Research
Folate
55 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
Profile of neural tube defects in pediatric patients in Nigeria: A systematic review.
Systematic review of 63 studies on neural tube defects (NTDs) in Nigeria, involving 3,390 patients. The review highlights trends in folate supplementation, showing an increase from 12.5% (1990-99) to 60.9% (2020-23), and a decline in mortality rates over the decades. Despite improvements, challenges remain in consistent folate supplementation and healthcare access.
Global folate deficiency among adolescent girls: A systematic review and meta-analysis.
This systematic review and meta-analysis assessed the global prevalence of folate deficiency among adolescent girls. The pooled global prevalence was found to be 26.9%, with the highest rate observed in Africa at 35.5%. The study highlights folate deficiency as a significant public health concern, particularly in low-resource settings.
Folate Intake and Breast Cancer Risk: A Systematic Review and Meta-Analysis.
Systematic review and meta-analysis evaluating the relationship between folate intake and breast cancer risk in adult women. Most studies found a direct association between folate intake and reduced breast cancer risk, but the meta-analysis indicated no significant effect, with results being inconsistent.
Folate and global health umbrella review series, part 2: syntheses on cancers.
Systematic review and meta-analysis examining the relationship between folate status and cancer risk. The evidence is equivocal, with low folate potentially increasing cancer risk and high-dose folic acid supplementation possibly having adverse effects. Highly suggestive associations were found for colorectal, oesophageal, and childhood brain and spinal tumours.
Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Systematic review and meta-analysis of 25 cohort studies with 423,304 participants examining folate intake and biomarkers in relation to mortality risk. Found significant inverse relation between dietary folate intake and risk of all-cause and CVD mortality, but not with folate biomarkers.
Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo.
This randomized, placebo-controlled trial measured plasma folate concentrations in Plasmodium falciparum-infected children treated with artemisinin combination therapy and single low-dose primaquine or placebo. The study found that SLDPQ and G6PD status did not compromise posttreatment plasma folate concentrations, supporting the safety of SLDPQ use without G6PD testing.
The effects of methyl nutrients on cognition and one carbon metabolism in older adults with mild cognitive impairment, A systematic review and meta-analysis.
Systematic review and meta-analysis evaluating the effects of methyl nutrient supplementation, specifically folate and vitamin B12, on cognitive function and one-carbon metabolism in older adults with mild cognitive impairment. The combined intervention of folate and vitamin B12 was found to slow cognitive decline, reduce serum homocysteine concentration, and elevate serum folate and vitamin B12 concentrations.
Folate exposures and risk of colorectal cancer: an umbrella review of meta-analyses of observational studies and randomised controlled trials.
Umbrella review of meta-analyses evaluating associations between folate exposures and colorectal cancer (CRC) risk. Moderate-quality evidence supports an inverse association between total folate intake and CRC risk, while low-quality evidence suggests inverse associations for dietary folate and folic acid supplements. Elevated circulating folate levels may provoke advanced-stage tumors, and folic acid supplements may increase adenoma recurrence risk.
Folic acid - importance for human health and its role in COVID-19 therapy.
Systematic review of literature on folic acid (B9) and its impact on human health, highlighting its role in preventing neural tube defects, megaloblastic anemia, and certain cancers, as well as its importance in immune function, particularly in the context of COVID-19. Emphasizes the need for nutritional education due to widespread deficiencies.
Impact of Methyl-Donor Micronutrient Supplementation on DNA Methylation Patterns: A Systematic Review and Meta-Analysis of in vitro, Animal, and Human Studies
Systematic review and meta-analysis of 57 studies on methyl-donor micronutrient supplementation and DNA methylation. Meta-analysis showed that high doses of folic acid increased DNA methylation in animal models, but human trials showed no significant changes compared to placebo. Heterogeneity in studies limits clinical recommendations.
Folate, folic acid, and chemotherapy-induced toxicities: A systematic literature review.
Systematic literature review on the intake and status of folate and folic acid in relation to chemotherapy-induced toxicities in cancer patients. A deficient folate status was associated with higher toxicities in antifolate treatments, while higher folate status was linked to increased toxicities in fluoropyrimidine treatments.
Homocysteine, folate, and nonalcoholic fatty liver disease: a systematic review with meta-analysis and Mendelian randomization investigation.
This systematic review and meta-analysis examined the associations of serum homocysteine and folate levels with non-alcoholic fatty liver disease (NAFLD). The meta-analysis included 22 observational studies with 30,368 participants, finding a positive association between homocysteine and NAFLD risk and an inverse association between folate and NAFLD risk. Mendelian randomization analyses supported these associations, suggesting a potential role for these substances in NAFLD.
Vitamin B12 and Folate as Risk Factors for Retinal Vein Occlusion: A Meta-Analysis.
