Folic Acid

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Latest Edit: Iva Lloyd, ND 2014-07-24 (EDT)

See Also Vitamins


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Folic acid is a water-soluble micronutrient which is also referred to as folate, folinic acid, folacin, and pteroglutaminic acid. It functions along with vitamin B12 in many of the same processes in the body especially in methylation reactions as a methyl donor (a methyl group is a compound with one carbon atom and three hydrogens). It is essential for proper metabolism of methionine and therefore in regulating homocysteine levels. Folic acid also plays a critical role in cellular division due to its role in DNA synthesis. Deficiencies in pregnancy can be detrimental, leading to neural tube defects and spina bifida.

Food Sources

The following foods have the highest concentration of folic acid. For a more expansive list on food sources of specific nutrients visit Health Canada's Dietary Reference Intakes for Vitamins or USDA's National Nutrient Database

Other food sources include:[1]

  • grains: whole grains
  • vegetables: green leafy vegetables like kale, spinach, beet greens, chard, asparagus, broccoli, cabbage and root vegetables
  • Other sources include: legumes

Uses

The following are the primary uses of Folic Acid. [2] [3]

  • Prevention of neural tube defects: Neural tube defects refers to defects which occur during the embryological stage where there is improper development of the neural tube which can lead to defects in the brain, spinal cord, body nerves, and the bones around these structures. Supplementation with folic acid during preconception and pregnancy can reduce the incidence of neural tube defects.
  • Atherosclerosis: Elevated homocysteine levels are found in a large number of individuals with heart disease and is considered an independent risk factor for developing a heart attack, stroke, or peripheral vascular disease. Folic acid helps with homocysteine metabolism. In larger doses it may also be helpful as a vasodilator and as an inhibitor of xanthine oxidase.
  • Osteoporosis: Elevated homocysteine likely plays a role in osteoporosis as well by interfering with crossing linking of collagen and leading to a defective bone matrix. Supplementation with folic acid can decrease homocysteine levels in postmenopausal women even without a frank deficiency demonstrated through a laboratory work-up.
Article Folate and Childhood Cancers, NMJ, [2], 2012 July
  • Lung Cancer: Folic acid has been shown to decrease risk of lung cancer.
  • Cervical Dysplasia: Abnormal Paps may actually reflect a folate deficiency rather than true dysplasia especially in women with high estrogen (i.e., those who are pregnant or on oral contraceptives) as estrogen antagonizes folate. Oral contraceptives appear to deplete tissue levels of folate even if serum levels are normal.
Article Vitamin B12, and Folate in the Treatment of Some Psychiatric Illnesses, J Orthomolecular Med; 2012; Vol27(3)
  • Depression: Similar to vitamin B12, folic acid is essential for methylation of a compound in the brain called BH4 which is important for the synthesis of serotonin and dopamine. Supplementation can improve mood by aiding in proper synthesis of these neurotransmitters.
  • Anti-aging: Folate serves to improve memory and slow aging. Also as one ages, folate absorption declines, thus giving more reason to supplement as one ages. Folic acid can also decrease hand tremors, unsteadiness, and possibly even other signs of aging.

Deficiency Symptoms

Folic acid deficiency is the most common vitamin deficiency in the world. Plant sources are the best sources of folic acid. Most deficiencies are due to poor dietary choices and a lack of vegetables and plants in the common diet. Alcohol consumption as well as a number of drugs deplete the vitamin. Rapidly dividing cells are the cells which are most affected (ex. cells of the gastrointestinal and genital tract and red blood cells). Symptoms can include:

Excess Symptoms

There are no issues with toxicity associated with folic acid. Yet, high doses may cause:

Assessment Procedure

Common Deficiency Tests[4]

  • Plasma Homocysteine - a high level indicates a deficiency
  • Serum Folate - a low level indicates a deficiency

Prescribing Considerations

  • Folic acid supplementation is available as folic acid (folate) and folinic acid (5-methyl-tetra-hydrofolate).
  • Folinic acid is the more active form and is more effective at raising body stores than folic acid [3].
  • The recommended dosages varies based on age and health status. To determine what your specific requirements are talk to your naturopathic doctor or other trained medical professional.
  • Infants: 25mg (under 6 months); 35mg (6-12 months)
  • Child: 50mg (1-3 years); 75mg (4-6 years); 100mg (7-10 years)
  • Adolescent: 150mg (Males and Females 11-14 years)
  • Adult: 200mg (Males 15+ years); 180mg (Females 15+ years)
  • Pregnancy: 400mg
  • Lactation: 280mg

