Folate Deficiency

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

Correction: Rossignol, D.A.; Frye, R.E. Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. J. Pers. Med. 2021, 11, 1141.

Rossignol DA, Frye RE · Journal of personalized medicine · 2022

In the original publication [...].

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.

Rossignol DA, Frye RE · Journal of personalized medicine · 2021

The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain; low 5-MTHF in the brain causes cerebral folate deficiency (CFD). CFD has been associated with autism spectrum disorders (ASD) and is treated with d,l-leucovorin (folinic acid). One cause of CFD is an autoantibody that interferes with the function of the FRα. FRα autoantibodies (FRAAs) have been reported in ASD. A systematic review was performed to identify studies reporting FRAAs in association with ASD, or the use of d,l-leucovorin in the treatment of ASD. A meta-analysis examined the prevalence of FRAAs in ASD. The pooled prevalence of ASD in individuals with CFD was 44%, while the pooled prevalence of CFD in ASD was 38% (with a significant variation across studies due to heterogeneity). The etiology of CFD in ASD was attributed to FRAAs in 83% of the cases (with consistency across studies) and mitochondrial dysfunction in 43%. A significant inverse correlation was

Benefits of Lactic Acid Bacteria Folate Synthesis in Foods and Risks Associated with Deficiency - a Review.

Siqueira MFF, Massaut KB, Radatz PB, de Souza Sigali S, de Lima Costa IH, Viana PF · Probiotics and antimicrobial proteins · 2026

Folate (vitamin B9) is an essential micronutrient found in both animal and plant foods, but it is highly heat-sensitive, leading to loss of this nutrient during thermal processing. To overcome folate deficiency, many regulatory agencies recommend fortifying foods with folic acid (a synthetic form of the vitamin), although its long-term safety remains debated. A promising alternative approach involves bio-enriched fermented foods produced by lactic acid bacteria (LAB). These LAB-fermented products, such as dairy products (yogurt, cheese), cereals, and vegetables, have demonstrated potential to regulate intestinal homeostasis, alleviate inflammatory diseases, and mitigate neurodegenerative symptoms. This study is a systematic review that aims to assess the ability of LAB to synthesize folate, highlighting studied genera and their applications, benefits, and risks of deficiency. The species Lactiplantibacillus plantarum stands out in folate production, in vitro and in situ. The field of F

Folate and Vitamin B12 Status in Latin America and the Caribbean: An Update.

Brito A, Mujica-Coopman MF, López de Romaña D, Cori H, Allen LH · Food and nutrition bulletin · 2015

Background: The current magnitude of folate and vitamin B12 deficiency in Latin America and the Caribbean is uncertain. To summarize data on plasma or serum vitamin B12 and folate concentrations in Latin America and the Caribbean reported since 1990, a period that covers the era before and after the introduction of folic acid fortification. A systematic review was conducted in 2012 and updated in 2014. Studies and surveys using biochemical biomarkers and conducted in apparently healthy individuals were identified. Folate deficiency in Latin America and the Caribbean appears not to be a public health problem (prevalence < 5%) after the introduction of folic acid fortification. However, there is some indication that high rates of low or marginal vitamin B12 status remain in most locations and across population groups. Adding vitamin B12 as a fortificant with folic acid may be the best strategy in areas where vitamin B12 deficiency is an established concern.

Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review.

M'Koma AE, Wise PE, Schwartz DA, Muldoon RL, Herline AJ · Diseases of the colon and rectum · 2009

Iron and/or vitamin B12 deficiency anemias, which have adverse effects on patients' quality of life, are commonly observed and often overlooked complications after restorative proctocolectomy. We performed a systematic review of publications on the prevalence of anemia as well as on the impact of anemia on a range of clinical, functional, quality of life, and economic outcomes in restorative proctocolectomy patients. This information is important to help healthcare providers through a comprehensive overview to increase awareness about a condition that could require therapy to improve patient healthcare and quality of life. We reviewed the English language publications on the incidence of anemia and its adverse effect after restorative proctocolectomy The United States National Library of Medicine database (MEDLINE), the Excerpta Medica database (EMBASE), the Cochran Library, and the Google search engine were searched for published articles on the prevalence and impact of anemia in pos

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.

