Re: metametrix ION test - change in reference ranges?

[Guest guest]

,

I am not a doc, but maybe the ref ranges for boys is different than girls.

And if they are not the same age, that might make a diff. Your doc should be

able to find this out from MM.

L

metametrix ION test - change in reference ranges?

I did an ION on my son in the spring, and just received my daughter's

ION results today. I'm confused at the difference in the reference

limits on my daughter's report vs. my son's. The reference limits

are different for everything! For example, in the essential amino

acids section (plasma), the reference range for lysine on my son's

report was 70-160, and so with 113, his result was not out of range.

On my daughter's report, the reference range for lysine is 88-301, and

so she was marked red for low normal with 108. Many of her amino acids

were marked in red where they were marked as normal on my son's, even

though their actual results for those amino's were similar. This sort

of thing appears throughout the reports, so now I am not sure which

reference ranges are correct, or why there is such a discrepancy. Any

help appreciated! These discrepencies make it really hard to know how

to interpret the results.

Many frequently asked questions and answers can be found at

<http://forums.autism-rxguidebook.com/default.aspx>

[Guest guest]

,

Although I don't know the specifics on this particular change, I have in

the past talked to a lab director at Metametrix because I made the same

observation regarding a different test . I also had two reports on the

same aged child done within a month's time with very different reference

ranges. What I was told is that they had gotten new equipment and

recallibrated the reference ranges in the weeks between the tests. That

much was OK, but what he said after that disturbed me, for he said they

recomputed the reference ranges using numbers from patients as their

reference population.

Of course, I was assuming their numbers were based on healthy control

children, but they apparently were not. If they use this method routinely,

then there is a distinct possibility that their ranges are changing over

time in the direction of how their patients are sick who come to their lab

for evaluation. That makes the ranges subject to the vicissitudes of whose

business they may be recruiting at the time. Since I had used their lab

almost a decade ago, I compared their very old ranges to the new ones and

found it very interesting that the ranges had migrated, for the most part,

in the direction that my daughter's report was different from the original

reference range.

Since I heard this information from them, I have gotten into the habit of

asking other labs what sorts of people constituted their reference

population, and I have found that few labs really do use normal healthy

controls with the right age range. Even university and medical school labs

seem to use patients rather than healthy controls who had no reason to come

to the doctor. This practice really surprised me, but there is a reason

for it that became more obvious the more directors I queried...They told me

that most doctors using these tests typically are trying to discover

genetic defects that might be treatable that cause HUGE swings in the

levels of certain compounds. The labs years ago set up their expectations

to provide accuracy good enough to find those errors, but not finer

ones....and certainly not the sorts of swings of values that we see

typically in autism, or typically in someone who is just sick, instead of

genetically impaired. That is why it makes sense, then, to study those

with autism as a group and see differences or similarities within this

population, and understand why they are there. This is a very different

process from looking for H's and L's on an individual lab report,

especially when you are comparing to a sick reference population.

By the way, I keep a database of all the different ranges I've collected

from all over the world and they bear very little resemblance to each other

even though they all say they are measuring the same thing. If you ask

them why this might be, they all say the same thing: it comes from

differences in equipment. I am far more convinced it is because their

reference populations are so different.

When I realized many years ago how discrepant the amino acid numbers were

from lab to lab, I standardized on the age-adjusted ranges from the Lepage

study, for they did use healthy control children and they noted the

differences between children of different ages.

I have been doing analyses on plasma amino acid reports now for several

years, basing my evaluations on what I've learned after several years of

studying the amino acid literature covering many disease processes, and

comparing that to the changes I saw within the autism population. Now I

have a database of over a hundred children with autism with whom to

compare. This has allowed me to find out what changes are typical of

children with autism, and how many other changes are due to other

things. What is exciting is that this can give a view that seems difficult

to come by using other methods, and may suggest to a doctor some other

areas of testing that might be helpful.

The most important thing I have learned in this study is this one thing:

fasting plasma amino acid levels for individual amino acids do not reflect

nutritional need for that amino acid. In other words, you cannot assume

that a low level in plasma means you have too little of that amino acid

nutritionally and need to supplement it. Likewise, if the level is high,

it does not mean you have too much. It is a WHOLE LOT more complicated

than that.

