Nutrients

Nutrition plays a pivotal role in depression, but dietary interventions are usually not personalized and do not consider patients microbial and human molecular functions. This preliminary study evaluated the effectiveness of precision supplements (PS) on depression symptoms as part of a personalized nutrition subscription plan that accounts for the gene expression activity of the microbiome and the human host. People with depression, 86 taking PS and 45 controls responded to the patient health questionnaire-9 (PHQ-9) at two time points an average of [~]6 months apart. Categorical changes were evaluated using the PHQ-9 score system, and clinically significant categorical differences were observed between the two groups (effect size = 0.48; p <0.001). The difference in differences was calculated using multiple group propensity score weighting adjusting for age, sex, BMI, and physical activity, and the PHQ-9 score decreased by [~]4 points ([~]29%) for the intervention group (t0: 13.75+-3.80, t1: 9.78+-6.42) vs Controls (t0: 14.07+-3.64, t1: 13.59 +-6.65). Thus, precision supplement use over [~]6 months significantly reduced depression symptoms, with 69.8% of the individuals in the intervention group improving their category to no/low depression vs. 15.6% in the control group.

In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomized controlled trial Pune Rural Intervention in Young Adolescents (PRIYA). The interventions included: 1) vitamin B12+multi-micronutrients the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) and proteins (B12+MMN), 2) vitamin B12 (B12 alone), and 3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-Adenosyl Methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.

In this double-blind placebo-controlled randomised intervention we investigated the potential benefits of a prebiotic supplement on childrens well-being in a home setting. The primary aim was to determine if this supplement could effectively reduce anxiety, improve mood, and enhance cognitive function, similar to findings in young adults. Fifty-three healthy children, aged 6 to 14, participated in an 8-week trial. The trial consisted of three testing time points; day zero marked the baseline measurement (T1) followed by a 28-day supplement intervention period during which they consumed 5.5 grams of galactooligosaccharides (GOS) daily under parental guidance. Endline measures (T2) were conducted on the last day of supplement consumption, with a final follow-up testing session (T3) on day 56. Primary outcomes were trait anxiety using a questionnaire and emotional behavior in a dot-probe task on responses to positive and negative images. Secondary outcomes encompassed depression levels, cognitive function tests, and dietary intake recorded in a 4-day food diary. Additionally, we explored whether parents emotional behavior had an impact on childrens responses. While our statistical analysis did not reveal significant effects of GOS, there were noteworthy trends. Trait anxiety levels decreased over time in both groups, with a more pronounced decrease in the GOS group. The GOS group exhibited reduced negative emotional responses compared to the placebo group, and post-trial depression levels decreased in the GOS group over time. Although parental emotional responses correlated with various emotional outcomes in children, they did not influence the intervention effects. In conclusion, these findings suggest positive trends in line with our hypotheses however further investigation with greater statistical power would be beneficial.

Key PointsThis section will be completed further ImportanceToddlerhood is a key window of opportunity for development of musculoskeletal system and microbiome. In this study we tested the efficacy of a synbiotic-based young child formula on bone and muscle strength and microbiome maturation in young children during motor-skill development. InterventionIn this randomized, double-blind controlled trial, children aged 2-3 years received either an experimental young child formula (EYCF) containing a combination of Limosilactobacillus reuteri DSM 17938 and galacto-oligosaccharides (GOS) or a minimally fortified milk (CM) for 6 months. A third arm remained on their habitual diet. Main outcomes and measuresBone quality (tibia speed of sound), muscle strength (handgrip), microbiota composition (shotgun metagenomics) and functionality (fecal metabolome) were evaluated at baseline, and after 3 months and 6 months of intervention. Microbiota and metabolomic features were associated to each other and to clinical bone and muscle readouts at the same timepoints. ResultsTibial speed of sound was significantly increased after 6 months (primary end point, p<0.01) and 3 months (p<0.05) of EYCF vs CM feeding. These effects on bone strength were paralleled by significantly higher muscle strength after 6 months in EYCF vs CM. The intervention significantly remodeled microbiome composition, with enrichment of L. reuteri, and higher bifidobacteria presence in the stools of EYCF vs CM children at both 3 and 6 months. Increased L. reuteri abundance after 6 months of EYCF consumption was associated with higher bone quality and muscle strength. Stool metabolomics were significantly modulated by EYCF consumption with 45 metabolites significantly modified and associated to microbiome compositional changes such as Bifidobacterium spp. and L. reuteri expansion. Pairing of metagenomic and metabolomic signatures induced by EYCF revealed an enrichment of tryptophane and indole metabolism which significantly associated to bone and muscle strength clinical outcomes. Conclusions and relevanceConsumption of an experimental young child formula containing a L. reuteri + GOS synbiotic improves musculoskeletal development in toddlers that was associated with a modulation of microbiota composition and functionality. These results provide novel mechanistic insights on gut-musculoskeletal crosstalk during early life and demonstrate that nutritional interventions targeting the microbiome can support healthy bone and muscle development and may contribute to functional motorskills acquisition during childhood. Trial registrationThe trial was registered at clinicaltrial.gov as NCT04799028

Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.

AimsIntravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) who are unresponsive to oral iron treatment or require rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of Chinese patients with IDA. Materials and methodsA previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with bodyweight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life was obtained from SF-36v2 data from the PHOSPHARE-IBD RCT. ResultsOver the five-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 versus 6.79). This resulted in iron procurement and administration cost savings of RMB 206 with FDI (RMB 3,519 versus RMB 3,312). Reduced incidence of hypophosphatemia resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over five years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention. ConclusionsResults showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.

Maternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.

BackgroundTo be universally applicable in treatment of severe COVID-19, novel therapies, especially those with little toxicity and low cost, are urgently needed. We report here the use of one such therapeutic combination involving two commonly used nutraceuticals, namely resveratrol and copper in patients with this disease. This study was prompted by pre-clinical reports that sepsis-related cytokine storm and fatality in mice can be prevented by oral administration of small quantities of resveratrol and copper. Since cytokine storm and sepsis are major causes of death in severe COVID-19, we retrospectively analyzed outcomes of patients with this condition who had received resveratrol and copper. Methods & FindingsOur analysis comprised of 230 patients with severe COVID-19 requiring inhaled oxygen who were admitted in a single tertiary care hospital in Mumbai between April 1 and May 13 2020. Thirty of these patients received, in addition to standard care, resveratrol and copper at doses of 5.6 mg and 560 ng, respectively, orally, once every 6 hours, until discharge or death. These doses were based on our pre-clinical studies, and were nearly 50 times and 2000 times less, respectively, than those recommended as health supplements. A multivariable-adjusted analysis was used to model the outcome of death in these patients and evaluate factors associated with this event. A binary logistic regression analysis was used, with age, sex, presence of comorbidities and receipt of resveratrol-copper as covariates. Data were updated as of May 30 2020. The number of deaths in resveratrol-copper and standard care only groups were 7/30 (23.3%, 95% CI 8.1%-38.4%) and 89/200 (44.5%, 95% CI 37.6%-51.3%), respectively. In multivariable analysis, age >50 years [odds ratio (OR) 2.558, 95% CI 1.454-4.302, P=0.0011] and female sex (OR 1.939, 95% CI 1.079-3.482, P=0.0267) were significantly associated, while presence of co-morbidities was not significantly associated (OR 0.713, 95% CI 0.405-1.256, P=0.2421) with death. There was a trend towards reduction in death in patients receiving resveratrol-copper (OR 0.413, 95% CI 0.164-1.039, P= 0.0604). ConclusionsWe provide preliminary results of a novel approach to the treatment of severe COVID-19 using a combination of small amounts of commonly used nutraceuticals, which is non-toxic and inexpensive, and therefore could be widely accessible globally. The nearly two-fold reduction in mortality with resveratrol-copper observed in our study needs to be confirmed in a randomized controlled trial.

Short-chain fatty acids (SCFAs) are circulating metabolites generated by gut microbiota. Recently, a link between age-related muscle loss and gut microbiota has been described, and SCFAs could play a mediating role in this relationship. Acetic, propionic, and butyric acid are the abundant forms and are considered to have health benefits, less is known about valeric and caproic acid. In a cross-sectional study including 155 healthy volunteers, we investigated the relationship between muscle area, as well as intramuscular adipose tissue measured by magnet resonance imaging and circulating SCFAs. SCFAs and additional parameters were measured from serum and sport activities recorded by means of a questionnaire. We found a significant positive association between valeric acid (VA) levels and the thigh cross-sectional muscle area in males. This relationship was independent of age, BMI and weekly training times and was not observed in females. No associations between other SCFAs and the thigh muscle cross-sectional area were observed. To our knowledge, this is the first human study demonstrating a significant relationship between thigh muscle mass and VA, supporting the thesis of the "gut-muscle axis" with VA as a possible interacting player, on the one hand, affected by sex differences, on the other.

