Price range: 1-2 containers: $5.95 each.     3-5:  $5.50   6+: $4.95

 

Research indicates that supplementing with folic acid during child-bearing years before pregnancy and during the first two months of pregnancy can significantly reduce the risk of birth defects. 

In addition, folic acid helps the body metabolize homocysteine, a chemical which may cause damage to the cardiovascular system when present in high concentrations in the blood stream. 

Folic acid supplementation can reduce homocysteine levels as well as reduce the risk of neural tube birth defects.

BACKGROUND:

Folic acid is an essential B vitamin.  The National Institutes of Health summarizes folic acid’s uses in the body: “It helps the body digest and utilize proteins and to synthesize new proteins when they are needed; it's essential for the production of red blood cells and the synthesis of DNA; it helps with tissue growth and cell function; it helps to increase appetite when needed; and it stimulates the formation of digestive acids.”

In a study conducted by the National Institutes of Health, supple-mentation with 400 micrograms of folic acid per day reduced the risk of developing a cleft lip by 33%.  Neural tube disorders are another kind of common birth defect.  Disorders of the neural tube in an unborn baby lead to malform-ations of the brain, spinal cord, and other regions.  Spina bifida is one type of neural tube disorder, and studies have shown that folic acid supple-mentation prior to conception can reduce the risk of developing this birth defect by up to 70%.

"We can certainly take away that folate is going to be beneficial for cognitive improvement when you have high homocysteine levels," --Maria Carrillo, director of medical and scientific relations at the Alzheimer's Association.

Folic acid can also reduce homocysteine levels.  High levels of homocysteine have been linked to an increased risk for heart attack, stroke, and even Alzheimer’s disease.   As the body ages, cognitive function declines and can result in dementia.  In a recently published Dutch study, older men who supplemented their diet with 800 micrograms of folic acid per day experienced improved cognitive function.

 

Folic acid is a crucial nutrient for pregnant women and for individuals with high homocysteine levels.  However, it is also an essential vitamin which plays several roles in the body’s normal, healthy functioning.  Therefore, supplementation with folic acid is a benefit to overall good health for all individuals.

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REFERENCES:

Abby SL, Harris IM, Harris KM. Homocysteine and cardiovascular disease. J Am Board Fam Pract 1998;11:391-8.

Aronow WS, Ahn C. Association between plasma homocysteine and peripheral arterial disease in older persons. Coron Artery Dis 1998;9:49-50.

JG, Eskes TK, Steegers-Theunissen RP. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 1999;69:99-104.

den Heijer M, Brouwer IA, Bos GM, Blom HJ, van der Put NM, Spaans AP, Rosendaal FR, Thomas CM, Haak HL, Wijermans PW, Gerrits WB. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol 1998;18:356-61.

Giles WH, Kittner SJ, Anda RF, Croft JB, Casper ML. Serum folate and risk for ischemic stroke. First National Health and Nutrition Examination Survey epidemiologic follow-up study. Stroke 1995;26:1166-70.

Green R, Miller JW. Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status. Semin Hematol 1999;36:47-64.

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National Institutes of Health:

 

“Folic Acid May Prevent Cleft Lip and Palate”

A new study finds that women who take folic acid supplements early in their pregnancy can substantially reduce their baby’s chances of being born with a facial cleft.

Researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, found that 0.4 milligrams (mg) a day of folic acid reduced by one third the baby’s risk of isolated cleft lip (with or without cleft palate). Folic acid is a B vitamin found in leafy vegetables, citrus fruits, beans, and whole grains. It can also be taken as a vitamin supplement, and it is added to flour and other fortified foods. The recommended daily dietary allowance for folate for adults is 400 micrograms or 0.4 mg.

“These findings provide further evidence of the benefits of folic acid for women,” said Allen J. Wilcox, M.D., Ph.D., lead NIEHS author on the new study published online in the British Medical Journal. “We already know that folic acid reduces the risk of neural tube defects, including spina bifida. Our research suggests that folic acid also helps prevent facial clefts, another common birth defect.” In the United States, about one in every 750 babies is born with cleft lip and/or palate.

“Folic acid deficiency causes facial clefts in laboratory animals, so we had a good reason to focus on folic acid in our clefts study,” said Wilcox. “It was one of our main hypotheses.”

The researchers examined the association between facial clefts and mothers’ intake of folic acid supplements, multivitamins, and folates in diet. The researchers found that folic acid supplementation of 400 micrograms or more per day reduced the risk of isolated cleft lip with or without cleft palate by one-third, but had no apparent effect on the risk of cleft palate alone.

“A mother’s nutrition during pregnancy is clearly an environmental factor that can affect the health of her fetus,” said NIEHS Director David A. Schwartz, M.D. The NIEHS researchers are continuing to analyze their data for evidence of other environmental exposures that increase the risk of facial clefts.

This population-based study was conducted in Norway, which has one of the highest rates of facial clefts in Europe and does not allow foods to be fortified with folic acid. The investigators contacted all families of newborn infants with clefts (either cleft lip with or without cleft palate (CLP) or cleft palate only (CPO)) born between 1996 and 2001 in Norway. The study included 377 babies with CLP and 196 with CLO; as well as 763 control babies randomly selected from all live births in Norway.

The researchers mailed two questionnaires to each of the mothers participating in the study. The first questionnaire mailed soon after delivery focused on general health information, including demographics, reproductive history and information about environmental exposures including smoking, alcohol and vitamins; whereas the second questionnaire focused on nutrition and diet during the pregnancy. Mothers who reported taking folic acid supplements and or multivitamins were asked to send in their empty bottles or labels to confirm dosage.

The nutrition questionnaire included questions on mothers’ fruit and vegetable consumption during the first three months of pregnancy.

The researchers estimated that 22 percent of isolated CLP cases in Norway could be averted if all pregnant women took 0.4 mg of folic acid per day.

In addition to funding from NIEHS, this research was supported by the Johan Throne Holst Foundation for Nutrition Research, and the Thematic Perinatal Nutrition at the Medical Facility of University of Oslo, Norway. Researchers at the University of Bergen, the University of Oslo, and the Departments of Plastic Surgery in Oslo and Bergen, Norway, also contributed to this study.

Reference: Wilcox AJ, Lie RT, Solvoll K, Taylor J, McConnaughey DR, Abyholm F, Vindenes H, Vollset SE, Drevon CA. “Folic Acid Supplements and the risk of facial clefts: A National population-based control study.” British Medical Journal, 2007.

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“Folic Acid Boosts Cognition in Older Adults”

(HealthDay News) -- Dutch researchers have added another chapter to the continuing debate over whether folic acid supplements can sharpen the aging mind. Their conclusion: The nutrient does improve cognitive function in older adults.

Previous studies on the subject have been split, although most have suggested that folic acid supplementation in people with high levels of the amino acid homocysteine in the blood helps with cognitive function. Higher homocysteine levels are associated with an increased risk for cardiovascular disease and stroke and possibly also Alzheimer's disease.

