Vitamin B9 (Folate)

Folate, also called vitamin B9, is a water-soluble B vitamin. Every cell uses it to move single carbon atoms from one molecule to another, says the NIH (the US National Institutes of Health). Those carbons end up in the building blocks of DNA, and in the methyl groups the body uses to recycle homocysteine.

Fast-dividing tissues feel a shortage first. That is why the main sign of deficiency is megaloblastic anemia, with unusually large red blood cells. Folic acid, chemically pteroylglutamic acid, is the synthetic form added to supplements and fortified grain.

Folate and folic acid are not the same thing. Natural food folates are unstable in light, oxygen and heat, while folic acid is the most chemically stable form. EFSA (the EU’s food safety agency) notes it is not a natural component of the diet.

Because the two are absorbed differently, labels use dietary folate equivalents (DFE), and 1 mcg (microgram) of folic acid counts as 1.7 mcg DFE. The name comes from the Latin folium, a leaf: folic acid was first isolated from spinach in 1941.

Timing is the part most readers do not know. The neural tube, which becomes the brain and spinal cord, closes 21 to 28 days after conception. That is often before a woman knows she is pregnant, and about half of US pregnancies are unplanned, according to the NIH.

So health agencies advise folic acid for everyone who could become pregnant, and the US and Canada added it to enriched grain in 1998. Outside pregnancy, deficiency is uncommon in the US. The evidence for extra folic acid against heart disease, cancer and dementia is mixed, as the studies below show.

Health benefits of folate

• ★★★Folic acid supplements cut neural tube defectsIn five trials, folic acid supplements cut the risk of neural tube defects, a type of birth defect, to 0.31 times. The US Preventive Services Task Force recommends 400 to 800 mcg a day for anyone who is planning to become pregnant or could.
• ★★★Lower homocysteine, a blood markerIn a pooled analysis of 25 trials, 0.4 mg of folic acid a day lowered homocysteine by 20%, and 0.8 mg by 23%. Homocysteine is a blood marker, not a health outcome.
• ★★★No clear effect on vascular events or deathsIn 8 trials in 37,485 people at high heart and blood vessel risk, folic acid (several with B6 and B12) cut homocysteine 25% on average. Major vascular events were 1.01 times as common, with no clear difference.
• ★★★No clear effect on cancerIn 13 trials with 49,621 people, folic acid pills gave 1.06 times the cancer rate of placebo over about 5 years. No specific cancer site was affected.
• ★★Fewer strokes, mostly where grain is unfortifiedAcross 21 trials, folic acid cut stroke risk by 10%, more where grain was unfortified (0.83 times the risk, against 1.04 where it was fortified). In Chinese adults with high blood pressure, adding 0.8 mg of folic acid to a blood pressure drug cut first strokes by 21%.

Foods high in folate

Beans and lentils lead our USDA ranking per serving. Cranberry beans give 366 mcg per cup (177 g), lentils 358 mcg per cup (198 g) and mung beans 321 mcg per cup (202 g). The Daily Value (the FDA label value) is 400 mcg DFE. Pinto beans, chickpeas and adzuki beans follow; the ranking below gives their amounts.

Per 100 g, peanuts (240 mcg), sunflower seeds (227 mcg), cranberry beans (207 mcg) and spinach (194 mcg) lead, followed by quinoa and lentils. Per 100 kcal, leafy vegetables and herbs win: spinach has 843 mcg, endive 835 mcg and bok choy 508 mcg, then come parsley and arugula.

The NIH table adds braised beef liver at 215 mcg DFE in 3 oz and boiled spinach at 131 mcg per ½ cup. Boiled black-eyed peas give 105 mcg per ½ cup, boiled asparagus 89 mcg for 4 spears and frozen boiled Brussels sprouts 78 mcg per ½ cup.

Grain foods matter because of fortification. Since January 1998 the US has required 140 mcg of folic acid per 100 g in enriched grain products. Canada has required 150 mcg per 100 g since November 1998. The NIH says this raised mean US folic acid intake by about 190 mcg a day.

