L-Methylfolate (Folate)

Helicobacter pylori infection, atrophic gastritis, and disabling dementia: the Japan Public Health Center-based Prospective Study.

Matsunaga T, Yamagishi K, Iso H, Yasuda N, Inoue M, Tsugane S · Environmental health and preventive medicine · 2026 · n=817

A meta-analysis reported a positive association between Helicobacter pylori (H. pylori) infection and dementia incidence. H. pylori infection leads to atrophic gastritis (AG) and affects the absorption of nutrients needed for nerve growth, such as vitamin B12 and folate. We aimed to clarify the associations of H. pylori IgG titer, AG, and their combination with disabling dementia incidence and to examine the interaction with vitamin B12 and folate. Anti-H. pylori immunoglobulin G (IgG) titer and pepsinogen levels were measured in 6,817 participants in 1993 (40-69 years), and the incidence of disabling dementia was followed during a median follow-up of 11.0 years. Associations of anti-H. pylori IgG titer, AG, and their combination with disabling dementia were examined using a multivariable-adjusted Cox proportional hazard model, with stratified analyses by dietary intake of vitamin B12 and folate. 1,325 (19.4%) developed disabling dementia during the follow-up period from 2006 to 2016

Causal relationship between B vitamins and neuropsychiatric disorders: A systematic review and meta-analysis.

Ye M, Yang X, Yan J, Yao Y, Lv H, Yue Z · Neuroscience and biobehavioral reviews · 2025

Recently, there has been an increasing interest in how diet and nutrition influence both physical and mental health. Numerous studies have highlighted the potential role of B vitamins in neuropsychiatric disorders (NPDs), yet the exact causal relationship between these nutrients and NPDs remains unclear. In our Mendelian randomization (MR) meta-analysis, we examined the links between B vitamins (VB6, VB12, and folate) and NPDs, utilizing data from previous MR studies, the UK Biobank, and FinnGen databases. Our MR analysis revealed a complex, multifaceted association: VB6 appears to protect against Alzheimer's disease (AD) but may increase the risk for conditions such as major depressive disorder and post-traumatic stress disorder. VB12 seems protective against autism spectrum disorder (ASD) but may heighten the risk for bipolar disorder (BD). Folate has shown protective effects against AD and intellectual disability (ID). The meta-analysis suggests that B vitamins may protect against c

Folate deficiency among women of reproductive age in Ethiopia: A systematic review and meta-analysis.

Gebremichael B, Roba HS, Getachew A, Tesfaye D, Asmerom H · PloS one · 2023

Folate deficiency (FD) can cause adverse health outcomes of public health significance. Although FD is a significant micronutrient deficiency in Ethiopia, concrete evidence is limited. Therefore, this systematic review and meta-analysis was designed to estimate the pooled prevalence of FD among women of reproductive age (WRA). A systematic literature search was performed using MEDLINE, Embase, CINAHL, Google Scholar, African Journals Online (AJOL), The Vitamin and Mineral Nutrition Information System (VMNIS) of the World Health Organization (WHO), Global Health Data Exchange (GHDx), and institutional repositories of major universities and research centers. Additionally, we scanned the reference lists of relevant articles. Two authors independently selected the studies, extracted the data, and the study risk of bias. Heterogeneity was assessed using the I2 statistic. We used a random-effects model to estimate the pooled mean serum/plasma folate and the pooled prevalence of FD. Begg's a

Folic Acid as a Potential Vitamin in Glycemic Control: A Systematic Review.

