MTHFR Gene
Methylenetetrahydrofolate Reductase - Folate Metabolism
Overview
The MTHFR gene encodes 5,10-methylenetetrahydrofolate reductase, a key enzyme in the folate metabolism cycle. This enzyme reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as the methyl donor for the remethylation of homocysteine to methionine.
Genetic variants in MTHFR can significantly impact folate metabolism, affecting methylation processes, cardiovascular health, and neurological function. Understanding your MTHFR genotype can help optimize your folate and B-vitamin supplementation strategy.
Common Genotypes
C677T TT (Homozygous)
High ImpactEnzyme Activity: Approximately 30% of normal activity
Clinical Significance: This variant is associated with reduced folate conversion efficiency, elevated homocysteine levels, and increased risk of cardiovascular and neurological issues.
Supplementation Recommendations
Supplement Form:
- • Methylfolate (5-MTHF) - Preferred form, bypasses MTHFR enzyme
- • Folinic Acid - Alternative active form
- • Avoid folic acid (synthetic form) as it requires MTHFR for conversion
Recommended Dosage:
- • Methylfolate: 1,000-5,000 mcg daily
- • Vitamin B12 (Methylcobalamin): 1,000-2,000 mcg daily
- • Vitamin B6 (P5P): 50-100 mg daily
- • Betaine (TMG): 500-1,000 mg daily (supports alternative methylation pathway)
Synergistic Nutrients:
- • Vitamin B12 (essential for methylation cycle)
- • Vitamin B6 (cofactor for homocysteine metabolism)
- • Choline and Betaine (alternative methylation pathways)
- • Riboflavin (B2) - supports MTHFR enzyme function
C677T CT (Heterozygous)
Moderate ImpactEnzyme Activity: Approximately 65% of normal activity
Clinical Significance: Moderate reduction in folate metabolism efficiency. May benefit from optimized folate supplementation.
Supplementation Recommendations
- • Methylfolate: 400-1,000 mcg daily
- • Vitamin B12: 500-1,000 mcg daily
- • Consider active B-vitamin complex for optimal support
C677T CC (Wild Type)
Normal FunctionEnzyme Activity: Normal (100%)
Clinical Significance: Normal folate metabolism. Standard folate supplementation is typically sufficient.
Research Evidence
Frosst et al. (1995): First identified the C677T variant and its association with elevated homocysteine levels.
Meta-analyses: Multiple studies have confirmed the link between MTHFR variants and cardiovascular risk, particularly when combined with low folate intake.
Clinical Practice: Genetic testing for MTHFR variants is increasingly used in personalized nutrition to optimize folate and B-vitamin supplementation strategies.
Important Considerations
- • Always consult with a healthcare provider before starting high-dose supplementation
- • MTHFR variants work in combination with other genetic and lifestyle factors
- • Regular monitoring of homocysteine levels may be recommended
- • Individual responses to supplementation can vary