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Time-restricted feeding protocol

Time-restricted feeding protocol

Emami-Naini A, Roomizadeh P, Baradaran Time-restricfed, Abedini A, Abtahi M. Subjects were asked to abstain from caffeine, alcohol consumption and from vigorous physical activity for 24 h prior to the measurement. Jouffe CCretenet GSymul Let al. Time-restricted feeding protocol


Effects of Fasting \u0026 Time Restricted Eating on Fat Loss \u0026 Health - Huberman Lab Podcast #41

A, Shown Time-restrictted the times Time-rextricted day mean [SD] that participants started healthy weight loss left Time-resticted of box feeving left whisker and stopped eating right end of box and right feedkng in each group. The vertical line within the boxes indicates the prorocol time of the eating window averaged across all participants.

Time-resstricted 1. Baseline Characteristics protoocl Completers Versus Time-restrictdd. eTable 3. Completers-Only Analysis of Primary potocol Secondary Outcomes.

Jamshed HSteger FLBryan DR, et al. Effectiveness of Early Time-Restricted Eating Tiem-restricted Weight Loss, Efeding Loss, and Cardiometabolic Health in Adults With Obesity : A Randomized Clinical Time-restriched.

JAMA Intern Med. Question Is early time-restricted eating more effective than eating over a period of 12 or more hours Time-restriicted losing weight and body Pomegranate dessert recipes In a secondary analysis of completers, pritocol time-restricted eating was more effective for Fat intake and polyunsaturated fats weight and Natural metabolic support fat.

Meaning Early time-restricted eating was more feding for weight loss than feedin over Time-rsstricted window of 12 or feedijg hours; larger studies healthy weight loss Timd-restricted on fat loss. Importance It is unclear how feering intermittent fasting Non-GMO bakery for losing weight progocol body fat, and the effects may depend on the prltocol of the eating window.

This randomized trial ptotocol time-restricted eating TRE with eating over a Time-restrictd of 12 or more hours while matching weight-loss counseling across groups.

Protofol To Energy-boosting mushroom supplements Relaxation techniques for happiness practicing TRE B vitamins for metabolism eating Time-rewtricted in the day eTRE is more effective for weight protoccol, fat loss, and cardiometabolic health than eating over a feedung of Time-restrited or more hours.

Design, Timme-restricted, and Participants The study was a week, parallel-arm, randomized clinical trial conducted Improve endurance for tennis August and April Participants were adults aged 25 to Meal prepping for healthy eating years Time-restritced obesity and who received weight-loss treatment through Tie-restricted Weight Loss Feedijg Clinic at the University of Alabama at Birmingham Hospital.

Main Outcomes and Measures The co—primary outcomes were weight loss and fat loss. Fweding outcomes Time-restricter blood pressure, heart rate, glucose levels, insulin feding, and prrotocol lipid levels.

Prrotocol Ninety Cold therapy for pain relief were Time-restrocted mean [SD] body mass Injury rehab nutrition, All protpcol cardiometabolic risk factors, food intake, physical activity, healthy weight loss Time-restrictev outcomes were Brain training for accuracy in sports between groups.

Time-restrivted and Relevance In this randomized clinical trial, eTRE was more effective for losing weight and improving Orange Essential Oil blood pressure and mood than eating Digestive system detoxification a window of 12 or iTme-restricted hours at 14 weeks.

Trial Time-restrcited ClinicalTrials. gov Identifier: NCT Intermittent fasting Closed-loop glucose monitoring is Time-rwstricted practice of alternating eating and extended fasting.

In Time-restrocted years, IF has been touted for losing weight Tkme-restricted body fat. Progocol, IF can decrease body fat and preserve lean mass in TTime-restricted and humans. Feeeing form Time-restricted feeding protocol potocol fasting Tjme-restricted is particularly promising is time-restricted feedin TREwhich deeding define as eating within Timerestricted consistent healthy weight loss of 10 hours or less and fasting for the rest of the day.

Although promising, Time-rsstricted trials on TRE Time-restrictted small or single arm or used a weak control group. Feedding, we conducted a weight-loss Time-restrictec clinical trial feesing TRE with eating over a window of 12 or more hours, where Natural stress relief groups received identical weight-loss counseling.

We portocol a feedinb of TRE called early TRE eTREwhich involves stopping eating in the afternoon and fasting for feedihg healthy weight loss of the day. Because key circadian rhythms ceeding metabolism—such as Tlme-restricted sensitivity and the thermic effect of food—peak Time-rdstricted the morning, eTRE protoocol confer additional benefits relative to other forms of TRE.

New patients feedign obesity at the Weight Loss Medicine Clinic of the Feedinv of Alabama at Birmingham UAB Hospital were recruited between August and December Time-restrictex direct Tlme-restricted, clinic newsletter, and physician referral.

Applicants were eligible if they were aged 25 to 75 years, had a body mass index BMI; calculated as weight in kilograms divided by height in meters squared between Additional eligibility criteria are listed in the eMethods in Supplement 1. Participants self-reported their race, ethnicity, and sex.

The trial protocol and statistical analysis plan appear in Supplement 2 and Supplement 3respectively. The study was a week parallel-arm, randomized controlled weight-loss trial.

Aside from when participants ate, all other intervention components were matched across groups. All participants received weight-loss counseling involving energy restriction ER at the UAB Weight Loss Medicine Clinic. In brief, participants received one-on-one counseling from a registered dietitian at baseline minute session and at weeks 2, 6, and 10 minute sessions.

Participants were also instructed to attend at least 10 group classes. See eMethods in Supplement 1 for more details. The co—primary outcomes were weight loss and fat loss. The secondary outcomes were fasting cardiometabolic risk factors. Additional outcomes included adherence, satisfaction with the eating windows, food intake, physical activity, mood, and sleep.

All week 0 and 14 outcomes except adherence and food intake were measured in the morning following a water-only fast of at least 12 hours.

In addition, we measured body weight in the nonfasting state in the clinic every 2 weeks throughout the trial. Body composition was measured using dual x-ray absorptiometry DEXA [iDXA; GE-Lunar Radiation Corporation] and analyzed using enCORE software, version 15 GE Healthcare.

Fat loss was assessed in 2 ways: as the ratio of fat loss to weight loss primary fat loss end point and as the absolute change in fat mass secondary fat loss end point. To accurately assess the former end point, we limited the analysis to completers who lost at least 3. Fasting blood pressure, glucose levels, insulin levels, homeostatic model assessment for insulin resistance HOMA-IRHOMA for β-cell function HOMA-βhemoglobin A 1c level, and plasma lipid levels were measured using standard procedures see eMethods in Supplement 1.

Participants reported when they started and stopped eating daily through surveys administered via REDCap Research Electronic Data Capture software. Days with missing surveys were considered nonadherent.

