The Journal of Nutrition
○ Elsevier BV
All preprints, ranked by how well they match The Journal of Nutrition's content profile, based on 21 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.
Herrera-Astorga, L.; Matho, C.; Pereira-Pagola, J.; Pomi, J.; Bilbao, L.; Farias, C.; Puyol, A.; Sotelo-Silveira, J.; Rodriguez-Camejo, C.; Hernandez, A.
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BackgroundGiven the links between early gut microbiota, breastfeeding, and maternal physiology, we characterized the intestinal microbiota of infants during exclusive breastfeeding (mean=5.4 months), examining its associations with breastmilk composition, fecal IgA, and maternal factors in Uruguayan primiparous mothers, with vaginal (V, n=20) or cesarean-section delivery (CS, n=14). MethodsWe analyzed fecal microbiota via 16S rRNA V4 sequencing and quantified stool IgA, breastmilk components (antibodies, hormones, macronutrients) using ELISA and standard biochemical methods. ResultsPrincipal Coordinates Analysis showed separation by delivery mode (PCo1:44.6%, PCo2:14.2%). Samples of CS-group displayed lower relative abundance (RA %) of Bacteroidetes/Firmicutes ratio, higher RA of Proteobacteria (50.7%vs35.5%), and decreased Bacteroides (2.5%vs31.8%) than V-group. Biochemical parameters didnt differ between groups. In the V-group, milk and fecal IgA correlated (r=+0.47), as did Bifidobacterium RA with milk IgA (r=+0.47). Fat content was associated with different microbial taxa in both groups. Only in CS-group milk carbohydrates correlated with Bifidobacterium (r=-0.679) and maternal stress with Flavonifractor in CS-group (r=+0.461). ConclusionResults indicate delivery mode can exert persistent impact on infant gut microbiota until the introduction of complementary feeding. Differences in correlation patterns between groups suggest distinct regulatory mechanisms of microbiota, possibly linked to physiological processes that differ according to delivery mode. ImpactO_LIThis is the first study to assess the gut microbiota composition of exclusively breastfed infants born to Uruguayan mothers, in parallel with analyses of breast milk composition and maternal perceived stress C_LIO_LIThe mode of delivery was associated with differences in gut microbiota composition at a mean age of 5.4 months. C_LIO_LIDifferent associations between milk composition and maternal perceived stress with predominant microbial taxa were found according to the type of delivery. C_LIO_LIThese findings provide a basis for studies on microbiota regulatory mechanisms influenced by maternal physiology according to delivery mode C_LI
Roth, D. E.; Khan, A. Z.; Roy, A. K.; Qamar, H.; Pell, L. G.; O'Callaghan, K. M.; Sarker, S. A. A.; Mahmud, A. A.; Haque, R.; Akter, S.; Sultana, S.; Raqib, R.
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BackgroundProbiotics may enhance host iron bioavailability, offering a strategy to address iron deficiency. Fecal iron may be a useful non-invasive biomarker of such effects in infants. ObjectiveTo examine the use of fecal iron quantification in a randomized placebo-controlled trial (RCT) of neonatal administration of Lactiplantibacillus plantarum ATCC 202195 (LP202195), with or without fructooligosaccharide (FOS), in Dhaka, Bangladesh. MethodsFecal iron quantification using atomic absorption spectrometry (AAS) was optimized using standards and reference materials, and pilot-tested using pooled stool aliquots (n=32) from an observational cohort of young infants in Bangladesh (aged 0-64 days). The optimized AAS assay was then applied to individual stool samples collected at 14 days of age (n=307) in a RCT in which newborns aged 0-4 days were randomly allocated to one of five groups: placebo, 1-or 7-day regimens of LP202195, with or without FOS. Serum ferritin was measured at 2 months postnatal age (n=251). Effects of the 1-and 7-day LP202195 regimens were estimated using linear regression and expressed as mean percent differences relative to placebo, with 95% confidence intervals (95%CI). ResultsThe optimized AAS fecal iron assay had acceptable accuracy (91-99%), precision (within-and between-run coefficients of variation <10%), and recovery (93-112%), with a reportable range of 0.2 to 80 mg Fe per 100 g dry stool. In pooled samples from the observational cohort, fecal iron varied with age and feeding status. In the RCT, fecal iron concentrations did not significantly differ following1-day (% difference=9.8%, 95%CI:-19%, 49%; P=0.54) or 7-days (% difference=-6.1%, 95%CI:-31%, 28%; P=0.69) of LP202195 administration, versus placebo (geometric mean concentration=4.3mg Fe/100g dry stool (95%CI:3.3, 5.6); n=53). Inferences were unchanged when groups were disaggregated by FOS co-administration (P>0.05 for all). Similarly, there were no effects of LP202195 on serum ferritin at 2 months of age (P>0.05 for all). ConclusionsFecal iron quantification by AAS was valid and feasibly implemented in a trial of neonatal administration of Lactiplantibacillus plantarum ATCC 202195. However, the assay is resource-intensive and may not be more informative than conventional measures of iron status when studying the effects of probiotics/synbiotics on iron bioavailability. Clinical Trial RegistryClinicalTrials.gov identifier: NCT05180201
Parker, J.; Kisho, A.; Hou, S.; Goodman, M.; Cravens, L.; Grap, M. E.; Pachon, H.