Aydoğdu GS, Akyakar B, Kalaycı Z, Uçar A, Gezmen-Karadağ M · Current nutrition reports · 2024

This systematic review aims to examine the relationship between serum folate level and folic acid supplements with glycemic control parameters (fasting blood glucose (FBG), insulin level, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and Hemoglobin A1C (HbA1c)) in adult individuals with current studies. In this study, which was designed as a systematic review, the searches were performed on Web of Science, Science Direct, Medline, Wiley, and Cochrane Library databases between April 10, 2023, and May 10, 2023, and the searches were updated between October 16, 2023, and November 14, 2023. Of the 1855 studies obtained from the screening, 17 met the criteria and were included in the systematic review. The PROSPERO system registered the study protocol (ID: CRD42023472434). Although no significant correlation was found between serum folate levels and glycemic control parameters in most of the cross-sectional studies included in this systematic review, most of the randomize

A Systematic Review of Symptoms of Pernicious Anemia.

Seage CH, Bennett A, Ward N, Semedo L, Plattel CHM, Suijker KIM · Food and nutrition bulletin · 2024 · n=103

Pernicious anemia (PA) is a type of macrocytic anemia caused by autoimmune gastritis. To facilitate timely diagnosis and treatment of PA there is a pressing need for improved understanding among Healthcare providers of the condition's symptoms and diagnostic criteria. This systematic review aims to extend existing clinical knowledge on the presentation of PA by determining which symptoms and clinical complications are reported in published adult case studies. Relevant studies were identified through electronic searches of PsycINFO, Embase, and MEDLINE, via OvidSP. During data extraction symptoms were categorized according to the International Classification of Diseases and were grouped based on frequency. Symptoms were documented for 103 adults with a diagnosis of PA; the most frequent symptoms were fatigue (55%), loss of sensation in limbs (32%), excessive weight loss (27%), and a sore tongue (23%). This review highlights the diverse symptomology of adults who are diagnosed with P

Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials.

Borges-Vieira JG, Cardoso CKS · Nutritional neuroscience · 2023 · n=256

This systematic review aimed to evaluate the efficacy of B vitamins and vitamin D therapy in improving the standard treatment of depression and anxiety disorders. We also aimed to gather the evidence supporting the recommendations for supplementation in clinical practice. Performed between March 2020 and September 2021, the main inclusion criteria were randomized controlled trials (RCTs), with patients ≥ 18 years old, both sexes, fulfilling target diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), or mild to severe depressive and anxiety symptoms. In addition, the RCTs were included if the scales to assess the severity of the symptoms were standardized rating scales in psychiatric. Trials that reported diagnoses of schizophrenia, perinatal depression, bipolar depression, sleep disorders, eating disorders, cancer, and multiple sclerosis in association with any of the mentioned diagnoses were excluded. We identified 20 RCTs that match

Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.

Wilson RD, Genetics Committee, Wilson RD, Audibert F, Brock JA, Carroll J · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC · 2015

To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the proper use and dosage of folic acid/multivitamin supplementation before and during pregnancy. Published literature was retrieved through searches of PubMed, Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary and key words (e.g., folic acid, prenatal multivitamins, folate sensitive birth defects, congenital anomaly risk reduction, pre-conception counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1985 and June 2014. Searches were updated on a regular basis and incorporated in the guideline to Jun

Toward an optimal use of folic acid: an advisory report of the Health Council of the Netherlands.

Weggemans RM, Schaafsma G, Kromhout D, Health Council of the Netherlands · European journal of clinical nutrition · 2009

In this report, benefits (preventing neural tube defects and folate deficiency), risks (masking vitamin B(12) deficiency), and uncertain effects (risk of colon cancer) of folic acid supplementation and fortification have been weighted. On the basis of the available evidence, the Health Council of the Netherlands advises the Dutch government to improve the use of folic acid approximately at the time of conception by increased education and the implementation of preconception care. It further recommends considering fortifying staple foods, provided that voluntary fortification of specific foods is banned, as otherwise children are at risk of having an excessively high intake of folic acid. Policy making in relation to fortification should take into account all possible health effects, even if the evidence is not strong.

The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

Wilson RD, Davies G, Désilets V, Reid GJ, Summers A, Wyatt P · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC · 2003

To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. Folic acid supplementation has been proven to decrease or minimize specific birth defects. A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. Peer-review process within the committee structure. The benefit is reduced lethal and severe morbidity birth defec

Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms.

