Re: Comments on Sue T.'s test results

[Guest guest]

Hi, Sue.

As we've discussed backchannel, I want to make some changes to the

comments I made on your test results, now that I have some new

informtion. As you know, since I wrote these comments you shared

with me backchannel that by the time you submitted urine samples for

both the Metabolic Analysis Profile and the Urine Amino Acids test,

you had already been on a new low-protein, high-carbohydrate diet

for a few weeks, but you were supplementing with branched-chain

amino acids. In addition, you shared with me that at the time you

submitted the urine sample for the Metabolic Analysis Profile, you

had been in a fasting condition for several hours overnight, while

the 24-hour urine sample for the urine amino acids test was

accumulated over a normal day that involved eating meals.

In addition to this information from you, I have also gone back and

reviewed some papers that I had read earlier but had forgotten

about, and was jogged by reading what Amy Yasko has been saying

about the transsulfuration pathway. This introduces a new

possibility to explain why your glutathione seems to be staying low.

I think all of these factors make your test results much more

understandable. So please ignore my earlier message. I'm going to

copy what I wrote before, and then change certain parts, using this

new information. This new revised writeup will then contain all my

current comments on your tests. Here it is:

I have now studied all the test results and updates you have sent me

recently, including the Great Smokies Metabolic Analysis Profile,

the two Doctor's Data urine metals panels, the Doctor's Data urine

iodide analysis, and the urine amino acids results, which I presume

are from Genova (Great Smokies). Here are some comments on these

results:

1. Your urea cycle is working well, and your ammonia is now under

control, based on your urea cycle amino acid ratio. That should be

very beneficial for your brain, in particular, since ammonia is a

neurotoxin. This improvement is likely due in large measure to your

new low-protein, high-carbohydrate diet, which should have resulted

in less ammonia production from the breakdown of amino acids.

2. Your capacity to carry on methylation reactions is now up to

normal, based on your normal 24-hour creatinine excretion. I think

this corresponds to your high-normal methionine level now, compared

to your low normal plasma methionine level in the test last December.

Since you are on a low-protein diet, the only way I can explain the

good methylation capacity and the high-normal methionine is that

your methylation cycle must be operating in such a way that quite a

bit of the homocysteine is being converted back to methionine. I

suggest that the supplementation of methyl B12 has helped to remove

a block in this cycle.

3. Your status of B-complex vitamins (not including B6 and B12) is

good, based on low levels of intermediate metabolites of the

branched-chain fatty acids, which you are supplementing.

4. Your folate status appears to be a little low, based on FIGLU,

histidine and sarcosine levels.

5. Your vitamin B12 status still appears to be a little low, also,

based on methylmalonate. I suspect that your supplementation of

valine, one of the branched-chain amino acids, may be placing more

demand on B12, which is needed for its breakdown.

6. Your vitamin B6 status also appears to be a little low, based on

beta alanine, alpha aminoadipic acid and alpha amino-N-butyric acid

levels.

7. There still appears to be some gut dysbiosis, based on beta

alanine and 2-hydroxyphenylacetic acid levels.

8. There is a high rate of excretion of taurine in the urine. This

is likely caused at least to some degree by the high beta alanine,

which in turn is likely being produced by unfriendly bacteria in the

gut. Another possible cause of the high taurine might be that it is

high in the plasma (for which we don't have data). High plasma

taurine would be expected from the high cysteine, since high

cysteine causes an upregulatin of the enzyme cysteine dioxygenase,

and a downregulation of glutamate cysteine ligase. The result is

that more of the sulfur metabolite flow is directed toward the

production of taurine, and less toward the production of glutathione.

9. It appears that at the time of the Metabolic Analysis Profile,

your metabolism was using as fuel primarily amino acds from the

breakdown of your own muscle protein and supplementary branched-

chain amino acids, and was not using much in the way of

carbohydrates or fats. I think this corresponds to the fact that

you had been fasting for several hours before submitting the urine

sample for this test, and that your reserves of glucose and glycogen

had likely become depleted. You had low pyruvate and lactate,

suggesting little output from glycolysis of carbohydrates. You also

had elevated levels of threonine and 3-methylhistidine, which

suggest that your skeletal muscle protein was being broken down and

burned for fuel more rapidly than normal. You had somewhat

elevated levels of leucine, isoleucine and valine (the BCAAs), and

also elevated succinate and fumarate. All of this probably results

from your supplementation of the BCAAs and burning them for fuel

(The low B6 status could also be contributing to the elevated BCAA

levels). Your low lysine was probably due to the low-protein diet,

and it suggests that you would also have had low carnitine (not

measured), which is made from lysine, and that would slow the import

of fatty acids into the mitochondria to be burned for fuel. You also

had low alanine. Alanine is the carrier of ammonia to the liver

from the muscles when the muscles use amino acids for fuel. Alanine

is also responsible for feeding the gluconeogenesis process in the

liver by its own breakdown, which produces glucose for the blood and

maintains its level. I expect that the need for gluconeogenesis was

very high at the time this sample was submitted, because you had

been fasting for several hours. I think that accounts for the high

consumption of alanine and thus a low excretion of alanine in the

urine.

