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Folate (folic acid)
A B vitamin in leafy greens, beans and fortified grains. Many US adults take it, and a US task force recommends folic acid for people who could become pregnant.
Explained simply · Last reviewed
What it is
Folate is a B vitamin, sometimes called vitamin B9. The Office of Dietary Supplements (ODS), part of the US National Institutes of Health, says it is naturally present in some foods, added to others, and sold as a dietary supplement. It reports that about 35% of adults in the United States take a supplement containing folic acid. The US Preventive Services Task Force recommends a daily folic acid supplement for people planning to or who could become pregnant.
More about Folate (folic acid)
The Office of Dietary Supplements (ODS), part of the US National Institutes of Health, says it is naturally present in some foods, added to others, and sold as a dietary supplement. It reports that about 35% of adults in the United States take a supplement containing folic acid. The US Preventive Services Task Force recommends a daily folic acid supplement for people planning to or who could become pregnant.
ODS says the body uses folate to make DNA and RNA and to turn homocysteine into methionine, and that cells need it to divide properly. It names megaloblastic anemia, in which red blood cells are large and abnormal, as the main sign of folate or vitamin B12 deficiency.
The name covers several forms, which ODS describes. Food folate occurs naturally in dark green leafy vegetables, fruits, nuts, beans, peas, seafood, eggs, dairy, meat, poultry and grains. Folic acid is the synthetic form used in most supplements and in fortified foods. ODS reports that since 1998 the US Food and Drug Administration has required it in enriched breads, cereals, flours, pasta, rice and other grain products, to reduce the risk of neural tube defects. Some supplements instead contain 5-MTHF, also sold as L-methylfolate or methylfolate.
ODS explains that the body absorbs folic acid more readily than food folate. For that reason intakes are counted in dietary folate equivalents (DFE), which put the different forms on a common scale. The claims below report what reviews and health authorities concluded about taking folate as a supplement.
Also known as: folic acid, vitamin B9, 5-MTHF, L-methylfolate, methylfolate, folacin
At a glance
Safety: known risks, 4 groups who should avoid it or take extra care and 3 documented interactions. See Safety ↓Claims made about Folate (folic acid), and how strong the evidence is for each:
- Prevents neural tube defects when taken before and in early pregnancyEvidence rating: Strong
- Prevents heart attacksEvidence rating: Evidence against
- Lowers the risk of stroke in people with vascular disease or low folate statusEvidence rating: Moderate
- Protects memory and thinking in older adultsEvidence rating: Evidence against
- Helps depression when added to antidepressantsEvidence rating: Limited
Longevity and aging claims
Claims made about Folate (folic acid) and aging, and how strong the evidence is for each. A change in a marker is not the same as a longer life.
Each rating follows our published rules and the sources cited for it. We don’t add our own medical judgment. How we rate
Safety
Read this before the ratings below.
Risks
- Large amounts of folate can correct the anemia caused by vitamin B12 deficiency, but not the nerve damage it causes. ODS reports a long-standing concern that this could mask a B12 deficiency until its neurological effects become irreversible. It says questions about this remain, and that the concern has shifted toward large amounts of folate bringing on or worsening the anemia and cognitive symptoms of B12 deficiency.
- ODS describes the effect of supplemental folic acid on cancer risk as unclear, especially for people with a history of colorectal adenomas or other cancers, and reports concerns that high intakes might speed the progression of precancerous lesions.
- The US Preventive Services Task Force reports that in a pooled analysis, folic acid alone or with vitamin B12 was associated with higher rates of any cancer over 2 to 6 years; those trials were limited to adults with raised homocysteine or a history of colorectal adenomas, so it calls the relevance to the general population uncertain. A 2017 Cochrane review reported no differences between B vitamins and placebo in serious adverse events (risk ratio 1.07, 95% CI 1.00 to 1.14; high-quality evidence); its summary table notes that cancer was the only adverse event reported.
- ODS reports that "intakes of 1,000 mcg per day or more of folic acid from supplements during the periconception period have been associated with lower scores on several tests of cognitive development in children at age 4–5 years than in children of mothers who took 400 mcg to 999 mcg."
- Folic acid beyond what the body can process circulates unmetabolized. ODS reports this has been linked to reduced numbers and activity of natural killer cells, part of the immune system, and says these possible effects are not well understood.
