Pub Date : 2025-12-01Epub Date: 2025-10-25DOI: 10.1016/j.clnu.2025.10.007
Rocco Barazzoni , John L. Sievenpiper , Laurence Genton , Cyril WC. Kendall , Maria D. Ballesteros-Pomar , Annalisa Giosuè , Yves Boirie , Laura Chiavaroli , Tommy Cederholm , Anne-Marie Aas , Cristina Cuerda , Charilaos Dimosthenopoulos , Nicolaas E. Deutz , Hana Kahleova , Lorenzo M. Donini , Ursula Schwab , Stephane M. Schneider , Gabriele Riccardi , Stanislaw Klek , Jordi Salas-Salvadó , Jeffrey I. Mechanick
Diabetes mellitus is a systemic chronic disease with growing prevalence and potential multiorgan complications leading to clinical, social, and economic burdens. Nutritional and metabolic derangements are important components of both type 1 (T1DM) and type 2 diabetes (T2DM), but assessment of nutritional state, body composition and muscle function is commonly neglected. Likely reasons include high prevalence of overweight, obesity, or excess visceral fat in highly-prevalent T2DM, potentially diverting attention from undernutrition risk. Diabetes and adiposity are mechanistically related to sarcopenia, defined as reduction of skeletal muscle strength and mass, through complex muscle-catabolic derangements, conferring additional risk for negative outcomes. Awareness of diabetes-induced muscle abnormalities remains low among healthcare professionals, patients and policymakers, contributing to research, knowledge and practice gaps. Lifestyle recommendations and treatments centered on nutritional care and physical activity to preserve and improve muscle mass and function remain poorly implemented. The European Society for Clinical Nutrition and Metabolism (ESPEN) and the Diabetes Nutrition Study Group (DNSG), reference group for the European Association for the Study of Diabetes, recognize sarcopenic diabetes as a distinct clinical condition and priority for research and education, and call for action to enhance awareness, stimulate research and promote consensus on sarcopenic diabetes diagnostic criteria, prevention and management.
{"title":"Sarcopenic diabetes is an under-recognized and unmet clinical priority. A call for action from the European Society for Clinical Nutrition and Metabolism and the Diabetes Nutrition Study Group","authors":"Rocco Barazzoni , John L. Sievenpiper , Laurence Genton , Cyril WC. Kendall , Maria D. Ballesteros-Pomar , Annalisa Giosuè , Yves Boirie , Laura Chiavaroli , Tommy Cederholm , Anne-Marie Aas , Cristina Cuerda , Charilaos Dimosthenopoulos , Nicolaas E. Deutz , Hana Kahleova , Lorenzo M. Donini , Ursula Schwab , Stephane M. Schneider , Gabriele Riccardi , Stanislaw Klek , Jordi Salas-Salvadó , Jeffrey I. Mechanick","doi":"10.1016/j.clnu.2025.10.007","DOIUrl":"10.1016/j.clnu.2025.10.007","url":null,"abstract":"<div><div>Diabetes mellitus is a systemic chronic disease with growing prevalence and potential multiorgan complications leading to clinical, social, and economic burdens. Nutritional and metabolic derangements are important components of both type 1 (T1DM) and type 2 diabetes (T2DM), but assessment of nutritional state, body composition and muscle function is commonly neglected. Likely reasons include high prevalence of overweight, obesity, or excess visceral fat in highly-prevalent T2DM, potentially diverting attention from undernutrition risk. Diabetes and adiposity are mechanistically related to sarcopenia, defined as reduction of skeletal muscle strength and mass, through complex muscle-catabolic derangements, conferring additional risk for negative outcomes. Awareness of diabetes-induced muscle abnormalities remains low among healthcare professionals, patients and policymakers, contributing to research, knowledge and practice gaps. Lifestyle recommendations and treatments centered on nutritional care and physical activity to preserve and improve muscle mass and function remain poorly implemented. The European Society for Clinical Nutrition and Metabolism (ESPEN) and the Diabetes Nutrition Study Group (DNSG), reference group for the European Association for the Study of Diabetes, recognize sarcopenic diabetes as a distinct clinical condition and priority for research and education, and call for action to enhance awareness, stimulate research and promote consensus on sarcopenic diabetes diagnostic criteria, prevention and management.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 208-218"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562793","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 : 2025-12-01Epub Date: 2025-10-31DOI: 10.1016/j.clnu.2025.10.018
Yaling Chen , Xiaohan Xu , Peipei Zhou , Meng Wang , Fang Yao , Liqin Chen , Wei Cheng , Haibo Qu , Changju Liu
Objectives to background and aims
Obesity is a major global health challenge associated with increased risks of diabetes and cardiovascular disease. Although calorie restriction and exercise are cornerstone strategies for weight management, long-term adherence remains difficult in real-world settings. This randomised controlled trial aimed to evaluate the effectiveness of a structured calorie-restricted dietary therapy package combined with exercise in achieving weight loss and improving metabolic and psychological outcomes among obese adults.
Methods
In this 12-month, parallel-group randomised controlled trial, 99 obese adults were randomly assigned to an intervention group (standardised meal kit + exercise) or a control group (standard dietary advice + exercise). Weight, glucose, lipid profiles, and mental health outcomes were assessed at baseline, 3, 6, and 12 months. LASSO regression was used to identify predictors of successful weight loss, and linear mixed-effects models evaluated associations between percentage weight loss and changes in glycaemic, lipid, and psychosocial outcomes.
