Background and aims Providing optimal nutrition to very preterm infants is a challenge, yet poor growth is associated with an increased risk for later developmental impairment. While nutritional support is mostly weight-directed, measuring Fat-Free Mass (FFM) and Fat Mass (FM) could provide better insight. We have investigated the association between preterm FFM accretion during the first months after admission and cognitive outcome at school age, and compared this with other growth metrics. Methods This study describes a prospective cohort of 100 preterm (<30wk gestational age) infants. Body composition (BC) was measured using PEAPOD® at corrected age (CA) 6 weeks and 6 months. Cognitive outcomes were assessed with WPPSI-III-NL at 5.5 years CA. Multiple linear regression was used for the association between BC and cognitive outcomes at 5.5 years, adjusted for baseline factors. Results FFM z-scores at 6 wk (B=6.15 [95% CI 1.50–10.80]) and 6 mo (B=6.04 [95% CI 2.20, 9.87]) CA, as well as FFM accretion rate (g/week, B=0.37 [95% CI 0.18–0.58]), were significantly associated with Full Scale IQ (FSIQ) scores at 5.5 years CA, independent of head circumference. FM, height and weight measures showed no significant association at 6mo. The association of FFM versus FSIQ at at 6 mo remained robust after adjusting for birthweight and neonatal illness, while it attenuated for 6 wk. Children with persisting low FFM z-scores between the two visits had low FSIQ (79.2 ± 17.3), while those who increased to normal before 6mo, had age-adequate IQ scores (96.7 ± 16.9). Conclusion FFM accretion in early infancy is associated with school-age cognition in very preterm infants, surpassing traditional weight or FM metrics. Incorporating monitoring FFM alongside head circumference could improve developmental risk stratification.
Background and Aims The Nutritional screening algorithm for patients with incurable cancer receiving palliative care (NutriPal) was recently created and the patients were classified into four degrees of nutritional risk. Previous study has shown that NutriPal is associated with nutritional and laboratory parameters and may have prognostic value for short-term mortality. However, structured recommendations aligned with each risk category have not yet been developed. This study aimed to develop and refine nutritional recommendations aligned with NutriPal risk categories, establish their content validity through expert consensus, and assess their perceived clinical applicability in patients with incurable cancer receiving palliative care Methods The initial version of the nutritional recommendations was prepared based on a literature review and brainstorming. Using the Delphi method, experts (n = 15) assessed the clarity, relevance, and importance of the items. Consensus was defined as ≥85% agreement. Pretests were conducted with clinical Registered Dietitian Nutritionists (n = 29) to evaluate the perceived clinical applicability of the recommendations. Items with ≥15% disagreements or doubts were reformulated and submitted to a second pretest. Results Fifteen nutritional recommendations were developed across six domains. Four rounds of Delphi and two pretests were needed for consensus to be reached. Most modifications occurred after the first Delphi round and the first pretest, while no items were added or removed during the process. The final recommendations were organized according to NutriPal risk categories within six domains: re-administration of NutriPal; symptom control; nutrient supply; nutritional assessment; nutritional support; and comfort. Conclusion This study developed a set of expert consensus-based nutritional recommendations aligned with NutriPal risk categories and demonstrated their perceived clinical applicability among dietitians.
Background & Aims The 2025–2030 Dietary Guidelines (DGA) shifted toward a model expanding animal-based proteins and fats, with unknown impacts on long-term survival. This study aimed to evaluate the association between adherence to the 2025-2030 DGA and all-cause and cause-specific mortality, compared with the traditional Mediterranean Diet (MedDiet). Methods Prospective cohort study of university graduates. A total of 17,855 participants [10,927 women (61.2%) and 6,928 men; mean age 37.2 years], initially free of chronic diseases, followed-up every two years. At baseline a validated 136-item semi-quantitative food frequency questionnaire was used to build two dietary indices: 1) A score of adherence to the 2025-2030 DGA (theoretical range 0-28 points); and 2) A well-known 9-item Mediterranean Diet Score (MDS) appraising adherence to the traditional MedDiet. The primary outcome was all-cause mortality, verified through the National Death Index. Secondary outcomes included cardiovascular (CVD) and cancer mortality. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) across categories (roughly quartiles: Q1-Q4) of dietary indices. Results Over a 14.3-year median follow-up, 525 deaths occurred. Comparing highest (Q4) to lowest (Q1) adherence, the 2025–2030 DGA showed no significant association with all-cause (HR=0.87; 95%CI:0.67-1.13), CVD (HR=1.62; 0.86-3.04), or cancer mortality (HR=0.82; 0.57-1.17). Conversely, high MedDiet adherence (Q4 vs. Q1) was inversely associated with all-cause (HR=0.68; 0.50-0.92), CVD (HR=0.39; 0.18-0.85), and cancer mortality (HR=0.59; 0.40-0.88). Specific plant-based DGA components and limiting processed meats showed independent inverse mortality associations. Conclusions Adherence to the DGA 2025–2030 does not appear to be associated with reduced mortality in this cohort. In contrast, the traditional MedDiet remains strongly associated with lower risks of premature death, including CVD deaths, and cancer deaths. Dietary recommendations should prioritize the MedDiet over the recent DGA 2025–2030 and particularly some features common to both dietary models. Clinical Trial Registry ClinicalTrials.gov NCT02669602.
