Search Results (758)

Background: High-carbohydrate high-fat (HCHF) diets have been associated with oxidative stress, impaired bone remodelling, and deterioration of skeletal integrity. Kelulut honey (KH), a stingless bee honey rich in antioxidant compounds, has demonstrated protective effects against bone loss; however, its effects on bone density, biomechanical properties, antioxidant status, and bone-related molecular markers remain incompletely understood. (2) Methods: Male Wistar rats were assigned to sham, negative control (NC), or KH-treated groups (200, 400, and 600 mg/kg). The NC and KH groups received an HCHF diet for 24 weeks, with KH administered during the final 12 weeks. Bone microarchitecture was evaluated using micro-computed tomography, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and biomechanical properties by three-point bending. Antioxidant enzyme activities, serum bone turnover markers, and bone-related gene expression were also assessed. (3) Results: HCHF feeding reduced BMD, load, stress, Young’s modulus, gluthatione peroxidase (GPx) activity, and superoxide dismutase (SOD) activity while increasing strain, displacement, serum C-terminal telopeptide of type 1 collagen (CTX-1) and receptor activator of nuclear factor-κB (RANK) levels, and runt-related transcription factor 2 (Runx2) expression. KH supplementation improved bone health by dose-dependently enhancing antioxidant defences, significantly increasing GPx and SOD activities, while catalase (CAT) activity was elevated at 600 mg/kg. The 400 mg/kg dose improved trabecular microarchitecture by increasing trabecular number, connectivity density and cortical area/total tissue area. KH also improved biomechanical properties, increasing load, stress, stiffness, and Young’s modulus while reducing displacement. Furthermore, KH attenuated HCHF-induced increases in Runx2 mRNA and RUNX2 protein and reduced osterix (Sp7), integrin Subunit Alpha 5 (Itga5), and calcitonin receptor (Calcr) mRNA expression. However, serum CTX-1 remained elevated in all KH-treated groups. (4) Conclusions: Overall, the findings suggest that KH may have potential as a natural intervention for mitigating diet-associated skeletal alterations, although further studies are required to clarify the underlying mechanisms. Full article

The intestinal epithelium is a dynamic tissue renewed by intestinal stem cells (ISCs) within the crypt niche. ISC behavior is regulated not only by intrinsic genetic programs but also by dietary composition, nutrient availability, microbial metabolites, and feeding rhythms. This narrative review synthesizes mechanisms through which diet influences ISC self-renewal, proliferation, differentiation, metabolic programming, and regenerative capacity. Dietary patterns exert context-dependent effects: caloric restriction, fasting, and structured feeding–fasting cycles may enhance epithelial regeneration through nutrient-sensing pathways, mitochondrial adaptation, and circadian regulation, whereas Western-type and high-fat diets may promote niche remodeling, inflammation, metabolic reprogramming, and tumorigenic risk. Macronutrients regulate ISC fate through carbohydrate metabolism, amino acid sensing, fatty acid oxidation, and lipid-derived signaling molecules. Micronutrients, including vitamins A, D, and B and minerals such as iron, zinc, selenium, and magnesium, contribute to epithelial differentiation, redox balance, and barrier integrity. Phytochemicals may modulate ISC function through Wnt/β-catenin, Nrf2, SIRT1, and epigenetic pathways or by stabilizing the epithelial microenvironment. The gut microbiota mediates diet–ISC interactions via short-chain fatty acids, bile acids, indole derivatives, and other metabolites. However, human evidence remains limited, and studies integrating human organoids, single-cell analyses, metabolomics, and chrononutrition are needed to inform personalized nutritional strategies for intestinal health. Full article

