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FOLATE BENEFITS AND SOURCES

Folic acid is a B vitamin. Our bodies use it to make new cells.
Everyone needs folic acid. But for women who can get
pregnant, it is really important! If a woman has enough folic
acid in her body before she is pregnant, it can help prevent
major birth defects of her baby?s brain and spine. These
birth defects are neural tube defects or NTDs. Women need
to take folic acid every day, starting before they are
pregnant to help prevent NTDs. CDC and the U.S. Public
Health Service urge every woman who could become
pregnant to get 400 micrograms (400 mcg) of synthetic folic
acid every day.

What is folic acid and what is folate?
Folate is a water-soluble B vitamin that occurs naturally in
food. Folic acid is the synthetic form of folate that is found in
supplements and added to fortified foods [1].

Folate gets its name from the Latin word "folium" for leaf. A
key observation of researcher Lucy Wills nearly 70 years
ago led to the identification of folate as the nutrient needed
to prevent the anemia of pregnancy. Dr. Wills demonstrated
that the anemia could be corrected by a yeast extract. Folate
was identified as the corrective substance in yeast extract in
the late 1930s, and was extracted from spinach leaves in
1941.

Folate helps produce and maintain new cells [2]. This is
especially important during periods of rapid cell division and
growth such as infancy and pregnancy. Folate is needed to
make DNA and RNA, the building blocks of cells. It also helps
prevent changes to DNA that may lead to cancer [3]. Both
adults and children need folate to make normal red blood
cells and prevent anemia [4]. Folate is also essential for the
metabolism of homocysteine, and helps maintain normal
levels of this amino acid.

What are the sources for folate? Which foods provide folate?

Leafy green vegetables (like spinach and turnip greens),
fruits (like citrus fruits and juices), and dried beans and peas
are all natural sources of folate [5].

In 1996, the Food and Drug Administration (FDA) published
regulations requiring the addition of folic acid to enriched
breads, cereals, flours, corn meals, pastas, rice, and other
grain products [6-9]. Since cereals and grains are widely
consumed in the U.S., these products have become a very
important contributor of folic acid to the American diet. A
single serving of many breakfast cereals also has the
amount of folic acid that you need each day. Check the
label! Look for cereals that have 100% daily value (DV) of
folic acid in a serving. The following list suggests a variety of
dietary sources of folate:

Breakfast cereals fortified with 100% of the DV, � cup 400
ug 100% DV
Beef liver, cooked, braised, 3 ounces 185 ug 45% DV
Cowpeas (blackeyes), immature, cooked, boiled, � cup 105
ug 25% DV
Breakfast cereals, fortified with 25% of the DV, � cup 100 ug
25% DV
Spinach, frozen, cooked, boiled, � cup 100 ug 25% DV
Great Northern beans, boiled, � cup 90 ug 20% DV
Asparagus, boiled, 4 spears 85 ug 20% DV
Rice, white, long-grain, parboiled, enriched, cooked, � cup
65 ug 15% DV
Vegetarian baked beans, canned, 1 cup 60 ug 15% DV
Spinach, raw, 1 cup 60 ug 15% DV
Green peas, frozen, boiled, � cup  50 ug 15% DV
Broccoli, chopped, frozen, cooked, � cup 50 ug 15% DV
Egg noodles, cooked, enriched, � cup 50 ug 15% DV
Broccoli, raw, 2 spears (each 5 inches long) 45 ug 10% DV
Avocado, raw, all varieties, sliced, � cup sliced 45 ug 10%
DV
Peanuts, all types, dry roasted, 1 ounce 40 ug 10% DV
Lettuce, Romaine, shredded, � cup 40 ug 10% DV
Wheat germ, crude, 2 Tablespoons 40 ug 10% DV
Tomato Juice, canned, 6 ounces 35 ug 10% DV
Orange juice, chilled, includes concentrate, � cup 35 ug
10% DV
Turnip greens, frozen, cooked, boiled, � cup 30 ug 8% DV
Orange, all commercial varieties, fresh, 1 small 30 ug 8% DV
Bread, white, 1 slice 25 ug 6% DV
Bread, whole wheat, 1 slice 25 ug 6% DV
Egg, whole, raw, fresh, 1 large 25 ug 6% DV
Cantaloupe, raw, � medium 25 ug 6% DV
Papaya, raw, � cup cubes 25 ug 6% DV
Banana, raw, 1 medium 20 ug 6% DV