The new study, published in the Jan. 20 issue of The Lancet, adds to the growing impression that adding folic acid can help brain functioning, at least in certain groups of people.

"We can certainly take away that folate is going to be beneficial for cognitive improvement when you have high homocysteine levels," said Maria Carrillo, director of medical and scientific relations at the Alzheimer's Association.

"This underscores the importance of B vitamins," added Richard Finnell, Regents Professor in the Center for Environmental and Genetic Medicine at Texas A&M's Health Science Center Institute of Biosciences and Technology at Houston. "They do more than protect babies against birth defects."

Folic acid, or folate, is a B vitamin probably best known for its role in helping to prevent neural-tube defects in newborns.

But folic acid also has several other functions: It helps the body digest and utilize proteins and to synthesize new proteins when they are needed; it's essential for the production of red blood cells and the synthesis of DNA; it helps with tissue growth and cell function; it helps to increase appetite when needed; and it stimulates the formation of digestive acids.

Food sources of folate include beans and legumes; citrus fruits and juices; wheat bran and other whole grains; dark, green leafy vegetables; poultry; pork; shellfish and liver, according to the National Institutes of Health.

Cognitive function, especially areas such as information processing speed and memory, decline with age. These cognitive changes have been linked to a risk of dementia.

For this study, first reported at the Alzheimer's Association's 2005 prevention conference, researchers randomly assigned 818 older adults in Holland, aged 50 to 70 years old, to receive 800 micrograms of folic acid supplementation daily or a placebo for three years.

All participants had low folate levels, as evidenced by elevated homocysteine concentrations.

Adults who received the folic acid supplementation had improved cognitive functioning, especially in the areas of memory and information processing speed. What's more, folate concentration increased 576 percent in those getting the supplements, and homocysteine levels fell 26 percent.

"Folate can help people with high homocysteine levels," Carrillo confirmed. "This is in line with what we have been thinking."

The same Dutch researchers, reporting in the Jan. 2 issue of the Annals of Internal Medicine, found that people who took a folic acid supplement had less decline in hearing low-frequency sounds over time, compared with people who didn't take the supplement.


Overview
Folic Acid is a B vitamin which is found naturally in leafy vegetables, citrus fruits, beans, and whole grains. Folate and folic acid are interchangeable terms; folic acid is the synthetic form of folate.

Scientists are in general agreement that folic acid reduces the risk of neural tube defects, which are serious birth defects, including spina bifida and anencephaly. In 1992, the Food and Drug Administration (FDA) recommended fortifying the nation’s food supply with folic acid, a strategy that has worked well in the past with other beneficial substances including iodine (in salt), vitamin D (in milk), and thiamin (in flour and bread). Folic acid began being added to breads and other grain products in January of 1998.

The neural tube defects that folic acid can prevent, including spina bifida and anencephaly, are among the most serious and frequently occurring birth defects. Spina bifida occurs when the fetus’ spinal column does not close to protect the spinal cord; this closure should happen within the first few weeks of the pregnancy. Spina bifida causes neurological problems and sometimes, varying levels of mental retardation. Anencephaly is a condition in which the baby’s brain does not develop properly and most or all of the brain tissue is absent. Anencephaly results in either stillbirth or death soon after delivery.

Scientists representing many public and private agencies and organizations, including the Food and Drug Administration, the Public Health Service, the Teratology Society, and the Spina Bifida Association of America recommend that women of childbearing age (15–45 years old) take folic acid as a part of their daily diet, not when they become pregnant which is often too late to prevent these birth defects.

A recent report by the National Center for Health Statistics examines the US incidences of spina bifida and anencepahlus over an 11-year period from 1991-2001 and shows significant decreases in the 2001 incidences of these birth defects as compared to the 1997 rates.

What is Folic Acid / Folate
Folic acid is a chemical that is essential to sustain human life and must be provided in adequate amounts through food or other dietary supplements. Folic acid is a B vitamin which scientists agree reduces the risk of neural tube defects, including spina bifida and anencephaly, by up to 70% when taken regularly by women of child bearing age. In order to be effective, folic acid must be taken during the first weeks of pregnancy when these neural tube defects occur.

Folate and folic acid are interchangeable terms. Folic acid is the synthetic form of folate, which is found naturally in some foods, including leafy vegetables, beans (legumes), citrus fruits, and whole grains.

Neural Tube Defects
According to the FDA (FDA February 29, 1996):

Neural tube defects (NTD), including spina bifida and anencephaly, are the most common disabling birth defects.

Approximately 2,500 infants are born each year in the U.S. with an NTD. About half of these cases are thought to be related to inadequate folate intake by the mother. Other NTDs have different causes that are not well understood.

Spina bifida is a condition in which the spinal cord is exposed. A majority of babies born with spina bifida grow to adulthood with varying degrees of disability, ranging to problems with bowel and bladder control, and paralysis. Many may require a series of operations and other treatments.

In anencephaly, infants die shortly after birth because most or all of the brain is absent.
Since NTDs develop very early in pregnancy (18-30 days after conception), often before a woman knows she is pregnant, it is essential that adequate intake of folic acid be maintained throughout the childbearing years.

Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice.

Spina Bifida

The FDA (FDA Consumer, May 1994) has stated:
Spina bifida is a defect of the spinal column. If the vertebrae (bones of the spinal column) surrounding the spinal cord do not close properly during the first 28 days after fertilization, the cord or spinal fluid bulge through, usually in the lower back.

While once all these children died, with proper medical treatment, about 85 to 90 percent of them now live to adulthood, according to the Spina Bifida Association of America. Depending on the severity of the condition, they have varying degrees of paralysis and incontinence.
There are two major forms of the condition. The mild form, spina bifida occulta ("hidden") is only a small gap in the spine, with a dimple in the skin covering it.

There are usually no symptoms. Some Americans have spina bifida occulta and don't even know they have it, according to the National Information Center for Children and Youth with Disabilities.

The more disabling form is spina bifida aperta, which produces an noticeable sac on the infant's back. A small sac, called a meningocele, produces little or no muscle paralysis or incontinence once it is repaired.

But in 90 percent of all spina bifida cases, a portion of the undeveloped spinal cord itself protrudes through the spine and forms a sac protruding on the baby's back. Any portion of the spinal cord outside the vertebrae is undeveloped or damaged, causing paralysis and incontinence. This is called a myelocele (or meningomyelocele), and it is what most people refer to as spina bifida.

The location of the sac determines how severely disabled the child will be. In general, the higher it is on the spinal column, the more paralysis there is.

Doctors must repair the opening of the spine shortly after birth or the child will die. Other major surgeries often follow in the child's first years. About 85 percent of children with spina bifida develop hydrocephalus, an accumulation of cerebrospinal fluid surrounding the brain. This fluid must be drained to the abdomen or bloodstream with a surgically implanted tube.

Some children with spina bifida develop foot and knee deformities caused by an interruption of spinal nerve circuits. Many patients require leg braces, crutches, and other devices to help them walk. They may have learning disabilities, and about 30 percent of children have slight to severe mental retardation, especially if they have chronic hydrocephalus. Chronic bladder infections and kidney problems require lifelong medical attention.

