Folic Acid and Methyltetrahydrofolate Supplementation in the Mouse Model with Hepatic Steatosis.

Background/objectives: The gene variant results in a thermolabile MTHFR enzyme associated with elevated plasma homocysteine in TT individuals. Health risks associated with the TT genotype may be modified by dietary and supplemental folate intake. Supplementation with methyltetrahydrofolate (methylTHF) may be preferable to folic acid because it is the MTHFR product, and does not require reduction by DHFR to enter one-carbon folate metabolism.

Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP Quant 500 kit.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.

Liquid biopsy to identify Barrett's oesophagus, dysplasia and oesophageal adenocarcinoma: the multicentre study.

Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).

Objective: To develop and test a blood-based assay for EAC and BE.

Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia () was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE.

The 10-year decreasing trend of youth soccer head injuries and concussions presenting to U.S. emergency departments.

Objectives: Nearly 3 million children participate in youth soccer annually in the United States. Popularity of youth soccer within recent years has prompted investigation describing youth-soccer concussion trends presenting to United States emergency departments (EDs).

Methods: Data from National Electronic Injury Surveillance System were analyzed for soccer players 2-18 years old sustaining concussions from January 2013 to December 2022.

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.

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease.

Chronic kidney disease (CKD) impacts 14% of adults in the United States, and African American (AA) individuals are disproportionately affected, with more than 3 times higher risk of kidney failure as compared to White individuals. This study evaluated the effects of base-producing fruit and vegetables (FVs) on cardiorenal outcomes in AA persons with CKD and hypertension (HTN) in a low socioeconomic area. The "Cardiorenal Protective Diet" prospective randomized trial evaluated the effects of a 6-week, community-based FV intervention compared to a waitlist control (WL) in 91 AA adults (age = 58.

Impacts of the Early COVID-19 Pandemic on Depressive Symptoms and Mental Health Among Student-Athletes.

Objective: Social distancing protocols due to the COVID-19 pandemic resulted in premature ending of athletic seasons and cancellation of upcoming seasons, placing significant stress on young athletes. Inability to play or forced early retirement has significant consequences on athlete's mental health, as demonstrated by an extensive body of injury literature. We hypothesize that premature suspension and cancellation of athletic events due to the COVID-19 pandemic leads to higher incidence of depressive symptoms among high-school and collegiate athletes.

Diet-Induced Severe Hyperhomocysteinemia Promotes Atherosclerosis Progression and Dysregulates the Plasma Metabolome in Apolipoprotein-E-Deficient Mice.

Atherosclerosis and resulting cardiovascular disease are the leading causes of death in the US. Hyperhomocysteinemia (HHcy), or the accumulation of the intermediate amino acid homocysteine, is an independent risk factor for atherosclerosis, but the intricate biological processes mediating this effect remain elusive. Several factors regulate homocysteine levels, including the activity of several enzymes and adequate levels of their coenzymes, including pyridoxal phosphate (vitamin B6), folate (vitamin B9), and methylcobalamin (vitamin B12).

Folate Deficiency and/or the Genetic Variant Mthfr Can Drive Hepatic Fibrosis or Steatosis in Mice, in a Sex-Specific Manner.

Scope: Disturbances in one-carbon metabolism contribute to nonalcoholic fatty liver disease (NAFLD) which encompasses steatosis, steatohepatitis, fibrosis, and cirrhosis. The goal is to examine impact of folate deficiency and the Mthfr variant on NAFLD.

Methods And Results: This study uses the new Mthfr mouse model for the human MTHFR variant.

A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis.

Ketogenic diets (KDs) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD). Apolipoprotein E deficient (ApoE ) mice were fed a KD (%kcal:81:1:18, fat/carbohydrate/protein), a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal:40:42:18, fat/carbohydrate/protein) for 12 weeks.

Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial.

