Pub Date : 2026-01-01Epub Date: 2025-12-02DOI: 10.1016/j.clnu.2025.12.001
Baochang He , Xixi Dong , Yichen Lin , Jianli Lin , Yu Qiu , Lisong Lin , Bin Shi , Jing Wang , Fa Chen
Background & Aims
Evidence suggests fatty acid metabolism may influence cancer progression, yet their role in oral cancer prognosis remains unclear. This study investigated associations between dietary fatty acid intake, erythrocyte membrane fatty acid composition, and overall survival in patients with oral cancer, and explored potential underlying mechanisms through network pharmacology and molecular docking analyses.
Methods
This prospective cohort study recruited 908 newly diagnosed oral cancer patients from October 2011 to June 2024. Dietary fatty acid intake was assessed using a validated food frequency questionnaire. Erythrocyte membrane fatty acid profiles were measured using gas chromatography. Patients were followed until February 2025, with overall survival as the primary outcome. Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between fatty acid levels and overall survival in oral cancer. Composite indices (dietary fatty acid index [DFAI] and erythrocyte fatty acid index [EFAI]) were constructed using LASSO regression to assess combined effects. Network pharmacology and molecular docking were employed to investigate potential mechanisms.
Results
In multi-adjusted Cox regression models, higher dietary intake of linolenic acid (C18:3), eicosatrienoic acid (C20:3), and docosahexaenoic acid (C22:6) were associated with reduced mortality risk (highest vs. lowest tertile: HR = 0.54, 95 % CI: 0.36–0.82; HR = 0.65, 95 % CI: 0.44–0.95; HR = 0.62, 95 % CI: 0.42–0.91, respectively; all P-trend<0.05). Among erythrocyte membrane fatty acids, significant protective associations were observed for very long-chain saturated fatty acids behenic acid (C22:0) and tricosanoic acid (C23:0), with 48 % and 56 % lower mortality risks in the highest tertile (all P for trend <0.05). Similar protective effects were found for omega-3 polyunsaturated fatty acids including α-linolenic acid (C18:3 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). Composite fatty acid indices showed that DFAI and EFAI were associated with 59 % and 85 % mortality reduction, respectively (both P < 0.001). Network pharmacology identified interleukin-6 (IL-6) as a key target in the fatty acid-oral cancer survival pathway. Molecular docking revealed favorable binding affinities between all six significant fatty acids and IL-6 (binding energies: −1.83 to −5.08 kcal/mol).
Conclusion
Higher dietary intake and erythrocyte membrane levels of specific polyunsaturated fatty acids and very long-chain saturated fatty acids are significantly associated with improved overall survival in oral cancer patients. These protective effects may be mediated through IL-6-related inflammatory pathways.
{"title":"Associations of dietary and erythrocyte membrane fatty acids with overall survival in oral cancer: A prospective cohort study with mechanistic exploration","authors":"Baochang He , Xixi Dong , Yichen Lin , Jianli Lin , Yu Qiu , Lisong Lin , Bin Shi , Jing Wang , Fa Chen","doi":"10.1016/j.clnu.2025.12.001","DOIUrl":"10.1016/j.clnu.2025.12.001","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Evidence suggests fatty acid metabolism may influence cancer progression, yet their role in oral cancer prognosis remains unclear. This study investigated associations between dietary fatty acid intake, erythrocyte membrane fatty acid composition, and overall survival in patients with oral cancer, and explored potential underlying mechanisms through network pharmacology and molecular docking analyses.</div></div><div><h3>Methods</h3><div>This prospective cohort study recruited 908 newly diagnosed oral cancer patients from October 2011 to June 2024. Dietary fatty acid intake was assessed using a validated food frequency questionnaire. Erythrocyte membrane fatty acid profiles were measured using gas chromatography. Patients were followed until February 2025, with overall survival as the primary outcome. Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between fatty acid levels and overall survival in oral cancer. Composite indices (dietary fatty acid index [DFAI] and erythrocyte fatty acid index [EFAI]) were constructed using LASSO regression to assess combined effects. Network pharmacology and molecular docking were employed to investigate potential mechanisms.</div></div><div><h3>Results</h3><div>In multi-adjusted Cox regression models, higher dietary intake of linolenic acid (C18:3), eicosatrienoic acid (C20:3), and docosahexaenoic acid (C22:6) were associated with reduced mortality risk (highest vs. lowest tertile: HR = 0.54, 95 % CI: 0.36–0.82; HR = 0.65, 95 % CI: 0.44–0.95; HR = 0.62, 95 % CI: 0.42–0.91, respectively; all <em>P</em>-trend<0.05). Among erythrocyte membrane fatty acids, significant protective associations were observed for very long-chain saturated fatty acids behenic acid (C22:0) and tricosanoic acid (C23:0), with 48 % and 56 % lower mortality risks in the highest tertile (all <em>P</em> for trend <0.05). Similar protective effects were found for omega-3 polyunsaturated fatty acids including α-linolenic acid (C18:3 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). Composite fatty acid indices showed that DFAI and EFAI were associated with 59 % and 85 % mortality reduction, respectively (both <em>P</em> < 0.001). Network pharmacology identified interleukin-6 (IL-6) as a key target in the fatty acid-oral cancer survival pathway. Molecular docking revealed favorable binding affinities between all six significant fatty acids and IL-6 (binding energies: −1.83 to −5.08 kcal/mol).</div></div><div><h3>Conclusion</h3><div>Higher dietary intake and erythrocyte membrane levels of specific polyunsaturated fatty acids and very long-chain saturated fatty acids are significantly associated with improved overall survival in oral cancer patients. These protective effects may be mediated through IL-6-related inflammatory pathways.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106534"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-01DOI: 10.1016/j.clnu.2025.11.016
Annie R. Curtis , Carla M. Prado , Liliana Orellana , Robin M. Daly , Judy Bauer , Linda Denehy , Lara Edbrooke , Brenton J. Baguley , Laura Alston , Nicholas Hardcastle , Jenelle Loeliger , Louise Moodie , Sharad Sharma , Nicole Kiss
Background and Aims
Early identification of cancer-related muscle loss is essential to enable timely interventions and mitigate adverse outcomes, including mortality. This scoping review aimed to identify routinely assessed clinical measures associated with low muscle mass or muscle loss to inform future global screening and assessment.
Methods
Medline Complete, CINAHL Complete and Embase databases were screened from January 2000 to October 2024. Eligible studies investigated factors associated with cancer-related muscle loss, included adults undergoing or previously treated for cancer, and assessed or estimated muscle mass.
