Pub Date : 2025-12-08DOI: 10.1016/j.clnu.2025.12.002
Ting Han , Jialu Zhuo , Xiaoting Wu , Qiang Chi , Bo Chen , Junqiang Chen , Wei Chen , Zhenyi Jia , Rui Zhao , Xinyu Zhang , Peng Zhang , Yuantian Mao , Xuan Xu , Qi Gao , Xiaoding Shen , Boshi Sun , Peiang Guo , Zhen Wang , Jun Yang , Huanlong Qin
Background and Aims
Malnourished patients, who undergo gastrointestinal (GI) surgery, have a higher risk of postoperative complications, including higher rates of morbidity and mortality. Generally, a low-fiber diet is recommended after GI surgery. This study investigated the tolerance and clinical outcomes of an enteral formula supplemented with partially hydrolyzed guar gum (PHGG)—a soluble, prebiotic dietary fiber known to benefit gastrointestinal health—in Chinese patients following GI surgery, using a standard fiber-free formula as the control..
Methods
This study enrolled 631 patients requiring enteral nutrition following GI surgery. Participants were subsequently randomized to receive either a fiber-enriched formula containing 15 g/L PHGG (experimental group, n = 313) or a standard fiber-free formula (control group, n = 318) for 5 days. Data on feeding effectiveness, tolerability, and clinical outcomes were subsequently collected.
Results
The incidence of diarrhea was 9.6 % (95 % confidence interval [CI]: 6.3 to 12.8) in the experimental group and 10.1 % (95 % CI: 6.8 to 13.4) in the control group, with an absolute difference of −0.5 (95 % CI: −5.1 to 4.2) confirming non-inferiority (P < 0.001). In patients who consumed ≥4500 kcal over 5 days (averaging 900 kcal/day), the experimental group showed significantly improved feeding tolerance, with a reduced prevalence of diarrhea and abdominal distension (10.4 % vs 24.7 %, P = 0.045; 19.4 % vs 38.4 %, P = 0.016). Patients with gastric cancer in the experimental group had significantly less abdominal distension (22.7 % vs 48.8 %; P = 0.014). Regarding weight preservation, the experimental group demonstrated benefits in weight preservation at discharge (%weight change: −1.39 vs −2.33, P = 0.049). Thirty days after surgery, the experimental group had better EQ-5D scores, especially in E4 pain/discomfort and E5 anxiety.
Conclusions
The PHGG-enriched enteral nutrition formulation is well-tolerated and non-inferior to a fiber-free formula among patients following GI surgery. To maximize its benefits on GI tolerance and body weight preservation, a daily intake of 800–900 kcal is suggested, though this warrants further validation. The trial protocol was registered at www.chictr.org.cn (Identifier: ChiCTR2000038429).
{"title":"Tolerability and efficacy of an enteral formula containing partially hydrolyzed guar gum in patients following gastrointestinal surgery: A prospective, multicenter, open-label, randomized controlled study","authors":"Ting Han , Jialu Zhuo , Xiaoting Wu , Qiang Chi , Bo Chen , Junqiang Chen , Wei Chen , Zhenyi Jia , Rui Zhao , Xinyu Zhang , Peng Zhang , Yuantian Mao , Xuan Xu , Qi Gao , Xiaoding Shen , Boshi Sun , Peiang Guo , Zhen Wang , Jun Yang , Huanlong Qin","doi":"10.1016/j.clnu.2025.12.002","DOIUrl":"10.1016/j.clnu.2025.12.002","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Malnourished patients, who undergo gastrointestinal (GI) surgery, have a higher risk of postoperative complications, including higher rates of morbidity and mortality. Generally, a low-fiber diet is recommended after GI surgery. This study investigated the tolerance and clinical outcomes of an enteral formula supplemented with partially hydrolyzed guar gum (PHGG)—a soluble, prebiotic dietary fiber known to benefit gastrointestinal health—in Chinese patients following GI surgery, using a standard fiber-free formula as the control..</div></div><div><h3>Methods</h3><div>This study enrolled 631 patients requiring enteral nutrition following GI surgery. Participants were subsequently randomized to receive either a fiber-enriched formula containing 15 g/L PHGG (experimental group, n = 313) or a standard fiber-free formula (control group, n = 318) for 5 days. Data on feeding effectiveness, tolerability, and clinical outcomes were subsequently collected.</div></div><div><h3>Results</h3><div>The incidence of diarrhea was 9.6 % (95 % confidence interval [CI]: 6.3 to 12.8) in the experimental group and 10.1 % (95 % CI: 6.8 to 13.4) in the control group, with an absolute difference of −0.5 (95 % CI: −5.1 to 4.2) confirming non-inferiority (<em>P</em> < 0.001). In patients who consumed ≥4500 kcal over 5 days (averaging 900 kcal/day), the experimental group showed significantly improved feeding tolerance, with a reduced prevalence of diarrhea and abdominal distension (10.4 % vs 24.7 %, <em>P</em> = 0.045; 19.4 % vs 38.4 %, <em>P</em> = 0.016). Patients with gastric cancer in the experimental group had significantly less abdominal distension (22.7 % vs 48.8 %; <em>P</em> = 0.014). Regarding weight preservation, the experimental group demonstrated benefits in weight preservation at discharge (%weight change: −1.39 vs −2.33, <em>P</em> = 0.049). Thirty days after surgery, the experimental group had better EQ-5D scores, especially in E4 pain/discomfort and E5 anxiety.</div></div><div><h3>Conclusions</h3><div>The PHGG-enriched enteral nutrition formulation is well-tolerated and non-inferior to a fiber-free formula among patients following GI surgery. To maximize its benefits on GI tolerance and body weight preservation, a daily intake of 800–900 kcal is suggested, though this warrants further validation. The trial protocol was registered at <span><span>www.chictr.org.cn</span><svg><path></path></svg></span> (Identifier: ChiCTR2000038429).</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106543"},"PeriodicalIF":7.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838347","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 : 2025-12-06DOI: 10.1016/j.clnu.2025.11.023
Elvira Marquez-Paradas , Gregorio Gil-Sanchez , Luna Barrera-Chamorro , Teresa Gonzalez-de la Rosa , Antonio D. Miguel-Albarreal , Alfredo Corell , Sergio Montserrat-de la Paz
Background and aims
Dietary fatty acids are central modulators of postprandial metabolism and inflammation, processes intimately linked to long-term cardiometabolic health. Circulating extracellular vesicles (EVs), particularly exosomes, have emerged as dynamic mediators of intercellular communication and may reflect acute physiological changes. However, the impact of distinct dietary fatty acids on EV phenotype during the postprandial period remains poorly understood. Our aim was to investigate the effect of isoenergetic meals enriched in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFAs) on classical immunometabolic markers and on the phenotypic profile and cellular origin of circulating EVs in healthy adults.
