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Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD., Competing Interests: Declaration of competing interest Christos S. Mantzoros has recused himself as EIC from handling this manuscript, reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. Christopher D Byrne has received an independent research grant from Echosens. France. W. Kim received honoraria for lectures from GSK, Hanmi, KOBIOLABS, and Novo Nordisk; consulting fees from Boehringer-Ingelheim, GSK, Novo Nordisk, Ildong, YUHAN, Hanmi, HK Inoen, Standigm, PharmaKing, Olix Pharma, TSD Life Sciences, Daewoong, QUEST, Therasid Bioscience, and Korea United Pharm; grants from GSK, Gilead, Novartis, Pfizer, Roche, Springbank, Ildong, BMS, DaeWoong, Hanmi, Novo Nordisk, Galmed, Enyo, and KOBIOLABS; stock options from KOBIOLABS and Lepidyne; and founded Remedygen outside the submitted work. Anoop Misra has received honorarium for lectures from Astra Zendeca, Boehringer Ingelgheim, Janssen, Lupin, Novo Nordisk and US Vitamins. Yusuf Yilmaz has served as a consultant or advisory board member for Zydus and Novo Nordisk. Boehringer Ingelheim. Wah Kheong Chan has served as a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Ming-Lung Yu has received research support (grant) from Abbvie, BMS, Gilead, Merck and Roche diagnostics, served as a consultant of Abbott, Abbvie, BMS, Gilead, Roche and Roche diagnostics, and speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. Vincent Wong has served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, Novo Nordisk, and Unilab. He has received a research grant from Gilead Sciences, and is a co-founder of Illuminatio Medical Technology. Giada Sebastiani has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. Jacob George has served on advisory Boards and receives honoraria for talks from Novo Nordisk, Astra Zeneca, Roche, BMS, Pfizer, Cincera, Pharmaxis, Boehringer Mannheim, CSL, Gilead, Eisai. Carolyn Newberry serves as a consultant for Nestle Nutrition Sciences. The other authors declare no conflict of interest related to the preparation of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus daily calorie restriction (CR) on sleep quality, duration, insomnia severity, and risk of obstructive sleep apnea in adults with obesity over one year. Methods: A total of 90 participants were randomized to one of three groups for 12 months: 8 h TRE (eating only between 12 p.m. and 8 p.m.); CR (25% daily calorie restriction) or a no-intervention control group. Results: By the end of the study, weight loss was 4.61 kg (95% CI; 7.37 to 1.85 kg; p ≤ 0.01) for the TRE group and 5.42 kg (CI; 9.13 to 1.71 kg; p ≤ 0.01) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI; 3.07 to 4.69]; p = 0.68]). Self-reported sleep quality, sleep duration, insomnia severity, and risk of obstructive sleep apnea did not change in the TRE or CR groups versus controls by month 12. Conclusions: These findings suggest that the weight loss produced by TRE and CR does not have any impact on various sleep parameters in adults with obesity over one year.

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain., Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined., Design: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out., Participants/setting: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups., Intervention: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations., Main Outcome Measures: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis., Statistical Analysis: Repeated measures ANOVA and mediation analysis were conducted., Results: Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence., Conclusions: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention., Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial., Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications., Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER)., Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults., Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention., Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.

Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management., Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity., Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included., Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52)., Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed., Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups., Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice., Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.

The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13-17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3-4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg ( p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3-4 correlated with greater weight loss at week-4 (r = -0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs.

This study examined the effects of time restricted eating (TRE) on sex hormones in males and females, versus daily calorie restriction (CR). Adults with obesity (n = 90) were randomized to 1 of 3 groups for 12-months: 8-h TRE (eating only between 12:00 to 8:00 pm, with no calorie counting); CR (25% energy restriction daily); or control. Body weight decreased (P < 0.01) in the TRE and CR groups, relative to controls, in males, premenopausal females, and postmenopausal females, by month 12. Total testosterone, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) levels did not change over time, or between groups, in males, premenopausal females, and postmenopausal females. Estradiol, estrone, and progesterone were only measured in postmenopausal females, and remained unchanged. These findings suggest that TRE produces significant weight loss but does not impact circulating sex hormone levels in males and females with obesity over 12 months, relative to CR and controls., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus calorie restriction (CR) and controls on sleep in adults with type 2 diabetes (T2D). Adults with T2D (n = 75) were randomized to 1 of 3 interventions for 6 months: 8 h TRE (eating only between 12 and 8 pm daily); CR (25% energy restriction daily); or control. Our results show that TRE has no effect on sleep quality, duration, insomnia severity, or risk of obstructive sleep apnea, relative to CR and controls, in patients with T2D over 6 months.

There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it. Mechanistically, the CCL22 receptor, C-C motif chemokine receptor 4 (CCR4), within eosinophils and its downstream focal adhesion kinase/p65/interleukin-4 signaling are essential for CCL22-mediated beige adipocyte formation. Moreover, CCL22 levels are inversely correlated with body weight and fat mass in mice and humans. Acute elevation of CCL22 levels effectively prevents diet-induced body weight and fat gain by enhancing adipose beiging. Together, our data identify the CCL22-CCR4 axis as an essential mediator for LN-controlled adaptive thermogenesis and highlight its potential to combat obesity and its associated complications.