Results
The search identified 22,270 studies, of which 292 were included. Most involved patients with upper and/or lower gastrointestinal cancers (50 %), undergoing surgery (44 %) or chemotherapy (27 %). Two-thirds (65 %) assessed muscle mass using computed tomography (CT) at the third lumbar vertebra. Other methods included CT-defined muscle mass of single muscles (e.g., psoas) (15 %), bioelectrical impedance analysis or spectroscopy (12 %), dual-energy x-ray absorptiometry (DXA) (7 %) or other (3 %). As the benchmark for muscle mass assessment in oncology, results focused on CT-defined muscle mass, with comparison to other methods. Twenty factors were identified. Thirteen showed a consistent association in unadjusted and/or adjusted analysis: age, body mass index (BMI), performance status, muscle strength, physical function, arm and leg circumference, body weight, body fat, weight loss, fatigue, energy or protein intake, and physical inactivity.
Conclusions
This review identified 13 factors consistently associated with CT-defined muscle loss which may help identify patients with cancer who are at risk and require further assessment and timely referral for evidence-based nutrition and exercise interventions.
{"title":"Exploring potential predictors of low muscle mass and muscle loss in adults with cancer: A scoping review","authors":"Annie R. Curtis , Carla M. Prado , Liliana Orellana , Robin M. Daly , Judy Bauer , Linda Denehy , Lara Edbrooke , Brenton J. Baguley , Laura Alston , Nicholas Hardcastle , Jenelle Loeliger , Louise Moodie , Sharad Sharma , Nicole Kiss","doi":"10.1016/j.clnu.2025.11.016","DOIUrl":"10.1016/j.clnu.2025.11.016","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Early identification of cancer-related muscle loss is essential to enable timely interventions and mitigate adverse outcomes, including mortality. This scoping review aimed to identify routinely assessed clinical measures associated with low muscle mass or muscle loss to inform future global screening and assessment.</div></div><div><h3>Methods</h3><div>Medline Complete, CINAHL Complete and Embase databases were screened from January 2000 to October 2024. Eligible studies investigated factors associated with cancer-related muscle loss, included adults undergoing or previously treated for cancer, and assessed or estimated muscle mass.</div></div><div><h3>Results</h3><div>The search identified 22,270 studies, of which 292 were included. Most involved patients with upper and/or lower gastrointestinal cancers (50 %), undergoing surgery (44 %) or chemotherapy (27 %). Two-thirds (65 %) assessed muscle mass using computed tomography (CT) at the third lumbar vertebra. Other methods included CT-defined muscle mass of single muscles (e.g., psoas) (15 %), bioelectrical impedance analysis or spectroscopy (12 %), dual-energy x-ray absorptiometry (DXA) (7 %) or other (3 %). As the benchmark for muscle mass assessment in oncology, results focused on CT-defined muscle mass, with comparison to other methods. Twenty factors were identified. Thirteen showed a consistent association in unadjusted and/or adjusted analysis: age, body mass index (BMI), performance status, muscle strength, physical function, arm and leg circumference, body weight, body fat, weight loss, fatigue, energy or protein intake, and physical inactivity.</div></div><div><h3>Conclusions</h3><div>This review identified 13 factors consistently associated with CT-defined muscle loss which may help identify patients with cancer who are at risk and require further assessment and timely referral for evidence-based nutrition and exercise interventions.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106531"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background and aims</h3><div>Cachexia, which is a complex metabolic disorder that is characterized by weight loss, muscle atrophy, and inflammation, is commonly associated with chronic diseases. However, the occurrence of cachexia among community-dwelling, middle-aged and older adults remains underexplored. This study aimed to assess the associations among cachexia, intrinsic capacity (IC) impairment, and mortality in adults aged 50 years and older.</div></div><div><h3>Methods</h3><div>We pooled data from three longitudinal cohort studies, which included 3112 individuals aged 50 years and older. The cachexia phenotype was defined using two algorithms suggested by the Asian Working Group for Cachexia (AWGC), even in the absence of specific index diseases. For Algorithm 1, patients were identified as having cachexia when they presented with weight loss or low body mass index (BMI) combined with one of the following: anorexia, decreased grip strength, or elevated C-reactive protein (CRP) levels. For Algorithm 2, the identification of cachexia required elevated CRP levels, along with weight loss or low BMI, combined with either anorexia or decreased grip strength. Importantly, the presence of a specific index disease was not necessary to define the cachexia phenotype using these criteria. Instead, we screened for the following index diseases as comorbid conditions: malignancy, congestive heart failure, chronic pulmonary disease, chronic kidney disease, severe liver disease, rheumatic or immune diseases, and acquired immunodeficiency syndrome (AIDS). IC was evaluated using the World Health Organization’s ICOPE framework (Step 1 screening; Step 2 in-depth assessment), which includes six domains: locomotor, vitality, vision, hearing, cognition, and psychological capacity. Logistic regression was used to assess the association between cachexia and IC impairment, and Cox proportional hazard models were used to examine the effect of cachexia on all-cause mortality.</div></div><div><h3>Results</h3><div>Among 3112 participants (median age 68.8 years, 43.7 % male) in the three cohorts, 5.4 % of participants were identified as having the cachexia phenotype using Algorithm 1, whereas only 0.4 % met the criteria for Algorithm 2. Notably, only 22 % of the participants with the cachexia phenotype (Algorithm 1) had at least one of the screened index diseases compared with 12 % in the non-cachexia group (<em>p</em> < 0.001). These findings demonstrate that the cachexia phenotype can be identified even in the absence of specific index diseases. The cachexia phenotype was significantly associated with impairments in multiple IC domains, including vitality (Step 1: aOR 8.44 [95 % CI 5.15–13.83], <em>p</em> < 0.001; Step 2: aOR 15.89 [10.72–23.56], <em>p</em> < 0.001), cognition (Step 1: aOR 1.75 [1.17–2.62], <em>p</em> = 0.007), and psychological capacity (Step 2: aOR 2.56 [1.39–4.73], <em>p</em> = 0.003). Individuals with the cachexia phenotype had a
