Comments on Marcia's case

[Guest guest]

Hi, Marcia.

I've been doing some thinking about your case over the past few

days. I understand the situation you are in with the dental work so

badly needed, glutathione being low and seemingly impossible to

raise up, genetic testing being expensive, and money being tight.

I've gone back over everything you've reported beginning with the

ION and initial RBC glutathione test results last July, and up

through the DMPS-challenged urine test and the unpleasant stuff that

followed that, as well as the second RBC glutathione test.

What I've tried to do is to see if I could explain all the

observations, and make a good guess about whether or not you have

genetic variations impacting your methylation cycle, without getting

the expensive genetic variations panel. When you got the ION test

results last July, it was before I knew of Amy Yasko's work. Now

that I have some understanding of that, I can bring that to bear on

your ION test results, which I couldn't do before (I'm sorry that

you have to suffer through my learning curve, Marcia.)

So here's what I've come up with:

I gather that you have increased your intake of eggs and methionine

since the ION test, and I don't know what effects those have had,

because we don't have later testing. My comments will apply to what

went on prior to the ION test.

Prior to the ION test, I think the situation was as follows: I

think that your dietary intake of methionine and cysteine was low.

This resulted from your low intake of animal-based protein: you

don't eat much meat because you don't like it, you didn't consume

much in the way of dairy products, and your chickens weren't laying

many eggs. You didn't respond well to whey protein, so you weren't

taking much of that.

I believe that this low intake of methionine accounted for your low

measured plasma methionine level.

This low methionine intake also meant that the production of SAMe

from methionine was low. SAMe is the main methylator in the body,

and 70% of its methylation capacity is used to make creatine, which

eventually breaks down to become creatinine. Your creatinine level

was below the normal range. I think the low SAMe production

accounts for that.

My best guess from all the evidence available is that you don't have

genetic variations that are impacting your methylation cycle.

Here's the evidence that I believe supports this conclusion:

1. Your methylmalonate and Figlu levels were normal. This

suggests that your B12 and folate statuses were normal.

2. When you used methyl B12, folinic acid, TMG and taurine, you

noticed no effect, except perhaps a small amount of improvement from

the methyl B12.

3. Your homocysteine level was normal. This in itself doesn't

prove anything, but at least it was not high or low, which would

indicate methylation cycle problems.

4. You have not reported sensitivity to sulfur-containing foods.

5. Your phenylalanine-to-tyrosine conversion was working well,

which means that you didn't have a shortage of tetrahydrobiopterin.

Since the BH4 cycle is coupled to the folate cycle, that suggests

that the folate cycle was O.K. too, and since it is coupled to the

methylation cycle, that suggests that the methylation cycle was

working O.K., too.

6. Your urea cycle appeared to be working O.K., even though the

amino acids in the urea cycle (arginine and citrulline) were low-

normal in concentrations.

So for what it's worth, I don't think you have genetic issues with

your methylation cycle. Am I positive of that? No, but you now

have the evidence for why I think that.

You did have low levels of neurotransmitters, but because your BH4

appears to be O.K. (as I discussed above), I think this must be due

to the low methylation capacity that resulted from the low SAMe. We

know that methylation is needed for production of the

neurotransmitters, and we know that your SAMe was low, because of

the low creatinine (above).

We know that you have low glutathione in your blood (from the two

RBC glutathione tests), in your facial nerve ganglia (because you

get cold sores) and probably also in your liver (because of your

steadily rising liver function enzymes). However, your kidneys

appear to have enough glutathione (based on the normal pyroglutamic

acid level in your urine). With low blood glutathione, I would

expect that the skeletal muscles would be low in glutathione, too.

This usually causes a partial blockade at aconitase, which raises

citric acid and lowers alpha ketoglutaric acid (5-oxo-glutaric

acid). However, this was not seen in your ION test. What was seen

was that succinate, fumarate and malate were elevated. This means

that coenzyme Q-10 was low, and there was also independent evidence

for this in the ION test. What I think was going on here was that

the Co Q-10 deficiency was acting so strongly farther on in your

Krebs cycle that the block due to glutathione depletion did not show

up. I realize that you said that you don't respond well to

supplementing Co Q-10, and we discussed idebenone, which you said

you were planning to look into. I don't know if you had a chance to

do that before everything else happened, but I think that would be a

good thing to try. I suspect that if you get the Co Q-10 status up,

though, then the Krebs cycle might be partially blocked by the low

glutathione status and the consequent rise in superoxide and perhaps

peroxynitrite. I suspect that this Co Q-10 block was holding the

oxidative metabolism down far enough that there wasn't much

superoxide generation, and I suspect that explains why the oxidative

stress indicators looked O.K. With low glutathione, I would have

expected to see oxidative stress, but I think this explains why it

wasn't there.

We know that you have elevated body burdens of some heavy metals,

for the following reasons:

1.Your DMPS-provoked urine collection test showed very high mercury

and high tin.

2. Your Clifford sensitivity test showed strong responses to

mercury, nickel, and some other metals.

3. We know you have low glutathione and we can infer that it has

been low for quite a long time, while you have had major exposure to

metals from your past dental work. Based on this, it is a foregone

conclusion that you would have elevated levels of metals in your

body.

What effects are these metals producing? We know that they are

provoking an immune response because of the results of the Clifford

test. We can infer that they are causing toxic effects, including

inhibiting various enzymes. These may include glutamate cysteine

ligase and glutathione reductase, both important in keeping the

level of glutathione up, which it is not. They may also be

inhibiting some of the enzymes in the methylation cycle. Even

though they don't appear to have genetic problems, they may be

partially blocked by the metals.

