It's not your genetic destiny.
MTHFR variants are common. They affect folate processing, but they don't determine your health fate.
What MTHFR actually does.
MTHFR is an enzyme that converts dietary folate into methylfolate—the active form your body can use.
Methylfolate is then used in the methylation cycle to convert homocysteine to methionine.
The two main MTHFR variants.
C677T (rs1801133)
Creates a "thermolabile" enzyme that works less efficiently.
About 10% of many populations are TT homozygous.
A1298C (rs1801131)
Affects BH4 recycling more than methylfolate production.
Compound Heterozygous
Having one copy of C677T AND one copy of A1298C. This combination has an intermediate effect and is often clinically significant.
The overblown importance.
MTHFR variants are real, but they're just one piece of a much larger puzzle.
What matters more
- • Overall nutrient status (folate, B12, B2, B6)
- • Diet quality and vegetable intake
- • Gut health and absorption
- • Other methylation genes (MTR, MTRR, COMT, CBS)
- • Lifestyle factors (stress, sleep, toxin exposure)
Common misconceptions
- • MTHFR ≠ broken methylation
- • Having a variant ≠ having problems
- • Methylfolate isn't always necessary
- • More methylfolate isn't always better
- • You can't blame everything on MTHFR
Genes don't act alone.
MTHFR doesn't determine your fate. It reveals where the system might need support.
Where it matters
MTHFR is expressed throughout the body, but its impact varies by tissue. Liver, brain, and placenta have high expression. A variant's effect depends heavily on local nutrient availability.
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."
What actually helps.
Riboflavin (B2)
The cofactor MTHFR needs (as FAD). Riboflavin can improve MTHFR function even with variants. Often overlooked.
Methylfolate (5-MTHF)
The active form that bypasses MTHFR entirely. Useful for those with reduced enzyme function. Start low.
Vitamin B12
Required to use methylfolate. Without B12, methylfolate can get "trapped" and unusable.
Betaine (TMG)
Provides an alternative methylation pathway via BHMT. Can support methylation without relying on MTHFR.
Avoid Folic Acid
Synthetic folic acid requires MTHFR to be converted. With reduced function, it can accumulate unconverted. Look for methylfolate or folinic acid instead.
What MTHFR connects to.
Homocysteine
Reduced MTHFR can lead to elevated homocysteine if folate/B12 status is also poor.
Methylation
MTHFR supplies methylfolate for the methylation cycle, affecting DNA methylation and neurotransmitter synthesis.
BH4
A1298C variant particularly affects BH4 recycling, impacting neurotransmitter synthesis.
COMT
Both MTHFR and COMT affect methylation. The combination matters more than either alone.