背景和目的苦胆病是一种复杂的代谢紊乱，以体重减轻、肌肉萎缩和炎症为特征，通常与慢性疾病相关。然而，恶病质在社区居民、中老年人中的发生情况仍未得到充分研究。本研究旨在评估50岁及以上成人恶病质、内在能力（IC）损伤和死亡率之间的关系。方法：我们汇集了三项纵向队列研究的数据，其中包括3112名年龄在50岁及以上的个体。使用亚洲恶病质工作组（AWGC）提出的两种算法定义恶病质表型，即使在没有特定指数疾病的情况下。对于算法1，当患者出现体重减轻或低体重指数（BMI）并伴有以下情况之一时，患者被确定为患有恶病质：厌食症、握力下降或c反应蛋白（CRP）水平升高。对于算法2，识别恶病质需要CRP水平升高，同时体重减轻或低BMI，并伴有厌食症或握力下降。重要的是，使用这些标准来定义恶病质表型并不需要特定指数疾病的存在。相反，我们筛选了以下指标疾病作为合并症：恶性肿瘤，充血性心力衰竭，慢性肺病，慢性肾病，严重肝病，风湿病或免疫疾病，以及获得性免疫缺陷综合征（艾滋病）。使用世界卫生组织的ICOPE框架（第1步筛查；第2步深入评估）对IC进行评估，其中包括六个领域：运动、活力、视觉、听觉、认知和心理能力。采用Logistic回归评估恶病质与IC损伤之间的关系，采用Cox比例风险模型检验恶病质对全因死亡率的影响。结果在三个队列的3112名参与者（中位年龄68.8岁，43.7%为男性）中，使用算法1确定5.4%的参与者具有恶病质表型，而只有0.4%的参与者符合算法2的标准。值得注意的是，只有22%的具有恶病质表型（算法1）的参与者至少有一种筛查的指标疾病，而非恶病质组的这一比例为12% （p < 0.001）。这些发现表明，即使在没有特定指数疾病的情况下，恶病质表型也可以被识别。恶病质表型与多个IC领域的损伤显著相关，包括活力（步骤1:aOR 8.44 [95% CI 5.15-13.83], p < 0.001；步骤2:aOR 15.89 [10.72-23.56], p < 0.001）、认知（步骤1:aOR 1.75 [1.17-2.62], p = 0.007）和心理能力（步骤2:aOR 2.56 [1.39-4.73], p = 0.003）。校正混杂因素后，恶病质表型个体的死亡风险显著高于非恶病质组（aHR 1.77 [95% CI 1.15-2.73], p = 0.010）。结论在没有特定指标疾病的情况下，恶病质表型与中老年人IC损伤和死亡率增加有关。早期识别和有针对性的干预对于减轻恶病质表型患者的功能衰退和提高生存率至关重要。
{"title":"Cachexia phenotype in community-dwelling, middle-aged and older adults and its impacts on intrinsic capacity and mortality: A pooled analysis of three cohorts","authors":"Liang-Kung Chen , Chi-Yun Wu , Wei-Ju Lee , Li-Ning Peng , Pi-Shan Hsu , Fei-Yuan Hsiao","doi":"10.1016/j.clnu.2025.11.011","DOIUrl":"10.1016/j.clnu.2025.11.011","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cachexia, which is a complex metabolic disorder that is characterized by weight loss, muscle atrophy, and inflammation, is commonly associated with chronic diseases. However, the occurrence of cachexia among community-dwelling, middle-aged and older adults remains underexplored. This study aimed to assess the associations among cachexia, intrinsic capacity (IC) impairment, and mortality in adults aged 50 years and older.</div></div><div><h3>Methods</h3><div>We pooled data from three longitudinal cohort studies, which included 3112 individuals aged 50 years and older. The cachexia phenotype was defined using two algorithms suggested by the Asian Working Group for Cachexia (AWGC), even in the absence of specific index diseases. For Algorithm 1, patients were identified as having cachexia when they presented with weight loss or low body mass index (BMI) combined with one of the following: anorexia, decreased grip strength, or elevated C-reactive protein (CRP) levels. For Algorithm 2, the identification of cachexia required elevated CRP levels, along with weight loss or low BMI, combined with either anorexia or decreased grip strength. Importantly, the presence of a specific index disease was not necessary to define the cachexia phenotype using these criteria. Instead, we screened for the following index diseases as comorbid conditions: malignancy, congestive heart failure, chronic pulmonary disease, chronic kidney disease, severe liver disease, rheumatic or immune diseases, and acquired immunodeficiency syndrome (AIDS). IC was evaluated using the World Health Organization’s ICOPE framework (Step 1 screening; Step 2 in-depth assessment), which includes six domains: locomotor, vitality, vision, hearing, cognition, and psychological capacity. Logistic regression was used to assess the association between cachexia and IC impairment, and Cox proportional hazard models were used to examine the effect of cachexia on all-cause mortality.</div></div><div><h3>Results</h3><div>Among 3112 participants (median age 68.8 years, 43.7 % male) in the three cohorts, 5.4 % of participants were identified as having the cachexia phenotype using Algorithm 1, whereas only 0.4 % met the criteria for Algorithm 2. Notably, only 22 % of the participants with the cachexia phenotype (Algorithm 1) had at least one of the screened index diseases compared with 12 % in the non-cachexia group (<em>p</em> < 0.001). These findings demonstrate that the cachexia phenotype can be identified even in the absence of specific index diseases. The cachexia phenotype was significantly associated with impairments in multiple IC domains, including vitality (Step 1: aOR 8.44 [95 % CI 5.15–13.83], <em>p</em> < 0.001; Step 2: aOR 15.89 [10.72–23.56], <em>p</em> < 0.001), cognition (Step 1: aOR 1.75 [1.17–2.62], <em>p</em> = 0.007), and psychological capacity (Step 2: aOR 2.56 [1.39–4.73], <em>p</em> = 0.003). Individuals with the cachexia phenotype had a","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106526"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-08DOI: 10.1016/j.clnu.2025.12.003
Ningyi Zou , Peijuan Zhou , Qing Zhou , Jizheng Ma , Shuo Feng , Peijing Rong , Shaoyuan Li
Dysregulation of glucose and lipid metabolism is a systemic disorder involving intricate interactions between the central nervous system, which governs stress and emotional regulation, and peripheral organs such as the gastrointestinal tract, liver, and pancreas. As a key component of the autonomic nervous system, the vagus nerve plays a pivotal role in regulating metabolic homeostasis through its widespread distribution and bidirectional communication along the gut-brain axis. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-pharmacological therapy for metabolic disorders, modulating autonomic function via brain-gut coordination to reduce food intake and enhance energy expenditure, thereby alleviating obesity, type 2 diabetes, and related conditions. However, the dynamic mechanisms by which taVNS maintains homeostatic balance through the gut-brain axis, as well as its novel targets, mediators, and pathways, remain elusive. Based on the concept of “brain-gut interaction for holistic regulation”, this review explores the potential mechanisms of taVNS in ameliorating glucose and lipid metabolic disorders, offering new perspectives and strategies for clinical intervention.