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BackgroundWheat flour, maize flour and rice (i.e. grains) fortification with folic acid is an important folate dietary source globally. There are no systematic reviews or meta-analyses evaluating the effect of mandatory grain fortification on folate insufficiency (using serum/plasma folate and red blood cell (RBC) folate), RBC folate levels or folate deficiency using RBC folate. This study assessed the effectiveness of mandatory grain fortification with folic acid on serum/plasma folate and red blood cell (RBC) folate levels and the risk of folate deficiency and insufficiency based on these biomarkers. MethodsWe searched PubMed and Embase with assistance from a professional library informationist. We selected studies from countries with mandatory grain fortification that include folic acid in standards if they reported primary pre- and post-fortification data on folate status outcomes. We ran meta-analyses in R using random effects models with results expressed as meta-differences of means (MDM) or meta-prevalence ratios (mPR) for continuous and binary outcomes respectively. All meta-estimates were accompanied by 95% confidence intervals (CI). ResultsWe screened 4,311 documents, identifying 31 articles which reported folate status outcomes (22 reported mean serum/plasma or RBC folate, 18 reported prevalence of folate deficiency or insufficiency). About 19% of studies were conducted in low- or middle-income countries. Mandatory fortification improved folate status, albeit with considerable heterogeneity across studies (I2[≥]73%). For serum/plasma folate levels, the MDM across all studies was 15.0 nmol/L (95% CI: 9.4-20.5). For serum/plasma folate insufficiency and deficiency, the mPR (95% CI) estimates were 0.17 (0.08-0.37) and 0.08 (0.03-0.23), respectively. For red blood cell folate levels, the MDM was 329.4 nmol/L (95% CI 243.9-414.9). For RBC folate insufficiency and deficiency, mPRs (95% CIs) were 0.16 (0.08-0.30) and 0.05 (0.01-0.46), respectively. ConclusionsMandatory grain fortification with folic acid increases blood folate levels and decreases the risk of folate insufficiency and folate deficiency.
Bishop, A. C.; Spradling-Reeves, K. D.; Shade, R.; Lange, K. J.; Birnbaum, S.; Favela, K.; Dick, E. J.; Nijland, M. J.; Li, C.; Nathanielsz, P. W.; Cox, L. A.
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BackgroundPoor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal nutrition exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model of moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and programs renal fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally, influencing responses to a high-fat, high-carbohydrate, high-salt (HFCS) diet. MethodsPregnant baboons ate chow (Control; CON) or 70% of control intake (MNR) from 0.16 gestation through lactation. MNR offspring were IUGR at birth. At weaning, all offspring (CON and IUGR females and males, n=3/group) ate chow. At ~4.5 years of age, blood, urine, and kidney biopsies were collected before and after a 7-week HFCS diet challenge. Kidney function, unbiased kidney gene expression, and untargeted urine metabolomics were evaluated. ResultsIUGR female and male kidney transcriptome and urine metabolome differed from CON at 3.5 years, prior to HFCS. After the challenge, we observed sex-specific and fetal exposure-specific responses in urine creatinine, urine metabolites, and renal signaling pathways. ConclusionsWe previously showed mTOR signaling dysregulation in IUGR fetal kidneys. Before HFCS, gene expression analysis indicated that dysregulation persists postnatally in IUGR females. IUGR male offspring response to HFCS showed uncoordinated signaling pathway responses suggestive of proximal tubule injury. To our knowledge, this is the first study comparing CON and IUGR postnatal juvenile NHP and the impact of fetal and postnatal life caloric mismatch. Perinatal history needs to be taken into account when assessing renal disease risk.
Kabir, P.; Sandalinas, F.; Bell, R.; Bourque, S.
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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.
Gallagher, K.; Ciulei, M. A.; Ba, D.; Beck, C.; Pobee, R. A.; Gernand, A. D.; Walker, R.
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Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as potential risk factors for poor iron status. Our objective was to examine the association between pre-pregnancy BMI and iron status in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n=1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cooks equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted Poisson regression models, adjusted for confounders (age, race/ethnicity, education, family income, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR)=1.28, 95%CI: 0.89-1.83; obesity, PR=0.75, 95%CI: 0.39-1.45; anemia: overweight, PR=1.08, 95%CI: 0.53-2.19; obesity, PR=0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that iron status in pregnancy does not differ by pre-pregnancy BMI. Since iron deficiency during pregnancy remains a significant public health concern, NHANES should consider measuring current iron status in upcoming cycles.
