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Sulfation, Sulfoxidation, Glutamate Toxicity, and the Thyroid Connection

picante

Senior Member
Messages
829
Location
Helena, MT USA
I have a bunch of puzzle pieces I'd like to spread out on the table and see if the mighty group brain can put them together for me. I have lots of data, but no idea what tests I should have done next or new remedies I might reasonably try.

The most recent discovery in the saga of my treatment is recorded here for posterity:
http://forums.phoenixrising.me/inde...arguments-confuse-me.21963/page-5#post-625201

Briefly, that is where I ditched reduced L-glutathione cream because I realized that it was provoking glutamate toxicity (and other problems). Thank you, @Freddd.

Since starting methylation supps a year ago, I've been experiencing severe problems with thiol-containing foods, and now I've found another co-traveler: http://forums.phoenixrising.me/inde...lfur-pst-and-sulfate-reducing-bacteria.39415/

@Changexpert and I have different symptoms, but for both of us, the sensitivity came on when we started trying methylation protocols. For me, it marked the return of the digestive problems I had before I started taking T3 for Hashimoto's thyroiditis. T3 controlled this for 6-7 years; it returned with my attempts at methylation.

Before that, I could eat eggs (as many as I wanted), chard, organic cheese, animal protein, and many other things that now knock me down for the count at very low threshholds. We are both in a blind alley with MeB12 and AdB12: for me, all it takes is one drop of liquid MeB12 applied on my skin (approx. 66 mcg) two days in a row. That triggers not being able to eat much of anything.

Strangely, that first day on one drop of MeB12 (AdB12) my cellular thyroid metabolism goes up and I feel better. A few hours after the 2nd day's dose, everything goes to hell.

The symptoms are the same set I have from ingesting glutamates such as autolyzed yeast extract, which I avoid like the plague: immediate helium-balloon bloatation, and I get intensely groggy (Zzzzzzz, I'm in the poppy field in Oz). The tiny doses of B12s aggravate this, and trigger insatiable potassium deficiency. Shoveling in the potassium then triggers B1 and zinc deficiencies, and I have to go off protein and B12s/mfolate to let all this sort itself out.

No, I don't have any +/+ CBS snps. The problems lie elsewhere. Given the +/+ snps I do have, I may be having trouble converting homocysteine to methionine (both pathways). And I suspect problems with conversion of glutamate-to-glutathione and glutamate-to-GABA (based on symptoms). I also suspect problems with sulfite-sulfate conversion.

Other clues I've been putting together:

Sulfite inhibits Glutamate Dehydrogenase: http://www.ncbi.nlm.nih.gov/pubmed/15273247

Glutamate & Thyroid: http://www.ncbi.nlm.nih.gov/pubmed/18543341 T(3) regulates extracellular glutamate levels by modulating the astrocytic glutamate transporters.

γ-Aminobutyric acid production by culturable bacteria from the human intestine

http://www.ncbi.nlm.nih.gov/pubmed/22612585
@Gondwanaland steered me here, so I'm trying a probiotic with Lactobacillus brevis in it now.
 

drob31

Senior Member
Messages
1,487
What foods cause a glutamate issue for you? I'm curious because you mention the bloating and brain fog, and I seem to get that from "something" as well, although I attributed it to hpa-axis signaling issues (hypothyroid myxedema via abnormal cortisol rhythm).
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
What foods cause a glutamate issue for you? I'm curious because you mention the bloating and brain fog, and I seem to get that from "something" as well, although I attributed it to hpa-axis signaling issues (hypothyroid myxedema via abnormal cortisol rhythm).
Hi, drob, I don't know anything about myxedema, and I don't get edema anywhere on my body, AFAIK. Is that something you can have only in the intestines?

I've always thought the bloating was neurological, since it happens before the food even gets to my intestines. Some of the worst dietary triggers for me are:
autolyzed yeast extract
"natural flavors"
sulfites
canned & bottled tomatoes, including pasta sauces
frozen peas
salad bar greens & restaurant salads (sprayed with s.th. to keep them crisp)
hydrolyzed protein
soy protein ______​

There are plenty of others (maltodextrin, enzymes) that are lesser evils, too, and I've avoided them all for years now. Once I bloated up for hours following a cup of Tazo tea at a friend's house. Checked the ingredients a couple weeks later, and it listed "natural flavors". There's also a possibility that the teabag was bleached with sulfite.

What's causing the reaction these days is usually thiol-containing foods like chard, eggs, garlic, etc., and when it gets to the runaway-train stage (from taking B12), any protein will do it.
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Hi @ahmo, thanks, but I'm trying and failing to make sense out of that article. For instance:
My next surprise came from the slow, painful realization that all food on this planet contains natural sources of sulfur dioxide (with the possible exception of distilled water.)
Sulfur dioxide is a preservative, and it's not in everything -- far from it.

The worst offenders are onion and garlic
Oh. Apparently the author has mixed up sulfur dioxide and thiols. That's sulfur bonded with hydrogen, not oxygen. https://en.wikipedia.org/wiki/Thiol

Upon digestion, thiamin is a very weak source of sulfur dioxide, so don't be concerned if your multi-vitamin contains a bit of it. Just don't swallow a high potency B supplement with 50 times the minimum daily requirement of thiamin. Biotin is another story. Biotin is an incredibly strong sulfite.
No, it looks like the sulfur compound in thiamine is thiazole, which is nitrogen and sulfur:
The thiazole ring is notable as a component of the vitamin thiamine (B1).
https://en.wikipedia.org/wiki/Thiazole

Biotin a sulfite??? Here's the chemical structure of biotin: https://en.wikipedia.org/wiki/Biotin
I don't see any SO3 (which has to have a 2- charge to be sulfite).