The NIH counts ½ cup of enriched white rice at 90 mcg DFE and ½ cup of enriched spaghetti at 74 mcg. A slice of white bread gives 50 mcg.

Cooking and storage change what reaches the plate. In a UK study, boiling kept only 49% of the folate in spinach and 44% in broccoli. Steaming caused no clear loss, even after 4.5 minutes for spinach and 15 minutes for broccoli. Grilled beef and boiled whole potatoes showed no clear change.

EFSA adds that natural folates are unstable in light, oxygen and heat. Food folate is also absorbed less completely than folic acid. But a 4-week trial in 72 adults put the difference at about 20%, less than the DFE system assumes.

How folate works

Most of the biochemistry below is well established, but the details come from reviews, cell work and tissue samples more than from trials. Five ideas cover it. Folate carries single carbons, fast-dividing cells need it first, and a transporter lets it into the body. Folic acid must be converted before use, and a common gene variant changes how well one enzyme works.

A sixth point is bookkeeping: food folate and folic acid are counted differently. Here is each one, and what has been seen in people.

It carries single carbons

Inside cells, folate works as tetrahydrofolate (THF), according to EFSA. THF picks up one-carbon units and hands them to enzymes that need them. Two jobs matter most. THF supplies carbons for the nucleotides in DNA and RNA.

And 5-methyl-THF passes a methyl group to homocysteine to make methionine, in a reaction that also needs vitamin B12 as methylcobalamin. Methionine then becomes SAM, which donates methyl groups to more than 100 enzymes. When folate runs short, homocysteine rises.

Cells that divide fast need it first

One folate-dependent step turns dUMP into dTMP, a DNA building block needed for cell division, the NIH says. When folate is short, uracil is built into DNA in place of thymine. In a laboratory study, folate deficiency put about 4 million uracil bases into the DNA of each human cell and caused chromosome breaks. Giving folate reversed both.

Tissues that turn over quickly, such as bone marrow, show the problem first, as unusually large red blood cells, according to EFSA.

A transporter lets it in

Food folates are first cut down to the single-unit form. They are then taken up in the upper small intestine by a pH-dependent transport system. At very high doses some also crosses by passive diffusion, as EFSA describes.

In 2006 researchers identified the human transporter, PCFT. They showed that a loss-of-function mutation in its gene causes hereditary folate malabsorption in one family. Colon bacteria make folate too, though how much of it the body uses is unclear, the NIH says.

The body must convert folic acid first

Folic acid has no vitamin activity until an enzyme, dihydrofolate reductase (DHFR), reduces it. Human liver does this slowly. In six liver samples, activity per gram averaged under 2% of rat liver, and it varied almost five-fold between samples. When DHFR is overwhelmed, unmetabolized folic acid shows up in the blood.

Whether it does any harm is not known, according to the NIH. A 2026 systematic review says the evidence does not establish that it independently causes harm.

A common gene variant changes how much you may need

The MTHFR enzyme makes 5-methyl-THF. People with two copies of the 677C>T variant (the TT type) have a less active enzyme. About 25% of Hispanic, 10% of white and Asian and 1% of African American people in the US are TT, the NIH says. EFSA puts it at 12% in northern and up to 24% in southern Europe.

EFSA built an allowance for the TT type into its adult reference intake. The enzyme needs riboflavin (vitamin B2) as a cofactor. In a 12-week trial, 1.6 mg of riboflavin a day lowered homocysteine by 22% on average, but only in adults with the TT type.

Even so, the American College of Medical Genetics says routine MTHFR testing has minimal clinical utility. The CDC (the US public health agency) advises 400 mcg of folic acid, not methylfolate, for people who could become pregnant, even with the variant.

Food folate and folic acid are counted differently

The DFE system treats folic acid taken with food as about 1.7 times as potent as food folate. It rests on an estimated 85% absorption for folic acid with food and about 50% for food folate, according to the NIH. EFSA kept the system for lack of better data but notes that its figures have not been confirmed in studies. One 4-week trial in 72 adults put food folate from fruit, vegetables and liver at about 80% of folic acid.

