Introducing menus of three weekly insect- or plant-based dinner meals slightly reduced meat consumption in Danish families: Results of a randomized intervention study.

The environmental concerns associated with excess meat consumption have emphasized the need for sustainable alternatives. Edible insects offer a promising alternative due to their environmental efficiency and nutritious profile, but their widespread adoption in Western diets remains a challenge. The objective of the study was to investigate the impact of exposing families (parents and children) to insect-based or plant-based dinner menus on dietary pattern, meat intake, and protein intake over a six-week intervention period. The study was a two-arm randomized equivalence trial comparing an insect-based menu to a plant-based control. Families received either an insect or plant-based menu to replace meat in dinner meals three times a week for six weeks, aiming to replace 20% of their meat protein intake. Dietary changes were assessed through dietary registrations and daily questionnaires. Both adults and children maintained their estimated daily total protein intake, while reducing daily meat protein intake. Neither group met the 20% weekly meat replacement goal. In the insect-based menu group, adults and children reached an average 5.5% and 2.3% weekly meat replacement, respectively. In the plant-based menu group, adults and children replaced 9.0% and 4.3%, respectively. Meat attachment had an effect on meat protein intake. The menus slightly reduced meat protein intake. The weekly frequency of meat meals slightly declined, but portions remained the same. By enhancing insect and plant-based food quality and understanding consumer behavior, insect- and plant-based products have the potential to be a complementary alternative in a sustainable dietary transition without sacrificing nutrition. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov: NCT05156853; clinicaltrials. gov/study/NCT05156853.

Comparison of 4-week versus 8-week dietitian-led FODMAP diet group education sessions in tertiary care clinical practice for irritable bowel syndrome: A service evaluation.

BACKGROUND: The implementation of the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet for irritable bowel syndrome (IBS) can be effectively delivered by dietitians in group settings. The initial FODMAP restriction phase is recommended to be followed for 4 weeks; however, limited efficacy data exist for 4-week FODMAP restriction in group education clinical practice. METHODS: We aimed to compare 4-week versus 8-week FODMAP group treatment pathways on clinical outcomes using a prospective service evaluation design of IBS patients attending FODMAP restriction (baseline) and reintroduction (follow-up) group sessions (between 2015 and 2019). Clinical outcomes included global symptom question (GSQ) measuring satisfactory relief, gastrointestinal symptom rating scale (GSRS), stool frequency (SF), stool consistency using Bristol stool form scale (BSFS), diet acceptability, patient satisfaction with group sessions and dietary adherence. Logistic regression was used to test for differences in treatment effects when clinical outcomes were compared between groups. RESULTS: Patients (n = 284) included were aged 18 to 86 years (mean ± SD [standard deviation], 44.6 ± 15.5), 80% female, and were split into 4-week (41%, 117/284) versus 8-week (59%, 167/284) pathways with no differences in baseline characteristics. Mean ± SD time gap between baseline and follow-up was 4.6 ± 0.9 weeks in the 4-week pathway and 9.6 ± 3.3 weeks in the 8-week pathway. When groups were compared at follow-up, no statistical differences were observed in any measures (GSQ, GSRS, SF, BSFS, dietary adherence, diet acceptability and patient satisfaction). CONCLUSION: A 4-week dietitian-led group FODMAP treatment pathway is as clinically effective and maintains patient acceptability when compared to 8-weeks and should be considered as part of routine clinical practice.

CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation.

Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using in vivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8+ tissue-resident memory T (TRM) cell development. TRM cells depended on mitochondrial translation and respiration. Conversely, three nutrient-dependent lysosomal signaling nodes-Flcn, Ragulator, and Rag GTPases-inhibited intestinal TRM cell formation. Depleting these molecules or amino acids activated the transcription factor Tfeb, thereby linking nutrient stress to TRM programming. Further, Flcn deficiency promoted protective TRM cell responses in the small intestine. Mechanistically, the Flcn-Tfeb axis restrained retinoic acid-induced CCR9 expression for migration and transforming growth factor ß (TGF-ß)-mediated programming for lineage differentiation. Genetic interaction screening revealed that the mitochondrial protein Mrpl52 enabled early TRM cell formation, while Acss1 controlled TRM cell development under Flcn deficiency-associated lysosomal dysregulation. Thus, the interplay between nutrients, organelle signaling, and metabolic adaptation dictates tissue immunity.