Methods
In a randomized crossover study, ten healthy participants (a total of 40 postprandial curves) received four test meals (SFA-, MUFA-, or ω3-LCPUFA-enriched emulsions, plus a fat-free control emulsion). Blood samples were collected at fasting, 2–3 h (postprandial peak), and 5–6 h (late postprandial phase). Clinical, biochemical, haematological, and immunological parameters were assessed. EVs were isolated from plasma, and 37 surface markers were analysed by multiplex flow cytometry to infer their cellular origin.
Results
Postprandial responses varied with fat quality. MUFA and ω3-LCPUFA meals induced broader immunometabolic activation than SFA. At the late postprandial phase, MUFA increased serum IgA, IgG, and IgM (p = 0.004, 0.013, and 0.020) and complement C1q and C3 (p = 0.008 and 0.004), whereas ω3-LCPUFA increased IgG and C3 (p = 0.027 and 0.046). Lymphocyte counts declined after all four meals (all p ≤ 0.007). EV concentration and mean diameter (∼100–150 nm) remained stable across interventions. Notably, MUFA intake enriched CD14+ (monocyte-derived) vesicles, ω3-LCPUFA enhanced EVs from endothelial and T-cell lineages in the late postprandial phase, and the SFA meal reduced expression of multiple lineage-specific markers.
Conclusions
Dietary fat composition modulates the postprandial phenotype and cellular origin of circulating EVs without altering their abundance or size. These findings support the use of EV phenotyping as a sensitive tool to monitor early immune-metabolic responses to nutritional interventions and may inform precision strategies for cardiometabolic disease prevention.
{"title":"Postprandial modulation of the surface profile and cellular origin of circulating extracellular vesicles by dietary fatty acid composition: A randomized crossover pilot study in young healthy adults","authors":"Elvira Marquez-Paradas , Gregorio Gil-Sanchez , Luna Barrera-Chamorro , Teresa Gonzalez-de la Rosa , Antonio D. Miguel-Albarreal , Alfredo Corell , Sergio Montserrat-de la Paz","doi":"10.1016/j.clnu.2025.11.023","DOIUrl":"10.1016/j.clnu.2025.11.023","url":null,"abstract":"<div><h3>Background and aims</h3><div>Dietary fatty acids are central modulators of postprandial metabolism and inflammation, processes intimately linked to long-term cardiometabolic health. Circulating extracellular vesicles (EVs), particularly exosomes, have emerged as dynamic mediators of intercellular communication and may reflect acute physiological changes. However, the impact of distinct dietary fatty acids on EV phenotype during the postprandial period remains poorly understood. Our aim was to investigate the effect of isoenergetic meals enriched in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFAs) on classical immunometabolic markers and on the phenotypic profile and cellular origin of circulating EVs in healthy adults.</div></div><div><h3>Methods</h3><div>In a randomized crossover study, ten healthy participants (a total of 40 postprandial curves) received four test meals (SFA-, MUFA-, or ω3-LCPUFA-enriched emulsions, plus a fat-free control emulsion). Blood samples were collected at fasting, 2–3 h (postprandial peak), and 5–6 h (late postprandial phase). Clinical, biochemical, haematological, and immunological parameters were assessed. EVs were isolated from plasma, and 37 surface markers were analysed by multiplex flow cytometry to infer their cellular origin.</div></div><div><h3>Results</h3><div>Postprandial responses varied with fat quality. MUFA and ω3-LCPUFA meals induced broader immunometabolic activation than SFA. At the late postprandial phase, MUFA increased serum IgA, IgG, and IgM (<em>p</em> = 0.004, 0.013, and 0.020) and complement C1q and C3 (<em>p</em> = 0.008 and 0.004), whereas ω3-LCPUFA increased IgG and C3 (<em>p</em> = 0.027 and 0.046). Lymphocyte counts declined after all four meals (all <em>p</em> ≤ 0.007). EV concentration and mean diameter (∼100–150 nm) remained stable across interventions. Notably, MUFA intake enriched CD14<sup>+</sup> (monocyte-derived) vesicles, ω3-LCPUFA enhanced EVs from endothelial and T-cell lineages in the late postprandial phase, and the SFA meal reduced expression of multiple lineage-specific markers.</div></div><div><h3>Conclusions</h3><div>Dietary fat composition modulates the postprandial phenotype and cellular origin of circulating EVs without altering their abundance or size. These findings support the use of EV phenotyping as a sensitive tool to monitor early immune-metabolic responses to nutritional interventions and may inform precision strategies for cardiometabolic disease prevention.</div></div><div><h3>Registration number of Clinical Trial</h3><div>NCT06051461.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106539"},"PeriodicalIF":7.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760783","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 : 2025-12-06DOI: 10.1016/j.clnu.2025.11.026
Zhongyang Guan , Blossom CM. Stephan , Lorenzo M. Donini , Joshua R. Lewis , Carla M. Prado , Richard L. Prince , David Scott , Kun Zhu , Marc Sim , Mario Siervo
Background and aims
Longitudinal studies have explored the association between sarcopenic obesity (SO) and the risk of cognitive impairment, yet findings remain mixed. This study aimed to investigate the associations of SO with risk of incident dementia in older women, using two diagnostic models: the Sarcopenic Obesity Global Leadership Initiative (SOGLI) and the load-capacity model.
Methods
We analysed data from 900 community-dwelling women (aged ≥70 years). SO was defined using two models: (1) the SOGLI criteria, based on low handgrip strength (HGS), low appendicular lean soft tissue to body weight (ALST/W) ratio, and high fat mass percentage (%FM); and (2) the load-capacity model, based on a high truncal fat mass to ALST (TrFM/ALST) ratio. Incident dementia events (hospitalisation and/or death) over 9.5 years were identified through linked health records using International Classification of Diseases (ICD) codes. Cox proportional hazards and Fine–Gray sub-distribution models were applied.
Results
Using the SOGLI criteria, SO was not significantly associated with the risk of overall dementia events compared with the non-sarcopenic, non-obesity group (hazard ratio [HR] 0.63, 95 % CI 0.39–1.03); however, SO was significantly associated with a reduced risk of dementia-related hospitalisation (HR 0.57, 95 % CI 0.33–0.98), mainly driven by the reduced risk observed with obesity. When defined by the load-capacity model, SO remained significantly associated with a reduced risk of overall dementia events (HR 0.54, 95 % CI 0.34–0.85). Restricted cubic spline (RCS) analyses demonstrated significant associations of lower HGS, lower %FM, higher ALST/W ratio, and lower TrFM/ALST ratio with increased risk of overall dementia events. Results remained consistent in sensitivity analyses excluding participants with BMI <21 kg/m2 (n = 67) or %FM below the 15th percentile (n = 135), and after further adjustment for age at highest education level..
