What is the source and manufacturer of Folic Acid (Vitamin B9)?

Sources and Manufacturers of Folic Acid (Vitamin B9)

Folic acid is a synthetic form of vitamin B9 that is manufactured commercially and is not naturally found in foods, while natural folates occur in various food sources such as green leafy vegetables, citrus fruits, and legumes. 1, 2

Natural Folate vs. Synthetic Folic Acid

Natural Folate Sources

• Green leafy vegetables - high natural folate content 1
• Citrus fruits - good dietary source 1, 3
• Pulses/legumes (edible seeds from legumes) - 200-300g cover the recommended daily allowance 1
• Nuts - contain significant folate 1, 3
• Eggs - moderate folate content 1
• Whole grain products - contain some folate 1
• Organ meats - particularly kidneys and liver contain high amounts 1

Synthetic Folic Acid

• Commercially synthesized through chemical processes 2
• Appears as a "yellow or yellowish-orange crystalline powder" 2
• More bioavailable than natural food folates 1, 4
• Used in:
  • Vitamin supplements 1
  • Fortified foods (breakfast cereals, enriched grain products) 1
  • Pharmaceutical preparations 2

Manufacturing Information

Folic acid is prepared synthetically by pharmaceutical manufacturers 2. The FDA drug label describes it as "N-[ρ-[[(2-amino-4-hydroxy-6-pteridinyl) methyl]-amino]benzoyl]-L-glutamic acid" with a specific chemical structure containing:

• A pteridine moiety
• A methylene bridge to para-aminobenzoic acid
• A peptide linkage to glutamic acid 2

Bioavailability Considerations

1. Absorption differences: Folic acid is almost twice as bioavailable as natural folate 1

2. Dietary folate equivalent (DFE) conversion:

   • 1 μg DFE = 1 μg food folate
   • 1 μg DFE = 0.6 μg folic acid from fortified food
   • 1 μg DFE = 0.5 μg folic acid supplement taken on empty stomach 1

3. Alternative forms: L-5-methyltetrahydrofolate (L-5-MTHF) is the predominant form of folate found naturally in circulation and is also available commercially as a crystalline calcium salt (Metafolin®) 4, 5

Food Fortification Programs

Since 1998, grain products in the United States have been fortified with folic acid 1 to reduce the incidence of neural tube defects 1. The US Public Health Service recommends that:

• Women of childbearing age consume 0.4 mg of folic acid daily 1
• Fortification occurs through three potential approaches:
  • Improvement of dietary habits
  • Fortification of food supply
  • Use of dietary supplements 1

Clinical Considerations

• Folic acid is water-soluble and excess is rapidly excreted in urine 1
• High doses of folic acid (but not natural folates) may mask vitamin B12 deficiency 4, 3
• For supplementation, a multivitamin containing vitamin B12 should be advised when recommending folic acid, especially for elderly patients 3

Recent Developments

Microencapsulation techniques have been developed to improve stability of folate forms in food products, particularly for L-5-MTHF which may have advantages over folic acid but is less stable in food matrices 5.

Human studies have shown that both microencapsulated L-5-MTHF and folic acid-fortified foods increase blood folate concentrations to a similar extent 5.

Human-focused research continues to explore folate's role in preventing various conditions beyond neural tube defects, including dementia and certain cancers 4.

Human-focused research continues to explore folate's role in preventing various conditions beyond neural tube defects, including dementia and certain cancers 4.