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Vitamin B9 (Folic acid)

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Overview
Dietary Sources
Available Forms
How to Take It
Precautions
Possible Interactions
Supporting Research

Overview

Vitamin B9, also called folate or folic acid, is one of 8 B vitamins. All B vitamins help the body convert food (carbohydrates) into fuel (glucose), which is used to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body use fats and protein. B complex vitamins are needed for a healthy liver, and healthy skin, hair, and eyes. They also help the nervous system function properly. Folic acid is the synthetic form of B9, found in supplements and fortified foods, while folate occurs naturally in foods.

All the B vitamins are water-soluble, meaning that the body does not store them.

Folic acid is crucial for proper brain function and plays an important role in mental and emotional health. It aids in the production of DNA and RNA, the body's genetic material, and is especially important when cells and tissues are growing rapidly, such as in infancy, adolescence, and pregnancy. Folic acid also works closely with vitamin B12 to help make red blood cells and help iron work properly in the body.

Vitamin B9 works with vitamins B6 and B12 and other nutrients to control blood levels of the amino acid homocysteine. High levels of homocysteine are associated with heart disease. However, researchers aren't sure whether homocysteine is a cause of heart disease or just a marker that indicates someone may have heart disease.

It's fairly common to have low levels of folic acid. Alcoholism, inflammatory bowel disease (IBD), and celiac disease can cause folic acid deficiency. Also, certain medications may lower levels of folic acid in the body. Folic acid deficiency can cause:

  • Poor growth
  • Tongue inflammation
  • Gingivitis
  • Loss of appetite
  • Shortness of breath
  • Diarrhea
  • Irritability
  • Forgetfulness
  • Mental sluggishness

Pregnant women need more folic acid to lower the risk of neural tube birth defects, including cleft palate, spina bifida, and brain damage. Neural tube defects are birth defects caused by abnormal development of the neural tube, a structure that eventually gives rise to the brain and spinal cord. Since folic acid has been added to many grain foods in the U.S., such as bread and cereal, neural tube defects have decreased dramatically.

Birth defects

As mentioned, pregnant women who don't get enough folic acid are more likely to have children with birth defects. Pregnant women should get 600 mcg of folic acid per day. Women who plan to become pregnant should make sure to get the recommended 400 mcg per day since many neural tube defects can happen shortly after conception and before a woman even knows she is pregnant. Prenatal vitamins contain the needed amount of folic acid for pregnant women.

Studies show that women who take folic acid supplements before conception and during the first trimester may reduce their risk of having children with neural tube defects by 72 to 100%. Other studies suggest that in the setting of folic acid fortification of grains, folic acid supplementation does not appear to offer further benefit for preventing spina bifida.

Folic acid may also help prevent miscarriage, although the evidence isn't clear.

Child development studies show that taking prenatal folic acid supplements at the time of conception is associated with a lower risk of autism. Other studies show that taking folic acid supplements in early pregnancy was associated with a reduced risk of severe language delay in children at age 3 years. And some research suggests that low folate levels during pregnancy is associated with a higher risk of emotional problems in the offspring.

Heart disease

Folate may help protect the heart through several methods. First, there is some evidence that getting enough folic acid in your diet can reduce your risk of heart disease, although this evidence is based on population studies and not more definitive clinical trials. There is not yet any evidence that taking folic acid supplements would help.

Also, many studies suggest that people with high levels of the amino acid homocysteine are roughly 1.7 times more likely to develop coronary artery disease and 2.5 times more likely to have a stroke than those with normal levels. B complex vitamins -- especially vitamins B9, B6, and B12 -- help lower homocysteine levels. However, there's no evidence that high homocysteine levels actually cause heart disease.

Most people who are concerned about heart disease should focus on getting enough B vitamins from healthy foods. In some cases, however, your doctor may recommend taking B vitamins to lower homocysteine levels. If you are worried about heart disease, ask your doctor whether taking a B vitamin supplement is right for you.

