Panda S. Circadian physiology of metabolism. Ulgherait M , Midoun AM , Park SJ , et al. Circadian autophagy drives iTRF-mediated longevity. Chaix A , Lin T , Le HD , Chang MW , Panda S. Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock.

Gallant AR , Lundgren J , Drapeau V. The night-eating syndrome and obesity. Obes Rev. Jakubowicz D , Barnea M , Wainstein J , Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Nighttime eating and breast cancer among Chinese women in Hong Kong.

Breast Cancer Res. Kogevinas M , Espinosa A , Castello A , et al. Effect of mistimed eating patterns on breast and prostate cancer risk MCC-Spain Study. Int J Cancer. Kinsey AW , Ormsbee MJ. The health impact of nighttime eating: old and new perspectives.

Ismail S , Manaf RA , Mahmud A. Comparison of time-restricted feeding and Islamic fasting: a scoping review. East Mediterr Health J.

Pifferi F , Terrien J , Marchal J , et al. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. Commun Biol. Levine ME , Suarez JA , Brandhorst S , et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.

Coelho-Junior HJ , Marzetti E , Picca A , Cesari M , Uchida MC , Calvani R. Protein intake and frailty: a matter of quantity, quality, and timing.

Bjerre N , Holm L , Quist JS , Faerch K , Hempler NF. Watching, keeping and squeezing time to lose weight: implications of time-restricted eating in daily life. Greaves CJ , Sheppard KE , Abraham C , et al.

Systematic review of reviews of intervention components associated with increased effectiveness in dietary and physical activity interventions. BMC Public Health. Longo VD , Panda S. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cienfuegos S , Gabel K , Kalam F , et al.

Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Crose A , Alvear A , Singroy S , et al. Time-restricted eating improves quality of life measures in overweight humans.

Peeke PM , Greenway FL , Billes SK , Zhang D , Fujioka K. Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial.

Nutr Diabetes. Jones R , Pabla P , Mallinson J , et al. Two weeks of early time-restricted feeding eTRF improves skeletal muscle insulin and anabolic sensitivity in healthy men.

Am J Clin Nutr. Chow LS , Manoogian ENC , Alvear A , et al. Time-restricted eating effects on body composition and metabolic measures in humans who are overweight: a feasibility study. Oxford University Press is a department of the University of Oxford.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Navbar Search Filter JNCI Cancer Spectrum This issue JNCI Portfolio Medicine and Health Books Journals Oxford Academic Mobile Enter search term Search.

Issues Advance Articles Submit Author Guidelines Open Access Why Publish with Us? JNCI Portfolio. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume 6. Article Contents Abstract. Reasons Why TRE May Lead to Human Benefit.

Data Availability. Journal Article. Time-Restricted Feeding Studies and Possible Human Benefit. Patrick Boyd, PhD , Patrick Boyd, PhD. Divisions of Cancer Control and Population Sciences, National Cancer Institute at the National Institutes of Health.

Oxford Academic. Brandy M Heckman-Stoddard, PhD. Division of Cancer Prevention, National Cancer Institute at the National Institutes of Health. Edward R Sauter, MD, PhD. Correspondence to: Edward R. sauter nih.

Revision received:. Corrected and typeset:. PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter JNCI Cancer Spectrum This issue JNCI Portfolio Medicine and Health Books Journals Oxford Academic Enter search term Search.

Abstract Metabolic syndrome consists of a constellation of clinical factors associated with an increased risk of cardiovascular disease, type 2 diabetes, and cancer.

Table 1. TRE time, h. On study. Blood pressure, lipid, glucose, insulin effects. Cienfuegos et al. a This is not meant to be an exhaustive list. Open in new tab. Table 2.

Adherence in a sample of TRE studies published Mean adherence rate. Drop-out rate. Adherence measurement. Adherence definition. Other notes. a Not explicitly defined or measured. Table 3. Grant No. funding period. Project title. Rationale or preliminary data. Study design.

sRAGE is thought to sequester AGE in the circulation by acting as a decoy receptor. TRE-mediated decreases in dietary AGE-induced tumor growth led to statistically significant increase in sRAGE.

The investigators hypothesize that increases in sRAGE due to TRE represent cancer risk modification by reducing AGE-RAGE toxicity in patients with prediabetes. The aims were to 1 assess the impact of TRE on AGE-RAGE toxicity in women at increased risk of breast cancer and 2 explore the mechanistic implications of TRF-induced sRAGE in dietary-AGE mouse tumor models.

A pilot RCT to examine the effect of TRF on AGE-RAGE toxicity among postmenopausal women with prediabetes, and a mechanistic in vivo model. The authors point out the adherence challenges that exist with daily fasting, indicating a need for innovation.

The aims were to compare the effects of TRE, daily CR, or control no dietary restrictions on 1 body weight, body composition, and intervention adherence; 2 circulating metabolic, inflammation, and oxidative stress—related biomarkers; 3 colonic mucosal gene expression profiles and mucosal inflammation, DNA damage, and cellular growth; and 4 maintenance of benefits on body weight or composition and systemic or mucosal CRC risk markers.

A controlled, parallel arm trial among adults with obesity randomized to 1 TRE, 2 daily CR, or 3 control, with no dietary restrictions. More evidence is needed regarding the relative advantages of IER over DER.

A week randomized trial among adults with VAT greater than the population median. The investigators hypothesize that TRE optimizes mitochondrial function through both cell-autonomous and systemic mechanisms, thereby reducing cancer risk. The aims were to 1 determine the impact of TRF on mitochondrial function in aged mice, 2 use metabolomics and mitochondria respiration assays to determine the impact of TRF on mitochondria function in normal and cancer cells, and 3 test the effect of TRE on mitochondrial function and cancer risk in humans using plasma collected from a recently concluded human TRE intervention study.

A comparative analysis of TRE in humans and mice. Animal models and human samples will be used to test the effect of daily fasting on mitochondrial function and cancer risk reduction. The aims were to 1 assess how TRE affects treatment-related adverse effects toxicity index based on CTCAE v.