Despite their need for medical attention, children with spina bifida can learn to care for many of their own needs. They often learn to catheterize themselves, for instance, so they can attend regular schools. With proper medical care, a person with spina bifida can live a long and productive life.


Testing for Neural Tube Defects

According to the FDA (FDA Consumer, May 1994):
A number of tests are available to diagnose neural tube defects before a baby is born.
One such test, the maternal serum alpha-fetoprotein (AFP) test, is a blood test for the mother at 16 to 18 weeks into the pregnancy. It was approved by FDA in the early 1980s as a prenatal test for neural tube defects (a second approved use is as an aid for a certain kind of testicular cancer).

The test measures alpha-fetoprotein, a substance produced by the fetus and secreted into the amniotic fluid, eventually entering the mother's blood. As it grows, the baby produces increased amounts of AFP. The level of AFP in mother's blood peaks at about 30 to 32 weeks.
Abnormally high amounts of AFP may indicate a baby has a neural tube defect. But the test is not perfect.

Up to 20 percent of spina bifida cases do not produce high levels of AFP, so the test does not detect them. And when the test does indicate a high level of AFP, a neural tube defect is present only 10 percent of the time. Most commonly, the AFP level is high because the pregnancy is just further along than was thought.

If a woman has an elevated AFP test, her doctor will usually give her a second AFP test, followed by ultrasound. If still no explanation for a high AFP value can be found, the physician may perform amniocentesis. In this test, the doctor takes a sample of the amniotic fluid and measures it for AFP levels. The results of these tests together will identify a high percentage of spina bifida cases.

History

The FDA (FDA Consumer 1996, 1999 update) has stated:
Scientists first suggested a link between neural tube birth defects and diet in the 1950s. The incidence of these conditions has always been higher in low socioeconomic groups in which women may have poorer diets. Also, babies conceived in the winter and early spring are more likely to be born with spina bifida, perhaps because the mother's diet lacks fresh fruits and vegetables--which are good sources of folate--during the early weeks of pregnancy.

In 1991, British researchers found that 72 percent of women who had one pregnancy with a neural tube birth defect had a lower risk of having another child with this birth defect when they took prescription doses of folic acid before and during early pregnancy.

Another study looked at folic acid intake in Hungarian women. The evidence indicated that mothers who had never given birth to babies with neural tube defects and who took a multivitamin and mineral supplement with folic acid had less risk in subsequent pregnancies for having babies with neural tube defects than women given a placebo.

In keeping with the recommendations of PHS and the FDA Food Advisory Committee called to study these issues, the Food and Drug Administration is requiring that folic acid be added to specific flour, breads and other grains. These foods were chosen for fortification with folate because they are staple products for most of the U.S. population, and because they have a long history of being successful vehicles for improving nutrition to reduce the risk of classic nutrient deficiency diseases.

These fortified foods include most enriched breads, flours, corn meals, rice, noodles, macaroni and other grain products.

Food fortification has been introduced effectively in the past. According to the FDA (FDA February 29, 1996), "Addition of iodine to salt was one of the earliest successful fortification programs. Iodine fortification was initiated in the U.S. in 1924 to prevent goiter, cretinism and other symptoms of severe iodine deficiency. In the early 1930s, vitamin D was first added to cow's milk to aid in absorption of calcium and phosphorus, preventing development of rickets".

One concern in fortifying foods with folic acid is that among the elderly, high levels of folic acid can complicate the prompt diagnosis of vitamin B12 deficiency (FDA February 29, 1996). In addition, there may be other adverse effects from high folic acid intakes and therefore, care should be taken to keep total folate consumption under 1 mg per day, except under the supervision of a physician. Along with this fortification, the PHS suggests two other ways to ensure the proper level of folic acid: improved dietary habits and daily use of folic acid supplements by women throughout their childbearing years (FDA February 29, 1996). The FDA rule is designed to keep total folic acid intake under the 1 mg level.


FDA regulation
Studies have shown that folic acid, when consumed daily before pregnancy and during the early months of pregnancy, can prevent up to 70 percent of disabling or fatal birth defects of the brain and spine known as neural tube defects. Therefore, the FDA now requires that Folic Acid be added to specific grain products.

Under the terms of the new FDA rule (FDA February 29, 1996):

Fortification levels will range from 0.43 milligrams to 1.4 mg per pound of product.
Fortification of grain products at these levels will allow the daily intake from all sources to remain below the recommended upper limit of 1 mg per day.

The amount of folic acid that will be consumed through foods fortified at these levels is considered safe for all population (age/gender) groups.

Manufacturers will be allowed to make claims on the labels that the fortified products contain folic acid and that adequate intake of the nutrient may reduce the risk of neural tube defects.
Evidence that these public health actions have been effective is presented in the 1999 National Health and Nutrition Examination Survey which reports a significant increase in serum folic acid concentrations in women of reproductive age as compared with survey values obtained for 1988-1994.


Who should take Folic Acid

According to the March of Dimes (MOD, 2002), folic acid should be taken by all women of reproductive age (from about 15-45 years old), who are capable of becoming pregnant, who are planning pregnancy, or are in early pregnancy.

Richard B. Johnston, Jr., M.D., medical director of the March of Dimes (MOD, 2002) has stated "In order to be effective in preventing birth defects, folic acid must be consumed before conception and during the first four weeks of pregnancy. Since nearly half of all pregnancies in this country are unplanned, all women capable of having a baby should be consuming folic acid every day."

The Teratology Society (Teratology Society 1997) recommends that "1) women in the childbearing age group take a daily vitamin supplement containing 0.4 mg of folic acid; 2) fortification of enriched cereal grain products be carried out to a level that will provide 0.4 mg of folic acid each day to at least 95% of women in the reproductive age group; and 3) research designed to understand the mechanism by which folic acid or metabolically related chemicals reduce the risk of birth defects be strongly encouraged".

Naturally occurring sources of Folic Acid
The March of Dimes Birth Defects Foundation warns women not to rely on these foods for enough folic acid to prevent serious birth defects in their future babies (March of Dimes 1997).

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FOLIC ACID

Written by: Jane Higdon, Ph.D., Linus Pauling Institute, Oregon State University
Reviewed by: Barry Shane, Ph.D., Professor, Department of Nutritional Sciences and Toxicology, University of California, Berkeley
Last updated 04/08/2002 Copyright 2000-2002 Linus Pauling Institute

The terms folic acid and folate are often used interchangeably for this water-soluble B-complex vitamin. Folic acid, the most stable form, occurs rarely in foods or the human body, but is the form most often used in vitamin supplements and fortified foods. Naturally occurring folates exist in many chemical forms. Folates are found in foods as well as in metabolically active forms, in the human body (1). In the following discussion forms found in food or the body will be referred to as "folates", while the form found in supplements or fortified foods will be referred to as "folic acid".

