Nutrients

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

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)

PurposeRiboflavin deficiency causes ariboflavinosis, and the purpose of this study is to investigate the potential biological factors underlying its occurrence. MethodsMale F344 rats were randomly assigned to R6 and R0 groups. The healthy controls (R6 group) was fed a riboflavin-normal diet (6 mg/kg riboflavin), while the R0 group was fed a riboflavin-deficient diet (0 mg/kg riboflavin) for 16 weeks. Following this period, the R0 group was switched to a riboflavin replenishment diet (6 mg/kg riboflavin) for an additional 4 weeks (weeks 17-20). The bacterial communities were analyzed using high-throughput 16S rRNA gene sequencing. ResultsRiboflavin deficiency induces ariboflavinosis in rats (66.7%), characterized by angular stomatitis and conjunctivitis. With riboflavin replenishment, ariboflavinosis was completely resolved. Riboflavin deficiency altered the gut microbiota co-occurrence network and composition. The potential mechanism is predicted to involve an increase in glycan biosynthesis and metabolism within the gut microbiota, particularly in lipopolysaccharide biosynthesis pathways. ConclusionsThese findings suggest that riboflavin deficiency induces ariboflavinosis by altering the gut microbiota, providing new insights into the mechanisms of riboflavin deficiency and its association with chronic inflammation. Clinical perspectivesRiboflavin is an essential nutrient that must be obtained through the diet, as the human body cannot synthesize it. Since riboflavin is not stored in the body, regular dietary intake is necessary. Riboflavin deficiency is prevalent worldwide and can lead to ariboflavinosis. However, the specific mechanisms underlying riboflavin deficiency-induced ariboflavinosis remain unclear. This study demonstrates that riboflavin deficiency causes ariboflavinosis (characterized by angular stomatitis and conjunctivitis) in rats and reveals a close relationship between riboflavin deficiency and alterations in gut microbiota composition. Gut dysbiosis appears to be a hallmark of ariboflavinosis and may serve as a promising diagnostic biomarker and therapeutic target for the condition.

Anaemia remains a significant public health issue in India, despite five of control programs. Anaemia affects 52-67% of target populations in India despite five decades of control programmes. We conducted a review of reviews and meta-analyses (SRMAs) of regional studies to evaluate daily versus intermittent oral iron and iron-folic acid (IFA) supplementation across age groups. We identified 21 SRMAs (17 high-quality, 4 moderate-quality) and 44 regional studies from India and South Asia. IFA prophylaxis consistently improved haemoglobin levels (4.1-8.8 g/L increase) and ferritin concentrations, reducing anaemia risk by 23-70% across all age groups. IFA prophylaxis consistently improved haemoglobin levels (4.1-8.8 g/L increase) and ferritin concentrations, reducing anaemia risk by 23-70% across all age groups. Daily and intermittent regimens showed similar haematological outcomes in children, adolescents, and women of reproductive age. Among pregnant women, daily supplementation was superior for haemoglobin and ferritin levels, though intermittent dosing had fewer gastrointestinal side effects. These findings support weekly IFA supplementation for non-pregnant beneficiaries as an evidence-based strategy, even in settings where anaemia prevalence exceeds 40%. Further research on long-term safety in non-iron-deficient populations is needed.

