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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.)

The effect of a healthy low-carbohydrate diet (HLCD) and time-restricted eating (TRE), alone or in combination, on body weight and gut microbiome beyond caloric restriction remains unclear. In this 12-week two-by-two factorial randomized trial with a 28-week follow-up among 96 participants with overweight or obesity, isocaloric-restricted feeding yields significant weight loss, ranging from 2.57 to 4.11 kg across different groups. Beyond caloric restriction, HLCD and TRE lead to additional reduction in body mass index. HLCD results in additional fat mass loss while TRE yields more lean mass loss. Additionally, HLCD leads to decreased fecal branched-chain amino acids, and TRE tends to yield an increased abundance of probiotic species involved in synthesizing short-chain fatty acids. Moreover, the effect of HLCD on reducing fat mass is sustained during the post-intervention follow-up. Overall, HLCD and TRE are effective in weight management and yield profound gut microbiome and metabolome alteration beyond caloric restriction. This study was registered at ChiCTR.org.cn (ChiCTR2200056363)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the impact of prolonged fasting on the physiological and biochemical alterations and metabolic shifts in healthy adults and to provide experimental data and theoretical support for the hypometabolic state induced by prolonged fasting. Thirteen volunteers were selected through public recruitment to undergo a 21-day complete fasting experiment. The experimental period lasted 34 days, including a 3-day baseline, 21-day completing fasting, 5-day calorie restriction and 5-day full recovery diet. Physiological indicators such as body weight, blood pressure, blood glucose, blood ketones, and blood uric acid were evaluated along with resting metabolic rate, routine blood tests, liver function, and heart function indexes employing traditional approaches. During the 21-day complete fasting period, there was a significant decrease in body weight (average - 14.96 ± 1.55%), a reduction in blood glucose (average - 21.63 ± 0.058%), an increase in blood ketones (from baseline 0.1 ± 0.04 mmol/L to 6.61 ± 1.25 mmol/L) and blood uric acid (from baseline 385.38 ± 57.78 µmol/L to 866.31 ± 172.01 µmol/L), a continuous decline in resting energy expenditure (average - 20.3 ± 11.13%), and the respiratory quotient tending towards fat metabolism. Most of the items in the complete blood count and liver indicators remained stable and within the normal range. Heart function showed functional adaptive changes without structural damage. Prolonged fasting can reduce the body's resting energy expenditure and adapt to body weight loss through physiological regulatory mechanisms without adverse effects on basic physiological functions or the structure of important organs. Under medical supervision, healthy adults can safely engage in prolonged fasting for up to 21 days with metabolic adaption and no damage to pivotal organ, which could provide potential technical support for human health and survival strategies in extreme conditions such as food shortages during long-duration manned spaceflight., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

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).)

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements., Methods: Following medical diagnosis of MASH, individuals were randomized to treatment (n = 16) or control (n = 8). Liver fat (magnetic resonance spectroscopy), 18-hour plasma biochemical measurements, and isotopically labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO 2 peak) were also measured mid-intervention. Those in the treatment group were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Controls continued physician-directed care., Results: Treatment induced significant (p <0.05) reductions in body weight, fat mass, and liver injury, while VO 2 peak (p <0.05) and non-esterified fatty acid suppression (p = 0.06) were improved. Both groups exhibited reductions in total energy intake, hemoglobin A1c, hepatic insulin resistance, and liver fat (p <0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO 2 peak and resolution of liver disease., Conclusions: Exercise and energy restriction elicited significant and clinically meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH., Impact and Implications: The mechanisms that underpin histologic improvement in individuals with metabolic dysfunction-associated steatohepatitis (MASH) are not well understood. This study evaluated the relationship between liver and metabolic health, testing how changes in one may affect the other. We investigated the effects of energy restriction and exercise on the association between multi-tissue insulin sensitivity and histologic improvements in participants with biopsy-proven MASH. For the first time, these results show that an improvement in peripheral (but not hepatic) insulin sensitivity and systemic markers of muscle function (i.e. cardiorespiratory fitness) were strongly related to resolution of liver disease. Extrahepatic disposal of substrates and improved fitness levels supported histologic improvement, confirming the addition of exercise as crucial to lifestyle interventions in MASH., Clinical Trial Number: NCT03151798., (Copyright © 2024 European Association for the Study of the Liver. All rights reserved.)

