Frontiers in Nutrition

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 [≥]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@24faeaorg.highwire.dtl.DTLVardef@1d52a29org.highwire.dtl.DTLVardef@1c2ff33org.highwire.dtl.DTLVardef@100a384_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundRecent meta-analyses of randomized controlled trials (RCTs) have raised concerns that treatment with omega-3 fatty acids may increase risk of atrial fibrillation (AF). However, these meta-analyses included at most eight trials. The aim of this current meta-analysis was to expand the search by including other eligible omega-3 RCTs with AF incidence data, incorporating both published and unpublished data. MethodsEligible studies were RCTs investigating daily doses of [≥]500 mg/d of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Additional inclusion criteria included [≥]12 months treatment with EPA/DHA, participants [≥] 50 years of age, and where possible, the absence of known AF/atrial flutter at baseline. The primary outcome was occurrence of new-onset AF. Our primary hypothesis was that risk for AF would simultaneously depend on both omega-3 dose (above or below 1500 mg/d) and background cardiovascular disease (CVD) risk status, and that their combined impact on AF risk would be synergistic. ResultsA total of 34 RCTs (36 datasets; n=114,326) were included in this meta-analysis. Only studies including patients at high-risk for CVD who were treated with high-doses of EPA/DHA (>1500 mg/day) showed a statistically significant increase in AF risk with a pooled odds ratio (OR) of 1.48 (95% CI, 1.21-1.81) and an absolute risk difference of 0.8% (0.40-1.1%). None of the other three groups showed statistically significant levels of AF risk (ORs 1.07 (high risk, low dose), 1.06 (low risk, low dose) and 0.95 (low risk, high dose). ConclusionThis meta-analysis suggests that treatment with EPA/DHA is most likely to increase risk for AF in patients at high-risk for CVD who are treated with high doses of EPA/DHA. The risk for AF should be balanced against the benefits of EPA/DHA in making treatment decisions.

BackgroundThe sodium-restricted rice diet (RD) was once the only effective treatment for malignant hypertension (MH); however, a modern, comprehensive data analysis is lacking. We determined patient survival and ocular improvements in 544 MH patients treated between 1942-1982. MethodsAt entry, systolic blood pressure (SBP) was [&ge;]170 mmHg and retinal hemorrhage (n = 312), hemorrhage with papilledema (n= 211) or papilledema alone (n = 21) were present. Dates of death were available for 454 patients; ocular data (at baseline and again before day 365) for 342 patients with hemorrhage and 143 with papilledema. We used actuarial analysis to determine survival and resolution of ocular findings. We used Cox proportional hazards to calculate mortality hazard ratio (HR), and period life tables to estimate loss of longevity. ResultsMedian initial SBP of 213.3 mmHg fell to 178.4 during year 1, and to [~]143 after 9 years. RD patients survived longer than untreated patients: 1890 vs 540 days for patients with hemorrhage alone; 510 vs 180 days with both hemorrhage and papilledema. Few patients reached their expected longevity; median loss of potential life was 15.4 years. Compared to patients whose SBP fell <15 mmHg by 4 weeks, those with a fall [&ge;] 37 mmHg had HR for mortality of 0.32. Retinal hemorrhages cleared in 260/342 patients; papilledema, in 133/143. ConclusionWith RD treatment blood pressure decreased, and ocular abnormalities largely resolved. Survival improved, but predicted longevity was not achieved. The RD helped MH and could still provide a useful adjunct to pharmacologic therapy.

