Vitamin B9 (Folic Acid)
Studies suggest that vitamin B9 may be associated with depression more than any other nutrient, and may play a role in the high incidence of depression in the elderly. Learn about the usage, dosage, side-effects of Vitamin B9.
Also Known As:folate, folic acid, folacin
- Dietary Sources
- Available Forms
- How to Take It
- Possible Interactions
- Supporting Research
Vitamin B9, also called folic acid or folate, is one of eight water-soluble B vitamins. All B vitamins help the body to convert carbohydrates into glucose (sugar), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, are essential in the breakdown of fats and protein. B complex vitamins also play an important role in maintaining muscle tone along the lining of the digestive tract and promoting the health of the nervous system, skin, hair, eyes, mouth, and liver.
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 during periods of high growth, such as infancy, adolescence and pregnancy. Folic acid also works closely together with vitamin B12 to regulate the formation of red blood cells and to help iron function properly in the body.
Vitamin B9 works closely with vitamins B6 and B12 as well as the nutrients betaine and S-adenosylmethionine (SAMe) to control blood levels of the amino acid homocysteine. Elevated levels of this substance appear to be linked to certain chronic conditions such as heart disease and, possibly, depression and Alzheimer's Disease. Some researchers have even speculated that there is a connection between high levels of this amino acid and cervical cancer, but the results of studies regarding this have been inconclusive.
Folic acid deficiency is the most common B vitamin deficiency. Animal foods, with the exception of liver, are poor sources of folic acid. Plant sources rich in folic acid are frequently not obtained in adequate amounts in the diet. Alcoholism, irritable bowel syndrome, and celiac disease contribute to deficiency of this important nutrient. Folic acid deficiency can cause poor growth, tongue inflammation, gingivitis, loss of appetite, shortness of breath, diarrhea, irritability, forgetfulness, and mental sluggishness.
Pregnancy can put a woman at risk for folic acid deficiency as the fetus easily depletes a mother's nutrient reserves.
Folic acid deficiency during pregnancy increases the risk for neural tube 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 central nervous system (the brain and spinal cord). In 1996, the U.S. Food and Drug Administration (FDA) authorized the addition of folic acid to many grain foods (such as bread and cereal). Since this time, the prevalence of neural tube defects in the United States has decreased.
Birth Defects: As mentioned, pregnant women who are deficient in folic acid are more likely to have children with birth defects. Many neural tube defects (such as spina bifida) are believed to be preventable if women of childbearing age supplement their diets with folic acid. This is why women planning on becoming pregnant should be taking a multivitamin with plenty of folate, and why all pregnant women receiving prenatal care are put on a prenatal vitamin.
Studies have found 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%. A recent study found that the prevalence of neural tube defects in the United States has decreased by 19% since the FDA authorized the fortification of grains with folic acid. Even though this connection seems strong, it is not known whether folic acid or factors other than this vitamin that contributed to this substantial decline.
Recent studies in test tubes brings into question whether there is a connection between elevated homocysteine (and, therefore, folate deficiency) in the mother and Down's syndrome in the child. Preliminary information also raises question about the possibility of folate supplements during pregnancy preventing the development of childhood leukemia. More research is needed in both of these areas before any conclusions can be drawn.
Miscarriage: Clinically, many naturopathic and other doctors recommend the use of vitamin B complex 50 mg per day with additional folic acid 800 to 1,000 mcg per day to try to prevent miscarriage (also known as spontaneous abortion). These practices for prevention of spontaneous abortion are supported by some studies suggesting a connection between impaired homocysteine metabolism and recurrent miscarriages. This conclusion is not without debate, however, with some experts arguing that it is difficult to determine from most studies to date whether it is low folate or other factors contributing to an increased incidence of spontaneous abortion. It is important to know that there are many, many reasons for a miscarriage. In fact, most commonly, there is no explanation for why a woman has miscarried.
Heart Disease: Folate can help protect the heart through several methods. First, there are studies that suggest that folate can help reduce risk factors for heart disease and the harm that they cause, including cholesterol and homocysteine (both of which can damage blood vessels). Secondly, by diminishing this damage, studies suggest that not only can folate help prevent build up of atherosclerosis (plaque), it may also help the blood vessels function better, improve blood flow to the heart, prevent cardiac events such as chest pain (called angina) and heart attack, and reduce the risk of death.
