Changes In Energy Intake Research Articles

The effects of non-nutritive sweeteners on energy and macronutrients intake in adults: a grade-assessed systematic review and meta-analyses of randomized controlled trials

ObjectivesThe effect of non-nutritive sweeteners (NNSs) on long-term satiety is not well understood. This systematic review and meta-analysis were performed to investigate the effect of NNSs on long-term total energy and macronutrients intake.MethodsOnline databases including Scopus, PubMed, ISI Web of Science, and Google Scholar were searched up to September 2024 to find relevant randomized control trials (RCTs). A random effects model was used for estimating the overall effects.ResultsThe results showed a reducing effect of NNSs consumption vs. sugar on total energy intake [total energy intake change = −175.26 kcal/day, 95% confidence interval (CI): −296.47 to −54.06, I2 = 61.19%] and carbohydrate intake [Hedges’ g = −0.35, 95% CI: −0.63 to −0.06, I2 = 58.99%]. While, NNSs intake vs. water was not associated with significant change in total energy intake [total energy intake change = 29.94 kcal/day, 95% CI: −70.37 to 130.24, I2 = 34.98%] and carbohydrate intake [Hedges’ g = 0.28, 95% CI: −0.02 to 0.58, I2 = 65.26%]. The Consumption of NNSs compared to the either sugar or water did not have a significant effect on fat intake [Hedges’ g sugar = 0.08, 95% CI: −0.10 to 0.26, I2 = 8.73%/ fat intake change water = 0.20 g/day, 95% CI: −3.48 to 3.88, I2 = 0%] and Protein intake [Hedges’ g sugar = 0.16, 95% CI: −0.11 to 0.42, I2 = 50.83%/Hedges’ g water = 0.00, 95% CI: −0.15 to 0.16, I2 = 0%].ConclusionIn summary, our findings suggest that NNSs consumption may be effective in reducing total energy and carbohydrate intake compared to sugar.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=432816, CRD42023432816.

Sex-specific dietary habits and their association with weight change in healthy adults

BackgroundDietary intake plays a pivotal role in the prevalence and management of obesity. While women and men exhibit differences in dietary habits and food-related behaviors, sex-based weight loss recommendations are lacking. This study aims to examine the impact of specific foods and food categories on weight reduction in men and women over a two-year period.MethodsA total of 8,548 participants from the 10K cohort, from 2019 to 2023, were included in the analysis (53.1% women, mean age 51.7 years). Anthropometric measurements and laboratory results were collected at baseline and at the two-year follow-up visit. Dietary assessment was based on daily food intake digitally logged through an application for at least 3 consecutive days at both timepoints. We compared intake of macronutrients, micronutrients, food groups and daily energy consumption between sex and body mass index (BMI) categories at baseline and weight change categories at follow-up. Using linear regression, we assessed the associations between food categories or specific foods and BMI at baseline as well as weight change percentage at follow-up.ResultsDietary habits varied by BMI and sex. Women and men living with obesity (BMI > 30 kg/m2) reported a greater intake of animal-based protein and lower intake of plant-based proteins and fats at baseline, as compared to participants with normal weight. In linear regression models predicting two-year weight change, including age, income, and baseline weight, the explained variance was 5.6% for men and 5.8% for women. Adding food categories and specific foods increased the explained variance to 20.6% for men and 17.5% for women. Weight reduction in men was linked to daily consumption of an egg (1.2% decrease) and beef (1.5% decrease), while in women, the most pronounced reductions were associated with an apple (1.2% decrease) and cashew nuts (3.4% decrease). Notably, total energy intake changes significantly impacted weight outcomes only in women.ConclusionsSex-specific dietary habits significantly influence weight change over time. In men, weight loss was primarily associated with the addition of animal-based protein, while in women, it was linked to caloric deficit and plant-based fat, suggesting that sex-based nutritional interventions may demonstrate greater efficacy.Trial registrationNCT05817734 (retrospectively registered January 31, 2023).

The dietary exposome: a brief history of diet, longevity, and age-related health in rodents.

It has been recognized for over a century that feeding animals less food than they would normally eat increases lifespan and leads to broad-spectrum improvements in age-related health. A significant number of studies have subsequently shown that restricting total protein, branched chain amino acids or individual amino acids in the diet, as well as ketogenic diets, can elicit similar effects. In addition, it is becoming clear that fasting protocols, such as time-restricted-feeding or every-other-day feeding, without changes in overall energy intake can also profoundly affect rodent longevity and late-life health. In this review, I will provide a historical perspective on various dietary interventions that modulate ageing in rodents and discuss how this understanding of the dietary exposome may help identify future strategies to maintain late-life health and wellbeing in humans.

Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice.

Fibroblast growth factor 23 (FGF23) is a bone-secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about the nonskeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with a high-fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the adiponectin-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio and increased brown fat Ucp1 expression in knockout mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.

Royal Jelly Exerts a Potent Anti-Obesity Effect in Rats by Activating Lipolysis and Suppressing Adipogenesis.

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis.

Responsiveness and Reliability of a Sipping Device to Measure Motivation in Normal-Weight Individuals and Bariatric Surgery Patients.

There is an urgent need to measure the motivation to taste a sweet fluid in order to determine the influence of sweet tastes on the potential choices and consumption of beverages in patients with obesity. Current methods utilize either survey instruments or arbitrary operant tasks. The sipometer enables the participant to utilize an actual ingestive behavioral response to measure motivation during access to beverages on either ad libitum (AL) or progressive time ratio (PR) schedules. We determined the sipometer's responsiveness and reliability as a test of change in motivation for sweet tastes after bariatric surgery. Participants (58 patients and 28 controls, BMI: 18.5-24.9 kg/m2) sham-consumed an aspartame-sweetened (S) and non-sweetened (N) beverage under AL and PR schedules at a pre-surgery/baseline and a 3-month and 24-month visit (patients only). Cumulative pressure (CumPres), a measure of effort, was the sum of the pressures exerted during sipping under each condition. Baseline CumPres for PRS was higher than ALS and ALN in patients (p < 0.03) and higher than PRN in controls (p = 0.009). At 3 months, CumPres did not differ amongst conditions in patients, but CumPres for PRS was higher than all other conditions in controls (p < 0.0005). There were no baseline group differences; however, patients' CumPres for PRS was lower than controls' at 3 months (p = 0.002). Patients' CumPres for PRS decreased non-significantly between the baseline and 3 months but increased at 24 months compared to 3 months (p = 0.025) and was no different from baseline. Controls' CumPres for PRS increased at 3 months (p = 0.0359), but CumPres for all conditions was correlated between visits (p's < 0.038). The sipometer is a reliable and sensitive measure of motivation to consume sweet beverages and may reflect changes in post-operative energy intake.

Effect of the Implementation of a Multiple-Behavior Self-Monitoring Intervention on Dietary Intake in Type 2 Diabetes: Secondary Data Analysis.

An electronic diary embedded in a mobile device to monitor lifestyle can be as effective as traditional methods. However, the efficacy of self-monitoring multiple behaviors for dietary intake has not been well studied in people with diabetes. This study aimed to compare the effect of using technology-assisted self-monitoring versus paper diaries on changes in dietary intake. This is a secondary analysis of data collected from 39 people with type 2 diabetes as part of a 3-month pilot clinical trial. Changes in energy intake and the contribution of total fat intake and total carbohydrate intake to total calories (%) from baseline to after intervention (3 months) were evaluated. In total, 26 (67%) of the 39 participants preferred mobile diaries over paper diaries. Participants in the mobile diary group showed slightly higher self-monitoring adherence. Linear mixed modeling results indicated a significant overall decrease in total energy intake (P=.005), dietary fat intake (P=.01), and carbohydrate intake (P=.08) from baseline to 3 months. No significant group differences were detected (P>.05). The implementation of a 3-month, multiple-behavior, self-monitoring intervention in Diabetes Self-Management Education programs has resulted in successful reduction in dietary intake (energy, fat, and carbohydrate), whichever self-monitoring method is chosen by participants according to their preferences. Long-term studies are needed to confirm our findings on dietary intake and examine other behavioral and disease outcomes that require monitoring.

Diet order significantly affects energy balance for diets varying in macronutrients but not ultraprocessing in crossover studies without a washout period