IntroductionFiber intake is the most common nutritional inadequacy in the Western diet, with most adults consuming less than half of the recommended intake with only 5% of adults meeting the RDI. A novel, short-chain beta-glucan derived from oats (scOat Fiber), with improved solubility, low viscosity and enhanced palatability, compared to conventional oat fibers, was investigated for its benefits as a source of fiber supplementation. MethodsA 14-day pilot study evaluated the gastrointestinal tolerance and functional benefits of scOat Fiber in 63 healthy adults randomized to receive 5, 10 or 20 g daily doses. The primary outcome, gastrointestinal tolerability, was assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcome included glycemic response during rice challenges, measured via continuous glucose monitoring (CGM). CGM was also used to explore overall glucose dynamics. Additional exploratory outcomes (mood, energy, appetite and sleep) were assessed via validated questionnaires. ResultsscOat Fiber was exceptionally well tolerated across all doses, with no increase in GSRS scores, which remained in the low to mild range. Significant reductions in total GSRS scores were observed, with benefits evident after just one week at 5 g/day and maintained over time at both 5 and 10 g/day groups. Evaluation of GSRS sub-categories revealed that the 5 g/day and 10 g/day dose groups experienced significant reductions in abdominal pain symptoms. Both dose groups also demonstrated a significant decrease in constipation at the end of the study. Postprandial glucose responses were attenuated following product use, with a significant reduction in peak glucose during rice challenges after 2 weeks in the 20 g/day group. Both 10 and 20 g/day doses were associated with significant improvement in glycemic metrics during the study, including reductions in glucose mean, all glycemic excursions, and an increase in time-in-range. Exploratory analysis suggested that scOat Fiber may improve mental health and concentration in participants with elevated baseline symptoms. ConclusionsDespite the lack of a placebo control and short duration, the dose-dependent nature of the results supports the potential of scOat Fiber as a well-tolerated and functional source of fiber with benefits including glycemic control, digestive health and mental health (NCT06739941)

Opioid use disorder (OUD) has been linked to cardiometabolic diseases in adults through reductions in adiponectin--an adipocytokine with insulin-sensitizing effects. Opioid use during pregnancy dysregulates neonatal growth and may predispose to adult-onset diseases, but the impact of maternal OUD on neonatal adiponectin has not been studied. We hypothesize that maternal OUD also reduces adiponectin level in offspring (primary outcome) and alters growth (secondary outcome). To test our hypothesis, we conducted a prospective, observational pilot study and compared the expression of salivary adiponectin receptor 1/ADIPOR1 and anthropometric and body composition (fat and fat-free mass) measurements between opioid-exposed and age-matched non-exposed neonates born at [&ge;]34 weeks gestation. Data were stratified by exposure and sex using a Students t-test. Significance was set at p<0.05. A total of 67 neonates (35 opioid-exposed, 32 non-exposed neonates) were enrolled. Compared to healthy, non-exposed neonates, the expression of ADIPOR1 was reduced in opioid-exposed neonates (0.27-fold, p<0.01), with the lowest expression in those requiring pharmacotherapy (0.048-fold, p<0.001). Despite the smaller anthropometric measurements in the exposed than non-exposed neonates (2915{+/-}625 grams vs. 3209{+/-}345 grams, p=0.02), opioid-exposed neonates had comparable adiposity to non-exposed neonates (8.60{+/-}4.52% vs. 8.53{+/-}4.00%, p=0.95). Less breast milk was used in the exposed than non-exposed group (25.7% vs. 71.9%, p<0.01). Maternal OUD may be associated with aberrant growth and excess adiposity in offspring through its effect on adiponectin signaling, predisposing these neonates to cardiometabolic risks.

The gut microbiota has been implicated in regulating body composition, insulin resistance, and energy metabolism through microbial metabolites, including short-chain fatty acids (SCFAs) and amino acids. However, evidence in adolescents, particularly regarding sex-specific differences and lifestyle such as alcohol intake, remains limited. Characterizing sex-specific metabolic signatures in adolescence may improve early identification of metabolic risk. To address this gap, we investigated associations between fecal metabolites, body composition, insulin resistance, and energy expenditure in 158 adolescents aged 18 from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000). Quantitative fecal metabolomics was performed using proton nuclear magnetic resonance (1H-NMR) spectroscopy, profiling 32 metabolites. Associations with body composition, insulin resistance, and energy expenditure were evaluated using sex-stratified univariate and multivariate modelling with false discovery rate (FDR [&le;] 0.05 and 0.2). Fecal acetate and ethanol were more associated with fat-free mass index (FFMI) and waist-to-height ratio (WHtR) than with body mass index (BMI) in females; in males, no associations remained after FDR. Lysine and leucine showed associations with BMI and insulin resistance in females. Acetate, butyrate, glucose, and methanol were associated with total energy expenditure (TEE) in females, whereas no association survived in males. Alcohol intake was positively associated with fecal ethanol, glucose, and methanol, and inversely with trimethylamine in females, while galactose showed a positive association in males. These findings demonstrate that gut microbiota-derived metabolites are related to body composition, insulin sensitivity, and energy balance in adolescents, particularly females, highlighting the utility of fecal metabolomics in exploring mechanisms underlying metabolic variation.

