MTRR Gene.
Methionine Synthase Reductase
The enzyme that keeps B12 in its active form so MTR can function.
What MTRR does.
MTRR is the helper enzyme for MTR. It reactivates B12 when it becomes oxidized and inactive.
The problem MTRR solves:
MTR uses methylcobalamin (active B12) to convert homocysteine to methionine. But occasionally, B12 gets oxidized and MTR "stalls."
MTRR reactivates the oxidized B12, getting MTR back to work. Without MTRR, MTR would permanently stall.
Think of it like:
MTR is the worker. B12 is the tool. MTRR is the mechanic that keeps the tool working. Even a great worker can't work with broken tools.
When MTRR is slow
- • B12 stays inactive longer
- • MTR function decreases
- • Higher B12 requirements
- • Homocysteine may rise
Common variants.
A66G (rs1801394)
Most common variantThe G allele (Ile22Met) may reduce enzyme activity. Homozygous GG associated with higher homocysteine in some studies.
Frequency: G allele: ~30-55% depending on population
Context matters
MTRR variants seem to matter most when combined with MTR variants or in the context of low B12 status. A single MTRR variant with optimal B12 levels may have minimal impact.
The MTR-MTRR partnership.
These two genes work together. Looking at them in isolation misses the point.
Gene combinations:
- ✓Both normal: Optimal B12 utilization
- ⚠MTR variant + normal MTRR: May compensate adequately
- ⚠Normal MTR + MTRR variant: May compensate adequately
- ✗Both variants: Higher B12 requirements likely; more vulnerable to deficiency
Genes don't act alone.
MTRR doesn't determine your fate. It reveals where the system might need support.
Where it matters
MTRR is expressed wherever MTR is active—essentially all tissues, with particular importance in rapidly dividing cells.
Expression depends on
- • Nutrient availability
- • Sunlight exposure
- • Toxin burden
- • Cell turnover rate
- • Age and hormonal status
SNPs are throttles, not defects
Genetic variants often slow down pathways to protect the system from overwhelm. They reveal where you need to go slower, not that you're broken.
The real question
Not "what does this gene do?" but "what is this pathway already struggling with that makes this gene relevant?"
Related patterns
"Genes don't cause outcomes. They reveal where the system is already under pressure."
B12 status trumps genetics.
Even with perfect MTRR genes, you can't reactivate B12 that isn't there.
B12 testing hierarchy:
Support strategies.
Optimize B12 intake
With MTRR variants, you may need more B12 to compensate for less efficient reactivation. Methylcobalamin or hydroxocobalamin are good choices.
Support riboflavin (B2)
MTRR uses FAD (from riboflavin/B2) as a cofactor. Adequate B2 status supports MTRR function.
Consider the whole cycle
MTRR supports MTR which uses methylfolate. The whole system needs to work together—B12, folate, and the genes that use them.
Check for B12 absorption issues
Low stomach acid, pernicious anemia, gut inflammation, and metformin use all impair B12 absorption. Genetics is only one piece.
MTRR keeps the methylation cycle running.
It's not the star of the show—but without it, the star can't perform.