Background & Aims Meal timing may influence energy expenditure (EE) and metabolic responses. However, the effects of different meal-timing schedules on free-living physical activity, 24-hour EE, respiratory exchange ratio (RER), and metabolic flexibility under matched energy intake and meal composition remain unclear. Methods In a randomized two-period crossover trial, eight healthy young men were allocated in a 1:1 ratio to either an early-to-late or late-to-early meal-timing sequence, with a washout period of at least 1 week between conditions. Participants followed each meal schedule for 7 days and stayed in a whole-room calorimetry chamber from the evening of Day 7 to the morning of Day 9. Identical meals were provided under both conditions, with matched energy intake, meal composition, fasting duration, and sleep–wake timing. Twenty-four-hour EE and RER were assessed from the morning of Day 8 to the morning of Day 9, while free-living physical activity and accelerometer-derived activity-related EE were assessed on Days 1–6. Results Accelerometer-derived estimates of activity-related EE during the free-living period did not differ between the early- and late-timed eating conditions (651 ± 112 vs. 656 ± 178 kcal/d, P = 0.922), and no significant differences were observed in 24-h step counts or time spent in different activity-intensity categories. Total 24-h EE did not differ significantly between early and late meal timing conditions (1879 ± 194 vs. 1856 ± 229; p=0.489). Although the 24-h mean RER was slightly higher in the late-timed condition (0.895 ± 0.019) than in the early-timed condition (0.879 ± 0.017), the difference did not reach statistical significance (p = 0.106, effect size d = 0.832). In contrast, RER during the sleep period (00:00–07:59) was significantly higher in the late-timed condition (0.897 ± 0.017) compared to early-timed eating (0.838 ± 0.027; p < 0.001). Moreover, the amplitude of 24-h RER variation—used as a surrogate for metabolic flexibility—was significantly lower with late-timed eating (0.131 ± 0.021 vs. 0.194 ± 0.030; p < 0.001). Conclusion In this 8-day controlled meal-timing intervention, late-timed eating did not alter free-living physical activity or accelerometer-derived activity-related EE, nor did it alter 24-h EE measured in the room chamber. However, it was associated with a higher sleep-period RER and a smaller 24-h RER range, consistent with lower metabolic flexibility and an attenuated overnight shift in fuel selection from carbohydrate toward fat.
The rapid expansion of pharmacological therapies for obesity, type 2 diabetes, and chronic kidney disease (CKD) has transformed clinical practice and broadened the therapeutic landscape for the management of metabolic diseases. These agents provide well-established cardiometabolic and renal benefits; however, their use should be understood within the context of an integrated approach, alongside interventions targeting lifestyle-related determinants of disease. Lifestyle-related factors, including dietary patterns and physical activity, remain central to the pathophysiology of metabolic diseases and CKD. At the same time, pharmacological modulation of metabolic pathways offers targeted therapeutic benefits, particularly in individuals at higher risk. Nutritional and pharmacological strategies act through complementary mechanisms and may provide synergistic effects when implemented concurrently and individualized according to clinical risk. Dietary interventions, particularly those rich in minimally processed foods and bioactive compounds, exert pleiotropic effects on processes such as inflammation, oxidative stress, mitochondrial dysfunction, premature aging, and gut dysbiosis, which are shared hallmarks of CKD. The growing use of pharmacological therapies in metabolic diseases and CKD highlights the importance of understanding how to integrate them with lifestyle-based strategies. Individualized therapeutic approaches that incorporate nutritional and pharmacological interventions, when indicated, may help optimize cardiometabolic and renal outcomes. Considering the chronic nature of these conditions, sustained strategies centered on diet and physical activity remain essential components for maintaining long-term metabolic and renal health.