The investigators will enroll adult patients with newly diagnosed localized rectal cancer stage II to III of normal or elevated BMI. Participants will be counseled to maintain their weight. All endpoints will be measured at least 3 times: at diagnosis prior to the onset of chemoradiation baseline , after chemoradiation treatment, and at tumor resection postintervention.

A 5-arm, wk pilot and feasibility trial. TRE may be an alternative to CR if it is able to produce similar benefits or better long term adherence. Rigorous multi-site RCTs are needed to examine TRE in relation to CR.

The aims were to 1 establish a scientific advisory board and other structures for the design of a full-scale RCT; 2 refine the mHealth behavior change and adherence tracking platform the HALLO-P Companion App to optimize delivery of the interventions; 3 conduct focus groups and a mo pilot RCT; 4 model aging biomarker changes for differing CR doses using repositories and the pilot; and 5 integrate new data, the scientific literature, and expert advice to prepare for the larger trial.

Investigators previously found that a high-fat diet restricted in time improves insulin resistance in the context of obesity. This study aimed to test whether a TRF dietary intervention can protect against breast cancer growth in mice and physiological changes linked to tumor growth.

This study will test a TRF intervention with a high-fat diet on mammary cancer outcomes in mice. Google Scholar Crossref. Search ADS. Google Scholar OpenURL Placeholder Text. Google Scholar PubMed. OpenURL Placeholder Text. This work is written by a US Government employee s and is in the public domain in the US.

Issue Section:. Download all slides. Views 3, More metrics information. Total Views 3, Month: Total Views: May 72 June July August September October November December January February March April May June 55 July 61 August September 64 October 84 November 72 December 80 January 81 February Email alerts Article activity alert.

New issue alert. In progress issue alert. Receive exclusive offers and updates from Oxford Academic. Citing articles via Web of Science 1. Latest Most Read Most Cited Leveraging clinical and genetic risk factors for risk prediction of eight cancers in the UK biobank. Medical financial hardship between young adult cancer survivors and matched non-cancer individuals in the United States.

Catastrophic health expenditures, insurance churn, and Non-Employment among women with breast cancer. Cannabis use among cancer patients and survivors in the United States: a systematic review.

Internet-based cognitive rehabilitation for working cancer survivors: results of a multicenter randomized controlled trial. More from Oxford Academic. Medicine and Health. About JNCI Cancer Spectrum Editorial Board Author Guidelines Facebook Twitter Recommend to Your Librarian Advertising and Corporate Services Journals Career Network Policies.

Online ISSN Copyright © Oxford University Press. About Oxford Academic Publish journals with us University press partners What we publish New features. Authoring Open access Purchasing Institutional account management Rights and permissions. Get help with access Accessibility Contact us Advertising Media enquiries.

Oxford University Press News Oxford Languages University of Oxford. Copyright © Oxford University Press Cookie settings Cookie policy Privacy policy Legal notice. This Feature Is Available To Subscribers Only Sign In or Create an Account.

Phillips et al. Crose et al. Wilkinson et al. Anton et al. Jamshed et al. Peeke et al. The primary outcome visits continued, but the diet consults were shifted from face-to-face to telehealth. Other than this period, the Australian border force laws in place meant the study visits remained largely unaffected, with the final follow-up visit completing around the time that Adelaide relaxed its border rules.

The prescribed menu included two meal replacements at breakfast approximately hours and lunch approximately hours to aid adherence and to ensure adequate nutrient intake. iTRE participants were instructed to consume their regular prestudy diet during each nonfasting day.

The prescribed menu included one meal replacement per day to aid adherence and to ensure adequate nutrient intake. The standard care group was given current guidelines in a booklet, with no counseling or meal replacements. All participants were instructed to maintain their usual physical activity levels throughout the trial.

At month 6, they were provided with the option to continue with the same weight loss plan or to modify to a weight maintenance plan. The secondary outcomes included changes in body weight, waist circumference, hip circumference, fat mass, fat-free mass, blood pressure, blood lipids cholesterol, low-density lipoprotein LDL , high-density lipoprotein HDL , plasma triglycerides , NEFA, HbA1c, plasma glucose, plasma insulin, serum high-sensitivity C-reactive protein hs-CRP , ALT, AST, β-hexosaminidase activity, physical activity and dietary intake.

During each metabolic visit, body weight, and waist and hip circumference were measured in a gown after voiding. Body weight was measured to the nearest 0. Waist circumference was measured at the mid-axillary line halfway point between lowest rib and the top of iliac crest , and hip circumference was measured at the widest circumference of the buttocks.

Body mass index was calculated as weight in kilograms per height in meters squared. Whole-body composition was measured by dual-energy X-ray absorptiometry DXA Lunar Prodigy; GE Health Care and was analyzed using enCORE software v. These were assessed in completers who lost at least 3.

The mean of the two lowest blood pressure readings was used. Prescribed daily energy requirements were calculated by averaging predicted daily energy expenditure from a published equation that uses gender, age, height and weight variables Participants were asked to self-report all their dietary intake via a smartphone application Easy Diet Diary, Xyris Software before each metabolic testing at baseline, and at months 2, 6 and The energy and macronutrients intakes were calculated by using FoodWorks Professional v.

Perceptions of diet easiness and satisfaction were assessed at months 2 and 6 using visual analog scales. ActiGraph data was downloaded and analyzed by using ActiLife 6 software by the investigators upon collection of the devices.

Participants attended the research facility at baseline, month 6 and month 18 for metabolic testing. Additional fasting samples were obtained following a h fast at month 2. Blood glucose was assayed by the hexokinase method Cobas Integra plus, Roche.

Plasma insulin was measured by radioimmunoassay HIK, Millipore. Whole-blood HbA1c, plasma triglycerides, NEFA, hs-CRP, ALT and AST, were measured using commercially available enzymatic kits on an automated clinical analyzer Indiko Plus, Thermo Fisher Scientific. AUC values were calculated using the trapezoidal rule.

The Matsuda index was calculated for insulin sensitivity estimation Insulin secretion was estimated using the insulinogenic index A subset of individuals had additional fasting bloods drawn at baseline, month 2 and month 6 to assess plasma β-hexosaminidase activity as a marker of glycosphingolipid metabolism relevant to liver health.