Results
By month 12, all participants in the intervention group achieved ≥5 % weight loss, with 59.18 % achieving ≥10 %, compared to 38.00 % and 6.00 % in the control group, respectively. Group assignment was the strongest predictor of weight loss success, followed by HDL levels and family history of obesity. Each 1 % reduction in body weight was significantly associated with lower FPG, 2hPG, TC, TG, and LDL-C, as well as improved SDS, SAS, and SF-36 scores. These associations remained significant after adjusting for confounders. However, interaction analyses showed no significant between-group differences in the effect of weight loss on outcomes.
Conclusion
A standardised dietary therapy package combining calorie restriction and exercise is a feasible and effective strategy to achieve clinically meaningful weight loss and improve metabolic and psychological health in obese adults. Although both groups experienced improvements, the structured intervention enhanced adherence and overall effectiveness.
{"title":"Evaluation of the effectiveness of a restricted diet therapy package combining standardised caloric intake with exercise in obese patients: A 12-month randomised controlled trial","authors":"Yaling Chen , Xiaohan Xu , Peipei Zhou , Meng Wang , Fang Yao , Liqin Chen , Wei Cheng , Haibo Qu , Changju Liu","doi":"10.1016/j.clnu.2025.10.018","DOIUrl":"10.1016/j.clnu.2025.10.018","url":null,"abstract":"<div><h3>Objectives to background and aims</h3><div>Obesity is a major global health challenge associated with increased risks of diabetes and cardiovascular disease. Although calorie restriction and exercise are cornerstone strategies for weight management, long-term adherence remains difficult in real-world settings. This randomised controlled trial aimed to evaluate the effectiveness of a structured calorie-restricted dietary therapy package combined with exercise in achieving weight loss and improving metabolic and psychological outcomes among obese adults.</div></div><div><h3>Methods</h3><div>In this 12-month, parallel-group randomised controlled trial, 99 obese adults were randomly assigned to an intervention group (standardised meal kit + exercise) or a control group (standard dietary advice + exercise). Weight, glucose, lipid profiles, and mental health outcomes were assessed at baseline, 3, 6, and 12 months. LASSO regression was used to identify predictors of successful weight loss, and linear mixed-effects models evaluated associations between percentage weight loss and changes in glycaemic, lipid, and psychosocial outcomes.</div></div><div><h3>Results</h3><div>By month 12, all participants in the intervention group achieved ≥5 % weight loss, with 59.18 % achieving ≥10 %, compared to 38.00 % and 6.00 % in the control group, respectively. Group assignment was the strongest predictor of weight loss success, followed by HDL levels and family history of obesity. Each 1 % reduction in body weight was significantly associated with lower FPG, 2hPG, TC, TG, and LDL-C, as well as improved SDS, SAS, and SF-36 scores. These associations remained significant after adjusting for confounders. However, interaction analyses showed no significant between-group differences in the effect of weight loss on outcomes.</div></div><div><h3>Conclusion</h3><div>A standardised dietary therapy package combining calorie restriction and exercise is a feasible and effective strategy to achieve clinically meaningful weight loss and improve metabolic and psychological health in obese adults. Although both groups experienced improvements, the structured intervention enhanced adherence and overall effectiveness.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 152-161"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470677","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 : 2025-12-01Epub Date: 2025-11-01DOI: 10.1016/j.clnu.2025.10.017
Michelle A.J. van Oeteren , David M. de Groot , Amée M. Buziau , Jean L.J.M. Scheijen , Marjo P.H. van de Waarenburg , Abraham A. Kroon , Simone J.P.M. Eussen , Pieter C. Dagnelie , Marleen M.J. van Greevenbroek , Alfons J.H.M. Houben , Steven J.R. Meex , Casper G. Schalkwijk , Martijn C.G.J. Brouwers
Background and aims
Fruits and sugar-sweetened beverages have opposing effects on cardiometabolic health, despite comparable amounts of fructose per serving. Here, we sought evidence for a role of the food matrix in modifying serum fructose dynamics and blood pressure.
Methods
We first performed multiple linear regression analyses to assess the association between energy-adjusted intake of fructose from different sources (total, fruit, fruit juice and sugar-sweetened beverages) and blood pressure (24-h ambulatory, 7-day ambulatory, and office) using data from The Maastricht Study, a large population-based cohort (n = 5,426–6,471). Next, we conducted a randomized crossover trial in which healthy individuals (n = 21) were exposed to a fixed amount of fructose (20g) from different matrices (apple, mashed apple, apple juice, and fructose dissolved in water), and measured the serum fructose and blood pressure response.
Results
The intake of fructose from sugar-sweetened beverages, but not from fruits or fruit juice, was associated with higher ambulatory 7-day mean blood pressure, higher office blood pressure, and greater risk of hypertension (OR: 1.29, 95%CI 1.12; 1.50 per 10g fructose). In the crossover study, pure fructose intake yielded the greatest serum fructose excursions (p < 0.05 for all comparisons). The systolic blood pressure response was higher after pure fructose compared to the other matrices (+1.8 mmHg, 95%CI 0.02; 3.5).
Conclusions
Here, we provide epidemiological and experimental evidence that highlights the relevance of the food matrix on fructose dynamics and blood pressure, independent of the caloric value of fructose.
