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One key goal of basic aging research is the development of reliable assays of both current and future health. These assays could dramatically accelerate progress toward developing health-extending interventions by obviating the need for full lifespan studies, especially if they were informative relatively early in life. One potential approach is the assessment of physiological resilience, defined as the ability to recover from an adverse event. Here, using CB6F1 mice, we evaluated four potential resilience assays, each quantifying recovery from a physiological challenge with clear relevance to humans. The challenges were: (1) anesthesia recovery, (2) restoration of hemoglobin levels after a blood draw, (3) speed of wound healing, and (4) survival after pathogen exposure. We evaluated how each changed with age and with interventions known to extend health in males only (17α-estradiol) or both sexes (calorie restriction). We found that three of the four (recovery from anesthesia, blood draw, and pathogen exposure) showed significant and expected age effects, but wound healing did not. None of the three age-sensitive assays responded to the health-extending interventions in the way we expected, and for some assays, including anesthesia response, interventions actually worsened outcomes. Possible explanations are: (1) our interventions were too brief, (2) the ages we evaluated were too young, (3) our assays did not capture important features of organismal resilience, or (4) organismal resilience is not as clearly related to current or future health as hypothesized. Future studies are needed to determine which of these interpretations is valid and to determine whether other resilience metrics may be more informative about current and future health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Corder 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: Intermittent fasting (IF) is an effective energy restricted dietary strategy to reduce body and fat mass and improve metabolic health in individuals with either an overweight or obese status. However, dietary energy restriction may impair muscle protein synthesis (MPS) resulting in a concomitant decline in lean body mass. Due to periods of prolonged fasting combined with irregular meal intake, we hypothesised that IF would reduce rates of MPS compared to an energy balanced diet with regular meal patterns., Aims: We assessed the impact of a short-term, ten days, alternate day fasting or a continuous energy restricted diet to a control diet on integrated rates of skeletal MPS in middle-aged males with overweight or obesity., Methods: Twenty-seven middle-aged males with overweight or obesity (age: 44.6 ± 5.4 y; BMI: 30.3 ± 2.6 kg/m 2 ) consumed a three-day lead-in diet, followed by a ten-day controlled dietary intervention matched for protein intake, as alternate day fasting (ADF: 62.5 energy (En)%, days of 25 En% alternated with days of 100 En% food ingestion), continuous energy restriction (CER: 62.5 En%), or an energy balanced, control diet (CON: 100 En%). Deuterated water (D 2 O) methodology with saliva, blood, and skeletal muscle sampling were used to assess integrated rates of MPS over the ten-day intervention period. Secondary measures included fasting plasma glucose, insulin, and gastrointestinal hormone concentrations, continuous glucose monitoring, and assessment of body composition., Results: There were no differences in daily rates of MPS between groups (ADF: 1.18 ± 0.13, CER: 1.13 ± 0.16, and CON: 1.18 ± 0.18 %/day, P > 0.05). The reductions in body mass were greater in ADF and CER compared to CON (P < 0.001). Lean and fat mass were decreased by a similar magnitude across groups (main time effect, P < 0.001; main group effect, P > 0.05). Fasting plasma leptin concentrations decreased in ADF and CER (P < 0.001), with no differences in fasting plasma glucose or insulin concentrations between groups., Conclusion: Short-term alternate day fasting does not lower rates of MPS compared to continuous energy restriction or an energy balanced, control diet with matched protein intake. The prolonged effects of IF and periods of irregular energy and protein intake patterns on muscle mass maintenance remain to be investigated. This trial was registered under Australian New Zealand Clinical Trial Registry (https://www.anzctr.org.au), identifier no. ACTRN12619000757112., Competing Interests: Conflict of interest None of the authors declared any conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Among older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use., Methods: All participants will receive the same group-mediated dietary intervention targeting 8-10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT + +PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT + +BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover., Discussion: BEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL., Clinical Trials Registration: NCT05764733., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Caloric restriction prolongs lifespan in model organisms and improves metrics of aging-related diseases in humans, but daily compliance is challenging. Intermittent fasting improves metrics of lipid and glucose metabolism in the setting of weight loss but whether these metrics are improved independent of weight loss is not known., Methods: We seek to address this gap with IFAST, a single-center, three-arm, prospective, randomized, controlled clinical trial. Eligible study participants are adults with no chronic medical conditions beyond prediabetes or overweight but who are at high risk for type 2 diabetes mellitus (T2D), defined as having a history of gestational diabetes or a first-degree relative with T2D. Participants will be randomized in a 1:2:2 schema to either a control group, a fasting group, or a fasting/weight maintenance group. The fasting groups will complete a 24-h fast one day per week for 12 weeks. The key mechanistic endpoint is change in triglyceride composition (defined by carbon content and degree of saturation) as measured by longitudinal metabolomics. The key safety endpoint is percent change from baseline in bone volume fraction (BV/TV; high-resolution peripheral quantitative CT) at the radius in the fasting group. Secondary endpoints include measures of insulin sensitivity (hyperinsulinemic-euglycemic clamp), clinical lipid profiling, systemic inflammation markers, hunger assessment, bone density, and bone microarchitecture with high-resolution peripheral quantitative CT., Conclusion: IFAST will investigate intrinsic metabolic benefits of intermittent fasting beyond weight loss., Trial Registration: ClinicalTrials.gov ID NCT05722873., Competing Interests: Declaration of competing interest This protocol is funded by National Institutes of Health (NIH)/NIDDK grant number R01 DK133578 (to PKF and MLS) and has received support through NIH grant UL1-TR-001857. PKF has served as a consultant for Regeneron, Xeris, Crinetics, Camurus, Amryt and Quest. These disclosures are not related to the content of the study. The remaining authors do not have conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Senoinflammation is characterized by an unresolved low-grade inflammatory process that affects multiple organs and systemic functions. This review begins with a brief overview of the fundamental concepts and frameworks of senoinflammation. It is widely involved in the aging of various organs and ultimately leads to progressive systemic degeneration. Senoinflammation underlying age-related inflammation, is causally related to metabolic dysregulation and the formation of senescence-associated secretory phenotype (SASP) during aging and age-related diseases. This review discusses the biochemical evidence and molecular biology data supporting the concept of senoinflammation and its regulatory processes, highlighting the anti-aging and anti-inflammatory effects of calorie restriction (CR). Experimental data from CR studies demonstrated effective suppression of various pro-inflammatory cytokines and chemokines, lipid accumulation, and SASP during aging. In conclusion, senoinflammation represents the basic mechanism that creates a microenvironment conducive to aging and age-related diseases. Furthermore, it serves as a potential therapeutic target for mitigating aging and age-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The potential benefits of combining lifestyle changes with weight loss pharmacotherapies for obesity treatment are underexplored. Building on recent clinical observations, this study aimed to determine whether "lead-in" calorie restriction before administering clinically approved weight loss medications enhances the maximum achievable weight loss in preclinical models., Methods: Diet-induced obese mice (DIO) were exposed to 7 or 14 days of calorie restriction before initiating treatment with semaglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist), tirzepatide (a GLP-1R/glucose insulinotropic peptide receptor (GIPR) co-agonist), or setmelanotide (a melanocortin-4 receptor (MC4R) agonist). Follow-up assessments using indirect calorimetry determined the contributions of energy intake and expenditure linked to consecutive exposure to dieting followed by pharmacotherapy., Results: Calorie restriction prior to treatment with semaglutide or tirzepatide enhanced the weight loss magnitude of both incretin-based therapies in DIO mice, reflected by a reduction in fat mass and linked to reduced energy intake and a less pronounced adaptive drop in energy expenditure. These benefits were not observed with the MC4R agonist, setmelanotide., Conclusions: Our findings provide compelling evidence that calorie restriction prior to incretin-based therapy enhances the achievable extent of weight loss, as reflected in a weight loss plateau at a lower level compared to that of treatment without prior calorie reduction. This work suggests that more intensive lifestyle interventions should be considered prior to pharmacological treatment, encouraging further exploration and discussion of the current standard of care., Competing Interests: Declaration of competing interest J.P. and C.C. are co-founders of Ousia Pharma ApS, a biotech company developing therapeutics for obesity treatment. The remaining authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Purpose: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS)., Methods: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months., Results: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS., Conclusion: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy., (© 2024. The Author(s).)

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.

Background: fasting-based strategies (FBS) and continuous caloric restriction (CCR) are popular methods for weight loss and improving metabolic health. FBS alternates between eating and fasting periods, while CCR reduces daily calorie intake consistently. Both aim to create a calorie deficit, but it is still uncertain as to which is more effective for short- and long-term weight and metabolic outcomes., Objectives: this systematic review and meta-analysis aimed to compare the effectiveness of FBS and CCR on these parameters in obese adults., Methods: after screening 342 articles, 10 randomized controlled trials (RCTs) with 623 participants were included., Results: both interventions led to weight loss, with a reduction of 5.5 to 6.5 kg observed at the six-month mark. However, the results showed that FBS led to slightly greater short-term reductions in body weight (-0.94 kg, p = 0.004) and fat mass (-1.08 kg, p = 0.0001) compared to CCR, although these differences are not clinically significant. Both interventions had similar effects on lean mass, waist and hip circumference, blood pressure, lipid profiles, and glucose metabolism. However, FBS improved insulin sensitivity, with significant reductions in fasting insulin (-7.46 pmol/L, p = 0.02) and HOMA-IR (-0.14, p = 0.02)., Conclusions: despite these short-term benefits, FBS did not show superior long-term outcomes compared to CCR. Both strategies are effective for weight management, but more research is needed to explore the long-term clinical relevance of FBS in obese populations.

Aging, an inevitable physiological process leading to a progressive decline in bodily functions, has been an abundantly researched domain with studies attempting to slow it down and reduce its debilitating effects. Investigations into the cellular and molecular pathways associated with aging have allowed the formulation of therapeutic strategies. Of these, caloric restriction (CR) has been implicated for its role in promoting healthy aging by modulating key molecular targets like Insulin/IGF-1, mTOR, and sirtuins. However, CR requires dedication and commitment to a strict regimen which poses a difficulty in maintaining consistency. To maneuver around cumbersome diets, Caloric Restriction Mimetics (CRMs) have emerged as promising alternatives by mimicking the beneficial effects of CR. This review elucidates the molecular foundations enabling CRMs like rapamycin, metformin, resveratrol, spermidine, and many more to function as suitable anti-aging molecules. Moreover, it explores clinical trials (retrieved from the clinicaltrials.gov database) aimed at demonstrating the efficacy of CRMs as effective candidates against age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease., (© 2024. The Author(s).)

Background/aims: This study examined the effects of a specially designed energy-restricted diet with alternate carbohydrate intake on body composition and cardiometabolic risk factors in overweight and obese adults. The aim was to assess whether the intervention could lead to significant weight loss, improve body composition, and reduce cardiometabolic risks., Methods: Sixty-five participants (34 women, 31 men) with an average BMI of 31.8 ± 9.1 kg/m 2 (women) and 34.1 ± 6.4 kg/m 2 (men) participated in a 14-week intervention. The diet included different days of carbohydrate intake and a 20% reduction in total daily energy consumption. Anthropometric measurements and biochemical parameters, including predictive indices of cardiometabolic risk, were determined at baseline and after the intervention., Results: The intervention resulted in a significant reduction in body weight (mean weight loss of 17%, p < 0.001), with 64.6% of participants achieving a weight loss of at least 10%. Muscle mass as a percentage of total body weight increased. Cardiometabolic improvements were observed in fasting blood glucose (from 5.4 to 4.9 mmol/L, p < 0.001) and LDL cholesterol (from 3.38 to 2.81 mmol/L, p < 0.001). Gender-specific differences were found, particularly in HDL-C, which decreased significantly in women ( p = 0.013), while there was a non-significant increase in men. Cardiometabolic indices, including the Visceral Adiposity Index (VAI) and the Cardiometabolic Index (CMI), also improved significantly., Conclusions: The alternate carbohydrate diet improved body composition, cardiometabolic health, and treatment adherence through metabolic flexibility. However, the short duration of this study and the lack of a control group suggest that further research is needed to assess long-term sustainability.

Background: Intermittent fasting may be an effective tool for weight loss, but it is still unclear from previous studies to date whether it is as effective as a continuous energy restriction in terms of reducing adipose tissue and whether it leads to unwanted muscle loss. Objectives: The aim of this study was to compare the effect of intermittent fasting (IF) with continuous energy restriction (CER) on the body weight and body composition and to assess the effect of intermittent fasting also in isolation from the energy restriction. Methods: After completion of a three-week dietary intervention, differences in the weight loss and differences in the body composition were compared between three groups. The first group consumed 75% of their calculated energy intake requirements in a six-hour time window. The second group consumed 75% of their calculated energy intake requirements without a time window and the third group consumed 100% of their calculated energy intake requirements in a six-hour time window. The changes in the weight and body composition were assessed by BIA. Results: Of the 95 randomized participants, 75 completed the intervention phase of the study. The highest mean weight loss was achieved by the IF with ER (energy restriction) group (2.3 ± 1.4 kg), followed by the CER group (2.2 ± 1.1 kg); the difference between the groups did not reach statistical significance. The lowest mean weight loss was observed in the IF without ER group (1.1 ± 1.2 kg), the difference reaching statistical significance compared to the IF with ER (p=0.003) and CER (p=0.012) groups. The highest mean adipose tissue loss was observed in the CER group (1.5 ± 1.2 kg) followed by the IF with ER group (1.3 ± 1.1 kg), with no statistically significant differences between the groups. A mean adipose tissue loss was found in the IF without ER group (0.9 ± 1.1 kg) with no statistically significant differences compared to the IF with ER and CER groups. The highest mean fat-free mass loss was found in the IF with ER group (1.1 ± 1.0 kg), followed by the CER group (0.65 ± 0.91 kg) with no statistically significant differences. The IF without ER group showed the lowest mean fat-free mass loss (0.2 ± 1.3 kg), which reached statistical significance compared to the IF with ER group (p=0.027). Conclusion: The results showed a comparable effect in the weight loss and body fat reduction regardless of the timing of the food intake. The diet quality, together with the energy intake, appeared to be one of the most important factors influencing the body composition., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Very low-energy diets (VLEDs) prescribed prior to bariatric surgery have been associated with decreased operative time, technical difficulty, and postoperative morbidity. To date, limited data are available regarding the impact of VLEDs prior to colorectal surgery. We designed this study to determine whether preoperative VLEDs benefit patients with obesity undergoing colorectal surgery., Methods: This is a single-center retrospective cohort study. Individuals undergoing elective colorectal surgery with a body mass index (BMI) of greater than 30 kg/m 2 from 2015 to 2022 were included. The exposure of interest was VLEDs for 2-4 weeks immediately prior to surgery. The control group consisted of patients prior to January 2018 who did not receive preoperative VLED. The primary outcome was 30 day postoperative morbidity. Multivariable logistic regression modeling was used to determine associations with 30 day postoperative morbidity., Results: Overall, 190 patients were included, 89 patients received VLEDs (median age: 66 years; median BMI: 35.9 kg/m 2 ; 48.3% female) and 101 patients did not receive VLEDs (median age: 68 years; median BMI: 32.1 kg/m 2 ; 44.6% female). One-hundred four (54.7%) patients experienced 30 day postoperative morbidity. Multivariable regression analysis identified three variables associated with postoperative morbidity: VLEDs [odds ratio (OR) 0.22, 95% confidence intervals (CI) 0.08-0.61, P < 0.01], Charlson comorbidity index (OR 1.25, 95% CI 1.03-1.52, P = 0.02), and rectal dissections (OR 2.71, 95% CI 1.30-5.65, P < 0.01)., Conclusions: The use of a preoperative VLED was associated with a significant reduction in postoperative morbidity in patients with obesity prior to colorectal surgery. A high-quality randomized controlled trial is required to confirm these findings., (© 2024. Springer Nature Switzerland AG.)

Objectives: Adherence to lifestyle interventions is crucial for the treatment of obesity. However, there is little research about adherence to lifestyle interventions in persons around retirement age. The objectives of this study are (1) to identify factors associated with the adherence to resistance training and a hypocaloric diet and (2) to describe the association between adherence and changes in body composition outcome parameters., Design: This secondary data analysis included three randomized controlled trials., Setting & Participants: The inclusion criteria of the participants were an age of 55-75 years, a BMI ≥ 25 kg/m 2 and receiving both a hypocaloric diet and resistance training. All participants were residing in the community., Measurements: Adherence to hypocaloric diet was measured through the mean dietary intake on the basis of a 3-day dietary record. If the participant consumed at least 600 kcal less than the individual caloric requirements, they were considered adherent. Adherence to resistance training was achieved if ≥67% of the recommended training sessions were attended over the course of the study periods., Results: 232 participants were included, 47.0% female, mean age 64.0 (±5.5) years. 80.2% adhered to resistance training and 51.3% adhered to a hypocaloric diet. Older age (Beta 0.41; 95% CI 0.05, 0.78; p = 0.028) and male sex (Beta 7.7; 95% CI 3.6, 11; p < 0.001) were associated with higher resistance training adherence. A higher BMI at baseline (Beta 6.4; 95% CI 3.6, 9.2; p < 0.001) and male sex (Beta 65; 95% CI 41, 88; p < 0.001) were associated with higher adherence to hypocaloric diet., Conclusion: We identified several associated factors (sex, age and BMI at baseline) that should be considered to promote adherence in future lifestyle intervention studies in persons around retirement age. We recommend including behavior change techniques in lifestyle interventions and consider sex-specific interventions to improve the adherence of women., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Gut microbiota dysbiosis is among the risk factors for breast cancer development, together with genetic background and dietary habits. However, caloric restriction has been shown to remodel the gut microbiota and slow tumor growth. Here, we investigated whether the gut microbiota mediates the preventive effects of long-term chronic or intermittent caloric restriction on breast cancer predisposition., Methods: 10-week-old transgenic breast cancer-prone mice were randomly assigned to dietary groups (ad libitum, chronic caloric restriction, and intermittent caloric restriction groups) and fed up to week 81. Stool samples were collected at weeks 10 (baseline), 17 (young), 49 (adult), and 81 (old). 16S rRNA gene sequencing was performed to identify the gut microbiota profile of the different groups. In order to investigate the breast cancer gut microbiota profile within genetically predisposed individuals regardless of diet, mammary tumor-bearing mice and mammary tumor-free but genetically prone mice were selected from the ad libitum group (n = 6)., Results: Intermittent caloric restriction increased the microbial diversity of adult mice and modified age-related compositional changes. A total of 13 genera were differentially abundant over time. Pathogenic Mycoplasma was enriched in the re-feeding period of the old intermittent caloric restriction group compared with baseline. Furthermore, mammary tumor-free mice showed shared gut microbiota characteristics with mammary tumor-bearing mice, suggesting an early link between genetic predisposition, gut microbiota, and breast cancer development., Conclusions: Our study revealed the role of gut microbes in the preventive effects of caloric restriction against breast cancer development, implying the significance of diet and microbiome interplay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Although behavioural interventions have been found to help control type 2 diabetes (T2D), it is important to understand how the delivery context can influence implementation and outcomes. The NHS committed to testing a low-calorie diet (LCD) programme designed to support people living with excess weight and T2D to lose weight and improve diabetes outcomes. Understanding what influenced implementation during the programme pilot is important in optimising rollout. This study explored the transferability of the NHS LCD Programme prior to wider adoption., Methods: Twenty-five interviews were undertaken with stakeholders involved in implementing the LCD programme in pilot sites (health service leads, referring health professionals and programme deliverers). Interviews with programme participants (people living with T2D) were undertaken within a larger programme of work, exploring what worked, for whom and why, which is reported separately. The conceptual Population-Intervention-Environment-Transfer Model of Transferability (PIET-T) guided study design and data collection. Constructs of the model were also used as a deductive coding frame during data analysis. Key themes were identified which informed recommendations to optimise programme transfer., Results: Population: Referral strategies in some areas lacked consideration of population characteristics. Many believed that offering a choice of delivery model would promote acceptability and accessibility of the eligible population., Intervention: Overall, stakeholders had confidence in the LCD programme due to the robust evidence base along with anecdotal evidence, but some felt the complex referral process hindered engagement from GP practices., Environment: Stakeholders described barriers to accessing the programme, including language and learning difficulties. Transferability: Multidisciplinary working and effective communication supported successful implementation., Conclusion: Referral strategies to reach underrepresented groups should be considered during programme transfer, along with timely data from service providers on access and programme benefits. A choice of delivery models may optimise uptake. Knowledge sharing between sites on good working practices is encouraged, including increasing engagement with key stakeholders., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: To assess the impact of intermittent fasting, with or without probiotic supplementation, versus a calorie-restricted diet on anthropometric measures, metabolic status and gonadal variables in women with polycystic ovary syndrome (PCOS)., Methods: This is a randomized, placebo-controlled, parallel-arm clinical trial. The effects of the 14:10 early time-restricted eating (eTRE) strategy alone or combined with probiotics, on obese women with PCOS, were investigated. Participants were divided into three groups: eTRE plus probiotics (n = 30), eTRE plus placebo (n = 30) and a control group following a standard three-meal-per-day diet with daily calorie restriction (DCR) (n = 30). Over 8 weeks, various anthropometric, metabolic, menstrual and gonadal variables were assessed., Results: A total of 90 individuals were included in the study, with a mean body weight of 81.4 kg, and a mean age of 30 years. Mean (standard deviation) weight loss was not different between the groups at week 8 (TRE + probiotic: -2.2 [1.6] kg vs. TRE + placebo: -2.9 [2.7] kg vs. DCR: -2.5 [1.7] kg). Results revealed that, while all three regimes led to reductions in body weight, body mass index, vascular risk indicators, hirsutism and acne scores, there were no statistically significant differences between the eTRE groups and the control group in terms of weight loss, or improvements in metabolic, menstrual and gonadal variables (P > .05). Additionally, combining probiotics with eTRE did not benefit hormonal and cardiometabolic factors (P > .05)., Conclusions: The eTRE alone or eTRE plus probiotics did not result in significantly greater weight loss or improvements in metabolic, menstrual and gonadal variables compared with the standard three-meal DCR diet., (© 2024 John Wiley & Sons Ltd.)

