S.'s case, was: Re: Rich, Kathy: Glutathione buiding and Phase 2 Detox

[Guest guest]

Hi, S.

Thank you for posting the results of your Genovations Detoxigenomic

panel and your homocysteine measurement. Also, thanks for reporting

the results of your B6 and P5P trial. I'm sorry that it caused you

to get toxic, but glad the I.V. glutathione helped to pull you out

of it.

I've been puzzling over your sulfur metabolism for a few days now.

As you will recall, I had suggested that the flow was too slow

through your transsulfuration pathway, because your plasma cysteine,

glutathione and sulfate all came out low, and that was the reason I

suggested supplementing with B6 and P5P, which help the enzymes in

the transsulfuration pathway. I had thought that we might find that

your homocysteine was high, suggesting a block somewhere in the

pathway between homocysteine to cysteine.

However, your homocysteine came out low as well. In addition, you

have reported that you can take ImmunoPro Rx and SAMe without any

problems. ImmunoPro Rx contains methionine, and SAMe is one step

beyond methionine in the methylation pathway, but before

homocysteine. Furthermore, you found that supplementing with B6 and

P5P made you feel worse. So that interpretation was certainly not

correct.

I think that your tolerance of ImmuonPro Rx and SAMe means that the

methylation cycle is not blocked, at least between SAMe and

homocysteine. I think that if it were, SAMe would build up when you

take it, and you would experience some symptoms from that, such as

being kind of hyper or having more sleep problems.

So if the pathway is open to homocysteine, and homocysteine and all

the metabolites after it in the transsulfuration and sulfoxidation

pathways that have been measured are low (we don't have values for

cystathionine or taurine), then there are only two ways I can think

of to explain that. The first possibility is that there is not

enough methionine and cysteine coming in from the gut to fill the

sulfur metabolism up to normal levels. So this either means the

total daily consumption of proteins containing these amino acids is

too low, or protein is not being digested and/or absorbed by the gut

as well as normal.

So my questions to test that possibility are (1) about how many

grams of total protein are you consuming per day, on a dry protein

basis, (2) what kind of protein is it, and in particular is very

much of it animal-based, and (3) how well is your digestive system

working? If you are eating a lot of animal-based protein and it is

not being digested and absorbed, I would expect quite a bit of foul-

smelling flatus to be produced as the intestinal bacteria have a

feast on the unabsorbed protein, so a report on whether that is

present would be helpful as well.

If it's not a problem of supply, then the other possibility is that

the kidneys are wasting sulfate at a higher than normal rate, and

that this depletion is propagating up the sulfur metabolism all the

way to the methylation cycle and is draining the sulfur metabolites

out too fast. It is known that mercury can inhibit the enzymes in

the kidneys that reabsorb sulfate back into the blood, it is also

known that the kidneys are the main target organ for mercury, and we

know that you had a high mercury level measured in your red blood

cells, which would suggest that there might be quite a bit of

mercury in your kidneys as well. So I think this is at least

plausible. I think the way to track this down would be to measure

the 24-hour sulfate loss to the urine. LabCorp offers this test.

If the 24-hour urine sulfate is low, that will mean that there is

not enough protein-based sulfur coming in from the gut, either

because the diet is too low in protein, or because it is not being

digested and absorbed well. If the 24-hour urine sulfate is in the

normal range, then I would say that the protein intake is adequate,

but the kidneys are dumping sulfate too readily, lowering the level

of plasma sulfate and the earlier sulfur metabolites. In this case,

I would suspect mercury as the culprit.

The other topic I've been pondering is your detox system, which of

course ties in with your sulfur metabolism, because glutathione and

sulfate are each responsible for one of the Phase II detox pathways,

and in addition, glutathione lies at the basis of the antioxidant

enzyme system, which among other things takes care of reducing the

oxidizing free radicals generated by the Phase I CYP450 enzymes.

Having both low glutathione and low sulfate, as you do, makes

detoxing difficult.

Starting with your Phase I CYP450 enzymes, you have polymorphisms in

CYP1B1, CYP2C9, and CYP3A4. CYP1B1 is not so significant, but the

other two are responsible for detoxing a wide range of drugs. Your

difficulties with the particular antibiotics that require these

enzymes for their detoxification is understandable in the light of

these polymorphisms.

