Folate

Definition

Purpose

Description

Precautions

Interactions

Complications

Parental concerns

Resources

Definition

Folate is a naturally occurring water-soluble vitamin that the body needs to remain healthy. Folic acid is a stable synthetic form of folate that is found in dietary supplements and is added to fortified foods such as flour and cereal. Humans cannot make folate or folic acid, so they must get it from foods in their diet or as a dietary supplement Folic acid and folate are both converted into an active form in that the body can use, although folic acid is more easily used (more bioavail-able) in the body. Folic acid is also called vitamin B₉

Purpose

Folate is necessary to create new DNA (genetic material) and RNA when cells divide. It plays a critical role in developing healthy red blood cells. Folate also helps protect DNA from damage that may lead to diseases such as cancer. Along with vitamins B₆ and

Folate (Folic Acid)

AI = Adequate Intake.

mcg = microgram.

(Illustration by GGS Information Services/Thomson Gale.)

B₁₂ , folate helps regulate the level of the amino acid homocysteine in the blood. Homocysteine regulation is related to cardiovascular health. In the fetus, folate is necessary for the proper development of the brain and spinal cord.

Description

Folate is one of eight B -complex vitamins. Its function is closely intertwined with that of vitamins B₆ and B₁₂ . Folate, from the Latin word folium meaning leaf, was discovered in the late 1930s in yeast and later found in spinach and other green leafy vegetables and in liver. Starting in 1998, the United States Food and Drug Administration (FDA) required certain foods, such as flour, corn meal, bread, cereal, rice, and pasta, to be fortified with a folic acid. In Canada and Chile fortification of flour is mandatory.

Folate’s role in health

Folate is essential for the normal development of the neural tube in the fetus. The neural tube develops into the brain and spinal cord. It closes between the third and fourth week after conception. Too little folate at this time can lead to serious malformations of the spine (spina bifida) and the brain (anencephaly). Because many women do not realize that they are pregnant so soon after conception, the United States has included folic acid in its fortified foods program. Adding folic acid to common foods made with grains has substantially reduced the number of babies born with neural tube defects in the United States.

The body also needs folate to produce healthy red blood cells. When not enough folate is present, the red blood cells do not divide; instead they grow abnormally large. These malformed cells have a reduced ability to carry oxygen to other cells in the body. This condition is called megaloblastic anemia. It is identical to the condition of the same name caused by too little vitamin B₁₂ . Folate also aids in the production of other new cells. Adequate supplies of folate are especially important in fetuses and infants because they are growing rapidly. However, since the lifespan of a red blood is only about four months, the body needs a continuous supply of folate throughout life to create healthy new replacement blood cells.

Folate acts together with vitamin B₆ and vitamin B₁₂ to lower the level of homocysteine in the blood. Homocysteine is an amino acid that is naturally produced when the body breaks down protein . Moderate to high levels of homocysteine in the blood are linked to an increased risk of cardiovascular disease (e.g. atherosclerosis, heart attack, stroke). The trio of folate, vitamin B₆ , and vitamin B₁₂ lower homocysteine levels. However, it is not clear whether taking large doses of these vitamins, either alone or in combination, will prevent heart disease from developing in healthy individuals. The official position of the American Heart Association stated in its Diet and Lifestyle Recommendations Revision 2006 is that “Available evidence is inadequate to recommend folic acid and other B vitamin supplements as a means to reduce CVD [cardiovascular disease] risk at this time.’

Damage to DNA appears to contribute to the development of many different cancers. Because folate helps protect against DNA damage, researchers have looked at whether it can reduce the risk of developing cancer. Results are mixed, with benefits seen for some cancers, but not for others. The American Cancer Society in its 2006 Guidelines on Nutrition and Physical Activity for Cancer Prevention states: “Folate deficiency may increase the risk of cancers of the color-ectal and breast, especially in people who consume alcoholic beverages. Current evidence suggests that to reduce cancer risk, folate is best obtained through consumption of vegetables, fruits, and enriched grain

KEY TERMS

Alzheimer’s disease— an incurable disease of older individuals that results in the destruction of nerve cells in the brain and causes gradual loss of mental and physical functions.

