Pub Date : 2026-01-22DOI: 10.1016/j.clnu.2026.106583
Carliene van Dronkelaar , Maarten R. Soeters , Philipp Schuetz , Carla M. Prado , Nicole Kiss , Michael Tieland , Hinke Kruizenga
Malnutrition is a multifactorial and complex condition with significant consequences for recovery, functional outcomes, and healthcare systems. Research in malnutrition is often limited by single-component interventions, heterogeneous study designs, and variable outcome measures. This perspective paper introduces a practical guiding framework for clinical nutrition research, emphasizing interdisciplinary, multifactorial approaches, co-designed interventions, and pragmatic, adaptive study designs. Evidence from several trials demonstrates that individualized nutritional support delivered by multidisciplinary teams improves clinical outcomes, yet challenges remain in recruitment, adherence, and balancing intervention intensity with patient burden. The framework provides a structured approach to intervention development, outcome selection, and implementation, while remaining flexible to accommodate innovation, context-specific adaptation, and emerging outcome measures. By integrating lessons from prior trials, globally, and promoting systematic reporting and feasibility assessment, this framework aims to enhance the design, comparability, and translational impact of future research in clinical nutrition in older and other clinically vulnerable populations. Adoption of such a framework can guide research prioritization, optimize intervention delivery, and ultimately improve patient recovery and quality of life.
{"title":"A holistic perspective on malnutrition in older adults: Towards an integrated clinical nutrition research guiding framework","authors":"Carliene van Dronkelaar , Maarten R. Soeters , Philipp Schuetz , Carla M. Prado , Nicole Kiss , Michael Tieland , Hinke Kruizenga","doi":"10.1016/j.clnu.2026.106583","DOIUrl":"10.1016/j.clnu.2026.106583","url":null,"abstract":"<div><div>Malnutrition is a multifactorial and complex condition with significant consequences for recovery, functional outcomes, and healthcare systems. Research in malnutrition is often limited by single-component interventions, heterogeneous study designs, and variable outcome measures. This perspective paper introduces a practical guiding framework for clinical nutrition research, emphasizing interdisciplinary, multifactorial approaches, co-designed interventions, and pragmatic, adaptive study designs. Evidence from several trials demonstrates that individualized nutritional support delivered by multidisciplinary teams improves clinical outcomes, yet challenges remain in recruitment, adherence, and balancing intervention intensity with patient burden. The framework provides a structured approach to intervention development, outcome selection, and implementation, while remaining flexible to accommodate innovation, context-specific adaptation, and emerging outcome measures. By integrating lessons from prior trials, globally, and promoting systematic reporting and feasibility assessment, this framework aims to enhance the design, comparability, and translational impact of future research in clinical nutrition in older and other clinically vulnerable populations. Adoption of such a framework can guide research prioritization, optimize intervention delivery, and ultimately improve patient recovery and quality of life.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106583"},"PeriodicalIF":7.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112627","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 : 2026-01-21DOI: 10.1016/j.clnu.2026.106578
Saurabh Mehta, Samantha L Huey, Padmini S Ghugre, Ramesh D Potdar, Sudha Venkatramanan, Jesse T Krisher, Caleb J Ruth, Harsha V Chopra, Aparna Thorat, Varsha Thakker, Lynn Johnson, Laura Powis, Yadurshini Raveendran, Jere D Haas, Julia L Finkelstein, Shobha A Udipi
This article has been retracted: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article is retracted at the request of the authors. During post-publication data re-analyses, the authors found four additional hemoglobin datapoints at the endpoint of the trial reported in the above-named article that move the p-value for the primary outcome - the impact of intervention on the change in hemoglobin concentrations across the duration of the trial - from 0.053 to 0.044. Furthermore, the WHO has recently released a revised set of cutoffs for anemia [WHO 2024], and the anemia cutoff for the age group of interest in this article, 12-23 months, was lowered from a hemoglobin concentration of 11 g/dL to 10.5 g/dL. As such, the authors wish to report these revised estimates of anemia based on the revised WHO cutoffs to keep the findings as updated as possible and useful for guidelines. The Editors considered this request and agreed to the retraction of the article. The authors were invited to submit a revised version of the article, which has been peer-reviewed and accepted for publication in the journal. This retraction notice will be updated with a link to the revised paper when it is published.
