Methyl Donor Nutrients Research Articles

Peripheral Blood ABCG1 Gene DNA Methylation: Mediating the Relationship between Dietary Intake of Methyl Donor Nutrients and Stroke Risk

Dysregulation of methyl donor nutrients interferes with DNA methylation and is associated with neurological diseases. ABCG1 gene regulates cholesterol to HDL-C, maintains lipid homeostasis, and has been linked to both methyl nutrition and neurological risks. The aim was to investigate whether there is an effect of ABCG1 DNA methylation on the relationship between intake of methyl donor nutrients and the risk of stroke occurrence. We hypothesize that the intake of methyl donor nutrients may influence stroke occurrence by modulating the methylation status of ABCG1. This study utilized a case-control design and selected 52 stroke patients along with 52 healthy controls from Northwest China. Dietary information was collected using a FFQ, and methylation levels were measured at 29 CpG sites of the ABCG1 gene. A significant linear trend was found between dietary intake of the methyl donor nutrient choline and CpG_19.20 methylation of the ABCG1 gene (β = -0.037, P = 0.033). Additionally, a significant association was observed between CpG_19.20 methylation and the risk of stroke (OR 2.325, 95% CI 1.210 - 4.466). Mediation analysis revealed that choline intake indirectly influenced stroke occurrence through its effect on CpG_19.20 methylation levels in the ABCG1 gene (β = -0.015, SE = 0.013, 95% CI = [-0.053, -0.001]). We found that DNA methylation at specific CpG sites of the peripheral blood ABCG1 gene mediates the association between dietary methyl donor nutrient intake and stroke risk in an adult population from Northwest China. New insights are provided on the prevention and treatment of stroke.

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.

Nutrigenetic and Epigenetic Mechanisms of Maternal Nutrition-Induced Glucolipid Metabolism Changes in the Offspring.

Maternal nutrition during pregnancy regulates the offspring's metabolic homeostasis, including insulin sensitivity and the metabolism of glucose and lipids. The fetus undergoes a crucial period of plasticity in the uterus; metabolic changes in the fetus during pregnancy caused by maternal nutrition not only influence fetal growth and development but also have a long-term or even life-long impact for the offspring. Epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNAs, play important roles in intergenerational and transgenerational effects. In this context, this narrative review comprehensively summarizes and analyzes the molecular mechanisms underlying how maternal nutrition, including a high-fat diet, polyunsaturated fatty acid diet, methyl donor nutrient supplementation, feed restriction, and protein restriction during pregnancy, impacts the genes involved in glucolipid metabolism in the liver, adipose tissue, hypothalamus, muscle, and oocytes of the offspring in terms of the epigenetic modifications. This will provide a foundation for the further exploration of nutrigenetic and epigenetic mechanisms for integrative mother-child nutrition and promotion of the offspring's health through the regulation of maternal nutrition during pregnancy. Note: This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.

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

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. 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. 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). 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.

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women.

One-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women. Data were obtained from the baseline of the Mother-Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24-32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire. Of 397 participants, 82.6% were in mid-pregnancy (24-27 gestational weeks) and 17.4% were in late-pregnancy (28-32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (β = -0.330, p < 0.05) and vitamin B6 (β = -0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (β = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (β = -0.181, p < 0.05). The blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.

Association of methyl donor nutrients dietary intake and sleep disorders in the elderly revealed by the intestinal microbiome.

Currently, sleep disorders (SD) in the elderly are gaining prominence globally and are becoming a significant public health concern. Methyl donor nutrients (MDNs), such as vitamin B6, vitamin B12, folate, and choline, have been reported to have the potential to improve sleep disorders. Moreover, MDNs help to maintain gut flora homeostasis, and are closely associated with the development of SD. Nevertheless, there has been a lack of comprehensive human studies examining the association between MDNs intake and SD. In our study, we comprehensively evaluated the association between MDNs intake and SD in the elderly and used 16S rRNA gene sequencing to explore the underlying mechanism. We found that the SD group (n = 91) had a lower methyl-donor nutritional quality index (MNQI) and a trend toward lower intake compared to the control group (n = 147). Based on the intestinal microbiome, the beta diversity of the intestinal flora was higher in the high methyl-donor nutritional quality (HQ) group compared to the low methyl-donor nutritional quality (LQ) group, and it was lower in the SD group compared to the control group. This suggests that MDNs may regulate sleep by modulating the abundance distribution of the microbiota. Subsequently, we performed correlation analyses between the relative abundance of the microbiota, MDNs intake, and the Pittsburgh Sleep Quality Index (PSQI), identifying five genera with potential regulatory roles. The KEGG pathway analysis indicated that energy metabolism and one-carbon metabolism might be the pathways through which MDNs modulate sleep. This study offers dietary guidance strategies for managing SD in the elderly and provides insights for targeted microbiota intervention.