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.

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p<0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p<0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR., (© 2024. The Author(s).)

Background: Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM., Methods: EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW)., Results: Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions., Conclusions: Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.

Background: Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health risks. However, there is no consensus on the optimal regimen for weight management in adults., Methods: We systematically searched PubMed, Embase, Web of Science, and Cochrane CENTRAL up to January 15, 2024, for randomized controlled trials (RCT) involving adults, evaluating the weight-loss effects of alternate day fasting (ADF), short-term fasting (STF), time-restricted eating (TRE), and continuous energy restriction (CER). The primary outcome was body weight, with secondary outcomes including BMI, fat mass, lean mass, waist circumference, fasting glucose, HOMA-IR, and adverse events. Bayesian network meta-analysis was conducted, ranking regimens using the surface under the cumulative ranking curve and the probability of being the best. Study quality was assessed using the Confidence in Network Meta-Analysis tool., Results: Data from 47 RCTs (representing 3363 participants) were included. ADF showed the most significant body weight loss (Mean difference (MD): -3.42; 95% Confidence interval (CI): -4.28 to -2.55), followed by TRE (MD: -2.25; 95% CI: -2.92 to -1.59). STF (MD: -1.87; 95% CI: -3.32 to -0.56) and CER (MD: -1.59; 95% CI: -2.42 to -0.79) rank third and fourth, respectively. STF lead to decline in lean mass (MD: -1.26; 95% CI: -2.16, -0.47). TRE showed benefits on fasting glucose (MD: -2.98; 95% CI: -4.7, -1.26). Subgroup analysis revealed all four caloric restriction regimens likely lead to modest weight loss after 1-3 months, with ADF ranked highest, but by 4-6 months, varying degrees of weight regain occur, particularly with CER, while interventions lasting 7-12 months may result in effective weight loss, with TRE potentially ranking first during both the 4-6 months and 7-12 months periods. ADF showing fewer and shorter-lasting physical symptoms., Conclusion: All four included regiments were effective in reducing body weight, with ADF likely having the most significant impact. Each regimen likely leads to modest weight loss after 1-3 months, followed by weight regain by 4-6 months. However, interventions lasting 7-12 months achieve greater weight loss overall., Trial Registration: PROSPERO: CRD42022382478., (© 2024. The Author(s).)

Background: Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy., Methods: We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: "Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis" (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves., Results: The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (-3.64, 9.52); 2.37 (-0.40, 5.15); 1.80 (-1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (-0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (-0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (-1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are -1.60 (-6.98, 3.78); -2.76 (-7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are -0.52 (-2.58, 1.55); -1.83 (-4.71, 1.04); -2.46 (-5.69,0.76).)., Conclusion: Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal.

Obesity is a complex chronic disease with increasing prevalence across the globe. Medical nutrition therapy (MNT) is an important component of obesity treatment, and low-calorie diets (LCDs) and very-low-calorie diets (VLCDs) are part of the MNT toolbox. This narrative review focuses on the latest evidence and clinical guidelines regarding the use and impact of meal replacements (MRs) as part of LCDs/VLCDs for the treatment of obesity and some associated complications. MRs can be used in conjunction with food as partial diet replacement (PDR) or can be used exclusively to serve as the sole source of dietary energy (total diet replacement [TDR]). Use of MR may be associated with better control of cravings and hunger typically observed during reduced calorie intake through effects of ketosis or stimuli narrowing, although the exact mechanisms for these effects remain unclear. Several clinical guidelines have endorsed the use of MRs as a part of MNT for obesity, primarily based on evidence that shows an average weight reduction of ~10 kg or more with TDR over at least 12 months in large, randomized controlled trials. When compared to usual care controls, these effects are 6-8 kg greater, and when compared to food-based diets, the effects are nearly twice the effect of a food-based diet. MR-based diets have been found to be safe and associated with improvements in quality of life. These diets are also effective for improving key cardiometabolic health outcomes, including dysglycaemia, blood pressure, lipids, and metabolic associated fatty liver. The effectiveness, safety, and associated health improvement makes MRs use a valuable strategy for several higher risk clinical scenarios where weight reduction is indicated., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background and Objectives: Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody and/or thyroglobulin antibody. In recent decades, HT disease has become more and more widespread. Patients always report multiple symptoms, even though their thyroid hormone levels are kept in normal ranges. However, no treatment exists to effectively reduce the levels of thyroid antibodies. Our study aims to determine whether calorie-restricted diet is helpful in improving health of HT patients., Methods and Study Design: This is a 3-month randomized controlled trial. HT patients will be randomized into a calorie-restricted (CR) group or a calorie-unrestricted control group. All the participants will be instructed to consume a diet that includes a combination of 45-55% calories from carbohydrates, 20-30% from fats, and 15-25% from proteins, according to current Chinese Dietary Guidelines. Participants in CR group need to limit their calories intake equal to their basal energy expenditure, which means that their daily caloric intake will be limited by about 20-30%., Results: The study population is planned to be 66 HT patients aged 18 to 65 years. The primary outcome is change of thyroid antibody levels from baseline. Secondary outcomes include the changes of non-hypothyroid symptoms scores, thyroid function indexes, morphology of thyroid, T lymphocyte subpopulations, inflammatory biomarkers and lipids from baseline to 12 weeks., Conclusions: This trial will have implications for nutrition treatment policy in regard to thyroid antibodies control, immune dysfunction and related non-hypothyroid symptoms improvement among HT patients., Competing Interests: All authors declare that they have no conflicts of interest