Function

One-carbon metabolism
The only function of folate coenzymes in the body appears to be mediating the transfer of one-carbon units (2). Folate coenzymes act as acceptors and donors of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids (3).

Nucleic acid metabolism
Folate coenzymes play a vital role in DNA metabolism through two different pathways.1) The synthesis of DNA from its precursors is dependent on folate coenzymes. 2) A folate coenzyme is required for the synthesis of methionine, and methionine is required for the synthesis of S-adenosylmethionine (SAM). SAM is a methyl group (one-carbon unit) donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA. Methylation of DNA may be important in cancer prevention (see Disease Prevention).

Amino acid metabolism
Folate coenzymes are required for the metabolism of several important amino acids. The synthesis of methionine from homocysteine requires a folate coenzyme as well as a vitamin B12 dependent enzyme. Thus, folate deficiency can result in decreased synthesis of methionine and a build up of homocysteine. Increased levels of homocysteine may be a risk factor for heart disease, as well as several other chronic diseases (see Disease Prevention).

Nutrient interactions

Vitamin B12 and vitamin B6
The metabolism of homocysteine, an intermediate in the metabolism of sulphur-containing amino acids, provides an example of the interrelationships among nutrients necessary to optimize physiological function and health. Healthy individuals utilize two different pathways to metabolize homocysteine (see diagram). One pathway (methionine synthase) results in the synthesis of methionine from homocysteine, and is dependent on a folate coenzyme and a vitamin B12-dependent enzyme. The other pathway converts homocysteine to another amino acid, cysteine, and requires two vitamin B6-dependent enzymes. Thus, the amount of homocysteine in the blood is regulated by three vitamins: folic acid, vitamin B12, and vitamin B6 (4).

Deficiency

Causes
Folate deficiency occurs in a number of situations. For example, low dietary intake and diminished absorption, as in alcoholism, can result in a decreased supply of folate. Certain conditions like pregnancy or cancer result in increased rates of cell division and metabolism, leading to an increase in the body's demand for folate (5). Several medications may also contribute to deficiency (see Drug interactions).

Symptoms
Individuals in the early stages of folate deficiency may not show obvious symptoms, but blood levels of homocysteine may increase (see Prevention). Rapidly dividing cells are most vulnerable to the effects of folate deficiency. When the folate supply to the rapidly dividing cells of the bone marrow is inadequate, blood cell division becomes abnormal resulting in fewer but larger red blood cells. This type of anemia is called megaloblastic or macrocytic anemia, referring to the large immature red blood cells. Neutrophils, a type of white blood cell, become hypersegmented, a change which can be found by examining a blood sample microscopically.

Because normal red blood cells have a lifetime in the circulation of approximately four months, it can take months for folate deficient individuals to develop the characteristic megaloblastic anemia. Progression of such an anemia leads to a decreased oxygen carrying capacity of the blood and may ultimately result in symptoms of fatigue, weakness, and shortness of breath (1). It is important to point out that megaloblastic anemia resulting from folate deficiency is identical to the megaloblastic anemia resulting from vitamin B12 deficiency, and further clinical testing is required to diagnose the true cause of megaloblastic anemia.

Disease Prevention

Pregnancy complications

NEURAL TUBE DEFECTS
Fetal growth and development is characterized by widespread cell division. Adequate folate is critical because of its roles in DNA and RNA synthesis. Neural tube defects (NTD) result in either anencephaly or spina bifida, which are devastating and sometimes fatal birth defects. The defects occur between the 21st and 27th days after conception, a time when many women do not realize they are pregnant (10). The risk of NTD in the United States prior to fortification of foods with folic acid was estimated to be one per 1000 pregnancies (1). Results of randomized trials have demonstrated 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the periconceptional period (about 1 month before and 1 month after conception). The results of these and other studies prompted the U.S. Public Health Service to recommend that all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent NTD.

The recommendation was made to all women of childbearing age, because adequate folic acid must be available very early in pregnancy, and because many pregnancies in the U.S. are unplanned. Despite the effectiveness of folic acid supplementation, it appears that less than half of women who become pregnant follow the recommendation (11). In order to decrease births affected by NTD, the FDA implemented legislation in 1998 requiring the fortification of all enriched grain products with folic acid (see Sources). The required level of folic acid fortification in the U.S. was estimated to provide 100 mcg of additional folic acid in the average person's diet, though it probably provides more than this, due to overuse of folic acid by food manufacturers (9).

OTHER PREGNANCY COMPLICATIONS

Adequate folate status may also prevent the occurrence of other types of birth defects, including certain heart defects and limb malformations. However, the support for these findings is not as consistent or clear as support for NTD prevention (10). Low levels of dietary folate during pregnancy have also been associated with increased risk of premature delivery and infant low birth weight.

More recently, elevated blood homocysteine levels, considered an indicator of functional folate deficiency, have been associated with increased incidence of miscarriage, as well as pregnancy complications like preeclampsia and placental abruption (12). Thus, it is reasonable to maintain folic acid supplementation throughout pregnancy, even after closure of the neural tube in order to decrease the risk of other problems in pregnancy.

Cardiovascular disease

HOMOCYSTEINE AND CARDIOVASCULAR DISEASE
The results of more than 80 studies indicate that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases (4). An analysis of the observational studies of blood homocysteine and vascular disease indicated that a prolonged decrease in plasma homocysteine level of only 1 micromole/liter resulted in about a 10% risk reduction (13). The mechanism by which homocysteine increases the risk of vascular disease remains the subject of a great deal of research, but may involve adverse effects on clotting, arterial vasodilation, and thickening of arterial walls (14). Although increased homocysteine levels in the blood have been consistently associated with increased risk of cardiovascular diseases, it is not yet clear whether lowering homocysteine levels will reduce cardiovascular disease risk.

Consequently, the American Heart Association recommends screening for elevated total homocysteine levels only in "high risk" individuals, for example those with personal or family history of premature cardiovascular disease, malnutrition or malabsorption syndromes, hypothyroidism, kidney failure, lupus, or individuals taking certain medications (nicotinic acid, theophylline, bile acid-binding resins, methotrexate, and L-dopa). Most research indicates that a plasma homocysteine level of < 10 micromoles/liter is associated with a lower risk of cardiovascular disease and a reasonable treatment goal for individuals at high risk (15).


FOLATE AND HOMOCYSTEINE
Folate-rich diets have been associated with decreased risk of cardiovascular disease. A study that followed 1,980 Finnish men for 10 years found that those who consumed the most dietary folate had only 45% the risk of an acute coronary event when compared with those who consumed the least dietary folate (16). Of the three vitamins that regulate homocysteine levels, folic acid has been shown to have the greatest effect in lowering basal levels of homocysteine in the blood, when there is no coexisting deficiency of vitamin B12 or vitamin B6 (see Nutrient interactions). Increasing folate intake through folate-rich foods or supplements has been found to lower homocysteine levels.

