Folate is the naturalform of vitamin B9 that the body needs to maintain its genetic building blocks, DNA and RNA. However, folate is water-soluble, meaning the body does not store it, and you need to replenish it regularly through your diet.
Folate isnaturally present in many foods, notably dark green vegetables, beans, and legumes. Vitamin supplements contain a synthetic form of folate known as folic acid. In the United States and most other developed nations, breakfast cereals, flour, bread, and other foods are fortified with folic acid to prevent folate deficiency within the general population.
This article explains folate's uses and benefits. It also covers precautions and how to take folate safely.
Dietary supplements are not regulated in the United States, meaning the Food and Drug Administration does not approve them for safety and effectiveness before products are marketed. When possible, choose a supplement that has been tested by a trusted third party, such as USP, ConsumerLabs, or NSF.
However, even if supplements are third-party tested, that doesn’t mean that they are necessarily safe for all people or effective in general. Therefore, it is important to talk to your healthcare provider about any supplements you plan to take and check in about any potential interactions with other supplements or medications.
- Active ingredient(s): Folate, folic acid
- Alternate name(s): Folic acid, folacin, B9
- Legal status:Available over-the-counter (OTC)
- Suggested dose: Daily value for adults is 400 micrograms (mcg), 600 mcg if pregnant, 500 mcg if breastfeeding
- Safety considerations: Large amounts may mask a B12 deficiency, increase cancer risk, and interact with some medications
Uses of Folate
Folate is essential to good health. It helps your body make genetic material, like DNA, which contains the biological instructions that make your body unique. In addition, it supports healthy cell division.
Research supports folate for preventing various health conditions, including cancer, stroke, neural tube defects, and aging-related macular degeneration (age-related vision loss), and treating depression.
Folate and other B vitamins metabolize homocysteine (an amino acid your body uses to make proteins). Since high levels of homocysteines can contribute to heart disease and stroke, some research has looked at the connection between folate and heart disease.
In a 2015 study published in JAMA, researchers evaluated whether folic acid therapy could reduce the risk of first-time stroke. The randomized, double-blind clinical trial included 20,702 adult participants with hypertension who had no stroke or myocardial infarction (heart attack) history.
Researchers randomly assigned participants to a combined enalapril (10 mg) and folic acid (0.8 mg) group or an enalapril (10 mg) only group. Enalapril (brand name Vasotec) is a medication that treats high blood pressure. The median treatment duration was 4.5 years. Compared to the enalapril-only group, the combined folic acid and enalapril group had a 21% lower risk of stroke.
A 2012 meta-analysis also looked at folic acid and stroke prevention. That analysis of 10 trials found that overall there was an 8% reduced stroke risk associated with folic acid supplementation. In addition, researchers concluded it was particularly effective in populations without folate food fortification.
Similarly, in a 2017 review, researchers evaluated 11 studies with 65,790 participants to see if folic acid supplementation reduced the incidence of stroke in people with cardiovascular disease (CVD).
The study found that supplementation significantly reduced stroke risk in people with CVD, especially in populations that ate no or little fortified grain.
Neural Tube Defects
Because of its role in genetic material and cell function, a significant amount of research has gone into the role of folate in preventing neural tube defects (NTDs). Neural tube defects (NTDs) are congenital disabilitiesof the brain or spinal cord that typically occur during the first month of pregnancy. The two most commonNTDs are spina bifida and anencephaly.
Researchers have long known that inadequate levels offolateandvitamin B12during pregnancy increase the risk of NTDs. Of the two, folate deficiency is much more common and more of a concern.
A 2016 systematic review and meta-analysis of 302 studies compared the prevalence of spina bifida between countries that mandate fortification and those that don't. Researchers found that spina bifida was lower in places that mandated folic acid fortification than in those where it was voluntary.
According to a 2015 Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report, the introduction of fortified foods led to a 28% decrease in spina bifida cases between 1995 and 2011.
Age-related macular degeneration (AMD) is an eye disorder characterized by the progressive loss of the center of the field of vision. The underlying cause of macular AMD is not well understood. However, some scientists believe that it results from inflammationand oxidative stresses placed on the eyes over a lifetime.
