Theory

The Methylation U-Curve

Too little is bad. Too much might be worse.

The Common Assumption

MTHFR variant means undermethylation. Undermethylation is bad. Therefore: take methylfolate, methylB12, and push methylation up.

This logic assumes more methylation is always better. Research says otherwise.

What the Research Shows

45-46%

of schizophrenia cases show overmethylation, not undermethylation

24-48h

High-dose methylfolate often triggers anxiety and panic within this window

The U-Shaped Curve

Too Low
Optimal
Too High

Problems (height) at both extremes. Narrow optimal zone in the middle.

Like many biological systems, methylation follows a U-shaped curve where both deficiency and excess cause pathology. The therapeutic window is narrow and highly individual.

What counts as "optimal" varies by person, by tissue, by life stage, and by current oxidative stress load. There is no universal target.

Signs You've Pushed Too Far

Anxiety or panic
Irritability, anger
Insomnia
Racing thoughts
Muscle tension or pain
Headaches
Heart palpitations
Worsening OCD symptoms

These often appear within days to weeks of starting or increasing methylation support.

The Theory

Having an MTHFR variant doesn't automatically mean you need more methylation. It means your body runs at a different setpoint.

Pushing "to fix MTHFR" can override protective mechanisms that exist for good reasons. The variant might be protecting you from oxidative stress, cancer, or other problems that come with high methylation.

The Methylation U-Curve Discussion