Conclusion
This is the first longitudinal study to examine the association between SO and dementia using either the SOGLI or load-capacity models. In this cohort of older women, SO was associated with a lower risk of dementia-related hospitalisation. These findings suggest that the relationship between obesity and dementia risk in late life may differ from current evidence regarding midlife, indicating potential age-specific effects. Further research is needed to clarify the underlying mechanisms and generalisability of these observations to broader populations..
背景和目的纵向研究探讨了肌肉减少型肥胖（SO）与认知障碍风险之间的关系，但研究结果仍不一致。本研究旨在通过两种诊断模型：肌少性肥胖全球领导倡议（SOGLI）和负荷能力模型，探讨老年女性SO与痴呆发生风险的关系。方法对900名年龄≥70岁的社区妇女进行数据分析。SO的定义采用两个模型：(1)SOGLI标准，基于低握力（HGS）、低阑尾瘦软组织与体重（ALST/W）比和高脂肪质量百分比（%FM）；(2)基于较高的躯干脂肪质量与ALST （TrFM/ALST）比率的荷载-能力模型。通过使用国际疾病分类（ICD）代码的相关健康记录确定9.5年以上的偶发性痴呆事件（住院和/或死亡）。采用Cox比例风险模型和Fine-Gray子分布模型。结果使用SOGLI标准，与非肌肉减少、非肥胖组相比，SO与总体痴呆事件的风险无显著相关（风险比[HR] 0.63, 95% CI 0.39-1.03）；然而，SO与痴呆相关住院风险降低显著相关（HR 0.57, 95% CI 0.33-0.98），主要是由于肥胖导致的风险降低。当用负荷能力模型定义时，SO仍然与总体痴呆事件风险降低显著相关（HR 0.54, 95% CI 0.34-0.85）。限制性三次样条（RCS）分析显示，较低的HGS、较低的%FM、较高的ALST/W比率和较低的TrFM/ALST比率与总体痴呆事件的风险增加有显著关联。排除BMI = 21 kg/m2 （n = 67）或%FM低于第15个百分点（n = 135）的参与者，并进一步调整最高教育水平的年龄后，敏感性分析的结果保持一致。结论：这是第一个使用SOGLI或负荷能力模型检验SO与痴呆之间关系的纵向研究。在这个老年妇女队列中，SO与痴呆相关住院的风险较低有关。这些发现表明，肥胖和老年痴呆风险之间的关系可能与目前关于中年的证据不同，这表明了潜在的年龄特异性影响。需要进一步的研究来澄清潜在的机制和这些观察结果在更广泛人群中的普遍性。
{"title":"Association of sarcopenic obesity with dementia risk in a cohort of older women","authors":"Zhongyang Guan , Blossom CM. Stephan , Lorenzo M. Donini , Joshua R. Lewis , Carla M. Prado , Richard L. Prince , David Scott , Kun Zhu , Marc Sim , Mario Siervo","doi":"10.1016/j.clnu.2025.11.026","DOIUrl":"10.1016/j.clnu.2025.11.026","url":null,"abstract":"<div><h3>Background and aims</h3><div>Longitudinal studies have explored the association between sarcopenic obesity (SO) and the risk of cognitive impairment, yet findings remain mixed. This study aimed to investigate the associations of SO with risk of incident dementia in older women, using two diagnostic models: the Sarcopenic Obesity Global Leadership Initiative (SOGLI) and the load-capacity model.</div></div><div><h3>Methods</h3><div>We analysed data from 900 community-dwelling women (aged ≥70 years). SO was defined using two models: (1) the SOGLI criteria, based on low handgrip strength (HGS), low appendicular lean soft tissue to body weight (ALST/W) ratio, and high fat mass percentage (%FM); and (2) the load-capacity model, based on a high truncal fat mass to ALST (TrFM/ALST) ratio. Incident dementia events (hospitalisation and/or death) over 9.5 years were identified through linked health records using International Classification of Diseases (ICD) codes. Cox proportional hazards and Fine–Gray sub-distribution models were applied.</div></div><div><h3>Results</h3><div>Using the SOGLI criteria, SO was not significantly associated with the risk of overall dementia events compared with the non-sarcopenic, non-obesity group (hazard ratio [HR] 0.63, 95 % CI 0.39–1.03); however, SO was significantly associated with a reduced risk of dementia-related hospitalisation (HR 0.57, 95 % CI 0.33–0.98), mainly driven by the reduced risk observed with obesity. When defined by the load-capacity model, SO remained significantly associated with a reduced risk of overall dementia events (HR 0.54, 95 % CI 0.34–0.85). Restricted cubic spline (RCS) analyses demonstrated significant associations of lower HGS, lower %FM, higher ALST/W ratio, and lower TrFM/ALST ratio with increased risk of overall dementia events. Results remained consistent in sensitivity analyses excluding participants with BMI <21 kg/m<sup>2</sup> (n = 67) or %FM below the 15th percentile (n = 135), and after further adjustment for age at highest education level..</div></div><div><h3>Conclusion</h3><div>This is the first longitudinal study to examine the association between SO and dementia using either the SOGLI or load-capacity models. In this cohort of older women, SO was associated with a lower risk of dementia-related hospitalisation. These findings suggest that the relationship between obesity and dementia risk in late life may differ from current evidence regarding midlife, indicating potential age-specific effects. Further research is needed to clarify the underlying mechanisms and generalisability of these observations to broader populations..</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106542"},"PeriodicalIF":7.4,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.clnu.2025.11.025
Dongni Yu , Mingzhu Zou , Bo cheng , Peng Yang , Dongni Huang , Qi Pan , Lixin Guo
Background and Aims
The 5:2 intermittent fasting meal replacement (5:2 MR) improved glycemic control and weight loss in adults with type 2 diabetes mellitus (T2DM).
Objective
This analysis further investigated the exploratory outcomes related to body composition and abdominal fat distribution.
Methods
This was a single-center analysis of a randomized, active-controlled trial (EARLY), which enrolled overweight and obese patients with early T2DM. A total of 85 participants were randomly assigned to receive metformin (n = 28), empagliflozin (n = 28), or 5:2 MR (n = 29) for 16 weeks. Body composition was assessed using InBody device, and the energy spectrum CT was used to measure abdominal fat distribution. Spearman's correlation coefficient was used to evaluate the associations between change in body mass index (BMI) and change in the exploratory outcomes.
Results
Compared with the metformin and empagliflozin groups, the 5:2 MR group showed the most significant reductions in BMI (least-squares mean, −3.41 kg/m2 [standard error, 0.31], P < 0.001), waist circumference (−8.83 cm [1.07], P < 0.001), waist-to-hip ratio (WHR) (−0.04 [0.01], P < 0.05), waist-to-height ratio (WHtR) (−0.05 [0.01], P < 0.001), body fat percentage (BF%) (−4.84 % [0.66], P < 0.05), abdominal cross-sectional area (ACSA) (−66.05 cm2 [9.46], P < 0.01), subcutaneous fat area (−58.27 cm2 [5.99], P < 0.001), and an increase in the liver-to-spleen (L/S) ratio) (0.43 [0.04], P < 0.01). In the 5:2 MR group, changes in BMI exhibited linear associations and significant positive correlations with changes in WHR (r = 0.411, P = 0.030), WHtR (r = 0.635, P < 0.001), BF% (r = 0.528, P = 0.020) and ACSA (r = 0.562, P = 0.003).