How can we understand your responses to various sulfur-containing

supplements? I'm puzzled by your ability to tolerate NAC well. For

one thing, NAC is able to move mercury into the brain, and there is

evidence that you have an elevated body burden of mercury. For

another thing, NAC should raise your liver's production of

glutathione. Since your glutathione has apparently been low for a

long time, raising it can be expected to cause a ramping up of the

immune system, and this would be expected to cause a Herxheimer

reaction, because you will have accumulated some infections while

your glutathione was depleted. As evidence of this, note that your

response to the whey protein supplements, which would cause the

liver to produce more glutathione, was fever, swollen lymph nodes,

sore throat and greater fatigue. These are not symptoms of an

allergic reaction to dairy products. They are symptoms of the

immune system fighting an infection, i.e. what amounts to a

Herxheimer reaction. So why doesn't NAC produce this same

response? Well, NAC is not imported by the liver cells as well as

is cysteine (from nondenatured whey). Perhaps that explains it. If

you raised the dose of NAC, perhaps you would experience a

Herxheimer reaction from it, also.

You also reported that you cannot tolerate methionine, that SAMe

gave you awful headaches, and that you don't tolerate MSM too well.

How can we explain these observations? I think the first two raise

your methylation capacity, and since it has been running so low,

this change must cause reactions to occur that produce the symptoms,

but I can't be more specific than that. What about the MSM? I'm

not sure, but perhaps the dose of sulfur was sufficient to overload

the sulfite oxidase pathway, so that sulfite rose, and that gave you

symptoms. Taking supplemental molybdenum may help with this.

You asked me about bupleurum and NT factor and why they are helping,

when the autism supplements did not. I've explained why I think the

autism supplements didn't help, i.e. because I don't think you have

genetic issues with your methylation cycle enzymes. Among other

things, this conclusion was based on your lack of response to the

autism supplements, so I think it was a worthwhile experiment, even

though you may have your doubts about that! I mean, it was probably

cheaper to try all those supplements than to get the genetic testing

done, and I'm fairly sure now that you don't have those genetic

issues. Concerning bupleurum, I don't know much about how it works,

but it is supposed to help the liver, among other things.

Concerning NT Factor, here's what I think: You probably recall the

results you got on the fatty acids part of your ION test. Your

fatty acids were high, including the essential omega-3 and omega-6

ones. What I suspect is that your body is not able to utilize them

to build phospholipids very well. I'm not sure why. Perhaps the

low glutathione or the high metal levels are blocking this. In any

case, if you can't use the EFAs to make phospholipids, your

membranes are going to be suffering. Now, enter NT Factor. This

stuff has ready-made phospholipids that are in good shape and can be

delivered directly to the membranes to be used. They are probably

building up your membranes, both the cell plasma membranes and the

mitochondrial membranes. That would improve mitochondrial function

as well as the function of the transport proteins and ion channels

in the membranes in general.

In view of all of the above, what do I think you should do at this

point? Well, I do think that even though it hasn't been very

successful so far, the best thing would be to keep working to try to

build up your glutathione. If you can still tolerate NAC well, I

would suggest taking that, because it won't provoke a rise in SAMe,

which the whey protein products will as a result of their high

methionine content, and it should help the liver to make

glutathione. However, putting in the RenewPro must be building

glutathione, too, because of the immune system ramp-up that

apparently occurs when you do it, so I would suggest keeping the

pressure on with this, also. I think that the liposomal glutathione

would also be a good form to use, because it will bypass any enzyme

inhibition that might be caused by the metals, it also won't provoke

a rise in SAMe and give you symptoms from that, and it should put

glutathione directly into all types of cells, including liver cells.

Other methods of getting whole glutathione into the blood (such as

the suppositories and the IVs) would probably be beneficial too,

even though the kidneys and the lungs get most of this glutathione.

I do think that your best bet is to build glutathione before you do

too much more that would involve vaporizing mercury from your dental

metals, because that will give you more exposure and push your

glutathione down further, perhaps provoking the kind of thing that

happened with the DMPS-provoked urine test, which I suspect bound

and carried out some glutathione and thereby dropped your

glutathione level further, as was shown in your second RBC

glutathione test.

I do think that you should increase you intake of animal-based

protein, if you haven't already done that. The lack of enough

animal-based protein in your diet may have been one of the factors

that prevented your glutathione from rising. Eggs should work, if

you eat enough of them. This should build your methionine and

refill your sulfur metabolism with sulfur metabolites, which I think

it needs. If you do this at the right rate, you should be able to

avoid unpleasant symptoms resulting from too rapid a rise in SAMe,

but still slowly get the levels of the sulfur metabolites up to

where they should be, thus supporting glutathione status.

If you haven't already done so, I would encourage you to try

idebenone, or even Co Q-10 to the degree you can tolerate it. This

should remove the block in your Krebs cycle and give you more

energy, particularly if the glutathione level can also be brought

up, removing the block that the superoxide and maybe peroxynitrite

would put into the Krebs cycle.

Since bupleurum and NT Factor appear to be helping, I would of

course suggest continuing them.

If you haven't already added molybdenum, I would suggest doing that

to raise the capacity of your sulfite oxidase pathway.

I would suggest continuing the 2 grams per day of vitamin C. That

will give you some antioxidant protection, which you need to

maintain in view of the low glutathione.

I guess that's it for now. I hope this helps. I'm sorry about your

continuing ordeal, Marcia. I hope your Easter is as happy as it can

be, under the existing circumstances.

Rich