Dietary patterns, genetic predisposition, and risk of cholelithiasis: a large-scale prospective cohort study.

Background: Limited epidemiological evidence exists concerning the impact of healthy dietary patterns on reducing the risk of cholelithiasis. We aimed to examine the association of seven established dietary patterns with subsequent cholelithiasis risk and whether this association was modified by genetic risk. Methods: We conducted a prospective cohort study from the UK Biobank, including 155,323 participants initially free of cholelithiasis and cholecystectomy. Dietary patterns were assessed using a validated food frequency questionnaire (Oxford WebQ), covering Mediterranean Diet Score (MED), alternate Mediterranean Diet Score(aMED), overall Plant-based Diet Index (PDI), healthy Plant-based Diet Index (hPDI), unhealthy Plant-based Diet Index (uPDI), Healthy Eating Index 2015 (HEI-2015) and EAT-lancet Score. Genetic risk was quantified and stratified by a polygenic risk score (PRS) incorporating 13 known cholelithiasis-associated loci. Cox proportional hazards regression was employed to estimate the association between dietary patterns, PRS, and cholelithiasis incidence, adjusting for potential confounders. Results: During a median follow-up of 13.3 years, 5,056 cases of cholelithiasis were identified. After adjusting for potential confounders, adherence to aMED and HEI-2015 dietary patterns reduced cholelithiasis risk by 10% (HR: 0.90; 95%CI: 0.83-0.98) and 11% (HR: 0.89; 95%CI: 0.82-0.96), respectively. A significant decrease in cholelithiasis risk was observed across PRS quintiles, low PRS was associated with a 16% reduced risk (HR: 0.84; 95%CI: 0.77-0.92). Participants with both high dietary scores and low genetic risk had the lowest cholelithiasis risk, with an HR of 0.76 (95%CI: 0.64-0.91) for aMED and 0.73 (95%CI: 0.61-0.88) for HEI-2015. Conclusion: Higher adherence to aMED and HEI-2015 might significantly decrease the risk of cholelithiasis, irrespective of genetic risk. Our results highlighted the potential of diet intervention for cholelithiasis prevention in the general population.

Modulation of circulating levels of advanced glycation end products and its impact on intima-media thickness of both common carotid arteries: CORDIOPREV randomised controlled trial.

BACKGROUND: Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD). METHODS: 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention. RESULTS: The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05). CONCLUSIONS: Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937.

HLA diversity unveils susceptibility and organ-specific occurrence of second primary cancers: a prospective cohort study.

BACKGROUND: Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence. METHODS: We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles. RESULTS: During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59-0.89; females: HR 0.81, 95% CI 0.70-0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03-1.56; females: HR 1.35, 95% CI 1.07-1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females. CONCLUSIONS: These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Background/Objective: Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. Methods: We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.7 ± 3.0 kg/m2, sex F 57%) comparing the effects of daily supplementation with 20 g of LM citrus pectin versus 10 g of maltodextrin as the control (N = 15 age 43.2 ± 11 y, BMI 25.18 ± 2.0 kg/m2, sex F 66%). The effects on mood and inflammation were also tested with LM pectin at 5 g, 10 g and 15 g (2 weeks each) in an independent cohort of n = 15 healthy volunteers (age 36 ± 21 y, BMI 23.5 ± 2.4 kg/m2, sex F 80%). We assessed serum levels of TNF-alpha (downstream from TLR-2 activation), IL-1 beta, IL-6, IL-10, INF-gamma, CRP, zonulin and TLR-2 concentration which were measured using ELISA in blood samples collected at both the baseline and follow-up visits. Validated measures of anxiety and depression were collected at baseline and follow-up. Results: Supplementation with 20 g of LM pectin resulted in decreases in the pro-inflammatory markers TNF-alpha, IL-1 beta, IL-6 and INF-gamma (all p < 0.05) and an increase in anti-inflammatory marker IL-10 (p = 0.01) at the end of the 4 weeks. No such effects were observed in the control group. In addition, a significant drop in anxiety scores (from 8.38 to 4.46, p < 0.006) was found with the 20 g/day intervention but not in the control arm. In the dose-response study, anti-inflammatory effects were seen only at 15 g for TNFα (p < 0.003) and a suggestive increase in IL-10 (p = 0.08), alongside a drop in TLR-2 (p < 0.027). No significant anti-inflammatory effects were observed at 5 g and 10 g doses of LM pectin supplementation. Significant dose-dependent drops in both anxiety and depression scores were found with 10 g (p < 0.001) and 15 g per day (p < 0.0002). Conclusions: The current study identifies anxiety-reducing and anti-inflammatory effects of supplementation with 15 g/day LM pectin in healthy humans. Further research is needed to elucidate the precise mechanism and to validate the efficient dose and minimum duration of supplementation.

