Beans, leafy greens and citrus are food sources of folate.

Vitamin B9 (folate and folic acid)

Water-soluble B vitamin (folate and folic acid) · also called Folate, folic acid, folacin, vitamin B9

Folate is a B vitamin found in beans, leafy greens and citrus fruit. Folic acid is the man-made form used in pills and added to some foods. The best-supported benefit is that folic acid taken around conception lowers neural tube defects such as spina bifida, and agencies advise it for anyone who could become pregnant. High amounts can hide vitamin B12 deficiency, so ask a doctor before taking it.

General information, not medical advice. Last substantive update October 26, 2026 · Not medically reviewed. A named clinician has not signed off on this page. How this page is made

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About Vitamin B9 (folate and folic acid)

Vitamin B9 is folate in food and folic acid in pills and fortified foods. The body needs it to make DNA and red blood cells. The clearest benefits are in pregnancy (fewer neural tube defects) and in correcting a shortage. Most other uses are weak or mixed. The main cautions are B12 masking, some medicine interactions and a bowel-polyp trial signal.

What it is

Vitamin B9 is a water-soluble B vitamin. Folate is the natural form in food, and folic acid is the man-made form used in supplements and added to foods (MedlinePlus). The NHS calls it folate, folacin or vitamin B9. The body does not store it for long, so it needs a regular supply (MedlinePlus, NHS).

We did not read a history of folate for this page, so none is given.

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Food sources (USDA data)

Good sources named by the NHS include broccoli, brussels sprouts, leafy greens, peas, chickpeas, kidney beans, liver (avoid liver in pregnancy) and breakfast cereals fortified with folic acid. MedlinePlus lists dark green leafy vegetables, dried beans and peas and citrus fruit, and enriched breads, cereals, flours and pasta with folic acid added.

USDA folate in micrograms of dietary folate equivalents (DFE): Lentils, cooked, boiled, no salt: 181 micrograms DFE per 100 g; about 358 micrograms DFE in 1 cup (198 g) [FDC 172421]; Black-eyed peas (cowpeas), cooked, boiled, no salt: 208 micrograms DFE per 100 g; about 356 micrograms DFE in 1 cup (171 g) [FDC 173759]; Chickpeas, cooked, boiled, no salt: 172 micrograms DFE per 100 g; about 282 micrograms DFE in 1 cup (164 g) [FDC 173757]; Red kidney beans, cooked, boiled, no salt: 130 micrograms DFE per 100 g; about 230 micrograms DFE in 1 cup (177 g) [FDC 175194]; Spinach, raw: 194 micrograms DFE per 100 g; about 58 micrograms DFE in 1 cup (30 g) [FDC 168462].

More: Asparagus, raw: 52 micrograms DFE per 100 g; about 70 micrograms DFE in 1 cup (134 g) [FDC 168389]; Broccoli, raw: 63 micrograms DFE per 100 g; about 57 micrograms DFE in 1 cup chopped (91 g) [FDC 170379]; Brussels sprouts, raw: 61 micrograms DFE per 100 g; about 54 micrograms DFE in 1 cup (88 g) [FDC 170383]; Avocado, raw: 81 micrograms DFE per 100 g; about 122 micrograms DFE in 1 cup cubes (150 g) [FDC 171705]; Orange, raw: 30 micrograms DFE per 100 g; about 39 micrograms DFE in 1 orange (131 g) (131 g) [FDC 169097].

These numbers describe foods and are not advice on how much to eat. In one 4-week trial of 72 adults, folate from fruit, vegetables and liver was about 80% as available to the body as folic acid. Fortified cereals vary and their amounts were not read.

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Official intake levels

The US Food and Nutrition Board reference intakes quoted by MedlinePlus: 400 micrograms a day for ages 14 and over, 600 in pregnancy, 500 while breastfeeding, and 150, 200 and 300 for ages 1 to 3, 4 to 8 and 9 to 13. The NHS gives 200 micrograms a day for UK adults. MedlinePlus advises avoiding more than 1,000 micrograms a day of folic acid, except for women with an earlier affected pregnancy who are planning to conceive. These are regulator statements, not advice to take any amount.

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What the research shows

Pregnancy: a Cochrane review of 5 trials (7391 women) found folic acid, alone or with other nutrients, cut neural tube defects (RR 0.31, 0.17 to 0.58; high-quality evidence). The review found no clear effect on cleft lip or palate, heart defects or miscarriage. The US Preventive Services Task Force (2023) gives a grade A recommendation for people planning or who could become pregnant.

Deficiency: the NHS says folic acid tablets are used to restore folate levels in folate-deficiency anaemia. We read no trial of this.

Heart and stroke: across 8 trials (37,485 people), folic acid lowered homocysteine about 25% with no effect on major vascular events (RR 1.01) or stroke (RR 0.96). A Cochrane review of 15 trials found slightly fewer strokes (RR 0.90) and no heart attack benefit. In a Chinese trial of 20,702 adults with high blood pressure, enalapril plus folic acid gave fewer first strokes than enalapril alone (HR 0.79).

Memory: one 3-year trial in 818 older adults found small gains for memory and processing speed. Bowel polyps: 1 mg a day did not reduce new polyps in 1021 people with earlier polyps. Methotrexate: Cochrane found folate cut side effects such as stomach upset (RR 0.74) and raised liver enzymes (RR 0.23).

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Food versus pills

The benefits proven in trials, fewer neural tube defects and fewer methotrexate side effects, were shown with folic acid pills, not with food folate. Foods give folate with fibre and other nutrients, and the NHS says most people can get what they need from a varied diet. A small trial found 5-MTHF raised blood folate more than folic acid, but no health-outcome trial of it was read.

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At a glance

Traditional uses history, not proof

Folate is a nutrient from food, not a traditional remedy
Folic acid is a standard medicine and supplement for pregnancy and folate deficiency

Studied for research

Neural tube defects, high certainty (Cochrane review, folic acid pills)
Folate-deficiency anaemia, moderate certainty (agency guidance, no trial read)
Heart attack and stroke, mixed certainty
Methotrexate side effects, moderate certainty (rheumatoid arthritis)
Memory in older adults, low certainty (one trial)
Bowel polyps and cancer, evidence against benefit
Methylfolate versus folic acid, insufficient evidence for health outcomes

Main compounds

Folate (natural food forms)
Folic acid (man-made form)
5-MTHF (methylfolate)

Common forms

Folic acid tablets (tested in most trials)
Folic acid with other vitamins or a blood pressure drug (some trials)
5-MTHF / l-methylfolate (one small single-dose trial)
Food folate (beans, leafy greens, citrus) is a different source and was not tested in the trials of birth defects

Research links: 2015 Cochrane review: folate and birth defects · 2023 US Preventive Services Task Force statement · 2017 Cochrane review: homocysteine lowering and heart events · Research Library · Genes & Biomarkers Library

What it is and its history

Accepted scientific name: Vitamin B9 (folate and folic acid). A water-soluble B vitamin, not an organism.
Synonyms: Folacin; Pteroylglutamic acid
Common names: Folate (English); Folic acid (English); Vitamin B9 (English); Folacin (English)
Family or group: B vitamins (water-soluble)
Harvest and processing: Folate occurs naturally in foods. Folic acid is made in a laboratory and added to supplements and to fortified foods such as enriched breads, cereals, flours, cornmeals, pastas and rice (MedlinePlus). Losses from cooking and storage were not researched.
Look-alikes and adulterants: Name: Folic acid; Note: The man-made form; the one tested in most trials.; Name: Folinic acid; Note: A related folate form used alongside methotrexate (Cochrane review).; Name: 5-MTHF / l-methylfolate; Note: A reduced folate form sold as a supplement; see the Evidence tab.; Name: Vitamin B12; Note: A different vitamin; deficiency of either causes a similar anaemia (NHS).

What is inside, and how it may work

What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.

Main compounds

Compound	Family	Where it is concentrated	Activity studied	Level of evidence
Folate (natural food forms)	B vitamin	Found in foods such as dark green leafy vegetables, dried beans and peas, and citrus fruit (MedlinePlus) USDA per 100 g (DFE): cooked lentils 181, cooked black-eyed peas 208, cooked chickpeas 172, raw spinach 194, raw asparagus 52 micrograms	The form in food. In a 4-week trial, folate from fruit, vegetables and liver had about 80% of the availability of folic acid. ^{18 13 12}	Human data
Folic acid	B vitamin (man-made form)	Not a natural food form; added to some enriched breads, cereals, flours and pasta, and used in pills Not read from a source for this page.	The form tested in the trials of neural tube defects, homocysteine, stroke, polyps and methotrexate. ^{3 1 2 13}	Human data
5-MTHF (methylfolate, l-methylfolate)	B vitamin (reduced folate)	Not found.	The main form in plasma. In a single-dose trial it raised blood folate more than folic acid. ⁹	Human data

Mechanisms, receptors and pathways

Target or pathway	Gene or receptor	What was found	Level
DNA production and red blood cell formation	Not specified in the sources read	MedlinePlus says folate helps produce DNA, helps tissues grow and cells work, and helps form red blood cells; it works with vitamins B12 and C in using and creating new proteins. The NHS says too little causes large red blood cells that cannot function properly. ^{13 14}	Human data
Homocysteine levels	Not specified	Folic acid lowered homocysteine by about 25% in a meta-analysis and by 26% in the FACIT trial. Lowering it did not prevent heart attacks in the trials read. ^{1 4}	Human data
MTHFR enzyme (677C to T variant)	MTHFR	The 677 T variant lowers the activity of the enzyme that makes 5-MTHF (abstract). In a single-dose crossover trial, 5-MTHF raised plasma folate more than folic acid in women with and without the variant. ⁹	Human data

Absorption, metabolism and elimination

Absorption: Folate from fruit, vegetables and liver had about 80% of the availability of folic acid in a 4-week trial of 72 adults (78% by labelled folic acid, 85% by serum folate).
Distribution: Not found.
Metabolism: Plasma folate was essentially 5-MTHF regardless of the form taken; unmetabolised folic acid appeared regularly in plasma after folic acid and rarely after 5-MTHF.
Elimination: MedlinePlus says folic acid is water-soluble, leftover amounts leave in the urine and the body does not store it; the NHS says there are no long-term stores.
Bioavailability: See absorption.