Conclusion
The 5:2 MR regimen may be more effective than metformin and empagliflozin in improving body composition and abdominal fat distribution in early T2DM, and is proposed as a therapeutic option.
背景和目的5:2间歇性禁食替代（5:2 MR）可改善2型糖尿病（T2DM）成人患者的血糖控制和体重减轻。目的进一步探讨与体成分和腹部脂肪分布相关的探索性结果。方法：本研究是一项随机、主动对照试验（EARLY）的单中心分析，招募了超重和肥胖的早期T2DM患者。共有85名参与者被随机分配接受二甲双胍（n = 28）、恩帕列净（n = 28）或5:2 MR （n = 29）治疗16周。使用InBody装置评估身体成分，使用能谱CT测量腹部脂肪分布。Spearman相关系数用于评价体重指数（BMI）变化与探索性结果变化之间的关系。结果与二甲双胍和依格列净组比较，5:2 MR组BMI（最小二乘平均值为- 3.41 kg/m2[标准误差，0.31],P < 0.001）、腰围（- 8.83 cm [1.07], P < 0.001）、腰臀比（- 0.04 [0.01],P < 0.05）、腰高比（- 0.05 [0.01],P < 0.001）、体脂率（- 4.84% [0.66],P < 0.05）、腹横截面积（- 66.05 cm2 [9.46], P < 0.01）、皮下脂肪面积（- 58.27 cm2 [5.99], P < 0.001），肝脾（L/S）比（0.43 [0.04],P < 0.01）增加。在5:2 MR组，BMI的变化与腰宽比（r = 0.411, P = 0.030）、腰宽比（r = 0.635, P < 0.001）、BF% （r = 0.528, P = 0.020）和ACSA （r = 0.562, P = 0.003）的变化呈线性相关和显著正相关。结论5:2 MR方案在改善早期T2DM患者体成分和腹部脂肪分布方面可能比二甲双胍和恩格列净更有效，可作为一种治疗方案。
{"title":"Effects of 5:2 intermittent fasting meal replacement on body composition and abdominal fat distribution in overweight and obese adults with early type 2 diabetes","authors":"Dongni Yu , Mingzhu Zou , Bo cheng , Peng Yang , Dongni Huang , Qi Pan , Lixin Guo","doi":"10.1016/j.clnu.2025.11.025","DOIUrl":"10.1016/j.clnu.2025.11.025","url":null,"abstract":"<div><h3>Background and Aims</h3><div>The 5:2 intermittent fasting meal replacement (5:2 MR) improved glycemic control and weight loss in adults with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Objective</h3><div>This analysis further investigated the exploratory outcomes related to body composition and abdominal fat distribution.</div></div><div><h3>Methods</h3><div>This was a single-center analysis of a randomized, active-controlled trial (EARLY), which enrolled overweight and obese patients with early T2DM. A total of 85 participants were randomly assigned to receive metformin (n = 28), empagliflozin (n = 28), or 5:2 MR (n = 29) for 16 weeks. Body composition was assessed using InBody device, and the energy spectrum CT was used to measure abdominal fat distribution. Spearman's correlation coefficient was used to evaluate the associations between change in body mass index (BMI) and change in the exploratory outcomes.</div></div><div><h3>Results</h3><div>Compared with the metformin and empagliflozin groups, the 5:2 MR group showed the most significant reductions in BMI (least-squares mean, −3.41 kg/m<sup>2</sup> [standard error, 0.31], P < 0.001), waist circumference (−8.83 cm [1.07], P < 0.001), waist-to-hip ratio (WHR) (−0.04 [0.01], P < 0.05), waist-to-height ratio (WHtR) (−0.05 [0.01], P < 0.001), body fat percentage (BF%) (−4.84 % [0.66], P < 0.05), abdominal cross-sectional area (ACSA) (−66.05 cm<sup>2</sup> [9.46], P < 0.01), subcutaneous fat area (−58.27 cm<sup>2</sup> [5.99], P < 0.001), and an increase in the liver-to-spleen (L/S) ratio) (0.43 [0.04], P < 0.01). In the 5:2 MR group, changes in BMI exhibited linear associations and significant positive correlations with changes in WHR (r = 0.411, P = 0.030), WHtR (r = 0.635, P < 0.001), BF% (r = 0.528, P = 0.020) and ACSA (r = 0.562, P = 0.003).</div></div><div><h3>Conclusion</h3><div>The 5:2 MR regimen may be more effective than metformin and empagliflozin in improving body composition and abdominal fat distribution in early T2DM, and is proposed as a therapeutic option.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"57 ","pages":"Article 106541"},"PeriodicalIF":7.4,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891179","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 : 2025-12-04DOI: 10.1016/j.clnu.2025.11.021
Olivera Djuric , Laura Bonvicini , Massimo Pellegrini , Eleonora Bruno , Patrizia Pasanisi , Giuliana Gargano , Patrizia Curtosi , Franco Berrino , Paolo Giorgi Rossi , Anna Villarini
<div><h3>Background & Aims</h3><div>Breast cancer recurrence risk is strongly influenced by metabolic and hormonal factors linked to adiposity and diet. The DIet ANd Androgens-5 (DIANA-5) randomized controlled trial was primarily designed to test whether adherence to a Mediterranean/macrobiotic diet, combined with moderate physical activity, could reduce the risk of breast cancer recurrence. In the present secondary analysis of the DIANA-5 trial, we investigated associations between dietary intake, anthropometric, metabolic and hormonal profile testing the hypothesis that improvement in metabolic and hormonal parameters after one year of intervention are mediated by increased consumption of recommended foods (“recommended food score”) and changes of body composition measures.</div></div><div><h3>Methods</h3><div>A total of 1542 women with early-stage breast cancer and presence of one or more endocrine/metabolic risk factors were randomized to receive either standard healthy lifestyle recommendations (n = 773) or intensive support including dietary counseling, cooking classes, and moderate physical activity reinforcement (n = 769). Anthropometric (BMI, waist circumference [WC], fat mass/fat-free mass ratio [FM/FFM]), metabolic (glycemia, insulin, HOMA index, total cholesterol, triglycerides, metabolic syndrome), and hormonal (testosterone) endpoints were assessed at baseline and after 12 months. Potential mediation effects of “recommended food score” and WC or FM/FFM on metabolic and hormonal changes were tested by using SPSS version 23 and the PROCESS macro v.4.0 for SPSS.</div></div><div><h3>Results</h3><div>604 and 551 women were available for mediation analyses in intervention and control groups, respectively. The dietary intervention improved all anthropometric, metabolic and hormonal measures. “Recommended food score” together with WC mediated 73 % of the effect of the intervention on glycemia, 67 % on insulin, 70 % on HOMA index, 96 % on total cholesterol, and 86 % on metabolic syndrome. With “recommended food score” and FM/FFM as mediators, proportions mediated were 86 % for glycemia, 73 % for insulin, 78 % for HOMA index, 126 % for total cholesterol, and 66 % for metabolic syndrome. Mediation effects of WC and FM/FFM on triglyceride changes were much weaker (38 % and 37 %, respectively). For all outcomes and all mediators, at least one path had a p-value <0.05.