Who should avoid it or take extra care
- People with low vitamin B12 or a B12 deficiency: large amounts of folate can correct the anemia without correcting the nerve damage, as described above.
- People with a history of colorectal adenomas or other cancers: ODS describes the effect of supplemental folic acid on cancer risk as especially unclear for them.
- Anyone who has had a pregnancy affected by a neural tube defect: the USPSTF recommendation does not cover them. ODS notes that other experts recommend higher amounts for this group, which exceed the upper limit and should be taken only under medical supervision.
- ODS advises that anyone taking the medications listed below on a regular basis should discuss their folate intake with their health care providers.
Documented interactions
- Methotrexate (for example Rheumatrex, Trexall): Methotrexate works against folate. ODS advises that people taking it for cancer consult their oncologist before taking folate supplements, because they could interfere with its anticancer effects. It also reports that folate supplements might reduce the gastrointestinal side effects of low-dose methotrexate taken for rheumatoid arthritis or psoriasis. Source [1]
- Antiepileptic medications (for example phenytoin/Dilantin, carbamazepine/Tegretol, valproate/Depacon): These medications can lower blood folate. Folate supplements might in turn lower blood levels of the medication, so ODS advises checking with a health care provider before taking folate supplements. Source [1]
- Sulfasalazine (Azulfidine): Sulfasalazine reduces how much folate the gut absorbs and can cause folate deficiency. ODS advises asking a health care provider whether to increase dietary folate, take a supplement, or both. Source [1]
Safety sources: Source [1]Source [2]Source [3]
What the evidence says
Each claim is rated on its own evidence. Ratings follow the scale on our methodology page.
Prevents neural tube defects when taken before and in early pregnancy Evidence rating: Strong
People planning a pregnancy take it hoping to protect their baby from birth defects of the spine and brain.
A 2015 Cochrane review found a lower risk of neural tube defects with folic acid, rated high quality; a US task force found a substantial net benefit, with high certainty.
A 2015 Cochrane review pooled five trials covering 6,708 births. Daily folic acid taken before conception and in early pregnancy, alone or with other vitamins and minerals, lowered the risk of neural tube defects such as spina bifida and anencephaly (risk ratio 0.31, 95% CI 0.17 to 0.58). The reviewers rated this finding high quality. Every trial used folic acid.
Four of the five trials (1,846 births) were in women who had already had an affected pregnancy (risk ratio 0.34, 95% CI 0.18 to 0.64), a group the task force recommendation below does not cover. Only one trial (4,862 births) assessed a first occurrence. It showed no clear effect (risk ratio 0.07, 95% CI 0.00 to 1.32), although no cases occurred in the folic acid group. The reviewers still conclude that folic acid prevents both first and repeat occurrences. They found no clear effect on other birth defects: cleft lip, cleft palate, congenital heart defects and other anomalies were each rated low quality, and miscarriage, which did not differ, moderate.
In 2023 the US Preventive Services Task Force reaffirmed its A recommendation. It concludes with high certainty that folic acid supplementation has a substantial net benefit for people planning to or who could become pregnant. It found adequate evidence that folic acid at usual doses is not associated with serious harms.
ODS states that clinical trial evidence shows adequate folic acid around conception prevents a substantial proportion of neural tube defects. It also reports that studies conducted since US food fortification began do not demonstrate a clear protective association, possibly because of food fortification effects, study design flaws, or inadequate sample sizes. This page rates the claim strong on the review's high-certainty finding together with the task force's A recommendation.
Sources: Source [1]Source [2]Source [3]
Prevents heart attacks Evidence rating: Evidence against
People take it hoping it will protect their heart and help them avoid a heart attack.
A 2017 Cochrane review found B vitamins that lower homocysteine made no difference to heart attacks, mostly in people with cardiovascular disease, and rated that high quality.
A 2017 Cochrane review of 15 trials in 71,422 people tested B-vitamin supplements that lower homocysteine (folic acid, vitamin B6 or vitamin B12, alone or combined), mostly in adults who already had cardiovascular disease. Compared with placebo, they made no difference to heart attacks (risk ratio 1.02, 95% CI 0.95 to 1.10; 12 trials, 46,699 people) or to death from any cause (risk ratio 1.01, 95% CI 0.96 to 1.06). The reviewers rated both high-quality evidence. ODS likewise states that folic acid and vitamin B12 supplements lower homocysteine but do not decrease the risk of cardiovascular disease.
