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Food & function · 2024
Migraine is a complex neurovascular disorder characterized by recurrent headache attacks that are often accompanied by symptoms such as vomiting, nausea, and sensitivity to sound or light. Preventing migraine attacks is highly important. Recent research has indicated that alterations in gut microbiota may influence the underlying mechanisms of migraines. This study aimed to investigate the effects of inulin supplementation on migraine headache characteristics, quality of life (QOL), and mental health symptoms in women with migraines. In a randomized double-blind placebo-controlled trial, 80 women with migraines aged 20 to 50 years were randomly assigned to receive 10 g day-1 of inulin or a placebo supplement for 12 weeks. Severity, frequency, and duration of migraine attacks, as well as depression, anxiety, stress, QOL, and headache impact test (HIT-6) scores, were examined at the start of the study and after 12 weeks of intervention. In this study, the primary outcome focused on the frequency of headache attacks, while secondary outcomes encompassed the duration and severity of headache attacks, QOL, and mental health. There was a significant reduction in severity (-1.95 vs. -0.84, P = 0.004), duration (-6.95 vs. -2.05, P = 0.023), frequency (-2.09 vs. -0.37, P < 0.001), and HIT-6 score (-10.30 vs. -6.52, P < 0.023) in the inulin group compared with the control. Inulin supplementation improved mental health symptoms, including depression (-4.47 vs. -1.45, P < 0.001), anxiety (-4.37 vs. -0.70, P < 0.001), and stress (-4.40 vs. -1.50, P < 0.001). However, no significant difference was observed between the two groups regarding changes in QOL score. This study provides evidence supporting the beneficial effects of inulin supplement on migraine symptoms and mental health status in women with migraines. Further studies are necessary to confirm these findings. Trial registration: Iranian Registry of Clinical Trials (https://www.irct.ir) (ID: IRCT20121216011763N58).
BMC research notes · 2024
The objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD). In this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30-40 kg/m2) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either "Prebiotic group" (received 10 g/day inulin) or "Placebo group" (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks. The trial was registered in the Iranian registry of clinical trials at 2018-08-02 ( https://www.irct.ir/ ; registration number: IRCT20100209003320N15).
Clinical nutrition ESPEN · 2025
Alcohol Use Disorder (AUD) is a psychiatric disorder characterized notably by gut microbial dysbiosis and insufficient dietary fiber (DF) intake. This study aims to investigate the effect of DF placebo-controlled intervention in patients suffering from AUD during a three-week period of alcohol withdrawal, in order to discover microbial-derived metabolites that could be involved in metabolic and behavioral status. A randomized, double-blind, placebo-controlled study was performed with 50 AUD patients supplemented with inulin (prebiotic DF) or maltodextrin (placebo) during 17 days. Fecal microbiota composition, plasma and fecal metabolomics (liquid chromatography coupled to mass spectrometry), blood markers of inflammation and hepatic alterations, and psychological assessment (questionnaires) were analyzed before and after the intervention. Fecal metabolomics revealed 14 metabolites significantly modified by inulin versus placebo treatment (increased N8-acetylspermidine and decreased indole-3-butyric acid, 5-amino valeric acid betaine (5-AVAB) and bile acids). Thirteen plasma metabolites differentiated both treatments (higher levels of long-chain fatty acids, medium-chain acylcarnitines and sphingomyelin species, and reduced 3-methylhistidine by inulin versus placebo). Fecal Lachnoclostridium correlated with 6 of the identified fecal metabolites, whereas plasma lipidic moieties positively correlated with fecal Ruminococcus torques group and Flavonifractor. Interestingly, parameters reflecting liver alterations inversely correlated with sphingomyelin (SM 36:2). Three weeks of inulin supplementation during alcohol withdrawal leads to specific and different changes in the plasma and fecal metabolome of AUD patients, some of these gut microbiota-related metabolites being correlated with liver function. NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.