In addition, high homocysteine could also contribute to AMD. Therefore, some researchers have looked at the relationship between folate and AMD due to this connection.
For example, a 2013 population-based cohort study from Australia evaluated the medical files of 1,760 adults with AMD over 10 years. Researchers observed that folate deficiency was associated with an increased risk of early and any AMD by 75% to 89%.
Moreover, a 2015 systematic review and meta-analysis of 11 studies examined the connection between homocysteine and vitamin B levels related to AMD. Researchers found that elevation in homocysteine levels correlated to a 30% increased risk of developing AMD. However, researchers did not observe a difference in folic acid levels between AMD participants and controls.
In addition, an older 2009 investigation published in JAMA evaluated whether combination therapy, including pyridoxine (B6), folic acid, and cyanocobalamin (synthetic B12), could affect AMD risk. The randomized, double-blind, placebo-controlled trial included 5,442 women over 40 years old with preexisting CVD or multiple CVD risk factors.
Researchers randomly assigned participants to either a placebo or a combination of 2.5 mg of folic acid, 50 mg pyridoxine hydrochloride, and 1 mg cyanocobalamin. After an average of 7.5 years of treatment, the experiment group reduced the risk of AMD by 35% to 40%.
Due to folate's role in genetic material and cell division, research has focused on the connection between folate and cancer. Results have been mixed, with some studies showing folate deficiency as a risk factor for cancer and others suggesting the opposite—that excessive folic acid intake increases the risk.
In a 2013 meta-analysis of epidemiological studies, researchers evaluated folate intake and the risk of bladder cancer. The research included seven cohort and six case-control studies. Overall, the groups with higher folate intake had a significantly decreased risk of bladder cancer.
Another 2014 systematic review and meta-analysis examined the relationship between higher dietary folate intake and breast cancer risk. The study included 16 prospective studies and 26 case-control studies. Researchers found that compared to those with folate intakes of less than 153 mcg, those with dietary intakes between 153 mcg and 400 mcg had a significantly decreased risk for breast cancer.
On the other hand, some research has found a potential tumor-promoting effect with folic acid supplementation.
For example, a 2012 systematic review and meta-analysis looked at the relationship between folic acid supplementation and cancer risk. In 10 randomized controlled trials, researchers found that overall cancer incidence among the folic acid supplementation group was borderline significantly increased compared to placebo. In addition, there was a moderate but statistically significant elevated risk of prostate cancer in the folic acid groups.
Still, other studies have found that folate does not affect cancer risk. For example, a 2013 meta-analysis of data on 50,000 people published inThe Lancet assessed the effects of supplementation on cancer rates. During a weighted treatment duration of 5.2 years, researchers found that folic acid had no significant impact on overall cancer incidence or site-specific cancers, including the large intestine, prostate, lung, and breast.
Folate's role in neurotransmitter (chemical messengers) synthesis and homocysteine metabolism has prompted research on its potential effect on depression.
A 2017 cohort study assessed the association between the duration of folic acid supplementation during pregnancy and the onset of postpartum depression (PPD, depression that occurs after childbirth) in Chinese people. In 1,592 participants, researchers assessed depression symptoms at 6-12 weeks postpartum. Compared to those who took folic acid for less than six months, those who took it for more than six months had a lower prevalence of PPD.
In addition, a 2018 systematic review and meta-analysis evaluated the use of folate in treating major depressive disorder. Researchers found that 5 mg or less of folate per day or 15 mg of methylfolate combined with selective serotonin reuptake inhibitor (SSRI) therapy was significantly beneficial compared to placebo.
On the other hand, other studies have found no benefits. For example, a 2015 longitudinal study evaluated the effects of intakes of folate and other B vitamins on depression risk. Participants who did not have depression at the study onset were assessed for three years. While B6 and B12 were associated with lower rates of depression, there was no association noted with folic acid.
In addition to the potential health benefits listed above, some people use folate to support autism and memory diseases.
You may develop a folate deficiency if you don't get enough from your diet or folic acid supplements. Although this is rare in the United States, deficiency can occur in people with certain risk factors.
