MTHFR Gene
The MTHFR gene produces the enzyme needed to convert folate (Vitamin B9) into its active form (methylfolate), essential for DNA repair and detoxification.
Deep Dive
Roughly 40% of the population carries an MTHFR variant that reduces this enzyme's efficiency by 30–70%. The two most studied variants are C677T and A1298C. When this enzyme underperforms, the body cannot adequately convert dietary folate into methylfolate — the active form required for the methylation cycle.
If you have this variant, standard 'Folic Acid' supplements can actually block your folate receptors, making the problem worse. This methylation defect is a root cause of chronic fatigue, elevated homocysteine (a major cardiovascular risk marker), and mental health struggles including depression and anxiety.
The solution for most carriers involves switching from synthetic folic acid to methylfolate (5-MTHF) and supporting the broader methylation pathway with co-factors like methylcobalamin (B12), pyridoxal-5-phosphate (B6), riboflavin (B2), and magnesium. However, the approach must be personalised — some slow COMT individuals cannot tolerate high-dose methyl donors and require a gentler protocol.