Vitamin B2 (riboflavin) is a key redox cofactor that may modulate gut microbial ecology, yet conventional supplements are absorbed proximally and have limited colonic exposure. We evaluated whether colon-targeted riboflavin alters microbiome composition, function and network structure as well as host biomarkers in healthy older adults. In a randomized, double-blind, placebo-controlled, parallel-group clinical trial (N=348; 50-70 years), participants received colon-targeted riboflavin (1.4, 10, or 75 mg/day) or placebo for 12 weeks. The primary endpoint was the change in fecal microbial composition, while secondary endpoints encompassed microbiome function, host health biomarkers, and clinical outcomes. Shotgun metagenomics and fecal/blood biomarkers were assessed at baseline, week 4, and week 12. Although no significant changes were observed between groups in overall community-wide diversity metrics (alpha and beta diversity), colon-delivered riboflavin significantly altered the relative abundance of several microbial taxa compared with placebo. The most pronounced effects on microbiome composition, function, and network structure were observed with the 10 mg dose at week 12, reflected by within-group increases in alpha diversity, the largest rise in total species counts, higher HACK index values indicating greater community resilience, and distinct shifts in KEGG module abundance, including enhanced potential for riboflavin biosynthesis. Supplementation with 75 mg riboflavin led to higher fecal butyrate concentrations at week 4 versus placebo, while the lowest dose (1.4 mg) significantly reduced the dysbiosis index within groups and modestly improved network structure across groups. All three doses (1.4, 10, and 75 mg) influenced keystone species abundance. No between-group differences were observed for gastrointestinal symptoms, quality-of-life measures, fecal pH, high-sensitivity C-reactive protein (hs-CRP), calprotectin, or soluble CD14, except for an increase in plasma riboflavin concentrations at 75 mg after 12 weeks, indicating colonic absorption. The product was safe and well-tolerated across all doses. These findings indicate that colon-targeted riboflavin can act as a functional modulator of the human gut microbiome, with the most consistent effects observed at 10 mg and additional dose-specific effects at 1.4 mg and 75 mg. Future studies are warranted to establish related health benefits, either as a standalone intervention or in combination with classical pre-, pro-, or postbiotics, particularly in target populations such as individuals with IBS, stress, mild cognitive decline, or early metabolic or inflammatory alterations.

Background: Creatine monohydrate (typically 5 to 20 g/day) has a well-established safety profile across diverse populations. Creatine hydrochloride (CR-HCl) is a highly soluble creatine formulation that may allow effective supplementation at substantially lower doses (750 mg to 3 g/day); however, controlled human safety data specific to CRHCl remain limited. Objective: To evaluate the short-term laboratory safety and tolerability of low dose CRHCl supplementation administered for 28 days in healthy adults. Methods: This single center, single arm, singl blind pilot safety study enrolled 11 healthy adults (10 females, 1 male; mean age 44.6 plus/minus 7.2 years). Participants consumed 750 mg/day CRHCl for 28 consecutive days while maintaining their usual diet and physical activity patterns. Fasting blood and urine samples were collected at baseline and Day 28. Laboratory assessments included hematological, lipid, and clinical chemistry biomarkers. Pre and post changes were evaluated using paired parametric and nonparametric tests, baseline-adjusted regression models, bootstrap confidence intervals, and false discovery rate (FDR) correction. Results: All participants completed the intervention. No clinically meaningful changes were observed in lipid parameters, hematologic indices, renal markers, or most chemistry analytes after adjustment for multiple comparisons. Fasting glucose increased modestly (8.1 mg/dL) prior to multiplicity adjustment but was not statistically significant after FDR correction and remained within reference ranges. Serum bicarbonate decreased slightly (2.4 mmol/L); although statistically detectable in parametric analysis, values remained within physiological limits and were not consistently supported by nonparametric testing.

ObjectivesGut microbiome-derived metabolites, including short-chain fatty acids (SCFA) and tryptophan derivatives, are key mediators of the gut-brain axis. We examined how early-life nutritional interventions influence these metabolites during critical neurodevelopmental periods. MethodsUsing a standardized ex vivo fermentation system, we assessed the effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals, amino acids), and their combinations on the gut microbiome of infants (2-4 months, n=6) and young children (2-3 years, n=6). ResultsBaseline microbiome composition differed by age: infants showed low -diversity and high interpersonal variability, while young children exhibited more adult-like profiles. Nutrient blends increased propionate/butyrate ratios and branched-chain fatty acids (BCFA) in young children, alongside B-vitamin and amino acid-derived metabolites, including neuroactive compounds (indole-3-carboxaldehyde, imidazoleacetic acid, pipecolinic acid). Combining nutrient blends with GOS produced synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both groups). GOS-containing treatments strongly promoted Bifidobacteriaceae, driving production of acetate, HICA, N-acetylated amino acids, aromatic lactic acids, and acetylagmatine; in young children, also butyrate and {gamma}-aminobutyric acid (GABA). DiscussionGOS alone and combined with nutrient blends modulated microbiome-derived metabolites linked to the gut-brain axis. Synergistic effects on GABA, acetylagmatine, and HICA suggest roles in neurotransmission, neuroprotection, and immune-brain signaling. Despite shared bifidogenic effects, age-specific differences indicate developmental stage influences intervention outcomes. Further studies should explore neurodevelopmental benefits of these combinations and metabolites.