Background: Obesity is a rapidly increasing health problem in China, causing massive economic and health losses annually. Many techniques have emerged to help people with obesity better adhere to intervention programs and achieve their weight loss goals, including food replacement and internet-delivered weight loss consultations. Most studies on weight loss interventions mainly focused on the change in body weight or BMI; however, body fat, especially visceral fat mass, is considered the main pathogenic factor in obesity. In China, more reliable evidence is required on this topic. Moreover, it is unclear whether an integrated weight loss program combining food replacement products, mobile app-based platforms, and daily body composition monitoring using a wireless scale is useful and practical in China., Objective: In this 2-arm, parallel-designed, randomized study, we explored the effectiveness and safety of the Metawell (Weijian Technologies Inc) weight loss program in China, which combines prepackaged biscuits, a wireless scale, and a mobile app., Methods: Participants in the intervention group were guided to use food replacement products and a scale for weight loss and monitoring, whereas participants in the control group received printed material with a sample diet and face-to-face education on weight loss at enrollment. The intervention lasted for 3 months, and follow-up visits were conducted at months 3 and 6 after enrollment. Dual-energy x-ray absorptiometry and quantitative computed tomography were used to assess body fat. A multilevel model for repeated measurements was used to compare differences between the 2 groups., Results: In total, 220 patients were randomly assigned to intervention (n=110) and control (n=110) groups. Participants in the intervention group had significantly greater decreases in BMI, total body fat, visceral adipose area, and subcutaneous adipose area (all P<.001) than those in the control group. However, the rate of change in lean mass was not significantly different between the 2 groups (P=.62). Further, 35 participants in the intervention group reported adverse events. Constipation was the most frequently reported adverse event (11/110), followed by dizziness (6/110), hypoglycemia (4/110), fatigue (3/110), and gastritis (3/35)., Conclusions: The Metawell program was effective for weight loss. After the intervention, participants in the intervention group lost more body weight and body fat while retaining muscle mass than those in the control group., (© Xi Wang, Suyuan Wang, Lingyu Zhong, Chenghui Zhang, Yanhong Guo, Mingxia Li, Li Zhao, Shuming Ji, Junjie Pan, Yunhong Wu. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Introduction: Obesity management strategies such as caloric restriction, very-low-calorie diets (VLCDs), and meal replacements can lead to moderate short-term weight loss. However, many patients face significant challenges in maintaining these results. Personalized interventions, including behavioral counseling and physical activity, have been shown to improve long-term adherence and success. Current clinical guidelines emphasize the pivotal role of dietitians in enhancing patient outcomes through nutritional therapy. When combined with pharmacotherapy and bariatric surgery, the focus shifts from mere weight loss to broader health improvements., Methods: This review explores the evolving role of dietitians in obesity management, advocating for a shift from a weight-centric approach to a more holistic model that prioritizes overall health gains. Key areas of interest include dietetic interventions' impact on metabolic health, cardiovascular function, gut microbiome balance, inflammation, and psychological well-being., Results: Dietetic interventions have been shown to provide significant health improvements beyond weight loss. These include enhanced metabolic and cardiovascular health, better gut microbiome balance, reduced inflammation, improved sleep quality, mental well-being, and overall quality of life. By focusing on non-scale victories such as improved insulin sensitivity, lipid profiles, and mental health, dietitians play a crucial role in driving long-term success in obesity management. These outcomes highlight the need to shift the focus from short-term weight loss to a more comprehensive view of health gains., Conclusions: The role of dietitians in obesity management is expanding to encompass a more comprehensive and individualized approach. Moving beyond a focus on weight reduction, this paradigm promotes long-term, patient-centered strategies that address the multifactorial nature of obesity. By combining dietary changes with regular physical activity and behavioral support, dietitians can contribute to sustained health improvements, treating obesity as a chronic, complex disease.

