Nutrients最新文献

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum's total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use.

Background/Objectives: The milk fat globule membrane (MFGM) is a complex structure of polar lipids, gangliosides, and glycoproteins that has demonstrated anti-inflammatory, neuroprotective, and gut-modulatory effects in preclinical and human studies, but its effects on adult psychological outcomes have not been systematically synthesised. Methods: We conducted a systematic literature search across multiple databases using combined relevant keywords and Medical Subject Headings terms, with manual reference checks to ensure comprehensiveness. Of the 35 articles initially identified, 3 randomised controlled trials met the inclusion criteria: adult participants (≥20 years); bovine MFGM supplementation; a placebo or control group; and outcomes measuring stress, anxiety, or depression. A random-effects meta-analysis was performed, calculating standardised mean differences for stress, anxiety, and depression outcomes. Results: MFGM supplementation produced small but statistically significant reductions in stress and anxiety. Effects on depression were non-significant, though directionally favourable. Risk-of-bias assessments were conducted using Cochrane criteria and indicated low concerns across trials. Publication bias was not indicated, but interpretation was limited by the small number of studies. Conclusions: Whilst the evidence for depression is inconclusive, bovine MFGM supplementation may confer modest benefits for stress and anxiety in adults and could be part of a nutritional strategy to support overall mental well-being.

Background/Objectives: Unhealthy lifestyles lead to chronic low-grade inflammation, increasing the risk of colorectal cancer. Few studies in East Asia have examined the association between the dietary inflammation potential and colorectal cancer incidence. Therefore, we aimed to investigate this association further in the Japanese population. Methods: This study included 38,807 men aged 45-74 years who participated in the Japan Public Health Center-based prospective study (JPHC Study). The energy-adjusted dietary inflammatory index (E-DII) was derived from a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Differences in risk due to a combination of E-DII and lifestyle were examined using interaction term. Results: During 14 years of follow-up, 1415 colorectal cancer cases occurred. A tendency to increased colorectal cancer risk was observed with consumption of pro-inflammatory diets among Japanese men (adjusted HR [95% CI] for the highest quintile: 1.20 [0.99-1.46], p trend = 0.08), with a significantly increased risk of colon cancer (HR: 1.28 [1.01-1.63], p trend = 0.03). A possible interaction was observed with alcohol consumption (p = 0.07), which was statistically significant for proximal colon cancer (HR: 1.14 [1.05-1.25] in drinkers; p interaction = 0.01). No significant interactions with other lifestyle factors were found. Conclusions: Consumption of pro-inflammatory diets increases colorectal cancer risk among Japanese men; alcohol consumption further increases this risk for drinkers. These findings suggest that colorectal cancer may be prevented through dietary modification.

Background/Objectives: Assessing the bioavailability of nutrients and bioactive compounds in vitro commonly relies on coupling standardized gastrointestinal digestion models with intestinal epithelial cell systems. However, digests produced using static digestion protocols such as INFOGEST often impair epithelial barrier integrity, limiting their direct application to intestinal models and reducing reproducibility across studies. Methods: This work systematically compared five commonly used digest conditioning strategies, including acidification, centrifugation, rapid freezing, and ultrafiltration using 10 kDa and 3 kDa molecular weight cut-off membranes, to identify the approach that best preserves intestinal epithelial viability and barrier function while enabling exposure at physiologically relevant concentrations. INFOGEST digests of yogurt were initially evaluated, followed by validation using biscuit and canned mackerel digests. Cell viability and monolayer integrity were assessed in differentiated Caco-2 cells using MTT assay and transepithelial electrical resistance (TEER) measurements. Results: Among the tested approaches, ultrafiltration using 3 kDa membranes consistently preserved epithelial viability and barrier integrity at a 1:10 dilution across all food matrices, whereas other conditioning methods failed to maintain TEER despite acceptable cell viability. At lower dilutions, food-dependent effects emerged, highlighting the importance of matrix-specific evaluation. Conclusions: These findings identify 3 kDa ultrafiltration as an effective and minimally invasive strategy to improve the compatibility of INFOGEST digests with intestinal cell models. By enabling reproducible exposure conditions that preserve epithelial integrity, this approach supports more reliable in vitro assessment of nutrient bioavailability and contributes to methodological standardization in nutrition research.