{"title":"The effects of dietary fructose on blood pressure are modified by the food matrix","authors":"Michelle A.J. van Oeteren , David M. de Groot , Amée M. Buziau , Jean L.J.M. Scheijen , Marjo P.H. van de Waarenburg , Abraham A. Kroon , Simone J.P.M. Eussen , Pieter C. Dagnelie , Marleen M.J. van Greevenbroek , Alfons J.H.M. Houben , Steven J.R. Meex , Casper G. Schalkwijk , Martijn C.G.J. Brouwers","doi":"10.1016/j.clnu.2025.10.017","DOIUrl":"10.1016/j.clnu.2025.10.017","url":null,"abstract":"<div><h3>Background and aims</h3><div>Fruits and sugar-sweetened beverages have opposing effects on cardiometabolic health, despite comparable amounts of fructose per serving. Here, we sought evidence for a role of the food matrix in modifying serum fructose dynamics and blood pressure.</div></div><div><h3>Methods</h3><div>We first performed multiple linear regression analyses to assess the association between energy-adjusted intake of fructose from different sources (total, fruit, fruit juice and sugar-sweetened beverages) and blood pressure (24-h ambulatory, 7-day ambulatory, and office) using data from The Maastricht Study, a large population-based cohort (n = 5,426–6,471). Next, we conducted a randomized crossover trial in which healthy individuals (n = 21) were exposed to a fixed amount of fructose (20g) from different matrices (apple, mashed apple, apple juice, and fructose dissolved in water), and measured the serum fructose and blood pressure response.</div></div><div><h3>Results</h3><div>The intake of fructose from sugar-sweetened beverages, but not from fruits or fruit juice, was associated with higher ambulatory 7-day mean blood pressure, higher office blood pressure, and greater risk of hypertension (OR: 1.29, 95%CI 1.12; 1.50 per 10g fructose). In the crossover study, pure fructose intake yielded the greatest serum fructose excursions (p < 0.05 for all comparisons). The systolic blood pressure response was higher after pure fructose compared to the other matrices (+1.8 mmHg, 95%CI 0.02; 3.5).</div></div><div><h3>Conclusions</h3><div>Here, we provide epidemiological and experimental evidence that highlights the relevance of the food matrix on fructose dynamics and blood pressure, independent of the caloric value of fructose.</div></div><div><h3>Registration</h3><div><span><span>https://onderzoekmetmensen.nl/en/trial/53397</span><svg><path></path></svg></span>; Unique identifier: NL-OMON53397.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 134-140"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470672","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 : 2025-12-01Epub Date: 2025-10-30DOI: 10.1016/j.clnu.2025.10.003
Clodagh E. Beattie , Borislavova Borislava , Harry A. Smith , Michael T. Ambler , Paul White , Danielle Milne , Aravind V. Ramesh , Alexander Ferriman , Thomas Fisher , Charlotte Horsley , Sherena Jackson , Chloe Jubainville , Kate Lobo , Hannah Maxfield , Javier T. Gonzalez , James A. Betts , Anthony E. Pickering , Matt Thomas
Background and aims
For intensive care unit (ICU) patients fed via a nasogastric (NG) tube, current guidelines recommend continuous feeding through the day and night. Emerging evidence in healthy individuals shows that NG feeding in an intermittent diurnal pattern promotes phasic hormonal, digestive and metabolic responses vital for effective nutrition, though this has not been studied in the critically ill population. This proof-of-concept study aimed to compare the effect of diurnal intermittent versus continuous enteral feeding on hormonal and metabolic outcomes in ICU patients.
Methods
We conducted a single-centre, randomised, open-label trial in the ICU. Adult ICU patients that were anticipated to require NG feeding for >48 h were randomised to an intermittent diurnal regimen (feeds at 8:00, 13:00 and 18:00), or continuous feeding with equivalent nutritional value, for 48 h. The primary outcome was peak plasma insulin within 3 h of delivering the first intermittent feed on the second study day, compared to the same time period in the continuous group. Secondary outcomes included feasibility, tolerability and metabolic profiles.
Results
Thirty patients were randomised to intermittent (n = 13) or continuous (n = 17) feeding. Two patients in the intermittent group were excluded from analysis. Both groups achieved their feed targets. Peak plasma insulin concentrations (mean ± SD) were significantly higher in the intermittent group versus continuous (295.1 ± 167.8 vs. 128.1 ± 57.2 pmol/L, p < 0.001). Plasma glucose concentrations were not significantly different between groups. There were no between-group differences in other plasma metabolites and there were no adverse events such as hyper-/hypo-glycaemia. There was evidence of increased bowel motility in the intermittent group.
Conclusion
Intermittent diurnal feeding, compared to continuous feeding, preserves the physiological insulin response in critically ill adults. Both regimens were well tolerated, supporting the need for a larger trial to assess other clinically important patient-centred outcomes.
Trial registration
This trial was registered prospectively at clinicaltrials.gov (study ID NCT06115044).
