Monday, June 11, 2012

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.

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.

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