Folic Acid: Everything you need to know

Although the terms folate and folic acid are often used interchangeably, the two vitamins have a lot of differences. Synthetic folic acid is structurally different from folate and has different biological effects in the body.

Folic acid is a water-soluble, multivitamin commonly used in supplements and fortified foods. It has a man-made version of folate, a B vitamin naturally found in many foods.
Folic acid is a man-made form of folate, so it should be obtained through the diet. Both of these vitamins are considered essential to contribute to an adequate diet. Folate is found in a number of plant and animal foods, including spinach, kale, broccoli, avocados, citrus fruits, eggs, and beef liver.
On the other hand, folic acid is added to foods like flour, breakfast cereals and breads. Folic acid is also sold in concentrated form in dietary supplements.
The human body needs Folic Acid for a variety of functions including:
Synthesis, repair and methylation - addition of a methyl group - DNA cell division Conversion of homocysteine ​​into methionine, an acid the amino is used for protein synthesis or converted to S-adenosylmethionine (SAMe), a compound that acts as a major methyl donor in the body and is needed for many cellular reactions Red blood cell construction and development Similarly, folate also affects several important metabolic processes. A folate deficiency causes negative health effects, including megaloblastic anemia, an increased risk of heart disease, certain cancers, and birth defects in infants.
Folate deficiency has many causes, including:
Poor diet Disease or surgery that affects the absorption of folate in the digestive system, including celiac disease, gastrectomy and short bowel syndrome Achlorhydria or hypochlorhydria (no or low stomach acid) Use of drugs that affect folate absorption, including methotrexate and sulfasalazine Alcoholism Pregnancy Anemia Many countries, including the United States, require cereal products The cup is fortified with folic acid to reduce the incidence of folate deficiency.
This is because folate deficiency is a common condition in a certain population, including older adults and pregnant women.

The body's stores of folate range from 10 to 30mg, most of which is stored in the liver, while the rest is stored in the blood and tissues. Normal blood folate levels are between 5 and 15 ng/mL. The main form of folate in the blood is called 5-methyltetrahydrofolate.
Synthetic folic acid is said to be 100% absorbable when consumed on an empty stomach, while the folic acid found in fortified foods is said to have only 85% absorption. Natural folate has a much lower absorption of about 50%.
When taken in supplement form, 5-methyltetrahydrofolate has the same or greater bioavailability than folic acid supplements. Because of this variation in absorption, the DFE- unit measures the difference between the absorption capacities of folic acid and folate; was developed according to the following equation:
1 mcg DFEs = 1 mcg natural food folate = 0.5 mcg folic acid taken as a supplement = 0.6 mcg folic acid from food
Adults need about 400 mcg DFE folate per day to supplement an adequate daily folate intake. Pregnant and nursing women have higher folate requirements and need to get 600 mcg and 500 mcg of DFE folate each day, respectively.
Recommendations are made for infants, children and adolescents as follows:
Newborns up to 6 months: 65 mcg DFE 7 to 12 months: 80 mcg DFE 1 to 3 years: 150 mcg DFE 4 to 8 age: 200 mcg DFE 9 to 13: 300 mcg DFE 14 to 18: 400 mcg DFE

