Folate, a B vitamin, plays a critical role in many biological processes. It participates in the crucial biological process known as methylation and plays an important role in cell division: without sufficient amounts of folate, cells cannot divide properly. Adequate folate intake can reduce the risk of heart disease and prevent serious birth defects, and it may lessen the risk of developing certain forms of cancer.
Folate requirements rise with age. The official US and Canadian recommendations for daily intake are as follows:
- 0-6 months: 65 mcg
- 7-12 months: 80 mcg
- 1-3 years: 150 mcg
- 4-8 years: 200 mcg
- 9-13 years: 300 mcg
- 14 years and older: 400 mcg
- 9-13 years: 300 mcg
- 14 years and older: 400 mcg
: 600 mcg
: 500 mcg
The National Institutes of Health's Office of Dietary Supplements offers this list of foods that are high in folate:149
||% Daily Value
|100% fortified breakfast cereal
|Beef liver, cooked, braised
|Spinach, frozen, cooked, boiled
|Enriched egg noodles, cooked
|25% fortified breakfast cereal
|Great Northern beans, boiled
|Enriched macaroni, cooked
|Enriched white, long-grain rice
|Frozen broccoli, chopped
|Tomato juice, canned
|Green peas, frozen, boiled
|Peanuts, dry roasted
Until recently, folate deficiency was fairly common in the developed world, causing thousands of children to be born with preventable birth defects.
However, in 1998, widespread fortification of cereal products began in the US. and Canada. As a result, the prevalence of folate deficiency has begun to decrease in these countries.
Deficiency appears to be most common today among individuals who are African-American, Hispanic, or of Asian/Pacific Islander race/ethnicity, as well as younger people and those who are overweight.
Various drugs may impair your body's ability to absorb or utilize folate, including
bile acid sequestrants
(such as cholestyramine and colestipol),
, oral medications used for diabetes, various antiseizure medications (
, and valproate), sulfasalazine and possibly other certain
, and the antibiotic
In addition, some of these drugs might put pregnant women at higher risk of giving birth to children with various kinds of birth defects; taking folate supplements may help reduce this risk.
may also affect folate slightly, but there doesn't appear to be a need for supplementation.
The use of folate supplements by
dramatically decreases the risk that their children will be born with a serious birth defect called neural tube defect.
This congenital problem consists of problems with the brain or spinal cord.
Folate supplements may also help prevent other types of birth defects, such as defects of the heart, palate, and urinary tract; conversely, drugs that impair folate action may increase risk of birth defects. (See
for a list of the drugs involved.) An
study suggests that folate supplements may reduce this risk in pregnant women taking such drugs.
Folate also lowers blood levels of homocysteine, which in turn has been hypothesized to reduce the risk of heart disease and other conditions. Studies conflict on the optimum dose of folate for this purpose; 100 to 400 mcg may produce some homocysteine-lowering effects, while 800 mcg daily may lead to maximum effects.
Note however, that there is as yet no meaningful evidence that reducing homocysteine is beneficial, and considerable evidence that it is not. Overall, studies of folate supplementation for reducing cardiovascular risk have failed to show benefit.
On a more positive note, a double-blind, placebo-controlled study of 728 Danish seniors with high homocysteine and relatively low folate intake found that use of folate supplements slowed the progression of age-related hearing loss.
See the full
article for additional information. Folate supplementation might also improve
in seniors with high homocysteine levels.
Based on preliminary evidence, folate has been suggested as a treatment for
One double-blind, placebo-controlled trial found that folate supplements at a dose of 500 mcg daily may help antidepressants work more effectively in women, but perhaps not in men.
However, another study randomized 909 older adults with mild depression to different treatment groups, which included a group that took folate (400 mcg) and
(100 mcg) daily for 2 years.
Folate and vitamin B
were no better than placebo at improving their depressive symptoms.
Observational studies hint that a deficiency in folate might predispose people to develop
of the cervix,
and that folate supplements may help prevent colon cancer, especially when taken for many years or by people with
However, observational studies are notoriously unreliable; large double-blind, placebo-controlled studies are needed to prove a treatment effective. One such study performed on folate for cancer prevention among 1,000 people over a 5-year period found folate ineffective for preventing early colon cancer.
However, a much smaller study involving 94 individuals with colon polyps (a precancerous condition) found that folate may reduce the risk of recurrent polyps over a 3-year period.
High-dose folate (10 mg daily) might be helpful for normalizing abnormalities in the appearance of the cervix (as seen under a microscope) in women taking oral contraceptives, but it does not appear to reverse actual
Some evidence suggests that folate supplements might reduce risk of
Folate deficiency may also increase the risk of
, although this has not yet been proven.
Folate supplements may reduce drug side effects in individuals taking the drug
for certain conditions.
Folate may also reduce side effects of the antiseizure drug
Folate supplements may help medications in the
family remain effective.