{"title":"Retraction notice to \"A randomized trial of iron- and zinc-biofortified pearl millet-based complementary feeding in children aged 12 to 18 months living in urban slums\" [Clin Nutr 41 (2022) 937-947].","authors":"Saurabh Mehta, Samantha L Huey, Padmini S Ghugre, Ramesh D Potdar, Sudha Venkatramanan, Jesse T Krisher, Caleb J Ruth, Harsha V Chopra, Aparna Thorat, Varsha Thakker, Lynn Johnson, Laura Powis, Yadurshini Raveendran, Jere D Haas, Julia L Finkelstein, Shobha A Udipi","doi":"10.1016/j.clnu.2026.106578","DOIUrl":"10.1016/j.clnu.2026.106578","url":null,"abstract":"<p><p>This article has been retracted: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article is retracted at the request of the authors. During post-publication data re-analyses, the authors found four additional hemoglobin datapoints at the endpoint of the trial reported in the above-named article that move the p-value for the primary outcome - the impact of intervention on the change in hemoglobin concentrations across the duration of the trial - from 0.053 to 0.044. Furthermore, the WHO has recently released a revised set of cutoffs for anemia [WHO 2024], and the anemia cutoff for the age group of interest in this article, 12-23 months, was lowered from a hemoglobin concentration of 11 g/dL to 10.5 g/dL. As such, the authors wish to report these revised estimates of anemia based on the revised WHO cutoffs to keep the findings as updated as possible and useful for guidelines. The Editors considered this request and agreed to the retraction of the article. The authors were invited to submit a revised version of the article, which has been peer-reviewed and accepted for publication in the journal. This retraction notice will be updated with a link to the revised paper when it is published.</p>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":" ","pages":"106578"},"PeriodicalIF":7.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028378","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 : 2026-01-20DOI: 10.1016/j.clnu.2026.106582
Mei Han , Fei Xu , Yao Dong , Jianguo Zhu , Shuguang Fang , Liming Zhao
Background and aims
This study aimed to systematically evaluate the genomic safety of Limosilactobacillus reuteri LR08 and to assess its effects on metabolic health, immune function, and gut microbiota composition in healthy adults..
Methods
Whole-genome sequencing and bioinformatics analyses were conducted to assess the presence of genes related to pathogenicity, antibiotic resistance, and biogenic amine synthesis. In vitro assays and animal studies evaluated hemolytic activity, cytotoxicity, and overall biosafety. A randomized, double-blind, placebo-controlled trial was performed in 48 healthy adults, who received either LR08 (30 billion CFU/day) or placebo for 8 weeks. Clinical, biochemical, and immune parameters were measured, and 16S rRNA sequencing was used to assess gut microbiota changes.
Results
Genomic analysis confirmed the absence of pathogenicity-related, antibiotic resistance, or biogenic amine synthesis genes. In vitro and animal tests demonstrated non-hemolytic, non-cytotoxic characteristics and overall safety. Clinically, LR08 significantly reduced serum uric acid (p < 0.001) and LDL-C levels (p = 0.007) compared with baseline. Compared with placebo, LR08 supplementation significantly increased salivary IgA (p = 0.039), IgM (p = 0.029), and calprotectin levels (p < 0.05). Gut microbiota analysis revealed increased α-diversity, enrichment of beneficial genera including Blautia and Romboutsia, and upregulation of pathways related to carbohydrate metabolism and genetic information processing..
Conclusions
L. reuteri LR08 demonstrates robust genomic safety and favorable effects on metabolic, immune, and gut microbiota profiles in healthy adults. These findings support its potential application as a safe probiotic for metabolic regulation, immune enhancement, and microbiota modulation..
{"title":"Safety and immune-regulating effects of Limosilactobacillus reuteri LR08: Preclinical and clinical evidence from a randomized controlled trial","authors":"Mei Han , Fei Xu , Yao Dong , Jianguo Zhu , Shuguang Fang , Liming Zhao","doi":"10.1016/j.clnu.2026.106582","DOIUrl":"10.1016/j.clnu.2026.106582","url":null,"abstract":"<div><h3>Background and aims</h3><div>This study aimed to systematically evaluate the genomic safety of <em>Limosilactobacillus reuteri</em> LR08 and to assess its effects on metabolic health, immune function, and gut microbiota composition in healthy adults..</div></div><div><h3>Methods</h3><div>Whole-genome sequencing and bioinformatics analyses were conducted to assess the presence of genes related to pathogenicity, antibiotic resistance, and biogenic amine synthesis. In vitro assays and animal studies evaluated hemolytic activity, cytotoxicity, and overall biosafety. A randomized, double-blind, placebo-controlled trial was performed in 48 healthy adults, who received either LR08 (30 billion CFU/day) or placebo for 8 weeks. Clinical, biochemical, and immune parameters were measured, and 16S rRNA sequencing was used to assess gut microbiota changes.</div></div><div><h3>Results</h3><div>Genomic analysis confirmed the absence of pathogenicity-related, antibiotic resistance, or biogenic amine synthesis genes. In vitro and animal tests demonstrated non-hemolytic, non-cytotoxic characteristics and overall safety. Clinically, LR08 significantly reduced serum uric acid (<em>p</em> < 0.001) and LDL-C levels (<em>p</em> = 0.007) compared with baseline. Compared with placebo, LR08 supplementation significantly increased salivary IgA (<em>p</em> = 0.039), IgM (<em>p</em> = 0.029), and calprotectin levels (<em>p</em> < 0.05). Gut microbiota analysis revealed increased α-diversity, enrichment of beneficial genera including <em>Blautia</em> and <em>Romboutsia</em>, and upregulation of pathways related to carbohydrate metabolism and genetic information processing..</div></div><div><h3>Conclusions</h3><div><em>L. reuteri</em> LR08 demonstrates robust genomic safety and favorable effects on metabolic, immune, and gut microbiota profiles in healthy adults. These findings support its potential application as a safe probiotic for metabolic regulation, immune enhancement, and microbiota modulation..</div></div><div><h3>Trial Registration Number</h3><div>NCT06875362 (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106582"},"PeriodicalIF":7.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131389","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 : 2026-01-20DOI: 10.1016/j.clnu.2026.106580
Yiwen Wang , Man Ching Lo , Murray Fisher , Katherine Desneves , Amy Nevin , Priya lyer
Pressure injuries (PIs) are a common and costly complication in adults with spinal cord injuries and disorders (SCI/D), with a global prevalence of 32 % and a lifetime risk exceeding 85 % in Australia. Nutrition is a key factor in the prevention and management of PIs, supporting wound healing, immune function, and overall recovery. This systematic review evaluated the quality, scope, and methodological rigour of 17 international clinical practice guidelines (CPGs) published since 2010 that included nutrition recommendations for PIs in adults with SCI/D. Using the AGREE II and the AGREE-REX tools, this review assessed overall guideline quality and nutrition-specific recommendations mapped to the Nutrition Care Process domains. Seven CPGs were rated high quality with AGREE II, and three with AGREE-REX. While most guidelines focussed on nutrition interventions, limited detail was provided on assessment and monitoring. Considerable variation was found in the rigour and specificity of recommendations. These findings underscore a need for high-quality, SCI/D-specific guidelines that offer consistent, evidence-based, actionable nutrition guidance, particularly in the under-represented areas of assessment and monitoring, to better support PI prevention and treatment in this vulnerable population.