Background/ObjectivesNutrient interactions in multi-ingredient supplements may influence absorption and bioavailability, yet pharmacokinetic data in this context remains limited. This clinical trial assessed the post-prandial absorption kinetics of key micronutrients in AG1, a comprehensive supplement containing vitamins, minerals, probiotics, and phytonutrients. MethodsIn a randomized, double-blind, placebo-controlled crossover trial 16 healthy adults (8 males and 8 females) consumed a single serving (13g) of AG1 or a taste- and appearance-matched placebo mixed in water, following a 10-hour overnight fast. Each condition was separated by a 1-week washout. Blood samples were collected pre-consumption and at 30, 60, 90, 120, 180, 240, 360, and 480 minutes post-ingestion. Plasma concentrations of folate, calcium, zinc, vitamin C, biotin, nicotinamide, pyridoxine, riboflavin, thiamin, and hesperidin were measured. Area under the curve (AUC0-480 min) was used to assess nutrient absorption. Safety and tolerability were assessed throughout the study. Statistical analysis included repeated measures ANOVA and paired t-tests. ResultsAG1 significantly increased AUC0-480 min values (p<0.05) for all measured nutrients except pyridoxine which revealed a strong trend (p = 0.075) and hesperidin (p = 0.224). Both AG1 and placebo were well tolerated, with no serious adverse events reported. ConclusionsAcute consumption of AG1 resulted in measurable increases in circulating levels of most of the tested micronutrients, indicating effective absorption and bioavailability. These findings support the potential of AG1 to contribute meaningfully to nutritional status and overall health.

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)

Front-of-pack nutrition labels (FOPLs) have been adopted as a key government strategy to address the significant burden of diet-related noncommunicable diseases. However, research on public knowledge and perceptions of FOPLs and their relationships with sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption remains limited. A cross-sectional study with 2870 individuals was conducted to explore their knowledge and perceptions of Nutri-Grade, a national front-of-pack nutrition labeling scheme introduced in Singapore in 2022. Knowledge was not significantly associated with SSB consumption; however, individuals who perceived these labels more positively were significantly less likely to consume SSBs daily (AOR=0.72, p<0.001) and consumed fewer types of SSBs weekly (IRR=0.91, p<0.001). Moderation analyses indicated that greater knowledge of Nutri-Grade FOPLs was associated with a higher likelihood of SSB consumption among younger individuals and those residing in areas with higher house prices. Additionally, individuals with positive perceptions were more likely to consume SSBs daily when living in areas with food court density exceeding 2.99 per km{superscript 2} (AOR = 1.12, p = 0.004). Individuals with positive perceptions of Nutri-Grade FOPL were also less likely to consume ASBs (AOR=0.69, p<0.001), whereas, in contrast to SSBs, greater knowledge of Nutri-Grade FOPLs was associated with increased ASB consumption (AOR=1.42, p<0.001). These findings indicate that informational labeling itself is insufficient to change consumption behavior. Although positive perceptions of Nutri-Grade FOPLs provide a protective effect, this effect diminishes when the food environment is taken into account.

