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
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.

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

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

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. Baltimore:
Williams & Wilkins, 1999. 2. Kamen B. Folate and antifolate pharmacology. Semin Oncol 1997;24:S18-30-S18-39.  3. Fenech
M, Aitken C, Rinaldi J. Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis
1998;19:1163-71. 4. Zittoun J. Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism. Rev Prat 1993;
43:1358-63. 5. U.S. Department of Agriculture, Agricultural Research Service. 2003. USDA National Nutrient Database for
Standard Reference, Release 16. Nutrient Data Laboratory Home Page. 6. Oakley GP, Jr., Adams MJ, Dickinson CM. More folic
acid for everyone, now. J Nutr 1996;126:751S-755S. 7. Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson
BE, Gluckman RA, Upson BM. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients
with coronary heart disease. N Engl J Med 1998;338:1009-15. 8. Daly S, Mills JL, Molloy AM, Conley M, Lee YJ, Kirke PN, Weir
DG, Scott JM. Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 1997;350:1666-9.
9. Crandall BF, Corson VL, Evans MI, Goldberg JD, Knight G, Salafsky IS. American College of Medical Genetics statement on
folic acid: Fortification and supplementation. Am J Med Genet 1998;78:381. 10. Institute of Medicine. Food and Nutrition Board.
Dietary Reference Intakes: Thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline.
National Academy Press. Washington, DC, 1998. 11. Suitor CW and Bailey LB. Dietary folate equivalents: Interpretation and
application. J Am Diet Assoc 2000;100:88-94. 12. Raiten DJ and Fisher KD. Assessment of folate methodology used in the
Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). J Nutr 1995;125:1371S-98S. 13. Bialostosky
K, Wright JD, Kennedy-Stephenson J, McDowell M, Johnson CL. Dietary intake of macronutrients, micronutrients and other
dietary constituents: United States 1988-94. Vital Heath Stat. 11(245) ed: National Center for Health Statistics, 2002:168. 14.
Lewis CJ, Crane NT, Wilson DB, Yetley EA. Estimated folate intakes: Data updated to reflect food fortification, increased
bioavailability, and dietary supplement use. Am J Clin Nutr 1999;70:198-207. 15. McNulty H. Folate requirements for health in
different population groups. Br J Biomed Sci 1995;52:110-9. 16. Stolzenberg R. Possible folate deficiency with postsurgical
infection. Nutr Clin Pract 1994;9:247-50. 17. Cravo ML, Gloria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, Cardoso
JN, Leitao CN, Mira FC. Hyperhomocysteinemia in chronic alcoholism: Correlation with folate, vitamin B-12, and vitamin B-6
status. Am J Clin Nutr 1996;63:220-4. 18. Pietrzik KF and Thorand B. Folate economy in pregnancy. Nutrition 1997;13:975-7.
19. Kelly GS. Folates: Supplemental forms and therapeutic applications. Altern Med Rev 1998;3:208-20. 20. Haslam N and
Probert CS. An audit of the investigation and treatment of folic acid deficiency. J R Soc Med 1998;91:72-3. 21. Shaw GM,
Schaffer D, Velie EM, Morland K, Harris JA. Periconceptional vitamin use, dietary folate, and the occurrence of neural tube
defects. Epidemiology 1995;6:219-26. 22. Mulinare J, Cordero JF, Erickson JD, Berry RJ. Periconceptional use of multivitamins
and the occurrence of neural tube defects. J Am Med Assoc 1988;260:3141-5. 23. Milunsky A, Jick H, Jick SS, Bruell CL,
MacLaughlin DS, Rothman KJ, Willett W. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of
neural tube defects. J Am Med Assoc 1989;262:2847-52. 24. MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LC. Impact of
folic acid fortification on the US food supply on the occurrence of neural tube defects. J Am Med Assoc 2001;285:2981-6. 25.
Gloria L, Cravo M, Camilo ME, Resende M, Cardoso JN, Oliveira AG, Leitao CN, Mira FC. Nutritional deficiencies in chronic
alcoholics: Relation to dietary intake and alcohol consumption. Am J Gastroenterol 1997;92:485-9. 26. Collins CS, Bailey LB,
Hillier S, Cerda JJ, Wilder BJ. Red blood cell uptake of supplemental folate in patients on anticonvulsant drug therapy. Am J
Clin Nutr 1988;48:1445-50. 27. Young SN and Ghadirian AM. Folic acid and psychopathology. Prog Neuropsychopharmacol
Biol Psychiat 1989;13:841-63. 28. Munoz-Garcia D, Del Ser T, Bermejo F, Portera A. Truncal ataxia in chronic anticonvulsant
treatment. Association with drug-induced folate deficiency. J Neurol Sci 1982;55:305-11. 29. Eller DP, Patterson CA, Webb GW.
Maternal and fetal implications of anticonvulsive therapy during pregnancy. Obstet Gynecol Clin North Am 1997;24:523-34. 30.
Baggott JE, Morgan SL, HaT, Vaughn WH, Hine RJ. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory
drugs. Biochem 1992;282:197-202. 31. Third Report of the National Cholesterol Education Program Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Cholesterol Education
Program, National Heart, Lung, and Blood Institute, National Institutes of Health, September 2002. NIH Publication No. 02-
5215. 32. Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, O'Leary DH, Wolf PA, Scaefer EJ,
Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J
Med 1995;332:286-91. 33. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ.
Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. J Am Med Assoc
1998;279:359-64. 34. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med