Aim: With increasing rates of global obesity and associated health issues, there is an ever-increasing need for weight management solutions to be more accessible. Mobile applications offer accessible support systems and have the potential to offer a viable and effective weight management solution as an alternative to traditional healthcare models., Objective: To evaluate the effectiveness of the SIMPLE mobile application for time-restricted eating in achieving weight loss (WL)., Methods: User data were analyzed between January 2021 and January 2023. In-app activity was calculated as the proportion of active days over 12, 26 and 52 weeks. A day is considered active if it contains at least one in-app action (e.g., logging weight, food, fasting, or physical activity). Users were categorized into four in-app activity levels: inactive (in-app activity <33%), medium activity (33%-66%), high activity (66%-99%), and maximal activity (100%). Weight change among in-app activity groups was assessed at 12, 26, and 52 weeks., Results: Out of 53,482 users, a positive association was found between the use of the SIMPLE app and WL. Active app users lost more weight than their less active counterparts. Active users had a median WL of 4.20%, 5.04%, and 3.86% at 12, 26, and 52 weeks, respectively. A larger percentage of active users-up to 50.26%-achieved clinically significant WL (≥5%) when compared to inactive users. A dose-response relationship between WL and app usage was found after adjusting for gender, age, and initial Body Mass Index; a 10% increase in app activity correlated with increased WL by 0.43, 0.66 and 0.69 kg at 12, 26, and 52 weeks, respectively., Conclusions: The study demonstrates that the SIMPLE app enables effective WL directly associated with the level of app engagement. Mobile health applications offer an accessible and effective weight management solution and should be considered when supporting adults to lose weight., Competing Interests: RH, DN and RS are employees of Simple.Life Apps Inc. The Simple.Life Apps Inc. administration had no role in the design of the study, in the collection, analyses, or interpretation of the data, in the writing of the manuscript, or in the decision to publish the results., (© 2024 Simple.Life Apps Inc. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0695.

Most adults with type 1 diabetes (T1DM) are either overweight or obese. As such, dietary management is recommended as an adjunct to insulin treatment to improve glycemic control and facilitate weight loss in these patients. Time-restricted eating (TRE) is a form of intermittent fasting that offers a simplified approach to treating obesity in T1DM. TRE typically involves restricting eating to 6 to 10 h per day, with water and medications allowed outside the eating window. This review examines the efficacy of TRE and other fasting protocols in improving weight and glycemic control in patients with obesity and T1DM. This review will also evaluate the safety of these regimens and provide advice to clinicians on implementing intermittent fasting in T1DM., Competing Interests: Declaration of interests K.A.V. received author fees from Hachette Book Group for the book The Every Other Day Diet and from Pan MacMillan Publishing for the book The Fastest Diet. K.A.V. also serves on two NIH Data Safety Monitoring Boards for the HALLO-P study and the DiAL Health study. S.R. received speaker fees from Eli Lilly. A.P.V. has participated in an advisory board for Rhythm Pharmaceuticals. L.S.C. has received two investigator initiated grants (product only) from Dexcom., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The goal of this narrative review is to summarize the effects of prolonged fasting on various metabolic health measures, including body weight, blood pressure, plasma lipids, and glycemic control. Prolonged fasting is characterized by consciously eating little to no food or caloric beverages for several days to weeks. Results reveal that prolonged fasting for 5-20 days produces potent increases in circulating ketones, and mild to moderate weight loss of 2-10%. Approximately two-thirds of the weight lost is lean mass, and one-third is fat mass. The excessive lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern. Systolic and diastolic blood pressure consistently decreased with prolonged fasting. However, the impact of these protocols on plasma lipids is less clear. While some trials demonstrate decreases in LDL cholesterol and triglycerides, others show no benefit. With regard to glycemic control, reductions in fasting glucose, fasting insulin, insulin resistance, and glycated hemoglobin (HbA1c) were noted in adults with normoglycemia. In contrast, these glucoregulatory factors remained unchanged in patients with type 1 or type 2 diabetes. The effects of refeeding were also examined in a few trials. It was shown that 3-4 months after the fast was completed, all metabolic benefits were no longer observed, even when weight loss was maintained. With regard to adverse events, metabolic acidosis, headaches, insomnia, and hunger were observed in some studies. In summary, prolonged fasting appears to be a moderately safe diet therapy that can produce clinically significant weight loss (>5%) over a few days or weeks. However, the ability of these protocols to produce sustained improvements in metabolic markers warrants further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality., Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004)., Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p  < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p  = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p  = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p  = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p  = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p  = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p  = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p  = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p  = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p  = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p  = 0.008)., Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER., Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Time-restricted eating (TRE) has become a popular strategy to treat obesity. TRE involves confining the eating window to 4-10 h per day and fasting for the remaining hours (14-20 h fast). During the eating window, individuals are not required to monitor food intake. The sudden rise in popularity of TRE is most likely due to its simplicity and the fact that it does not require individuals to count calories to lose weight. This feature of TRE may appeal to certain individuals with obesity, and this could help produce lasting metabolic health improvements. The purpose of this review is to summarize current evidence from randomized clinical trials of TRE (without calorie counting) on body weight and metabolic risk factors. The efficacy of TRE in various populations groups, including those with obesity, type 2 diabetes (T2DM), and polycystic ovary syndrome (PCOS), is also examined., Competing Interests: Declaration of interests K.A.V. received author fees from Hachette Book Group for the book The Every Other Day Diet and from Pan MacMillan Publishing for the book The Fasted Diet. She also serves on two Data Safety Monitoring Boards (DSMBs) for the NIH HALLO-P study and the DiAL Health study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied., Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use., Design, Setting, and Participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets., Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets., Main Outcomes and Measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure., Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively., Conclusions and Relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events., Trial Registration: ClinicalTrials.gov Identifier: NCT04258332.