IntroductionDepression is highly prevalent among young adults worldwide. While research links health behaviours, such as dietary intake, to depression, few studies have examined these associations among young adults in low- and middle-income countries, including South Africa. This study investigated whether dietary intake was associated with an increased risk of depression in a cohort of young South African adults, aged 20-30 years, as part of the Global burden of disease Lifestyle And mental Disorder (GLAD) project. MethodsThis five-year prospective cohort study was conducted in the North West Province of South Africa in accordance with the GLAD project protocol (DERR1-10.2196/65576). Dietary exposures were evaluated using three non-consecutive 24-hour dietary recalls, measuring daily intake of various food groups and nutrients as defined by the Global Burden of Disease study. Depression outcomes were assessed at baseline (N=1039) and follow-up (N=551) using the Patient Health Questionnaire (PHQ-9, cut-off [&ge;]10). Logistic and Poisson regression analyses were performed, with results presented as odds ratios (OR) and relative risk ratios (RR), respectively. Four models were run: unadjusted, sociodemographic-adjusted, total energy (TE) intake-adjusted and fully adjusted (including sociodemographic information and TE intake). For longitudinal analyses of incident depression, baseline depression cases were additionally excluded (n=403). ResultsParticipants (average age 24.55 years) had a balanced distribution of sex (51.4% female) and race (48.6% Black), and a 29.45% baseline prevalence of depression. Higher milk intake was associated with a lower risk of incident depression (RR=0.94, 95% CI 0.91-0.98) in the TE-adjusted longitudinal model. Cross-sectionally, higher sugar-sweetened beverage consumption associated with higher odds of depression, while higher calcium intake (OR=0.48, 95% CI 0.31; 0.76) and vegetable consumption (OR=0.74, 95% CI 0.61, 0.91) were associated with lower odds of depression after TE intake adjustment. Higher fibre intake was associated with lower odds of depression in the unadjusted model. ConclusionHigher daily milk intake was associated with a lower risk of depression, while higher calcium, vegetable, and fibre intake were associated with a lower prevalence of depression in young adults. These findings suggest that prevention strategies for common mental disorders could include dietary approaches within mental health care.

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.

Both preclinical and clinical studies have revealed the indisputable importance of intestinal bacterial community composition in pathogenesis of various disease states, from obesity to neurodegeneration. Diet remains one of the most important factors shaping human intestinal microbiota composition. In this study, we investigated diet-microbiome interactions in a healthy cohort of 88 participants from Atlanta and Calgary. We examine microbial composition (16S rRNA sequencing) with dietary records using Spearman Correlation tests with Benjamini-Hochberg multiple hypothesis correction to make community-level comparisons between dietary scores and microbial diversity index scores. Predictive models were used for molecular-level comparisons between microbial gene pathways and molecules. Among generalized dietary and microbial indices, we identified a negative association between dietary whole grain consumption and a microbial dysbiosis score. Comparisons between dietary food groups and bacterial family abundance reveal significant associations between dairy consumption and Lactobacillaceae abundance, dietary unsaturated to saturated fatty acid ratio and Clostridia Cluster Family XIII, salt intake and Lachnospiraceae, and consumption of greens and beans and Veillonellaceae. Predictive models of microbial gene pathways and molecules reveal significant positive associations between several dietary fatty acids and microbial short-chain fatty acid fermentation pathways, and between dietary lignans and archaeal methanogenesis pathways. Overall, these associations may inform future explorations on specific dietary interventions to impact the gut microbiome. IMPORTANCEIn this study, we compare dietary records and composition of intestinal microbes in a cohort of 88 participants. We identified associations between dietary consumption of dairy and the presence of dairy-consuming bacteria called Lactobacteriaceae and between consumption of dietary fats and the presence of fat-consuming bacteria called Clostridia. Using predictive analysis, we identify specific fatty acids associated with specific biochemical pathways found in Clostridia that might underlie these associations, in addition to an association between archaeal microbes and dietary consumption of estrogen-binding molecules called lignans, which are commonly found in whole grains and vegetables. Overall, our study generates useful associations between diet and intestinal microbes that can be tested in experiments that may help scientists use diet to control intestinal microbes in order to improve human health.