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Isolated compounds versus whole extracts

Food and pills are different. Food folate (beans, leafy greens, citrus) comes with fibre and other nutrients and had about 80% of folic acid's availability in one small trial. Every benefit proven in trials here (neural tube defects, methotrexate side effects) was shown with folic acid pills, not with food folate. Trials of homocysteine lowering also used pills. The NHS and MedlinePlus say most people can get enough folate from a varied diet.

Nutritional composition

Food values are USDA FoodData Central SR Legacy (April 2018) in micrograms of dietary folate equivalents (DFE) per 100 g, read 2026-10-26 from the project's saved copy of the USDA records. Per-portion figures are calculated from them: Lentils, cooked, boiled, no salt: 181 micrograms DFE per 100 g; about 358 micrograms DFE in 1 cup (198 g) [FDC 172421]; Black-eyed peas (cowpeas), cooked, boiled, no salt: 208 micrograms DFE per 100 g; about 356 micrograms DFE in 1 cup (171 g) [FDC 173759]; Chickpeas, cooked, boiled, no salt: 172 micrograms DFE per 100 g; about 282 micrograms DFE in 1 cup (164 g) [FDC 173757]; Red kidney beans, cooked, boiled, no salt: 130 micrograms DFE per 100 g; about 230 micrograms DFE in 1 cup (177 g) [FDC 175194]; Spinach, raw: 194 micrograms DFE per 100 g; about 58 micrograms DFE in 1 cup (30 g) [FDC 168462]; Asparagus, raw: 52 micrograms DFE per 100 g; about 70 micrograms DFE in 1 cup (134 g) [FDC 168389]; Broccoli, raw: 63 micrograms DFE per 100 g; about 57 micrograms DFE in 1 cup chopped (91 g) [FDC 170379]; Brussels sprouts, raw: 61 micrograms DFE per 100 g; about 54 micrograms DFE in 1 cup (88 g) [FDC 170383]; Avocado, raw: 81 micrograms DFE per 100 g; about 122 micrograms DFE in 1 cup cubes (150 g) [FDC 171705]; Orange, raw: 30 micrograms DFE per 100 g; about 39 micrograms DFE in 1 orange (131 g) (131 g) [FDC 169097]. Fortified breakfast cereals and enriched breads are named as folic acid sources by the NHS and MedlinePlus, but their amounts were not read, so none are given. US reference intakes (MedlinePlus, from the Food and Nutrition Board): infants 65 micrograms (0 to 6 months) and 80 (7 to 12 months) as adequate intakes; 150 (1 to 3 years); 200 (4 to 8 years); 300 (9 to 13 years); 400 for males and females 14 and older; 600 in pregnancy; 500 while breastfeeding. The NHS gives a UK figure of 200 micrograms a day for adults. These are reference statements, not advice on how much to take.

7benefits and uses looked at

18studies and sources checked

High certaintybest evidence rating found

4lab markers tracked in trials

1 high certainty2 moderate certainty1 mixed findings1 low certainty1 not enough evidence1 evidence against

What was looked at

The 7 benefits and uses checked for Vitamin B9 (folate and folic acid), each with how strong the evidence is. Tap one to open it.

Neural tube defects (spina bifida and similar birth defects)High certainty
Folate-deficiency anaemia (correcting low folate)Moderate certainty
Heart attack and stroke (homocysteine lowering)Mixed findings
Memory and thinking in older adultsLow certainty
Bowel polyps (colorectal adenomas) and bowel cancerEvidence against
Side effects of methotrexate (rheumatoid arthritis)Moderate certainty
Methylfolate (5-MTHF) compared with folic acidNot enough evidence

Lab markers tracked in the studies

Serum folate (folate in the blood)Plasma homocysteineNeural tube defect rate in babiesVitamin B12 status

What is Vitamin B9 (folate and folic acid) good for?

The main studied uses and how strong the human evidence is for each. Almost all trial benefits were shown with folic acid pills, not with food folate.

Neural tube defects (spina bifida and similar)High certaintyFolic acid around conception lowered neural tube defects: RR 0.31 (95% CI 0.17 to 0.58) across 5 trials of 7391 women, rated high-quality evidence by Cochrane. A 1991 trial in 1817 high-risk women found RR 0.28. This was shown with folic acid pills, not food folate. Agencies give separate advice for pregnancy; see the Safety tab. Folate-deficiency anaemiaModerate certaintyToo little folate makes red blood cells grow too large and work poorly. The NHS says folic acid tablets are used to restore folate levels and usually need to be taken for 4 months. No trial was read; this rests on NHS and MedlinePlus pages. B12 deficiency can look the same, so a doctor should check both. Heart attack and strokeMixed findingsAcross 8 trials of 37,485 people, folic acid lowered homocysteine about 25% but did not change heart attacks, stroke (RR 0.96), cancer or death. A Cochrane review of 15 trials found slightly fewer strokes (RR 0.90, high-quality) and no heart attack difference. A Chinese trial of 20,702 adults with high blood pressure found fewer first strokes with enalapril plus folic acid (HR 0.79). Side effects of methotrexate (rheumatoid arthritis)Moderate certaintyIn 6 trials (624 people), folic or folinic acid cut stomach side effects (RR 0.74), raised liver enzymes (RR 0.23) and stopping methotrexate (RR 0.39), and did not significantly change how well methotrexate worked. Used only as a prescriber directs. Memory and thinking in older adultsLow certaintyOne 3-year trial in 818 older adults found small gains in memory and processing speed with folic acid (memory Z-score difference 0.132). A US survey linked high blood folate with more cognitive impairment when vitamin B12 was low. Not shown to prevent dementia. Bowel polyps and bowel cancerEvidence againstIn 1021 people with earlier bowel polyps, folic acid 1 mg a day did not reduce new polyps (RR 1.04, 0.90 to 1.20) and was linked to more advanced lesions at the second follow-up (RR 1.67, 1.00 to 2.80). Not shown to prevent bowel cancer; people with a history of polyps or cancer should ask a doctor. Methylfolate (l-methylfolate) versus folic acidNot enough evidenceIn one small single-dose trial in 24 women, 5-MTHF raised blood folate more than folic acid, with or without the MTHFR 677 TT variant. Blood levels only; no trial of health outcomes was read, and neural tube protection is shown for folic acid.

Benefits, one by one

Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.

Neural tube defects (spina bifida and similar birth defects)

High certainty

Folic acid taken before and in early pregnancy lowered the number of babies born with neural tube defects. A Cochrane review of 5 trials rated this high-quality evidence. Food folate was not what these trials tested.

3 studiesFolic acid (the man-made form) in the trials, alone or in multivitami…

Studies, doses and limits

What the trials found

The 2015 Cochrane review pooled 5 trials (7391 women). Folic acid, alone or with other vitamins and minerals, cut neural tube defects (RR 0.31, 95% CI 0.17 to 0.58; high-quality evidence) and cut recurrence in women with an earlier affected pregnancy (RR 0.34, 0.18 to 0.64). The effect was not changed by the daily amounts compared (400 micrograms or higher) or by whether folic acid was given alone or with other nutrients. The 1991 MRC Vitamin Study in 1817 high-risk women found 6 affected pregnancies on folic acid against 21 without it (RR 0.28, 0.12 to 0.71); the other vitamins in that trial did not protect. The US Preventive Services Task Force (2023) rates the net benefit substantial with high certainty.

Results

The best-supported benefit of folic acid. It applies to the time around conception, which is why agencies speak of taking it before pregnancy.

Effect sizes as reported

Cochrane: RR 0.31 (0.17 to 0.58) for any folate versus none; recurrence RR 0.34 (0.18 to 0.64). MRC trial: RR 0.28 (0.12 to 0.71).

Why this rating

High. Cochrane graded the neural tube evidence high quality, with a consistent result from several trials and a large earlier trial. Limits: only one trial had low risk of bias, and the recurrence trials were in women with a past affected pregnancy.

Form and dose studied

Folic acid (the man-made form) in the trials, alone or in multivitamins. The review's amounts are not advice.