Background: Although Calorie Restriction (CR) is primarily considered in obesity management, behavioral studies of CR and its methodology of implementation are not well-defined. Objective: The study aimed to determine the efficacy of the extensively researched method of CR-abrupt calorie restriction (ACR) and a newly proposed gradual calorie restriction (GCR) in terms of body weight, behavioral and biochemical parameters in the obese animal model-C57BL/6J mice. Design: Male obese mice were subjected to GCR regimen for 14 weeks which was compared and evaluated for anxiety-like behavior and stress levels with ACR. Plasma corticosterone was measured before initiation of CR and every three weeks following GCR and ACR, whereas plasma insulin was measured twice-after obesity induction and post 14 weeks of CR. The behavioral assessments were conducted before inducing CR and every three weeks following ACR and GCR. Results: A significant anxiety-like behavior and an increase in plasma corticosterone were observed in mice on GCR during the critical initial six weeks of CR ( p  < 0.05). Both groups showed a decrease in plasma glucose levels; however, the GCR group showed a significant reduction ( p  < 0.01). There was a significant decrease in social interaction in both groups with an increase in the latency period and a decrease in time spent with the stranger animal during the social interaction test ( p  < 0.05). Conclusion: The mice on GCR regimen demonstrated lesser anxiety-like behavior and low plasma corticosterone levels compared to those on ACR. This gives us a new avenue in CR research to evaluate the methodologies of implementing CR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/objectives: Weight loss outcomes vary individually. Magnetic resonance imaging (MRI)-based evaluation of adipose tissue (AT) might help to identify AT characteristics that predict AT loss. This study aimed to assess the impact of an 8-week low-calorie diet (LCD) on different AT depots and to identify predictors of short-term AT loss using MRI in adults with obesity., Methods: Eighty-one adults with obesity (mean BMI 34.08 ± 2.75 kg/m², mean age 46.3 ± 10.97 years, 49 females) prospectively underwent baseline MRI (liver dome to femoral head) and anthropometric measurements (BMI, waist-to-hip-ratio, body fat), followed by a post-LCD-examination. Visceral and subcutaneous AT (VAT and SAT) volumes and AT fat fraction were extracted from the MRI data. Apparent lipid volumes based on MRI were calculated as approximation for the lipid contained in the AT. SAT and VAT volumes were subdivided into equidistant thirds along the craniocaudal axis and normalized by length of the segmentation. T-tests compared baseline and follow-up measurements and sex differences. Effect sizes on subdivided AT volumes were compared. Spearman Rank correlation explored associations between baseline parameters and AT loss. Multiple regression analysis identified baseline predictors for AT loss., Results: Following the LCD, participants exhibited significant weight loss (11.61 ± 3.07 kg, p < 0.01) and reductions in all MRI-based AT parameters (p < 0.01). Absolute SAT loss exceeded VAT loss, while relative apparent lipid loss was higher in VAT (both p < 0.01). The lower abdominopelvic third showed the most significant SAT and VAT reduction. The predictor of most AT and apparent lipid losses was the normalized baseline SAT volume in the lower abdominopelvic third, with smaller volumes favoring greater AT loss (p < 0.01 for SAT and VAT loss and SAT apparent lipid volume loss)., Conclusions: The LCD primarily reduces lower abdominopelvic SAT and VAT. Furthermore, lower abdominopelvic SAT volume was detected as a potential predictor for short-term AT loss in persons with obesity., (© 2024. The Author(s).)

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.)

This article summarizes the lessons learned from the COCKTAIL study: an open, three-armed, single-center study including patients with obesity scheduled for treatment with Roux-en-Y gastric bypass (RYGB) or nonsurgical calorie restriction, and a normal- to overweight control group. The clinical implications of the results from multiple peer-reviewed articles describing the effects of RYGB, severe caloric restriction, weight loss, and type 2 diabetes on the in vivo activity and protein expression of drug-metabolizing enzymes (cytochrome P450 (CYP) 1A2, 2C9, 2C19, and 3A) and transporters (DMETs; organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein (P-gp)) are discussed in the perspective of three clinically relevant questions: (1) How should clinicians get the dose right in patients after RYGB? (2) Will drug disposition in patients with obesity be normalized after successful weight loss? (3) Are dose adjustments needed according to obesity and diabetes status? Overall, RYGB seems to have a lower impact on drug disposition than previously assumed, but clinicians should pay close attention to drugs with a narrow therapeutic range or where a high maximum drug concentration may be problematic. Whether obesity-related alterations of DMETs normalize with substantial weight loss depends on the DMET in question. Obesity and diabetes downregulate the in vivo activity of CYP2C19 and CYP3A (only obesity) but whether substrate drugs should be dose adjusted is also dependent on other factors that influence clearance, that is, liver blood flow and protein binding. Finally, we recommend frequent and individualized follow-up due to high inter- and intraindividual variability in these patients, particularly following RYGB., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