1998;49:31-62. 35. Boers GH. Hyperhomocysteinaemia: A newly recognized risk factor for vascular disease. Neth J Med 1994;
45:34-41. 36. Selhub J, Jacque PF, Wilson PF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of
homocysteinemia in an elderly population. J Am Med Assoc 1993;270:2693-98. 37. Mayer EL, Jacobsen DW, Robinson K.
Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27. 38. Malinow MR. Plasma homocyst(e)ine and
arterial occlusive diseases: A mini-review. Clin Chem 1995;41:173-6. 39. Flynn MA, Herbert V, Nolph GB, Krause G.
Atherogenesis and the homocysteine-folate-cobalamin triad: Do we need standardized analyses? J Am Coll Nutr 1997;16:258-
67. 40. Fortin LJ and Genest J, Jr. Measurement of homocyst(e)ine in the prediction of arteriosclerosis. Clin Biochem 1995;28:
155-62. 41. Siri PW, Verhoef P, Kok FJ. Vitamins B6, B12, and folate: Association with plasma total homocysteine and risk of
coronary atherosclerosis. J Am Coll Nutr 1998;17:435-41. 42. Eskes TK. Open or closed? A world of difference: A history of
homocysteine research. Nutr Rev 1998;56:236-44. 43. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R,
Vermaak WJ. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 1996;98:177-84.  44.
Bostom AG, Rosenberg IH, Silbershatz H, Jacques PF, Selhub J, D?Agostino RB, Wilson PW, Wolf PA. Nonfasting plasma total
homocysteine levels and stroke incidence in elderly persons: the framingham study. Ann Intern Med 1999; 352-5. 45. Stanger
O, Semmelrock HJ, Wonisch W, Bos U, Pabst E, Wascher TC. Effects of folate treatment and homocysteine lowering on
resistance vessel reactivity in atherosclerotic subjects. J Pharmacol Exp Ther 2002: 303:158-62. 46. Doshi SN, McDowell IF,
Moat SJ, Payne N, Durrant HJ, Lewis MJ, Goodfellos J. Folic acid improves endothelial function in coronary artery disease via
mechanisms largely independent of homocysteine. Circulation. 2002;105:22-6. 47. Doshi SN, McDowell IFW, Moat SJ, Lang D,
Newcombe RG, Kredean MB, Lewis MJ, Goodfellow J. Folate improves endothelial function in coronary artery disease.
Arterioscler Thromb Vasc Biol 2001;21:1196-1202. 48. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, McPartlin J,
Scott J. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161:695-700.
Homocysteine 49. Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT. Low dietary folate intake is associated with
an excess incidence of acute coronary events: The kuopio ischemic heart disease risk factor study. Circulation 2001;103:2674-
80. 50. Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements. Meta-analysis of
randomized trials. Br. Med. J 1998;316:894-8. 51. Schnyder, G., Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG,
Hess OM., Decreased rate of coronary restenosis after lowering of plasma homocystein levels. N Eng J Med 2001;345:1593-
60. 52. Jennings E. Folic acid as a cancer preventing agent. Med Hypothesis 1995;45:297-303. 53. Freudenheim JL, Grahm S,
Marshall JR, Haughey BP, Cholewinski S, Wilkinson G. Folate intake and carcinogenesis of the colon and rectum. Int J
Epidemiol 1991;20:368-74. 54. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett
WC. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24. 55. Su
LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann
Epidemiol 2001;11:65-72. 56. Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS. Effect of glutamine on methotrexate
efficacy and toxicity. Ann Surg 1998;227:772-8. 57. Wolff JE, Hauch H, Kuhl J, Egeler RM, Jurgens H. Dexamethasone
increases hepatotoxicity of MTX in children with brain tumors. Anticancer Res 1998;18:2895-9. 58. Kepka L, De Lassence A,
Ribrag V, Gachot B, Blot F, Theodore C, Bonnay M, Korenbaum C, Nitenberg G. Successful rescue in a patient with high dose
methotrexate-induced nephrotoxicity and acute renal failure. Leuk Lymphoma 1998;29:205-9. 59. Branda RF, Nigels E,
Lafayette AR, Hacker M. Nutritional folate status influences the efficacy and toxicity of chemotherapy in rats. Blood 1998;92:2471-
6. 60. Shiroky JB. The use of folates concomitantly with low-dose pulse methotrexate. Rheum Dis Clin North Am 1997;23:969-
80. 61. Keshava C, Keshava N, Whong WZ, Nath J, Ong TM. Inhibition of methotrexate-induced chromosomal damage by folinic
acid in V79 cells. Mutat Res 1998;397:221-8. 62. Morgan SL and Baggott JE. Folate antagonists in nonneoplastic disease:
Proposed mechanisms of efficacy and toxicity. In: Bailey LB, ed. Folate in Health and Disease. New York: Marcel Dekker, 1995:
405-33. 63. Morgan SL BJ, Alarcon GS. Methotrexate in rheumatoid arthritis. Folate supplementation should always be given.
Bio Drugs 1997;8:164-75. 64. Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood
folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: Implications
for cardiovascular disease prevention. J Rheumatol 1998;25:441-6. 65. Hathcock JN. Vitamins and minerals: Efficacy and
safety. Am J Clin Nutr 1997;66:427-37. 66. Dietary Guidelines Advisory Committee, Agricultural Research Service, United
States Department of Agriculture (USDA). HG Bulletin No. 232, 2000. 67. Center for Nutrition Policy and Promotion, United
Stated Department of Agriculture. Food Guide Pyramid, 1992 (slightly revised 1996).

Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate.
However, this information is not intended to replace a medical advice. Consult your doctor for any questions.         
Folate Benefits and Sources