{"title":"Nutrition care in adults with spinal cord injuries and disorders with pressure injuries: A systematic review of clinical practice guidelines","authors":"Yiwen Wang , Man Ching Lo , Murray Fisher , Katherine Desneves , Amy Nevin , Priya lyer","doi":"10.1016/j.clnu.2026.106580","DOIUrl":"10.1016/j.clnu.2026.106580","url":null,"abstract":"<div><div>Pressure injuries (PIs) are a common and costly complication in adults with spinal cord injuries and disorders (SCI/D), with a global prevalence of 32 % and a lifetime risk exceeding 85 % in Australia. Nutrition is a key factor in the prevention and management of PIs, supporting wound healing, immune function, and overall recovery. This systematic review evaluated the quality, scope, and methodological rigour of 17 international clinical practice guidelines (CPGs) published since 2010 that included nutrition recommendations for PIs in adults with SCI/D. Using the AGREE II and the AGREE-REX tools, this review assessed overall guideline quality and nutrition-specific recommendations mapped to the Nutrition Care Process domains. Seven CPGs were rated high quality with AGREE II, and three with AGREE-REX. While most guidelines focussed on nutrition interventions, limited detail was provided on assessment and monitoring. Considerable variation was found in the rigour and specificity of recommendations. These findings underscore a need for high-quality, SCI/D-specific guidelines that offer consistent, evidence-based, actionable nutrition guidance, particularly in the under-represented areas of assessment and monitoring, to better support PI prevention and treatment in this vulnerable population.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106580"},"PeriodicalIF":7.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077060","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}
Clinical evidence for anamorelin in pancreatic cancer is extremely limited, despite its approval in Japan. This study provides the first prospective evaluation of anamorelin specifically in pancreatic cancer, aiming to assess real-world efficacy and safety and to identify factors contributing to treatment-response heterogeneity through integrated biomarker analyses.
Methods
This prospective, single-center, observational study enrolled 24 patients with unresectable or metastatic pancreatic cancer who developed cachexia. Efficacy was evaluated in patients who received anamorelin for >1 month. The primary endpoint was change in LBM from baseline, and secondary endpoints included the LBM-based response rate. Responders were defined as those who maintained or increased LBM during treatment. Safety assessment focused on treatment-related adverse events, particularly hyperglycemia.
Results
Seventeen patients were included in the efficacy analysis (median age, 68 years; median weight loss, 8.3 %). The mean LBM increased by 0.9 and 1.4 kg at 1 and 2 months, respectively. Quality-of-life scores related to appetite, weight gain, and total scores improved significantly at 1 month. Ten patients (58.8 %) were classified as responders, showing significant LBM gains from baseline (+2.4 kg at 1 month, +3.4 kg at 2 months, p < 0.001). Handgrip strength also improved in responders compared with non-responders at 2 months (+1.7 kg vs −2.0 kg, p < 0.01). Serum levels of insulin-like growth factor-1, inflammatory cytokines, ghrelin, and leptin levels did not differ significantly between baseline and 1 month. However, lower baseline body mass index (BMI) was strongly associated with response (sensitivity 85.7 %, specificity 90.0 %, area under the curve [AUC] 0.886, cutoff 20.4 kg/m2; p = 0.008). In the safety analysis (n = 23), 34.8 % experienced hyperglycemia of any grade, and 26.1 % developed grade ≥2 hyperglycemia—higher than in NSCLC trials. Median time to onset was 4.5 days (range, 2–18). Baseline diabetes was significantly associated with grade ≥2 hyperglycemia. This event was highly predictable by low pre-treatment ΔC-peptide levels (6–0 min; sensitivity 100.0 %, specificity 91.7 %, cut-off 1.03 ng/mL, AUC 0.967; p = 0.0032).
Conclusions
Anamorelin effectively improved LBM and appetite/QOL domains in pancreatic cancer, particularly in patients with low BMI. However, hyperglycemia—especially in those with impaired insulin secretion—requires careful monitoring. Baseline BMI and insulin secretion capacity should be evaluated before initiating therapy, and these findings provide preliminary insight into treatment response heterogeneity in pancreatic cancer cachexia.
