This study investigated whether simulated gastrointestinal (SGI) digestion enhances the release of bioactive peptides from yogurt and improves their associated bioactivities. Yogurt was subjected to INFOGEST-based SGI digestion. Bioactivities were evaluated using ACE and DPP-IV inhibition and DPPH radical scavenging assays. Protein degradation was assessed by SDS-PAGE, and peptides were identified by UPLC–LTQ Orbitrap mass spectrometry, followed by in silico peptide screening and molecular docking. Compared with undigested yogurt, SGI digestion markedly enhanced ACE inhibitory, DPP-IV inhibitory, and antioxidant activities, with IC50: 9.6 µg/mL, 300.3 µg/mL, and 530.7 µg/mL, respectively. SDS-PAGE confirmed extensive protein hydrolysis, accompanied by increased peptide content. Peptidomic analysis identified 129 oligopeptides, predominantly < 1.5 kDa, with 31 prioritized as predicted bioactive candidates. Selected peptides exhibited favorable predicted interactions with ACE, DPP-IV, Keap1, and DPPH. SGI digestion promotes the release of low-molecular-weight peptides with enhanced in vitro bioactivities, providing a peptide-level framework for prioritizing yogurt-derived peptide candidates for future validation. Further experimental validation is needed before functional food, nutraceutical, or therapeutic applications can be proposed.
Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and perinatal morbidity. Although n-3 polyunsaturated fatty acids (PUFAs) in fish may prevent HDP, evidence from Japanese populations, particularly regarding the preconception period, remains limited. To examine associations between fish and PUFA intake before and during pregnancy and the risk of HDP using data from a nationwide Japanese birth cohort. This analysis included 86,009 women from the Japan Environment and Children’s Study. Dietary fish and n-3/n-6 PUFAs intake was assessed using a validated food-frequency questionnaire administered in early pregnancy (median gestational age, 15.0 weeks [interquartile range (IQR) 12.0–19.0]) to capture intake before pregnancy, and in mid to late pregnancy (median gestational age, 27.0 weeks [IQR 25.0–30.0]). Participants were categorized into quintiles of intake. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95
Global diets exert substantial pressure on both public and planetary health. At the same time, diets are becoming more monotonous, with growing reliance on a limited number of staple species. Food biodiversity, the variety of biological species in the diet, and dietary environmental impact represent complementary, but distinct, dimensions of sustainable diets. However, because these dimensions capture different aspects of sustainability, it remains unclear whether diets with higher food biodiversity are also associated with lower environmental impacts. We examined associations between food biodiversity, measured as Dietary Species Richness (DSR), and six environmental impact indicators using data from the Dutch National Food Consumption Survey (DNFCS) 2012–2016. DSR scores (DSR Total, DSR Plant, DSR Animal) were calculated as the total unique species consumed over two 24-hour dietary recalls, regardless of quantities consumed. Environmental impacts associated with food consumption over the same recall period were derived from the Dutch life cycle assessment (LCA) food database (RIVM, v2019). Linear regression analyses were conducted, adjusting for age, sex, educational level, seasonality, mean daily energy intake, and weight of total food intake. Higher DSR scores were generally associated with higher environmental impacts, including greenhouse gas emissions (β = 0.107, 95
The beneficial effects of Mediterranean Diet (MD) during pregnancy are well established. However, validated tools adapted to assess adherence to the MD during pregnancy and across different cultural contexts remain limited. This study aimed to translate, cross-culturally adapt, and validate an Italian version of the pregnancy-adapted Mediterranean Diet Adherence Screener (ITpreg-MEDAS), derived from the original Spanish preg-MEDAS questionnaire. We hypothesized that the ITpreg-MEDAS would show adequate construct validity and would be associated with markers of diet quality during pregnancy. The preg-MEDAS is a 17-item questionnaire designed to assess adherence to the MD among pregnant women. The Italian version was developed following a six steps process in accordance with established methodological guidelines: forward translation, synthesis I, blind-back translation, synthesis II, pre-testing, and validation. Psychometric properties were evaluated by assessing internal consistency, test-retest reliability, and construct validity, in a sample of Italian pregnant women. The preg-MEDAS was translated and cross-cultural adapted, requiring some semantic revisions. All 25 Italian pregnant women involved in the pre-testing in pre-testing found it clear and comprehensible. A total of 116 Italian pregnant women participated in the validation phase, with a mean ITpreg-MEDAS score of 7.2 ± 2.5 out of 17, indicating medium adherence to the MD. Reliability was confirmed by good test-retest correlation (r = 0.756) and acceptable internal consistency (Cronbach’s α = 0.623). The ITpreg-MEDAS is a reliable and valid Italian version of the preg-MEDAS questionnaire, providing a simple tool to assess adherence to the Mediterranean Diet during pregnancy in both clinical practice and research.