Rimal, R.; Rimal, A.; Pradhan, P. U.
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Maternal dietary diversity is vital for the health of both mothers and children during lactation, yet it is often compromised in low- and middle-income countries. This cross-sectional study among 251 lactating mothers in Tarakeswor Municipality, Nepal, assessed dietary diversity using a 24-hour dietary recall and the Minimum Dietary Diversity for Women (MDD-W) indicator. Overall, 68.1% of mothers achieved the minimum dietary diversity ([≥]5 of 10 food groups), with a mean score of 5.03 {+/-} 1.25. In multivariable analysis, higher odds of meeting MDD were observed among mothers with secondary or higher education (aOR = 7.5; 95% CI: 3.8-15.0), employment (aOR = 2.9; 95% CI: 1.4-5.8), joint or extended family structure (aOR = 3.7; 95% CI: 1.9-7.0), the highest wealth quintile (aOR = 4.2; 95% CI: 1.9-9.1), food-secure households (aOR = 4.5; 95% CI: 2.3-7.9), adequate nutrition knowledge (aOR = 5.2; 95% CI: 2.7-9.8), [≥]4 antenatal care visits (aOR = 1.9; 95% CI: 1.0-3.4), and higher empowerment (aOR = 3.9; 95% CI: 1.9-7.8). These findings highlight substantial socioeconomic disparities in maternal dietary diversity and underscore the need for integrated, equity-focused nutrition interventions in rapidly urbanizing settings in low- and middle-income countries.
Sulistyoningrum, D. C.; Sullivan, T. R.; Skubisz, M.; Palmer, D. J.; Wood, S.; Snel, M. F.; Trim, P. J.; Makrides, M.; Green, T. J.; Best, K. P.
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BackgroundPregnant women are advised to take folic acid supplements before conception and during the first three months of pregnancy. Many women continue folic acid supplementation throughout pregnancy, and concerns have been raised about associations between excess folic acid intake and adverse child health outcomes. Unmetabolized folic acid (UMFA) is found in serum at higher folic acid intakes and has been proposed as a biomarker for excess folic acid intake. ObjectiveTo determine if removing folic acid from prenatal multivitamin and mineral supplements after 12 weeks of pregnancy reduces concentrations of serum UMFA at 36 weeks gestation. DesignA double-blind, parallel-group, randomized controlled trial. Women with a singleton pregnancy 12-16-weeks gestation were randomly assigned to a multi-micronutrient supplement containing no folic acid (intervention) or 800 {micro}g folic acid/day (control) from enrolment until 36 weeks gestation. Maternal serum was analyzed for UMFA and secondary outcomes of red blood cell and serum folate at 36 weeks gestation. ResultsUMFA was detected in most of the 103 randomized women (86% >limit of detection). However, only 12% (n=11/90) of serum samples were above the limit of quantification (0.55 nmol/L), preventing analysis of UMFA concentrations. Fewer women had detectable UMFA in the no folic acid group compared to the 800 {micro}g folic acid group (72% [n=33/46] vs. 98% [n=43/44]; p = 0.001). Maternal serum and red blood cell folate concentrations were lower in the no folic acid intervention group compared to the control group (median 23.2 vs. 49.3 nmol/L, 1335 vs. 1914 nmol/L, respectively; p< 0.,001) and no woman was classified as folate deficient. ConclusionsRemoving folic acid from prenatal multivitamin and mineral supplements reduced the number of women with detectable UMFA at 36 weeks gestation, however, differences in UMFA concentration between treatment groups were not quantifiable.
Tan, X.; Tan, P. Y.; Gong, Y. Y.; Moore, J. B.