Safety

  • Children: No adverse effects have been reported in children or would be predicted. However, prophylactic use of folic acid (and iron) may be contraindicated for children in malarial environments.
  • Adults: generally regarded as safe
  • Seniors: generally regarded as safe
  • Pregnancy: Increased intake of folic acid is important preconception and specifically required during pregnancy.
  • Breastfeeding: Folate enters breast milk and is beneficial.
  • Cautions and Contraindications:
  • Folic acid supplementation can mask a vitamin B12 deficiency. Therefore, supplementation of folic acid may reverse the signs of macrocyticanemia but will not correct the neurological symptoms associated with a B12 deficiency. Nerve damage can result. Folic acid and B12 status should be checked together. Folic acid supplementation is contraindicated in cases where B12 status is unknown.
  • Folic acid supplementation should not be utilized with individuals who have elevated histamine because it can aggravate a tendency towards depression, schizophrenia and other adverse effects.

Drug Interactions

  • Drug Interactions include:[5]
Supportive or Beneficial:
  • Chloramphenicol - Drug interferes with hematopoietic processes and may cause aplastic anemia. Folic acid may prevent or reduce adverse effects.
  • Fenofibrate, Bezafibrate, and Related Fibrates - Drug is known to elevate total homocysteine. Folic acid supplementation may lower homocysteine and enhance therapeutic strategy.
  • Fluoxetine and Related Selective Serotonin Reuptake Inhibitor and Serotonin-Norepinephrine Reupake Inhibitor (SSRI and SSRI/SNRI) Antidepressants - Folate deficiency may be associated with depressive disorders and lack of response to SSRIs. Concomitant folic acid may increase responsive to drug by improving tryptophan, phenylalanine, and serotonin status. Improvements in homocysteine levels may also contribute to the benefit.
  • Levodopa and Related Antiparkinsonian Medications - Drug can elevate homocysteine levels. Folic acid, along with B6 and B12 may help to maintain healthy homocysteine levels and reduce adverse effects of the therapy. Caution regarding high-dose Vitamin B6 use with carbidopa and benserazide.
  • Lithium - Co-administration of folic acid may enhance therapeutic efficacy of lithium therapy.
  • Mercaptopurine, Azathiopurine, and Thioguanine (Thiopurines) - Limited evidence indicates that concomitant folate may protect bone marrow, moderate drug adverse effects, and enhance tolerance to the drug.
  • Nitroglycerin and Related Nitrates - Co-administration of folic acid can attenuate tolerance to drug by enhancing regeneration and bioavailability of BH4; it also supports therapeutic strategy of reducing cardiovascular risk.
Addresses Drug-Induced Deficiency:
  • Acetylsalicylic Acid (Aspirin) and Salsalate - Drug can inhibit folate-dependent enzymes, interfere with folate metabolism, and increase urinary excretion of folate. Synergy is possible with low-dose ASA in stroke prevention.
  • Antacids, Histamine (H2) Antagonists, and Gastric Acid-Suppresive Medications - Drug can impair folic acid absorption and availability due to interference with normal acidic-alkaline balance in the GI environment.
  • Anticonvulsant Medications, Including Phenobarbital, Phenytoin, and Valproic Acid - Drugs decrease absorption of folate (and vitamin B12) and anemia and elevated homocysteine are common. This is a very serious concern and serum levels of medication, folate, and homocysteine ought to be carefully monitored.
  • Bile Acid Sequestrants - Drug likely impairs absorption and bioavailability of folic acid, vitamin B12, and other fat soluble nutrients. Co-administration is recommended as part of a comprehensive cardiovascular support strategy. Separate intake.
  • Colchicine - Drug may decrease folate levels.
  • Isoniazid, Rifampin, and Related Antitubercular Agents - Drug adversely affects action of folate and potentially induces depletion.
  • Metformin and Related Biguanides - Metformin is known to elevate homocysteine, but evidence is not conclusive as to degree to which biguanides deplete folate. Metformin also impairs absorption of B12; this may be corrected with concomitant calcium. Maintaining low homocysteine levels is important for overall reduction of cardiovascular risk.
  • Neomycin - Drug can decrease absorption and increase elimination of folate and other nutrients.
  • Nitrous Oxide - Drug can interfere with activity of folate and B12, potentially depleting both. Prudence suggests supplementation with acid or 5-MTHF (and B12) starting 1 week before major N2O anesthesia.
  • Nonsteroidal Anti-inflammatory Drugs (NSAIDs) - Many NSAIDs exert antifolate activity by impairing or competitively interfering with folate absorption, metabolism, and transport. Chronic use can lead to deficiency.
  • Oral Contraceptives - Drug (especially with higher estrogendoses) can impair folate metabolism and may cause depletion especially in women with compromised folate status. Folic acid particularly important with cervical dysplasia and possibility of pregnancy after drug termination.
  • Pancreatic Enzymes, Pancreatin, and Related Proteolytic Enzymes - Simultaneous intake of pancreatin and other proteolytic enzymes may impair folic acid absorption. Particularly important with individuals with pancreatic insufficiency.
  • Pyrimethamine - Drug depletes serum folic acid levels and interferes with hematopoiesis especially in combination with other antifolates.
  • Sulfasalazine - Drug interferes with absorption, bioavailability, and activity of folic acid most likely acting as a competitive inhibitor and impairing activity of folate-dependent enzymes. Folic acid supplementation is particularly important for those at risk of dysplasia or cancer (i.e., individuals with ulcerative colitis).
  • Tetracycline Antibiotics - Drug and vitamin may bind and inhibit absorption and availability of both agents when ingested simultaneously. Antibiotic can also induce depletion of folic acid and other nutrients. Separate intake.
  • Triamterene and Related Potassium-Sparing Diuretics - Drug impairs folate absorption and bioavailability possibly by acting as a competitive inhibitor of folate intestinal absorption. It can lead to depletion and therefore teratogenesis and hyperhomocysteinemia. Drug may also decrease biologically active folates by acting as a weak antagonist in the folic acid synthesis pathway. Concomitant folic acid may mitigate such effects and contributes to strategic goal of reducing cardiovascular and stroke risk by lowering homocysteine levels.
  • Trimethoprim-sulfamethoxazole (Sulfonamide Antibiotics) - Drug inhibits conversion of folate to its active form. Teratogenicity and macrocytic anemia are known adverse effects. Folic acid co-administration could theoretically interfere with drug activity but evidence indicates that interference is unlikely with low-dose intake.
  • Zidovudine (AZT), Reverse-transcriptase Inhibitor (nucleoside) Anti-Retroviral Agents -Macrocytosis, anemia, and granulocytopenia are common adverse effects associated with AZT therapy. co-administration of B12 and folic acid may not prevent or reduce drug-induced myelotoxicity.
Other:
  • Antifolates, and Related Antimetabolites, Including Lometrexol, Methotrexate, Pemetrexed - Drugs inherently carry significant risk of folate deficiency and attendant toxicity as they are made to competitively inhibit folate and interfere with folate-related enzymes. Folic acid may impair antineoplastic activity of the drugs, however, may be necessary for reducing adverse effects and sometimes critical against toxicity. Only to be considered with close supervision and active management in an integrative oncology setting.

