MTHFR Variants
Methylenetetrahydrofolate reductase gene variants — affect folate metabolism and methylation capacity.
Optimal Range
Wild type (no variants) · C677T/A1298C variants are common
Why It Matters
MTHFR variants (present in ~40% of the population) reduce the enzyme's efficiency, impairing methylation — a critical process for DNA repair, detoxification, and neurotransmitter production. Methylfolate supplementation can compensate.
Understanding MTHFR Variants
MTHFR (methylenetetrahydrofolate reductase) is a key enzyme in the folate cycle that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-MTHF) — the active form of folate used in the methylation cycle. The methylation cycle is one of the body's most fundamental biochemical processes, responsible for DNA synthesis and repair, epigenetic regulation, neurotransmitter production, detoxification, and homocysteine recycling.
Two common variants reduce MTHFR enzyme function: C677T and A1298C. The C677T variant is more clinically significant — one copy reduces enzyme activity by approximately 35%, while two copies (homozygous) reduce activity by approximately 70%. These variants are remarkably common: approximately 10–15% of the North American population is homozygous for C677T, and up to 40% carry at least one copy of either variant.
The practical consequences of impaired MTHFR function include elevated homocysteine (due to reduced recycling), impaired DNA methylation, suboptimal neurotransmitter production (particularly serotonin, dopamine, and norepinephrine), and potentially increased risk of neural tube defects in offspring. For individuals with MTHFR variants, supplementation with methylfolate (5-MTHF) rather than folic acid is preferred, as folic acid requires MTHFR to be converted to the active form. Methylcobalamin (active B12) and pyridoxal-5-phosphate (active B6) support the methylation cycle from complementary pathways.