Zhang C, Chen Y, Hou F, Li Y, Wang W, Guo L · Nutrients · 2025 · n=50

Background/Objectives: Research on the safety and efficacy of high-dose folinic acid in Chinese children with autism spectrum disorder (ASD) is limited, and the impact of folate metabolism gene polymorphisms on its efficacy remains unclear. This trial aimed to evaluate the safety and efficacy of high-dose folinic acid intervention in Chinese children with ASD and explore the association between folate metabolism gene polymorphisms and efficacy. Methods: A 12-week randomized clinical trial was conducted, including 80 eligible children with ASD, randomly assigned to an intervention group (n = 50) or a control group (n = 30). The intervention group was administered folinic acid (2 mg/kg/day, max 50 mg/day) in two divided doses. Efficacy was measured using the Psycho-Educational Profile, Third Edition (PEP-3) at baseline and 12 weeks by two trained professionals blind to the group assignments. Methylenetetrahydrofolate reductase (MTHFR C677T, MTHFR A1298C), methionine synthase (MTR A2756G)

Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.

Panda PK, Sharawat IK, Saha S, Gupta D, Palayullakandi A, Meena K · European journal of pediatrics · 2024 · n=40

Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 &

Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder.

Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV · Seminars in pediatric neurology · 2020

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that currently has no approved medical therapy to address core symptoms or underling pathophysiological processes. Several compounds are under development that address both underlying pathophysiological abnormalities and core ASD symptoms. This article reviews one of these treatments, d,l-leucovorin calcium (also known as folinic acid) for treatment of folate pathway abnormalities in children with ASD. Folate is a water-soluble B vitamin that is essential for normal neurodevelopment and abnormalities in the folate and related pathways have been identified in children with ASD. One of these abnormalities involves a partial blockage in the ability of folate to be transported into the brain utilizing the primary transport mechanism, the folate receptor alpha. Autoantibodies which interfere with the function of the folate receptor alpha called folate receptor alpha autoantibodies have been identified in 58%-76% o

Clinical concerns and considerations for leucovorin use in autism spectrum disorder.

Howard C, Mekhail J, Ravikoff LM, Milanaik R · Current opinion in pediatrics · 2026

To provide pediatric clinicians with an overview of current research on leucovorin use in children with autism spectrum disorder (ASD) and a guide to patient evaluation and treatment. An association between cerebral folate deficiency (CFD) and ASD has been suggested in some studies. Autoantibodies that block folate entry into the brain are a cause of CFD and have been detected in 71% of patients with ASD. Leucovorin is a synthetic drug that increases folate concentrations in the brain despite the presence of autoantibodies. Certain studies have indicated reductions in communication deficits in nonverbal children with ASD, particularly those with these autoantibodies, following consistent leucovorin use. However, other studies have found no change in symptoms despite leucovorin intake. The American Academy of Pediatrics (AAP) currently does not recommend use of leucovorin in children with ASD. Due to recent popularity among policymakers and on social media, many pediatricians have rep

Micronutrients in Autoimmune Diseases: Shining a Light on Vitamin D, Cobalamin, Folate, and Iron Metabolism.

Triggianese P, Ramirez GA, Cedola F, Nicola S, Costanzo G, Brussino L · Nutrients · 2026

Background: Autoimmune diseases (AIDs) are characterized by chronic inflammation and tissue damage resulting from abnormal immune responses. While genetic and environmental factors play significant roles in disease development, essential micronutrient deficiencies (MNDs) represent a critical and often overlooked contributor. Methods: This review examines the interactions between micronutrients and immune cells, focusing on vitamin D, vitamin B12, folate (FA), and iron, and their roles in AIDs, such as rheumatoid arthritis, autoimmune thyroid disorders, multiple sclerosis, systemic lupus erythematosus, and other connective tissue diseases. We explore the immunomodulatory effects of these micronutrients, their impact on immune tolerance, and the mechanisms by which MNDs contribute to disease progression. Results: MNDs are commonly observed in patients with AIDs and are associated with worsening immune dysregulation, increased inflammation, and disease severity. Vitamin D plays a pivotal

Intake of one-carbon metabolism nutrients and risk of rheumatoid arthritis: a prospective UK biobank cohort study.