背景和目的：对于重症监护病房（ICU）患者通过鼻胃管喂食，目前的指南建议白天和晚上持续喂食。在健康个体中出现的新证据表明，以间歇性的昼夜模式喂养NG可促进对有效营养至关重要的阶段性激素、消化和代谢反应，尽管尚未在危重患者群体中进行研究。这项概念验证性研究旨在比较每日间歇和连续肠内喂养对ICU患者激素和代谢结局的影响。方法：我们在ICU进行了一项单中心、随机、开放标签的试验。预计需要NG喂养48小时的成年ICU患者被随机分配到间歇性日间方案（8:00,13:00和18:00喂养）或具有同等营养价值的连续喂养48小时。主要结局是在第二个研究日首次间歇性喂养后3小时内血浆胰岛素峰值，与连续组的同一时间段相比。次要结局包括可行性、耐受性和代谢特征。结果：30例患者随机分为间歇喂养组（n = 13）和连续喂养组（n = 17）。2例间歇组患者被排除在分析之外。两组都达到了饲料目标。间歇组血浆胰岛素峰值浓度（平均±SD）显著高于连续组（295.1±167.8比128.1±57.2 pmol/L, p < 0.001）。各组间血浆葡萄糖浓度无显著差异。其他血浆代谢物组间无差异，无高血糖/低血糖等不良事件。有证据表明，间歇性组的肠道蠕动有所增加。结论：与连续喂养相比，间歇喂养可保留危重症成人的胰岛素生理反应。两种方案的耐受性都很好，因此需要进行更大规模的试验来评估其他临床重要的以患者为中心的结果。试验注册：本试验在clinicaltrials.gov网站前瞻性注册（研究编号NCT06115044）。
{"title":"Does Intermittent Nutrition Enterally Normalise hormonal and metabolic responses to feeding in critically ill adults? The DINE-normal proof-of-concept study","authors":"Clodagh E. Beattie , Borislavova Borislava , Harry A. Smith , Michael T. Ambler , Paul White , Danielle Milne , Aravind V. Ramesh , Alexander Ferriman , Thomas Fisher , Charlotte Horsley , Sherena Jackson , Chloe Jubainville , Kate Lobo , Hannah Maxfield , Javier T. Gonzalez , James A. Betts , Anthony E. Pickering , Matt Thomas","doi":"10.1016/j.clnu.2025.10.003","DOIUrl":"10.1016/j.clnu.2025.10.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>For intensive care unit (ICU) patients fed via a nasogastric (NG) tube, current guidelines recommend continuous feeding through the day and night. Emerging evidence in healthy individuals shows that NG feeding in an intermittent diurnal pattern promotes phasic hormonal, digestive and metabolic responses vital for effective nutrition, though this has not been studied in the critically ill population. This proof-of-concept study aimed to compare the effect of diurnal intermittent versus continuous enteral feeding on hormonal and metabolic outcomes in ICU patients.</div></div><div><h3>Methods</h3><div>We conducted a single-centre, randomised, open-label trial in the ICU. Adult ICU patients that were anticipated to require NG feeding for >48 h were randomised to an intermittent diurnal regimen (feeds at 8:00, 13:00 and 18:00), or continuous feeding with equivalent nutritional value, for 48 h. The primary outcome was peak plasma insulin within 3 h of delivering the first intermittent feed on the second study day, compared to the same time period in the continuous group. Secondary outcomes included feasibility, tolerability and metabolic profiles.</div></div><div><h3>Results</h3><div>Thirty patients were randomised to intermittent (n = 13) or continuous (n = 17) feeding. Two patients in the intermittent group were excluded from analysis. Both groups achieved their feed targets. Peak plasma insulin concentrations (mean ± SD) were significantly higher in the intermittent group versus continuous (295.1 ± 167.8 vs. 128.1 ± 57.2 pmol/L, p < 0.001). Plasma glucose concentrations were not significantly different between groups. There were no between-group differences in other plasma metabolites and there were no adverse events such as hyper-/hypo-glycaemia. There was evidence of increased bowel motility in the intermittent group.</div></div><div><h3>Conclusion</h3><div>Intermittent diurnal feeding, compared to continuous feeding, preserves the physiological insulin response in critically ill adults. Both regimens were well tolerated, supporting the need for a larger trial to assess other clinically important patient-centred outcomes.</div></div><div><h3>Trial registration</h3><div>This trial was registered prospectively at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> (study ID NCT06115044).</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 81-89"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457961","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 : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.clnu.2025.11.001
Tommy Cederholm, Rocco Barazzoni, Elisabet Rothenberg, Kremlin Wickramasinghe, Cristina Cuerda, Stéphane Schneider, Stanislaw Klek
{"title":"A new diagnosis code in ICD-11 for Undernutrition in Adults – A historic achievement for the clinical nutrition community","authors":"Tommy Cederholm, Rocco Barazzoni, Elisabet Rothenberg, Kremlin Wickramasinghe, Cristina Cuerda, Stéphane Schneider, Stanislaw Klek","doi":"10.1016/j.clnu.2025.11.001","DOIUrl":"10.1016/j.clnu.2025.11.001","url":null,"abstract":"","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 219-221"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573253","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}
Critically ill patients are believed to experience a dynamic progression of energy metabolism according to the severity and phase of the illness. Although optimizing nutrition and physical therapy to the metabolic profile is recommended for better outcomes, the mechanisms for disease-related metabolic changes remain unclear. This study aimed to elucidate key metabolites and pathways associated with time-course metabolic changes and clinical parameters in acute-phase critically ill patients using untargeted metabolomics.
Methods
We conducted a single-center prospective case series study on critically ill adults expected to require mechanical ventilation for at least 7 days in our intensive care unit. Data collection was started within 48 h of ICU admission, and daily serum samples from day 1 to day 7 were collected. Untargeted metabolomics was performed using liquid chromatography/mass spectrometry. Statistical analyses included principal component analysis, (orthogonal) partial least squares discriminant analysis, and pathway analysis.
Results
Ten patients were analyzed during the study period from July 2021 to September 2022. A total of 123 metabolites were annotated by untargeted metabolomics, with significant time-course changes in galactonic acid, ornithine, and l-arginine. Pathway analysis indicated alterations in the arginine biosynthesis pathway. A subgroup analysis showed distinct metabolic profiles for sepsis and non-sepsis patients, with creatine phosphate, uric acid, and creatinine being significant markers. In sepsis patients, metabolic changes strongly correlated with the sequential organ failure assessment (SOFA) score.
Conclusion
Using untargeted metabolomics, we annotated several metabolites and metabolic pathways strongly associated with time-course changes in the metabolic profile. In addition, it is suggested that nutritional therapy can be optimized according to specific pathophysiology.