背景和目的尽管anamorelin在日本获得批准,但其治疗胰腺癌的临床证据极其有限。本研究首次对anamorelin在胰腺癌中的特异性治疗进行了前瞻性评估,旨在通过综合生物标志物分析评估真实世界的疗效和安全性,并确定导致治疗-反应异质性的因素。方法:本前瞻性、单中心、观察性研究纳入24例不可切除或转移性恶性肿瘤患者。对接受阿纳莫瑞林治疗1个月的患者进行疗效评估。主要终点是LBM较基线的变化,次要终点包括基于LBM的缓解率。应答者被定义为在治疗期间维持或增加LBM的人。安全性评估侧重于治疗相关的不良事件,特别是高血糖。结果17例患者纳入疗效分析(中位年龄68岁,中位体重减轻8.3%)。在1个月和2个月时,平均体重分别增加0.9和1.4公斤。与食欲、体重增加和总分相关的生活质量评分在1个月时显著改善。10名患者(58.8%)被归类为应答者,显示出较基线显著的体重增加(1个月+2.4 kg, 2个月+3.4 kg, p < 0.001)。在2个月时,有反应者的握力也比无反应者有所改善(+1.7 kg vs - 2.0 kg, p < 0.01)。血清胰岛素样生长因子-1、炎症细胞因子、胃饥饿素和瘦素水平在基线和1个月之间没有显著差异。然而,较低的基线体重指数(BMI)与疗效密切相关(敏感性85.7%,特异性90.0%,曲线下面积[AUC] 0.886,截止值20.4 kg/m2; p = 0.008)。在安全性分析中(n = 23), 34.8%的患者出现了任何级别的高血糖,26.1%的患者出现了≥2级的高血糖,高于NSCLC试验。中位发病时间为4.5天(范围2-18天)。基线糖尿病与≥2级高血糖显著相关。低预处理ΔC-peptide水平(6-0 min;敏感性100.0%,特异性91.7%,截止值1.03 ng/mL, AUC 0.967; p = 0.0032)可高度预测该事件。结论sanamorelin能有效改善胰腺癌患者的LBM和食欲/生活质量域,特别是对低BMI患者。然而,高血糖——尤其是那些胰岛素分泌受损的人——需要仔细监测。在开始治疗前应该评估基线BMI和胰岛素分泌能力,这些发现为胰腺癌恶病质的治疗反应异质性提供了初步的见解。
{"title":"Prospective study of anamorelin in pancreatic cancer cachexia: Clinical and translational insights into response heterogeneity","authors":"Ryosuke Matsukane , Haruna Minami , Nao Fujimori , Keijiro Ueda , Yasuhiro Komori , Yu Takamatsu , Takahiro Ueda , Minako Kimura , Chitose Matsuzaki , Takanori Tanaka , Aimi Morito , Saki Kuwahara , Masako Hashimoto , Satoshi Hirai , Tomiko Yokoyama , Shigeru Ishida , Takeshi Hirota , Yoshihiro Ogawa , Mayako Uchida","doi":"10.1016/j.clnu.2026.106581","DOIUrl":"10.1016/j.clnu.2026.106581","url":null,"abstract":"<div><h3>Background & aims</h3><div>Clinical evidence for anamorelin in pancreatic cancer is extremely limited, despite its approval in Japan. This study provides the first prospective evaluation of anamorelin specifically in pancreatic cancer, aiming to assess real-world efficacy and safety and to identify factors contributing to treatment-response heterogeneity through integrated biomarker analyses.</div></div><div><h3>Methods</h3><div>This prospective, single-center, observational study enrolled 24 patients with unresectable or metastatic pancreatic cancer who developed cachexia. Efficacy was evaluated in patients who received anamorelin for >1 month. The primary endpoint was change in LBM from baseline, and secondary endpoints included the LBM-based response rate. Responders were defined as those who maintained or increased LBM during treatment. Safety assessment focused on treatment-related adverse events, particularly hyperglycemia.</div></div><div><h3>Results</h3><div>Seventeen patients were included in the efficacy analysis (median age, 68 years; median weight loss, 8.3 %). The mean LBM increased by 0.9 and 1.4 kg at 1 and 2 months, respectively. Quality-of-life scores related to appetite, weight gain, and total scores improved significantly at 1 month. Ten patients (58.8 %) were classified as responders, showing significant LBM gains from baseline (+2.4 kg at 1 month, +3.4 kg at 2 months, p < 0.001). Handgrip strength also improved in responders compared with non-responders at 2 months (+1.7 kg vs −2.0 kg, p < 0.01). Serum levels of insulin-like growth factor-1, inflammatory cytokines, ghrelin, and leptin levels did not differ significantly between baseline and 1 month. However, lower baseline body mass index (BMI) was strongly associated with response (sensitivity 85.7 %, specificity 90.0 %, area under the curve [AUC] 0.886, cutoff 20.4 kg/m<sup>2</sup>; p = 0.008). In the safety analysis (n = 23), 34.8 % experienced hyperglycemia of any grade, and 26.1 % developed grade ≥2 hyperglycemia—higher than in NSCLC trials. Median time to onset was 4.5 days (range, 2–18). Baseline diabetes was significantly associated with grade ≥2 hyperglycemia. This event was highly predictable by low pre-treatment ΔC-peptide levels (6–0 min; sensitivity 100.0 %, specificity 91.7 %, cut-off 1.03 ng/mL, AUC 0.967; p = 0.0032).</div></div><div><h3>Conclusions</h3><div>Anamorelin effectively improved LBM and appetite/QOL domains in pancreatic cancer, particularly in patients with low BMI. However, hyperglycemia—especially in those with impaired insulin secretion—requires careful monitoring. Baseline BMI and insulin secretion capacity should be evaluated before initiating therapy, and these findings provide preliminary insight into treatment response heterogeneity in pancreatic cancer cachexia.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106581"},"PeriodicalIF":7.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077063","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 : 2026-01-19DOI: 10.1016/j.clnu.2026.106579
Alysha S. Thompson , Nicola P. Bondonno , Yan Lydia Liu , Farah Qureshi , Laura D. Kubzansky , Claudia Trudel-Fitzgerald , Julia K. Boehm , Eric B. Rimm , Aedín Cassidy
Background and aim
Higher dietary flavonoid intake has been associated with lower risks of mortality and major chronic disease, yet its relationship with psychological well-being (PWB), a key contributor to health and quality of life, remains unclear. This study aimed to investigate bidirectional associations between dietary flavonoid intake and two PWB facets: happiness (positive emotional state) and optimism (generalized expectation of positive outcomes). Specifically, we examined whether (1) overall flavonoid-rich dietary patterns (flavodiet score), (2) intake of specific flavonoid-rich foods, and (3) total flavonoid and subclass intakes were each associated with happiness and optimism over time.