Background & Aims While circulating lipid biomarkers are widely used, little is known about the absolute tissue reserves of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) in humans or their availability during severe systemic illness. We therefore mapped absolute PUFA concentrations across major human tissues and examined whether fatal COVID-19 is associated with depletion of long-chain n–3 substrate pools. Methods Absolute fatty acid concentrations (mg/g wet tissue) were quantified across nine tissues (adipose tissue, brain, heart, lungs, liver, spleen, skeletal muscle, small intestine, and kidney) using gas chromatography with flame-ionization detection (GC-FID). Whole-body fatty-acid reserves were then estimated from tissue concentrations and organ weights. The cohort included sudden-death controls and patients with fatal COVID-19 pneumonia. Results Controls exhibited distinct organ-specific lipid signatures with high n–3 concentrations in adipose tissue and brain. In fatal COVID-19, we observed a coherent cross-organ reduction in long-chain n–3 substrate pools driven primarily by depletion of EPA and DPA. DHA showed tissue-specific preservation or relative elevation, most notably in brain, adipose tissue, and spleen. Adipose tissue, the primary reservoir, showed a severe imbalance characterized by an approximately 3.3-fold increase in the n–6/n–3 ratio (median 50.66 vs. 15.56; p = 0.004) and lower total n–3 content (0.93 vs. 2.76 mg/g; p = 0.004). Brain tissue displayed species-specific remodeling: EPA and DPA were lower in COVID-19, whereas DHA was relatively higher (EPA, 0.018 vs. 0.16 mg/g; p = 0.004). In the lungs, EPA was similarly depleted (0.015 vs. 0.34 mg/g; p = 0.004), and the myocardium shifted toward a pro-inflammatory profile with an elevated n–6/n–3 ratio (16.87 vs. 4.01; p = 0.004). Estimated whole-body n–3 reserves were lower in the COVID-19 group (41.7 g vs. 86.6 g). Conclusions This study establishes a comprehensive quantitative human tissue map of absolute PUFA reserves and suggests that severe systemic illness, exemplified here by fatal COVID-19, is associated with coherent depletion of long-chain n–3 substrates across organs. These findings support the concept that tissue substrate availability may be a clinically relevant constraint on resolution signalling during acute metabolic stress.
Background and Aims It is discussed that eating vegetables before carbohydrates may reduce the increase of postprandial glucose and improve insulin secretion. However, findings of studies investigating the effectiveness are inconclusive. Therefore, the aim of this systematic review and meta-analysis was to assess the effects on glycemic control in adults with and without health conditions. Methods PubMed and the Cochrane Library were searched until September 2025. Randomized controlled trials (RCTs) examining the effect of a vegetable preload before carbohydrate consumption on postprandial and fasting glucose, insulin and HbA1c levels in adults were selected. Results In total, we included 18 RCTs. Using risk of bias tool RoB 2 ten trials were rated with moderate risk of bias and eight with a high risk. With very low certainty of evidence the intervention reduced postprandial glucose and insulin concentration after 30 minutes (MD (95% CI): −1.21 mmol/L [−1.75, −0.68] and −13.14 μU/mL [−18.63, −7.65]) and 60 minutes (−0.52 mmol/L [−0.67, −0.37]; and −12.03 μU/mL [−18.27, −5.78]) compared to their controls without vegetable preloads. After 120 minutes, postprandial glucose and insulin values were higher compared to the controls (0.24 mmol/L [0.06, 0.42] and 7.10 μU/mL [1.94, 12.26]). In people with type 2 diabetes, the intervention reduced HbA1c (baseline: 8.3 ± 1.7%, after 24 months: 6.8 ± 0.8%). Conclusion Although this meta-analysis shows short-term improvements in glucose and insulin concentrations and individual studies indicate beneficial effects on HbA1c, the interpretability of these results is severely restricted due to methodological limitations. PROSPERO registration number: CRD42024529101.
