Current Developments in Nutrition

Plant-based foods are complex systems, where a multitude of bioactive molecules, such as (poly)phenols and carotenoids are the outcome of endless interactions defining food chemical composition. Significant progress has been made to develop reliable food composition databases that can be used to assess the intake of dietary plant bioactives. However, many lesser-known phytochemicals, like glucosinolates and monoterpenoids are often excluded, also due to the fragmented information available in the literature. Therefore, we present PhytoFooD, a comprehensive phytochemical food database that collects qualitative and quantitative information on 1,067 bioactive compounds in 1,410 plant-based foods. We evaluated the intake of main plant bioactives in European diets and demonstrated the role of concentration variability within foods in intake assessments. This database represents a promising tool for dietary intake assessors and researchers in nutrition, paving the way for a comprehensive and accurate knowledge of our diet and the interconnected health effects of plant bioactives.

This work explores the dietary intake of plant bioactives in the European adult population. The information available in the scientific literature is quite fragmented, with only partial knowledge of dietary bioactive intake and their health effects, and without harmonised figures across populations and phytochemical families. In this context, we comprehensively evaluated the intake of (poly)phenols, terpenoids, N-containing compounds, and miscellaneous phytochemicals in the European adult population, using public data from 26 countries reporting on 38,944 individuals. Further research was conducted to investigate the contributions of classes, subclasses, and individual compounds, as well as their relationships. Main food sources of each class and subclass of phytochemicals were also identified. Finally, variability in phytochemical intake across European countries was evaluated. This work significantly advances the current knowledge of plant bioactive intake and sets the stage for future research in nutrition and health fields.

Changes in gut microbiota composition due to diet impact health. Fiber-rich diets promote beneficial microbiota and reduce the risk of metabolic diseases, while low-fiber, calorie-dense diets are linked to dysbiosis and increased disease risk. This study examines the effects of a Western diet (WD) and explores dietary fiber supplements as potential modifiers of those effects. 10-week-old C57Bl/6J male mice were fed control (low-fat) or WD (high-fat, high-sucrose) containing 0% fermentable fiber (FF) or WD supplemented with 20% FF (fructooligosaccharides, FOS; guar gum, GG, or pectin, Pec). After 19 weeks, analysis of the cecal metagenome using whole-genome shotgun sequencing, metabolome by untargeted and targeted LC-MS/MS, and tissue RNA and protein expression by RT-PCR and immunoblotting was undertaken. WD-FF reduced metabolic derangements from WD while also improving GM diversity and altering cecal metabolites, particularly tryptophan metabolism. A profound increase in cecal indole levels (targeted metabolomics) was noted in WD vs WD-FF groups. As the primary indole-oxidizing enzyme, CYP2E1 generates indoxyl sulfate, which contributes to oxidative stress and a leaky gut. Mice on WD displayed higher expression of Cyp2e1 mRNA in the gut. In the liver, the levels of both CYP2E1 protein and mRNA were higher in the WD group compared to the WD-FOS group, with protein levels also higher than in the WD-Pec group and mRNA levels higher than in the WD-GG group. mRNA expression of markers of oxidative stress, inflammation, and leaky barrier was significantly higher in the liver and intestine of the WD vs the WD-FF groups. FFs reduced high plasma indoxyl sulfate levels (except in WD-GG), and boosted short-chain fatty acids and indole acetic acid. Our data suggest that WD disrupts GM tryptophan metabolism, possibly by altering the balance between indole-producing and utilizing gut bacteria. Dietary fiber supplementation exerts protective effects, in part, by mitigating this imbalance.