The American journal of clinical nutrition · 2025
Beneficial short-chain fatty acids (SCFAs) are produced through intestinal microbial fiber fermentation. Using stable tracer methodology and compartmental modeling, we observed lower SCFA production in older (OAs) than in young adults (YAs) in both an accessible [that is, systemic circulation; whole-body production] and inaccessible [potentially representing intestine absorbing microbially produced SCFAs (U2)] pool. We now investigated whether fiber supplementation increases SCFA production in OAs and whether concentrations reflect production rate changes. In this randomized, placebo-controlled, double-blind crossover study, 21 YAs (20-29 y) and 40 OAs (59-87 y) adults were supplemented with inulin or placebo (maltodextrin) for 7 d (final intake: 30 g/d). Before and after interventions, participants collected stool and received an intravenous pulse containing [U-13C]-labeled SCFAs followed by blood draws. We measured plasma tracer enrichments, plasma and fecal concentrations by gas chromatography-mass spectrometry and performed compartmental analysis. Data are mean (95% confidence interval). Inulin evoked a 44% increase in butyrate production (μmol/min) in the inaccessible pool {YA: 28-44 [+16.2 (4.3, 28.1); P = 0.038], OA: 14-20 [+6.1 (2.2, 9.9); P = 0.011]} and were not different between YAs and OAs. In addition, a 34% increase in propionate production in YA only. We found a 50%-60% increase in fecal acetate, propionate, and butyrate and a 34% increase in plasma butyrate in OA, whereas in YA only 34% increase in fecal acetate. Plasma but not fecal concentrations correlated positively with SCFA production in the inaccessible pool (R2 = 0.20-0.45; P < 0.001). OAs have a lower SCFA production. Inulin intake increases SCFA production. Tracer pulse approach detects SCFA metabolism changes more sensitively than plasma or fecal concentration measurements (NCT04459156).
Journal of food science · 2025
Colorectal cancer (CRC) incidence rises with age, driven by factors such as diet. Inulin, a soluble fiber found in plants like Jerusalem artichoke and chicory, may influence CRC risk by modulating gut microbiota and improving metabolic profiles. This systematic review and meta-analysis evaluate the effects of inulin on CRC in animal models and explore its underlying mechanisms. A comprehensive search of nine databases led to the selection of 12 studies from an initial pool of 114 articles, based on predefined inclusion criteria. Standardized meta-analyses were performed for eligible studies. Results indicate that inulin supplementation significantly reduced aberrant crypt foci count in rats (SMD = -3.805, 95% CI, -7.348 to -0.262, p < 0.001), increased cecal weight (SMD = 6.723, 95% CI, 3.395-10.051, p = 0.000), enhanced colonic lactobacillus counts (SMD = 1.307, 95% CI, 0.644-1.970, p = 0.000), decreased coliform bacteria (SMD = -1.659, 95% CI, -2.147 to -1.171, p = 0.000), and elevated colonic short-chain fatty acids (SCFAs) levels, including acetate (SMD = 3.50, 95% CI, 1.111-5.890, p < 0.001), propionate (SMD = 3.081, 95% CI, 1.416-4.746, p < 0.001), and butyrate (SMD = 4.471, 95% CI, 2.464-6.478, p < 0.001). This systematic review demonstrates inulin's chemopreventive effects against CRC in animal models by enhancing beneficial gut bacteria (e.g., lactobacillus) and boosting SCFAs. Findings advocate integrating inulin-rich foods/supplements into prevention strategies for precision prebiotic development via SCFA-mediated epigenetic and antitumor mechanisms.
Nutrition bulletin · 2025
Manipulation of the mouse gut microbiome has been shown to increase gut-derived short-chain fatty acids and improve exercise capacity. Associations between exercise performance and gut microbiome composition and metabolites have also been identified in human studies. Yet there is little direct evidence that prebiotics are able to increase acetate production and improve exercise capacity in human participants. We conducted a randomised controlled cross-over trial with 21 healthy and active males (35.0 ± 6.9 years; 24.4 ± 2.7 kg/m2) to investigate the effect of 15 g of inulin (prebiotic) on exercise performance (15 km cycle time trial), compared to placebo. Time to completion of a 15 km time trial was the primary outcome, while plasma acetate concentration and markers of inulin fermentation (breath H2 concentration) and muscle oxygenation were measured to explore potential mechanisms of action. Time to complete the 15 km time trial was not affected by inulin mean difference between inulin and placebo trials: (-10.37 s, 95% CI [-150.8, 130.1 s], p = 0.884). The marker of inulin fermentation (H2 concentration increase from baseline) was significantly higher in inulin compared to placebo condition (+42.61 ppm, 95% CI [30.04, 55.19], p = 0.001 and +31.13 ppm, 95% CI [3.73, 58.51], p = 0.029, respectively), but plasma acetate concentration did not differ between conditions. Likewise, markers of muscle oxygenation were not different between inulin and placebo. Our current results do not support the acute use of prebiotics to improve exercise performance in adults. Possible explanations for the absence of ergogenic effects may be that the timing between prebiotic ingestion and exercise was too short to allow for complete fermentation into acetate, participants were in a fasted rather than a fed state, or that the single dose of supplement was insufficient. These factors, together with advanced methods (stable isotope studies) should be investigated in a follow-up study to elucidate the fate and role of colonic-derived acetate during exercise.