This study aimed to better understand the relationship between bone-related biomarkers and nutrient stress in the context of metabolic health. We investigated plasma osteocalcin (OC) during an oral glucose challenge and experimental hyperinsulinemia in Type 2 diabetes (T2DM) and lean healthy controls (LHC). Older individuals with obesity and T2DM (n = 9) and young LHCs (n = 9) underwent a 75g oral glucose tolerance test (OGTT) and a 40 mU/m 2 /min hyperinsulinemic-euglycemic clamp. Plasma undercarboxylated OC (ucOC) and total OC were measured at baseline, 60mins, and 120mins of the OGTT and clamp via ELISA. In addition, plasma alkaline phosphatase (ALP), leptin, adiponectin, Vitamin D and insulin were measured and indices of insulin sensitivity and β-cell function were derived. The T2DM group had lower (p<0.05) ucOC and ucOC:total OC ratio than LHC during both the OGTT and clamp. Further, baseline ucOC was positively correlated to indices of β-cell function and negatively correlated to indices of insulin resistance when both groups were combined (all p<0.05). Suppression of OC observed in T2DM may be related to glucose intolerance and insulin resistance. Similarly, our data suggest that the observed phenotypic differences between groups are likely a product of long-term glucose dysregulation rather than acute flux in glucose or insulin., Competing Interests: The authors have no conflicts to report., (© 2023 The Authors.)

The purpose of this secondary analysis is to compare the effects of two popular weight loss regimens, time-restricted eating (TRE) and daily calorie restriction (CR), on mood and quality-of-life measures in adults with obesity. Ninety participants were randomized to one of three interventions for 12 months: 8 h TRE (eating only between 12:00 and 8:00 p.m., with no calorie counting); CR (25% energy restriction daily); or no-intervention control group. Questionnaires were administered to measure mood (Beck Depression Inventory-II (BDI-II), and Profile of Mood States (POMS)) and quality of life (Rand 36-Item Short Form) at baseline and month 12. Body weight decreased in the TRE group (-4.87%, 95%CI: -7.61, -2.13) and CR group (-5.30%, 95%CI: -9.06, -1.54) versus controls, with no difference between TRE and CR. The BDI-II depression score did not change in the TRE or CR group, versus controls, by month 12. Likewise, there were no changes in any of the POMS subscales (tension, depression, anger, fatigue, anger, confusion, or vigor) or the total mood disturbance score in the TRE or CR group versus controls. As for quality of life, there were no significant changes in the SF-36 constructs of mental health, bodily pain, and general physical health in the TRE or CR group versus controls. However, there was a trend towards increased vitality in the TRE group (7.77 [95% CI: 0.15, 15.39] p = 0.05) relative to controls. There were no associations between changes in body weight, physical activity, mood, and quality of life in any group by the end of the study. These findings suggest that TRE and CR produce similar degrees of weight loss, but impact neither mood nor quality of life in adults with obesity over 12 months. Future well-powered studies will be needed to confirm these findings.