Diets high in fat and refined carbohydrates reliably mimic key features of metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatic lipid accumulation, oxidative stress, and ongoing liver injury. This study evaluated the long-term, low-dose administration of Callistemon citrinus ethanolic leaf extract and its primary bioactive compounds: d-limonene, ellagic acid, gallic acid, and p-coumaric acid to prevent lipotoxicity in rats fed a high-fat–sucrose diet (HFSD). Sixty male Wistar rats were randomly divided into 10 groups: normal control group, an untreated HFSD group, and eight HFSD groups treated for 23 weeks with metformin, C. citrinus extract, the individual bioactive compounds, or a mixture of these compounds. We assessed body and organ weights, liver macroscopic features, serum markers of liver injury, oxidative stress biomarkers, histopathological changes, and hepatic fatty acid profiles. HFSD feeding induced significant body weight gain, hepatomegaly, severe tissue damage, elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), glucose and triglycerides, alongside heightened hepatic oxidative stress, and altered saturated fatty acid profiles. Conversely, treatment with metformin and the natural compounds attenuated HFSD-induced liver injury to varying degrees. Improvements in histopathological severity and serum liver enzymes correlated with decreased oxidative stress biomarkers. Notably, ellagic acid, gallic acid, d-limonene, and the bioactive mixture, significantly improved hepatic fatty acid profiles, whereas p-coumaric acid exhibited more modest effects. These results demonstrate that long-term administration of low-dose treatment can successfully improve all evaluated metabolic, biochemical, and histological parameter, suggesting that modulating oxidative stress and liver lipid composition is strongly linked to the mitigation of liver injury in this experimental MAFLD model. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) frequently experience food-related symptoms and express a strong need for dietary guidance, yet evidence-based recommendations remain limited. This often leads to self-imposed dietary restrictions, potentially compromising nutritional intake and food-related quality of life (Fr-QoL). The primary aim of this study was to evaluate changes in Fr-QoL, following personalized feedback on an IBD-specific food frequency questionnaire and access to an online nutritional knowledge portal over a 6-month period. Secondary exploratory outcomes included changes in dietary intake and diet quality. Methods: In this nationwide pre–post study, 108 patients with IBD completed baseline and 6-month assessments. Dietary intake was measured using the validated GINQ-FFQ and Fr-QoL using a 29-item questionnaire. Nutrient intake was compared with EFSA reference values. Participants received automated personalized feedback and had access to educational tools and dietitian resources. Changes over time were analyzed using paired statistical tests. Results: A significant improvement in Fr-QoL was observed (mean difference 8.1 points, 95% CI 5.5–10.7; p < 0.001; Cohen’s d = 0.39). Baseline intake was characterized by high fat and low fiber consumption. After 6 months, total energy intake decreased (p < 0.001), along with reductions in protein, fat, carbohydrates, fiber, and several micronutrients, including iron, folate, vitamin B6, vitamin C, potassium, magnesium, and zinc. Diet quality did not improve, and adherence to EFSA guidelines remained suboptimal. The digital tools were positively evaluated. Conclusions: In this single-arm pre–post study, Fr-QoL scores were higher at follow-up than at baseline among participants who completed both assessments, whereas dietary intake and overall diet quality did not improve. The findings support the feasibility and acceptability of the developed digital tools for dietary assessment and nutrition education, although their effectiveness requires further evaluation in controlled studies. Additional strategies, including structured dietitian-led support combined with digital resources, may be required to optimize nutritional outcomes in patients with IBD. Full article

Background/Objectives: Loss of skeletal muscle mass is linked to functional decline and adverse health outcomes. Evidence on long-term associations between macronutrient-based dietary patterns and muscle mass decline remains limited. This study examined this association in a prospective cohort of Korean adults aged 40–69 years. Methods: Participants were categorized into four groups by macronutrient energy proportion: high-carbohydrate (HCHO, carbohydrate > 65% of total energy), high-fat (HF, fat > 30%), high-protein (HP, protein > 20%), and normal diets (ND). Cox models estimated associations between dietary patterns and decline in height-adjusted skeletal muscle mass, including sensitivity analyses using stricter decline thresholds (≥3%, ≥5%, and a reduction exceeding the least significant change); linear mixed-effects models evaluated longitudinal muscle mass changes. Results: A total of 9516 adults were included. During a median follow-up of 5.6 years (IQR 3.8–9.8), 6971 participants developed a decline in skeletal muscle mass relative to baseline. Adjusted hazards were higher for HCHO (aHR 1.12, 95% CI 1.04–1.21) and HP (aHR 1.20, 95% CI 1.01–1.42) versus ND, whereas HF showed no significant association (aHR 0.73, 95% CI 0.46–1.15). These associations were attenuated and no longer significant under stricter thresholds. Mixed-effects models showed no significant group effects or group-by-time interactions. Conclusions: HCHO and HP patterns were associated with a higher risk of muscle mass decline, but this was not consistent under stricter thresholds, and longitudinal trajectories did not differ across patterns. These findings should be considered preliminary. Further studies should clarify the roles of macronutrient quality, food sources, and overall dietary patterns in muscle health. Full article

