Theory

MTHFR as Purposeful Slowdown

What if your "broken" methylation is actually protecting you?

The Conventional View

You have an MTHFR variant. Your methylation is reduced by 35-70%. The standard advice: supplement with methylfolate to "fix" it. Push that methylation back up to where it "should" be.

But what if this advice is backwards?

The Longevity Paradox

90+

The MTHFR T allele appears more frequently in people aged 90 and older. If it were purely harmful, it should disappear with age.

32%

The TT genotype (homozygous variant) shows a 32% reduced risk of prostate cancer. The "dysfunction" provides protection.

The Theory: Protection Through Slowdown

Methylation isn't free. Every time your body methylates something, it generates oxidative stress through the SAM-ubiquinone pathway. More methylation = more reactive oxygen species = more cellular damage.

MTHFR variants slow this process down. Less methylation means less oxidative stress, less mitochondrial damage, and potentially longer life. The body may be trading short-term capacity for long-term protection.

This explains why methionine restriction (which also reduces methylation) extends lifespan by up to 45% in animal studies. It's not despite the reduced methylation. It's because of it.

The Tradeoff

High Methylation Provides

  • Better DNA synthesis and repair
  • Normal homocysteine levels
  • Proper neurotransmitter methylation
  • Adequate gene expression regulation

High Methylation Costs

  • Higher mitochondrial ROS production
  • More oxidative damage to proteins and DNA
  • Accelerated aging markers
  • Depleted glutathione reserves

Context determines which side of this equation matters more for you.

When Slowdown Protects

High toxic burden
Slower methylation prevents formation of more toxic methylated compounds (like methylmercury)
Already high oxidative stress
Less ROS generation when the system is already overwhelmed
Depleted glutathione
Reduced demand on antioxidant reserves
Post-developmental life
Less need for rapid cell division, more benefit from protection
Cancer-prone tissues
Slower growth, increased apoptosis of damaged cells

The Implication

Rather than asking "How do I fix my MTHFR?" the better question might be: "What is my body protecting me from?"

For someone with high oxidative stress, pushing methylation "to fix the genetics" may actually override a protective mechanism. The variant isn't the problem. It's the messenger.

MTHFR as Purposeful Slowdown Discussion