{"title":"Analysis of the time-course change of acute-phase energy metabolism in critically ill patients using untargeted metabolomics","authors":"Akiyuki Yamamoto , Akifumi Eguchi , Takehiko Oami , Shigenobu Ishida , Kengo Kondo , Nanami Hata , Kenichi Sakurai , Taka-aki Nakada , Taku Oshima","doi":"10.1016/j.clnu.2025.10.005","DOIUrl":"10.1016/j.clnu.2025.10.005","url":null,"abstract":"<div><h3>Background and aims</h3><div>Critically ill patients are believed to experience a dynamic progression of energy metabolism according to the severity and phase of the illness. Although optimizing nutrition and physical therapy to the metabolic profile is recommended for better outcomes, the mechanisms for disease-related metabolic changes remain unclear. This study aimed to elucidate key metabolites and pathways associated with time-course metabolic changes and clinical parameters in acute-phase critically ill patients using untargeted metabolomics.</div></div><div><h3>Methods</h3><div>We conducted a single-center prospective case series study on critically ill adults expected to require mechanical ventilation for at least 7 days in our intensive care unit. Data collection was started within 48 h of ICU admission, and daily serum samples from day 1 to day 7 were collected. Untargeted metabolomics was performed using liquid chromatography/mass spectrometry. Statistical analyses included principal component analysis, (orthogonal) partial least squares discriminant analysis, and pathway analysis.</div></div><div><h3>Results</h3><div>Ten patients were analyzed during the study period from July 2021 to September 2022. A total of 123 metabolites were annotated by untargeted metabolomics, with significant time-course changes in galactonic acid, ornithine, and <span>l</span>-arginine. Pathway analysis indicated alterations in the arginine biosynthesis pathway. A subgroup analysis showed distinct metabolic profiles for sepsis and non-sepsis patients, with creatine phosphate, uric acid, and creatinine being significant markers. In sepsis patients, metabolic changes strongly correlated with the sequential organ failure assessment (SOFA) score.</div></div><div><h3>Conclusion</h3><div>Using untargeted metabolomics, we annotated several metabolites and metabolic pathways strongly associated with time-course changes in the metabolic profile. In addition, it is suggested that nutritional therapy can be optimized according to specific pathophysiology.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 3-10"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415496","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 : 2025-12-01Epub Date: 2025-11-01DOI: 10.1016/j.clnu.2025.10.020
Lucia Kerkhof, Ronald P. Mensink, Jogchum Plat, Kevin M.R. Nijssen, Peter J. Joris
Background and aims
Reduced brain vascular function contributes to age-related cognitive decline. While peanut consumption may improve cognitive performance, the underlying mechanisms remain unclear. This study aimed to investigate the longer-term effects of skin-roasted peanut consumption on brain vascular function and cognitive performance in older adults.
Methods
In a randomized, single-blind, controlled crossover trial, 31 healthy individuals (age [mean ± SD]: 67 ± 4 years; BMI: 26.7 ± 3.3 kg/m2) consumed 60 g/day of unsalted, skin-roasted peanuts or no peanuts (control) for 16 weeks, separated by an 8-week washout. During follow-up, brain vascular function was assessed by quantifying global cerebral blood flow (CBF) using arterial spin labeling magnetic resonance imaging, which was the primary outcome. Cognitive performance was evaluated using the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Results
The consumption of peanuts was well-tolerated and median compliance was excellent: 100 % (interquartile range [IQR] 99–100 %). Compared with control, peanut consumption significantly increased global CBF by 3.6 % (intervention effect: 1.5 mL/100 g/min, 95 % CI [0.3, 2.6], p = 0.014) and gray matter CBF by 4.5 % (2.2 mL/100 g/min, 95 % CI [0.9, 3.6], p = 0.002). Verbal memory improved by 5.8 % during the delayed recall condition of the verbal recognition memory (VRM) task (+1.4 words correct (95 % CI [0.0, 2.7], p = 0.043). No beneficial effects were found in executive function and psychomotor speed outcomes. Systolic blood pressure (−5 mmHg; 95 % CI [-8, −2], p = 0.004) and pulse pressure (−4 mmHg; 95 % CI [-7, −1], p = 0.006) decreased during the peanut intervention.
Conclusions
Daily consumption of skin-roasted peanuts for 16 weeks improved brain vascular function in healthy older men and women. These favorable effects may underlie the observed improvements in verbal memory, highlighting a potential mechanism by which increased peanut intake beneficially affects cognitive performance.
Clinical trial registry
This trial was registered at clinicaltrial.gov as NCT05724654.
