II. Indications: Supplementation

  1. Pregnancy
  2. Elevated Homocysteine levels
  3. Coronary Artery Disease prevention (disproven)

III. Physiology

  1. Folate is a precursor to Tetrahydrofolate (THF)
  2. Tetrahydrofolate (THF) is a single carbon (or methyl group) donor important to many reactions
    1. THF donates a methyl group in the formation of Purines (including thymine in DNA)
    2. THF is needed to convert Glycine to Serine
    3. THF is needed to convert Homocysteine to Methionine (with Vitamin B12 as a Cofactor)
      1. Lowers Homocysteine levels (but does not appear to lower CAD risk)

IV. Pharmacokinetics

  1. Folate in supplements is twice as Bioavailable as food

V. Preparations: Sources

  1. Meat
  2. Dark green leafy vegetables
    1. Spinach
    2. Romaine lettuce
  3. Dry beans
  4. Peanuts
  5. Wheat germ
  6. Yeast
  7. Enriched whole cereal grains (140 ug/100 grams grain)

VI. Dosing

  1. General
    1. Typical U.S. intake: 50-500 mcg/day
    2. Recommended Daily Allowance (RDA): 400 mcg/day
  2. Coronary Artery Disease prevention (not recommended)
    1. Folate 400 mcg to 5 mg (depending on Homocysteine)
    2. Not recommended due to low efficacy (lowers Homocysteine but not CAD risk)

VII. Dosing: Pregnancy

  1. General population
    1. Folate 400 mcg (600 Dietary Folate Equivalents or DFE) daily (as found in Prenatal Vitamins)
    2. Start at least 1 month before conception
    3. Continue for at least first 3 months of pregnancy (12 weeks postconceptions)
      1. Typically continued throughout pregnancy and Lactation
  2. Moderate risk
    1. Folic Acid 1000 mcg (1500 Dietary Folate Equivalents or DFE) daily
      1. Start at least 3 months before conception and continue at least until 12 weeks post-conception
      2. Some guidelines recommend the 4000 to 5000 mcg dose as given to high risk patients (see below)
    2. Indications
      1. Insulin Dependent Diabetes Mellitus
      2. Seizure Disorder or anticonvulsant use
      3. Obesity (BMI>35 kg/m2)
      4. Neural Tube DefectFamily History
  3. High risk
    1. Folic Acid 4000-5000 mcg daily
      1. Start at least 3 months before conception and continue at least until 12 weeks post-conception
    2. Indications
      1. Prior Neural Tube Defect
      2. Folic Acid Antagonist use (e.g. Methotrexate)
      3. Prior delivery complicated by Folic Acid Deficiency associated birth defect
        1. Cleft Palate
        2. Congenital Heart Disease
        3. Limb defect
        4. Urinary tract anomaly
        5. Hydrocephalus

VIII. Signs: Deficiency

X. Efficacy: Coronary Artery Disease

  1. Possible Protective against cardiovascular disease
    1. Low intake associated with higher Homocysteine levels
    2. Higher Homocysteine levels associated with CAD, CVA
  2. References
    1. Boushey (1995) JAMA 274:1049 [PubMed]
    2. Malinow (1998) N Engl J Med 338:1009 [PubMed]

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Related Studies

Cost: Medications

folic acid (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
FOLIC ACID 1 MG TABLET Generic $0.03 each