Methylenetetrahydrofolate Reductase

Definition

Enzyme crucial in the folate cycle converting 5,10-methylene tetrahydrofolate into 5-methyl tetrahydrofolate. Polymorphisms of this gene affect folate, homocysteine metabolism, and DNA methylation.

How it works

The MTHFR enzyme plays a central role in converting folate into its active, usable form for DNA methylation and nucleotide synthesis. Polymorphisms C677T and A1298C reduce enzymatic activity, affecting folate cycling and potentially increasing homocysteine levels. Elevated homocysteine is a cardiovascular and neurological risk factor. Individuals with these MTHFR variants benefit from higher folate, vitamin B12, and betaine intake.

Role

MTHFR regulates folate metabolism and cellular methylation capacity, influencing detoxification, DNA repair, and disease prevention.

Examples

• Polymorphism C677T - reduces enzymatic activity by 35% in heterozygotes, 70% in homozygotes
• Polymorphism A1298C - less pronounced effect
• Increased homocysteine in carriers
• Increased risk of neural tube defects during pregnancy

Recommendations

If you have the MTHFR C677T or A1298C polymorphism, increase your intake of dietary folates (leafy green vegetables, legumes) and consider a folate active supplement (5-methyl tetrahydrofolate). Ensure optimal B12 levels and sufficient choline to support methylation.

Key takeaway

MTHFR status is a major genetic determinant justifying personalized folate and vitamin B intake.

Related terms