Objective: The objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD)., Results: In this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30-40 kg/m 2 ) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either "Prebiotic group" (received 10 g/day inulin) or "Placebo group" (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks., Trial Registration: The trial was registered in the Iranian registry of clinical trials at 2018-08-02 ( https://www.irct.ir/ ; registration number: IRCT20100209003320N15)., (© 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.

The very-low calorie ketogenic diet (VLCKD) is recommended as an effective dietary approach for the management of obesity. This study investigated changes in circulating biomarkers of redox homeostasis induced by a multiphase VLCKD in obese individuals. A total of 40 obese subjects were prescribed a multiphasic VLCKD for eleven weeks. Anthropometric measurements, body composition parameters, calorimetric measures, and standard laboratory markers of glucose and lipid metabolism were evaluated at baseline (T 0 ) and at the end of the dietary intervention (T 1 ). Additionally, circulating markers of oxidative damage and antioxidant status were analyzed in serum and erythrocytes. Compared to T 0 , at T 1 the multiphase VLCKD induced significant weight loss and reduction of waist circumference, with beneficial effects on body composition parameters and the glucose/lipid biochemical profile. Moreover, a decrease in serum markers of oxidative damage was reported at T 1 , while no changes in serum markers of antioxidant status and in erythrocyte redox markers were observed. In addition, a significant association was found between variations in anthropometric measurements, body composition, glucose metabolism parameters, and changes in circulating markers of oxidative damage. Regression models showed that variation in lipofuscin was significant predictor of changes in body mass index, fat mass, visceral adiposity, and insulin sensitivity. In conclusion, this study demonstrated that the multiphase VLCKD improves serum redox balance by reducing markers of oxidative damage in obese individuals, highlighting the interplay between adiposity, glucose metabolism, and redox homeostasis in the pathogenesis of obesity. Furthermore, these data provide a rationale for future investigations aimed at testing serum lipofuscin as a reliable redox marker in obesity., Competing Interests: Declaration of competing interest The Authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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/objectives: Obesity is a major risk factor for knee osteoarthritis (OA), and weight loss is crucial for its management. This pilot study explores the effects of a Very Low-Calorie Ketogenic Diet (VLCKD) in women with obesity and symptomatic knee OA., Methods: Women with symptomatic knee OA and obesity, defined as a body mass index (BMI) ≥ 30 kg/m 2 , were eligible for the VLCKD protocol. The intervention included a ketogenic phase from baseline (T0) to the 8th week (T8), followed by a progressive reintroduction of carbohydrates over the next 12 weeks, ending at the 20th week (T20). Body mass index (BMI), the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, the EuroQol 5D (EQ-5D), and the 36-item Short Form Health Survey (SF-36) were assessed at all time points. Generalized estimating equations were used to analyze the association between BMI and patient-reported outcomes across the study period., Results: Twenty participants started the study, but four discontinued the intervention, with two of these being due to adverse effects. The mean age of the 16 patients who completed the 20-week program was 57.3 ± 5.5 years, and their mean BMI was 40.0 ± 4.8 kg/m 2 . The mean BMI significantly decreased to 37.5 ± 4.5 at T4, 36.3 ± 4.6 at T8, and 34.8 ± 4.8 at T20 (all p < 0.001 compared to baseline). The total WOMAC score improved from a mean of 43.6 ± 16.9 at T0 to 30.2 ± 12.8 at T4 ( p = 0.005) and further to 24.7 ± 10.6 at T8 ( p = 0.001) and to 24.8 ± 15.9 at T20 ( p = 0.005). The reduction in BMI was significantly correlated with the improvements in WOMAC, EQ-5D, and SF-36 over time. No major adverse effects were observed., Conclusions: A 20-week VLCKD in women with obesity and knee OA significantly reduced their weight and improved their outcomes, warranting further research. This trial is registered with number NCT05848544 on ClinicalTrials.gov.