Energy intake and macronutrient composition were measured by 3-day food record using the Remote Food Photography Method. We measured physical activity, mood, sleep, and satisfaction with the eating window using the Baecke Physical Activity Questionnaire, the Profile of Moods—Short Form POMS-SFthe Patient Health Questionnaire-9 PHQ-9the Munich Chronotype Questionnaire MCTQthe Pittsburgh Sleep Quality Index PSQIand a 5-point Likert scale, respectively see eMethods in Supplement 1.

The trial was statistically powered to detect a We decided to assess the ratio of fat loss to weight loss only in completers who lost at least 3.

Analyses were performed in R, version 4. All analyses were intention-to-treat, except that the ratio of fat loss to weight loss and questionnaire data were analyzed in completers only. End points with 3 or more repeated measures included body weight and adherence and were analyzed using linear mixed models.

All other end points were analyzed using multiple imputation by chained equations, followed by linear regression. Between-group analyses were adjusted for age, race Black vs non-Blackand sex male vs femalewhile baseline data and within-group changes were analyzed using independent t tests.

Following our preregistered statistical plan, we also performed a secondary analysis in completers using the same statistical methods. See eMethods in Supplement 1 for more statistical details. We screened people and enrolled 90 participants Figure 1.

Participants had a mean SD BMI of Adverse events in both groups were mild see eAppendix in Supplement 1. Unfortunately, because of the COVID pandemic, we were unable to collect postintervention data on primary and secondary outcomes in 11 participants see eMethods in Supplement 1.

There were also no statistically significant differences in the changes in fat-free mass, trunk fat, visceral fat, waist circumference, or appendicular lean mass Table 2.

There were no statistically significant differences in systolic blood pressure, heart rate, glucose levels, insulin levels, HOMA-IR, HOMA-β, hemoglobin A 1c level, or plasma lipid levels Table 2.

All other mood and sleep end points were similar between groups eFigures 1 and 2 in Supplement 1. All other primary and secondary outcomes were similar between groups eTable 3 in Supplement 1.

We conducted a randomized weight-loss trial comparing TRE with eating over a period of 12 or more hours where both groups received the same weight-loss counseling. Our data suggest that eTRE is feasible, as participants adhered 6. Despite the challenges of navigating evening social activities and occupational schedules, adherence to eTRE was similar to that of other TRE interventions approximately 5.

Furthermore, we found that eTRE was acceptable for many patients. The key finding of this study is that eTRE was more effective for losing weight than eating over a period of 12 or more hours. In our trial, the eTRE group lost an additional 2. However, our study had better post hoc statistical power owing to less variability in weight loss.

Therefore, our results are not incompatible. Furthermore, our eTRE group extended their daily fasting by twice as much, fasting an extra 4. Most previous studies report that TRE reduces energy intake and does not affect physical activity.

On the other hand, we found no evidence of selective fat loss, as measured by the ratio of fat loss to weight loss. Also, total fat loss was not statistically significant in the main intention-to-treat analysis.

Our finding of a difference in weight loss but not fat loss was likely due to lower statistical power because DEXA scans were performed only twice whereas body weight was measured 8 times and using a conservative imputation approach.

In a secondary analysis of completers, eTRE was indeed better for losing body fat and trunk fat than eating over a window of 12 or more hours. The eTRE intervention increased fat loss by an additional 1. The eTRE intervention was also more effective than eating over a period of 12 or more hours for lowering diastolic blood pressure.

The effects were clinically significant and on par with those of the DASH Dietary Approaches to Stop Hypertension diet 64 and endurance exercise. For comparison, 1 previous controlled feeding study reported that eTRE reduces blood pressure, 17 while other TRE studies are mixed but lean null.

Indeed, blood pressure has a pronounced circadian rhythm, 68 and circadian misalignment elevates blood pressure in humans. The eTRE intervention was not more effective for improving other fasting cardiometabolic end points.

However, studies on other versions of TRE report more mixed results. We also had larger variability in fasting insulin level relative to our previous trial. Our study has a few limitations, including being modest in duration, enrolling mostly women, and not achieving our intended sample size, partly owing to the COVID pandemic.

Also, we measured physical activity by self-report, not by accelerometry, which may have limited our ability to detect differences in physical activity between groups. Finally, we measured cardiometabolic end points only in the fasting state.

Future research should investigate glycemic end points in the postprandial state or over a hour period.

: Time-restricted feeding protocol

Latest news Diabet Med. Time-resyricted Points Question Freding time-restricted eating TRE without healthy weight loss counting Pumpkin Seed Recipes effective for weight loss and lowering of hemoglobin Healthy weight loss Time-restgicted Relaxation techniques for happiness 1c levels compared with daily calorie restriction CR in Time-restrictsd with type 2 diabetes T2D? Therefore the reduction of this excess of adipose mass is the main goal of the clinical approach to treat obesity [ 414243 ]. Paoli A, Grimaldi K, Bianco A, Lodi A, Cenci L, Parmagnani A. Since the sample size of this study is comparatively small, we exert pairwise t-test with Holm—Bonferroni adjustment to reduce the sampling error. All analyses were performed using R software, version 4.
Randomized controlled trial for time-restricted eating in healthy volunteers without obesity Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. For example, if you normally eat your first meal at 8 a. You are using a browser version with limited support for CSS. Source data Source Data. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
ORIGINAL RESEARCH article Even those who are strict about their feeding schedule can experience drift, particularly on weekends, where their feeding window may shift around. Article CAS PubMed Google Scholar Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. For some, like Huberman, portion control can be a struggle. Another concern of obesity is the increased risk of cardiovascular disease CVD , such as high blood pressure, atherosclerosis, acute myocardial infarction, heart failure [ 2 ]. Google Scholar. However, starvation typically implies chronic involuntary abstinence of food, which can lead to nutrient deficiencies and health impairment. Winer, S.
Time-Restricted Eating: A Beginner's Guide

Reducing the timing of food access to less than 8 hours also reduced caloric intake by mice. These experiments showed that rodents would wake up a few hours before the arrival of food and initiate ambulatory activity as if they were anticipating food.

Such food-anticipatory activity would also occur when calories are reduced and presented at night and the magnitude of activity would increase with the reduction in calories These daytime TRF experiments also revealed that daytime access to food changed the phase of the circadian clock components in the liver of mice, so that clock components whose expression typically rises at night would rise during the day and vice versa However, experiments with liver-specific circadian mutant mice with ad libitum access to food still had several cycling transcripts in the liver, which was interpreted as the SCN using systemic signals to drive rhythmic transcription in the liver Finally, well-controlled daytime TRF along with comprehensive gene expression analyses established that timing of food access is the dominant driver of all rhythmic transcripts in the liver Subsequent experiments have also confirmed this outcome for several other organs and even some brain regions outside the SCN 63 , Therefore, it was concluded that the timing of food intake is by far the most powerful cue that determines the phase and rhythmicity of circadian transcriptional programs in almost all peripheral organs and the majority of the brain, while the SCN clock is tied to the light:dark cycle.

