Folate: What You Need To Know

Many of us have heard of either folic acid, folate, or vitamin B9, all common names for this important vitamin. But what many of us don’t know is what it is and how it can be beneficial. Keep reading to learn .more about the various benefits of folate, from supporting pregnancy to improving immune function, as well as how much you need and how to prevent deficiency.

What is folate?

Folate is a water-soluble B vitamin, also commonly referred to as vitamin B9, that can be found in both foods and dietary supplements. Folate is utilized in the body for a number key functions, the first being DNA synthesis and repair. Folate allows for the synthesis of thymidine, which is one of the four deoxyribonucleic acids essential for DNA synthesis and repair. (12) Folate is also necessary for the conversion of homocysteine to methionine, a process that yields the byproduct S-adenosylmethionine (SAMe). SAMe is involved in methylation, including the methylation of lipids, peptides, and cytosine (an important part of DNA). Methylation is the addition of a methyl group (CH₃) to a substance to help it function properly. (12)

Folate vs. folic acid: are they the same?

While the two are often confused, folate and folic acid differ in both form and source. Folate is present naturally in some foods and can also be found in supplement form. Folate is present in foods as a polyglutamate, meaning it has multiple glutamate attachments, and as a result, is more difficult for our bodies to break down. (15) When consuming foods with folate, your body is not able to utilize as much folate as is present in the food. (15) Folic acid, on the other hand, is a synthetic (manufactured, not naturally occurring), fully oxidized form of vitamin B9 with only one glutamate attachment; therefore, it is said to be in monoglutamate form. (15) Folic acid is absorbed by the body more effectively than folate. Once absorbed, folic acid is then converted to folate. (15) Folic acid is also the form of vitamin B9 used to fortify certain foods, particularly grains (e.g., breads, pastas, rice, etc). Fortification is the addition of vitamins or minerals to commonly consumed foods with the intent of preventing common deficiencies on a large scale. (9)

Did you know? Folic acid is used to fortify foods because it is heat-stable (is not destroyed by heat exposure), while naturally occurring folate is not. (3) This is essential because most fortified foods containing folic acid (e.g., breads, pastas, rice, etc) are usually heated or cooked prior to consumption.

Foods high in folate

Folate is present naturally in many foods, some of which you might not expect! Some foods that naturally contain folate include:

• Liver (3 oz., braised – 215 mcg folate)
• Spinach (½ cup, boiled – 131 mcg folate)
• Asparagus (4 spears, boiled – 89 mcg folate)
• Brussel sprouts (½ cup, frozen, boiled – 78 mcg folate)
• Kidney beans (½ cup, canned – 46 mcg folate)
• Orange juice (¾ cup – 35 mcg folate)
• Peanuts (1 oz, dry roasted – 27 mcg folate) (15)

Folate is found naturally in green leafy vegetables.

Folate and folic acid benefits

The various benefits of folate and folic acid include improving immune function and inflammatory bowel disease, enhancing cognitive function, and preventing cardiovascular-related events and neural tube defects in pregnancy.

Inflammatory bowel disease

Patients with inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, have been found to occasionally have low serum folate levels. Low folate levels in IBD patients is associated with increased disease severity. This suggests that folate supplementation in these patients could improve disease prognosis and decrease associated lesions such as skin or mouth ulcers. (8) One study observed serum folate and B12 levels in patients with IBD. While patients did not have significant differences in B12 levels, they did have significantly reduced serum folate levels. This study also stated that patients with ulcerative colitis, specifically, had lower serum folate concentration. As a result, patients with IBD may benefit from routine screening for serum folate concentrations. (16) Additionally, these patients have an increased risk of developing cancer, and folate supplementation has been shown to reduce the risk of colorectal cancer in IBD patients. (16)

Cognitive function

Improving cognitive health is a key benefit of folate. As previously mentioned, folate metabolism is essential for the conversion of homocysteine to methionine. Abnormally high levels of homocysteine is linked with increased risk of depression symptoms, thus adequate folate levels may reduce the risk of depression and mental health-related issues. Further, S-adenosylmethionine (SAMe), produced from methionine, is the principal methyl donor of the brain and with adequate folate levels, may help reduce depressive symptoms. (5) SAMe is also essential for synthesizing cysteine (an essential portion of DNA) as well as the methylation of lipids and peptides. (12) Mitochondrial dysfunction and oxidative stress can be caused by post-traumatic stress disorder (PTSD), repetitive stress, and sleep deprivation. Elevated homocysteine is also linked to mitochondrial dysfunction. Due to folate’s ability to reduce homocysteine levels via the conversion of homocysteine to methionine, folate has the potential to improve the function of mitochondria, therefore improving cognitive health. (5)