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IntroductionTraditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can co-exist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A status and weight status (both under- and overweight) in children and young people. MethodsOvid Medline, Ovid Embase, Scopus, and Cochrane databases were systematically searched for observational studies assessing micronutrient status (blood, serum, or plasma levels of iron, zinc, or vitamin A biomarkers) and weight status (body mass index or other anthropometric measurement) in humans under 25 years of any ethnicity and gender. Risk of bias assessment was conducted using the American Dietetic Association Quality Criteria Checklist. Where possible, random effects restricted maximum likelihood (REML) meta-analyses were performed. PROSPERO (CRD42020221523). ResultsAfter screening, 83 observational studies involving 190,443 participants from 44 countries were identified, with many studies having reported on more than one micronutrient and/or weight status indicator. Iron was the most investigated micronutrient, with 46, 28, and 27 studies reporting data for iron, zinc, and vitamin A status, respectively. Synthesizing 16 records of odds ratio (OR) from 7 eligible studies, overnutrition (overweight and obesity) increased odds of iron deficiency (OR [95%CI]: 1.51 [1.20, 1.82], p<0.0001, I2=40.7%). Odds appeared to be higher for children living with obesity (1.88 [1.33, 2.43], p<0.0001 I2=20.6%) in comparison to those with overweight (1.31 [0.98, 1.64], p<0.0001 I2=40.5%), although between group differences were not significant (p=0.08). ConclusionsOvernutrition is associated with increased risk of iron deficiency, but not zinc or vitamin A deficiencies, with an inverted U-shaped relationship observed between iron status and bodyweight. Our results highlight significant heterogeneity in the reporting of micronutrient biomarkers and how deficiencies were defined. Inflammation status was rarely adequately accounted for, and the burden of iron deficiency may well be under-recognised, particularly in children and young people living with overnutrition. Key questionsO_ST_ABSWhat is already known on this topicC_ST_ABS-summarise the state of scientific knowledge on this subject before you did your study and why this study needed to be done O_LILow-and middle-income countries are increasingly facing a double burden of malnutrition; that is, the coexistence of undernutrition (stunting, wasting, underweight) with overnutrition (overweight and obesity). C_LIO_LIWhile the relationship between undernutrition and critical micronutrients for childhood growth and development (e.g., iron, zinc, and vitamin A) is well established, less is known about the risk of micronutrient deficiencies in children and adolescents with overweight or obese, a hidden form of malnutrition. C_LIO_LIThere are limited data summarising associations between biomarkers of the most commonly limiting micronutrients and body weight status, particularly in children and young people. C_LI What this study adds-summarise what we now know as a result of this study that we did not know before O_LIOvernutrition increases the risk of iron deficiency, but not zinc or vitamin A deficiencies. C_LIO_LIThere is an inverted U-shaped relationship observed between iron status and bodyweight in children and young people, with iron deficiencies observed more frequent in both under- and overnutrition. C_LIO_LIStudies done to date have been heterogeneous in terms of populations studied, diagnostic criteria, and approaches to data analysis; few followed current guidelines for measuring inflammation and defining micronutrient deficiencies. C_LI How this study might affect research, practice or policy-summarise the implications of this study O_LIIncreased recognition by healthcare practitioners that children and young people living with overweight, or obesity are likely to be iron deficient; thereby improving clinical practice and care. C_LIO_LIThe gaps in evidence highlighted are addressed, with more research from currently underrepresented counties examining micronutrient deficiencies and the double burden of malnutrition. C_LIO_LIThe weaknesses in study design and reporting highlighted are addressed, with improved quality and reporting of micronutrient assessment in children and young people. C_LI
Soh, B. X. P.; Vignes, M.; Smith, N. W.; McNabb, W. C.; von Hurst, P. R.
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BackgroundPoorly planned vegan diets may incur deficiencies in indispensable amino acids (IAAs) and certain micronutrients. Targeted dietary modifications are necessary to improve nutrient adequacy for optimal health. ObjectiveOptimisation modelling was applied to identify combinations of plant-based foods within an individuals existing diet to address protein and IAA shortfalls in a sample of New Zealand vegans grouped into three clusters with varied daily dietary patterns. MethodsShortfalls for protein and IAAs were calculated by comparing daily intakes to individual requirements. An energy-tailored optimisation using linear programming was used: diets with lower energy intake had foods added while those with excess energy had energy-dense and low-protein foods replaced with protein-rich alternatives. The modified diets had to 1) meet protein and IAA shortfalls, 2) respect serving size constraints for added foods, and 3) remain within individual energy boundaries while minimising the weight of food added. Post-optimisation analysis assessed changes in intake of protein, amino acids, dietary fibre and selected micronutrients with results compared across clusters. ResultsProtein and IAA shortfalls were more prevalent in cluster 1 (85% of daily diets) compared to clusters 2 (61.1%) and 3 (30.8%). Legumes and pulses contributed most to total protein and lysine with lower energy costs, while nuts and seeds contributed most to methionine and leucine, but with higher energy. Optimisation resolved shortfalls in 93.2% of the daily diets. The remaining 52 diets - mainly from clusters 1 and 2 - could not reach adequacy due to large protein and IAA deficits and limited energy capacity. Post-optimisation micronutrient analysis showed continued risks of shortfalls for calcium, vitamin B12 and iodine. ConclusionMathematical optimisation can enhance the protein adequacy of vegan diets while preserving individual acceptability. However, full nutritional adequacy remains challenging in energy-constrained diets with large nutrient deficits.
Ndukwe, C.; Ndubuka, N.; Ndubuka, J.; Udey, C.; Dankwah, E.
