Folate 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 rolls 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.

Folate deficiencyElderly 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.


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.

Evidence from the Framingham Heart Study, an ongoing analysis of the risk factors for heart disease which began almost 50 years ago and involves over 1000 men and women, supports the links between folate, homocysteine and heart disease. During the study, researchers examined the relationship between intake of folate from foods and supplements with blood plasma folate and homocysteine concentrations among 885 elderly people. The results showed that plasma folate was significantly greater and homocysteine lower in women than in men. Users of supplements, breakfast cereals, or green leafy vegetables had significantly greater plasma folate and lower homocysteine levels than non- users. Plasma folate concentration was also greater in those who drank orange juice.

In a study published in 1998, researchers at the Cleveland Clinic conducted a study to investigate the relationships between homocysteine, B vitamins, and vascular diseases. The study involved 750 patients with documented vascular disease and 800 control patients matched for age and sex. The results showed that those in the top 20 per cent for homocysteine concentrations had a greater risk of vascular disease. Those in the lowest 10 per cent of folate intakes also had an increased risk of disease.

A 1996 Canadian study of the relationship between fatal coronary heart disease and folic acid levels in 5000 men and women found that the risk of coronary heart disease increased as folic acid levels decreased. Those in the lowest intake group were 69 per cent more likely to die of heart disease than those with the highest intakes.

Low blood folic acid levels also seem to increase heart attack risk in young women. In a 1997 study, researchers at the University of Washington measured the homocysteine, folic acid and vitamin B12 levels in 79 heart attack survivors under 45 and compared these with levels in 386 healthy control subjects. Those with the highest homocysteine levels had 2.3 times the risk of heart attack compared to those with the lowest levels. Those with the highest levels of folic acid had around half the risk of heart attack compared with those with the lowest levels.

Results from the US Physicians Health Study published in 1996 found a mall link between low folate levels and risk of heart attack, but this was not statistically significant.

Folate deficiencyNervous 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.


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.

Colorectal cancer

In a study published in 1996, researchers examined the relationship between folate status and colorectal cancer in male smokers aged 50 to 69 involved in the Alpha-Tocopherol Beta carotene (ATBC) Study. The researchers measured folate levels in 144 cases of colorectal cancer and 276 healthy people. Those with higher dietary folate intakes had a reduced risk of colon cancer. Men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet.

Cervical dysplasia

Low blood levels of folic acid may increase the risk of cervical dysplasia (precancerous changes in the cells lining the cervix), possibly by enhancing the effect of other risk factors. Researchers from the University of Alabama in Birmingham investigated the links between folate deficiency and cervical dysplasia in 294 young women with the disorder and 170 healthy women. They also assessed the impact of factors such as smoking, oral contraceptive use, human papillomavirus (HPV) infection, and number of sexual partners. The results showed that at low folate levels the risk of dysplasia caused by HPV infection was increased.

Other symptoms

Low folic acid may also contribute to rheumatoid arthritis and osteoporosis, constipation, cataracts, headaches and infertility.

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Folate health
Folate absorption
Folate deficiency
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Folate recommended daily
Folate overdose
Folate supplements
Folate pregnancy
Folate interactions



Other Vitamins:

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Beta carotene
Vitamin B6
Vitamin B12
Pantothenic acid
Vitamin C
Vitamin D
Vitamin E
Vitamin K