The null in the glutathione transferase enzyme GSTM1, combined with

the slow metabolizer polymorphism R197Q in the N-acetyl transferase

enzyme are likely causing difficulties in Phase II glutathione

conjugation and formation of mercapturic acids for disposal of some

toxins, perhaps including mercury. The polymorphism in SOD2 causes

an increase in the rate of production of hydrogen peroxide from

mitochondrial superoxide. This may also be interacting with the

GSTM1 null, because the glutathione transferase enzymes play a role

in quenching hydroperoxides as well as in conjugating other toxins

for disposal. As I had predicted, the null in GSTM1 may also

explain the inability of the Spectracell functional test to show a

deficit in glutathione function, while this test did show a deficit

in total antioxidant function, and the comprehensive detox panel

clearly showed glutathione depletion and a state of oxidative stress.

You are probably already aware of this, but in view of the

polymorphisms in important parts of your detox system, I think it

will be very important for you to minimize your exposure to and

intake of toxins by both ingestion and inhalation. This means

trying to breath clean air, drink pure water, and eat foods that are

organic to the degree possible. It also means minimizing exposure

to chemicals such as pharmaceuticals (I realize that this is

difficult, given that you are trying to knock out some pathogens),

pesticides, cosmetics, hair sprays, solvents, and household cleaning

products. I think it would be worth considering regularly taking

small amounts of substances such as activated charcoal that will

bind toxins in your gut and carry them out, in order to assist your

detox system. Including generous amounts of fiber in your diet

would also be a good idea.

You mentioned asking Genovations to send me an original copy of the

report, and asked for an address. Yes, I would like to have a copy

of that, and you can ask them to send it to Rich Van Konynenburg,

444 Ontario Drive, Livermore, CA 94550.

Yes, the Essential GSH might be a good way to get glutathione in

after you pull your PICC line. I'm glad it worked well for Dr.

Vrchota. I'm also glad she's enthusiastic about the DAN!

treatments. I, too, think they have a lot of promise for helping

PWCs.

You asked about using UltraClear. Given your current situation, I'm

not convinced that that would be very productive, since I don't

think it has very high levels of the substances you are lacking. I

think it would be a good idea to measure the 24-hour urine sulfate

first, to try to understand what's going on with the sulfur

metabolism. I guess that's what I have to suggest for now. Again,

I hope this helps.

Rich

>

> Rich et all,

>

> I've got my Genovations results back and of course have a few more

> questions. Rich, your prediction was correct; I have a null for

> GSTM1 (glutathione s-transferase). SNP's for phase 2

detoxification

> are:

> R197Q (N-acetyl transferase, a slow metabolizer SNP)

> SOD2 (oxidative protection for the mitochondria

>

> SNP's for phase 1 detox are: CYP1B1, CYP2C9, AND CYP3A4

>

> HOMEOCYSTEINE CAME BACK LOW - <2.00 (3.-10.0). I had also had it

> checked last June as part of a Hemex panel. It was 5.0 then (5.0-

> 15.0)

>

> Over the last month I tried supplementing with vitamin B6 and P-5-

> P. I took 2-300 or B6 for a couple of days and 17-34 mg of P5P

and

> got toxic - twice. I don't know if it did anything more than

> mobilize toxins. I had to get some IV glutto help get over it and

> that has helped. My HgB and RBC's did go up though so maybe I

> needed the B6. I've read that lyme depletes B6.

>

> I saw my physician and she thinks I should try detoxing with

> Metagenics Ultra Clear. I'm not to hep on the idea. I don't

think

> I'm strong enough to tolerate the toxin release and the diet

itself

> is drastic. - I don't consider a bowl of vegetables a meal; I'd

> rather not eat!! Rich - Vrchota was curious to what your thoughts

> were on using Ultra Clear to help clear the phase2 pathway. She

> also suggested I have Genovations send you an original MD color

copy

> that includes all the drug interactions. I've got a release, if

> you're interested and give me your address I'll have them sent.

>

> She is hoping to get a computer program where she can plug in all

> the SNP's and nulls for a patient and then the drugs she's

> considering prescribing to see what the interactions are. It's

> pretty confusing, the lists are multiple pages. She's also pretty

> excited about the DAN stuff and thinks it will really help her

> patients, she's trying to digest it all and is hoping you'll do

> another poster!!

>

> Vrchota also thought that Wellness's Essential GSH would work

better

> for me (she used it recently when exposed to toxic fumes and food

> and got a great response). I'm pulling my PICC in 10 days and no

> longer will have ready IV access.

>

> I'm interested in any feedback you have or questions others may

have.

>

> I much appreciate your generosity,

> S.