For adults without heart disease the evidence is thinner. Among the placebo-controlled trials, the review's subgroup analysis puts one trial, of 490 people, in that group. Its result was too imprecise to show an effect either way (risk ratio 0.98, 95% CI 0.14 to 6.87).
The review analyses a separate trial on its own: 20,702 Chinese adults with high blood pressure and no history of stroke or heart attack. It compared folic acid plus the blood-pressure drug enalapril with enalapril alone and found no clear difference in heart attacks (risk ratio 1.04, 95% CI 0.60 to 1.82; moderate certainty). The US Preventive Services Task Force found cardiovascular event rates in folic acid trials in adults without known cardiovascular disease too low to draw conclusions.
Sources: Source [1]Source [2]Source [3]
Lowers the risk of stroke in people with vascular disease or low folate status Evidence rating: Moderate
People take it hoping to lower their risk of having a stroke.
A 2017 Cochrane review found slightly fewer strokes with B vitamins, mostly in people with cardiovascular disease, rated high quality; ODS reports lower risk especially where folate status is low.
In its comparison with placebo, the same 2017 Cochrane review found a small reduction in stroke with homocysteine-lowering B vitamins. Of the people taking them, 4.3% had a stroke, against 5.1% on placebo (risk ratio 0.90, 95% CI 0.82 to 0.99; 10 trials, 44,224 people), rated high-quality evidence. Those figures cover the placebo-controlled trials only. They enrolled almost entirely people who already had cardiovascular disease and mostly gave B vitamins in combination rather than folic acid alone. Restricted to the six trials at low risk of bias, the reduction was no longer statistically significant (risk ratio 0.90, 95% CI 0.80 to 1.02).
ODS describes a large trial in regions of China without folic acid fortification. Among 20,702 adults with high blood pressure but no history of stroke or heart attack, folic acid plus the blood-pressure drug enalapril reduced the risk of stroke by 21% compared with enalapril alone. The effect was more pronounced in those with the lowest folate levels at the start. The Cochrane review treats that trial as a separate comparison. Its summary table rates the reduction high certainty (risk ratio 0.79, 95% CI 0.68 to 0.93); its abstract describes the effect as uncertain.
ODS concludes that folic acid alone or with other B vitamins reduces the risk of stroke, especially in populations with low folate status, which it notes are less common in countries such as the United States that fortify food with folic acid. For community-dwelling adults without a known deficiency, the US Preventive Services Task Force found the evidence on single-nutrient supplements insufficient to weigh benefits against harms for preventing cardiovascular disease.
Because the sources differ on how far the benefit reaches beyond people with vascular disease or low folate status, this page rates the claim moderate, below the strong that the review's certainty alone would allow.
Sources: Source [1]Source [2]Source [3]
Protects memory and thinking in older adults Evidence rating: Evidence against
Older adults take it hoping to keep their memory and thinking sharp.
A 2018 Cochrane review of 14 trials in cognitively healthy older adults found B vitamins probably make little or no difference to overall thinking for up to 5 years, at moderate certainty.
A 2018 Cochrane review included 14 trials with 27,882 cognitively healthy adults, mostly in their 60s and 70s and mostly with a history of heart or blood-vessel disease. They were given folic acid, vitamin B12, vitamin B6 or a combination. The reviewers concluded that B vitamins probably have little or no effect on overall cognitive function at any point up to 5 years (moderate certainty). They may also have no effect at 5 to 10 years (low certainty).
In the review, memory, executive function and processing speed showed the same pattern, with certainty ranging from high for one measure to very low for several. One small very-low-certainty estimate of executive function over 3 to 12 months favored placebo (standardized mean difference 0.39, 95% CI 0.07 to 0.71). The one trial counting new cases of cognitive impairment found no difference (moderate certainty).
The reviewers found no evidence that any vitamin or mineral strategy has a meaningful effect on cognitive decline or dementia, while noting that the evidence does not permit definitive conclusions. ODS similarly reports that most clinical trials have not shown folic acid to affect cognitive function or dementia, though some found benefits in subgroups such as people with raised homocysteine. It calls for more trials.
Sources: Source [1]Source [2]
Helps depression when added to antidepressants Evidence rating: Limited
People with depression take it alongside their antidepressant, hoping it will lift their mood further.
ODS, part of the US National Institutes of Health, reports mixed trial results for folate added to antidepressants, calls the evidence limited, and says more research is needed.