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Scurvy, resulting from vitamin C deficiency, is linked to serious health outcomes, including impaired collagen synthesis, anemia, and delayed wound healing. Once considered largely eradicated in high-income countries, scurvy has re-emerged among specific Canadian populations, driven by factors such as inadequate dietary intake, socioeconomic disparities, and limited access to nutritious foods. Despite growing awareness, evidence regarding its prevalence, risk factors, and public health responses in Canada remains sparse and fragmented. To address this knowledge gap, this study protocol outlines a scoping review designed to: (a) assess the prevalence and incidence of scurvy and vitamin C deficiency in Canada; (b) identify at-risk populations and contributing factors; (c) describe associated health outcomes; and (d) map existing nutritional interventions and public health strategies for prevention and management. Our review will follow the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis (Chapter 11: Scoping review) and the Arksey and OMalley methodological framework. Keywords will be identified and used to develop search strings used for a comprehensive search of various databases. The review will adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Our study selection process will systematically screen titles/abstracts and full texts of potentially relevant articles to ensure a comprehensive analysis through thematic analysis. We will implement a clearly defined extraction process to gather the most pertinent articles, maximizing the quality and impact of our research. Ethical approval is not required because this study will review publicly available data and will not involve human participants. Our scoping review will synthesize evidence on scurvy and vitamin C deficiency in Canada, identifying knowledge gaps, contributing factors such as food insecurity, and vulnerable populations. Findings will inform research priorities, guide public health policies, and support targeted interventions to prevent deficiency and enhance nutritional health for Canadians.
Heyden, K. E.; Fiddler, J. L.; Xiu, Y.; Malysheva, O. V.; Handzlik, M. K.; Phinney, W. N.; Stiles, L.; Stabler, S. S.; Metallo, C.; Caudill, M. A.; Field, M. S.
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Adequate thymidylate (dTMP or the "T" base in DNA) levels are essential for stability of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Folate and vitamin B12 (B12) are essential cofactors in folate-mediated one carbon metabolism (FOCM), a metabolic network which supports synthesis of nucleotides (including dTMP) and methionine. Perturbations in FOCM impair dTMP synthesis, causing misincorporation of uracil (or a "U" base) into DNA. During B12 deficiency, cellular folate accumulates as 5-methyltetrahdryfolate (5-methyl-THF), limiting nucleotide synthesis. The purpose of this study was to determine how B12 deficiency and dietary folate interact to affect mtDNA integrity and mitochondrial function in mouse liver. Mice expressing reduced methionine synthase (Mtr) levels were used to create a functional B12 deficiency. Folate accumulation, uracil levels, mtDNA content, and oxidative phosphorylation capacity were measured in male Mtr+/+ and Mtr+/- mice weaned onto either a folate-sufficient control diet (2 mg/kg folic acid, C) or a folate-deficient diet (FD, lacking folic acid) for 7 weeks. Mtr heterozygosity led to increased liver 5-methyl-THF levels. Mtr+/- mice consuming the C diet also exhibited a 40-fold increase in uracil in liver mtDNA. However, the combination of Mtr heterozygosity and exposure to the FD diet partially alleviated the level of uracil accumulation in mtDNA. Furthermore, Mtr+/- mice exhibited a 25% decrease in liver mtDNA content and a 20% decrease in maximal oxygen consumption rates. Impairments in mitochondrial FOCM are known to lead to increased uracil in mtDNA. This study demonstrates that impaired cytosolic dTMP synthesis also leads to increased uracil in mtDNA.
Kostrikov, S.; Johnsen, K. B.; Larsen, A. B.; Andresen, T. L.; Moos, T.
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Background and objectivesBrain capillary endothelial cells (BCECs) express transferrin receptor 1 (TfR1) to ensure sufficient iron transport into the brain across the blood-brain barrier (BBB). Our main objective was to examine adult mice subjected to dietary iron deficiency (ID) for possible changes in the content of TfR1 in BCECs and the influence thereof on the uptake and transport of high-affinity anti-transferrin receptor IgG1 antibodies (clone Ri7217). Material and methodsWe subjected adult, female mice to dietary ID for 8 weeks. Iron and copper were measured using inductively coupled plasma mass spectrometry (ICP-MS) in various tissues, including total brain and isolated brain capillaries. Possible effects of ID on cerebral angioarchitecture were estimated using 3D confocal microscopy of optically cleared brain samples with endothelium labelled using intravenous injection of wheat germ agglutinin with subsequent machine learning-based segmentation and vascular tracing. TfR1 was quantified using ELISA. Ri7217 antibodies were conjugated with 1 nm nanogold and brain uptake quantified using ICP-MS. ResultsID significantly reduced the iron content in isolated brain capillaries, liver, spleen, kidney, heart and skeletal muscles. ID increased the copper content in the brain. Analysis of cerebral cortex angioarchitecture revealed no changes following dietary ID except for a minor increase in tortuosity of small-caliber vessels. TfR1 protein was unchanged in the total brain and isolated brain capillaries. In contrast, uptake of nanogold-conjugated Ri7217 increased in the total brain, the supernatant fraction of isolated brain capillaries representing the post-vascular compartment, liver, spleen, and dissected retinae. ConclusionsTargeting TfR1 in ID revealed increased uptake and transport across the BBB of Ri7217 antibodies. Possibly the elevated transport of transferrin receptors through BCECs is due to the increased trafficking of transferrin receptor-containing vesicles in ID, which appeared to have no major effects on the brain angioarchitecture.