Importance: Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type 2 diabetes (T2D)., Objective: To determine whether TRE is more effective for weight reduction and glycemic control than daily calorie restriction (CR) or a control condition in adults with T2D., Design, Setting, and Participants: This 6-month, parallel-group, randomized clinical trial was performed between January 25, 2022, and April 1, 2023, at the University of Illinois Chicago. Participants were aged 18 to 80 years with obesity and T2D. Data analysis was based on intention to treat., Interventions: Participants were randomized to 1 of 3 groups: 8-hour TRE (eating 12 to 8 pm only, without calorie counting), CR (25% energy restriction daily), or control., Main Outcomes and Measures: The primary outcome measure was change in body weight by month 6. Secondary outcomes included changes in hemoglobin A1c (HbA1c) levels and metabolic risk factors., Results: Seventy-five participants were enrolled with a mean (SD) age of 55 (12) years. The mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39 (7) and the mean (SD) HbA1c level was 8.1% (1.6%). A total of 53 participants (71%) were women. One participant (1%) was Asian, 30 (40%) were Hispanic White, 40 (53%) were non-Hispanic Black, and 4 (5%) were non-Hispanic White. Participants in the TRE group were adherent with their eating window on a mean (SD) of 6.1 (0.8) days per week, and 17 (68%) in the CR group were adherent with their prescribed calorie goals over 6 months. The mean (SD) reduction in energy intake was -313 (509) kcal/d for TRE, -197 (426) kcal/d for CR, and -16 (439) kcal/d for controls. By month 6, body weight decreased significantly in the TRE group (-3.56% [95% CI, -5.92% to -1.20%]; P = .004) but not the CR group (-1.78% [95% CI, -3.67% to 0.11%]; P = .06), relative to controls. Levels of HbA1c decreased in the TRE (-0.91% [95% CI, -1.61% to -0.20%]) and CR (-0.94% [95% CI, -1.59% to -0.30%]) groups, relative to controls, with no differences between the TRE and CR groups. Time in euglycemic range, medication effect score, blood pressure, and plasma lipid levels did not differ among groups. No serious adverse events were reported., Conclusions and Relevance: This randomized clinical trial found that a TRE diet strategy without calorie counting was effective for weight loss and lowering of HbA1c levels compared with daily calorie counting in a sample of adults with T2D. These findings will need to be confirmed by larger RCTs with longer follow-up., Trial Registration: ClinicalTrials.gov Identifier: NCT05225337.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS owns 50% of the shares in Zuman International, which receives royalties for books AS has written and payments for presentations. AS additionally reports receiving presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics, and serving on the Nestlé Health Science Optifast VLCD advisory board from 2016 to 2018. ALA is Principal Investigator on two publicly funded trials where the intervention is provided by WW (formerly Weight Watchers) at no cost. KS has received in kind support as meals from ‘Lite and Easy’ for a clinical trial of weight stigma in young women in the last 5 years. ER has previously received research funding from Unilever and the American Beverage Association for unrelated work. JAY reports unrelated grant funds to NICHD supporting his research from Soleno Therapeutics, Rhythm Pharmaceuticals, and Hikma Pharmaceuticals. HFS has previously received a salary from Novo Nordisk unrelated to the present work. YSD has previously received a salary from Novo Nordisk unrelated to the present work. HAR has received funding from the National Institutes of Health in the area of adult and pediatric weight management. HAR is a committee member for the evidence-based practice guidelines for pediatric weight management for the American Psychological Association and for the Evidence Analysis Library for the Academy of Nutrition and Dietetics for the topic of adult weight management and the prevention of type 2 diabetes. MIC is an employee and shareholder at WW International, Inc. TKK has received professional fees from Novo Nordisk, Nutrisystem, Gelesis and Johnson & Johnson. CKM has received research grants and research agreements from Commission on Dietetic Registration, Academy of Nutrition and Dietetics, Ohio State University (InFACT), Novartis, University of Michigan’s Michigan Institute for Clinical and Health Research, Elizabeth Blackwell Institute for Health Research, Egg Board, PCORI, Department of Defense, Access Business Group International LLC, IDEA Public Schools, Louisiana LIFT Fund, WW, Pack Health, American Society for Nutrition, RAND Corporation, Richard King Mellon Foundation (RKMF), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Evidation Health, Leona M. and Harry B. Helmsley Charitable Trust, State of Louisiana- Federal American Rescue Plan (ARP), United States Department of Agriculture (USDA), National Institute for Health Research (NIHR), National Science Foundation (NSF), Lilly, National Institutes of Health (NIH). CKM has served on advisory boards for EHE Health, Wondr Health, and the Nutrition Obesity Research Center at the University of Alabama Birmingham and consulted to Kitchry, Metagenics, WW, Florida Hospital, Gila Therapeutics, Zafgen, OpenFit/MXCXM Health Inc. CKM developed intellectual property (IP) to quantify dietary adherence and his institution has licensed this IP, resulting in receiving royalties via the institution from the licensing fees. CKM is part of US and European patent applications for a weight loss approach called the Body weight Management and activity tracking system and also occasionally gives lectures and talks where he is provided with an honorarium, including talks to the Obesity Action Coalition and Indiana University Bloomington. Finally, CKM serves as a developer and facilitator for continuing education events sponsored by the Commission on Dietetic Registration, and is a Planning Committee Member for the Bray Course. The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the Public Health Service, the Department of Health and Human Services, USUHS, or the U.S. Department of Defense., (Copyright: © 2023 Jebeile et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Time-restricted eating (TRE), without calorie counting, has become a popular weight loss strategy, yet long-term randomized trials evaluating its efficacy are limited., Objective: To determine whether TRE is more effective for weight control and cardiometabolic risk reduction compared with calorie restriction (CR) or control., Design: 12-month randomized controlled trial. (ClinicalTrials.gov: NCT04692532)., Setting: University of Illinois Chicago from January 2021 to September 2022., Participants: 90 adults with obesity., Intervention: 8-hour TRE (eating between noon and 8:00 p.m. only, without calorie counting), CR (25% energy restriction daily), or control (eating over a period of 10 or more hours per day). Participants were not blinded., Measurements: Change in body weight, metabolic markers, and energy intake by month 12., Results: Seventy-seven persons completed the study. Mean age was 40 years (SD, 11), 33% were Black, and 46% were Hispanic. Mean reduction in energy intake was -425 kcal/d (SD, 531) for TRE and -405 kcal/d (SD, 712) for CR. Compared with the control group, weight loss by month 12 was -4.61 kg (95% CI, -7.37 to -1.85 kg; P  ≤ 0.01) (-4.87% [CI, -7.61% to -2.13%]) for the TRE group and -5.42 kg (CI, -9.13 to -1.71 kg; P  ≤ 0.01) (-5.30% [CI, -9.06% to -1.54%]) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI, -3.07 to 4.69 kg; P  = 0.68]) (0.43% [CI, -3.48% to 4.34%])., Limitation: Not blinded, not powered to detect relatively large differences in weight loss, and lack of adjustment for multiple comparisons., Conclusion: Time-restricted eating is more effective in producing weight loss when compared with control but not more effective than CR in a racially diverse population., Primary Funding Source: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0052.

Background: Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate., Methods: To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low., Results: We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20-104] participants and follow-up period of 13 [8-36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A 1c , and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants., Conclusions: This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality., (© 2023. The Author(s).)

Obesity is associated with low-grade inflammation. Weight loss, by means of dietary restriction, has been shown to reduce systemic inflammation. Intermittent fasting has recently gained popularity as a weight loss diet, but its effects on inflammatory markers in individuals with obesity have yet to be summarized. Accordingly, this review examined how the two main forms of intermittent fasting, i.e., time restricted eating (TRE) and alternate day fasting (ADF), impact body weight and key circulating inflammatory markers (i.e., C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6)), in adults with obesity. Results from this review reveal that TRE with various eating window durations (4-10 h per day) has no effect on circulating levels of CRP, TNF-alpha or IL-6, with 1-5% weight loss. As for ADF, reductions in CRP concentrations were noted when >6% weight loss was achieved. However, ADF had no effect on TNF-alpha or IL-6 concentrations, with this degree of weight loss. Thus, intermittent fasting has little or no effect on key inflammatory markers, but more research is warranted to confirm these preliminary findings., Competing Interests: KV received author fees from Hachette Book Group for the book, “The Every Other Day Diet.” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mulas, Cienfuegos, Ezpeleta, Lin, Pavlou and Varady.)