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.

Background Maternal iron requirements increase substantially during pregnancy, and ferritin concentrations typically decline as gestation progresses. However, the physiologic significance of this decline remains uncertain, and whether reductions in maternal iron stores relate to birth outcomes is unclear. Objectives To examine associations between maternal ferritin trajectories during pregnancy and postpartum and infant anthropometric outcomes. Methods We conducted a secondary longitudinal analysis of 1,496 mother - infant pairs from the Alberta Pregnancy Outcomes and Nutrition cohort. Serum ferritin was measured longitudinally in the second and third trimesters and at three months postpartum, with limited first-trimester data available. Values below 15 g/L indicated iron deficiency. Multivariable linear regression assessed associations between inflammation-adjusted third-trimester serum ferritin and infant birthweight and length. Change in serum ferritin between the second and third trimesters ({delta} ferritin) was examined as a marker of late-gestation iron mobilization. Postpartum serum ferritin was modelled using restricted cubic splines to account for nonlinear associations with birth weight and length. Results Ferritin concentrations declined progressively across pregnancy, with 61% of women classified as iron deficient in the third trimester. Lower inflammation-adjusted third-trimester ferritin was associated with higher birthweight, corresponding to approximately 84g higher birthweight per 2.7 - fold decrease in ferritin (p < 0.001). Women experiencing the largest decline in ferritin between the second and third trimester delivered infants approximately 155 g heavier than those with minimal change (p = 0.001). Higher birthweight was associated with greater odds of postpartum iron deficiency (OR per 1 kg = 1.83; 95% CI: 1.12 - 2.99). Conclusions In this healthy cohort, maternal iron depletion in late pregnancy was associated with higher birthweight, consistent with preferential fetal iron transfer. Women delivering larger infants exhibited higher odds of iron deficiency, suggesting sustained maternal iron depletion following greater fetal iron accretion.

As plant-based (PB) diets become more common among UK children, understanding their nutritional adequacy and environmental impact is vital. This study assessed nutrient intake and dietary greenhouse gas emissions among children following omnivorous, vegetarian, and vegan diets. A cross-sectional analysis was conducted using three-day weighed food diaries from 39 UK children aged 2-12 years (omnivore n=15; and PB: vegetarian n=11; vegan n=13). Nutrients were analysed with and without supplementation using Nutritics software. GHGEs were calculated at the ingredient level (kgCO2e/day) and grouped by Eatwell Guide food categories. No dietary group met all nutrient reference values. Omnivores exceeded recommended intakes for saturated fat and free sugars while failing to meet the recommended intake for fibre, whereas PB children had intakes of these nutrients in the healthy range. PB diets were adequate in protein and vitamin B12 even in the absence of supplementation. Vegan children also met iron requirements from diet alone, whereas omnivore and vegetarian children did not meet iron targets without supplementation. Vitamin D intake was insufficient across all groups when supplements were excluded, with only vegan children achieving recommended levels through supplementation. Zinc requirements were met only by vegetarian children with the aid of supplements and were not met by vegan or omnivore children with or without supplementation. Iodine intake remained inadequate in vegan children even with supplementation. Mean daily GHGEs differed significantly between diet groups (p < 0.001): omnivores having the highest emissions, while vegans had the lowest emissions: 46% lower than omnivores, and 20% lower than vegetarians. Well-planned PB diets can meet most nutrient needs in UK children when supported by fortified foods and supplements, while substantially reducing dietary GHGEs compared with omnivorous diets. Shifting away from animal protein and dairy provides the greatest opportunity for improving both nutritional quality and environmental sustainability.