Methods
Data were drawn from the Nurses’ Health Study to form two analytical samples. Flavonoid intake measured in 1990 (n = 44,659) was examined in relation to sustained happiness (1992–2000) while intake in 2002 (n = 36,723) was analysed in relation to sustained optimism (2004–2012). Secondary analyses assessed whether higher baseline levels of each PWB facet were associated with sustained higher flavonoid intake, over up to 18 years. Associations were assessed using generalized estimating equations, adjusting for potential confounders.
Results
Higher flavodiet scores were associated with a 3–6 % higher likelihood of sustained happiness [RRQ4vsQ1 (95 % CI): 1.03 (1.02–1.05)] and optimism [RRQ4vsQ1 (95 % CI): 1.06 (1.01–1.11)]. Specific flavonoid-rich foods (strawberries, apples, oranges, grapefruit, blueberries) were associated with a 3–16 % greater likelihood of sustained PWB, across the two facets. Similarly, total flavonoid and subclass intakes were associated with a 2–18 % greater likelihood of sustained PWB. Women with higher baseline levels of happiness or optimism were also more likely to sustain a higher flavonoid intake.
Conclusions
Consuming ∼3 servings/day of flavonoid-rich foods is associated with sustained PWB, and higher baseline PWB is associated with sustained higher flavonoid intake over up to 18 years. This bidirectional relationship suggests that integrated interventions targeting both diet and well-being may help promote long-term health and reduce chronic disease risk.
{"title":"Dietary flavonoid intake and psychological well-being – A bidirectional relationship","authors":"Alysha S. Thompson , Nicola P. Bondonno , Yan Lydia Liu , Farah Qureshi , Laura D. Kubzansky , Claudia Trudel-Fitzgerald , Julia K. Boehm , Eric B. Rimm , Aedín Cassidy","doi":"10.1016/j.clnu.2026.106579","DOIUrl":"10.1016/j.clnu.2026.106579","url":null,"abstract":"<div><h3>Background and aim</h3><div>Higher dietary flavonoid intake has been associated with lower risks of mortality and major chronic disease, yet its relationship with psychological well-being (PWB), a key contributor to health and quality of life, remains unclear. This study aimed to investigate bidirectional associations between dietary flavonoid intake and two PWB facets: happiness (positive emotional state) and optimism (generalized expectation of positive outcomes). Specifically, we examined whether (1) overall flavonoid-rich dietary patterns (flavodiet score), (2) intake of specific flavonoid-rich foods, and (3) total flavonoid and subclass intakes were each associated with happiness and optimism over time.</div></div><div><h3>Methods</h3><div>Data were drawn from the Nurses’ Health Study to form two analytical samples. Flavonoid intake measured in 1990 (n = 44,659) was examined in relation to sustained happiness (1992–2000) while intake in 2002 (n = 36,723) was analysed in relation to sustained optimism (2004–2012). Secondary analyses assessed whether higher baseline levels of each PWB facet were associated with sustained higher flavonoid intake, over up to 18 years. Associations were assessed using generalized estimating equations, adjusting for potential confounders.</div></div><div><h3>Results</h3><div>Higher flavodiet scores were associated with a 3–6 % higher likelihood of sustained happiness [RR<sub>Q4vsQ1</sub> (95 % CI): 1.03 (1.02–1.05)] and optimism [RR<sub>Q4vsQ1</sub> (95 % CI): 1.06 (1.01–1.11)]. Specific flavonoid-rich foods (strawberries, apples, oranges, grapefruit, blueberries) were associated with a 3–16 % greater likelihood of sustained PWB, across the two facets. Similarly, total flavonoid and subclass intakes were associated with a 2–18 % greater likelihood of sustained PWB. Women with higher baseline levels of happiness or optimism were also more likely to sustain a higher flavonoid intake.</div></div><div><h3>Conclusions</h3><div>Consuming ∼3 servings/day of flavonoid-rich foods is associated with sustained PWB, and higher baseline PWB is associated with sustained higher flavonoid intake over up to 18 years. This bidirectional relationship suggests that integrated interventions targeting both diet and well-being may help promote long-term health and reduce chronic disease risk.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106579"},"PeriodicalIF":7.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077176","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 : 2026-01-14DOI: 10.1016/j.clnu.2026.106577
Philipp Schuetz , Frank Carrera-Gil , Carla Wunderle
