Definition: a water-soluble vitamin of the B-complex group.
Alternative Name: Vitamin B9.
Function: Folic acid acts as a coenzyme (with vitamin B-12 and vitamin C) in the breakdown (metabolism) of proteins and in the synthesis of new proteins. It is necessary for the production of red blood cells and the synthesis of DNA (which controls heredity), as well as tissue growth and cell function. It also increases the appetite and stimulates the formation of digestive acids.
Synthetic folic acid supplements may be used in the treatment of disorders associated with folic acid deficiency, and may also be part of the recommended treatment for certain menstrual problems and leg ulcers. Most people in the United States have an adequate dietary intake of folic acid because it is plentiful in the food supply.
Pregnant women often require additional supplementation as prescribed by the health care provider. Adequate folic acid is important to women in their childbearing years because it has been shown to prevent some kinds of birth defects, including neural tube defects. Women in this age group should make an effort to consume foods that are good sources of folic acid. Recent studies published by the Centers for Disease Control (CDC) suggest that women who receive supplements of folic acid BEFORE CONCEPTION may reduce the risk for neural tube defects by 50%. Women who plan to become pregnant may want to discuss taking a multivitamin with their health care provider. Specific recommendations for each vitamin depends on age, gender, and other factors (such as pregnancy).
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. 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: the only function of folate coenzymes in the body appears to be mediating the transfer of one-carbon units. 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. 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.
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.
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. 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.
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. Several medications may also contribute to deficiency.
Symptoms: Individuals in the early stages of folate deficiency may not show obvious symptoms, but blood levels of homocysteine may increase. 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. 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.
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. The risk of NTD in the United States prior to fortification of foods with folic acid was estimated to be one per 1000 pregnancies. 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. 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. 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.
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. 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. 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 diseases (heart disease, stroke, and peripheral vascular diseases): Homocysteine and cardiovascular diseases: The results of more than 80 studies indicate that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases. 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. 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. 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.
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. 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.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. 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.
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, randomized intervention trials regarding colorectal cancer have been very promising.
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. Alcohol interferes with the absorption and metabolism of folate. 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. 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.
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. 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.
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. 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. 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. 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 or folate levels were associated with a doubling of the risk of developing Alzheimer's disease in 370 elderly men and women followed over 3 years. 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. Those with plasma homocysteine levels greater than 14 micoromoles/liter had nearly double the risk of developing Alzheimer's disease.
Folic acid is a B vitamin. It is used in our bodies to make new cells. 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 called neural tube defects or NTDs. Women need to take folic acid every day starting before they are pregnant to help prevent NTDs.
As a woman, you need folic acid every day, whether you're planning to get pregnant or not, for the healthy new cells your body makes daily. Think about your skin, hair, and nails. Theseand other parts of your body make new cells each day. You might think that you can get all the folic acid and other vitamins you need from the food you eat each day. But it is hard to eat a diet that has all the nutrients you need every day. Even with careful planning, you might not get all the vitamins you need from your diet alone. That's why it's important to take a vitamin with folic acid every day.
Today's woman is busy. You know that you should exercise, eat right, and get enough sleep. You might wonder how you can fit another thing into your day. But it only takes a few seconds to take a vitamin to get all the folic acid you need. Make it easy to remember. Try taking a vitamin when you brush your teeth. Or take it with your morning coffee, after your shower, or when you brush your hair. Seeing the vitamin bottle on the bathroom or kitchen counter can help you remember it, too. If you have children, take your vitamin when they take theirs.
Focus on Folic Acid Benefits, by Deborah Condon, 27/09/2004
A new study has confirmed that adding folic acid to food can dramatically reduce the incidence of spina bifida and other birth defects. Around seven babies born in Ireland every month have spina bifida or other neural tube defects (NTDs). Up to 50% of these babies die around the time of their birth and most of the survivors are left severely disabled. However research has shown that folic acid, when taken by expectant mothers, can reduce the risk of a baby being born with an NTD. In fact, even women who are trying to conceive are recommended to take it.
This latest study looked at the situation in the Canadian province of Newfoundland and Labrador, where in 1998, the Canadian government introduced the mandatory fortification of some foods, including flour and pasta, with folic acid. The aim of this move was to ensure that all women of childbearing age increased their intake of the B-group vitamin. The researchers found that following this food fortification, women on average were taking in an additional 70 micrograms of folic acid per day. Furthermore the incidence of NTDs in the province dropped form an average of 4.36 defects per 1,000 births between 1991 and 1997 (prior to fortification), to an average of 0.96 defects per 1,000 births between 1998 and 2001.
According to the researchers, prior to the move, this Canadian province had one of the highest rates of NTDs in Canada and North America. Not surprisingly, the study supports the continuation of this food fortification strategy.
Details of this study are published in BMC Pregnancy and Childbirth. The Department of Health here recommends that every woman in Ireland who is planning to become pregnant should take an extra 400 micrograms of folic acid daily prior to conception and throughout the first 12 weeks of pregnancy.
Related Papers
Vitamins and Minerals