Folic acid benefits

What is folic acid good for?

Folate is required for DNA and RNA synthesis, cell division and the processing of some amino acids. In deficiency, red blood cells become larger than normal and immature (megaloblastic anemia); the NIH lists weakness, fatigue, difficulty concentrating, irritability, headache, palpitations and shortness of breath as its symptoms. ^[1]

Two situations must be distinguished here. Giving folate when there is deficiency is a treatment; whether extra supplementation improves another health outcome when there is no deficiency is a separate claim, and each claim has been tested with its own studies. The NIH’s “Folate and health” section examines these claims in seven areas: autism spectrum disorder, cancer, cardiovascular disease and stroke, dementia and cognitive function, depression, neural tube defects, and also preterm birth and congenital anomalies. ^[1]

Does folic acid prevent neural tube defects?

Yes; this is the use of folic acid with the strongest evidence. The Cochrane review pooled five trials (7,391 women) and reported in the first comparison (6,708 births) that folic acid, alone or together with other vitamins, reduced neural tube defects: RR 0.31 (95% CI 0.17–0.58), high-quality evidence. For recurrence in those who had previously had a pregnancy with a neural tube defect, RR was 0.34 (0.18–0.64; four trials, 1,846 births). ^[2]

In the single trial that assessed only first occurrence (incidence), there were no cases in the folic acid group, but the result was not significant (RR 0.07; 0.00–1.32; 4,862 births). According to subgroup analyses, the effect did not vary across daily doses of 400 µg and above. Folic acid showed no clear effect for cleft palate, cleft lip, congenital heart defects or miscarriage (evidence quality for these results is low to moderate). The review’s authors conclude that folic acid prevents neural tube defects but has no clear effect on other birth defects. ^[2]

Timing, dose and high-risk groups are covered on the pregnancy page.

What does folic acid do for homocysteine and cardiovascular disease?

High homocysteine levels have been associated with cardiovascular disease risk; because folate and other B vitamins take part in homocysteine metabolism, it was hypothesized that these vitamins might lower the risk. The NIH reports that folic acid (and B12) supplements lower homocysteine level but do not reduce cardiovascular disease risk, while appearing to provide protection for stroke. ^[1]

The Cochrane review (15 randomized trials, 71,422 participants, follow-up 1–7.3 years) compared homocysteine-lowering interventions, that is, B6, B9 or B12 supplements alone or together, with placebo. There was no difference in heart attack (RR 1.02; 95% CI 0.95–1.10; 12 trials, 46,699 participants), nor in all-cause death (RR 1.01; 0.96–1.06; 11 trials). For serious adverse events, RR was 1.07 (1.00–1.14; eight trials, 35,788 participants). For stroke, however, there was a small difference: RR 0.90 (0.82–0.99; 10 trials, 44,224 participants; 4.3% and 5.1%). In two trials comparing high doses with low doses, the stroke result remained uncertain. ^[3]

The limits of this result are clear: the intervention examined is not folic acid alone but B6, B9 and B12 supplements; the stroke effect is small and the upper end of the confidence interval is very close to 1. The NIH’s assessment is also that stroke protection is seen particularly in populations with low folate levels. ^[1]

Does folic acid affect cancer risk?

The question asked here is not whether deficiency increases cancer risk, but whether extra folic acid supplementation changes cancer incidence. The meta-analysis by Vollset and colleagues combined individual participant data from 13 randomized trials comparing folic acid with placebo, lasting at least 1 year and with at least 500 participants (49,621 participants; ten trials of cardiovascular disease prevention, three in patients with colorectal adenomas). With a mean of 5.2 years of administration, no significant difference was found in overall cancer incidence (RR 1.06; 95% CI 0.99–1.13); no significant effect was seen at specific sites including colon, prostate, lung and breast either. The authors note that the doses in these trials were an order of magnitude higher than the mean dose in fortification. ^[4]

The NIH reports that an expert panel convened in 2015 by the National Toxicology Program and the NIH Office of Dietary Supplements concluded that folic acid supplements do not reduce cancer risk in people with adequate baseline folate levels. Effects beyond five years and the associations shown by observational studies are different questions; therefore neither “prevents cancer” nor “causes cancer” is a proven conclusion. ^[1]

What has been shown for folic acid in depression and cognitive function?