Background & aims Autophagy activation is a promising strategy to counteract age-related cellular dysfunction. While preclinical studies suggest dietary protein restriction can induce autophagy via mTORC1 inhibition, direct human evidence using dynamic, flux-based measurements remains limited. The aim of this study was to determine whether a low protein diet could modulate autophagic flux in humans. Methods We conducted a randomized crossover trial in which 74 healthy adults were randomized to receive two 4-week interventions of either average-protein (20% energy) or reduced-protein (10% energy) diets prescribed to maintain calculated energy balance, separated by a 4-week washout period. The primary outcome was autophagic flux measured in whole blood using a validated assay that preserves PBMCs in their physiological environment during lysosomal inhibition. Secondary outcomes included metabolic markers, body composition, and self-reported health metrics. Results Sixty-three participants completed both interventions (mean ± SD age 29.5 ± 7.2 yrs; BMI 24.0 ± 3.2 kg/m2). Reducing protein intake did not alter autophagic flux (adjusted mean difference: -8.46 ng LC3B-II/mg protein/h; 95% CI: -24.06 to 7.14; p = 0.28). Metabolomic profiling confirmed effective dietary separation, with lower circulating urea following reduced protein intake. Small differences in body weight and muscle mass were observed, while fat mass was unaffected. Fasting glucose, insulin, lipids, blood pressure, and quality of life did not differ between the two diets. Conclusions Moderate protein restriction does not increase basal autophagy in circulating immune cells of healthy adults, suggesting protein reduction alone, without caloric deficit, may be insufficient to activate autophagy in human blood. Clinical trial registry number Australian New Zealand Clinical Trials Registry Identifier ACTRN12623000260628https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382790
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving therapy for refractory shock; however, gastrointestinal (GI) complications have been reported in up to 50% of these patients and contribute substantially to morbidity and mortality. While early enteral nutrition (EN) improves outcomes in critical illness, enteral feeding intolerance (EFI) is common during VA-ECMO, and concerns regarding bowel ischemia frequently delay nutritional support. VA-ECMO introduces unique pathophysiological mechanisms – including non-pulsatile flow, retrograde aortic perfusion, and systemic inflammation – that alter gut perfusion and promote intestinal injury. This may create a complex interaction in which impaired intestinal barrier integrity facilitates bacterial translocation and potentially amplifies multiorgan dysfunction. Upper GI bleeding has been reported in approximately 10% of patients, driven by acquired coagulopathies and mandatory anticoagulation. Acute bowel ischemia affects 5%-9%, with mortality exceeding 75%, while EFI affects 33%-53%. Despite the clinical importance of these complications, current evidence remains fragmented, and the mechanisms underlying GI dysfunction during VA-ECMO have not been comprehensively synthesized. This narrative review summarizes the current evidence on the pathophysiological mechanisms, clinical manifestations, prognostic implications, and nutritional management of GI dysfunction in adult patients receiving VA-ECMO, highlighting current knowledge gaps and priorities for future research.
Background and Aims Sarcopenia, adipopenia, and body mass are recognized as prognostic factors in cancer, but their combined effects on survival remain unclear. This study aims to construct a comprehensive body composition grading system (BCS) and assess its prognostic value for cancer patients. Method Clinical case data from 5,629 cancer patients were retrospectively analyzed. The BCS (Levels I-V) was constructed based on sarcopenia grading (defined by skeletal muscle index, ASMI), adiposity reduction (defined by fat mass index, FMI), and body mass index (BMI). Survival curves were analyzed using the Kaplan-Meier method, while Cox regression analysis explored associations between BCS and survival outcomes. Additionally, logistic regression analysis was utilized to examine the relationship between the BCS and severe malnutrition/cachexia. Results The Kaplan-Meier method revealed a stepwise increase in survival probability from Grade I to Grade V (49.8% vs. 53.7% vs. 64.1% vs. 68.0% vs. 72.0%, Log-rank p < 0.001). In unadjusted Cox proportional hazards models, with Grade V as the reference, the risk of adverse prognosis increased progressively with lower grades. After adjusting for confounders, the BCS retained independent prognostic value: hazard ratios for Grades IV, III, II, and I relative to Grade V were 1.266, 1.404, 1.891, and 2.177, respectively. Subgroup analyses indicated that the BCS was universally applicable across various cancer stages and types. Logistic regression validated the BCS as a robust diagnostic tool for severe malnutrition and an effective method for risk stratification. Specifically, relative to Grade V, the odds of cachexia increased progressively with higher severity grades: odds ratios of 1.567 for Grade IV, 3.233 for Grade III, 8.099 for Grade II, and 10.508 for Grade I were observed. A higher BCS demonstrated significant correlations with multiple functional domains and symptom scales. Furthermore, multivariate logistic regression established the BCS as an independent factor associated with elevated risk of lower overall quality of life. Conclusions The BCS is an independent prognostic factor for cancer survival, closely related to severe malnutrition and cancer cachexia. It serves as a reference for clinical nutritional interventions and treatment decisions.
