Facts, Articles, Research

What the science says (1990–2026): Folic Acid

These citations support correction of deficiency, specified forms, and elemental amounts — the same logic used in MD's Choice formulas. They are not claims that a supplement treats disease.

MRC Vitamin Study 1991 Lancet; Czeizel 1992; USPHS 1992; 2023–2025 prenatal guidance. 400 mcg folic acid before conception and in early pregnancy cuts neural-tube defects. That finding has held for more than 30 years.

These products are not intended to diagnose, treat, cure, or prevent disease. Historic monograph text below is kept for the original library.

Folic Acid

1946 Angler reported synthesis of folic acid

I. Structure

II. Functions

Different THF derivatives (Figure 1) participate as coenzymes in one-carbon donating/receiving reactions
Folate as Ns, NTM methylene THF is required for synthesis of serine from glycine
Regeneration of methionine from homocysteine involves folate as Ns methyl THF
Metabolism of histidine through urocanic acid and formiminoglutamate (FIGLU) to yield glutamic acid requires THF
THF derivatives are involved in purine and pyrimidine synthesis so folate is essential for cell division
1. Conversion of deoxy UMP to deoxy TMP which is required for DNA synthesis
2. N¹⁰ formyl THF is needed for purine ring formation
N⁵, N¹⁰ methylene THF is involved in production of glycine for synthesis of heme
Interaction of folate and vitamin B₁₂ in anemia (Folate trap hypothesis)
1. Methyl folate, the dominant form in the body's folate pool, is metabolically inactive (except as a methyl donor to convert homocysteine to methionine)
2. Methyl folate can be returned to the active folate Pool only via a B₁₂dependent step
3. In absence of sufficient vitamin B12 methyl folate accumulates
4. A vitamin B₁₂ containing enzyme transfers a methyl group from methyl folate to homocysteine converting it to methionine
5. This regenerates THF from which 5, 10-methylene THF is made
6. 5, 10-methylene THF delivers its methyl group to deoxyuridylate converting it to thymidylate which is necessary for synthesis of DNA
7. Deficiency of either B~2 or 5, 10-methylene THF inhibits adequate DNA synthesis causing many hematopoietic cells to die in the bone marrow; anemia results

III. Sources

Folates are most abundant in plant food sources, especially when raw
1. Green leafy materials
2. Whole grains and cereal byproducts
3. Beans
Organ meats and animal byproducts

IV. Metabolism

Digestion, absorption, transport
1. Folate in foods is hydrolyzed to the monoglutanate form
2. g-glutamylcarboxypeptidases (also called conjugases)
3. Folate is transported across cell membranes by a carrier system believed to be saturable and pH, energy, and Na dependent
4. Absorption is most efficient in the jejunum
5. In the intestinal cell, folate is reduced to THF and methylated to N⁵ methyl THF
6. Most of the folate in portal circulation is N⁵ methyl THF
7. Within the liver, folate is present as about 33% THF, 37% N⁵ methyl THF, 23% N¹⁰ formyl THF and 7% as N⁵ formyl THF
8. In blood, folate is found as monoglutomate, 2/3 bound to protein and 1/3 free
9. Folate is transported into tissue cells by a carrier mediated process that may or may not require ATP
10. Within cells THF is converted into a polyglutamate form to become a functional coenzyme
Excretion
1. Normally, the body tenaciously retains absorbed folate
2. Very little is excreted in urine
  1. Folate binding proteins
  2. Tubular resorption in kidney
3. Although much of absorbed folate is secreted by liver into bile, it is reabsorbed

V. Requirements

Recommended allowances
1. Pig 0.5-2 mg/Kg
2. Chick 1 mg/Kg
3. Human 0.4-0.8 mg/day
Factors affecting requirement
1. Conjugase required for cleaving polyglutamate into monoglutanate form of folate is inhibited by several factors
  1. Zinc deficiency
  2. Chronic alcoholism
  3. Inhibitors in legumes, lentils, cabbage and oranges
2. Inflammatory bowel disease
3. Achlorhydria (insufficient HCL in gastric juice)
4. Malignancies
5. Oral contraceptives
6. Anticonvulsants used in treatment of epilepsy

VI. Deficiency

Megaloblastic, macrocytic anemia in most species
1. Release into the circulation of large, immature ethrocytes, often containing excess hemoglobin
2. Also occurs due to a deficiency of vitamin B₁₂
Folate deficiency is suspected in the initiation of cancer
May be a risk factor for cardiac disease
Plasma homocyst(e)ine levels may be increased in the presence of decreased plasma folate
Increased neural tube defects in pregnant woman (see J. Am. Coll. Nutr. 15:121. 1996)

VII. Toxicity

Folate supplements exceeding .4 mg/day are considered pharmacologic
Some reports suggest no adverse effects of 10 mg/day for 5 years
Other studies indicate 15 mg/day is toxic in same individuals
1. Insomnia
2. Malaise
3. Irritability
4. Diminished Zn status
5. Gastrointestinal problems
Folate supplementation can mask vitamin B₁₂ deficiency
1. Alleviates megaloblastic anemia due to vitamin B₁₂ deficiency
2. Fails to prevent neurologic damage due to vitamin B₁₂ deficiency

For individual consultation or questions about our products, call
1-800-628-0997

Folate / Folic acid — C₁₉H₁₉N₇O₆

A B vitamin with a pterin ring. Cells need it to copy DNA. That is why it matters before and during early pregnancy. Folate is the food form; folic acid is the stable supplement form.

Need help choosing a formula?

For individual consultation or questions about our products, call 1-800-628-0997

Call 1-800-628-0997 Contact Us

Vitamin A	Vitamin B1 (Thiamin)	Vitamin B2 (Riboflavin)	Vitamin B3 (Niacin)
Vitamin B5 (Pantothenic Acid)	Vitamin B6	Vitamin B12	Vitamin C
Vitamin D	Vitamin E	Vitamin K	Biotin
Folic Acid

Calcium	Magnesium	Phosphorus	Sodium, Potassium, Chloride
Sulfur (Sulfer)

Boron	Chromium	Cobalt	Copper
Fluorine	Iodine	Iron	Manganese
Molybdenum	Nickel (Nickle)	Selenium	Silicon
Tin	Vanadium	Zinc	Ultra Trace

Aluminum	Arsenic	Cadmium	Lead
Mercury

What the science says (1990–2026): Folic Acid

Folic Acid

Vitamins, Major Elements, Trace Elements, Toxic Elements

Vitamins

Major Elements

Trace Elements

Toxic Elements

Need help choosing a formula?