Amino acid— molecules that are the basic building blocks of proteins.

B-complex vitamins— a group of water-soluble vitamins that often work together in the body. These include thiamine (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid (B₅), pyridoxine (B₆), biotin (B₇ or vitamin H), folate/folic acid (B₉), and coba-lamin (B₁₂).

Dietary supplement— a product, such as a vitamin, mineral, herb, amino acid, or enzyme, that is intended to be consumed in addition to an individual’s diet with the expectation that it will improve health.

Diuretic— a substance that removes water from the body by increasing urine production.

Enzyme— a protein that change the rate of a chemical reaction within the body without themselves being used up in the reaction Ribonucleic acid (RNA) —A molecule that helps decode genetic information (DNA) and is necessary for protein synthesis.

Vitamin— a nutrient that the body needs in small amounts to remain healthy but that the body cannot manufacture for itself and must acquire through diet.

Water- soluble vitamin—a vitamin that dissolves in water and can be removed from the body in urine.

products.” The American Cancer Society does not endorse taking megadoses of folic acid to prevent cancer.

Clinical trials are underway to determine safety and effectiveness of folate/folic acid both alone and in combination with other vitamins in preventing cancer, cardiovascular disease, and dementias such as Alzheimer’s disease. Cognitive decline and some forms of dementia, including Alzheimer’s disease, are associated with lower folate levels, which is common amongst older people in some countries. Individuals interested in participating in a clinical trial at no charge can find a list of open trials at <http://www.clinicaltrials.gov>

Normal folate requirements

The United States Institute of Medicine (IOM) of the National Academy of Sciences has developed values called Dietary Reference Intakes (DRIs) for vitamins and minerals . The DRIs consist of three sets of numbers. The Recommended Dietary Allowance (RDA) defines the average daily amount of the nutrient needed to meet the health needs of 97-98% of the population. The Adequate Intake (AI) is an estimate set when there is not enough information to determine an RDA. The Tolerable Upper Intake Level (UL) is the average maximum amount that can be taken daily without risking negative side effects. The DRIs are calculated for children, adult men, adult women, pregnant women, and breastfeeding women.

The IOM has not set RDA s for folate in children under one year old because of incomplete scientific information. Instead, it has set AI levels for this age group. RDA s and ULs for folate are measured in micrograms (mcg). Unlike the UL for many vitamins, the UL for folate/folic acid refers only to folic acid that comes from fortified food or that is in folic acid dietary supplements, multivitamins, or B-complex vitamins. There is no UL for folate found in natural plant and animal foods. Dietary supplements containing more than 1,000 mcg (1 mg) of folic acid require a prescription. 1 mcg of folate from natural food sources is equal in biological activity in humans to 0.6 mcg of folic acid from supplements or fortified food.

The following are the daily RDAs and IAs and ULs for folic aside for healthy individuals:

• children birth-6 months: AI 65 mcg; UL not established
• children 7-12 months: AI 89 mcg; UL not established
• children 1-3 years: RDA 150 mcg; UL 300 mcg
• children 4-8 years: RDA 200 mcg; UL 400 mcg
• children 9-13 years: RDA 300 mcg; UL 600 mcg
• children 14-18 years: 400 RDA mcg; UL 800 mcg
• adults age 19 and older: RDA 400 mcg; UL 1,000 mcg
• pregnant women: RDA 600 mcg; UL 1,000 mcg
• breastfeeding women: RDA 500 mcg; 1,000 mcg

Sources of folate

People need a continuous supply of folate from their diet because of the role it plays in creating new blood cells. Because folate is water-soluble, little is stored in the body; any excess is excreted in urine. Since the folic acid fortification program began in 1998, most healthy Americans get enough folate from their diet. The exception is pregnant women who should, under medical supervision, take a folic acid supplement (400 mcg for most women and higher does for those who have already had a baby with a neural tube defect). Good natural sources of folate include beef liver, green leafy vegetables, and dried beans. Cooking animal products does not reduce the folate content much, but cooking vegetables can reduce the amount of folate by up to 40% depending on the vegetable and the cooking method.