BackgroundCrossover studies can induce order effects, especially when they lack a washout period. ObjectivesWe performed secondary analyses comparing groups of subjects randomly assigned to different diet orders in 2 inpatient crossover studies originally designed to compare within-subject differences in ad libitum energy intake. One study compared minimally processed low-carbohydrate (LC) compared with low-fat (LF) diets, and the other matched macronutrients and compared minimally processed food (MPF) with ultraprocessed food (UPF) diets. MethodsDiet order group comparisons of changes in body weight and body composition, and differences in energy expenditure and food intake were assessed over 4 wk in 20 adults randomly assigned to either the LC followed immediately by the LF diet (LC → LF) or the opposite order (LF → LC), and 20 adults randomly assigned to either the MPF followed by the UPF (MPF → UPF) diets or the opposite order (UPF → MPF). ResultsSubjects randomly assigned to LC → LF lost 2.9 ± 1.1 kg more body weight (P <0.001) and 1.5 ± 0.6 kg more body fat (P = 0.03) than the LF → LC group, likely because the LC → LF group consumed 921 ± 304 kcal/d less than the LF → LC group (P = 0.003). These energy intake differences were driven by the last 2 wk (−1610 ± 312 kcal/d; P < 0.0001), perhaps because of carryover effects of gut adaptations during the first 2 wk arising from large differences in the mass of food (1296 ± 215 g/d; P <0.00001) and fiber consumed (58 ± 6 g/d; P <0.00001). There were no significant diet order effects on energy intake, body weight, or body composition changes between UPF → MPF and MPF → UPF groups. ConclusionsDiet order significantly affected energy intake, body weight, and body fat in a 4-wk crossover inpatient diet study varying in macronutrients, but not in a similarly structured study varying in ultraprocessed foods.This trial was registered at clinicaltrials.gov as NCT03407053 and NCT03878108.

Exercise-induced appetite suppression: An update on potential mechanisms.

The first systematic reviews of the effects of exercise on appetite-regulation and energy intake demonstrated changes in appetite-regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity-dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise-induced appetite suppression clearly involves acylated ghrelin, glucagon-like peptide-1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise-induced appetite suppression, lactate has garnered the most support through invitro and invivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise-induced appetite suppression may include sex hormones, growth-differentiation factor 15, Lac-Phe, brain-derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation.

The implications of policy modeling assumptions for the projected impact of sugar-sweetened beverage taxation on body weight and type 2 diabetes in Germany

BackgroundEvaluating sugar-sweetened beverage (SSB) taxation often relies on simulation models. We assess how assumptions about the response to SSB taxation affect the projected body weight change and subsequent health and economic impacts related to type 2 diabetes mellitus (T2DM) using Germany as an example.MethodsIn the main analysis, we estimated changes in energy intake by age and sex under a 20% value-added tax on SSBs in Germany using marginal price elasticities (PE) and applied an energy equilibrium model to predict body weight changes. We then quantified the impact of several assumption modifications: SSB own-PE adjusted for consumption (M1)/based on alternative meta-analysis (M2); SSB consumption adjusted for underreporting (M3); substitution via marginal (M4a) or adjusted (M4b) cross-PE/as % of calorie change (M4c). We also assessed scenarios with alternative tax rates of 10% (S1) or 30% (S2) and including fruit juice (S3). We calculated overweight and obesity rates per modification and scenario. We simulated the impact on T2DM, associated healthcare costs, and disability-adjusted life years (DALYs) over the lifetime of the 2011 German adult population with a Markov model. Data included official demographics, national surveys, and meta-analyses.ResultsA 20% value-added tax in Germany could reduce the number of men and women with obesity by 210,800 [138,800; 294,100] and 80,800 [45,100; 123,300], respectively. Over the population’s lifetime, this would lead to modest T2DM-related health and economic impacts (76,700 DALYs [42,500; 120,600] averted; €2.37 billion [1.33; 3.71] costs saved). Policy impacts varied highly across modifications (all in DALYs averted): (M1) 94,800 [51,500; 150,700]; (M2) 164,200 [99,500; 243,500]; (M3) 52,600 [22,500; 91,100]; (M4a) -18,100 [-111,500; 68,300]; (M4b) 25,800 [-31,400; 81,500]; (M4c) 46,700 [25,300; 77,200]. The variability in policy impact related to modifications was similar to the variability between alternative policy scenarios (all in DALYs averted): (S1) 26,400 [9,300; 47,600]; (S2) 126,200 [73,600; 194,500]; (S3) 342,200 [234,200; 430,400].ConclusionsPredicted body weight reductions under SSB taxation are sensitive to assumptions by researchers often needed due to data limitations. Because this variability propagates to estimates of health and economic impacts, the resulting structural uncertainty should be considered when using results in decision-making.

The Effect of the Menstrual Cycle on Energy Intake: A Systematic Review and Meta-analysis.