β-Hexosaminidase activity was measured using a plasma sample as described in Leaback et al. and Whyte et al. Plasma samples were thawed on ice, vortexed and diluted in ice-cold 0. Saline solution 0. M; 2.

Fluorescence was read on a GloMax microplate reader Promega. During each clinic visit, participants were asked to report if they had experienced any health-related conditions. They were also prompted to report any physical symptoms through the use of a check box for example, fatigue, constipation, diarrhea, headache, light-headedness since the proceeding visit.

All serious adverse events were immediately reported to the study physician and data safety monitoring committee. For each assessment period baseline to month 6, and month 7 to month 18 , the number of individuals with at least one event was compared between groups when there were at least four individuals with at least one event across all groups.

The design was changed after the first interim analysis to a single additional final analysis of postprandial glucose AUC owing to slow accrual and the coronavirus pandemic.

This change was agreed by the independent data safety monitoring committee 2. We assume a pre—post intervention correlation of 0. The primary analysis of month 6 postprandial glucose AUC between iTRE and CR was assessed using baseline and stratification factor sex, AUSDRISK adjusted linear regression.

Other analyses also included the standard care and where appropriate the month 2 assessment. The latter were modeled using mixed effects linear regressions with a random intercept per individual and adjusted for assessment month 2 versus month 6 and the pairwise interaction with treatment group as fixed effects.

Residual and random effect distributions were assessed to ensure that the model distributional assumptions were not violated. Fasting triglycerides, hs-CRP, AST, ALT, Matsuda index, insulinogenic index and step counts outcomes were log-transformed.

With three groups and two assessment times there are a number of potential secondary outcome comparisons. We prespecified that pairwise comparisons of secondary analyses would be performed only if the overall effect of treatment group was significant in a likelihood ratio test with the nested submodel excluding treatment.

For these overall tests, mixed effects models did not include the month by group interaction that is, the likelihood ratio test statistic was compared against the chi-squared distribution with two degrees of freedom for all outcomes irrespective of the month 2 assessment.

Month 18 assessments were analyzed separately using linear regressions similarly to secondary outcomes without a month 2 assessment. A post hoc analysis was performed repeating these regressions in which the iTRE group was divided into those who chose to maintain the initial iTRE weight loss plan and those who chose to modify to a weight maintenance plan.

Nonfasting weight assessments were analyzed using linear mixed effects regression assuming piecewise linear effects assumed for the interventions over two periods: months 0—6 and months 7—18, and both random intercepts and slopes for individuals.

No multiple test adjustments were performed and as such secondary analyses are considered exploratory. Statistical analysis was performed using R v.

We also report post hoc calculations of the probabilities of benefit—that is, different from zero—both separately and jointly. The analyses were in individuals with both HbA1c and postprandial glucose measures at month 6. Six individuals had HbA1c data but were missing postprandial glucose change data, and were excluded from this analysis.

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article. Anonymized data from this study are available on request from the corresponding author for 36 months from date of publication with a full research plan for academic use only.

The data are not publicly available as they contain information that could compromise research participant consent. Diabetes Prevention Program Research Group et al. Lancet , — Article Google Scholar.

Uusitupa, M. et al. Prevention of type 2 diabetes by lifestyle changes: a systematic review and meta-analysis. Nutrients 11 , Article CAS PubMed PubMed Central Google Scholar. Evert, A. Nutrition therapy for adults with diabetes or prediabetes: a consensus report.

Diabetes Care 42 , — Article PubMed PubMed Central Google Scholar. Patikorn, C. Intermittent fasting and obesity-related health outcomes: an umbrella review of meta-analyses of randomized clinical trials. JAMA Netw.

Open 4 , e Harvie, M. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women.

The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J. Article CAS PubMed Google Scholar. Di Francesco, A.

A time to fast. Science , — Lawson, C. Animal models of GM2 gangliosidosis: utility and limitations. Tiribuzi, R. Alzheimers Dis. Hultberg, B. beta-Hexosaminidase isoenzymes A and B in middle-aged and elderly subjects: determinants of plasma levels and relation to vascular disease.

Kim, H. Renal tubular damage marker, urinary N -acetyl-β- d -glucosaminidase, as a predictive marker of hepatic fibrosis in type 2 diabetes mellitus. Diabetes Metab. Article PubMed Google Scholar. Montgomery, M. Hexosaminidase A HEXA regulates hepatic sphingolipid and lipoprotein metabolism in mice.

FASEB J. Teong, X. Evidence gaps and potential roles of intermittent fasting in the prevention of chronic diseases. Acosta-Rodriguez, V. Pak, H. Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice.

Froy, O. Effect of intermittent fasting on circadian rhythms in mice depends on feeding time. Ageing Dev. Regmi, P. Time-restricted eating: benefits, mechanisms, and challenges in translation.

iScience 23 , Liu, D. Calorie restriction with or without time-restricted eating in weight loss. Thomas, E. Early time-restricted eating compared with daily caloric restriction: a randomized trial in adults with obesity.

Obesity Silver Spring 30 , — Jamshed, H. Effectiveness of early time-restricted eating for weight loss, fat loss, and cardiometabolic health in adults with obesity: a randomized clinical trial. JAMA Intern.

Anton, S. Flipping the metabolic switch: understanding and applying the health benefits of fasting. Obesity Silver Spring 26 , — Trepanowski, J.

Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. Sundfor, T. Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: a randomized 1-year trial.

Shankar, S. Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of beta-cell function: results from the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series.

Diabetes Care 39 , — Berry, S. Human postprandial responses to food and potential for precision nutrition. Lind, M. The association between HbA1c, fasting glucose, 1-hour glucose and 2-hour glucose during an oral glucose tolerance test and cardiovascular disease in individuals with elevated risk for diabetes.

PLoS ONE 9 , e Cavalot, F. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. Antoni, R.

Intermittent v. Templeman, I. A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults. Gao, Y. Effects of intermittent or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants.

Jones, R. Two weeks of early time-restricted feeding eTRF improves skeletal muscle insulin and anabolic sensitivity in healthy men. Karpe, F. Fatty acids, obesity, and insulin resistance: time for a reevaluation.

Diabetes 60 , — Phillips, D. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion.