BackgroundDiets rich in monounsaturated fatty acids (MUFAs) and fiber support gastrointestinal health and the microbiome; however, the effect of whole foods relative to their isolated nutrients remains under-investigated. ObjectiveDetermine the impact of avocado consumption on gastrointestinal health and microbiome beyond the individual effects of MUFAs and fiber. MethodsAdults with overweight and obesity (n=43, mean age=41y, BMI=31.6kg/m2) completed a randomized, crossover, controlled feeding study with three 4-wk dietary interventions separated by 2-wk washouts: average American (AA), oleic acid + fiber (OF) nutrients, and avocado (AV). The base diet was supplemented with 209g avocado (AV), or isocaloric snacks high in MUFA/fiber (OF) or low in MUFA/fiber (AA). Outcomes included fecal microbiome (shotgun metagenomics), fecal microbial metabolites (short-chain [SCFA] and branched-chain [BCFA] fatty acids, phenols, indoles, and bile acids), intestinal permeability (24h urinary sweetener excretion), systemic (CRP, IL-6, LBP) and gut (fecal calprotectin and sIgA) inflammatory markers, and gastrointestinal tolerance symptoms. Statistical analysis included linear mixed models, Friedman tests, and multivariable association analysis. ResultsFecal acetate and total SCFAs were 28% and 18% higher in AV and OF conditions, compared to AA (p<0.001 & p=0.019, respectively). Total secondary bile acids in the AV condition were 34% and 24% lower compared to OF (p<0.001) and AA (p=0.011), respectively. Alistipes communis ({beta}=0.85, q=0.03) and Bacteroides uniformis ({beta}=0.50, q=0.14) were higher following AV, whereas Lachnospira eligens ({beta}=1.79, q <0.001) was higher following OF, compared to AA. Microbial genes involved in pectin, cellulose, and hemicellulose degradation were enriched in AV and OF. Fecal calprotectin was lower in AV (30%; p=0.03) and OF (26%; p=0.04) compared to AA, while sIgA was 34% lower following AV, compared to AA (p=0.01). ConclusionsAvocado and MUFA/fiber-matched control had similar fermentation, but distinct secondary bile acid and microbial profiles, emphasizing the food matrix and gut microbiome as key determinants of diet-health relations. Clinical Trial Registry number and website where it was obtainedhttps://clinicaltrials.gov/study/NCT05941728?intr=NCT05941728&rank=1

Background and ObjectivesRecent large-scale studies have consistently linked healthy dietary patterns to improved cardiometabolic health; however, the underlying biological pathways remain largely unclear, especially in non-European populations. In this study, we leverage data from four population-based cohorts (UK Biobank, NEO study, GNHS, and 10K) to investigate both common and cohort-specific biological pathways linking healthy dietary patterns to cardiometabolic disease through multi-omics profiling. Material and methodsIn each cohort, we first assessed the associations between each of the five major dietary pattern scores (i.e., AMED, hPDI, DII, AHEI, and EDIH) and cardiometabolic disease risk using Cox or logistic regression models. To explore the potential mediating role, metabolomics and proteomics measurements were incorporated into the models. All models were adjusted for relevant confounders, and false discovery rate correction was applied to account for multiple testing. ResultsWith a total of 71,679 individuals without pre-existing cardiometabolic disease across four participating cohorts (UKB: 54,024, NEO: 4,838, GNHS: 3,201, and 10K: 9,616), we confirmed that adherence to healthy dietary patterns was associated with a 5-10% reduced risk of cardiometabolic disease. Three common biological pathways were identified: (1) mediation via large HDL particles and apolipoprotein F; (2) mediation via DNAJ/Hsp40 and triglyceride-rich lipoproteins; and (3) mediation via CRHBP-regulated HPA axis activity affecting triglyceride-rich lipoproteins. ConclusionsOur integrative multi-omics analysis across diverse populations identifies novel biomarkers that connect healthy dietary patterns with cardiometabolic risk. These findings deepen our understanding of the biological mechanisms underlying diet-related disease and hold promise for enhancing the development of precision nutrition interventions.

This study investigated the effects of Lactiplantibacillus plantarum VB165, a probiotic strain with intrinsic -glucosidase inhibitor (AGI) activity, on metabolic disorders in high-fat diet (HFD)-induced insulin-resistant (IR) mice. Male C57BL/6 mice were divided into four groups: normal control diet (NCD), NCD supplemented with VB165, HFD, and HFD supplemented with VB165. After 16 weeks, VB165 supplementation significantly attenuated HFD-induced weight gain and reduced epididymal and inguinal white adipose tissue indices. VB165 also improved glucose intolerance and insulin resistance (IR), as demonstrated by oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), and lowered fasting blood glucose, fasting insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. Additionally, it ameliorated dyslipidemia by reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), while alleviating hepatic steatosis and adipocyte hypertrophy. Mechanistically, VB165 enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1 and Occludin), reduced systemic inflammation by lowering LPS, IL-6, and IL-1{beta}. Gut microbiota analysis revealed that VB165 modulated community composition, suppressing HFD-enriched genera (e.g., Ileibacterium and Coriobacteriaceae_UCG_002) and promoting beneficial taxa (e.g., Faecalibaculum and Oscillibacter). These findings demonstrate that L. plantarum VB165 improves HFD-induced metabolic disorders via multi-target mechanisms, highlighting its potential as a probiotic intervention for IR and related metabolic diseases.