{"title":"Brain-gut interaction for holistic regulation: Transcutaneous auricular vagus nerve stimulation in modulating glucose and lipid metabolic disorders","authors":"Ningyi Zou , Peijuan Zhou , Qing Zhou , Jizheng Ma , Shuo Feng , Peijing Rong , Shaoyuan Li","doi":"10.1016/j.clnu.2025.12.003","DOIUrl":"10.1016/j.clnu.2025.12.003","url":null,"abstract":"<div><div>Dysregulation of glucose and lipid metabolism is a systemic disorder involving intricate interactions between the central nervous system, which governs stress and emotional regulation, and peripheral organs such as the gastrointestinal tract, liver, and pancreas. As a key component of the autonomic nervous system, the vagus nerve plays a pivotal role in regulating metabolic homeostasis through its widespread distribution and bidirectional communication along the gut-brain axis. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-pharmacological therapy for metabolic disorders, modulating autonomic function via brain-gut coordination to reduce food intake and enhance energy expenditure, thereby alleviating obesity, type 2 diabetes, and related conditions. However, the dynamic mechanisms by which taVNS maintains homeostatic balance through the gut-brain axis, as well as its novel targets, mediators, and pathways, remain elusive. Based on the concept of “brain-gut interaction for holistic regulation”, this review explores the potential mechanisms of taVNS in ameliorating glucose and lipid metabolic disorders, offering new perspectives and strategies for clinical intervention.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106544"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-22DOI: 10.1016/j.clnu.2025.11.014
Robert Martindale , Manpreet S. Mundi , Dan Waitzberg , Elisabeth De Waele , Marialaura Scarcella , Michele Umbrello , Philip C. Calder , Jesmond Dalli , Zudin Puthucheary , Arthur R.H. van Zanten
Acute inflammation is a crucial biological response necessary for host defense and tissue repair, but unresolved inflammation can contribute to adverse outcomes across critical illness, cardiovascular disease, neurodegeneration, and cancer. Emerging evidence emphasizes that the resolution of inflammation is an active biosynthetic process mediated in part by specialized pro-resolving mediators (SPMs), lipid-derived molecules generated from omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA). These mediators—including resolvins, protectins, and maresins—exert potent immunomodulatory actions that restore tissue homeostasis and attenuate inflammation without immunosuppression. Despite the established role of SPMs, clinical and preclinical studies demonstrate that SPM biosynthesis is often impaired in disease states, limiting the efficacy of omega-3 PUFA-based nutritional interventions. To explore the potential of standardized SPM enrichment in enteral nutrition (EN), a multidisciplinary panel of experts conducted a Delphi-based consensus process. Consensus statements were developed supporting the rationale for enriching EN with preformed SPMs or their stable precursors to overcome compromised endogenous biosynthesis and enhance clinical benefits. Preliminary human studies suggest that such enrichment may reduce inflammation, improve immune function, and contribute to better outcomes in conditions such as obesity, atherosclerosis, infections, and chronic pain. The panel emphasized the need for rigorously designed clinical trials to determine whether enteral SPMs have measurable clinical effects and, if so, to define effective dosing strategies. Overall, SPM-enriched EN represents a potential advancement in the nutritional modulation of inflammation, warranting further investigation to guide evidence-based clinical application.
{"title":"Integrating downstream mediators of Omega-3 fatty acids into enteral nutrition for improved patient care: An expert panel consensus","authors":"Robert Martindale , Manpreet S. Mundi , Dan Waitzberg , Elisabeth De Waele , Marialaura Scarcella , Michele Umbrello , Philip C. Calder , Jesmond Dalli , Zudin Puthucheary , Arthur R.H. van Zanten","doi":"10.1016/j.clnu.2025.11.014","DOIUrl":"10.1016/j.clnu.2025.11.014","url":null,"abstract":"<div><div>Acute inflammation is a crucial biological response necessary for host defense and tissue repair, but unresolved inflammation can contribute to adverse outcomes across critical illness, cardiovascular disease, neurodegeneration, and cancer. Emerging evidence emphasizes that the resolution of inflammation is an active biosynthetic process mediated in part by specialized pro-resolving mediators (SPMs), lipid-derived molecules generated from omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA). These mediators—including resolvins, protectins, and maresins—exert potent immunomodulatory actions that restore tissue homeostasis and attenuate inflammation without immunosuppression. Despite the established role of SPMs, clinical and preclinical studies demonstrate that SPM biosynthesis is often impaired in disease states, limiting the efficacy of omega-3 PUFA-based nutritional interventions. To explore the potential of standardized SPM enrichment in enteral nutrition (EN), a multidisciplinary panel of experts conducted a Delphi-based consensus process. Consensus statements were developed supporting the rationale for enriching EN with preformed SPMs or their stable precursors to overcome compromised endogenous biosynthesis and enhance clinical benefits. Preliminary human studies suggest that such enrichment may reduce inflammation, improve immune function, and contribute to better outcomes in conditions such as obesity, atherosclerosis, infections, and chronic pain. The panel emphasized the need for rigorously designed clinical trials to determine whether enteral SPMs have measurable clinical effects and, if so, to define effective dosing strategies. Overall, SPM-enriched EN represents a potential advancement in the nutritional modulation of inflammation, warranting further investigation to guide evidence-based clinical application.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106529"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to obesity, insulin resistance, and reproductive dysfunction. While dietary modification is central to management, the optimal approach remains unclear. This systematic review and meta-analysis evaluated the effects of the ketogenic diet on anthropometric, metabolic, and endocrinological outcomes in women with PCOS.
Methods
A systematic search of five databases (inception–February 2025) identified studies reporting outcomes in women with PCOS following a ketogenic diet. Meta-analyses compared pre- and post-ketogenic diet outcomes (primary analysis) and ketogenic diet versus other diets (secondary analysis). Summary mean differences (MDs) with 95 % confidence intervals (CIs) were calculated using a random-effects model. Risk of bias and evidence quality were assessed using validated tools and the GRADE approach.
Results
Fifteen studies were included in the review, of which ten met the criteria for inclusion in the meta-analysis. Most participants in the included studies had a BMI exceeding 25 kg/m2. In the primary analysis, ketogenic diet led to significant reductions in BMI (MD: −3.38 kg/m2, 95 % CI: 2.53 to 4.23, I2 = 0 %), weight (MD: −10.77 kg, 95 % CI: 8.73 to 12.81, I2 = 0 %), and waist circumference (MD: −8.93 cm, 95 % CI: 5.66 to 12.19; I2 = 44 %). Reductions were also observed in luteinising hormone (LH) levels (MD: 4.07, 95 % CI: 3.36 to 4.79, I2 = 0 %), menstrual cycle duration (MD: 26.06, 95 % CI: 2.28 to 49.85, I2 = 68 %), and insulin resistance (MD: 2.43; 95 % CI: 1.16 to 3.69, I2 = 95 %). In the secondary analysis, ketogenic diet showed superior effects on BMI (MD: −1.65, 95 % CI: −2.76 to −0.55, I2 = 0 %) and weight loss (MD: −4.98, 95 % CI: −9.05 to −0.91, I2 = 7 %) as well as LH levels (MD 1.68, 95 % CI: −3.18 to −0.19, I2 = 30 %) and insulin resistance (MD: −1.71, 95 % CI: −2.98 to −0.43, I2 = 90 %) compared to other diets, though results for androgen and lipid parameters were inconsistent. Heterogeneity was high for most of the studied outcomes.