How much is enough? Look for 100% DV (Daily Value)
One easy way a person can be sure he is getting enough
folic acid is to take a vitamin that has folic acid in it every
day. Folic acid pills and most multivitamins sold in the United
States have 100% of the daily value (DV) of folic acid; check
the label to be sure. Another way to get enough is to eat a
serving of breakfast cereal every day that has been
enriched with 100% of the daily value of folic acid. Not every
cereal has this amount. Check the label on the side of the
box, and look for one that has ?100%? next to folic acid.

When can folate deficiency occur?
A deficiency of folate can occur when an increased need for
folate is not matched by an increased intake, when dietary
folate intake does not meet recommended needs, and when
folate excretion increases. Medications that interfere with the
metabolism of folate may also increase the need for this
vitamin and risk of deficiency [1,15-19].

Medical conditions that increase the need for folate or result
in increased excretion of folate include: pregnancy and
lactation (breastfeeding), alcohol abuse, malabsorption,
kidney dialysis, liver disease and certain anemias.

What medications interfere with folate?
Medications that interfere with folate utilization include: anti-
convulsant medications (such as dilantin, phenytoin and
primidone), metformin (sometimes prescribed to control
blood sugar in type 2 diabetes), sulfasalazine (used to
control inflammation associated with Crohn's disease and
ulcerative colitis), triamterene (a diuretic), methotrexate
(used for cancer and other diseases such as rheumatoid
arthritis) and barbiturates (used as sedatives)

What are the signs and symptoms for low blood folate or
folate deficiency?
Folate deficient women who become pregnant are at greater
risk of giving birth to low birth weight, premature, and/or
infants with neural tube defects. In infants and children,
folate deficiency can slow overall growth rate. In adults, a
particular type of anemia can result from long term folate
deficiency. Other signs of folate deficiency are often subtle.
Digestive disorders such as diarrhea, loss of appetite, and
weight loss can occur, as can weakness, sore tongue,
headaches, heart palpitations, irritability, forgetfulness, and
behavioral disorders [1,20]. An elevated level of
homocysteine in the blood, a risk factor for cardiovascular
disease, also can result from folate deficiency.

Many of these subtle symptoms are general and can also
result from a variety of medical conditions other than folate
deficiency. It is important to have a physician evaluate these
symptoms so that appropriate medical care can be given.
Do women of childbearing age and pregnant women have a
special need for folate?
Folic acid is very important for all women who may become
pregnant. Adequate folate intake during the periconceptual
period, the time just before and just after a woman becomes
pregnant, protects against neural tube defects [21]. Neural
tube defects result in malformations of the spine (spina
bifida), skull, and brain (anencephaly) [10]. The risk of
neural tube defects is significantly reduced when
supplemental folic acid is consumed in addition to a healthful
diet prior to and during the first month following conception
[10,22-23]. Since January 1, 1998, when the folate food
fortification program took effect, data suggest that there has
been a significant reduction in neural tube birth defects [24].
Women who could become pregnant are advised to eat
foods fortified with folic acid or take a folic acid supplement
in addition to eating folate-rich foods to reduce the risk of
some serious birth defects. For this population, researchers
recommend a daily intake of 400 ug of synthetic folic acid
per day from fortified foods and/or dietary supplements [10].