Who was studied

Women planning pregnancy or pregnant, including those with an earlier affected pregnancy.

Limits

Few trials. No included trial looked at maternal blood folate or anaemia at term. The review found no clear effect on cleft lip or palate, heart defects or miscarriage.

Why researchers looked

Neural tube defects happen when the baby's brain and spinal cord do not close fully in early pregnancy.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Authoritative guidance

Folate is needed to make DNA and new cells (MedlinePlus). The trials read did not test how folic acid prevents these defects.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab for B12 masking and for the official statements on pregnancy.

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Folate-deficiency anaemia (correcting low folate)

Moderate certainty

When the body does not get enough folate, red blood cells grow too large and cannot work properly. The NHS says folic acid tablets are used to restore folate levels. We read no trial of this, because treating a deficiency is long-standing medical practice.

4 studiesFolic acid tablets prescribed by a clinician; food folate differs fro…

Studies, doses and limits

What the trials found

The NHS says a lack of folate causes the body to make abnormally large red blood cells that cannot function properly. Symptoms include extreme tiredness, pins and needles, a sore red tongue and mouth ulcers, and it can also affect memory and mood. Causes include a long-standing poor diet (uncommon), some medicines such as anticonvulsants and proton pump inhibitors, and other conditions. Diagnosis is by symptoms and a blood test. Folic acid tablets are used to restore folate levels and usually need to be taken for 4 months. The NHS warns that vitamin B12 deficiency can cause the same anaemia, and that nerve problems from B12 deficiency can become permanent if it is missed. MedlinePlus lists diarrhoea, mouth ulcers, swollen tongue and poor growth as other signs of low folate.

Results

Supplements correct a real shortage. There is no good evidence in the sources read that extra folic acid gives energy or other benefit to people who already get enough.

Effect sizes as reported

No trial effect sizes were read.

Why this rating

Moderate. This rests on two UK and US health agency pages (NHS pages last reviewed 2023 and 2020) and not on a trial or review read for this page. Established medical practice, but diagnosis and treatment need a clinician and a B12 check.

Form and dose studied

Folic acid tablets prescribed by a clinician; food folate differs from pills.

Who was studied

People with low folate, often found by a blood test.

Limits

No trial or meta-analysis of folic acid for deficiency anaemia was read. The NHS pages are not systematic reviews.

Why researchers looked

Folate is needed to make healthy red blood cells, so too little shows up as a particular type of anaemia.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Authoritative guidance

Folate helps the body make DNA and form red blood cells (MedlinePlus, NHS).

A proposed mechanism does not show that the effect happens in people.

Self-treating tiredness with folic acid can hide B12 deficiency. See the Safety tab.

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Heart attack and stroke (homocysteine lowering)

Mixed findings

Large trials of folic acid (alone or with B6 and B12) found no effect on heart attacks. Pooled results show a small lower stroke risk. A big Chinese trial of a blood-pressure pill with folic acid also found fewer first strokes. Results come mostly from people already at higher risk.

3 studiesFolic acid pills, mostly with other B vitamins or a blood-pressure dr…

Studies, doses and limits

What the trials found

A meta-analysis of 8 trials (37,485 people at raised risk) found no significant effect of folic acid on major vascular events (rate ratio 1.01, 0.97 to 1.05), coronary events (1.03) or stroke (0.96, 0.87 to 1.06), nor on cancer or death over a median 5 years. A Cochrane review of 15 trials (71,422 people) found no difference for heart attack (RR 1.02) or death (RR 1.01) but slightly fewer strokes (RR 0.90, 0.82 to 0.99; high-quality evidence), with B6, B9 or B12 given alone or together. The CSPPT trial in 20,702 Chinese adults with high blood pressure found first stroke 2.7% with enalapril plus folic acid 0.8 mg versus 3.4% with enalapril alone (HR 0.79, 0.68 to 0.93); heart attack and death were not different.

Results

No heart attack benefit. A possible small stroke benefit, strongest in one large trial in people with high blood pressure.

Effect sizes as reported

Meta-analysis stroke RR 0.96 (0.87 to 1.06); Cochrane stroke RR 0.90 (0.82 to 0.99); CSPPT first stroke HR 0.79 (0.68 to 0.93).

Why this rating

Mixed. The two reviews disagree slightly on stroke (not significant in one, small benefit in the other), and the big stroke result is from one trial of a combination pill. Heart attack results are consistently null.

Form and dose studied

Folic acid pills, mostly with other B vitamins or a blood-pressure drug. Not food folate.

Who was studied

People at raised cardiovascular risk, many with high blood pressure.

Limits

Trials mixed folic acid with B6 and B12. Results may not apply to people who are not at raised risk or to food folate.

Why researchers looked

High homocysteine is linked with vessel disease, and folic acid lowers homocysteine, so trials tested whether that protects the heart and brain.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Human trial

Folic acid lowers homocysteine by about 25% (meta-analysis). Whether that explains any stroke effect was not tested in the abstracts.

A proposed mechanism does not show that the effect happens in people.

No safety signal was seen in these trials, but see the Safety tab for B12 masking.

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Memory and thinking in older adults

Low certainty

One 3-year trial in 818 older adults found small gains on some memory and speed tests with folic acid. It is a single study. A separate US survey found high blood folate was not good news when vitamin B12 was low.

2 studiesFolic acid pills in the trial; the survey did not separate pills from…

Studies, doses and limits

What the trials found

In the FACIT trial, 818 older adults in the Netherlands took folic acid or placebo for 3 years. The three-year change in memory (difference in Z scores 0.132, 0.032 to 0.233) and information processing speed (0.087, 0.016 to 0.158) was better with folic acid, while the gain in sensorimotor speed was borderline (0.064, -0.001 to 0.129). In a survey of 1459 older Americans, high serum folate was linked with more cognitive impairment (OR 2.6, 1.1 to 6.1) when vitamin B12 was low, and with less (OR 0.4, 0.2 to 0.9) when B12 was normal. That survey cannot show cause.

Results

A small, single-trial signal for some tests. Not shown to prevent dementia, and linked with worse results when B12 is low.

Effect sizes as reported

FACIT: memory Z-score difference 0.132 (0.032 to 0.233). Survey: low B12 plus high folate, cognitive impairment OR 2.6 (1.1 to 6.1).

Why this rating

Low. One trial, five test domains and test scores rather than dementia. The survey is observational. No review of several trials was read.

Form and dose studied

Folic acid pills in the trial; the survey did not separate pills from fortified food.

Who was studied

Older adults in the Netherlands (trial) and older US adults (survey).

Limits

No repeat trial was read. The abstract does not say whether participants were deficient at the start.

Why researchers looked

Researchers tested whether folic acid slows the decline in thinking that comes with age.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Hypothesis

Not shown. The authors point to homocysteine lowering, but the abstract does not test it.

A proposed mechanism does not show that the effect happens in people.

Folic acid can hide B12 deficiency, which harms thinking and nerves. Ask a doctor to check B12 first. See the Safety tab.

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Bowel polyps (colorectal adenomas) and bowel cancer

Evidence against

A large trial in people who already had bowel polyps found folic acid did not reduce new polyps, and hinted at more advanced polyps. Folic acid is not shown to prevent bowel cancer.

2 studiesFolic acid pills in the trial, not food folate.

Studies, doses and limits

What the trials found

In the Aspirin/Folate Polyp Prevention Study, 1021 people with a recent adenoma took folic acid or placebo, with colonoscopy follow-up. At about 3 years, at least one adenoma occurred in 44.1% on folic acid and 42.4% on placebo (RR 1.04, 0.90 to 1.20). Advanced lesions were 11.4% versus 8.6% (RR 1.32, 0.90 to 1.92). At the second follow-up advanced lesions were 11.6% versus 6.9% (RR 1.67, 1.00 to 2.80, P = .05). Folic acid was associated with a higher risk of having 3 or more adenomas and of cancers outside the bowel. The authors conclude it does not reduce adenoma risk and that possible harm needs study.

Results

No protection from folic acid pills, and a possible signal of harm in people who already have polyps.

Effect sizes as reported

First follow-up RR 1.04 (0.90 to 1.20); second follow-up advanced lesions RR 1.67 (1.00 to 2.80).

Why this rating

Evidence against benefit in this population. One large randomised trial; the harm signals are borderline and were not the main outcome.

Form and dose studied

Folic acid pills in the trial, not food folate.

Who was studied

People with a recent history of colorectal adenomas.

Limits

People without prior polyps were not studied. Food folate was not tested.

Why researchers looked

Lab and population studies had suggested folate might protect the bowel lining.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Hypothesis

Not tested in the abstract.

A proposed mechanism does not show that the effect happens in people.

People with a history of polyps or cancer should ask a doctor before taking folic acid pills; the NHS lists cancer among conditions to tell a doctor about.

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Side effects of methotrexate (rheumatoid arthritis)

Moderate certainty

Doctors prescribe folic acid with the medicine methotrexate. A Cochrane review found it reduced stomach upset, liver enzyme rises and the number of people who stopped the drug, without clearly weakening the arthritis treatment. This is for use under a prescriber.