What has been seen in people

The clearest result is about pregnancy. In a Cochrane review of five trials, folic acid cut neural tube defects by more than two thirds. The NIH says the mechanism has not been fully established, though. Folic acid at 0.4 mg a day also lowers homocysteine by 20%.

But lowering homocysteine did not mean fewer heart attacks, cancers or deaths in a meta-analysis of 8 trials. The stroke result depends on the setting: a 10% drop across 21 trials, with the clearest effect where grain is not fortified.

The biochemistry of deficiency is direct, too: in pregnancy, folic acid lowered the risk ratio for megaloblastic anemia to 0.21. All of these are among the study cards above.

How much folate do you need?

Adults need 400 mcg of dietary folate equivalents (DFE) a day, according to the US recommended dietary allowance (RDA). EFSA’s population reference intake in the EU is 330 mcg DFE for adults. One mcg DFE equals 1 mcg of food folate. It also equals 0.6 mcg of folic acid with food, from fortified food or a supplement, or 0.5 mcg taken on an empty stomach.

Pregnancy raises the US allowance to 600 mcg DFE a day. EFSA sets an adequate intake of 600 mcg DFE, noting that the evidence is weaker than for non-pregnant adults. Breastfeeding is 500 mcg DFE in both systems; EFSA adds 130 mcg DFE a day to cover folate lost in milk. For older adults the US allowance stays at 400 mcg DFE from age 19 on, and EFSA’s adult value covers all adults.

Women and teenage girls who could become pregnant are advised to get 400 mcg of folic acid a day from supplements, fortified foods or both. That comes on top of the folate in food. The US Preventive Services Task Force recommends 400 to 800 mcg of folic acid a day. It advises starting at least one month before conception and continuing through the first 2 to 3 months of pregnancy.

People with alcohol use disorder, celiac disease, inflammatory bowel disease or other malabsorption are at higher risk of low folate. EFSA says the MTHFR TT type raises the requirement.

Folate deficiency: signs and who is at risk

Megaloblastic anemia is the main sign, and it can also come from vitamin B12 deficiency. Its symptoms include weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations and shortness of breath, according to the NIH. Deficiency can also cause a sore tongue and shallow mouth ulcers, changes in skin, hair or nail color, gut symptoms and a high homocysteine level. EFSA notes that irritability and forgetfulness are less frequent and usually mild.

In pregnancy, low folate raises the risk of neural tube defects. The NIH says it has also been associated with low birth weight and preterm delivery. Frank deficiency is rare in the US, where less than 0.5% of children aged 1 to 18 have a deficient red blood cell folate. It usually comes together with other deficiencies.

The NIH lists the groups most at risk. Among them are people with alcohol use disorder. In Portugal, where food is not fortified, over 60% of people with chronic alcoholism had low folate status.

Women of childbearing age are another group. In US data, 19% of girls aged 14 to 18 and 17% of women aged 19 to 30 fell short of the average requirement. That was even counting supplements.

People who absorb less are also at risk. They include those with celiac disease, atrophic gastritis and inflammatory bowel disease, where 20% to 60% of patients are deficient. Methotrexate, antiepileptic drugs and sulfasalazine can also lower folate or its absorption.

A serum folate above 3 ng/mL indicates adequacy, according to the NIH. A red blood cell folate above 140 ng/mL indicates adequate status over the longer term. Serum folate reflects recent intake, so red blood cell folate is the better long-term measure.

EFSA uses different adequacy cut-offs: 10 nmol/L in serum and 340 nmol/L in red blood cells. It based them on where homocysteine levels off.

Homocysteine rises when folate is short, but kidney problems and B12 deficiency raise it too, so it is not specific. Large amounts of folic acid can correct the anemia of B12 deficiency without fixing the nerve damage. So a low folate result and a B12 result are best read together by a doctor.

Forms of folate: absorption and effects

Folate supplements differ in what the molecule is, how it is counted and how the body handles it. Folic acid is the synthetic, fully oxidized form in most supplements and in fortified grain. 5-methyltetrahydrofolate (5-MTHF, also sold as L-methylfolate or methylfolate) is the main folate in blood, and the form the body makes from folic acid.