Background/Objectives: Essential amino acids' (EAAs) biological effects depend on both gastrointestinal stability and intestinal bioavailability. A commercially available EAA blend has previously shown to be highly bioaccessible and able to inhibit the DPP-IV enzyme both directly and at a cellular level following simulated digestion in vitro. In light with this consideration, the present study aimed to evaluate the intestinal in vitro bioavailability of GAF subjected to INFOGEST digestion (iGAF) and to investigate the metabolic effects of its bioavailable fraction on muscle cells using an integrated Caco-2/C2C12 co-culture model. Methods: Differentiated Caco-2 cell lines were treated with iGAF, and amino acid transport was quantified by ion-exchange chromatography. The basolateral fraction containing bioavailable EAAs was used to treat differentiated C2C12 myotubes for 24 h. Western blot analyses were performed to assess the activation of anabolic and metabolic pathways, including mTOR, Akt, GSK3, AMPK and GLUT-4. Results: More than 50% of each EAA present in iGAF crossed the Caco-2 monolayer, with BCAAs and phenylalanine particularly enriched in the basolateral fraction. Exposure of C2C12 myotubes to the bioavailable iGAF stimulated mTORC1 activation and increased the phosphorylation of Akt and GSK3, indicating an enhanced anabolic response. At a cellular level, iGAF also elevated the p-AMPK/AMPK ratio, suggesting activation of energy-sensing pathways. Moreover, GLUT4 protein levels and glucose uptake were significantly increased. Conclusions: The study focuses exclusively on a cellular model, and results suggested that iGAF is highly bioavailable in vitro and that its absorbed fraction activates key anabolic and metabolic pathways of skeletal muscle cells, enhancing both protein synthesis signaling and glucose utilization in vitro.

Background/Objectives: Limited information exists on how dietary patterns change in adults who experience weight regain vs. those who maintain weight loss after lifestyle interventions. Methods: Five hundred fifty-two adults (60 ± 1.0 years, 33.8 ± 0.4 kg/m²) with type 2 diabetes mellitus from the Look AHEAD Trial achieved ≥ 7% weight loss after Year 1, completed follow-up visits through Year 4, and provided three 134-item food frequency questionnaires. Weight "regain" (WLR) was defined as regaining ≥ 50% of the initial weight lost. Dietary patterns were determined using established DASH diet scores (scale: 0-9) and principal component analysis (PCA; higher scores = more adherent). Repeated measures linear mixed models assessed group and sex differences in dietary patterns. Results: Dietary patterns were similar between groups during weight loss (baseline to Year 1). WLR DASH scores decreased more from Year 1 to Year 4 compared to "maintain" (WLM) (WLR: Y1: 5.66 ± 0.14, Y4: 4.60 ± 0.14; WLM: Y1: 5.49 ± 0.13, Y4: 4.92 ± 0.13; difference-p < 0.01). Of the two PCA-derived dietary patterns, Pattern 1 (vegetable, fruit, and fish) decreased more in WLR (WLR: Y1: 0.12 ± 0.16, Y4: -0.14 ± 0.16, WLM: Y1: 0.06 ± 0.14, Y4: 0.25 ± 0.15; difference-p < 0.01), while Pattern 2 (low-fiber grains and high-fat animal proteins) increased in WLR (WLR: Y1: 0.40 ± 0.11, Y4: 0.61 ± 0.11, WLM: Y1: 0.34 ± 0.10, Y4: 0.21 ± 0.10, difference-p < 0.01). Sex differences showed that only WLR women and WLM men increased sweets from Y1 to Y4 (WLR women Y1: 0.26 ± 0.04, Y4: 0.41 ± 0.04; p < 0.01; WLM men: Y1: 0.23 ± 0.04, Y4: 0.38 ± 0.04; p < 0.01). Conclusions: These data demonstrate that differences in dietary patterns between WLR and WLM emerge after the initial weight loss intervention with some sex differences. This suggests that longer-term shifts in dietary patterns after lifestyle interventions may influence weight loss maintenance.

Background: Large positive responses to placebo are common in clinical trials and pose a major challenge when evaluating different treatments, including new foods. Standard between-group comparisons may fail to detect true effects when placebo improvements are significant. We aimed to demonstrate how a simple dose-response correlation method can help differentiate genuine positive responses from those experienced with placebo through secondary analysis of a randomized controlled clinical trial of powdered Rosa-canina fruits.

Methods: Data were reanalyzed from a multicenter, double-blind, randomized, placebo-controlled trial (N = 120; ClinicalTrials.gov NCT01459939) evaluating the effects of standardized Rosa-canina powder in hip and knee osteoarthritis (OA). Participants received fixed doses, leading to variability in mg/kg exposure due to different body weights. Pearson correlations between dose/kg and changes in WOMAC pain and function at 6 and 12 weeks were calculated separately for the active and placebo groups. Standard between-group comparisons were also performed.

