The Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction.

Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes, as well as CXCR4-CXCL12 and S1P-S1P1R interactions, contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within "safe haven" compartments.

Caloric restriction disrupts the microbiota and colonization resistance.

Diet is a major factor that shapes the gut microbiome1, but the consequences of diet-induced changes in the microbiome for host pathophysiology remain poorly understood. We conducted a randomized human intervention study using a very-low-calorie diet (NCT01105143). Although metabolic health was improved, severe calorie restriction led to a decrease in bacterial abundance and restructuring of the gut microbiome. Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota. Weight loss was associated with impaired nutrient absorption and enrichment in Clostridioides difficile, which was consistent with a decrease in bile acids and was sufficient to replicate metabolic phenotypes in mice in a toxin-dependent manner. These results emphasize the importance of diet-microbiome interactions in modulating host energy balance and the need to understand the role of diet in the interplay between pathogenic and beneficial symbionts.

Network meta-analysis of three different forms of intermittent energy restrictions for overweight or obese adults.

This network meta-analysis aimed to compare the efficacy of three forms of intermittent energy restriction (IER), including alternate-day fasting (ADF), the 5:2 diet, and time-restricted feeding (TRF), in overweight or obese adults. A literature search was conducted in PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) to find relevant randomized controlled trials (RCTs) until August 10, 2022. The modified Cochrane risk of bias assessment tool was applied to assess the methodological quality of eligible studies. Random network meta-analysis was conducted using STATA 14.0. Sixteen RCTs were included, with 1228 patients. Overall, the methodological quality ranged from low to moderate. ADF was superior to CER and 5:2 diet in reducing waist circumference, whereas 5:2 diet was superior to CER in reducing BMI. Regarding fat mass and drop-out, all forms of IER were comparable. Sensitivity analyses indicated that the type of individuals had no influence on the pooled results; nevertheless, ADF significantly reduced weight compared to CER and achieved significant waist circumference reduction compared to CER, 5:2 diet, and TRF. ADF may be preferentially prescribed for overweight or obese adults. More large-scale and high-quality studies are required, however, to investigate the effect of TRF on overweight and obesity.

Weight-Reducing Dietary Intervention Increases the Ability of Hyperinsulinemia to Suppress Serum Ghrelin Concentration in Individuals with Obesity.

BACKGROUND: Ghrelin is an orexigenic peptide secreted mainly by the stomach. Serum ghrelin concentrations are suppressed after a meal, probably due to insulin release. Individuals with obesity are characterized by a lower fasting serum ghrelin and a lower ghrelin decrease after a meal. The effect of weight loss on the ability of insulin to suppress serum ghrelin concentration remains unknown. OBJECTIVE: The aim of the present study was to analyze the effect of weight-reducing dietary intervention on the ability of hyperinsulinemia to suppress serum ghrelin concentration in young individuals with uncomplicated obesity. METHODS: We examined 38 individuals with marked overweight or obesity, who underwent a 12-wk dietary intervention program. Serum ghrelin concentration was measured before and after a 2-h hyperinsulinemic-euglycemic clamp, both pre- and post-intervention. Twenty normal-weight individuals served as a control group and were examined at baseline only. RESULTS: Individuals with overweight/obesity were characterized by a lower fasting serum ghrelin concentration than normal-weight individuals (P = 0.006). Insulin decreased serum ghrelin concentration in both groups (P < 0.001); however, this decrease was markedly lower in individuals with overweight/obesity than in normal-weight individuals (99.70 ± 136.37 vs. 215.45 ± 250.28 pg/mL; P = 0.026). Fasting serum ghrelin concentration increased after the intervention. After weight-reducing dietary intervention, the decrease in serum ghrelin concentration after the clamp was significantly greater than the pre-intervention value (99.70 ± 136.37 vs. 221.82 ± 228.75 pg/mL; P = 0.002). CONCLUSIONS: Weight-reducing dietary intervention restores the ability of hyperinsulinemia to suppress serum ghrelin concentration. It may suggest an enhanced feeling of satiety after moderate weight loss in individuals with overweight/obesity.

