In this study, the effects of atmospheric cold plasma (ACP) as a non-thermal sterilization method on the quality of different muscle tissues parts in Large yellow croaker (Larimichthys crocea) during refrigerated storage were systematically investigated. The results of this study demonstrate that atmospheric cold plasma treatment (ACP, 40 kV, 90 s) significantly inhibited the accumulation of TVB-N and TBARS (p < 0.05) in fish samples while effectively mitigating the decline in water-holding capacity. Compared with the control group, the total sulfhydryl content in dorsal and ventral muscles increased significantly by 20 and 45%, respectively, and Ca2+-ATPase activity was also significantly enhanced by 14 and 20% (p < 0.05) after treatment. Furthermore, ACP treatment significantly maintained the color parameters (L, a, b*) and textural properties (hardness, elasticity, etc.) of fish meat (p < 0.05). ACP has an inhibitory effect on post-oxidation. GC-MS analysis detected 60 volatile compounds, with significantly reduced aldehyde levels in the treated group, demonstrating effective inhibition of undesirable flavor formation. These findings collectively indicate that ACP treatment effectively delays quality deterioration in fish during refrigerated storage through multiple synergistic mechanisms.
{"title":"Effect of atmospheric cold plasma on the quality of fish meat from different parts of larger yellow croaker during refrigeration.","authors":"Chenyi Yang, Jiaxi Cai, Shanggui Deng, Mengyuan Xu, Huiqi Dai, Sitong Shan, Yuanpei Gao, Ruizhi Yang, Hao Lan","doi":"10.3389/fnut.2026.1750328","DOIUrl":"10.3389/fnut.2026.1750328","url":null,"abstract":"<p><p>In this study, the effects of atmospheric cold plasma (ACP) as a non-thermal sterilization method on the quality of different muscle tissues parts in Large yellow croaker (<i>Larimichthys crocea</i>) during refrigerated storage were systematically investigated. The results of this study demonstrate that atmospheric cold plasma treatment (ACP, 40 kV, 90 s) significantly inhibited the accumulation of TVB-N and TBARS (<i>p</i> < 0.05) in fish samples while effectively mitigating the decline in water-holding capacity. Compared with the control group, the total sulfhydryl content in dorsal and ventral muscles increased significantly by 20 and 45%, respectively, and Ca<sup>2+</sup>-ATPase activity was also significantly enhanced by 14 and 20% (<i>p</i> < 0.05) after treatment. Furthermore, ACP treatment significantly maintained the color parameters (L<i>, a</i>, b*) and textural properties (hardness, elasticity, etc.) of fish meat (<i>p</i> < 0.05). ACP has an inhibitory effect on post-oxidation. GC-MS analysis detected 60 volatile compounds, with significantly reduced aldehyde levels in the treated group, demonstrating effective inhibition of undesirable flavor formation. These findings collectively indicate that ACP treatment effectively delays quality deterioration in fish during refrigerated storage through multiple synergistic mechanisms.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1750328"},"PeriodicalIF":4.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12886045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27eCollection Date: 2025-01-01DOI: 10.3389/fnut.2025.1725495
Li Liu, Yanyan Meng, Lianyi Hu, Runa A, Ying Zhang, Zhuye Gao
Background: Cardiometabolic multimorbidity (CMM) is a growing public health challenge, with limited practical biomarkers available for early detection. Given the established relationship between impaired lipid as well as glucose homeostasis and CMM, this study aims to examine the association between the cholesterol, high-density lipoprotein, and glucose (CHG) index and CMM risk.
Methods: A nationwide prospective cohort (CHARLS, 2011-2018; n = 8,425) and a multi-community cross-sectional cohort (Beijing, 2021; n = 1,734) were analyzed. In the CHARLS cohort, Cox proportional hazards models were used to assess the association between the CHG index and incident CMM. In both cohorts, logistic regression and restricted cubic splines (RCS) were employed to examine the cross-sectional association between CHG and CMM. Time-dependent receiver operating characteristic (ROC) curves evaluated predictive performance in CHARLS cohort, while conventional ROC analysis was used in the multi-community cohort. Subgroup analyses, interaction tests, and sensitivity analyses further evaluated result reliability.
Results: In the CHARLS cohort, 491 (5.8%) individuals developed incident CMM over 7 years of follow-up. CHG levels were significantly elevated in patients with CMM (p < 0.001). Overall, the CHG index was associated with incident CMM (OR = 1.97, 95% CI: 1.53-2.53; HR = 1.82, 95% CI: 1.45-2.27). A nonlinear positive association was found in both cohorts. The CHG index demonstrated stable predictive accuracy over time (AUCs: 0.67 at 3 years, 0.64 at 5 years, 0.63 at 7 years). These findings were robustly validated in the multi-community cohort, where the CHG index was also significantly associated with prevalent CMM (OR = 2.82, 95% CI: 2.04-3.90). Subgroup analyses confirmed robustness across populations, especially among those without baseline cardiometabolic disease.
Conclusion: An elevated CHG index is independently associated with an increased risk of CMM across both prospective and cross-sectional studies. It serves as a robust and reproducible predictor for the early identification of CMM in diverse Chinese populations.