Age-related hearing loss

One study suggests that folic acid supplements help slow the progression of age-related hearing loss in elderly people with high homocysteine levels and low folate in their diet. It isn't known whether healthy seniors would benefit.

Age-related macular degeneration (AMD)

One large study found that women who took 2,500 mcg of folic acid along with 500 mg of vitamin B6 and 1,000 mcg of cyanocobalamin (vitamin B12) daily reduced their risk of developing AMD, an eye disease that can cause loss of vision.

Depression

The evidence about whether folic acid can help relieve depression is mixed. Some studies show that 15 to 38% of people with depression have low folate levels in their bodies, and those with very low levels tend to be the most depressed. One study found that people who did not get better when taking antidepressants had low levels of folic acid. A double-blind, placebo-controlled study found that taking 500 mcg of folic acid daily helped the antidepressant Prozac work better in women, but possibly not men. Another study found that taking folic acid and vitamin B12 was no better than placebo in relieving depression in older people.

Cancer

Folic acid in the diet seems to protect against the development of some forms of cancer, including:

  • Cancer of the colon
  • Breast cancer
  • Cervical cancer
  • Pancreatic cancer
  • Stomach cancer

However, this evidence is based on population studies that show people who get enough folate in their diet have lower rates of these cancers. Researchers don't know exactly how folate might help prevent cancer. Some think that folic acid keeps DNA healthy and prevents mutations that can lead to cancer. There is no evidence that taking folic acid supplements helps prevent cancer. The best course of action is to make sure you eat a balanced diet with enough folate, which will help protect you against a number of diseases.

Low dietary intake of folate may increase the risk of developing breast cancer, particularly for women who drink alcohol. Regular use of alcohol -- more than 1½ to 2 glasses per day -- is associated with higher risk of breast cancer. One large study, involving over 50,000 women followed over time, suggests that adequate intake of folate may reduce the risk of breast cancer associated with alcohol.

Dietary Sources

Rich sources of folate include:

  • Spinach
  • Dark leafy greens
  • Asparagus
  • Turnips
  • Beets
  • Mustard greens
  • Brussels sprouts
  • Lima beans
  • Soybeans
  • Beef liver
  • Brewer's yeast
  • Root vegetables
  • Whole grains
  • Wheat germ
  • Bulgur wheat
  • Kidney beans
  • White beans
  • Lima beans
  • Mung beans
  • Salmon
  • Orange juice
  • Avocado
  • Milk

In addition, all grain and cereal products in the U.S. are fortified with folic acid.

Available Forms

Vitamin B9 is found in multivitamins, including children's chewable and liquid drops, and B complex vitamins. It is also sold separately. It is a good idea to take folic acid as part of or along with a multivitamin because other B vitamins are needed for it to work. It is available in a variety of forms, including tablets, soft gels, and lozenges.

How to Take It

Most people (except pregnant women) should be able to get enough folic acid from their diets.

Check with a knowledgeable health care provider before taking folic acid supplements or giving them to children.

Daily recommendations for dietary folic acid are:

Pediatric

  • Infants, 0 to 6 months: 65 mcg (adequate intake)
  • Infants, 7 to 12 months: 80 mcg (adequate intake)
  • Children, 1 to 3 years: 150 mcg (RDA)
  • Children, 4 to 8 years: 200 mcg (RDA)
  • Children, 9 to 13 years: 300 mcg (RDA)
  • Teens, 14 to 18 years: 400 mcg (RDA)

Adult

  • Men and women, 19 years and older: 400 mcg (RDA)
  • Pregnant women: 600 mcg (RDA)
  • Breastfeeding women: 500 mcg (RDA)

Amounts used in studies for heart disease range from 400 to 1,200 mcg. However, high levels of folate can hide a vitamin B12 deficiency, and should be taken only under a doctor's supervision. If you are considering taking a folic acid supplement, ask your doctor to help you determine the right dose for you.