A supplement regimen of 400 mcg of folic acid, 2 mg of vitamin B6, and 6 mcg of vitamin B12 has been advocated by the American Heart Association if an initial trial of a folate-rich diet (see Sources) is not successful in adequately lowering homocysteine levels (15). Although increased folic acid intake has been found to decrease homocysteine levels, it is not presently known whether increasing folic acid intake will result in decreased rates of cardiovascular diseases. However, several randomized placebo-controlled trials are presently being conducted to determine whether homocysteine lowering through folic acid supplementation reduces the incidence of cardiovascular diseases. Since the initiation of fortification of the U.S. food supply with folic acid, blood homocysteine levels in the population have declined (9).

Cancer
Cancer is thought to arise from DNA damage in excess of ongoing DNA repair and/or the inappropriate expression of critical genes. Because of the important roles played by folate in DNA and RNA synthesis and methylation it is possible for folate intake to affect both DNA repair and gene expression. The consumption of at least five servings of fruits and vegetables daily has been consistently associated with a decreased incidence of cancer. Fruits and vegetables are excellent sources of folate, which may play a role in their anti-carcinogenic effect. Observational studies have found diminished folate status to be associated with cancers of the cervix, colon and rectum, lung, esophagus, brain, pancreas, and breast. Intervention trials in humans have been conducted mainly with respect to cervical and colorectal (colon and rectal) cancer. While the results in cervical cancer have been inconsistent (2), randomized intervention trials regarding colorectal cancer have been very promising (17, 18).

Colorectal cancer
The role of folate in preventing colorectal cancer provides an example of the complexity of the interactions between genetics and the nutritional environment. In general, observational studies have found relatively low folate intake and high alcohol intake to be associated with increased incidence of colorectal cancer (1, 19, 20). Alcohol interferes with the absorption and metabolism of folate (5). In a prospective study of more than 45,000 male health professionals, current intake of more than two alcoholic drinks per day doubled the risk of colon cancer. The combination of high alcohol and low folate intake yielded an even greater risk of colon cancer. However, increased alcohol intake in individuals who consumed 650 mcg or more of folate per day was not associated with an increased risk of colon cancer (21). In some studies, individuals who are homozygous for the C677T MTHFR polymorphism (TT) have been found to be at decreased risk for colon cancer when folate intake is adequate. However, when folate intake is low and/or alcohol intake is high individuals with the (T/T) genotype have been found to be at increased risk of colorectal cancer (22, 23).

Breast cancer
A number of prospective studies have found that even moderate alcohol intake is associated with an increased risk of breast cancer in women. Recently, the results of two prospective studies suggested that increased folate intake may reduce the risk of breast cancer in women who regularly consume alcohol (24-26). A very large prospective study of over 88,000 nurses found no relationship between folic acid intake and breast cancer in women who consumed less than one alcoholic drink per day. However, in those women consuming at least one alcoholic drink per day, folic acid intake of at least 600 mcg daily resulted in about half the risk of breast cancer compared with women who consumed less that 300 mcg of folic acid daily (26).

Alzheimer's disease and cognitive impairment
The role of folate in nucleic acid synthesis and methylation reactions is essential for normal brain function. Over the past decade several investigators have described associations between decreased folate levels and cognitive impairment in the elderly (27). A large cross-sectional study of elderly Canadians found that those individuals with low folate levels were more likely to have dementia, be institutionalized, and be depressed. However, these findings could reflect the poorer nutritional status of institutionalized elderly and individuals with dementia. In the same study, low folate levels were associated with an increased likelihood of short-term memory problems in elderly individuals who did not show signs of dementia (28).

In a recent study of 30 elderly nuns, who lived in the same convent, ate the same diet, and had similar lifestyles, researchers found a strong association between decreased blood folate levels and the severity of brain atrophy related to Alzheimer's disease after their deaths (29). Moderately increased homocysteine levels, as well as decreased folate and vitamin B12 levels have also been associated with Alzheimer's disease and vascular dementia. Low serum vitamin B12 (< 150 pmol/L) or folate (< 10 nmol/L) levels were associated with a doubling of the risk of developing Alzheimer's disease in 370 elderly men and women followed over 3 years (30). In a sample of 1,092 men and women without dementia followed for an average for 10 years, those with higher plasma homocysteine levels at baseline had a significantly higher risk of developing Alzheimer's disease and other types of dementia (31). Those with plasma homocysteine levels greater than 14 micoromoles/liter had nearly double the risk of developing Alzheimer's disease.

Sources

Food sources
Green leafy vegetables (foliage) are rich sources of folate and provide the basis for its name. Citrus fruit juices, legumes, and fortified cereals are also excellent sources of folate (1). A number of folate-rich foods are listed in the table below along with their folate content in micrograms (mcg). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database.

Supplements
The principal form of supplementary folate is folic acid. It is available in single ingredient and combination products, such as B-complex vitamins and multivitamins. Doses greater than or equal to 1 mg require a prescription (32).

Safety

Toxicity
No adverse effects have been associated with the consumption of excess folate from foods. Concerns regarding safety are limited to synthetic folic acid intake. Deficiency of vitamin B12, though often undiagnosed, may affect a significant number of people, especially older adults (see Vitamin B12). One symptom of vitamin B12 deficiency is megaloblastic anemia, which is indistinguishable from that associated with folate deficiency (see Deficiency). Large doses of folic acid given to an individual with an undiagnosed vitamin B12 deficiency could correct megaloblastic anemia without correcting the underlying vitamin B12 deficiency, leaving the individual at risk of developing irreversible neurologic damage.

Most cases of this sort of neurologic progression in vitamin B12 deficiency have been seen at doses of folic acid of 5,000 mcg (5 mg) and above. In order to be very sure of preventing irreversible neurological damage in B12 deficient individuals, the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1,000 mcg (1 mg daily). The board also noted that vitamin B12 deficiency is very rare in women in their childbearing years, making the consumption of folic acid at or above 1000 mcg/day unlikely to cause problems (1), although there is limited data on the effects of large doses.

Drug interactions
When taken in very large therapeutic dosages, for example in the treatment of severe arthritis, nosteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen may interfere with the metabolism of folate. Routine low dose use of NSAIDs has not been found to adversely affect folate status. The anticonvulsant, phenytoin, has been shown to inhibit the intestinal absorption of folate, and several studies have associated decreased folate status with long-term use of the anti-convulsants, phenytoin, phenobarbital, and primidone (33). However, few studies controlled for differences in folate intake between anticonvulsant users and nonusers. Taking folic acid at the same time as the cholesterol-lowering agents, cholestyramine and colestipol, may decrease the absorption of folic acid (32). Methotrexate is a folic acid antagonist used to treat a number of diseases, including rheumatoid arthritis and psoriasis. Some of the side effects of methotrexate are similar to those of severe folate deficiency, and increased dietary folate or supplemental folic acid may decrease side effects without reducing the efficacy of methotrexate. A number of other medications have been shown to have antifolate activity, including trimethoprim (an antibiotic), pyrimethanine (an antimalarial), triamterene (a blood pressure medication), and sulfasalazine (a treatment for ulcerative colitis). Early studies of oral contraceptives (birth control pills) containing high doses of estrogen indicated an adverse effect on folate status, which has not been supported by more recent studies on low dose oral contraceptives, in which dietary folate was controlled (1).