背景:心脏代谢多病(CMM)是一个日益严峻的公共卫生挑战,可用于早期检测的实用生物标志物有限。鉴于脂质和葡萄糖稳态受损与CMM之间的既定关系,本研究旨在研究胆固醇、高密度脂蛋白和葡萄糖(CHG)指数与CMM风险之间的关系。方法:对全国前瞻性队列(CHARLS, 2011-2018; n = 8,425)和多社区横断面队列(北京,2021;n = 1,734)进行分析。在CHARLS队列中,使用Cox比例风险模型来评估CHG指数与事件CMM之间的关系。在这两个队列中,采用logistic回归和限制性三次样条(RCS)来检验CHG和CMM之间的横断面相关性。时间依赖的受试者工作特征(ROC)曲线评估CHARLS队列的预测效果,而传统的ROC分析用于多社区队列。亚组分析、相互作用试验和敏感性分析进一步评估了结果的可靠性。结果:在CHARLS队列中,491人(5.8%)在7 年的随访中出现了突发CMM。结论:在前瞻性和横断面研究中,CHG指数升高与CMM风险增加独立相关。它可作为中国不同人群CMM早期识别的可靠且可重复的预测因子。
{"title":"Association between the CHG index and cardiometabolic multimorbidity: a nationwide prospective cohort and multi-community cross-sectional study.","authors":"Li Liu, Yanyan Meng, Lianyi Hu, Runa A, Ying Zhang, Zhuye Gao","doi":"10.3389/fnut.2025.1725495","DOIUrl":"10.3389/fnut.2025.1725495","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic multimorbidity (CMM) is a growing public health challenge, with limited practical biomarkers available for early detection. Given the established relationship between impaired lipid as well as glucose homeostasis and CMM, this study aims to examine the association between the cholesterol, high-density lipoprotein, and glucose (CHG) index and CMM risk.</p><p><strong>Methods: </strong>A nationwide prospective cohort (CHARLS, 2011-2018; <i>n</i> = 8,425) and a multi-community cross-sectional cohort (Beijing, 2021; <i>n</i> = 1,734) were analyzed. In the CHARLS cohort, Cox proportional hazards models were used to assess the association between the CHG index and incident CMM. In both cohorts, logistic regression and restricted cubic splines (RCS) were employed to examine the cross-sectional association between CHG and CMM. Time-dependent receiver operating characteristic (ROC) curves evaluated predictive performance in CHARLS cohort, while conventional ROC analysis was used in the multi-community cohort. Subgroup analyses, interaction tests, and sensitivity analyses further evaluated result reliability.</p><p><strong>Results: </strong>In the CHARLS cohort, 491 (5.8%) individuals developed incident CMM over 7 years of follow-up. CHG levels were significantly elevated in patients with CMM (<i>p</i> < 0.001). Overall, the CHG index was associated with incident CMM (OR = 1.97, 95% CI: 1.53-2.53; HR = 1.82, 95% CI: 1.45-2.27). A nonlinear positive association was found in both cohorts. The CHG index demonstrated stable predictive accuracy over time (AUCs: 0.67 at 3 years, 0.64 at 5 years, 0.63 at 7 years). These findings were robustly validated in the multi-community cohort, where the CHG index was also significantly associated with prevalent CMM (OR = 2.82, 95% CI: 2.04-3.90). Subgroup analyses confirmed robustness across populations, especially among those without baseline cardiometabolic disease.</p><p><strong>Conclusion: </strong>An elevated CHG index is independently associated with an increased risk of CMM across both prospective and cross-sectional studies. It serves as a robust and reproducible predictor for the early identification of CMM in diverse Chinese populations.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1725495"},"PeriodicalIF":4.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12886036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27eCollection Date: 2026-01-01DOI: 10.3389/fnut.2026.1758733
Nabeel Ahmed Farooqui, Ata Ur Rehman, Asif Iqbal Khan, Hidayat Ullah, Muhsin Ali, Waleed Yousuf, Yamina Alioui, Aamna Atta, Mohammad Abusidu, Bilal Saleh, Eslam Ghaleb, Yanxia Li, Yi Xin, Nimra Zafar Siddiqui, Liang Wang
Introduction: Immunocompetence reflects the immune system's capacity to mount effective responses against antigens. Cyclophosphamide (CYP), a chemotherapeutic and experimental immunosuppressive agent, disrupts T-helper (Th)1/Th2 balance and compromises immune organ integrity. Bioactive peptides derived from the sea cucumber Apostichopus japonicus, which is rich in type I collagen, have shown emerging immunomodulatory potential.
Methods: A collagenase-derived sea cucumber protein hydrolysate (SCPH) was prepared using Clostridium collagenase-I and characterized for amino acid composition and peptide profiles. BALB/c mice were administered CYP (80 mg/kg, i.p.) to induce immunosuppression, followed by oral SCPH treatment. Body weight, spleen and thymus indices, leukocyte counts, Th1/Th2-associated gene expression (IFNG, TBX21, IL4, GATA3), serum cytokines and immunoglobulins, and splenic histology and immunohistochemistry were evaluated.