This rating rests on ODS. It reports that low folate status has been linked to depression in some, but not all, studies. It reports that trials of folic acid added to antidepressant medication have had mixed results: one meta-analysis it describes found a possible benefit on low-quality evidence, and another found no significant effect.
ODS reports that 5-MTHF (methylfolate) might have more promise than folic acid as an add-on, again on low-quality evidence. It notes that guidelines from the British Association for Psychopharmacology and the Canadian Network for Mood and Anxiety Treatments state it might be effective alongside SSRI antidepressants.
It concludes that limited evidence suggests certain forms and doses of folate might help alongside depression treatment, and that more research is needed. It adds that many of the doses studied exceed the upper limit and should be taken only under medical supervision. The research concerns folate used alongside antidepressants, not on its own.
Sources: Source [1]
Longevity and aging
What the cited sources report about lifespan, death from any cause, and markers studied in connection with aging. A change in a marker is not the same as a longer life. Each outcome is rated on its own evidence, on the same scale as the claims above.
Lowers the risk of death from any cause Evidence rating: Evidence against
People take it hoping it will help them live longer.
A 2017 Cochrane review of 11 trials in 44,817 people, mostly with cardiovascular disease, found B vitamins that lower homocysteine made no difference to death from any cause, rated high quality.
A 2017 Cochrane review pooled 11 trials in 44,817 people, followed for 1 to 7.3 years. They compared B vitamins which lower homocysteine, a blood marker, with placebo or standard care. The review groups ten of the trials as including people with a history of cardiovascular disease. Two gave folic acid alone. The other nine gave folic acid or another folate (5-MTHF) together with vitamin B12, with or without vitamin B6, and two of those also had a group given vitamin B6 alone.
The review found no difference between the groups in death from any cause (11.7% against 12.3%; risk ratio 1.01, 95% CI 0.96 to 1.06), which it rated high-quality evidence. The seven trials at low risk of bias gave a similar result (risk ratio 1.03, 95% CI 0.95 to 1.12). The reviewers' trial sequential analysis concluded that no more trials are needed for this outcome, while a Bayes factor analysis they also report found that the data did not favor either hypothesis.
For adults without cardiovascular disease this analysis holds one trial, of 490 people, too imprecise to show an effect either way (risk ratio 0.20, 95% CI 0.01 to 4.04). The review analyzed separately a trial of 20,702 Chinese adults with high blood pressure that compared folic acid plus the blood-pressure drug enalapril with enalapril alone over a median of 4.5 years. Deaths from any cause did not clearly differ (2.9% against 3.1%; risk ratio 0.94, 95% CI 0.81 to 1.10), also rated high-quality evidence.
ODS summarizes the review as concluding that folic acid supplementation alone or in combination with vitamin B6 and vitamin B12 does not affect the risk of death from any cause.
Sources: Source [1]Source [2]
How and when to take it
What the cited sources say about taking it. Ask your doctor or pharmacist what applies to you.
What the USPSTF recommends for people who could become pregnant
The US Preventive Services Task Force states: "The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 mcg) of folic acid." It adds: "To achieve benefit, persons planning to or who could become pregnant should start daily folic acid supplementation at least 1 month prior to anticipated conception and continue through the first 2 to 3 months of pregnancy." The recommendation does not apply to people who have had a previous pregnancy affected by a neural tube defect, who are at very high risk for other reasons, or who take medicines known to block folic acid, such as methotrexate, carbamazepine and valproic acid. Source [1]
The upper limit covers synthetic folate only
ODS explains that the upper limit applies to the synthetic forms of folate in supplements and fortified foods, and that none is set for folate from food, because high intakes from food have not been reported to cause harm. For that reason the upper limits below are in micrograms, not micrograms of dietary folate equivalents. It adds that they do not apply to people taking high doses under medical supervision. Source [1]
Which form the evidence used
Supplements are sold in several forms. This is what the sources on this page say about them — which form the research used, and any comparison those sources themselves made. Where they made none, this page does not rank the forms.
