Methylation pathways panel

richvank

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Hi, all.

So far, I think that nearly everyone with ME/CFS who has taken the methylation pathways panel offered by Health Diagnostics and Research Institute (formerly Vitamin Diagnostics, Inc.) in New Jersey has been found to have abnormalities on this panel. The Glutathione Depletion--Methylation Cycle Block hypothesis for the pathogenesis of ME/CFS predicts that this would be the case. This hypothesis would be consistent with XMRV involvement, either in contributing to causation of at least some cases of ME/CFS or as an acquired passenger, benefiting from immune dysfunction resulting from glutathione depletion as a result of other initial causes.

I think there is a good chance that this panel could serve as the biomarker panel for diagnosis of ME/CFS, as well as the gauge of progress in treatment. A clinical treatment study that I think supports this possibility can be found at www.cfsresearch.org

I have no financial interest in this lab or this panel.

For others who might be interested in getting this panel, here's the contact information:



Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block, draining of folate metabolites from the cells, and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block.

The panel requires an order from a physician or a chiropractor. It costs $300 plus the cost of shipping the blood samples to the lab. The best way to order the panel is by fax, on a clinicians letterhead.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 4930
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., at the lab is willing to help clinicians with interpretation of the panel by phone, or you can use the interpretive comments below:



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 Health Diagnostics and Research Institute 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. of the
Health Diagnostics and Research Institute.

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.


Best regards

Rich
 

wciarci

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Hi Rich, I am about to go onto the simplified methylation protocol, as you know I have been taking many supplements over the last few years but not the exact supplements in the exact amounts of your protocol. Should I take the test and if so, should I stop all supplements and for how long? Thanks

WendyC
 

richvank

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Hi Rich, I am about to go onto the simplified methylation protocol, as you know I have been taking many supplements over the last few years but not the exact supplements in the exact amounts of your protocol. Should I take the test and if so, should I stop all supplements and for how long? Thanks

WendyC
Hi, Wendy.

I do recommend taking this panel, because it will tell you your current status with regard to the partial methylation cycle block and glutathione.

In the clinical study we ran, the patients continued to take the supplements as we repeated this panel at 3, 6, and 9 months, and we saw very systematic (but relatively slow) changes in the results, so based on that experience, my opinion is that it is O.K. to continue taking the supplements, because the partial methylation cycle block and glutathione depletion are rather "stubborn" abnormalities. If they are present, they will show up whether or not supplementation is continued.

I hope this testing and treatment pay off for you.

Best regards,

Rich
 

wciarci

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Thanks Rich, I will order the test and the supplements. I will continue with the B12 shots but ask my doctor to change to a better form. I did sublingual for a while but still needed the shots for the B12 to be 'normal'.

Wendy
 

Wayne

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Thanks much Rich for your succinct post. A lot of good actionable information.

I, like I assume most others on this board, anticipate getting tested for XMRV in the coming months. I was wondering f you had any thoughts on whether it would be desirable to do either the XMRV testing or the methylation panel first.

Thanks.

Wayne
 
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I really want to get this test done. Is there a way to get it done with out a doctor? I will see if the new Osteopath I am seeing July 1st will let me order through her.
 

richvank

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Thanks much Rich for your succinct post. A lot of good actionable information.

I, like I assume most others on this board, anticipate getting tested for XMRV in the coming months. I was wondering f you had any thoughts on whether it would be desirable to do either the XMRV testing or the methylation panel first.

Thanks.

Wayne
Hi, Wayne.

XMRV is becoming more interesting, but it may be a while before it is really settled what its role is in CFS, and also before a treatment is available that has had some testing. In view of that, I would suggest doing the methylation pathways panel first, because there is treatment available now for partial methylation cycle block and glutathione depletion.

Best regards,

Rich
 

richvank

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I really want to get this test done. Is there a way to get it done with out a doctor? I will see if the new Osteopath I am seeing July 1st will let me order through her.
Hi, bigdreams.

This panel requires an order signed by a physician or a chiropracter. Hopefully your new osteopath will be receptive.

Best regards,

Rich
 

Sparrowhawk

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If someone could point me to where on PR there may be results from people who took this test and used it to guide their methylation protocol, I would be most grateful, thanks.

I gather most folks just do the 23andMe test, run it through genetic genie, and supplement accordingly on a hit or miss basis? I'd prefer to be a bit more guided if my results merit such an approach.
 

Valentijn

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I gather most folks just do the 23andMe test, run it through genetic genie, and supplement accordingly on a hit or miss basis? I'd prefer to be a bit more guided if my results merit such an approach.
I've been working on a list of methylation-related SNPs taken from 23andMe results, which is quite a bit larger than the Yasko list and supported by actual research. So far it's just individual lists in http://forums.phoenixrising.me/index.php?forums/genetic-testing-and-snps.12/ entitled "Interesting (gene) Variations", where (gene) is VDR, MTHFR, etc.

Currently you'd have to search your results manually to find the SNPs, but we should be getting a program online somewhere soon to do it automatically.
 

Helen

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If someone could point me to where on PR there may be results from people who took this test and used it to guide their methylation protocol, I would be most grateful, thanks.

I gather most folks just do the 23andMe test, run it through genetic genie, and supplement accordingly on a hit or miss basis? I'd prefer to be a bit more guided if my results merit such an approach.
I am glad to see that you lift this topic that I think is most important when looking for the cause of ME/CFS - and as a guide for treatment.

Rich told me that he had got more than 200 test reports, Methylation Pathways Panels, from PWME´s, and all but a few showed a blocked methylation. I wish there would be a study with this Methylation Pathways Panel, correlated with SNP´s, preferable MTHFR and MTRR/MTR as they affect the methylation most. Maybe you have seen the seminar that Rich had in Sweden? About 44:42 in the first video part of it he says "that´s the key to the whole thing"
http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/

In this link there are two test reports from globalpilot http://forums.phoenixrising.me/inde...hylation-panel-figlu-cysteine-nagalase.10998/ . I haven´t found more.

I have done the same testing, but unfortunately I am not able to scan the results and show them in an input. A friend of mine had them done too. We found the testresults very useful as a base for a methylation protocol as our gene tests don´t tell what´s really going on in the body.

If anyone, who has been diagnosed with ME, that has had a Methylation Pathways Panel done, would post it I think that would be most interesting for a ME researcher interested in methylation. Even more interesting together with SNP`s.

Maybe someone reading this would start a new thread on this topic? As English isn´t my native language I think someone else would do it much better than me.
 

Sparrowhawk

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Wow Helen you are quite fluent if English is not your native language.

I intend to wait to see what the 23and Me results show, and if I do have those issues then check on current methylation.

I did watch the entire Sweden lecture last weekend, it was really enlightening. Rich seems to have had a great talent for breaking things down into understandable chunks. Super clarity.
 

Sparrowhawk

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I've been working on a list of methylation-related SNPs taken from 23andMe results, which is quite a bit larger than the Yasko list and supported by actual research. So far it's just individual lists in http://forums.phoenixrising.me/index.php?forums/genetic-testing-and-snps.12/ entitled "Interesting (gene) Variations", where (gene) is VDR, MTHFR, etc.

Currently you'd have to search your results manually to find the SNPs, but we should be getting a program online somewhere soon to do it automatically.
. I look forward to reviewing the thread and to the eventual resource you described that will assist folks to compare their results with your list. What a great resource to provide, well done.
 

pemone

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Can someone tell me is the Health Diagnostics Methylation pathways panel still considered to be the best test for expression of methylation issues?

What is cost of this test?