Meta-analysis evaluating the association between serum vitamin B12/folate levels and retinal vein occlusion (RVO). No significant difference in vitamin B12 levels between RVO patients and controls, but plasma folate levels were significantly lower in RVO patients.
Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review.
Systematic review investigating the association between maternal one-carbon metabolism and foetal/neonatal brain growth. Maternal folate levels were associated with increased foetal head size and cerebellar growth, while folate deficiency was linked to reduced foetal brain volume. Preconceptional folic acid supplementation increased foetal head size.
Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.
Systematic review and meta-analysis evaluating the effect of adjunct therapy with folate (L-Methylfolate or folic acid) on depression scores, response, and remission rates in patients with major depression. The analysis of 6 randomized control trials showed significantly lower depression scores and improved response and remission rates with folate adjunct therapy compared to SSRI/SNRI monotherapy.
The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review.
Systematic review of 23 studies examining the use of folate supplements in psychiatric disorders. Findings suggest folate, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes in major depressive disorder, schizophrenia, autism spectrum disorder, bipolar affective disorder, and ADHD, with minimal side effects.
Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta‐Analysis
This systematic review and meta-analysis investigates the associations between paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. It finds evidence of positive associations between folate concentrations and sperm parameters, as well as increased sperm concentration after folic acid supplementation. Additionally, it shows significant alterations in sperm epigenome methylation and associations between low folate intake and increased risk of congenital malformations.
Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.
Meta-analysis of 29 RCTs with 22,250 participants examining the effect of folate supplementation on insulin resistance and type 2 diabetes outcomes. Folate supplementation lowered fasting insulin and HOMA-IR but showed no overall effects on fasting glucose or HbA1c. Insufficient data to conclusively determine the effect on the development of type 2 diabetes.
Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.
A population-based randomized trial in northern China examined the association between plasma and RBC folate concentrations in women of reproductive age. The study estimated a plasma folate insufficiency threshold corresponding to the RBC folate insufficiency threshold for optimal neural tube defect prevention. The threshold was influenced by BMI, MTHFR genotype, and vitamin B-12 status.
Serum folate levels in bipolar disorder: a systematic review and meta-analysis
Systematic review and meta-analysis investigating serum folate levels in bipolar disorder (BD) patients. The analysis included six articles with 481 BD patients and 760 controls, finding significantly lower serum folate levels in BD patients compared to controls.
Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis.
Systematic review and meta-analysis of RCTs examining folate/folic acid/methylfolate/folinic acid supplementation with antipsychotics in schizophrenia treatment. Pooled treatments improved negative symptoms but not total, positive, general, or depressive symptoms. The treatment was well tolerated with a lower incidence of serious adverse events.
Effects and safety of periconceptional oral folate supplementation for preventing birth defects.
This meta-analysis reviewed randomized trials on periconceptional folate supplementation in 7391 women to assess its effects on preventing neural tube defects (NTDs) and other congenital anomalies. The analysis found that folic acid supplementation significantly reduces the risk of NTDs but does not have a clear effect on other birth defects.
Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis
Systematic review and meta-analysis of 16 prospective studies and 26 case-control studies assessing the association between dietary folate intake and breast cancer risk. Findings suggest a U-shaped relationship, with reduced breast cancer risk for women with daily dietary folate intake between 153 and 400 μg, especially for those with higher alcohol consumption.
Background and rationale of the SU.FOL.OM3 study: double-blind randomized placebo-controlled secondary prevention trial to test the impact of supplementation with folate, vitamin B6 and B12 and/or omega-3 fatty acids on the prevention of recurrent ischemic events in subjects with atherosclerosis in the coronary or cerebral arteries.
The SU.FOL.OM3 study is a double-blind randomized placebo-controlled trial evaluating the impact of supplementation with folate, vitamin B6, B12, and/or omega-3 fatty acids on the prevention of recurrent ischemic events in subjects with atherosclerosis. The study will include 3,000 patients with a history of myocardial infarction, unstable angina, or ischemic stroke, supplemented and followed for five years.
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial.
RCT evaluating the effect of methylfolate, pyridoxal-5'-phosphate, and methylcobalamin supplementation on homocysteine and LDL-C levels in 54 patients with MTHFR, MTR, and MTRR polymorphisms. The treatment group showed significant reductions in homocysteine and LDL-C levels compared to placebo, with more pronounced effects in homozygous minor allele carriers.
Caveat emptor: Folate in unipolar depressive illness, a systematic review and meta-analysis.
Systematic review and meta-analysis evaluating the efficacy of folate and its derivatives in unipolar depression. Significant benefit was found only when folate or methylfolate was used as an adjunct to SSRI therapy, with all evidence graded as low or very low quality.