Zhang S, Xia B, Kang Y, Wang Y, Liang Z, He Q · European journal of nutrition · 2025 · n=440

One-carbon metabolism (OCM) nutrients are essential for methylation processes and may be involved in the pathogenesis of rheumatoid arthritis (RA), but prospective evidence remains limited. This study aimed to investigate the association between dietary OCM nutrients and RA risk, and their interactions with genetic and lifestyle factors. A total of 189,440 participants from the UK Biobank were included. Dietary intake was assessed using repeated 24-hour recalls. Nutrient levels were estimated based on McCance and Widdowson's The Composition of Foods and the USDA Food and Nutrient Database for Dietary Studies. Cox proportional hazards models were used to evaluate the independent and joint associations of OCM nutrients, genetic risk, and RA risk. Nonlinear associations were examined using restricted cubic spline. During a median follow-up of 13.43 years, 1,751 RA cases were identified. Participants in the highest quartile of OCM nutrient intake had a significantly lower risk of RA comp

Vitamin B12 or folate deficiency anaemia

National Health Service (NHS)

This NHS page details the causes, symptoms, diagnosis, and treatment of vitamin B12 and folate deficiency anaemia, offering patient-friendly information.

Néevo®/NéevoDHA® P.L.U.S. Program (Progress Through Learning, Understand & Support)

n=53 · NCT01358552 · TERMINATED · TERMINATED

This is an observational study in which patients who have been prescribed Néevo®/NéevoDHA® are invited to participate in surveys about their pregnancy and experiences with Néevo®/NéevoDHA®. The purpose of this study is to increase the understanding of the role of L-methylfolate among patients who are candidates for Néevo®/NéevoDHA®, provide patients with personalized education and support during their pregnancies, and contribute to the overall understanding of the needs and concerns of women facing intermediate- to high-risk pregnancies.

A Retrospective Analysis of Neevo® and Neevo®DHA Compared to a Standard Prenatal Vitamin in Anemia During Pregnancy (N-001)

n=100 · NCT01062958 · COMPLETED · COMPLETED

This study is a multi-site, retrospective chart review to determine the effect of Neevo® or Neevo®DHA (with higher folate and B12) versus standard prenatal vitamins on hemoglobin (Hgb) levels in pregnant women throughout the course of pregnancy. Neevo® is a prescription medical food indicated for the dietary management of women under a doctor's care who face high risk pregnancies, older overactive bladder (OB) patients and patients unable to fully metabolize folic acid. Data will be collected from existing patient charts of subjects administered Neevo® or Neevo®DHA daily compared to subjects administered a prenatal vitamin daily.

Randomized Clinical Trial of Folate Therapy/Placebo for Reduction of Homocysteine Serum Levels in Uremic Patients and Influence on Cardiovascular Mortality

n=186 · NCT00317005 · COMPLETED · COMPLETED

Homocysteine recently gained access to the category of risk factor for the development of atherosclerotic cardiovascular disease in the general population. Chronic renal failure patients, even before being introduced to dialysis therapy have almost universal elevation of serum homocysteine; when on dialysis their mortality is above 50% related to cardiovascular disease that we might now speculate, with a contribution of potentially toxic levels of the aminoacid homocysteine.

Folate monograph

Natural Medicines Database

This monograph provides comprehensive, evidence-based information on Folate, including its uses, dosing, safety, and potential interactions. It typically details the scientific evidence supporting its applications for various health conditions.