Cardiovascular diseases

Through folic acid supplementation, one has the ability to maintain or improve cardiovascular health. With compromised endothelial functioning found in cardiovascular diseases (CVD), nitric oxide (NO) is decreased. Nitric oxide is a vasodilator that is antithrombotic, antiangiogenic, and anti-inflammatory. When oxidative stress (imbalances in the body) is increased, NO may uncouple, producing superoxide radicals rather than NO. These radicals are harmful to the tissues, cause constriction in the vessels, and ultimately increase the risk and severity of CVD. (17) Folate has the potential to reverse endothelial dysfunction (abnormal narrowing of blood vessels), which is associated with cardiovascular diseases (CVD). If enough folate is absorbed by the intestines, the extra folate then enters the bloodstream and is taken up by cells and converted to 5-methyl-THF, inducing NO synthesis. Folate intake increases NO synthase coupling, which results in increased nitric oxide production. This increase of NO may be associated with decreased CVD risk. (17)

Immune function

Folate has antiviral properties and is important for proper immune function, especially for those who are immunocompromised. Folate has several beneficial effects when it comes to supporting the immune system. (1)(13) Innate immunity consists of the immune system with which you are born, physical barriers (e.g., skin, nose, mouth, lungs, digestive and urinary tracts), (19) and your general inflammatory response. Folate has the ability to maintain this innate immunity. This is done through the natural killer (NK) cells of the immune system. These cells kill bad bacteria in your body to protect you from infection. (13) Dysfunction of NK cells may be caused by harm to cellular metabolic pathways, protein synthesis, and proliferation. Folate may play a role in all of these processes, and therefore, folate supplementation may aid in prevention of NK cell dysfunction. (1) Adaptive, or acquired, immunity is made up of T cells and B cells that help you build up your immune system as you are exposed to viruses and bacteria throughout your lifetime. Folate aids in cell-mediated immunity and is important for the proper building of antibodies when exposed to antigens. Folate also supports the T helper cell 1 (Th1) immune-mediated response to pathogens. (13) A recent review outlined the role folic acid may play in immune function. The authors outlined how folic acid supplementation can help regulate immune system functioning, and with certain diseases, such as cancer, it could provide an immunosuppressive effect, which would slightly reduce the abilities of the immune system, therefore reducing production of cancerous cells. (1) This review also identified that in certain autoimmune diseases, such as Type 1 diabetes, it could deplete the immune system. (1) With autoimmune diseases, the immune system is overworked. With folic acid providing immunosuppressive effects, the immune system is able to work in an appropriate manner. Lastly, this review highlights the importance of monitoring folic acid supplementation in an individualized manner.

Pregnancy

Whether you are pregnant or thinking about having a baby, folate is of utmost importance before and during pregnancy. Folate has the ability to increase fertility and decrease the time it takes to conceive. (7) Women with the highest levels of serum folate also have roughly two times the chance for having a live birth compared to women with the lowest levels of serum folate. This can also be beneficial for in vitro fertilization (IVF) patients, as folate supplementation in women increases the chances of conceiving. (7) Additionally, folic acid supplementation may prevent neural tube defects. The rapidly developing neural tube in the fetus has extremely high requirements for nucleotides used in DNA synthesis. With adequate folate metabolism, this DNA synthesis is well established, resulting in a viable and healthy neural tube and reduced risk of spina bifida. (10) Spina bifida is a type of neural tube defect that results when the neural tube does not close completely during fetal growth, which can result in a damaged spinal cord and nerves. (2) Fortunately, these conditions are easily prevented with adequate folate intake and supplementation. (10)  

Folic acid supplementation is highly recommended before and during pregnancy.

How much folate do I need?

