My Story - Page 4

[tanyalynn]

I wanted to summarize a bit of Cutler's book on detox pathways, wasn't sure where to do it but I figured I might as well do it here cause it's been helpful to me.

I can't figure out any phase 1 only test substance except caffeine--everything goes through phase 1, but some is excreted after that, and some needs further processing. I wanted to write up a better list of what goes where with phase 2 to help folks problem-solve. There's some overlap between various phase 2 pathways, but I think the more toxic among us have had a cascade effect, where one or more pathways gets relatively full, putting extra pressure on another, which then backs up (more to detox than nutrients needed to make these processes go), and it cascades into, well, me.

After phase 1 processing, various drugs, chemicals and foods need further processing by different pathways, some of them are:

glutathione conjugation--
-acetaminophen (tylenol), penicillin, tetracycline, ethacrynic acid
-toxic metals (like mercury, but I think most--not sure about aluminum), styrene, acrolein, ethyl oxide, benzo pyrenes, methylparathion, chlorobenzene, anthracene, tetrachlorvinphos, petroleum distillates, naphthalene (I think many of those are environmental chemicals, the cleaning/furniture/clothing stuff we're supposed to avoid)
-dietary/endogenous origin: bacterial toxins, aflatoxin (from peanuts, I think), lipid peroxides, ethyl alcohol (is this the kind in alcoholic drinks?), quercitin, N-acetylcysteine, prostaglandins, bacterial toxins, bilirubin, leukotreine A4

sulfation--
-acetaminophen, methyl dopa, minoxidil, metaraminol, phenylephrine
-aniline, pentachbrophenol, terpenes, amines, hydroxylamines, phenols
-dietary/endogenous origin: DHEA, quercitin, bile acids, safrole, tyramine, thyroxine, estrogens, testosterone, cortisol, catecholamines, melatonin, 3-hydroxy coumarin, 25 hydroxy vitamin D, ethyl alcohol, CCK, cerebrosides

The Feingold diet limits several of the things in sulfation.

**I wonder if people low in D but who are also on Feingold or sensitive to this stuff should supplement D, or wait til they get their sulfation going better before starting.

glycine conjugation (a kind of amino acid conjugation)--
-salicylates, nicotinic acid, chlorpheniramine, brompheniramine
-benzoic acid, phenylacetic acid, napthylactic acid, aliphatic acid, organic acid
-dietary/endogenous origin: bile acids, cinnamic acid (is this related to cinnamon, I wonder?), PABA, plant acids

taurine conjugation (a different kind of amino acid conjugation)--
-propionic acid, caprylic acid
-bile acids, stearic acid, palmitic acid, myristic acid, lauric acid, decanoic acid, butyric acid (lots of saturated fats here)

glucuronidation--
-salicylates, morphine, acetaminophen, benzodiazepines, meprobamate, clofibric acid, naproxen, digoxin, phenylbutazone, valproic acid, steroids, lorazepam, ciramadol, propranolol, oxezapam
-carbamates, phenols, thiophenol, aniline, N-hydroxy-2-napthylamine
-dietary/endogenous origin: bilirubin, estrogens, melatonin, bile acids, vitamins A, E, D and K, steroid hormone

acetylation--
-clonazepam, dapsone, mescaline, isoniazid, hydralazine, procainemide, benzidine, sulfonamides (Jacqueline confirms these are sulfa drugs), promizole
-2 aminofluorine, anilines
-dietary/endogenous origin: serotonin, PABA, histamine, tryptamine, caffeine, choline, tyramine, coenzyme A

**acetylation is apparently, as far as people know, mostly genetic in terms of how fast it is, so to some extent, people are stuck with this one--though then again, maybe the keys to turn it faster just haven't been well-publicized yet

methylation--
-thioracil, isoetharine, rimiterol, dobutamine, butanephrine, eluophed, morphine, levaphanol, nalorphine
-paraquat, beta carbolines, isoquinolines, mercury, lead, arsenic, thallium, tin, pyridine
-dietary/endogenous origin: dopamine, epinephrine, histamine, norepinephrine, l-dopa, apomorphine, hydroxyestradiols

**so those of us with weak adrenals that are relying on adrenaline (epinephrine) surges to keep going are slowing down our methylation. Argh.

[Theloose]

Very interesting, thanks! It looks similar to the tuberose stuff, but a lot more specific. I'll definitely come back later to reread

[lil_miss_understood]

Yes, sulfonamides are sulfa drugs.

[tanyalynn]

I want to add in a bit about DH, because fundamentally I don't understand why he's different from me. Both of us have really, really worn down adrenals, and it seems to be completely different causes. I suspect his gut is very leaky, probably would show up a ton of things if I did some IgG testing on him, and I think it's interrelating to his adrenals--our HCP wants to work on his adrenals first before she thinks his gut will get better (we suspect lots of bacterial imbalance).