Depression. The question here is the contribution of folate as an add-on to antidepressant treatment. In the FolATED trial, 475 adults with moderate-to-severe depression at three centers in Wales who were taking or about to start an antidepressant (people with folate or B12 deficiency were excluded) received 5 mg per day of folic acid or placebo added for 12 weeks. Folic acid did not significantly improve any measured outcome; according to the study abstract, SF-12 mental health scores were significantly lower in the folic acid group (by 3.0%; 95% CI −5.2% to −0.8%). The authors state that the findings call into question guidelines recommending folic acid for depression and that methylfolate may be a better candidate. ^[5]

By contrast, a 2021 meta-analysis pooled six randomized trials in which folate (L-methylfolate or folic acid) was given in addition to an SSRI/SNRI. In the analysis of five trials, the Hamilton depression score was lower in the folate add-on group (mean difference −2.16; 95% CI −3.62 to −0.69); the response rate was RR 1.36 (1.16–1.59) and the remission rate RR 1.39 (1.00–1.92; p = 0.05). ^[6] The number of trials is small and folic acid and L-methylfolate were assessed together; the effect of folic acid alone cannot be derived from this result. Read together, these two results leave the effect of folate as an add-on treatment contradictory.

Memory and dementia. The 2008 Cochrane review evaluated eight randomized trials comparing folic acid (with or without B12) with placebo (four in healthy older adults, four in people with cognitive impairment or dementia). In unselected healthy older adults, there was no adequate evidence of benefit for cognitive function and mood. In a single trial of selected healthy older adults with high homocysteine levels, 800 µg per day of folic acid for three years showed benefit in global function, memory storage and information processing speed; in people with cognitive impairment, response to cholinesterase inhibitors was increased in one small pilot study (Alzheimer’s patients, 1 mg per day of folic acid), and other trials showed no benefit in cognitive function. The authors conclude that there is no consistent evidence that folic acid improves cognitive function in older adults. ^[7]

Does folic acid increase fertility in men?

Folic acid and zinc are commonly found in supplements marketed for male fertility. In the multicenter, placebo-controlled trial by Schisterman and colleagues published in JAMA, 2,370 men from couples in the US planning infertility treatment received 5 mg per day of folic acid and 30 mg of elemental zinc or placebo for 6 months. The live birth rate did not differ between groups (34% and 35%; risk difference −0.9%; 95% CI −4.7% to 2.8%). Sperm concentration, motility, morphology, volume and total motile sperm count were not significantly different either; DNA fragmentation was higher in the supplement group (29.7% and 27.2%) and gastrointestinal complaints were more frequent. ^[8]

This is a trial assessing folic acid and zinc together, not folic acid alone; participants are men from couples undergoing infertility treatment, and the dose was far above the general recommended amount.

What can be said for hair, skin and energy?

The NIH reports that folate deficiency can cause sores in the mouth and on the tongue, as well as changes in skin, hair or nail color. This is a finding of deficiency; it is not a result showing that supplements improve hair loss, skin or energy in a person without deficiency. Hair, skin and general energy are not among the NIH’s seven review areas listed above. ^[1]

Summary of the evidence

Situations where benefit is and is not expected

The evidence distinguishes situations where benefit has been shown for a specific goal and population from those that only appear biologically plausible. Preventing neural tube defects in women who could become pregnant is in the first group. Correcting the deficiency in people diagnosed with folate deficiency is treatment. Heart attack, cancer and cognitive function in unselected people are in the second group: no benefit was seen in randomized trials in these areas. Stroke and depression lie between these two ends, with low certainty.

Like every supplement, folic acid can interact with medications and, in high amounts, can mask B12 deficiency; these topics are on the hub page.

This guide does not recommend personal doses.