A change in implicit behavioural tendencies toward foods may contribute to the maintenance of calorie restriction in Anorexia Nervosa (AN). To test this hypothesis, we assessed approach-avoidance tendencies toward different categories of stimuli using a novel mobile version of the approach-avoidance task (AAT). The sample included 66 patients with restrictive AN and 84 healthy controls, all females. All participants performed the AAT in which they were required to approach or avoid stimuli (high-calorie foods, low-calorie foods, and neutral objects) by respectively pulling their phone towards themselves of pushing it away. Both the response time and the force of each movement were collected by means of the smartphone's accelerometer. The results revealed that patients with AN had a reduced tendency to approach food stimuli compared to healthy controls, who instead presented faster and stronger movements in approaching rather than avoiding foods as compared to neutral objects. This finding was particularly pronounced in patients with greater levels of malnutrition. No differences were instead observed comparing high-calorie and low-calorie foods. The observed reduction in the natural tendency to approach food stimuli is consistent with patients' eating behaviour and may contribute to the maintenance of calorie restriction, thus representing a possible target for novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors have no competing financial interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: To explore the effectiveness of the Metawell programme on cardiometabolic risk factors in China, which combines meal replacement biscuits, a wireless scale, and a mobile phone application., Methods: In this two-arm, parallel-design randomized study, 220 participants were randomly assigned to an intervention (n = 110) and a control (n = 110) group. Participants in the intervention group were instructed to use meal replacement products and scales for weight loss and monitoring, whereas participants in the control group received printed materials containing a sample diet and face-to-face weight loss education at enrolment. The trial lasted 6 months, including a weight loss period in Months 1-3 and a weight maintenance period in Months 3-6. Generalized estimating equations were used to compare differences between the two groups., Results: The median (interquartile range) ages of the intervention and control groups were 32.00 (28.00, 39.00) years and 33.00 (28.25, 41.00) years, with body mass indices of 28.20 (26.30, 30.95) kg/m 2 and 27.70 (26.02, 29.70) kg/m 2 , respectively. Participants in the intervention group experienced significantly greater decreases in waist circumference, hip circumference, triglycerides, total cholesterol: high-density lipoprotein cholesterol ratio, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance index compared to the control group (p < 0.01). Among participants who did not regain weight during the maintenance period after weight loss, the reductions in systolic and diastolic blood pressure were significantly greater in the intervention group than in the control group (p < 0.05)., Conclusions: The Metawell programme of caloric restriction and remote monitoring can be adapted to overweight and obese people in China to reduce their cardiometabolic risk factors. Furthermore, there was a better improvement in blood pressure in participants who maintained the effects of weight loss., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Very low-calorie diet (VLCD) can induce weight loss and diabetes remission (DR) amongst people with obesity and recent-onset type 2 diabetes (T2D). We aimed to determine the effectiveness and acceptability of VLCD in achieving DR amongst Sri Lankan adults with T2D., Methods: A retrospective analysis was conducted in a diabetes practice where VLCD-based Diabetes Remission Programme (VDRP) was offered for adults (>18 years) with T2D for <3 years and body mass index over 25 kg/m 2 . VLCD (~800 kcal/day, provided with/without diet replacement formula) was offered for 8-12 weeks, followed by gradual food reintroduction and exercise. DR was defined as HbA1c <6.5% at least 3 months after stopping glucose-lowering medications., Results: A total of 170 participants who enrolled in the VDRP (mean age 38.4 years [±11.1], men 68%, mean baseline HbA1c 86.9 [±18.1] mmol/mol (10.1 [±2.1]%), median duration of T2D 2 years [IQR 1-2]) and 87 (51%) of them followed the programme (attended at least one follow-up visit). Amongst the individuals who followed the VDRP, 40.2% achieved DR (35/87), compared with 2.4% (2/83) amongst those who did not follow the VDRP (aHR 9.3, 95% CI 2.2-16.4, p = 0.002). The proportion achieving normoglycaemia (HbA1c < 6.5%) but continued to take glucose-lowering medication was 20/87 among VDRP followers and 20/85 amongst VDRP non-followers. The commonest reasons for not following the VDRP were too restrictive dietary quantity (92%) and difficulties in finding recommended food items (67%). Majority (79%) would recommend VDRP to others., Conclusions: VDRP is effective in achieving T2D remission amongst Sri Lankan adults with recently diagnosed T2D and obesity. Over half of the participants followed the programme and over 75% would recommend it to others, indicating good acceptability., (© 2024 Diabetes UK.)

As the population ages, promoting healthy aging through targeted interventions becomes increasingly crucial. Growing evidence suggests that dietary interventions can significantly impact this process by modulating fundamental molecular pathways. This review focuses on the potential of targeted dietary strategies in promoting healthy aging and the mechanisms by which specific nutrients and dietary patterns influence key pathways involved in cellular repair, inflammation, and metabolic regulation. Caloric restriction, intermittent fasting, the Mediterranean diet, as well as the ketogenic diet showed promising effects on promoting healthy aging, possibly by modulating mTORC1 AMPK, an insulin signaling pathway. By understanding the intricate interplay between diet and molecular pathways, we can develop personalized dietary strategies that not only prevent age-related diseases, but also promote overall health and well-being throughout the aging process.

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease.

Accurate weight predictions are essential for weight management program patients. The freely available National Institutes of Health Body Weight Planner (NIH-BWP) returns expected weights over time but overestimates weight when patients consume a low-calorie diet. This study sought to increase the accuracy of NIH-BWP predicted weights for people on low-calorie diets. People enrolled in a weight management program were included if they received meal replacements with defined caloric content for the 3 months of the weight loss phase of the program. The Ottawa Weight Loss Prediction Model (OWL-PM) modelled the relative difference between observed and NIH-BWP predicted weights using longitudinal analysis methods based on patient factors. OWL-PM was externally validated. 1761 people were included (mean age 46 years, 73.3% women) with a mean (SD) baseline weight in pounds and body mass index of 271.9 (55.6) and 43.9 (7.4), respectively. At the end of the program's weight loss phase, people lost a median (IQR) of 17.1% (14.8-19.5) of their baseline weight. Observed weight relative to NIH-BWP predicted weights had a median value of - 4.9% but ranged from - 32.1% to + 28.5%. After adjustment, weight overestimation by NIH-BWP was most pronounced in male patients, people without diabetes and with increased observation time. OWL-PM returned expected weights at 3 months that were significantly more accurate than those from NIH-BWP alone (mean difference observed vs. expected [95% CI] 6.7lbs [6.4-7.0] vs. 12.6lbs [12.1-13.0]). In the external validation cohort (n = 106), OWL-PM was significantly more accurate than NIH-BWP (mean squared error 24.3 vs. 40.0, p = 0.0018). OWL-PM incorporated patient-level covariates to significantly increase weight prediction accuracy of NIH-BWP in patients consuming a low-calorie diet., (© 2024. The Author(s).)