In population health the highly cited Atherosclerosis Risk in Communities study indicated a U-shaped association between carbohydrate intake and mortality, whilst the Prospective Urban Rural Epidemiology study linked higher fat intake to lower mortality risks. The Malaysia Lipid Study reported high-fat and high-carbohydrate dietary patterns were associated with increased cardiometabolic risks, including insulin resistance and small dense LDL particles generation. This animal model study therefore was purposely designed to evaluate metabolic outcomes of carbohydrate–fat permutations in Zucker diabetic fatty (ZDF) and Zucker lean (Z_lean) rats by using ¹H Nuclear Magnetic Resonance (NMR) metabolomics. Twenty-four ZDF rats were randomly divided into four groups (n = 6 per group): control (standard diet), Diet A (54%-energy carbohydrate, 32%-energy fat, 14%-energy protein) mimicking a recommended adult Malaysian diet, Diet B (49%-energy carbohydrate, 37%-energy fat, 14%-energy protein) mimicking a low-carbohydrate, moderate high-fat diet, and metformin treatment (100 mg/kg), which effectively represents a 5%-energy exchange in isocaloric meals. An additional six Z_lean were given Diet A (n = 3) and Diet B (n = 3). The intervention lasted eight weeks. Using log-transformed data, analysis of variance (ANOVA) revealed significant differences between the groups for eleven metabolites (1,6-anhydro-β-D-glucose, 2-hydroxyvalerate, acetate, 3-aminoisobutyrate, 3-hydroxybutyrate, carnitine, choline, citrate, creatine, lactate, and N-methylhydantoin) (all p < 0.05) which remained significant even after false discovery rate (FDR) correction. Majorly elevated metabolites in both ZDF and Z_lean rats were 3-hydroxybutyrate, N-methylhydantoin, 3-aminoisobutyrate, and carnitine, indicating dietary influences independent of diabetes status. Conversely, citrate and 1,6-anhydro-β-D-glucose levels showed distinct patterns across the groups, with Z_lean rats exhibiting lower levels and ZDF rats showing higher levels compared to healthy controls, suggesting potential genetic or physiological influences. Other metabolites such as creatine, acetate, choline and 2-hydroxyvalerate showed varied trends, highlighting metabolic complexities. Compared to the control group, metformin treatment generally resulted in lower levels of metabolites, except for acetate, which was higher, indicating improved insulin sensitivity. The findings indicated moderate high-fat diets may exacerbate metabolic disturbances as seen in both ZDF and Z_lean rats, while metformin treatment generally improved metabolic profiles. Full article

Background: Diets high in fat and carbohydrates, like fructose, trigger colon inflammation, increase intestinal permeability, and drive dysbiosis. However, the effects of obesogenic diets on gut microbiota, including Clostridium and Bacteroides, remain unknown. Understanding how these diets damage the colon is critical. Methods: Using a controlled preclinical obesity model, we compared the effects over time of High-Fat Diet (HFD), High-Fructose Diet (HFrD), and their combination (HFHFrD). Diet-induced dysbiosis was assessed at 4 and 8 weeks via qPCR using primers specific to bacterial phyla and species. In addition, intestinal inflammation, atrophy, and mucin production were evaluated by digital pathology after 8 weeks of diet exposure. Results: both HFrD and HFHFrD mice exhibited marked intestinal inflammation, atrophy, and damage, alongside altered production of neutral and mixed mucins. HFD-fed mice displayed a 15-fold surge in Clostridium/Bacteroides ratio at 4 weeks. At 8 weeks, HFrD-fed mice showed a striking 10-fold rise in microbial relative abundance compared to the other diets. Both HFrD and HFHFrD triggered an early increase in Bacteroides species, but significance emerged only at 8 weeks. Conclusions: Although all obesogenic diets induced inflammation, atrophy, epithelial damage, and altered mucin patterns, HFrD and HFHFrD caused pronounced disruptions to barrier function and dysbiosis. Critically, HFD consistently raised the Firmicutes/Bacteroidetes ratio at 4 and 8 weeks, while the Clostridium/Bacteroides ratio spiked only at 4 weeks. Obesogenic diets fundamentally shifted microbial load and diversity. Therefore, bacterial ratios, such as Clostridium/Bacteroides, may signal dysbiosis and tissue damage from obesogenic diets, but further research is required for confirmation. Full article