Associations of dietary methyl donor nutrients with common psychological conditions (depression, anxiety and stress) among reproductive-aged women in Kabul, Afghanistan

BackgroundHigher levels of methyl donor nutrients may be associated with better psychological conditions. Little is known about the association of methyl donor nutrients with psychological conditions among women especially in Asian countries such as Afghanistan.MethodThis cross-sectional study was conducted in Kabul, Afghanistan to assess the association of methyl donor nutrients with common psychological conditions (depression, anxiety and stress) among reproductive-aged women using multistage random sampling to choose one health center from each municipality out of four cardinal directions. Finally a sample of 421 reproductive-aged women with a mean BMI of 23.3 ± 5.0 kg/m2 and an age range of 15–45 years were collected. All women’s dietary intakes were obtained using a 24-recall questionnaire. Depression, Anxiety and Stress Scale − 21 Items (DASS-21) was used to assess psychological conditions. Chi-square tests and one-way ANOVAs were performed to assess general characteristics. Residual model test while adjusting for energy intake was used to assess nutrient intake of methyl donor nutrients and food groups. We fitted logistic regression models to assess risk for Common mental health problems (CMHPs) based on methyl donor tertiles.ResultWe observed that there is no significant association between methyl donor nutrients and psychological disorders in both crude and adjusted models (depression, OR = 0.95, CI: 0.48; 1.88; anxiety, OR = 0.88, CI: 0.43, 1.79; stress, OR = 0.73, CI: 0.38, 1.40), (p > 0.05).ConclusionOverall, we did not find any significant association between methyl donor nutrients and depression, anxiety and stress.

Methyl donor diet attenuates intimal hyperplasia after vascular injury in rats

Environmental factors, particularly dietary habits, play an important role in cardiovascular disease susceptibility and progression through epigenetic modification. Previous studies have shown that hyperplastic vascular intima after endarterectomy is characterized by genome-wide hypomethylation. The purpose of this study was to investigate whether methyl donor diet affects intimal hyperplasia and the possible mechanisms involved. Intimal hyperplasia was induced in SD rats by carotid artery balloon injury. From 8 d before surgery to 28 d after surgery, the animals were fed a normal diet (ND) or a methyl donor diet (MD) supplemented with folic acid, vitamin B12, choline, betaine, and zinc. Carotid artery intimal hyperplasia was observed by histology, the effect of MD on carotid protein expression was analyzed by proteomics, functional clustering, signaling pathway, and upstream-downstream relationship of differentially expressed proteins were analyzed by bioinformatics. Results showed that MD attenuated balloon injury-induced intimal hyperplasia in rat carotid arteries. Proteomic analysis showed that there were many differentially expressed proteins in the common carotid arteries of rats fed with two different diets. The differentially expressed proteins are mainly related to the composition and function of the extracellular matrix (EMC), and changes in the EMC can lead to vascular remodeling by affecting fibrosis and stiffness of the blood vessel wall. Changes in the levels of vasculotropic proteins such as S100A9, ILF3, Serpinh1, Fbln5, LOX, HSPG2, and Fmod may be the reason why MD attenuates intimal hyperplasia. Supplementation with methyl donor nutrients may be a beneficial measure to prevent pathological vascular remodeling after injury.

Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts.

We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professionals Follow-Up Study (1986-2016). Dietary data were collected every 2-4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance-weighted fixed-effects meta-analyses. During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00-1.11]) but not after additional adjustment for red meat intake (1.04 [0.99-1.10]). No evidence of association was observed between intakes of folate and diabetes. The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.