The prevalence of overweight and obesity in women of reproductive age leads to significant health risks, including adverse metabolic and reproductive outcomes. Effective dietary interventions are critical to improving health outcomes in this population. This study investigates the impact of a 12-week diet intervention on metabolic markers of adipose tissue in overweight women of reproductive age, determining whether calorie restriction or low-starch diets are more effective, while also accounting for salivary amylase activity. A total of 67 overweight women of reproductive age were enrolled in a randomized controlled trial (RCT). Participants were divided into high-salivary-amylase (HSA) and low-salivary-amylase (LSA) groups based on baseline salivary amylase activity measured using a spectrophotometric method. Each group was further subdivided into two dietary intervention groups: calorie restriction (CR) and low starch (LS), resulting in four subgroups (HSA-CR, HSA-LS, LSA-CR, LSA-LS), along with a control group (CTR) of normal-weight individuals (no intervention). Participants were assigned to a calorie-restricted diet or a low-starch diet for 12 weeks. Key metabolic markers of adipose tissue, including insulin sensitivity, adipokines, cytokines, and lipid profiles, were measured at baseline (T0), 30 min after consuming starch-containing muesli (T1), and 12 weeks after intervention (T2). Active GLP-1, glucagon, and C-peptide levels were assessed to clarify the hormonal mechanisms underlying the dietary effects. Salivary amylase activity was also measured to examine its role in modulating glucose and GLP-1 responses. Both diet interventions led to significant improvements in metabolic markers of adipose tissue, though different ones. Calorie restriction improved insulin sensitivity by effectively reducing visceral fat mass and enhancing insulin signaling pathways. In contrast, the low-starch diet was linked to a reduction in the coefficient of glucose variation influenced partly by changes in GLP-1 levels. Our findings highlight the importance of personalized diet strategies to optimize metabolic health in this demographic.

Background: Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota., Methods and Findings: A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n 2 p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study., Conclusions: We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials., Trial Registration: This trial was registered with ClinicalTrials.gov (NCT05200468)., Competing Interests: Declaration of conflict of interest Laura A. Velázquez-Villegas received research funding from Laboratorios Senosiain S.A. de C.V., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The Manchester Intermittent versus Daily Diet App Study (MIDDAS) tested the feasibility and potential efficacy of two remotely delivered low-energy diet (LED) programmes (800 kcal/day) to support weight loss and remission of type 2 diabetes: continuous [CLED] (8 weeks of daily LED) and intermittent [ILED] (2 days of LED/week for 28 weeks). Understanding participant experiences can help us to understand the acceptability of LED programmes to people with type 2 diabetes, informing future programme development and implementation., Methods: Twenty participants (10 CLED; 10 ILED) took part in interviews conducted at the end of the active weight loss phase (CLED week 12, ILED week 28). Interviews were transcribed and analysed thematically using the template analysis approach, with an a priori focus on acceptability. Four themes are presented: prospective acceptability, intervention coherence and perceived effectiveness, opportunity costs and self-efficacy., Results: Both remotely supported CLED and ILED interventions appeared acceptable to participants. CLED participants found the rapid initial weight loss phase comparatively easy and highly motivating but expressed more concerns around weight maintenance. ILED participants found the more gradual weight loss initially frustrating but expressed greater confidence in their longer-term adherence. The importance of continued individualised support from healthcare professionals was emphasised, and evidence of weight loss and improvement in other medical markers through monitoring via the mobile phone app was useful., Conclusion: Different approaches to remotely delivered LEDs appear acceptable; therefore asking patients which approach may be more acceptable to them may be a useful way to offer individualised and tailored support., (© 2024 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

This study investigated the combined effects of resistance exercise training (RET) and alternate-day calorie restriction (ADCR) on body composition, insulin resistance (IR), insulin resistance-related biomarkers (adipokine adipsin and hepatokine soluble EFGR), and weight loss in obese men. The findings revealed that RET + ADCR induced the greatest reductions in body weight, body fat percentage, and waist-to-hip ratio (WHR) compared to RET and ADCR alone ( p  < 0.05). Additionally, RET + ADCR resulted in the most significant improvements in IR, as measured by HOMA-IR, and in circulating levels of adipsin and soluble EFGR ( p  < 0.05). These findings suggest that combining RET and ADCR may be a more effective strategy for improving metabolic health, including body composition, IR, and metabolic tissues' functions, in obese men than either intervention alone.

Background: Obesity may increase surgical complexity in patients undergoing abdominal surgery by limiting visualization and increasing the risk of peri-operative complications. A preoperative reduction in weight and liver volume may improve surgical outcomes. The aim of our study was to evaluate the efficacy of a low-calorie diet (LCD) versus a very low-calorie diet (VLCD) in reducing weight and liver volume prior to laparoscopic surgery., Methods: A systematic search was conducted using the following inclusion criteria: obese patients undergoing preoperative weight loss using a VLCD or LCD, evaluation of liver volume reduction, and the use of an imaging modality before and after the diet., Results: A total of 814 patients from 21 different studies were included in this systematic review and meta-analysis, with 544 female patients (66.8%) and a mean age range between 24 and 54 years old. There was a total mean weight loss of 6.42% and mean liver volume reduction of 16.7%. Meta-analysis demonstrated that a preoperative diet (LCD or VLCD) significantly reduced weight [SMD = - 0.68; 95% CI (- 0.93, - 0.42), I 2  = 82%, p ≤ 0.01] and liver volume [SMD = - 2.03; 95% CI (- 4.00, - 0.06), I 2  = 94%, p ≤ 0.01]. When assessed individually, a VLCD led to significant weight reduction [SMD = - 0.79; CI (- 1.24; - 0.34), p ≤ 0.01, I 2  = 90%], as did an LCD [SMD = - 0.60; CI (- 0.90; - 0.29), p ≤ 0.01, I 2  = 68%). Similarly, there was a significant reduction in liver volume following a VLCD [SMD = - 1.40; CI (- 2.77, - 0.03), p ≤ 0.01, I 2  = 96%], and an LCD [SMD = - 2.66; CI (- 6.13, 0.81), p ≤ 0.01, I 2  = 93%]. However, there was no significant difference between the two regimens., Conclusions: Preoperative restrictive calorie diets are effective in reducing weight and liver volume prior to laparoscopic surgery. Whilst a VLCD was better than an LCD at reducing both weight and liver volume, the difference was not significant., (© 2024. The Author(s).)