Increasing attention has been paid to individuals who report gastrointestinal symptoms following wheat consumption. In addition to wheat allergy and celiac disease, non-celiac gluten sensitivity (NCGS) has been proposed as a clinical entity. Despite persistent symptoms, many affected individuals continue to consume wheat-containing foods. We aimed to investigate the impact of replacing wheat-based foods with gluten-reduced foods, specifically yellow pea pasta (YPP), bread (YPB), and chips (YPC), on the abdominal symptoms, quality of life (QOL), and gut microbiota in healthy individuals who habitually consume wheat frequently. Thirty men and women aged 18–64 years with habitual high wheat intake were enrolled and divided into two groups based on the presence or absence of abdominal symptoms. Participants followed a 4-week gluten-reduced diet intervention using YPP, YPB, and YPC. Abdominal symptoms, QOL, gut microbiota, and selected blood biomarkers were evaluated before and after the intervention. The intervention led to significant improvement in abdominal distension, abdominal pain or discomfort, feeling of incomplete evacuation, hard stools, and urgent need for defecation. Baseline QOL differences between groups were no longer evident. Analysis of gut microbiota revealed maintenance and/or an increase in short-chain fatty acid-producing bacteria, with significant correlations observed between specific bacterial shifts and symptom improvement. Yellow pea–based products (YPP, YPB, and YPC) may represent a promising dietary strategy for alleviating abdominal symptoms in individuals with high wheat consumption. This study was registered in the UMIN Clinical Trials Registry (UMIN Trial ID: UMIN000056466).
Whereas an increasing number of families choose a vegan or a vegetarian diet, the effects of a plant-based nutrition on height and BMI of children and their IGF-1- and IGFBP-3-serum concentrations as measures for growth and development are not entirely described. 7344 serum samples were investigated from 2,508 healthy participants in the age of 3 months to 19 years. Anthropometric measurements as well as IGF-1-, and IGFBP-3-serum concentrations were compared between dietary groups using optimal 1:3 pair matching (from the age of 10). Vegan children were shorter than vegetarians after adjustment for pubertal status (β = −0.59, p = 0.006) but the height of vegetarians was not different from omnivores. Vegans showed lower BMI-SDS than vegetarians, most prominently in the TS-adjusted model (β = −1.01, p = 0.009). Omnivores had the highest BMI-SDS (0.32 SDS). Vegans had lower IGF-1 levels than vegetarians and omnivores in the age-adjusted model (ß = −0.52, p = 0.031). Vegetarians exhibited lower IGF-1 concentrations than omnivores in age- and TS- adjusted models. Vegans showed significantly lower IGFBP-3-SDS than vegetarians in TS-adjusted models (β = −0.75, p = 0.042). IGFBP-3 values were lower in vegetarians than in omnivores after adjustment for age (β = −0.18, p = 0.005). Children following a vegan diet are significantly smaller and have a lower BMI than their peers. Both, vegetarian and vegan diets are associated with lower BMIs and lower IGF-1 and IGFBP-3 values. These findings highlight the potential relevance of dietary composition for growth childhood. LIFE Child is registered with Clinical Trials.gov (NCT02550236) since October 2010. https://clinicaltrials.gov/study/NCT02550236.
