Bottom Line: Folate is used to prevent certain types of anemia and birth defects. It may reduce the risk of certain cancers.
Folate is a vitamin of the vitamin B complex. The main food sources of folate include fortified breakfast cereals and breads, liver, Brussels sprouts, potatoes, spinach, chickpeas and brewer's yeast. It is also available in supplemental form as folic acid. Folate deficiency can result in the reduction of essential cell division and can lead to anemia. The vitamin has been shown to reduce the risk of neural tube defects and is vital for pregnant women. Higher levels of folate have been shown to reduce the risk for breast cancer, pancreatic cancer and colon cancer.
To treat Alzheimer's disease Studies have linked low folate levels with Alzheimer's disease. Research also shows a possible link between the intake of folate and decreased risk of Alzheimer's.
To prevent cancer Clinical studies have shown that higher levels of folate reduce the risk for breast, pancreatic and colon cancers. Folic acid supplementation does not appear to affect the risk of prostate cancer.
To prevent heart disease Low folic acid levels have been linked to higher homocysteine levels, a risk factor for death caused by diseases of the heart and blood vessels. However, further studies are needed to understand this association.
To treat chronic fatigue syndrome Folic acid was ineffective in treating chronic fatigue syndrome.
To prevent neural tube birth defects Studies have shown a significant decrease in the risk of neural tube (tissue in the embryo that develops into the brain and the spinal cord) defects as a result of increased dietary folate.
Cardiovascular Disease & Stroke A study of 3,680 patients with cerebral infarction (blockage of blood supply to the brain) examined the effect of folic acid, vitamin B6 and vitamin B12 on stroke. Participants were randomly assigned to receive either high or low doses of the studied vitamins once a day for two years. The high-dose group had a greater reduction in total homocysteine, but neither group experienced a decreased risk of stroke, coronary heart disease events or death. A randomized controlled trial of seventy-five subjects with coronary artery disease divided subjects into three groups: placebo, folic acid alone, or folic acid plus vitamins C and E. After four months, subjects who received folic acid supplements were found to have significant increases in plasma folate and improvement in blood flow. However, it is unclear whether these changes reduced cardiovascular events. Five hundred fifty-three subjects were examined in a randomized controlled trial of a homocysteine-lowering therapy regimen containing folic acid. The subjects had all previously undergone angioplasty (a procedure to unblock blood vessels) and were assigned to receive either placebo or a combination of folate, vitamin B12 and vitamin B6 for six months. Subjects in the treatment arm had significantly lower homocysteine levels and few major adverse effects.
Cancer A population-based case-control study observed 1,321 cases of breast cancer and 1,382 control cases to examine the relationship between dietary folate intake and breast cancer risk. High folate intake was found to reduce breast cancer risk, and the reduction was even more pronounced in women who also consumed high levels of methionine, vitamin B12 and vitamin B6. A 20-year study of 14,407 subjects examining the association between folate intake and colon cancer risk found higher folate intake to reduce colon cancer risk in men, especially in non-drinkers. A prospective analysis of 27,101 healthy male smokers between the ages of 50 and 69 found that dietary folate can reduce pancreatic cancer risk. One study of 88,756 women found that long-term (more than 15 years) supplementation of folic acid significantly lowered the risk of colon cancer risk.
Neural-tube defects This study was done to determine the effects of folic acid in reducing neural-tube defects in babies in China. A daily dose of 400 micrograms of folic acid was suggested to women starting from their premarital exam to the end of the first trimester. Researchers report a reduction in risk of neural tube defects in fetuses or infants of women who took the folic acid supplement compared to those who did not take it. This effect was seen both in women from areas with high neural-tube defects and in areas with low rates.
Folate and folic acid are water-soluble vitamins of the vitamin B complex. Folate is naturally available in green leafy vegetables, whereas folic acid is the synthetic supplemental form and has higher bioavailability than folate from food sources (1). Higher levels of dietary folate have been shown to reduce the risk for breast cancer (2), pancreatic cancer (3) and colon cancer (4)(5)(6). However, folic acid supplementation does not seem to affect the risk of prostate cancer (7) or colorectal adenoma in patients with a history colorectal adenoma without carcinoma (8). Furthermore, a combination of folic acid, and vitamins B6 and B12 had no effect on overall of invasive cancer or breast cancer (33). Low levels of folate in the blood are associated with certain forms of cancer (9). Folate has been shown to reduce the risk of neural tube defects (10) and is essential during pregnancy. Data also suggest nearly 50% reduction in risk of medulloblastoma in children of women who took folic acid supplements during pregnancy (11). High folate intake may reduce chromosomal aberrations in sperm of healthy men (12). Folic acid was also effective in decreasing levels of homocysteine, a risk factor for cardiovascular disease mortality (13)(14)(15), and reducing blood pressure in smokers (5)(16). However, studies on the risk of stroke yielded mix results (17)(18)(19)(20). Folic acid supplementation was ineffective in the treatment of chronic fatigue syndrome (21). Due to its antagonistic effects, folic acid can reduce the side effects of methotrexate when used for rheumatoid arthritis (22)(23). However, it may decrease the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia (24) and psoriasis (25). In addition, folic acid supplementation improved cognitive function in older adults (26) and response to cholinesterase inhibitors in patients with putative Alzheimer's disease (27). In individuals chronically exposed to arsenic, folic acid supplementation lowers blood arsenic concentrations by facilitating urinary excretion (28). Certain prescription drugs for epilepsy (29) may lower folate levels. Folic acid has low risk of adverse reactions and supplementation is recommended for many conditions. However, high doses (more than 1 mg /day) can mask the symptoms of Vitamin B12 deficiency. Patients are advised to consult their physicians before using high doses of folic acid.
