Function of folic acid? in the body

Genetic material
Folic acid is essential for the synthesis of DNA and RNA, the genetic material of cells. It plays a vital role in the growth and reproduction of all body cells, maintaining the genetic code, regulating cell division and transferring inherited characteristics from one cell to another.

Metabolism
Folic acid is essential for protein metabolism. As part of its role in protein metabolism, folate converts the amino acid known as homocysteine to methionine. High levels of homocysteine have been linked to an increased risk of cardiovascular disease.

Blood
The formation of healthy red and white blood cells requires folic acid.

Brain and nervous system
Folic acid is involved in the production of neurotransmitters such as serotonin and dopamine, which regulate brain functions including mood, sleep and appetite. Folic acid is essential for the development of the brain, spinal cord and skeleton in the fetus.

Absorption and metabolism
Folic acid is absorbed from the small intestine. The amount of folic acid absorbed from food depends on the source but the average is around 50 per cent. Research shows that synthetic forms of folic acid are absorbed better than natural food forms with around 85 per cent of supplemental folic acid being absorbed if it is taken with a small amount of food.

Around 50 per cent of body stores are in the liver. The amount stored may last for about four months before symptoms of deficiency develop.

Deficiency
Folate deficiency is the most common nutritional deficiency in the world. Diets low in vegetables, frequent alcohol and prescription drug use and the sensitivity of folate to light and heat contribute to this widespread deficiency. The elderly, alcoholics, psychiatric patients, people taking certain medications and women taking the contraceptive pill may be at greatest risk of folate deficiency. Prolonged stress, viral infections and chronic liver disease are also risk factors.

When folate intake is inadequate, levels in serum fall, levels in red blood cells also fall, homocysteine concentration rises and finally, changes in the blood cell-producing bone marrow and other rapidly dividing cells occur. Ultimately, folate acid deficiency affects the growth and repair of all the cells and tissues of the body.

Because red blood cells have a lifespan of 120 days, folate levels in the blood can be lowered for many weeks before symptoms of anemia become apparent. Tests which rely on anemia to diagnose folate deficiency may therefore not be appropriate.

As many as 5 to 15 per cent of people may have a particular type of genetic mutation in the DNA which codes for an enzyme involved in homocysteine metabolism. This leads to higher homocysteine concentrations and therefore an increased risk of heart disease; and in women, of having babies with neural tube defects. Such people have higher folate requirements than those who do not have this type of genetic mutation, and may need supplements.

Elderly people
Many elderly people are at risk of folate deficiency. In a study published in 1996, Canadian researchers investigated folate and vitamin B12 intakes and body levels in 28 men and 30 women aged over 65 years. The results showed that 57 per cent of men and 67 per cent of women were at risk of deficiency.

Folate deficiency may cause or worsen the mental difficulties which older people often experience. In a 1996 study, Spanish researchers analyzed the relationship between mental and functional capacities and folate status in a group of 177 elderly people. In this study, almost 50 per cent of the people had folate intakes below recommended values. Those with poor test results had significantly lower folate levels.

Blood
Folic acid deficiency causes macrocytic anemia in which the red blood cells are fewer in number, larger in size and contain less oxygen-carrying hemoglobin than normal cells. The symptoms of anemia are lethargy, apathy, breathlessness, poor body temperature regulation, pallor, forgetfulness, irritability and stomach disorders.

Cardiovascular disease
Many studies have shown that low folic acid levels are linked to an increased risk of atherosclerosis and heart disease. Folic acid may exert its protective effects on the cardiovascular system by reducing the levels of homocysteine in the blood. Homocysteine is a product of protein breakdown which can damage the cells which line the arteries and promote the clumping together of platelets which increases clot formation. Homocysteine levels are influenced by dietary intakes of folate, vitamin B6 and vitamin B12. They also vary according to race, gender, age and certain disease conditions.
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Nervous system
Folic acid deficiency causes mood disorders with symptoms of irritability, forgetfulness and hostility. Low levels may play a role in depression, possibly due to a reduction in neurotransmitter levels.

In a study published in 1996, USDA researchers investigated the relationships between plasma concentrations of homocysteine and vitamins B12 and B6 and folate, and cognitive test scores in 70 men, aged 54 to 81 years old. Lower concentrations of vitamin B12 and folate and higher concentrations of homocysteine were associated with poorer results on the tests.

Folate deficiency may also be linked to depression. Borderline low or deficient folate levels have been detected in as many as 38 per cent of adults diagnosed with depressive disorders. Low folate levels have also been linked to poorer response to the antidepressant drug Prozac. In a study published in 1997, researchers examined the relationships between levels of folate, vitamin B12, and homocysteine in 213 depressed patients taking Prozac. The results showed that people with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to the drug.

Gastrointestinal system
Symptoms of folic acid deficiency also include loss of appetite, inflamed tongue, gastrointestinal problems and diarrhea. Folic acid deficiency can damage the lining of the gut and reduce absorption of other nutrients which can lead to malnutrition.

Neural tube defects
Folic acid deficiency may affect up to a third of all pregnant women and is associated with birth defects. Pregnant women who are folic acid-deficient risk having babies with neural tube defects, such as anencephaly (failure of the brain to develop) and spina bifida (failure of the spinal column to close). The risk of neural tube defects in the US is around one per 1000 pregnancies. The high risk period for folate deficiency-related birth defects is around one month before conception until around one month after. Many women are unaware that they are pregnant during this time so maintaining adequate folic acid levels is vital for any woman who might become pregnant. (See page 104)

Cancer
Folate deficiency may play a role in cancer development, particularly cancers of the cervix, lung and colon. It may be that folate deficiency itself is not carcinogenic but may contribute to an increased risk of cancer as deficiency may affect the repair of DNA and increase chromosome fragility. It may also diminish the ability of the immune system to fight cancer cells and viruses. Deficiency has been shown to affect a gene involved in suppressing tumor formation.
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Sources
The best sources of folate are liver, brewer’s yeast and dark green leafy vegetables such as spinach and kale. Dried beans, green vegetables, oranges, avocados and whole wheat products are also good sources.