Background: Hepatic lipid metabolism disorder has been linked to a wide range of diseases. Aspalathin is a flavonoid enriched in rooibos tea and has shown capacity to protect against hyperlipidemia, oxidative stress and inflammation. In the current study, we investigated the functional role of aspalathin in regulating liver metabolism and gut microbiota in the context of a high-fat diet (HFD). Methods: Male mice were fed a control diet or HFD, then HFD-fed animals were treated with or without aspalathin-rich extract (ASE). Hepatic neutral lipids were detected using oil red O staining and a colorimetric assay. Expression of cholesterol metabolism-, lipogenesis- and fatty acid β-oxidation-associated genes was measured. Gut microbiota was analyzed using 16S rRNA sequencing and bioinformatic approaches. Results: HFD-fed mice had markedly higher levels of triglycerides and cholesteryl esters and downregulated expression of cholesterol metabolism-, transport- and lipogenesis-related genes in the liver. ASE administration counteracted HFD-induced effects. In addition, HFD altered the composition, diversity and metabolic pathways of the gut microbiota. The richness of beneficial bacteria, particularly the butyrate-producing bacteria, was significantly decreased. The altered metabolic pathways are involved in the metabolism of carbohydrates, lipids, amino acids and nucleotides, as well as mitochondrial function. ASE treatment reversed most of the alterations back to the characteristics of the control group. Conclusions: Our results demonstrated the potential of ASE improving liver lipid metabolism and gut microbiota in the scenario of a high-fat diet, providing insights into future studies on the mechanism of ASE regulating lipid metabolism disorder. Full article

Background/Objectives: AI tools are becoming increasingly common, including in areas related to health and diet. However, there are no studies indicating the nutritional value of diets generated by large language models (LLMs). The aim of this study was to analyse the nutritional value of diets generated by three major language models. Methods: Three LLMs were used in the study: ChatGPT, Gemini and Copilot. Using each of these, 35-day meal plans were generated for three energy variants: 2000 kcal, 2500 kcal and 3000 kcal. The meal plans were then analysed using dietary software. Results: All LLMs generated meal plans with an insufficient energy value (p < 0.001, one-sample t-test) by 284–546 kcal, depending on the model and the targeted energy content. The meal plans were characterised by an excessively high proportion of energy from protein and an excessively low proportion of energy from fat. Carbohydrates were planned in the correct amounts. ChatGPT and Copilot generated meal plans with a generally adequate vitamin and mineral content. Gemini generated meal plans that were often deficient, particularly for diets with lower energy values. Conclusions: Diets generated by LLMs have many shortcomings. Unsupervised use of LLM-generated meal plans by non-expert users may produce nutritionally inaccurate diets and should not replace professional dietary counselling. Full article

Malignant tumors require substantial energy sources for proliferation, and dietary composition may influence colorectal carcinogenesis through metabolic and microbiome-related mechanisms. This study investigated the association of low-carbohydrate high-fat dietary patterns with macroscopic tumor burden, morphologic inflammatory cell infiltration, and gut microbiome alterations using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colitis-associated colorectal cancer. Male C57BL/6 mice received AOM followed by three cycles of DSS and were fed a standard diet (SD), high-carbohydrate diet (HCD), low-carbohydrate high-fat lard-based diet (HFL), or low-carbohydrate high-fat coconut oil-based diet (HFC). Body weight, colon length, splenic weight, macroscopic tumor formation, hematoxylin and eosin (H&E)-based inflammatory cell infiltration, and gut microbiome composition were analyzed. The HFL and HFC groups exhibited higher body weights and relatively preserved colon lengths compared with the SD and HCD groups. Tumor number and total tumor size were reduced in the HFL and HFC groups. Total lymphocyte-like inflammatory cell infiltration was not increased in the high-fat diet groups, whereas per-tumor values were interpreted cautiously because they are affected by tumor number. Gut microbiome analysis demonstrated altered microbial composition, increased alpha diversity, and distinct temporal microbial dynamics in the high-fat diet groups. Because the HFL and HFC diets simultaneously changed carbohydrate content, fat content, fat source, and caloric density, these findings should be interpreted as exploratory effects of low-carbohydrate high-fat dietary patterns rather than independent effects of carbohydrate restriction, total fat, or fat source. Full article