Folate plays an important role in DNA synthesis due to its involvement in the synthesis of purines, pyrimidines, glycine, and methionine. Deficiency can result in the reduction of cell division and is most easily seen in tissues with high rates of cell turnover (30). Folate may enhance the proliferative capacity of bone marrow (24). Studies show that folic acid supplementation improves endothelial function in patients with coronary atherosclerosis (31) and in smokers (16). The reduction in colon cancer risk for women using folic acid is significant after 15 years of supplementation (32). Both oral and intravenous administration routes have comparable homocysteine-lowering effects (13). Folate bioavailability tends to be higher in supplements and fortified foods than in high-folate foods (1). Dietary folate intake was more strongly associated with lower breast cancer risk in women who also consumed high levels of folate cofactors (methionine, vitamin B12, and vitamin B6) (2).
Patients with pernicious anemia should speak to their physicians first before using folic acid as it may mask the symptoms of megaloblastic anemia (30).
Concurrent use of antibiotics may produce falsely low results for serum and erythrocyte folate. Estrogen-containing compounds including oral contraceptives may reduce blood levels of folate (30).
Su LJ,.Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann.Epidemiol 2001;11:65-72. Data from the NHANES I Epidemiologic Follow-up Study (NHEFS) was studied to ascertain the association between folate intake and colon cancer risk. The NHEFS consists of 14,407 subjects with 20 years of follow-up. Researchers found a significant inverse association between dietary folate intake and colon cancer in men who consumed more than 249 micrograms per day of folate when compared with men who consumed less than 103 micrograms per day of folate. Furthermore, a significant relationship was also seen in non-drinkers. Association between colon cancer and folate intake did not reach statistical significance in women drinkers.
Van Guelpen B, Hultdin J, Johansson I, et al. Low folate levels may protect against colorectal cancer. Gut 2006;55(10):1461-6. This prospective study was conducted to determine the association between folate levels and the risk of developing colorectal cancer. This is the first study to look at the plasma folate levels unlike the earlier ones that examined the benefits of oral folic acid supplementation. The study involved 226 persons with colorectal cancer and 437 matched controls from the Northersn Sweden Health and Disease Cohort. Researchers observed a bell-shaped association between plasma folate levels and the risk of colorectal cancer. Persons in the highest folate quintile were four times as likely to develop colorectal cancer compared to those in the lowest quintile. These results contradict the data available so far, but the low folate status of the subjects may be the reason. Further studies with long-term follow up are needed to confirm the benefits of folic acid supplementation.
Connelly PJ, et al. A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease. Int J Geriatr Psychiatry 2008;23(2):155-160. A pilot randomized, double-blind, placebo-controlled study of 57 participants with Alzheimer's disease sought to determine if folic acid supplementation could improve the patients' response to cholinesterase inhibitors. Consecutive patients were either given placebo or folic acid (1 mg daily) and their Mini-Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL) and Social Behavior (SB) scores as well as homocysteine levels were assessed at baseline and 3 and 6 months after treatment initiation. Although MMSE scores were not affected by folic acid supplementation, IADL and IADL/SB scores were. Further studies of larger population sizes will confirm whether folic acid supplementation is beneficial in the treatment of Alzheimer's disease. Durga J, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369(9557):208-216. In the Folic Acid and Carotid Intima-media Thickness (FACIT) trial, 818 participants (50-70 years of age) with homocysteine concentrations ranging from 13-26 ìmol/L randomly received placebo or folic acid (800 ìg daily) for 3 years during which cognitive function was assessed by 5 separate tests including memory, word fluency, and sensorimotor, complex, and information processing speeds. Participants that received folic acid experienced benefits in memory, speed of information processing, and sensorimotor speed as compared to those receiving placebo, indicating that folic acid supplementation may improve cognitive function in older adults. Further studies are necessary to determine if individuals with low or high homocysteine levels would also benefit in folic acid supplementation.