Collectively, many studies indicate that patients with elevated levels of the amino acid homocysteine are roughly 1.7 times more likely to develop coronary artery disease (coronary arteries supply blood to the heart, blockage there can lead to a heart attack) and 2.5 times more likely to suffer from a stroke than those with normal levels. Homocysteine levels can be reduced by taking folate (the general recommendation is at least 400 micrograms [mcg] per day, but some studies suggest that this daily amount must be at least 650 to 800 mcg.) Folate needs vitamins B6 and B12 and betaine to function properly and to fully metabolize homocysteine.
The American Heart Association recommends that, for most people, an adequate amount of folate and these other B vitamins be obtained from the diet, rather than taking extra supplements. Under certain circumstances, however, supplements may be necessary. Such circumstances include elevated homocysteine levels in someone who already has heart disease or who has a strong family history of heart disease that developed at a young age.
Alzheimer's Disease: Folic acid and vitamin B12 are critical to the health of the nervous system and to a process that clears homocysteine from the blood. As stated earlier, homocysteine may contribute to the development of certain illnesses such as heart disease, depression, and Alzheimer's Disease. Elevated levels of homocysteine and decreased levels of both folic acid and vitamin B12 have been found in people with Alzheimer's Disease, but the benefits of supplementation for this or other types of dementia are not yet known.
Osteoporosis: Keeping bones healthy throughout life depends on getting sufficient amounts of specific vitamins and minerals, including phosphorous, magnesium, boron, manganese, copper, zinc, folic acid, and vitamins C, K, B12, and B6.
In addition, some experts believe that high homocysteine levels may contribute to the development of osteoporosis. If this is the case, then there may prove to be a role for dietary or supplemental vitamins B9, B6, and B12.
Vitamin B9 and depression: Studies suggest that vitamin B9 (folate) may be associated with depression more than any other nutrient, and may play a role in the high incidence of depression in the elderly. Between 15% and 38% of people with depression have low folate levels in their bodies and those with very low levels tend to be the most depressed. Many healthcare providers recommend a B complex multivitamin that contains folate as well as vitamins B6 and B12 to improve symptoms. If the multivitamin with these B vitamins is not enough to bring elevated homocysteine levels down, the physician may then recommend higher amounts of folate along with vitamins B6 and B12. Again, these three nutrients work closely together to bring down high homocysteine levels, which may be related to the development of depression.
Cancer: Folic acid appears to protect against the development of some forms of cancer, particularly cancer of the colon, as well as breast, esophagus, and stomach, although the information regarding stomach cancer is more mixed. It is not clear exactly how folate might help prevent cancer. Some researchers speculate that folic acid keeps DNA (the genetic material in cells) healthy and prevents mutations that can lead to cancer.
Population-based studies have found that colorectal cancer is less common among individuals with very high dietary intakes of folic acid. The reverse appears to be true as well: low folic acid intake increases risk of colorectal tumors. To have a significant effect on reducing the risk of colorectal cancer, it appears that at least 400 mcg of folic acid per day over the course of at least 15 years is required. Similarly, many clinicians recommend folic acid supplementation to people who are at high risk for colon cancer (for example, people with a strong family history of colon cancer).
Similarly, one population-based study also found that cancers of the stomach and esophagus are less common among individuals with high intakes of folic acid. Researchers interviewed 1095 patients with cancer of the esophagus or stomach as well as 687 individuals who were free of cancer in three health centers across the United States. They found that patients who consumed high amounts of fiber, beta-carotene, folic acid, and vitamin C (all found primarily in plant-based foods) were significantly less likely to develop cancer of the esophagus or stomach than those who consumed low amounts of these nutrients. Another important, good-sized study, however, did not find any connection between folic acid intake and stomach cancer. The possibility of some protection from folate against stomach cancer in particular needs clarification and, therefore, more research is warranted.