Recent advances in wolfberry polysaccharides and whey protein-based biopolymers for regulating the diversity of gut microbiota and its mechanism: A review.

Imbalances in gut microbiota diversity are associated with various health issues, including obesity and related disorders. There is a growing interest in developing synergistic biopolymers based on wolfberry polysaccharides and whey protein to address these problems due to their potential health benefits. This review explores recent advances in understanding how functional foods based on Lycium barbarum polysaccharides (LBP) and whey protein (WP) influence gut microbiota diversity and their underlying mechanisms. We examine the impact of these biopolymers on microbial composition and functionality, focusing on their roles in improving health by regulating gut microbiota. The combined effects of WP and LBP significantly enhance gut microbiome metabolic activities and taxonomic diversity, offering promising avenues for treating obesity and related disorders.

MIND Diet Impact on Multiple Sclerosis Patients: Biochemical Changes after Nutritional Intervention.

There is substantial evidence supporting the neuroprotective effects of the MIND diet in neurodegenerative diseases like Parkinson's and Alzheimer's. Our aim was to evaluate the impact of a nutritional intervention (NI) with this diet on multiple sclerosis (MS) patients. The study was conducted in two stages. In the first stage, two groups were included: MS patients before the NI (group A) and healthy control subjects (group B). In this stage, groups (A) and (B) were compared (case-control study). In the second stage, group (A) was assessed after the NI, with comparisons made between baseline and final measurements (before-and-after study). In the case-control stage (baseline evaluation), we found significant differences in fatigue scores (p < 0.001), adherence to the MIND diet (p < 0.001), the serum levels of brain-derived neurotrophic factor (BDNF) (p < 0.001), and higher oxidative status in the MS group, with lower levels of reduced glutathione (p < 0.001), reduced/oxidised glutathione ratio (p < 0.001), and elevated levels of lipoperoxidation (p < 0.002) and 8-hydroxy-2'-deoxyguanosine (p < 0.025). The before-and-after intervention stage showed improvements in fatigue scores (p < 0.001) and physical quality-of-life scores (MSQOL-54) (p < 0.022), along with decreases in the serum levels of glial-derived neurotrophic factor (GDNF) (p < 0.041), lipoperoxidation (p < 0.046), and 8-hydroxy-2'-deoxyguanosine (p < 0.05). Consumption of the MIND diet is linked to clinical and biochemical improvement in MS patients.

Efficacy, Safety and Acceptability of a Very-Low-Energy Diet in Adolescents with Obesity: A Fast Track to Health Sub-Study.

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.

Exploring the Effect of an Obesity-Prevention Intervention on Various Child Subgroups: A Post Hoc Subgroup Analysis of the Kiel Obesity Prevention Study.