Protein is a central component of artificial nutrition, yet its optimal dose and timing remain controversial. Provision of both insufficient and excessive protein is associated with adverse outcomes. Inadequate intake promotes negative nitrogen balance, muscle wasting, impaired tissue healing and repair, and increased risk of infection, whereas excessive protein may exceed metabolic capacity, causing azotemia, hepatic or renal strain, and reduced metabolic flexibility — particularly in patients with renal dysfunction. Emerging evidence indicates that the optimal protein dose is strongly influenced by patient-specific characteristics and evolves throughout the course of illness, supporting an individualized, phase-adapted strategy for protein provision rather than a fixed universal target. During early critical illness, catabolism predominates and high protein doses may not be effectively utilized. In contrast, during recovery and stabilization, higher protein targets appear beneficial for restoring lean body mass and functional capacity. This dynamic trajectory underscores the need to abandon universal recommendations in favor of personalized prescriptions. Although instruments such as nitrogen balance, body composition analysis, and indirect calorimetry can provide information about protein dosage, their routine use in clinical practice is limited and interpretation in acute illnesses remains difficult. Pragmatic, bedside strategies and the phenotyping of patients using biomarkers are, therefore, needed to tailor protein provision according to disease stage, organ function, and anabolic capacity. This opinion paper explores mechanistic insights, evidence from clinical trials, and guidelines on protein supplementation, explores biomarker-driven personalization, and highlights ongoing challenges and future research priorities in nutritional therapy.
{"title":"Proteins in artificial nutrition: toward an individualized and phase-specific prescription","authors":"Philipp Schuetz , Frank Carrera-Gil , Carla Wunderle","doi":"10.1016/j.clnu.2026.106577","DOIUrl":"10.1016/j.clnu.2026.106577","url":null,"abstract":"<div><div>Protein is a central component of artificial nutrition, yet its optimal dose and timing remain controversial. Provision of both insufficient and excessive protein is associated with adverse outcomes. Inadequate intake promotes negative nitrogen balance, muscle wasting, impaired tissue healing and repair, and increased risk of infection, whereas excessive protein may exceed metabolic capacity, causing azotemia, hepatic or renal strain, and reduced metabolic flexibility — particularly in patients with renal dysfunction. Emerging evidence indicates that the optimal protein dose is strongly influenced by patient-specific characteristics and evolves throughout the course of illness, supporting an individualized, phase-adapted strategy for protein provision rather than a fixed universal target. During early critical illness, catabolism predominates and high protein doses may not be effectively utilized. In contrast, during recovery and stabilization, higher protein targets appear beneficial for restoring lean body mass and functional capacity. This dynamic trajectory underscores the need to abandon universal recommendations in favor of personalized prescriptions. Although instruments such as nitrogen balance, body composition analysis, and indirect calorimetry can provide information about protein dosage, their routine use in clinical practice is limited and interpretation in acute illnesses remains difficult. Pragmatic, bedside strategies and the phenotyping of patients using biomarkers are, therefore, needed to tailor protein provision according to disease stage, organ function, and anabolic capacity. This opinion paper explores mechanistic insights, evidence from clinical trials, and guidelines on protein supplementation, explores biomarker-driven personalization, and highlights ongoing challenges and future research priorities in nutritional therapy.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106577"},"PeriodicalIF":7.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049112","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 : 2026-01-09DOI: 10.1016/j.clnu.2026.106575
Eric Fontaine
In this article, I explore how energy metabolism depends on proper mitochondrial function. Adenosine triphosphate (ATP), the main source of energy for cells, is mainly produced in the mitochondria as a result of the fusion of hydrogen produced by the breakdown of nutrients with oxygen. This reaction allows protons to be pumped across the inner mitochondrial membrane, creating a gradient that powers ATP synthesis. However, ATP production is not perfectly efficient. Some oxygen is consumed without generating ATP due to proton leaks or other processes that utilize the gradient. Diet, hormones, and cellular signals can alter mitochondrial efficiency: for example, hyperthyroidism and polyunsaturated fatty acid deficiency cause uncoupling, while hypothyroidism and nitric oxide increase coupling but reduce maximum ATP production. I also point out that the use of ATP depends on its thermodynamic value, which is reflected in the Adenosine triphosphate/Adenosine diphosphate ratio ([ATP]/[ADP] ratio). A decrease in this ratio can selectively reduce certain ATP-consuming processes, as shown in studies on metformin and imeglimin. In cases of stress or nutritional deficiency, cells can consume ATP without performing useful work, leading to inefficiency or even cell death when the [ATP]/[ADP] ratio collapses. Knowing that these concepts are quite complex, I have simplified them to make clear that mitochondria are more than just passive “powerhouses of cells”.