Folic acid (the synthetic form in most supplements and fortified foods), What the sources supportDetails
This is the form the neural tube defect evidence rests on. Every trial in the cited Cochrane review used folic acid, and the reviewers found no randomized trials of 5-MTHF. The US Preventive Services Task Force recommendation is for folic acid. ODS reports that the CDC recommends folic acid, not 5-MTHF, for people who could become pregnant, even if they carry the common 677C>T MTHFR gene variant. On absorption, ODS states that at least 85% of folic acid is bioavailable when taken with food, against about 50% of the folate naturally present in food. Source [1]Source [2]Source [3]
5-MTHF (L-methylfolate, methylfolate), What the sources supportDetails
ODS states that the bioavailability of 5-MTHF in supplements is the same as or greater than that of folic acid. That is about absorption, not about preventing birth defects: the Cochrane reviewers found no randomized trials of 5-MTHF for that, and wrote that the best form for periconceptional supplements is not yet established. ODS also says that some people with an MTHFR gene variant might benefit from 5-MTHF, although it calls the research on this inconclusive. It notes that factors for converting 5-MTHF to dietary folate equivalents have not been formally established, so manufacturers may use their own, up to a cap the FDA sets. For its use alongside antidepressants, see the depression rating below. Source [1]Source [2]
Reference intake values
Quoted exactly as published by the cited authority. These are population reference values, not a recommendation for you. Ask your doctor or pharmacist what applies to your situation.
Teens, 14–18 years
- Recommended intake
- 400 mcg DFE
- Upper limit
- 800 mcg
- Source
- Source [1]
Adults, 19+ years
- Recommended intake
- 400 mcg DFE
- Upper limit
- 1,000 mcg
- Source
- Source [1]
Pregnancy, 14–18 years
- Recommended intake
- 600 mcg DFE
- Upper limit
- 800 mcg
- Source
- Source [1]
Pregnancy, 19+ years
- Recommended intake
- 600 mcg DFE
- Upper limit
- 1,000 mcg
- Source
- Source [1]
Lactation, 14–18 years
- Recommended intake
- 500 mcg DFE
- Upper limit
- 800 mcg
- Source
- Source [1]
Lactation, 19+ years
- Recommended intake
- 500 mcg DFE
- Upper limit
- 1,000 mcg
- Source
- Source [1]
What the upper limits count: “Based on the metabolic interactions between folate and vitamin B12, the FNB established a UL for the synthetic forms of folate available in dietary supplements and fortified foods.” Source [1]
Sources
- Effects and safety of periconceptional oral folate supplementation for preventing birth defectsCochrane Database of Systematic Reviews, 2015 · Systematic review · Primary source · Certainty: low
- Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation StatementJAMA, 2023 · Health authority summary · Primary source
- Folate: Fact Sheet for Health ProfessionalsNIH Office of Dietary Supplements, 2022 · Health authority summary · Primary source
- Homocysteine-lowering interventions for preventing cardiovascular eventsCochrane Database of Systematic Reviews, 2017 · Systematic review · Primary source · Certainty: high
- Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation StatementJAMA, 2022 · Health authority summary · Primary source
- Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late lifeCochrane Database of Systematic Reviews, 2018 · Systematic review · Primary source · Certainty: very low
Page history
Show all 7 changes to this page
- — Rewritten to the content style guideline; ratings and sources unchanged.
- — Corrected a sentence in the heart attack summary. It described the Chinese folic acid and enalapril trial as the one trial the Cochrane review lists as enrolling people with no history of cardiovascular disease; the review's subgroup analysis names a different trial of 490 people for that, and analyses the enalapril trial separately. The sentence now says so and describes that trial's participants as having no history of stroke or heart attack. No rating changed.
- — Added a longevity section. Lowering the risk of death from any cause is rated evidence-against, from the 2017 Cochrane review of homocysteine-lowering B vitamins already cited on this page. No existing claim or rating changed.
- — Added a note under the reference intakes quoting what the NIH ODS upper limit counts: the synthetic folate in dietary supplements and fortified foods. It replaces a site-wide sentence that said upper limits count only supplements and medications, which was wrong for folate. No value or rating changed.
- — Published. All five claims, the safety section and every source passed the site's source and wording reviews. Unread comments on the 2022 USPSTF statement and the owner's confirmation of the neural-tube-defect certainty stay logged in docs/08-open-decisions.md.
- — Revised after source review. The stroke claim is now scoped to people with vascular disease or low folate status and reports the Chinese folic acid and enalapril trial. The neural tube defect summary now separates first occurrence from recurrence and notes the post-fortification studies. No rating changed.
- — Drafted. Neural tube defect prevention rated strong, stroke moderate, depression limited; heart attack prevention and protecting memory and thinking rated evidence-against.