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Folic Acid

Other common name(s): folate, folacin, vitamin B9

Scientific/medical name(s): pteroylglutamic acid

Description

Folic acid, or folate, is a B vitamin found in many beans, grains, fortified breakfast cereals, pasta, and green vegetables. It helps the body build and maintain DNA and is important in helping the body make new cells, especially red blood cells.

Overview

Low levels of folic acid in the blood have been linked with higher rates of colorectal cancer and some other types of cancer, as well as with certain birth defects. It is not clear whether consuming recommended (or higher) amounts of folic acid—from foods or in supplements—can lower cancer risk in some people. These issues are being studied. High doses of folic acid can interfere with the action of some chemotherapy drugs, such as methotrexate.

How is it promoted for use?

Folic acid, or folate, is a B vitamin. It is promoted mainly as part of a healthy diet to reduce the risk of birth defects of the brain and spine (such as underdeveloped brain and spina bifida or "open spine"). Some people believe that it helps reduce the risk of certain types of cancer and heart disease. It may also be promoted for prevention of Alzheimer's disease, high blood pressure, and chronic fatigue syndrome.

What does it involve?

The terms "folate" and "folic acid" are often used interchangeably, although they are slightly different. Folate is a naturally occurring vitamin found in dark leafy green vegetables, citrus fruits, liver, and in smaller amounts in many other foods (broccoli, beans, peas, eggs, etc.). Folic acid is a man-made form of this vitamin that is easier for the body to absorb and use. It is found in fortified grain-based cereals, grains, and breads. Supplements are sold in tablet and powder form in drug stores and health food stores. Most multivitamins and all prenatal vitamins contain folic acid.

In the United States, the current recommended dietary allowance (RDA) of folic acid is 400 micrograms (mcg or µg) per day for teens and adults, 500 micrograms per day for women who are breast-feeding, and 600 micrograms per day for pregnant women.

What is the history behind it?

Folic acid was first identified in the 1930s as a substance that helped prevent anemia (low red blood cell levels) during pregnancy. It is named after the Latin word for leaf (folium), because it was first found in spinach and other green leafy vegetables.

The first studies that looked at the link between folic acid and cancer took place in the 1960s and 1970s. After noting that cells from the cervix in folate-deficient women looked a lot like cells showing early signs of cancer, researchers began to suspect a link between the two. By the 1990s, studies looking at large groups of people found that certain types of cancer, such as cervical and colorectal cancer, were linked to lower blood levels of folic acid.

The importance of folic acid in preventing birth defects of the brain and spine led the Food and Drug Administration (FDA) to require that grain-based foods, cereals, and dietary supplements be enriched with folate starting in 1998. These neural tube defects are a type of birth defect in which the brain, spinal cord, or their protective coverings do not fully develop. These defects occur early in fetal development, often starting before the woman even knows she is pregnant. Spina bifida is one of the more common types of neural tube defects.

What is the evidence?

Evidence of folic acid's ability to reduce certain birth defects in infants when taken by the mother before and during pregnancy is fairly strong, but its effects on other conditions are still under study.

How folic acid might affect cancer risk is not exactly clear. Cells need folic acid to make and repair DNA when they divide to create new cells, and it. Folic acid may be involved in how cells turn certain genes on and off. Scientists believe low levels of folic acid can lead to changes in the chemicals that affect DNA, which may alter how well cells can repair themselves or divide without making mistakes. These changes might in turn lead to cancer.

Some studies that looked at large groups of people have found a link between lower intake of folic acid and higher risk of certain types of cancer. But these studies were done at different times and looked at different groups of people around the world, which can make it harder to compare findings and draw conclusions. The United States has enriched grain products with folate since 1998. This means it is likely that far fewer Americans are now folic acid–deficient than before 1998 (or in other countries that don't enrich foods). Therefore, it is difficult to know how the results from previous studies might apply to people today, as today's baseline folate levels here are likely higher.