Folinic acid is another reduced form, studied mainly as a medicine. Food folate is a mix of polyglutamates that the gut trims before absorbing them.

The honest bottom line: nearly all comparisons measure blood folate, not health. Folic acid is the only form tested in the large trials that prevented neural tube defects, according to a 2026 review. The EU claim covers folic acid too.

In one 24-week trial, 5-MTHF raised red blood cell folate more than folic acid. In EFSA’s review of longer trials, it raised it about the same. It also produced less unmetabolized folic acid. We found no trial that compared the forms head to head for neural tube defects, stroke or any other health outcome.

So the popular idea that methylfolate works better, especially for people with MTHFR variants, rests on blood measurements. The NIH says 5-MTHF might be more beneficial for some people with the variant, while the CDC still advises folic acid.

Mixtures matter too. The first-occurrence neural tube trial used a multivitamin with 0.8 mg of folic acid. The heart and brain trials used folic acid with vitamins B6 and B12, so their results belong to the combinations.

The outcome trials above used folic acid for neural tube defects, stroke, cancer, depression (5 mg) and pre-eclampsia (4 mg). The methotrexate review used folic or folinic acid, and the depression add-on trial used L-methylfolate (15 mg).

Form	Activity or conversion	What studies show	Source
Folic acid	1 mcg DFE = 0.6 mcg with food or 0.5 mcg on an empty stomach, so 1 mcg counts as 1.7 mcg DFE on a label	About 85% is absorbed with food and nearly 100% without, according to the NIH. It is the only form tested in the large neural tube defect trials and the form named in the EU claim. A dose of 0.4 mg a day lowered homocysteine by 20%. Human liver converts it slowly, and in a US survey 38% of adults aged 60 and older had unmetabolized folic acid in their blood. The US and EU upper levels cover this form.	1, 2, 6, 10, 12, 13, 14, 15
5-MTHF (L-methylfolate; calcium or glucosamine salt)	Not formally established. The FDA allows a factor of 1.7, as for folic acid, or a maker’s own factor not above 1.7	The NIH says its bioavailability is the same as or greater than folic acid. EFSA found it similar at 100 to 400 mcg a day in trials of 16 to 24 weeks. In 144 women, 416 mcg raised red blood cell folate more than 400 mcg of folic acid over 24 weeks, and in 24 women a single dose gave a higher peak level, with unmetabolized folic acid rare. A review of three trials found less unmetabolized folic acid, but two trials of red blood cell folate disagreed. L-methylfolate at 15 mg a day helped in one of two depression trials. We found no trial for neural tube defects.	1, 2, 4, 5, 6, 7
Folinic acid (5-formyl-THF, leucovorin)	Not stated	Pooled with folic acid in six trials in rheumatoid arthritis, it cut the gut side effects of methotrexate. In a 12-week trial in 48 children with autism and language impairment, 2 mg per kg a day improved verbal communication. We found no trial of folinic acid for neural tube defects.	8, 9
Food folate	1 mcg DFE = 1 mcg food folate	A mix of reduced forms that are unstable in light, oxygen and heat. The DFE system assumes about 50% absorption. In one 4-week trial in 72 adults, food folate from fruit, vegetables and liver had about 80% of the bioavailability of folic acid.	1, 2, 3

Here are the head-to-head and form-specific studies, strongest evidence first, 8 in all.

Is folate safe? Supplements, dose and interactions

Folate from food is not a safety concern. EFSA says natural food folate is considered safe. The US sets no upper level for it, because high intakes from food have not been reported to cause adverse effects. The limits cover synthetic folic acid from supplements and fortified foods.

The US tolerable upper intake level (UL, the daily maximum) is 1,000 mcg for adults and 800 mcg for ages 14 to 18. It is 600 mcg for ages 9 to 13, 400 mcg for ages 4 to 8 and 300 mcg for ages 1 to 3. It is counted in mcg of folic acid, not DFE, so 1,000 mcg of folic acid equals 1,667 mcg DFE. It applies in pregnancy and breastfeeding too, but not to people taking higher doses under medical supervision.