IntroductionStudies show, malnourished women of childbearing age with environmental enteric dysfunction (EED) exhibit small intestinal enteropathy resembling that in malnourished children residing in the same community. However, currently there are no universally accepted protocols for validation of these facts. Our current protocol is designed to better understand the mechanism of transmission of the microbiota of mothers with EED to their children perpetuates intergenerational undernutrition. We plan to compare the small intestinal (SI) and fecal microbiota along with plasma, duodenal, and fecal proteomes/ metabolomes and histopathologic evidence of EED in non-pregnant women with and without malnutrition. We also plan to see and compare the effect of microbiota-directed balanced energy protein (MD-BEP) supplementation on these biological parameters between malnourished non-pregnant and pregnant women. Methods and analysisThis is a community-based intervention study where pregnant women and non-pregnant women of reproductive age (18-35 years) will be screened through household surveys from the Bauniabadh and adjacent slum area of Mirpur, Dhaka (pregnant and non-pregnant cohorts, n=90 each). Using Body Mass Index (BMI), both the groups will be categorized into undernourished (BMI <18.5kg/m2, n=60 each with pregnant and non-pregnant cohort) and well-nourished (BMI >20-24.9 kg/ m2, n=30, each with pregnant and non-pregnant cohort). Upper gastro-intestinal (UGI) endoscopy will be performed on non-pregnant women (both well-nourished and undernourished cohorts) and biopsy samples will be collected for diagnosis of environmental enteric dysfunction (EED) by histopathological scoring. We will compare the small intestinal (SI) and fecal microbiota and the plasma, duodenal, and fecal proteomes/ metabolomes of the undernourished non-pregnant cohort with histopathologic evidence of EED with the well-nourished non-pregnant cohort with no histopathologic evidence of EED (Aim IA). Furthermore, we will perform an intervention study (Aim IB). The undernourished non-pregnant cohort will be randomized into two groups (n=30/arm) and receive daily dietary supplementation with either shelf-stable microbiota-directed balanced energy protein (MD-BEP) or ready-to-use supplementary food balanced energy protein (RUSF-BEP) for 90 days. After cessation of the intervention they will be further followed up for another 270 days and biological samples will be collected at scheduled time points. The well-nourished non-pregnant cohort will not receive any nutritional intervention will serve as a reference control group. The undernourished pregnant cohort will also be randomly (n=30/arm) assigned to receive either MD-BEP or RUSF-BEP daily for 6 months until the child birth and thereafter for 3 months and followed up for another 9 months. During this period anthropometry will be measured and biological samples including fecal and plasma samples will be collected from the mothers and their infants in scheduled time points. Anthropometric, socio-demographic and laboratory assay data will be compared between the groups and candidate EED biomarkers will be correlated with nutritional status, histological analyses and score of EED, plus assessments of microbial community structure will be examined. Ethics and disseminationEthics approval was obtained from the Ethical Review Committee of icddr,b (protocol no: PR-22117; Version 1.2; 29 November 2022). Results of this study will be submitted for publication in peer-reviewed journals. Trial registration numberClinicalTrials.gov ID: NCT05862363. Registered on 08 February 2023. https://clinicaltrials.gov/study/NCT05862363

