Histadelia and Methylation. Part II: B12 and folate

Folic acid accumulation, methyl-B12, and histadelic bipolar disorder

Dr. Walsh, 2008:  "For most undermethylated persons, folate and B12 are critical to therapy. However, psychiatric patients with abnormal levels of norepinephrine, dopamine, or serotonin are an exception to this rule. They represent a special case, in which the methyl/folate ratio in the brain becomes the predominant concern."

We are focused here on our step #1 in the methylation cycle:
Homocysteine  --via methyl folate + methyl B12--  yields methionine
See: Diagram of the methylation cycle.


Here is what is supposed to happen:

1A
Folic acid  --methylene-tetrahydro-folate-reductase + SAM--  yields a methyl-folate (5-MTHF)
That is:
Folic acid is methylated by 5-MTHF-R to create 5-MTHF  (methylene-tetrahydro-folate), a methyl folate, the active form of folic acid.

1B
Homocysteine  --via methionine synthase + methyl B12*--  yields Methionine
That is:
Methyl is transferred from 5-MTHF  to B12, creating methyl-B12 (methyl-cobalamin).  
The enzyme, methionine synthase, transfers the methyl from methyl-B12 to homocysteine, converting it into methionine.

* Or via the betaine (trimethylglycine) pathway: HCY + TMG  yields  Methionine + DMG 

This pathway is enhanced when the b12/methionine path is suppresed, but is not very efficient in some people anyway.

Histadelics can have problems methylating folate due to:

1 Genetic MTHFR  dysfunction (relatively common in schizophrenia, bipolar and autism).

2 Insufficient methyl.

Why should histadelics limit folic acid?

— Histadelic generally already show excess accumulation of folic acid and deteriorate when given folate supplements.

— As Walsh has proposed, folic acid can increase synaptic reuptake, reducing serotonin and dopamine availability in the synapse, worsening the already severe depression of histadelia. (Specifically, folate modifies histones so as to generate acetylase enzymes, which promote expression of transporters, which remove serotonin and dopamine from the synapse, decreasing levels available to interact with receptors.) Increased synaptic reuptake turns out to be more critical to histadelic mood than the potentially supportive effect of folate on methylation. (See Walsh 2010: Depression)

— Other potential problems: difficulty joining methyl to the folic acid or transferring that methyl to B12. Or, folic acid may trap methyl molecules.

Therapeutic approaches  (Walsh)
External methyl sources are given to ramp up the methylation cycle:
   Methionine, SAMe, increased dietary methyl,  as relevant.
Supplemental methyl B12 (or betaine, if indicated) may be needed to insure that homocysteine is metabolized to methionine.
Again, supplemental folic acid is not recommended as it will just increase already high levels of folate.
Note: If  folic acid is not excessive, restriction is harmful to health and is not indicated.

Next post: Histadelia, B12 and glutathione

For more info on histadelia and bipolar disorder, see my book, Natural Healing for Bipolar Disorder

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment bipolar disorder, or any other medical condition, please consult a knowledgeable physician.