Folic acid is a B vitamin needed for cell replication and growth. Folic acid helps form
building blocks of DNA, the body’s genetic information, and building blocks of RNA,
needed for protein synthesis in all cells. Therefore, rapidly growing tissues, such as those
of a fetus, and rapidly regenerating cells, like red blood cells and immune cells, have a high need for folic acid. Folic
acid deficiency results in a form of anemia that responds quickly to folic acid
and relatively consistent scientific data showing a substantial health benefit.
Contradictory, insufficient, or preliminary studies
suggesting a health benefit or minimal health benefit.
For an herb, supported by traditional use but minimal
or no scientific evidence. For a supplement, little scientific support and/or minimal health
Who is likely to be deficient?
Many people consume less than the recommended amount of folic acid. Scientists have found
that people with heart disease commonly have
elevated blood levels of homocysteine, a
laboratory test abnormality often controllable with folic acid supplements. This suggests that
many people in Western societies have a mild folic acid deficiency. In fact, it has been
suggested that increasing folic acid intake could prevent an estimated 13,500 deaths from
cardiovascular diseases each year.1
Deficiency of folic acid can be precipitated by situations wherein the body requires
greater than normal amounts of the vitamin, such as pregnancy, infancy, leukemia, exfoliative dermatitis,
and diseases that cause the destruction of blood cells.3
The relationship between folic acid and prevention of neural tube defects is partly thought to result from
the high incidence of folate deficiency in many societies. To protect against neural tube
defects, the U.S. Food and Drug Administration has mandated that some grain products provide
supplemental folic acid at a level expected to increase the dietary intake by an average of
100 mcg per day per person. As a result of folic acid added to the food supply, fewer
Americans will be depleted compared with the past. In 1999, scientific evidence began to
demonstrate that the folic acid added to the U.S. food supply was having positive effects,
including a partial lowering of homocysteine levels.4 In the same year, however, a
report from the North Carolina Birth Defects Monitoring Program suggested the current level of
folic acid fortification has not reduced the incidence of neural-tube defects.5
Many doctors and the Centers for Disease Control in Atlanta6 believe that optimal
levels of folic acid intake may still be higher than the amount now being added to food by
several hundred micrograms per day. A low blood level of folate has also been associated with
an increased risk of miscarriage.7
People with kidney failure have an increased risk of folic acid deficiency.8
Recipients of kidney transplants often have elevated homocysteine levels, which may respond to
supplementation with folic acid.9 The usual recommended amount of 400 mcg per day
may not be enough for these people, however. Larger amounts (up to 2.4 mg per day) may produce
a better outcome, according to one double-blind trial.10
Folate deficiency is more prevalent among elderly African American women than among elderly
Which form is best?
Folic acid naturally found in food is much less available to the body compared with
synthetic folic acid found both in supplements
and added to grain products in the United
States. Women with a recent history of giving birth to babies with neural tube defects participated in a study to
determine which form of folic acid is best absorbed—dietary folic acid or folic acid
from supplements.12 They received either orange juice containing 400 mcg of folic acid per day or a
supplement containing the same amount. Overall, the supplement folic acid was better absorbed
than the folic acid from orange juice.
How much is usually taken?
Many doctors recommend that all women who are or who could become pregnant take 400 mcg per day in order to reduce the
risk of birth defects. Some doctors also
extend this recommendation to other people in an attempt to reduce the risk of heart disease by lowering homocysteine levels. Since the FDA mandated addition
of folic acid to grain products, many people
who eat grains have followed the new recommendation of supplementing only 100 mcg of folic
acid per day. However, studies have found that this amount of folic acid is inadequate to
maintain normal folate levels in a significant percentage of the groups assessed.13
It now appears that, for pregnant women, supplementing with at least 300 mcg (and optimally
400 mcg) of folic acid per day is sufficient to prevent a folate deficiency, even if dietary
intake is low.
Are there any side effects or interactions?
With the exception of rare cases of allergic reactions,14 folic acid is not
generally associated with side effects.15 However, folic acid supplementation can
interfere with the laboratory diagnosis of vitamin
B12 deficiency, possibly allowing the deficiency to progress undetected to the point of
irreversible nerve damage.16 Although vitamin B12 deficiency is uncommon, no one
should supplement with 1,000 mcg or more of folic acid without consulting a doctor.
Vitamin B12 deficiencies often occur without anemia (even in people who do not take folic
acid supplements). Some doctors do not know that the absence of anemia does not rule out a B12
deficiency. If this confusion delays diagnosis of a vitamin B12 deficiency, the patient could
be injured, sometimes permanently. This problem is rare and should not happen with doctors
knowledgeable in this area using correct testing procedures.
Folic acid is needed by the body to utilize vitamin B12. Proteolytic enzymes inhibit folic acid
absorption.17 People taking proteolytic enzymes are advised to supplement with
Are there any drug
Certain medicines may interact with folic acid. Refer to drug interactions for a list of those medicines.
References (To view, roll mouse over the "References" heading; to hide, click on the heading)
1. Russel RM. A minimum of 13,500 deaths annually from coronary artery
disease could be prevented by increasing folate intake to reduce homocysteine levels.
2. Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss,
vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999;69:564–71.
3. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency. A
Guide for the primary care physician. Arch Intern Med 1999;159:1289–98
4. Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid
fortification on plasma folate and total homocysteine concentrations. N Engl J Med
5. Meyer RE, Oakley GP Jr. Folic acid fortification. Lancet
6. Oakley GP Jr. Eat right and take a multivitamin. N Engl J
Med 1998;338:1060–1 [editorial].
7. Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels
as risk factors for recurrent early pregnancy loss. Obstet Gynecol
8. Makoff R. Vitamin replacement therapy in renal failure patients.
Miner Electrolyte Metab 1999;25:349–51 [review].
9. Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of
hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial.
Ann Intern Med 1997;127:1089–92.
10. Beaulieu AJ, Gohh RY, Han H, et al. Enhanced reduction of fasting
total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid
supplementation in renal transplant recipients. Arterioscler Thromb Vasc Biol
11. Stabler SP, Allen RH, Fried LP, et al. Racial differences in
prevalence of cobalamin and folate deficiencies in disabled elderly women. Am J Clin
12. Neuhouser ML, Beresford SA, Hickok DE, Monsen ER. Absorption of
dietary and supplemental folate in women with prior pregnancies with neural tube defects and
controls. J Am Coll Nutr 1998;17:625–30.
13. Bailey L. New standard for dietary folate intake in pregnant women.
Am J Clin Nutr 2000;71(Suppl):1304S–7S [review].
14. Smith J, Empson M, Wall C. Recurrent anaphylaxis to synthetic folic
acid. Lancet 2007;370:652
15. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief
review. Am J Clin Nutr 1989;50:353–8.
16. Wald NJ, Bower C. Folic acid, pernicious anaemia, and prevention of
neural tube defects. Lancet 1994;343:307.
17. Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid
absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369–73.
The information presented in Aisle7 is for informational purposes only.
It is based on scientific studies (human, animal, or in vitro), clinical experience,
or traditional usage as cited in each article. The results reported may not necessarily occur
in all individuals. For many of the conditions discussed, treatment with prescription or over
the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist
for any health problem and before using any supplements or before making any changes in