Scientific reports · 2025
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that causes joint dysfunction and is associated with changes in serum levels of some biomarkers. The present study investigated the effect of inulin supplementation on pain intensity, clinical outcomes, and quality of life in patients with RA.In a randomized, triple-blind, parallel clinical trial, 60 patients over 18 years of age with RA were randomly assigned to receive either 10 g of inulin or maltodextrin per day for 8 weeks. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were assessed using biochemical kits at the beginning and end of the study. Clinical outcomes were also evaluated, including morning stiffness and pain intensity measured by the Visual Analog Scale (VAS), hand grip measured by a sphygmomanometer (Seca), disease activity assessed using the Disease Activity Score 28 (DAS-28), and overall quality of life determined by the Health Assessment Questionnaire (HAQ).The number of swollen joints, tender joints, pain intensity, and DAS-28 significantly decreased in both groups. However, hand grip, morning stiffness, ESR, CRP, and HAQ improved significantly only in the intervention group. After the intervention, in the intervention group compared to the control group, serum CRP levels significantly decreased (P = 0.02), while serum ESR levels showed no significant reduction (P = 0.45). The number of tender joints (P = 0.002), the number of swollen joints (P = 0.04), DAS-28, HAQ, morning stiffness, and hand grip strength (P = 0.02) significantly improved, but pain intensity did not change (P = 0.11).Inulin appears to benefit inflammatory status, disease activity, and clinical outcomes in patients with rheumatoid arthritis. Incorporating it into their treatment protocol could be valuable for managing their condition.Trial registration: Our study was approved in the Iranian Registry of Clinical Trials ( www.irct.ir ) on 10/5/2023, with the registration number IRCT20230506058098N1.
Scientific reports · 2025
The gut microbiota plays a key role in regulating energy balance via gut-brain axis (GBA). Dysbiosis can disrupt this communication, contributing to obesity. This study aimed to assess the effects of inulin supplementation on GBA-related amino acids and bioactive molecules in children with obesity. Children aged 7-15 were randomly assigned to 3 treatment groups for 6 months: inulin supplementation, isocaloric maltodextrin (placebo), or dietary fiber advice. Plasma amino acids and bioactive molecules were analyzed using LC-MS/MS at baseline and month 6. Relationships of changes in GBA-related compounds with changes in gut microbiota were evaluated. By month 6, principal component analysis trajectories showed clustering across all groups, involving 154 children, but indicated potential metabolic shifts, particularly in the inulin group. S-plots identified significant changes in GBA-related compounds, with only the inulin group showing marked increases in putrescine, spermine, and tyrosine from baseline (all P < 0.0001). Inulin supplementation significantly upregulated putrescine over time compared to the placebo group (P = 0.021), suggesting enhanced GBA communication. Changes in specific GBA-related compounds in the inulin group were significantly associated with gut microbiota changes. These findings indicate that inulin effectively modulates GBA-related bioactive molecules, potentially mediating its effect on childhood obesity management through putrescine, spermine, and tyrosine.Clinical Trial Registry number: NCT03968003. Registered 30/05/2019.