Population aging poses major challenges for the management of type 2 diabetes mellitus (T2DM), particularly because inadequate protein intake, physical inactivity, and gut microbial dysbiosis may contribute to systemic oxidative stress and chronic low-grade inflammation (inflammaging). The present study investigated the combined effects of protein supplementation (P), synbiotic plus protein supplementation (SP), and resistance training (RT) on physical performance, body composition, glycemic control, inflammatory and oxidative stress parameters in older adults with T2DM. This randomized, triple-blinded clinical trial included men aged ≥ 65 years with T2DM. Fifty-one participants were randomly allocated to one of three intervention groups: Control (n = 17), Protein (P; n = 17), or Synbiotic + Protein (SP; n = 17). Following withdrawals and losses to follow-up, 40 participants completed the intervention and were included in the final analyses (Control, n = 13; P, n = 13; SP, n = 14). All groups showed improvements in physical performance and an enhanced redox balance, as indicated by higher uric acid levels (an endogenous antioxidant) and lower plasma iron concentrations. Although all groups exhibited increased activities of the muscle damage markers lactate dehydrogenase and creatine kinase, the Protein group demonstrated greater improvements in muscle strength, reduced insulin resistance, and lower oxidative damage associated with heme-iron species. Furthermore, the pro-inflammatory cytokines IFN-γ and IL-6 were elevated in the Protein group, which may reflect their physiological role in exercise-induced metabolic adaptation and energy homeostasis rather than a detrimental inflammatory response. Protein supplementation combined with RT was associated with improvements in muscle strength, physical performance, insulin resistance, and selected biomarkers of oxidative stress. Under the conditions of the present study, the addition of synbiotic supplementation did not provide further benefits beyond those achieved with protein supplementation and resistance training alone.
Osteoporosis is a widespread metabolic bone disorder among postmenopausal women and is characterized by reduced bone mineral density and an elevated risk of fractures. Beyond the role of individual nutrients in bone health, increasing attention has been paid to the broader implications of dietary patterns for environmental sustainability. Food production systems, particularly those heavily dependent on animal-based foods, are among the main contributors to greenhouse gas emissions, highlighting the need for dietary approaches that support both human health and environmental protection. In this context, the Planetary Health Diet Index (PHDI) has been developed as an integrated measure of diet quality and sustainability, promoting plant-based foods and limiting environmentally intensive food sources. Accordingly, this study examined the association between adherence to the PHDI and the risk of osteoporosis among postmenopausal women in Tehran. In this hospital-based case–control study, 440 postmenopausal women (220 cases and 220 controls) were recruited. Bone mineral density was determined using dual-energy X-ray absorptiometry (DEXA). Dietary intake, demographic variables, and physical activity were assessed through validated questionnaires. Independent t-tests and multivariable logistic regression analyses adjusted for age, body mass index (BMI), and total energy intake were conducted using SPSS version 27. Statistical significance was set at p < 0.05. A total of 440 postmenopausal women (220 cases and 220 controls) were included in the study. Compared with controls, women with osteoporosis had significantly higher body weight (74.81 ± 11.92 vs. 71.01 ± 9.85 kg; p < 0.001) and body mass index (29.09 ± 4.13 vs. 27.91 ± 5.47 kg/m²; p = 0.011), and lower physical activity levels (1531.86 ± 830.59 vs. 1967.24 ± 866.34 MET-min/week; p < 0.001). In multivariable logistic regression analyses adjusted for age, BMI, total energy intake, alcohol consumption, and physical activity, higher PHDI scores were independently associated with lower odds of osteoporosis (adjusted OR = 0.923; 95
Meal-induced thermogenesis (MIT) and cold-induced thermogenesis (CIT) are components of adaptive thermogenesis, both potential contributors to energy balance and body composition. This study examined sex differences in thermogenic and thermoregulatory responses to a meal and to cold exposure, and evaluated their associations with body composition in young adults. Sixty-three adults (68