BackgroundFor very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC) is rich in anti-inflammatory milk factors and considered an alternative. Our objective was to investigate if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants. MethodsIn a secondary analysis of a multicenter, randomized controlled trial (NCT03537365), very preterm infants (26-31 weeks gestation, 23% small for gestational age, SGA) were randomized to receive BC (ColoDan, Biofiber, Denmark, n=113) or a conventional fortifier (PreNAN, Nestle, Switzerland, n=116). Infection was defined as antibiotic treatment for five or more consecutive days. Levels of 29 cytokines and chemokines were measured in plasma before and after start of fortification. ResultsInfants fortified with BC showed more infection episodes (20 vs. 12%, P<0.05) and tendency to higher cumulative infection risk (hazard ratio, HR 1.9, P=0.06), particularly for SGA infants (HR 3.6, P<0.05). Additionally, BC-fortified infants had higher levels of TH2 related cytokines and chemokines (IL-10, MDC, MCP4) and reduced levels of cytokines related to TH1/TH17 responses (IL-15, IL-17, GM-CSF). The differences were most pronounced in SGA infants, displaying higher levels of TH2-related IL-4, IL-6, and IL-13, and lower interferon-{gamma} and IL-1 levels in the BC group ConclusionInfants fortified with BC show delayed transition from TH2-to TH1-biased systemic immunity, especially for SGA infants. This was associated with more frequent antibiotic use, indicating elevated sensitivity to infection. Thus, an anti-inflammatory milk supplement like BC may delay systemic immune development in preterm infants with effects depending on weight at birth.

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

BackgroundBifidobacterium longum supplementation can be used to regulate bowel movement; however, individuals vary in the response to B. longum treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates diet or drug effects. Here, we investigated intestinal features related to B. longum effectiveness in increasing bowel movement frequency. ResultsA randomized, double-blind controlled crossover trial was conducted with twenty Japanese subjects selected from 50 participants. The subjects received a two-week dietary intervention consisting of B. longum in acid-resistant seamless capsules or similarly encapsulated starch powder. Bowel movement frequency was recorded daily, and time-series fecal collection was conducted for metabologenomic analyses. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predictable by machine learning based on the metabologenomic features of the fecal samples collected before B. longum intake. Between responders and non-responders, the abundances of nine bacterial genera and of three compounds were significantly different. ConclusionsThus, the gut microbiome and metabolome composition have a strong impact on B. longum supplementation effectiveness in increasing bowel movement frequency, and gut metabologenomics enables B. longum supplementation effect prediction before intake. These findings have implications for the development of personalized probiotic treatments. Trial registrationUMIN-CTR, UMIN000018924. Registered 07 September 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021894

The gut-brain axis plays a key role in the bidirectional communication between the gastrointestinal system and the brain, with gut microbiota significantly influencing cognitive function. While synbiotic and probiotic interventions have shown potential cognitive benefits, results across studies remain mixed. This randomized, controlled, repeated-measures study investigated the effects of a 15-day synbiotic intervention on cognitive performance in 28 healthy women (aged 18-32), assigned to either a synbiotic or no-treatment control group. Cognitive performance was assessed before and after the intervention using the Parametric Auditory Working Memory Task and the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT). Compared to the control group, participants in the synbiotic group demonstrated selective improvements in attention, particularly in overall visual attention and visual sustained attention, as indicated by significant group-by-time interactions (ps < .05). No significant changes were observed in auditory working memory or inhibitory control. These results suggest that short-term synbiotic supplementation may selectively enhance visual attention without broadly affecting executive functions.

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)

Whey protein phospholipid concentrate (WPPC), a byproduct of whey protein processing, is high in phospholipids and glycoconjugates which serve as substrates for fatty acids and sugar monomers (e.g. sialic acid) critical to neuronal myelin synthesis in the brain. This led us to hypothesize that WPPC will improve cognitive impairment induced by a high fat (HF) diet by promoting myelin turnover and improving myelin-dependent processes associated with encoding and storing memory. Male Wistar rats were randomized to one of four diets starting at weaning to [~]6.5 months on age: a low-fat (LF) diet containing 10% fat by weight, a HF diet containing 45% fat by weight to induce cognitive impairment, and a HF diet containing either 1.6% or 10% WPPC by weight (n=12 per diet). Rats were subjected to cognitive testing after 2 and 4 months of dietary intervention and then implanted with chronic bipolar electrodes to measure axonal evoked responses within the entorhinal cortex-hippocampal circuitry. Phospholipid and sphingolipid components of myelin were quantified in the hippocampus. There were no significant differences in cognition measured by novel object recognition after 2 months of supplementation. At 4 months, rats on the HF diet performed significantly worse than rats on the LF, HF1.6 and HF10 diets. The beneficial effects of WPPC on cognition were due to a partial reversal in evoked response impairments in hippocampal memory storage. Additionally, hippocampus sphingolipids were higher in rats on the HF diet compared to the LF, HF1.6 and HF10 groups. These findings demonstrate that WPPC prevented cognitive impairment induced by a HF diet by regulating entorhinal cortex-hippocampal circuitries associated with memory storage, though modulating myelin turnover.