What Causes a Folate Deficiency?
Certain groups are vulnerable to folate deficiency, including:
- Pregnant people
- Younger children (whose intake may fall short due to their rapid growth)
- People with alcohol use disorder
- Those with malabsorption disorders, like celiac disease
- People with the MTHFR gene variant, which impairs folate conversion
- People using oral contraceptives
- Those taking the diabetes medication Glucophage (metformin)
- Those on the auto-immune disease medication methotrexate
To further reduce the risk of NTD, healthcare providers will routinely recommend folate supplements and a daily multivitamin during pregnancy. In addition, those who could may become pregnant should take a daily 0.4-milligram (400-microgram) folic acid supplement. That's because NTDs can occur before a person knows they are pregnant.
How Do I Know If I Have a Folate Deficiency?
A folate deficiency may need to be correctly identified and diagnosed by a healthcare provider through specific labs. However, some identifying factors may signal a deficiency.
Megaloblastic anemia, a type of anemia with large red blood cells, is a clinical sign of folate deficiency. Symptoms include:
- Trouble concentrating
- Heart palpitations
- Shortness of breath
In addition to symptoms of megaloblastic anemia, other symptoms associated with folate deficiency include:
- Tongue and mouth ulcers
- Skin, hair, or fingernail changes
- Gastrointestinal symptoms
- Elevated blood homocysteine levels
Why People With IBD Are Often Deficient in Folic Acid
What Are the Side Effects of Folate?
Your provider may recommend you take folate if you are pregnant, breastfeeding, or deficient. As an essential nutrient sourced from food, folate is not associated with side effects or risks. However, consuming a supplement like folate may have potential side effects. These side effects may be common or severe.
Common Side Effects
Folic acid supplements may cause some common side effects, including:
- Skin rash
Severe Side Effects
Severe side effects are primarily associated with excessive supplementation. One main concern is that while high folate levels can correct megaloblastic anemia (a health condition caused by folate deficiency), it does not reverse the neurological damage from B12 deficiency. So, if you have both, high folate intake can sometimes mask B12 deficiency until it's too late to correct it.
In addition, excessive folate may increase certain health risks, including some cancers and cognitive impairment.
Dosage: How Much Folate Should I Take?
Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs.
The recommended daily allowance (RDA) of folate can vary by age and pregnancy status as follows:
- 65 mcg per day for infants up to 6 months
- 80 mcg per day for infants 7-12 months
- 150 mcg per day for toddlers 1-3 years
- 200 mcg per day for kids 4-8 years
- 300 mcg per day for kids 9-13 years
- 400 mcg per day for people over 14
- 600 mcg per day during pregnancy
- 500 mcg per day during lactation
A healthcare provider may recommend 1-5 mg of folic acid for deficiency.
What Happens If I Take Too Much Folate?
To avoid toxicity, be aware of the appropriate dosage (above) and keep the safe upper intake levels in mind. The Institute of Medicine: Food and Nutrition Board establishes the upper intake levels (ULs) for folate supplements and fortified foods.
Upper Intake Levels
- Birth to 1 year: Unknown
- 1-3 years: 300 mcg
- 4-8 years: 400 mcg
- 9-13 years: 600 mcg
- 14-18 years: 800 mcg
- 19 and older: 1,000 mcg
If you consume more than this amount or more than what is recommended by your healthcare provider, you may want to go to the emergency room.
Some groups are at risk of taking excess folate, including older adults and children who take supplements and eat fortified foods.
Although dietary folate cannot interact with pharmaceutical or over-the-counter medications, certain drugs can interfere with how your body metabolizes folate. These include:
- Anticonvulsants like Dilantin (phenytoin), Tegretol (carbamazepine),orvalproic acid
- Azulfidine (sulfasalazine), used to treat ulcerative colitis and rheumatoid arthritis
- Birth control pills
- Metformin, used to controlblood sugar
- Methotrexate, used to treat certain cancers and autoimmune diseases
It is essential to carefully read the ingredient list and nutrition facts panel to know which ingredients are in the supplement you take. Please review this supplement label with your healthcare provider to discuss any potential interactions with foods, other supplements, and medications.