BACKGROUND: This study investigated potential subgroups of children within the Kiel Obesity Prevention Study (KOPS) for differing treatment effects for the outcome measures of overweight or obesity at 4 years. The KOPS study delivered a multicomponent school intervention to cohorts of children in Kiel but found no overall effect on the weight status outcome. However, KOPS authors suggested there may be subgroup variations in treatment effect. Data were collected as part of the KOPS for samples of 6-year-olds between 1996 and 2001, with 4-year follow-up measurements between 2000 and 2004. METHODS: The present study conducted a post hoc subgroup analysis of the odds of obesity or overweight at 4-year follow-up compared to normal weight (n = 1646). A generalized linear mixed-effects model, including a treatment-subgroup interaction term, was used to estimate subgroups as a moderator of the treatment effects on the outcomes of obesity or overweight at 4-year follow-up. RESULTS: The findings indicated several subgroup-treatment interaction effects relating to physical activity indicators. TV or PC not being one of a child's top 3 activities at baseline was associated with a significantly decreased odds ratio of obesity at 4 years in the intervention group (OR, 0.04; 95% CI, 0.004 to 0.45) compared to the non-intervention group (OR, 0.96; 95% CI, 0.29 to 3.14), p = 0.02. Weekly activity in a sports club at baseline was associated with a decreased odds ratio of overweight at 4 years in the intervention group (OR, 0.38; 95% CI, 0.16 to 0.85) compared to the non-intervention group (OR, 0.91; 95% CI, 0.70 to 1.17). This was a significant difference (p = 0.04). CONCLUSIONS: These findings suggest that children's baseline physical activity may impact treatment effects on the outcomes of overweight and obesity, creating opportunities to increase the effectiveness of interventions on preventing obesity.

Family meals on prescription as treatment for childhood obesity-a randomized controlled trial.

The aim with the present study was to evaluate the effects and tolerability of Family Meals on Prescription, a 3-month intensive dietary intervention with a participatory approach on body mass index (BMI) and metabolic health in children living with obesity. In this prospective randomized controlled trial, children aged 5-15 years were included from the Pediatric Obesity outpatient Clinics in Halland, Sweden. Participants were randomly assigned to receive lifestyle treatment with or without Family Meals on Prescription (FMP) consisting of a subsidized prepacked grocery bag including recipes and provisions for five Family Meals per week for 3 months. The primary endpoint was changed in BMIz after 3, 12 and 18-24 months and secondary endpoints included to assess tolerability of FMP and effects on metabolic biomarker and frequency of shared meals. Eighty-nine children (51.7% female) entered the study, 54 patients in the intervention group and 35 in the control group. There were no significant differences between the groups concerning gender, age or level of obesity at baseline. The Family Meal on Prescription intervention combined with lifestyle treatment led to a significantly greater reduction in BMIz than lifestyle treatment alone after the 3-month long intervention (- 0.17 vs + 0.01, p < 0.01); however, this difference was not sustained throughout the study period, and in fact, the control group had a greater reduction in BMIz after 18-24 months.A subsidized prepacked grocery bag may be a novel, well-tolerated and effective tool in the treatment of childhood obesity. The fact that the BMIz reduction shown at the end of the intervention did not persist over time emphasized the need of long-term treatment. Registered at clinicaltrals.gov 27 Nov 2020, retrospectively registered: clinicaltrials.gov number 19002468. https://clinicaltrials.gov/study/NCT05225350 What is Known: • Swedish data shows that lifestyle treatment alone is not sufficient for many families undergoing treatment for childhood obesity. • Regular family meals and mealtime routines have been shown to be important for nutritional health and dietary patterns in children and adolescents. What is New: • This intervention with a participatory approach involving prepacked family meals was well tolerated and led to a significant reduction in BMIz during the intervention. • That fact that these results were not sustained over time indicates a need to evaluate longer interventions, and that childhood obesity is a chronic and complex disease which requires long-time treatments.

Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial.