Horowitz, M. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 36 , — Hutchison, A. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial. Obesity Silver Spring 27 , — CAS PubMed Google Scholar.

Hemmingsen, B. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database Syst. PubMed Google Scholar. Dashti, H. Late eating is associated with cardiometabolic risk traits, obesogenic behaviors, and impaired weight loss.

Article PubMed Central Google Scholar. Early time-restricted feeding improves hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans.

Sutton, E. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.

Cell Metab. Vujović, N. Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity. Wehrens, S. Meal timing regulates the human circadian system.

Van Namen, M. Supervised lifestyle intervention for people with metabolic syndrome improves outcomes and reduces individual risk factors of metabolic syndrome: a systematic review and meta-analysis.

Metabolism , Keirns, B. Fasting, non-fasting and postprandial triglycerides for screening cardiometabolic risk. Pattern of serum beta-hexosaminidase in liver cirrhosis. Poon, P. Plasma N -acetyl-beta- d -glucosaminidase activities and glycaemia in diabetes mellitus.

Diabetologia 24 , — Whiting, P. Serum and urine N -acetyl-beta- d -glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics. Acta 92 , — Lipina, C. Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance: evidence and mechanisms.

FEBS Lett. Jensen, M. Circulation , S—S Rationale and protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes.

Res Clin. An update to the study protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes.

Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids The National Academies Press, Matsuda, M. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.

Diabetes Care 22 , — Leaback, D. Studies on glucosaminidase. fluorimetric assay. Biochem J. Whyte, L. IBRO Neurosci. Download references. This work was supported by the National Health and Medical Research Council Project Grant APP was supported by an Australian Government Research Training Program Scholarship from The University of Adelaide.

This work was supported by a Diabetes Australia Research Program Grant Y21G-SART awarded to T. and L. The funder had no role in the design of this study and the interpretation of the study results. We thank all the trial participants.

Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. Xiao Tong Teong, Kai Liu, Andrew D.

Vincent, Julien Bensalem, Bo Liu, Lijun Zhao, Christine Feinle-Bisset, Gary A. Wittert, Amy T. Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Vincent, Julien Bensalem, Bo Liu, Kathryn J. Hattersley, Lijun Zhao, Timothy J. Sargeant, Gary A. You can also search for this author in PubMed Google Scholar.

and G. designed the study. wrote the statistical analysis plan, performed randomization and statistical analysis. and A. collected the blood samples. provided clinical support and supervision.

analyzed the data. and T. measured the β-hexosaminidase activity. All authors critically revised the draft and approved the final manuscript.

Michael Mosley's TV documentary Eat Fast, Live Longer and book The Fast Diet , followed by journalist Kate Harrison's book The Diet based on her own experience, and subsequently by Dr.

Jason Fung's bestseller The Obesity Code. IF generated a steady positive buzz as anecdotes of its effectiveness proliferated. In the Obesity Code, Fung successfully combines plenty of research, his clinical experience, and sensible nutrition advice, and also addresses the socioeconomic forces conspiring to make us fat.

He is very clear that we should eat more fruits and veggies, fiber, healthy protein, and fats, and avoid sugar, refined grains, processed foods, and for God's sake, stop snacking.

IF makes intuitive sense. The food we eat is broken down by enzymes in our gut and eventually ends up as molecules in our bloodstream. Carbohydrates, particularly sugars and refined grains think white flours and rice , are quickly broken down into sugar, which our cells use for energy. If our cells don't use it all, we store it in our fat cells as, well, fat.

But sugar can only enter our cells with insulin, a hormone made in the pancreas. Insulin brings sugar into the fat cells and keeps it there. Between meals, as long as we don't snack, our insulin levels will go down and our fat cells can then release their stored sugar, to be used as energy.

We lose weight if we let our insulin levels go down. The entire idea of IF is to allow the insulin levels to go down far enough and for long enough that we burn off our fat. Initial human studies that compared fasting every other day to eating less every day showed that both worked about equally for weight loss, though people struggled with the fasting days.

So, it's very reasonable to choose a reduced calorie plant-based, Mediterranean-style diet. But research suggests that not all IF approaches are the same, and some IF diets are indeed effective and sustainable, especially when combined with a nutritious plant-based diet.

Our metabolism has adapted to daytime food, nighttime sleep. Nighttime eating is well associated with a higher risk of obesity, as well as diabetes. Based on this, researchers from the University of Alabama conducted a study with a small group of obese men with prediabetes.

They compared a form of intermittent fasting called "early time-restricted feeding," where all meals were fit into an early eight-hour period of the day 7 am to 3 pm , or spread out over 12 hours between 7 am and 7 pm. Both groups maintained their weight did not gain or lose but after five weeks, the eight-hours group had dramatically lower insulin levels and significantly improved insulin sensitivity, as well as significantly lower blood pressure.

The best part? The eight-hours group also had significantly decreased appetite. They weren't starving. Just changing the timing of meals, by eating earlier in the day and extending the overnight fast, significantly benefited metabolism even in people who didn't lose a single pound.

But why does simply changing the timing of our meals to allow for fasting make a difference in our body? An in-depth review of the science of IF recently published in New England Journal of Medicine sheds some light.

Fasting is evolutionarily embedded within our physiology, triggering several essential cellular functions. Flipping the switch from a fed to fasting state does more than help us burn calories and lose weight. 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. Another study reported that young men ate about fewer calories per day when they limited their food intake to a 4-hour period 4.

However, other studies have shown that some people do not actually eat fewer calories during time-restricted eating 2 , 5. Diet records rely on participants to write down what and how much they eat. Unfortunately, diet records are not very accurate 6. Whether or not it actually decreases the amount of food eaten probably varies by individual.

Time-restricted eating may have several health benefits, including weight loss, better heart health and lower blood sugar levels. However, other studies in normal-weight people have reported no weight loss with eating windows of similar duration 2 , 9. Whether or not you will experience weight loss with time-restricted eating probably depends on whether or not you manage to eat fewer calories within the eating period If this style of eating helps you eat fewer calories each day, it can produce weight loss over time.

If this is not the case for you, time-restricted eating may not be your best bet for weight loss. Several substances in your blood can affect your risk of heart disease, and one of these important substances is cholesterol.