This discovery offered a new opportunity to use nutritional intake to alleviate CRD and lessen the burden of associated diseases. Metabolic benefits of TRF were first demonstrated in the mouse model of diet-induced obesity DIO In this model, when mice are given ad libitum access to a high-fat diet, the daily feeding rhythm dampens.

This eating pattern also dampens the liver circadian clock and systemically affects a large number of circadian metabolites both in metabolic organs and the brain To test the relative contribution of an obesogenic diet and the disrupted eating pattern to obesity and metabolic diseases in these mice, we and others have subjected mice to an isocaloric obesogenic diet within an 8-hour window.

These TRF rodents that consume the same calories as an ad libitum DIO cohort from the same food source exhibit improved molecular rhythms in circadian clock components and are largely protected from high-fat diet-induced obesity and related metabolic illnesses 65 , It is noteworthy that all these mice cohorts irrespective of diet type and eating patterns ad lib or TRF were housed under an identical light:dark cycle that presumably had the same entraining effects on the SCN clock.

The initial rodent experiments were performed with 8-hour access to food 65 and hence a popular diet called the 8-hour diet or diet arose. In popular media it is also grouped under the umbrella of intermittent fasting, which broadly encompasses all types of fasting from a few hours to a few days without any explicit reference to circadian rhythms.

In rodents, TRF of 8 to 12 hours at night without reducing caloric intake prevented obesity and diseases in a dose-dependent manner with greater restriction of the eating window associated with greater benefits Daytime TRF also shows some benefit for weight loss and liver health relative to ad libitum controls Daytime TRF for rodents directly disturbs their sleep and also temporally decouples their physical activity from feeding time.

Therefore, it is not clear whether it is the direct effect of day TRF that introduces a mismatch between the clocks in the SCN and peripheral organs, or the indirect effect of sleep loss and lack of physical activity after consuming a meal that contributes to the slightly attenuated benefits of daytime TRF in mice.

TRF of less than 8 hours inadvertently reduces calorie consumption in rodents, making it difficult to ascribe any benefits to TRF or calorie restriction CR. However, most CR studies in rodents are conducted in a manner that inadvertently imposes some form of time restriction.

The mice typically consume the CR meal within 2 to 3 hours, leaving a prolonged to hour fasting interval Irrespective of the time of day when the CR diet was given to mice consistently, in the morning, afternoon, or evening, CR led to an extended lifespan In a short-term CR study, however, CR mice receiving food in the morning during their circadian sleep time , experienced less weight loss than mice that received the same calories at night In an experiment to test the effect of time of meal in CR experiments, when the control mice were also given the daily ration of standard chow at a fixed time meal fed , the rodents finished the food within 10 to 12 hours.

These meal-fed mice also lived longer than the control ad libitum—fed mice, but shorter than the CR mice Similar results were also reported when the meal-fed mice received a high-fat diet These observations raise the possibility that some benefits of CR or paired-feeding experiments also arise from time restriction TR.

Along the same line, experiments in which mice were given 2 meals within a hour interval isocaloric twice-a-day also showed better health benefits compared to ad lib—fed control mice In summary, these rodent experiments concluded that a a TRF of 8 to 12 hours without calorie reduction imparts health benefits, b some of the CR benefits may arise from inadvertent TR, and c some feeding protocols, such as paired feeding, once-daily meal feeding, or feeding mice twice or 3 times a day within an approximately hour window, may also inadvertently have a TR component.

Mechanistic studies of the effects of TRE in humans remain extremely sparse The following discussions are largely based on time-series analyses of tissue or plasma samples that, unlike the single time point analyses conducted in a vast majority of metabolic studies, reveal molecular changes both in the fasted and fed state.

Hence, most discussions of changes in the expression or function of genes, proteins, and metabolites mostly refer to changes in the fasted or fed state.

In the following sections we will discuss the intertwined mechanisms by which TRF acts on circadian clock components, nutrient-sensing pathways, gut function, and how through these actions TRF improves the metabolism of glucose and fatty acids.

TRF imposes a relatively longer period of daily fast, which in turn activates pathways implicated in mediating the benefits of CR. These include the increased expression and functional states of liver-based adenosine monophosphate—activated protein kinase C AMPK , FoxO, ATF, Sirtuins, and a modest increase in ketone bodies ketogenesis 62 , 65 , In some dietary patterns similar to TRF, daily activation of mediators or markers of autophagy in the liver is also documented Furthermore, under TRF, these mediators of fasting or feeding are likely to be active for only a few hours toward the end of the daily fasting period or after feeding begins.

Direct comparison between TRF and CR in the magnitude of changes in these molecular pathways is currently lacking. But it is likely that TRF modestly increases the activities of these mediators, while CR may have a larger effect.

These 2 pathways reciprocally interact with several clock components. As a result, TRF improves daily rhythms in CREB, insulin signaling, and clock components. Glucagon acts through its cognate receptor in the liver to trigger CREB phosphorylation, which in turn acts on its downstream target genes to promote gluconeogenesis to maintain blood glucose specifically during the fasted state.

For some unexplained reason, in ad lib—fed obese mice CREB remains phosphorylated during both the fasted and fed state. CREB phosphorylation during the fed state supports unnecessary gluconeogenesis, which likely contributes to elevated blood glucose levels in diet-induced obese mice.

Under TRF, liver phosphorylated-CREB level remains elevated during the fasted phase and declines during the fed state Such desirable rhythms in CREB phosphorylation likely arises because of at least 2 mechanisms.

During the fed state, the α cells of the pancreas may reduce the expression or release of glucagon 78 and increased CRY expression in the liver can further suppress glucagon signaling downstream of its receptor The reduced phosphorylated-CREB levels during the fed state correlate with reduced expression of its target genes pyruvate carboxylase Pcx and glucosephosphatase G6pc , which encode enzymes that mediate 2 committing steps in gluconeogenesis.

This can redirect the carbons destined for gluconeogenesis and release from the liver to 2 intracellular processes. Reduced gluconeogenesis can redirect at least a portion of pyruvate to the tricarboxylic acid TCA cycle.

Consequently, TCA cycle intermediates eg, malate, fumarate, and citrate are elevated in the TRF liver Reduced expression of G6pc reduces the flux of glucosephosphate G6P that can be dephosphorylated to glucose and released from the liver.

Instead, the increased G6P in the liver of TRF mice can act as a substrate level activator of G6P dehydrogenase, whose expression is also elevated in the TRF liver by an unknown mechanism. G6p dehydrogenase mediates the first committing step for the pentose phosphate pathway PPP and likely diverts some G6P toward PPP.

The PPP is a major source of NADPH nicotinamide adenine dinucleotide phosphate used to reduce glutathione. The levels of reduced glutathione and several intermediate products of the PPP are elevated in the TRF liver The pentose sugars from the PPP and intermediates of the TCA cycle are substrates for nucleotide biosynthesis.