BACKGROUND: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo. OBJECTIVE: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age. METHODS: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The green-MED group further consumed green tea (3-4 cups/d) and Mankai green shake (Wolffia globosa aquatic plant) (+800 mg/d polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic resonance imaging (MRI). We used hippocampal occupancy (HOC) score (hippocampal and inferior lateral-ventricle volumes ratio) as a neurodegeneration marker and brain-age proxy. We applied multivariate linear regression models. RESULTS: Of 284 participants [88% male; age = 51.1 y; body mass index = 31.2 kg/m2; hemoglobin A1c (HbA1c) = 5.48%; APOE-ε4 genotype = 15.7%], 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC deviations (i.e., younger brain age) presented lower body weight [r = -0.204; 95% confidence interval (CI): -0.298, -0.101], waist circumference (r = -0.207; 95% CI: -0.310, -0.103), diastolic (r = -0.186; 95% CI: -0.304, -0.072), systolic blood pressure (r = -0.189; 95% CI: -0.308, -0.061), insulin (r = -0.099; 95% CI: -0.194, -0.004), and HbA1c (r = -0.164; 95% CI: -0.337, -0.006) levels. After 18 mo, greater changes in HOC deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (ß = -0.254; 95% CI: -0.392, -0.117), HOMA-IR (ß = -0.200; 95% CI: -0.346, -0.055), fasting glucose (ß = -0.155; 95% CI: -0.293, -0.016), and c-reactive protein (ß = -0.153; 95% CI: -0.296, -0.010). Improvement in diabetes status was associated with greater HOC deviation changes than either no change in diabetes status (0.010; 95% CI: 0.002, 0.019) or with an unfavorable change (0.012; 95% CI: 0.002, 0.023). A decline in HbA1c was further associated with greater deviation changes in the thalamus, caudate nucleus, and cerebellum (P < 0.05). Greater consumption of Mankai and green tea (green-MED diet components) were associated with greater HOC deviation changes beyond weight loss. CONCLUSIONS: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green tea may contribute to a more youthful brain age. This trial was registered at clinicaltrials.gov at clinicaltrials.gov as NCT03020186.

The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol.

Background: Schizophrenia, schizoaffective disorder, and bipolar affective disorder are debilitating psychiatric conditions characterized by a chronic pattern of emotional, behavioral, and cognitive disturbances. Shared psychopathology includes the pre-eminence of altered affective states, disorders of thoughts, and behavioral control. Additionally, those conditions share epidemiological traits, including significant cardiovascular, metabolic, infectious, and respiratory co-morbidities, resulting in reduced life expectancy of up to 25 years. Nutritional ketosis has been successfully used to treat a range of neurological disorders and preclinical data have convincingly shown potential for its use in animal models of psychotic disorders. More recent data from open clinical trials have pointed toward a dramatic reduction in psychotic, affective, and metabolic symptoms in both schizophrenia and bipolar affective disorder. Objectives: to investigate the effects of nutritional ketosis via a modified ketogenic diet (MKD) over 14 weeks in stable community patients with bipolar disorder, schizoaffective disorder, or schizophrenia. Design: A randomized placebo-controlled clinical trial of 100 non-hospitalized adult participants with a diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia who are capable of consenting and willing to change their diets. Intervention: Dietitian-led and medically supervised ketogenic diet compared to a diet following the Australian Guide to Healthy Eating for 14 weeks. Outcomes: The primary outcomes include psychiatric and cognitive measures, reported as symptom improvement and functional changes in the Positive and Negative Symptoms Scale (PANSS), Young Mania Rating Scale (YMS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Scale and the Cambridge Cognitive Battery. The secondary metabolic outcomes include changes in body weight, blood pressure, liver and kidney function tests, lipid profiles, and markers of insulin resistance. Ketone and glucose levels will be used to study the correlation between primary and secondary outcomes. Optional hair cortisol analysis will assess long-term stress and variations in fecal microbiome composition. Autonomic nervous system activity will be measured via wearable devices (OURA ring and EMBRACE wristband) in the form of skin conductance, oximetry, continuous pulse monitoring, respiratory rate, movement tracking, and sleep quality. Based on the encouraging results from established preclinical research, clinical data from other neurodevelopment disorders, and open trials in bipolar disorder and schizophrenia, we predict that the ketogenic metabolic therapy will be well tolerated and result in improved psychiatric and metabolic outcomes as well as global measures of social and community functioning. We additionally predict that a correlation may exist between the level of ketosis achieved and the metabolic, cognitive, and psychiatric outcomes in the intervention group.

Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.

AIM: To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide. METHODS: In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs. RESULTS: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period. CONCLUSIONS: An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission.

A Dietary Intervention in Adults with Overweight or Obesity Leads to Weight Loss Irrespective of Macronutrient Composition.

Obesity is a critical public health issue, necessitating effective weight loss interventions. While various dietary regimens have been explored, individual responses to interventions often vary. This study involved a 3-month dietary intervention aiming at assessing the role of macronutrient composition and the potential role of genetic predisposition in weight loss among Greek adults. This randomized clinical trial followed the CONSORT principles, recruiting 202 participants overall; 94 received a hypocaloric, high-protein diet and 108 received a high-carbohydrate, hypocaloric diet. Genetic predispositions were assessed through 10 target variants known for their BMI associations. Participants' weight and BMI values were recorded at baseline and post-intervention (n = 202 at baseline, n = 84 post-intervention) and an imputation method was applied to account for the observed missing values. Participants experienced a statistically significant weight loss across all dietary regimens (p < 0.001). Genetic analyses did not display statistically significant effects on weight loss. No significant differences in weight loss were observed between macronutrient groups, aligning with the POUNDS Lost and DIETFITS studies. This study underscores the importance of dietary interventions for weight loss and the potential contributions of genetic makeup. These findings contribute to obesity management within the Greek population and support the need for further research in personalized interventions.

Dietary and Lifestyle Management of Functional Hypothalamic Amenorrhea: A Comprehensive Review.

Functional Hypothalamic Amenorrhea (FHA) is a condition characterized by the absence of menstruation, which is increasingly affecting young women. However, specific recommendations for treating and preventing this condition are lacking. Based on a review of the available literature, this article provides practical and feasible dietary management recommendations for healthcare professionals and researchers in women's health and nutrition. It answers the question of what interventions and nutritional recommendations are necessary to restore menstrual function in women struggling with FHA. Physicians recommend an energy availability threshold of 30 kcal/kg FFM/day to prevent FHA. Also, energy availability below and above this threshold can inhibit LH pulsation and cause menstrual disorders. In addition, the risk of menstrual disorders increases with a decrease in the caloric content of the diet and the duration of the energy deficit, and women with FHA have significantly lower energy availability than healthy women. It is essential to ensure that adequate kilocalories are provided throughout the day (regular meals that are a source of proper glucose) to avoid a negative energy balance, as glucose has been proven to affect LH pulses and T3 and cortisol concentrations in the body. Dietary intervention should focus on increasing the caloric content of the diet, thus increasing energy availability and restoring energy balance in the body. Treatment and diagnosis should also focus on body composition, not just body weight. An increase in body fat percentage above 22% may be required to restore menstrual function. In women with FHA, even an increase in body fat mass of one kilogram (kg) increases the likelihood of menstruation by 8%. It is advisable to reduce the intensity of physical activity or training volume, while it is not advisable to give up physical activity altogether. It is also important to ensure adequate intake of micronutrients, reduce stress, and incorporate cognitive-behavioral therapy.

A Starch- and Sucrose-Reduced Diet Has Similar Efficiency as Low FODMAP in IBS-A Randomized Non-Inferiority Study.