Here, we present a protocol for conducting magnetic resonance imaging proton density fat fraction (MRI-PDFF) to measure intrahepatic triglyceride (IHTG) content in adults with non-alcohol fatty liver disease (NAFLD). We describe steps for screening patients for NAFLD, MRI-PDFF scanning, and using MRI-PDFF data to quantify IHTG. This protocol can be repeated sequentially and used in weight loss trials. However, it is limited to patients with NAFLD as it does not assess non-alcoholic steatohepatitis or hepatic fibrosis. For complete details on the use and execution of this protocol, please refer to Ezpeleta et al. (2023). 1 ., Competing Interests: Declaration of interests K.A.V. received author fees from Hachette Book Group for the book, “The Every Other Day Diet”., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective : This study investigated how alternate-day fasting (ADF) combined with aerobic exercise impacts body weight and sleep in adults with non-alcoholic fatty liver disease (NAFLD). Methods : Adults with obesity and NAFLD (n = 80) were randomized into one of four groups for 3 months: combination of ADF (600 kcal "fast day," alternated with an ad libitum intake "feast day") and moderate-intensity aerobic exercise (five sessions per week, 60 min/session); ADF alone; exercise alone; or a no-intervention control group. Results : By month 3, body weight and intrahepatic triglyceride content decreased ( p < 0.001, group × time interaction) in the combination group versus the exercise group and control group, but not versus the ADF group. Sleep quality, measured by the Pittsburgh Sleep Quality Inventory (PSQI), did not change in the combination group (baseline: 6.0 ± 0.7; month 3: 5.6 ± 0.7), ADF group (baseline: 8.9 ± 1.0; month 3: 7.5 ± 0.8), or exercise group (baseline: 6.4 ± 0.6; month 3: 6.7 ± 0.6), versus controls (baseline: 5.5 ± 0.7; month 3: 4.6 ± 0.5). Wake time, bedtime, sleep duration, and insomnia severity did not change (no group x time interaction) over the course of the study in any group. Risk for obstructive sleep apnea was present in 30% of combination subjects, 75% of ADF subjects, 40% of exercise subjects, and 75% of controls, and did not change in the intervention groups, versus controls, by month 3. No associations were observed between changes in body weight, intrahepatic triglyceride content, and any sleep outcome. Conclusions : The weight loss induced by ADF combined with exercise does not improve sleep quality, duration, insomnia severity, or risk of obstructive sleep apnea in individuals with NAFLD.

Objective: The objective of this meta-analysis was to compare the effectiveness of different intermittent fasting (IF) regimens on weight loss, in the general population, and compare these to traditional caloric energy restriction (CER)., Methods: Three databases were searched from 2011 to June 2021 for randomized controlled trials (RCTs) that assessed weight loss and IF, including alternate day fasting (ADF), the 5:2 diet, and time-restricted eating (TRE). A random effect network analysis was used to compare the effectiveness between the three regimens. Meta-regression analysis was presented as weighted mean differences of body weight loss., Results: The exploratory random effects network analysis of 24 RCTs (n = 1768) ranked ADF as the most effective, followed by CER and TRE. The meta-analysis showed that IF regimens resulted in similar weight loss to CER (mean difference 0.26 kg, 95% CI: -0.31 to 0.84; p = 0.37). Compliance was generally high (>80%) in trials shorter than 3 months., Conclusions: The present meta-analysis concludes that IF is comparable to CER and a promising alternative for weight loss. Among the three regimens, ADF showed the highest effectiveness for weight loss, followed by CER and TRE. Further well-powered RCTs with longer durations of intervention are required to draw solid conclusions., (© 2022 Société des Produits Nestlé S.A. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objective: Concerns have been raised regarding the impact of time-restricted eating (TRE) on sex hormones in females. This study examined how TRE affects sex steroids in premenopausal and postmenopausal females., Methods: This is a secondary analysis of an 8-week TRE study (4- to 6-hour eating window) conducted in adults with obesity. Men and perimenopausal females were excluded. Females were classified into two groups based on menstrual status: premenopausal (n = 12) or postmenopausal (n = 11)., Results: After 8 weeks, body weight decreased in premenopausal females (-3% ± 2%) and postmenopausal females (-4% ± 2%) (main effect of time, p < 0.001), with no difference between groups (no group × time interaction). Circulating levels of testosterone, androstenedione, and sex hormone binding globulin (SHBG) did not change in either group (no group × time interaction). Dehydroepiandrosterone (DHEA) concentrations decreased (p < 0.05) in premenopausal (-14% ± 32%) and postmenopausal females (-13% ± 34%; main effect of time, p = 0.03), with no difference between groups. Estradiol, estrone, and progesterone were measured only in postmenopausal females, and they remained unchanged., Conclusions: In premenopausal females, androgens and SHBG remained unchanged during TRE, whereas DHEA decreased. In postmenopausal females, estrogens, progesterone, androgens, and SHBG did not change, but DHEA was reduced., (© 2022 The Obesity Society.)