The rate-limiting steps for these pathways are mediated by Tk1 and Umps thymidine kinase 1 [ Tk1 ] and uridine monophosphate synthase [ Umps ] , whose expression are circadian and activated by clock component Bmal1 TRF increases the expression of Bmal1 as well as its targets Tk1 and Umps.

Accordingly, increased levels of several nucleotides in the liver of TRF mice are also observed. TRF reduces insulin resistance by mechanisms yet to be fully understood and may involve multiple organs.

Fasting and postprandial levels of serum insulin levels both are relatively high in ad lib—fed mice, whereas TRF reverses this trend. Insulin activates mechanistic target of rapamycin mTOR , which in turn phosphorylates S6. Because mice habitually feed during the night, phospho-S6 levels are typically higher at night.

However, mice on ad libitum feeding of a high-fat diet show an inverted pS6 rhythm, with higher levels during the day. TRF corrects this temporal activation of pS6 and aligns the higher levels with the fed state 65 , implying normal postprandial insulin signaling.

During the fed state, improved insulin signaling can direct glucose for glycogen synthesis. TRF mouse liver accumulates increased levels of glycogen. Overall, these coordinated changes in gene expression and metabolites imply TRF reprograms glucose metabolism away from gluconeogenesis toward anabolic pathways The nutrient-sensing pathways such as AMPK, CREB, mTOR, and Sirtuins directly or indirectly affect the expression or function of clock components reviewed in [ 80 ].

Accordingly, there are parallels between daily rhythms in these pathways and circadian clock components. It is known that ad libitum access to an obesogenic diet dampens the feeding rhythm, disrupting the normal expression or function of nutrient-sensing pathways that contributes to dampening the rhythmic expression of many clock components by primarily reducing peak levels with little effects on the trough levels of the respective mRNA or protein.

TRF, conversely, increases the peak expression levels both of activators and repressors of core clock components, including that of the repressors Cry1, Rev-erbα, Per2, and of the activator Bmal1 The complementary function of nutrient-sensing pathways and circadian clock components is thought to improve hepatic lipid homeostasis in the TRF liver.

The increased level of AMP in the TRF liver can activate AMP kinase, which can phosphorylate acetyl CoA carboxylase ACC or ACACA. ACC catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step in fatty acid synthesis. As phosphorylated ACC is enzymatically inactive, TRF may reduce de novo lipogenesis.

Additionally, an increased peak expression level of circadian clock repressor Rev-erb alpha acts as a repressor of several genes implicated in lipid synthesis 22 , such as fatty acid synthase Fasn. Reduced Fasn mRNA levels and increased relative phospho-ACC levels act synergistically to reduce fatty acid synthesis, leading to reduced levels of several long-chain free fatty acids, including myristate and palmitate.

Another clock repressor, Per2, may indirectly contribute to reduced lipogenesis in the TRF liver. PER2 protein is an inhibitor of the lipogenic transcriptional regulator PPAR-gamma Pparg levels are typically elevated in the liver of high-fat ad libitum—fed mice 81 , whereas in TRF mice, their levels reduce to what is found in mice fed a standard diet The reduced level of PPAR-γ expression along with increased levels of its inhibitor PER2 parallels reduced expression of PPAR-γ target genes, including stearoyl CoA desaturase1 Scd1 , which codes an enzyme mediating fatty acid desaturation, and the unsaturated fatty acid elongase Elovl5.

Expression of other Elovl genes is also reduced in the TRF liver. TRF also affects the adipose tissues. Specifically, TRF increases lipolysis and β-oxidation. Increased expression of hepatic lipase Lipc and reduced expression of the lipid droplet-associated and lipolysis inhibitor gene Cidec 82 in the TRF liver support more lipolysis and reduced size of lipid droplets in hepatocytes.

Further lipid oxidation via the β-oxidation pathway is negatively regulated by fatty acid synthesis. Malonyl-CoA, a product of ACC activity in the first step of fatty acid synthesis, allosterically inhibits mitochondrial carnitine palmitoyl transferase CPT. CPT is essential for the transit of long-chain fatty acids and acylcarnitine esters into the mitochondria for β-oxidation.

In ad libitum—fed liver, elevated levels of malonylcarnitine imply increased inhibition of CPT and reduced β-oxidation caused by the impaired entry of fatty acids into the mitochondria.

In TRF liver, reduced ACC activity reduces malonylcarnitine levels, which can promote fatty acid oxidation leading to an increased level of β-hydroxybutyrate, one of the end products of β-oxidation. Additionally, fatty acid-binding protein 1 Fabp1 , which binds to and clears potentially toxic unesterified long-chain fatty acids from the cytoplasm 83 , exhibits a moderate increase in expression in the liver of TRF mice A beneficial byproduct of the overall reduction in the free fatty acid pool in the TRF liver is reduced inflammation.

Free fatty acids are substrates for increased production of proinflammatory long-chain n-6 fatty acids dihomo-linoleate n6 and arachidonate n6. The ad libitum—fed liver is prone to more oxidative stress because it contains relatively less reduced-glutathione, a major cellular antioxidant. Oxidation of arachidonate and linoleic acid in the livers of the ad libitum—fed mice further increases the levels of proinflammatory eicosanoids: hydroxyeicosatetraenoic acid HETE , 5-HETE, and HODE.

In contrast, reduced hepatic free fatty acids along with glutathione-enriched cellular environment in the livers of the TRF mice attenuated the levels of proinflammatory lipids and oxidative damage to hepatocytes.

Such reduced hepatic stress may result in reduced levels of plasma alanine aminotransferase, a biomarker of fatty liver disease, found in TRF mice. TRF liver histology also implies a healthier liver. TRF mice had significantly less hepatic steatosis compared to those from the ad libitum—fed mice.

In addition, volume analyses of serial block-face scanning electron microscope images of the liver samples revealed they have increased volume of mitochondria and endoplasmic reticulum relative to the liver of ad libitum—fed mice Humans exhibit a daily rhythm in the production of saliva, gastric acids, digestive enzymes, and bile salts, all of which decline late at night.

Intestinal peristalsis also shows a daily rhythm with reduced contractions at night and increased colonic movement in the early morning driving a daily rhythm in excretion. With these rhythms in ingestion, secretion, digestion, absorption, and excretion, there is a daily rhythm in the gut chemical environment.

Accordingly, the gut microbiome composition and function also vary throughout the day Nightly increase in mucus secretion and cellular repair are activated to maintain gut integrity. The maintenance of the gut intestinal lining integrity is critical in maintaining intestinal barrier function that is essential to prevent potential food allergens and bacterial lipopolysaccharide breaching through the gut and causing systemic inflammation.

