Histadelia and Other Approaches for Bipolar Disorder

Readers interested in reviewing entries for histadelia (brain undermethylation and folate accumulation) can start at the 12/3/10 post on histadelia and bipolar depression and go on from there.
Most of the posts which follow are on histadelia, although from July 21 to Aug 20, 2011,  I talk about histapenia, in many ways the opposite biotype.
The early histadelia posts are more basic. Recently, I have turned the focus to histadelia biochemistry.
Remember, though histadelia is the largest biotype in bipolars, any combo of pyroluria, histapenia, allergies/immune dysfunction, oxidative stress, metal metabolism issues, Candida, blood sugar problems, hormone imbalances, toxicity, neurological disorders, etc., may be the relevant factor(s) for a specific individual.
 
To get a comprehensive view, you may want to look through my book,  Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.


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

Bipolar Histadelia and Sulfur: V-e. A Summary.

Histadelia (brain undermethylation) is the primary imbalance in an estimated 35% of bipolars. Most histadelics have problems in the trans-sulfuration pathway, because it is so closely connected to the methylation cycle.  On the one hand, methylation cycle distortions change precursor availability and enzyme activation in the trans-sulfuration pathway. On the other, insufficient sulfur antioxidants and high oxidative stress, will interfere with formation of methyl-B12 and divert too much homocysteine into forming sulfur compounds, compromising the methylation cycle. (Walsh)
To resolve sulfur issues, increasing glutathione and other antioxidants turns out to be sufficient for some histadelics. However, in a significant number of cases, attention to some of the other trans-sulfuration issues we have been discussing becomes necessary.
See part 4 and 5 of this diagram.

How trans-sulfuration problems can impact histadelia and bipolar symptoms:

1 Skyrocketing oxidative stress can compromise brain methylation. Causes may include:
— overactive SUOX, creating a buildup of ammonia and toxic sulfurs, and fostering excitotoxicity
— a buildup of toxic sulfur compounds due to poor sulfite to sulfate conversion.
— drastically reduced formation of glutathione and sulfur antioxidants

Glutathione then becomes much less available to connect to B12 and enable formation of methyl-B12. Blocking this step, formation of methionine and SAM, and methylation of DNA and proteins are impeded.*
For a review of undermethylation symptoms, see here and here. 

2  Poor sulfation compromises normal metabolism of mood-altering molecules and toxins.

— If sulfate is low (whether due to excess urinary loss, or reduced sulfate formation), then sulfation tends to be compromised. This leads to phenol accumulation and increased sensitivity reactions, inflammation,  and oxidative stress.
—  Poor sulfation can also compromise amine metabolism. This can lead to an accumulation of stimulatory neurotransmitters and altered regulation of estrogen and cortisol, contributing to anxiety, tension, irritability, insomnia, mania, etc.

3 Formation of taurine may be compromised.
—   Taurine is a critical inhibitory neurotransmitter, lack of which would tend to destabilize mood, and foster overstimulation, neurological instability, tension, irritability, etc.

4  Increasing toxicity compromises brain function.
Toxicity can be due variously to lack of sulfur antioxidants and glutathione, poor metabolism of sulfurs, phenol and amine accumulation, overproduction of ammonia (which creates brain fog) and sulfur compounds, excitotoxicity and profound oxidative stress. Toxicity can attack receptor accuracy, second messaging, axonal transmission, neurotransmitter systems, astrocyte activity, as well as specific brain structures. Functional deterioration may manifest as learning or behavior disorders, depression, mood instability, OCD, dementia, etc.,  and in severe cases in the very young, especially if metal metabolism is suppressed, autistic symptoms. (See Notes, next post.)

*The betaine pathway may take up some of the slack in some individuals. Nevertheless, problems with the transsulfuration pathway generally foster undermethylation.


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 for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician.
 
For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder
                available here.

To contact me, click here.

Histadelia and Methylation. Part IVB: SAM to HCY

1. In giving up its methyl to proteins and DNA, SAM becomes SAH.

2. SAH then releases adenosine and re-forms homocysteine. 
See diagram here.

SAH accumulation when adenosine is over-elevated
This latter reaction (2), however, is suppressed if adenosine and homocysteine are already excessive. Moreover, the reaction itself is reversible.

When SAH accumulates, it suppresses methylation (by inactivating methyltransferases).

This situation is usually due to severe oxidative stress, interfering with both methylation and glutathione availability.*

* Note: And is common in autistics. A study by Dr. S. Jill James, for instance, finds methionine, SAM and glutathione low, but excessive SAH, adenosine, homocysteine and oxidized glutathione. Sulfur antioxidants, including glutathione are excessively low, but excreted in the urine. Severe oxidative stress (compounded by metal metabolism dysfunction) interferes with methionine formation via methyl B12, thus compromising methylation. Further discussion of autism chemistry here.

Histadelic bipolar treatment (Walsh) 

(In presence of severe oxidative stress, creating SAH and perhaps some HCY accumulation.)

1 Supply glutathione to create homocysteine from SAH, and to attach methyl to B12 so it will convert HCY to methionine. Or, methyl-B12 may need to be provided directly.

2 Address any factors worsening oxidative stress, such as metal metabolism dysfunction.


On the other hand, if the cycle proceeds normally, we get:
SAM methylation reactions  --via methyl transferase--   yield SAH
SAH  --via  SAH hydrolase--- yields adenosine + homocysteine

At homocysteine we come to diverging paths

1 Homocysteine may continue within the methylation cycle.
2 However, when more glutathione is needed to support the methyl B12/ methionine synthase step, which turns homocysteine into methionine,
homocysteine is diverted down the transsulfuration pathyway to create more glutathione.

See Dr. Deth's discussion of this choice point here:
 

Our next post, will explain more about the Trans-Sulfuration Pathway, which, when functioning well, creates critical sulfur antioxidants, and ultimately transforms or eliminates problematic sulfur compounds and other toxins.

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 for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician. 


For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder
 

Histadelia and Methylation. Part IB. What is Methylation?

Methyl is CH3, a carbon with three attached hydrogens.
Methylation, simply put, is the addition of methyl to a molecule.
An example: Serotonin is methylated to form melatonin.

The connection to histadelia

High histamine.  Methylation is needed to metabolize histamine. When insufficient, histamine accumulates. An inherited tendency to brain under-methylation seems to be a major cause of histadelia.
Low catecholamines and serotonin. Undermethylation of both the dopamine/norepinephrine cycle and the serotonin cycle often leads to low levels of these neurotransmitters.
Folic acid accumulation. Since folic acid is not being easily methylated into its more active form, it tends to accumulate.

What the methylation cycle does:
   1. Provides methyl to create phosphatidylcholine, melatonin, epinephrine, carnitine, Co-Q10, creatine, and other molecules critical to mental and physical functioning.
  2. Helps govern (usually silencing) gene expression (the process by which DNA manifests the directives encoded within it, by causing specific proteins or RNA to be produced).
  3. Helps regulate the formation of taurine, cysteine, glutathione and other sulfur molecules. 

Both the neurotransmitter under-methylation and the elevated histamine contribute to histadelic characteristics.

For more info, see my book, Natural Healing for Bipolar Disorder