What is Quatrofol (folate supplement)?

What is Quatrofol?

Quatrofol is a branded form of (6S)-5-methyltetrahydrofolate (5-MTHF), which is the biologically active, reduced form of folate that the body can directly utilize without requiring metabolic conversion. 1

Chemical Structure and Classification

Quatrofol represents a specific formulation of 5-MTHF, which belongs to the folate family—a group of molecules that vary by oxidation state, one-carbon substitution groups (methyl, methylene, methenyl, formyl, formimino), and glutamate side-chain length. 1 Unlike synthetic folic acid, 5-MTHF is already in the reduced, bioactive form that functions as tetrahydrofolate in cellular metabolism. 1

Key Advantages Over Folic Acid

The primary clinical advantage of Quatrofol (5-MTHF) is that it bypasses the enzymatic conversion step required for folic acid, making it particularly valuable for individuals with MTHFR polymorphisms who cannot efficiently convert folic acid to its active form. 2

Specific benefits include:

• Direct bioavailability: Does not require reduction by dihydrofolate reductase, the enzyme that converts folic acid to tetrahydrofolate 3, 4
• Avoids unmetabolized folic acid (UMFA): Eliminates concerns about accumulation of unmetabolized folic acid in circulation, which can occur with supraphysiological doses of synthetic folic acid 2
• Effective in enzyme deficiency: Works in patients with genetic polymorphisms affecting folate metabolism, particularly MTHFR variants 2

Clinical Applications

Quatrofol is primarily used in fertility support and pregnancy supplementation, where it offers superior safety and efficacy compared to folic acid. 2 The standard recommendation for neural tube defect prevention is 400 mcg daily for women of childbearing age. 1

Primary indications:

• Preconception and pregnancy: Prevention of neural tube defects with equivalent or superior efficacy to folic acid 2
• MTHFR polymorphism carriers: Individuals who cannot efficiently metabolize folic acid 2
• Fertility enhancement: Supporting one-carbon metabolism essential for DNA synthesis and cell division 2

Biological Function

5-MTHF (the active component of Quatrofol) serves as a cofactor in one-carbon metabolism, which is required for:

• DNA and RNA synthesis: Essential for purine and thymidylate production 1
• Amino acid metabolism: Particularly homocysteine remethylation to methionine 1
• Methylation reactions: Critical for gene expression and neurotransmitter synthesis 1

Safety Profile

Quatrofol has an excellent safety profile with minimal risk of toxicity at recommended doses, and unlike high-dose folic acid, does not carry the same concerns about masking vitamin B12 deficiency or causing neurological complications. 2 The upper tolerable limit for synthetic folic acid is 1 mg/day, established primarily to avoid masking B12 deficiency. 1 However, 5-MTHF formulations like Quatrofol may have different safety considerations since they don't accumulate as unmetabolized folic acid. 2

Important safety considerations:

• No UMFA accumulation: Avoids potential deleterious effects of unmetabolized folic acid 2
• B12 interaction: When supplementing with any folate form, concurrent B12 supplementation should be considered, especially in elderly populations 5
• Drug interactions: Caution needed in patients on anticonvulsants, methotrexate, or other folate antagonists 4, 6

Dosing Context

While specific Quatrofol dosing depends on the formulation, standard folate recommendations apply:

• General population: 330-400 mcg dietary folate equivalents daily 1
• Pregnancy/lactation: Approximately 600 mcg daily (double the standard dose) 1
• Neural tube defect prevention: 400-800 mcg daily periconceptionally 1
• High-risk patients (prior NTD): 4 mg daily 1

The key distinction is that 5-MTHF (Quatrofol) is already bioactive, so dose equivalency with folic acid may differ based on individual metabolic capacity. 2