Choline consumption reduces CVD risk via body composition modification.

Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target.

Association of Methyl Donor Nutrients' Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome.

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among the elderly, presenting a significant public health concern. However, there is currently a deficiency in pharmacological interventions that can effectively cure or significantly reverse the progression of cognitive impairment. Methyl donor nutrients (MDNs), including folic acid, choline, and vitamin B12, have been identified as potential enhancers of cognitive function. Nevertheless, there remains a dearth of comprehensive research investigating the connection between the dietary intake of MDNs and CI. In our study, we comprehensively assessed the relationship between MDNs' dietary intake and CI in older adults, utilizing 16S rRNA gene sequencing to investigate the potential underlying mechanisms. The results showed an obvious difference in the methyl-donor nutritional quality index (MNQI) between the dementia (D) group and the dementia-free (DF) group. Specifically, there was a lower MNQI in the D group than that in the DF group. For the gut microbiome, the beta diversity of gut flora exhibited higher levels in the high methyl-donor nutritional quality (HQ) group as opposed to the low methyl-donor nutritional quality (LQ) group, and lower levels in the D group in comparison to the DF group. Subsequently, we performed a correlation analysis to examine the relationship between the relative abundance of microbiota, the intake of MDNs, and Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with potential regulatory functions. Additionally, KEGG pathway analyses suggested that the one-carbon metabolism, chronic inflammation, and DNA synthesis potentially serve as pathways through which MDNs may be promising for influencing cognitive function. These results implied that MDNs might have the potential to enhance cognitive function through the regulation of microbiota homeostasis. This study offers dietary recommendations for the prevention and management of CI in the elderly.

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes.

Maternal nutrition during pregnancy and lactation plays an important role in the neurodevelopment of offspring. One-carbon (1C) metabolism, which centers around folic acid and choline, as well as other B vitamins, plays a key role during the closure of the neural tube of the developing fetus. However, the impact of these maternal nutritional deficiencies during pregnancy on offspring health outcomes after birth remains relatively undefined. Furthermore, maternal dietary deficiencies in folic acid or choline may impact other health outcomes in offspring - making this a valuable model. This protocol aims to outline the procedure for inducing a deficiency in 1C metabolism in female mice through dietary modifications. Females are placed on diets at weaning, up to 2 months of age, for 4-6 weeks prior to mating and remain on diet throughout pregnancy and lactation. Offspring from these females can be evaluated for health outcomes. Females can be used multiple times to generate offspring, and tissues from females can be collected to measure for 1C metabolite measurements. This protocol provides an overview of how to induce maternal dietary deficiencies in folic acid or choline to study offspring health outcomes.

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

Usual Choline Intake of Australian Children 6-24 Months: Findings from the Australian Feeding Infants and Toddlers Study (OzFITS 2021).

(1) Background: Despite the important role choline plays in child development, there are no data on dietary choline intake in early childhood in Australia. (2) Aim: In this cross-sectional study, we estimated the usual total choline intake and the proportion exceeding the Adequate Intake (AI) and determined the main dietary sources of choline in infants 6-12 months (n = 286) and toddlers 12-24 months (n = 475) of age. (3) Methods: A single 24-h food record with repeats collected during the 2021 Australian Feeding Infants and Toddlers Study (OzFITS 2021) was used to estimate dietary choline intake. (4) Results: The mean choline intake was 142 ± 1.9 mg/day in infants and 181 ± 1.2 mg/day in toddlers. Only 35% of infants and 23% of toddlers exceeded the AI for choline based on Nutrient Reference Values (NRVs) for Australia and New Zealand. Breastmilk was the leading source of choline, contributing 42% and 14% of total choline intake in infants and toddlers, respectively; however, egg consumers had the highest adjusted choline intakes and probability of exceeding the AI. (5) Conclusions: Findings suggest that choline intake may be suboptimal in Australian infants and toddlers. Further research to examine the impact of low choline intake on child development is warranted.

Choline-An Underappreciated Component of a Mother-to-Be's Diet.

The nutritional status of the mother-to-be has a key impact on the proper development of the fetus. Although all nutrients are important for the developing baby, recent research indicates the importance of adequate choline intake during the periconceptional period, pregnancy, and lactation. Choline plays a key role in the biosynthesis of cell membranes, supporting liver function, neurotransmission, brain development, and DNA and histone methylation. Choline participates in the formation of a child's nervous system, supports its cognitive development, and reduces the risk of neural tube defects. The human body is incapable of producing sufficient choline to meet its needs; therefore, it must be obtained from the diet. Current data indicate that most women in their reproductive years do not achieve the recommended daily intake of choline. The presented narrative review indicates the importance of educating mothers-to-be and thereby increasing their awareness of the effects of choline on maternal and child health, which can lead to a more aware and healthy pregnancy and proper child development.

Dietary choline intake in European and non-european populations: current status and future trends-a narrative review.