The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis.
Systematic review and meta-analysis evaluating the effect of folate and folate plus zinc supplementation on endocrine parameters and sperm characteristics in sub-fertile men. Folate plus zinc showed a positive effect on sperm concentration, morphology, and serum folate level compared to placebo, while folate alone improved sperm concentration.
Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis.
Meta-analysis examining the association between serum folate and vitamin B12 concentrations and inflammatory bowel disease (IBD). Findings indicate that IBD patients have significantly lower serum folate levels compared to controls, particularly in ulcerative colitis, while vitamin B12 levels did not differ significantly.
Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation.
The FolATED trial evaluated the clinical and cost-effectiveness of folic acid as an adjunct to antidepressant medication in 475 adults with moderate to severe depression. The study found no significant improvement in mental health measures or cost-effectiveness, suggesting that folic acid is not effective in augmenting antidepressant treatment.
A Randomized Controlled Trial of Folate Supplementation When Treating Malaria in Pregnancy with Sulfadoxine-Pyrimethamine
This randomized, placebo-controlled, double-blind trial investigated the effect of folate supplementation on the efficacy of sulfadoxine-pyrimethamine (SP) for treating uncomplicated malaria in pregnant women. The study found that 5 mg folate supplementation compromised the efficacy of SP, with a higher treatment failure rate compared to placebo.
Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder.
Open-label clinical trial comparing combination therapy of antidepressants with low-dose methylfolate versus antidepressant monotherapy in 44 patients with depressive disorder. The combination therapy showed a 40.33% improvement in depression symptoms compared to 26.43% in monotherapy, with no significant effect on time-lag of outcomes or remission rate.
Large –scale wheat flour folic acid fortification program increases plasma folate levels among women of reproductive age in urban Tanzania
A prospective cohort study evaluated the effectiveness of Tanzania's food fortification program with folic acid among 600 non-pregnant women of reproductive age. Plasma folate levels significantly improved at six and twelve months, reducing the prevalence of folate deficiency from 26.9% at baseline to 5% at twelve months.
A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease.
Phase II RCT of a nutraceutical formulation (folate, alpha-tocopherol, B12, S-adenosyl methionine, N-acetyl cysteine, acetyl-L-carnitine) in 106 individuals with Alzheimer's disease. The NF cohort showed improved cognitive performance and mood compared to placebo within 3 months. Non-significant improvements were reported in Neuropsychiatric Inventory.
Fiber-multivitamin combination therapy: a beneficial influence on low-density lipoprotein and homocysteine.
RCT evaluating a 90% soluble fiber combined with folate and B vitamins on lipid and homocysteine levels in hyperlipidemia patients. The treated group showed significant reductions in LDL-C and ApoB levels, with no adverse changes in TG or HDL-C levels, and a reduction in homocysteine.
Associations of Homocysteine, Folate, and Vitamin B12 with Osteoarthritis: A Mendelian Randomization Study
Mendelian randomization study investigating the causal effects of homocysteine, folate, and vitamin B12 on osteoarthritis (OA). Homocysteine showed adverse effects on OA, while folate and vitamin B12 showed protective effects, particularly on weight-bearing joints and in females.
Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays.
A short-term human study evaluated the bioavailability of folate from spinach, Camembert cheese, and wheat germs compared to pteroylmonoglutamic acid. The study used a cross-over design with 24 subjects. Spinach showed the highest bioavailability, followed by wheat germs and Camembert cheese, highlighting the variability of folate bioavailability from different food sources.
Enhancement of recovery from psychiatric illness by methylfolate.
Double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in 123 patients with major depression or schizophrenia. Methylfolate significantly improved clinical and social recovery compared to placebo, with differences in outcome scores increasing over time.
Enhancement of recovery from psychiatric illness by methylfolate.
Double-blind, placebo-controlled trial of methylfolate (15 mg daily) in 123 patients with major depression or schizophrenia. Methylfolate significantly improved clinical and social recovery compared to placebo, with differences in outcome scores increasing over time.
High serum folate is associated with brain atrophy in older diabetic people with vitamin B12 deficiency
Observational study of 146 older non-demented diabetic individuals examining the interaction between high serum folate and vitamin B12 deficiency on brain volume. Significant gray matter atrophy was observed in subjects with high folate status and VB12 deficiency, suggesting a potential link to increased neurodegeneration.
Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study.
Pilot RCT of a vitamin/nutriceutical formulation in 12 patients with moderate to later-stage Alzheimer's disease. The formulation delayed decline in cognition and mood, with improvements in Dementia Rating Scale and Neuropyschiatric Inventory scores compared to placebo.
Cotrimoxazole and folate metabolism.