Energy intake may differ across the menstrual cycle, with some studies identifying greater energy intake in the luteal phase (LP) compared with the follicular phase (FP) and others finding no clear differences. To date, no study has systematically synthesized the available data to draw more definite conclusions while considering any methodological inconsistencies between studies. The aim was to conduct a systematic review/meta-analysis in an effort to determine if there are differences in energy intake between the FP and LP. A systematic search strategy was developed and the search was conducted in 5 databases for studies that investigated any changes in energy intake across menstrual phases. Using Covidence, studies were identified and included if they contained individuals between the ages of 18 and 45 years, maintained an average body mass index (BMI) of 18.5-25 kg/m2, had no history of disordered eating, and included energy intake and menstrual cycle measurements in the FP and LP. Effect sizes were calculated for each study and a random-effects model was used to pool the results of each study. Fifteen datasets were included consisting of 330 female participants with a mean age of 26 ± 4 years and mean BMI of 22.4 ± 2.3 kg/m2. Overall, there was a statistically significant difference (standardized mean difference = 0.69; P = .039) with increased energy intake in the LP compared with the FP (crude 168 kcal⋅d-1 average difference between phases). Energy intake was found to be greater in the LP compared with the FP, providing insight into the effect of the menstrual cycle on energy intake. However, there were repeated methodological inconsistencies and future work should strive to utilize best practices for both energy intake measurement and menstrual phase specification.

Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study

IntroductionIt is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes.MethodsWe performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes.ResultsAt 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks.ConclusionIn this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake.Trial registrationUniversity Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/).

The Effect of 24 h Shift Work on the Nutritional Status of Healthcare Workers: An Observational Follow-Up Study from Türkiye.

This study aimed to determine changes in energy and nutrient intakes over three consecutive days, including the day of the shift, and the days before and after the shift, in healthcare workers working in a 24 h shift system. This study is an observational follow-up study conducted with a total of 500 volunteer healthcare professionals. Food consumption records were taken over 3 consecutive days: pre-shift (off day), shift day (24 h shift), and post-shift (off day). Mean daily intakes of energy, carbohydrate, protein, fat, saturated fat, caffeine, vitamins B1, B2, niacin, B6, folate, and B12, potassium, magnesium, phosphorus, iron, and zinc are listed from highest to lowest as shift day > pre-shift > post-shift (p < 0.05 for all pairwise comparisons). While fiber, vitamin C, and calcium intakes were similar on the shift day and pre-shift day, they were significantly lower on the post-shift day (p < 0.05). The lowest dietary reference intake percentages on the post-shift day were calcium, fiber, and folate, respectively. In the present study, significant differences were detected in the energy, micronutrient-intake, and macronutrient-intake levels between the pre-shift day, shift day, and post-shift day of healthcare workers. Awareness should be increased regarding the decreased nutrient intake seen especially on the first day after a 24 h shift, and appropriate precautions should be taken to increase calcium, fiber, and folate intake levels.

#2481 Reduction in ultra-processed food by providing medically tailored healthy food baskets to patients with CKD: the HELPFUL trial

