How do you improve detox impairment?

[minniemom2011]

I recently had a NutrEval test done through Genova. It showed that I suffer from detox impairment due to high methionine, taurine, and beta-alinine. I also have slightly impaired methylation, excessive oxidative stress, and neurotransmitter imbalance.

How on earth do I begin to repair all of this? Thanks for any suggestions!

 

[richvank]

I recently had a NutrEval test done through Genova. It showed that I suffer from detox impairment due to high methionine, taurine, and beta-alinine. I also have slightly impaired methylation, excessive oxidative stress, and neurotransmitter imbalance.

How on earth do I begin to repair all of this? Thanks for any suggestions!

Hi, minniemom2011.

I would suggest that you (together with your physician) consider running the methylation pathways panel from Health Diagnostics and Research Institute in New Jersey. This will likely show that you have a partial methylation cycle block and glutathione depletion. If this is the case, the Glutathione Depletion--Methylation Cycle Block hypothesis likely fits your case, as has turned out to be true for nearly all PWMEs/PWCs who have been tested. If this hypothesis fits your case, then the Simplified Treatment Approach which is based on it is likely to be helpful to you.

Lifting the partial methylation cycle block, when it is present, will bring the sulfur metabolism back to normal function. This includes bringing the detox system back up, lowering oxidative stress by raising glutathione, and helping the synthesis and metabolism of the neurotransmitters.

Below is contact information for the panel, a discussion of interpretation of the panel results, and the most recent version of the Simplified Treatment Approach protocol. Papers describing the GD-MCB hypothesis can be found at http://www.aboutmecfs.org/Trt/TrtGSHIntro.aspx

I hope this is helpful. You can find more discussion of this type of treatment in this section of the forums.

Best regards,

Rich


Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead. The current cost is $295, including the mailer to send the blood samples to the lab.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.



Interpretation of the Health Diagnostics and Research Institute
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., at 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.


April 18, 2009


SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROME (Revised)

(Extracted from the full treatment program
developed by Amy Yasko, Ph.D., N.D.
which is used primarily in treating autism [1])

SUPPLEMENTS

1. FolaPro [2]: tablet (200mcg) daily
2. Actifolate [3]: tablet daily
3. General Vitamin Neurological Health Formula [4]: start with tablet and work up dosage as tolerated to 2 tablets daily
4. Phosphatidyl Serine Complex [5]: 1 softgel capsule daily
5. Activated B12 Guard [6]: 1 sublingual lozenge daily

All these supplements can be obtained from http://www.holisticheal.com, or all but the third one can be obtained from other sources.
The first two supplement tablets are difficult to break into quarters. We recommend that you obtain (from any pharmacy) a good-quality pill splitter to assist with this process. They can, alternatively, be crushed into powders, which are then separated on a flat surface using a knife or single-edged razor blade, and the powders can be mixed together. They can be taken orally with water, with or without food.
These supplements can make some patients sleepy, so in those cases they take them at bedtime. They can be taken at any time of day, with or without food.
GO SLOWLY. As the methylation cycle block is lifted, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.


[1] Yasko, Amy, and Gordon, Garry, The Puzzle of Autism, Matrix Development Publishing, Payson, AZ, 2006, p. 49.
[2] FolaPro is a registered trademark of Metagenics, Inc.
[3] Actifolate is a registered trademark of Metagenics, Inc.
[4] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
[5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center.
[6] Activated B12 Guard is a registered trademark of Perque LLC.

 

[pken]

Hi minniemon2011,

Can you give a little more information about your food intake/diet on an average day? And do you take any supplements or medication (or were you when you took the test)?

 

[August59]

I recently had a NutrEval test done through Genova. It showed that I suffer from detox impairment due to high methionine, taurine, and beta-alinine. I also have slightly impaired methylation, excessive oxidative stress, and neurotransmitter imbalance.

How on earth do I begin to repair all of this? Thanks for any suggestions!

I saw that you had posted your results under Diagnostic Testing and wanted to post the link to that post so that someone would have access to it in case they wanted to review. It is a very comprehensive test.

http://forums.aboutmecfs.org/showthread.php?10459-Can-anyone-help-with-NutrEval-results

 

[minniemom2011]

Hi minniemon2011,

Can you give a little more information about your food intake/diet on an average day? And do you take any supplements or medication (or were you when you took the test)?

Sure pken. I am on a very limited diet due to multiple food sensitivities. A typical day for me is basically meat and veggies and even those are limited. I don't know if you're familiar with Weston Price or Nourishing Traditions, but that is the type of diet I follow - very traditional foods. I was a vegetarian for about 2 years and drastically changed my eating habits about 4-5 months ago.

I eat chicken, beef, or bison usually for my meat and I eat a fairly high fat diet - though mostly all animal fats. I don't eat any gluten, soy, or dairy. I also try to eat/drink a lot of fermented foods for probiotics, like kefir, sauerkraut juice, beet kvass, etc. The only veggies I seem to be able to tolerate right now are broccoli, green beans, and peas with some occasional winter squash, but I also try to eat very low carb since I'm trying to follow an anti-candida diet as well.

I know a lot of people fear high fat and low carb, but I've done my research on that and feel comfortable with it. I definitely have seen a huge improvement after starting this diet a few months ago as well.

I stopped all supplements 4 days before the test. Normally, however, I take milk thistle, fermented cod liver oil, vitamin C, vitamin D, betaine HCL with meals, selenium, and synthroid.