First, detoxification: based on how he and his parents can drink caffeinated beverages without consequence (never get jittery, and his dad had no problem stopping cigarettes after his tour in Vietnam, whereas my parents had a heckuva time stopping), I think our bodies work very differently. Maybe if we detoxify nicotine slowly, it hangs around and affects us more, but if we detoxify it quickly our bodies don't become needy so soon? And so it's easier to quit?

So I think DH has fast phase 1. He and his brother and sister all have histories of getting injured and the painkillers they've been given wear off really fast. And in general, if DH got hurt and needed ibuprofen (working on different ways of dealing with stuff like this) he needed a lot higher doses than average to get pain relief (haven't figured out exactly how ibuprofen is detoxified--looked it up, at least glutathione is involved, not sure if other pathways as well). I think acetaminophen had the same problem, and it goes down lots of different detox pathways.

So maybe he has fast phase 2, or at least matched to his phase 1. People in his family have stuff like high blood pressure (I think mag deficiency related) and type 2 diabetes (I know some trace minerals are involved).

Everyone, basically (excepting the tiny minority who hang out in much higher numbers here) in the US is fairly deficient in lots of stuff, so our bodies have to prioritize how we use our nutrients. Maybe somehow his body prioritizes to detoxification, so other stuff (like his leaky gut and tendency toward high BP) are because his body is short-changing nutrients for that stuff? People in my family don't get type 2 diabetes despite less-than-stellar diets. But we get thyroid problems at the drop of a hat--somehow that makes sense with the heavy metal-glutathione issue, but I don't know where we used all our zinc and selenium. DH really didn't eat a stellar diet, it wasn't impressive, so that's not the difference.

eta: oh yeah, this is part of why I think DH's magnesium need and DD's magnesium need is based on doing more stuff--I think in some ways, they're just better at doing stuff, people in DH's family don't have mood issues (no one gets depression, anxiety, allergies, none of that) and in general through their middle years, the issues are just the likely-impending type 2 diabetes, vs me having allergies, mood stuff, thyroid stuff. So I think his higher mag need is related to doing useful stuff, vs for example DS's and my need for extra vit K, which just seems like inefficiency to me.

[tanyalynn]

Originally Posted by TanyaLopez

Well, I'm going to see how high we can go with magnesium for DH, and I may experiment with taurine as well. And our HCP had recommended choline citrate with the magnesium, I need to understand that a bit more (the choline citrate is a liquid, very tart). I think the cysteine-regulation part is the weakest in DH's family, other folks in his family have KP too. They make tons of glutathione, so that's not their issue, and while they may not really consume enough vitamin A in the Price-sense, I don't think they're any worse than anyone else out there. But I think they use up a lot of magnesium, my daughter certainly needs a lot, so I think the lack of magnesium is showing up as a a cysteine issue.

Thanks for the keratin page on your detoxpuzzle site, Shannon, apparently I need to read new things about 5 times before things click and I figure out something likely to play with.

http://www.detoxpuzzle.com/keratin.php
For anyone who hasn't seen it lately.

Originally Posted by whoMe

So I think kp is a sign that calcium ion channels are open. And magnesium is used to help regulate those channels. So open calcium channels creates an increased need for magnesium, as well as kp. At least that's my guess

Originally Posted by TanyaLopez

that's interesting, cause my next guess for family history stuff was taurine, for sulfate. I don't see it in terms of food sensitivities, but in my MIL' s osteoarthritis. And mag and taurine are both important for calcium cahannels, i hadn't quite looked at it that way (screen issues, more typos than usual, sorry).

so, do open calcium channels _create_ an increased need for mag, or are they a symptom of mag deficiency? I need to copy all this to my thread, i think I'm finally getting somewhere. Now I just need to figure out what choline does, and why choline citrate would be different.

Originally Posted by whoMe

I don't know anything about choline yet. From the mag link (I think?) both taurine and magnesium are used to close the channels. mag first, then taurine for the rest.

I think that the main issue is that the channels are open - but why? it's probably different for everyone. It might be glutamate/ammonia or it might be vit D/low calcium or it might be inflammation (not sure on that link yet, but it's got to be there) or any number of things.

The picture in my head is that everyone has billions of calcium channels, and at any given time, some are open and some are closed. We need Mg and taurine to regulate the open ones. In people with kp and other issues with open calcium channels, more are open then there should be, and so suddenly we need way more mag/taurine to try and regulate them back to normal. So open channels/mag deficiency totally would go hand in hand, with channels being held open increasing the requirement for mag (which is where i think we are with dd) and an outright mag deficiency might cause the same symptoms as though the channels were being held open.