Background: Hospital canteens provide an effective setting for improving the dietary habits of users. The study evaluates the food choices of users after an educational and environmental intervention, considering nutritional composition and environmental impact, and to compare the results with pre-intervention choices. Methods: A cross-sectional study was conducted in three hospital canteens (C1, C2, C3) in northeastern Italy, during two index weeks in September 2022 (T0) and 2023 (T1). An intervention was introduced between T0 and T1, consisting of posters on healthy eating, descriptive norm messages, and environmental changes regarding fruit and vegetables. Photos of lunch trays were collected, and choices were analyzed for nutritional composition and sustainability. Results: 2,851 trays were analyzed: 1,227 at T0 (798 in C1, 228 in C2 and 201 in C3) and 1,624 at T1 (1,005 in C1, 348 in C2, 271 in C3). In C1 and C3, there was an increase in median energy (+30 kcal; +135 kcal) compared to pre-intervention meals, while in C2 there was a decrease (-118 kcal). Despite a slight improvement in macronutrient composition, at T1 meals in all canteens were still high in lipids (30%E; 39%E; 35%E) and low in carbohydrates (44%E; 39%E; 41%E). The fibre value fell within the recommended range only in C1 and C3. The median carbon (CF) and water (WF) footprints of meals in all canteens remained high: at T1 CF ranged from 966 gCO2eq. to 1,227 gCO2eq. and WF from 1,025 L H2O to 1,207 L H2O. Conclusion: The intervention has led to partial improvements in food choices. To achieve more significant results, it may be necessary to implement a parallel intervention on food offer.

BackgroundHigher-quality diets have been associated with lower levels of ectopic fat deposited in the viscera and liver, which is hypothesized to be mediated in part by the gut microbiota. ObjectivesWe tested this hypothesis in a multi-ethnic imaging study using global (microbiome-wide) testing as well as a high-dimensional multiple-mediators regression framework to identify bacterial genera in the human gut that mediate the association between diet quality and ectopic adiposity. MethodsWe analyzed the cross-sectional data of 1,400 older adults (age 60-77) from five racial/ethnic groups in the Multiethnic Cohort Adiposity Phenotype Study (2013-2016). Overall diet quality was defined by adherence to the MIND diet. The relative abundance of 151 bacterial genera was quantified from 16S rRNA gene sequencing of the stool samples. Visceral fat, liver fat, and the presence of MASLD (metabolic dysfunction-associated steatotic liver disease) were determined based on magnetic resonance imaging (MRI). We used high-dimensional mediation analysis (HDMA) to estimate gut microbial mediation in the linear regression of visceral fat or liver fat, or in logistic regression of MASLD, on the MIND adherence score, adjusted for potential confounders. ResultsHigher diet quality was associated with lower ectopic adiposity: 12% less visceral fat area, 23% less liver fat, and a 49% less likelihood of having MASLD, comparing the highest to the lowest quartile of the MIND score. Using a distance-based global test, we confirmed overall significant microbial mediation of the inverse diet-ectopic fat association. From HDMA, four bacterial genera were identified as mediating the protective association with visceral fat, with the largest mediation conferred by Lachnospiraceae UCG.001 (12.2%). Two genera (Lachnoclostridium, Weissella) were shown to mediate the MIND association with both liver fat and MASLD. In particular, Lachnoclostridium mediated 13.6% of the liver fat association and 10.8% of the MASLD association, and Lachnospiraceae UCG.001 additionally mediated 12.1% of the liver fat association. ConclusionsOur results support the hypothesis that the gut microbiota contributes to conveying the effect of diet quality on preferred body fat distribution, e.g., involving bacteria that are known to produce short-chain fatty acids (Lachnospiraceae) or secondary bile acids (Lachnoclostridium).