Partial Meal Replacement for Weight Loss after Stroke: Results of a Pilot Clinical Trial.

INTRODUCTION: Over half of patients with acute ischemic stroke are overweight or obese as defined by a body mass index (BMI) ≥25 kg/m2. Professional and government agencies recommend weight management for these persons to improve risk factors for cardiovascular disease, including hypertension, dyslipidemia, vascular inflammation, and diabetes. However, approaches to weight loss have not been adequately tested specifically in patients with stroke. In anticipation of a larger trial with vascular or functional outcomes, we tested the feasibility and safety of a 12-week partial meal replacement (PMR) intervention for weight loss in overweight or obese patients with a recent ischemic stroke. METHODS: This randomized open-label trial enrolled participants from December 2019 to February 2021 (with hiatus from March to August 2020 due to COVID-19 pandemic restrictions on research). Eligible patients had a recent ischemic stroke and BMI 27-49.9 kg/m2. Patients were randomized to a PMR diet (OPTAVIA® Optimal Weight 4 & 2 & 1 Plan®) plus standard care (SC) or SC alone. The PMR diet consisted of four meal replacements supplied to participants, two meals with lean protein and vegetables (self-prepared or supplied), and a healthy snack (also self-prepared or supplied). The PMR diet provided 1,100-1,300 calories per day. SC consisted of one instructional session on a healthy diet. Co-primary outcomes were ≥5% weight loss at 12 weeks and to identify barriers to successful weight loss among participants assigned to PMR. Safety outcomes included hospitalization, falls, pneumonia, or hypoglycemia requiring treatment by self or others. Due to the COVID-19 pandemic, study visits after August 2020 were by remote communication. RESULTS: We enrolled 38 patients from two institutions. Two patients in each arm were lost and could not be included in outcome analyses. At 12 weeks, 9/17 patients in the PMR group and 2/17 patients in the SC group achieved ≥5% weight loss (52.9% vs. 11.9%; Fisher's exact p = 0.03). Mean percent weight change in the PMR group was -3.0% (SD 13.7) and -2.6% (SD 3.4) in the SC group (Wilcoxon rank-sum p = 0.17). No adverse events were attributed to study participation. Some participants had difficulty completing home monitoring of weight. In the PMR group, participants reported that food cravings and dislike for some food products were barriers to weight loss. CONCLUSION: A PMR diet after ischemic stroke is feasible, safe, and effective for weight loss. In future trials, in-person or improved remote outcome monitoring may reduce anthropometric data variation.

Low-calorie diets are effective for weight loss in patients undergoing benign upper gastrointestinal surgery: a systematic review and meta-analysis.

BACKGROUND: Obesity may increase surgical complexity in patients undergoing abdominal surgery by limiting visualization and increasing the risk of peri-operative complications. A preoperative reduction in weight and liver volume may improve surgical outcomes. The aim of our study was to evaluate the efficacy of a low-calorie diet (LCD) versus a very low-calorie diet (VLCD) in reducing weight and liver volume prior to laparoscopic surgery. METHODS: A systematic search was conducted using the following inclusion criteria: obese patients undergoing preoperative weight loss using a VLCD or LCD, evaluation of liver volume reduction, and the use of an imaging modality before and after the diet. RESULTS: A total of 814 patients from 21 different studies were included in this systematic review and meta-analysis, with 544 female patients (66.8%) and a mean age range between 24 and 54 years old. There was a total mean weight loss of 6.42% and mean liver volume reduction of 16.7%. Meta-analysis demonstrated that a preoperative diet (LCD or VLCD) significantly reduced weight [SMD = - 0.68; 95% CI (- 0.93, - 0.42), I2 = 82%, p ≤ 0.01] and liver volume [SMD = - 2.03; 95% CI (- 4.00, - 0.06), I2 = 94%, p ≤ 0.01]. When assessed individually, a VLCD led to significant weight reduction [SMD = - 0.79; CI (- 1.24; - 0.34), p ≤ 0.01, I2 = 90%], as did an LCD [SMD = - 0.60; CI (- 0.90; - 0.29), p ≤ 0.01, I2 = 68%). Similarly, there was a significant reduction in liver volume following a VLCD [SMD = - 1.40; CI (- 2.77, - 0.03), p ≤ 0.01, I2 = 96%], and an LCD [SMD = - 2.66; CI (- 6.13, 0.81), p ≤ 0.01, I2 = 93%]. However, there was no significant difference between the two regimens. CONCLUSIONS: Preoperative restrictive calorie diets are effective in reducing weight and liver volume prior to laparoscopic surgery. Whilst a VLCD was better than an LCD at reducing both weight and liver volume, the difference was not significant.