BACKGROUND AND AIMS:Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with antiplatelet properties. This effect is at the core of protection of EPA against ischemic events. On the other side, it has raised concerns of increased risk of delayed cessation of bleeding. This might be critical in the event of an intracerebral haemorrhage (ICH). We explored whether higher circulating EPA status at hospital admission for ICH (mirroring EPA intake during the weeks prior to the event) relate to a higher risk for adverse outcomes. METHODS:We used gas-chromatography to determine EPA in serum phospholipids of 177 ICH patients. We performed neuroimaging and sequential evaluations of neurological deficits using the National Institutes of Health Stroke Scale (NIHSS). We recorded early neurological deterioration and mortality during hospitalization and at 90 days. We constructed multivariate models adjusting for age, NIHSS score, ICH location, and hematoma volume at admission. We examined the association between EPA and prevalence of adverse outcomes (in-hospital mortality; 90-day mortality; early neurologic deterioration). RESULTS:There were 27 cases of in-hospital mortality, 41 cases of 90-day mortality and 35 cases of early neurologic deterioration. Compared to participants at T1 (lowest tertile) of EPA, those at T3 (highest tertile) showed a lower risk of in-hospital mortality (adjusted hazard ratio [95% confidence interval] = 0.05 [0.00,0.55]). A similar pattern was observed when considering EPA continuously. Statistical significance remained when only considering lobar ICH (14 cases/58 patients). No other relevant associations were observed. DISCUSSION:Higher circulating levels of EPA at hospital admission for ICH were unrelated to a worse prognosis. Actually, some associations pointed to benefits, in particular for lobar ICH. This helps dispelling concerns surrounding this omega-3 regarding amplified damage in a critical bleeding event such as an ICH.
Background & Aims The Dietary Approaches to Stop Hypertension (DASH) intervention was developed in the 1990s to study blood pressure-lowering effects of a diet high in potassium, calcium, and magnesium, as well as fiber and protein. Various DASH indices were developed in the 2000s to study the health effects of such a DASH eating pattern in observational studies. Here, we propose a modified DASH index (mDASH) incorporating relevant updated evidence. We evaluated the reliability and validity of the new index and its ability to predict hypertension (HTN) risk in the prospective Framingham Heart Study Second Generation cohort and cross-validated its predictive ability in the younger Third Generation cohort. Methods Food frequency questionnaires were used to derive a food-based mDASH diet index. We began with the key components of the original DASH diet: fruits, vegetables, and low-fat dairy and then modified this base model by replacing low-fat dairy with total dairy. We then iteratively added other dietary components to develop the final mDASH index. Test-retest reliability was assessed across four examination cycles (exams 5-8), and construct validity was determined by comparing the target nutrient composition of mDASH with that of other indices. Finally, predictive validity through Cox regression models was assessed by comparing the ability of mDASH (versus earlier DASH indices) to predict incident HTN. Results The final mDASH index ranged from 8-40 points and included: total fruit; total vegetables (including potatoes); total dairy (both full-fat and low-fat); fish/seafood; whole grains; legumes, nuts, and seeds; red and processed meats; and sugar-sweetened beverages. Moderate-to-strong Pearson correlations (r=0.56–0.70) were found amongst mDASH scores across four exams, while construct validity was supported by similarly strong correlations (r=0.51-0.71) between mDASH scores and key DASH nutrients—calcium, potassium, magnesium, fiber, and protein. Lastly, the mDASH pattern was strongly predictive of HTN risk. In the Second Generation cohort, those in the highest (versus lowest) mDASH quintile had a 27% lower risk of HTN (p-trend across quintiles=0.0056), a finding that was comparable to that of an earlier DASH index by Fung (p-trend=0.0255) and similar to a 35% lower risk (p-trend=0.0004) associated with the highest adherence to the DASH index by Günther. A final DASH index by Dixon was not statistically significantly (p-trend=0.1434) associated with HTN risk. In the validation cohort (FHS Third Generation), highest adherence to mDASH index was associated with a 20% lower HTN risk (95% CI: 0.61, 1.04). Conclusions We developed an updated, valid, and reliable eight-component mDASH index that performed as well as or better than existing indices in predicting HTN. This modified diet pattern provides more food choices in a DASH pattern without compromising its beneficial associations with blood pressure.