Linus Pauling Institute Recommendation
Researchers at the Linus Pauling Institute feel that there exists ample scientific evidence to suggest that adequate folate intake is helpful in lowering the risk of cardiovascular diseases, some forms of cancer, neural tube defects and other poor outcomes of pregnancy, especially in genetically susceptible individuals. The Linus Pauling Institute recommends that adults take a 400 mcg supplement of folic acid daily, in addition to folate and folic acid consumed in the diet. A daily multivitamin-mineral supplement, containing 100 % of the Daily Value (DV) for folic acid will provide 400 mcg of folic acid/day. Even with a larger than average intake of folic acid from fortified foods, it is unlikely that an individual's daily folic acid intake would regularly exceed the tolerable upper intake level of 1,000 mcg/day established by the Food and Nutrition Board (see Safety).

Older adults (65 years and older)
The recommendation for 400 mcg/day of supplemental folic acid as part of a daily multivitamin/multimineral supplement, in addition to a folate-rich diet, is especially relevant for older adults because blood homocysteine levels tend to increase with age (see Disease Prevention.)

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WEBMD:

“Fortify Yourself: Folic Acid Fights Heart Disease”

By Jeanie Lerche Davis, WebMD Medical News        
May 30, 2000 -- In a new study, folic acid-fortified breakfast cereal beat out vitamin supplements and fruits and veggies as the best way to help people with high levels of a dangerous protein in their blood decrease their risk of heart disease.

Having too much of this protein, called homocysteine, is a genetic condition that may be as big a risk factor for heart disease as high cholesterol. Homocysteine has been shown to promote the formation of blockages in the blood vessels that supply the heart. In many studies, folic acid has been shown to lower homocysteine levels in the blood.

These studies have shown that both fortified cereals and folic acid supplements (in tablet form) can work. But nutritionists have long encouraged people to get important nutrients like folic acid from fruits and vegetables.

The new research, published in the American Journal of Clinical Nutrition, provides strong evidence that fortified cereals and supplements are more effective at reducing homocysteine levels, says Jim I. Mann, MD, PhD, a researcher with the Department of Human Nutrition at the University of Otago in Dunedin, New Zealand.

His study of 65 people with high homocysteine levels showed that after 12 weeks, those who ate cereals fortified with folic acid or took folic acid supplements had a significant decrease in homocysteine levels.

All the study participants ate a diet consisting of no more than 30% fat. Some took the supplements; others ate three to four daily servings of the fortified cereal. The third group, who simply ate a diet of foods naturally high in folic acid -- such as spinach, broccoli, potatoes, oranges, and bread -- did not have a significant decrease in homocysteine levels.

The difference, Mann says, is that folic acid appears not to be absorbed into the body as well when consumed in fruits and vegetables. Based on findings from other studies, folic acid may reduce heart disease risk by as much as 30 to 40%, he says.

Some studies have shown that twice as much folic acid from supplements and breakfast cereal is absorbed than from other foods, Godfrey Oakley, MD, visiting professor of epidem-iology at the Rollins School of Public Health at Emory University in Atlanta, tells WebMD.

Most people get about 200 micrograms (mcg) of folic acid in their diets, says Oakley, who was not involved in Mann's study. "If you take a multivitamin supplement or eat a cereal like Total or Product 19 or Smart Start, which are fortified, you get an additional 400 mcg folic acid." The participants in the new study all took in 600 mcg of folic acid a day, whether through food or supplements.

Multivitamins also are a good idea because they contain vitamin B-12, which also has been shown to lower homocysteine levels, Oakley says.

Oakley calls folic acid supplementation "one of the largest public health opportunities of our lifetime.

"Hang onto your seat," he says. "One study estimates that 50,000 fewer Americans would die from heart disease if they took multivitamins. This prevention could all be done by a stroke of a pen from the FDA, if the government would require putting folic acid in bread.

"The real take-home message," he tells WebMD, "is to eat right and to take a multivitamin. If you do that, you'll lower your homocysteine level. And I believe the evidence is strong that this will decrease the risk of heart attack."

 Vital Information:
•          Folic acid can reduce the risk of heart disease because it lowers levels of homocysteine in the blood.
•          A new study shows that folic acid from fortified breakfast cereal or from a supplement pill is the best way to lower homocysteine -- even better than eating foods that are naturally high in folic acid.
•          One expert says that many deaths from heart disease could be prevented if all Americans took a daily multivitamin, or if the FDA required bread to be fortified with folic acid.
 

“Benefits of Folic Acid Keep Growing “
By  Greg Fulton , WebMD Medical News

Dec. 10, 1999 (Atlanta) -- Supplementing the body's natural levels of folic acid could become an effective prevention against some types of coronary disease, according to a study in the December issue of the Journal of the American College of Cardiology.

Proper levels of folic acid have already been linked to the prevention of neural tube disorder birth defects, such as spina bifida. Spina bifida occurs when the fetus's spinal column does not form properly during pregnancy.

The new study is based on folic acid's ability to break down a damaging amino acid called homocysteine that clings to the interior lining of blood vessels. The damage done by homocysteine can heighten the clogging of the vessels, known as atherosclerosis, which is one of several coronary diseases researchers say folic acid could help fight.

"We've known for a short period of time that elevated levels of homocysteine are related to vascular disease," Stephanie Dunlap, DO, medical director of the heart failure and cardiac transplant program at the University of Illinois at Chicago, tells WebMD.

"Homocysteine's effect on the arteries is similar to bad cholesterol, but if you're someone who has vascular disease but a normal cholesterol level, you should ask your doctor to check your homocysteine level and check the folate levels. Folic acid might stop injury to the vessel, which could prevent coronary disease," says Dunlap, who reviewed the study for WebMD.

The study found that homocysteine levels were reduced by 15% after eight weeks of treatment. Seventeen patients received a 10 mg folic acid pill daily, after which the ability of the vessels to adjust for blood flow was significantly improved.

"Our vessels are under stress to get bigger or smaller as needed to adapt for blood flow," says Dunlap.

But the study found that 12 weeks after the treatment ended, the benefits of folic acid supplementation ended also, leading the authors to suggest that long-term supplementation may be necessary.

The study also focused on patients with higher than normal levels of homocysteine, meaning it's unclear whether increased folic acid could benefit people with normal homocysteine levels.
Folic acid levels can be increased through diet or by taking supplements. In 1996, the FDA mandated that grain foods be fortified with folic acid by manufacturers, which included foods such as flour, corn meal, pasta, and rice. Folic acid is also concentrated in orange juice, green leafy vegetables, beans, liver, and other fruits.

This effort was done to lower the rate of birth neural tube defects. The U.S. Public Health Service recommends a daily intake of 400 micrograms of folic acid. The CDC estimates that food fortification has generally increased folic acid intake by 100 micrograms per day, which Dunlap says leaves a lot of room for people to do better on their own.