European review for medical and pharmacological sciences · 2026
Several factors, as genetics, diet, and gut microbiota, are associated with the development of type 1 diabetes (T1D). Akkermansia muciniphila, an abundant bacterium in human microbiota, has anti-inflammatory properties and can correct metabolic disorders. The effects of the administration of inulin, a prebiotic which increases Akkermansia muciniphila gut levels, are unknown in subjects with T1D. 49 subjects with T1D, age 46 [37-53] years, 30 females (61%), duration of disease 20 [11-27] years, HbA1c 64 [59-72] mmol/mol, were randomized in group A (inulin 3 g twice daily for 3 months + insulin, n=24) and in group B (insulin alone, n=25). Body weight, glycated hemoglobin (HbA1c), daily insulin units, continuous glucose monitoring (CGM) metrics, and Bristol stool scale (BSS) score were collected at enrollment and after 3 months. After 3 months, subjects in group A showed a significant decrease in body weight [group A -2 (-3; 0) kg and group B 0 (-1; 1) kg, p=0.03] and daily insulin units [group A -1.5 UI (-3.1; 0) vs. group B 0.6 (0; 1.7), p=0.01]. After 3 months, changes in HbA1c and CGM were similar between groups. In both groups, there was no change in BSS score (p=0.39) nor in Akkermansia muciniphila gut levels. Inulin was associated with a slight body weight decrease and insulin need reduction, but not with an increase in Akkermansia muciniphila levels. More studies are required to explore this issue.
Nutrients · 2026
Background: Emerging evidence links the gut microbiome to chronic pain processing. Inulin, a prebiotic fibre, modulates the gut microbiome, while physiotherapy-supported exercise (PSE) improves pain and function. We evaluated the effects of inulin supplementation with and without PSE on knee osteoarthritis (OA) pain. Methods: In a 2 × 2 factorial RCT, 117 community-dwelling adults with knee OA received 6 weeks of: (A) 20 g/day inulin, (B) digital PSE (Joint Academy™), (C) inulin +PSE, or (D) 10 g/day maltodextrin. Primary outcome: pain (Numerical Rating Scale). Secondary: 30 s sit-to-stand (30-CST), timed up and go (TUG), grip strength, and quantitative sensory testing. Serum short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1) were measured. The study was not powered to detect synergistic interaction. Results: A total of 117 participants (58.1% female; mean ± SD age = 67.5 ± 9.4 years; BMI = 29.5 ± 5.3 kg/m2; NRS = 3.96 ± 2.67) completed the trial. Pain improved with inulin (baseline-adjusted between-group mean difference (Δ) = -1.11 [95%CI -2.18, -0.04], p = 0.045) and PSE (Δ = -1.55 [95%CI -2.52, -0.58], p = 0.002) compared to placebo, with no synergistic effect. PSE improved TUG (p = 0.02) and 30-CST (p = 0.0004), while inulin improved grip strength (p = 0.002), pressure pain thresholds (p = 0.009) and temporal summation (p = 0.025) compared to placebo and had significantly lower dropout rates (3.6%) compared with PSE (21% p < 0.01). Only inulin increased SCFA butyrate (p = 0.0248) and GLP-1 (p = 0.0109), and higher GLP-1 was associated with improved grip strength, suggesting a gut-muscle link. Conclusions: Inulin and PSE each produced meaningful pain reductions. Only inulin improved pain sensitivity and grip strength, the latter paralleled by increased GLP-1, and had much higher rates of retention compared to PSE.
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society · 2024
We aimed to clarify the clinical utility of measuring serum pancreatic enzymes after endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of predicting post-ERCP pancreatitis (PEP) by a meta-analysis of diagnostic test accuracy studies. Studies on the prediction accuracy of PEP by serum amylase or lipase measured at 2, 3, and 4 h after ERCP were collected. A literature search was performed in PubMed and the Cochrane Library database for studies published between January 1980 and March 2023. The quality of individual studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Data were analyzed using Meta-DiSc 2.0 software. We searched the databases and identified 20 observational studies (12,313 participants). PEPs were defined according to criteria by Cotton or modified Cotton, revised Atlanta criteria, or the Japanese criteria. Meta-analysis of eight studies (4389 participants) showed a pooled sensitivity of 71.1% (95% confidence interval [CI] 56.1-82.5) and pooled specificity of 91.2% (95% CI 85.9-94.6) for the serum amylase cut-off value at 3 times the upper limit of normal (ULN). Another meta-analysis of five studies (1970 participants) showed a pooled sensitivity of 85.8% (95% CI 61.9-95.7) and pooled specificity of 85.3% (95% CI 81.9-88.1) for the serum lipase cut-off value at 3 times ULN. Despite a high risk of bias due to various reference standards, this updated meta-analysis and the utility assessment by a decision tree showed the utility of serum amylase or lipase levels more than 3 times ULN measured 2-4 h after ERCP for predicting PEP.