BACKGROUND:Casein glycomacropeptide supplemented with amino acids (CGMP-AA) is used in the treatment of phenylketonuria (PKU). However, its acute metabolic effects when consumed with other foods remain poorly understood. This study investigated the impact CGMP-AA consumed alone or with two low-protein meals providing carbohydrates with either fibre or fat. METHODS:In this randomised crossover trial, fifteen healthy adults (27.0 ± 7.9 y; 7 females) consumed: A) CGMP-AA alone; B) CGMP-AA with low-protein bread and unpeeled apple; or C) CGMP-AA with low-protein bread and olive oil. Blood samples were collected over 120 min to assess glucose, insulin, C-peptide, amino acids, and appetite-related hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY)). RESULTS:Co-ingestion with low-protein foods had limited effects on total essential and large neutral amino acid concentrations over 120 min, but increased Tyr incremental area under the curve (iAUC(0-120min)) and peak concentration (Cmax) compared with CGMP-AA alone. Meal B elicited the highest glucose, insulin, and C-peptide iAUC(0-120min) and Cmax, followed by meal C, whereas meal A induced minimal glycaemic and insulinaemic excursions. Meal C produced the greatest GIP response, whereas GLP-1 and PYY did not differ between test meals. CONCLUSIONS:In healthy adults, CGMP-AA elicited distinct acute postprandial responses depending on whether it was consumed alone or with low-protein foods. CGMP-AA consumed with food is not metabolically equivalent to CGMP-AA consumed alone, and carbohydrate-with-fibre and carbohydrate-with-fat meal contexts affect distinct aspects of the postprandial response. These findings should be confirmed in individuals with PKU before being translated into dietary recommendations.
Background and Aims Pentadecanoic acid (C15:0) is an odd-chain saturated fatty acid increasingly proposed as a candidate essential fatty acid due to emerging evidence linking it to metabolic, inflammatory, and cellular resilience. However, its metabolic context within broader fatty-acid networks remain insufficiently characterized. Methods We conducted a retrospective clinical chart review of 449 patients at an academic integrative medical center between January 2018 and March 2024. Circulating C15:0 and related fatty acids were measured using the NutrEval® comprehensive metabolic assessment. Patients were stratified by C15:0 reference ranges; due to the small sample size, the normal and high reference range groups were combined (low: < 0.07 % total fatty acids; normal/high: ≥ 0.07 % total fatty acids). Linear regression models compared pentadecanoic acid to various fatty acids. Significance thresholds were determined using BH-adjusted p-values (FDR < 0.05). Results Of the 449 patients, 69/449 (15.4%) were in the “low” cohort. C15:0 demonstrated significant positive associations with several odd-chain and very long-chain saturated fatty acids, including palmitoleic acid (16:1 n7), margaric acid (C17:0), tricosanoic acid (C23:0), behenic acid (C22:0), and lignoceric acid (C24:0), as well as select omega-6 polyunsaturated fatty acids, including arachidonic acid (AA), gamma-linolenic acid (GLA), dihomogamma-linolenic acid (DGLA), and docosatetraenoic acid (DTA). Significant negative associations were observed with stearic acid (C18:0), nervonic acid (24:1 n9), vaccenic acid (18:1 n7), eicosadienoic acid (20:2 n6), and the linoleic acid:DGLA ratio. These patterns suggest coordinated regulation across lipid classes rather than isolated biochemical effects. Conclusions Circulating C15:0 occupies a distinct position within lipidomic networks associated with metabolic resilience, inflammatory balance, membrane integrity, and neurologic health. The observed associations likely reflect shared metabolic regulation, dietary exposure, and enzymatic flux rather than direct fatty-acid synergy. These findings support the interpretation of C15:0 as a clinically relevant nutrient embedded within broader lipid metabolism and provide evidence to inform ongoing evaluation of its status as an essential fatty acid.
BACKGROUND & AIMS:Healthy dietary patterns are associated with a lower risk of cardiovascular disease (CVD). Proteomic correlates of healthy dietary patterns are understudied and may provide mechanistic insight and suggest putative markers between diet and CVD risk. We investigated the prospective association of a dietary proteomic score with cardiometabolic risk factors and CVD in a multi-generational cohort of middle-aged adults. METHODS:We examined participants from the Framingham Heart Study Generation 2 (n = 1611, mean age 55 ± 10, 55.4% women) and Generation 3 (n = 862, mean age 46 ± 8, 56.6% women) who had complete dietary, proteomic, and covariate data, and were free from prevalent CVD. We analyzed plasma proteins using DNA aptamer-based technology, and three dietary pattern indices were derived from a semiquantitative food frequency questionnaire. With elastic net regression, we identified 11 diet-related proteins and created a weighted DPS, which had the strongest correlation with the DASH diet score (r = 00.30, p < 0.0001). RESULTS:Over a median of 25 and 13 years we observed 533 CVD events. A 1-standard deviation (SD) increase in dietary proteomic score was associated with a 54% lower prevalence of Metabolic Syndrome (P ≤ 0.001) in multivariable-adjusted logistic regression models. Using multivariable Cox regression models adjusted for adjusting for lifestyle factors and the Dietary Approaches to Stop Hypertension (DASH) diet score, a 1-SD increase in the dietary proteomic score was associated with a 20% lower risk of CVD (HR [95% CI], 0.80 [0.73, 0.88]) and those in the highest tertile of the dietary proteomic score, compared to the lowest, had a 38% reduced risk of CVD (0.62 [0.49, 0.78]). However, these associations were attenuated after further adjustment for known cardiometabolic risk factors (1-SD: HR 0.94, [0.85, 1.04]; T3 vs T1: 0.81 [0.63, 1.03]). CONCLUSION:A dietary proteomic score of three healthy dietary pattern indices was strongly associated with prevalent metabolic health cross-sectionally and incident CVD prospectively. These findings provide insight into the mechanisms linking diet quality and cardiometabolic health, and suggest future dietary proteomic studies in independent populations, as well as incorporating proteomics into dietary intervention trials.