The modern Western diet (MWD) provides high linoleic acid (LA) exposure, typically contributing 6-9% of total caloric intake. These high LA levels have fueled a longstanding debate regarding whether this dietary pattern confers benefit or risk. Importantly, LA intake is disproportionately elevated among lower socioeconomic populations due to greater reliance on industrial seed oils and ultra-processed foods. Despite decades of research, controlled dietary intervention studies directly evaluating the biological consequences of varying LA exposure remain limited. The current randomized, double-blind intervention compared the effects of a 12-week Low LA diet (2.5% energy) versus a High LA diet (10.0% energy) in healthy adults. Primary outcomes included plasma highly unsaturated fatty acid (HUFA) concentrations and ex vivo zymosan-stimulated whole-blood oxylipin generation. Fifty- two participants completed the intervention. High LA exposure resulted in a marked reduction in plasma n-3 eicosapentaenoic acid (EPA) concentrations compared with the LowLA arm. In contrast, levels of arachidonic acid (ARA), dihomo-gamma-linolenic acid (DGLA) and docosahexaenoic acid (DHA) did not differ by dietary LA exposure. Analysis of oxylipin species revealed that levels of EPA-derived relative to ARA-derived mediators were significantly reduced in the High LA arm. These findings reveal that higher dietary LA selectively suppresses EPA pools and EPA-derived oxylipins without altering ARA, shifting the lipid mediator balance toward a more n-6-dominant profile.

Background: Accurate dietary assessment is essential for precision nutrition and effective nutrition surveillance. However, portion size estimation remains a persistent challenge, particularly in culturally diverse regions such as Central Asia. Traditional self-reporting tools often yield inconsistent results due to communal eating practices and unfamiliarity with standard measures. Objective: To address these limitations, this study aimed to compare three methods: unassisted human judgment, visual food atlas assistance, and an artificial intelligence (AI) model, using Central Asian food items. Methods: In this cross-sectional study, 128 participants from Astana, Kazakhstan, visually estimated portion sizes of 51 foods and 8 beverages from standardized photographs. Participants were randomized into two groups: one using unassisted visual estimation and the other aided by a regionally tailored digital food atlas. Additionally, an AI model trained on Central Asian food images was evaluated. Actual food weights served as the reference standard. Accuracy was assessed using Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE) across food types and portion sizes. Results: The atlas-assisted group demonstrated the highest accuracy, with the lowest MAE (80.81g) and MAPE (44.76%) across all portions. The AI model showed promising results for average portions (MAE: 79.07g, MAPE: 67.91%) but underperformed on small portions, particularly for meat-based items. Unassisted estimates were the least accurate (MAE: 133.86g, MAPE: 79.40%). Across food categories, visual aids consistently improved accuracy, while AI demonstrated variability by texture and portion size. Conclusions: Culturally adapted visual atlases significantly enhance portion size estimation accuracy in non-Western, communal-eating contexts. While AI models hold promise for dietary assessments, particularly with standard portions and beverages, further refinement is needed for complex food items and small portion types. These findings support the integration of visual and AI-based tools into region-specific dietary monitoring strategies.

Obesity and related cardiometabolic diseases pose significant global health challenges. Konjac glucomannan, a soluble dietary fiber, has shown promise in managing these conditions. However, rigorous studies are necessary to establish its benefits on human health. We designed a parallel-arm, triple-blind, placebo-controlled RCT to test the effects of glucomannan (3 g/day, 12 weeks) on body weight and composition, lipid profile, glucose metabolism, inflammation, adipokines, intestinal permeability, gut microbiota, and fecal metabolites in 40 adults. Participants were randomly assigned to either the glucomannan or placebo group, with both groups adhering to personalized hypocaloric diets and moderate physical activity. Outcomes were analyzed as intention-to-treat using linear mixed-effect models. Irrespective of the treatment, our intervention reduced body weight (mean: -2.39 kg; 95% CI: -3.38, -1.40), BMI (-0.83 kg/m2; -1.15, -0.52), and waist (-2.70 cm; -3.87, -1.53). Glucomannan promoted additional benefits not obtained with the placebo, reducing body fat measured by DEXA (body fat%: -2.16%; -3.04, -1.28; VAT: -20.0 cm2; - 29.2, -10.8; FMI: -0.98 kg/m2; -1.34, -0.62), LDL (-14.1 mg/dL; -23.4, -4.9), and the atherogenic index (-0.50; -0.80, -0.21). It also diminished the Framingham score of 10-year risk of coronary heart disease (-0.370; -0.625, -0.115), C reactive protein (-1.01 mg/L; -2.18, 0.15), leptin (-2.06 ng/mL; -4.48, 0.365), and leptin/adiponectin (-0.282; -0.603, 0.040). The two treatments had similar intakes, physical activity, and adherence to the intervention. There were no adverse effects. This intervention fostered health benefits in a population at high risk of cardiometabolic diseases. Konjac glucomannan was an effective co-adjuvant for further reducing risk factors.

