Why choose folic acid (Vitamin B9) over folate for supplementation?

Folate vs. Folic Acid: Why Choose One Over the Other?

Folate (5-methyltetrahydrofolate) is generally preferable to folic acid for supplementation because it bypasses potential metabolic conversion issues that affect a significant portion of the population, reducing risks associated with unmetabolized folic acid while providing the same benefits.

Understanding the Difference

Folate and folic acid are not the same thing, despite often being used interchangeably:

• Folic acid: Synthetic form found in supplements and fortified foods
• Folate (5-MTHF): Natural bioactive form found in food and the only form normally found in circulation

Advantages of Folate (5-MTHF) Over Folic Acid

Metabolic Efficiency

• Folic acid must be converted to the active form (5-MTHF) in the body
• Many people have genetic polymorphisms (MTHFR variants) that impair this conversion
• Folate bypasses this metabolic block, making it immediately bioavailable 1, 2

Reduced Risk of Masking B12 Deficiency

• Folic acid can mask vitamin B12 deficiency symptoms while neurological damage continues
• The FDA drug label specifically warns: "Folic acid in doses above 0.1 mg daily may obscure pernicious anemia... while neurologic manifestations remain progressive" 3
• Folate (5-MTHF) has less potential to mask B12 deficiency symptoms 4, 2

Avoidance of Unmetabolized Folic Acid (UMFA)

• High doses of folic acid can lead to unmetabolized folic acid circulating in the bloodstream
• UMFA has been associated with potential negative health effects 5, 6
• Using 5-MTHF prevents these potential negative effects 2

Drug Interactions

• Folic acid may interact with certain medications:
  • May antagonize anticonvulsant action of phenytoin
  • May interact with drugs that inhibit dihydrofolate reductase
• Folate (5-MTHF) reduces these drug interactions 3, 2

Clinical Applications and Recommendations

Pregnancy and Neural Tube Defect Prevention

• Both forms effectively reduce neural tube defects when taken periconceptionally
• Folate (5-MTHF) is preferred during pregnancy due to its ability to bypass metabolic blocks 1
• The USPSTF recommends folic acid supplementation for all women planning or capable of pregnancy to prevent neural tube defects 7

Special Populations

• MTHFR Polymorphism: People with this common genetic variant benefit more from folate (5-MTHF) 1, 2
• Elderly: Higher risk of B12 deficiency makes folate (5-MTHF) a safer choice to avoid masking symptoms 3
• Patients on certain medications: Those taking anticonvulsants or methotrexate may benefit from folate 3, 2

Potential Risks of Excessive Folic Acid

• Masking B12 deficiency symptoms while neurological damage progresses 3
• Possible increased risk of wheeze and respiratory tract infections in offspring 7
• Potential association with insulin resistance when combined with low B12 7
• Possible increased risk of certain cancers, though evidence is inconsistent 7, 5

Common Pitfalls to Avoid

• Not checking B12 status: Always assess B12 levels when supplementing with either form, especially in older adults
• Assuming equivalence: Folic acid and folate are not interchangeable for all people
• Overdosing: More is not always better - follow recommended dosages
• Ignoring genetic factors: MTHFR polymorphisms affect approximately 30-40% of the population

Conclusion

While both forms can effectively increase folate status, folate (5-MTHF) offers several advantages over folic acid, particularly for those with genetic polymorphisms affecting folate metabolism. The choice between them should consider individual factors such as genetic status, medication use, and risk of B12 deficiency.