Precautions

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

At the recommended daily allowance, side effects from folic acid are rare. Very high doses can cause:

  • Stomach problems
  • Sleep problems
  • Skin reactions
  • Confusion
  • Loss of appetite
  • Nausea
  • Seizures

Talk to your doctor before taking more than 800 mcg of folic acid. Folic acid can hide the symptoms of an underlying vitamin B12 deficiency, which can cause permanent damage to the nervous system. Taking any one of the B vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, you may want to take a B complex vitamin, which includes all the B vitamins.

People who are being treated for seizures or cancer should not take folic acid without talking to their doctors.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use folic acid supplements without first talking to your doctor.

Antibiotics, tetracycline -- Folic acid should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. Folic acid, either alone or in combination with other B vitamins, should be taken at different times from tetracycline. All vitamin B complex supplements act in this way and should be taken at different times from tetracycline.

Phenytoin (Dilantin) -- Phenytoin, an anti-seizure medication, may lower levels of folate in the body. However, folic acid may interfere with the way phenytoin works, raising the risk of seizures. Ask your doctor before taking folic acid supplements.

Pyrimethamine (Daraprim) -- Pyrimethamine is a medication used to prevent and treat malaria and to treat toxoplasmosis. Folic acid may make this medication less effective.

Chemotherapy medications -- Folic acid may raise the amounts of 5-fluorouracil and capecitabine (Xeloda) to dangerous levels in the body. If you are undergoing chemotherapy, ask your oncologist before taking any supplements or herbs.

Medications that lower levels of folic acid -- The following medications may interfere with the body's absorption of folate, meaning you may need to take a folic acid supplement while taking them. Talk to your doctor first.

  • Antacids.
  • H2 blockers -- Used to reduce stomach acid, including cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac).
  • Proton pump inhibitors -- Used to reduce stomach acid, including someprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), and rabeprazole (Aciphex).
  • Bile acid sequestrants -- Used to lower cholesterol, including colestipol (Colestid), cholestyramine (Questran), and colsevelam (Welchol).
  • Anti-seizure medications -- Including phenobarbital, primidone (Mysoline), and carbamazepine (Tegretol).
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Including ibuprofen (Advil, Motrin) and naproxen (Aleve).
  • Sulfasalazine (Azulfidine) -- Used to treat inflammatory bowel disease (IBD) and rheumatoid arthritis (RA).
  • Triamterene (Dyrenium) -- A diuretic (water pill).
  • Cycloserine -- An antibiotic.
  • Pyrimethamine (Daraprim) -- Used to prevent and treat malaria and to treat toxoplasmosis.
  • Trimethoprim -- An antibiotic used to treat urinary tract infections.

When taken for long periods of time, these medications, as well as other anti-inflammatory medicines, can increase the body's need for folic acid.

Methotrexate -- Methotrexate, a medication used to treat cancer, rheumatoid arthritis (RA), and psoriasis, reduces the amount of folic acid in the body. If you take methotrexate for RA or psoriasis, your doctor may prescribe a higher dose of folic acid, which helps reduce the side effects of methotrexate. People taking methotrexate for cancer, however, should not take folic acid supplements unless their doctor tells them to. Folic acid may interfere with methotrexate's effects on cancer.

Supporting Research

Abularrage CJ, Sidawy AN, White PW, Aidinian G, Dezee KJ, Weiswasser JM, Arora S. Effect of folic Acid and vitamins B6 and B12 on microcirculatory vasoreactivity in patients with hyperhomocysteinemia. Vasc Endovascular Surg. 2007 Aug-Sep;41(4):339-345.

Ahrens K, Yazdy M, Mitchell A, Werler M. Folic acid intake and spina bifida in the era of dietary folic acid fortification. Epidemiology. 2011; 22(5):731-737.

Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, Manson JE. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299(17):2027-2036.

Alpert JE, Mischoulon D, Nierenberg AA, Fava M. Nutrition and depression: focus on folate. Nutrition. 2000;16:544-581.