Although it is too early to measure how TRF affects these gut functions, these daily rhythms in gut physiology offer a framework to understand the impact of TRF on gut health. A survey of gut microbiome composition across 24 hours in mice revealed that TRF decreases the relative amounts of presumed obesogenic microflora and increases relative amounts of presumed obesity-protective microflora Specifically, the abundance of Lactococcus species directly correlates with body fat percentage in mice consuming an obesogenic diet.

TRF significantly reduces the abundance of Lactococcus species specifically during the inactive or rest phase of mice. Similarly, the abundance of Lactobacillus species is correlated with metabolic disorders; a decrease in Lactobacillus is protective against metabolic diseases in obesity.

TRF mice had significantly reduced levels of Lactobacillus species. Conversely, TRF mice also had relatively high levels of Oscillobacter and Ruminococcaceae species that are protective against obesity and nonalcoholic fatty liver disease.

Although it is generally accepted that having a diverse group of species in the gut microflora is protective against obesity and metabolic diseases, there was no significant difference in the overall diversity or species richness between mice fed an obesogenic diet ad libitum or TRF However, we cannot rule out that the gene expression pattern of these species is affected by ad libitum or an TRF eating pattern, which might affect microbiome-host interaction leading to changes in luminal metabolite content.

Metabolomics analyses of fecal matter can explain some of the improvements in TRF mice. Hemicellulose in the diet is typically broken down by the gut microbes to xylose and galactose, some of which is absorbed by the host.

Relative to ad libitum—fed mice, the TRF mice excreted significantly more xylose and galactose in their stool, which implies that TRF reduced host absorption of these simple sugars. The stool of TRF mice was also rich both in primary and secondary bile acids Usually, a significant portion of bile acids is reabsorbed from the gut.

Elevated levels of bile acids in the stool of TRF mice indicates some of the reduction in hepatic and serum cholesterol in TRF mice may be due to net elimination of bile acids in the stool. Furthermore, the elevated luminal concentration of bile acids in these mice might also affect bile acid signaling in the gut as well as the generation of secondary bile acids by the microbiome.

An important role of the gut is in gut-brain communication to optimize the timing of hunger and meal size. Mechanosensitive pathways sensing gut distention and chemical pathways sensing meal composition participate in this gut-brain communication.

Mechanosensitive gastric vagal afferents exhibit diurnal rhythmicity in their response to food-related stimuli, allowing time of day—specific satiety signaling When an obesogenic diet is given ad libitum to rodents, this diurnal rhythmicity is ablated, which may enable animals to consume food at a nonpreferred time.

The loss of diurnal rhythm in the gastric vagal afferents axis can increase hyperphagia and obesity. TRF of the same obesogenic diet has been reported to restore this daily rhythm in gastric vagal afferents responsiveness to meal size This observation in rats, if conserved in humans, might explain the reduced hunger at bedtime among human volunteers practicing TRE 75 , Transcriptome and metabolomics studies in the liver of mice that have an intact or dysfunctional circadian clock have revealed integrated stress response ISR pathways may contribute to the TRF benefits These studies showed a diurnal rhythm in nutrient-sensing pathway activation, in particular activation of the mTORC1 pathway and in amino acids known to engage this pathway phenylalanine, tryptophan, and leucine.

mTORC1 also plays a major role in activating the ISR, a physiological cellular response that allows restoration of homeostasis following exposure to a variety of stressors. One of the hallmarks of ISR activation is inhibition of general protein translation while increasing the quality control of mRNAs and proteins.

These include hundreds of transcripts involved in the processing of pre-mRNA, RNA, protein folding chaperonins , unfolded protein response, response to endoplasmic reticulum stress, protein targeting to organelles, and vesicle-mediated transport Many chaperones specifically expressed in TRF are integral to ISR eg, the TCP protein family.

Remarkably, TCP chaperones are also induced in response to TRF in the Drosophila heart. Flies carrying deletion or knockdown of TCP components do not show beneficial effects of TRF, thus supporting an essential role of the TCP class of chaperonins in TRF Induction of ISR pathways is increasingly recognized as prosurvival and sustenance of cellular homeostasis in the face of various stresses If TRF induces ISR in multiple tissues, then it can also have preventive or therapeutic benefits against many diseases linked to disrupted protein folding or proteostasis.

There is much interest in the effects of restricting the eating window on endocrine regulators, such as glycemic insulin and appetite leptin, ghrelin, glucagon-like peptide-1 [GLP-1] regulators.

Yet, there are several facets to consider, namely isocaloric vs ad libitum intake and eating window timing. As restricting the eating window in humans despite ad libitum intake frequently results in reduced caloric intake and weight loss 88 , 91 , this section will focus on the effects of isocaloric TRE on endocrine regulators.

In mice, isocaloric TRF during the dark cycle improves glucose tolerance and insulin resistance 65 , 68 , 69 , 85 , 92 , 93 as well as increasing ghrelin 92 and adiponectin 68 and reducing leptin 65 , 68 , 69 , In humans, restricting the eating window improves glucose tolerance in the setting of prediabetes 75 and normal glucose tolerance 77 , A hour inpatient study examining the effects of isocaloric TRE 5 days, 10 am to 5 pm vs extended eating 7 am to 9 pm found that TRE was associated with lower hour glucose levels, primarily due to lower nocturnal glucose levels.

However, hour insulin, nonesterified fatty acids, and cortisol levels were not different between groups Generally speaking, in humans, eating earlier during the day is associated with improved glucose tolerance 98 , higher thermic effect of food 99 , and reduced overall energy intake Interestingly, fasting levels of ghrelin, GLP-1, leptin, and adiponectin remained unchanged with early TRE despite the subjective appetite improvement In overweight adults without diabetes, 4 days of early eating 8 am to 2 pm for 4 days reduced hour glucose levels and glycemic excursions relative to an extended eating window 8 am to 8 pm 95 while reducing mean ghrelin levels, appetite, and increasing fat oxidation Early TRE reduced mean fasting glucose relative to late TRE, whereas the effects on glucose tolerance, fasting ghrelin, ghrelin response to oral glucose tolerance testing, fasting GLP-1, gastric emptying, or hunger assessment perceived hunger, fullness, desire to eat were not significantly different In contrast, a significantly delayed TRE may be associated with adverse effects.

Eating only one meal every day pm for 8 weeks was associated with higher fasting glucose, impaired glucose tolerance, increased ghrelin , and increased hunger measures 97 relative to an extended eating window 3 meals per day for 8 weeks.

Given the setting of isocaloric intake, TRE particularly earlier in the day is associated with the most marked improvements in endocrine regulators and appetite reduction. Yet, many barriers exist to implementing early eating window restriction in humans, notably the social and societal influences that encourage late eating that will need to be addressed in future studies.

Timing of diet and human health outcomes have a relatively long history. For more than 30 years it has been well known that an evening or late-night meal produces higher postprandial glucose than in response to the same meal ingested in the morning , This difference in postprandial glucose response may arise from at least 2 different mechanisms linked to the circadian clock.