BackgroundObservational studies have linked high adherence to the "Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay" (MIND) diet to improved cognitive functions in older adults. The underlying peripheral and central mechanisms of this association remain poorly understood, although multiple nutrients in the MIND diet are known for their anti-inflammatory effects. Therefore, we explored the cross-sectional relation between MIND diet adherence (Dutch version), systemic inflammation, neuroinflammation, and cognitive functioning in older adults. In addition, we examined the role of intestinal barrier permeability in MIND diet associations with (neuro)inflammation. MethodsWe included 88 older adults (60-75 year) at risk of cognitive decline. MIND-NL diet adherence was assessed using a food frequency questionnaire. Systemic inflammation (C-reactive protein levels, white blood cell-counts and neutrophil-to-lymphocyte ratio) and intestinal barrier permeability (lipopolysaccharide-binding protein, zonulin, and lipopolysaccharide) markers were measured in blood. Neuroinflammation-associated metabolites (myo-inositol, choline and creatine) were measured in the dorsolateral prefrontal cortex with proton magnetic resonance spectroscopy (1H-MRS). Cognitive functioning was assessed with a neuropsychological test battery. ResultsLinear models showed that both MIND diet adherence and systemic inflammation did not predict neuroinflammation or cognition independently. However, MIND diet adherence significantly moderated the relation between systemic inflammation and neuroinflammation ({beta}=-0.11, p=0.04) as well as between systemic inflammation and cognition ({beta}=0.044, p=0.02). Specifically, in individuals with lower MIND diet adherence (identified as scores [&le;]7), systemic inflammation was positively related to neuroinflammation, and negatively to cognition. Similarly, MIND diet adherence significantly moderated the relation between intestinal barrier permeability and neuroinflammation ({beta}=-0.17, p=0.05). Finally, within participants with lower MIND adherence (median split at [&le;]8.75), systemic inflammation mediated the relation between the intestinal barrier permeability and neuroinflammation ({beta}=0.427 [0.072; 0.891], p=0.04). ConclusionOur findings suggest that higher MIND diet adherence might protect against the detrimental effect of systemic inflammation on neuroinflammation and cognitive functioning. Moreover, we demonstrated that greater adherence to the MIND diet may specifically protect against the systemic inflammation-mediated relationship between intestinal barrier permeability and neuroinflammation. These findings should be confirmed in randomised controlled trials.

ObjectiveTo investigate the burden of environmental enteric dysfunction (EED) and its association with water, sanitation, and hygiene (WASH) and linear growth amongst infants in rural Central Java, Indonesia. Study designA longitudinal study of 119 infants aged between 5-19 months was conducted in five villages of Wonosobo District, Central Java, Indonesia. Anthropometric measurements of infants and their mothers were performed at baseline and 5-month follow-up alongside a quantitative questionnaire on household, socio-economic, WASH and caregiving variables and stool sample collection for the investigation of alpha-1-antitrypsin (AAT), neopterin (NEO), and myeloperoxidase (MPO) levels. Linear mixed-effects regression models estimated the associations between WASH and height-for-age z-score (HAZ) on log-transformed EED biomarkers. ResultsBiomarkers increased from baseline to follow-up despite a declining trend with age and 68.7%, 79.0%, and 71.4% of infants experienced elevated AAT, NEO, and MPO respectively follow-up. Infants had higher AAT if they averaged > 30 minutes playing on soiled surfaces per day ({beta} = 0.11, p<0.05). NEO was elevated in infants with diarrhoea ({beta} = 1.04, p<0.05), municipal water source ( = {beta} 0.71, p<0.05), and in infants who mouthed soiled fomites weekly ({beta} = 0.55, p<0.05). Infants in houses with municipal water source had higher MPO ({beta} = 0.56, p<0.05) and higher MPO if mouthing soil weekly ({beta} = 0.41, p<0.05). Compared to infants at risk of stunting, stunted infants at baseline had lower AAT at follow-up ({beta} = -0.39, p<0.05) while infants with HAZ > -1 had lower AAT at baseline ( = -0.43, p<0.05). HAZ at baseline was positively associated with NEO at follow-up ({beta} = 0.36, p<0.05). MPO was higher in infants with HAZ > -1 at follow-up ({beta} = 0.59, p<0.05) and stunted infants ({beta} = -0.54, p<0.05) compared to infants at risk of stunting. ConclusionElevated EED biomarker levels were frequent and associated weakly with WASH and HAZ with bi-directionality, highlighting the need for quality birth cohort studies to improve understanding of EED and develop interventions.

