Folic acid is a vitamin, also called flocain, folate, and vitamin B₉, that is a member of the vitamin B complex. A yellow crystalline derivative of glutamic acid, folic acid helps produce and maintain new cells. This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folic acid also plays a crucial role in the activities of various enzymes involved in the manufacture of nucleic acids (notably DNA and RNA) and helps prevent changes to DNA that may lead to cancer. Both adults and children need folic acid to make erythrocytes (red blood cells) and thus prevent anemia. Folic acid is also essential for the metabolism of homocysteine, and helps maintain normal levels of this amino acid.

 

Sources of folic acid

Foods that are especially rich in folic acid include green leafy vegetables (such as spinach), mushrooms, liver, nuts, dried beans, peas, egg yolk, and wholemeal bread. A varied that incorporates fresh vegetables and fruit generally provides enough folic acid for the body's needs. If you don't get enough folic acid from the foods you eat, you can also take it as a dietary supplement.

 

Folic acid deficiency

A deficiency of folic acid can occur when an increased need for folic acid is not matched by an increased intake, when dietary folic acid intake does not meet recommended needs, and when folic acid excretion increases. Medications that interfere with the metabolism of folic acid may also increase the need for this vitamin and risk of deficiency.

Medical conditions that increase the need for folic acid or result in increased excretion of folic acid include:

 

· pregnancy and lactation (breastfeeding)
· alcohol abuse
· malabsorption
· kidney dialysis
· liver disease
· certain anemias

 

Medications that interfere with folic acid 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)
· barbiturates (used as sedatives)

 

Signs and symptoms of folic acid deficiency

· Folic acid 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, folic acid deficiency can slow overall growth rate.
· In adults, a particular type of anemia can result from long term folic acid deficiency. · Other signs of folic acid 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. An elevated level of homocysteine in the blood, a risk factor for cardiovascular disease, also can result from folic acid deficiency.

 

Many of these subtle symptoms are general and can also result from a variety of medical conditions other than folic acid deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

 

Folic acid during pregnancy

Folic acid is very important for all women who may become pregnant. Adequate folic acid intake during the periconceptual period, the time just before and just after a woman becomes pregnant, protects against neural tube defects. Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthy diet prior to and during the first month following conception. Since January 1, 1998, when the folate food fortification program in the U.S. took effect, data suggest that there has been a significant reduction in neural tube birth defects. Women who could become pregnant are advised to eat foods fortified with folic acid or take a folic acid supplement in addition to eating folic acid-rich foods to reduce the risk of some serious birth defects. For this population, researchers recommend a daily intake of 400 μg of synthetic folic acid per day from fortified foods and/or dietary supplements.

 

Who else may need extra folic acid?

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

 

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

 

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

 

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 folic acid deficiency. With folic acid 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 cell. Your physician can determine whether an anemia is associated with folic acid 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 folic acid in food. Medical doctors treating individuals with these disorders will evaluate the need for a folic acid supplement.

 

Issues and controversies about folic acid

 

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. 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. Elevated homocysteine levels may impair endothelial vasomotor function, which determines how easily blood flows through blood vessels. 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.

 

A deficiency of folic acid, vitamin B₁₂, or vitamin B₆ may increase blood levels of homocysteine, and folic acid supplementation has been shown to decrease homocysteine levels and to improve endothelial function. At least one study has linked low dietary folic acid intake with an increased risk of coronary events. The folic acid fortification program in the U.S. has decreased the prevalence of low levels of folic acid and high levels of homocysteine in the blood in middle-aged and older adults. 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.

 

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 folic acid with a greater risk of cancer. Folic acid is involved in the synthesis, repair, and function of DNA, our genetic map, and there is some evidence that a deficiency of folic acid can cause damage to DNA that may lead to cancer. Several studies have associated diets low in folic acid with increased risk of breast, pancreatic, and colon cancer. 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. 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 folic acid are less likely to develop colon cancer. However, associations between diet and disease do not indicate a direct cause. Researchers are continuing to investigate whether enhanced folic acid intake from foods or 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

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

 

Unfortunately, methotrexate can be toxic, producing side effects such as inflammation in the digestive tract that may make it difficult to eat normally. Leucovorin is a form of folic acid that can help "rescue" or reverse the toxic effects of methotrexate. 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. 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, sarcoidosis, primary biliary cirrhosis, and inflammatory bowel disease. Low doses of methotrexate can deplete folic acid stores and cause side effects that are similar to folic acid deficiency. Both high folic acid diets and supplemental folic acid may help reduce the toxic side effects of low dose methotrexate without decreasing its effectiveness. Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement.

 

Caution about folic acid supplements

Beware of the interaction between vitamin B12 and folic acid Intake of supplemental folic acid should not exceed 1,000 micrograms (1 mg) per day to prevent folic acid from triggering symptoms of vitamin B12 deficiency. 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.

 

Health risks

Folic acid 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. 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. Anyone taking such medications should consult with a medical doctor before taking a folic acid supplement.