Folate (Folic Acid)
The main form of folate in plasma is 5-methyl-THF. Dietary folate equivalents (DFEs) were developed to reflect the higher bioavailability of folic acid than that of food folate. Frank folate deficiency is rare in the United States, but some individuals might have marginal folate status. People with alcohol use disorder frequently have poor-quality diets that contain insufficient amounts of folate. During pregnancy, demands for folate increase because of its role in nucleic acid synthesis. Some women of childbearing age get insufficient amounts of folate even if they take dietary supplements.
Where to get it
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Active compounds & mechanisms
Key compounds: 5-methyl-THF, Folic acid
Research & evidence
Strong support Some support Weak or no supportColours show how well the sources back each point. The reason is next to each one.
Adequate folic acid intake around the time of conception by women prevents a substantial proportion of neural tube defects (NTDs). Women with insufficient folate intakes are at increased risk of giving birth to infants with NTDs.
Strong evidenceStrong support. Stated plainly by NIH or an FDA label
Study details
NIH ODS says: "adequate periconceptional folic acid consumption by women prevents a substantial proportion of NTDs" "Women with insufficient folate intakes are at increased risk of giving birth to infants with NTDs [2]."
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Neural Tube Defects; Folate Deficiency View source
NIH ODS describes a possible inverse association between mothers' folic acid intake around the time of conception and the risk of ASD (autism spectrum disorder).
Limited evidenceSome support. The source hedges (“may” or “associated with”)
Study details
NIH ODS says: "a possible inverse association between mothers' periconceptional folic acid intakes and risk of ASD"
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Autism Spectrum Disorder View source
The effects of supplemental folic acid on cancer risk are unclear.
Limited evidenceSome support. Reviewers rated the certainty low
Study details
NIH ODS says: "the effects of supplemental folic acid on cancer risk are unclear"
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Cancer View source
Additional research is needed to fully understand the association between folate status and depression.
Limited evidenceSome support. Reviewers rated the certainty low
Study details
NIH ODS says: "Additional research is needed to fully understand the association between folate status and depression."
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Depression View source
For preterm birth, congenital heart defects and other anomalies, the results of these studies have been inconsistent.
Mixed evidenceSome support. Results are mixed
Study details
NIH ODS says: "but the results of these studies have been inconsistent"
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Preterm Birth, Congenital Heart Defects, and Other Anomalies View source
Folate does not appear to improve cognitive function in individuals with or without cognitive impairment.
Not supported by current evidenceWeak or no support. Trials found no clear benefit
Study details
NIH ODS says: "does not appear to improve cognitive function in individuals with or without cognitive impairment"
Source: NIH ODS, Folate — Health Professional Fact Sheet (Updated October 4, 2018), Folate and Health: Dementia, Cognitive Function, and Alzheimer's Disease View source
Dosage
| Form | Amount |
|---|---|
| Any form | No standard dose is listed by our sources. |
Side effects
Well documented Reported (case reports, anecdotal or one study) None reportedThe circle shows how well documented an effect is, not how serious it is. A rarely reported effect can still be serious, so always read ‘When to stop’.
| Effect | Frequency | When to stop |
|---|---|---|
| Nausea or digestive discomfort at high dosesReportedCase reports only | Uncommon at recommended doses | Stop and talk to a doctor if you notice any unexpected or concerning symptoms. |
| High-dose folic acid may mask vitamin B12 deficiencyWell documentedListed plainly by NIH, MSK or LiverTox | Relevant at doses above 1,000 mcg/day | If neurological symptoms develop, consult a doctor. |
Safety & interactions
Safety
NIH ODS lists a Tolerable Upper Intake Level (UL), the maximum daily intake unlikely to cause adverse health effects. The ULs do not apply to individuals taking high doses of supplemental folate under medical supervision. Little is known about the long-term effects of high folic acid doses in children. The potential negative health consequences of excess folate are not well understood and warrant further research.
Contraindications
No specific contraindications are listed by our sources. If you take methotrexate, an antiepileptic drug or sulfasalazine, see Drug interactions.
Drug interactions
NIH ODS says methotrexate, used to treat cancer and autoimmune diseases, is a folate antagonist.
NIH ODS lists antiepileptic drugs such as phenytoin (Dilantin), carbamazepine (Carbatrol, Tegretol, Equetro, Epitol) and valproate (Depacon), which are used to treat epilepsy, in its folate drug interactions section. Our sources don't describe the effect.
NIH ODS lists sulfasalazine (Azulfidine), which is used primarily to treat ulcerative colitis, in its folate drug interactions section. Our sources don't describe the effect.
Established: stated plainly by an authoritative source. Documented: supported by case reports or trial data. Theoretical: based on mechanism, animal data, or a cautious listing. Always check with your pharmacist or prescriber.
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