BackgroundPrevious research on diet and hip fracture risk focused on selected foods and nutrients. ObjectiveTo conduct a diet-wide association study of hip fracture risk. MethodsThe study population comprised 541,887 postmenopausal women in the Million Women Study. Dietary information was assessed using a validated food frequency questionnaire in 2000-2004, and calibrated using a 24-hour dietary recall from a subset 10 years later. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 99 dietary factors and risk of incident hip fracture, ascertained through linkage to hospital admission data. ResultsAfter an average of 19.7 years of follow-up, 27,318 incident hip fractures occurred. In multivariable-adjusted models, 60 dietary factors were associated with hip fracture risk after correction for multiple testing (False Discovery Rate p-value <0.05). The five foods most significantly associated with hip fracture risk (based on p-value) were chicken (HR and 95% CI = 0.84, 0.80-0.87 per 20 g/day), vegetables (0.88, 0.85-0.91 per 100 g/day), pasta (0.87, 0.83-0.91 per 20 g/day), chips (1.14, 1.10-1.18 per 25 g/day), and fizzy drinks (1.18, 1.12-1.24 per 50 g/day). The five nutrients with the strongest associations were protein (0.79, 0.75-0.84 per 15 g/day), zinc (0.81, 0.77-0.86 per 2 mg/day), carotene (0.91, 0.88-0.94 per 1000 {micro}g/day), fiber (0.89, 0.85-0.92 per 5 g/day), and niacin (0.82, 0.77-0.87 per 10 mg/day). The results were consistent across subgroups of body mass index, smoking, alcohol consumption, health status, physical activity, menopausal hormone use, deprivation status, and in analyses excluding the first five years of follow-up. ConclusionsMany "healthy" foods were associated with lower risk of hip fracture, and "unhealthy" foods with higher risk. Further research is needed to assess whether these associations reflect causal relationships, are indicators of a healthier overall diet, or represent confounding from other lifestyle factors.

Obesity prevalence continues to rise in the United States, with a disproportionate burden falling to West Virginia. To investigate the metabolic effects of region-specific dietary patterns, we developed the West Virginia Obesogenic Diet (WV-OD), a compositionally defined rodent diet based on nutritional analyses of meals consumed by obese individuals in the state. The WV-OD closely mirrors the macronutrient profile of the average American diet while incorporating regional features such as a greater sodium level and significantly less fiber. We compared the metabolic effects of the WV-OD to a matched control diet (WV-CD) and to a widely used high-fat diet (HFD, 60% of calories derived from fat) in male and female C57BL/6J mice. After 19 weeks, WV-OD-fed males exhibited weight gain and adiposity comparable to HFD-fed counterparts, along with glucose intolerance and hepatic triglyceride accumulation confirming the obesogenic and metabolically disruptive properties of the WV-OD. Unlike HFD-fed mice, WV-OD-fed males also displayed elevated circulating cholesterol and cholesterol esters without corresponding increases in hepatic total cholesterol. When compared to the HFD, the WV-OD did not increase uric acid or xanthine oxidoreductase (XOR) content of liver or circulation; however, both males and females on the WV-OD demonstrated trends towards elevated plasma uric acid. Interestingly, while exhibiting a similar caloric intake on either diet, the WV-OD females did not demonstrate significant fat accretion or metabolic dysfunction compared to females subjected to the 60% HFD. In toto, these findings: 1) establish the WV-OD as a regionally-grounded, yet broadly representative tool for modeling diet-induced obesity and metabolic dysfunction, 2) offer a physiologically relevant alternative to extreme-fat dietary models in preclinical research and 3) highlight sex-based differences in response to diet-induced obesity.