2 studiesFolic acid or folinic acid prescribed alongside methotrexate. Amounts…

Studies, doses and limits

What the trials found

A Cochrane review of 6 trials (624 people with rheumatoid arthritis taking methotrexate) found folic or folinic acid lowered stomach and gut side effects (RR 0.74, 0.59 to 0.92), raised liver enzymes (RR 0.23, 0.15 to 0.34) and stopping methotrexate for any reason (RR 0.39, 0.28 to 0.53). Mouth sores showed a non-significant trend (RR 0.72, 0.49 to 1.06). Blood-cell side effects could not be judged. Folate did not significantly change how well methotrexate worked on arthritis. The NHS lists preventing methotrexate side effects as a use of folic acid.

Results

Fewer side effects in people already on methotrexate.

Effect sizes as reported

GI side effects RR 0.74; raised liver enzymes RR 0.23; stopping methotrexate RR 0.39.

Why this rating

Moderate. Cochrane rated the evidence moderate for each outcome except blood side effects (low).

Form and dose studied

Folic acid or folinic acid prescribed alongside methotrexate. Amounts are for the prescriber.

Who was studied

Adults with rheumatoid arthritis on methotrexate.

Limits

Rheumatoid arthritis only. Other conditions treated with methotrexate were not covered in the abstract.

Why researchers looked

Folic acid or folinic acid is given alongside methotrexate to reduce its side effects (NHS).

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Authoritative guidance

Not described in the abstract.

A proposed mechanism does not show that the effect happens in people.

Use only as prescribed; the timing and amount are the prescriber's decision.

^{10 15}

Methylfolate (5-MTHF) compared with folic acid

Not enough evidence

5-MTHF is a folate form sold as l-methylfolate. In a small single-dose trial it raised blood folate more than folic acid, including in women with a common MTHFR gene variant. No trial in the sources read tested health outcomes.

1 studies5-MTHF (l-methylfolate) versus folic acid, single doses (400 and 416 …

Studies, doses and limits

What the trials found

In a crossover trial, 24 healthy women (16 with the MTHFR 677 TT genotype, 8 with CC) took single doses of folic acid and of 5-MTHF. Plasma folate AUC and peak were significantly higher, and time to peak shorter, with 5-MTHF in both genotypes. Unmetabolised folic acid appeared in the blood regularly after folic acid and rarely after 5-MTHF. The abstract does not say what that means for health.

Results

A blood-level difference after one dose. No trial of birth defects, anaemia or other outcomes with 5-MTHF was read.

Effect sizes as reported

Higher plasma folate AUC and peak with 5-MTHF; numbers not given in the abstract.

Why this rating

Insufficient for health outcomes. One small single-dose trial of blood levels in 24 women.

Form and dose studied

5-MTHF (l-methylfolate) versus folic acid, single doses (400 and 416 micrograms).

Who was studied

Healthy women, by MTHFR genotype.

Limits

No outcomes beyond blood folate. Not a test of birth-defect prevention, which was shown with folic acid only.

Why researchers looked

The MTHFR 677 TT variant lowers the activity of the enzyme that makes 5-MTHF (abstract), so researchers compared the two forms in women with and without it.

Traditional use

Folate is a food nutrient and folic acid is the man-made form used in pills and added to some foods. Long use of folate-rich foods is not proof that extra pills treat any condition.

Proposed mechanism Human trial

Plasma folate was essentially 5-MTHF whichever form was given (abstract).

A proposed mechanism does not show that the effect happens in people.

Neural tube defect prevention is shown for folic acid; see the Evidence tab. Ask a doctor before switching forms.

⁹

Connections to the rest of health

How Vitamin B9 (folate and folic acid) connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.

Explore every connection: goals, body systems, organs, symptoms, genes

Kind of connection Connected to Search

A. Wellness goals

Connected to	Kind of connection	Evidence status	Context	Studies
Womens Wellness	Demonstrated clinical effect	High certainty	Neural tube defects (spina bifida and similar birth defects): Folic acid taken before and in early pregnancy lowered the number of babies born with neural tube defects. A Cochrane review of 5 trials rated this high-quality evidence. Food folate was not what these trials tested.	^{3 6 11}
Energy Vitality		Moderate certainty	Folate-deficiency anaemia (correcting low folate): When the body does not get enough folate, red blood cells grow too large and cannot work properly. The NHS says folic acid tablets are used to restore folate levels. We read no trial of this, because treating a deficiency is long-standing medical practice.	^{14 15 13 16}
Heart Health		Mixed findings	Heart attack and stroke (homocysteine lowering): Large trials of folic acid (alone or with B6 and B12) found no effect on heart attacks. Pooled results show a small lower stroke risk. A big Chinese trial of a blood-pressure pill with folic acid also found fewer first strokes. Results come mostly from people already at higher risk.	^{1 7 5}
Focus Memory		Low certainty	Memory and thinking in older adults: One 3-year trial in 818 older adults found small gains on some memory and speed tests with folic acid. It is a single study. A separate US survey found high blood folate was not good news when vitamin B12 was low.	^{4 8}
Healthy Aging		Evidence against	Bowel polyps (colorectal adenomas) and bowel cancer: A large trial in people who already had bowel polyps found folic acid did not reduce new polyps, and hinted at more advanced polyps. Folic acid is not shown to prevent bowel cancer.	^{2 15}
Joint Health	Demonstrated clinical effect	Moderate certainty	Side effects of methotrexate (rheumatoid arthritis): Doctors prescribe folic acid with the medicine methotrexate. A Cochrane review found it reduced stomach upset, liver enzyme rises and the number of people who stopped the drug, without clearly weakening the arthritis treatment. This is for use under a prescriber.	^{10 15}
Womens Wellness		Not enough evidence	Methylfolate (5-MTHF) compared with folic acid: 5-MTHF is a folate form sold as l-methylfolate. In a small single-dose trial it raised blood folate more than folic acid, including in women with a common MTHFR gene variant. No trial in the sources read tested health outcomes.	⁹

B. Body systems

Connected to	Kind of connection	Evidence status	Context	Studies
Reproductive System	Biological association	High certainty	Studied for: Neural tube defects (spina bifida and similar birth defects)	^{3 6 11}
Nervous System	Biological association	High certainty	Studied for: Neural tube defects (spina bifida and similar birth defects) Studied for: Memory and thinking in older adults	^{3 6 11 4 8}
Blood	Biological association	Moderate certainty	Studied for: Folate-deficiency anaemia (correcting low folate) Studied for: Methylfolate (5-MTHF) compared with folic acid	^{14 15 13 16 9}
Circulatory System	Biological association	Moderate certainty	Studied for: Folate-deficiency anaemia (correcting low folate) Studied for: Heart attack and stroke (homocysteine lowering)	^{14 15 13 16 1 7 5}
Digestive System	Biological association	Evidence against	Studied for: Bowel polyps (colorectal adenomas) and bowel cancer Studied for: Side effects of methotrexate (rheumatoid arthritis)	^{2 15 10}
Musculoskeletal System	Biological association	Moderate certainty	Studied for: Side effects of methotrexate (rheumatoid arthritis)	^{10 15}

E. Health conditions

Connected to	Kind of connection	Evidence status	Context	Studies
Neural tube defects	Demonstrated clinical effect	Clinically supported	Folic acid around conception lowered neural tube defects (Cochrane RR 0.31, high-quality evidence). Preparation or compound: Folic acid supplement	^{3 6}
Vitamin B12 deficiency	Adverse effect or risk	Documented risk	Folic acid can mask B12 deficiency symptoms (NHS, MedlinePlus). Folic acid above 1 mg a day can mask B12 deficiency (NHS, MedlinePlus). Preparation or compound: Folic acid above 1 mg a day	^{16 13}

I. Biomarkers

Connected to	Kind of connection	Evidence status	Context	Studies
Serum folate (folate in the blood)	Biological association	Moderate certainty	Measured in trials: increased. A lab change is not the same as a health benefit.	^{4 12}
Plasma homocysteine	Biological association	High certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{1 4}
Neural tube defect rate in babies	Biological association	High certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{3 6}
Vitamin B12 status	Biological association	Low certainty	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{8 16 13}

J. Genes, receptors and enzymes

Connected to	Kind of connection	Evidence status	Context	Studies
MTHFR	Preliminary mechanism	Human	The 677C to T variant lowers activity of the enzyme that makes 5-MTHF; 5-MTHF raised plasma folate more than folic acid in both genotypes in one small trial.	⁹

K. Biological pathways

Connected to	Kind of connection	Evidence status	Context	Studies
Vitamin B12	Preliminary mechanism	Human	Works with folate; folic acid can mask B12 deficiency.	^{16 8}
Homocysteine	Preliminary mechanism	Human	Lowered about 25% by folic acid in trials.	¹

L. Active compounds

Connected to	Kind of connection	Evidence status	Context	Studies
Folate (natural food forms)	Biological association	Human	The form in food. In a 4-week trial, folate from fruit, vegetables and liver had about 80% of the availability of folic acid. Preparation or compound: Found in foods such as dark green leafy vegetables, dried beans and peas, and citrus fruit (MedlinePlus)	^{18 13 12}
Folic acid	Biological association	Human	The form tested in the trials of neural tube defects, homocysteine, stroke, polyps and methotrexate. Preparation or compound: Not a natural food form; added to some enriched breads, cereals, flours and pasta, and used in pills	^{3 1 2 13}
5-MTHF (methylfolate, l-methylfolate)	Biological association	Human	The main form in plasma. In a single-dose trial it raised blood folate more than folic acid.	⁹

Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 26, 2026).