Several studies have found that folic acid may be linked to a lower risk of colon cancer. A large study that tracked U.S. nurses from 1980 to 1994 reported that the women who took in more than 400 mcg of folic acid per day were much less likely to get colon cancer than those with a lower intake (less than 200 mcg). An even larger study involving both men and women found a weaker link overall between taking supplements that contained folic acid and a lower risk of death from colon cancer. In that study, taking folic acid was somewhat more strongly linked to lower risk of colon cancer death in people who had 2 or more alcoholic drinks a day. Other studies have reported results like this, but the large EPIC study in Europe reported no significant link between colon or rectal cancer risk and folic acid levels in the blood.

Studies of folic acid and breast cancer have also had mixed results. The large study of nurses mentioned above found that folate intake did not have a significant effect on breast cancer risk overall. But women who had one or more alcoholic drinks a day and took in enough folate had lower breast cancer risk than those who drank and did not take in enough folate.

A 2003 study of more than 66,000 older women showed that women who drank more alcohol were more likely to have breast cancer. But in this study, the drinkers with higher folic acid intakes did not have less breast cancer.

Some studies that looked at large groups of people have found folic acid is linked to lower rates of ovarian cancer in women who have at least one drink a day, but research in this area is not conclusive.

Some research has also suggested that folic acid may be linked to lower risk of cancers of the pancreas, esophagus, and stomach. Further research is needed to clarify these findings.

Whether folic acid works against cancer may also depend on when it is taken. Some researchers think that folic acid may not be helpful, and could even be harmful, in people who already have cancer or pre-cancerous conditions. For example, two randomized, controlled trials found that folic acid supplements had no effect on women who already had pre-cancerous conditions of the cervix. Along those same lines, drugs that block folic acid are routinely used to treat cancer. This seems contradictory, but folic acid is used to make DNA and RNA. These substances are needed by normal cells as well as cancerous cells.

Overall, the evidence that folic acid can help prevent some types of cancer is promising but not conclusive. It is also unclear whether folic acid can help to offset some of the known cancer-boosting effects of alcohol. Further research involving randomized, controlled clinical trials is needed to find out what effect folic acid may have on the risk of cancer.

A study published in 2010 combined the results of 8 large clinical trials of folic acid supplements. The conclusion was that folic acid supplements had no significant effect on the risk heart attacks, strokes, or cancer (considering all types of cancer combined).

At this time, it is hard to say how each single nutrient or combination of nutrients affects a person's risk of cancer. On the other hand, studies of large groups of people have shown that those who eat lots of vegetables and low amounts animal fat, meat, and/or calories have lower risks for some of the most common types of cancer.

Until more is known about this, the American Cancer Society (ACS) recommends eating a variety of healthful foods--with most of them coming from plant sources--rather than relying on supplements. Supplements may help some people, such as pregnant women, women of childbearing age, and people with restricted food intakes. If a supplement is taken, the best choice for most people is a balanced multivitamin/mineral supplement that contains no more than 100% of the "Daily Value" of most nutrients. The ACS also recommends that those who drink alcohol should limit the amounts they consume.

Are there any possible problems or complications?

This product is sold as a dietary supplement in the United States. Unlike companies that produce drugs (which must be tested before being sold), the companies that make supplements are not required to prove to the Food and Drug Administration that their supplements are safe or effective, as long as they don't claim the supplements can prevent, treat, or cure any specific disease.
Some such products may not contain the amount of the herb or substance that is on the label, and some may include other substances (contaminants). Actual amounts per dose may vary between brands or even between different batches of the same brand. In 2007, the FDA wrote new rules to improve the quality of manufacturing for dietary supplements and the proper listing of supplement ingredients. But these rules do not address the safety of the ingredients or their effects on health.
Most such supplements have not been tested to find out if they interact with medicines, foods, or other herbs and supplements. Even though some reports of interactions and harmful effects may be published, full studies of interactions and effects are not often available. Because of these limitations, any information on ill effects and interactions below should be considered incomplete.