Abstract Background and Aims Over the past decade, there has been a growing interest in classifying foods based on the extent and purpose of industrial processing according to the NOVA system, which outlines four main food categories: unprocessed and minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods (UPFs). The latter is characterized by industrial formulations with an elevated content of additives, sugar, unhealthy fat, and sodium. Increased consumption of UPFs can worsen metabolic derangements that develop as kidney function decreases in patients with chronic kidney disease (CKD). We evaluated food intake according to the NOVA food classification system before and after a medically tailored meal intervention with plant-based food baskets for patients with CKD who had hyperkalemia at inclusion and received sodium zirconium cyclosilicate (SZC) to normalize plasma potassium. Additionally, we aimed to assess the diets’ environmental impact by evaluating the greenhouse gas emissions (GHGE) associated with these dietary changes. Method Data were based on a six-week feasibility one-arm clinical study, the HELPFUL trial (identifier: NCT04207203), that enrolled 26 adult patients with CKD stages 4 and 5, not on dialysis and with plasma potassium 5.1-6.5 mmol/L at inclusion. In the first 3 weeks, patients were guided to adhere to a low-protein and low-potassium diet with concomitant use of SZC. The following 3 weeks, patients received food baskets containing fruits, vegetables, legumes, nuts, and either white meat, fish or egg to provide a healthy low-protein high-potassium diet. To assess dietary changes, 24-hour food recalls were collected at weeks 0, 3 and 6 and subsequently classified according to the NOVA classification. The mean adequacy ratio to the dietary recommended intake (DRI) of 11 nutrients (MAR-11 score) was calculated to assess dietary quality. Furthermore, the 24-hour food recalls were linked to GHGE estimations for analysis of environmental impact using the RISE food climate database which is representative of Swedish food consumption. Statistical analyses using Friedman's test or ANOVA for repeated measures were employed to identify significant differences before and after the plant-based food basket intervention. This study was funded by Astra Zeneca. Results The plasma potassium (mmol/L) normalized after the use of SZC (week 0: 5.52 ± 0.3; week 3: 4.72 ± 0.4; week 6: 4.8 ± 0.4; P &amp;lt; 0.01). Figure 1 shows changes in energy intake according to the NOVA classification. A significant reduction in UPF consumption (P = 0.024) was observed. In the post-hoc analysis, the change between week 3 and 6 was borderline significant (P = 0.052) while that between week 0 and 6 was statistically significant (P = 0.008). The healthy food basket diet led to a significant increase in dietary fibers (P = 0.002) and servings of fruits (P &amp;lt; 0.01), vegetables (P = 0.04), nuts (P &amp;lt; 0.01), poultry (P = 0.02), and fish (P &amp;lt; 0.001) and reduced servings of red meat (P = 0.03). As a result, the MAR-11 score increased significantly (P = 0.021). The GHGE analysis of carbon dioxide equivalents revealed no differences between emissions (median and interquartile range) in week 0 [1.79 (1.24; 3.13)], week 3 [1.79 (1.47; 2.74)] and week 6 [1.87 (1.51; 2.61)]. Conclusion Delivering medically tailored healthy food baskets to patients with CKD with concomitant use of SZC led to increased dietary quality and decreased UPF intake. However, these beneficial changes were not aligned with a decrease in GHGE, highlighting the complex relationship between dietary choices and environmental impact.

Efficacy and safety of N-acetyl-L-leucine in patients with ataxia telangiectasia: A randomized, double-blind, placebo-controlled, crossover clinical trial

BackgroundAtaxia telangiectasia (AT) is an autosomal recessive multisystem disorder. Most patients have progressive cerebellar ataxia, oculocutaneous telangiectasia, frequent pulmonary infection, and an increased risk of malignancies. Although N-acetyl-dl-leucine (ADLL) has shown some efficacy in patients with AT, its more pharmacologically active enantiomer, N-acetyl-l-leucine (NALL), has just recently been investigated in ataxic individuals. The current study assessed the efficacy of NALL in patients with AT. MethodsThis 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT. After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1–4 g/day NALL or a placebo for six weeks. Subjects then had a 4-week washout before crossing over to the other treatment for an additional six weeks. The Spinocerebellar Ataxia Functional Index (SCAFI) and the Scale for Assessment and Rating of Ataxia (SARA) score assessed patients' motor function. Quality of life (QOL) was evaluated by a specialist using the PedsQL questionnaire. Fasting blood samples were taken from all subjects before and after each intervention to determine potential side effects. ResultsAlthough patients' nausea and constipation were improved, the results failed to reveal any significant benefits of NALL treatment on ataxia symptoms. NALL treatment had no significant effects on SARA, SCAFI-9HPT (9-hole peg test) nondominant, SCAFI-9HPT dominant, or SCAFI-8WMT (8 m walking time) (p > 0.05). Our patient's Physical Health score in Child self-report and Parent proxy-report did not significantly change in the treatment group compared to the placebo (p > 0.05). Furthermore, there were no significant changes in energy and macronutrient intake after NALL treatment. None of the volunteers reported serious or moderate side effects. ConclusionsTo the best of our knowledge, this was the first placebo-controlled, randomized clinical trial exploring NALL's potential effects for treating AT. Despite improvements in some symptomss, NALL intervention failed to improve motor function significantly. However, patients' nausea and constipation were improved by NALL, which can be a relevant benefit clinically.

Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity.

To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.

Sex-Dependent Metabolic Effects in Diet-Induced Obese Rats following Intermittent Fasting Compared with Continuous Food Restriction.