Pomegranate (Punica granatum), a shrub belonging to the Lythraceae family, has long been recognized for its diverse pharmacological benefits, including potential roles in managing inflammation and diabetes. The present study explored the insulin-secretory and β-cell proliferative properties of the ethanol extract of P. granatum fruit peel (EEPG) and assessed its influence on glucose regulation in high-fat-fed diet-induced obese mice (HFDi-OM) through in vivo and in silico studies. In vitro, EEPG was found to activate cAMP-dependent pathways and regulate K_ATP channels, thereby enhancing glucose-stimulated insulin secretion from BRIN-BD11 β-cells, with partial reliance on extracellular calcium. EEPG promoted β-cell proliferation, as indicated by an increase in Ki-67 positive cells, and displayed inhibitory effects on glucose diffusion and starch hydrolysis, suggesting a capacity to delay carbohydrate digestion and absorption. Furthermore, EEPG demonstrated antioxidant activity by neutralizing free radicals. In an acute test, EEPG (at doses of 150 and 250 mg/5 mL/kg) improved oral glucose tolerance and elevated plasma insulin levels. Long-term oral treatment for 21 days to HFDi-OM led to a significant reduction in fasting blood glucose, body weight, and food and fluid intake. It also enhanced gastrointestinal motility and improved lipid profiles by increasing HDL and lowering total cholesterol, LDL, and triglycerides. The therapeutic properties of EEPG are likely attributed to its rich bioactive components, including flavonoids (quercetin, kaempferol, catechin, and epicatechin) and phenolic acids (ellagic acid), which exhibited strong multi-target binding affinities in in silico molecular docking studies toward SUR1, PDE4, PI3K, and α-amylase, thereby supporting enhanced insulin secretion, β-cell function and glucose homeostasis. Full article

The impacts of various feed substrates and processing treatments (boiling and extrusion) designed to reduce plant-derived antinutritional factors on the growth and development, nutritional composition, and intestinal microbiota of black soldier fly larvae (BSFL) were evaluated. The research revealed that, except for the soybean flour group, the cottonseed meal group and the treatment group with antinutritional factors removed showed better growth trends compared to the Gainesville House Fly Diet group. The heat-processed groups had higher maximum larval weights, survival rates, and feed conversion rates than the untreated groups. Additionally, BSFL fed with high-protein and high-fat experimental diets generally exhibited higher fat and protein contents. Plant-derived antinutritional factors in the test substrates significantly affected the intestinal microbiota and their metabolic pathways in BSFL. Gut microbiota—including phyla such as Firmicutes, Proteobacteria, and Bacteroidetes, along with various lactic acid—and short-chain fatty acid-producing genera—and metabolic pathways related to carbohydrates, amino acids, cofactors, and vitamins, play crucial roles in helping BSFL resist plant antinutritional factors. Full article

A ketogenic diet (KD) is a low-carbohydrate, high-fat dietary approach. Beyond treating neurologic disorders, KDs have attracted significant media attention for their potential to improve obesity and diabetes. The diet induces a metabolic shift from glucose toward fatty acid oxidation and ketone body production. This shift leads to ketosis, which may reduce hunger, partly through the anorexigenic effects of ketone bodies, thereby contributing to weight loss and improved metabolic parameters, including glycaemic control and insulin sensitivity. In particular, the positive effects of KDs lower insulin demand and may thereby improve β-cell function. However, the long-term efficacy, safety, and sustainability of KDs, especially for diabetes, remain debated. This review offers current insights into the effects of ketogenesis and ketosis, as well as the potential mechanisms underlying them. We explore the metabolic effects of KDs in obesity and diabetes, drawing on preclinical and clinical studies, and suggest that combining KDs with antidiabetic agents may provide synergistic benefits. However, combining KDs with these pharmacotherapies, particularly SGLT-2 inhibitors, requires careful clinical supervision because of potential risks, including euglycaemic diabetic ketoacidosis. We explore how a KD alters the composition of the gut microbiota, thereby affecting host health. We conclude by highlighting challenges and future directions for optimising KD-based therapies and by outlining the limitations of the current review. Full article