Conclusion
The ketogenic diet appears to be a promising dietary intervention for improving weight, insulin sensitivity, and reproductive hormone profiles in women with PCOS and a BMI exceeding 25 kg/m2. Nonetheless, the considerable heterogeneity among included studies and variations in study quality warrant cautious interpretation of these findings. Further high-quality, long-term randomized controlled trials are needed to more definitively establish the efficacy and safety of the ketogenic diet in women with PCOS.
{"title":"The effects of ketogenic diet on polycystic ovary syndrome: A systematic review and meta-analysis","authors":"Elisavet Arsenaki , Dimitra Stathi , Konstantinos Katsikas Triantafyllidis , Yeshey Seldon , Stergios Bobotis , George Lockett , Shaun Haran , Maria Kyrgiou , Srdjan Saso , Konstantinos S. Kechagias","doi":"10.1016/j.clnu.2025.11.019","DOIUrl":"10.1016/j.clnu.2025.11.019","url":null,"abstract":"<div><h3>Background and aim</h3><div>Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to obesity, insulin resistance, and reproductive dysfunction. While dietary modification is central to management, the optimal approach remains unclear. This systematic review and meta-analysis evaluated the effects of the ketogenic diet on anthropometric, metabolic, and endocrinological outcomes in women with PCOS.</div></div><div><h3>Methods</h3><div>A systematic search of five databases (inception–February 2025) identified studies reporting outcomes in women with PCOS following a ketogenic diet. Meta-analyses compared pre- and post-ketogenic diet outcomes (primary analysis) and ketogenic diet versus other diets (secondary analysis). Summary mean differences (MDs) with 95 % confidence intervals (CIs) were calculated using a random-effects model. Risk of bias and evidence quality were assessed using validated tools and the GRADE approach.</div></div><div><h3>Results</h3><div>Fifteen studies were included in the review, of which ten met the criteria for inclusion in the meta-analysis. Most participants in the included studies had a BMI exceeding 25 kg/m<sup>2</sup>. In the primary analysis, ketogenic diet led to significant reductions in BMI (MD: −3.38 kg/m<sup>2</sup>, 95 % CI: 2.53 to 4.23, I<sup>2</sup> = 0 %), weight (MD: −10.77 kg, 95 % CI: 8.73 to 12.81, I<sup>2</sup> = 0 %), and waist circumference (MD: −8.93 cm, 95 % CI: 5.66 to 12.19; I<sup>2</sup> = 44 %). Reductions were also observed in luteinising hormone (LH) levels (MD: 4.07, 95 % CI: 3.36 to 4.79, I<sup>2</sup> = 0 %), menstrual cycle duration (MD: 26.06, 95 % CI: 2.28 to 49.85, I<sup>2</sup> = 68 %), and insulin resistance (MD: 2.43; 95 % CI: 1.16 to 3.69, I<sup>2</sup> = 95 %). In the secondary analysis, ketogenic diet showed superior effects on BMI (MD: −1.65, 95 % CI: −2.76 to −0.55, I<sup>2</sup> = 0 %) and weight loss (MD: −4.98, 95 % CI: −9.05 to −0.91, I<sup>2</sup> = 7 %) as well as LH levels (MD 1.68, 95 % CI: −3.18 to −0.19, I<sup>2</sup> = 30 %) and insulin resistance (MD: −1.71, 95 % CI: −2.98 to −0.43, I<sup>2</sup> = 90 %) compared to other diets, though results for androgen and lipid parameters were inconsistent. Heterogeneity was high for most of the studied outcomes.</div></div><div><h3>Conclusion</h3><div>The ketogenic diet appears to be a promising dietary intervention for improving weight, insulin sensitivity, and reproductive hormone profiles in women with PCOS and a BMI exceeding 25 kg/m<sup>2</sup>. Nonetheless, the considerable heterogeneity among included studies and variations in study quality warrant cautious interpretation of these findings. Further high-quality, long-term randomized controlled trials are needed to more definitively establish the efficacy and safety of the ketogenic diet in women with PCOS.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106535"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-29DOI: 10.1016/j.clnu.2025.11.017
Emanuele Cereda , Valeria Borioli , Marilisa Caraccia , Anna Uggè , Francesca De Simeis , Raffaele Bruno , Angelo Guido Corsico , Antonio Di Sabatino , Paolo Pedrazzoli , Riccardo Caccialanza
Background
Acute diseases responsible for hospitalization negatively affect protein-calorie balance, as well as the capacity of patients to cope with it. In those who still retain spontaneous feeding, oral nutritional supplements (ONSs) administration is an effective support strategy, but evidence on the timing they should be provided along with nutritional counseling during hospitalization is lacking. Hence, we evaluated the efficacy of the systematic use of ONSs since hospital admission.
Methods
In a single-site, open-label, randomized, controlled trial (NCT02763904; July 2016–July 2024), acutely hospitalized adults (N = 220) at nutritional risk (NRS-2002 ≥ 3), without severe hypophagia (defined as food intake <50 % of estimated calorie requirements) and with an expected length of stay (LOS) ≥7 days were randomized to receive, along with nutritional counseling, high-protein ONSs systematically since admission or on-demand since day 8. The primary endpoint was the change in phase angle (PhA) on day 8. Secondary outcomes were the change in PhA at discharge and in muscle strength, body weight and protein-calorie intake over the hospital stay. LOS and the rate of acquired infections were also evaluated.
Results
A total of 201 patients were re-assessed at day 8 and at discharge. Systematic ONSs (n = 100) resulted in improved PhA at day 8 (mean difference, 0.47 [95%CI, 0.31–0.62]; P < 0.001) and at discharge (mean difference, 0.49 [95%CI, 0.33–0.64]; P < 0.001). A significant effect was also found for body weight and protein-calorie intake at all time-points (P < 0.001) and for muscle strength at discharge (P = 0.042). LOS was also reduced (−2 days; P = 0.044).
Conclusions
In acutely hospitalized adult patients at nutritional risk and without severe hypophagia, the systematic use of ONSs since admission improved body composition, muscle function, and protein-calorie intake, and reduced LOS.