3.1 Prevention of Birth Defects and Pregnancy Complications One of the most common uses of folic acid and folate is in the prevention of birth defects, specifically neural tube defects, including spina bifida and congenital malformations. brain - when a baby is born without parts of the brain or skull.
Maternal folate status is a predictor of risk for neural tube defects, leading to health policies in many countries recommending folic acid supplementation for women who are or may be pregnant. pregnant.
For example, the US Preventive Services Task Force, an independent national group of experts on disease prevention, recommends that all women who are planning to become pregnant or likely to become pregnant take the supplement every other day. 400 to 800 mcg folic acid daily, starting at least 1 month before becoming pregnant and continuing for the first 2 months of pregnancy.
Folic acid supplements are prescribed to pregnant women to prevent birth defects and may also help prevent pregnancy-related complications, including preeclampsia.
3.2 Treatment of Folate Deficiency Folate deficiency can occur for many reasons, including inadequate intake, surgery, pregnancy, alcoholism, and malabsorption diseases. Deficiency can lead to serious side effects, including megaloblastic anemia, birth defects, mental impairment, impaired immune function, and depression. Both folic acid and folate supplements are used to treat folate deficiency.
3.3 Boosts Brain Function Research has shown that low blood folate levels are associated with poor brain function and an increased risk of dementia and increased risk of mental impairment in the elderly. Studies have demonstrated that folic acid supplements can improve brain function in people with mental impairment and help treat Alzheimer's disease.
A 2019 study in 180 adults with mild cognitive impairment (MCI) demonstrated that supplementing with 400mcg of folic acid daily for 2 years significantly improved brain functions, including IQ speech and decreased levels of several proteins involved in Alzheimer's disease development and progression. Another study in 121 people with newly diagnosed Alzheimer's disease who were being treated with donepezil found that those who took 1,250 mcg of folic acid daily for 6 months had improved cognitive performance and reduced inflammatory markers, compared with those who took 1,250 mcg of folic acid daily for 6 months. with donepezil users.
3.4 Treating Depression People with depression have been shown to have lower blood folate levels than people without depression. Studies show that folic acid and folate supplements can reduce symptoms of depression when used in combination with antidepressants.
A systematic review demonstrated that, when used in conjunction with antidepressants, treatment with folate-based supplements, including folic acid and methylfolate, significantly reduced symptoms. depression, compared to taking antidepressants alone. Furthermore, a finding based on 7 studies found that treatment with folate-based supplements along with antipsychotic drugs resulted in greater reductions in negative symptoms in people with schizophrenia, compared with with antipsychotic medication alone.

3.5 Reduce the risk of heart disease Taking folate supplements, including folic acid, can help improve heart health and reduce the risk of heart disease. Increased levels of the amino acid homocysteine ​​are associated with an increased risk of developing heart disease.
Homocysteine ​​blood levels are determined by both nutritional and genetic factors. Folate plays a key role in homocysteine ​​metabolism, and low folate levels can contribute to high homocysteine ​​levels, known as hyperhomocysteine. Research has shown that folic acid supplements can reduce homocysteine ​​levels and the risk of heart disease.
For example, a review based on 30 studies and over 80,000 people demonstrated that folic acid supplements reduced the overall risk of heart disease by 4% and the risk of stroke by 10%.
Furthermore, folic acid supplements can help lower blood pressure, a well-known risk factor for heart disease. Additionally, folic acid supplements have been shown to improve blood flow, which may help improve cardiovascular function.
3.6 Other benefits Folic acid supplementation has also been associated with the following benefits:
Diabetes . Folate supplements may help improve blood sugar control, reduce insulin resistance, and enhance cardiovascular function in people with diabetes. These supplements may also help reduce diabetes complications, including neuropathy of fertility. A folate supplement intake of more than 800 mcg per day is associated with higher success rates in women undergoing assisted reproductive technology. Adequate folate is also essential for oocyte quality. Inflammation. Folic acid and folate supplements have been shown to reduce markers of inflammation, including C-reactive protein (CRP), in different populations, including women with polycystic ovary syndrome (PCOS). and children with epilepsy. Reduce drug side effects. Folate-based supplements may help reduce the incidence of side effects associated with the use of certain medications, including methotrexate, an immunosuppressive drug used to treat rheumatoid arthritis, a disease psoriasis and some cancers. Kidney disease. Due to impaired kidney function, hypercholesterolemia occurs in more than 80% of people with chronic kidney disease. Folic acid supplementation may help reduce homocysteine ​​levels and the risk of heart disease in this population.

Some people have genetic variations that affect the way they metabolize folate. Genetic polymorphisms in folate-metabolizing enzymes, such as methylenetetrahydrofolate reductase (MTHFR), may affect health by interfering with folate levels in the body.
One of the most popular variants is the C677T. People with the C677T variant had lower enzyme activity. As such, they may have elevated homocysteine ​​levels, which can increase the risk of heart disease.
People with severe MTHFR deficiency may produce 5-methyltetrahydrofolate, the biologically active form of folate, and may have extremely low folate levels. In addition to C677T, there are many other variants that affect folate metabolism, including MTRR A66G, MTHFR A1298C, MTR A2756G, and FOLH1 T484C. These variations can also increase the risk of birth defects, migraines, depression, miscarriage, anxiety, and some cancers.
The rate of genetic variation affecting folate metabolism varies depending on ethnicity and geographic location. For example, the C677T mutation is more common in American Indians, Mestizos, and Han Chinese. Recommended treatment usually includes the addition of bioactive 5-methyltetrahydrofolate and other B vitamins.