BackgroundThere is growing evidence that individuals with different skin phototypes require tailored approaches to achieve optimal photoprotection. Individuals with darker skin phototypes are more prone to UVA1- and visible light-induced pigmentation, whereas lighter phototypes are more susceptible to shorter wavelengths such as UVB and UVA2. Thus, skin phototype is an important determinant of sunscreen efficacy. In the present study we have asked if ethnicity - independent of phototype - is another factor affecting sunscreen efficacy. Objectives(i) To determine the overall photoprotective effects of two sunscreen formulations against UVA1, visible light (VL), and combined visible light plus UVA1, and (ii) to compare the photoprotective efficacy of both products between Han Chinese and Caucasian participants. MethodsForty healthy volunteers (N=20 Han Chinese; N=20 Caucasian), matched for phototype, constitutive pigmentation, gender, and age, were exposed to VL, UVA1, and combined VL plus UVA1 to induce pigmentation responses following standardized irradiation protocols. Skin responses across treated and untreated sites were analysed using linear mixed-effects models. ResultsAcross all participants, both sunscreen formulations provided significant protection against VL, UVA1, and combined VL plus UVA1. Notably, photoprotective efficacy against UVA1-induced immediate (IPD) and persistent pigment darkening (PPD) differed significantly between ethnic groups, with one formulation showing stronger protection in Han Chinese. ConclusionThis study indicates that ethnicity could influence sunscreen efficacy. Thus, sunscreens should not only be tailored to different phototypes, but also consider ethnic background.

BackgroundCaloric restriction (CR) improves markers of biological aging, yet long-term effects on the human metabolome remain unclear. ObjectiveThis study examined the effects of CR (2 years) in healthy adults without obesity on circulating metabolites linked to aging and metabolic adaptations. MethodsUntargeted metabolomics was performed using fasted plasma samples collected at baseline, 12, and 24 months (BL, 12M, 24M) from CALERIE participants randomized to CR or ad libitum (AL) control. A total of 864 known metabolites were identified and grouped into nine biologically coherent super pathways to support pathway-level interpretation (amino acid, peptide, carbohydrate, energy, lipid, nucleotide, cofactors and vitamins, xenobiotics, and partially characterized molecules). Principal component analysis (PCA) summarized metabolite variation, and linear mixed models assessed intervention effects on each PC in group-by-time interactions. ResultsThree principal components showed significant group-by-time interactions: PC2 (carbohydrate), PC5 (partially characterized molecules), and PC4 (lipid). Carbohydrate (PC2) and partially characterized metabolites (PC5) decreased from baseline to 12M in both groups; from 12M to 24M, levels stabilized in CR but increased in AL for PC2, while PC5 continued to decline in CR and increased in AL. Lipid metabolites (PC4) decreased in CR and increased in AL at 12M, with the pattern reversing from 12M to 24M. Key contributors included malto-saccharides and related carbohydrate intermediates for PC2, glutamine degradants and lactone sulfates for PC5, and sphingolipids for PC4. ConclusionThis study provided insights into metabolic changes during CR, particularly for carbohydrate and lipid metabolism. Carbohydrate and lipid metabolites that were reduced by CR during the weight loss phase (BL to 12M) followed by stabilization or compensatory responses during the weight maintenance phase (12M to 24M) may link CR-induced changes in metabolism to inflammation. Future research is needed to tease out CR adaptations versus diet related changes in metabolites and explore the functional significance of these metabolic changes during CR for aging and long-term metabolic health. ConclusionCR produced distinct, time-dependent shifts in carbohydrate and lipid pathways. Early reductions during weight loss followed by stabilization or compensatory responses during weight maintenance suggest dynamic metabolic remodeling that may relate to inflammation-linked mechanisms. Further work is needed to distinguish CR-specific adaptations from dietary influences and to clarify the functional significance of these metabolic changes for aging and long-term metabolic health.