{"title":"The 2025 Sir David Cuthbertson Lecture: Energy metabolism: Beyond calories, feeding the mitochondria","authors":"Eric Fontaine","doi":"10.1016/j.clnu.2026.106575","DOIUrl":"10.1016/j.clnu.2026.106575","url":null,"abstract":"<div><div>In this article, I explore how energy metabolism depends on proper mitochondrial function. Adenosine triphosphate (ATP), the main source of energy for cells, is mainly produced in the mitochondria as a result of the fusion of hydrogen produced by the breakdown of nutrients with oxygen. This reaction allows protons to be pumped across the inner mitochondrial membrane, creating a gradient that powers ATP synthesis. However, ATP production is not perfectly efficient. Some oxygen is consumed without generating ATP due to proton leaks or other processes that utilize the gradient. Diet, hormones, and cellular signals can alter mitochondrial efficiency: for example, hyperthyroidism and polyunsaturated fatty acid deficiency cause uncoupling, while hypothyroidism and nitric oxide increase coupling but reduce maximum ATP production. I also point out that the use of ATP depends on its thermodynamic value, which is reflected in the Adenosine triphosphate/Adenosine diphosphate ratio ([ATP]/[ADP] ratio). A decrease in this ratio can selectively reduce certain ATP-consuming processes, as shown in studies on metformin and imeglimin. In cases of stress or nutritional deficiency, cells can consume ATP without performing useful work, leading to inefficiency or even cell death when the [ATP]/[ADP] ratio collapses. Knowing that these concepts are quite complex, I have simplified them to make clear that mitochondria are more than just passive “powerhouses of cells”.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"57 ","pages":"Article 106575"},"PeriodicalIF":7.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974240","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 : 2026-01-08DOI: 10.1016/j.clnu.2025.106554
Hajar Nabeel Shakir Shakir , Antonio Javier Alias-Castillo , Daniel Bertini-Pérez , Lola Rueda-Ruzafa , Pablo Roman , Diana Cardona
Background and Aims
Depression is a multifactorial disorder influenced by genetic, biochemical, psychological, and environmental factors, and it significantly impacts quality of life. Probiotics, especially Lactobacillus and Bifidobacterium strains, have been proposed as adjunct therapies due to their capacity to modulate gut microbiota and the gut–brain axis. This systematic review and meta-analysis aimed to evaluate the effectiveness of probiotic supplementation on depressive symptoms and inflammatory status in individuals with depression.
Methods
Articles were identified through searches in databases including PubMed, Scopus, CINAHL, and Zenodo, using terms related to depression, microbiome, and probiotics. The search, conducted between January and February 2025, yielded 780 articles. After removing duplicates and applying eligibility criteria, 13 studies were included in the systematic review and 7 in the meta-analysis.
Results
Probiotic supplementation was significantly associated with improvement in depressive symptoms (p < 0.00001). However, no significant changes were found in inflammatory biomarkers, including interleukin-6 (p = 0.45) and tumor necrosis factor-alpha (p = 0.21).
Conclusions
These results suggest that probiotics may help alleviate depressive symptoms, although their effect on inflammation remains uncertain. Further high-quality studies are necessary to clarify underlying mechanisms and determine the clinical relevance of probiotics as adjunctive therapy in depression..
{"title":"Effectiveness of probiotic supplementation in managing depressive symptoms and inflammatory status in patients with depression: A systematic review and meta-analysis","authors":"Hajar Nabeel Shakir Shakir , Antonio Javier Alias-Castillo , Daniel Bertini-Pérez , Lola Rueda-Ruzafa , Pablo Roman , Diana Cardona","doi":"10.1016/j.clnu.2025.106554","DOIUrl":"10.1016/j.clnu.2025.106554","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Depression is a multifactorial disorder influenced by genetic, biochemical, psychological, and environmental factors, and it significantly impacts quality of life. Probiotics, especially <em>Lactobacillus</em> and <em>Bifidobacterium</em> strains, have been proposed as adjunct therapies due to their capacity to modulate gut microbiota and the gut–brain axis. This systematic review and meta-analysis aimed to evaluate the effectiveness of probiotic supplementation on depressive symptoms and inflammatory status in individuals with depression.</div></div><div><h3>Methods</h3><div>Articles were identified through searches in databases including PubMed, Scopus, CINAHL, and Zenodo, using terms related to depression, microbiome, and probiotics. The search, conducted between January and February 2025, yielded 780 articles. After removing duplicates and applying eligibility criteria, 13 studies were included in the systematic review and 7 in the meta-analysis.</div></div><div><h3>Results</h3><div>Probiotic supplementation was significantly associated with improvement in depressive symptoms (p < 0.00001). However, no significant changes were found in inflammatory biomarkers, including interleukin-6 (p = 0.45) and tumor necrosis factor-alpha (p = 0.21).</div></div><div><h3>Conclusions</h3><div>These results suggest that probiotics may help alleviate depressive symptoms, although their effect on inflammation remains uncertain. Further high-quality studies are necessary to clarify underlying mechanisms and determine the clinical relevance of probiotics as adjunctive therapy in depression..</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106554"},"PeriodicalIF":7.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049111","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 : 2026-01-07DOI: 10.1016/j.clnu.2026.106574
Michelle C. Paulus , Max Melchers , Imre W.K. Kouw , Myrthe Vestering , Alain R. Viddeleer , Arthur R.H. van Zanten
Background and Aims
Reduced skeletal muscle mass at Intensive Care Unit (ICU) admission is associated with increased mortality. Bedside techniques, including bioelectrical impedance analysis (BIA), ultrasonography (US), and calf circumference (CC), may help to estimate skeletal muscle mass in critically ill patients. This study aimed to investigate the accuracy of these bedside methods in assessing muscle mass compared to lumbar 3 (L3) CT-derived skeletal muscle index (CT-SMI) and determine cut-offs for reduced muscle mass upon ICU admission.