Results: CYP treatment induced body weight loss, reduced immune organ indices, altered leukocyte profiles, and disrupted Th1/Th2-associated markers. SCPH administration partially reversed these changes by restoring spleen and thymus indices, normalizing circulating immune cell levels, upregulating Th1-associated genes (IFNG, TBX21), and downregulating Th2-associated genes (IL4, GATA3). SCPH also increased serum Th1 mediators (IFNG, IgG, IgM) while reducing Th2-associated markers (IL-4, IL-10, IgA, sIgA). Histological and immunohistochemical analyses confirmed improved splenic architecture with elevated T-bet and reduced GATA3 expression.
Discussion/conclusion: These findings indicate that SCPH promotes Th1-biased immune rebalancing in CYP-induced immunosuppressed mice, suggesting its potential as a marine-derived immunonutritional agent. Further mechanistic studies are warranted to explore its therapeutic and translational applications.
{"title":"Sea cucumber protein hydrolysate restores the Th1/Th2 paradigm in cyclophosphamide-induced immunosuppressed mice.","authors":"Nabeel Ahmed Farooqui, Ata Ur Rehman, Asif Iqbal Khan, Hidayat Ullah, Muhsin Ali, Waleed Yousuf, Yamina Alioui, Aamna Atta, Mohammad Abusidu, Bilal Saleh, Eslam Ghaleb, Yanxia Li, Yi Xin, Nimra Zafar Siddiqui, Liang Wang","doi":"10.3389/fnut.2026.1758733","DOIUrl":"10.3389/fnut.2026.1758733","url":null,"abstract":"<p><strong>Introduction: </strong>Immunocompetence reflects the immune system's capacity to mount effective responses against antigens. Cyclophosphamide (CYP), a chemotherapeutic and experimental immunosuppressive agent, disrupts T-helper (Th)1/Th2 balance and compromises immune organ integrity. Bioactive peptides derived from the sea cucumber <i>Apostichopus japonicus</i>, which is rich in type I collagen, have shown emerging immunomodulatory potential.</p><p><strong>Methods: </strong>A collagenase-derived sea cucumber protein hydrolysate (SCPH) was prepared using Clostridium collagenase-I and characterized for amino acid composition and peptide profiles. BALB/c mice were administered CYP (80 mg/kg, i.p.) to induce immunosuppression, followed by oral SCPH treatment. Body weight, spleen and thymus indices, leukocyte counts, Th1/Th2-associated gene expression (IFNG, TBX21, IL4, GATA3), serum cytokines and immunoglobulins, and splenic histology and immunohistochemistry were evaluated.</p><p><strong>Results: </strong>CYP treatment induced body weight loss, reduced immune organ indices, altered leukocyte profiles, and disrupted Th1/Th2-associated markers. SCPH administration partially reversed these changes by restoring spleen and thymus indices, normalizing circulating immune cell levels, upregulating Th1-associated genes (IFNG, TBX21), and downregulating Th2-associated genes (IL4, GATA3). SCPH also increased serum Th1 mediators (IFNG, IgG, IgM) while reducing Th2-associated markers (IL-4, IL-10, IgA, sIgA). Histological and immunohistochemical analyses confirmed improved splenic architecture with elevated T-bet and reduced GATA3 expression.</p><p><strong>Discussion/conclusion: </strong>These findings indicate that SCPH promotes Th1-biased immune rebalancing in CYP-induced immunosuppressed mice, suggesting its potential as a marine-derived immunonutritional agent. Further mechanistic studies are warranted to explore its therapeutic and translational applications.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1758733"},"PeriodicalIF":4.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12886032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27eCollection Date: 2025-01-01DOI: 10.3389/fnut.2025.1664787
Jiaqian Zhong, Chuang Fan, Lin Li, Jiaming Wang, Huo Li, Zhongbo Bian, Hao Wang, Zhangming Pei, Hongchao Wang, Wenwei Lu, Juan Li
Objective: Chronic inflammation is prevalent in peritoneal dialysis (PD) patients, however, the potential impact of diet-related inflammation on PD patients has not been fully investigated. We aimed to explore the association between the Energy-adjusted dietary inflammatory index (E-DII) and malnutrition status in PD patients.
Methods: A total of 147 PD patients from Shanghai Changzheng Hospital were included in this cross-sectional study. E-DII were calculated from the dietary data collected using a validated Food Frequency Questionnaire (FFQ). Malnutrition was determined according to the Malnutrition-Inflammation Score (MIS). Least absolute shrinkage and selection operator (LASSO) regression was carried out to screen the key nutrients associated with the risk of malnutrition. Univariate and multivariate logistic regression analyses were employed to explore the association between the key nutrients, E-DII and malnutrition.
Results: The mean E-DII score was -0.367, ranging from -2.958 to 2.379. The mean duration of PD was 47.9 months. The overall prevalence of malnutrition was 48.3%. The key dietary nutrient associated with malnutrition was total fiber. In fully adjusted model, higher total fiber intake was associated with a lower risk of malnutrition in PD patients (ORtertile 3 vs. 1 = 0.29, 95% CI: 0.10-0.80, p = 0.018). Conversely, a higher E-DII score was associated with a higher risk of malnutrition (ORtertile 3 vs. 1 = 3.64, 95% CI: 1.25-10.64, p = 0.018).
