What is Folic Acid?
This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Folic acid, also known as vitamin B9, is a water-soluble vitamin that plays a crucial role in various bodily functions, including DNA synthesis, repair, and methylation. It is essential for the formation of red blood cells and the proper development of the neural tube in embryos. This article explores the biochemical properties of folic acid, its health benefits, and its role in disease prevention and management. Other names include: 5′-methyltetrahydrofolate, 5′-methyltetrahydrofolic acid, 5′-MTHF, Acide Folique, Acide Ptéroylglutamique, Acide Ptéroylmonoglutamique, Acido Folico, B Complex Vitamin, Complexe de Vitamines B, Complexe Vitaminique B, Dihydrofolate, Dihydrofolic Acid, Folacin, Folacine, Folate, Folinic Acid, L-methylfolate, Methylfolate, Méthylfolate, Methylfolic Acid, Pteroylglutamic Acid, Pteroylmonoglutamic Acid, Pteroylpolyglutamate, Tetrahydrofolate, Tétrahydrofolate, Vitamin B9, Vitamine B9.
Biochemistry and Metabolism
Folic acid is the synthetic form of folate, which naturally occurs in foods such as dark green leafy vegetables. Once ingested, folic acid is converted into its active form, tetrahydrofolate (THF), which participates in one-carbon metabolism. This metabolic pathway is vital for the synthesis of nucleotides and the remethylation of homocysteine to methionine, a process crucial for DNA synthesis and repair3.
Health Benefits of Folic Acid
Prevention of Neural Tube Defects
One of the most well-documented benefits of folic acid is its role in preventing neural tube defects (NTDs) such as spina bifida. Adequate folic acid intake before conception and during early pregnancy significantly reduces the risk of these congenital malformations2 4. Studies have shown that increasing folic acid intake can lead to a substantial reduction in the incidence of NTDs, with higher doses providing greater protective effects2.
Cardiovascular Health
Folic acid is also known for its ability to lower homocysteine levels in the blood, a risk factor for cardiovascular diseases. Elevated homocysteine levels are associated with an increased risk of arterial disease, dementia, and Alzheimer’s disease. Supplementation with folic acid, often in combination with vitamin B12, has been shown to reduce homocysteine levels, potentially lowering the risk of these conditions1 10.
Cognitive Function
There is ongoing research into the effects of folic acid on cognitive function, particularly in the elderly. While some studies have found no significant benefit of folic acid supplementation on cognitive measures, others suggest that it may help in reducing serum homocysteine concentrations, which is linked to cognitive decline1.
Role in Disease Processes of Folic Acid
Cancer
Folic acid plays a dual role in cancer prevention and progression. While it helps in DNA synthesis and repair, thereby preventing cancer initiation, high levels of folic acid may facilitate the growth of existing preneoplastic cells. This dual effect necessitates a cautious approach to folic acid supplementation, especially in populations at risk for cancer5.
Chronic Inflammatory and Autoimmune Diseases
Folic acid deficiency is common in chronic inflammatory and autoimmune conditions such as rheumatoid arthritis and psoriasis. Supplementation can help manage these conditions by reducing homocysteine levels and potentially lowering the risk of cardiovascular events associated with these diseases10.
Safety and Recommendations
Fortification and Supplementation
Many countries have implemented folic acid fortification programs to reduce the incidence of NTDs. However, there is ongoing debate about the optimal levels of fortification and supplementation. Excessive intake of folic acid, particularly from supplements, may lead to unmetabolized folic acid in the blood, which has been associated with potential adverse effects, including masking vitamin B12 deficiency and influencing DNA methylation5 7.
Special Populations
Pregnant women and those planning to conceive are advised to take folic acid supplements to prevent NTDs. The recommended dose varies, with some guidelines suggesting higher doses for women with a history of NTD-affected pregnancies6 8.
Learn more with Consensus:
👨🏻🦳Does folic acid supplementation help reduce the incidence of cognitive decline in the elderly?🦵🏽Is folic acid deficiency common in chronic inflammatory conditions like rheumatoid arthritis?
Adverse Effects of Folic Acid
Exacerbation of Vitamin B-12 Deficiency Symptoms
High folic acid intake can worsen clinical and biochemical signs of vitamin B-12 deficiency, such as anemia and cognitive impairment, particularly in the elderly2 3 5.
Cancer Risk
Some studies suggest that excessive folic acid intake may increase the risk of certain cancers, although the evidence is not conclusive2 4 5.
Neurocognitive Health
There are concerns that high folic acid levels might affect neurocognitive health, potentially exacerbating conditions like cognitive impairment and dementia, especially in individuals with low vitamin B-12 levels2 3 9.
Insulin Resistance and Gestational Diabetes
High maternal folate levels have been linked to increased insulin resistance in offspring and a higher risk of gestational diabetes mellitus (GDM)3 7.
Unmetabolized Folic Acid (UMFA)
The presence of unmetabolized folic acid in the bloodstream is a potential issue, with unclear health implications, but it is a concern for its possible role in adverse health outcomes2 5.