{"title":"Systematic high-calorie, high-protein oral nutritional support in hospitalized, moderately hypophagic patients at nutritional risk: A randomized-controlled trial","authors":"Emanuele Cereda , Valeria Borioli , Marilisa Caraccia , Anna Uggè , Francesca De Simeis , Raffaele Bruno , Angelo Guido Corsico , Antonio Di Sabatino , Paolo Pedrazzoli , Riccardo Caccialanza","doi":"10.1016/j.clnu.2025.11.017","DOIUrl":"10.1016/j.clnu.2025.11.017","url":null,"abstract":"<div><h3>Background</h3><div>Acute diseases responsible for hospitalization negatively affect protein-calorie balance, as well as the capacity of patients to cope with it. In those who still retain spontaneous feeding, oral nutritional supplements (ONSs) administration is an effective support strategy, but evidence on the timing they should be provided along with nutritional counseling during hospitalization is lacking. Hence, we evaluated the efficacy of the systematic use of ONSs since hospital admission.</div></div><div><h3>Methods</h3><div>In a single-site, open-label, randomized, controlled trial (NCT02763904; July 2016–July 2024), acutely hospitalized adults (N = 220) at nutritional risk (NRS-2002 ≥ 3), without severe hypophagia (defined as food intake <50 % of estimated calorie requirements) and with an expected length of stay (LOS) ≥7 days were randomized to receive, along with nutritional counseling, high-protein ONSs systematically since admission or on-demand since day 8. The primary endpoint was the change in phase angle (PhA) on day 8. Secondary outcomes were the change in PhA at discharge and in muscle strength, body weight and protein-calorie intake over the hospital stay. LOS and the rate of acquired infections were also evaluated.</div></div><div><h3>Results</h3><div>A total of 201 patients were re-assessed at day 8 and at discharge. Systematic ONSs (n = 100) resulted in improved PhA at day 8 (mean difference, 0.47 [95%CI, 0.31–0.62]; P < 0.001) and at discharge (mean difference, 0.49 [95%CI, 0.33–0.64]; P < 0.001). A significant effect was also found for body weight and protein-calorie intake at all time-points (P < 0.001) and for muscle strength at discharge (P = 0.042). LOS was also reduced (−2 days; P = 0.044).</div></div><div><h3>Conclusions</h3><div>In acutely hospitalized adult patients at nutritional risk and without severe hypophagia, the systematic use of ONSs since admission improved body composition, muscle function, and protein-calorie intake, and reduced LOS.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106532"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-06DOI: 10.1016/j.clnu.2025.11.026
Zhongyang Guan , Blossom CM. Stephan , Lorenzo M. Donini , Joshua R. Lewis , Carla M. Prado , Richard L. Prince , David Scott , Kun Zhu , Marc Sim , Mario Siervo
Background and aims
Longitudinal studies have explored the association between sarcopenic obesity (SO) and the risk of cognitive impairment, yet findings remain mixed. This study aimed to investigate the associations of SO with risk of incident dementia in older women, using two diagnostic models: the Sarcopenic Obesity Global Leadership Initiative (SOGLI) and the load-capacity model.
Methods
We analysed data from 900 community-dwelling women (aged ≥70 years). SO was defined using two models: (1) the SOGLI criteria, based on low handgrip strength (HGS), low appendicular lean soft tissue to body weight (ALST/W) ratio, and high fat mass percentage (%FM); and (2) the load-capacity model, based on a high truncal fat mass to ALST (TrFM/ALST) ratio. Incident dementia events (hospitalisation and/or death) over 9.5 years were identified through linked health records using International Classification of Diseases (ICD) codes. Cox proportional hazards and Fine–Gray sub-distribution models were applied.
Results
Using the SOGLI criteria, SO was not significantly associated with the risk of overall dementia events compared with the non-sarcopenic, non-obesity group (hazard ratio [HR] 0.63, 95 % CI 0.39–1.03); however, SO was significantly associated with a reduced risk of dementia-related hospitalisation (HR 0.57, 95 % CI 0.33–0.98), mainly driven by the reduced risk observed with obesity. When defined by the load-capacity model, SO remained significantly associated with a reduced risk of overall dementia events (HR 0.54, 95 % CI 0.34–0.85). Restricted cubic spline (RCS) analyses demonstrated significant associations of lower HGS, lower %FM, higher ALST/W ratio, and lower TrFM/ALST ratio with increased risk of overall dementia events. Results remained consistent in sensitivity analyses excluding participants with BMI <21 kg/m2 (n = 67) or %FM below the 15th percentile (n = 135), and after further adjustment for age at highest education level..
Conclusion
This is the first longitudinal study to examine the association between SO and dementia using either the SOGLI or load-capacity models. In this cohort of older women, SO was associated with a lower risk of dementia-related hospitalisation. These findings suggest that the relationship between obesity and dementia risk in late life may differ from current evidence regarding midlife, indicating potential age-specific effects. Further research is needed to clarify the underlying mechanisms and generalisability of these observations to broader populations..
背景和目的纵向研究探讨了肌肉减少型肥胖（SO）与认知障碍风险之间的关系，但研究结果仍不一致。本研究旨在通过两种诊断模型：肌少性肥胖全球领导倡议（SOGLI）和负荷能力模型，探讨老年女性SO与痴呆发生风险的关系。方法对900名年龄≥70岁的社区妇女进行数据分析。SO的定义采用两个模型：(1)SOGLI标准，基于低握力（HGS）、低阑尾瘦软组织与体重（ALST/W）比和高脂肪质量百分比（%FM）；(2)基于较高的躯干脂肪质量与ALST （TrFM/ALST）比率的荷载-能力模型。通过使用国际疾病分类（ICD）代码的相关健康记录确定9.5年以上的偶发性痴呆事件（住院和/或死亡）。采用Cox比例风险模型和Fine-Gray子分布模型。结果使用SOGLI标准，与非肌肉减少、非肥胖组相比，SO与总体痴呆事件的风险无显著相关（风险比[HR] 0.63, 95% CI 0.39-1.03）；然而，SO与痴呆相关住院风险降低显著相关（HR 0.57, 95% CI 0.33-0.98），主要是由于肥胖导致的风险降低。当用负荷能力模型定义时，SO仍然与总体痴呆事件风险降低显著相关（HR 0.54, 95% CI 0.34-0.85）。限制性三次样条（RCS）分析显示，较低的HGS、较低的%FM、较高的ALST/W比率和较低的TrFM/ALST比率与总体痴呆事件的风险增加有显著关联。排除BMI = 21 kg/m2 （n = 67）或%FM低于第15个百分点（n = 135）的参与者，并进一步调整最高教育水平的年龄后，敏感性分析的结果保持一致。结论：这是第一个使用SOGLI或负荷能力模型检验SO与痴呆之间关系的纵向研究。在这个老年妇女队列中，SO与痴呆相关住院的风险较低有关。这些发现表明，肥胖和老年痴呆风险之间的关系可能与目前关于中年的证据不同，这表明了潜在的年龄特异性影响。需要进一步的研究来澄清潜在的机制和这些观察结果在更广泛人群中的普遍性。