Background: AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation., Aim: We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition., Methods: Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR., Results: The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR., Conclusion: Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Energy restriction (ER) is a nutrition method to reduce the amount of energy intake while maintaining adequate nutrition. In clinical medicine, applications of ER have been implicated in longevity, mortality, metabolic, immune, and psychological health. However, there are limited studies showing the clinical benefit of ER within the immediate surgical setting. A specific, clinically oriented summary of the potential applications of ER is needed to optimize surgery outcomes for patients. The purpose of this article is to examine how ER can be used for perioperative optimization to improve outcomes for the patient and surgeon. It will also explore how these outcomes can feasibly fit in with enhanced recovery after surgery protocols and can be used as a method for nutrition optimization in surgery. Despite evidence of caloric restriction improving outcomes in critically ill surgical patients, there is not enough evidence to conclude that ER, perioperatively across noncritically ill cohorts, improves postoperative morbidity and mortality in elective surgeries. Nevertheless, a contemporary account of how ER techniques may have a significant role in reducing risk factors of adverse surgical outcomes in this cohort, for example, by encouraging preoperative weight loss contributing to decreased operating times, is reviewed., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Pilot trials indicate that both a low glycemic load (GL) diet and calorie restriction (CR) can be implemented successfully in people with multiple sclerosis (pMS) and may improve MS symptoms and physical function, but large randomized clinical trials (RCTs) have not yet been conducted. The purpose of this study is to test these interventions alone and in combination to determine their efficacy for improving clinical and patient reported outcomes (PROs) in pMS., Methods: This 32-week, two-arm, RCT at two centers will randomly assign 100 adults with relapsing-remitting or secondary progressive MS to a low GL diet (n = 50) or a standard GL diet (n = 50). Both diet groups will complete two study phases: a eucaloric phase (16 weeks) and a CR phase (16 weeks). Groceries for the study meal plans will be delivered to participants' homes weekly. The primary outcome is physical function, measured by timed 25-ft walk test. Secondary outcomes are pain, fatigue, mood, and anxiety., Discussion: This will be the most rigorous intervention trial to date of a low GL diet and CR in adults with MS, and among the first to assess the impact of intentional weight loss on MS symptoms. Results will provide valuable insight for recommending dietary change, weight loss, or both to adults with MS. These non-drug interventions pose few risks and have potential to yield significant improvements in MS symptoms., Trial Registration Id: NCT05327322., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Polycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of licorice on obesity indices, glycemic indices, and lipid profiles in women with PCOS., Methods: This randomized, double-blind, placebo-controlled trial was performed on 66 overweight/obese women with PCOS. The participants were randomly assigned to receive either 1.5 gr/day licorice extract plus a low-calorie diet (n = 33) or placebo plus a low-calorie diet (n = 33) for 8 weeks. Participants' anthropometric indices and body composition were assessed using standard protocols. Fasting blood sugar (FBS), insulin levels, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein-cholesterol (HDL-C) were measured using enzymatic kits. The homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA of β-cell function (HOMA-B) were calculated using valid formulas., Results: Between-group comparisons demonstrated significant differences between the groups in terms of obesity indices (body weight, BMI, and body fat), lipid profiles (TG, TC, LDL-C, and HDL-C), FBS and insulin levels, HOMA-IR, and HOMA-B at the end of the study (P < 0.05). Supplementation with licorice plus a low-calorie diet was also more effective in improving all parameters than a low-calorie diet alone after adjusting for confounders (baseline values, age, weight changes, and physical activity changes) (P < 0.05)., Conclusion: The findings showed that licorice consumption leads to improvements in obesity indices, glucose homeostasis, and lipid profiles compared to placebo. Due to possible limitations of the study, further research is needed to confirm these findings., (© 2024. The Author(s).)

Roux-en-Y gastric bypass (RYGB) is the most effective treatment for severe obesity. A very low-calorie diet (VLCD) is another effective dietary intervention to treat obesity. This study evaluated the effect of a VLCD versus RYGB on weight reduction, changes in body composition and the resolution of comorbidities during a 12-week period. Individuals with obesity at the obesity clinic, Ramathibodi Hospital, Mahidol University, Thailand with a body mass index (BMI) ≥ 37.5 kg/m 2 or ≥32.5 kg/m 2 with obesity-related complications were recruited. Treatment options, either RYGB or VLCD, were assigned depending on patients' preferences and physicians' judgment. The analysis included 16 participants in the RYGB group and 15 participants in the VLCD group. Baseline characteristics were similar between groups; nevertheless, the participants in the VLCD group were significantly younger than those in the RYGB group. The number of patients with type 2 diabetes (T2D) was slightly higher in the RYGB group (43.8% vs. 33.3%, p = 0.552). Additionally, patients in the RYGB group had a longer duration of T2D and were treated with anti-diabetic agents, while VLCD patients received only lifestyle modifications. At 12 weeks, total and percentage weight loss in the RYGB and VLCD groups, respectively, were as follows: -17.6 ± 6.0 kg vs. -15.6 ± 5.1 kg ( p = 0.335) and -16.2% ± 4.3% vs. -14.1% ± 3.6% ( p = 0.147). Changes in biochemical data and the resolution of comorbidities were similar between the groups at 12 weeks. A 12-week VLCD resulted in similar weight loss and metabolic improvement compared with RYGB. Large-scale studies with long follow-up periods are needed to elucidate whether VLCD is a viable alternative treatment to bariatric surgery.

Background: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-β1), and other indicators in the presence and absence of ovaries in AKI female rats., Methods: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI., Results: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin., Conclusion: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-β1 in ovary-intact animals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Low-carbohydrate diets (LCDs) have gained interest due to their favorable effects on health outcomes, such as inflammation. However, further research is needed to ascertain the overall effects of LCDs on inflammatory parameters, but at the same time considering weight loss and calorie intake. Thus, a systematic review and meta-analysis of randomized clinical trials was performed to investigate the effects of LCDs compared with low-fat diets (LFDs), with and without caloric restriction, on inflammatory markers in adults. PubMed, Scopus, and Web of Science were searched through March 2022 to select intervention studies addressing LCDs vs. LFDs, in which the following circulating inflammatory markers were used: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL-6). Analyses were conducted comparing LCDs vs. LFDs through weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (95% CIs) using random effects models. The systematic review and meta-analysis included a total of 51 studies with a total sample of 4,164 adults, with or without other chronic diseases. Intervention durations ranged from 2-144 weeks. LCDs, compared with LFDs, significantly decreased body weight [WMD = -1.35%, p = 0.001], CRP [SMD = -0.1, p = 0.03], and IL-6 [SMD = -0.15, p = 0.09]. However, LCDs did not significantly decrease TNF-α [SMD = -0.02, p = 0.7] compared to LFDs. In conclusion, LCDs have a beneficial effect on markers of inflammation by decreasing CRP and IL-6; this effect has an association with weight loss. However, LCDs were not more effective than LFDs in decreasing TNF-α., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model., Methods: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks., Results: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aβ40, Aβ42, IL-1β, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet., Conclusions: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims/hypothesis: Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes., Methods: In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [ 18 F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change., Results: One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected., Conclusions/interpretation: The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks., Trial Registration: ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants., (© 2024. The Author(s).)