Conclusion: Diets high in total fiber were associated with a reduced risk of malnutrition in PD patients. On the other hand, pro-inflammatory diets are associated with an increased risk of malnutrition in PD patients. Further studies are needed to validate and develop strategies to reduce the dietary inflammatory burden in PD patients.
目的:慢性炎症在腹膜透析(PD)患者中普遍存在,然而,饮食相关炎症对PD患者的潜在影响尚未得到充分研究。我们旨在探讨PD患者能量调节饮食炎症指数(E-DII)与营养不良状况之间的关系。方法:选取上海市长征医院PD患者147例进行横断面研究。E-DII是根据使用经过验证的食物频率问卷(FFQ)收集的饮食数据计算的。根据营养不良炎症评分(MIS)判定营养不良。最小绝对收缩和选择算子(LASSO)回归进行筛选与营养不良风险相关的关键营养素。采用单因素和多因素logistic回归分析探讨关键营养素、E-DII与营养不良之间的关系。结果:E-DII平均评分为-0.367,范围为-2.958 ~ 2.379。PD的平均持续时间为47.9 个月。营养不良的总体发生率为48.3%。与营养不良相关的主要膳食营养素是总纤维。在完全调整模型中,较高的总纤维摄入量与PD患者较低的营养不良风险相关(ORtertile 3 vs. 1 = 0.29,95% CI: 0.10-0.80, p = 0.018)。相反,较高的E-DII评分与较高的营养不良风险相关(ORtertile 3 vs. 1 = 3.64,95% CI: 1.25-10.64, p = 0.018)。结论:总纤维含量高的饮食与PD患者营养不良的风险降低有关。另一方面,促炎饮食与PD患者营养不良风险增加有关。需要进一步的研究来验证和制定减少PD患者饮食炎症负担的策略。
{"title":"Association between dietary inflammation index and malnutrition status in peritoneal dialysis patients: a cross-sectional study.","authors":"Jiaqian Zhong, Chuang Fan, Lin Li, Jiaming Wang, Huo Li, Zhongbo Bian, Hao Wang, Zhangming Pei, Hongchao Wang, Wenwei Lu, Juan Li","doi":"10.3389/fnut.2025.1664787","DOIUrl":"10.3389/fnut.2025.1664787","url":null,"abstract":"<p><strong>Objective: </strong>Chronic inflammation is prevalent in peritoneal dialysis (PD) patients, however, the potential impact of diet-related inflammation on PD patients has not been fully investigated. We aimed to explore the association between the Energy-adjusted dietary inflammatory index (E-DII) and malnutrition status in PD patients.</p><p><strong>Methods: </strong>A total of 147 PD patients from Shanghai Changzheng Hospital were included in this cross-sectional study. E-DII were calculated from the dietary data collected using a validated Food Frequency Questionnaire (FFQ). Malnutrition was determined according to the Malnutrition-Inflammation Score (MIS). Least absolute shrinkage and selection operator (LASSO) regression was carried out to screen the key nutrients associated with the risk of malnutrition. Univariate and multivariate logistic regression analyses were employed to explore the association between the key nutrients, E-DII and malnutrition.</p><p><strong>Results: </strong>The mean E-DII score was -0.367, ranging from <i>-</i>2.958 to 2.379. The mean duration of PD was 47.9 months. The overall prevalence of malnutrition was 48.3%. The key dietary nutrient associated with malnutrition was total fiber. In fully adjusted model, higher total fiber intake was associated with a lower risk of malnutrition in PD patients (OR<sub>tertile</sub> 3 vs. 1 = 0.29, 95% CI: 0.10-0.80, <i>p</i> = 0.018). Conversely, a higher E-DII score was associated with a higher risk of malnutrition (OR<sub>tertile</sub> 3 vs. 1 = 3.64, 95% CI: 1.25-10.64, <i>p</i> = 0.018).</p><p><strong>Conclusion: </strong>Diets high in total fiber were associated with a reduced risk of malnutrition in PD patients. On the other hand, pro-inflammatory diets are associated with an increased risk of malnutrition in PD patients. Further studies are needed to validate and develop strategies to reduce the dietary inflammatory burden in PD patients.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1664787"},"PeriodicalIF":4.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12886001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with established hepatoprotective properties, has garnered attention for its potential role in metabolic health. This study provides scientific validation for these traditional uses by demonstrating UDCA's protective mechanisms against non-alcoholic fatty liver disease (NAFLD) through gut microbiota modulation and metabolic regulation. This study elucidates the therapeutic mechanisms of UDCA against high-fat diet-induced NAFLD through integrated microbiota-metabolomics analysis.
Methods: Using a 12-week murine NAFLD model, oral UDCA (15 mg/kg/day and 30 mg/kg/day) was administered to evaluate its hepatoprotective effects. Hepatic steatosis and injury were assessed via serum ALT/AST levels, lipid profiles, and histopathology. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified bile acid metabolites, while 16S rRNA sequencing analyzed gut microbiota composition. Serum metabolomics and network pharmacology were employed to identify metabolic pathways and mechanistic targets, respectively. Molecular analyses (qPCR/Western blot) assessed PPARγ/Nrf2/NF-κB signaling.