The following list gives the approximate folate/ folic acid content for some common foods:

• asparagus, cooked, 1/2 cup: 132 mcg
• spinach, cooked, 1/2 cup: 131 mcg
• turnip greens, cooked, 1/2 cup: 135 mcg
• broccoli, steamed 1/2 cup: 85 mcg
• beets, boiled; 1/2 cup: 68 mcg
• great northern beans, cooked 1/2 cup: 90 mcg
• pinto beans, cooked, 1/2 cup: 147 mcg
• navy beans, cooked, 1/2 cup: 127 mcg
• tomato juice, canned, 6 ounces: 35 mcg
• raspberries 1/2 cup: 16 mcg
• corn, yellow, cooked, 1/2 cup: 37 mcg
• breakfast cereal, fortified 100%, 3/4 cup: 400 mcg
• bread, white or whole wheat 1 slice: 25 mcg
• rice, white, enriched long-grain, cooked, 1/2 cup: 65 mcg
• bread, whole wheat, 1 slice: .07 mg
• bread, white, enriched, 1 slice: .09 mg

Folate deficiency

Most healthy people in the United States get enough folate in their diet because folate is added to many common foods such as bread; however, this is not the case elsewhere.In Europe, low intakes are commonly reported particularly in teenage girls and older people. Causes of folate deficiency include inadequate intake, impaired absorption, (celiac disease, Crohn’s disease, certain medications), inability of the body to use folate (enzyme deficiencies), increased folate needs (pregnancy, cancer), or increased loss or excretion (kidney dialysis, alcoholism). As a group, the elderly are the largest group at risk to develop folate deficiency.

The major symptom of folate deficiency in pregnant women is having a baby born with a brain or spinal cord abnormality. Other symptoms of folate deficiency include slow growth in infants and children, megaloblastic anemia, digestive problems such as diarrhea, sore tongue, irritability, forgetfulness and changes in mental state. These changes can also have other causes and should be evaluated by a healthcare professional.

Precautions

Since many pregnancies are unplanned and unrecognized until after the critical period for brain and spinal cord formation, any woman who may become pregnant should be careful to include enough folate in her diet and folic acid supplements should be taken before and in the first trimester of pregnancy.

Folic acid may mask vitamin B₁₂ deficiency. Folic acid supplements will reverse anemia symptoms, but they do not stop nerve damage caused by B₁₂ deficiency. Permanent nerve damage may result. People with suspected folate deficiency who begin taking folic acid supplements should also be evaluated for vitamin B₁₂ deficiency.

Interactions

The following medications may interfere with the ability of the body to absorb and use folate. Individuals taking these medications should check with their physician about the effects they may have on folate/ folic acid levels in the body:

• seizure medications such as dilantin, phenytoin, and primidone.
• metaformin (Fortamet, Glucophage, Glucophage XR, Riomet) used to treat type 2 diabetes.
• sulfasalazine used to treat Chron’s disease and inflammatory bowel disease.
• triameterene, a diuretic or “water pill’
• barbiturate sedatives.
• methotrexate, used to treat cancer, rheumatoid arthritis, and psoriasis.
• drugs used to treat gastroesophageal reflux disease (GERD), such as omeprazole (Prilosec), lansoprazole (Prevacid), cimetidine (Tagamet), famotidine (Pep-sid), nizatidine (Axid), or ranitidine (Zantac).

Complications

No complications are expected when folate/folic acid is taken within recommended levels. Complications related to deficiencies are discussed above. Complications of excess folic acid intake at levels above 1,000 mcg daily over an extended period can include seizures in individuals taking anticonvulsant medications and general irritability, and restlessness in otherwise healthy individuals.

Parental concerns

Parents need to be aware that infants and rapidly growing children are at higher risk for folate deficiency. Parents of children with digestive disorders or allergies to wheat products should discuss the need for a folic acid supplement with their pediatrician.