Innovative non-pharmacological lifestyle strategies to treat non-alcoholic fatty liver disease (NAFLD) are critically needed. This study compared the effects of alternate day fasting (ADF) combined with exercise to fasting alone, or exercise alone, on intrahepatic triglyceride (IHTG) content. Adults with obesity and NAFLD (n = 80, 81% female, age: 23-65 years) were randomized to 1 of 4 groups for 3 months: combination of ADF (600 kcal/2,500 kJ "fast day" alternated with an ad libitum intake "feast day") and moderate-intensity aerobic exercise (5 session per week, 60 min/session); ADF alone; exercise alone; or a no-intervention control group. By month 3, IHTG content was significantly reduced in the combination group (-5.48%; 95% CI, -7.77% to -3.18%), compared with the exercise group (-1.30%; 95% CI, -3.80% to 1.20%; p = 0.02) and the control group (-0.17%; 95% CI, -2.17% to 1.83%; p < 0.01) but was not significantly different versus the ADF group (-2.25%; 95% CI, -4.46% to -0.04%; p = 0.05). Body weight, fat mass, waist circumference, and alanine transaminase (ALT) levels significantly decreased, while insulin sensitivity significantly increased in the combination group compared with the control group. Lean mass, aspartate transaminase (AST), HbA1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups. Combining intermittent fasting with exercise is effective for reducing hepatic steatosis in patients with NAFLD but may offer no additional benefit versus fasting alone., Competing Interests: Declaration of interests K.A.V. received author fees from Hachette Book Group for the book The Every Other Day Diet., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: Approximately 42% of American adults are living with obesity, increasing their risk of colorectal cancer (CRC). Efficacious approaches to prevent and treat obesity may reduce CRC incidence. Daily calorie restriction (Cal-R) is the most common approach to treating obesity, yet clinically meaningful weight loss is elusive owing to waning adherence. Time-restricted eating (TRE) consists of consuming foods within a specified time frame, creating a natural calorie deficit. TRE in animals shows cancer protective effects. In humans, TRE is safe and acceptable among adults with obesity, producing ~3% to 5% weight loss and reductions in oxidative stress and insulin resistance. However, TRE has not been tested rigorously for CRC preventive effects., Methods: The authors describe a 12-month randomized controlled trial of 8-hour TRE (ad libitum 12 PM-8 PM), Cal-R (25% restriction daily), or Control among 255 adults at increased risk for CRC and with obesity., Results: Effects on the following will be examined: 1) body weight, body composition, and adherence; 2) circulating metabolic, inflammation, and oxidative stress biomarkers; 3) colonic mucosal gene expression profiles and tissue microenvironment; and 4) maintenance of benefits on body weight/composition and CRC risk markers., Conclusions: This study will examine efficacious lifestyle strategies to treat obesity and reduce CRC risk among individuals with obesity., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

In a randomized controlled trial, Yoshino et al. 1 examined the effects of a worksite-based intensive lifestyle therapy on body weight, glycemic control, and diabetes remission, in adults with obesity and type 2 diabetes., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intermittent fasting is a popular diet for weight loss, but concerns have been raised regarding the effects of fasting on the reproductive health of women and men. Accordingly, we conducted this literature review to clarify the effects of fasting on reproductive hormone levels in humans. Our results suggest that intermittent fasting decreases androgen markers (i.e., testosterone and the free androgen index (FAI)) while increasing sex hormone-binding globulin (SHBG) levels in premenopausal females with obesity. This effect was more likely to occur when food consumption was confined to earlier in the day (eating all food before 4 pm). In contrast, fasting did not have any effect on estrogen, gonadotropins, or prolactin levels in women. As for men, intermittent fasting reduced testosterone levels in lean, physically active, young males, but it did not affect SHBG concentrations. Interestingly, muscle mass and muscular strength were not negatively affected by these reductions in testosterone. In interpreting these findings, it is important to note that very few studies have been conducted on this topic. Thus, it is difficult to draw solid conclusions at present. From the limited data presented here, it is possible that intermittent fasting may decrease androgen markers in both genders. If this is the case, these results would have varied health implications. On the one hand, fasting may prove to be a valuable tool for treating hyperandrogenism in females with polycystic ovarian syndrome (PCOS) by improving menstruation and fertility. On the other hand, fasting may be shown to decrease androgens among males, which could negatively affect metabolic health and libido. More research is warranted to confirm these preliminary findings.

Intermittent fasting diets have become very popular in the past few years, as they can produce clinically significant weight loss. These diets can be defined, in the simplest of terms, as periods of fasting alternating with periods of eating. The most studied forms of intermittent fasting include: alternate day fasting (0-500 kcal per 'fast day' alternating with ad libitum intake on 'feast days'); the 5:2 diet (two fast days and five feast days per week) and time-restricted eating (only eating within a prescribed window of time each day). Despite the recent surge in the popularity of fasting, only a few studies have examined the health benefits of these diets in humans. The goal of this Review is to summarize these preliminary findings and give insights into the effects of intermittent fasting on body weight and risk factors for cardiometabolic diseases in humans. This Review also assesses the safety of these regimens, and offers some practical advice for how to incorporate intermittent fasting diets into everyday life. Recommendations for future research are also presented., (© 2022. Springer Nature Limited.)