Association between nutrient intake related to the one-carbon metabolism and colorectal cancer risk: a case–control study in the Basque Country

PurposeEpidemiologic evidence for the association between methyl-donor nutrient intake and colorectal cancer (CRC) risk remains inconclusive. We aimed to examine the relationship between intake of vitamins of the B group, methionine, total choline and betaine and CRC risk, in a population from the CRC screening programme in the Basque Country.DesignThis observational study included 308 patients with CRC and 308 age- and sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic, and health status information was collected. Conditional logistic regression was used to estimate the odds ratios (ORs) for CRC risk.ResultsThe adjusted ORs for CRC risk decreased with higher intakes of choline and betaine (p < 0.05). After further adjustment for folate, high intake of choline and betaine remained associated with a reduced CRC risk (adjusted model for choline, OR third tertile vs first tertile = 0.45, 95% CI 0.26–0.80, p = 0.006; for betaine, OR third tertile vs first tertile = 0.27, 95% CI 0.16–0.47, p < 0.001). Regarding the other nutrients, our findings indicated a non-significant decrease in CRC risk with the high level of intake.ConclusionsOur data suggest that choline and betaine intake influence CRC risk in the studied population.

OR18-03-23 Maternal Methyl Donor Nutrients Supplementation to a High-Fat High-Sucrose Diet Modulates Systemic Vitamin D Signaling and Renal Inflammation Among Adult Offspring

OR18-03-23 Maternal Methyl Donor Nutrients Supplementation to a High-Fat High-Sucrose Diet Modulates Systemic Vitamin D Signaling and Renal Inflammation Among Adult Offspring

P07-050-23 Serum Methyl-Donor Nutrient Status in Relation to the Risk of Gestational Diabetes Mellitus

P07-050-23 Serum Methyl-Donor Nutrient Status in Relation to the Risk of Gestational Diabetes Mellitus

Associations between maternal folate status and choline intake during pregnancy and neurodevelopment at 3-4 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) study.

Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children's neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3-5 years of age, their children's neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence - Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children - Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = -0.44; 95%CI -0.81, -0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children's intelligence, language, memory, or motor outcomes at 3-4 years of age; however, their interaction may have aninfluence children's executive functions.

Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor-enriched diet.

Fetal alcohol exposure at any stage of pregnancy can lead to fetal alcohol spectrum disorder (FASD), a group of life-long conditions characterized by congenital malformations, as well as cognitive, behavioral, and emotional impairments. The teratogenic effects of alcohol have long been publicized; yet fetal alcohol exposure is one of the most common preventable causes of birth defects. Currently, alcohol abstinence during pregnancy is the best and only way to prevent FASD. However, alcohol consumption remains astoundingly prevalent among pregnant women; therefore, additional measures need to be made available to help protect the developing embryo before irreparable damage is done. Maternal nutritional interventions using methyl donors have been investigated as potential preventative measures to mitigate the adverse effects of fetal alcohol exposure. Here, we show that a single acute preimplantation (E2.5; 8-cell stage) fetal alcohol exposure (2 × 2.5 g/kg ethanol with a 2h interval) in mice leads to long-term FASD-like morphological phenotypes (e.g. growth restriction, brain malformations, skeletal delays) in late-gestation embryos (E18.5) and demonstrate that supplementing the maternal diet with a combination of four methyl donor nutrients, folic acid, choline, betaine, and vitamin B12, prior to conception and throughout gestation effectively reduces the incidence and severity of alcohol-induced morphological defects without altering DNA methylation status of imprinting control regions and regulation of associated imprinted genes. This study clearly supports that preimplantation embryos are vulnerable to the teratogenic effects of alcohol, emphasizes the dangers of maternal alcohol consumption during early gestation, and provides a potential proactive maternal nutritional intervention to minimize FASD progression, reinforcing the importance of adequate preconception and prenatal nutrition.

Methyl Donor Micronutrients: A Potential Dietary Epigenetic Target in Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an aberrant immune response and persistent inflammation. Its pathogenesis remains unknown; however, a complex interaction between environmental, genetic, and epigenetic factors has been suggested to cause disease onset. Several studies have demonstrated that epigenetic alterations, such as DNA hypomethylation, miRNA overexpression, and altered histone acetylation, may contribute to SLE onset and the disease's clinical manifestations. Epigenetic changes, especially methylation patterns, are modifiable and susceptible to environmental factors such as diet. It is well known that methyl donor nutrients, such as folate, methionine, choline, and some B vitamins, play a relevant role in DNA methylation by participating as methyl donors or coenzymes in one-carbon metabolism. Based on this knowledge, this critical literature review aimed to integrate the evidence in animal models and humans regarding the role of nutrients in epigenetic homeostasis and their impact on immune system regulation to suggest a potential epigenetic diet that could serve as adjuvant therapy in SLE.