Results: UDCA treatment significantly ameliorated high-fat diet-induced NAFLD, as demonstrated by improved serum ALT/AST levels, attenuated hepatic steatosis, and reduced histopathological damage. UPLC-MS/MS analysis revealed a marked reorganization of bile acid metabolism, characterized by elevated non-12α-hydroxylated bile acids (UDCA, TUDCA) and enhanced alternative synthesis via CYP27A1 upregulation. 16S rRNA sequencing identified UDCA-driven restructuring of the gut microbiota, with specific enrichment of short-chain fatty acid-producing Muribaculum spp. and suppression of pro-inflammatory Prevotella (CAG-485). Serum metabolomics further confirmed these benefits, showing increased eicosapentaenoic acid (anti-inflammatory) and decreased long-chain acylcarnitines (lipid peroxidation markers). At the molecular level, UDCA activated PPARγ/Nrf2 antioxidative signaling while inhibiting NF-κB-mediated inflammation, and network pharmacology analysis identified 225 potential targets (including TNF-α, IL6, and NF-κB) within lipid/atherosclerosis pathways, collectively underscoring UDCA's multimodal protective mechanisms against NAFLD.
Conclusion: These findings validate UDCA's multifaceted hepatoprotection via microbiota-bile acid crosstalk and metabolic-inflammatory modulation. The study provides a mechanistic basis for UDCA's traditional use in hepatobiliary disorders by integrating microbial, metabolic, and molecular evidence.
{"title":"Ursodeoxycholic acid alleviates high-fat diet-induced liver injury by modulating gut microbiota-mediated bile acid metabolism: an integrated microbiota-metabolomics analysis.","authors":"Xueyun Dong, Wen Sun, Hao Xu, Yunhan Xie, Jiayuan He, Xuehui Liu, Xinyu Liu, Asmaa Ali, Min Chen, Leilei Zhang, Liang Wu, Keke Shao","doi":"10.3389/fnut.2026.1714100","DOIUrl":"10.3389/fnut.2026.1714100","url":null,"abstract":"<p><strong>Purpose: </strong>Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with established hepatoprotective properties, has garnered attention for its potential role in metabolic health. This study provides scientific validation for these traditional uses by demonstrating UDCA's protective mechanisms against non-alcoholic fatty liver disease (NAFLD) through gut microbiota modulation and metabolic regulation. This study elucidates the therapeutic mechanisms of UDCA against high-fat diet-induced NAFLD through integrated microbiota-metabolomics analysis.</p><p><strong>Methods: </strong>Using a 12-week murine NAFLD model, oral UDCA (15 mg/kg/day and 30 mg/kg/day) was administered to evaluate its hepatoprotective effects. Hepatic steatosis and injury were assessed via serum ALT/AST levels, lipid profiles, and histopathology. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified bile acid metabolites, while 16S rRNA sequencing analyzed gut microbiota composition. Serum metabolomics and network pharmacology were employed to identify metabolic pathways and mechanistic targets, respectively. Molecular analyses (qPCR/Western blot) assessed PPARγ/Nrf2/NF-κB signaling.</p><p><strong>Results: </strong>UDCA treatment significantly ameliorated high-fat diet-induced NAFLD, as demonstrated by improved serum ALT/AST levels, attenuated hepatic steatosis, and reduced histopathological damage. UPLC-MS/MS analysis revealed a marked reorganization of bile acid metabolism, characterized by elevated non-12α-hydroxylated bile acids (UDCA, TUDCA) and enhanced alternative synthesis <i>via</i> CYP27A1 upregulation. 16S rRNA sequencing identified UDCA-driven restructuring of the gut microbiota, with specific enrichment of short-chain fatty acid-producing <i>Muribaculum</i> spp. and suppression of pro-inflammatory <i>Prevotella</i> (<i>CAG-485</i>). Serum metabolomics further confirmed these benefits, showing increased eicosapentaenoic acid (anti-inflammatory) and decreased long-chain acylcarnitines (lipid peroxidation markers). At the molecular level, UDCA activated PPARγ/Nrf2 antioxidative signaling while inhibiting NF-κB-mediated inflammation, and network pharmacology analysis identified 225 potential targets (including TNF-<i>α</i>, IL6, and NF-κB) within lipid/atherosclerosis pathways, collectively underscoring UDCA's multimodal protective mechanisms against NAFLD.</p><p><strong>Conclusion: </strong>These findings validate UDCA's multifaceted hepatoprotection <i>via</i> microbiota-bile acid crosstalk and metabolic-inflammatory modulation. The study provides a mechanistic basis for UDCA's traditional use in hepatobiliary disorders by integrating microbial, metabolic, and molecular evidence.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1714100"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aims to evaluate the efficacy of Guiling Prescription (GP)-a medicinal food homologous formula-in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia.
Methods: Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses.
Results: GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9.
Conclusion: GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.