10. Although this is somewhat masked by reliance on your own

muscle protein and supplementary branched-chain amino acids for

fuel at the time of the test, it appears to me that your glutathione

level is still below normal. One piece of evidence for this is the

low pyroglutamic acid, which suggests that the kidneys are low in

glutathione. Another is the high normal level of citric acid,

together with low normal levels of the Krebs metabolites that follow

it (cis-aconitic and isocitric acids), which suggests a partial

block at aconitase, which low glutathione is known to produce, via a

rise in superoxide and probably also peroxynitrite. Had you been

burning more carbohydrates at the time of the test, as would have

been evidenced by more elevated pyruvate and lactate, I think this

partial block would have shown up more clearly.

11. It is interesting that you had very high cysteine

excretion in the urine. I suspect that this reflects a high plasma

level of cysteine, also, though we don't have data for that

directly. It isn't clear to me why your cysteine is elevated. As

you know, you do not have the main CBS SNP that speeds up the CBS

reaction and moves more sulfur metabolite flow from homocysteine

down the transsulfuration pathway, and it also appears, as noted

above, that you are getting considerable flow from homocysteine back

to methionine. But, as you pointed out to me, we don't know yet

whether you have any of the other CBS SNPs, and since you did have

an ammonia issue, this seems like a possibility.

As noted above, it is known that high cysteine causes upregulation

of the cysteine dioxygenase pathway down to taurine and sulfate, and

downregulation of the production of glutathione, and this may

account for your low glutathione status. Another possibility is

that the rate-limiting enzyme for the synthesis of glutathione

(glutamate cysteine ligase) may be blocked by mercury or another

heavy metal toxin. Mercury is known to block this enzyme at high

enough concentrations, and we know from the urine metals tests that

you are currently excreting measurable amounts of mercury in your

urine. Whether your mercury level is high enough to block this

enzyme, I don't know.

12. The high level of iodide in your urine does indeed suggest that

you should cease the transdermal use of Lugol's solution, which you

reported that you have done. I'm glad you tested this. Too much

iodine supplementation can lead to thyroid problems.

13. Your first two sequential urine metals tests show that you can

indeed influence your levels of essential elements using Amy Yasko's

protocols. The use of EDTA may have removed some nickel, since the

rate of excretion of that appears to have dropped. EDTA is not an

especially good chelator for mercury. I agree that it appears that

the EDTA pulled down both your copper and your iron level, and

stopping it does appear to be a good idea, so that you can get your

iron level back up.

All in all, Sue, I think you are making progress. In view of all

these test results, in addition to the things you have already done,

I would suggest the following:

1. Increase your supplementation of folate, as Folapro and folinic

acid. I'm not sure on the dosage, but maybe doubling what you are

taking now would be a good idea.

2. Increase your supplementation of methyl B12, again maybe

doubling it.

3. Take supplemental B6, or even better, P5P. You could try 100 mg

per day of B6, or perhaps 20 mg of P5P per day.

4. Consider some type of treatment for the gut dysbiosis. We have

discussed this, and I know you are looking for options that don't

involve taxing your detox system, which has genetic issues. Perhaps

Dr. Serafina Corsello's bowel treatment approach would help.

See " The Ageless Woman " (http://www.corsello.com).

5. Consider taking one of the liposomal forms of glutathione,

starting with a low dose to see how well you tolerate it, and

working up. If mercury is indeed blocking your production of

glutathione, this would bypass that problem.

Rich

[Guest guest]

Hi, Sue.

>

> Hi Rich,

>

> I appreciate the revised review and I am grateful that you are

able to help me so much. I agree with most everything that you

mention(as much as I can understand).

***You're certainly welcome.

>

> I am wondering if the small amount of the EDTA may have moved

metals around and that is why I have noticed some hormonal issues

that I mentioned a week or so ago. There is never a for sure safe

way not to stir the metals up and have them be redistributed when

someone is chelating.

***Maybe so. I gather that Amy doesn't recommend using much of

that, just enough to adjust the metals coming out in the urine on an

unchallenged basis, is that right? I do think that your glutathione

is still down, so using a chelator in that condition probably will

put the metals in other places.

>

> I don't believe Dr. Amy believes in increasing the Folapro and

Intrinsic B12 over 1/4 tablet each per day(even with adults) at amy

point in any of her programs(see www.holistichealth.com). I believe

she thinks it would be adding too many Methyl donors and would

stress the system. I can raise my daily Methyl B12 though more

supplementation(which I will do per Rich).

***O.K. It does seem that your FIGLU, histidine and sarcosine

levels are all saying that you need more, but you will have to do

what seems best. Amy's a pretty sharp cookie, so maybe she's

right. I'm just going by the biochemical indicators of low folate.

> I must say my neuro eye light flashing and tingling and numbness

and light shows in my head are much better from following her

program. I am improving.

***That's great. I'm guessing that lowering the ammonia may be a

big part of the reason. Ammonia is bad news in the brain.

>

> I will keep everyone posted on my progress . . . but I may

become worse again before getting a lot better. I still need to kill

the gut bugs and that means I have to deal with my Liver enzyme P450

issues. I've got the " double whammy " so to speak when it comes to

problems with genetic variations in various systems within the body.

***Thanks, Sue. Yes, you do have a challenge there. I guess there

are two parts to that. One is that some of the agents used to

combat the bugs may be absorbed and have to be detoxed, and the

other is that the bugs may put out endotoxins when you kill them,

which may be absorbed and have to be detoxed. I think you can have

some control over the first part, but probably not over the second

part. You may be able to take some activated charcoal to bind some

of the toxing while you are doing this, though.

>

> Best to all,

> Sue T

***Rich