Impact of Methyl-Donor Micronutrient Supplementation on DNA Methylation Patterns: A Systematic Review and Meta-Analysis of in vitro, Animal, and Human Studies

Background: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear. Objectives: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation. Methods: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation. Results: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as “high risk” or “some concerns.” Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo. Conclusion: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.

Supplementation of Methyl-Donor Nutrients to a High-Fat, High-Sucrose Diet during Pregnancy and Lactation Normalizes Circulating 25-Dihydroxycholecalciferol Levels and Alleviates Inflammation in Offspring.

A Western-style diet that is high in fat and sucrose has been shown to alter DNA methylation and epigenetically modify genes related to health risk in offspring. Here, we investigated the effect of a methyl-donor nutrient (MS) supplemented to a high-fat, high-sucrose (HFS) diet during pregnancy and lactation on vitamin D (VD) status and inflammatory response in offspring. After mating, 10-week-old female Sprague-Dawley (SD) rats (n = 10/group) were randomly assigned to one of the four dietary groups during pregnancy and lactation: (1) control diet (CON), (2) CON with MS (CON-MS), (3) HFS, and (4) HFS with MS (HFS-MS). Weanling offspring (three weeks old) were euthanized and sacrificed (n = 8-10/sex/group). The remaining offspring (n = 10/sex/group) were randomly assigned to either a CON or an HFS diet for 12 weeks and sacrificed at 15 weeks of age. Our results indicated that prenatal MS supplementation, but not postnatal diet, restored low vitamin D status and suppressed elevation of proinflammatory cytokine induced by maternal HFS in the offspring. Furthermore, both prenatal and postnatal diets modulated the abundance of Lactobacillus spp. and Bacteroides spp. in the offspring, a shift that was independent of vitamin D status. Collectively, our data support a role for MS in restoring the perturbation of VD status and normalizing maternal HFS-induced inflammation in the offspring. Further investigation is warranted to elucidate the methylation status of VD metabolism-related pathways in the offspring, as well as the immunomodulatory role of vitamin D during the progression of obesity.

Comparative analysis of methyl–donor nutrient intakes and RCPM cognitive performance among school-aged children

Evidence shows a link between methyl-donor nutrient intakes and a child's cognitive ability. However, this is less known among Ghanaian children who might be at higher risk of methyl-donor nutrient deficiencies. This study showed comparative analysis of methyl-donor nutrient intakes and Raven's Coloured Progressive Matrices (RCPM) test performance among 2073 Ghanaian school children aged 9-13 years across four regions of Ghana. Data for the present study were obtained from the Child Nutrition, Fitness, and Cognition project; a cross-sectional survey conducted in four regions of Ghana. Dietary methyl-donor nutrient values were based on repeated 24h recall data collected during the study periods. Cognitive tests were performed on the 2073 children using Raven's Coloured Progressive Matrices (RCPM) test. We found dietary zinc (adjusted: β=0.21, p=0.003) and methionine (adjusted: β=0.60, p=0.044) intakes to be associated with RCPM scores in the linear regression model. School children living in Northern Region (adjusted OR=0.6, p<0.001, 95% CI=0.4-0.7) and Volta Region (adjusted OR=0.7, p=0.006, 95% CI=0.5-0.9) had lower odds of scoring above the 50th percentile on the RCPM test compared with those living in Greater Accra Region. Children who consumed below the RDA for dietary folate (unadjusted OR=0.8, p=0.055, 95% CI=0.7-1.0) and zinc (unadjusted OR=0.8, p=0.049, 95%CI=0.7-1.0) had lower odds of scoring above the 50th percentile on the RCPM test compared with those who consumed above the RDA for dietary folate and zinc respectively. Children who consumed below the EAR for dietary vitamin B12 (unadjusted OR=0.7, p=0.004, 95% CI=0.6-0.9) had reduced odds of scoring above the 50th percentile on the RCPM test compared with those who consumed above the EAR for dietary vitamin B12. Higher dietary methionine intake was strongly associated with higher RCPM scores. Regional differences, and children's dietary consumption below the EAR/RDA for dietary folate, vitamin B12, and zinc were associated with poor RCPM test performance. School children's nutrient intake should be prioritized for improved cognition.