Amino acid levels must be seen in context with each other, because

different organ systems, in response to metabolic demands, will alter the

amount of a particular amino acid that they will add or take away from the

blood. This has nothing to do with the whole body's need for that amino

acid nutritionally, with the exception that if all the essential amino

acids are low at the same time, it does suggest that overall protein

absorption may not be adequate, whether that is due to diet or to GI

problems. There are several humoral factors that tend to elevate or depress

almost all the amino acids at once. That is important if you have a report

with too many H's or too many L's, because it would be a big

misinterpretation to think that meant that you needed to make nutritional

adjustments based on things being out of range.

One of the proofs of this principle is that if you compare the relative

percentages of the different amino acids in different places in the body

where they can be measured (plasma, whole blood, red blood cells, CSF,

urine) the amounts of the different amino acids in proportion to the other

amino acids in different places are very, very different.. This means the

interpretation needs to be specific to the rules that apply to a particular

compartment, like the plasma. What are the amino acids doing in blood

plasma? (Each one is different!) How is the level of that amino acid

different from what you would see if you measured inside cells of the

liver, or cells of the kidney, or cells of pancreas, etc.? What does that

difference mean?

Changes in these levels do mean that the body is regulating the amount of

that amino acid in the blood for a particular purpose. The literature is

rife with explanations of what these highs and lows of particular amino

acids may mean: especially in context with changes in the other amino

acids. So, what I look at mostly is RATIOS of amino acids: something you

cannot get from the lab report without doing some extra work and knowing

what to observe. That means my evaluation will be different from the

interpretation you will get from a lab that is set up to identify errors of

metabolism. Most of what I find out is from reports where a lab has said:

" This report shows no known errors of metabolism. " which means, to them,

" normal " . Most of you who have done this sort of testing know that you can

get that sort of " normal " interpretation even when many, many items are

outside the reference range.

The other thing important to know about this particular report is that you

always want to do this test fasting (like an overnight fast) because that

way you are not measuring what is travelling to the blood from the last

meal, but you are measuring what organs are taking from or adding to the

blood. (By the way, if we had some doctors doing blood draws in front of

or behind different organs, the results of what was in plasma would look

very different. We know this from animal studies where they have done just

that.

Two things are quite consistent in the autism population on this test, and

that is cystine being low, ranging from being right at the mean or lower

than the mean and practically never above the mean but most often, in

autism, well below the reference range. Tryptophan can also be quite

low. Ornithine tends high, and citrulline tends low.

, if after reading all this, if you would like me to look at your amino

acid reports, feel free to write me offlist about it. The holidays and

other events that have made me far too busy since early fall, have made it

where I cannot promise speed in this evaluation. I have quite a backlog,

but I am certainly willing to take a look, if you'd like, and are willing

to wait. I also would be grateful if you could send me the new ranges, as

I'd like to see how they've moved, but of course, that should be on the

report if you send it to me.

I hope this helps.

At 07:12 PM 12/23/2004 +0000, you wrote:

>I did an ION on my son in the spring, and just received my daughter's

>ION results today. I'm confused at the difference in the reference

>limits on my daughter's report vs. my son's. The reference limits

>are different for everything! For example, in the essential amino

>acids section (plasma), the reference range for lysine on my son's

>report was 70-160, and so with 113, his result was not out of range.

>On my daughter's report, the reference range for lysine is 88-301, and

>so she was marked red for low normal with 108. Many of her amino acids

>were marked in red where they were marked as normal on my son's, even

>though their actual results for those amino's were similar. This sort

>of thing appears throughout the reports, so now I am not sure which

>reference ranges are correct, or why there is such a discrepancy. Any

>help appreciated! These discrepencies make it really hard to know how

>to interpret the results.

>

>

>

>

>

>

>

>

>Many frequently asked questions and answers can be found at

><http://forums.autism-rxguidebook.com/default.aspx>

>

>

[Guest guest]

Thank you for this extremely informative post. If a child has

very low cystine should they be supplemented with NAC even if they

have a yeast overgrowth or would this be a case where it is more

complicated than just supplementing what is low?