Background: Folic acid (FA) is the oxidized form of folate found in supplements and FA-fortified foods. Most FA is reduced by dihydrofolate reductase to 5-methyltetrahydrofolate (5mTHF); the latter is the form of folate naturally found in foods. Ingestion of FA increases the plasma levels of both 5mTHF and unmetabolized FA (UMFA).

Linking biomarkers with healthy lifestyle outcomes after stroke: Supplementary results of a 12-month randomized controlled trial.

Background And Aims: Participation in a healthy lifestyle intervention such as the Diabetes Prevention Program Group Lifestyle Balance-adapted for stroke (GLB-CVA) may reduce stroke burden. Identifying biomarkers associated with lifestyle changes may enhance an individualized approach to stroke recovery. We investigated metabolic biomarkers related to cardiovascular and neurological function in individuals with stroke in the GLB-CVA study and healthy (non-stroke) individuals.

Prenatal folic acid and vitamin B imbalance alter neuronal morphology and synaptic density in the mouse neocortex.

Previous reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at the cellular level of either deficient or excessive FA supply by comparably reducing dendritic arborization of cortical projection neurons. Here, we report that excessive amounts of FA decrease arborization of deep layer projection neurons, but not upper layer neurons and that reduced complexity of deep layer neurons is not observed when folic acid is replaced by folinic acid, a stable reduced form of folate.

Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring.

Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet-induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice.

Atorvastatin rescues hyperhomocysteinemia-induced cognitive deficits and neuroinflammatory gene changes.

Background: Epidemiological data suggests statins could reduce the risk of dementia, and more specifically, Alzheimer's disease (AD). Pre-clinical data suggests statins reduce the risk of dementia through their pleiotropic effects rather than their cholesterol lowering effects. While AD is a leading cause of dementia, it is frequently found co-morbidly with cerebral small vessel disease and other vascular contributions to cognitive impairment and dementia (VCID), which are another leading cause of dementia.

Micronutrients in High-Fat Diet Modify Insulin Resistance and Its Regulatory Genes in Adult Male Mice.

Scope: Obesity and insulin resistance (IR) are associated with epigenetic changes of gene expression. However, the relationship between micronutrients, epigenetic regulation of gene expression, and IR during development of diet-induced obesity has yet to be defined. Our objective is to describe the effect of micronutrient addition to diets on IR and its related genes during obesity development.

Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring.

Maternal one-carbon metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcomes in offspring.

Targeted metabolomic analysis in Parkinson's disease brain frontal cortex and putamen with relation to cognitive impairment.

We performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson's disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression.

Dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke in middle-aged male and female mice.

Nutrition is a modifiable risk factor for ischemic stroke. As people age their ability to absorb some nutrients decreases, a primary example is vitamin B12. Older individuals with a vitamin B12 deficiency are at a higher risk for ischemic stroke and have worse stroke outcome.

Revisiting One-Carbon Metabolites in Human Breast Milk: Focus on S-Adenosylmethionine.

Breastfeeding is the gold standard for early nutrition. Metabolites from the one-carbon metabolism pool are crucial for infant development. The aim of this study is to compare the breast-milk one-carbon metabolic profile to other biofluids where these metabolites are present, including cord and adult blood plasma as well as cerebrospinal fluid.

Methylenetetrahydrofolate reductase deficiency and high-dose FA supplementation disrupt embryonic development of energy balance and metabolic homeostasis in zebrafish.

Folic acid (synthetic folate, FA) is consumed in excess in North America and may interact with common pathogenic variants in methylenetetrahydrofolate reductase (MTHFR); the most prevalent inborn error of folate metabolism with wide-ranging obesity-related comorbidities. While preclinical murine models have been valuable to inform on diet-gene interactions, a recent Folate Expert panel has encouraged validation of new animal models. In this study, we characterized a novel zebrafish model of mthfr deficiency and evaluated the effects of genetic loss of mthfr function and FA supplementation during embryonic development on energy homeostasis and metabolism.

Genetic expression changes and pathologic findings associated with hyperhomocysteinemia in human autopsy brain tissue.

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking.