Folic Acid (5-MTHF)
GOOD SOURCES: Green leafy veggies, liver, lima beans, and whole grain cereals
DRI: 300-400 mg/d (0.3-0.4 mg/d); for women who are on birth control pills, this increases dramatically. After stopping BCPs, they must take 800 mg/d for at least 30 days before getting pregnant.
FUNCTIONS: Folic acid is essential for the biosynthesis of the purines and the pyrimidine , thymine.
It is converted to tetrahydrofolic acid (THF) which is the biologically active form. THF receives one-carbon fragments from donors (ie. serine, glycine, & histidine) and transfers them to intermediates in the synthesis of amino acids and the nucleotides mentioned above. See the diagram below.
All Nutrient Functions:
- High stomach pH (low stomach acid) decreases folic acid absorption
- Needed for the production of red blood cells
- Needed for the synthesis of nucleic acids
- Key role in one carbon metabolism (methylation reactions) as it accepts & donates methyl groups
- Precursor to SAMe (S-adenosylmethionine)
- Influences telomere length via DNA methylation
- Cofactor in the metabolism of methionine, histidine, tryptophan, glycine, serine, and formate
- Required for the conversion of homocysteine into methionine
- Affects noradrenaline and serotonin receptors in the brain
- Inhibits NMDA receptors
- Building block in synthesis of serotonin, dopamine, and norepinephrine
- Low folate causes poor response to anti-depressant medications
- Improves response to the anti-depressant drug fluoxetine
- The lower the folate, the more severe the depression in some individuals
- May improve response to erectile dysfunction meds (PDE5 inhibitors)
- Cofactor in mitochondrial respiratory process
- Improves endothelial function
- Increases nitric oxide (NO) production in vascular endothelial cells
- Cofactor to enzyme nitric oxide synthase
- Enhances the availability of nitric oxide cofactors such a tetrahydrobiopterin
- Improves flow mediated dilation
- Lowers risk of colonic neoplasia in patients with ulcerative colitis
- Detoxifies excess estrogen via methylation pathway
- Regulates estrogen’s effect on genes
- Plays a key role in cellular immunity (synthesis of white blood cells)
- Low folate status linked to severity of allergic response to asthma
- Increased rates of cell division (i.e. pregnancy, cancer) increases folate requirements
- Rapidly dividing cells are the most vulnerable to folate deficiency
- Alcohol interferes with the absorption and metabolism of folate
- Methotrexate (cancer, arthritis, and psoriasis drug) is a folate antagonist
- Individuals with homozygous C–> T in the C677T MTHFR (methylene tetrahydrofolate reductase) gene have higher folate requirements that those without two copies of this gene
- Synthesis of active form of folic acid requires B2, B3, B6, zinc, Vitamin C and serine
- Folate supplementation may increase Vitamin B12 requirements or aggravate neurological symptoms stemming from B12 deficiency
DEFICIENCIES: Folic acid deficiency is probably the most common vitamin deficiency in the U.S. (especially amoung pregnant females and alcoholics). Deficiency is manifested two ways: the first is Megaloblastic anemia because there isn’t enough synthesized nucleotides; the second is developmental abnormalities of the neural tube in the fetus.
The anemia is due to diminished synthesis of purines and thymidine. Therefore, the erythropoeitic cells are not able to make DNA or divide. Vitamin B12 deficiency can also cause this disorder (but at a different step). Make sure to evaluate the exact cause of megaloblastic anemia before instituting therapy. Deficiency can be brought on by increased demand (as in pregnant or lactating women), poor absorption, alcoholism, or medications (that inhibit dihydrofolate reductase such as methotrexate).
Neural tube development of the fetus is critically dependant on folic acid. Women considering getting pregnant should ensure intake of 0.4 mg/d. This amount must be consumed early because the neural tube develops very early in development (before most women know that they are pregnant). Supplementation should not exceed 1 mg/d to avoid complicating a vitamin B12 deficiency.
Deficiency Functions:
- Deficiency causes neural tube defects such as spina bifida and cleft palate in newborns
- Deficiency linked with cancers, especially colon and breast, although excess supplementation of folic acid has been linked with cancer cell proliferation and estrogen-related breast caner
- Deficiency reduces estrogen and circulating testosterone
- Deficiency alters cholinergic metabolism in the brain
- Deficiency reduces proliferation of lymphocytes
TOXICITY: Masks vitamin B12 deficiency (mainly in elderly)
