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Monograph: Folate

Folate

Based on a systemic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration.

Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food, and folic acid is the synthetic form of this vitamin. Folic acid is well-tolerated in amounts found in fortified foods and supplements. Sources include cereals, baked goods, leafy vegetables (spinach, broccoli, lettuce), okra, asparagus, fruits (bananas, melons, lemons), legumes, yeast, mushrooms, organ meat (beef liver, kidney), orange juice and tomato juice. Folic acid is frequently used in combination with other B vitamins in vitamin B complex formulations.

Folic acid supplements are effective for increasing folate levels in blood and decreasing symptoms associated with low folate levels.Folic acid supplementation, with and without other B vitamins, reduce levels of homocysteine in blood (a cardiovascular risk factor).

Folic acid supplements are suggested for use in women of childbearing age in order to prevent neural tube defects. Neural tube defect risk appears to have decreased in many countries since folic acid fortification of flour and cereals.

Folic acid is also of interest with respect to cognitive enhancement, cancer, psychiatric illnesses and cardiovascular conditions, although conclusions may not be drawn for many of these uses at this time. Some concern exists with respect to increased folic acid intake masking symptoms of vitamin B12 deficiency, especially in the elderly population.

Tradition/Theory 

AIDS, anemia (associated with inflammatory bowel disease), anti-aging, appetite stimulation, autism, canker sores, celiac disease, critical illness, Crohn’s disease, dental conditions, fistula (abnormal connection between organs), fractures (risk reduction), gastritis (stomach inflammation), genetic damage (X-ray induced chromosomal damage), infertility, inflammatory bowel disease, insomnia, ischemic heart disease (decreased blood supply to the heart), lichen planus (itchy mouth rash), liver disease, macular degeneration (eye disease), mood, myofascial pain (chronic muscle pain), osteoporosis, peripheral neuropathy (damage of peripheral nerves such as toes and fingertips), restless leg syndrome, retinal vein occlusion (blockage of veins in the eye), schizophrenia, sickle Cell anemia, spinal cord injury, ulcerative colitis, weight loss.

Dosing 

Adults (18 years and older) 

The daily suggested intake levels of folic acid are as follows: males over 13 years, 400 micrograms; females over 13 years, 400-600 micrograms; pregnancy all ages, 400-600 micrograms; breastfeeding females of all ages, 500 micrograms. The maximum daily intake level of folic acid for people 19 years and older (including pregnant or breastfeeding women), 1,000 micrograms.

For anemia caused by folate deficiency, 1-5 milligrams has been taken by mouth daily until recovery.

For antiseizure drug-induced folate deficiency, 15 milligrams has been taken by mouth daily under the supervision of a qualified healthcare provider.

For bipolar disorder, 200 international units of folic acid has been taken by mouth daily for 52 weeks in patients stabilized on lithium. Three milligrams of folic acid have been taken by mouth daily for three weeks in patients starting valproic acid therapy.

For cancer (general), 0.2-40 milligrams of folate or folic acid (either taken alone or in combination with aspirin, vitamins B6 or B12) has been taken by mouth daily for three to eight years, with mixed results.

For cognitive effects, 0.75-15 milligrams of folic acid has been taken by mouth daily for 1-36 months.

For colorectal cancer, 0.5-5 milligrams of folic acid has been taken by mouth daily for three to eight years with mixed results.

For chronic kidney disease, 2-15 milligrams of folic acid has been taken by mouth daily, every other day or three times weekly, for a follow- up duration of 1-3.6 years.

For depression, 0.5-3 milligrams or 200 international units of folic acid or 15-50 milligrams of methylenetetrahydrofolate have been taken by mouth daily for three to 52 weeks.

For diabetes, 5 milligrams of folic acid has been taken by mouth daily for one to six months.

For folate deficiency, 250-1,000 micrograms has been taken by mouth daily. In addition, for severe folate deficiency, 1-5 milligrams has been taken by mouth daily until blood levels are corrected and documented by a qualified healthcare professional.

For fragile X syndrome, 10-250 milligrams of folic acid has been taken by mouth daily for two to eight months with a lack of effect on symptoms.

For heart disease, 0.8-40 milligrams of folic acid have been taken by mouth daily for three to 88 months.

For high homocysteine levels, 0.2-5 milligrams of folic acid has been taken by mouth For 21-168 days.

For high blood pressure, 5-10 milligrams of folic acid has been taken by mouth for two to six weeks.

For methotrexate toxicity, 1-27.5 milligrams of folic acid or 1-20 milligrams of folinic acid has been taken by mouth daily or weekly for up to 12 weeks.

For the prevention of birth defects, wheat flour fortified with folic acid has been taken by mouth before pregnancy and during the first two months of pregnancy. Doses of 0.36-5 milligrams have been taken by mouth daily.

For the prevention of pregnancy complications (other), 0.25-5 milligrams of folic acid have been taken by mouth daily for 12-24 weeks.

For stroke, 0.5-40 milligrams of folic acid have been taken by mouth daily for 6-88 months. For vein clots, 5 milligrams of folic acid has been taken by mouth once daily during pregnancy.

For vitiligo, 5 milligrams has been taken by mouth twice daily.

For gum overgrowth caused by phenytoin, folic acid has been applied to the gum. For pregnancy-related gum disease, folic acid has been applied to the gum.

Children (under 18 years old) 

The daily suggested intake levels of folic acid are as follows: babies 0-6 months, 65 micrograms; 7 to 12 months, 80 micrograms; children 1-3 years, 150 micrograms; 4-8 years, 200 micrograms; males 9-13 years, 300 micrograms; males over 13 years, 400 micrograms; and females 9-13 years, 300 micrograms.