Methods
A prospective, single-centre, cohort study conducted between May 2023 and April 2025. Patients (≥18 years) with an expected ICU stay ≥3 days were included. Bedside parameters (<48 h of ICU admission) included multifrequency BIA-derived skeletal muscle mass (BIA-SMM) and fat-free mass (BIA-FFM)), US-derived rectus femoris cross-sectional area (US-RFCSA) and quadriceps muscle layer thickness (US-QMLT), and CC (adjusted for BMI). These were compared to L3 CT-SMI and CT-derived skeletal muscle area (CT-SMA) retrieved 7 days before to 24 h after ICU admission. Correlations between CT and bedside methods were assessed. Reduced muscle mass was defined using CT-based SMI cut-offs (females <38 cm2/m2; males <50 cm2/m2) to determine cut-off values of bedside parameters using ROC analyses.
Results
Fifty-six ICU patients (70 % male) were included, showing 64 % having reduced skeletal muscle mass. Correlations of CT-SMI with BIA and US parameters were weak to moderate (r = 0.36–0.45, all p < 0.05), while CT-SMA correlated moderately with BIA-FFM (r = 0.57) and BIA-SMM (r = 0.62, both p < 0.001) but not with US-RFCSA, US-QMLT, and CC (p > 0.05). Cut-offs for reduced skeletal muscle mass were BIA-FFMI: 23.8 kg/m2 and 20.0 kg/m2; BIA-SMMI: 13.4 kg/m2 and 10.7 kg/m2; adjusted CC: 36.8 cm and 33.8 cm, in males and females, respectively, and US-RFCSA: 4.3 cm2 and US-QMLT: 2.3 cm (both sexes).
Conclusion
At ICU admission, correlations between bedside methods and L3 CT-derived muscle mass were low to moderate. Cut-off values were derived to detect reduced skeletal muscle upon ICU admission. However, further validation is required before clinical implementation.
{"title":"Comparing bedside and CT-derived muscle mass assessment methodologies at intensive care unit admission: A critical step towards bedside detection of reduced muscle mass","authors":"Michelle C. Paulus , Max Melchers , Imre W.K. Kouw , Myrthe Vestering , Alain R. Viddeleer , Arthur R.H. van Zanten","doi":"10.1016/j.clnu.2026.106574","DOIUrl":"10.1016/j.clnu.2026.106574","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Reduced skeletal muscle mass at Intensive Care Unit (ICU) admission is associated with increased mortality. Bedside techniques, including bioelectrical impedance analysis (BIA), ultrasonography (US), and calf circumference (CC), may help to estimate skeletal muscle mass in critically ill patients. This study aimed to investigate the accuracy of these bedside methods in assessing muscle mass compared to lumbar 3 (L3) CT-derived skeletal muscle index (CT-SMI) and determine cut-offs for reduced muscle mass upon ICU admission.</div></div><div><h3>Methods</h3><div>A prospective, single-centre, cohort study conducted between May 2023 and April 2025. Patients (≥18 years) with an expected ICU stay ≥3 days were included. Bedside parameters (<48 h of ICU admission) included multifrequency BIA-derived skeletal muscle mass (BIA-SMM) and fat-free mass (BIA-FFM)), US-derived <em>rectus femoris</em> cross-sectional area (US-RFCSA) and <em>quadriceps</em> muscle layer thickness (US-QMLT), and CC (adjusted for BMI). These were compared to L3 CT-SMI and CT-derived skeletal muscle area (CT-SMA) retrieved 7 days before to 24 h after ICU admission. Correlations between CT and bedside methods were assessed. Reduced muscle mass was defined using CT-based SMI cut-offs (females <38 cm<sup>2</sup>/m<sup>2</sup>; males <50 cm<sup>2</sup>/m<sup>2</sup>) to determine cut-off values of bedside parameters using ROC analyses.</div></div><div><h3>Results</h3><div>Fifty-six ICU patients (70 % male) were included, showing 64 % having reduced skeletal muscle mass. Correlations of CT-SMI with BIA and US parameters were weak to moderate (r = 0.36–0.45, all p < 0.05), while CT-SMA correlated moderately with BIA-FFM (r = 0.57) and BIA-SMM (r = 0.62, both p < 0.001) but not with US-RFCSA, US-QMLT, and CC (p > 0.05). Cut-offs for reduced skeletal muscle mass were BIA-FFMI: 23.8 kg/m<sup>2</sup> and 20.0 kg/m<sup>2</sup>; BIA-SMMI: 13.4 kg/m<sup>2</sup> and 10.7 kg/m<sup>2</sup>; adjusted CC: 36.8 cm and 33.8 cm, in males and females, respectively, and US-RFCSA: 4.3 cm<sup>2</sup> and US-QMLT: 2.3 cm (both sexes).</div></div><div><h3>Conclusion</h3><div>At ICU admission, correlations between bedside methods and L3 CT-derived muscle mass were low to moderate. Cut-off values were derived to detect reduced skeletal muscle upon ICU admission. However, further validation is required before clinical implementation.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"57 ","pages":"Article 106574"},"PeriodicalIF":7.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974164","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}