Yeah?

Originally Posted by TanyaLopez

I think I see what you mean. For some people, just a lack of magnesium could cause this, but for others, something else is opening Ca channels and artificially inflating the need and so you end up low on mag, and long-term depleting taurine. I can see supplementing magnesium, that doesn't seem inappropriate to me, but taurine? That seems like band-aid, we should be consuming plenty. But if mag is low for whatever reason, i wonder if taurine can try, to some extent, to be used as a replacement, and then it gets low. I don't really understand the taurine connection for sulfate, but cysteine and sulfate have been coming up for a while, and I know magnesium is an issue, and it seems like more than coincidence that taurine is coming up linking them. Given the health issues I'm seeing in DH's family.

I just need to figure out the neurotransmitter implications of choline and taurine and make sure it's not idiotic to supp both at the same time, and then I think it could help (hopefully) DH.

Pulled all this over from the Keratosis Pilaris thread.

[tanyalynn]

I want a link to the sulfur sensitivity thread because I need to re-read it AGAIN.

[tanyalynn]

Another cool quote from whoMe...

I forget which thread to put this in, but low magnesium can make for low vit D levels...
From Shils Modern Nutrition in Health and Disease:
"People with hypoparathyroidism, malabsorption syndromes, and rickets have been reported to be resistant to therapeutic doses of vitamin D until Mg was simultaneously administered... Patients with hypocalcemia and Mg deficiency have also been reported to be resistant to pharmacologic doses of vitamin D."

And I'm reading The Calcium Lie right now (while I was lying in the sun trying to make vitamin D), and the link he makes to a bad ratio of calcium to magnesium (not enough mag) putting stress on the adrenals and causing further mineral imbalances is interesting, DH's family has a _lot_ of the health issues that he discusses. Makes me wonder if maybe, just maybe, we can fix the nutrients, the digestion will heal, and maybe one day gluten could be okay, at least in some forms--spelt bread would make him happy. But the chain of A happens, causing B, causing C looks very relevant to him in particular, and his family in general, although he's the worst off in terms of feeling bad, but the older generation is the worst off in terms of severity of conditions.

[tanyalynn]

And yet ANOTHER cool quote from whoMe (following my question)... this is just for reference so I know where to find it.

Originally Posted by TanyaLopez

whoMe, quick folate question. Food folate naturally comes in 2 forms, the 5-mthf form and the other one (can you tell I'm having problems with the folate terms?). Do the C677 homozygous MTHF people need 2x the food folate just because they can't use the other form, which is about half of what's in real food? Is it that simple, or am I missing something?

And did I already ask, does it make sense that the A1298 homozygous people can probably just consume extra folic acid (to get their 800mcg), and they'll convert it into folate fine, but then they need the extra circulating folate so they convert enough to recycle their BH4? And this is why the food-fortifier people added folic acid, because it's only blatantly bad for the C677 homozygous people, and probably subtly bad for the people with one C677 gene? Because that would be a smaller subset of the population, and the subtle stuff would be hard to see among all the other nutrient issues people usually have.

Originally Posted by whoMe

I don't honestly know where the 2x comes in. Let's see if I can summarize what I do know:

folic acid is in supplements
folinic acid is in foods (and supplements)
methyl folate is in foods (and designer supplements)

folinic acid is used for purines/DNA stuff
methyl folate is used for methylation stuff

folic acid and folinic acid are on the same side, MTHFR-wise

converting from the folinic side to the methyl side stresses the C677T gene
converting from the methyl side to the folinic side stresses the A1298C gene
converting from the methyl side to the folinic side regenerates BH4

so if you have 2x C677T, then you're going to have a REALLY hard time creating methyl folate - so have a rough time making methyl groups

if you have one of each, then you're going to have a sorta hard time converting to methyl folate, and then (my interpretation) the enzyme will be 'in use' so that it also has trouble converting back to folinic and recycling BH4. So you end up kinda low in methyl groups and kinda low in BH4.

if you have 2x A1298C, then it's a lot less clear, cause there isn't the obvious methyl group stuff. My guess is that BH4 would be the biggest issue?

folic acid isn't blatantly bad. folate status is key to a bunch of health issues, and folic acid *does* raise serum folate levels - in everyone. The issue is that the efficiency isn't great in everyone, and that the unconverted folic acid competes for transport/utilization with the active folate. So it's subtle - blood tests show great folate levels, but the body still feels a deficiency. It's this last part that nobody seems to have caught on to yet, and that probably explains a lot of the confusion and at least a little bit of the negative effects synthetic vitamins have on some people. (And I didn't come up with that on my own, but I can't remember now where I read it )