</div></div><div><h3>Conclusions</h3><div>Most benefits of the DIANA-5 lifestyle intervention were mediated by dietary adherence and reductions in WC and FM/FFM. The proportion of effects mediated on metabolic syndrome, glucose and glycemic tolerance is high enough to suggest that these are the main effectors. The results on triglyceride blood levels suggest that further mechanism, possibly physical activity and energy intake should be investigated.</div></div><div><h3>Clinical Trial Registry number</h3><div>NCT05019989. Available at: <span><span>https://clinicaltrials.gov/se
背景和目的乳腺癌复发风险受与肥胖和饮食相关的代谢和激素因素的强烈影响。饮食和雄激素-5 （DIANA-5）随机对照试验的主要目的是测试是否坚持地中海/长寿饮食，并结合适度的体育活动，可以降低乳腺癌复发的风险。在目前对DIANA-5试验的二次分析中，我们调查了饮食摄入、人体测量、代谢和激素特征之间的关系，验证了干预一年后代谢和激素参数的改善是通过增加推荐食物的摄入（“推荐食物评分”）和身体成分测量的变化来调节的假设。方法共纳入1542例存在一种或多种内分泌/代谢危险因素的早期乳腺癌患者，随机分为两组，一组接受标准健康生活方式建议（n = 773），另一组接受强化支持，包括饮食咨询、烹饪课程和适度体育锻炼（n = 769）。在基线和12个月后评估人体测量（BMI、腰围[WC]、脂肪质量/无脂肪质量比[FM/FFM]）、代谢（血糖、胰岛素、HOMA指数、总胆固醇、甘油三酯、代谢综合征）和激素（睾酮）终点。“推荐食物评分”和WC或FM/FFM对代谢和激素变化的潜在中介作用通过SPSS version 23和PROCESS macro v.4.0进行检验。结果干预组604例，对照组551例。饮食干预改善了所有人体测量、代谢和激素测量。“推荐食物评分”和WC共同介导干预对血糖影响的73%，对胰岛素影响的67%，对HOMA指数影响的70%，对总胆固醇影响的96%，对代谢综合征影响的86%。以“推荐食物评分”和FM/FFM作为媒介，血糖的介导比例为86%，胰岛素的介导比例为73%，HOMA指数的介导比例为78%，总胆固醇的介导比例为126%，代谢综合征的介导比例为66%。WC和FM/FFM对甘油三酯变化的中介作用要弱得多（分别为38%和37%）。对于所有结局和所有中介，至少有一条路径的p值为<；0.05。结论DIANA-5生活方式干预的大部分益处是通过饮食依从性和WC和FM/FFM的降低介导的。对代谢综合征、葡萄糖和糖耐量介导的影响比例足够高，表明这些是主要的影响因素。血液中甘油三酯水平的结果表明，进一步的机制，可能是体力活动和能量摄入应该进行调查。临床试验注册号：bernct05019989。可在：https://clinicaltrials.gov/search?cond=NCT05019989。
{"title":"Diet, body composition and metabolic and hormonal profile in women at high risk of breast cancer recurrence: A secondary mediation analysis of the DIANA-5 trial","authors":"Olivera Djuric , Laura Bonvicini , Massimo Pellegrini , Eleonora Bruno , Patrizia Pasanisi , Giuliana Gargano , Patrizia Curtosi , Franco Berrino , Paolo Giorgi Rossi , Anna Villarini","doi":"10.1016/j.clnu.2025.11.021","DOIUrl":"10.1016/j.clnu.2025.11.021","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Breast cancer recurrence risk is strongly influenced by metabolic and hormonal factors linked to adiposity and diet. The DIet ANd Androgens-5 (DIANA-5) randomized controlled trial was primarily designed to test whether adherence to a Mediterranean/macrobiotic diet, combined with moderate physical activity, could reduce the risk of breast cancer recurrence. In the present secondary analysis of the DIANA-5 trial, we investigated associations between dietary intake, anthropometric, metabolic and hormonal profile testing the hypothesis that improvement in metabolic and hormonal parameters after one year of intervention are mediated by increased consumption of recommended foods (“recommended food score”) and changes of body composition measures.</div></div><div><h3>Methods</h3><div>A total of 1542 women with early-stage breast cancer and presence of one or more endocrine/metabolic risk factors were randomized to receive either standard healthy lifestyle recommendations (n = 773) or intensive support including dietary counseling, cooking classes, and moderate physical activity reinforcement (n = 769). Anthropometric (BMI, waist circumference [WC], fat mass/fat-free mass ratio [FM/FFM]), metabolic (glycemia, insulin, HOMA index, total cholesterol, triglycerides, metabolic syndrome), and hormonal (testosterone) endpoints were assessed at baseline and after 12 months. Potential mediation effects of “recommended food score” and WC or FM/FFM on metabolic and hormonal changes were tested by using SPSS version 23 and the PROCESS macro v.4.0 for SPSS.</div></div><div><h3>Results</h3><div>604 and 551 women were available for mediation analyses in intervention and control groups, respectively. The dietary intervention improved all anthropometric, metabolic and hormonal measures. “Recommended food score” together with WC mediated 73 % of the effect of the intervention on glycemia, 67 % on insulin, 70 % on HOMA index, 96 % on total cholesterol, and 86 % on metabolic syndrome. With “recommended food score” and FM/FFM as mediators, proportions mediated were 86 % for glycemia, 73 % for insulin, 78 % for HOMA index, 126 % for total cholesterol, and 66 % for metabolic syndrome. Mediation effects of WC and FM/FFM on triglyceride changes were much weaker (38 % and 37 %, respectively). For all outcomes and all mediators, at least one path had a p-value <0.05.</div></div><div><h3>Conclusions</h3><div>Most benefits of the DIANA-5 lifestyle intervention were mediated by dietary adherence and reductions in WC and FM/FFM. The proportion of effects mediated on metabolic syndrome, glucose and glycemic tolerance is high enough to suggest that these are the main effectors. The results on triglyceride blood levels suggest that further mechanism, possibly physical activity and energy intake should be investigated.</div></div><div><h3>Clinical Trial Registry number</h3><div>NCT05019989. Available at: <span><span>https://clinicaltrials.gov/se","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106537"},"PeriodicalIF":7.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789177","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}
The “obesity paradox,” where higher body mass index (BMI) is linked to lower mortality, has been observed in coronary artery disease (CAD) patients. One hypothesis is that weight loss in cancer patients may confound this association. This study examined the obesity paradox in CAD patients without cancer and investigated the roles of nutritional and inflammatory status.