Resources

BOOKS

Berkson, Burt and Arthur J. Berkson. Basic Health Publications User’s Guide to the B-complex Vitamins. Laguna Beach, CA: Basic Health Publications, 2006.

Fragakis, Allison. The Health Professional’s Guide to Popular Dietary Supplements Chicago: American Dietetic Association, 2003

Gaby, Alan R., ed. A-Z Guide to Drug-Herb-Vitamin Interactions Revised and Expanded 2nd Edition: Improve Your Health and Avoid Side Effects When Using Common Medications and Natural Supplements Together New York: Three Rivers Press, 2006.

Lieberman, Shari and Nancy Bruning. The Real Vitamin and Mineral Book: The Definitive Guide to Designing Your Personal Supplement Program. 4th ed. New York: Avery, 2007.

Pressman, Alan H. and Sheila Buff. The Complete Idiot’s Guide to Vitamins and Minerals 3rd ed. Indianapolis, IN: Alpha Books, 2007.

Rucker, Robert B., ed. Handbook of Vitamins. Boca Raton, FL: Taylor & Francis, 2007.

Department of Health Folic Acid and the Prevention of Disease. Report on Health and Social Subject. London, The Stationery Office, 2000.

PERIODICALS

Kushi, Lawrence H., Tim Byers, Colleen Doyle, et al.

“American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention.’ CA: Cancer Journal for Clinicians., 56 (2006):254-281. <http://caonline.amcancersoc.org/cgi/content/full/56/5/254>

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta GA 30329-4251. Telephone: 800 ACS-2345. Website: <http://www.cancer.org>

American Heart Association. 7272 Greenville Avenue, Dallas, TX 75231. Telephone: (800) 242-8721. Website: <http://www.americanheart.org>

British Nutrition Foundation. 52-54 High Holborn, London WC1V 6RQ telephone: 0207 404 6504, fax: 0207 404 6757. Website: <http://www.nutrition.org.uk>

Linus Pauling Institute. Oregon State University, 571 Weniger Hall, Corvallis, OR 97331-6512. Telephone: (541) 717-5075. Fax: (541) 737-5077. Website: <http://lpi.oregonstate.edu>

Office of Dietary Supplements, National Institutes of Health. 6100 Executive Blvd., Room 3B01, MSC 7517, Bethesda, MD 20892-7517 Telephone: (301)435-2920. Fax: (301)480-1845. Website: <http://dietary-supplements.info.nih.gov> .

Scientific Advisory Committee on Nutrition Folate and Disease Prevention. <http://www.sacn.gov.uk>

OTHER

American Cancer Society “Vitamin B Complex.’ American Cancer Society, October 6, 2005. <http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Vitamin_B6.asp?sitearea=ETO>

American Heart Association Nutrition Committee. “Diet and Lifestyle Recommendations Revision 2006.’ American Heart Association, June 19, 2006.<http://www.americanheart.org/presenter.jhtml?identifier=3040741>

Gentilli, Angela. “Folic Acid Deficiency.’ emedicine.com, May 22, 2006. <http://www.emedicine.com/med/topic802.htm>

Higdon, Jane. “Vitamin A.’Linus Pauling Institute-Oregon State University, April 2, 2002. <http://lpi.oregonstate.edu/infocenter/vitamins/VitaminA>

Maryland Medical Center Programs Center for Integrative Medicine. “Vitamin B9 (Folic Acid).’ University of Maryland Medical Center, April 2002. <http://www.umm.edu/altmed/ConsSupplements/VitaminB9FolicAcidcs>

Medline Plus. “’ U. S. National Library of Medicine, August 1, 2006. <http://www.nlm.nih/gov/medlineplus/druginfo/natural/patient-folate.html>

Office of Dietary Supplements. ’Dietary Supplement Fact Sheet: Vitamin D.“National Institutes of Health, August 22, 2005. <http://ods.od.nih.gov/factsheets/Folate_pf.asp>

Tish Davidson, A.M.

Folic acid see Folate