RCT comparing serum-folate levels in 13 inpatients receiving cotrimoxazole to 8 controls not receiving antibacterial therapy. The microbiological assay showed a decline in folic-acid levels after cotrimoxazole, but the radioisotope technique showed no significant change, suggesting assay interference rather than true folate depression.
Role of Folate in Liver Diseases
Narrative review discussing the role of folate in liver diseases. Folate deficiency is linked to increased risk of liver fibrosis, cirrhosis, and other liver diseases. The review summarizes studies on folate's role in liver disease pathophysiology and its potential as a therapeutic target.
Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis
This narrative review discusses the use of folate receptor-mediated transporters in cancer therapy and diagnosis. It focuses on the development of folic acid-conjugated drug transporters for targeted drug delivery to cancer cells, highlighting recent advances in nanocarriers and small molecule drug conjugates for brain and breast cancer.
Scientific opinion on the tolerable upper intake level for folate
The EFSA Panel on Nutrition, Novel Foods and Food Allergens reviewed the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews assessed the risk of adverse health effects from excess folate intake, including neuropathy and cancer risks. The ULs for folic acid remain unchanged for all population groups, with specific levels set for different age groups.
Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop.
The paper summarizes an NIH workshop discussing the metabolic and clinical effects of excess folates/folic acid. It highlights concerns about potential adverse effects of excess folic acid intake, such as exacerbation of vitamin B-12 deficiency and increased cancer risk, while noting the lack of conclusive evidence to change public health recommendations.
Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis
Narrative review of seven studies with 709 patients assessing folate supplementation on methotrexate (MTX) treatment for rheumatoid arthritis. Folate reduced the incidence of hepatotoxicity and gastrointestinal side-effects of MTX and promoted compliance by reducing patient withdrawal. No significant difference was found between high-dose and low-dose folate on MTX efficacy or toxicity.
Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study.
Open-label study of 24 individuals with Alzheimer's disease receiving a nutraceutical formulation containing folate, alpha-tocopherol, B12, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine. Participants maintained baseline cognitive performance and behavioral and psychological symptoms of dementia over 12 months, contrasting with expected decline in placebo groups.
Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells
The study developed folate-based nanolipoplexes for gene transfer into human epithelial cells. Folate-modified lipid formulations showed comparable expression levels to lipoplexes and no cytotoxicity. The mechanism involved folate receptor-mediated endocytosis, validated by reduced expression with free folate addition.
Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension.
Open-label pilot study of a vitamin/nutriceutical formulation in 14 individuals with early-stage Alzheimer's disease over 12 months, with a 16-month caregiver extension. Participants improved in Dementia Rating Scale and Clock-drawing tests, with caregivers reporting improvements in Neuropsychiatric Inventory and maintenance in ADL performance. The formulation showed promise compared to historical data for donepezil, galantamine, naproxen, and rofecoxib.
Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression.
This study assessed the efficacy of folinic acid (leucovorin) as an adjunctive treatment for adults with major depressive disorder (MDD) who had an inadequate response to SSRIs. In an 8-week open trial with 22 participants, folate levels increased significantly, and HAM-D-17 scores decreased, indicating modest effectiveness of leucovorin as an adjunct treatment.
The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection
The paper discusses the potential protective role of folic acid supplementation during pregnancy against SARS-CoV-2 infection. It references studies suggesting folic acid may reduce viral replication by inhibiting key viral proteases, though the exact mechanism remains undetermined.
Laboratory assessment of folate (vitamin B9) status
The paper reviews the laboratory assessment of folate (vitamin B9) status, discussing its role in cellular processes and the implications of deficiency and excess. It highlights the use of serum/plasma folate levels and red cell folate content as markers, and explores the clinical use of measuring specific folate species.
Maternal folate nutrition and offspring health: evidence and current controversies
This narrative review discusses the role of maternal folate nutrition, particularly periconceptional folic acid supplementation, in preventing neural tube defects and its potential benefits for offspring neurodevelopment and cognitive performance. It highlights the effectiveness of mandatory folic acid fortification in reducing neural tube defects and addresses controversies and challenges in current policies and practices.
Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
The study developed a folic acid-modified liposome system loaded with a diacid metabolite of norcantharidin (DM-NCTD) to enhance antitumor potency against hepatocellular carcinoma. The DM-NCTD/FA-PEG liposomes showed stronger cytotoxicity effects on H22 hepatoma cells and improved tumor-targeting efficiency in vivo, inhibiting tumors in H22 tumor-bearing mice better than free DM-NCTD or DM-NCTD/PEG liposomes.
Utilizing the folate receptor for active targeting of cancer nanotherapeutics
This mini-review focuses on recent studies using folate nanoconjugates to target the folate receptor, which is overexpressed on many tumor types, for improved cancer detection and treatment.