ContextVitamin B12 deficiency is common among vegans and vegetarians due to limited intake of animal-derived foods. Identifying safe, plant-based sources of vitamin B12 is essential to address this nutritional gap. AimsThis study evaluated the efficacy and safety of Chlorella vulgaris tablets in improving vitamin B12 deficiency. Settings and DesignA double-blind, randomized, placebo-controlled trial was conducted among 46 healthy adults with vitamin B12 deficiency (serum levels 107-210 pmol/L). Methods and MaterialParticipants were randomized (1:1) to receive C. vulgaris (1 g twice daily) or identical placebo for 12 weeks. Primary outcome was change in serum vitamin B12; secondary outcomes included folic acid, homocysteine, methylmalonic acid (MMA), and quality of life (WHO-QoL). Assessments were conducted at baseline and week 12, with safety monitored through liver and kidney function tests and adverse event reporting. Statistical Analysis UsedSample size (n=46) was calculated with 90% power and 10% dropout allowance. Data were analyzed using SPSS v22. Non-parametric tests were applied after normality assessment, with p<0.05 considered significant. ResultsOf 46 participants (mean age 35.5 {+/-} 11.2 years; 69.6% female), mean serum vitamin B12 levels were significantly higher in the C. vulgaris group than in the placebo group at 12 weeks (214.4 {+/-} 160.8 vs 55.9 {+/-} 15.0 ng/mL; P < .001). No significant differences were observed in folic acid, homocysteine, MMA, or QoL scores between groups. No adverse events were reported. ConclusionsSupplementation with Chlorella vulgaris significantly improved serum vitamin B12 levels, suggesting its potential as a safe, plant-based alternative for managing vitamin B12 deficiency. Key MessagesO_LIPlant-based Chlorella vulgaris improved vitamin B12 levels significantly C_LIO_LIRandomized trial in B12-deficient healthy adults over 12 weeks C_LIO_LINo adverse effects observed on liver or kidney function tests C_LIO_LIQuality of life improved across all domains in the intervention group C_LI

Background: Intracranial atherosclerosis is a major cause of ischemic stroke. Asymptomatic intracranial atherosclerotic stenosis (ICAS) represents a subclinical and potentially modifiable stage preceding ischemic stroke, yet the nutritional factors associated with asymptomatic ICAS remain poorly defined. This study aimed to identify dietary factors associated with asymptomatic ICAS in community-dwelling older adults. Methods: This cross-sectional, population-based study included 962 Japanese adults aged {greater than or equal to}65 years from the Yahaba Active Aging and Healthy Brain study, conducted in Yahaba town, Japan, between July 2016 and July 2017. Asymptomatic ICAS was defined as {greater than or equal to}50% intracranial arterial stenosis evaluated by magnetic resonance angiography (MRA) without a history of stroke or transient ischemic attack. All participants underwent dietary assessment using a food frequency questionnaire. We examined the association between nutritional factors and ICAS using multivariable logistic regression models with adjustment for age, sex, hypertension, dyslipidemia, diabetes mellitus, body mass index, smoking, and alcohol use. Results: After exclusions, 850 participants were analyzed. The mean age was 73.4 {plus minus} 6.5 years, and 52% were female. ICAS was identified in 135 participants (15.9%). Participants in the highest quartile of dietary fiber intake had lower odds of ICAS than those in the lowest quartile (OR, 0.45; 95% CI, 0.26-0.80). Potassium intake showed a similar inverse association (OR, 0.49; 95% CI, 0.27-0.89). When both nutrients were included in the multivariable model as continuous variables, neither remained significant, with moderate collinearity (variance inflation factor, 4.16). Conclusions: Higher dietary fiber intake was inversely associated with asymptomatic ICAS among community-dwelling older Japanese adults. Potassium intake also showed an inverse association, although this relationship was less consistent after accounting for collinearity with dietary fiber.