BackgroundPrediabetes is associated with an increased risk of progression to type 2 diabetes. While dietary interventions in prediabetes traditionally primary focus on energy and macronutrient intake, the role of eating timing has recently been highlighted. This study aimed to examine the relationships between components of eating timing patterns and glycaemic parameters in prediabetes. MethodsIn 297 individuals with prediabetes, i.e. impaired fasting glucose or impaired glucose tolerance (age 59.4 {+/-} 9.0 y, BMI 31.3 {+/-} 6.2 kg/m2), glycaemic traits were assessed using the oral glucose tolerance test (OGTT). Parameters of eating timing pattern (eating timing itself, daily calorie distribution, and meal number) were extracted from four-day food records. Eating start (ES) was defined as the start of the first caloric event of the day. ResultsAmong eating timing components, the most associations with glycaemic parameters were observed for ES. Individuals with late ES showed higher fasting insulin (p = 0.006), AUC insulin (p = 0.020), insulinogenic index (p = 0.049), HOMA-IR (p = 0.004), and lower Matsuda insulin sensitivity index (p = 0.004) compared to those with early ES, even after adjustment for age, sex, daily energy intake, and body fat. Participants with late ES had decreased insulin clearance (p<0.001) upon comparable glucose and C-peptide levels. ConclusionLate ES is associated with estimates of lower insulin sensitivity and hyperinsulinemia in prediabetes, independent of energy intake and body fat. Our findings suggest that an earlier ES is related to improved glucose metabolism which might lower the risk of progression to diabetes.

Poor sleep is linked to consumption of sugary foods/beverages and high neural responsivity to palatable food cues. Yet, whether hedonic liking for sweet taste explains these associations remains unclear. We examined cross-sectional associations of five sleep traits (chronotype, sleep duration, insomnia frequency, snoring, daytime dozing) and a composite sleep score with sweet food liking, and total and free sugar intake in 76,734 UK Biobank participants (39-72 years, 56.3% female). Models adjusted for age, sex, ethnicity, socioeconomic deprivation, and body mass index (Bonferroni-corrected =0.0025). Evening chronotype, more frequent insomnia and daytime dozing, and lower composite sleep score were associated with higher sweet food liking. Associations with intake were stronger for free than total sugar. Evening chronotype was associated with higher free sugar intake (g/day: {beta}=1.523, 1.309-1.737; g/1000 kcal: {beta}=0.450, 0.361-0.538), and daytime dozing showed a dose-response (dozing often vs never/rarely: g/day {beta}=6.307, 4.631-7.983). Snoring was associated with higher absolute (but not energy-adjusted) free sugar intake. A healthier sleep score was associated with lower free sugar intake (g/day {beta}=-2.193 [-2.464 to -1.922]; g/1000 kcal {beta}=-0.691 [-0.804 to -0.579]) but higher energy-adjusted total sugar intake ({beta}=0.633 [0.485-0.781]). Mediation analyses indicated sweet liking accounted for 15%-91% of several sleep trait and free sugar intake associations (indirect effects p<0.001). Poorer sleep health, particularly evening chronotype and daytime sleepiness, was associated with greater sweet liking and higher free sugar intake, with sweet liking partially mediating associations between sleep traits and sugar consumption. Sweet-taste liking may represent an underexamined pathway linking sleep/circadian disruption to free sugar intake.