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 1 ½ to 2 glasses per day) is associated with increased risk of breast cancer. One extremely large study, involving over 50,000 women who were followed over time, suggests that adequate intake of folate may lessen the risk of breast cancer associated with alcohol.
Cervical Dysplasia: Folate deficiency appears to be linked to cervical dysplasia (changes in the cervix [the first part of the uterus] that are either precancerous or cancerous and generally detected by pap smear). Studies evaluating the use of folate supplementation to lower the risk of developing such changes to the uterus have not been promising, however. For now, experts recommend getting adequate amounts of folate in the diet for all women (see How To Take It), which may be particularly important for those with risk factors for cervical dysplasia such as an abnormal pap smear or genital warts.
Inflammatory Bowel Disease (IBD): People with ulcerative colitis and Crohn's disease (both inflammatory bowel diseases) often have low levels of folic acid in their blood cells. This may be due, at least in part, to sulfasalazine and/or methotrexate use, two medications that can diminish levels of folate. Other researchers speculate that folate deficiencies in Crohn's disease patients may be due to decreased intake of folate in the diet and poor absorption of this nutrient in the digestive tract.
Some experts suggest that folic acid deficiencies may contribute to the risk of colon cancer in those with IBDs. Although preliminary studies suggest that folic acid supplements may help reduce tumor growths in people with these conditions, further research is needed to determine the precise role of folic acid supplementation in people with IBDs.
Burns: It is especially important for people who have sustained serious burns to obtain adequate amounts of nutrients in their daily diet. When skin is burned, a substantial percentage of micronutrients may be lost. This increases the risk for infection, slows the healing process, prolongs the hospital stay, and even increases the risk of death. Although it is unclear which micronutrients are most beneficial for people with burns, many studies suggest that a multivitamin including the B complex vitamins may aid in the recovery process.
Male Infertility: In a study of 48 men, researchers found that men with low sperm counts also had low levels of folic acid in their semen. It is not clear whether folic acid supplementation would improve sperm count, however.
Rich sources of folic acid include spinach, dark leafy greens, asparagus, turnip, beet and 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 oysters, salmon, orange juice, avocado, and milk. In March of 1996, the FDA authorized the addition of folic acid to all enriched grain products and made manufacturers comply to this rule by January of 1998.
Vitamin B9 can be found in multivitamins (including children's chewable and liquid drops), B complex vitamins, or are sold individually. It is a good idea to take folate as part of or along with a multivitamin because other B vitamins are needed for folate activation. It is available in a variety of forms including tablets, softgels, and lozenges. Vitamin B9 is also sold under the names folate, folic acid, and folinic acid. While folic acid is considered the most stable form of vitamin B9, folinic acid is the most efficient form for raising body stores of the nutrient.
Most people (except pregnant women) get adequate folic acid from their diet. Under certain circumstances, however, a healthcare professional may recommend a therapeutic dose as high as 2,000 mcg per day for an adult.
It is important to check with a knowledgeable healthcare provider before taking supplements and before giving folic acid supplements to a child.
Daily recommendations for dietary folic acid are listed below:
Infants under 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) Adolescents 14 to 18 years: 400 mcg (RDA) Adult
19 years and older: 400 mcg (RDA) Pregnant women: 600 mcg (RDA) Breastfeeding women: 500 mcg (RDA) Amounts recommended for heart disease range from 400 to 1,200 mcg.
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.
Side effects from folic acid are rare. Very high doses (above 15,000 mcg) can cause stomach problems, sleep problems, skin reactions, and seizures.
Folic acid supplementation should always include Vitamin B12 supplementation (400 to 1000 mcg daily) because folic acid can mask an underlying vitamin B12 deficiency, which can cause permanent damage to the nervous system. In fact, taking any one of the B complex vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, it is generally important to take a B complex vitamin with any single B vitamin.
If you are currently being treated with any of the following medications, you should not use folic acid supplements without first talking to your healthcare provider.
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 therefore be taken at different times from tetracycline.)
Aspirin, Ibuprofen, and Acetaminophen: When taken for long periods of time, these medications, as well as other anti-inflammatories can increase the body's need for folic acid.