I have such a minimal understanding of chemistry, it's almost embarrassing to catch these errors.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
i_dunno-1374.gif
sorry for the wasted time.:whistle:
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
@ahmo, I've just gone on a little day trip to try and find out what pyroluria is. Naturally, I ran across a lot of your posts. I filled out the questionnaire you linked (somewhere). My score was 10, which is a strong "maybe".

In my case, sun sensitivity is not really a factor, but hormonal regulation, character traits, joint problems, histamine sensitivity, and sugar problems all weighed in strongly.

I noticed on one thread that you said you had never had the HPU-Urine test. Is that because it was too problematic to go off of B vitamins for 5 days?

Quoting from Klinghardt:
KPU is caused by the defect of several of the 8 enzymes needed for the synthesis of heme
Heme is needed for liver detox reactions (cytochromes), Cystathionine synthase, Catalase, Heme-hemopexin for MT translation, Guanylate cyclase, Sulfite- reductase, NOS, Pyrrolase.
KPU patients have low serum glutathione levels, high NO levels, low histamine

I'm wondering if my increased problems with thiols and sulfites are because my heme went down. Is it possible that the methylation supps could do this to someone with pyroluria???

I'm going to quote you:
I'd used B6, along w/ B3 and B1 in high doses for some years to calm my nervous system. After learning about pyroluria, I switched to active B6, P5P. My headspace changed dramatically, by Day 5. A host of negative thoughts ceased. In that moment, 5 days into a handful of supps that were nearly what I'd been taking for years, the unbearable burden of continuing research to get me out of the hole of my illness shifted. From that moment on, it became an interesting challenge. This was not attitudinal, this was biochemical.

I relate to your biochemical shift, because I experience these frequently. For no discernible reason, I shift from bleak to cheery. And I also see that I'm taking a lot of the supplements Klinghardt lists on page 18 (same link as above), but at lower doses.

Sometimes I feel like you and @Gondwanaland are the snowplows going ahead and clearing the road for me. (There's a Montana image for you. :angel:)

If I have the energy, I'll be on the phone to my ND tomorrow. Boa noite, ZZZzzzz:sleep:
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
I noticed on one thread that you said you had never had the HPU-Urine test. Is that because it was too problematic to go off of B vitamins for 5 days?
No. I wasn't on many supps at that time. Newly on GAPS, ditch all supps. I learned of pyroluria from a GAPS forum as well as MTHFR. I was innundated with alphabet soup, and when I requested homocysteine and MTHFR tests from my GP, forgot to ask for pyroluria. The first time I took the test, my score was low. When I kept seeing references, I retook it, answering for problems I was no longer having. This pushed my score high enough to warrant a gtry. I ordered the supps, and 5 days after receiving them, life was different. BTW, my urine histamine and homocysteine tests showed nothing of note. I haven't bothered to recheck homocysteine, as I'm now doing evderything possible to right this pathway. And histamines are no longer a daily problem, post-FMN.

I'm wondering if my increased problems with thiols and sulfites are because my heme went down. Is it possible that the methylation supps could do this to someone with pyroluria???
No idea.

Sometimes I feel like you and @Gondwanaland are the snowplows going ahead and clearing the road for me. (There's a Montana image for you. :angel:)
deblayer.gif
Here's how it feels from this side:
deneiger.gif
:hug:
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Hemoglobin + MCH always come with a standard RBC count
And those are valid measurements of heme? As needed for the functions Klinghardt lists?
Heme is needed for liver detox reactions (cytochromes), Cystathionine synthase, Catalase, Heme-hemopexin for MT translation, Guanylate cyclase, Sulfite- reductase, NOS, Pyrrolase.

What I'm trying to get at is whether there is a kind of triage happening if there isn't enough heme for everything. Would it go first to hemoglobin, and sacrifice Cytochrome P450 or sulfite reductase?

Who on PR has knowledge in this area?
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
Here's Rich Van K on the relation between pyroluria and the methylation cycle:
KPU stand for kryptopyrroluria. A more proper name for it is HPU or Hemopyrrollactamuria. If you read Scott Forsgren's paper, which Sushi cited, you can get the whole story.

The main things are that it involves an abnormality in the metabolism of heme, and it causes depletion of some important nutrients, including zinc and vitamin B6. The tie-in with methylation is that these are cofactors for enzymes in the methylation cycle and related pathways, so that if they become depleted, even though a person treats with B12 and folate to lift the methylation cycle block, the methylation cycle can still remain blocked. I think that HPU might account for some of the treatment failures of the methylation treatment.

Dr. Klinghardt is finding HPU in a lot of his patients, and I think he reported at the last Lyme Induced Autism conference that it can be a major barrier to restoring the methylation.

I think the corollary would be that treating the methylation cycle block could aggravate pyroluria, since the more you turn on methylation, the more you would deplete the things that are already depleted in pyroluria.

I'm inviting anyone to critique this if you have knowledge about it. Mine is next to nil.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
I began by supplementing for pyroluria: zinc, se, molybd, manganese, p5p. Over time, with detox and methylation protocol, I need less of all of these. Except molybd, which is important for sulfur. And am not having HPU symptoms return.
 

Gondwanaland

Senior Member
Messages
5,077
I think the corollary would be that treating the methylation cycle block could aggravate pyroluria, since the more you turn on methylation, the more you would deplete the things that are already depleted in pyroluria.

I'm inviting anyone to critique this if you have knowledge about it. Mine is next to nil.
When taking high doses of B12 and/or B9, one stimulates RBC synthesis. Think about it.

Well if we consider that all B vits are needed for RBC shynthesis, and if one OD in some Bs and does not compensate the other Bs accordingly, and does not add the needed minerals accordingly, one will certainly run into problems.

My 2 cents.
 
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