Evidence at a glance: what changed in 3 lab markers

Tap a number to show only those markers. Counts are markers, not people.

Other21

The evidence

The research centre for Vitamin B9 (folate and folic acid). Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.

Evidence by outcome

Neural tube defects (spina bifida and similar birth defects) 3 studies High certainty Folate-deficiency anaemia (correcting low folate) 4 studies Moderate certainty Heart attack and stroke (homocysteine lowering) 3 studies Mixed findings Memory and thinking in older adults 2 studies Low certainty Bowel polyps (colorectal adenomas) and bowel cancer 2 studies Evidence against Side effects of methotrexate (rheumatoid arthritis) 2 studies Moderate certainty Methylfolate (5-MTHF) compared with folic acid 1 study Not enough evidence

Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).

How we rate evidence

High certainty

Several well-run trials or reviews agree; further research is unlikely to change the picture much.

Moderate certainty

Good trials point the same way, but some doubt remains.

Low certainty

Small, short or inconsistent trials. The finding could change with better research.

Very low certainty

Very little or very weak human data. Treat as a possibility only.

Mixed findings

Trials or reviews disagree with each other.

Not enough evidence

Not enough human research to say either way.

Evidence against

Good research found no benefit, or found harm.

We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We started from our existing vitamin B9 summary, re-read NHS and MedlinePlus pages, took food values from saved USDA FoodData Central records, and re-read PubMed abstracts for reviews and trials. Only abstracts were read for studies. Items we could not verify are flagged in the research gaps.

Study library: every study we checked 18

Design Research type Year from Search

Study	Design	People	Product, dose, length	Result
Clarke 2010 Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med · PMID 20937919 · DOI	Systematic review meta analysis	37485 8 large placebo-controlled trials of folic acid in 37,485 people at raised risk of cardiovascular disease	Folic acid supplementation to lower homocysteine Supplement Median 5 years of follow-up · vs Placebo	Folic acid lowered homocysteine by an average of 25%. It had no significant effect on major vascular events (rate ratio 1.01, 0.97 to 1.05), major coronary events (1.03, 0.97 to 1.10), stroke (0.96, 0.87 to 1.06), cancer (1.05, 0.98 to 1.13), cancer death (1.00, 0.85 to 1.18) or death from any cause (1.02, 0.97 to 1.08). Major vascular events RR 1.01; stroke RR 0.96; all-cause death 1.02 (Stroke 0.87 to 1.06) Methods, limits and funding Outcomes: Major vascular events, coronary events, stroke, cancer, death Limitations: People already at raised cardiovascular risk. Follow-up was about 5 years, so longer-term effects are not shown. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists NIH and US government support. Read: abstract
Cole 2007 Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA · PMID 17551129 · DOI	Randomized trial	1021 1021 men and women with a recent history of colorectal adenomas (polyps) and no earlier invasive large-bowel cancer	Folic acid Supplement 1 mg a day (the trial dose) Colonoscopy follow-up at about 3 years, then 3 or 5 years later · vs Placebo (aspirin or placebo given in a separate randomisation)	At the first follow-up, 44.1% on folic acid and 42.4% on placebo had at least one adenoma (RR 1.04, 0.90 to 1.20). Advanced lesions were 11.4% versus 8.6% (RR 1.32, 0.90 to 1.92). At the second follow-up adenomas were 41.9% versus 37.2% (RR 1.13, 0.93 to 1.37) and advanced lesions 11.6% versus 6.9% (RR 1.67, 1.00 to 2.80, P = .05). Folic acid was linked to a higher risk of 3 or more adenomas and of cancers outside the bowel. The authors conclude 1 mg a day does not reduce adenoma risk and that possible harm needs more research. Adenoma RR 1.04 at first follow-up (0.90 to 1.20) Methods, limits and funding Outcomes: At least one new colorectal adenoma; advanced lesions; number of adenomas Limitations: People who already had adenomas; says nothing about people without them or about food folate. Some results were borderline and the trial was not designed to prove harm. Funding and conflicts: The abstract does not state funding. The PubMed record lists NIH extramural support. Registration: NCT00272324 Read: abstract
De-Regil 2015 Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev · PMID 26662928 · DOI	Systematic review meta analysis	7391 5 trials, 7391 women (2033 with a past pregnancy affected by a neural tube defect, 5358 without)	Folic acid alone, or with other vitamins and minerals Supplement Before and around conception (periconceptional) · vs No treatment, placebo, or vitamins and minerals without folic acid	Folic acid reduced neural tube defects (RR 0.31, 95% CI 0.17 to 0.58; 5 studies; 6708 births; high-quality evidence). It lowered recurrence in women with an earlier affected pregnancy (RR 0.34, 0.18 to 0.64; 4 studies; 1846 births). The one study of first occurrence found no events in the folic acid group (RR 0.07, 0.00 to 1.32). No clear effect on cleft palate (RR 0.73), cleft lip (RR 0.79), heart defects (RR 0.57), miscarriage (RR 1.10, moderate-quality) or other birth defects (RR 0.94); these were low-quality evidence apart from miscarriage. NTD RR 0.31 (high-quality evidence); recurrence RR 0.34 (NTD 0.17 to 0.58; recurrence 0.18 to 0.64) Methods, limits and funding Outcomes: Neural tube defects (NTD), other birth defects, miscarriage Limitations: Only one trial had low risk of bias. Trials of other outcomes were few. No included trial assessed neonatal death, maternal blood folate or anaemia at term. Funding and conflicts: The abstract does not state funding. The PubMed record lists NIH and non-US government research support for the review. Read: abstract
Durga 2007 Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet · PMID 17240287 · DOI	Randomized trial	818 818 older adults in the Netherlands (FACIT trial)	Folic acid Supplement 800 micrograms a day (the trial dose) 3 years · vs Placebo	Serum folate rose by 576% and homocysteine fell by 26% with folic acid. The 3-year change was better with folic acid for memory (difference in Z scores 0.132, 0.032 to 0.233) and information processing speed (0.087, 0.016 to 0.158). The sensorimotor speed gain was borderline (0.064, -0.001 to 0.129). The authors say it improved domains of cognitive function that tend to decline with age. Memory Z-score difference 0.132 (0.032 to 0.233) Methods, limits and funding Outcomes: Change in memory, sensorimotor speed, complex speed, information processing speed and word fluency; blood folate and homocysteine Limitations: One trial in older adults; five domains tested; the abstract does not say whether anyone was folate deficient. Test scores are not the same as dementia risk. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists non-US government support. Registration: NCT00110604 Read: abstract
Huo 2015 Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA · PMID 25771069 · DOI	Randomized trial	20702 20,702 adults with high blood pressure and no earlier stroke or heart attack, China (CSPPT trial)	Enalapril 10 mg plus folic acid 0.8 mg in one pill Supplement 0.8 mg folic acid a day (as used in the trial) Median 4.5 years · vs Enalapril 10 mg alone	First stroke 2.7% with enalapril plus folic acid versus 3.4% with enalapril alone (HR 0.79, 0.68 to 0.93); first ischaemic stroke 2.2% versus 2.8% (HR 0.76, 0.64 to 0.91); combined cardiovascular events 3.1% versus 3.9% (HR 0.80, 0.69 to 0.92). Haemorrhagic stroke (HR 0.93), heart attack (HR 1.04) and death from any cause (HR 0.94) did not differ significantly. No significant difference in adverse events. First stroke HR 0.79 (0.68 to 0.93) Methods, limits and funding Outcomes: First stroke; heart attack; combined cardiovascular events; death Limitations: Chinese adults with high blood pressure; the authors say the result fits benefit in adults with high blood pressure and low baseline folate. Combination pill, so folic acid alone is not isolated. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists non-US government support. Registration: NCT00794885 Read: abstract
MRC Vitamin Study Research Group 1991 Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet · PMID 1677062	Randomized trial	1817 1817 women at high risk of a neural tube defect pregnancy because of a previous affected pregnancy, 33 centres in 7 countries	Folic acid, a mix of seven other vitamins, both, or neither Supplement Around conception · vs Neither (factorial design); other vitamins as a separate arm	Of 1195 pregnancies with known outcome, 27 had a neural tube defect: 6 in the folic acid groups and 21 in the other two groups, a 72% protective effect (RR 0.28, 95% CI 0.12 to 0.71). The other vitamins showed no significant protection (RR 0.80, 0.32 to 1.72). No demonstrable harm from folic acid, though the study could not detect rare or slight harms. RR 0.28 with folic acid (0.12 to 0.71) Methods, limits and funding Outcomes: Neural tube defects in the pregnancy Limitations: Women with a previous affected pregnancy only; says little about first pregnancies. 1195 of 1817 had a known outcome. Published 1991. Funding and conflicts: Funding is not stated in the abstract. Read: abstract
Martí-Carvajal 2017 Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev · PMID 28816346 · DOI	Systematic review meta analysis	71422 15 randomised trials, 71,422 people	Homocysteine-lowering supplements: vitamins B6, B9 (folic acid) or B12, alone or combined Supplement 1 to 7.3 years · vs Placebo (and low versus high dose comparisons)	No difference versus placebo for heart attack (RR 1.02, 0.95 to 1.10), death from any cause (RR 1.01, 0.96 to 1.06) or serious adverse events (RR 1.07, 1.00 to 1.14); all high-quality evidence. Stroke was slightly lower (4.3% versus 5.1%; RR 0.90, 0.82 to 0.99; 10 trials; 44,224 people; high-quality evidence). Trial sequential analyses suggest more trials are unlikely to change the findings. Stroke RR 0.90; heart attack RR 1.02 (Stroke 0.82 to 0.99) Methods, limits and funding Outcomes: Heart attack, stroke, death from any cause, serious adverse events Limitations: Mixes folic acid with B6 and B12 products. One mega-trial (enalapril plus folic acid) drives much of the stroke result. Funding and conflicts: Funding is not stated in the abstract. Read: abstract
Morris 2007 Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr · PMID 17209196 · DOI	Observational cross sectional	1459 1459 older participants in the 1999-2002 US National Health and Nutrition Examination Survey	Blood folate and vitamin B12 status (not a supplement trial) Supplement Single survey	In people with low vitamin B12 status, high serum folate (above 59 nmol/L) was linked with anaemia (OR 3.1, 1.5 to 6.6) and cognitive impairment (OR 2.6, 1.1 to 6.1). In people with normal B12, high folate was linked with less cognitive impairment (OR 0.4, 0.2 to 0.9). The authors conclude the folate link depends on B12 status. Low B12 plus high folate: anaemia OR 3.1 (1.5 to 6.6) Methods, limits and funding Outcomes: Anaemia, macrocytosis (large red cells), cognitive impairment Limitations: Cross-sectional, so it cannot show cause. The abstract does not separate folic acid pills from fortified food. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists NIH and US government support. Read: abstract
Prinz-Langenohl 2009 [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol · PMID 19917061 · DOI	Randomized crossover trial	24 24 healthy women: 16 with the MTHFR 677 TT genotype and 8 with CC	[6S]-5-methyltetrahydrofolate (5-MTHF, often sold as l-methylfolate) versus folic acid Supplement Single oral doses: folic acid 400 micrograms and 5-MTHF 416 micrograms Single dose, plasma folate measured for 8 hours · vs Folic acid (crossover)	Plasma folate AUC and peak were significantly higher, and time to peak shorter, with 5-MTHF than with folic acid in both genotypes. Plasma folate was essentially 5-MTHF whichever form was given. Unmetabolised folic acid in plasma occurred regularly after folic acid but rarely after 5-MTHF. The authors suggest 5-MTHF could be an alternative to folic acid. Higher plasma folate with 5-MTHF (Not given in the abstract) Methods, limits and funding Outcomes: Plasma folate (area under the curve, peak level, time to peak) Limitations: Single doses in 24 women; measures blood levels, not health outcomes. The abstract does not say what unmetabolised folic acid means for health. Funding and conflicts: Funding is not stated in the abstract. Read: abstract
Shea 2013 Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev · PMID 23728635 · DOI	Systematic review meta analysis	624 6 trials, 624 people with rheumatoid arthritis taking methotrexate	Folic acid or folinic acid Supplement Lower doses were the focus; amounts not given in the abstract · vs Placebo or no folate	Folate lowered stomach and gut side effects (RR 0.74, 0.59 to 0.92), raised liver enzymes (RR 0.23, 0.15 to 0.34) and stopping methotrexate for any reason (RR 0.39, 0.28 to 0.53). Mouth sores showed a non-significant trend (RR 0.72, 0.49 to 1.06). Blood-cell side effects could not be judged. Folate did not significantly change how well methotrexate treated arthritis. Evidence rated moderate for each outcome except blood side effects (low). GI side effects RR 0.74; raised liver enzymes RR 0.23 (GI 0.59 to 0.92) Methods, limits and funding Outcomes: Methotrexate side effects; arthritis disease activity Limitations: Rheumatoid arthritis only; folic acid and folinic acid pooled. Used with a prescriber, not a self-treatment. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists non-US government support. Read: abstract
US Preventive Services Task Force 2023 Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA · PMID 37526713 · DOI	Guideline	Persons planning to become pregnant or who could become pregnant	Folic acid supplement Supplement Recommendation statement: 0.4 to 0.8 mg (400 to 800 micrograms) of folic acid daily	The US Preventive Services Task Force (USPSTF) concludes there is high certainty that folic acid supplementation has a substantial net benefit in preventing neural tube defects in offspring, and recommends a daily supplement of 0.4 to 0.8 mg (grade A). Grade A recommendation; high certainty of substantial net benefit (Not applicable) Methods, limits and funding Outcomes: Benefit and harm assessment for neural tube defects Limitations: A guideline statement, not a trial. The abstract does not describe the evidence base in detail. Funding and conflicts: The abstract states no funding. Read: abstract
Winkels 2007 Bioavailability of food folates is 80% of that of folic acid. Am J Clin Nutr · PMID 17284745 · DOI	Randomized trial	72 72 healthy adults, 4 weeks	Food folate (fruit, vegetables and liver) compared with folic acid capsules Supplement Diet with 369 micrograms of food folate a day versus a low-folate diet (73 micrograms) plus 92, 191 or 289 micrograms of folic acid 4 weeks · vs Folic acid capsules at known amounts (labelled folic acid tracer)	Food folate had 78% (95% CI 48% to 108%) the bioavailability of folic acid by the labelled-folate method and 85% (52% to 118%) by change in serum folate. The authors conclude about 80% of folic acid, and that a folate-rich diet can improve folate status more than is often assumed. About 80% of folic acid (48% to 108% (isotope method)) Methods, limits and funding Outcomes: Bioavailability of food folate relative to folic acid Limitations: Small trial; wide intervals. Fruit, vegetables and liver only, not beans or fortified foods. Funding and conflicts: Funding is not stated in the abstract. The PubMed record lists non-US government support. Read: abstract
s-medlineplus-folic-acid MedlinePlus: Folic acid in diet · Source	Health agency n/a			Methods, limits and funding Read: full-text
s-nhs-folate-anaemia NHS: Vitamin B12 or folate deficiency anaemia · Source	Health agency n/a			Methods, limits and funding Read: full-text
s-nhs-folic-acid NHS medicines: Folic acid · Source	Health agency n/a			Methods, limits and funding Read: full-text
s-nhs-vitamin-b NHS: B vitamins and folic acid · Source	Health agency n/a			Methods, limits and funding Read: full-text
s-ods-folate NIH Office of Dietary Supplements: Folate fact sheet for health professionals · Source	Health agency n/a			Methods, limits and funding Read: not-read
s-usda-folate-foods USDA FoodData Central (SR Legacy, April 2018 release): folate in foods · Source	Reference database n/a			Methods, limits and funding Read: full-text