Folate supplementation may reduce blood arsenic levels in people who have been exposed to this toxic substance.
Very high dosages of folate may be helpful for
although some authorities suggest that it was actually a contaminant of folate that caused the benefit seen in some studies.
Furthermore, other studies have found no benefit at all.
Based on intriguing but not yet definitive evidence, folate in various dosages has been suggested as a treatment for
(in combination with vitamin B
restless legs syndrome
(splotchy loss of skin pigmentation).
Other conditions for which it has been suggested include
appear to be helpful for
enhancing mental function
What Is the Scientific Evidence for Folate?
Prevention of Birth Defects and Other Benefits
Very strong evidence tells us that regular use of folate by
can reduce the risk of neural tube defect (NTD) by 50% to 80%.
NTDs include conditions like spina bifida, when the baby's spine does not completely close during early pregnancy, and
anencephaly, when the upper section (head and skull) of the neural tube does not develop. To reduce the chance of NTDs, women of reproductive age are encouraged to take daily folate supplements.
A systematic review of 5 trials involving 6,105 women reinforced the evidence that folate supplementation can prevent NTDs in both women who have had a baby with an NTD and those who have not.
Participants took daily doses between 360 mcg to 4 mg with or without additional supplements. There was not enough information, though, to say whether folate can reduce the risk of developing other conditions, like cleft lip or cleft palate.
Less direct evidence suggests that folate can help prevent other kinds of birth defects, especially among women using medications that interfere with folate.
A study involving 38,954 children found that the use of
supplementation during early pregnancy reduced the children’s chance of having a severe language delay at 3 years of age.
One study found that people with depression who do not respond well to antidepressants are likely to be low in folate.
A 10-week, double-blind, placebo-controlled trial of 127 individuals with severe major
found that folate supplements at a dose of 500 mcg daily significantly improved the effectiveness of fluoxetine (Prozac) in female participants.
Improvement in male participants was not significant, but blood tests taken during the study suggested that higher intake of folate might be necessary for men.
Methotrexate Side Effects
is used in cancer chemotherapy as well as for treating inflammatory diseases such as
. While often highly effective, it can produce a number of severe side effects. These include liver toxicity as well as gastrointestinal distress. In addition, use of methotrexate is thought to raise levels of homocysteine, potentially increasing risk of heart disease.
Supplementation with folate may help. Methotrexate is called a "folate antagonist" because it prevents the body from converting folate to its active form. In fact, this inactivation of folate plays a role in methotrexate's therapeutic effects. This leads to an interesting Catch-22: Methotrexate use can lead to folate deficiency, but taking extra folate could theoretically prevent methotrexate from working properly.
However, evidence suggests that individuals who take methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely use folate supplements.
Not only does the methotrexate continue to work properly, but its usual side effects may decrease as well.
For example, in a 48-week, double-blind, placebo-controlled trial of 434 individuals with active rheumatoid arthritis, use of folate helped prevent liver inflammation caused by methotrexate.
This effect allowed more participants to continue methotrexate therapy; the development of liver inflammation often requires people to stop using the drug. A slightly higher dose of methotrexate was needed to reach the same level of benefit as taking methotrexate alone, but researchers felt this was worth it.
In the study just described, folate supplements did not reduce the incidence of mouth sores and nausea. However, in other studies, folate supplements did reduce these side effects, both in individuals receiving methotrexate for rheumatoid arthritis
and in those with psoriasis.
In addition, two studies of individuals with rheumatoid arthritis found that use of folate supplements corrected the methotrexate-induced rise in homocysteine without affecting disease control.
: Folate supplements have been found safe only as supportive treatment in the specific conditions noted above. It is not known, for example, whether folate supplements are safe for use by individuals taking methotrexate for cancer treatment.
Folate at nutritional doses is extremely safe. The only serious potential problem is that folate supplementation can mask the early symptoms of vitamin B
deficiency (a special type of anemia), potentially allowing more irreversible symptoms of nerve damage to develop. For this reason, when taking more than 400 mcg daily, it is important to get your B
level checked. See the article on
for more information.
Very high dosages of folate, greater than 5 mg (5,000 mcg) daily, can cause digestive upset. The maximum recommended dosage of folate for pregnant or nursing women is 1,000 mcg daily (800 mcg if under 19 years old).
Media reports that use of folate by pregnant women may increase their risk of breast cancer are based on a single study of highly questionable validity.
At present, this is not considered a significant concern, but further research will follow.
As mentioned previously, the antiseizure drug
may interfere with folate absorption. However, folate may reduce the effectiveness of phenytoin.
If you are taking phenytoin, you should consult with a physician about the proper dosage of folate for you.
Also, as noted above, individuals who are taking the drug methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely take folate supplements at the same time. However, if you are taking methotrexate for any other purpose, do not take folate except on the advice of a physician.