BACKGROUND: Choline is a nutrient necessary for the proper functioning of the body with a multidimensional impact on human health. However, comprehensive studies evaluating the dietary intake of choline are limited. The aim of this narrative review is to analyze current trends in choline intake in European and non-European populations. The secondary aim was to discuss possible future choline trends. METHODS: The search strategy involved a systematic approach to identifying relevant literature that met specific inclusion criteria. Observational studies and randomized clinical trials were searched for in PubMed and Scopus databases from January 2016 to April 2024. This review includes the characteristics of study groups, sample sizes, methods used to assess choline intake and time period, databases used to determine intake, choline intakes, and the main sources of choline in the diet. The review considered all population groups for which information on choline intake was collected. RESULTS: In most studies performed in Europe after 2015 choline intake did not exceed 80% of the AI standard value. The mean choline intake for adults in different European countries were 310 mg/day, while the highest value was reported for Polish men at 519 mg/day. In non-European countries, mean choline intakes were 293 mg/day and above. The main reported sources of choline in the diet are products of animal origin, mainly eggs and meat. The available data describing the potential intake of these products in the EU in the future predict an increase in egg intake by another 8% compared to 2008-2019 and a decrease in meat intake by about 2 kg per capita from 2018 to 2030. CONCLUSIONS: In the last decade, choline intake among adults has been insufficient, both in Europe and outside it. In each population group, including pregnant women, choline intake has been lower than recommended. Future choline intake may depend on trends in meat and egg consumption, but also on the rapidly growing market of plant-based products. However, the possible changes in the intake of the main sources of choline may lead to either no change or a slight increase in overall choline intake.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. METHODS: Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). RESULTS: Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. CONCLUSIONS: Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality.

BACKGROUND: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. METHODS: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. RESULTS: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60-0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. CONCLUSION: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.

Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha (Ppara) and low-density lipoprotein receptor (Ldlr), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.

Disrupted one-carbon metabolism in heifers negatively affects their health and physiology.

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ±â€…12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60 g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.

The feeding of one-carbon metabolites (including methionine and B vitamins) has been shown to improve fetal growth and milk production in species such as mice, sheep, and dairy cattle. Extending this to beef cattle around the time of breeding is a growing area of research. Our group previously determined that one-carbon metabolite supplementation to beef heifers altered the abundance of circulating methionine-folate cycle intermediates in a dose-dependent manner. Therefore, we aimed to determine a whole-body response to one-carbon metabolite supplementation in heifers by measuring the effects on specific physiological systems as well as a total systemic response. We determined that treatments that negatively altered the methionine-folate cycle yielded a fundamental negative whole-body response to supplementation.

An inverse association of dietary choline with atherosclerotic cardiovascular disease among US adults: a cross-sectional NHANES analysis.

BACKGROUND: The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study was conducted in 5525 individuals from the NHANES between 2011 and 2018. Participants were categorized into the ASCVD (n = 5015) and non-ASCVD (n = 510) groups. Univariable and multivariable-adjusted regression analyses were employed to investigate the relationship between diet choline and pertinent covariates. Logistic regression analysis and restricted cubic spline analysis were used to evaluate the association between choline intake and ASCVD. RESULTS: ASCVD participants had higher choline intake compared to those without ASCVD. In the higher tertiles of choline intake, there was a greater proportion of males, married individuals, highly educated individuals, and those with increased physical activity, but a lower proportion of smokers and drinkers. In the higher tertiles of choline intake, a lower proportion of individuals had a history of congestive heart failure and stroke. After adjusting for age, gender, race, ethnicity, and physical activity, an inverse association between choline intake and heart disease, stroke, and ASCVD was found. A restricted cubic spline analysis showed a mirrored J-shaped relationship between choline and ASCVD, stroke and congestive heart failure in males. There was no association between dietary choline and metabolic syndrome. CONCLUSION: An inverse association was observed between choline intake and ASVCD among U.S. adults. Further large longitudinal studies are needed to test the causal relationship of choline and ASVCD.

Association of Egg Intake With Alzheimer's Dementia Risk in Older Adults: The Rush Memory and Aging Project.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer's dementia and AD is unknown. OBJECTIVES: To examine the association of egg consumption with Alzheimer's dementia risk among the Rush Memory and Aging Project cohort. METHODS: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants' first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer's dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer's dementia. RESULTS: This study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer's dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer's dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer's dementia was mediated through dietary choline. CONCLUSIONS: These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer's dementia and AD pathology, and the association with Alzheimer's dementia is partially mediated through dietary choline.

Maternal One-Carbon Nutrient Intake and Risk of Being Overweight or Obese in Their Offspring-A Transgenerational Prospective Cohort Study.

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.

Role of one-carbon nutrient intake and diabetes during pregnancy in children's growth and neurodevelopment: A 2-year follow-up study of a prospective cohort.

BACKGROUND & AIMS: Both maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B12, have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort. METHODS: In this study, women with (n = 18) and without (n = 20) GDM were recruited at 25-33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-h dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children's developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status. RESULTS: We found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children's buccal cells was not associated with any maternal 1C nutrients. CONCLUSIONS: In conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes.

Dietary intake of methyl donor nutrients in relation to metabolic health status, serum levels of brain-derived neurotrophic factor and adropin.