"I think it's possible to get the right amounts through diet," she says, "if we can go back to eating a better diet. But supplements also work, and there seem to be more reasons over time to increase folate levels."
 
Vital Information:
•          Elevated levels of homocysteine are associated with coronary disease because it damages blood vessel walls.
•          In a group of study subjects, taking folic acid supplements for eight weeks reduced homocysteine levels by 15%, but once supplementation ceased, so did the homocysteine reduction.
•          Folic acid is found in orange juice, leafy green vegetables, beans, liver, and fortified grains.
 © 1999 WebMD Inc. All rights reserved.

“Folic acid against Down's?”
April 22, 2003
There seems to be a link between two disparate birth defects, Down's syndrome and neural tube defects, and that link is folic acid, an international research group reports.

Studies of pregnancy outcomes in Israel and Ukraine find that families with a high incidence of neural tube defects also have an unexpectedly high incidence of Down's syndrome, says a report in the April 19 issue of The Lancet. The research was done by a group led by Howard Cuckle, a professor of reproductive endocrinology at the University of Leeds in England.
Abnormal metabolism of folic acid appears to underlie both defects, the researchers say.
Folic acid occurs naturally in poultry, liver, dark green leafy vegetables, legumes and fortified cereal.

Researchers are confident of their belief
The link between folic acid and neural tube detects is well established; the US Public Health Service recommends that women who are pregnant or might become pregnant take 400 micrograms of folic acid daily to prevent the defect, which affects the brain and spinal cord. But the new study is among the first to suggest a link with Down's syndrome, which causes mental retardation.

The researchers are confident enough of their belief, Cuckle says, to have begun a trial in which pregnant women at high risk of having a baby with Down's syndrome will be given massive doses of folic acid - 5 milligrams a day, more than 10 times the recommended amount.

New study in the pipeline
"We are enrolling about a thousand women in Israel, and within a couple of years we expect to have a handle on it," he says.

The criterion for entry in the study is simply age, since the incidence of Down's syndrome is known to be higher in older women, Cuckle says, and he sees no reason why any pregnant woman should not take the supplement. "As far as we know, it does no harm," he says.

Careful observation led to report
The report originated with an observation by doctors at the Interregional Medico-Genetics Centre in Ukraine of a higher-than-expected incidence of neural tube defects in babies born to women referred to the centre because of a history or diagnosis in the womb of Down's syndrome.

Led by Cuckle, researchers then began examining the number of cases of Down's syndrome in women seen at the Danek Gertner Institute of Human Genetics in Tel Aviv and other centres in the area because of a high risk of neural tube defects.

Overall, the two research centres reported 11 cases of Down's syndrome in the 1 492 families at high risk of neural tube defects, about five times the expected incidence. And there were seven cases of neural tube defects in the 1 847 pregnancies at high risk of Down's syndrome, compared to an expected incidence of 1,37.

Flaw in folic acid metabolism
Laboratory research points to a flaw in folic acid metabolism as a common, underlying mechanism for both conditions, Cuckle says.

Dr Nancy Green, medical director of the March of Dimes Birth Defects Foundation, calls the new study "an interesting but very preliminary finding." The foundation's advice is that all women of childbearing age should take the daily 400-microgram folic acid supplements recommended by the American Public Health Service.

Larger doses for certain women
But there are women who can benefit from much larger doses, she says. Four micrograms a day are recommended for women who have borne a child with a neural tube defect or have a neural tube defect themselves. Such large doses "may be helpful" for women who are obese or have diabetes, Green says.

And the 5-milligram dose being used in the Israeli study appears to do no harm "as far as we can tell, but it hasn't been studied," Green says. "I would add some caution to that." – (HealthScout News)    

 

Folic acid, also known as folate, is a B-vitamin that can be found in some enriched foods and vitamin pills. If women have enough of it in their bodies before pregnancy, this vitamin can decrease the risk for neural tube  defects (NTDs), which are birth defects of the baby's brain (anencephaly) or spine (spina bifida).

For many women, an easy way to be sure you're getting enough folic acid is to take a vitamin with folic acid in it. The U.S. Public Health Service recommends that all women who could possibly become pregnant get 400 micrograms (or 0.4 mg) of folic acid every day. This could prevent up to 70% of some types of serious birth defects. But to do this, women need folic acid before they get pregnant. That's why you should always get enough folic acid every day even if you're not thinking about a baby any time soon. Folic acid has been added to some foods, such as enriched breads, pastas, rice, and cereals.  A few cereals have 100 percent of the folic acid you need.

No one expects an unplanned pregnancy. But they happen -  every day. In fact, about half of all pregnancies are not planned.  That's why you should get enough folic acid every day if there's any chance you could get pregnant.  Because by the time you know you're pregnant, your baby's brain and spine are already formed.

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Folic Acid Now. So your body's ready when you are. . .

What is folic acid?
Folic acid is a water soluble B-vitamin that helps build healthy cells. "Water soluble" means it does not stay in your body for very long, so you need to take it every day to help prevent neural tube defects. During periods of rapid growth, such as pregnancy and fetal development, the body's requirement for this vitamin increases.

There are two different forms of folic acid:

1.         Synthetic form. This form is found in:
o          multivitamins
o          fortified bread and grain products, like breakfast cereals
o          folic acid prescriptions (Women at increased risk for spina bifida need a prescription for folic acid. Please speak with your health care provider.)

2.         Natural form (also called "folate"). This form is available in foods like:
o          leafy green vegetables, such as broccoli and spinach
o          some fruits and juices, like orange juice

Our bodies absorb the synthetic form of folic acid more easily than the natural form.
A diet rich in folate is important, however the average American diet does not supply enough folic acid.

Folic acid recommendation
SBAA advises the 60 million women of childbearing age not to depend on food alone for folic acid. SBAA urges women to follow the 1992 U.S. Public Health Service folic acid recommendations:

•          Women who could become pregnant should take 400 micrograms (mcg) of folic acid through a vitamin. (This amount is also written as 0.4 milligrams (mg).)

•          Women at increased risk for spina bifida should take 4000 micrograms (mcg) of folic acid by prescription for 1 to 3 months before becoming pregnant. (This amount is also written as 4.0 milligrams (mg).)

Many things can affect a baby, including family genes and things women may come in contact with during pregnancy. Taking folic acid cannot guarantee having a healthy baby, but it can help.
Since NTDs occur early in pregnancy, often before a woman knows she is pregnant, it is important to take folic acid every day. Taking folic acid before and during early pregnancy reduces the risk of spina bifida and other neural tube defects.

Recent prevention studies
Randomized control trials and observational studies have shown that if all women who could become pregnant were to take a multivitamin with the B-vitamin folic acid, the risk of neural tube defects could be reduced by up to 75%.

For women at higher risk for spina bifida or other neural tube defects, an increased level of folic acid is recommended by prescription. Research has shown that 4000 micrograms of folic acid reduces the risk of neural tube defects for these women.