Folate plays an essential role in fetal growth and development. For example, it is necessary for cell division and tissue growth. This is why maintaining optimal folate levels is important both before and during pregnancy. Since the 1990s, flours and other foods have been fortified with folic acid based on research findings linking low folate status in pregnant women to an increased risk of neural tube defects in children.
In addition to its protective effect against birth defects, folic acid supplementation during pregnancy may improve neurological development and brain function in children, as well as protect against autism spectrum disorders.
However, other studies have concluded that high folic acid intake and high levels of unmetabolized folic acid in the blood can have negative effects on neurodevelopment and increase the risk of autism. Folate is also important for maternal health, and folic acid supplementation has been shown to reduce the risk of pregnancy-related complications, including preeclampsia. In addition, high maternal folate levels were associated with a significantly reduced risk of preterm birth.
The recommended amount of folate for women during pregnancy is 600 mcg DFE.

6.1 Unmetabolized Folic Acid As mentioned above, due to differences in metabolism, only large amounts of folic acid through fortified foods or supplements can result in inadequate folic acid levels. High metabolism in the blood.
Eating foods rich in folate or taking natural forms of folate, such as 5-methyltetrahydrofolate, does not lead to excessively high blood levels of folic acid. Although some studies have shown that high maternal folic acid levels reduce the risk of autism and improve mental outcomes in children, other studies have shown that folic acid levels are not converted High blood chemistry can increase the risk of autism and negatively affect the neurological development of children.
A recent study of 200 mothers found that mothers with higher blood folate levels at 14 weeks of gestation were more likely to have children with autism spectrum disorder (ASD). The researchers found that folic acid was not metabolized in a larger number of women who had children with ASD, compared with women who had children without ASD. This suggests that folic acid supplementation around the 14th week of pregnancy is more common in women whose children later develop ASD. However, unmetabolized folic acid was not found in the blood of people taking less than 400 mcg per day.
6.2 Vitamin B12 Deficiency Another risk of taking too high a dose of folic acid is that the user may not notice a vitamin B12 deficiency.
This is because taking large doses of folic acid can treat megaloblastic anemia, a condition characterized by the production of large, abnormal, underdeveloped red blood cells that causes vitamin B12 deficiency anemia. cause.
However, folic acid supplementation does not correct the nerve damage that occurs with vitamin B12 deficiency. For this reason, vitamin B12 deficiency may go unnoticed until potentially irreversible neurological symptoms appear.
6.3 Other Precautions In addition to the potential side effects listed above, there are several other risks associated with taking high doses of folic acid:
Cancer risk. A review of 10 studies found a significant increase in the incidence of prostate cancer in those taking folic acid supplements. Mental breakdown. Studies have shown that high doses of folic acid supplements can lead to rapid mental decline in elderly people with low vitamin B12 levels. Reduced immune function. Many studies have shown that high doses of folic acid supplements can suppress immune function by reducing the activity of immune cells.

As mentioned above, the recommended dosage for folic acid is 400 mcg DFE per day for adults, 600 mcg DFE for pregnant women, and 500 mcg DFE for nursing women.
Although this amount can be met through daily diet, supplement use is a convenient way to meet folate needs for many people, especially those at risk of deficiency. deficits, including pregnant women and the elderly. Folate and folic acid can be found in many forms and are often added to multi-nutrient supplements, including multivitamins and B-complex vitamins. Dosages vary widely, but most supplements provide about 680 to 1,360 mcg DFE (400 to 800 mcg folic acid).
UL for synthetic folate in supplements and fortified foods is as follows
Adults: 1000 mcg 14 to 18 years: 800 mcg 9 to 13 years: 600 mcg 4 to 8 years: 400 mcg 1 to 3 years : 300 mcg Furthermore, Folate supplements may interact with a number of commonly prescribed medications, including:
Methotrexate. Methotrexate is a medicine used to treat certain cancers and autoimmune diseases. Epilepsy medication. Folic acid can interfere with antiepileptic drugs, such as Dilantin, Carbatrol, and Depacon. Sulfasalazine. Sulfasalazine is used to treat ulcerative colitis. If you are taking one of the medications listed above, consult your doctor before taking folic acid supplements.

Reference article: Healthline.com