Birth control medications, anticonvulsants for seizures (namely, phenytoin and carbamazapine), and cholesterol-lowering medications (namely, bile acid sequestrants including cholestyramine, colestipol, and colesevelam) may reduce the levels of folic acid in the blood as well as the body's ability to use this vitamin. Extra folate when taking any of these medications may be recommended by your healthcare provider. When taking bile acid sequestrants for cholesterol, folate should be taken at a different time of day.
Sulfasalazine, a medication used for ulcerative colitis and Crohn's disease, may reduce the absorption of folic acid, leading to lower levels of folic acid in the blood.
Methotrexate, a medication used to treat cancer and rheumatoid arthritis, increases the body's need for folic acid. Folic acid reduces the side effects of methotrexate without decreasing its effectiveness.
Other Antacids, cimetidine, and ranitidine (used for ulcers, heartburn, and related symptoms) as well as metformin (used for diabetes) may inhibit the absorption of folic acid. It is best, therefore, to take folic acid at a different time from any of these medications.
Barbiturates, such as pentobarbital and phenobarbital, used for seizures, may impair folic acid metabolism.
Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutrition Rev. 1997;5(5):145-149.
Alpert JE, Mischoulon D, Nierenberg AA, Fava M. Nutrition and depression: focus on folate. Nutrition. 2000;16:544-581.
Antoon AY, Donovan DK. Burn Injuries. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. Philadelphia, Pa: W.B. Saunders Company; 2000:287-294.
Baggott JE, Morgan SL, Ha T, et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J. 1992;282(Pt 1):197-202.
Bailey LB, Gregory JF. Folate metabolism and requirements. J Nutr. 1999;129(4):779-782.
Ballal RS, Jacobsen DW, Robinson K. Homocysteine: update on a new risk factor. Cleve Clin J Med. 1997;64:543-549.
Bendich A, Deckelbaum R, eds. Prevention Nutrition: The Comprehensive Guide for Health Professionals. Totowa, NJ: Humana Press; 1997.
Biasco G, Zannoni U, Paganelli GM, et al. Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis. Cancer Epidemiol Biomarkers Prevent. 1997;6:469-471.
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.
Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutrition Rev. 1996;54(12):382-390.
Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA. 1995;274:1049-1057.
Bronstrup A, Hages M, Prniz-Langenohl R, Pietrzik K. Effects of folic acid and combinations of folic acid and vitamin B12 on plasma homocysteine concentrations in healthy, young women. Am J Clin Nutr. 1998;68:1104-1110.
Butterworth CE Jr, Hatch KD, Macaluso M, et al. Folate deficiency and cervical dysplasia. JAMA. 1992;267(4):528-533.
Butterworth CE Jr, Hatch KD, Soong SJ, et al. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am J Obstet Gynecol. 1992;166(3):803-809.
Cancers, Nutrition and Food. Washington, DC: World Cancer Research Fund/American Institute for Cancer Research; 1997.
Childers JM, Chu J, Voigt LF, et al. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol Biomarkers Prev. 1995;4(2):155-159.
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.
Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Veland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55:1449-1455.
Cravo ML, Albuquerque CM, Salazar de Sousa L, et al. Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effects of folate supplementation. Am J Gastroenterol. 1998;93:2060-2064.
De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr. 1998;128:797-803.
Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing. 1998;27:485-491.
Eikelboom JW, Lonn E, Genest J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131:363-375.
Endresen GK, Husby G. Methotrexate and folates in rheumatoid arthritis [in Norwegian]. Tidsskr Nor Laegeforen. 1999;119(4):534-537.
Giles WH, Kittner SJ, Croft JB, Anda RF, Casper ML, Ford ES. Serum folate and risk for coronary heart disease: Results from a cohort of US adults. Ann Epidemiol. 1998;8:490-496.
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.
Goggin T, Gough H, Bissessar A, Crowley M, Baker M, Callaghan N. A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy. Q J Med. 1987;65(247):911-919.
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.
Giuliano AR, Gapstur S. Can cervical dysplasia and cancer be prevented with nutrients? Nutr Rev. 1998;56(1):9-16.
Hall J. Folic acid for the prevention of congenital anomalies. Eur J Pediatr. 1998;157(6):445-450.
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.