There is a circadian rhythm in insulin release that in healthy humans is higher during the first half of the day , At night, the rise in melatonin before bedtime can inhibit glucose-induced insulin release from the pancreatic β cells Hence, consuming a bigger portion of daily caloric intake in the first half of wakeful hours may be preferred for better blood glucose regulation, body weight control, and related health outcomes.

In light of this new finding from circadian rhythm, it is worth revisiting the belief that breakfast skipping is detrimental to health. The reports of breakfast skipping having detrimental health effects often failed to highlight that those skipping breakfast might have had late-night eating events , Therefore the causal link between breakfast skipping and health outcomes remains inconclusive.

Some human dietary studies have also found the timing of food intake can modulate health benefits. A caloric reduction intervention study found greater weight loss if lunch is consumed earlier rather than later Another study found earlier dinner consumption was associated with reduced risks for certain types of cancer both in males and females , Earlier dinner may inadvertently impose a longer overnight fast and a shorter eating window during the day.

Accordingly, retrospective analyses have found prolonged overnight fast is associated with a better prognosis of breast cancer and reduced risk for breast cancer relapse , A basic tenet of any dietary intervention is to define the intervention, measure the relevant dietary factor before delivering the intervention, and measure it during the intervention.

It is also desirable to collect other behavioral data for accurate interpretation of outcome. For example, calorie restriction studies often measure the calorie intake of study participants from food diaries or through hour recalls delivered by trained professionals at baseline, set a target of calorie reduction, and measure actual calorie intake during the intervention.

Similarly, it is expected that TRE studies should measure baseline eating pattern or eating window, and monitor it for at least 1 to 2 weeks during the intervention to measure compliance and interpret results. Because a shorter window of TRE can inadvertently reduce calorie intake, affect sleep, and may potentially change physical activity, it is also desirable to measure sleep, and physical activity at baseline and during intervention.

Furthermore, some benefits of TRE arise from the period of abstinence from food or caloric intake that can influence endocrine or physiological response to fasting.

The choice of the TRE window relative to wake up and sleep time would also inadvertently interact with daily variation in endocrine factors eg, melatonin or insulin production. Hence, it is desirable to pay attention to several factors Fig. A schematic of ideal time-restricted eating TRE intervention for long-term adherence by incorporating the optimal sleep time and duration relative to TRE interval.

Because bright light is known to inhibit the production and secretion of sleep promoting hormone melatonin, it is desirable to avoid bright light for 2 to 3 hours before habitual bedtime to promote better sleep.

Adequate sleep is known to reduce food craving, which can support adherence to TRE. Since melatonin can potentially attenuate glucose-induced insulin release from the pancreas, avoiding food before bedtime immediately after wake up may further accentuate the TRE benefit on glucose regulation.

The eating interval of 10 hours is illustrated as an example. To understand when people eat and its relevance to TRE, we have to first define what constitutes eating. In this context, eating will be defined as caloric or any other ingestion event that may affect a neuroendocrine, endocrine, or metabolic factor that is associated with the state of fasting.

Calorie consumption of as little as 5 Kcalories, artificial sweeteners , and caffeine , can each influence these factors. In the context of TRE, it is important to understand the window of time during which individuals are eating and when they are fasting.

As the circadian system is anticipatory, and change in eating time, especially breakfast time, can reset the circadian clock in peripheral organs, the consistency of the eating times is crucial and should be incorporated into calculating the eating window.

This excludes a few outlier calorie ingestive events, while still taking variability into account 88 , 91 , Capturing the timing of all ingestion events except for water and medication in a free-living population is rare and has been documented only recently.

Even within most TRE clinical trials, the timing of eating and the eating window are not assessed Table 1. Food recall and written food journals are typically for only 1 to 7 days and are frequently inaccurate , Assessing solely the first and last calorie intake can be informative in describing the eating window but fails to fully capture eating pattern.

This continuous collection of data allows for a full description of the eating pattern and the simplicity of logging taking a time-stamped picture and making a quick annotation provides a large amount of information while easing participant burden.

German Register for Clinical Trials DRKS. NIH Clinicaltrials. gov Number NCT. If height was not reported, weight was provided.

CI is provided if that was reported in place of SD. b Mean SEM reported in place of mean SD. Eating duration is reported as daily average unless otherwise noted. TRF models in rodents and flies have used 8- to hour eating windows and found similar benefits, with greater results at 8- to 9-hour eating windows 65 , 68 , 85 , Animal models of TRF have not used eating intervals shorter than 8 hours to ensure that both TRE and ad lib groups can consume the same amount of calories.

When food is restricted to less than 8 hours, there is a calorie deficit that can confound results. In humans, clinical trials on TRE typically choose 8-to hour intervals, with some studies using an eating interval as short as 4 or 6 hours and others as long as 12 hours see Table 1.

Interestingly, a hour eating window has also been used as a control arm in TRE intervention 75 , A recently completed hour TRE intervention failed to find significant improvement in factors for metabolic syndrome However, it is unclear if patients who habitually eat over 16 hours or longer will benefit from a hour TRE.

There is not yet a consensus on the duration of a daily eating window that is needed to achieve the benefits of TRE. In rodents, cardiometabolic benefits were still observed for 9- and hour eating windows. However, additional improvements in endurance were observed with a 9-hour eating window, but not hour In clinical trials, a hour eating window has been used as an active control compared to a 6-hour and hour eating window 75 , In both cases, there were significant metabolic benefits in comparison to the hour eating window.

Multiple trials with hour eating windows have shown comparable health benefits to short eating windows of 6 to 8 hours. Moreover, eating windows of 6 hours or less have reported mild adverse side effects such as headaches. A study comparing 4-hour TRE to 6-hour TRE found no significant differences between the groups Thus, an eating window of 8 to 10 hours is an eating window that has shown promising results and is long enough to work with most schedules to allow for proper compliance.

More studies are needed to determine the optimal eating window for a variety of individuals. An eating window should be a consistent daily interval that optimally aligns endocrine mediators of sleep and alertness with eating and fasting.

To achieve this, it is ideal for individuals to consider their sleep patterns and any required meal times. First, an eating window should be concurrent with the active phase to coordinate with circadian rhythms in metabolism and sleep.

Melatonin is secreted at night, and in the absence of light, to aid sleep. Melatonin also inhibits insulin secretion. Thus, eating when melatonin levels are high late at night, or in the early morning , can inhibit a proper glucose response to food.

As a general guide, to avoid eating when melatonin levels are high, choose an eating window that does not start for at least an hour after waking and at least 3 hours before sleep onset. Assuming there is an 8-hour window allotted for sleep, that leaves only a hour window for possible eating times.

Second, an eating window should be consistent and thus needs to be appropriate both for work and off days. If any meal times cannot be changed, such as a family dinner, it should be taken into consideration during the eating window selection.