{"title":"Guiling prescription attenuates hyperuricemia via multi-target regulation of uric acid metabolism, renal protection, and inflammation: insights from metabolomics and network pharmacology.","authors":"YuKun Wang, RenJie Ding, Yaxuan Guo, TianHui Zhou, Huichun Zhao, HuiWu Liu, XueMei Qin, XiaoXia Gao","doi":"10.3389/fnut.2025.1738623","DOIUrl":"10.3389/fnut.2025.1738623","url":null,"abstract":"<p><strong>Background: </strong>This study aims to evaluate the efficacy of Guiling Prescription (GP)-a medicinal food homologous formula-in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia.</p><p><strong>Methods: </strong>Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses.</p><p><strong>Results: </strong>GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9.</p><p><strong>Conclusion: </strong>GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1738623"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Plant-based diets may lower breast cancer risk, but their impact on breast cancer-related mortality is unclear. We explored associations of plant-based dietary patterns (Healthful Plant-Based Diet Index [HPDI/PDI]) and micronutrient intake with breast cancer incidence and all-cause mortality in patients.
Methods: Using data of UK Biobank (UKB; 67,045 cancer-free participants; 3,397 breast cancer patients) and Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed dietary scores and micronutrient intake via multivariate Cox regression, restricted cubic splines, and predictive models (concordance index, Random Forest, and time-dependent ROC).
Results: Among 67,045 breast cancer-free participants, the highest HPDI tertile was associated with 11% lower breast cancer risk (HR = 0.89, 95%CI: 0.82-0.98) vs. lowest tertile (4% reduction per SD increase, HR = 0.96, 95%CI: 0.93-1.00). Among 3,397 breast cancer patients, the highest HPDI tertile showed 28% lower mortality (HR = 0.72, 95%CI: 0.55-0.95) vs. lowest (11% reduction per SD, HR = 0.89, 95%CI: 0.79-1.00). Individuals with high PDI scores exhibited a 39% lower risk of cancer compared to those with low scores in CLHLS (HR = 0.61, 95%CI: 0.41-0.92). Higher intakes of vitamins B2 and C, calcium, and magnesium were inversely associated with risk and mortality, while each SD increase in sodium raised mortality risk by 15% (HR = 1.15, 95%CI: 1.01-1.32). Predictive models showed optimal 5-year performance overall; micronutrients alone best predicted breast cancer risk across timepoints, while HPDI peaked for 5-year mortality prediction (AUC = 0.625). The combined model achieved superior 10-year prognosis.
Conclusions: High adherence to a healthful plant-based diet, together with sufficient intake of key micronutrients and reduced sodium consumption, may contribute to breast cancer prevention and improved survival outcomes.
{"title":"Plant-based dietary patterns, micronutrient status and breast cancer outcomes: a joint analysis of UK Biobank and Chinese longitudinal healthy longevity survey.","authors":"Weizhe Xu, Wen Gu, Yanqiu Huang, Shuli Li, Honglin Liu, Xun Zhu","doi":"10.3389/fnut.2025.1748611","DOIUrl":"10.3389/fnut.2025.1748611","url":null,"abstract":"<p><strong>Background: </strong>Plant-based diets may lower breast cancer risk, but their impact on breast cancer-related mortality is unclear. We explored associations of plant-based dietary patterns (Healthful Plant-Based Diet Index [HPDI/PDI]) and micronutrient intake with breast cancer incidence and all-cause mortality in patients.</p><p><strong>Methods: </strong>Using data of UK Biobank (UKB; 67,045 cancer-free participants; 3,397 breast cancer patients) and Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed dietary scores and micronutrient intake via multivariate Cox regression, restricted cubic splines, and predictive models (concordance index, Random Forest, and time-dependent ROC).</p><p><strong>Results: </strong>Among 67,045 breast cancer-free participants, the highest HPDI tertile was associated with 11% lower breast cancer risk (HR = 0.89, 95%CI: 0.82-0.98) vs. lowest tertile (4% reduction per SD increase, HR = 0.96, 95%CI: 0.93-1.00). Among 3,397 breast cancer patients, the highest HPDI tertile showed 28% lower mortality (HR = 0.72, 95%CI: 0.55-0.95) vs. lowest (11% reduction per SD, HR = 0.89, 95%CI: 0.79-1.00). Individuals with high PDI scores exhibited a 39% lower risk of cancer compared to those with low scores in CLHLS (HR = 0.61, 95%CI: 0.41-0.92). Higher intakes of vitamins B2 and C, calcium, and magnesium were inversely associated with risk and mortality, while each SD increase in sodium raised mortality risk by 15% (HR = 1.15, 95%CI: 1.01-1.32). Predictive models showed optimal 5-year performance overall; micronutrients alone best predicted breast cancer risk across timepoints, while HPDI peaked for 5-year mortality prediction (AUC = 0.625). The combined model achieved superior 10-year prognosis.</p><p><strong>Conclusions: </strong>High adherence to a healthful plant-based diet, together with sufficient intake of key micronutrients and reduced sodium consumption, may contribute to breast cancer prevention and improved survival outcomes.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1748611"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26eCollection Date: 2025-01-01DOI: 10.3389/fnut.2025.1698973
Dandan Shao, Linyu He, Dayang Zhong, Kun Li, Xianming Zhang