Methods
We analysed 1,252 CAD patients without a history of cancer who underwent percutaneous coronary intervention. Patients were categorized into BMI <25 kg/m2 (n = 843) and BMI ≥25 kg/m2 (n = 409). The primary outcome was 5-year all-cause mortality. Nutritional status was evaluated using the prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI), while inflammation was assessed by neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR).
Results
During the follow-up period, 73 deaths occurred (56 in BMI <25 kg/m2 vs. 17 in BMI ≥25 kg/m2). Patients with low BMI had significantly lower PNI and GNRI (both P < 0.001), but no significant differences in NLR or PLR. Kaplan–Meier analysis showed poorer survival in people without obesity (P < 0.001). In multivariable analysis, higher BMI remained an independent protective factor (HR 0.87, 95 % CI 0.81–0.94, P < 0.001). However, PNI and GNRI had superior prognostic discrimination compared to BMI. The predictive model's C-statistic improved significantly when PNI and NLR were added to conventional risk factors, with notable gains in net reclassification and discrimination indices (both P < 0.001).
Conclusions
The obesity paradox in non-cancer CAD patients remains evident and appears more closely related to nutritional status than BMI alone. Lower BMI was associated with malnutrition, not increased inflammation. Simple markers such as PNI and NLR offer additional prognostic value and may aid in better risk stratification of CAD patients.
{"title":"Nutritional and inflammatory status in the obesity paradox of coronary artery disease","authors":"Yuichiro Shirahama , Noriaki Tabata , Masanobu Ishi , Hiroaki Kusaka , Shinsuke Hanatani , Hiroki Usuku , Eiichiro Yamamoto , Yasuhiro Izumiya , Kenichi Tsujita","doi":"10.1016/j.clnu.2025.11.024","DOIUrl":"10.1016/j.clnu.2025.11.024","url":null,"abstract":"<div><h3>Background and aims</h3><div>The “obesity paradox,” where higher body mass index (BMI) is linked to lower mortality, has been observed in coronary artery disease (CAD) patients. One hypothesis is that weight loss in cancer patients may confound this association. This study examined the obesity paradox in CAD patients without cancer and investigated the roles of nutritional and inflammatory status.</div></div><div><h3>Methods</h3><div>We analysed 1,252 CAD patients without a history of cancer who underwent percutaneous coronary intervention. Patients were categorized into BMI <25 kg/m<sup>2</sup> (n = 843) and BMI ≥25 kg/m<sup>2</sup> (n = 409). The primary outcome was 5-year all-cause mortality. Nutritional status was evaluated using the prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI), while inflammation was assessed by neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR).</div></div><div><h3>Results</h3><div>During the follow-up period, 73 deaths occurred (56 in BMI <25 kg/m<sup>2</sup> vs. 17 in BMI ≥25 kg/m<sup>2</sup>). Patients with low BMI had significantly lower PNI and GNRI (both P < 0.001), but no significant differences in NLR or PLR. Kaplan–Meier analysis showed poorer survival in people without obesity (P < 0.001). In multivariable analysis, higher BMI remained an independent protective factor (HR 0.87, 95 % CI 0.81–0.94, P < 0.001). However, PNI and GNRI had superior prognostic discrimination compared to BMI. The predictive model's C-statistic improved significantly when PNI and NLR were added to conventional risk factors, with notable gains in net reclassification and discrimination indices (both P < 0.001).</div></div><div><h3>Conclusions</h3><div>The obesity paradox in non-cancer CAD patients remains evident and appears more closely related to nutritional status than BMI alone. Lower BMI was associated with malnutrition, not increased inflammation. Simple markers such as PNI and NLR offer additional prognostic value and may aid in better risk stratification of CAD patients.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"57 ","pages":"Article 106540"},"PeriodicalIF":7.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to obesity, insulin resistance, and reproductive dysfunction. While dietary modification is central to management, the optimal approach remains unclear. This systematic review and meta-analysis evaluated the effects of the ketogenic diet on anthropometric, metabolic, and endocrinological outcomes in women with PCOS.
Methods
A systematic search of five databases (inception–February 2025) identified studies reporting outcomes in women with PCOS following a ketogenic diet. Meta-analyses compared pre- and post-ketogenic diet outcomes (primary analysis) and ketogenic diet versus other diets (secondary analysis). Summary mean differences (MDs) with 95 % confidence intervals (CIs) were calculated using a random-effects model. Risk of bias and evidence quality were assessed using validated tools and the GRADE approach.
Results
Fifteen studies were included in the review, of which ten met the criteria for inclusion in the meta-analysis. Most participants in the included studies had a BMI exceeding 25 kg/m2. In the primary analysis, ketogenic diet led to significant reductions in BMI (MD: −3.38 kg/m2, 95 % CI: 2.53 to 4.23, I2 = 0 %), weight (MD: −10.77 kg, 95 % CI: 8.73 to 12.81, I2 = 0 %), and waist circumference (MD: −8.93 cm, 95 % CI: 5.66 to 12.19; I2 = 44 %). Reductions were also observed in luteinising hormone (LH) levels (MD: 4.07, 95 % CI: 3.36 to 4.79, I2 = 0 %), menstrual cycle duration (MD: 26.06, 95 % CI: 2.28 to 49.85, I2 = 68 %), and insulin resistance (MD: 2.43; 95 % CI: 1.16 to 3.69, I2 = 95 %). In the secondary analysis, ketogenic diet showed superior effects on BMI (MD: −1.65, 95 % CI: −2.76 to −0.55, I2 = 0 %) and weight loss (MD: −4.98, 95 % CI: −9.05 to −0.91, I2 = 7 %) as well as LH levels (MD 1.68, 95 % CI: −3.18 to −0.19, I2 = 30 %) and insulin resistance (MD: −1.71, 95 % CI: −2.98 to −0.43, I2 = 90 %) compared to other diets, though results for androgen and lipid parameters were inconsistent. Heterogeneity was high for most of the studied outcomes.
Conclusion
The ketogenic diet appears to be a promising dietary intervention for improving weight, insulin sensitivity, and reproductive hormone profiles in women with PCOS and a BMI exceeding 25 kg/m2. Nonetheless, the considerable heterogeneity among included studies and variations in study quality warrant cautious interpretation of these findings. Further high-quality, long-term randomized controlled trials are needed to more definitively establish the efficacy and safety of the ketogenic diet in women with PCOS.