Purcell, S. A.; Cohen, T. R.; Gosselin, E. K.; Hildebrand, H.; Drapeau, V.; Panahi, S.
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Background/ObjectivesAssessment of energy requirements and intake is central to the nutrition care process, yet current practices among registered dietitians (RDs) are not well characterized. This study examined how RDs assess energy requirements and intake, including perceived accuracy and resources, and differences by setting and experience. MethodsA cross-sectional bilingual online survey was administered to RDs in Canada. The survey collected information on practice setting and experience, access to variables influencing energy requirements/intake, tool use, and opinions on accuracy and resource needs. Descriptive statistics and comparisons were made by practice setting (clinical, community, other) and years in practice (<5, 5-10, >10 years). Results212 RDs completed the survey (62% clinical, 16% community, 22% other settings; 36% <5 years, 23% 5-10 years, 42% >10 years of practice). Participants rated importance of assessing energy requirements and energy intake as moderately high (6.8{square}{+/-}{square}2.2, 7.1{square}{+/-}{square}2.3 out of 10, respectively) and had regular access to variables needed to calculate energy requirements and intake (e.g., age, sex, weight, disease), although access to body composition, sleep, and stress was limited. Commonly-used tools included body weight-based equations and 24-hour recalls. Confidence was highest for delivering interventions and lowest for assessing intake (p < 0.001), especially among less experienced RDs (p = 0.002). Most respondents expressed interest in improved tools for assessing energy requirements (76%) and intake (74%). ConclusionCurrent RD practices vary, and access to key data is limited, underscoring the need for validated, accessible tools and training to support accurate energy assessment in dietetic care.
Issarapu, P.; Arumalla, M.; Antoun, E.; di Gravio, C.; Ward, K.; Fall, C. H. D.; Prentice, A. M.; Chandak, G. R.; Silver, M. J.
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BackgroundDifferences in body composition during childhood can influence long-term health, with notable links to cardiometabolic disorders in later life. While genetic associations with body composition traits are well-studied, less is known about the role of epigenetic mechanisms, particularly in low- and middle-income countries where the burden of cardiometabolic disease is high. We investigated links between DNA methylation and three compartments of body composition: fat mass, lean mass, and bone measures using data from children enrolled in the Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa (EMPHASIS) study. ResultsWe conducted an epigenome-wide association study (EWAS) of 11 body composition traits assessed through dual-energy X-ray absorptiometry in children from India (age = 5-7 years, n = 686) and The Gambia (age = 7-9 years, n = 289), with blood DNA methylation measured at approximately 800,000 CpGs sites on on the Illumina EPIC array. Cohort-specific analysis identified 15 unique differentially methylated CpGs (dmCpGs) associated with traits across all three compartments of body composition (p<3.6x10-8). Cross-cohort meta-analysis revealed 4 loci associated with lean mass and bone area. Notably, dmCpGs mapping to the SOCS3 gene, previously linked to height in Indian, African and European populations, were associated with lean mass and bone area in both the Indian cohort and combined meta-analyses. Region-level EWAS identified differentially methylated regions (DMRs), linked to lean mass and bone area mapping to SOCS3 and P4HB genes overlapping identified dmCpGs associated with the same phenotypes. Other DMRs mapped to genes including BPNT1, RNU5F-1, LTA, HIF1A, HIF1A-AS1, MTHFD1, and TRIM72 were associated with multiple traits. ConclusionWe report novel DNA methylation signatures associated with body composition traits in children from two low- and middle-income countries, highlighting a potential role for epigenetic mechanisms in shaping early-life body composition.
Godfrey, K. M.; Titcombe, P.; El-Heis, S.; Albert, B. B.; Tham, E. H.; Barton, S. J.; Kenealy, T.; Chong, M. F.-F.; Nield, H.; Chong, Y. S.; Chan, S.-Y.; Cutfield, W.