Hope

>

>

> >I did an ION on my son in the spring, and just received my daughter's

> >ION results today. I'm confused at the difference in the reference

> >limits on my daughter's report vs. my son's. The reference limits

> >are different for everything! For example, in the essential amino

> >acids section (plasma), the reference range for lysine on my son's

> >report was 70-160, and so with 113, his result was not out of range.

> >On my daughter's report, the reference range for lysine is 88-301, and

> >so she was marked red for low normal with 108. Many of her amino acids

> >were marked in red where they were marked as normal on my son's, even

> >though their actual results for those amino's were similar. This sort

> >of thing appears throughout the reports, so now I am not sure which

> >reference ranges are correct, or why there is such a discrepancy. Any

> >help appreciated! These discrepencies make it really hard to know how

> >to interpret the results.

> >

> >

> >

> >

> >

> >

> >

> >

> >Many frequently asked questions and answers can be found at

> ><http://forums.autism-rxguidebook.com/default.aspx>

> >

> >

[Guest guest]

In a message dated 12/27/2004 7:33:38 PM Eastern Standard Time,

parent616@... writes:

> >Amino acid levels must be seen in context with each other, because

> >different organ systems, in response to metabolic demands, will

> alter the

> >amount of a particular amino acid that they will add or take away

> from the

> >blood. This has nothing to do with the whole body's need for that

> amino

> >acid nutritionally, with the exception that if all the essential amino

> >acids are low at the same time, it does suggest that overall protein

> >absorption may not be adequate, whether that is due to diet or to GI

> >problems. There are several humoral factors that tend to elevate or

> depress

> >almost all the amino acids at once. That is important if you have a

> report

> >with too many H's or too many L's, because it would be a big

> >misinterpretation to think that meant that you needed to make

> nutritional

> >adjustments based on things being out of range.

-

This is VERY interesting. I was disturbed because my son's last AA test

showed him very low in almost every amino acid tested. He is now on a

compounded

custom blend that requires about 2 tablespoons of AA powder per day. There is

NO way that I can get that much in him, so I've been giving as much as I can

(about 1.5 t).

I found it strange that he went from very few AA deficiencies to a whole

bunch 6 months later. Of course, his custom blend now costs about 5 times what

his old one did.

What sort of testing would you recommend before I reorder?

Thanks so much-

Sue

[Guest guest]

I did the AA blood test in France (NATAF LAB) and to my surprise a

lot of amino acids were too high. He have sleeping problems, so I

was surprised that his tryptophane GABA and Taurine was very high

and out of range. (As well as histidine and tyrosine). What does it

means? Are those tests reliable?

I stop supplementing with GABA and Taurine…

Thanks

Liora

> In a message dated 12/27/2004 7:33:38 PM Eastern Standard Time,

> parent616@h... writes:

>

> > >Amino acid levels must be seen in context with each other,

because

> > >different organ systems, in response to metabolic demands, will

> > alter the

> > >amount of a particular amino acid that they will add or take

away

> > from the

> > >blood. This has nothing to do with the whole body's need for

that

> > amino

> > >acid nutritionally, with the exception that if all the

essential amino

> > >acids are low at the same time, it does suggest that overall

protein

> > >absorption may not be adequate, whether that is due to diet or

to GI

> > >problems. There are several humoral factors that tend to

elevate or

> > depress

> > >almost all the amino acids at once. That is important if you

have a

> > report

> > >with too many H's or too many L's, because it would be a big

> > >misinterpretation to think that meant that you needed to make

> > nutritional

> > >adjustments based on things being out of range.

>

> -

> This is VERY interesting. I was disturbed because my son's last

AA test

> showed him very low in almost every amino acid tested. He is now

on a compounded

> custom blend that requires about 2 tablespoons of AA powder per

day. There is

> NO way that I can get that much in him, so I've been giving as

much as I can

> (about 1.5 t).

>

> I found it strange that he went from very few AA deficiencies to a

whole

> bunch 6 months later. Of course, his custom blend now costs about

5 times what

> his old one did.

>

> What sort of testing would you recommend before I reorder?

> Thanks so much-

> Sue

>

>

>

[Guest guest]

Thank you very much to everyone who has responded to my questions!

Thank you and Dr. M!