Birth defects happen in the first few weeks of pregnancy,
often before a woman finds out that she is pregnant. All
women should get in the habit of taking folic acid daily even
when they are not planning to get pregnant. For folic acid to
help, a woman needs to take every day, starting before she
becomes pregnant.

The B vitamin folic acid helps prevent birth defects. If a
woman has enough folic acid in her body before and while
she is pregnant, her baby is less likely to have a major birth
defect of the brain or spine.

Most women do not know how important folic acid is for their
bodies and for the health of a baby they might have in the
future. They also do not know that a woman needs to take
folic acid every day, starting before she is pregnant, for it to
work to prevent birth defects.

Birth defects of a baby?s brain or spine happen in the first
few weeks of pregnancy, often before a woman knows that
she is pregnant. That is why it is important for a woman to
get enough folic acid each day, starting before she is
pregnant.
A woman?s body uses folic acid to make healthy new cells
for her baby. Scientists are not sure how folic acid works to
prevent birth defects, but they do know that it is needed for
making the cells that will form a baby?s brain, spine, organs,
skin, and bones.
Every woman needs folic acid for the healthy new cells her
body makes every day . . . even if she is not planning to get
pregnant.

Who else may need extra folic acid to prevent a deficiency?
People who abuse alcohol, those taking medications that
may interfere with the action of folate (including, but not
limited to those listed above), individuals diagnosed with
anemia from folate deficiency, and those with malabsorption,
liver disease, or who are receiving kidney dialysis treatment
may benefit from a folic acid supplement.

Folate deficiency has been observed in alcoholics. A 1997
review of the nutritional status of chronic alcoholics found
low folate status in more than 50% of those surveyed [25].
Alcohol interferes with the absorption of folate and increases
excretion of folate by the kidney. In addition, many people
who abuse alcohol have poor quality diets that do not
provide the recommended intake of folate [17]. Increasing
folate intake through diet, or folic acid intake through fortified
foods or supplements, may be beneficial to the health of
alcoholics.

Anti-convulsant medications such as dilantin increase the
need for folate [26-27]. Anyone taking anti-convulsants and
other medications that interfere with the body's ability to use
folate should consult with a medical doctor about the need to
take a folic acid supplement [28-30].

Anemia is a condition that occurs when there is insufficient
hemoglobin in red blood cells to carry enough oxygen to
cells and tissues. It can result from a wide variety of medical
problems, including folate deficiency. With folate deficiency,
your body may make large red blood cells that do not
contain adequate hemoglobin, the substance in red blood
cells that carries oxygen to your body's cells [4]. Your
physician can determine whether an anemia is associated
with folate deficiency and whether supplemental folic acid is
indicated.

Several medical conditions increase the risk of folic acid
deficiency. Liver disease and kidney dialysis increase
excretion (loss) of folic acid. Malabsorption can prevent your
body from using folate in food. Medical doctors treating
individuals with these disorders will evaluate the need for a
folic acid supplement [1].

What are the health benefits of folate supplements?
Folic Acid and Cardiovascular Disease
Cardiovascular disease involves any disorder of the heart
and blood vessels that make up the cardiovascular system.
Coronary heart disease occurs when blood vessels which
supply the heart become clogged or blocked, increasing the
risk of a heart attack. Vascular damage can also occur to
blood vessels supplying the brain, and can result in a stroke.

Cardiovascular disease is the most common cause of death
in industrialized countries such as the US, and is on the rise
in developing countries. The National Heart, Lung, and
Blood Institute of the National Institutes of Health has
identified many risk factors for cardiovascular disease,
including an elevated LDL-cholesterol level, high blood
pressure, a low HDL-cholesterol level, obesity, and diabetes
[31]. In recent years, researchers have identified another
risk factor for cardiovascular disease, an elevated
homocysteine level. Homocysteine is an amino acid normally
found in blood, but elevated levels have been linked with
coronary heart disease and stroke [32-44]. Elevated
homocysteine levels may impair endothelial vasomotor
function, which determines how easily blood flows through
blood vessels [45]. High levels of homocysteine also may
damage coronary arteries and make it easier for blood
clotting cells called platelets to clump together and form a
clot, which may lead to a heart attack [38].

