervention. Pavlou VCienfuegos SLin S, et al. Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes : A Randomized Clinical Trial. JAMA Netw Open.

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