Auerhahn C. Daily folic acid supplementation for 3 years reduced age related hearing loss. Evid Based Nurs. 2007 Jul;10(3):88.

Bleie O, Semb AG, Grundt H, Nordrehaug JE, Vollset SE, Ueland PM, et al. Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease. J Intern Med. 2007 Aug;262(2):244-253.

Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care. CMAJ. 2000;163(1):21-29.

Celik T, Iyisoy A, Yuksel UC, Isik E. Homocysteine-lowering vitamins and cardiovascular mortality: Are they really effective? Int J Cardiol. 2007 Aug 7; [Epub ahead of print].

Choi S-W, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000:130:129-132.

Chowers Y, Sela B, Holland R, Fidder H, Simoni FB, Bar-Meir S. Increased levels of homocysteine in patients with Crohn's disease are related to folate levels. Am J Gastroenterol. 2000;95(12):3498-3502.

Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women. Arch Intern Med. 2009;169:335-341.

de Bree A, van Mierlo LA, Draijer R. Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2007;86(3):610-617.

Durga J, Verhoef P, Anteunis LJ, et al. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med. 2007;146:1-9.

Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. Case-control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer. 2000;89(2):376-382.

Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LYC. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001;285(23):2981-2236.

Jänne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med. 2000;342(26):1960-1968.

Kliegman. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA: Saunders, An Imprint of Elsevier. 2011.

Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Scientific Statement: AHA Dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation. 2000;102(18):2284-2299.

Mayne ST, Risch HA, Dubrow R, et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev. 2001;10:1055-1062.

Nilsen RM, Vollset SE, Rasmussen SA, Ueland PM, Daltveit AK. Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study. Am J Epidemiol. 2008;167(7):867-874.

Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. Homocysteine metabolism in children with Down syndrome: in vitro modulation. Am J Genet. 2001;69(1):88-95.

Rock CL, Michael CW, Reynolds RK, Ruffin MT. Prevention of cervix cancer. Crit Rev Oncol Hematol. 2000;33(3):169-185.

Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk [communication]. J Natl Cancer Inst. 2000;92(3):266-269.

Roth C, Magnus P, Schjolberg S, et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011; 306(14):1566-1573.

Schnyder G. Decreased rate of coronary restinosis after lowering of plasma homocysteine levels. N Engl J Med. 2001;345(22):1593-1600.

Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001;12(4):420-428.

Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008;87(3):517-533.

Snowdon DA. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr. 2000;71:993-998.

Steenweg-de Graaff J, Roza SJ, Steegers EA, et al. Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study. Am J Clin Nutr. 2012; 95(6):1413-1421.

Su LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol. 2001;11(1):65-72.

Suren P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013; 309(6):570-577.

Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother. 2000;34(1):57-65.

Thompson JR, Gerald PF, Willoughby ML, Armstrong BK. Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukemia in childhood: a case-controlled study. Lancet. 2001;358(9297):1935-1940.

Thomson SW, Heimburger DC, Cornwell PE, et al. Correlates of total plasma homocysteine: folic acid, copper, and cervical dysplasia. Nutrition. 2000;16(6):411-416.

Title LM, Cummings PM, Giddens K, Genest JJ, Jr., Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol. 2000;36(3):758-765.

Torkos S. Drug-nutrient interactions: a focus on cholesterol-lowering agents. Int J Integrative Med. 2000;2(3):9-13.

Wald DS. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med. 2001;161:695-700.

Wang HX. Vitamin B12 and folate in relation to the development of Alzheimer's disease. Neurology. 2001;56:1188-1194.

Windham GC, Shaw GM, Todoroff K, Swan SH. Miscarriage and use of multi-vitamins or folic acid. Am J Med Genet. 2000;90(3):261-262.

Wong WY, Thomas CM, Merkus JM, Zielhuis GA, Steegers-Theunissen RP. Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril. 2000;73(3):435-442.

Review Date: 6/19/2013
Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.
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