ObjectiveThe aim of the study was to investigate knowledge, attitudes and practices (KAP) of Italian general practitioners regarding the use of food supplements. Subject and MethodsA 62-question survey, adapted from a tool used among pharmacists, was sent to Italian general practitioners. The survey contains two sections: A) KAP questions (28 true/false, 34 on a 5-point Likert scale) and B) socio-demographic questions. Results233 questionnaires were collected from March to July 2024. 44.6% of responders were male, 54.9% female. The majority (68.2%) came from an urban environment and 53.65% worked with other colleagues. Most of the general practitioners (69.1%) showed an adequate knowledge of the subject (> 60% of correct answers). The overall reliability of the test was rated as acceptable (alfa>0.7). 98.7% of general practitioners agreed that they have an important role in prescribing dietary supplements, and 98.3% are involved in lifestyles counselling, but only 66.52% felt that they had adequate training on this subject. ConclusionGeneral practitioners recognize their pivotal role in supplement prescription, but, even if their knowledge scores were adequate, they feel a need of more specific education on the topic.

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

PurposeAdequate hydration is vital for health, yet many people do not meet fluid recommendations. This study aimed to characterise the role of water and sugar-sweetened beverages in hydration across different levels of socioeconomic status (SES) in the UK. MethodsIn a pre-registered cross-sectional study, participants (N = 1,112) recalled beverages consumed on the previous day and reported urine colour as an indicator of their hydration status. We analysed water intake (H1), sugar-sweetened beverage (SSB) intake (H2), and SES (education; H3) as predictors of hydration status using stepwise binomial logistic regression adjusted for health, demographic, and lifestyle covariates. ResultsForty percent of participants were classified as underhydrated. Higher water intake was associated with a greater likelihood of adequate hydration: Drinking one extra glass of water per day (250 ml) increased the odds of being adequately hydrated by about 16%. However, SSB intake was not associated with hydration unless intake from other drink sources was held constant. Having a higher versus lower level of education was not significantly associated with hydration status, although finer-grained and income-based analyses suggested modest socioeconomic differences. ConclusionWater intake--rather than SSB intake--is the primary correlate of adequate hydration in this UK sample. Public health initiatives should emphasise the importance of water for hydration, invest in ways to make water more appealing, and promote the use of urine colour as a marker of hydration status.

BackgroundPacked lunches are a common feature of early childhood food provision, yet evidence describing their nutritional composition in early years settings remains limited. Understanding the foods provided during this developmental period is important, given the potential influence of early dietary exposures on later health. AimTo characterise the composition, nutritional quality, cost, and dietary patterns of packed lunches brought from home in Early Childhood Education and Care settings, and to examine variation by child age and area-level deprivation. MethodsA cross-sectional analysis was conducted using a remote food photography method to assess packed lunches provided for children aged 1-4 years attending early years settings across Essex, UK. Food items were categorised into predefined groups, and nutrient composition was estimated. Area-level deprivation was determined using the English Index of Multiple Deprivation (2019). Non-parametric tests assessed between-group differences. Principal components analysis (PCA) was used to identify patterns of co-occurring foods. ResultsA total of 389 packed lunches were analysed. Starchy foods (82%), fruit (81%), dairy or alternatives (72%), and savoury snacks (74%) were commonly provided, while vegetables were less frequent and fish was rarely observed (1.5%). Overall, 97.7% of lunches contained at least one ultra-processed food (UPF), with a median of three UPF items per lunch and 74% of total energy derived from UPFs. Median energy provision was 400 kcal (IQR 309-518). Nutrient composition was broadly similar across deprivation groups, although cake and biscuit counts and UPF item counts were modestly higher in more deprived areas. The median estimated lunch cost was {pound}1.79 and did not differ by deprivation. ConclusionsPacked lunches in early years settings frequently contained ultra-processed foods and showed considerable variability in nutritional quality. Socioeconomic differences were limited, suggesting that contemporary packed lunch practices may reflect influences operating across population groups. Further research across diverse regions is warranted to better understand the provision of packed lunches and their implications for early dietary exposure.

