Folic Acid

• Definition: Folic acid, also known as vitamin B9, is a water-soluble nutrient crucial for various bodily functions.
• Key Roles: Primarily involved in red blood cell production and DNA synthesis.
• Primary Prevention: Prevents neural tube defects (NTDs) like spina bifida in pregnant women.
• Supplementation Use: Addresses nutritional gaps and supports overall health, especially in individuals with dietary restrictions or increased needs.

• Pregnancy and Fetal Development: Significantly reduces NTD risk (spina bifida, anencephaly) (1). Recommended daily intake: 400-800 mcg for pregnant women.
• Cognitive Function: Maintains cognitive health, potentially preventing or slowing cognitive decline and dementia (2). Often works synergistically with B6 and B12.
• Cardiovascular Health: Lowers homocysteine levels, reducing cardiovascular disease risk (heart attacks, strokes, peripheral artery disease) (3).
• Metabolic Health: Involved in amino acid, nucleic acid, and lipid metabolism; may regulate blood sugar and improve insulin sensitivity, reducing type 2 diabetes risk (4).
• Cancer Prevention: Some studies suggest a potential role in preventing certain cancers (colorectal, breast, pancreatic), but further research is needed (5).
• Physical Performance and Energy: Essential for red blood cell production, carrying oxygen to tissues and supporting physical performance; may reduce fatigue and improve exercise performance (6).
• Mental Health: Plays a role in neurotransmitter (serotonin, dopamine) synthesis; some research suggests it may alleviate depression symptoms (7).
• Immune System: Essential for proper immune system function, protecting against infections and diseases (8).
• Important Note: Excessive intake (above 1000 mcg/day) may have adverse effects, such as masking vitamin B12 deficiency. Consult a healthcare professional before supplementation.

References:

1. Centers for Disease Control and Prevention. (2020). Folic Acid and Prevention of Birth Defects of the Brain and Spine.
2. [Reference 2 needed]
3. [Reference 3 needed]
4. [Reference 4 needed]
5. [Reference 5 needed]
6. [Reference 6 needed]
7. [Reference 7 needed]
8. [Reference 8 needed]

• Active Form: Converted to tetrahydrofolate (THF), a coenzyme in amino acid, nucleotide, and other biomolecule metabolism.
• Mechanism of Action:
  • Dietary Intake & Absorption: Ingested and absorbed in the small intestine.
  • Conversion to THF: Converted to dihydrofolate (DHF) by dihydrofolate reductase (DHFR), then to THF.
  • One-Carbon Unit Transfer: THF donates one-carbon units to enzymes, facilitating biomolecule synthesis.
• Affected Pathways:
  • Nucleotide Synthesis: Essential for purine (adenine, guanine) and pyrimidine (thymine, cytosine, uracil) synthesis.
  • Amino Acid Metabolism: Involved in metabolism of histidine, serine, and glycine.
  • Homocysteine Metabolism: Regulates homocysteine levels by donating one-carbon units to methionine synthase (converting homocysteine to methionine).
  • Methylation Reactions: Involved in methylation reactions via methionine synthase.

• Molecular Formula: C19H19N7O6
• IUPAC Name: (2S)-2-[(4-[(2-Amino-5-methyl-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl)methyl]amino)benzoyl]amino]pentanedioic acid
• Key Structural Features:
  • Pteridine ring (pyrimidine and pyrazine rings fused).
  • Para-Aminobenzoic Acid (PABA) moiety.
  • Glutamic acid moiety.
  • Conjugated double bonds.
• Properties:
  • Appearance: Yellow-orange crystalline powder, melting point ~250°C (dec).
  • Solubility: Moderately soluble in water (~1.6 mg/mL at 25°C), soluble in dilute acids and bases.
  • Stability: Stable in neutral and slightly acidic solutions; degrades in alkaline solutions or with exposure to light, heat, or oxygen.
  • pH Dependence: Solubility and stability are pH-dependent, optimal at pH 6-8.
  • Biological Activity: Precursor to tetrahydrofolate (THF).

Natural Sources:

• Leafy greens (spinach, kale, collard greens).
• Legumes (beans, lentils, peas).
• Citrus fruits (oranges, grapefruits, lemons).
• Whole grains (brown rice, quinoa, whole-wheat bread).
• Nuts and seeds (almonds, sunflower seeds, pumpkin seeds).

Extraction/Synthesis Methods:

• Fermentation (using microorganisms like bacteria and yeast).
• Chemical synthesis (from guanidine, malonic acid, and p-aminobenzoic acid).
• Extraction from yeast (Saccharomyces cerevisiae).

Quality Considerations for Supplements:

• Purity (≥ 95%).
• Stability (protect from light, heat, and moisture).
• Bioavailability (consider 5-methyltetrahydrofolate (5-MTHF) or folinic acid).
• Regulatory compliance (GMPs, third-party testing).
• Accurate label claims.
• Consider formulations with complementary nutrients (e.g., vitamin B12).