BACKGROUND AND AIMS:Dairy products are considered beneficial for musculoskeletal health, but limited evidence supports their benefits on knee osteoarthritis (KOA) prevention. This study aimed to examine associations between total and specific dairy product intake and the risk of KOA in East Asian adults. METHODS:This 11-year cohort study included 10,411 community-dwelling Japanese individuals aged 40-74 years. Demographic data, body size, information on lifestyle factors, and medical history were collected using a self-administered questionnaire at the baseline survey conducted in 2011-2013. A validated semi-quantified food frequency questionnaire was used to assess the intake of total dairy products, milk, and fermented dairy products (cheese and yogurt). Energy-adjusted intake was calculated using the residual method. Incident symptomatic radiographic KOA, defined as Kellgren-Lawrence grade ≥2 among individuals presenting with knee symptoms, was ascertained by participating medical institutions. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). RESULTS:Mean age of participants was 57.9 years. Median intakes (g/day) of milk, cheese, yogurt, and total dairy products were 27, 1, 8, and 118, respectively. Higher quartiles of total dairy intake were associated with lower hazards of KOA (P for trend = 0.0174), with the third (HR = 0.81, 95%CI: 0.67-0.99) and fourth (HR = 0.79, 95%CI: 0.65-0.97) quartiles having lower hazards than the first quartile. Similarly, higher levels of fermented dairy intake were associated with lower hazards of KOA (P for trend = 0.0007), with the third (HR = 0.81, 95%CI: 0.67-0.99) and fourth (HR = 0.72, 95%CI: 0.58-0.87) intake groups having lower hazards than the zero intake group. Similar trends were observed in sex-stratified analyses (P for trend = 0.0396 for males, 0.0081 for females). Whereas no association was observed for milk intake (P for trend = 0.1615), the frequencies of cheese and yogurt intake were independently associated with KOA hazards (P for trend = 0.0228 and 0.0272, respectively). CONCLUSIONS:Higher dairy intake is associated with a reduced risk of KOA among middle-aged and older individuals with relatively low dairy intake. The observed association appears to be largely driven by the intake of fermented dairy products rather than milk.
BACKGROUND & AIMS:Biochemical leak (BL) after pancreaticoduodenectomy (PD) is common and may progress to clinically relevant postoperative pancreatic fistula (CR-POPF), especially in older patients with limited physiological reserve. Nutritional strategies specifically tailored to the BL phase are not well defined in current perioperative management protocols, leaving this vulnerable population without targeted support during the critical early postoperative period. We aimed to assess whether early nasojejunal feeding (ENJF) improves outcomes compared with conventional oral feeding (COF) in older patients with BL after PD. METHODS:We conducted a two-center retrospective observational cohort study, designed to emulate a target-trial, among patients aged ≥65 years who developed BL by postoperative day (POD) 3 after PD (January 2022-December 2024). Patients received either ENJF (POD 3-6) or COF. Propensity scores based on 16 predefined fistula-risk factors were used for inverse-probability weighting. The primary endpoint was 30-day CR-POPF; secondary endpoints included general postoperative complications (POCs, Clavien-Dindo grade II), severe POCs (grade ≥ III), and 90-day mortality. RESULTS:Among 933 screened patients, 348 BL-positive patients were included. ENJF was associated with lower CR-POPF incidence than COF (23.0 % vs 45.4 %; OR 0.36; 95 % CI 0.26-0.50; P < 0.001). General POCs were lower (62.4% vs 70.2%; OR 0.70; 95% CI 0.51-0.97; P = 0.029), as were severe POCs (13.8 % vs 30.7 %; OR 0.36; 95 % CI 0.25-0.53; P < 0.001); 90-day mortality was 0 % vs 4.6 % (P = 0.038). ENJF was associated with earlier fulfillment of ≥80 % caloric and protein targets, required less parenteral nutrition, and more favorable trajectories of hemoglobin, prealbumin, and inflammatory markers during PODs 7-14. CONCLUSIONS:In older PD patients with BL, ENJF after BL detection was associated with improved nutritional recovery and fewer POCs. These findings support consideration of BL-guided nutritional reassessment within a risk-stratified perioperative nutritional strategy, pending prospective validation.