ObjectivesTo examine whether complete absence of vegetable and fruit consumption (Zero Vegetable or Fruit - ZVF) independently associates with anemia among children aged 0-59 months in Tajikistan, and to identify key maternal and socioeconomic determinants of childhood anemia. DesignCross-sectional analysis using recent 2023, nationally representative Demographic and Health survey data from Tajikistan. SettingNational population based study across all regions of Tajikistan (urban and rural areas) using two stage stratified cluster sampling. Participants2,355 children in age group 0-59 months with complete data on hemoglobin levels and dietary intake in the preceding 24 hours residing in households selected from 2023 Tajikistan Demographic and Health Survey were included in this study. Main Outcome MeasuresPrimary outcome, childhood anemia status (hemoglobin <10.5g/dl for 6-23 months, <11g/dl for 24-59 months, altitude-adjusted per WHO 2024 criteria). ResultsAmong Tajik children under 5 years, 36.1% of children consumed no vegetables or fruits in the preceding 24 hours and the prevalence of anemia was 33.2%. Adjusted odds in our study revealed no association of ZVF consumption with anemia (OR=0.85, 95% CI: 0.63 to 1.14). Significant associations emerged for maternal anemia which increased child anemia odds by 48% (OR=1.48, 95% CI: 1.16 to 1.88), richest index had 60% lower anemia odds compared to the poorest (OR=0.39, 95% CI: 0.27 to 0.56) and low birth size increased anemia risk two fold (OR=1.92, 95% CI: 1.31 to 2.81).Each additional daily meal consumption reduced anemia odds by 14% (OR=0.86, 95% CI: 0.76 to 0.98). ConclusionsChild anemia in Tajikistan is not primarily driven by specific dietary factors but maternal nutritional status during pregnancy, birth outcomes, and socioeconomic disparities are main drivers. This novel null finding on ZVF intake, underscores that non dietary drivers predominate, informing targeted interventions aligned with SDG2 (Zero hunger). Thus integrated approaches aim to address maternal nutrition, antenatal care, wealth inequalities, and feeding frequency promotion. What is already known on this topicOver 40% of children under five globally are affected by childhood anemia with dietary factors like low fruit and vegetable intake considered important contributors. However, the specific impact of complete absence (zero consumption) of vegetables and fruits on childhood anemia needs to be explored particularly in Central Asian countries like Tajikistan as here the dietary pattern differ from other low- and middle-income settings. What this study addsThis first nationally representative Central Asian study showed that downstream factor thats the zero vegetable or fruit consumption had no association with childhood anemia in Tajikistan. Instead upstream factors like maternal anemia during pregnancy, household wealth disparities, small birth size, and meal frequency emerged as primary determinants, challenging dietary-centric intervention approaches. How this study might affect research, practice or policyThese findings redirect anemia prevention strategies towards integrated interventions addressing maternal nutrition during pregnancy, poverty alleviation, improved antenatal care for fetal growth monitoring, and feeding frequency promotion rather than focusing solely on vegetable or fruit consumption. This evidence informs sustainable development goals (SDG) aligned nutrition policies requiring upstream determinants to be prioritized alongside dietary diversity programs in similar settings. Key PointsO_ST_ABSCore IssuesC_ST_ABSThis study explored whether complete absence of vegetable and fruit consumption (ZVF) associates with childhood anemia (below five years) in Tajikistan thereby challenging dietary-centric intervention approaches by examining maternal and socioeconomic determinants. FindingsThe research found no significant association between zero vegetable or fruit consumption with childhood anemia, but identified maternal anemia during pregnancy, household wealth disparities, small birth size, and meal frequency as primary drivers. MeaningThis novel null finding of our research redirects anemia prevention strategies from dietary diversity alone toward integrated upstream interventions addressing maternal nutrition, poverty alleviation, antenatal care quality, and feeding frequency informing SDG-aligned policies in Central Asia and similar Lower-and Middle-income countries.