Guideline: Daily iron and folic acid supplementation in pregnant women

WHO

The WHO guideline provides recommendations on daily iron and folic acid supplementation for pregnant women to improve maternal and infant health outcomes. It is a key international public health guideline.

Inositol, neural tube closure and the prevention of neural tube defects.

Greene ND, Leung KY, Copp AJ · Birth defects research · 2017

Susceptibility to neural tube defects (NTDs), such as anencephaly and spina bifida is influenced by genetic and environmental factors including maternal nutrition. Maternal periconceptional supplementation with folic acid significantly reduces the risk of an NTD-affected pregnancy, but does not prevent all NTDs, and "folic acid non-responsive" NTDs continue to occur. Similarly, among mouse models of NTDs, some are responsive to folic acid but others are not. Among nutritional factors, inositol deficiency causes cranial NTDs in mice while supplemental inositol prevents spinal and cranial NTDs in the curly tail (Grhl3 hypomorph) mouse, rodent models of hyperglycemia or induced diabetes, and in a folate-deficiency induced NTD model. NTDs also occur in mice lacking expression of certain inositol kinases. Inositol-containing phospholipids (phosphoinositides) and soluble inositol phosphates mediate a range of functions, including intracellular signaling, interaction with cytoskeletal protein

Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.

Czeizel AE, Dudás I, Vereczkey A, Bánhidy F · Nutrients · 2013

Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of prevention is better than a pound of care".

Influence of mineral and vitamin supplements on pregnancy outcome.

Hovdenak N, Haram K · European journal of obstetrics, gynecology, and reproductive biology · 2012

The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) a

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

Nutritional adequacy of the EAT-Lancet diet: a Swedish population-based cohort study.

Stubbendorff A, Ericson U, Hallström E, Samuelsson J, Sonestedt E, Ibsen DB · The Lancet. Planetary health · 2026 · n=970

The EAT-Lancet planetary health diet emphasises plant-based foods while including moderate amounts of animal-sourced foods. Simulation-based modelling studies suggest that the diet can provide adequate micronutrients, but concerns remain about potential deficiencies as studies have used different methodologies and few have assessed nutrient intakes using both dietary and biomarker data in population-based studies. This study aimed to evaluate nutrient adequacy, defined as the ability of a diet to provide sufficient essential vitamins and minerals to meet physiological requirements, in relation to adherence to the EAT-Lancet diet and assess how methodological differences in measuring adherence impact the findings. Data was derived from the Swedish Malmö Diet and Cancer cohort (baseline 1991-96), including 25 970 participants. Dietary intake was assessed through a validated diet history method, and nutrient intakes were calculated. Seven different EAT-Lancet diet scores were

The aetiology and prevalence of preoperative anaemia in patients undergoing major surgery (ALICE): an international, prospective, observational cohort study.

Choorapoikayil S, Baron DM, Spahn DR, Lasocki S, Boryshchuk D, Yeghiazaryan L · The Lancet. Global health · 2025 · n=2830

Preoperative anaemia is a major risk factor for perioperative morbidity. Because iron deficiency is widely assumed to be the main cause of anaemia in surgical patients, treatment efforts have focused mostly on iron supplementation. However, the aetiology of anaemia is multifactorial. To further understand the underlying causes and consider a comprehensive approach to anaemia management, we studied the prevalence and aetiology of preoperative anaemia in patients undergoing major surgery. This prospective, multicentre, observational cohort study was done in 79 hospitals in 20 countries on five continents; patients were aged at least 18 years, undergoing major surgery, and had a postoperative in-hospital stay of at least 24 h. Patients donating autologous blood before surgery were excluded. Data were extracted from the electronic hospital information system and from self-reported information during preoperative examination. The primary outcomes were the prevalence of anaemia, defined as

Risk of meningomyelocele mediated by the common 22q11.2 deletion.

Vong KI, Lee S, Au KS, Crowley TB, Capra V, Martino J · Science (New York, N.Y.) · 2024

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke.