A deficiency of folate, vitamin B12 or vitamin B6 may
increase blood levels of homocysteine, and folate
supplementation has been shown to decrease homocysteine
levels and to improve endothelial function [46-48]. At least
one study has linked low dietary folate intake with an
increased risk of coronary events [49]. The folic acid
fortification program in the U. S. has decreased the
prevalence of low levels of folate and high levels of
homocysteine in the blood in middle-aged and older adults
[50]. Daily consumption of folic-acid fortified breakfast cereal
and the use of folic acid supplements has been shown to be
an effective strategy for reducing homocysteine
concentrations [51].

Evidence supports a role for supplemental folic acid for
lowering homocysteine levels, however this does not mean
that folic acid supplements will decrease the risk of
cardiovascular disease. Clinical intervention trials are
underway to determine whether supplementation with folic
acid, vitamin B12, and vitamin B6 can lower risk of coronary
heart disease. It is premature to recommend folic acid
supplementation for the prevention of heart disease until
results of ongoing randomized, controlled clinical trials
positively link increased folic acid intake with decreased
homocysteine levels AND decreased risk of cardiovascular
disease.

Folic Acid and Cancer
Some evidence associates low blood levels of folate with a
greater risk of cancer [52]. Folate is involved in the
synthesis, repair, and function of DNA, our genetic map, and
there is some evidence that a deficiency of folate can cause
damage to DNA that may lead to cancer [52]. Several
studies have associated diets low in folate with increased
risk of breast, pancreatic, and colon cancer [53-54]. Over
88,000 women enrolled in the Nurses' Health Study who
were free of cancer in 1980 were followed from 1980 through
1994. Researchers found that women ages 55 to 69 years in
this study who took multivitamins containing folic acid for
more than 15 years had a markedly lower risk of developing
colon cancer [54]. Findings from over 14,000 subjects
followed for 20 years suggest that men who do not consume
alcohol and whose diets provide the recommended intake of
folate are less likely to develop colon cancer [55]. However,
associations between diet and disease do not indicate a
direct cause. Researchers are continuing to investigate
whether enhanced folate intake from foods or folic acid
supplements may reduce the risk of cancer. Until results
from such clinical trials are available, folic acid supplements
should not be recommended to reduce the risk of cancer.

Folic Acid and Methotrexate for Cancer
Folate is important for cells and tissues that rapidly divide
[2]. Cancer cells divide rapidly, and drugs that interfere with
folate metabolism are used to treat cancer. Methotrexate is a
drug often used to treat cancer because it limits the activity
of enzymes that need folate.

Unfortunately, methotrexate can be toxic, producing side
effects such as inflammation in the digestive tract that may
make it difficult to eat normally [56-58]. Leucovorin is a form
of folate that can help "rescue" or reverse the toxic effects of
methotrexate [59]. There are many studies underway to
determine if folic acid supplements can help control the side
effects of methotrexate without decreasing its effectiveness
in chemotherapy [60-61]. It is important for anyone receiving
methotrexate to follow a medical doctor's advice on the use
of folic acid supplements.

Folic Acid and Methotrexate for Non-Cancerous Diseases
Low dose methotrexate is used to treat a wide variety of non-
cancerous diseases such as rheumatoid arthritis, lupus,
psoriasis, asthma, sarcoidoisis, primary biliary cirrhosis, and
inflammatory bowel disease [62]. Low doses of methotrexate
can deplete folate stores and cause side effects that are
similar to folate deficiency. Both high folate diets and
supplemental folic acid may help reduce the toxic side
effects of low dose methotrexate without decreasing its
effectiveness [63-64]. Anyone taking low dose methotrexate
for the health problems listed above should consult with a
physician about the need for a folic acid supplement.