Type 2 diabetes can potentially be prevented by targeted lifestyle and weight loss interventions. Time restricted eating (TRE) is a form of intermittent fasting that has emerged as a novel diet strategy to reduce body weight and improve glycaemic control. TRE involves eating within a certain window of time (usually 4 to 10 h), and water-fasting for the remaining hours of the day. The purpose of this review is to summarize the effects of TRE on body weight and markers of glycaemic control in human subjects. We also aim to provide mechanistic insights into the effect of TRE on insulin sensitivity and glucose tolerance. Results to date reveal that TRE produces mild weight loss (1%-4% from baseline) and energy restriction, when food consumption is restricted to 4-10 h/day. TRE also reduces fasting insulin and improves insulin sensitivity in individuals with prediabetes and those with obesity. Moreover, TRE improves glucose tolerance and decreases serum glucose excursions. The possible mechanisms underlying these benefits include increased autophagic flux, mild elevations in ketone bodies, a reduction in oxidative stress, and the stimulation of β-cell responsiveness. While these preliminary results offer promise for the use of TRE in the prevention of type 2 diabetes, larger and longer-term human trials will be needed to confirm these findings., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Background: Time restricted feeding (TRF) involves deliberately restricting the times during which energy is ingested. Preliminary findings suggest that 8-10-h TRF improves sleep. However, the effects of shorter TRF windows (4-6 h) on sleep, remain unknown., Aims: This study compared the effects of 4-h versus 6-h TRF on sleep quality, duration, insomnia severity and the risk of obstructive sleep apnea., Methods: Adults with obesity ( n = 49) were randomized into one of three groups: 4-h TRF (eating only between 3 and 7 p.m.), 6-h TRF (eating only between 1 and 7 p.m.), or a control group (no meal timing restrictions) for 8 weeks., Results: After 8 weeks, body weight decreased ( p < 0.001) similarly by 4-h TRF (-3.9 ± 0.4 kg) and 6-h TRF (-3.4 ± 0.4 kg), versus controls. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), did not change by 4-h TRF (baseline: 5.9 ± 0.7; week 8: 4.8 ± 0.6) or 6-h TRF (baseline: 6.4 ± 0.8; week 8: 5.3 ± 0.9), versus controls. Wake time, bedtime, sleep duration and sleep onset latency also remained unchanged. Insomnia severity did not change by 4-h TRF (baseline: 4.4 ± 1.0; week 8: 4.7 ± 0.9) or 6-h TRF (baseline: 8.3 ± 1.2; week 8: 5.5 ± 1.1), versus controls. Percent of participants reporting obstructive sleep apnea symptoms did not change by 4-h TRF (baseline: 44%; week 8: 25%) or 6-h TRF (baseline: 47%; week 8: 20%), versus controls., Conclusion: These findings suggest that 4- and 6-h TRF have no effect on sleep quality, duration, insomnia severity, or the risk of obstructive sleep apnea.

Intermittent fasting has grown in popularity as a weight loss strategy in recent years. In particular, time restricted eating (TRE) has been popularized in the diet industry with dozens of books touting its ability to promote weight loss and improve glucose regulation. TRE involves confining the eating window to a specified number of hours per day (usually 4-10 h), and fasting (with zero-calorie beverages) for the remaining hours of the day. While several studies of TRE have been performed in rodent models, human studies are only now emerging. The goal of this review is to summarize the effects of TRE on body weight and cardiometabolic disease risk factors in human subjects. Accumulating evidence shows that TRE may spontaneously decrease energy intake by 20-30% under ad libitum conditions, producing small but statistically significant weight loss of 1-4%. In addition, TRE may significantly decrease systolic and diastolic blood pressure independent of weight loss. Further, improvements in fasting insulin and insulin resistance have also been reported. Taken together, these preliminary data suggest that TRE produces mild weight loss, and also may improve some aspects of cardiometabolic health by lowering blood pressure and insulin resistance., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Importance: Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date., Objective: To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes., Evidence Review: PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low., Findings: A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence., Conclusions and Relevance: In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.

Background: Time restricted feeding (TRF) involves confining the eating window to a specific number of hours, and fasting for the remaining hours of the day., Objective: This study examined if changes in body weight and metabolic risk factors during TRF, differ between premenopausal and postmenopausal women., Methods: This is a secondary analysis of an 8-week TRF study (4-6 h eating window, 18-20 h fasting window daily) conducted in adults with obesity. Male participants were excluded, and female subjects were classified in two groups based on menstrual status: premenopausal (n = 13), or postmenopausal (n = 19). Perimenopausal women were excluded from the original study., Results: Body weight decreased by week 8 in premenopausal women (-3.3 ± 0.4%) and postmenopausal women (-3.3 ± 0.5%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Adherence was excellent in both groups, with premenopausal women adhering to their prescribed eating window on 6.2 ± 0.1 d/week, and postmenopausal women adhering to their window on 6.2 ± 0.2 d/week. Fat mass, lean mass, fasting insulin, insulin resistance, and 8-isoprostane (marker of oxidative stress) were reduced similarly in both groups (main effect of time, P < 0.05 for all comparisons). Visceral fat mass, relative skeletal muscle index (RSMI), blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, HbA1c, TNF-alpha and IL-6 remained unchanged in both groups by week 8., Conclusion: These findings suggest that the weight loss and metabolic benefits of TRF do not differ between premenopausal and postmenopausal women with obesity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This review aims to summarize the effects of intermittent fasting on markers of cardiometabolic health in humans. All forms of fasting reviewed here-alternate-day fasting (ADF), the 5:2 diet, and time-restricted eating (TRE)-produced mild to moderate weight loss (1-8% from baseline) and consistent reductions in energy intake (10-30% from baseline). These regimens may benefit cardiometabolic health by decreasing blood pressure, insulin resistance, and oxidative stress. Low-density lipoprotein cholesterol and triglyceride levels are also lowered, but findings are variable. Other health benefits, such as improved appetite regulation and favorable changes in the diversity of the gut microbiome, have also been demonstrated, but evidence for these effects is limited. Intermittent fasting is generally safe and does not result in energy level disturbances or increased disordered eating behaviors. In summary, intermittent fasting is a safe diet therapy that can produce clinically significant weight loss (>5%) and improve several markers of metabolic health in individuals with obesity.