The effect of diet-induced weight loss on circulating homocysteine levels in people with obesity and type 2 diabetes.

BACKGROUND/AIMS: Having type 2 diabetes (T2D) in combination with being overweight results in an additional increase in cardiovascular disease (CVD) risk. In addition, T2D and obesity are associated with increased levels of total homocysteine (tHcy), possibly contributing to the CVD risk. Weight loss dieting has positive effects on several CVD risk factors, but whether it affects tHcy remains unclear. Therefore, the aim of this study was to determine the effect of a calorie restricted diet on tHcy in overweight people with T2D. METHODS: In this post-hoc analysis of the POWER study, adults with T2D and a BMI greater than 27 kg/m² were included from the outpatient diabetes clinic of the Erasmus Medical Center, Rotterdam. The patients were subjected to a very low-calorie diet with fortified meal replacements for 20 weeks. Before and after this intervention, blood samples were collected to measure tHcy and other CVD risk factors like glycaemic and lipid parameters. RESULTS: 161 overweight participants with T2D were included, with a mean age of 54 years (range 26-74), mean weight of 104.6 ± 19.9 kg and mean HbA1c of 62.7 ± 14.3 mmol/mol. At baseline, men displayed higher tHcy than women, and tHcy level was positively correlated with body weight and triglyceride levels, while it was negatively correlated with renal function and HDL cholesterol. During the intervention, bodyweight was reduced by a mean of 9.7% (from 104.6 ± 19.9 to 94.5 ± 18.1 kg p < 0.001), and all measured glycaemic and lipid blood parameters improved significantly. However, tHcy remained unchanged (from 12.1 ± 4.1 to 12.1 ± 4.2 umol/L, p = 0.880). The change in tHcy during the intervention was negatively associated with the change in weight and BMI (p = 0.01 and p = 0.008, respectively). People who lost < 10 kg (n = 92) had a mean tHcy change of -0.47 umol/L, while people who lost more than ≥ 10 kg (n = 69) had a mean tHcy change of 0.60 umol/L (p = 0.021). CONCLUSION: In conclusion, our data show that a calorie restricted diet does not affect tHcy in people with T2D and obesity, despite the use of meal replacements fortified with folic acid and vitamin B12. Our data showed a negative correlation between change in tHcy levels and weight loss, suggesting that people who lost more weight (> 10 kg) showed an increase in tHcy. Future studies should explore the potential increase in tHcy induced by weight loss dieting and target the question if tHcy reduction strategies during weight loss could be clinically beneficial.

The relationship between hedonic hunger and self-stigmatisation in terms of weight and self-esteem in adult people living with obesity.