Abstract Background: Enhanced Recovery After Surgery (ERAS) optimizes perioperative management for colorectal cancer (CRC), improving short-term outcomes, but its impact on long-term outcomes remains inconclusive, supporting the need for this meta-analysis. This study evaluates the effect of perioperative ERAS (therapy-focused) on 1-, 2-, 3-, and 5-year postoperative survival in patients with CRC. Methods: We conducted a systematic review and meta-analysis following a pre-registered protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Embase, Medline Ovid, and Cochrane Library Wiley were searched up to December 31, 2025, for clinical studies reporting long-term postoperative survival outcomes of patients with CRC undergoing ERAS implementation. Of 1,063 retrieved reports, 10 studies (5,876 patients) were included in Kaplan-Meier-based meta-analyses and eight studies (5,556 patients) in aggregated data meta-analyses. Data extraction was performed independently by two reviewers, with study quality and risk of bias assessed using the Newcastle-Ottawa Scale (NOS) and RevMan software. Effect sizes were pooled using fixed-or random-effects models according to heterogeneity, with cross-validation and subgroup analyses examining the influence of tumor stage and ERAS adherence. The pre-specified primary outcome was postoperative overall survival (OS) [&ge;]12 months, and the secondary outcome was disease-free survival (DFS). Results: ERAS significantly improved OS at 1 year (93.2%, 95% CI: 92.3-94.2 vs. 90.2%, 95% CI: 89.1-91.2), 2 years (86.7% vs. 81.3%), 3 years (81.1% vs. 72.4%), 5 years (70.9% vs. 60.6%) (all P<0.01). The pooled HR for mortality was 0.72 (95% CI: 0.63-0.83, P<0.01), indicating a 28% reduction in long-term mortality. Stage I-II tumors and ERAS adherence [&ge;]70% conferred the greatest benefits. DFS did not show a statistically significant improvement (HR=0.90, 95% CI: 0.68-1.19, P=0.45). Included studies were of moderate to high quality (NOS score 6-9). Conclusions: Perioperative ERAS significantly improves 1- to 5-year OS and reduces long-term mortality in patients with CRC, with the greatest benefits in early-stage disease and high adherence. These findings support ERAS as a critical component of comprehensive CRC care.

BackgroundValidated food portion size photographs can increase accuracy of estimatingportion sizes during dietary surveys. Our objective was to assess the validity of food portion size photographs in estimating portion sizes to be used in 24-hour dietary recall food consumption study. MethodsWe recruited two hundred and six women of reproductive age (13-45 years) residing in Roysambu sub-county in the northern parts of Nairobi City, Kenya. Eleven foods from the Photographic Food Atlas for Kenyan Adolescents (9-14 years) were examined. Participants were served pre-weighed portions. After eating, each participant was asked to estimate the amount of food they consumed, using the Food Atlas. Validity was assessed by calculating percentage of estimates within and outside of {+/-}10% of consumed portion size, the mean percent difference between estimated and consumed portions, Spearmans correlation coefficients, and Pearsons chi-square test. ResultsThe proportion of participants with estimates within {+/-} 10% of the consumed portion size ranged between 15-65%. Mean differences between the consumed and estimated portion sizes varied -45% for stewed beans to +60% for watermelon. Generally, small portions were overestimated while large portions were underestimated. Correlation coefficients ranged from 0.12 to 0.77 and all the coefficients were statistically significant except for watermelon (p=0.22). Accuracy of estimations was not associated with participants age or educational level. ConclusionsThe validity of the tested food proportion size photographs was adequate for quantifications of most food items. However, the studys findings also indicated that further improvement is needed before wider use in Kenya.

IntroductionMechanistic research has shown that prior obesity induces durable transcriptomic and epigenetic reprogramming in adipose tissue that persists after weight loss and predisposes individuals to weight regain. This phenomenon, termed obesogenic memory (OM), is currently conceptualized primarily as a molecular process. We propose extending OM beyond adipose tissue biology to include interacting biological and sociocultural processes through which past exposures shape present physiological regulation and health-related behavior. MethodsIn-depth qualitative interviews were conducted with individuals living with obesity (n=31) and with healthcare professionals (n=18). The data were analyzed abductively to examine participants lived experiences of obesogenesis. ResultsWe developed a three-phase model of OM comprising memorizing, remembering, and rescribing. The memorizing phase describes the initial acquisition and encoding of biological and sociocultural obesogenic influences. The remembering phase captures the persistence of these influences, contributing to long-term obesity maintenance. The rescribing phase refers to processes through which obesogenic influences may be attenuated or reversed, creating conditions for sustainable health behavior change. ConclusionExtending OM to include sociocultural dimensions provides a more comprehensive understanding of obesity persistence. This integrative framework identifies multilevel targets for obesity prevention and treatment that acknowledge past exposures while supporting resilience and long-term weight management.