A diet with low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) is established treatment for irritable bowel syndrome (IBS), with well-documented efficiency. A starch- and sucrose-reduced diet (SSRD) has shown similar promising effects. The primary aim of this randomized, non-inferiority study was to test SSRD against low FODMAP and compare the responder rates (RR = ∆Total IBS-SSS ≥ -50) to a 4-week dietary intervention of either diet. Secondary aims were to estimate responders of ≥100 score and 50% reduction; effects on extraintestinal symptoms; saturation; sugar craving; anthropometric parameters; and blood pressure. 155 IBS patients were randomized to SSRD (n = 77) or low FODMAP (n = 78) for 4 weeks, with a follow-up 5 months later without food restrictions. The questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS) were completed at baseline and after 2 and 4 weeks and 6 months. Weight, height, waist circumference, and blood pressures were measured. Comparisons were made within the groups and between changes in the two groups. There were no differences between groups at baseline. The responder rate of SSRD was non-inferior compared with low FODMAPs at week 2 (79.2% vs. 73.1%; p = 0.661;95% confidence interval (CI) = -20-7.2) and week 4 (79.2% vs. 78.2%; p = 1.000;95%CI = -14-12). Responder rate was still high when defined stricter. All gastrointestinal and extraintestinal symptoms were equally improved (p < 0.001 in most variables). SSRD rendered greater reductions in weight (p = 0.006), body mass index (BMI) (p = 0.005), and sugar craving (p = 0.05), whereas waist circumference and blood pressure were equally decreased. Weight and BMI were regained at follow-up. In the SSRD group, responders at 6 months still had lowered weight (-0.7 (-2.5-0.1) vs. 0.2 (-0.7-2.2) kg; p = 0.005) and BMI (-0.25 (-0.85-0.03) vs. 0.07 (-0.35-0.77) kg/m2; p = 0.009) compared with baseline in contrast to non-responders. Those who had tested both diets preferred SSRD (p = 0.032). In conclusion, a 4-week SSRD intervention was non-inferior to low FODMAP regarding responder rates of gastrointestinal IBS symptoms. Furthermore, strong reductions of extraintestinal symptoms were found in both groups, whereas reductions in weight, BMI, and sugar craving were most pronounced following SSRD.

An internet-based platform with a low-calorie dietary intervention improves cardiometabolic risk factors in overweight and obese people in China: Half-year follow-up results of a randomized controlled trial.

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/m2 and 27.70 (26.02, 29.70) kg/m2, 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.

A whole-food, plant-based intensive lifestyle intervention improves glycaemic control and reduces medications in individuals with type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: We conducted the largest and longest clinical trial comparing a whole-food, plant-based intervention with standard medical care (SMC) in individuals with type 2 diabetes. METHODS: We randomised (parallel-arm; computerised 1:1 randomisation ratio) 169 adults aged 18-75 years with type 2 diabetes in the Marshall Islands to an intensive whole-food, plant-based intervention with moderate exercise (PB+Ex) or SMC for 24 weeks. The PB+Ex intervention included 12 weeks of meals, exercise sessions and group classes. Primary outcomes were glycaemic control (HbA1c, glucose, insulin and HOMA-IR) and glucose-lowering medication use. Secondary outcomes included lipids, blood pressure, heart rate and C-reactive protein. Only lab analysts were blinded. RESULTS: Compared with SMC (n=90 randomised; n=70 analysed), the PB+Ex (n=79 randomised; n=66 analysed) intervention decreased HbA1c by an additional 14 mmol/mol (1.3%) at week 12 (-22 vs -7 mmol/mol [-2.0% vs -0.7%]; p<0.0001) and 8 mmol/mol (0.7%) at week 24 (-16 vs -8 mmol/mol [-1.4% vs -0.7%]; p=0.01). Concomitantly, 63% of medicated PB+Ex participants reduced their glucose-lowering medications (vs 24%; p=0.006), and 23% of PB+Ex participants with a baseline HbA1c <75 mmol/mol (<9%) achieved remission. Additionally, the PB+Ex intervention reduced weight (-2.7 kg; p<0.0001), C-reactive protein (-11 nmol/l; p=0.005) and cardiovascular medication use compared with SMC. At intermediate timepoints, it improved glucose, insulin, HOMA-IR, cholesterol, triglycerides and heart rate, but not at week 24. CONCLUSIONS/INTERPRETATION: A whole-food, plant-based lifestyle intervention was more effective for improving glycaemic control than SMC. It also reduced the need for diabetes and cardiovascular medications and induced diabetes remission in some participants. Therefore, it is an effective, evidence-based lifestyle option for individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03862963 FUNDING: This research was funded by the Department of the Army (W81XWH-05-1-0547). CJH received support through a National Institutes of Health Predoctoral T32 Obesity Fellowship (T32 HL105349).