Nutrient Interactions

  • Nutrient Interactions include: [5]
  • B Vitamins (Vitamin B2, Vitamin B6, Vitamin B12) - B vitamins work synergistically with folic acid so adequate amounts of each need to be available for optimum functioning.
  • Vitamin C - plays a key role in the conversion of folic acid to its active form and helps to reduce folic acid excretion.
  • Zinc - Bioavailability of dietary folate is increased by the action of folate conjugase, a zinc-dependent enzyme.

References

  1. Medlineplus [1]
  2. Hoffer Abram, Prousky Jonathan (2006) Naturopathic Nutrition, A Guide to Nutrient-Rich Food & Nutritional Supplements for Optimum Health, CCNM Press
  3. 3.0 3.1 Murray Michael T (2005) Encyclopedia of Nutritional Supplements, The Essential Guide for Improving Your Health Naturally, Prima Publishing Cite error: Invalid <ref> tag; name "murray" defined multiple times with different content
  4. Bralley J Alexander and Lord Richard S (2005) Laboratory Evaluations in Molecular Medicine, Nutrients, Toxicants, and Cell Regulators Institute for Advances in Molecular Medince, GA
  5. 5.0 5.1 Stargrove Mitchell Bebell, Treasure Jonathan, McKee Dwight L (2008) Herb, Nutrient, and Drug Interactions, Clinical Implications and Therapeutic Strategies. Mosby