Background/ObjectivesHuman lactoferrin (hLF) is glycoprotein of commercial interest as a food ingredient for gut health. Here, we report an exploratory analysis evaluating the effects of Helaina hLF (effera(R)), produced by Komagataella phaffii, on the adult gut microbiome and fecal metabolites in comparison to bovine LF (bLF). MethodsIn a randomized, double-blind, parallel-arm, controlled trial, 66 healthy adults received either high-dose (HD) effera(R) (3.4 g/day), low-dose (LD) effera(R) (0.34 g/day), or bLF (3.4 g/day) supplementation for 28 days. Fecal samples were collected at baseline (Day 0), Day 28, Day 56, and Day 84 and analyzed for microbial diversity, taxonomic shifts, and volatile fatty acids (VFA). ResultsAlpha-diversity remained stable across all groups. Beta-diversity showed no main effect of treatment; however, bLF was associated with significant visit-related shifts, as assessed by weighted UniFrac. At the phylum level, significant changes associated with effera(R) were observed, including decreases in Bacillota (LD) and Verrucomicrobiota (HD), and notable genera increases in Lachnospira, Paraprevotella, and Faecalibacterium (HD), while bLF was associated with an increase in Roseburia. Both effera(R) and bLF were associated with decreases in Blautia and Dorea. VFA analysis revealed that bLF increased absolute total short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) concentrations, while both effera(R) groups produced proportional changes in SCFAs, individual BCFAs, and acetate. ConclusionsIn healthy adults, effera(R) supplementation promoted a proportional increase in acetate and supported potentially beneficial taxa while maintaining microbial diversity, without disrupting community structure. (clinicaltrials.gov: NCT06012669).

BackgroundThe surgical stress response is a predictable, physician-managed metabolic state triggered by anesthesia and tissue injury, marked by insulin resistance and hypercatabolism that create unique nutritional needs unmet by standard, pre-surgical fasting diets. We developed a multi-nutrient medical food to support perioperative metabolic homeostasis and piloted its safety/tolerability and exploratory outcomes. MethodsIn a single-center pilot trial (n=67) of adults undergoing elective abdominal, cardiac/thoracic, gynecological, or orthopedic surgery, participants were allocated to medical food or no-treatment control. The product was taken twice preoperatively (evening before and 4 h pre-op) with standard care. Primary safety outcomes were adverse events, postoperative nausea/vomiting (PONV), 30-day readmission, and infections. Exploratory outcomes were fasting glucose, HbA1c, electrolytes, cortisol, pre-operative emotional state, and post-operative pain. ResultsAll participants completed the intervention. No product-attributed adverse events occurred. Gastric clearance was achieved within 2 h in all, and there were no 30-day readmissions or infections. PONV occurred in 30.3% vs 35.3% (risk ratio 0.86, 95% CI 0.43-1.71, p=0.796). Post-operative glycemia favored the intervention; at 48 hr the intervention group showed lower glucose (HL -9 mg/dL, g=0.35, p=0.030), while earlier timepoints were nonsignificant. Post-operative magnesium was numerically lower with intervention (4.76 vs 5.10) without statistical significance; other electrolytes and cortisol showed minimal differences. Post-operative pain was 5.33 vs 5.62 (g=0.19, p=0.43). Positive pre-operative emotion was more frequent with intervention (17/33 vs 9/34; risk ratio 1.95, p=0.046). ConclusionThe medical food was safe and well tolerated without increased PONV or readmissions. Preliminary metabolic and emotional signals justify a larger, adequately powered efficacy trial. Clinical Relevancy StatementThis pilot trial demonstrates that a preoperative multi-nutrient medical food was well tolerated and feasible to administer in a routine clinical setting: all participants achieved gastric clearance within 2 hours of the pre-operative dose, with no increase in PONV and no readmissions. Exploratory findings indicate potential benefits that could nutritionally support recovery if confirmed. These results support the feasibility of administering a targeted nutrition intervention shortly before surgery and justify evaluation in a larger efficacy trial. Clinical Trial RegistrationNCT07359222