Folic acid fortification
In 1998, breads and enriched cereal grain products were fortified with synthetic folic acid by order of the Food and Drug Administration (FDA). All U.S. wheat, rice and corn are fortified at the rate of 140 micrograms per 100 grams of grain, thus providing most people with 100 micrograms of folic acid daily.

The addition of folic acid to all food grains was based on research at the time, which indicated that only about 25 percent of women of childbearing age regularly consume enough folic acid in the form of a vitamin supplement.

SBAA was very active in the movement to urge the FDA to mandate folic acid fortification, knowing its role in reducing the incidence of spina bifida and neural tube defects. In fact, the current fortification levels have reduced the number of cases of spina bifida and anencephaly annually by an estimated 19%. Reference: JAMA 2001;285:2981-2986

“Folic acid prevents breast cancer”
SHANGHAI, CHINA. A team of American and Chinese researchers has discovered that folic acid (folate) is highly effective in preventing breast cancer in both pre- and postmenopausal women. Their investigation involved 1321 women with breast cancer and 1382 healthy controls. The women were between the ages of 25 and 64 years when they enrolled in the Shanghai Breast Cancer Study during 1996-98.

The researchers found a clear correlation between dietary intake of folic acid and the risk of breast cancer. Women with a daily intake of 345 micrograms or higher had a 38 per cent lower risk than did women with an intake of less than 195 micrograms – after adjustment for total vegetable, fruit and animal food intake. The protective effect of folic acid was even more pronounced in women who also had a high dietary intake of vitamin B6, vitamin B12 and methionine. Women with a daily intake equal to or higher than 345 micrograms of folic acid, 8.47 micrograms of vitamin B12, 2 mg of vitamin B6, and 1.9 grams of methionine had a 53 per cent lower risk of breast cancer than did women with daily intakes at or below 195 micrograms of folic acid, 1.32 micrograms of vitamin B12, 1.35 mg of vitamin B6, and 1.27 grams of methionine.

Researchers believe that folic acid exerts its protective effect by preventing errors in DNA replication and by helping to regenerate methionine, a vital component in DNA synthesis. They also point out that both vitamin B12 and vitamin B6 are vital cofactors required for folic acid to "do its job". NOTE: Most multivitamins have levels of folic acid, vitamin B6 and vitamin B12 well above the levels found to be beneficial in the Shanghai study.

Shrubsole, Martha J., et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Research, Vol. 61, October 1, 2001, pp. 7136-41


FOLIC ACID FORTIFICATION

Background:

The U.S. Public Health Service recommended in September 1992 that all women of childbearing age consume 400 micrograms (ug) of folic acid daily to reduce their risk of having a pregnancy affected with spina bifida or other neural tube defects. Folic acid is a B vitamin. For women, this amount of folic acid on a daily basis spina bifida or anencephaly, both of which are neural tube defects (NTDs) in the baby.

PHS suggested several approaches by which this level could be reached:
•          Improved dietary habits
•          Fortification of the U.S. food supply
•          Daily use of folic acid supplements by women throughout their childbearing years.

FDA Action:

In keeping with the recommendations of PHS and the FDA Food Advisory Committee called to study these issues, the Food and Drug Administration is requiring that folic acid be added to specific flour, breads and other grains. These foods were chosen for fortification with folate because they are staple products for most of the U.S. population, and because they have a long history of being successful vehicles for improving nutrition to reduce the risk of classic nutrient deficiency diseases.

These fortified foods include most enriched breads, flours, corn meal, rice, noodles, macaroni and other grain products.

Under the terms of the new rule:
•          Fortification levels will range from 0.43 milligrams to 1.4 mg per pound of product.
•          fortification of grain products at these levels will allow the daily intake from all sources to remain below the recommended upper limit of 1 mg per day.
•          The amount of folic acid that will be consumed through foods fortified at these levels is considered safe for all population (age/gender) groups.
•          Manufacturers will be allowed to make claims on the labels that the fortified products contain folic acid and that adequate intake of the nutrient may reduce the risk of neural tube defects.

FDA also emphasizes that adequate levels of folic acid, in the form of folate, can be obtained by eating natural sources such as:
•          Leafy dark green vegetables
•          Legumes (dried beans and peas)
•          Citrus fruits and juices
•          Most berries

In addition, women can assure adequate intake by taking dietary supplements containing folic acid.

The new rule takes account of the finding in PHS' recommendation that total folate consumption should be kept under 1 mg per day. This is because higher intake may complicate the diagnosis of pernicious anemia, one form of vitamin B12 deficiency, which especially affects older people.

Neural Tube Defects:
Neural tube defects, including spina bifida and anencephaly, are a common birth defect.
•          Approximately 2,500 infants are born each year in the U.S. with an NTD. About half this number are though to be related to inadequate folate intake by the mother. Other NTDs have different causes that are not well understood.
•          Spina bifida is a condition in which the spinal cord is exposed. A majority of babies born with spina bifida grow to adulthood with varying degrees of disability, ranging to problems with bowel and bladder control, and paralysis. Many may require a series of operations and other treatments.
•          In anencephaly, infants die shortly after birth because most or all of the brain is absent.
Since NTDs develop very early in pregnancy (18-30 days after conception), often before a woman knows she is pregnant, it is essential that adequate intake of folic acid be maintained throughout the childbearing years.

Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice.

Pernicious Anemia & Recommended Daily Limit

Because the effects of high intakes of folic acid are not well known, but do include complicating the diagnosis of vitamin B12 deficiency, care should be taken to keep total folate consumption under 1 mg per day, except under the supervision of a physician.

•          About 10 to 20 percent of the elderly are diagnosed as having low vitamin B12 levels.
•          The effects of folic acid at levels between 1 and 5 mg are not well known, but include complication the diagnosis of vitamin B12 deficiency.
•          Among persons with pernicious anemia, one form of vitamin B12 deficiency, adverse effects have been reported with daily intakes of 5 mg folic acid and above.
•          Because FDA has a mandate to set fortification levels that are safe for all population groups, lack of long term data makes it impossible to conclude that continuous intakes of 1 mg or more daily would be safe.

The FDA rule is designed to keep total folic acid intake under the 1 mg level.

History of Food Fortification:
Addition of iodine to salt was one of the earliest successful fortification programs. Iodine fortification was initiated in the U.S. in 1924 to prevent goiter, cretinism and other symptoms of severe iodine deficiency.

In the early 1930s, vitamin D was first added to cow's milk to aid in absorption of calcium and phosphorus, preventing development of rickets.

In 1938, voluntary enrichment of flours and breads was initiated to prevent the development of deficiency diseases in the general population. Enrichments included thiamin for beriberi, niacin for pellagra, riboflavin essential for proper functioning of vitamin B6 and niacin, and iron for iron deficiency anemia. Mandatory requirements were effective in 1943.

There are various other fortification requirements to enhance the quality of food such as vitamin A added to low and nonfat cow's milk and certain other dairy products, and lysine added to certain corn products to enhance protein quality.


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