Background: Inter-individual variability in lipid response to dietary interventions complicates cardiometabolic prevention in overweight and obese women. Although several dietary strategies improve lipid profiles on average, predictors of comprehensive, multi-marker lipid improvement remain unclear. Objective: To identify baseline clinical predictors of comprehensive lipid improvement across seven dietary interventions and to evaluate the performance of three machine learning (ML) classifiers in predicting a composite Global Score. Methods: This secondary analysis pooled individual-level data from 284 overweight or obese women enrolled in three randomized controlled trials (RCTs). Participants were assigned to continuous energy restriction (CER), intermittent energy restriction (IER), intermittent energy and carbohydrate restriction (IECR), IECR with added protein and fat (IECR+PF), high-carbohydrate, high-monounsaturated-fat, or daily energy-restriction diets. Eleven baseline clinical features served as predictors. Four binary lipid improvement scores (TC/HDL, LDL/HDL, non-HDL cholesterol, TG/HDL) were calculated from baseline to week 12, and a composite Global Score was defined as TRUE only when all four improved. Three ML classifiers (J48, Logistic Model Tree [LMT], Random Forest) were evaluated using stratified 10-fold cross-validation. Results: Overall, 30–35% achieved improvement in the Global Score. Improvement rates varied across diets, with High Mono and High Carb showing the highest rates (48.4%). LMT performed best (AUC = 0.66; accuracy = 70%). Baseline TG, BMI, age, total cholesterol, and weight were the strongest predictors. Conclusions: Comprehensive lipid improvement varies across dietary strategies and is influenced by baseline triglycerides, adiposity, age, and diet type. ML-based stratification may support personalized dietary prescriptions. Full article

Background: Critical illness leads to profound metabolic, neuroendocrine and immune disorders that affect the prognosis of patients treated in intensive care units (ICUs). The ketogenic diet, a high-fat and low-carbohydrate eating model, is gaining increasing importance as a potential metabolic intervention in the ICU. Preliminary data suggest that the ketogenic diet (KD) may support the control of seizures in a super-refractive epileptic state (SRSE), stabilize glycemia, reduce insulin demand, and modulate the immune response in sepsis. The aim of this review was to present a synthetic presentation of the current state of knowledge regarding use of the KD in intensive care patients. Methods: The review was carried out in accordance with the guidelines of the Joanna Briggs Institute and PRISMA-ScR. PubMed, Scopus, EBSCO, Web of Science, Google Scholar and Cochrane Library databases were searched (10–19 April 2026) using the Population–Concept–Context model. Full-text observational studies, randomized trials and reviews of the use of KDs in ICU patients were included. Data extraction was performed independently by two reviewers. Results: Of the 42 publications identified, seven studies were included in the analysis. The KD was feasible and safe in both critically ill adults and children. In SRSE, most patients achieved stable ketosis within a few days, which often allowed for reduction or discontinuation of anesthetics. In sepsis, the KD led to glycemic stabilization, reduced insulin demand and reduced immune deregulation; in one study, “after day 4, none of the patients in the KD group required insulin treatment.” The KD also showed beneficial effects on cellular bioenergetics and mitochondrial function. The safety profile was acceptable and adverse reactions were manageable with appropriate monitoring. Conclusions: The KD represents a promising, non-pharmacological metabolic intervention in intensive care, particularly in the treatment of SRSE and in the stabilization of glucose metabolism in sepsis and other critical conditions. Despite the growing number of positive clinical observations, the available evidence remains limited due to small samples, heterogeneous protocols, and a lack of randomized trials. Further, well-designed prospective studies are needed to determine optimal KD implementation protocols and identify the patient populations that benefit most. Full article