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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.)

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.)

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.)

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.)

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.

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.

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.)

Background: Intermittent energy restriction (IER) has shown early success in adolescents with obesity, however efficacy trials are needed. This study aims to determine if IER results in lower body mass index (BMI) z-score after 52 weeks in metabolically unhealthy adolescents with obesity compared with continuous energy restriction (CER)., Methods/design: This is a prospective, randomised, multi-centre trial conducted in tertiary care settings, with three phases: jumpstart (weeks 0-4); intensive intervention (weeks 5-16); continued intervention and/or maintenance (weeks 17-52). During the jumpstart phase, all participants follow a very low energy diet (∼800kcal/3350kJ/day), then transition to their allocated intervention: IER or CER. IER involves three energy-restricted days/week, consuming one-third of daily energy requirements (∼600-700kcal/2500-2950kJ/day), and four days/week of a healthy meal plan. The CER, which is current standard care, has individually tailored energy prescription based on age and sex (13-14years, 1430-1670kcal/6000-7000kJ/day; 15-17years, 1670-1900kcal/7000-8000kJ/day). The study will recruit 186 (93 per arm) treatment-seeking adolescents aged 13-17years with obesity and at least one metabolic co-morbidity. The primary outcome is change in BMI z-score at 52 weeks. Secondary outcomes are changes at 4, 16 and 52 weeks in: body composition; diet quality, food choices and food patterns; cardio-metabolic risk factors; physical activity and sedentary behaviour; sleep and psycho-behavioural measures., Discussion: This study challenges existing clinical paradigms that CER is the only method for weight management in metabolically unhealthy adolescents. If successful, IER may offer an alternate medical nutrition therapy approach for those seeking treatment in tertiary settings., Clinical Trial Registration Number: ACTRN12617001630303., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown., Methods: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SI is ; 95 observations)., Results: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P = .02), then stabilized (P = .39); HOMA-IR remained stable posttransplant (P = .92). Adjusting for age and BMI, higher SI is was associated with lower HbA1c following transplant (P = .03). Greater IS as measured by lower HOMA-IR and higher SI is was associated with lower fasting C-peptide (both P ≤ .04) and also with higher exenatide dose (both P ≤ .01). More islets transplanted were associated with higher SI is (P < .0001). Lower leptin at transplant predicted lower HOMA-IR and higher SI is after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤ .01)., Conclusions: Insulin sensitivity measured by SI is was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background & Aims: Alternate day fasting (ADF; 25% energy intake "fast day", alternated with an ad libitum intake "feed day") is effective for weight loss. Whether or not ADF modulates hunger, fullness and gut peptides in a way that enhances dietary compliance and weight loss, remains unknown. Accordingly, this study examined the effect of ADF on postprandial appetite ratings and gut peptides., Methods: Obese subjects (n = 59) participated in an 8-week ADF protocol where food was provided on the fast day., Results: Body weight decreased (P < 0.0001) by 3.9 ± 0.6 kg after 8 weeks of diet. Reductions (P < 0.05) in fat mass (-2.2 ± 0.2 kg), fat free mass (-1.4 ± 0.2 kg), visceral fat mass (-0.1 ± 0.1 kg), and resting metabolic rate (RMR; -104 ± 28 kcal/day) were also observed. Fasting leptin and insulin decreased (P < 0.05), while AUC ghrelin levels increased (P < 0.05). Despite these metabolic changes, there was no increase in subjective hunger by the end of the study. Furthermore, fullness and PYY increased (P < 0.05). Fat free mass and RMR were not related to hunger or ghrelin at any time point., Conclusion: These findings suggest that the absence of a compensatory increase in hunger in conjunction with an increase in sensations of fullness may contribute to the weight loss efficacy of an 8-week ADF regimen., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Intermittent fasting (IF) regimens have gained considerable popularity in recent years, as some people find these diets easier to follow than traditional calorie restriction (CR) approaches. IF involves restricting energy intake on 1-3 d/wk, and eating freely on the nonrestriction days. Alternate day fasting (ADF) is a subclass of IF, which consists of a "fast day" (75% energy restriction) alternating with a "feed day" (ad libitum food consumption). Recent findings suggest that IF and ADF are equally as effective as CR for weight loss and cardioprotection. What remains unclear, however, is whether IF/ADF elicits comparable improvements in diabetes risk indicators, when compared with CR. Accordingly, the goal of this review was to compare the effects of IF and ADF with daily CR on body weight, fasting glucose, fasting insulin, and insulin sensitivity in overweight and obese adults. Results reveal superior decreases in body weight by CR vs IF/ADF regimens, yet comparable reductions in visceral fat mass, fasting insulin, and insulin resistance. None of the interventions produced clinically meaningful reductions in glucose concentrations. Taken together, these preliminary findings show promise for the use of IF and ADF as alternatives to CR for weight loss and type 2 diabetes risk reduction in overweight and obese populations, but more research is required before solid conclusions can be reached., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The ability of modified alternate-day fasting (ADF; ie, consuming 25% of energy needs on the fast day and ad libitum food intake on the following day) to facilitate weight loss and lower vascular disease risk in obese individuals remains unknown., Objective: This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on body weight and coronary artery disease (CAD) risk indicators in obese adults., Design: Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase., Results: Dietary adherence remained high throughout the controlled food intake phase (days adherent: 86%) and the self-selected food intake phase (days adherent: 89%). The rate of weight loss remained constant during controlled food intake (0.67 +/- 0.1 kg/wk) and self-selected food intake phases (0.68 +/- 0.1 kg/wk). Body weight decreased (P < 0.001) by 5.6 +/- 1.0 kg (5.8 +/- 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 +/- 2% to 42 +/- 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P < 0.01) by 21 +/- 4%, 25 +/- 10%, and 32 +/- 6%, respectively, after 8 wk of ADF, whereas HDL cholesterol remained unchanged. Systolic blood pressure decreased (P < 0.05) from 124 +/- 5 to 116 +/- 3 mm Hg., Conclusion: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This trial was registered at clinicaltrials.gov as UIC-004-2009.