However, other research using a similar length of eating window did not show any benefits on cholesterol levels 9. Both studies used normal-weight adults, so the inconsistent results may be due to differences in weight loss.

When participants lost weight with time-restricted eating, their cholesterol improved. When they did not lose weight, it did not improve 8 , 9.

Several studies have shown that slightly longer eating windows of 10—12 hours may also improve cholesterol. Having too much sugar in your blood can lead to diabetes and damage several parts of your body. Time-restricted eating is very simple — simply choose a certain number of hours during which you will eat all your calories each day.

If you are using time-restricted eating to lose weight and improve your health, the number of hours you allow yourself to eat should be less than the number you typically allow. For example, if you normally eat your first meal at 8 a. and keep eating until around 9 p. To use time-restricted eating, you would reduce this number.

For example, you may want to choose to only eat during a window of 8—9 hours. Because time-restricted eating focuses on when you eat rather than what you eat, it can also be combined with any type of diet, such as a low-carb diet or high-protein diet. If you exercise regularly , you may wonder how time-restricted eating will affect your workouts.

One eight-week study examined time-restricted eating in young men who followed a weight-training program. It found that the men performing time-restricted eating were able to increase their strength just as much as the control group that ate normally A similar study in adult men who weight trained compared time-restricted eating during an 8-hour eating window to a normal eating pattern.

Based on these studies, it appears that you can exercise and make good progress while following a time-restricted eating program. However, research is needed in women and those performing an aerobic exercise like running or swimming.

Time-restricted eating is a dietary strategy that focuses on when you eat, rather than what you eat. By limiting all your daily food intake to a shorter period of time, it may be possible to eat less food and lose weight.

Make your journey into scheduled eating a little more manageable. When you lose weight, your body responds by burning fewer calories, which is often referred to as starvation mode.

This article investigates the…. Discover which diet is best for managing your diabetes. Getting enough fiber is crucial to overall gut health. Let's look at some easy ways to get more into your diet:. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep?

Health Conditions Discover Plan Connect. Nutrition Evidence Based Time-Restricted Eating: A Beginner's Guide.

Evert, A. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care 42 , — Article PubMed PubMed Central Google Scholar. Patikorn, C. Intermittent fasting and obesity-related health outcomes: an umbrella review of meta-analyses of randomized clinical trials.

JAMA Netw. Open 4 , e Harvie, M. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.

Int J. Article CAS PubMed Google Scholar. Di Francesco, A. A time to fast. Science , — Lawson, C. Animal models of GM2 gangliosidosis: utility and limitations.

Tiribuzi, R. Alzheimers Dis. Hultberg, B. beta-Hexosaminidase isoenzymes A and B in middle-aged and elderly subjects: determinants of plasma levels and relation to vascular disease. Kim, H. Renal tubular damage marker, urinary N -acetyl-β- d -glucosaminidase, as a predictive marker of hepatic fibrosis in type 2 diabetes mellitus.

Diabetes Metab. Article PubMed Google Scholar. Montgomery, M. Hexosaminidase A HEXA regulates hepatic sphingolipid and lipoprotein metabolism in mice.

FASEB J. Teong, X. Evidence gaps and potential roles of intermittent fasting in the prevention of chronic diseases. Acosta-Rodriguez, V. Pak, H. Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. Froy, O.

Effect of intermittent fasting on circadian rhythms in mice depends on feeding time. Ageing Dev. Regmi, P. Time-restricted eating: benefits, mechanisms, and challenges in translation.

iScience 23 , Liu, D. Calorie restriction with or without time-restricted eating in weight loss. Thomas, E.

Early time-restricted eating compared with daily caloric restriction: a randomized trial in adults with obesity. Obesity Silver Spring 30 , — Jamshed, H. Effectiveness of early time-restricted eating for weight loss, fat loss, and cardiometabolic health in adults with obesity: a randomized clinical trial.

JAMA Intern. Anton, S. Flipping the metabolic switch: understanding and applying the health benefits of fasting. Obesity Silver Spring 26 , — Trepanowski, J.

Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. Sundfor, T. Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: a randomized 1-year trial.

Shankar, S. Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of beta-cell function: results from the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series.

Diabetes Care 39 , — Berry, S. Human postprandial responses to food and potential for precision nutrition. Lind, M. The association between HbA1c, fasting glucose, 1-hour glucose and 2-hour glucose during an oral glucose tolerance test and cardiovascular disease in individuals with elevated risk for diabetes.

PLoS ONE 9 , e Cavalot, F. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study.

Antoni, R. Intermittent v. Templeman, I. A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults.

Gao, Y. Effects of intermittent or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants. Jones, R. Two weeks of early time-restricted feeding eTRF improves skeletal muscle insulin and anabolic sensitivity in healthy men.

Karpe, F. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 60 , — Phillips, D. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion.

Horowitz, M. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 36 , — Hutchison, A.

Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial. Obesity Silver Spring 27 , — CAS PubMed Google Scholar. Hemmingsen, B. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

Cochrane Database Syst. PubMed Google Scholar. Dashti, H. Late eating is associated with cardiometabolic risk traits, obesogenic behaviors, and impaired weight loss. Article PubMed Central Google Scholar. Early time-restricted feeding improves hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans.

Sutton, E. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.

Cell Metab. Vujović, N. Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity. Wehrens, S. Meal timing regulates the human circadian system.

Van Namen, M. Supervised lifestyle intervention for people with metabolic syndrome improves outcomes and reduces individual risk factors of metabolic syndrome: a systematic review and meta-analysis.

Metabolism , Keirns, B. Fasting, non-fasting and postprandial triglycerides for screening cardiometabolic risk. Pattern of serum beta-hexosaminidase in liver cirrhosis.

Poon, P. Plasma N -acetyl-beta- d -glucosaminidase activities and glycaemia in diabetes mellitus. Diabetologia 24 , — Whiting, P. Serum and urine N -acetyl-beta- d -glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics.

Acta 92 , — Lipina, C. Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance: evidence and mechanisms. FEBS Lett. Jensen, M.

Circulation , S—S Rationale and protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes. Res Clin. An update to the study protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes.

Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids The National Academies Press, Matsuda, M.

Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22 , — Leaback, D. Studies on glucosaminidase.

fluorimetric assay. Biochem J. Whyte, L. IBRO Neurosci. Download references. This work was supported by the National Health and Medical Research Council Project Grant APP was supported by an Australian Government Research Training Program Scholarship from The University of Adelaide.

This work was supported by a Diabetes Australia Research Program Grant Y21G-SART awarded to T. and L. The funder had no role in the design of this study and the interpretation of the study results.

We thank all the trial participants. Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. Xiao Tong Teong, Kai Liu, Andrew D. Vincent, Julien Bensalem, Bo Liu, Lijun Zhao, Christine Feinle-Bisset, Gary A. Wittert, Amy T. Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Vincent, Julien Bensalem, Bo Liu, Kathryn J. Hattersley, Lijun Zhao, Timothy J. Sargeant, Gary A. You can also search for this author in PubMed Google Scholar.

and G. designed the study. wrote the statistical analysis plan, performed randomization and statistical analysis. and A. collected the blood samples. provided clinical support and supervision. analyzed the data. and T. measured the β-hexosaminidase activity. All authors critically revised the draft and approved the final manuscript.

had full access to the data and had primary responsibility for the final publication. Correspondence to Leonie K. Nature Medicine thanks Jonathan Little, Krista Varady, Luke Ouma and the other, anonymous, reviewer s for their contribution to the peer review of this work.

Primary Handling Editor: Jennifer Sargent, in collaboration with the Nature Medicine team. Points indicate prior blue , posterior red and observed means black. We note that our prior belief was for a correlation of 0. Treatment group trajectories were compared using linear mixed effects regression assuming piecewise linear effects assumed for the interventions over two time periods: month 0—6 and month 7—18, and both random intercepts and slopes for individuals.

Springer Nature or its licensor e. a society or other partner holds exclusive rights to this article under a publishing agreement with the author s or other rightsholder s ; author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions. Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nat Med 29 , — Download citation.

Received : 19 September Accepted : 02 March Published : 06 April Issue Date : April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. nature nature medicine articles article.

Download PDF. Subjects Obesity Randomized controlled trials. Abstract Intermittent fasting appears an equivalent alternative to calorie restriction CR to improve health in humans.

Randomized controlled trial for time-restricted eating in healthy volunteers without obesity Article Open access 22 February Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial Article Open access 15 January Effects of intermittent or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants Article Open access 26 May Full size image.

Table 1 Baseline characteristics Full size table. Table 2 Changes in glycemic, cardiovascular and liver markers during a 6-month intervention period and following a month follow-up period Full size table.

Table 3 Changes in body weight and body composition during a 6-month intervention period and following a month follow-up period Full size table. Table 4 Safety outcomes Full size table.

Discussion This randomized controlled trial demonstrated that iTRE was superior to CR for improving postprandial glucose tolerance in adults at increased risk of developing type 2 diabetes. Methods Study design and participants This open-label, three-arm, parallel group sequential randomized controlled trial was conducted between 26 September and 30 November and involved a 6-month intervention phase followed by a month follow-up.

Body composition During each metabolic visit, body weight, and waist and hip circumference were measured in a gown after voiding. Dietary intake Prescribed daily energy requirements were calculated by averaging predicted daily energy expenditure from a published equation that uses gender, age, height and weight variables Meal tests Participants attended the research facility at baseline, month 6 and month 18 for metabolic testing.

Blood analysis Blood glucose was assayed by the hexokinase method Cobas Integra plus, Roche. Safety outcomes During each clinic visit, participants were asked to report if they had experienced any health-related conditions. Similar content being viewed by others.

Data availability Anonymized data from this study are available on request from the corresponding author for 36 months from date of publication with a full research plan for academic use only.

Code availability No unique software or computational code was created for this study. References Diabetes Prevention Program Research Group et al. Article Google Scholar Uusitupa, M. Article CAS PubMed PubMed Central Google Scholar Evert, A.

Article PubMed PubMed Central Google Scholar Patikorn, C. Article PubMed PubMed Central Google Scholar Harvie, M. Article CAS PubMed PubMed Central Google Scholar Harvie, M. Article CAS PubMed Google Scholar Di Francesco, A. Article PubMed PubMed Central Google Scholar Lawson, C.

Article CAS PubMed PubMed Central Google Scholar Tiribuzi, R. Article CAS PubMed Google Scholar Hultberg, B. Article CAS PubMed Google Scholar Kim, H. Article PubMed Google Scholar Montgomery, M. Article CAS PubMed Google Scholar Teong, X.

Article PubMed Google Scholar Acosta-Rodriguez, V. Article CAS PubMed PubMed Central Google Scholar Pak, H. Article CAS PubMed PubMed Central Google Scholar Froy, O.

Article CAS PubMed Google Scholar Regmi, P. Article CAS PubMed PubMed Central Google Scholar Liu, D. Article CAS PubMed Google Scholar Thomas, E. Article CAS PubMed Google Scholar Jamshed, H. Article PubMed Google Scholar Anton, S.

Article PubMed Google Scholar Trepanowski, J. Article PubMed PubMed Central Google Scholar Sundfor, T. Article CAS PubMed Google Scholar Shankar, S. Article CAS PubMed PubMed Central Google Scholar Berry, S. Article CAS PubMed PubMed Central Google Scholar Lind, M. Although some individuals with obesity are metabolically fit, with a metabolic profile like nonobese individuals 1 , obesity 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. IF involves restricting caloric intake to specific hours of the day or to specific days of the week or month.

Although TRF or TRE does not overtly attempt to reduce caloric intake, preliminary evidence from small studies suggests that TRF or TRE may lead to a concomitant reduction in total caloric intake 4 , 5 as well as improvements in metabolic health and weight loss.

Unique features of TRF or TRE, including the fact that one does not have to restrict calories but only when calories are consumed, may facilitate adherence and long-term weight loss maintenance 6. There are at least 2 reasons why TRE has gained popularity in recent years.

First, TRE restricts the time of eating each day, but not the calories consumed during the eating window. This is unique among dietary strategies, which generally restrict calories, macronutrients, or food types. As such, TRE may be appealing to people who want to improve their health but do not want to reduce their caloric consumption or restrict their dietary content.

