Vitamin Diagnostics Methylation Test

jeffrez

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This is a question for richvank, but also anyone else who has had this test. I'm wondering if there is a sample results printout anywhere so we can see exactly what is measured and reported by this test, how well it then tailors or guides treatment, etc.

If it's $300 basically just to say, "yes, you have a methylation block," I'm not sure it's really worth the cost if the treatment is then going to be the same anyway. In that case, just do the protocol. On the other hand, if it specifically identifies where the problem is, tailors treatment to those problems or specific blockages, etc. then I suppose it might be useful. I'd just like to take a look and see what it's about. Or, if the report is simply in the form of a series of values ("X is 34 in a range of 0-50," etc.), knowing what those are would be helpful. Thanks for any info.
 

richvank

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This is a question for richvank, but also anyone else who has had this test. I'm wondering if there is a sample results printout anywhere so we can see exactly what is measured and reported by this test, how well it then tailors or guides treatment, etc.

If it's $300 basically just to say, "yes, you have a methylation block," I'm not sure it's really worth the cost if the treatment is then going to be the same anyway. In that case, just do the protocol. On the other hand, if it specifically identifies where the problem is, tailors treatment to those problems or specific blockages, etc. then I suppose it might be useful. I'd just like to take a look and see what it's about. Or, if the report is simply in the form of a series of values ("X is 34 in a range of 0-50," etc.), knowing what those are would be helpful. Thanks for any info.
Hi, Mr. Kite.

If you join the Yahoo cfs_yasko group at http://health.groups.yahoo.com/group/CFS_Yasko/ you can look in the Files section of the website in the file named "VD methylation panel files (add yours!)" and find several results of this panel.

The value of running this panel, in my opinion, is not only that it does show the condition of the methylation cycle, the folate metabolism, and glutathione, and it makes it possible to determine to some degree what is causing a partial block, if present, but it also gives baseline values so that after a period of treatment, a comparison can be made to see the progress of the treatment. This has been found to be helpful, because improvement can extend over months to years, depending on the status of the person and their body burdens of toxins. Because of detox and die-off symptoms, it is not always possible to gauge the improvement based on symptoms alone. It's true that many people have gone ahead and tried the treatment without running this panel first. Some have later expressed the view that they wish they had run the panel, because later on they have decided to run it when they find that the treatment seems to be helping, but then they have had no initial values with which to compare, which they have wished they had.

I will go even farther and say that in my opinion, this test panel has a good chance of being the best biomarker panel for CFS diagnosis that we have. I realize that most of the "official" CFS community is not even aware of this panel, so I don't expect early adoption of my point of view! :)-) Nevertheless, that gives you an idea of how significant I believe it is.

Here is a discussion of this panel and my suggestions for interpreting it:


Interpretation of the Vitamin Diagnostics
Methylation Pathways Panel

by
Rich Van Konynenburg, Ph.D.


Several people have asked for help in interpreting the results of
their Vitamin Diagnostics, Inc., methylation pathway panels. Here are my
suggestions for doing so. They are based on my study of the
biochemistry involved, on my own experience with interpreting more
than 120 of these panel results to date, and on discussion of some of
the issues with Tapan Audhya, Ph.D., who is the director of the
Vitamin Diagnostics lab.

The panel consists of measurement of two forms of glutathione
(reduced and oxidized), adenosine, S-adenosylmethionine (SAM) , S-
adenosylhomocysteine (SAH), and seven folic acid derivatives or
vitamers.

According to Dr. Audhya, the reference ranges for each of these
metabolites was derived from measurements on at least 120 healthy
male and female volunteer medical students from ages 20 to 40, non-
smoking, and with no known chronic diseases. The reference ranges
extend to plus and minus two standard deviations from the mean of
these measurements.