The maximum daily intakes are as follows: for children 1-3 years-old, 300 micrograms; for children 4-8 years-old, 400 micrograms; for children 9-13 years-old, 600 micrograms; and for adolescents 14-18 years-old, 800 micrograms. Folic acid injection contains benzyl alcohol (1.5 percent), and extreme care should be used when given to newborns.Folic acid injections should be given by a health care provider.

For fragile X syndrome, 10-250 milligrams has been taken by mouth daily for 2-8 months with a lack of effect on symptoms.

For general health maintenance, 0.005-15 milligrams has been taken by mouth daily for two weeks to 18 months, with mixed results.

Safety 

Allergies Avoid in people with known allergy or sensitivity to product ingredients in folic acid-containing supplements.

Side Effects & Warnings 

Folate is likely safe when added to foods in the following amounts: in breakfast cereals, below 400 micrograms per serving; in infant formula, 4 micrograms per 100 kilocalories of Infant formula; in corn grits, 1 milligram per pound; in meal-replacement products, 200-400 micrograms per serving, with the amount depending on whether the food is used once or more than once daily.

Use cautiously if taken above the suggested or maximum daily intake levels.

Folate may cause bitter taste, bloating, blood flow problems (caused by narrowed vessels), breathing difficulty, changes in urine color, confusion, cramps, diarrhea, dizziness, fatigue, gas, hair loss, headache, impaired judgment, increased asthma risk (in children of women taking folic acid during late pregnancy), increased cancer risk, increased seizure frequency, inflammation (such as in the mouth), lung muscle spasms, mood swings (excitability or irritability), nausea, overactivity, psychotic behavior, skin symptoms (flushing, hives, itching, rash, and redness), sleep problems, vivid dreaming, and weight changes.

Folate may cause low blood pressure. Caution is advised in people taking drugs or herbs and supplements that lower blood pressure.

Folate may lower blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Use cautiously in combination with aspirin or in supplemental doses above the maximum daily intake without the care of a medical professional. Injections of folic acid containing benzyl alcohol should only be used under the care of a doctor.

Use cautiously in people who have or are at risk of anemia, cancer, lung disorders, malaria, nervous system disorders, seizure disorders, skin conditions and stomach problems.

Avoid using with a combination of B vitamins after heart surgery or in people taking anticancer agents or folic acid antagonists (blockers), unless prescribed by a health care professional.

Avoid in people with known allergy or sensitivity to product ingredients in folic acidcontaining supplements.

Pregnancy & Breast 

Feeding The U.S. Preventive Services Task Force and other groups suggests that all women planning to be pregnant take a daily supplement containing 0. 4-0.8 milligrams (400-800 micrograms) of folic acid. It is suggested that all women capable of becoming pregnant consume folate in order to reduce the risk of the fetus developing birth defects.

Folic acid is likely safe to use during breastfeeding under the supervision of a qualified health care provider.

Interactions 

Interactions with Drugs 

Folate may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

Folate may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure.

Folate may also interact with agents that promote urination, alcohol, Alzheimer’s agents, aminosalicylic acid, antacids, antibiotics, anticancer agents, antidepressants, anti-malaria agents, anti-seizure agents, aspirin, birth control, cholestyramine, colestipol, conjugated estrogens, cycloserine, folic acid antagonists, H2 blockers, heart agents, homocysteine-lowering agents, iron, methotrexate, methylprednisolone sodium succinate (Solu-Medrol®), nervous system agents, nitroglycerin, nonsteroidal anti-inflammatories (NSAIDs), omega-3 fatty acids, pancreatic extracts, pemetrexed disodium, pentamidine, phenytoin, proton pump inhibitors, sulfasalazine Sulfonamides, tobacco, trimethoprim, vitamin A, vitamin B12, warfarin and zinc.

Interactions with Herbs & Dietary Supplements 

Folate may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Folate may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.

Folate may also interact with aged garlic extract, alcohol, Alzheimer’s herbs and supplements, antacids, antibacterials, anticancer herbs and supplements, antidepressants, anti-inflammatories, anti-malaria herbs and supplements, antioxidants, anti-seizure herbs and supplements, B vitamins, birth control, green tea, heart herbs and supplements, herbs and supplements that promote urination, homocysteine-lowering herbs and supplements, iron, leaf concentrate, multiple micronutrients, nervous system herbs and supplements, omega-3 fatty acids, pancreatic extracts, phytoestrogens, probiotics, salicylates, vitamin A, vitamin B12 and zinc.

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  1117. Duffield-Lillico, A. J., Reid, M. E., Turnbull, B. W., Combs, G. F., Jr., Slate, E. H., Fischbach, L. A., Marshall, J. R., and Clark, L. C. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol.Biomarkers Prev. 2002;11(7):630-639. View Abstract
  1118. No author. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 7-6-2002;360(9326):23-33. View Abstract
  1119. Hennekens, C. H., Buring, J. E., Manson, J. E., Stampfer, M., Rosner, B., Cook, N. R., Belanger, C., LaMotte, F., Gaziano, J. M., Ridker, P. M., Willett, W., and Peto, R. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N.Engl.J.Med. 5-2-1996;334(18):1145-1149. View Abstract
  1120. Cooper, K., Squires, H., Carroll, C., Papaioannou, D., Booth, A., Logan, R. F., Maguire, C., Hind, D., and Tappenden, P. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol.Assess. 2010;14(32):1-206. View Abstract



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