INTRODUCTION: This study aimed to determine the factors influencing the hedonic hunger status of overweight adults and to examine the relationship between hedonic hunger, self-stigmatisation and self-esteem in terms of weight. METHODS: This cross-sectional study was conducted with 353 people living with obesity who applied to the Endocrine and Internal Medicine Clinic in Samsun, Turkey, between June and October 2022. The data were collected using the Personal Information Form, Power of Food Scale (PFS), Weight Self-Stigmatisation Questionnaire (WSSQ) and Self-Liking/Self-Competence Scale (SLSC) through face-to-face survey method. RESULTS: About 53.3% of the participants were ≥45 years old, 80.5% were married and 69.1% had previously followed weight loss diet. It was found that those who were aged <45 years, single, those who perceived themselves as overweight, those who had used weight loss diets before and those whose waist-hip ratio were normal had higher hedonic hunger scores (p < 0.05). A negative and significant correlation was found between PSF-Tr general dimension scores and SLSC general dimension, whereas a significant and positive correlation was observed between PSF-Tr general dimension scores and WSSQ general dimension (p < 0.05). CONCLUSION: As hedonic hunger increased in adults with overweight, self-esteem decreased, and self-stigmatisation in terms of weight increased. Effective interventions are needed to cope with the hedonic hunger that contributes to obesity and to prevent the stigma and low self-esteem experienced by people living with obesity because of their excess weight.

Do people with type 2 diabetes find continuous and intermittent low-energy diets for weight loss and diabetes remission acceptable?

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

Alternative models to support weight loss in chronic musculoskeletal conditions: effectiveness of a physiotherapist-delivered intensive diet programme for knee osteoarthritis, the POWER randomised controlled trial.

OBJECTIVES: To determine if physiotherapists can deliver a clinically effective very low energy diet (VLED) supplementary to exercise in people with knee osteoarthritis (OA) and overweight or obesity. METHODS: 88 participants with knee OA and body mass index (BMI) >27 kg/m2 were randomised to either intervention (n=42: VLED including two daily meal replacement products supplementary to control) or control (n=46: exercise). Both interventions were delivered by unblinded physiotherapists via six videoconference sessions over 6 months. The primary outcome was the percentage change in body weight at 6 months, measured by a blinded assessor. Secondary outcomes included BMI, waist circumference, waist-to-hip ratio, self-reported measures of pain, function, satisfaction and perceived global change, and physical performance tests. RESULTS: The intervention group lost a mean (SD) of 8.1% (5.2) body weight compared with 1.0% (3.2) in the control group (mean (95% CI) between-group difference 7.2% (95% CI 5.1 to 9.3), p<0.001), with significantly lower BMI and waist circumference compared with control group at follow-up. 76% of participants in the intervention group achieved ≥5% body weight loss and 37% acheived ≥10%, compared with 12% and 0%, respectively, in the control group. More participants in the intervention group (27/38 (71.1%)) reported global knee improvement than in the control group (20/42 (47.6%)) (p=0.02). There were no between-group differences in any other secondary outcomes. No serious adverse events were reported. CONCLUSION: A VLED delivered by physiotherapists achieved clinically relevant weight loss and was safe for people with knee OA who were overweight or obese. The results have potential implications for future service models of care for OA and obesity. TRIAL REGISTRATION NUMBER: NIH, US National Library of Medicine, Clinicaltrials.gov NCT04733053 (1 February 2021).

Body dissatisfaction and dieting among Finnish adolescents: a 20-year population-based time-trend study.

Body image has an important role in the health and development of adolescents. Body dissatisfaction and dieting can become chronic and continue into adulthood. There is a lack of recent, comprehensive studies on ongoing trends on body dissatisfaction. This study assessed time-trend changes in self-reported body dissatisfaction and dieting among Finnish adolescents at four assessment points. Representative samples of adolescents (N = 6660) aged 13-16 years participated in school-based, cross-sectional studies in 1998 (N = 1458), 2008 (N = 2044), 2014 (N = 1809), and 2018 (N = 1349), respectively. The studies were similar in design, methodology, and geographical recruitment areas. Body dissatisfaction and dieting were assessed with a questionnaire including items derived from the DSM-IV criteria for anorexia and bulimia nervosa. From 1998 to 2018, dieting and fears related to gaining weight decreased among females. Body dissatisfaction reduced among females, and their wishes to become thinner became less prevalent. Consuming large amounts of food at one time consistently decreased among females and males and there were no changes in the rates of willful vomiting. The number of females in the 90th percentile with the most severe symptoms decreased. The results indicate that body dissatisfaction and disturbed dieting improved among females during the 20-year study. Despite these positive developments, the overall level of symptoms among females remained substantial, indicating that females have much higher levels of body dissatisfaction and dieting than males.