Background: Diet is a modifiable risk factor for cardiometabolic disease, yet establishing causality remains challenging. Mendelian randomisation (MR) leverages genetic variants as instrumental variables (IVs) to enable causal inference. Method: Using two-sample MR, we assessed the causal effects of four principal component-derived dietary patterns (DPs) - Unhealthy, Healthy, Meat-based, Pescatarian - on twelve cardiometabolic outcomes: body mass index, coronary artery disease, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, type 2 diabetes, fasting glucose and insulin, and glycated haemoglobin. Two sets of IVs were employed: conventional genome-wide significant variants associated with each DP, rigorously filtered for pleiotropy and directionality; and biologically informed variants in chemosensory receptor genes, given the role of taste and smell perception in shaping food choices. Results: Using conventional IVs, the Pescatarian DP reduced fasting insulin ({beta}IVW = -0.10 pmolL-1 per SD increase in Pescatarian DP score, 95% Confidence interval [CI] [-0.15, -0.04]; P = 1.19x10-3), which survived multiple sensitivity analyses. Associations between the Unhealthy DP and elevated blood pressure and glycated haemoglobin were likely undermined by heterogeneity and pleiotropy, with insufficient IVs for robust sensitivity testing. Chemosensory receptors yielded null findings, reflecting insufficient power. Conclusion: Rigorously filtered conventional IVs supported the causal nature of well-established diet-disease relationships, demonstrating MR's utility in strengthening causal inference in nutritional epidemiology. Chemosensory IVs demonstrated limited utility for DPs, likely reflecting the heterogeneous and complex sensory profiles of overall diets. Future efforts should consider using guideline-based dietary scores to facilitate translation of findings.

ObjectivesCardiovascular diseases (CVDs) remain a global health priority, with oral health linked to cardiovascular risk. However, existing studies have mainly focused on limited periodontal measures and lack analyses of multidimensional oral health. MethodsUsing data from 4,564 participants in the China Multi-Ethnic Cohort, this study employed an exposure-wide analysis to systematically examine associations between multidimensional oral health indicators and multiple CVD-related outcomes, and to evaluate the role of blood and urine-based biomarkers as potential mediators. ResultsWe found that indicators regarding caries, periodontal status, and occlusal function were significantly associated with carotid plaque prevalence. Sex-stratified analyses confirmed that all significant associations were concentrated in females, instead of males. Age-stratified analyses showed distinct patterns, with meaningful associations concentrated among participants under 65, where indicators regarding caries, periodontal status, and occlusal function were related to the FRS. In adults aged 65 and older, only the number of functional tooth units was associated with carotid plaque. Mediation analyses identified multiple blood biomarkers, including hemoglobin A1c and Platelet Large Cell Ratio, as partial mediators. ConclusionsThese findings indicate that multidimensional oral health correlates with cardiovascular outcomes, with obvious sex and age differences, and that blood biomarkers play an important mediating role. Our findings provide new insights that extend beyond traditional periodontal associations by highlighting the relevance of multidimensional oral health to cardiovascular risk, supporting its consideration in cardiovascular prevention.

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aimed at assessing whether adherence to dietary recommendations for fruit and vegetable intake and overall diet quality achieves flavanol intake levels of 500 mg/day, the amount proven to mediate cardiovascular benefits in the COSMOS trial. Flavanol intake was objectively evaluated using two validated and complementary biomarkers, 5-(3{square},4{square}-dihydroxyphenyl)-{gamma}-valerolactone metabolites (gVLMB) and structurally related (-)-epicatechin metabolites (SREMB), in two geographically distinct studies: COSMOS (US; n=6,509) and EPIC-Norfolk (UK; n=24,154). The results showed that higher fruit and vegetable intakes and diet quality (assessed via the alternative healthy eating index-aHEI) were associated with increased flavanol intake in COSMOS. Nevertheless, fewer than 25% of participants meeting dietary guidelines achieved an estimated flavanol intake of [&ge;]500 mg/day. Similar findings were observed in EPIC-Norfolk as well as through flavanol intake simulations considering fruits and vegetables commonly consumed in the US diet. In conclusion, adherence to existing dietary guidelines does not yield flavanol intake levels comparable to those shown to provide cardiovascular benefits in COSMOS. Thus, specific dietary reference values for flavanols may still be necessary if aiming to increase the intake of these dietary compounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/26346949v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@2966f5org.highwire.dtl.DTLVardef@269232org.highwire.dtl.DTLVardef@483edborg.highwire.dtl.DTLVardef@116a957_HPS_FORMAT_FIGEXP M_FIG C_FIG