What are the side effects of folic acid supplements?
Beware of the interaction between vitamin B12 and folic acid
Intake of supplemental folic acid should not exceed 1,000
micrograms (μg) per day to prevent folic acid from
triggering symptoms of vitamin B12 deficiency [10]. Folic acid
supplements can correct the anemia associated with vitamin
B12 deficiency. Unfortunately, folic acid will not correct
changes in the nervous system that result from vitamin B12
deficiency. Permanent nerve damage can occur if vitamin
B12 deficiency is not treated.

It is very important for older adults to be aware of the
relationship between folic acid and vitamin B12 because they
are at greater risk of having a vitamin B12 deficiency. If you
are 50 years of age or older, ask your physician to check
your B12 status before you take a supplement that contains
folic acid. If you are taking a supplement containing folic
acid, read the label to make sure it also contains B12 or
speak with a physician about the need for a B12 supplement.

What are the side effects of too much folic acid?
Folate intake from food is not associated with any health
risk. The risk of toxicity from folic acid intake from
supplements and/or fortified foods is also low [65]. It is a
water -soluble vitamin, so any excess intake is usually
excreted in urine. There is some evidence that high levels of
folic acid can provoke seizures in patients taking anti-
convulsant medications [1]. Anyone taking such medications
should consult with a medical doctor before taking a folic
acid supplement.

The Institute of Medicine has established a tolerable upper
intake level (UL) for folate from fortified foods or
supplements (i.e. folic acid) for ages one and above. Intakes
above this level increase the risk of adverse health effects.
In adults, supplemental folic acid should not exceed the UL
to prevent folic acid from triggering symptoms of vitamin B12
deficiency [10]. It is important to recognize that the UL refers
to the amount of synthetic folate (i.e. folic acid) being
consumed per day from fortified foods and/or supplements.
There is no health risk, and no UL, for natural sources of
folate found in food.

QUESTIONS AND ANSWERS
The purpose of these questions and answers is to provide
information to women of childbearing age on the importance
of consuming 400 micrograms of folic acid every day.

Q:  What are neural tube defects (NTDs)?
Neural tube defects (NTDs) are major birth defects of a
baby?s brain or spine. They happen when the neural tube
(that later turns into the brain and spine) doesn?t form right,
and the baby?s brain or spine is damaged. This happens
within the first few weeks a woman is pregnant, often before
a woman knows that she is pregnant. The two most common
neural tube defects are spina bifida (spi-na bif-a-da) and
anencephaly (an-en-sef-a-lee). These birth defects can
cause lifelong disability or death. Many neural tube defects
(up to 70%) can be prevented by sufficient intake of folic
acid. The folic acid supplementation should start before
pregnancy.

Q:  What are spina bifida and anencephaly?
Spina bifida and anencephaly are two common types of
neural tube defects. About 3,000 pregnancies in the United
States are affected by spina bifida or anencephaly each
year. Many of these defects could be prevented if all women
got enough of the B vitamin folic acid every day starting
before they get pregnant.

Spina bifida occurs when the spine and back bones do not
close all the way. When this happens, the spinal cord and
back bones do not form as they should. A sac of fluid comes
through an opening in the baby?s back. Much of the time,
part of the spinal cord is in this sac and it is damaged. Most
children born with spina bifida live full lives, but they often
have lifelong disabilities and need many surgeries.  Children
born with spina bifida don?t all have the same needs. Some
children?s problems are much more severe than others.
Even so, with the right care, most of these children will grow
up to lead full and productive lives.

Anencephaly occurs when the brain and skull bones do not
form right. When this happens, part or all of the brain and
skull bones might be missing. Babies with this defect die
before birth (miscarriage) or shortly after birth.

Q:  Who can have a baby with a neural tube defect in the
United States?
Any woman in the United States can have a baby with a
neural tube defect. If a woman can get pregnant, she is at
risk for having a neural tube defect-affected pregnancy. No
one can predict which women will have a pregnancy affected
by a neural tube defect. All women are at risk.