What we do not know yet

No trial of folic acid for treating folate-deficiency anaemia was read; that rests on NHS and MedlinePlus pages.
The NIH Office of Dietary Supplements fact sheet could not be read (HTTP 403), so its upper intake level and food table are not used.
The heart, memory and bowel results are for folic acid pills in specific groups and may not apply to food folate or to healthy people.
No trial of methylfolate for health outcomes was read.
History, depression, autism, kidney and liver safety, product quality and amounts in fortified foods were not researched.
Several NHS pages used have passed their stated next-review dates.

How new research is added

New studies are found by a saved PubMed search and placed in a review queue before the page changes.

Lab markers

What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".

Other 4

●

Serum folate (folate in the blood)

Increased in trials

The amount of folate in the liquid part of the blood.

Moderate certainty

Results and what it means

Why it was measured

A blood test used to look at folate status.

Statistical vs. clinical meaning

Folic acid pills raise blood folate a lot. Food folate raises it less per microgram.

Safety implication

None specific beyond the Safety tab.

Study	Result	People	Product
⁴	Serum folate rose by 576% (95% CI 539 to 614) with folic acid versus placebo	818 older adults in the Netherlands	Folic acid for 3 years versus placebo
¹²	Food folate was about 80% as available to the body as folic acid (78% by labelled folate, 85% by change in serum folate)	72 healthy adults for 4 weeks	Folate-rich diet versus folic acid capsules

^{4 12}

▼

Plasma homocysteine

Lowered in trials

An amino acid in the blood. Higher levels are linked in observational studies with heart and vessel disease.

High certainty

Results and what it means

Why it was measured

Used in trials as a marker to test whether lowering it protects the heart and brain.

Statistical vs. clinical meaning

Folic acid reliably lowers homocysteine, but lowering it did not prevent heart attacks in the trials read.

Safety implication

None specific.

Study	Result	People	Product
¹	Folic acid lowered homocysteine by an average of 25%, with no change in heart and vessel events	37,485 people at raised cardiovascular risk (8 trials)	Folic acid versus placebo, median 5 years
⁴	Homocysteine fell 26% (24 to 28) with folic acid	818 older adults	Folic acid for 3 years versus placebo

^{1 4}

▼

Neural tube defect rate in babies

Lowered in trials

The number of babies born with a neural tube defect such as spina bifida.