BackgroundMany foods have an antioxidant activity and nutrition may mitigate COVID-19. Some of the countries with a low COVID-19 mortality are those with a relatively high consumption of traditional fermented foods. To test the potential role of fermented foods in COVID-19 mortality in Europe, we performed an ecological study. MethodsThe European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of fermented vegetables, pickled/marinated vegetables, fermented milk, yoghurt and fermented sour milk. We obtained the COVID-19 mortality per number of inhabitants from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for data on potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people older than 64 years (2019), unemployment rate (2019) and percentage obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models - with log of population as an offset - to model the death rate while accounting for over-dispersion. ResultsOf all the variables considered, including confounders, only fermented vegetables reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of fermented vegetables, the mortality risk for COVID-19 decreased by 35.4% (95% CI: 11.4%, 35.5%). Adjustment did not change the point estimate and results were still significant. DiscussionThe negative ecological association between COVID-19 mortality and consumption of fermented vegetables supports the a priory hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of fermented vegetables is common.

BackgroundCholine is an essential micronutrient crucial for fetal neurodevelopment. Numerous rodent studies reveal that maternal prenatal choline deficiency produces lifelong offspring cognitive deficits and that maternal choline supplementation produces lifelong improvements to offspring cognition. Few studies have evaluated this question in humans, and with mixed results. Nonetheless, the available data raise concerns about the low choline intakes of pregnant women and highlight the need for knowledge on the functional consequences of various choline intakes during pregnancy. To address this, the present study evaluates the cognitive and affective functioning of adolescents born to women who participated in a randomized controlled trial of two levels of choline intake during pregnancy. MethodsIn a double-blind controlled choline feeding trial, (N = 26) third-trimester pregnant women were randomly assigned to daily choline consumption at 480 mg/d or 930 mg/d. In this 14-year follow-up, the offspring (n = 21) of these women will complete cognitive tests proctored over conferencing software. We will also assess facets of mental health using the Achenbach System of Empirically Based Assessment. These assessments will test the hypothesis that third trimester maternal choline intake exerts lasting effects on offspring attention, memory, executive function, and mental health. Significance and ImpactWe hypothesize that adolescent offspring born to women in the 930 mg/d group will perform better in domains of memory, attention, executive function, and mental health than offspring of the 480 mg/d group. This study is unique because total maternal choline intake is precisely known, and the offspring are followed into adolescence, a time when group differences are indicative of lifelong effects of the prenatal intervention. The findings will provide important new information concerning the lasting functional consequences of maternal choline intake during pregnancy for offspring neurobehavioral health, thereby informing dietary recommendations and supplementation policies for pregnant women. Trial registrationClinicalTrials.gov: NCT05859126

BackgroundObservational studies have demonstrated inverse associations between vegetable intake and cardiovascular diseases. However, the results are prone to residual confounding. The separate effects of cooked and raw vegetable intake remain unclear. This study aims to investigate the association between cooked and raw vegetable intake with cardiovascular outcomes using Mendelian randomization (MR). MethodsWe identified 15 and 28 genetic variants associated statistically and biologically with cooked and raw vegetable intake, which were used as instrumental variables to estimate the associations with coronary heart disease (CHD), stroke, heart failure (HF) and atrial fibrillation (AF). In one-sample analysis using individual participant data from UK Biobank, we adopted two stage least square approach. In two-sample analysis, we used summary level statistics from genome-wide association analyses. The independent effects of cooked and raw vegetable intake were examined with multivariable MR analysis. The one-sample and two-sample estimates were combined via meta-analysis. Bonferroni correction was applied for multiple comparison. ResultsIn the meta-analysis of 1.2 million participants on average, we found null evidence for associations between cooked and raw vegetable intake with CHD, HF, or AF. Raw vegetable intake was nominally associated with stroke (odds ratio [95% confidence interval] 0.82 [0.69 - 0.98] per 1 serving increase daily, p = 0.03), but this association did not pass corrected significance level. ConclusionsCooked and raw vegetable intake was not associated with CHD, AF or HF. Raw vegetable intake is likely to reduce risk of stroke, but warrants more research. Solely increasing vegetable intake may have limited protection, if any, on cardiovascular health. This calls for more rigorous assessment on health burden associated with low vegetable consumption.