背景和目的脑血管功能的降低会导致与年龄相关的认知能力下降。虽然食用花生可能会提高认知能力，但潜在的机制尚不清楚。本研究旨在探讨皮肤烤花生食用对老年人脑血管功能和认知能力的长期影响。方法在一项随机、单盲、对照交叉试验中，31名健康个体（年龄[mean±SD]: 67±4岁；BMI: 26.7±3.3 kg/m2）连续16周食用60 g/天的无盐、皮烤花生或不食用花生（对照组），并进行8周的洗脱期。在随访期间，通过动脉自旋标记磁共振成像量化脑血流（CBF）来评估脑血管功能，这是主要结果。认知表现采用剑桥神经心理测试自动化电池（CANTAB）进行评估。结果花生耐受良好，中位依从性极好：100%（四分位间距[IQR] 99 - 100%）。与对照组相比，花生摄入显著增加了3.6%（干预效果：1.5 mL/100 g/min, 95% CI [0.3, 2.6], p = 0.014）和4.5% （2.2 mL/100 g/min, 95% CI [0.9, 3.6], p = 0.002）的脑灰质CBF。在言语识别记忆（VRM）任务的延迟回忆条件下，言语记忆提高了5.8%（+1.4个单词正确率）（95% CI [0.0, 2.7], p = 0.043）。在执行功能和精神运动速度方面没有发现有益的影响。收缩压（- 5 mmHg, 95% CI [-8, - 2], p = 0.004）和脉压（- 4 mmHg, 95% CI [-7, - 1], p = 0.006）在花生干预期间下降。结论连续16周每天食用皮烤花生可改善健康老年男女的脑血管功能。这些有利的影响可能是观察到的言语记忆改善的基础，强调了增加花生摄入量有益影响认知表现的潜在机制。临床试验注册本试验在clinicaltrial.gov注册为NCT05724654。
{"title":"Longer-term skin-roasted peanut consumption improves brain vascular function and memory: A randomized, single-blind, controlled crossover trial in healthy older adults","authors":"Lucia Kerkhof, Ronald P. Mensink, Jogchum Plat, Kevin M.R. Nijssen, Peter J. Joris","doi":"10.1016/j.clnu.2025.10.020","DOIUrl":"10.1016/j.clnu.2025.10.020","url":null,"abstract":"<div><h3>Background and aims</h3><div>Reduced brain vascular function contributes to age-related cognitive decline. While peanut consumption may improve cognitive performance, the underlying mechanisms remain unclear. This study aimed to investigate the longer-term effects of skin-roasted peanut consumption on brain vascular function and cognitive performance in older adults.</div></div><div><h3>Methods</h3><div>In a randomized, single-blind, controlled crossover trial, 31 healthy individuals (age [mean ± SD]: 67 ± 4 years; BMI: 26.7 ± 3.3 kg/m<sup>2</sup>) consumed 60 g/day of unsalted, skin-roasted peanuts or no peanuts (control) for 16 weeks, separated by an 8-week washout. During follow-up, brain vascular function was assessed by quantifying global cerebral blood flow (CBF) using arterial spin labeling magnetic resonance imaging, which was the primary outcome. Cognitive performance was evaluated using the Cambridge Neuropsychological Test Automated Battery (CANTAB).</div></div><div><h3>Results</h3><div>The consumption of peanuts was well-tolerated and median compliance was excellent: 100 % (interquartile range [IQR] 99–100 %). Compared with control, peanut consumption significantly increased global CBF by 3.6 % (intervention effect: 1.5 mL/100 g/min, 95 % CI [0.3, 2.6], p = 0.014) and gray matter CBF by 4.5 % (2.2 mL/100 g/min, 95 % CI [0.9, 3.6], p = 0.002). Verbal memory improved by 5.8 % during the delayed recall condition of the verbal recognition memory (VRM) task (+1.4 words correct (95 % CI [0.0, 2.7], p = 0.043). No beneficial effects were found in executive function and psychomotor speed outcomes. Systolic blood pressure (−5 mmHg; 95 % CI [-8, −2], p = 0.004) and pulse pressure (−4 mmHg; 95 % CI [-7, −1], p = 0.006) decreased during the peanut intervention.</div></div><div><h3>Conclusions</h3><div>Daily consumption of skin-roasted peanuts for 16 weeks improved brain vascular function in healthy older men and women. These favorable effects may underlie the observed improvements in verbal memory, highlighting a potential mechanism by which increased peanut intake beneficially affects cognitive performance.</div></div><div><h3>Clinical trial registry</h3><div>This trial was registered at <span><span>clinicaltrial.gov</span><svg><path></path></svg></span> as NCT05724654.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 170-179"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475125","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 : 2025-12-01Epub Date: 2025-11-22DOI: 10.1016/j.clnu.2025.11.009
Binbin Peng , Jia Li , Ziyi Yang , Mingxin Zhang , Wei Zhao , Chao Sun
Background & aims
Growth differentiation factor (GDF)-15 plays pivotal roles in pathophysiology and is linked to anorexia, wasting conditions, and adverse outcomes. However, its clinical implementation as a biomarker among cirrhosis remains enigmatic; thus, we explored the relationships between serum GDF-15 and diverse endpoints, including nutritional status, all-cause mortality, and health deficit.
Methods
This observational study analyzed 287 patients hospitalized due to acute decompensating episodes (median age 64 years, 55.8 % male). Malnutrition risk, various body composition, health deficit, and underlying disease severity were assessed by the RFH-NPT scale, CT scans, handgrip strength/frailty index, and CTP/MELD-Na score, respectively.
Results
The median concentrations of GDF-15 were 4.75 (Q1, Q3: 3.25, 7.54) ng/mL. Higher GDF-15 levels were related to a more prevalent malnutrition risk and more detrimental disease severity. Patients with increased GDF-15 had more impairment of renal/hepatic function, lower zinc levels, and marked hypoalbuminemia, addressing metabolic imbalance. Moreover, participants with higher GDF-15 also exhibited more significant health deficit like multidimensional frailty. Multivariate Cox analysis indicated that increased GDF-15 independently predicted 1-year mortality after adjustment for coexisting nutritional status and underpinning disease burden (CTP: HR: 1.07, 95%CI: 1.01, 1.13, P = 0.013; MELD-Na: HR: 1.06, 95%CI: 1.01, 1.12, P = 0.044).
Conclusions
Serum GDF-15 concentrations were higher in patients with decompensated cirrhosis at risk of malnutrition. Furthermore, this biomarker was closely linked to an increased risk of adverse outcomes and health deficit. It has potential as a complementary biomarker for assessing the prognosis in the context of cirrhosis.