Some things can increase a woman?s chance of having a
baby with a neural tube defect: 1. Previous neural tube
defect -affected pregnancy. 2. Diabetes when the blood
sugar is out of control. 3. Some medicines (like some of
those that treat epilepsy). 4. Obesity. 5. High temperatures
in early pregnancy, and 6. Hispanic ethnicity.

Q:  What are the costs linked with neural tube defects?
The average cost of caring for a child born with spina bifida
for life is about $636,000.00 per child. This is only an
average cost, and for many families the total cost might be
well above $1,000,000. And it?s not just the money. The
physical and emotional tolls upon the families affected are
high as well. That?s why it?s so important that women take
folic acid every day to help prevent these birth defects.

Q:  Are women getting enough folic acid?
Most women in the United States do not get enough folic
acid to help prevent birth defects. The average woman gets
less than the amount needed from her diet alone. That?s
why all women who can get pregnant are urged to take a
vitamin with folic acid or eat a serving of fully fortified
breakfast cereal each day.

Q:  Can women get too much folic acid?
It?s unlikely that women will be hurt from getting too much
folic acid. We don?t know of an amount that is dangerous.
Yet, for most women, consuming more than 1,000 mcg of
folic acid daily is of no benefit. Unless their doctor advises
them to take more, most women should limit the amount they
take to 1,000 mcg a day.

Q: Why can?t I wait until I?m pregnant?or planning to get
pregnant to start taking folic acid?
Birth defects of the brain and spine happen in the first few
weeks of pregnancy, often before a woman finds out she is
pregnant. By the time she realizes she is pregnant, it might
be too late to prevent those birth defects. Also, half of all
pregnancies in the United States are unplanned. These are
two reasons why it is important for all women who can get
pregnant to be sure to get 400 mcg folic acid every day,
even if they aren?t planning a pregnancy any time soon.

Q: I can?t swallow large pills. How can I take a vitamin with
folic acid?
A woman can get her vitamin with folic acid in one of several
ways. She can take a multivitamin or a small single
supplement of folic acid. These days, multivitamins with folic
acid come in chewable chocolate or fruit flavors, liquids, and
large oval or smaller round pills. A single serving of many
breakfast cereals also has the amount of folic acid that a
woman needs each day. Check the label! Look for cereals
that have 100% daily value of folic acid in a serving.

Q: Vitamins cost too much. How can I get the vitamin with
folic acid that I need?
Many stores offer a single folic acid supplement for just
pennies a day. Another good choice is a store brand
multivitamin, which includes more of the vitamins a woman
needs each day. Unless her doctor suggests a special type,
she does not have to choose among vitamins for women or
active people, or even one to go with a low carbohydrate
diet. A basic multivitamin meets the needs of most women.

Q: How can I remember to take a vitamin with folic acid every
day?
A woman may combine taking her vitamin with another habit.
Taking a vitamin when she brushes her teeth, has her
morning coffee, finishes her shower, or brushes her hair may
make it easier to remember. Seeing the vitamin bottle on the
bathroom or kitchen counter could help her remember it.
She might even take a vitamin when her children take theirs.
That sets a good example!

Q:  Are there other health benefits of taking folic acid?
Folic acid might help to prevent some other birth defects,
such as cleft lip and palate and some heart defects. There
might also be other health benefits of taking folic acid for
both women and men. More research is needed to confirm
these other health benefits.

Content source for the section of question and answer:
National Center on Birth Defects and Developmental
Disabilities. For detailed information and any questions,
please, consult with your doctor.

CONTENT SOURCE FOR OTHER SECTIONS: Dietary
Supplement Fact Sheet: Folate, Office of Dietary
Supplements, January 16, 2006

References 1. Herbert V. Folic Acid. In: Shils M, Olson J,
Shike M, Ross AC, ed. Nutrition in Health and Disease.
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