BACKGROUND AND AIMS:Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS) was introduced as a clinical endotype of chronic critical illness and is frequently observed in patients with sepsis. Although nutritional therapy may affect immune function and disease progression, the relationship between malnutrition, nutritional delivery, and PIICS remains unclear. We herein investigated the incidence and outcomes of PIICS and examined its relationship with acute-phase nutritional therapy and Global Leadership Initiative on Malnutrition (GLIM) malnutrition in intensive care unit (ICU) patients with sepsis. METHODS:This was a secondary analysis of the multicenter prospective ILOSS study including adult (≥18 years) ICU patients with sepsis admitted between 2020 and 2021. PIICS was defined as a hospital stay ≥14 days and at least two of the following on day 14: lymphocyte count <800/μL, C-reactive protein >2.0 mg/dL, and albumin <3.0 g/dL. Malnutrition was defined using GLIM criteria. The primary outcome was the composite of in-hospital mortality or severe functional dependence, defined as Barthel index <60 at hospital discharge. A multivariable logistic regression analysis identified risk factors for PIICS, and energy and protein intakes on days 1-14 were compared between the PIICS and non-PIICS groups. RESULTS:Among 250 patients, 127 (50.8%) developed PIICS. The PIICS group had higher SOFA scores on ICU admission and the higher use of mechanical ventilation and renal replacement therapy during the ICU stay. GLIM malnutrition was more prevalent in the PIICS group. The primary outcome was more frequent in patients with PIICS at discharge (56.7% vs. 32.8%) and at 12 months (55.7% vs. 31.4%). GLIM malnutrition was independently associated with PIICS (OR 1.80, 95% CI 1.02-3.18; p = 0.04). Among patients without GLIM malnutrition at admission, energy and protein intakes on days 8-14 were lower in patients who subsequently developed PIICS. CONCLUSION:Approximately 50% of ICU patients with sepsis developed PIICS. Patients with PIICS had higher mortality and worse physical function and quality of life after discharge, although these differences attenuated over time. Pre-existing GLIM malnutrition seemed to be associated with an increased risk of developing PIICS. A causal relationship between nutritional delivery and PIICS development in patients with/without malnutrition requires further investigation.
BACKGROUND AND AIMS:Reduced maternal folate status is widely accepted as a major causative factor for neural tube defects, but its association with other birth defects remains unclear. This study aimed to evaluate the association between maternal 5-methyltetrahydrofolate (5-MTHF) levels and the risk of birth defects. METHODS:This prospective cohort study was conducted in a large obstetrics and gynecology hospital in Beijing, China. Pregnant women were recruited in their first trimester between December 2020 and November 2021, with baseline characteristics and blood samples collected at enrollment. Participants were followed until 42 days postpartum. After excluding those with missing baseline information, non-singleton pregnancies, loss to follow-up, or undetermined birth defect status, 6578 women were included in the primary analysis. Maternal red blood cell (RBC) and plasma 5-MTHF concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary outcome was structural birth defects and chromosomal abnormalities in offspring, including live births, stillbirths, and pregnancy terminations due to fetal abnormalities. Causality was assessed using two-sample Mendelian randomization. RESULTS:Among all participants (median gestational age at recruitment, 8.5 weeks), 355 (5.4%) offspring were diagnosed with birth defects. Maternal RBC but not plasma 5-MTHF concentrations were significantly lower in women with affected offspring. Subcategory analysis revealed a negative association between RBC 5-MTHF and the risk of congenital heart defects, eye, ear, face, and neck defects, musculoskeletal system defects, and chromosomal abnormalities. The incidence of birth defects decreased from the cohort-wide rate of 5.4% to 4.4% when RBC 5-MTHF levels exceeded 700 nmol/L, representing a relative risk reduction (RRR) of 18%. Two-sample Mendelian randomization based on the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism indicated potential causality. CONCLUSION:Low early-pregnancy RBC 5-MTHF levels were associated with an increased risk of birth defects.