Other Health Concerns
Excessive folic acid intake may interfere with zinc absorption, affect seizure control in epileptic patients, and lower natural killer cell activity in elderly women3 8.
Learn more with Consensus:
🌟What are the adverse effects of folic acid?
How has Folic Acid Improved Patient Outcomes?
Cardiovascular Health and Homocysteine Levels
Folic acid supplementation significantly reduces plasma homocysteine levels, which is associated with improved endothelial function in patients with high homocysteine concentrations1 5. However, it does not significantly reduce clinical endpoints in patients with stable coronary artery disease on statin treatment1.
Diabetes Management
Folic acid, especially when combined with vitamin B12, improves glycemic control, insulin resistance, and serum adiponectin levels in patients with type 2 diabetes mellitus2.
Schizophrenia Treatment
Folic acid supplementation, when added to antipsychotic treatment, improves negative symptoms in schizophrenia patients and is well-tolerated, though it does not significantly affect other symptom domains3.
Prevention of Birth Defects
Periconceptional folic acid supplementation significantly reduces the risk of neural tube defects (NTDs) in newborns. It does not have a clear effect on other birth defects such as cleft palate or congenital cardiovascular defects4 9.
Cognitive Function in the Elderly
Folic acid supplementation improves cognitive performance and reduces peripheral inflammatory cytokine levels in elderly individuals with mild cognitive impairment (MCI)8.
Chronic Kidney Disease (CKD)
Folic acid, when combined with enalapril, significantly slows the progression of chronic kidney disease and reduces the rate of renal function decline in patients with mild-to-moderate CKD7.
Uric Acid Levels in Hypertensive Patients
Folic acid supplementation reduces serum uric acid levels and the incidence of new-onset hyperuricemia in hypertensive patients10.
Learn more with Consensus:
🛌How has folic acid improved patient outcomes?
Folic Acid Mechanisms of Action
DNA Synthesis and Repair
Folic acid is converted into tetrahydrofolate, which acts as a carrier for one-carbon units in enzymatic reactions essential for DNA and RNA synthesis and repair2 7.
Homocysteine Regulation
Folic acid helps lower homocysteine levels, which is beneficial for cardiovascular health. This is achieved through its role in the remethylation cycle, converting homocysteine to methionine3 6 10.
Nitric Oxide Synthesis
Folic acid enhances endothelial nitric oxide (eNO) synthesis, which is crucial for vascular health. It stimulates the regeneration of tetrahydrobiopterin (H4B), a cofactor necessary for eNO synthesis, and inhibits superoxide generation, thereby increasing the half-life of nitric oxide6 10.
Cell Growth and Division
Folic acid is vital for rapid cell division and growth, particularly during fetal development. It is involved in the synthesis of nucleotides and amino acids, which are building blocks for new cells2 9.
Immunomodulation
Folic acid has immunomodulatory effects, such as increasing the frequency of regulatory T cells (Treg) and altering DNA methylation patterns, which can help in conditions like alcoholic liver disease8.
Cancer and Neural Tube Defects
Folic acid can activate the pro-oncogene STAT3 via the Folate Receptor alpha (FRα), contributing to cell proliferation in cancer cells. It also plays a preventive role in neural tube defects by ensuring proper cell division and growth during early fetal development5 9.
Absorption and Bioavailability
Folic acid is absorbed more efficiently than natural folates. It is converted into its active forms in the liver, which are then utilized in various metabolic processes7.
Learn more with Consensus:
🧫Can folic acid activate pro-oncogenes such as STAT3, contributing to cell proliferation in cancer?🌌What is folic acid mechanism of action?
Common Complaints Associated with Folic Acid Use
Exacerbation of Vitamin B12 Deficiency Symptoms
High folic acid intake can worsen clinical and biochemical signs of vitamin B12 deficiency, such as anemia and cognitive impairment, especially in the elderly1 3.
Cognitive Decline and Dementia
There is no significant benefit of folic acid supplementation on cognitive function or mood in elderly individuals, whether healthy or with mild to moderate cognitive impairment or dementia. High doses may even lead to a decline in cognitive function in some cases3 6.
Insulin Resistance in Offspring
Maternal high folic acid intake has been linked to increased insulin resistance in offspring, particularly in populations with high prevalence of vitamin B12 deficiency1 5.
Potential Genetic and Ethnic Variations
Certain genetic polymorphisms, such as the 19 bp deletion in the DHFR gene, can increase the risk of adverse effects like unilateral retinoblastoma in offspring and lower cognitive scores in the elderly when high folic acid intake is involved1.
Reduced Natural Killer Cell Activity
Excessive folic acid intake may be associated with lower natural killer cell activity, which could impact immune function, particularly in elderly women1.
General Safety Concerns
Despite the benefits of folic acid in preventing neural tube defects, there are concerns about its safety in high doses, with potential side effects including variations in epigenetic programming and long-term health effects2 4.
Learn more with Consensus:
Disclaimer
The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.
If you are experiencing a medical emergency, please seek immediate attention from a healthcare provider.