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 Sulfurs: Part V-c: Sulfites to Sulfates

Another subset of high-oxidative-stress, undermethylated bipolars have problems converting sulfites to sulfates. Overloaded sulfites transform into toxic sulfur compounds which increase the burden on antioxidants and detox agents, using up glutathione. Moreover the sulfates which should have been formed are important antioxidant and detox agents, which help spare glutathione. So, again, we can have difficulty joining methyl to B12, impeding formation of methionine and SAM, thereby fostering undermethylation.

Difficulty metabolizing sulfites to sulfates can be due to

A simple lack of molybdenum.

Chronic overload of sulfur compounds.

Underactivity of the enzyme, SUOX (sulfite oxidase) which catalyzes the oxidation of sulfite to sulfate.  

The basic chemistry is 
Sulfite + molybdenum + B6 (P5P) + SUOX  yields  Sulfate
See Methionine cycle, step 4, lower half of diagram. 

or lower right of this diagram

CONSIDERATIONS.
Check for elevated urinary sulfites.
Doing okay with sulfates and taurine (which converts to a sulfate without using SUOX), but reacting to sulfur supplements and foods, especially eggs, suggests sulfite to sulfate conversion problems.

Sulfates are needed in nerve, bone and cartilege formation, mucin creation, liver detox, and catecholamine inactivation. Thus, the following conditions may be associated with low sulfate formation (or with low sulfation):

—Overstimulation: Sulfation inactivates thyroid hormone and catecholamines (e.g., dopamine).  (Interesting overview at http://what-when-how.com/molecular-biology/sulfation-molecular-biology/)
— Inflammation.
—Migraines.
—Arthritis and other joint/cartilege maintenance and repair problems (think MSM and glucosamine).
—Digestive symptoms: leaky gut, irritable bowel, low stomach acid, gall bladder hypofunction (problems with fats), low digestive enzymes, constipation.

TREATMENT APPROACHES  (Petryka,  Roberts)

Molybdenum (in legumes) helps form sulfate (as well as BH4 -- see previous post). Low uric acid or intolerance to alcohol can also suggest low molybdenum.
P5P (a form of B6) may also be needed.
However, too much of either can be counterproductive.
Hydroxy B12, boron, and vitamin E (along with the molybdenum 2x/day) may help increase SUOX activity. (Roberts)
Restict/avoid sulfites. (An upbeat non-medical discussion of sulfites here).
 

Sulfates, if depleted, will be helpful: 
—Epsom salt (magnesium sulfate).  Can be added to baths, but this is contraindicated if there is any danger of falling asleep in the bath, or if taking antipsychotics, anxiety or sleep meds, or consuming alcohol or other suppressants. An epsom salt foot soak, epsom sprays, or creams may be used instead.  Or a combo of sources.  E.g., see enzyme stuff, about half-way down the page. 

—Taurine.
—MSM, glutathione sulfate, or NAC may or may not help.

Phenol and salicylate restriction is often indicated as sulfates are used up in their metabolism. More on phenols and salicylates next post.

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 at  boragebooks.com/orderBooks.html