Second, studies have shown that many of the health benefits of IF in general, and TRE specifically, are not simply the result of reduced free radical production or weight loss.

Instead, these health benefits are due to evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation 7.

Preclinical studies consistently show the robust disease modifying effect of TRF or other forms of IF on a wide range of chronic disorders, including obesity 8 , cardiovascular disease 8 , cancer 9 , and neurodegenerative diseases A key component of why TRE promotes health and improves metabolic functioning is that it facilitates metabolic switching 11 , Metabolic switching has potential utility for the treatment of obesity and related metabolic conditions, including metabolic syndrome and type 2 diabetes Metabolic switching not only provides ketones during fasting but also elicits responses that bolster physiologic performance and disease resistance 7.

Metabolic syndrome has been associated with an increased risk of cardiovascular disease, type 2 diabetes, and cancer 2. Weight loss decreases the risk of developing metabolic syndrome and its components: central obesity, hypertension, prediabetes, and dyslipidemia This caloric reduction is similar to diets with intentional daily caloric restriction CR , suggesting that TRE may be a more sustainable strategy for weight loss than standard diets Almost two-thirds Long-term adherence assessment is important to determine if a diet will be successful in the real world.

Several key features of TRE promote adherence relative to CR. Additionally, TRE alternates periods of ad libitum intake with periods of fasting, which may reduce conflict with the homeostatic drive to eat and prevent dietary lapses resulting from prolonged negative energy balance 3.

However, reported TRE studies have lasted for days to weeks, and long-term adherence investigations are needed. On the other hand, TRE is not for everyone. Some individuals find the long periods between eating windows undesirable. Adhering to a TRE diet is likely not wise for type 1 diabetics, because metabolic switching, which can occur with TRE, may lead to diabetic ketoacidosis Finally, many people initiate a diet with the primary goal to lose weight, with metabolic improvement as a secondary benefit.

TRE does not lead to weight loss among all individuals, especially if the individual is able to consume as many or more calories than they did prior to initiating a TRE diet. For individuals whose primary purpose is weight loss, they may not adhere to TRE in the long term. Many studies suggest that TRE provides beneficial metabolic effects, regardless of the degree of CR For example, a randomized isocaloric study evaluating TRE showed a decrease in the average blood sugar level and reduced insulin resistance Likewise, a crossover randomized trial 20 demonstrated that short-term TRE improved nocturnal glycemic control.

The metabolic improvement observed with TRF and TRE in some studies despite no loss of weight has led to speculation that triggering the fasting response daily or at specific times is in itself beneficial. This would explain why dietary dilution, a form of CR in which mice eat all day to compensate for the low density of energy in their diet, does not result in lifespan extension.

Hence, chronic CR may improve health, at least in part, through an extended period of fasting Most preclinical studies suggest that when an animal eats influences the metabolic effects.

On the other hand, it was found that TRF prevented obesity and metabolic syndrome in mice lacking a circadian clock Some studies in humans support an influence of when one eats on metabolic impact and suggest that eating at night is harmful because it makes a person prone to obesity Women with metabolic syndrome who consumed 3 daily meals whose primary meal was at breakfast showed greater weight loss and waist circumference reduction and more reduction in fasting glucose, insulin, and Homeostatic Model Assessment for Insulin Resistance HOMA-IR 27 than those whose primary meal was at dinner.

There was also a larger decrease in mean triglyceride levels, glucose, ghrelin, and insulin levels and higher rates of satiety in the breakfast group.

Men with prediabetes have also shown health benefits eg, improved insulin sensitivity, blood pressure, and oxidative stress from eating earlier in the day over a 6-hour window compared with a control group who consumed a similar number of calories over a hour window Not all human studies support the idea that eating earlier during the day is metabolically superior to eating later in the day.

For example, it appears that evening protein ingestion might be beneficial, leading to increased whole body and muscle protein synthesis This is thought to be due to the fact that casein is a slow release protein and eating before sleep might prolong the anabolic milieu.

Perhaps the largest evidence for late eating being metabolically beneficial compared with an unrestricted eating time is Ramadan, the ninth month in the Islamic calendar, which is observed worldwide by Muslims with daily daylight fasting, prayer, and community.

A study that compared TRE with Ramadan fasting found that the 2 fasting strategies had similar characteristics and positive health effects TRE does not require CR but often leads to fewer calories being eaten than a control diet that does not restrict when one can eat 5.

CR has demonstrated many health benefits, but also potential downsides, at least in animal studies. Diet composition plays an important role in human health throughout the lifespan, and the optimal composition of dietary protein, especially animal protein, appears to change with age.

On the other hand, the development of frailty in elderly individuals because of the loss of muscle mass negatively influences overall mortality. Frailty has been linked both to low daily protein consumption and to protein consumption at only 1 meal Thus, any diet in the elderly that restricts overall daily protein or when protein can be consumed such as TRE could be harmful, whereas a diet higher in protein that is consumed during at least 3 daily meals should at least partially mitigate muscle mass loss There are also potentially negative social consequences associated with TRE in humans Social support plays a critical role in how successful a CR dietary intervention is for an individual 36 , and social support with TRE should be no different.

Conversely, being able to share the benefits of TRE with close others can strengthen relationships and resulting social support to increase TRE adherence.

Most of what we know about the benefits from TRF and TRE comes from animal studies Thus far, human studies have generally been of small size and short duration, even those published in the last 3 years Table 1.

When assessed, participants generally lost weight, resulting in a lower body mass index. Assessments of metabolic function, including blood pressure, changes in lipids, glucose level, fasting insulin, and insulin resistance were not consistently noted to improve on a TRE diet.

Overall, adherence to the TRE intervention was high across these short-term studies Table 2. Sample of TRE studies published a. This is not meant to be an exhaustive list. Not explicitly defined or measured.

Interest in understanding the metabolic effects of TRF and TRE has increased among the lay public and in the scientific community. NIH funding can be used as a barometer with which to assess the growing interest in TRE and to determine future research directions.