This review examines the effects of two popular intermittent fasting regimens on sleep in adults with overweight and obesity. Specifically, the effects of time restricted eating (TRE; eating all food within a 4-10 h window) and alternate day fasting (ADF; 600 kcal fast day alternated with ad libitum feast day) on sleep quality, sleep duration, sleep latency, sleep efficiency, insomnia severity, and risk of obstructive sleep apnea, will be summarized. The role of weight loss will also be discussed. Results from our review reveal that the majority of these trials produced weight loss in the range of 1-6% from baseline. Sleep quality and sleep duration remained unaltered with TRE and ADF, as assessed by the Pittsburgh Sleep Quality Index (PSQI). The effects of intermittent fasting on sleep latency and sleep efficiency are mixed, with one study showing worsening of these parameters, and others showing no effect. Insomnia severity and the risk of obstructive sleep apnea remained unchanged in the trials assessing these metrics. Taken together, these preliminary findings suggest that TRE and ADF produce mild to moderate weight loss (1-6%) but their effects on sleep remain unclear. Solid conclusions are difficult to establish since participants in the studies had healthy sleep durations and no clinical insomnia at baseline, leaving little room for improvement in these metrics. Moreover, none of the trials were adequately powered to detect statistically significant changes in any measure of sleep. Future well-powered trials, conducted in individuals with diagnosed sleep disturbances, will be necessary to elucidate the effect of these popular diets on sleep.

Purpose of Review: Time-restricted eating (TRE) is a form of intermittent fasting that involves confining the eating window to 4-10 h and fasting for the remaining hours of the day. The purpose of this review is to summarize the current literature pertaining to the effects of TRE on body weight and cardiovascular disease risk factors., Recent Findings: Human trial findings show that TRE reduces body weight by 1-4% after 1-16 weeks in individuals with obesity, relative to controls with no meal timing restrictions. This weight loss results from unintentional reductions in energy intake (~350-500 kcal/day) that occurs when participants confine their eating windows to 4-10 h/day. TRE is also effective in lowering fat mass, blood pressure, triglyceride levels, and markers of oxidative stress, versus controls. This fasting regimen is safe and produces few adverse events. These findings suggest that TRE is a safe diet therapy that produces mild reductions in body weight and also lowers several key indicators of cardiovascular disease in participants with obesity.

Background and Aims: This study examined if the weight loss and metabolic benefits of alternate day fasting (ADF) varies according to sex and menopausal status in adults with obesity., Methods and Results: This secondary analysis pooled the data of men and women (n = 75) who participated in three 12-week ADF studies (500 kcal fast day; alternated with an ad libitum intake feast day). Body weight decreased in premenopausal women (-4.6 ± 3.2%), postmenopausal women (-6.5 ± 3.2%) and men (-6.2 ± 4.4%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Energy intake on fast days was higher than prescribed in all groups (∼400-500 excess kcal consumed), with no differences between groups. Fat mass, lean mass, fasting insulin, and insulin resistance, and blood pressure decreased similarly in all groups (main effect of time, P < 0.05 for all comparisons). LDL cholesterol decreased more in postmenopausal versus premenopausal women (group × time interaction, P = 0.01). Fasting glucose, HDL cholesterol, and triglycerides remained unchanged in all groups., Conclusion: These findings suggest that the weight loss and metabolic benefits of ADF do not generally vary according to sex or menopausal status in adults with obesity., Trial Registration: Clinicaltrials.gov, NCT00960505; NCT03528317., Competing Interests: Declaration of Competing Interest KAV has a consulting relationship with the sponsor of the research, Nestle Health Sciences. The other authors have no conflicts of interest to disclose., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: Alternate day fasting (ADF) has been shown to lower body weight and improve subjective appetite by increasing fullness. What remains unknown, however, is whether carbohydrate restriction during ADF would provide additional weight loss benefits by helping to lower hunger as well. Accordingly, this study examined the effect of 6-months of ADF combined with a low carbohydrate diet on fasting and postprandial appetite ratings., Methods: Adults with obesity (n = 31) participated in ADF (600 kcal "fast day" alternated with an ad libitum "feast day") with a low-carbohydrate background diet (30% carbohydrates, 35% protein, and 35% fat). The 6-month trial consisted of a 3-month weight loss period followed by a 3-month weight maintenance period., Results: After 6-months of an ADF-low carbohydrate diet, body weight decreased (P < 0.01) by 6.2 ± 1.0 kg, relative to baseline. Subjective hunger and fullness did not change throughout the study. Fasting insulin decreased (P < 0.05) by 3.3 ± 1.3 μlU/mL by month 6, relative to baseline. Fasting glucose and insulin resistance, remained unchanged over the course of the study. Hunger and fullness were not related to body weight, glucoregulatory factors or energy intake., Conclusions: These findings suggest that ADF combined with a low carbohydrate diet is not associated with any changes in appetite, relative to baseline., Trial Registration: Clinicaltrials.gov, NCT03528317., Competing Interests: Declaration of competing interest KAV has a consulting relationship with the sponsor of the research, Nestle Health Sciences. The other authors have no competing interests to disclose., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)