<p><strong>Background: </strong>In recent years, the identification of reliable prognostic indicators for critically ill patients has become increasingly crucial. The Geriatric Nutritional Risk Index (GNRI), a simple and objective tool for assessing malnutrition risk, has demonstrated significant prognostic value across various disease conditions. This study aims to investigate and validate the clinical utility of GNRI in predicting 28-day mortality among critically ill patients with sepsis-associated pneumonia.</p><p><strong>Material and method: </strong>We conducted a retrospective analysis using two distinct cohorts. Critically ill elderly people with sepsis-associated pneumonia were included. The derivation cohort consisted of critically ill patients with sepsis-associated pneumonia extracted from the MIMIC-IV database, while the validation cohort comprised consecutively enrolled patients meeting identical criteria from Jinyang Hospital Affiliated to Guizhou Medical University between March 2023 and March 2025. Key baseline variables including demographics, comorbidities, and severity scores were analyzed. We employed restricted cubic spline regression, multivariable logistic and Cox regression, and Kaplan-Meier analysis to assess associations between GNRI and mortality. Using LASSO regression for variable selection coupled with multivariable Cox proportional hazards modeling, we developed a prognostic nomogram across three distinct risk strata. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with predictive performance quantified by the area under the curve (AUC).</p><p><strong>Result: </strong>The final analysis included 2,230 critically ill patients with sepsis-associated pneumonia, with observed 28-day ICU and in-hospital mortality rates of 26.64% and 26.59%, respectively. In fully adjusted models, both continuous GNRI and categorical GNRI showed significant associations with 28-day ICU mortality across cohorts. The hazard ratios were 0.99 (95% CI: 0.98-1.00) for continuous GNRI; 0.69 (0.51-0.93) for moderate vs. high nutritional risk; and 0.41 (0.25-0.69) for no vs. high nutritional risk. Similar associations were observed for 28-day in-hospital mortality (no vs. high nutritional risk: HR: 0.59, 95% CI: 0.36-0.98). Restricted cubic spline analysis revealed a nonlinear relationship between continuous GNRI and both 28-day ICU and in-hospital mortality. When combined with conventional critical illness severity scores, GNRI provided incremental predictive value for 28-day mortality. ROC curve analysis demonstrated that our risk model outperformed conventional ICU severity scores in identifying high-risk sepsis-associated pneumonia patients. Our novel nomogram demonstrated superior predictive performance for 28-day mortality, achieving area under the curve (AUC) values of 0.71 (training), 0.70 (internal validation), and 0.70 (external validation), consistently exceeding the performance
{"title":"Association between the geriatric nutritional risk index and 28-day mortality in critically ill sepsis-associated pneumonia patients: retrospective study based on two cohorts.","authors":"Dandan Shao, Linyu He, Dayang Zhong, Kun Li, Xianming Zhang","doi":"10.3389/fnut.2025.1698973","DOIUrl":"10.3389/fnut.2025.1698973","url":null,"abstract":"<p><strong>Background: </strong>In recent years, the identification of reliable prognostic indicators for critically ill patients has become increasingly crucial. The Geriatric Nutritional Risk Index (GNRI), a simple and objective tool for assessing malnutrition risk, has demonstrated significant prognostic value across various disease conditions. This study aims to investigate and validate the clinical utility of GNRI in predicting 28-day mortality among critically ill patients with sepsis-associated pneumonia.</p><p><strong>Material and method: </strong>We conducted a retrospective analysis using two distinct cohorts. Critically ill elderly people with sepsis-associated pneumonia were included. The derivation cohort consisted of critically ill patients with sepsis-associated pneumonia extracted from the MIMIC-IV database, while the validation cohort comprised consecutively enrolled patients meeting identical criteria from Jinyang Hospital Affiliated to Guizhou Medical University between March 2023 and March 2025. Key baseline variables including demographics, comorbidities, and severity scores were analyzed. We employed restricted cubic spline regression, multivariable logistic and Cox regression, and Kaplan-Meier analysis to assess associations between GNRI and mortality. Using LASSO regression for variable selection coupled with multivariable Cox proportional hazards modeling, we developed a prognostic nomogram across three distinct risk strata. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with predictive performance quantified by the area under the curve (AUC).</p><p><strong>Result: </strong>The final analysis included 2,230 critically ill patients with sepsis-associated pneumonia, with observed 28-day ICU and in-hospital mortality rates of 26.64% and 26.59%, respectively. In fully adjusted models, both continuous GNRI and categorical GNRI showed significant associations with 28-day ICU mortality across cohorts. The hazard ratios were 0.99 (95% CI: 0.98-1.00) for continuous GNRI; 0.69 (0.51-0.93) for moderate vs. high nutritional risk; and 0.41 (0.25-0.69) for no vs. high nutritional risk. Similar associations were observed for 28-day in-hospital mortality (no vs. high nutritional risk: HR: 0.59, 95% CI: 0.36-0.98). Restricted cubic spline analysis revealed a nonlinear relationship between continuous GNRI and both 28-day ICU and in-hospital mortality. When combined with conventional critical illness severity scores, GNRI provided incremental predictive value for 28-day mortality. ROC curve analysis demonstrated that our risk model outperformed conventional ICU severity scores in identifying high-risk sepsis-associated pneumonia patients. Our novel nomogram demonstrated superior predictive performance for 28-day mortality, achieving area under the curve (AUC) values of 0.71 (training), 0.70 (internal validation), and 0.70 (external validation), consistently exceeding the performance","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1698973"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26eCollection Date: 2025-01-01DOI: 10.3389/fnut.2025.1743065
Anda Zhao, Yiting Chen, Zhen Li, Qing Fan, Jiang Wu
Background: While sleep quality and chronotype are critical to wellbeing, the role of dietary diversity remains scarcely investigated, particularly among young and middle-aged adults. This study aimed to examine the associations of dietary diversity with sleep quality and chronotype, and to explore whether depression mediates these relationships.