This exploratory study examined the associations of human milk oligosaccharides (HMOs) and N-/O-glycans in human milk with infectious and allergic outcomes during infancy. This prospective cohort study included 200 Japanese mother–infant dyads selected from the Japanese Human Milk Study Cohort. Human milk samples were collected at 1–2 months postpartum, and 11 HMOs and 28 N-/O-glycans were measured. HMOs were measured as absolute concentrations, whereas N-/O-glycans were expressed as relative abundances based on normalized LC–MS signal intensity. Infant histories of infections and allergies during the first year of life were assessed using self-administered questionnaires. Associations between milk glycan components and infant health outcomes were evaluated using Firth’s penalized likelihood logistic regression. To aid interpretation of multiple glycan-outcome comparisons, q values were calculated within each outcome at each step of the hierarchical analysis using the Benjamini–Hochberg procedure for controlling the false discovery rate. In Firth logistic regression analyses, several milk glycans showed nominal associations with infectious or allergic outcomes. Total sialic acid, disialylated N-glycans (N51 and N57), and 6′-sialyllactose showed nominal associations with lower odds of bronchitis, whereas total HMO showed a nominal association with higher odds of otitis media. However, no individual HMO showed a nominal association with this outcome. For food allergy, 3-fucosyllactose, lacto-N-fucopentaose II, and fucosyl-sialyl O-glycan (O24) showed nominal associations with lower odds, whereas 2′-fucosyllactose showed a nominal association with higher odds in the overall analysis. However, all infants who developed food allergy were born to secretor mothers, and several food allergy findings were attenuated in the analysis restricted to secretor mothers. For atopic dermatitis, high-mannose–type N-glycans, particularly N12 and N33, showed nominal associations with higher odds. No glycan-outcome association had a q value below 0.05 within each outcome and step of the hierarchical analysis. Several human milk glycans showed nominal associations with infectious or allergic outcomes during infancy. However, none had a q value below 0.05 after false discovery rate correction. These findings should be interpreted as exploratory and hypothesis-generating and require validation in larger independent cohorts.
We aimed to develop a culturally specific Chinese Planetary Health Diet Score (CPHDS) and to evaluate its associations with environmental footprints and all-cause mortality. We constructed a 14-component CPHDS (range 0–140) based on the 2019 EAT-Lancet Commission recommendations, the latest Chinese Dietary Guidelines, and existing dietary scoring frameworks, while incorporating adaptations specific to Chinese dietary practices and nutritional characteristics. Using data from the China Health and Nutrition Survey (1991–2015), we included 19,660 adults without cardiovascular disease or cancer at baseline. Dietary intake was repeatedly assessed using three consecutive 24-hour dietary recalls, and mortality data were collected through household surveys. Linear mixed-effects models and time-varying Cox proportional hazards models were used to evaluate the associations of the CPHDS with diet-related environmental impacts and all-cause mortality, respectively. The mean CPHDS was 50.3 (SD 11.3) points. A higher CPHDS was associated with reduced greenhouse gas emissions [β per 10
Low-grade systemic inflammation is a hallmark of excess adiposity and contributes to cardiometabolic risk. Adherence to the Mediterranean diet has been associated with reduced inflammation. However, evidence linking Mediterranean diet to composite inflammatory indices derived from routine blood tests is limited, particularly in individuals seeking weight loss interventions. In this cross-sectional study, 1,738 adults requesting a weight loss dietary program underwent anthropometric assessment, body composition evaluation, and fasting blood sampling. Adherence to the Mediterranean diet was assessed using the 14-item Mediterranean Diet Adherence Screener (MEDAS). Hematologic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and monocyte-to-HDL ratio (MHR), were calculated. After adjustments for sex, age, BMI, body fat percentage, metabolic syndrome, smoking status, physical activity, education level, and marital status, each 1-point increase in MEDAS score was associated with lower NLR (β = − 0.065; 95
Vitamin K is hypothesised to support vascular integrity and neuronal function through vitamin K-dependent proteins, yet epidemiological evidence for its role in dementia, particularly distinguishing vitamin K1 and K2, is limited. This aetiological study examined associations between dietary vitamin K1 and K2 with incident dementia in a large Danish cohort. We included 54,968 dementia-free participants (47.5
Ageing is associated with a decline in gastrointestinal (GI) functions, but data on GI symptoms in older adults remain limited. This study assessed the prevalence of GI symptoms, irritable bowel syndrome (IBS), and faecal short-chain fatty acids (SCFAs) in older adults, and associations between GI symptoms and faecal SCFAs, dietary intake, and BMI. 907 older adults (66–69 years, 50.7