EFSA’s folate opinion describes the EU level, set by the Scientific Committee on Food in 2000. It is 1 mg of folic acid a day for adults, including pregnant and breastfeeding women. It falls to 200 mcg at ages 1 to 3, and is 800 mcg at ages 15 to 17.

The reason is vitamin B12. The level was set from case reports of B12-deficient patients who relapsed neurologically on folic acid. The lowest observed effect was at 5 mg a day, and a safety factor of five was applied.

• Masking and worsening B12 deficiency. Folic acid can reverse the anemia of B12 deficiency while the nerve damage goes on. EFSA names irreversible damage to the spinal cord as the risk. The NIH says the concern has shifted to high folate worsening the anemia and cognitive symptoms of B12 deficiency. In US seniors with low B12, high serum folate went with more anemia and cognitive impairment.
• Cancer. Trials are mixed. In 1,021 people with past adenomas, 1 mg of folic acid did not lower adenoma risk. It was linked to more advanced lesions in the second round. Norwegian heart patients given folic acid plus B12 had more cancer. A meta-analysis of 13 trials found no clear effect of folic acid on overall cancer. In 2015 an expert panel convened by the National Toxicology Program and the NIH reported. It concluded that folic acid does not reduce cancer risk in people with adequate folate status.
• High doses and unmetabolized folic acid. In limited research, single doses of 300 or 400 mcg of folic acid produced detectable unmetabolized folic acid in the blood. Doses of 100 or 200 mcg did not. The NIH says the health effects are not well understood. About 5% of US adults aged 51 to 70 get more folic acid than the upper level, mostly from supplements. In pregnancy, 4 mg a day started between 8 and 16 weeks did not prevent pre-eclampsia. The NIH also cites a study of intake around conception. It linked 1,000 mcg or more to lower child test scores at age 4 to 5 than 400 to 999 mcg.
• Drug interactions. Methotrexate is a folate antagonist (it works against folate). People taking it for cancer should ask their oncologist before taking folate. In rheumatoid arthritis, though, folic or folinic acid cut its gut side effects without weakening its effect. Antiepileptic drugs such as phenytoin, carbamazepine and valproate can lower folate, and folate might lower their levels, so ask your doctor first. Sulfasalazine blocks folate absorption.
• Who should ask a doctor. Anyone with known or possible B12 deficiency, a history of colorectal adenomas or cancer, or epilepsy. Also anyone taking methotrexate or sulfasalazine, and anyone considering more than 1,000 mcg of folic acid. Some experts advise 4 to 5 mg after a pregnancy with a neural tube defect; such doses should only be taken under medical supervision.

How to get more folate

• Best foods. Cranberry beans give 366 mcg per cup, lentils 358 mcg and mung beans 321 mcg in our ranking. Spinach holds 194 mcg per 100 g. The NIH adds braised beef liver at 215 mcg DFE in 3 oz and boiled spinach at 131 mcg per ½ cup.
• Keep cooking short. Boiling kept only 49% of the folate in spinach and 44% in broccoli, while steaming caused no clear loss. So steaming keeps more than boiling.
• If you could become pregnant. Take 400 mcg of folic acid a day from a supplement, fortified food or both, in addition to the folate in food. Health agencies say to start at least a month before conception. In one trial of 144 women, red blood cell folate was still rising after 24 weeks.

History of folate

The story starts with anemia in pregnancy. In the early 1930s Lucy Wills worked in Bombay (now Mumbai) on severe anemia in poor, pregnant textile workers. She ruled out infection and parasites and linked the anemia to a poor, monotonous diet. She found that liver and spreads made from yeast corrected it.

The unknown protective substance was first called the Wills factor. She reported her work in the British Medical Journal in 1931.

The substance went by several names, among them vitamin M, vitamin Bc and Lactobacillus casei factor. Then folic acid was isolated from spinach in 1941, and industrial synthesis followed in 1945. Soon afterward a physician showed that folic acid gave a prompt blood response in many macrocytic anemias, though not in pernicious anemia.

In 1964 Bryan Hibbard published on the role of folic acid in pregnancy, with particular reference to anemia, abruption and abortion.

