- GeneMTHFR, methylenetetrahydrofolate reductase
- Variants testedrs1801133 (C677T), rs1801131 (A1298C)
- What it controlsConverting folic acid into 5-MTHF, the active form
- If reducedAbout 30% of normal enzyme activity with two copies of 677T
- What changesFolate supplied as methylfolate, with B12, B6 and riboflavin
What the gene does
Folate from food and supplements arrives in forms your cells can't use directly. One enzyme performs the final step that turns it into 5-methyltetrahydrofolate, the version that circulates and does the work. MTHFR builds that enzyme.
That step feeds the methylation cycle, which recycles homocysteine back into methionine and supplies methyl groups to hundreds of downstream reactions. Slow the step and folate piles up in unusable forms while the usable pool stays thin.
What the variant changes
The C677T variant swaps one amino acid and destabilises the enzyme. Two copies leaves roughly a third of normal activity, one copy leaves an intermediate level. A1298C has a milder effect on its own, and the two can occur together in the same person.
This shows up in blood. A meta-analysis of 40 studies found 677TT carriers had consistently lower blood folate than CC carriers, across both trials and observational work.
What it means for you
If you carry a reduced-activity genotype, taking more folic acid doesn't fix the problem, because the bottleneck is the conversion rather than the supply. Methylfolate is already in the active form, so it skips the weakened step entirely.
Folate also doesn't work alone. B12 accepts the methyl group, B6 handles the next branch, and riboflavin is the cofactor the MTHFR enzyme itself binds. Riboflavin status changes how strongly the genotype affects homocysteine, which is a practical reason to supply B2 alongside folate rather than on its own.
What your formula does
Where a reduced-activity genotype shows up, your formula supplies folate as 5-MTHF rather than folic acid, at a dose scaled to how much activity the genotype predicts you've lost, with B12, B6 and riboflavin alongside it.
The full literature review. MTHFR variation, folate activation and the case for methylfolate, covering both variants and ten published human studies. Read it (10 references)
Find out which version you carry
One saliva test reads MTHFR alongside 56 other nutritional markers, then builds a formula around the answer.
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