Folic acid is considered a safe and necessary dietary nutrient. Because it is a water-soluble vitamin, most excess folic acid is excreted in the urine. However, if taken in extremely large doses, it may cause symptoms such as upset stomach or trouble sleeping.

Folic acid can also mask symptoms of vitamin B12 deficiency by correcting the anemia caused by low vitamin B12 levels. But vitamin B12 deficiency can still cause nervous system damage, which folic acid cannot correct. In fact, high doses of folic acid can worsen the nervous system damage, and continued B12 deficiency can allow the damage to become permanent. Vitamin B12 deficiency is more common in older people. If you are 50 or older, ask your doctor to check your B12 status before you start taking vitamin supplements with folic acid. If you are taking a supplement that contains folic acid, be sure it also contains B12. Or, talk with your doctor about whether you need a B12 supplement along with the folic acid.

High doses of folic acid may also interfere with the actions of the chemotherapy drug methotrexate and other drugs like it. Always tell your doctor and pharmacist about any supplements and herbs you are taking.

Relying on supplements alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.

Additional resources

More information from your American Cancer Society

The following information on complementary and alternative therapies may also be helpful to you. These materials may be found on our Web site (www.cancer.org) or ordered from our toll-free number (1-800-227-2345).

Dietary Supplements: What Is Safe?

Complementary and Alternative Methods and Cancer

Placebo Effect

Learning About New Ways to Treat Cancer

Learning About New Ways to Prevent Cancer

The ACS Operational Statement on Complementary and Alternative Methods of Cancer Management

References

Clarke R. Halsey J, Lewington S, et al. Effects of lowering homocystein levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality. Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med 2010; 170:1622-1631.

Eussen SJ, Vollset SE, Igland J, et al. Plasma folate, related genetic variants, and colorectal cancer risk in EPIC. Cancer Epidemiol Biomarkers Prev. 2010 May;19(5):1328-1340.

Feigelson HS, Jonas CR, Robertson AS, et al. Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cancer. Epidemiol Biomarkers Prev. 2003;12:161-164.

Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998;129:517-524.

Hoffbrand AV. Megaloblastic anemias. In Fauci AS, Braunwald E, Kasper DL, et al (eds) Harrison's Principles of Internal Medicine 17th Ed. New York: McGraw Hill Medical 2008; 643-651.

Jacobs EJ, Connell CJ, Patel AV, et al. Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States). Cancer Causes Control. 2001;12:927-934.

Kushi LH, Byers T, Doyle C, et al; American Cancer Society 2006 Nutrition and Physical Activity Guidelines Advisory Committee. American Cancer Society guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2006;56:254-281.

Larsson SC, Giovannucci E, Wolk A. Dietary folate intake and incidence of ovarian cancer: the Swedish Mammography Cohort. J Natl Cancer Inst. 2004;96:396-402.

Mason JB, Levesque T. Folate: effects on carcinogenesis and the potential for cancer chemoprevention. Oncology (Williston Park). 1996;10:1727-1744.

MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338:131-137.

National Institutes for Health Office of Dietary Supplements. Dietary supplement fact sheet: Folate. Accessed at http://ods.od.nih.gov/factsheets/folate/ on December 21, 2010.

National Women's Health Information Center. Folic acid: Frequently asked questions. Accessed at www.womenshealth.gov/faq/folic-acid.cfm on December 21, 2010.

PDRhealth Web site. Folic acid. Accessed at www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/fol_0110.shtml on June 4, 2008. Content no longer available.

USDA National Nutrient Database for Standard Reference. Accessed at www.nal.usda.gov/fnic/foodcomp/search/ on December 22, 2010.

Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA. 1999;281:1632-1637.

Note: This information may not cover all possible claims, uses, actions, precautions, side effects or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for consultation with your doctor, who is familiar with your medical situation.

Last Medical Review: 03/07/2011
Last Revised: 03/07/2011