Imagawa M. Extra-intestinal complications of ulcerative colitis: hematologic complication [in Japanese]. Nippon Rinsho. 1999;57(11):2556-2561.
JÃ¤nne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med. 2000;342(26):1960-1968.
Kirschmann GJ, Kirschmann JD. Nutrition Almanac. 4th ed. New York: McGraw-Hill;1996:64-67.
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.
Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Dig Dis Sci. 1993;38(9):1614-1618.
Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol. 1997;18(6):526-530.
Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid. Ann Pharmacother. 1998;32:947-961.
Lobo A, Naso A, Arheart K, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with levels of vitamins B6 and B12. Am J Cardiol. 1999;83:821-825.
Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular disease. A statement for healthcare professionals from the nutrition committee, American Heart Association. Circulation. 1999;99:178-182.
Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998;338:1009-1015.
Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther. 1982;4(6):423-440.
Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol. 1996;27(3):517-527.
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.
Meyer NA, Muller MJ, Herndon DN. Nutrient support of the healing wound. New Horizons. 1994;2(2):202-214.
Miller AL, Kelly GS. Homocysteine metabolism: nutritional modulation and impact on health and disease. Altern Med Rev. 1997;2(4):234-254.
Miller AL, Kelly GS. Methionine and homocysteine metabolism and the nutritional prevention of certain birth defects and complications of pregnancy. Altern Med Rev. 1996;1(4):220-235.
Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folic acid levels and hyperhomocysteinemia during long-term, low-dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998;25:441-446.
Morgan S, Baggott J, Vaughn W, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. Ann Intern Med. 1994;121:833-841.
Morselli B, Neuenschwander B, Perrelet R, Lippunter K. Osteoporosis diet [in German]. Ther Umsch. 2000;57(3):152-160.
Moscow JA. Methotrexate transport and resistance. Leuk Lymphoma. 1998;30(3-4):215-224.
Nutrients and Nutritional Agents. In: Kastrup EK, Hines Burnham T, Short RM, et al, eds. Drug Facts and Comparisons. St. Louis, Mo: Facts and Comparisons; 2000:4-5.
Omray A. Evaluation of pharmacokinetic parameters of tetracylcine hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull. 1981;23(VI):33-37.
Ortiz Z, Shea B, Suarez-Almazor ME, et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol. 1998;25:36-43.
Quere I, Bellet H, Hoffet M, Janbon C, Mares P, Gris JC. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril. 1998;69(1):152-154.
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.
Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998;279:359-364.
Ringer D, ed. Physician's Guide to Nutriceuticals. St. Joseph, Mich: Nutritional Data Resources; 1998.
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.
Schnyder G. Decreased rate of coronary restinosis after lowering of plasma homocysteine levels. N Engl J Med. 2001;345(22):1593-1600.
Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M. Phenytoin-folic acid interaction: a lesson to be learned. Clin Neuropharmacol. 1999;22(5):268-272.
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.
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.
Steger GG, Mader RM, Vogelsang H, SchÃ¶fl R, Lochs H, Ferenci P. Folate absorption in Crohn's disease. Digestion. 1994;55:234-238.
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.
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.
Tucker KL, Selhub K, Wilson PW, Rosenberg IH. Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J Nutr. 1996;126:3025-3031.
Verhaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. Circulation. 1999;100(4):335-338.
Wald DS. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med. 2001;161:695-700.
Wallock LM. Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Fertil Steril. 2001;75(2):252-259.
Wang HX. Vitamin B12 and folate in relation to the development of Alzheimer's Disease. Neurology. 2001;56:1188-1194.
Watkins ML. Efficacy of folic acid prophylaxis for the prevention of neural tube defects. Ment Retard Dev Disab Res Rev. 1998;4:282-290.
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.
Wolf PA. Prevention of stroke. Lancet. 1998;352 (suppl III):15-18.
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.
Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J. A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev. 1999;8(3):209-217.
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.
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Staff, H. (2008, November 5). Vitamin B9 (Folic Acid), HealthyPlace. Retrieved on 2021, September 28 from https://www.healthyplace.com/alternative-mental-health/supplements-vitamins/vitamin-b9-folic-acid