{"title":"Growth differentiation factor-15 is associated with adverse outcome, malnutrition risk and health deficit in decompensated cirrhosis","authors":"Binbin Peng , Jia Li , Ziyi Yang , Mingxin Zhang , Wei Zhao , Chao Sun","doi":"10.1016/j.clnu.2025.11.009","DOIUrl":"10.1016/j.clnu.2025.11.009","url":null,"abstract":"<div><h3>Background & aims</h3><div>Growth differentiation factor (GDF)-15 plays pivotal roles in pathophysiology and is linked to anorexia, wasting conditions, and adverse outcomes. However, its clinical implementation as a biomarker among cirrhosis remains enigmatic; thus, we explored the relationships between serum GDF-15 and diverse endpoints, including nutritional status, all-cause mortality, and health deficit.</div></div><div><h3>Methods</h3><div>This observational study analyzed 287 patients hospitalized due to acute decompensating episodes (median age 64 years, 55.8 % male). Malnutrition risk, various body composition, health deficit, and underlying disease severity were assessed by the RFH-NPT scale, CT scans, handgrip strength/frailty index, and CTP/MELD-Na score, respectively.</div></div><div><h3>Results</h3><div>The median concentrations of GDF-15 were 4.75 (Q1, Q3: 3.25, 7.54) ng/mL. Higher GDF-15 levels were related to a more prevalent malnutrition risk and more detrimental disease severity. Patients with increased GDF-15 had more impairment of renal/hepatic function, lower zinc levels, and marked hypoalbuminemia, addressing metabolic imbalance. Moreover, participants with higher GDF-15 also exhibited more significant health deficit like multidimensional frailty. Multivariate Cox analysis indicated that increased GDF-15 independently predicted 1-year mortality after adjustment for coexisting nutritional status and underpinning disease burden (CTP: HR: 1.07, 95%CI: 1.01, 1.13, P = 0.013; MELD-Na: HR: 1.06, 95%CI: 1.01, 1.12, P = 0.044).</div></div><div><h3>Conclusions</h3><div>Serum GDF-15 concentrations were higher in patients with decompensated cirrhosis at risk of malnutrition. Furthermore, this biomarker was closely linked to an increased risk of adverse outcomes and health deficit. It has potential as a complementary biomarker for assessing the prognosis in the context of cirrhosis.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 273-281"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653802","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}
In old adult patients with sarcopenia hospitalized for rehabilitation, the superior clinical benefit of a muscle-targeted formula (MTF; whey protein-based enriched with leucine and vitamin D) over an iso-caloric protein-free one was assessed through the IRIS trial (NCT03120026). The aim of this study is to further evaluate the economic benefit in the Italian context.
Methods
A cost-consequence secondary analysis was developed. Clinical inputs were evaluated over the course of the year in terms of nutrition cost, rehabilitation cost and modality of discharge (cost of staying at home vs institution) in three different payer perspectives: (1) hospital, including only nutrition and rehabilitation costs; (2) third-party payer (TPP), including also the economic consequences of patients discharged to an institution; and (3) societal perspective, including also the economic impact on families due to home assistance. For each one, the mean annual cost per patient was calculated. An estimation of the additional number of patients that could be hospitalized each year in Italy using the MTF was also computed.
Results
The MTF was less expensive in all three perspectives considered. Mean saving per patient by perspective was: hospital, € 1536; TPP, € 10,540; societal, € 14,363. Rehabilitation was faster in patients taking the MTF resulting in lower costs to manage sarcopenia, though savings were mostly driven by patients being discharged at home instead of an institution. Finally, assuming a use of the MTF ranging from 50 % to 80 %, about 495,214–792,342 bed days could be saved meaning that 10,538–18,067 additional patients may be treated every year.
Conclusions
Costs associated with the nutritional support of adult patients with sarcopenia hospitalized for rehabilitation with a MTF were inferior than an iso-caloric formula in all payer perspectives. Furthermore, LOS was shorter and more patients could be hospitalized with the same number of beds.
{"title":"Budget impact analysis of a muscle-targeted nutritional intervention for sarcopenia","authors":"Emanuele Cereda , Massimiliano Povero , Luca Castello , Riccardo Caccialanza , Lorenzo Pradelli , Mariangela Rondanelli","doi":"10.1016/j.clnu.2025.10.019","DOIUrl":"10.1016/j.clnu.2025.10.019","url":null,"abstract":"<div><h3>Background</h3><div>In old adult patients with sarcopenia hospitalized for rehabilitation, the superior clinical benefit of a muscle-targeted formula (MTF; whey protein-based enriched with leucine and vitamin D) over an iso-caloric protein-free one was assessed through the IRIS trial (NCT03120026). The aim of this study is to further evaluate the economic benefit in the Italian context.</div></div><div><h3>Methods</h3><div>A cost-consequence secondary analysis was developed. Clinical inputs were evaluated over the course of the year in terms of nutrition cost, rehabilitation cost and modality of discharge (cost of staying at home vs institution) in three different payer perspectives: (1) hospital, including only nutrition and rehabilitation costs; (2) third-party payer (TPP), including also the economic consequences of patients discharged to an institution; and (3) societal perspective, including also the economic impact on families due to home assistance. For each one, the mean annual cost per patient was calculated. An estimation of the additional number of patients that could be hospitalized each year in Italy using the MTF was also computed.</div></div><div><h3>Results</h3><div>The MTF was less expensive in all three perspectives considered. Mean saving per patient by perspective was: hospital, € 1536; TPP, € 10,540; societal, € 14,363. Rehabilitation was faster in patients taking the MTF resulting in lower costs to manage sarcopenia, though savings were mostly driven by patients being discharged at home instead of an institution. Finally, assuming a use of the MTF ranging from 50 % to 80 %, about 495,214–792,342 bed days could be saved meaning that 10,538–18,067 additional patients may be treated every year.</div></div><div><h3>Conclusions</h3><div>Costs associated with the nutritional support of adult patients with sarcopenia hospitalized for rehabilitation with a MTF were inferior than an iso-caloric formula in all payer perspectives. Furthermore, LOS was shorter and more patients could be hospitalized with the same number of beds.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 162-169"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475505","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 : 2025-12-01Epub Date: 2025-10-29DOI: 10.1016/j.clnu.2025.10.011
Yixi Sun , Ruiyuan Zhang , Ling Tian , Tingting Liu , Yang Pan , Xiao Sun , Zhijie Huang , Jia Fan , Jing Chen , Kai Zhang , Shengxu Li , Wei Chen , Lydia A. Bazzano , Jiang He , Joshua D. Bundy , Tanika N. Kelly , Changwei Li
Background
Inosine has been investigated as a dietary supplement for athlete performance, inflammation, and neurological disease. A recent study in a hypercholesterolemic rat model has shown its potential for treating atherosclerosis.