How To Store Folate
Store folic acid in a cool, dry place. Keep it away from direct sunlight. Discard after one year or as indicated on the packaging.
Although many people use the terms folate and folic acid interchangeably, there are key differences. Folate is an umbrella term for many forms of B9 vitamins, including:
- Folic acid
- Dihydrofolate (DHF)
- Tetrahydrofolate (THF),
- 5, 10-methylenetetrahydrofolate (5, 10-MTHF)
- 5-methyltetrahydrofolate (5-MTHF)
Folic acid is a synthetic form of folate and is the most common supplement form. Manufacturers also use it in food fortification.
While folate immediately converts in the digestive tract into the active form of vitamin B9, called 5-methyl-THF (5-MTHF), folic acid needs to enter the bloodstream and reach the liver and other tissues for conversion.
5-MTHF is another folate supplement form. In the U.S., around 25% of Hispanic people, 10%-15% of White people, and 6% of African Americans have a gene variant known as MTHFR C677T. This variant can further affect the ability to metabolize folic acid.
People with a mutation in the C677T gene have an increased risk of having a baby with an NTD. Some sources recommend supplementing with MTHF rather than inactive folic acid.
Frequently Asked Questions
How do you know if you have folate deficiency?
Signs of folate deficiency are often subtle. Unexplained fatigue and weakness are often the first signs. It is usually only after symptoms are severe that healthcare providers identify folate deficiency anemia. It is differentiated from other types of anemia in that the reduced red blood cell count will be accompanied by the appearance of large, misshapen, immature red blood cells called megaloblasts.
Learn More:Health Benefits of Folic Acid
Is folate the same thing as folic acid?
While folate and folic acid are often used interchangeably, they aren't exactly the same thing. Folic acid is a synthetic form of folate often found in vitamins and added to fortified foods.
Learn More:The Functions of the Liver
Sources of Folate and What To Look For
Folate is naturally present in various foods, including vegetables (especially dark green leafy vegetables), fruits, nuts, beans, peas, seafood, eggs, dairy, meat, poultry, and grains. Folate from food sources is best because it is easier for your body to process. However, folate is also available in the form of folic acid through supplementation and food fortification.
Food Sources of Folate
Among the foods especially rich in folate are:
- Beef liver: 215 mcg per 3-ounce serving
- Spinach (cooked): 131 mcg per 1/2-cup serving
- Black-eyed peas: 101 mcg per 1/2-cup serving
- Breakfast cereals (fortified): 100 mcg per 1-cup serving
- Asparagus: 89 mcg per 4 spears
- Brussel sprouts: 78 mcg per 1/2-cup serving
- Romaine lettuce (shredded): 64 mcg per 1-cup serving
- Avocado: 59 mcg per 1/2-cup serving
- White rice (cooked): 54 mcg per 1/2-cup serving
- Broccoli: 52 mcg per 1/2-cup serving
- Mustard greens (cooked): 52 mcg per 1/2 cup serving
In addition, in the U.S., manufacturers add 140 mcg folic acid/100 gto grains and cereals.
Supplement Sources of Folate
Although researchers once thought that folic acid was absorbed better than folate, they now know it metabolizes very slowly. Moreover, much of the folic acid you consume will remain unmetabolized and linger in the system. There have also been concerns that excessive accumulation of unmetabolized folic acid may promote tumor growth, although this has yet to be definitively proven.
Generally speaking, if you consume enough folate in your diet, you won't need to take a folic acid supplement. However, daily folate intake is required to maintain a healthy pregnancy, ensure normal fetal development, and prevent severe congenital disabilities. Therefore, health experts recommend that pregnant people and those who could become pregnant receive 400 mcg of folic acid daily.
Folate is a B vitamin essential for building your body's genetic material. Many foods naturally contain folate, especially green, leafy vegetables. Manufacturers also fortify grains and cereals with folic acid, a synthetic form of folate. In addition, folic acid is available in supplement form.
Folate deficiency is rare in the U.S., thanks to fortification. However, because too little folate can cause congenital disabilities, it's critical that people who are pregnant or who could become pregnant take a folic acid supplement.