Neural tube defects came next. In 1991 the Medical Research Council trial showed that folic acid prevented repeat defects, with a 72% protective effect. In 1992 a Hungarian trial of a multivitamin with folic acid showed fewer first occurrences.

The US Food and Drug Administration authorized adding folic acid to enriched grain in March 1996, with compliance mandatory by January 1998. Canada followed in November 1998. The NIH reports that US neural tube defect rates have fallen 28% since 1998.

The EU authorized its folic acid claim in 2014, and the US Preventive Services Task Force reaffirmed its grade A recommendation in 2023.

Frequently asked questions about folate

What is the difference between folate and folic acid?

Folate is the family of forms found naturally in food, and folic acid is the synthetic form used in supplements and fortified grain. Folic acid is the most stable and is absorbed better: about 85% with food and nearly 100% on an empty stomach. Food folate is estimated at 50%, though one 4-week trial of 72 adults put it at about 80% of folic acid. The body must convert folic acid before using it. The label unit DFE puts both on one scale, with 1 mcg of folic acid counting as 1.7 mcg DFE.

How much folic acid should I take before and during pregnancy?

The NIH advises everyone who could become pregnant to get 400 mcg of folic acid a day, on top of the folate in food. It can come from supplements, fortified foods or both. The US Preventive Services Task Force recommends 400 to 800 mcg a day. It advises starting at least one month before conception and continuing through the first 2 to 3 months of pregnancy. The US allowance in pregnancy is 600 mcg DFE a day. After a pregnancy with a neural tube defect, some experts advise 4,000 to 5,000 mcg, which should be taken only under medical supervision.

Is methylfolate better than folic acid?

It has not been shown to be better for health. In 144 women, 416 mcg of 5-MTHF raised red blood cell folate more than 400 mcg of folic acid over 24 weeks. A review of three trials found less unmetabolized folic acid with 5-MTHF. But the large neural tube defect trials used folic acid. The CDC advises folic acid even for people with the MTHFR 677C>T variant. The American College of Medical Genetics says routine MTHFR testing has minimal clinical utility.

Can you take too much folic acid?

Yes, from supplements and fortified foods, though not from food folate. The US upper level is 1,000 mcg of folic acid a day for adults, and the EU level described by EFSA is 1 mg. The main worry is that folic acid can reverse the anemia of vitamin B12 deficiency while nerve damage goes on. Trials in cancer are mixed, and the health effects of unmetabolized folic acid are not well understood.

Does folic acid prevent stroke or heart disease?

It may help prevent stroke in places where grain is not fortified, but it does not prevent heart attacks. A meta-analysis of 21 trials found 10% fewer strokes (0.90 times the risk). That was 0.83 in areas without fortified grain and 1.04 where grain is fortified. A pooled analysis of 8 trials with 37,485 people found no clear effect on stroke (0.96). The HOPE-2 trial found no fewer cardiovascular deaths or heart attacks. Most of these trials gave folic acid with vitamins B6 and B12.

Does cooking destroy folate?

Partly, depending on the food and the method. In a UK study, boiling kept 49% of the folate in spinach and 44% in broccoli, while steaming caused no clear loss. Grilled beef and boiled whole potatoes did not change clearly. EFSA says natural folates are unstable in light, oxygen and heat.

Which foods are highest in folate?

Beans and lentils lead our USDA ranking per serving. Cranberry beans give 366 mcg per cup, lentils 358 mcg, mung beans 321 mcg and pinto beans 294 mcg. Per 100 g, peanuts (240 mcg), sunflower seeds (227 mcg) and spinach (194 mcg) are near the top. The NIH lists braised beef liver at 215 mcg DFE in 3 oz. Enriched grains add folic acid by law in the US and Canada.

What is a normal folate level in a blood test?

The NIH says a serum folate above 3 ng/mL indicates adequacy, and a red blood cell folate above 140 ng/mL adequate longer-term status. EFSA uses 10 nmol/L in serum and 340 nmol/L in red blood cells. So the cut-offs depend on who sets them and which unit the lab uses. Serum folate reflects recent meals. Homocysteine is not specific, because kidney problems and B12 deficiency also raise it, so a doctor reads folate and B12 together.