Iron deficiency (ID) is the most common nutritional deficiency worldwide, often caused by insufficient dietary intakes. Oral supplementation is one of the means to improve iron status. This study evaluated the efficacy and safety of two low-dose iron supplements - >Your< Iron Forte Capsules (YIFC) and Ferrous Sulfate Capsules (FSC) - in individuals with dietary ID. One hundred and one participants (mean age 30.6 years; 98% women) with low iron stores (mean serum ferritin 16.1 {micro}g/L) were randomized to receive either YIFC or FSC once daily for 12 weeks. Changes in blood indices and iron-related parameters were assessed at four and 12 weeks of intervention relative to baseline. The primary outcome was the change in hemoglobin (Hb) after 12 weeks. Eighty-seven participants completed the study. Both supplements significantly increased Hb at 12 weeks (YIFC: mean 6.52 g/L, p<0.001; FSC: mean 5.71 g/L, p<0.001). Product-related adverse events (AEs) were few (17% of all AEs) and of mild to moderate intensity only. One participant receiving FSC withdrew due to a probable product-related AE. The frequencies of product-related AEs were similar between study arms, however, statistically significantly more AEs judged to be definitely related to the product occurred in in the FSC arm. While product-related AEs were confined to the gastrointestinal tract in the YIFC arm, they affected multiple organ systems in the FSC arm. Supplementation with either YIFC or FSC proved as an effective, well-tolerated, and safe strategy for improving iron status in non-anemic dietary iron deficiency. In terms of the AE profile, supplementation with YIFC may offer advantages over supplementation with FSC.

Background: The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on nutrition for cancer patients provides evidence based dietary recommendations that is routinely deployed by dieticians in oncology settings. Although these can be culturally adapted, they do not adequately address inter individual variability in treatment related gastrointestinal symptoms and appetite, issues that increase malnutrition risk in cancer patients. Ayurveda, on the other hand, lacks nutrient based guidelines but offers a well grounded dietary framework to assess digestive function and personalise diets. This study investigated the feasibility of combining the two approaches in a clinical setting. Methods: Consenting adult cancer patients diagnosed with any type and stage of cancer were recruited. At baseline, digestive strength, dietary intake, quality and frequency and Patient Generated Subjective Global Assessment (PGSGA) score were recorded. Based on this, personalised meal plans (MPs) that combine nutrient guidelines from ESPEN and traditional food concepts to support digestive strength were provided to participants. Follow ups ranged from 4 weeks to 6 months, at which digestive strength and PGSGA was noted. To evaluate against a benchmark, meal plans were theoretically constructed using Ayurveda concepts (traditional MP) or ESPEN guidelines (Standard MP) alone. Results: Data is presented for 33 participants, of which 52% had weak digestive strength. Baseline intake averaged 879 kcal/day, well below the recommended 1400 to 1600 kcal/ day level. Traditional MPs improved energy intake but were protein insufficient, aspects that were addressed in the standard MPs. Diet quantity (1417 kcal/day), quality and frequency improved on the integrated MP, with 3 patients achieving optimal digestive strength. Personalised counselling reduced malnutrition risk, as reported by PGSGA score. Conclusion: Customising dietary advice by overlaying nutrient guidelines with Ayurveda dietary concepts is feasible. The evaluation of digestive strength holds promise for personalising nutrition therapy. Trial Registration: CTRI/2023/07/055657

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