Adolescence is a critical phase characterized by temporary insulin resistance and a tendency for a later chronotype, potentially influencing the risk of developing type 2 diabetes (T2D) later in life. This study explores how morning and evening carbohydrate (CHO) intake during adolescence are prospectively related to T2D risk factors—such as insulin resistance (HOMA2-IR), liver fat indices, and subclinical inflammation— in adulthood while considering the role of chronotype. This analysis utilizes data from 224 DONALD study participants (58
To determine whether folate supplementation may reduce the incidence of Hirschsprung disease (HSCR) by regulating the methylation level of growth arrest-specific 5 (GAS5). The m6A methylation deficiency model and folate supplementation model were created using the m6A inhibitor 3-Deazaadenosine (DAZ) and folate, respectively. The effects of folate on the morphology, mortality, and number of HuC/D positive neurons in zebrafish were observed. The methylation level and proliferation ability of mouse enteric neural crest stem cells (ENCSCs) were detected by m6A ELISA and EdU assay respectively. Human HSCR cases and control tissues were collected. The expression level of GAS5 in intestinal tissues was detected by qRT-PCR. M6A ELISA, actinomycin D, and MeRIP qRT-PCR were used to detect the effect of folate on m6A methylation levels, GAS5 stability, and the content of m6A-modified GAS5 in N2a cells. The RIP assay was used to detect the content of GAS5 bound to YTH N6-methyladenosine RNA binding protein F2 (YTHDF2) under different folate concentrations. Supplementation of folate can ameliorate the decreased ENCSC proliferation ability caused by low m6A methylation level, reduce embryonic mortality of zebrafish and increase the number of HuC/D positive neurons at 96 hpf. Furthermore, folate may reduce the expression of the demethylase alkB homologue 5 (ALKBH5), weaken ALKBH5's demethylation effect on GAS5, promote the degradation of GAS5 by YTHDF2, and subsequently reduce the expression of GAS5. Additional folate supplementation during early embryonic development may serve as a strategy for preventing HSCR.
Prospective cohort studies analyzing the effect of plant versus animal protein intake on mortality in relatively young individuals from Mediterranean populations are limited. Moreover, a limited number of studies have performed repeated measurements of protein intake. We evaluated the relationship between plant versus animal protein intake (at baseline and at the ten-year follow-up) and mortality in the “Seguimiento Universidad de Navarra” (SUN) project. The SUN project is a prospective, multi-purpose, dynamic cohort study of Spanish university graduates. Plant and animal protein intake were assessed using a semi-quantitative food frequency questionnaire (FFQ) previously validated in Spain. Participants were divided into quartiles based on their intake of protein. Cox regression models were used, with the first quartile serving as the reference category. A total of 17,989 subjects (10,961 women and 7028 men) were included in the analysis. During 251.363 person-years of follow-up (median follow-up time: 12 years), 460 deaths were identified. The mean age at baseline was 38 years with a standard deviation of 12 years. Participants in the highest quartile of plant protein intake had a 35
This study aimed to investigate whether genetic variability, assessed through polygenic risk scores (PRSs), predicts blood pressure (BP) changes in individuals with systemic arterial hypertension (SAH), and to explore potential interactions between genetic risk and dietary interventions. This study represents a secondary analysis of data from the Brazilian multicentre trial (NUPRESS), which compared a Dietary Approach to Stop Hypertension (DASH) diet (control group) with a multicomponent intervention (intervention group) over 180 days in adults with SAH. Participants underwent anthropometric assessment, cardiovascular risk evaluation, dietary assessment, and genotyping using a genomic microarray. Single nucleotide polymorphisms (SNPs) associated with BP changes were identified and used to construct PRSs. Multiple linear regression models were employed to examine associations between PRSs, dietary interventions, and changes in systolic (ΔSBP) and diastolic BP (ΔDBP). A total of 114 SNPs were associated with ΔSBP and 101 with ΔDBP. The resulting PRSs showed strong correlations with both ΔSBP (r = 0.85; p < 0.0001) and ΔDBP (r = 0.84; p < 0.0001). No significant effect of dietary intervention on BP changes was observed, and no interaction was identified between PRSs and dietary approach for ΔSBP (p = 0.98) or ΔDBP (p = 0.13). PRSs derived from BP-associated SNPs were strong predictors of BP changes over six months, independent of dietary intervention. These findings support the potential utility of genetic profiling in predicting individual variability in BP response, although replication in independent cohorts is warranted. Main study trial registration number NCT03793881 on ClinicalTrials.gov.