[Formula diets for weight loss - chances and challenges]. / Formula-Diäten für den Gewichtsverlust ­ Chancen und Herausforderungen.

INTRODUCTION: Formula diets, through the use of industrially manufactured meal replacement products, lead to effective and rapid weight reduction and improvement in obesity-associated comorbidities. The specific composition of these meal replacement products simplifies the adherence to calorie goals and ensures the supply of essential nutrients during significant energy restriction. Despite numerous potential applications, evidence from randomized controlled studies, and simplicity in practical implementation, challenges persist. Monotony and social restrictions complicate adherence and acceptance. The use of formula diets for sustainable weight loss requires integration into a multimodal treatment approach with the goal of long-term changes in eating and activity behaviour. This includes accompanying nutritional counselling, promotion of physical activity, evaluation of adjuvant pharmacological or interventional therapies, as well as psychological support. The development of new incretin-based anti-obesity medications has opened another application field for formula products. There is optimization potential in expanding the product range and combining it with digital applications to enhance acceptance and reach a larger patient group.

Weight Loss in Underserved Patients - A Cluster-Randomized Trial.

BACKGROUND: Evidence of the effectiveness of treatment for obesity delivered in primary care settings in underserved populations is lacking. METHODS: We conducted a cluster-randomized trial to test the effectiveness of a high-intensity, lifestyle-based program for obesity treatment delivered in primary care clinics in which a high percentage of the patients were from low-income populations. We randomly assigned 18 clinics to provide patients with either an intensive lifestyle intervention, which focused on reduced caloric intake and increased physical activity, or usual care. Patients in the intensive-lifestyle group participated in a high-intensity program delivered by health coaches embedded in the clinics. The program consisted of weekly sessions for the first 6 months, followed by monthly sessions for the remaining 18 months. Patients in the usual-care group received standard care from their primary care team. The primary outcome was the percent change from baseline in body weight at 24 months. RESULTS: All 18 clinics (9 assigned to the intensive program and 9 assigned to usual care) completed 24 months of participation; a median of 40.5 patients were enrolled at each clinic. A total of 803 adults with obesity were enrolled: 452 were assigned to the intensive-lifestyle group, and 351 were assigned to the usual-care group; 67.2% of the patients were Black, and 65.5% had an annual household income of less than $40,000. Of the enrolled patients, 83.4% completed the 24-month trial. The percent weight loss at 24 months was significantly greater in the intensive-lifestyle group (change in body weight, -4.99%; 95% confidence interval [CI], -6.02 to -3.96) than in the usual-care group (-0.48%; 95% CI, -1.57 to 0.61), with a mean between-group difference of -4.51 percentage points (95% CI, -5.93 to -3.10) (P<0.001). There were no significant between-group differences in serious adverse events. CONCLUSIONS: A high-intensity, lifestyle-based treatment program for obesity delivered in an underserved primary care population resulted in clinically significant weight loss at 24 months. (Funded by the Patient-Centered Outcomes Research Institute and others; PROPEL ClinicalTrials.gov number, NCT02561221.).

Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming.

BACKGROUND: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized. METHODS: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model. RESULTS: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model. CONCLUSIONS: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.

Association of diabetes risk reduction diet with renal cancer risk in 101,755 participants: a prospective study.

BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial.

OBJECTIVE: To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients. METHODS: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28) ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000-1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05. RESULTS: The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; -0.51 [95% CI -1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 -2.0 [95% CI -7.00, 3.1], P = 0.46 between groups). CONCLUSION: Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307.

The impact and utility of very low-calorie diets: the role of exercise and protein in preserving skeletal muscle mass.