Methods: Data were derived from the 2024-2025 China Nutrition and Sleep Survey (CNSS), including 4,128 adults aged 20-59 years. Dietary diversity indices, including total dietary diversity scores (DDS), plant-based DDS, animal-based DDS, anti-inflammatory diet diversity index (AIDDI) and protein-enriched diet diversity index (PEDDI), were calculated from food frequency questionnaires. Sleep quality, chronotype, and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Morningness-Eveningness Questionnaire-5 (MEQ-5), and the Patient Health Questionnaire-9 (PHQ-9), respectively. Linear and logistic regression analyses were performed, with propensity score matching (PSM) applied to reduce confounding. Mediation and interaction analyses were further conducted.
Results: Higher dietary diversity indices were significantly associated with lower PSQI scores and higher MEQ-5 scores, both before and after PSM. Depression might be partially involved in the observed associations with sleep quality and chronotype. The associations between dietary diversity and sleep quality were stronger among females, older adults, non-drinkers, and those with regular exercise or depressive symptoms, whereas associations with chronotype were generally consistent across subgroups.
Conclusions: Greater dietary diversity is associated with better sleep quality and earlier chronotype, with depressive symptoms potentially playing a role in explaining these associations.
{"title":"Dietary diversity and its associations with sleep quality and chronotype in young and middle-aged adults.","authors":"Anda Zhao, Yiting Chen, Zhen Li, Qing Fan, Jiang Wu","doi":"10.3389/fnut.2025.1743065","DOIUrl":"10.3389/fnut.2025.1743065","url":null,"abstract":"<p><strong>Background: </strong>While sleep quality and chronotype are critical to wellbeing, the role of dietary diversity remains scarcely investigated, particularly among young and middle-aged adults. This study aimed to examine the associations of dietary diversity with sleep quality and chronotype, and to explore whether depression mediates these relationships.</p><p><strong>Methods: </strong>Data were derived from the 2024-2025 China Nutrition and Sleep Survey (CNSS), including 4,128 adults aged 20-59 years. Dietary diversity indices, including total dietary diversity scores (DDS), plant-based DDS, animal-based DDS, anti-inflammatory diet diversity index (AIDDI) and protein-enriched diet diversity index (PEDDI), were calculated from food frequency questionnaires. Sleep quality, chronotype, and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Morningness-Eveningness Questionnaire-5 (MEQ-5), and the Patient Health Questionnaire-9 (PHQ-9), respectively. Linear and logistic regression analyses were performed, with propensity score matching (PSM) applied to reduce confounding. Mediation and interaction analyses were further conducted.</p><p><strong>Results: </strong>Higher dietary diversity indices were significantly associated with lower PSQI scores and higher MEQ-5 scores, both before and after PSM. Depression might be partially involved in the observed associations with sleep quality and chronotype. The associations between dietary diversity and sleep quality were stronger among females, older adults, non-drinkers, and those with regular exercise or depressive symptoms, whereas associations with chronotype were generally consistent across subgroups.</p><p><strong>Conclusions: </strong>Greater dietary diversity is associated with better sleep quality and earlier chronotype, with depressive symptoms potentially playing a role in explaining these associations.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1743065"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.
Objective: This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).
Methods: In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (n = 13) or placebo (n = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.
Results: Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (p = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (p = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (p < 0.001 and p = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (p = 0.029). No severe adverse events related to the intervention were reported.
Conclusion: Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.
{"title":"Efficacy of 42-month oral administration of glucoraphanin in preventing cognitive decline in individuals at elevated risk of dementia, including those with mild cognitive impairment: a randomized, double-blind, placebo-controlled pilot study.","authors":"Sunao Shimizu, Shuya Kasai, Chieko Suzuki, Tomoya Kon, Hiroyuki Suganuma, Shigenori Suzuki, Koichi Murashita, Shigeyuki Nakaji, Kazushige Ihara, Masahiko Tomiyama, Ken Itoh","doi":"10.3389/fnut.2026.1740494","DOIUrl":"10.3389/fnut.2026.1740494","url":null,"abstract":"<p><strong>Background: </strong>Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.</p><p><strong>Objective: </strong>This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (<i>n</i> = 13) or placebo (<i>n</i> = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.</p><p><strong>Results: </strong>Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (<i>p</i> = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (<i>p</i> = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (<i>p</i> < 0.001 and <i>p</i> = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (<i>p</i> = 0.029). No severe adverse events related to the intervention were reported.</p><p><strong>Conclusion: </strong>Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"13 ","pages":"1740494"},"PeriodicalIF":4.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}