This is exactly my concern - if the reference ranges are changing,

what really indicates a deficiency? My son's test from 8 months ago

had some AA values close to my daughter's (we just got her results),

but some of these were marked low on her test and not his - the big

difference was the change in the reference range. So was he deficient,

and it just wasn't indicated on his test? It all seems very subjective

to me now.

> In a message dated 12/27/2004 7:33:38 PM Eastern Standard Time,

> parent616@h... writes:

>

> > >Amino acid levels must be seen in context with each other, because

> > >different organ systems, in response to metabolic demands, will

> > alter the

> > >amount of a particular amino acid that they will add or take away

> > from the

> > >blood. This has nothing to do with the whole body's need for that

> > amino

> > >acid nutritionally, with the exception that if all the essential

amino

> > >acids are low at the same time, it does suggest that overall protein

> > >absorption may not be adequate, whether that is due to diet or to GI

> > >problems. There are several humoral factors that tend to elevate or

> > depress

> > >almost all the amino acids at once. That is important if you have a

> > report

> > >with too many H's or too many L's, because it would be a big

> > >misinterpretation to think that meant that you needed to make

> > nutritional

> > >adjustments based on things being out of range.

>

> -

> This is VERY interesting. I was disturbed because my son's last AA

test

> showed him very low in almost every amino acid tested. He is now on

a compounded

> custom blend that requires about 2 tablespoons of AA powder per day.

There is

> NO way that I can get that much in him, so I've been giving as much

as I can

> (about 1.5 t).

>

> I found it strange that he went from very few AA deficiencies to a

whole

> bunch 6 months later. Of course, his custom blend now costs about 5

times what

> his old one did.

>

> What sort of testing would you recommend before I reorder?

> Thanks so much-

> Sue

>

>

>

[Guest guest]

Hope,

It is almost always more complicated than supplementing what is low. A

fasting plasma amino acid test tells you about organ to organ transfers

going on, not nutritional supply. However, if the ratio of essential

amino acids to non-essential amino acids is low, it can indicate a problem

with adequate protein nutrition. If both are low, it can indicate hormonal

regulation, not nutritional problems in protein. Individually, low values

of a particular amino acid does not necessarily mean poor nutrition of that

one amino acid.

Levels of certain amino acids in the blood change as SIGNALLING or

responses to signalling in the body. It is important to know what signals

are possible, which is why I've spent a few years studying this area. It

is NOT simple.

We still don't know why cystine tends to be below the reference range

and/or at the mean or below the mean of the reference range for at least

98% of the children I've gotten these tests from. If this were not a major

issue in autism, cystine would be normally distributed about the mean when

you look at a big population of kids with autism. Cystine is THE MOST

abnormal amino acid, but other patterns in the amino acid profile have

gotten to be familiar to me as I've done comparisons. (Cystine is two

cysteines linked together by a sulfur-sulfur bond.)

One reason for suspecting there may be a specific lack of cystine/cysteine)

in this population is the also frequent finding of low

glutathione. Glutathione is an " escorted " version of

cysteine. Glutathione is less reactive than cysteine, so it makes a better

form for sulfur to travel through the blood. However, the kidneys break

glutathione down and deliver cysteine to the blood. Macrophages are also

an important delivery system for cysteine, BUT, the tests we see in the

autism community are not looking at whole blood, inclusive of blood

cells. A good part of the time, changes in the quantity of amino acids in

plasma may reflect a movement of the amino acids in circulation from the

plasma compartment to the blood cells, but not directly...this is done in

particular organs as the blood cells pass through. You learn about that

when you study the amino acids in blood cells.

Sulfur compounds are so reactive that the cysteine may be binding some

other thiol that is elevated in the blood. Unfortunately, at this point,

no lab offers a complete enough profile to understand this issue, and for

the vast majority of labs, measuring sulfur compounds is the most

challenging and the most subject to error. Since no one lab has a clearly

demonstrated expertise in this area, it is hard to know how one lab

compares with another. I just know that in a self-policing group of about

80 labs, they found the measurement of cystine or cysteine to be all over

the map when they were analyzing the same sample. Not a pretty picture!