{"title":"The effects of ketogenic diet on polycystic ovary syndrome: A systematic review and meta-analysis","authors":"Elisavet Arsenaki , Dimitra Stathi , Konstantinos Katsikas Triantafyllidis , Yeshey Seldon , Stergios Bobotis , George Lockett , Shaun Haran , Maria Kyrgiou , Srdjan Saso , Konstantinos S. Kechagias","doi":"10.1016/j.clnu.2025.11.019","DOIUrl":"10.1016/j.clnu.2025.11.019","url":null,"abstract":"<div><h3>Background and aim</h3><div>Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to obesity, insulin resistance, and reproductive dysfunction. While dietary modification is central to management, the optimal approach remains unclear. This systematic review and meta-analysis evaluated the effects of the ketogenic diet on anthropometric, metabolic, and endocrinological outcomes in women with PCOS.</div></div><div><h3>Methods</h3><div>A systematic search of five databases (inception–February 2025) identified studies reporting outcomes in women with PCOS following a ketogenic diet. Meta-analyses compared pre- and post-ketogenic diet outcomes (primary analysis) and ketogenic diet versus other diets (secondary analysis). Summary mean differences (MDs) with 95 % confidence intervals (CIs) were calculated using a random-effects model. Risk of bias and evidence quality were assessed using validated tools and the GRADE approach.</div></div><div><h3>Results</h3><div>Fifteen studies were included in the review, of which ten met the criteria for inclusion in the meta-analysis. Most participants in the included studies had a BMI exceeding 25 kg/m<sup>2</sup>. In the primary analysis, ketogenic diet led to significant reductions in BMI (MD: −3.38 kg/m<sup>2</sup>, 95 % CI: 2.53 to 4.23, I<sup>2</sup> = 0 %), weight (MD: −10.77 kg, 95 % CI: 8.73 to 12.81, I<sup>2</sup> = 0 %), and waist circumference (MD: −8.93 cm, 95 % CI: 5.66 to 12.19; I<sup>2</sup> = 44 %). Reductions were also observed in luteinising hormone (LH) levels (MD: 4.07, 95 % CI: 3.36 to 4.79, I<sup>2</sup> = 0 %), menstrual cycle duration (MD: 26.06, 95 % CI: 2.28 to 49.85, I<sup>2</sup> = 68 %), and insulin resistance (MD: 2.43; 95 % CI: 1.16 to 3.69, I<sup>2</sup> = 95 %). In the secondary analysis, ketogenic diet showed superior effects on BMI (MD: −1.65, 95 % CI: −2.76 to −0.55, I<sup>2</sup> = 0 %) and weight loss (MD: −4.98, 95 % CI: −9.05 to −0.91, I<sup>2</sup> = 7 %) as well as LH levels (MD 1.68, 95 % CI: −3.18 to −0.19, I<sup>2</sup> = 30 %) and insulin resistance (MD: −1.71, 95 % CI: −2.98 to −0.43, I<sup>2</sup> = 90 %) compared to other diets, though results for androgen and lipid parameters were inconsistent. Heterogeneity was high for most of the studied outcomes.</div></div><div><h3>Conclusion</h3><div>The ketogenic diet appears to be a promising dietary intervention for improving weight, insulin sensitivity, and reproductive hormone profiles in women with PCOS and a BMI exceeding 25 kg/m<sup>2</sup>. Nonetheless, the considerable heterogeneity among included studies and variations in study quality warrant cautious interpretation of these findings. Further high-quality, long-term randomized controlled trials are needed to more definitively establish the efficacy and safety of the ketogenic diet in women with PCOS.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106535"},"PeriodicalIF":7.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1016/j.clnu.2025.12.001
Baochang He , Xixi Dong , Yichen Lin , Jianli Lin , Yu Qiu , Lisong Lin , Bin Shi , Jing Wang , Fa Chen
Background & Aims
Evidence suggests fatty acid metabolism may influence cancer progression, yet their role in oral cancer prognosis remains unclear. This study investigated associations between dietary fatty acid intake, erythrocyte membrane fatty acid composition, and overall survival in patients with oral cancer, and explored potential underlying mechanisms through network pharmacology and molecular docking analyses.
Methods
This prospective cohort study recruited 908 newly diagnosed oral cancer patients from October 2011 to June 2024. Dietary fatty acid intake was assessed using a validated food frequency questionnaire. Erythrocyte membrane fatty acid profiles were measured using gas chromatography. Patients were followed until February 2025, with overall survival as the primary outcome. Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between fatty acid levels and overall survival in oral cancer. Composite indices (dietary fatty acid index [DFAI] and erythrocyte fatty acid index [EFAI]) were constructed using LASSO regression to assess combined effects. Network pharmacology and molecular docking were employed to investigate potential mechanisms.
Results
In multi-adjusted Cox regression models, higher dietary intake of linolenic acid (C18:3), eicosatrienoic acid (C20:3), and docosahexaenoic acid (C22:6) were associated with reduced mortality risk (highest vs. lowest tertile: HR = 0.54, 95 % CI: 0.36–0.82; HR = 0.65, 95 % CI: 0.44–0.95; HR = 0.62, 95 % CI: 0.42–0.91, respectively; all P-trend<0.05). Among erythrocyte membrane fatty acids, significant protective associations were observed for very long-chain saturated fatty acids behenic acid (C22:0) and tricosanoic acid (C23:0), with 48 % and 56 % lower mortality risks in the highest tertile (all P for trend <0.05). Similar protective effects were found for omega-3 polyunsaturated fatty acids including α-linolenic acid (C18:3 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). Composite fatty acid indices showed that DFAI and EFAI were associated with 59 % and 85 % mortality reduction, respectively (both P < 0.001). Network pharmacology identified interleukin-6 (IL-6) as a key target in the fatty acid-oral cancer survival pathway. Molecular docking revealed favorable binding affinities between all six significant fatty acids and IL-6 (binding energies: −1.83 to −5.08 kcal/mol).
Conclusion
Higher dietary intake and erythrocyte membrane levels of specific polyunsaturated fatty acids and very long-chain saturated fatty acids are significantly associated with improved overall survival in oral cancer patients. These protective effects may be mediated through IL-6-related inflammatory pathways.