{"title":"Association of sarcopenic obesity with dementia risk in a cohort of older women","authors":"Zhongyang Guan , Blossom CM. Stephan , Lorenzo M. Donini , Joshua R. Lewis , Carla M. Prado , Richard L. Prince , David Scott , Kun Zhu , Marc Sim , Mario Siervo","doi":"10.1016/j.clnu.2025.11.026","DOIUrl":"10.1016/j.clnu.2025.11.026","url":null,"abstract":"<div><h3>Background and aims</h3><div>Longitudinal studies have explored the association between sarcopenic obesity (SO) and the risk of cognitive impairment, yet findings remain mixed. This study aimed to investigate the associations of SO with risk of incident dementia in older women, using two diagnostic models: the Sarcopenic Obesity Global Leadership Initiative (SOGLI) and the load-capacity model.</div></div><div><h3>Methods</h3><div>We analysed data from 900 community-dwelling women (aged ≥70 years). SO was defined using two models: (1) the SOGLI criteria, based on low handgrip strength (HGS), low appendicular lean soft tissue to body weight (ALST/W) ratio, and high fat mass percentage (%FM); and (2) the load-capacity model, based on a high truncal fat mass to ALST (TrFM/ALST) ratio. Incident dementia events (hospitalisation and/or death) over 9.5 years were identified through linked health records using International Classification of Diseases (ICD) codes. Cox proportional hazards and Fine–Gray sub-distribution models were applied.</div></div><div><h3>Results</h3><div>Using the SOGLI criteria, SO was not significantly associated with the risk of overall dementia events compared with the non-sarcopenic, non-obesity group (hazard ratio [HR] 0.63, 95 % CI 0.39–1.03); however, SO was significantly associated with a reduced risk of dementia-related hospitalisation (HR 0.57, 95 % CI 0.33–0.98), mainly driven by the reduced risk observed with obesity. When defined by the load-capacity model, SO remained significantly associated with a reduced risk of overall dementia events (HR 0.54, 95 % CI 0.34–0.85). Restricted cubic spline (RCS) analyses demonstrated significant associations of lower HGS, lower %FM, higher ALST/W ratio, and lower TrFM/ALST ratio with increased risk of overall dementia events. Results remained consistent in sensitivity analyses excluding participants with BMI <21 kg/m<sup>2</sup> (n = 67) or %FM below the 15th percentile (n = 135), and after further adjustment for age at highest education level..</div></div><div><h3>Conclusion</h3><div>This is the first longitudinal study to examine the association between SO and dementia using either the SOGLI or load-capacity models. In this cohort of older women, SO was associated with a lower risk of dementia-related hospitalisation. These findings suggest that the relationship between obesity and dementia risk in late life may differ from current evidence regarding midlife, indicating potential age-specific effects. Further research is needed to clarify the underlying mechanisms and generalisability of these observations to broader populations..</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106542"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-17DOI: 10.1016/j.clnu.2025.106550
Laurence Genton , Miguel Leon Sanz , Marianna Arvanitakis , María D. Ballesteros-Pomar , Lia Bally , Rocco Barazzoni , Cécile Bétry , Rosa Burgos , Cristina Cuerda , Alia Hadefi , Stanislav Klek , Meliha Mahmutovic , Didier Quilliot , Diana Rubin , Stéphane M. Schneider , Mireille J. Serlie , Tinh-Hai Collet
Malnutrition affects up to 30 % of the general population, and especially older people with polymorbid conditions. In parallel, the prevalence of diabetes increases with age affecting over 800 million adults worldwide. Healthcare providers are increasingly challenged to care for patients with diabetes that require nutritional support. To address this issue, the ESPEN Special Interest Group "Nutrition and Diabetes", aims to provide guidance for health care providers that treat these patients. This paper had three aims: 1) to summarise the guidelines and recommendations regarding nutritional support and diabetes or stress hyperglycaemia provided by scientific societies, 2) to review the associations of nutritional disorders with diabetes and its pharmacological treatments, and 3) to identify the challenges of optimal nutritional care for patients with diabetes and stress hyperglycaemia. To this end, we conducted a systematic search of guidelines and recommendations on nutritional support for patients with diabetes or stress hyperglycaemia, that have been published in English by national and international societies over the last 15 years. Our systematic search showed that published guidelines and recommendations rarely addressed the practical management of blood glucose control according to the modality of nutritional support. The literature on the association of malnutrition with diabetes and its pharmacological treatment is very limited. The identified challenges include the multidisciplinary and multiprofessional continuity of care between the hospital and ambulatory settings, the ideal pattern of hospital food, the choice of oral nutritional supplements, the adjustment of diabetes management to nutritional support, and diabetes technology to support nutritional care in these patients.
{"title":"Challenges of nutritional support in patients with diabetes: A position paper of the ESPEN special interest group","authors":"Laurence Genton , Miguel Leon Sanz , Marianna Arvanitakis , María D. Ballesteros-Pomar , Lia Bally , Rocco Barazzoni , Cécile Bétry , Rosa Burgos , Cristina Cuerda , Alia Hadefi , Stanislav Klek , Meliha Mahmutovic , Didier Quilliot , Diana Rubin , Stéphane M. Schneider , Mireille J. Serlie , Tinh-Hai Collet","doi":"10.1016/j.clnu.2025.106550","DOIUrl":"10.1016/j.clnu.2025.106550","url":null,"abstract":"<div><div>Malnutrition affects up to 30 % of the general population, and especially older people with polymorbid conditions. In parallel, the prevalence of diabetes increases with age affecting over 800 million adults worldwide. Healthcare providers are increasingly challenged to care for patients with diabetes that require nutritional support. To address this issue, the ESPEN Special Interest Group \"Nutrition and Diabetes\", aims to provide guidance for health care providers that treat these patients. This paper had three aims: 1) to summarise the guidelines and recommendations regarding nutritional support and diabetes or stress hyperglycaemia provided by scientific societies, 2) to review the associations of nutritional disorders with diabetes and its pharmacological treatments, and 3) to identify the challenges of optimal nutritional care for patients with diabetes and stress hyperglycaemia. To this end, we conducted a systematic search of guidelines and recommendations on nutritional support for patients with diabetes or stress hyperglycaemia, that have been published in English by national and international societies over the last 15 years. Our systematic search showed that published guidelines and recommendations rarely addressed the practical management of blood glucose control according to the modality of nutritional support. The literature on the association of malnutrition with diabetes and its pharmacological treatment is very limited. The identified challenges include the multidisciplinary and multiprofessional continuity of care between the hospital and ambulatory settings, the ideal pattern of hospital food, the choice of oral nutritional supplements, the adjustment of diabetes management to nutritional support, and diabetes technology to support nutritional care in these patients.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106550"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-29DOI: 10.1016/j.clnu.2025.11.007