The recommended daily allowance (RDA) of folate is the same for men and women at 400 mcg per day. However, for pregnant women, the RDA is 600 mcg per day to promote a healthy pregnancy and improve the baby’s overall health. Folate requirements by age group:

• Birth to 6 months – 65 mcg folate
• 7 to 12 months – 80 mcg folate
• 1 to 3 years – 150 mcg folate
• 4 to 8 years – 200 mcg folate
• 9 to 13 years – 300 mcg folate
• 14+ years – 400 mcg folate
• Pregnancy – 600 mcg folate
• Lactation – 500 mcg folate (15)

Folate deficiency

Due to the correlation between folate levels and DNA synthesis, it is important to avoid folate deficiency. Low folate levels cause impaired DNA synthesis, which can result in low red blood cell count due to the need for heavy cell replication. When red blood cell count is diminished, it could result in megaloblastic anemia, a macrocytic anemia (meaning the red blood cells are enlarged) condition that may present as weakness or fatigue, headaches, palpitations, and shortness of breath. (14)(18) Impaired DNA synthesis can also result in severe DNA repair issues and chromosomal abnormalities. (12) There is a link between folate deficiency and increased cancer risk. Since folate is essential for the methylation of cytosine in DNA, decreased cytosine methylation resulting from folate deficiency increases pro-oncogenic expression (potential to cause cancer) and increases the risk for potential for malignancy. Insufficient thymidine can also result in DNA damage, thus increasing the risk of cancer. (12) Folate deficiency is also associated with mental health issues, such as symptoms of depression or anxiety. (18) Other neurological symptoms may include irritability, cognitive decline, and psychosis. Glossitis (inflamed tongue), angular stomatitis (swollen, red patches on the corners of lips), and ulcers are also complications that may present with folate deficiency. (11) Identifying if you are at risk of developing a deficiency or already are deficient is key. Folate deficiency can be prevented through dietary intake of folate-rich foods and through supplementation. In general, deficiency is easily reversed by folic acid supplementation. If you believe you are at risk for deficiency, be sure to speak with your integrative healthcare practitioner. (11)

Did you know? Folate deficiency has been identified in 16% of patients taking antiepileptic drugs. (11)

Folic acid supplements

Various multivitamins, prenatals, and B complex vitamins contain folic acid. Folic acid supplementation may be best taken on an empty stomach. When taken as a supplement with food, about 85% of folic acid becomes available to our body. When taken without food, surprisingly close to 100% of the supplement becomes bioavailable. (15)    

Folic acid is a common dietary supplement found in multivitamins, prenatals, and B complexes.

Who can benefit from taking folic acid or folate supplements?

In the general population, folate deficiency is uncommon. However, there are a few groups who may be at an increased risk of developing this deficiency. For those at higher risk, a folic acid or folate supplement may be indicated. High-risk individuals include:

• Individuals with alcohol use disorder
• Individuals with malabsorption disorders
• Individuals with MTHFR polymorphisms
• Pregnant women
• Women of childbearing age (15)

Folic acid side effects

You may wonder, “Are there side effects if I take too much folic acid?” The upper intake level (UL) for folic acid is 1,000 mcg per day. (6) Although research is still being conducted to observe any adverse effects associated with high folic acid intake, this UL was created to prevent delayed diagnosis of vitamin B12 deficient individuals. The occurrence of vitamin B12 deficiency, especially in women of childbearing age, is rare and this is more precautionary than dangerous to individuals supplementing with folic acid. (6) The masking of B12 deficiency is due to normal pyrimidine synthesis (since there is an abnormally high amount of folic acid in the body). With normal pyrimidine synthesis (DNA synthesis), B12 deficiency is unable to be detected, since folic acid and B12 have connected mechanism pathways. (4)

The bottom line

Ultimately, folate can benefit your body from head to toe. Having adequate folate levels can improve inflammatory bowel disease symptoms and reduce complications, as well as boost cognitive function and prevent long-term risks. It can also reduce risk of cardiovascular disease, improve immune system health, and promote a healthy pregnancy and baby. It is key to recognize the difference between folic acid and folate since this can determine how your body is absorbing and utilizing it. One must understand the possible deficiency of this vitamin as well as any side effects, such as anemia, increased cancer risk, and neurological complications. If you’re a patient, speak to your integrative healthcare practitioner before supplementing with folate or folic acid.