Tuberculosis (Edinburgh, Scotland) · 2024
Isoniazid-induced pancreatitis is a potentially serious adverse drug reaction, however, the frequency of its occurrence is unknown. We conducted a systematic review to explore this adverse drug reaction comprehensively. We performed an advanced search in PubMed, Web of Science, Scopus, Ovid, and Embase for studies that reported isoniazid-induced pancreatitis. From the extracted data of eligible cases, we performed a descriptive analysis and a methodological risk of bias assessment using a standardized tool. We included 16 case reports from eight countries comprising 16 patients in our systematic review. Most of the isoniazid-induced pancreatitis cases were extrapulmonary tuberculosis cases. We found the mean age across all case reports was 36.7 years. In all the cases, discontinuation of isoniazid resulted in the resolution of pancreatitis. We found the latency period for isoniazid-induced pancreatitis to be ranged from 12 to 45 days after initiation of isoniazid therapy. A low threshold for screening of pancreatitis by measuring pancreatic enzymes in patients on isoniazid presenting with acute abdominal pain is recommended. This would facilitate an early diagnosis and discontinuation of isoniazid, thus reducing the severity of pancreatitis and preventing the complications of pancreatitis.
Frontiers in endocrinology · 2024
The immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed. No study has yet evaluated whether serum exocrine pancreatic enzymes could delineate immunotherapy responders and non-responders. In this novel study, we sought to identify longitudinal trends in the most commonly measured circulating exocrine enzymes before and after treatment with anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) in individuals with new-onset type 1 diabetes (n=34). We defined response to immunotherapy as participants with at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. In the overall study (n=89), 42% of treated and 17% of placebo participants met this definition. Due to constraints of sample availability, we compared longitudinal serum amylase, lipase, and trypsin levels in a subset of responders to therapy (n=4-6), placebo "responders" (n=2), treated non-responders (n=16), and placebo non-responders (n=10). There were no differences in amylase levels between groups at baseline or six months post-treatment. Baseline levels of lipase and trypsin tended to be lower in responders; however, these variations were not significant in this small study sample. Lipase and trypsin improved to 115% of baseline in responders to immunotherapy six months after treatment and declined to 80-90% of baseline in non-responders and placebo participants (p=0.03). This difference was not present before the six-month time point. Our findings provide preliminary evidence that the exocrine pancreatic enzymes lipase and trypsin may be useful biomarkers of response to immunotherapy in type 1 diabetes. Further studies with larger numbers of participants are warranted.
Acta gastro-enterologica Belgica · 2025
The association between dipeptidyl peptidase-4 (DPP-4) inhibitors, known as gliptins, and acute pancreatitis raises growing concern. A systematic search of PubMed, Scopus and Web of Science was conducted for studies published between January 2005 and July 2024. Studies focusing on gliptin-induced pancreatitis were selected based on predefined criteria. While gliptins are effective in managing type 2 diabetes mellitus, several case reports and observational studies suggest a potential risk for inducing acute pancreatitis. Proposed mechanisms include increased pancreatic activity and cellular stress. Clinical presentation often includes abdominal pain and elevated pancreatic enzymes, necessitating prompt diagnosis and discontinuation of the offending agent. Early recognition and management, including discontinuation of the drug and supportive care, are crucial. Balancing benefits and risks of gliptin therapy is essential for ensuring patient safety and optimal outcomes. This review underscores the importance of vigilance among healthcare providers and the need for further research to develop safer therapeutic strategies.