Objectives: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF., Methods: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression., Results: Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e., with ketones) and dietary strategies that impact ketogenesis., Conclusion: This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies in preventing progression and improving outcomes in the context of HF., Competing Interests: The authors declare no conflicts of interest.

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

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.

Background: Breast Cancer (BC) prevention strategies range from lifestyle changes such as increasing physical activity and reducing body weight to preventive drugs like tamoxifen, known to reduce BC incidence in high-risk women. Sex Hormone Binding Globulin (SHBG) is related to BC risk due to its ability to bind circulating estradiol at high affinity and to regulate estradiol action. A study protocol is presented based on the assessment of the effect of different interventions such as tamoxifen at 10 mg every other day (LDT), intermittent caloric restriction (ICR) two days per week, lifestyle intervention (LI, step counter use) and their combination on the modulation of SHBG and several other biomarkers associated to BC., Methods: A randomized phase II biomarker study will be conducted in 4 Italian centers. Unaffected women aged between 18 and 70 years, carriers of a germline pathogenetic variant (BRCA1, BRCA2, PALB2, or other moderate penetrance genes), or with a >5% BC risk at 10 years (according to the Tyrer-Cuzick or the Breast Cancer Surveillance Consortium Risk models) or with a previous diagnosis of intraepithelial neoplasia will be eligible. A total of 200 participants will be randomized to one of the four arms: LDT; LDT + ICR; LI; LI + ICR. Interventions will span six months, with baseline and follow-up clinic visits and interim phone calls., Discussion: The aim of the study is to verify whether LDT increases circulating SHBG more than LI with or without ICR after 6 months. Secondary objectives include assessing HOMA-index, inflammatory markers, adiponectin/leptin ratio, quality of life (QoL), safety, toxicity, mammographic density, and changes in microbiome composition across groups. The study's innovation lies in its inclusion of diverse BC risk categories and combination of pharmaceutical and behavioral interventions, potentially enhancing intervention efficacy while balancing tamoxifen's side effects on QoL, especially menopausal symptoms., Trial Registration: EuCT number:2023-503994-39-00; Clinical trials.gov NCT06033092., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guerrieri-Gonzaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obesity is 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.