Objective
This study aimed to investigate the associations between plasma inosine and lipid parameters, and to discover potential mediating pathways.
Methods
We profiled inosine and 886 known metabolites in plasma samples from 1,121 participants of a biracial cohort. Linear regression models assessed inosine's association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), log transformed triglycerides (log-TG), and TC to HDL-C ratio (TC/HDL-C), adjusting for relevant covariates. Significant findings were replicated in 78 adults from the Protein and Blood Pressure (ProBP) study, a cross-over randomized control trial by testing longitudinal associations between inosine changes and lipid changes after dietary supplementation of soy protein, milk protein, and carbohydrates. For a replicated association, we employed two complementary approaches to identify potential mediators for enrichment analysis.
Results
In the discovery cohort, inosine was positively associated with HDL-C (β = 1.77, 95 % confidence interval [CI]: 0.003 to 3.54) and negatively associated with TC/HDL-C (β = −0.24, 95 % CI: −0.41 to −0.08) and log-TG (β = −0.08, 95 % CI: −0.15 to −0.02). These results were replicated in ProBP after soy protein intervention with inosine changes leading to increase of HDL-C (β = 1.82, 95 % CI: 0.36 to 3.27) and decrease of TC/HDL-C (β = −0.14, 95 % CI:-0.28 to −0.002) and TG (β = −12.79, 95 % CI: −21.00 to −4.58). Sex-stratified analyses revealed a more pronounced association in women than men, particularly for HDL-C. Six metabolites and 29 enriched pathways of high confidence were identified.
Conclusion
In humans, inosine is associated with better profiles of HDL-C, TC/HDL-C, and log-TG, with more pronounced effects in women for HDL-C.
The ProBP trial was registered at ClinicalTrials.gov as NCT00107744.
{"title":"Associations of plasma inosine with lipid parameters in a biracial community cohort","authors":"Yixi Sun , Ruiyuan Zhang , Ling Tian , Tingting Liu , Yang Pan , Xiao Sun , Zhijie Huang , Jia Fan , Jing Chen , Kai Zhang , Shengxu Li , Wei Chen , Lydia A. Bazzano , Jiang He , Joshua D. Bundy , Tanika N. Kelly , Changwei Li","doi":"10.1016/j.clnu.2025.10.011","DOIUrl":"10.1016/j.clnu.2025.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Inosine has been investigated as a dietary supplement for athlete performance, inflammation, and neurological disease. A recent study in a hypercholesterolemic rat model has shown its potential for treating atherosclerosis.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the associations between plasma inosine and lipid parameters, and to discover potential mediating pathways.</div></div><div><h3>Methods</h3><div>We profiled inosine and 886 known metabolites in plasma samples from 1,121 participants of a biracial cohort. Linear regression models assessed inosine's association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), log transformed triglycerides (log-TG), and TC to HDL-C ratio (TC/HDL-C), adjusting for relevant covariates. Significant findings were replicated in 78 adults from the Protein and Blood Pressure (ProBP) study, a cross-over randomized control trial by testing longitudinal associations between inosine changes and lipid changes after dietary supplementation of soy protein, milk protein, and carbohydrates. For a replicated association, we employed two complementary approaches to identify potential mediators for enrichment analysis.</div></div><div><h3>Results</h3><div>In the discovery cohort, inosine was positively associated with HDL-C (β = 1.77, 95 % confidence interval [CI]: 0.003 to 3.54) and negatively associated with TC/HDL-C (β = −0.24, 95 % CI: −0.41 to −0.08) and log-TG (β = −0.08, 95 % CI: −0.15 to −0.02). These results were replicated in ProBP after soy protein intervention with inosine changes leading to increase of HDL-C (β = 1.82, 95 % CI: 0.36 to 3.27) and decrease of TC/HDL-C (β = −0.14, 95 % CI:-0.28 to −0.002) and TG (β = −12.79, 95 % CI: −21.00 to −4.58). Sex-stratified analyses revealed a more pronounced association in women than men, particularly for HDL-C. Six metabolites and 29 enriched pathways of high confidence were identified.</div></div><div><h3>Conclusion</h3><div>In humans, inosine is associated with better profiles of HDL-C, TC/HDL-C, and log-TG, with more pronounced effects in women for HDL-C.</div><div>The ProBP trial was registered at ClinicalTrials.gov as NCT00107744.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 113-123"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470611","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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