The American journal of tropical medicine and hygiene · 2026
Scrub typhus, caused by Orientia tsutsugamushi, is a common endemic vector-borne disease in Asia that can lead to a range of systemic complications, including the rare but potentially life-threatening manifestation of acute pancreatitis. We conducted a systematic review of all reported cases of scrub typhus-associated acute pancreatitis from 1943 to 2024 using PubMed, including English, Japanese, and Chinese literature, and analyzed a total of 14 cases, including one newly identified case at our institution. Diagnostic criteria were based on compatible clinical features, elevated pancreatic enzymes, and characteristic imaging findings. The median age of patients was 47 years (range 22-75), with 69.2% of patients being male. The most frequent clinical manifestations were fever (100%), abdominal pain (92.3%), and thrombocytopenia (30.8%). Over one-third of the patients developed multiple organ dysfunction syndrome (MODS) or shock, and the mortality rate was 23.1%, with all fatalities occurring in patients with MODS. Most patients received doxycycline or azithromycin along with supportive care. The newly reported case presented with rapidly progressive pancreatitis requiring intensive care and multiple organ support, but the patient eventually recovered. These findings highlight that acute pancreatitis is an underrecognized yet severe complication of scrub typhus, often associated with poor outcomes when MODS is present. Clinicians in endemic regions should consider pancreatitis in the differential diagnoses when evaluating scrub typhus patients with abdominal symptoms or systemic inflammation. Prompt recognition and timely, aggressive management may improve survival and reduce complications in affected patients.
Panminerva medica · 2025
Malnutrition is associated with poor outcomes. Exocrine pancreatic insufficiency (EPI) may be an overlooked factor contributing to malnutrition. Early nutritional support improves the prognosis of critically ill patients. The effect of pancreatic enzyme preparations on nutritional status and prognosis in critically ill patients requires further study. An exploratory, single-center, randomized controlled trial was conducted in critically ill adult patients. A total of 768 patients admitted to the Department of Critical Care Medicine between November 2021 and August 2022 were screened, and 317 patients who met the inclusion criteria were randomized into the pancreatic enzyme replacement therapy (PERT) group or the non-pancreatic enzyme replacement therapy (NOT PERT) group. Neither group received a specific enteral nutrition formula. The formula was selected according to the patient's condition to provide the required calories and protein. The primary outcome was the change in the cross-sectional area of the rectus femoris muscle (RFCSA). Secondary outcomes included changes in rectus femoris muscle echogenicity, retinol-binding protein, and prealbumin levels; duration of mechanical ventilation; APACHE II scores; and 14-day and 28-day mortality. This trial was registered in ChiCTR under identifier 2100052385. RFCSA decreased over time. PERT combined with enteral nutrition appeared to slow the decline in RFCSA but had no significant effect on rectus femoris muscle echogenicity. PERT had no significant effect on retinol-binding protein, prealbumin, or the duration of mechanical ventilation. No significant differences were observed in APACHE II scores, 14-day mortality, or 28-day mortality. PERT may serve as an effective adjunct to nutritional support in critically ill patients.
Metabolism: clinical and experimental · 2026
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert cardiometabolic benefits beyond weight loss, yet their systemic proteomic mechanisms remain incompletely defined. We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures. In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout. Plasma and serum samples underwent SomaScan v4.1 profiling of 6249 proteins. Mixed-effects models tested Time×Treatment interactions with and without weight adjustment. Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature. Liraglutide significantly modulated 124 proteins (57 FDR < 0.05); 85 % of effects persisted after weight adjustment, indicating largely weight-independent actions. Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated. Myostatin (MSTN) was strongly suppressed (log₂ fold change -0.41; p = 1.7 × 10-6), with concurrent rises in its inhibitors WFIKKN2 and BMPR1A. Liraglutide shared 70-75 % directional overlap with semaglutide, with 25-30 % unique effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways. A semaglutide-based classifier distinguished liraglutide from placebo (AUC = 0.82; sensitivity 0.89; specificity 0.60). Downregulated proteins were genetically linked to coronary artery disease and type 2 diabetes (FDR < 0.05). Short-term liraglutide reproduces the core GLP-1RA proteomic fingerprint while uniquely suppressing myostatin and vascular remodeling pathways. These rapid, largely weight-independent molecular responses indicate early cardioprotective and myostatin-inhibitor signaling changes that could be relevant for future muscle-preserving strategies, supporting individualized GLP-1RA use beyond weight loss alone.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition · 2024
Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there's a lack of studies on grape seed extract's (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 μM vs. 4.59±1.19 μM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. -0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. -12.0±37.5; 3.80±14.8 vs. -3.92±9.55; 5.08 5.26 vs. -7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study.
BMC complementary medicine and therapies · 2024
Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).
BMC oral health · 2024
To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans). This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias. Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content. The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.