High certainty

Results and what it means

Why it was measured

A clinical outcome that trials of folic acid in pregnancy measured.

Statistical vs. clinical meaning

Fewer neural tube defects with folic acid around conception.

Safety implication

See the Safety tab on B12 masking.

Study	Result	People	Product
³	RR 0.31 (0.17 to 0.58) for any folate versus none; high-quality evidence	5 trials, 7391 women	Folic acid, alone or with other nutrients, around conception
⁶	6 of 27 affected pregnancies on folic acid groups versus 21 in the others (RR 0.28, 0.12 to 0.71)	1817 high-risk women	Folic acid, other vitamins, both or neither

^{3 6}

↕

Vitamin B12 status

Mixed results in trials

Blood vitamin B12 (or methylmalonic acid) used to see if B12 is low.

Low certainty

Results and what it means

Why it was measured

Folic acid above 1 mg a day can mask the symptoms of B12 deficiency (NHS), so B12 is looked at alongside folate.

Statistical vs. clinical meaning

Low B12 changes what high folate means. An association, not proof of cause.

Safety implication

Folic acid above 1 mg a day can mask B12 deficiency (NHS, MedlinePlus).

Study	Result	People	Product
⁸	With low B12, high serum folate went with anaemia (OR 3.1) and cognitive impairment (OR 2.6)	1459 older US adults	Survey of blood levels, not a supplement trial

^{8 16 13}

Safety

What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.

Main points to know 5

Folic acid can hide vitamin B12 deficiency. The NHS says doses of folic acid higher than 1 mg a day can mask the symptoms of vitamin B12 deficiency, which can eventually damage the nervous system if it is not spotted and treated, and that this matters most for older people. MedlinePlus says the same and advises avoiding more than 1,000 micrograms a day of folic acid, except for women with a history of an affected pregnancy who are planning to conceive. In a US survey of older adults with low B12, high blood folate went with anaemia and cognitive impairment (an association only). Authoritative guidance ^{16 13 8}
Official upper limit and the NIH fact sheet. MedlinePlus (reviewed 3 February 2025) says to avoid more than 1,000 micrograms a day of folic acid from supplements and fortified foods, except in the case above, and the NHS says 1 mg or less a day is unlikely to cause harm. This is the regulators' statement, not advice to take any amount. The NIH Office of Dietary Supplements fact sheet, which states the formal tolerable upper intake level, could not be read (HTTP 403), so that source is not quoted. Authoritative guidance ^{13 16 17}
Folic acid pills for people with a history of bowel polyps or cancer. In a trial of 1021 people with a recent bowel adenoma, folic acid 1 mg a day did not reduce new adenomas and was linked to a higher risk of three or more adenomas and of non-bowel cancers; advanced lesions were more frequent at the second follow-up (RR 1.67, 1.00 to 2.80). The NHS lists cancer among conditions to tell a doctor about before taking folic acid. This is a trial of pills, not of food folate. Controlled trial ^{2 15}
Medicines that interact with folic acid. The NHS lists epilepsy medicines (phenytoin, phenobarbital, primidone), the antibiotics chloramphenicol and co-trimoxazole, sulfasalazine, lithium and aspirin as medicines that may not mix well with folic acid. Tell your doctor or pharmacist about every medicine and supplement you take. Authoritative guidance ¹⁵
Taking too many multivitamin tablets. The NHS says an extra dose of folic acid on its own is unlikely to cause problems, but taking too many multivitamin tablets or capsules can be dangerous. If you have taken more than the number on the label, get help from NHS 111 (UK) or your local poison centre or emergency number. Authoritative guidance ¹⁵

Side effects 4

Effect	How often	Severity and recovery	Evidence
Bloating, wind, nausea and loss of appetite (tablets); also diarrhoea, vomiting and an itchy skin rash (liquid) The NHS says to tell a pharmacist or doctor if side effects bother you or do not go away.	No frequency given.	mild Not described.	Authoritative guidance ¹⁵
Serious allergic reaction (anaphylaxis): swollen face, throat or tongue, raised itchy rash, difficulty breathing Call NHS 111 or the local emergency number.	Rare (the NHS says rarely).	can be severe Not described.	Authoritative guidance ¹⁵
Masking of vitamin B12 deficiency, which can allow nerve damage to go unnoticed	Not given.	can be serious over time The NHS says nervous-system problems from B12 or folate deficiency can sometimes be permanent.	Authoritative guidance ^{16 14 13}
Possible higher risk of three or more bowel adenomas and of non-bowel cancers on folic acid 1 mg a day in people with earlier adenomas A borderline, secondary result in one trial; the authors call for more research.	Advanced lesions 11.6% versus 6.9% at second follow-up (RR 1.67, 1.00 to 2.80, P = .05)	unclear Not described.	Controlled trial ²

Liver

No liver injury from folic acid is described on the pages read. In people taking methotrexate for rheumatoid arthritis, a Cochrane review found folic or folinic acid lowered the chance of raised liver enzymes (RR 0.23, 0.15 to 0.34). A liver-safety source such as LiverTox was not searched. ¹⁰

How often. No frequency was found.

Monitoring. No agency monitoring advice was found.

This is a safety connection. It is not evidence that Vitamin B9 (folate and folic acid) supports liver health.

Medicines and supplements 7

With	Why it matters	Importance	Evidence	What to do
Methotrexate prescription	Not described in the sources read.	Folic acid or folinic acid is prescribed alongside methotrexate to reduce side effects; in rheumatoid arthritis it did not significantly change how well methotrexate treated the arthritis (Cochrane, moderate-quality).	Systematic review Moderate certainty ^{10 15}	Take only as the prescriber directs.
Epilepsy medicines (phenytoin, phenobarbital, primidone) prescription	The NHS page does not state a mechanism or direction.	Listed by the NHS as medicines that may not mix well with folic acid. The NHS deficiency page also says anticonvulsants can affect how much folate the body absorbs.	Authoritative guidance Low certainty ^{15 14}	Tell your epilepsy doctor before starting folic acid. Do not stop or change epilepsy medicine yourself.
Antibiotics chloramphenicol and co-trimoxazole; sulfasalazine; lithium; aspirin prescription	The NHS page does not state a mechanism.	Listed by the NHS as medicines that may not mix well with folic acid. No further detail was read.	Authoritative guidance Low certainty ¹⁵	Ask a pharmacist before combining.
Proton pump inhibitors (PPIs) prescription	The NHS says certain medicines, including PPIs and anticonvulsants, can affect how much folate and B12 the body absorbs.	Linked with folate or B12 deficiency, not with a harmful interaction on taking folic acid.	Authoritative guidance Low certainty ¹⁴	If you take one long term and feel tired or have tingling, ask a doctor to check folate and B12.
Alcohol other	The NHS says alcohol can affect how well folic acid works. No mechanism given.	Listed in the NHS folic acid page.	Authoritative guidance Low certainty ¹⁵	Ask a pharmacist or doctor about alcohol if you take folic acid.
Vitamin B12 supplements or B12 deficiency supplement	Folic acid above 1 mg a day can mask B12 deficiency symptoms (NHS, MedlinePlus).	Not a harmful interaction between pills, but a missed diagnosis. People with vitamin B12 deficiency anaemia or pernicious anaemia may not be suited to folic acid on its own (NHS).	Authoritative guidance Moderate certainty ^{16 15 13}	Ask a doctor to check B12 first.
Other medicines and supplements other	No mechanism found.	The NHS says to tell your doctor about any other medicines, herbal remedies, vitamins or supplements. Absence of a listed interaction here is not proof there is none.	Not established Not enough evidence ¹⁵	Ask a pharmacist.

Who should check first 6

Situation	Advice	Evidence
Vitamin B12 deficiency anaemia or pernicious anaemia	The NHS says folic acid may not be suitable. Ask a doctor to treat B12 first.	Authoritative guidance ¹⁵
Coronary stent, or cancer	The NHS lists both as conditions for which folic acid may not be suitable and says to tell your doctor about any medical conditions.	Authoritative guidance ¹⁵
Past allergic reaction to folic acid or an ingredient in the product	Do not take it. Check the leaflet and ask a pharmacist.	Authoritative guidance ¹⁵
Pregnancy and planning pregnancy	The NHS recommends a 400 microgram folic acid supplement for anyone pregnant, trying or who could become pregnant, until 12 weeks of pregnancy, and 5 mg for some women at higher risk after speaking to a doctor. The USPSTF (2023) recommends 0.4 to 0.8 mg daily for people planning or who could become pregnant. Ask a midwife, doctor or pharmacist, especially before a multivitamin.	Authoritative guidance ^{16 15 11}
Breastfeeding	The NHS says folic acid can usually be taken while breastfeeding but to check with a pharmacist or doctor first. MedlinePlus lists a higher recommended intake while breastfeeding (500 micrograms).	Authoritative guidance ^{15 13}
Children	The NHS says most adults and children over 12 months can take folic acid tablets or liquid on their own, and that multivitamins with folic acid are not recommended for children under 12. A doctor or pharmacist should guide use.	Authoritative guidance ¹⁵

Overdose, product quality and regulators

Summary. Folic acid from pills was not described as toxic at ordinary levels in the sources read. The concerns are B12 masking, interactions, a possible signal in people with earlier bowel adenomas, and overdosing on multivitamins.