Association between methyl donor nutrients and metabolic health status in overweight and obese adolescents

Limited evidence is available regarding the association of methyl donor nutrients and adolescents’ metabolic health. Therefore, we investigated the relation between a combination of methyl donor nutrients and metabolic health status of overweight and obese Iranian adolescents. In this cross-sectional study, 203 overweight/obese adolescents were included, using a multistage cluster random-sampling method. Dietary intakes were assessed by a validated food frequency questionnaire. Methyl donor nutrient score (MDNS) was constructed based on deciles of vitamins B2, B6, B9, B12, methionine, choline and betaine. Glycemic profile, lipid profile, blood pressure and anthropometric indices were collected. Participants were classified as metabolically healthy obese or unhealthy obese (MUO) based on International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Mean age of adolescents was 13.98 pm 1.61 y and 50.2% of them was girls. After controlling all of the confounders, individuals in the top tertile of MDNS, had lower odds of MUO (OR 0.36; 95% CI 0.13–0.95) according to IFD criteria. Considering IDF/HOMA-IR criteria, an inverse marginally significant association was observed between the highest tertile of MDNS and odds of MUO (OR 0.36; 95% CI 0.12–1.02) in the fully-adjusted model. Furthermore, significant inverse association was found between each unit increase in MDNS and odds of MUO based on IDF criteria, but not for IDF/HOMA-IR definition. We found that overweight/obese adolescents with higher dietary intakes of methyl donor nutrients were less likely to be metabolically unhealthy. Further studies are needed to confirm the findings.

Supplementation of a High-Fat High-Sucrose Diet With Methyl-Donor Nutrients During Pregnancy and Lactation Modulates the Colonic Vitamin D Signaling Pathway in Weaned Rats

ObjectivesSuboptimal vitamin D status is highly prevalent in obese individuals, predisposing them to higher risks for gastrointestinal and immunological dysfunctions. Evidence has shown that maternal methyl-donor nutrient supplementation (MS) can modify DNA methylation status and improve metabolic health in their offspring. Here, we investigated if MS supplementation in an obesogenic diet during pregnancy and lactation can modulate the vitamin D signaling pathway and gut immunity in offspring at weaning.MethodsAfter mating, 12-week-old female Sprague-Dawley rats were randomly assigned (n = 10/group) to receive control diet (CON), CON supplemented with methyl-donor nutrients (CON-MS), high-fat high-sucrose diet (HFS), or HFS supplemented with methyl-donor nutrients (HFS-MS). Diets were given during gestation and lactation periods. At weaning (21 days), the offspring (n = 6/group/sex) were euthanized. Serum, colonic mucosa, and cecal content were collected for analysis.ResultsSerum levels of 25-hydroxycholecalciferol (25D) in weaned pups from CON-MS and HFS-MS dams were 50% greater (P < 0.001) than pups born to CON dams but did not differ from pups born to HFS dams. Diets did not affect serum 25D levels in dams. Gene expressions of colonic vitamin D receptor (VDR), and its downstream target, cathelicidin, in pups from HFS-MS dams was 3-fold (P < 0.008) and 2.5-fold (P < 0.062) lower, respectively, than pups of HFS dams, and did not differ from pups of CON or CON-MS dams. A positive correlation was demonstrated between colonic VDR and the mRNA expressions of colonic pro-inflammatory modulators, TLR4, IL-1β, and IL-6, and the tight junction protein, ZO-1, respectively.ConclusionsOur results support a role for MS in regulating colonic vitamin D signaling in offspring born to HFS dams, independent of maternal vitamin D status. The upregulation of VDR and the production of antimicrobial peptide, cathelicidin, in pups born to HFS dams could be a compensatory mechanism to suppress colonic low-grade inflammation induced by maternal high-fat diet. Further investigation is warranted to delineate the role of MS in vitamin D-mediated immune regulation, and whether an early establishment of vitamin D status is essential for health outcomes in adulthood.Funding SourcesThis study is supported by Texas State University startup and indirect cost return funds.