PURPOSE OF REVIEW: Very low-calorie diets (VLCD) are used as a weight loss intervention, but concerns have been raised about their potential negative impact on lean mass. Here, we review the available evidence regarding the effects of VLCD on lean mass and explore their utility and strategies to mitigate reductions in skeletal muscle. RECENT FINDINGS: We observed that VLCD, despite their effects on lean mass, may be suitable in certain populations but have a risk in reducing lean mass. The extent of the reduction in lean mass may depend on various factors, such as the duration and degree of energy deficit of the diet, as well as the individual's starting weight and overall health. SUMMARY: VLCD may be a viable option in certain populations; however, priority needs to be given to resistance exercise training, and secondarily to adequate protein intake should be part of this dietary regime to mitigate losing muscle mass.

Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial.

BACKGROUND: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. OBJECTIVE: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. DESIGN: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring-13C6] phenylalanine tracer infusion with the collection of bilateral muscle biopsies. RESULTS: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). CONCLUSION: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. TRIAL REGISTRY: clinicaltrials.gov (ID: NCT03326284).

Additional effects of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes: A systematic review and meta-analysis.

AIMS: This systematic review and meta-analysis evaluates the additional effect of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes. METHODS: Embase, Medline, Web of Science and Cochrane Central databases were evaluated, and 11 studies were included. Random-effects meta-analysis was performed on body weight and measures of body composition and glycaemic control, to compare the effect of hypocaloric diet plus exercise with hypocaloric diet alone. RESULTS: Exercise interventions consisted of walking or jogging, cycle ergometer training, football training or resistance training and duration varied from 2 to 52 weeks. Body weight and measures of body composition and glycaemic control decreased during both the combined intervention and hypocaloric diet alone. Mean difference in change of body weight (-0.77 kg [95% CI: -2.03; 0.50]), BMI (-0.34 kg/m2 [95% CI: -0.73; 0.05]), waist circumference (-1.42 cm [95% CI: -3.84; 1.00]), fat-free mass (-0.18 kg [95% CI: -0.52; 0.17]), fat mass (-1.61 kg [95% CI: -4.42; 1.19]), fasting glucose (+0.14 mmol/L [95% CI: -0.02; 0.30]), HbA1c (-1 mmol/mol [95% CI: -3; 1], -0.1% [95% CI: -0.2; 0.1]) and HOMA-IR (+0.01 [95% CI: -0.40; 0.42]) was not statistically different between the combined intervention and hypocaloric diet alone. Two studies reported VO2max and showed significant increases upon the addition of exercise to hypocaloric diet. CONCLUSIONS: Based on limited data, we did not find additional effects of exercise to hypocaloric diet in adults with overweight or obesity and type 2 diabetes on body weight, body composition or glycaemic control, while cardio-respiratory fitness improved.

The addition of exercise to a weight loss diet on inflammatory markers: a systematic review and Meta-analysis of controlled clinical trials.

This systematic review and meta-analysis of controlled clinical trials was performed to evaluate the effects of weight-loss diets plus exercise compared with weight-loss diets alone on inflammatory biomarkers in adults. PubMed, Scopus, EMBASE, Web of Science (ISI), and Google Scholar were searched up to April 2021. Overall effects were derived using a random effects model. The overall quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty-nine trials were included in this systematic review and meta-analysis. The meta-analysis showed no significant difference in serum high sensitivity C-reactive protein (hs-CRP) [weighted mean difference (WMD) = -0.004 mg/l, 95% CI: -0.140, 0.132, P = 0.954], interleukin-6 (IL-6) (WMD = -0.039 pg/ml, 95% CI: -0.233 to 0.156, P = 0.696), and tumor necrosis factor-α (TNF-α) (WMD = 0.405 ng/ml, 95% CI: -1.036 to 0.226, P = 0.209) after adding exercise to a weight-loss diet compared with a weight-loss diet alone. Subgroup analysis revealed that exercise plus a weight-loss diet significantly reduced TNF-α in studies greater than 16 weeks in duration (WMD = -0.742 ng/ml, 95% CI: -1.384 to -0.1, P = 0.024). This systematic review and meta-analysis indicate that exercise in addition to a weight-loss diet does not have a significant effect on further reducing inflammatory markers compared to a weight loss diet alone.