Aims: NHS England commissioned independent service providers to deliver the NHS Low-Calorie Diet Programme pilot. Previous research has illustrated a drift in the fidelity of behaviour change techniques (BCTs) during the delivery of the programme provided through face-to-face group or one-to-one behavioural support. The aim of this study was to assess the delivery fidelity of the BCT content in the digital delivery of the programme., Methods: Online, app chat and phone call support content was coded using The Behaviour Change Technique Taxonomy. BCTs delivered by each service provider (N = 2) were calculated and compared to the BCTs specified in the NHS service specification and those specified in the providers' programme plans., Results: Between 78% and 83% of the BCTs identified in the NHS service specification were delivered by the service providers. The fidelity of BCT delivery to those specified in providers' programme plans was 60%-65% for provider A, and 82% for provider B., Conclusions: The BCT content of the digital model used in the NHS-LCD programme adhered well to the NHS service specification and providers' plans. It surpassed what has been previously observed in face-to-face services provided through group or one-on-one behavioural support models., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: To perform a meta-analysis to investigate the effects of intermittent fasting (IF), as compared with either a control diet (CON) and/or calorie restriction (CR), on body composition and cardiometabolic health in individuals with prediabetes and type 2 diabetes (T2D)., Methods: PubMed, Web of Science, and Scopus were searched from their inception to March 2024 to identify original randomized trials with parallel or crossover designs that studied the effects of IF on body composition and cardiometabolic health. Weighted mean differences (WMDs) or standardized mean differences with 95% confidence intervals (CIs) were calculated using random-effects models., Results: Overall, 14 studies involving 1101 adults with prediabetes or T2D were included in the meta-analysis. IF decreased body weight (WMD -4.56 kg [95% CI -6.23 to -2.83]; p = 0.001), body mass index (BMI; WMD -1.99 kg.m 2 [95% CI -2.74 to -1.23]; p = 0.001), glycated haemoglobin (HbA1c; WMD -0.81% [95% CI -1.24 to -0.38]; p = 0.001), fasting glucose (WMD -0.36 mmol/L [95% CI -0.63 to -0.09]; p = 0.008), total cholesterol (WMD -0.31 mmol/L [95% CI -0.60 to -0.02]; p = 0.03) and triglycerides (WMD -0.14 mmol/L [95% CI -0.27 to -0.01]; p = 0.02), but did not significantly decrease fat mass, insulin, low-densitiy lipoprotein, high-density lipoprotein, or blood pressure as compared with CON. Furthermore, IF decreased body weight (WMD -1.14 kg [95% CI -1.69 to -0.60]; p = 0.001) and BMI (WMD -0.43 kg.m 2 [95% CI -0.58 to -0.27]; p = 0.001), but did not significantly affect fat mass, lean body mass, visceral fat, insulin, HbA1c, lipid profiles or blood pressure., Conclusion: Intermittent fasting is effective for weight loss and specific cardiometabolic health markers in individuals with prediabetes or T2D. Additionally, IF is associated with a reduction in body weight and BMI compared to CR, without effects on glycaemic markers, lipid profiles or blood pressure., (© 2024 John Wiley & Sons Ltd.)

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.)

Background: The beneficial effects of n-3 polyunsaturated fatty acids (PUFA) in reducing high blood triglyceride (TG) levels have been well demonstrated. This study aimed to investigate the effect of chia seeds on blood TG and its associated cardiometabolic factors in hypertriglyceridaemic individuals., Methods: This three-group randomised controlled trial compared the effects of a low-calorie diet (n = 22), a low-calorie diet with chia seeds (30 g/day, n = 22) or a low-calorie diet with concentrated fish oil (1.8 g/day of n-3 long-chain PUFAs, n = 22) in patients with hypertriglyceridaemia. Anthropometrics, fasting blood lipids, proprotein convertase subtilisin/kexin type 9, insulin, adiponectin, leptin and interleukin-6 levels were measured., Results: After 8 weeks, the mean reduction in weight exhibited by the three groups was not statistically different (2.0, 2.7 and 2.8 kg, respectively, for the control, fish oil and chia seed groups). The plasma TG decreased in both the chia seed and fish oil groups in comparison to the control group (p = 0.001). However, no significant difference was observed between the chia seed and fish oil groups (change from baseline mean: 145.2 and 136.7 mg/dL for the chia seed and fish oil groups, respectively). The consumption of chia seeds was associated with a reduction in diastolic blood pressure (change from baseline mean: 8.4 mmHg) compared to the other two groups. No significant alterations were observed in the other blood biochemical factors between the three groups., Conclusions: In people with moderate hypertriglyceridaemia, a low-calorie diet with 30 g of chia seeds compared to fish oil supplements containing 1.8 g of long-chain PUFAs has a similar effect on reducing plasma TG levels, whereas it has a higher blood pressure-lowering effect., (© 2024 British Dietetic Association.)

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.)

Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 a genetic disorder characterized by the development and enlargement of multiple kidney cysts, leading to progressive kidney function decline. To date, Tolvaptan, the only approved treatment for this condition, is able to slow down the loss of annual kidney function without stopping the progression of the disease. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the drug's impact on quality of life. The recent literature suggests that cystic cells are subject to several metabolic dysregulations, particularly in the glucose pathway, and mitochondrial abnormalities, leading to decreased oxidative phosphorylation and impaired fatty acid oxidation. This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions' effect.