{"title":"Associations of dietary and erythrocyte membrane fatty acids with overall survival in oral cancer: A prospective cohort study with mechanistic exploration","authors":"Baochang He , Xixi Dong , Yichen Lin , Jianli Lin , Yu Qiu , Lisong Lin , Bin Shi , Jing Wang , Fa Chen","doi":"10.1016/j.clnu.2025.12.001","DOIUrl":"10.1016/j.clnu.2025.12.001","url":null,"abstract":"<div><h3>Background & Aims</h3><div>Evidence suggests fatty acid metabolism may influence cancer progression, yet their role in oral cancer prognosis remains unclear. This study investigated associations between dietary fatty acid intake, erythrocyte membrane fatty acid composition, and overall survival in patients with oral cancer, and explored potential underlying mechanisms through network pharmacology and molecular docking analyses.</div></div><div><h3>Methods</h3><div>This prospective cohort study recruited 908 newly diagnosed oral cancer patients from October 2011 to June 2024. Dietary fatty acid intake was assessed using a validated food frequency questionnaire. Erythrocyte membrane fatty acid profiles were measured using gas chromatography. Patients were followed until February 2025, with overall survival as the primary outcome. Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between fatty acid levels and overall survival in oral cancer. Composite indices (dietary fatty acid index [DFAI] and erythrocyte fatty acid index [EFAI]) were constructed using LASSO regression to assess combined effects. Network pharmacology and molecular docking were employed to investigate potential mechanisms.</div></div><div><h3>Results</h3><div>In multi-adjusted Cox regression models, higher dietary intake of linolenic acid (C18:3), eicosatrienoic acid (C20:3), and docosahexaenoic acid (C22:6) were associated with reduced mortality risk (highest vs. lowest tertile: HR = 0.54, 95 % CI: 0.36–0.82; HR = 0.65, 95 % CI: 0.44–0.95; HR = 0.62, 95 % CI: 0.42–0.91, respectively; all <em>P</em>-trend<0.05). Among erythrocyte membrane fatty acids, significant protective associations were observed for very long-chain saturated fatty acids behenic acid (C22:0) and tricosanoic acid (C23:0), with 48 % and 56 % lower mortality risks in the highest tertile (all <em>P</em> for trend <0.05). Similar protective effects were found for omega-3 polyunsaturated fatty acids including α-linolenic acid (C18:3 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). Composite fatty acid indices showed that DFAI and EFAI were associated with 59 % and 85 % mortality reduction, respectively (both <em>P</em> < 0.001). Network pharmacology identified interleukin-6 (IL-6) as a key target in the fatty acid-oral cancer survival pathway. Molecular docking revealed favorable binding affinities between all six significant fatty acids and IL-6 (binding energies: −1.83 to −5.08 kcal/mol).</div></div><div><h3>Conclusion</h3><div>Higher dietary intake and erythrocyte membrane levels of specific polyunsaturated fatty acids and very long-chain saturated fatty acids are significantly associated with improved overall survival in oral cancer patients. These protective effects may be mediated through IL-6-related inflammatory pathways.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"56 ","pages":"Article 106534"},"PeriodicalIF":7.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.clnu.2025.11.003
Hamza Khan
{"title":"Comment on “Effect of red meat consumption on cardiovascular risk factors: A systematic review and Bayesian network meta-analysis of randomized controlled trials”","authors":"Hamza Khan","doi":"10.1016/j.clnu.2025.11.003","DOIUrl":"10.1016/j.clnu.2025.11.003","url":null,"abstract":"","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Page 222"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620831","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 : 2025-12-01DOI: 10.1016/j.clnu.2025.11.004
Claudia J. Lucassen , Yaren Zügül , Anneke Droop , Bert A. Bonsing , Alexander L. Vahrmeijer , Nynke Michiels , Shirin Shahbazi Feshtali , E.T. Daniël Souwer , Johanneke E.A. Portielje , J. Sven D. Mieog , Frederiek van den Bos
Background and aims
Frailty and sarcopenia are associated with morbidity and mortality in older patients with cancer. The aim of this study was to examine the association of frailty with skeletal muscle index (SMI) and muscle attenuation (MA) on preoperative CT-scans in older patients with pancreatic cancer.
Methods
A single-center retrospective study was performed in patients aged ≥70 years with pancreatic cancer. Frailty was assessed by an abbreviated GA screening. Preoperative SMI and MA were determined by computed tomography (CT) scan analysis. The association of frailty and individual frailty domains with SMI and MA was assessed using linear regression analyses.
Results
101 patients were included of which 15 (14.9 %) were frail. Frailty was associated with lower SMI (adjusted β: −5.07 cm2/m2; 95 % CI: −8.77–1.36) and MA (adjusted β: −5.70 HU; 95 % CI: −9.63–1.77). Both impaired functionality and risk of delirium were associated with lower SMI (adjusted β: −7.01 cm2/m2; 95 % CI: −11.69–2.33 and adjusted β: −4.58 cm2/m2; 95 % CI: −8.22–0.95, respectively). Impaired functionality was also associated with lower MA (adjusted β: −6.88 HU; 95 % CI: −11.89–1.87).
Conclusion
Frailty and impaired functionality were associated with lower SMI and MA. Risk of delirium was independently associated with lower SMI in preoperative older patients with pancreatic cancer. These results suggests that SMI and MA should be included in standard GA screening to better identify high-risk patients and enable more targeted treatment selection.
{"title":"Both skeletal muscle index and muscle attenuation are associated with frailty in preoperative older patients with pancreatic cancer","authors":"Claudia J. Lucassen , Yaren Zügül , Anneke Droop , Bert A. Bonsing , Alexander L. Vahrmeijer , Nynke Michiels , Shirin Shahbazi Feshtali , E.T. Daniël Souwer , Johanneke E.A. Portielje , J. Sven D. Mieog , Frederiek van den Bos","doi":"10.1016/j.clnu.2025.11.004","DOIUrl":"10.1016/j.clnu.2025.11.004","url":null,"abstract":"<div><h3>Background and aims</h3><div>Frailty and sarcopenia are associated with morbidity and mortality in older patients with cancer. The aim of this study was to examine the association of frailty with skeletal muscle index (SMI) and muscle attenuation (MA) on preoperative CT-scans in older patients with pancreatic cancer.</div></div><div><h3>Methods</h3><div>A single-center retrospective study was performed in patients aged ≥70 years with pancreatic cancer. Frailty was assessed by an abbreviated GA screening. Preoperative SMI and MA were determined by computed tomography (CT) scan analysis. The association of frailty and individual frailty domains with SMI and MA was assessed using linear regression analyses.</div></div><div><h3>Results</h3><div>101 patients were included of which 15 (14.9 %) were frail. Frailty was associated with lower SMI (adjusted β: −5.07 cm<sup>2</sup>/m<sup>2</sup>; 95 % CI: −8.77–1.36) and MA (adjusted β: −5.70 HU; 95 % CI: −9.63–1.77). Both impaired functionality and risk of delirium were associated with lower SMI (adjusted β: −7.01 cm<sup>2</sup>/m<sup>2</sup>; 95 % CI: −11.69–2.33 and adjusted β: −4.58 cm<sup>2</sup>/m<sup>2</sup>; 95 % CI: −8.22–0.95, respectively). Impaired functionality was also associated with lower MA (adjusted β: −6.88 HU; 95 % CI: −11.89–1.87).</div></div><div><h3>Conclusion</h3><div>Frailty and impaired functionality were associated with lower SMI and MA. Risk of delirium was independently associated with lower SMI in preoperative older patients with pancreatic cancer. These results suggests that SMI and MA should be included in standard GA screening to better identify high-risk patients and enable more targeted treatment selection.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"55 ","pages":"Pages 242-248"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620829","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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