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BackgroundMaternal vitamin status preconception and during pregnancy have important consequences for pregnancy outcome and offspring development. Changes in status from preconception to early and late pregnancy and postpartum have been inferred from cross-sectional data, with lower pregnancy concentrations often ascribed to plasma volume expansion, but without truly longitudinal data from preconception through pregnancy and post-delivery, and sparse data on the influence of supplementation. This study characterized longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6-months post-delivery, and determined the influence of supplementation. Methods and FindingsBetween 2015-2017, 1729 UK, Singapore and New Zealand women aged 18-38 years planning conception were recruited from the community to a double-blind controlled trial and randomized to a standard (control) or an intervention supplement preconception and throughout pregnancy. Vitamins common to both supplements were folic acid and {beta}-carotene, with the intervention additionally including riboflavin, vitamins B6, B12 and D in amounts available in over-the-counter supplements, alongside iron, calcium and iodine (control and intervention) and myo-inositol, probiotics and zinc (intervention only). We measured maternal plasma concentrations of B-vitamins, vitamin D and insufficiency/deficiency markers (homocysteine, hydroxykynurenine-ratio, methylmalonic acid), at recruitment and 1-month after commencing intervention preconception, in early and late pregnancy, and post-delivery (6-months after supplement discontinuation). From all timepoint data, we derived standard deviation scores (SDS) to characterize longitudinal changes in controls and differences between control and intervention participants. At recruitment preconception, significant proportions had marginal or low plasma status for folate (29.2% <13.6 nmol/L), riboflavin (7.5% <5 nmol/L, 82.0% [≤]26.5 nmol/L), vitamin B12 (9.1% <221 pmol/L) and vitamin D (48.7% <50 nmol/L). Among controls, plasma concentrations showed differing longitudinal patterns from preconception; riboflavin fell through early/late pregnancy, 25-hydroxyvitamin D was unchanged in early pregnancy, and vitamin B6 and B12 concentrations declined through pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation, with 54.2% developing a low late pregnancy vitamin B6 (pyridoxal 5-phosphate <20 nmol/L). Preconception, the control/intervention groups had similar baseline vitamin concentrations; 1-month after supplement commencement, plasma concentrations became substantially higher in intervention participants; riboflavin by 0.77 SDS (95%CI 0.68-0.87), vitamin B6 1.07 (0.99-1.14), vitamin B12 0.55 (0.46-0.64) and vitamin D 0.51 (0.43-0.60), with the higher levels maintained during pregnancy and marked reduction in insufficiency/deficiency markers (lower homocysteine, hydroxykynurenine-ratio, methylmalonic acid) and the late pregnancy prevalence of vitamin D <50 nmol/L reduced from 35.1% to 8.5%. Plasma vitamin B12 was still higher in the intervention group 6-months post-delivery. ConclusionSignificant proportions of preconception women have marginal or low status of folate, riboflavin, vitamin B12 and vitamin D, and many develop markers of vitamin B6 deficiency in late pregnancy. In the absence of supplementation, maternal plasma vitamin concentrations show differing longitudinal patterns from preconception to early and late pregnancy, suggesting plasma volume expansion does not wholly account for lower gestational concentrations. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of deficiency/depletion markers before and during pregnancy, and a higher maternal plasma vitamin B12 was maintained during the recommended lactational period.
Cetinkaya, H.; Valentine, C. J.; Dingess, K. A.; Ollberding, N. J.; Summer, S. S.; Meredith, N. A.; Maria, S. D.; Morrow, A. L.; Nommsen-Rivers, L. A.
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BackgroundPoor diet quality and high body mass index (BMI) contribute to inflammation, which may influence human milk composition and exclusive breastfeeding (EBF) duration. ObjectiveWe evaluated maternal diet and prepregnancy BMI as predictors of human milk C-reactive protein (CRP) and long chain fatty acid concentrations (%LCFA), and EBF duration. MethodsWe utilized the Global Exploration of Human Milk Study-Cincinnati subset (n=114), where healthy dyads continued follow-up if [≥]75% of feeds were breastmilk at 4 weeks postpartum. We computed a Dietary Inflammatory Index (DII) from diet recalls obtained between 4-13 weeks postpartum, where higher score indicates a more proinflammatory diet. Milk CRP and fatty acid analyses were performed on week 4 milk. We compared milk CRP across 4 combinations of DIIxBMI using the Kruskal Wallis test, with BMI categorized as normal versus elevated (<25 versus >25 kg/m2), and DII split at the median. Linear regression was used to examine DII and BMI as predictors of %LCFA. Logistic regression was used to examine DII tertiles and BMI as predictors of EBF duration. ResultsMilk CRP concentrations differed across DIIxBMI groups (p=0.009): the low DII/normal BMI group had the lowest milk CRP (n=30, median [Q1, Q3], 64.3 [38.2, 121.4] ng/mL) versus all other groups (n=70, 124.1 [71.2, 181] ng/mL, p=0.022). Lower milk %LCFA was predicted by higher DII score ({beta}{+/-}SE = -0.68 {+/-} 0.21, p=0.002, n=103) and higher BMI ({beta}{+/-}SE = -0.13 {+/-} 0.01, p=0.043, n=114). Having the highest DII tertile and elevated BMI lowered the odds of EBF at week 6 (OR [95% CI]: 0.26 [0.07, 0.85]) compared to the referent group (low or medium DII, normal BMI). ConclusionsMilk CRP concentrations were lowest in women with a more anti-inflammatory diet and normal BMI. Both higher BMI and proinflammatory diet predict lower milk %LCFA and lower EBF prevalence at week 6.
Nyofane, M.; Hoffman, M. A.; Botha, T.; Feucht, U.