Daniel Habich , Angela Horvath , Nicole Feldbacher , Lavra Rebol , Maximilian Nepel , Tobias Madl , Hans-Jörg Habisch , Franziska Baumann-Durchschein , Stefan Fürst , Johannes Plank , Florian Rainer , Walter Spindelböck , Rudolf E. Stauber , Elisabeth Tatscher , Martin Wagner , Gernot Zollner , Vanessa Stadlbauer
<div><h3>Background & Aims</h3><div>Liver cirrhosis is associated with gut microbiome dysbiosis, intestinal inflammation and gut barrier dysfunction, contributing to reduced quality of life and the development of complications. We showed in a retrospective study that <span>l</span>-ornithine-<span>l</span>-aspartate (LOLA) was associated with improvement in taxonomic composition of the microbiome. Here we prospectively studied the influence of LOLA on the gut microbiome, quality of life, sarcopenia and the gut barrier.</div></div><div><h3>Methods</h3><div>In this phase 4 study, patients with liver cirrhosis and hepatic encephalopathy grade 0–2 received LOLA 18 g/day orally for 3 months. We studied faecal microbiome composition (primary endpoint abundance of the genus <em>Flavonifractor)</em>, microbiome function, quality of life, serum ammonia levels, sarcopenia and frailty, biomarkers of the gut liver axis and the stool, serum and urine metabolome.</div></div><div><h3>Results</h3><div>We screened 258 patients with liver cirrhosis, included 65, of whom 52 patients (40 % female, age 62 (58; 65)) completed the study. LOLA intake decreased the abundance of the genus <em>Romboutsia</em>, increased the abundance of the genus <em>Enterococcus,</em> but did not alter other microbiome parameters. LOLA improved one out of 8 dimension of quality of life (vitality) and decreased serum ammonia concentrations. The subgroup of patients with improved ammonia concentrations responded with a halt in further muscle mass declined over the study period. Diamine oxidase, a marker of intestinal mucosal condition, decreased and LPS binding protein increased. Metabolomic analysis indicated an increase in alanine concentration.</div></div><div><h3>Conclusions</h3><div>LOLA improved one quality of life dimension (vitality) and biomarker of the gut–liver axis, altered innate immune response, faecal microbiome and metabolome. LOLA prevented muscle loss only in patients with elevated ammonia concentrations at baseline. LOLA may therefore be a useful adjunct treatment to improve quality of life in cirrhosis and a promising intervention for muscle loss prevention in hyperammonemic patients.</div></div><div><h3>Clinical Trials Registration number</h3><div>clinicaltrials.gov NCT05737030.</div></div><div><h3>Impact and implication</h3><div>We conducted a 12-week prospective cohort study to test the effect of the ammonia lowering drug <span>l</span>-ornithine-<span>l</span>-aspartate (LOLA) on the gut microbiome, biomarkers along the gut-liver-axis, muscle health and quality of life in patients with liver cirrhosis and hepatic encephalopathy. Although our primary endpoint was not reached, LOLA slightly altered microbiome composition and function and improved vitality, a clinically relevant patient reported outcome parameter. LOLA also improved biomarkers for the gut-liver-axis, innate immune response and prevented muscle loss in patients with elevated ammonia levels at baselin
{"title":"An observational study on the effect of l-ornithine-l-aspartate (LOLA) on the gut microbiome in liver cirrhosis. A single center phase 4 study","authors":"Daniel Habich , Angela Horvath , Nicole Feldbacher , Lavra Rebol , Maximilian Nepel , Tobias Madl , Hans-Jörg Habisch , Franziska Baumann-Durchschein , Stefan Fürst , Johannes Plank , Florian Rainer , Walter Spindelböck , Rudolf E. Stauber , Elisabeth Tatscher , Martin Wagner , Gernot Zollner , Vanessa Stadlbauer","doi":"10.1016/j.clnu.2025.11.007","DOIUrl":"10.1016/j.clnu.2025.11.007","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Liver cirrhosis is associated with gut microbiome dysbiosis, intestinal inflammation and gut barrier dysfunction, contributing to reduced quality of life and the development of complications. We showed in a retrospective study that <span>l</span>-ornithine-<span>l</span>-aspartate (LOLA) was associated with improvement in taxonomic composition of the microbiome. Here we prospectively studied the influence of LOLA on the gut microbiome, quality of life, sarcopenia and the gut barrier.</div></div><div><h3>Methods</h3><div>In this phase 4 study, patients with liver cirrhosis and hepatic encephalopathy grade 0–2 received LOLA 18 g/day orally for 3 months. We studied faecal microbiome composition (primary endpoint abundance of the genus <em>Flavonifractor)</em>, microbiome function, quality of life, serum ammonia levels, sarcopenia and frailty, biomarkers of the gut liver axis and the stool, serum and urine metabolome.</div></div><div><h3>Results</h3><div>We screened 258 patients with liver cirrhosis, included 65, of whom 52 patients (40 % female, age 62 (58; 65)) completed the study. LOLA intake decreased the abundance of the genus <em>Romboutsia</em>, increased the abundance of the genus <em>Enterococcus,</em> but did not alter other microbiome parameters. LOLA improved one out of 8 dimension of quality of life (vitality) and decreased serum ammonia concentrations. The subgroup of patients with improved ammonia concentrations responded with a halt in further muscle mass declined over the study period. Diamine oxidase, a marker of intestinal mucosal condition, decreased and LPS binding protein increased. Metabolomic analysis indicated an increase in alanine concentration.</div></div><div><h3>Conclusions</h3><div>LOLA improved one quality of life dimension (vitality) and biomarker of the gut–liver axis, altered innate immune response, faecal microbiome and metabolome. LOLA prevented muscle loss only in patients with elevated ammonia concentrations at baseline. LOLA may therefore be a useful adjunct treatment to improve quality of life in cirrhosis and a promising intervention for muscle loss prevention in hyperammonemic patients.</div></div><div><h3>Clinical Trials Registration number</h3><div>clinicaltrials.gov NCT05737030.</div></div><div><h3>Impact and implication</h3><div>We conducted a 12-week prospective cohort study to test the effect of the ammonia lowering drug <span>l</span>-ornithine-<span>l</span>-aspartate (LOLA) on the gut microbiome, biomarkers along the gut-liver-axis, muscle health and quality of life in patients with liver cirrhosis and hepatic encephalopathy. Although our primary endpoint was not reached, LOLA slightly altered microbiome composition and function and improved vitality, a clinically relevant patient reported outcome parameter. LOLA also improved biomarkers for the gut-liver-axis, innate immune response and prevented muscle loss in patients with elevated ammonia levels at baselin","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106522"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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