Jadavji NM, Emmerson JT, MacFarlane AJ, Willmore WG, Smith PD · Neurobiology of disease · 2017

Folates are B-vitamins that play an important role in brain function. Dietary and genetic deficiencies in folate metabolism result in elevated levels of homocysteine which have been linked to increased risk of developing a stroke. Reducing levels of homocysteine before or after a stroke through B-vitamin supplementation has been a focus of many clinical studies, however, the results remain inconsistent. Animal model systems provide a powerful mechanism to study and understand functional impact and mechanisms through which supplementation affects stroke recovery. The aim of this study was to understand the role of B-vitamins in stroke pathology using in vivo and in vitro mouse models. The first objective assessed the impact of folate deficiency prior to ischemic damage followed by B-vitamins and choline supplementation. Ischemic damage targeted the sensorimotor cortex. C57Bl/6 wild-type mice were maintained on a folic acid deficient diet for 4weeks prior to ischemic damage to increased

Folic Acid

CDC

The CDC offers information on folic acid, emphasizing its importance in preventing neural tube defects and promoting public health. It includes details on recommended intake and fortified foods.

Relative Bioavailability of Folic Acid and L-5-Methlytetrahydrofolate

n=150 · NCT01584050 · COMPLETED · COMPLETED

Folic acid, a form of the vitamin folate, is added to grain products in Canada to help reduce birth defects. Folic acid is the synthetic form of folate and is very stable (doesn't break down) when added to foods. There are emerging health concerns about chronic folic acid consumption. Recently another more natural form of folate, L-5-methyltetrahydrofolate (L-MTHF) has become available. The investigators plan to conduct a randomized trial in women to determine if supplements containing L-MTHF consumed over three months raises blood folate levels as much as supplements containing folic acid. The investigators hypothesize that L-MTHF will increase red cell folate over 12 weeks to same extent as equimolar folic acid.

The Study of Association Between Obesity and Iron Deficiency Anaemia in Nonpregnant Indonesian Women

n=165 · NCT06622551 · ENROLLING_BY_INVITATION · ENROLLING_BY_INVITATION

This clinical trial aims to learn if there is a relationship between OWT/OB and IDA in nonpregnant women of reproductive age and its impact on iron supplementation. The main questions it aims to answer are: * Is there any independent association between overweight/obesity and iron deficiency anemia in nonpregnant women after controlling for potential confounding factors? * Does the effect of iron supplementation on iron status vary between overweight/obese and normal-weight nonpregnant women (as measured by multiple iron biomarkers)? Researchers will compare several biomarkers between the case and control groups after the intervention is given for 90 days. Participants will: * Visit the research center before the intervention given and after 90 days * Take daily iron-folic acid supplements for 90 days * Keep a diary of their supplement's intake

Impact of Iron/Folic Acid Versus Folic Acid Supplements During Pregnancy on Maternal and Children's Health: A Randomized Controlled Trial in China

n=2367 · NCT02221752 · COMPLETED · COMPLETED

According to a national study in 2002, the prevalence of ID, IDA, and ID+IDA among pregnant women in China was 42.6%, 9.1%, and 61.7% respectively. A similar study in Hebei province at the same time showed that the prevalence of IDA among pregnant and lactating mothers was 46.39% and 47.21% respectively. There was a significant difference between urban and rural areas. Women living in rural areas had higher chances of having IDA (p\<0.01). WHO and UNICEF recommend taking iron, folic acid and multiple micronutrients during pregnancy. However, we don't know much about their influence on maternal and infant health and their clinical effectiveness. Health Department of China recommends taking 400ug folic acid before pregnancy and during early pregnancy. But for various reasons, not all expecting mothers take this advice. Besides, we don't have a national level technical standard of how to take nutrition supplements during pregnancy. Therefore, it's crucial for us to study if iron/folic acid or folic acid only can prevent perinatal complications, as well as their influences on infant and toddler health. The purpose of this study is to test whether taking iron/folic acid and folic acid only from early pregnancy until delivery will lower the chances of pregnancy complications, and to see how supplements affect gestation results. As well, it will evaluate a) whether taking iron supplement during pregnancy can prevent IDA during pregnancy; b) whether taking iron supplement can increase mother and fetus iron storage; and c) how mother's iron level affects newborn's iron level. We hope to understand nutrition conditions during pregnancy and investigate the relations between pregnancy diet and complications during pregnancy, weight gain during pregnancy, and newborn birth weight. We will evaluate the influence of taking iron and folic acid during pregnancy on the health of infants and toddlers.

Folate Deficiency

TRIP Database

The TRIP Database offers a comprehensive search results page for 'Folate Deficiency,' aggregating evidence from various sources including guidelines, systematic reviews, and primary research. It is a powerful tool for rapidly finding evidence-based information.