Folic Acid (Vitamin B9)
Also known as: Folate, Pteroylgutamic acid, Vitamin B, Folacin, Methylfolate, L-Methylfolate, L-5-Methylfolate, Levomefolic acid, 5-Methyltetrahydrofolate (5-MTHF), folic acid
Overview
Folic acid is a synthetic form of the essential B vitamin folate and is widely available as a dietary supplement and in fortified foods. Folic acid is the most widely available form of supplemental folate due to its high stability and bioavailability. Folate, or vitamin B9, is required for many vital biological pathways, including DNA synthesis, repair, and methylation; neurotransmitter synthesis; and the metabolism of homocysteine and other amino acids. Accordingly, a folate deficiency may increase the risk of various diseases and can negatively affect fetal development during pregnancy. The human body can’t make folate (apart from small amounts produced by the intestinal microbiome), so folate must be consumed in the diet or through supplementation. Folate occurs naturally in a variety of foods, including green leafy vegetables, legumes, citrus fruit, eggs, and liver. Additionally, some countries have mandated the fortification of certain cereal grains with folic acid (e.g., wheat, corn, rice), resulting in widespread exposure to folic acid through foods like bread and cereal. While folic acid can serve a therapeutic role in certain contexts, supplementation in excess may have risks.
Benefits
The effects of folic acid are primarily due to the role that folate plays as a coenzyme in one-carbon metabolism — a series of metabolic pathways that are vital for normal cellular functioning. As a coenzyme, folate carries and donates one-carbon units that are required for processes like nucleic acid (DNA and RNA) synthesis and repair, amino acid metabolism (most notably the conversion of homocysteine to methionine), and cell division. During pregnancy, folate is especially important to support the rapidly growing fetus and the increased blood volume of the mother. Folic acid supplementation can effectively reduce homocysteine levels by increasing the metabolism of homocysteine to methionine, which is proposed to be the mechanism by which folic acid can reduce inflammation and positively affect some aspects of cardiovascular health (e.g., stroke risk, endothelial function). By increasing the production of methionine, folate increases levels of S-adenosylmethionine (SAMe), which is involved in the synthesis of neurotransmitters like serotonin and dopamine and regulates gene expression through DNA methylation.
How it works
Folic acid is an effective treatment for megaloblastic anemia and for the prevention of neural tube defects (NTDs) when taken during early pregnancy or before conception. Folic acid is also routinely recommended for people taking low-dose methotrexate (as used for some autoimmune conditions) and sulfasalazine, to reduce medication side effects and prevent deficiency, respectively. Folic acid supplementation reliably reduces plasma homocysteine concentrations, most notably in people with elevated homocysteine and low folate levels at baseline. These reductions in homocysteine may have beneficial cardiovascular effects, including a reduction in the risk of stroke (particularly in regions without folate fortification), improved endothelial function, and reduced atherosclerosis progression.
Side effects
Folic acid is most often taken at a dosage of 400 to 800 micrograms (μg), i.e., 0.4 to 0.8 mg, daily. The tolerable upper intake level (UL) of folic acid is 1,000 μg (1 mg) daily. This represents the maximum daily dose unlikely to cause adverse effects and was set based on the concern of folic acid masking vitamin B12 deficiency. In some circumstances, a higher dosage may be warranted. For the prevention of NTDs during pregnancy, folic acid can be dosed at 400 μg (0.4 mg) daily, ideally starting a minimum of 4 weeks before conception and continuing until at least the end of the first trimester. In women with a previous pregnancy affected by NTDs, the recommended dose may be much higher (4 to 5 mg daily). For reducing homocysteine levels, the maximum benefit can be achieved with folic acid 800 μg (0.8 mg) daily. When used for depression in addition to antidepressant medication, the best evidence currently suggests a dose of L-methylfolate 15 mg daily. For reducing the side effects of low-dose methotrexate (as used for some autoimmune conditions), a dosage of 500 to 1000 μg (0.5 to 1 mg) daily appears to be effective. The recommended daily allowance (RDA) of folate for adults is 400 μg dietary folate equivalents (DFEs) daily, as per the Institute of Medicine. This represents the average amount of folate that is thought to meet the nutritional requirements of most healthy people. Natural dietary folate has a lower bioavailability than folic acid, so DFEs are used to convert between the two.
Dosage
Folic acid is generally considered safe and well-tolerated when taken at appropriate dosages. When taken during pregnancy, observational studies suggest higher doses of folic acid may be associated with an increased risk of gestational diabetes, childhood asthma, and impaired psychomotor and neurological development. Folic acid can mask the signs of vitamin B12 deficiency. Left untreated, a vitamin B12 deficiency can lead to irreversible cognitive impairment and neuropathy (a type of nerve damage). This could be avoided by supplementing with vitamin B12 at the same time or having your blood levels of vitamin B12 checked to ensure they are normal. Importantly, natural folates found in food and supplemental L-methylfolate don’t carry this risk. Folic acid might lower the effectiveness of some medications, including anti-epileptic medications (e.g., phenytoin), which could increase the risk of seizures, and high-dose methotrexate used for cancer treatment.
FAQs
What is folic acid?
Folic acid is a synthetic form of the essential B vitamin folate and is widely available as a dietary supplement and in fortified foods. Folic acid is the most widely available form of supplemental folate due to its high stability and bioavailability. Folate, or vitamin B9, is required for many vital biological pathways, including DNA synthesis, repair, and methylation; neurotransmitter synthesis; and the metabolism of homocysteine and other amino acids. Accordingly, a folate deficiency may increase the risk of various diseases and can negatively affect fetal development during pregnancy. The human body can’t make folate (apart from small amounts produced by the intestinal microbiome), so folate must be consumed in the diet or through supplementation. Folate occurs naturally in a variety of foods, including green leafy vegetables, legumes, citrus fruit, eggs, and liver. Additionally, some countries have mandated the fortification of certain cereal grains with folic acid (e.g., wheat, corn, rice), resulting in widespread exposure to folic acid through foods like bread and cereal. While folic acid can serve a therapeutic role in certain contexts, supplementation in excess may have risks.
What are the benefits and risks of folic acid fortification?
Folic acid fortification refers to the addition of folic acid to the food supply — most commonly through the enrichment of wheat, rice, and corn — in an attempt to reduce the potential consequences of folate deficiency. Fortification became mandatory in the United States and Canada in 1998, and today over 80 countries follow similar practices. The rationale for fortification was to prevent NTDs — a group of potentially fatal birth defects that can occur within the first four weeks of pregnancy, particularly in the context of folate deficiency. To reap the benefits, a woman ideally needs to start supplementing at least 4 weeks before conception, and because many pregnancies are unplanned, fortification ensures that women are universally exposed to folic acid. Observational research suggests that countries that introduced mandatory fortification have seen 30 to 60% reductions in the rates of NTDs.
What are the main causes and signs/symptoms of folate deficiency?
Folate deficiency can occur for several reasons, including: - Insufficient dietary intake - Certain medications (e.g., methotrexate, antiepileptics, oral contraceptives) - Impaired absorption (e.g., celiac disease, gastric bypass, alcohol use disorder)
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