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BackgroundThe increasing population of HIV-exposed-uninfected (HEU) infants are known to be at risk of poor nutritional status and suboptimal growth, with biological risk factors implicated, yet the cost to families of feeding infants is often overlooked. ObjectiveThe study compared the infant feeding practices and costs and macronutrient intake of HEU vs HIV-unexposed-uninfected (HUU) six-month-old infants in the Gauteng Province of South Africa. MethodsA cross-sectional study investigated 46 HEU and 55 HUU infants aged six months and utilised a single quantified 24-hr recall and the FoodFinder program for meal analysis. The estimation of diet cost utilised supermarket food prices based on the 24-hr recall method. ResultsMothers of HEU infants had significantly lower income (p<0.01) and educational attainment (p=0.03). The infant feeding practices differed between HEU vs HUU infants (p=0.05): exclusive breastfeeding (50.0% vs 34.0%) and mixed breastfeeding (38.1% vs 64.2%). Common complementary foods for HEU versus HUU infants included commercial infant cereals (CIC) (48.7% vs 70.9%; p=0.04); fruits and vegetables (33.3% vs 15.7%; p=0.05) and maize meal porridge (25.6% vs 15.7%; p=0.24), respectively. The mean daily cost of diet of HEU vs HUU infants was 8.55{+/-}7.35ZAR ($0.68{+/-}0.59USD) vs 10.97{+/-}7.92ZAR($0.88{+/-}0.63 USD); (p=0.10). Regarding the complementary feeding, there were non-significant differences in protein, fat, and carbohydrate intakes (p>0.05) and their costs per daily intake (p>0.05) between the groups. ConclusionThere are no significant differences in cost, feeding and macronutrient intakes between HEU and HUU. Suboptimal breastfeeding practices remains an issue within the first six months. More sustained effort is required to support and promote exclusive breastfeeding.
Dofat, A.; Jacob, R.; Jacobs, K.; Ahrens, M.; Howe, W. M.
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Dietary choice plays a critical role in metabolic and neurological health, yet the biological factors that shape macronutrient preference remain poorly understood. Evidence from both humans and rodents suggests potential sex differences in the attractiveness of specific nutrients, though findings have been inconsistent and often rely on self-report or diets with mixed macronutrient composition. The present study examined sex differences in macronutrient preference and food-directed behavior in mice using a controlled three-food choice paradigm. Adult male (n = 12) and female (n = 11) C57BL/6J mice were given simultaneous access to foods consisting of fat, sucrose, or a fat-carbohydrate combination across 14 days. Intake, latency to approach, and time spent near each food source were quantified, and estrous cycle stage was monitored in females. Female mice consumed significantly more food than males overall, driven by a selective increase in fat intake. Behavioral measures paralleled these results, with females spending more time in proximity to fat-associated food zones. In contrast, males preferentially consumed the fat-carbohydrate combination and showed weaker nutrient-specific engagement. Estrous cycle stage modestly influenced feeding behavior, with estrus associated with increased overall intake and greater consumption of combination diets, reflecting elevated carbohydrate intake. These findings demonstrate robust sex differences in macronutrient preference and suggest that hormonal state may selectively modulate nutrient-specific feeding behavior.
B R, N.; Rai, S.; Sarin, P.; Suthar, S. B.; Mahajan, H.; Vancha Reddy, A.; G, V.; Banjara, S. K.; Rajendran, A.; R, N. K.; Ajmera, S.; Sengupta, S.; Parasannanavar, D.
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BackgroundModerate acute malnutrition (MAM) remains a major health challenge in India despite ongoing efforts of government nutrition programs. Finger millet (Ragi), a nutrient-dense, climate-resilient crop rich in calcium, fiber, and bioactive compounds, offers potential advantages over conventional cereal-based ready-to-use therapeutic foods (RUTF). This trial evaluated the effects of finger millet-based supplement on anthropometry, body composition, dietary adequacy among MAM children aged 18-59 months. Material & methodsIn this open-label, randomized community-based trial, 221 MAM children were allocated to receive either a finger millet-with-dates supplement (FMD) or the standard wheat/rice-based Balamrutham plus with dates (BMD) for 8 weeks in Anganwadi centers in Hyderabad, India. Anthropometry, body composition (InBody S10), dietary intake (three-day recall), biomarkers, and compliance were assessed at baseline and endpoint, with follow-ups at days 100 and 160. Growth trends were evaluated using repeated-measures ANOVA. Results136 children completed the intervention (FMD: 71; BMD: 65); compliance exceeded 80%. By day 40, both groups showed significant gains in weight (6.3-6.4%), height (2.4%), and MUAC (3.5-6.2%), which continued through day 160. The FMD group showed greater improvements in mineral mass, bone mineral content, and skeletal muscle mass, whereas the BMD group demonstrated higher increases in protein mass and fat-free mass. Dietary recall revealed markedly low micronutrient adequacy among MAM children. No major adverse events were reported. ConclusionFinger millet-based supplementation achieved comparable or superior improvements to cereal-based RUTF, supporting its integration into ICDS and POSHAN 2.0 as a sustainable approach to MAM management.