Animal. Not reviewed.

Human doses studied. Described only inside the studies table.

High dose or long term signals. Above 1 mg a day: B12 masking (NHS, MedlinePlus). In one trial of 1 mg a day for several years in people with earlier adenomas, a borderline signal of more advanced lesions (RR 1.67, P = .05).

Overdose response. NHS: too many multivitamin tablets can be dangerous; get help from NHS 111.

Genotoxicity. Not researched.

Product quality (label accuracy, contaminants) was not researched for this page. The NHS notes that the folic acid added to foods is much lower in amount than in medicines or supplements.

Unmetabolised folic acid in the blood. After a single dose of folic acid, unmetabolised folic acid appeared in plasma regularly, and rarely after 5-MTHF. The abstract does not say what this means for health. ⁹

Body	Action	Date
NHS (UK) (United Kingdom)	B vitamins and folic acid: 400 micrograms folic acid supplement for anyone pregnant, trying or who could become pregnant until 12 weeks; more than 1 mg a day can mask B12 deficiency; 1 mg or less unlikely to cause harm. source	2020-08-03
NHS (UK) (United Kingdom)	Folic acid medicine page: uses, side effects, who may not take it, interactions, pregnancy, breastfeeding, alcohol. source	2026-05-05
NHS (UK) (United Kingdom)	Vitamin B12 or folate deficiency anaemia: symptoms, causes and treatment. source	2023-02-20
MedlinePlus (US National Library of Medicine) (United States)	Folic acid in diet: recommended intakes and advice to avoid more than 1,000 micrograms a day of folic acid except in women with an earlier affected pregnancy who plan to conceive. source	2025-02-03
US Preventive Services Task Force (United States)	Recommends a daily supplement of 0.4 to 0.8 mg (400 to 800 micrograms) of folic acid for people planning or who could become pregnant (grade A). source	2023-08-01

When to get medical help

Swollen face, lips, tongue or throat, a raised itchy rash or difficulty breathing after taking folic acid (possible anaphylaxis): call your local emergency number or NHS 111.
Swallowed more than the label number of multivitamin tablets or capsules: get help from NHS 111 or your local poison centre.
Pins and needles, vision problems, memory problems or confusion, especially if you take folic acid and have not had vitamin B12 checked: see a doctor soon, because nerve damage from B12 deficiency can become permanent.

Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.

General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.

Frequently asked questions

What is the difference between folate and folic acid?

Folate is the natural form in food. Folic acid is the man-made form used in supplements and added to some foods such as enriched bread and cereal. Both are vitamin B9.

^{13 16}

Does folic acid prevent spina bifida?

Folic acid taken around conception lowered neural tube defects such as spina bifida in a Cochrane review of 5 trials (RR 0.31, high-quality evidence). It reduces the chance; it does not remove it.

^{3 6}

What do health agencies say about folic acid before pregnancy?

The NHS recommends a 400 microgram folic acid supplement for anyone pregnant, trying or who could become pregnant, until 12 weeks of pregnancy. The US Preventive Services Task Force recommends 0.4 to 0.8 mg daily for people who could become pregnant. Some higher-risk women are told to use a higher amount by their doctor. Ask your doctor, midwife or pharmacist.

^{16 11}

Which foods are high in folate?

Per USDA, cooked black-eyed peas have 208 micrograms DFE per 100 g, cooked lentils 181, cooked chickpeas 172 and raw spinach 194. The NHS also names broccoli, brussels sprouts, peas and kidney beans, and fortified breakfast cereals.

^{18 16}

Is folate from food the same as folic acid pills?

Not quite. In a 4-week trial of 72 adults, folate from fruit, vegetables and liver was about 80% as available as folic acid. The trial benefits for pregnancy were shown with folic acid pills.

^{12 3}

Can folic acid hide vitamin B12 deficiency?

Yes. The NHS and MedlinePlus say folic acid above 1 mg a day can mask B12 deficiency symptoms, which can eventually damage the nervous system. Ask a doctor to check B12.

^{16 13}

Is l-methylfolate better than folic acid?

Not shown. In one single-dose trial in 24 women, 5-MTHF raised blood folate more than folic acid. We read no trial showing better health outcomes, and the proof for preventing neural tube defects is with folic acid.

^{9 3}

Does folic acid prevent heart disease or stroke?

Not heart attacks. Across 8 trials, folic acid lowered homocysteine about 25% but did not change major vascular events (RR 1.01). Stroke results are small and mixed (RR 0.96 in one review, 0.90 in a Cochrane review).

^{1 7}

Does folic acid improve memory?

One 3-year trial in 818 older adults found small gains in memory and processing speed. It is a single study and does not show it prevents dementia. A US survey linked high blood folate with more cognitive impairment when B12 was low.

^{4 8}

Does folic acid prevent bowel cancer?

Not shown. In 1021 people with earlier bowel polyps, folic acid 1 mg a day did not reduce new polyps and was linked to more advanced lesions at follow-up. Ask a doctor if you have had polyps or cancer.

Why is folic acid given with methotrexate?

Cochrane found folic or folinic acid cut stomach side effects (RR 0.74) and raised liver enzymes (RR 0.23) in people with rheumatoid arthritis taking methotrexate, without significantly changing how well methotrexate worked. Take it only as your prescriber directs.

^{10 15}

Does folic acid interact with medicines?

The NHS lists epilepsy medicines (phenytoin, phenobarbital, primidone), chloramphenicol, co-trimoxazole, sulfasalazine, lithium and aspirin, and says alcohol can affect how well it works. Tell your pharmacist or doctor about everything you take.

¹⁵

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Editorial transparency

Written by: AlternativeMed editorial team. Research compiled with AI assistance, then checked against the sources listed.
Medical review: None. This page has not been reviewed by a physician or pharmacist.
First published: 2026-10-26
Last substantive update: 2026-10-26
How we research: We started from our existing vitamin B9 summary, re-read NHS and MedlinePlus pages, took food values from saved USDA FoodData Central records, and re-read PubMed abstracts for reviews and trials. Only abstracts were read for studies. Items we could not verify are flagged in the research gaps.
How we rate evidence: See "How we rate evidence" in the Evidence tab.
Independence: No product is promoted on this page. No affiliate links are shown. Funding is not stated in the abstracts of the studies cited; where PubMed lists public research support this is noted in the data.

Sources 18

Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.

Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE et al.. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals.. Arch Intern Med. 2010. PMID 20937919. DOI 10.1001/archinternmed.2010.348. (abstract)
Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS et al.. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.. JAMA. 2007. PMID 17551129. DOI 10.1001/jama.297.21.2351. (abstract)
De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects.. Cochrane Database Syst Rev. 2015. PMID 26662928. DOI 10.1002/14651858.CD007950.pub3. (abstract)
Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB et al.. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.. Lancet. 2007. PMID 17240287. DOI 10.1016/S0140-6736(07)60109-3. (abstract)
Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF et al.. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.. JAMA. 2015. PMID 25771069. DOI 10.1001/jama.2015.2274. (abstract)
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.. Lancet. 1991. PMID 1677062. (abstract)
Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events.. Cochrane Database Syst Rev. 2017. PMID 28816346. DOI 10.1002/14651858.CD006612.pub5. (abstract)
Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.. Am J Clin Nutr. 2007. PMID 17209196. DOI 10.1093/ajcn/85.1.193. (abstract)
Prinz-Langenohl R, Brämswig S, Tobolski O, Smulders YM, Smith DE, Finglas PM et al.. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase.. Br J Pharmacol. 2009. PMID 19917061. DOI 10.1111/j.1476-5381.2009.00492.x. (abstract)
Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T et al.. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.. Cochrane Database Syst Rev. 2013. PMID 23728635. DOI 10.1002/14651858.CD000951.pub2. (abstract)
US Preventive Services Task Force. Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement.. JAMA. 2023. PMID 37526713. DOI 10.1001/jama.2023.12876. (abstract)
Winkels RM, Brouwer IA, Siebelink E, Katan MB, Verhoef P. Bioavailability of food folates is 80% of that of folic acid.. Am J Clin Nutr. 2007. PMID 17284745. DOI 10.1093/ajcn/85.2.465. (abstract)
. MedlinePlus: Folic acid in diet. . . (full-text)
. NHS: Vitamin B12 or folate deficiency anaemia. . . (full-text)
. NHS medicines: Folic acid. . . (full-text)
. NHS: B vitamins and folic acid. . . (full-text)
. NIH Office of Dietary Supplements: Folate fact sheet for health professionals. . . (not-read)
. USDA FoodData Central (SR Legacy, April 2018 release): folate in foods. . . (full-text)

Where to buy

Check the label first. Whatever you buy, look for these:

The amount of the active ingredient per serving, not just the front-label claim
A third-party testing mark (USP, NSF or ConsumerLab)
Other ingredients and allergens
Ask a pharmacist about interactions with your medicines

Talk to a pharmacist or doctor before you start any supplement, especially if you take medicines. See the Safety tab for interactions.

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Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.