Results: Both groups showed significant improvement, over 50%, with no statistically significant differences between them in WOMAC pain or function. However, only the active group, which received a food supplement, exhibited a consistent negative correlation between body weight and symptom improvement at 6 and 12 weeks, suggesting greater benefit with higher dose per kilogram of body weight. No dose-response relationship was observed in the placebo recipients. Therefore, weight-stratified plots revealed an exposure-response gradient in the active group.

Conclusions: Dose-response correlation analysis uncovered positive effects of Rosa-canina as a nutrient that were not detectable through standard between-group comparisons. This is consistent with findings from earlier rose-hip research. This low-cost, easy-to-implement method may help distinguish active effects from placebo responses in trials with large nonspecific improvements. Incorporating such analyses could improve the identification of nutrients containing biologically active preparations and support dose selection in future clinical research.

Background/Objectives: Carotenoids are bioactive pigments with well-established antioxidant and immunomodulatory properties, yet their impact on gut microbiota remains poorly understood from a chemical standpoint. This study explores how carotenoid structure and gastrointestinal stability shape microbial responses combining in vitro fermentation with bioinformatic analyses. Methods: Individual carotenoids (beta (β)-carotene, lutein, lycopene) and combined carotenoids, as well as algal-derived extracts were subjected to 48 h in vitro fermentation, and microbial composition and activity were assessed through sequencing and computational analysis. Results: β-carotene and lycopene promoted acid-tolerant taxa such as Escherichia-Shigella, whereas lutein, due to its higher polarity, supported more transient fluctuations. Mixtures and algal carotenoids exhibited synergistic effects, sustaining beneficial genera including Bifidobacterium and Bacteroides and promoting structured ecological trajectories. Conclusions: These findings provide a chemistry-driven perspective on how carotenoids act as modulators of microbial ecosystems, with direct implications for the formulation of carotenoid-enriched functional foods and dietary interventions.

Background/Objectives: The study aimed to characterize perioperative complications and their relationship with nutritional risk in gastrointestinal cancer patients undergoing surgical treatment. Methods: An observational, prospective, and multicenter study was carried out in 469 patients with gastrointestinal malignancies undergoing elective major abdominal surgical procedures in public hospitals throughout Spain. Complications developed during hospitalization and at 30 days after surgery were recorded, and the patients' nutritional status was evaluated using the MUST screening tool. Results: Colorectal and gastric cancer were the most common tumors. Complications during hospitalization occurred in 146 patients (rate 31.1%). Infections accounted for 68.5% of complications, in particular surgical site infections (SSIs), followed by paralytic ileus (40.4%). At 30 days, the complication rate was 9%, with infections as the most common events. In patients with severe nutritional risk at discharge (MUST score ≥ 2), the percentage of patients with complications was 24.7% as compared to 9.2% in patients without complications (p < 0.0001). Conclusions: Clinicians should be aware of the high frequency of SSIs and that complications are higher among patients with severe nutritional risk. These findings emphasize the need for routine nutritional screening and targeted perioperative support in cancer patients undergoing gastrointestinal cancer surgery.

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities-obesity, hypertension and type 2 diabetes-create a milieu of metabolic derangements, low-grade systemic inflammation (i.e., metainflammation), endothelial dysfunction, and coronary microvascular disease. Emerging data indicate that the gut-heart axis is a potential amplifier of this process. Cardiometabolic comorbidities promote gut dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, and disruption of the intestinal barrier, leading to endotoxemia and upregulation of pro-inflammatory pathways such as TLR4- and NLRP3-mediated signaling. Concomitantly, beneficial gut-derived metabolites (acetate, propionate, butyrate) decrease, while detrimental metabolites increase (e.g., TMAO), potentially fostering myocardial fibrosis, diastolic dysfunction, and adverse remodeling. SCFAs-acetate, propionate, and butyrate-may exert pleiotropic actions that directly target HFpEF pathophysiology: they may provide a CPT1-independent energy substrate to the failing myocardium, may improve lipid and glucose homeostasis via G protein-coupled receptors and AMPK activation, and may contribute to lower blood pressure and sympathetic tone, reinforce gut barrier integrity, and act as anti-inflammatory and epigenetic modulators through the inhibition of NF-κB, NLRP3, and histone deacetylases. This review summarizes current evidence linking gut microbiota dysfunction to cardiometabolic HFpEF, elucidates the mechanistic role of SCFAs, and discusses nutritional approaches aimed at enhancing their production and activity. Targeting gut-heart axis and SCFAs pathways may represent a biologically plausible and low-risk approach that could help attenuate inflammation and metabolic dysfunctions in patients with cardiometabolic HFpEF, offering novel potential therapeutic targets for their management.