The first NCI proposal on TRF or TRE was submitted in FY Of the TRF or TRE proposals submitted to NCI prior to FY, only 1 5R01CA was awarded. This R01 focused entirely on preclinical studies. Increased interest in the possible beneficial effects of IF and TRF or TRE on cancer led the NCI to address the topic as a provocative question PQ PQ2: How does intermittent fasting affect cancer incidence, treatment response, or outcome?

Although the PQ2 required human studies, supportive preclinical studies were allowed. It is notable that 4 of the 5 submitted PQ2 grants that received fundable scores addressed TRF or TRE rather than other forms of IF Table 3.

A sample of funded NIH grants on TRE and IF a. There is excitement in the health-care community about the potential of TRE to improve metabolic dysfunction in those with metabolic syndrome and to assist with weight loss among individuals with overweight or obesity.

This potential benefit, combined with the ability to maintain usual dietary preferences during the daily eating window, has led many lay individuals to practice TRE as well. There is reason to believe this approach will produce greater adherence than standard CR diets; however, future studies focusing on long-term adherence are needed.

Preclinical studies demonstrate convincing evidence of weight loss in obese animals and improvement in metabolic parameters in those with metabolic dysfunction.

Studies in humans are not as consistent in their findings, though this may be due to their mostly being of small sample size and short duration.

Thus, it is still not certain if TRE is beneficial in humans. If it is, many questions regarding who is most likely to benefit remain, such as the following: 1 Are the metabolic benefits more likely among individuals with overweight and obesity than among normal-weight individuals?

and 5 Are there circumstances in which TRE may be harmful? To help answer these questions, the NCI issued a PQ in on IF, which includes TRE.

Five proposals have been funded, 4 R01s and 1 R Each addresses how TRE influences cancer, some with an entirely human focus, others combining human and animal studies to delve in the mechanism s by which TRE may work.

The NIA has issued a request for information to evaluate if sustained reductions in caloric intake and related dietary practices influence health span and longevity, funding 2 planning projects: 1 in younger and a second in older individuals.

Because there is a lack of prospective studies evaluating long-term adherence to TRE, the NIA funded study that evaluates TRE in older individuals for a year should provide important information in this regard.

An important limitation of this report relates to the fact that there are relatively few human TRE studies, especially those that have been conducted for 1 year or longer. Our understanding of whether and how TRE works will continue to expand in the coming years.

The promise of TRE is great, especially given its good short-term adherence profile, preliminary evidence from observational and epidemiologic studies that long-term adherence is feasible, as well as the possibility that metabolic benefit can be achieved even in the absence of weight loss.

Author contributions: PB: methodology, data curation, writing-review and editing. SGO: methodology, data curation, writing-review and editing. BMH-S: conceptualization, writing-review and editing. ERS: conceptualization, methodology, data curation, writing-original draft, writing-review and editing.

Disclaimers: Opinions expressed by the authors are their own and this material should not be interpreted as representing the official viewpoint of the US Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute.

Korduner J , Bachus E , Jujic A , Magnusson M , Nilsson PM. Metabolically healthy obesity MHO in the Malmo diet cancer study - epidemiology and prospective risks. Obes Res Clin Pract. doi: Google Scholar. Esposito K , Chiodini P , Colao A , Lenzi A , Giugliano D. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis.

Diabetes Care. Patterson RE , Sears DD. Metabolic effects of intermittent fasting. Annu Rev Nutr. Gabel K , Cienfuegos S , Kalam F , Ezpeleta M , Varady KA.

Time-restricted eating to improve cardiovascular health. Curr Atheroscler Rep. Wilkinson MJ , Manoogian ENC , Zadourian A , et al. Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome.

Cell Metab. Perspective: time-restricted eating compared with caloric restriction: potential facilitators and barriers of long-term weight loss maintenance. Adv Nutr. de Cabo R , Mattson MP.

Effects of intermittent fasting on health, aging, and disease. N Engl J Med. Chaix A , Zarrinpar A , Miu P , Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Das M , Ellies LG , Kumar D , et al.

Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models. Nat Commun. Mattson MP , Longo VD , Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. Anton SD , Moehl K , Donahoo WT , et al. Flipping the metabolic switch: understanding and applying the health benefits of fasting.

Obesity Silver Spring. Schuppelius B , Peters B , Ottawa A , Pivovarova-Ramich O. Time restricted eating: a dietary strategy to prevent and treat metabolic disturbances. Front Endocrinol Lausanne.

Anton SD , Lee SA , Donahoo WT , et al. The effects of time restricted feeding on overweight, older adults: a pilot study. Russo A , Autelitano M , Bisanti L.

Metabolic syndrome and cancer risk. Eur J Cancer. Phillips NE , Mareschal J , Schwab N , et al. The effects of time-restricted eating versus standard dietary advice on weight, metabolic health and the consumption of processed food: a pragmatic randomised controlled trial in community-based adults.

Adafer R , Messaadi W , Meddahi M , et al. Marinac CR , Nelson SH , Breen CI , et al. Prolonged nightly fasting and breast cancer prognosis. JAMA Oncol. Goerl B. To skip or not to skip: does intermittent fasting help people with diabetes?

Accessed May 9, Jamshed H , Beyl RA , Della Manna DL , Yang ES , Ravussin E , Peterson CM. Early time-restricted feeding improves hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans.

Parr EB , Devlin BL , Radford BE , Hawley JA. Sutton EF , Beyl R , Early KS , Cefalu WT , Ravussin E , Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.

Di Francesco A , Di Germanio C , Bernier M , de Cabo R. A time to fast. Panda S. Circadian physiology of metabolism. Ulgherait M , Midoun AM , Park SJ , et al. Circadian autophagy drives iTRF-mediated longevity.

Chaix A , Lin T , Le HD , Chang MW , Panda S. Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock.

Gallant AR , Lundgren J , Drapeau V. The night-eating syndrome and obesity. Obes Rev. Jakubowicz D , Barnea M , Wainstein J , Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women.

Nighttime eating and breast cancer among Chinese women in Hong Kong. Breast Cancer Res. Kogevinas M , Espinosa A , Castello A , et al. Effect of mistimed eating patterns on breast and prostate cancer risk MCC-Spain Study. Int J Cancer.