Recently, intermittent fasting has gained relevance as a strategy to lose weight and improve health as an alternative to continuous caloric restriction. However, the metabolic impact and the sex-related differences are not fully understood. The study aimed to compare the response to a continuous or intermittent caloric restriction in male and female rats following a previous induction of obesity through a cafeteria diet by assessing changes in body weight, energy intake, metabolic parameters, and gene expression in liver hepatic and adipose tissue. The continuous restriction reduced the energy available by 30% and the intermittent restriction consisted of a 75% energy reduction on two non-consecutive days per week. The interventions reduced body weight and body fat in both sexes, but the loss of WAT in females was more marked in both models of caloric restriction, continuous and intermittent. Both caloric restrictions improved insulin sensitivity, but more markedly in females, which showed a more pronounced decrease in HOMA-IR score and an upregulation of hepatic IRS2 and Sirt1 gene expression that was not observed in males. These findings suggest the fact that females are more sensitive than males to reduced caloric content in the diet.

Effect of calorie labelling in the out-of-home food sector on adult obesity prevalence, cardiovascular mortality, and social inequalities in England: a modelling study

England implemented a menu calorie labelling policy in large, out-of-home food businesses in 2022. We aimed to model the likely policy impact on population-level obesity and cardiovascular disease mortality, as well as the socioeconomic equity of estimated effects, in the adult population in England. For this modelling analysis, we built a comparative assessment model using two scenarios: the current implementation scenario refers to actual deployment only in large (≥250 employees), out-of-home food businesses, whereas the full implementation scenario refers to deployment in every out-of-home food business. We compared each scenario with a counterfactual: the scenario in which no intervention is implemented (ie, baseline). For both scenarios, we modelled the impact of the policy through assumed changes in energy intake due to either consumer response or product reformulation by retailers. We used data from the Office for National Statistics and the National Diet and Nutrition Survey 2009-19, and modelled the effect over 20 years (ie, 2022-41) to capture the long-term impact of the policy and provided mid-period results after 10 years. We used the Monte Carlo approach (2500 iterations) to estimate the uncertainty of model parameters. For each scenario, the model generated the change in obesity prevalence and the total number of deaths prevented or postponed. The current implementation scenario was estimated to reduce obesity prevalence by 0·31 percentage points (absolute; 95% uncertainty interval [UI] 0·10-0·35), which would prevent or postpone 730 cardiovascular disease deaths (UI 430-1300) of the 830 000 deaths (UI 600 000-1 200 000) expected over 20 years. However, the health benefits would be increased if calorie labelling was implemented in all out-of-home food businesses (2·65 percentage points reduction in obesity prevalence [UI 1·97-3·24] and 9200 cardiovascular disease deaths prevented or postponed [UI 5500-16 000]). Results were similar in the most and the least deprived socioeconomic groups. This study offers the first modelled estimation of the impact of the menu calorie labelling regulation on the adult population in England, although we did not include a cost-effectiveness analysis. Calorie labelling might result in a reduction in obesity prevalence and cardiovascular disease mortality without widening health inequalities. However, our results emphasise the need for the government to be more ambitious by applying this policy to all out-of-home food businesses to maximise impact. European Research Council.

The alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 reduces food intake in male rats

Obesity is a prevalent disease, but effective treatment options remain limited. Agonists of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) promote negative energy balance in mice, but these effects are not well-studied in rats. We tested the hypothesis that central administration of the α7nAChR agonist PHA-543613 (PHA) would decrease food intake and body weight in adult male Sprague Dawley rats. Intracerebroventricular (ICV) PHA administration in chow-fed rats produced a suppression of energy intake and weight gain over 24 h. Next, to evaluate effects of ICV PHA on palatable food intake, rats were maintained on a choice diet of rodent chow and 45 % high fat diet (HFD); under these conditions, ICV PHA produced no significant changes in energy intake from either food, or body weight gain, in the 24 h post-injection. However, when given a choice of chow or a higher-fat 60 % HFD, ICV PHA reduced intake of 60 % HFD, but not chow; body weight gain was also suppressed. Further experiments evaluating conditioned taste avoidance (CTA) and pica in response to ICV PHA suggested that the suppressive food intake and body weight effects after ICV injection of PHA were not due to nausea/malaise. Finally, an operant conditioning study showed that responding on a progressive ratio schedule of reinforcement for high-fat food pellets decreased after ICV PHA. Collectively, these studies show that PHA reduces energy intake under some but not all dietary conditions. Importantly, central PHA decreases both food intake as well as motivation for highly palatable, energy dense foods in rats without inducing nausea/malaise, suggesting that the α7nAChR could be a viable target for developing treatments for obesity.

Effects of physical form of β-lactoglobulin and calcium ingestion on GLP-1 secretion, gastric emptying and energy intake in humans: a randomised crossover trial.

The aim of this study was to assess whether adding Ca2+to aggregate or native forms of β-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l-1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l-1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).