Glutathione: This is a measurement of the concentration of the
reduced (active) form of glutathione (abbreviated GSH) in the blood
plasma. From what I've seen, most people with chronic fatigue
syndrome (PWCs) have values below the reference range. This means
that they are suffering from glutathione depletion. As they undergo
the simplified treatment approach to lift the methylation cycle
block, this value usually rises into the normal range over a period
of months. I believe that this is very important, because if
glutathione is low, vitamin B12 is likely unprotected and reacts with toxins
that build up in the absence of sufficient glutathione to take them
out. Vitamin B12 is thus “hijacked,” and not enough of it is able to
convert to methylcobalamin, which is what the methylation cycle needs
in order to function normally. Also, many of the abnormalities and
symptoms in CFS can be traced to glutathione depletion.

Glutathione (oxidized): This is a measurement of the concentration
of the oxidized form of glutathione (abbreviated GSSG) in the blood
plasma. In many (but not all) PWCs, it is elevated above the normal
range, and this represents oxidative stress.

Adenosine: This is a measure of the concentration of adenosine in the
blood plasma. Adenosine is a product of the reaction that converts
SAH to homocysteine. In some PWCs it is high, in some it is low, and
in some it is in the reference range. I don't yet understand what
controls the adenosine level, and I suspect there is more than one
factor involved. In most PWCs who started with abnormal values, the
adenosine level appears to be moving into the reference range with
methylation cycle treatment, but more data are needed.

S-adenosymethionine (RBC) (SAM): This is a measure of the
concentration of SAM in the red blood cells. Most PWCs have values
below the reference range, and treatment raises the value. S-
adenosylmethionine is the main supplier of methyl groups in the body,
and many biochemical reactions depend on it for their methyl
groups. A low value for SAM represents low methylation capacity, and
in CFS, it appears to result from a partial block at the enzyme methionine
synthase. Many of the abnormalities in CFS can be tied to lack of
sufficient methyation capacity.

S-adenosylhomocysteine (RBC) (SAH): This is a measure of the
concentration of SAH in the red blood cells. In CFS, its value
ranges from below the reference range, to within the reference range,
to above the reference range. Values appear to be converging toward
the reference range with treatment. SAH is the product of reactions
in which SAM donates methyl groups to other molecules.

Sum of SAM and SAH: When the sum of SAM and SAH is below 268
micromoles per deciliter, it appears to suggest the presence of
upregulating polymorphisms in the cystathione beta synthase (CBS)
enzyme, though this may not be true in every case.

Ratio of SAM to SAH: A ratio less than about 4.5 also represents low
methylation capacity. Both the concentration of SAM and the ratio of
concentrations of SAM to SAH are important in determining the
methylation capacity.

5-CH3-THF: This is a measure of the concentration of 5-methyl
tetrahydrofolate in the blood plasma. It is normally the most
abundant form of folate in the blood plasma. It is the form that
serves as a reactant for the enzyme methionine synthase, and is thus
the most important form for the methylation cycle. Many PWCs have a
low value, consistent with a partial block in the methylation cycle.
The simplified treatment approach includes FolaPro, which is
commercially produced 5-CH3-THF, so that when this treatment is used,
this value rises in nearly every PWC. If the concentration of 5-CH3-
THF is within the reference range, but either SAM or the ratio of SAM
to SAH is below the reference values, it suggests that there is a
partial methylation cycle block and that it is caused by
unavailability of sufficient bioactive B12, rather than
unavailability of sufficient folate. I have seen this frequently,
and I think it demonstrates that the “hijacking” of B12 is the root
cause of most cases of partial methylation cycle block. Usually
glutathione is low in these cases, which is consistent with lack of
protection for B12, as well as with toxin buildup.

10-Formyl-THF: This is a measure of the concentration of 10-formyl
tetrahydrofolate in the blood plasma. It is usually on the low side in PWCs.
This form of folate is involved in reactions to form purines, which
form part of RNA and DNA as well as ATP.

5-Formyl-THF: This is a measure of the concentration of 5-formyl
tetrahydrofolate (also called folinic acid) in the blood plasma.
Most but not all PWCs have a value on the low side. This form is not used
directly as a substrate in one-carbon transfer reactions, but it can
be converted into other forms of folate. It is one of the
supplements in the simplified treatment approach, which helps to
build up various other forms of folate.