BACKGROUND AND AIMS: There is a lack of evidence on dietary intake of methyl donor nutrients with metabolic health status and related biomarkers. Thus, this study aimed to assess the relation between methyl donor nutrients intake and metabolic health status with regarding the interactive roles of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. METHODS: This cross-sectional survey was conducted among 527 Iranian adults (45.7% female) selected by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate participants' dietary intake. Metabolic unhealthy status was defined by Wildman criteria as having ≥ 2 of hyperglycemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, chronic inflammation, and insulin resistance. Concentrations of metabolic parameters, BDNF and adropin were determined using fasting blood samples. RESULTS: An inverse association was found between methyl donor nutrients intake and metabolically unhealthy status in multivariable-adjusted model (ORT3 vs. T1 = 0.30; 95%CI: 0.12-0.75). This association was especially significant among overweight/obese adults and was stronger in women. Additionally, consumption of vitamin B6 and choline was separately related to reduced odds of metabolically unhealthy status. Methyl donor intake was not significantly related to low BDNF (ORT3 vs. T1 = 0.93; 95%CI: 0.60-1.44) and adropin (ORT3 vs. T1 = 0.71; 95%CI: 0.44-1.15). However, the interaction between high methyl donor nutrients intake and high BDNF was related to lower odds of metabolically unhealthy status in multivariable-adjusted model (ORMDNS∗BDNF = 0.27; 95%CI: 0.11-0.67). CONCLUSION: Higher intake of methyl donor nutrients, alone and in interaction with BDNF levels, was associated with decreased odds of metabolically unhealthy status in Iranian adults.

Plant- and Animal-Derived Dietary Sources of Phosphatidylcholine Have Differential Effects on Immune Function in The Context of A High-Fat Diet in Male Wistar Rats.

BACKGROUND: Phosphatidylcholine (PC) derived from eggs has been shown to beneficially modulate T cell response and intestinal permeability under the context of a high-fat diet. OBJECTIVES: The objective of this study was to determine whether there is a differential effect of plant and animal-derived sources of PC on immune function. METHODS: Four-week-old male Wistar rats were randomly assigned to consume 1 of 4 diets (n = 10/group) for 12 wk, all containing 1.5 g of total choline/kg of diet but differing in choline forms: 1-Control Low-Fat [CLF, 20% fat, 100% free choline (FC)]; 2-Control High-Fat (CHF, 50% fat, 100% FC); 3-High-Fat Egg-derived PC (EPC, 50% fat, 100% Egg-PC); 4-High-Fat Soy-derived PC (SPC, 50% fat, 100% Soy-PC). Immune cell functions and phenotypes were measured in splenocytes by ex vivo cytokine production after mitogen stimulation and flow cytometry, respectively. RESULTS: The SPC diet increased splenocyte IL-2 production after PMA+I stimulation compared with the CHF diet. However, the SPC group had a lower proportion of splenocytes expressing the IL-2 receptor (CD25+, P < 0.05). After PMA+I stimulation, feeding EPC normalized splenocyte production of IL-10 relative to the CLF diet, whereas SPC did not (P < 0.05). In mesenteric lymph node lymphocytes, the SPC diet group produced more IL-2 and TNF-α after PMA+I stimulation than the CHF diet, whereas the EPC diet group did not. CONCLUSIONS: Our results suggest that both egg- and soy-derived PC may attenuate high-fat diet-induced T cell dysfunction. However, egg-PC enhances, to a greater extent, IL-10, a cytokine involved in promoting the resolution phase of inflammation, whereas soy-PC appears to elicit a greater effect on gut-associated immune responses.

Higher dietary methyl donor micronutrient consumption is associated with higher muscle strength in adults: a cross-sectional study.

Methyl donor micronutrients might affect muscle strength via DNA methylation. We aimed to evaluate the combined relationship of dietary methyl donor micronutrients containing betaine, choline, methionine, vitamin B12, vitamin B6 and folate on muscle strength. This cross-sectional study was conducted on 267 subjects including 113 men and 154 women. Dietary intake of micronutrients was assessed utilising a validated 168-item semi-quantitative FFQ, and methyl donor micronutrient score (MDMS) was calculated. The muscle strength of the participants was measured using a digital handgrip dynamometer. The association was determined using linear regression analysis. The mean age of participants was 36·8 ± 13·2 years. After taking into account potential confounding variables, there was no significant association between dietary methyl donor micronutrient score (MDMS) and the mean left-hand muscle strength (ß: 0·07, se: 0·05, P = 0·07); however, the changes were significant in the mean right-hand muscle strength (ß: 0·09, se: 0·04, P = 0·03). There was also a significant positive relationship between mean muscle strength and methyl donors' intake after fully adjusting for potential confounders (ß: 0·08, se: 0·04, P = 0·04). In conclusion, our findings revealed that higher dietary methyl donor micronutrient consumption is associated with enhanced muscle strength. As a result, advice on a higher intake of methyl donor-rich foods including grains, nuts, dairy products and seafood might be recommended by dietitians as a general guideline to adhere to. Additional prospective studies are needed to confirm the findings.