Maybe Dr. M. can pipe in here, but my understanding is that on a clinical

level, the DAN docs have found that if a child has yeast problems, avoiding

the oral route for sulfur supplements is to be preferred. That is a big

reason why several transdermal products appeared on the scene a few years

ago and why some doctors give IV sulfur supplements.

Other listmates, since Hope asked about this, would any of you like to

share your experiences on NAC and yeast issues? Has anyone taken NAC

orally and it did not worsen a yeast problem? If your answer is yes, can

you give us a little background on how you think your child may be

different from the ones you've heard about where it was a problem?

Thanks,

At 12:32 AM 12/28/2004 +0000, you wrote:

>Thank you for this extremely informative post. If a child has

>very low cystine should they be supplemented with NAC even if they

>have a yeast overgrowth or would this be a case where it is more

>complicated than just supplementing what is low?

>

>Hope

[Guest guest]

Sue,

If you'll write me offlist, I'll arrange to look at your child's

profile. What I look at is specific ratios, which can only be done with

the whole profile in hand, but that might suggest some other testing to be

done, but it would be guesswork for me to comment without seeing the

specfics in his report.

Within my database, I have repeat tests from a number of children, and it

is important to know that these repeat tests can be very, very different.

My daughter did not have autism, but had gross motor delays, but we had her

tested. Her results were so different on her second test (nine months

later) that I called the second lab to complain, expecting that they had

made a mistake. Now, years later, I have learned what explains the

difference in her two tests, and by the time the second test was done, she

had experienced about nine months of gf/cf diet, epsom salts, and some

vitamins and was doing a WORLD better. That change in a positive direction

is obvious from looking at her profile...but not really because there were

fewer L's and H's, but because of what was high and what was low in each

profile.

When she was four, there were 2 L's and 12 H's. When she was five, there

were 5 L's and 4 H's. We had a custom amino acid formula made up based on

her first profile, and it was a disaster. I found the bottle a few years

ago, and more than half of the capsules were still in there because we had

to stop it because it made things worse. The changes in her second profile

were probably eight months separated from the use of that formula. This is

a big reason I decided to study this area to try to see if I could learn

how to interpret these tests based on insights from the medical literature,

instead of from common assumptions about these ups and downs happening

because of changes in nutrition.

Basically, at this point, I believe that if there are indications of poor

protein assimilation, it is far better to give protein orally in a form

that is closer to food...like a partially digested protein powder, than it

is to give already completely separated amino acids such as what you might

get in a customized formula. My understanding is that your intestines

actually do a far better job absorbing dipeptides and tripeptides than

individual amino acids. Does anyone here know if the " base " from these

customized formulas includes amino acids in free form only, or if some of

it is still linked to other amino acids?

I would love to hear from parents who have tried both ways of

supplementation, and can compare the results for us.

At 01:19 PM 12/28/2004 -0500, you wrote:

>In a message dated 12/27/2004 7:33:38 PM Eastern Standard Time,

>parent616@... writes:

>

> > >Amino acid levels must be seen in context with each other, because

> > >different organ systems, in response to metabolic demands, will

> > alter the

> > >amount of a particular amino acid that they will add or take away

> > from the

> > >blood. This has nothing to do with the whole body's need for that

> > amino

> > >acid nutritionally, with the exception that if all the essential amino

> > >acids are low at the same time, it does suggest that overall protein

> > >absorption may not be adequate, whether that is due to diet or to GI

> > >problems. There are several humoral factors that tend to elevate or

> > depress

> > >almost all the amino acids at once. That is important if you have a

> > report

> > >with too many H's or too many L's, because it would be a big

> > >misinterpretation to think that meant that you needed to make

> > nutritional

> > >adjustments based on things being out of range.

>

>-

>This is VERY interesting. I was disturbed because my son's last AA test

>showed him very low in almost every amino acid tested. He is now on a

>compounded

>custom blend that requires about 2 tablespoons of AA powder per

>day. There is

>NO way that I can get that much in him, so I've been giving as much as I can

>(about 1.5 t).

>

>I found it strange that he went from very few AA deficiencies to a whole

>bunch 6 months later. Of course, his custom blend now costs about 5 times

>what

>his old one did.

>

>What sort of testing would you recommend before I reorder?

>Thanks so much-

>Sue

>

>

>