A shift towards predominantly plant-based diets is emphasized for health and environmental sustainability, but it may affect nutrient adequacy and bone health. We investigated the effects of plant-forward meals in Finnish early childhood education and care (ECEC) centres on bone metabolism and intakes of bone nutrients in 3–5-year-old children. ECEC centres were cluster-randomized for 10 months into 11 intervention (more plant-based products and less red meat served and moderation in milk consumption encouraged; n = 55 children for individual-level study) and 12 control (maintained regular meals; n = 61 children) ECEC centres. In the intervention arm, 18 children and in the control arm 28 children provided complete (baseline and endpoint) blood samples and dietary data (food frequency questionnaire). Circulating biomarkers (e.g. serum tartrate-resistant acid phosphatase 5b [S-TRAP5b], total and bone-specific alkaline phosphatase [S-ALP; S-BAP], 25-hydroxyvitamin D [S-25(OH)D], and plasma parathyroid hormone) and intakes of calcium, vitamin D, phosphorus, and protein were analysed using mixed models. The intervention group had higher bone formation marker S-BAP (0.05 log-U/L, 95 https://clinicaltrials.gov/ct2/show/NCT05249946 .
Dietary fibre may influence bile acid (BA) metabolism via interactions with gut microbiota. We hypothesised that dietary fibres with distinct fermentative properties, resistant starch (RS) and polydextrose (PD), would differentially alter BA profiles in plasma and faeces through gut microbiota-mediated mechanisms. BA profiles were analysed by ultra-performance liquid chromatography mass spectrometry in plasma (n = 74) and faeces (n = 50) from a double-blind, randomised, placebo-controlled 2 × 2 factorial trial. Healthy participants consumed 23 g/day Hi-maize®260 (type 2 RS) and/or 12 g/day Litesse®Ultra™ (PD) for 50 days. The intervention effects of RS and PD on BA profile were investigated using general linear models and beta regression models. Genus abundances derived from 16 S rRNA gene sequencing were used to investigate fibre-specific microbial correlations with BA profiles. Supplementation with RS, but not PD, increased a range of conjugated BAs and deoxycholic acid (FDR < 0.05). Concentrations of taurochenodeoxycholic acid (FDR = 0.027) and taurine conjugated BAs (FDR = 0.049) in plasma correlated positively with Akkermansia abundance in response to RS. Although neither RS nor PD altered BA concentrations in faeces, RS decreased (p = 0.032) and PD increased (p = 0.012) faecal proportions of primary BAs. PD reduced secondary BA transformation ratios (p < 0.05), along with shifts in related microbial associations. There were negative correlations between plasma primary conjugated BAs and faecal secondary BAs in response to RS specifically (p < 0.05). RS increased plasma BAs, particularly conjugated BAs, whereas PD reduced faecal secondary BA transformation. The distinct impacts of RS and PD on BA profiles and fibre-specific microbial associations may underlie their differential metabolic effects. Trail registration The DISC Study was registered with https://clinicaltrials.gov/ (Identifier NCT01214681) in 2010.