THF: This is a measure of the concentration of tetrahydrofolate in
the blood plasma. In PWCs it is lower than the mean normal value of 3.7
nanomoles per liter in most but not all PWCs. This is the
fundamental chemically reduced form of folate from which several
other reduced folate forms are made. The supplement folic acid is
converted into THF by two sequential reactions catalyzed by
dihydrofolate reductase (DHFR). THF is also a product of the
reaction of the methionine synthase enzyme, and it is a reactant in
the reaction that converts formiminoglutamate (figlu) into
glutamate. If figlu is high in the Genova Diagnostics Metabolic
Analysis Profile, it indicates that THF is low.

Folic acid: This is a measure of the concentration of folic acid in
the blood plasma. Low values suggest folic acid deficiency in the
current diet. High values are sometimes associated with inability to
convert folic acid into other forms of folate, such as because of
polymorphisms in the DHFR enzyme. They may also be due to high
supplementation of folic acid.

Folinic acid (WB): This is a measure of the concentration of folinic
acid in the whole blood. See comments on 5-formyl-THF above. It
usually tracks with the plasma 5-formyl-THF concentration.

Folic acid (RBC): This is a measure of the concentration of folic
acid in the red blood cells. The red blood cells import folic acid
when they are initially being formed, but during most of their
approximately four-month life, they do not normally import, export, or use
it. They simply serve as reservoirs for it, giving it up when they
are broken down. Many PWCs have low values. This can be
caused by a low folic acid status in the diet over the previous few
months, since the population of RBCs at any time has ages ranging
from zero to about four months. However, in CFS it can also be
caused by damage to the cell membranes, which allows folic acid to
leak out of the cells. Dr. Audhya reports that treatment with omega-
3 fatty acids can raise this value over time.

Rich
 

kerrilyn

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Rich, I'd like to ask you the same question about the Genova MAP test. Not about the validity because I was thinking it would be good to have baseline info to start. But if the same above information applies, I was wondering if there is supplied reference info or where to find what the results will mean? Thanks.
 

richvank

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Rich, I'd like to ask you the same question about the Genova MAP test. Not about the validity because I was thinking it would be good to have baseline info to start. But if the same above information applies, I was wondering if there is supplied reference info or where to find what the results will mean? Thanks.
Hi, kerrilyn.

The MAP test is also an excellent panel, and it gives "a lot of bang for the buck," because it analyzes many different organic acids, representing several parts of the overall metabolism, from a single urine sample.
I use it a lot when I consult on cases. It's best run along with some other tests, because they complement each other, and the whole is thus "greater than the sum of its parts." Urine or plasma amino acids testing, as well as urine or red blood cell or whole blood elements analysis are two of the others that help a lot if done together with the MAP test. Of course, they all cost money!

Unfortunately, it isn't easy to explain how to interpret the MAP test. It does come with sort of a general interpretation, which is mostly based on looking for nutritional deficiencies, and is put together by a computer program that selects sections based on which things come out very high or very low, and that is somewhat helpful, but the subtleties of chronic fatigue syndrome aren't included in this program, and it really takes some study of the biochemistry and some experience to sort out what all the results mean. Some help can be gotten from the book by Lord and Bralley, which is sold on the Metametrix.com site, but there are still things that aren't included in that book. I continue to learn about more aspects of this test as I analyze different cases.

If I could give straightforward guidance about interpretation of the MAP test, I would. As far as the partial methylation cycle block is concerned, if both methylmalonic and formiminoglutamic acids are elevated on the MAP test, it's very likely that this partial block is present. If pyroglutamic acid is low or high, that's an indication of glutathione depletion. Another indication of glutathione depletion is if there is a fairly big drop between citric acid and the ones that follow it in the Krebs cycle. This last one doesn't always work, though, because some PWCs have sort of a general collapse of the Krebs cycle, so that citric acid is low, too. I guess those are the general clues I can give, but it's really best to look at this set of tests together to try to sort out what's going on.

Best regards,

Rich