Frailty is an age-related syndrome characterized by biological dysfunction and reduced physiological reserve in response to stressors. Its prevalence is increasing with population aging, resulting in a substantial health burden due to adverse outcomes on health, such as cardiovascular disease and mortality. Ultra-processed foods (UPFs), defined as industrial formulations made primarily from processed ingredients, have received increasing attention due to their potential role in the development and progression of frailty. This systematic review and meta-analysis examined the association between ultra-processed food intake and the risk of frailty in older adults. This study systematically searched for all relevant studies published up to January 2026. Ten observational studies involving 105327 participants, comprising 6 prospective and 4 cross-sectional studies, were included in the systematic review, of which 6 were eligible for meta-analysis. Random-effects models were employed to estimate pooled effect sizes and 95% confidence intervals (95% CIs). Meta-analysis showed that higher consumption of UPFs was significantly associated with an increased risk of frailty (pooled OR = 1.43, 95% CI = [1.02-2.005], p = 0.041). Narrative synthesis further supported a positive association between UPF intake and frailty or related outcomes. Our findings suggest that a higher consumption of ultra-processed foods may contribute to frailty risk, potentially through inflammatory pathways. However, given the high heterogeneity, results should be interpreted with caution. Overall, our findings suggest that reducing UPF consumption may be a promising target for public health strategies to prevent frailty in ageing populations.

BackgroundHuman milk (HM) bioactive components can have immune modulatory functions, impact the gut microbiome, and may result in functional benefits when added to infant formula (IF). In this single-arm, prospective, intervention study, we tested the effectiveness of an IF with a whey protein concentrate co-enriched in -lactalbumin, milk fat globule membrane (MFGM), and Sn-2 palmitate resulting in protein and lipid profiles observed in HM. The outcomes tested were feeding tolerance, Bifidobacteria abundance, and intestinal and immune health of Chinese infants. MethodsPredominantly formula-fed (FF) and breastfed (BF) infants were enrolled between 3 and 28 days and assigned to the FF (N= 60) or BF (N=60) group, per their feeding practice, for 6 weeks. The primary endpoint was Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score assessed using a validated IGSQ-13 questionnaire after 6 weeks of intervention; non-inferiority of FF vs BF was tested. Secondary endpoints included fecal Bifidobacteria abundance assessed using shotgun metagenomics sequencing; fecal short chain fatty acids (SCFAs) analyzed by ultra-performance liquid chromatography-tandem mass spectrometry; fecal markers of immune response, inflammation, intestinal barrier integrity (secretory immunoglobulin A sIgA), cytokines, calprotectin, 1 antitrypsin, lipocalin-2) assessed using enzyme-linked immunosorbent assay; stool consistency assessed using gastrointestinal (GI) diary; anthropometric assessments; quality of life; physician reported adverse events; and use of medications. ResultsGood GI tolerance was observed in both groups at V2 (mean{+/-}SD IGSQ score FF: 19.9{+/-}7.4; BF: 16.8{+/-}4.2); difference of means 1.35 [95% CI: -1.312, 4.012]). After 6 weeks, Bifidobacterium genus relative abundance was not significantly different between the groups. Total SCFAs were significantly higher (p<0.05) in the FF versus BF group, driven by increased levels of valeric and propanoic acids (p<0.05 for both). The IGSQ domain scores, stool consistency, fecal markers of immunity, inflammation, and intestinal barrier integrity (except lipocalin-2 which was significantly higher in BF vs FF), anthropometric Z-scores, common illnesses, antibiotic use, and adverse events were not significantly different between groups at week 6. ConclusionsOur results support the effectiveness of this tested infant formula in supporting good GI tolerance, growth, specific intestinal and immune health markers, and Bifidobacteria abundance similar to that of the BF group. Trial registrationNCT04880083 (2021-05-06)