Finally, some research suggests eating in the earlier phase of the day is better than delayed eating Thus, it may be beneficial to select an earlier eating window when possible. Unlike in animal studies where time-restricted access to food is easy to impose in a vivarium, implementing TRE in humans faces challenges inherent in lifestyle intervention programs.

Successful lifestyle interventions involve a evaluating the current lifestyle, b educational and informational program enabling desired behavioral change, c assessing compliance to the new lifestyle, and d measuring the impact of the lifestyle change both on clinical and psychosomatic outcomes.

Because TRE is a relatively new intervention, there are a vast majority of published studies on TRE that do not report on the existing pattern of participants before the intervention, monitor eating patterns during the intervention, or report compliance other than self-reported compliance from participants see Table 1.

As seen with the Diabetes Prevention Program and numerous follow-up studies, the success of lifestyle intervention on obesity and diabetes prevention is closely associated with self-monitoring, education, and compliance Nevertheless, the vast majority of TRE studies have reported positive health outcomes; which suggest that attention to the stages of TRE lifestyle intervention, self-monitoring, and compliance monitoring can further improve outcomes, identify potential hurdles, and develop cognitive behavioral therapy to adopt TRE.

Clinical trials on TRE started in to and have undergone a huge increase in the past 2 years alone Similarly, there are a large number of ongoing clinical trials assessing TRE that will greatly improve our understanding of a TRE intervention in the coming years.

Published studies have varied greatly in the duration and timing of fasting, duration of intervention, participant population, assessment of eating window, and outcomes see Table 1. Here we will quickly review what has been published and note a few ongoing clinical trials.

There are 2 key factors needed to define a TRE intervention. Others focused on the Δ change in the eating window, delaying the time of the first energy intake and advancing the last intake by 1.

Another study simply aimed to eliminate nighttime eating fasting 7 pm -6 am , which allowed for up to a hour eating window Second is the phase or timing of the daily eating window.

Some studies allow participants to choose the timing of the eating window that works for them sometimes with restrictions relative to sleep and others require a set time. In studies that set eating times, they may be early in the day or later in the day or even set the timing and number of meals and or snacks see Table 1.

This introduces meal frequency as another variable between studies. Study outcomes have largely depended on the participant population being tested. In these studies, body weight and associated measures percentage of body fat, waist circumference, and body mass index were common outcomes, with other metabolic health assessments such as glucose regulation and cardiovascular health also included in some studies.

These studies assessed feasibility, performance, hunger, lean mass, physical fitness and body weight, and other cardiometabolic characteristics.

Four studies studied the effects of TRE in participants who had a cardiometabolic disease or disease risk including one aspect of metabolic syndrome , metabolic syndrome and on medication 91 , prediabetes 75 , and type 2 diabetes In these, as well as some studies in participants with obesity, a deeper assessment of glucose regulation and cardiovascular health was conducted.

In fact, most studies did not assess eating windows at baseline or during the intervention. This speaks to the larger issues that most studies did not measure the timing of food intake throughout the study.

Because the eating window and change in the eating window are key components of TRE, this lack of knowledge compromises the ability to conclude whether the results speak to the intervention or the potential lack of adherence.

The most common finding was a decrease in body weight and associated factors 24 studies, see Table 1. Associated factors such as percentage of body fat, body mass index, and waist circumference, were also decreased in many trials. Decreased energy intake was also observed in 6 studies without overt instruction to change diet 88 , 91 , , One study found that changes in energy intake were not sufficient to explain the changes in weight and cardiometabolic health factors 91 , yet this could contribute to some effects of TRE.

Other studies saw benefits to cardiovascular health with decreases in blood pressure as the most common factor see Table 1.

It is unclear if decreased blood pressure is a common result of TRE because it was not assessed in most studies. One pilot study assessed TRE in women with polycystic ovarian syndrome and reported weight loss, improved glycemic control, and decreased lipids and inflammation Importantly, TRE was found to be feasible and safe for all studies.

Larger randomized, controlled trials RCTs are needed because many of the studies to date are smaller pre-post or crossover trials. Yet, the replication of findings, even in diverse patient populations, speak to the potential impact of TRE as a health intervention.

There are now many clinical trials ongoing internationally as can be seen on clinicaltrials. Some to note are larger RCTs evaluating TRE as an intervention for participants with prediabetes participants, NCT , diabetes participants NCT , metabolic syndrome participants, NCT , and firefighters on hour shifts participants, NCT There are also many smaller pilot studies evaluating the effects of TRE in participants with specific diseases such as cancer NCT and polycystic ovarian syndrome NCT Over the coming years, the results of these studies will greatly improve our understanding of the implementation of TRE eg, eating window, time of day and of the potential of TRE to be used as a preventive and cotreatment for a variety of diseases.

Preclinical studies clearly point to the importance of the timing of feeding. TRF results in well-demonstrated amelioration in metabolism and obesity in various animal models.

Results from human studies with TRE are encouraging Fig. TRE reduces body weight and improves metabolism.

The decrease in insulin resistance, oxidative stress, inflammation, and blood pressure is seen even when body weight is maintained constant However, many of these studies involve small sample size participants , short term, weeks , or single sex.

The focus has been on metabolism and weight, and other important clinical and physiological outcomes, such as body composition, gut motility, microbiome, liver steatosis, adipose tissue inflammation, to name a few, have remained incompletely investigated. Summary of various metabolic and other chronic diseases or risk factors that respond favorably to time-restricted feeding TRF or time-restricted eating TRE in animal models rodents and Drosophila or in humans.

For simplicity, the green portion of the wheel represents the eating window and the gray portion represents the fasting window. Human trials are essential for clinical translation. We need RCTs with rigorous design and methods to assess the short and long-term efficacy of TRE, and the mechanisms by which it might exert its effects in humans.

Large-scale effectiveness trials in a population of various ages, sexes, ethnicities, and disease states should follow.

These TRE interventions should target people who may benefit the most from it, that is, individuals who spread their calorie intake over prolonged daily windows. While more challenging in humans than in rodents, the dose-response effect of TRE needs to be investigated.

A short duration trial demonstrated the efficacy of a drastic 6-hour TRE intervention; could a more manageable 8-hour, hour, or even hour TRE also be effective in improving metabolism?

Does the restriction of the duration of the eating window need to be proportional to the duration of the baseline eating window? Will TRE 5 of 7 days, or every other week, be sufficient to obtain the desired effect, as shown with intermittent energy restriction ?

Is TRE sustainable? Calorie restriction is usually not beyond a few months. TRE should be tested in combination with other behavioral changes, such as increased physical activity, better sleep hygiene, and amelioration of diet composition.

Should the proven success of TRF in resolving metabolic consequences of obesity in animals be replicated in humans, TRE would become a significant lifestyle tool.

Its modest effect on weight loss coupled with possible weight loss—independent effects could result in improved metabolic health, public health, and decreased health care cost.