Food processing such as boiling and heating can destroy folic acid. It can also be destroyed by being stored unprotected at room temperature for long periods.
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Recommended dietary allowances
In 1989, the government lowered the RDAs from 400 mcg to 200 mcg for men and 180 mcg for women. Increasing awareness of the importance of folic acid in preventing birth defects and cardiovascular disease led in 1998 to the raising of RDAs to 400 mcg. The tolerable upper intake level has been set at 1000 mcg per day.

USA

Men 400 mcg

Women 400 mcg

Pregnancy 600 mcg

Lactation 500 mcg
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The RDA for pregnant women doubles due to the role of folic acid in cell growth in the baby and for increased blood volume and expanding tissues in the mother. Folic acid is the vitamin most closely related to pregnancy outcome.

Supplements
Folic acid is the type of folate usually found in supplements and fortified foods, as it is the most stable. Some supplements contain folinic acid, the most active form of folate.

Pregnant women, the elderly, and those with absorption difficulties are likely to benefit from supplements. Any condition that increases metabolic rate, such as infection and hyperthyroidism; and any condition that increases cell turnover, such as rapid tissue growth or hemolytic anemia, increases folate requirements. Anyone taking medications that increase folate requirements may also benefit from supplements.
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Toxic effects of excess intake
Toxicity is considered rare. Symptoms are gastrointestinal disturbances, sleep problems and possible allergic skin reactions. These effects can occur at doses above 15 mg.

Therapeutic effects of supplements

Pregnancy

In 1992, the US Public Health Service issued a recommendation that all women capable of becoming pregnant should consume 400 mcg of folic acid daily in order to avoid the risk of neural tube defects in their babies. Around 50 per cent of neural tube defects may be preventable by increasing folate intakes. Eating foods naturally high in folic acid, eating fortified foods and taking supplements are good ways of increasing folic acid intake to recommended levels. Adequate consumption of folic acid should begin before and continue during at least the first four weeks after conception when the fetal neural tube is being formed.

Research suggests that in women who have previously had a child with a neural tube defect, folic acid in doses of up to 4 mg daily can reduce the risk of recurrence by about 70 per cent. This is something to be discussed with a doctor as such large amounts of folic acid are only available on prescription.
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Cardiovascular disease
Folic acid supplements may reduce the risk of coronary heart disease by reducing homocysteine levels. In a paper published in the British Medical Journal in 1998, researchers analyzed the results of randomized controlled trials that assessed the effects of folic acid-based supplements on blood homocysteine concentrations. The data included that from 1114 people in 12 trials. They found that 0.5 to 5 mg folic acid daily reduced blood homocysteine concentrations by 25 per cent.
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Cancer
Several studies suggest that folic acid supplements can help to reduce the risk of cancerous changes in several areas such as the cervix, lung and gastrointestinal tract.

Colorectal cancer
In a study published in 1997, researchers at the Cleveland Clinic investigated the links between folate and cancerous changes in 98 patients with ulcerative colitis. Patients taking folic acid supplements had a 30 per cent lower risk of developing cancerous changes in the bowel. The lower the folate levels, the more advanced the degree of cancerous changes in the cells. In a 1997 Italian study, researchers also studied the effects of folate supplements on pre-cancerous cell changes in ulcerative colitis. The results showed that folate reduced these changes. Folic acid may also help to prevent the pre-cancerous changes in lung tissue caused by smoking.

Cervical dysplasia
Folic acid supplementation may protect abnormal cells from becoming cancerous and may reverse cervical dysplasia in some cases. A 1996 study done at the University of Alabama at Birmingham suggests that supplements may be useful in preventing the initial changes but do not appear to affect the progress of established disease. Some researchers have found a higher risk of abnormalities in cervical tissue in women using oral contraceptives and suggest that folic acid supplements are beneficial in preventing cervical dysplasia in these women.

Anemia
Folic acid is used to treat folic acid deficiency anemia and for supplementation in those suffering from sickle cell disease.
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Interactions with other nutrients
Folic acid requires vitamin B12, niacin and vitamin C to be converted to its biologically active form. Vitamin C helps to reduce folic acid excretion. High folic acid intakes may reduce zinc absorption, although the effect is likely to be a subtle one.

Interactions with drugs
NSAIDs such as aspirin, ibuprofen and acetaminophen can increase folate requirements if taken for long periods. Anticonvulsant drugs such as phenytoin and phenobarbital also raise folate requirements which may be of particular concern as these drugs are often taken for long periods. Methotrexate increases requirements and it is recommended that people taking this drug for long periods also take folic acid supplements. Cholestyramine, chloramphenicol, estrogen, colchicine, antacids, antituberculosis drugs, trimethoprim, sulfasalazine, corticosteroid drugs and tobacco can raise folic acid requirements. Chronic alcohol use leads to folic acid deficiency.

Cautions
Large amounts of folic acid can mask anemia caused by vitamin B12 deficiency. Although this is rare, in some cases it may lead to permanent nerve damage. Amounts greater than 400 mcg per day should not be taken by anyone with anemia unless a diagnosis of pernicious anemia is ruled out.

Folic acid can interfere with the effectiveness of anticonvulsant drugs such as phenytoin and can result in an increase in seizure activity if large doses are taken.