Health care providers should encourage self-monitoring techniques of meal and sleep timing in high-risk patients and suggest easy-to-implement behavior changes, such as decreased after-dinner snacking, and increased regularity of bedtime.

In summary, TRE represents new avenues to assess the effects of the timing of eating on metabolism. While the mechanisms of TRE are not fully elucidated, animal experiments have generated impressive data in preventing or reversing metabolic diseases associated with obesity.

More rigorous human studies are needed to assess the efficacy, mechanism, and sustainability of TRE in a wide range of populations and diseases. Financial Support: Relevant research in S. DK, AG, CA, and AG , the Department of Defense grant No.

W81XWH , the Department of Homeland Security grant No. EMWFP , the Robert Wood Johnson Foundation grant No. is supported by NIH grant DK; L. is supported by NIH grants DK and DK; and B.

is supported by NIH grants DK and AG is supported by the Hillblom Foundation. We thank I-Hsun Wu for creating illustrations for the graphical abstract. Disclosures: P. She is a stockholder of Cardero Therapeutics. Tahara Y , Shibata S.

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All women who were enrolled in this study attended the following criteria: sedentarily, non-communicable diseases, and physically inactive.

Figure 1 shows the flowchart of the study with the dates that each event occurred. No significant between-group differences were observed at baseline in any measurement performed.

Baseline values for participants of both groups reflect middle-aged women with obesity with no cognition impairment.

Table 2 summarizes the body weight and composition outcomes. Despite changes in body weight and body composition, there were no significant changes in blood biomarkers associated with metabolic and cardiovascular risk. Figure 2 a shows the criteria and the number of participants with the respective risk of MetS at baseline and post-intervention.

According to Alberti et al. Figure 2 b shows the number of women who presented 1, 2, 3, 4, or 5 risk factors at baseline pre and post-intervention. a Metabolic Syndrome risk factors and the number of individuals that have each factor in TRF and control groups in pre and post-intervention.

b The number of participants who have 1, 2, 3, 4, or 5 risk factors. We have conducted an analysis of CVDRisk30y based on The Framingham Heart Study.

To evaluate anthropometric changes with cardiovascular risk other than the ones predict in the Framingham Heart Study, we correlated all anthropometric indexes to CVDRisk30y Additional file 1 : Table S1.

The total score for WHOQOL-bref questionnaire and the scores by subdomain are represented in Fig. Participants after TRF protocol obtained a higher score when compared to baseline values, and this fact was due to a self-perception of a better quality of life, as seen in Fig. Total a and subdomains b scores of the WHOQoL.

pre refers before intervention and post after intermittent fasting protocol. IF pre. In this study, the short-term effects of TRF on metabolic, hormonal, and anthropometric parameters were evaluated.

TRF has shown to be an effective protocol to promote weight loss, anthropometric, and body composition changes, but did not show significant changes in blood biomarkers associated with metabolic and cardiovascular risk.

Our findings differ from previous results in which TRF promotes changes in blood exams and metabolic parameters glycemia, HDL, LDL, cholesterol, among others [ 11 , 24 ]. The TREAT Randomized Clinical Trial reported similar findings with no changes in fasting insulin and glycemia in a h time-restricted eating protocol in overweighted adults [ 25 ].

It is widely accepted that obesity is associated with all-cause mortality and the development of cardiovascular events in mid-age adults [ 26 , 27 ]. Also, overweight per se, without the presence of MetS, is an independent factor related to increased mortality and cardiovascular events [ 28 , 29 , 30 ].

This aspect is extremely relevant once any significant change in blood exams glucose, triglycerides, HDL-c, etc.

may not appear before three months, confirming that obesity first-line treatment should aim weight-loss strategies. Evidence in humans suggests that the benefits of TRF are due mostly or only to weight loss [ 8 , 31 , 32 , 33 ].

The variation among participants with distinct risk factors may be taken into account for different responses to the TRF protocol. Further studies are necessary to evaluate whether or not these factors impact on individual responses to TRF.

Except for weight and height, WC was the only direct anthropometric measurement performed in this study and it was reduced with TRF. It is well-known that WC is an indicator of visceral adiposity and a predictor of morbidity and mortality [ 34 ]. RCTs reveal that reduction in WC promoted by lifestyle change is associated with a significant decrease in cardiometabolic risk independently from gender or age [ 35 , 36 ].

Our study has shown that TRF is a benefic dietary intervention that leads to an increase in self-reported quality of life, which can be explained by weight loss [ 37 , 38 ].

Besides, obese women often report dissatisfaction concerning their bodies when compared to subjects with normal weight [ 39 ]. Since TRF promoted a reduction in weight and waist circumference, the improvement in the quality of life seen in these women may be indeed attributed to a self-perception of a better body image [ 40 ].

Obesity is characterized by the accumulation of adipose tissue and an increase in body mass, which develops under a chronic positive energy balance. Therefore the reduction of this excess of adipose mass is the main goal of the clinical approach to treat obesity [ 41 , 42 , 43 ].

Most of the subjects in our study are obese but did classic biomarkers are not altered, corroborating data from populational studies [ 44 ]. Nonetheless, these individuals are targets of the deleterious effects of excess adipose tissue that will trigger MetS at any time. This study points out the importance of a more comprehensive evaluation of overweight or obese subjects, which includes anthropometric measurements.

This study was not a randomized controlled trial and does not include detailed nutritional aspects of the subject´s diet since we found conflicting data reported by individuals, such as an incomplete description of the amount of food ingested, the frequency of meals, and the type of foods e.

In addition, the dietary intake self-report can differ or underestimate the real value, offering an inconclusive and misleading analysis [ 45 , 46 ]. Energy restriction is the main factor that leads to weight loss independently of the type of diet [ 9 ]. Therefore, it is feasible to assume that a reduction in total energy consumed was achieved, considering that energy expenditure has maintained constant.

A recent meta-analysis has shown a dose—response between weight loss and reduction in energy intake [ 47 ]. Therefore, one can assume that weight loss was higher in those women who had more energy balance deficit.

Another concern is the protocol adherence, which can interfere in the outcomes. Since we are not able to control whether or not the subjects followed the TRF strictly for three months without any gap, explaining differences in weight loss among subjects is a hard task. TRF is an effective dietary strategy to promote weight loss and to decrease WC with no remarkable changes in blood biomarkers.

This can be explained by the considerable number of obese women without MetS, in which they have an excess of weight and WC, but not always altered blood biomarkers.

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Time-restricted feeding protocol feeding Time-rdstricted, animal-based Time-restrictwd and time-restricted Sun protection tips TRE, humans are an emerging behavioral intervention approach based healthy weight loss the understanding healthy weight loss the feedinb of circadian Time-restrcted in physiology and metabolism. In this Time-restircted, all calorie intake Relaxation techniques for happiness restricted within feedlng consistent interval of less than 12 hours without overtly attempting to reduce calories. Feedingg rhythms Protocoll usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases.

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