 

[minniemom2011]

Hi, minniemom2011.

I would suggest that you (together with your physician) consider running the methylation pathways panel from Health Diagnostics and Research Institute in New Jersey. This will likely show that you have a partial methylation cycle block and glutathione depletion. If this is the case, the Glutathione Depletion--Methylation Cycle Block hypothesis likely fits your case, as has turned out to be true for nearly all PWMEs/PWCs who have been tested. If this hypothesis fits your case, then the Simplified Treatment Approach which is based on it is likely to be helpful to you.

Lifting the partial methylation cycle block, when it is present, will bring the sulfur metabolism back to normal function. This includes bringing the detox system back up, lowering oxidative stress by raising glutathione, and helping the synthesis and metabolism of the neurotransmitters.

Below is contact information for the panel, a discussion of interpretation of the panel results, and the most recent version of the Simplified Treatment Approach protocol. Papers describing the GD-MCB hypothesis can be found at http://www.aboutmecfs.org/Trt/TrtGSHIntro.aspx

I hope this is helpful. You can find more discussion of this type of treatment in this section of the forums.

Best regards,

Rich


Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead. The current cost is $295, including the mailer to send the blood samples to the lab.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.



Interpretation of the Health Diagnostics and Research Institute
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., at 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.


April 18, 2009


SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROME (Revised)

(Extracted from the full treatment program
developed by Amy Yasko, Ph.D., N.D.
which is used primarily in treating autism [1])

SUPPLEMENTS

1. FolaPro [2]: tablet (200mcg) daily
2. Actifolate [3]: tablet daily
3. General Vitamin Neurological Health Formula [4]: start with tablet and work up dosage as tolerated to 2 tablets daily
4. Phosphatidyl Serine Complex [5]: 1 softgel capsule daily
5. Activated B12 Guard [6]: 1 sublingual lozenge daily

All these supplements can be obtained from http://www.holisticheal.com, or all but the third one can be obtained from other sources.
The first two supplement tablets are difficult to break into quarters. We recommend that you obtain (from any pharmacy) a good-quality pill splitter to assist with this process. They can, alternatively, be crushed into powders, which are then separated on a flat surface using a knife or single-edged razor blade, and the powders can be mixed together. They can be taken orally with water, with or without food.
These supplements can make some patients sleepy, so in those cases they take them at bedtime. They can be taken at any time of day, with or without food.
GO SLOWLY. As the methylation cycle block is lifted, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.


[1] Yasko, Amy, and Gordon, Garry, The Puzzle of Autism, Matrix Development Publishing, Payson, AZ, 2006, p. 49.
[2] FolaPro is a registered trademark of Metagenics, Inc.
[3] Actifolate is a registered trademark of Metagenics, Inc.
[4] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
[5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center.
[6] Activated B12 Guard is a registered trademark of Perque LLC.

Thanks so much for all of this Rich! It gives me a lot to read and research.

 

[minniemom2011]

I saw that you had posted your results under Diagnostic Testing and wanted to post the link to that post so that someone would have access to it in case they wanted to review. It is a very comprehensive test.

http://forums.aboutmecfs.org/showthread.php?10459-Can-anyone-help-with-NutrEval-results

Thanks so much for posting the link to my test results!

 

[minniemom2011]

Hi, minniemom2011.

I would suggest that you (together with your physician) consider running the methylation pathways panel from Health Diagnostics and Research Institute in New Jersey. This will likely show that you have a partial methylation cycle block and glutathione depletion. If this is the case, the Glutathione Depletion--Methylation Cycle Block hypothesis likely fits your case, as has turned out to be true for nearly all PWMEs/PWCs who have been tested. If this hypothesis fits your case, then the Simplified Treatment Approach which is based on it is likely to be helpful to you.

Lifting the partial methylation cycle block, when it is present, will bring the sulfur metabolism back to normal function. This includes bringing the detox system back up, lowering oxidative stress by raising glutathione, and helping the synthesis and metabolism of the neurotransmitters.

EDIT: I just looked at my NutrEval test results again and see that it actually shows high glutathione levels.

Hi Rich,
Thanks again for all this information. I thought the Genova NutrEval test I had done was supposed to show whether or not I had a methylation cycle block. Can you see if that is represented on my test results? http://forums.aboutmecfs.org/showthread.php?10459-Can-anyone-help-with-NutrEval-results

Is there any real harm in assuming one has a partial methylation cycle block and glutathione depletion and treating for it without having the panel done?

 

[pken]

Sure pken. I am on a very limited diet due to multiple food sensitivities. A typical day for me is basically meat and veggies and even those are limited. I don't know if you're familiar with Weston Price or Nourishing Traditions, but that is the type of diet I follow - very traditional foods. I was a vegetarian for about 2 years and drastically changed my eating habits about 4-5 months ago.

I eat chicken, beef, or bison usually for my meat and I eat a fairly high fat diet - though mostly all animal fats. I don't eat any gluten, soy, or dairy. I also try to eat/drink a lot of fermented foods for probiotics, like kefir, sauerkraut juice, beet kvass, etc. The only veggies I seem to be able to tolerate right now are broccoli, green beans, and peas with some occasional winter squash, but I also try to eat very low carb since I'm trying to follow an anti-candida diet as well.

I know a lot of people fear high fat and low carb, but I've done my research on that and feel comfortable with it. I definitely have seen a huge improvement after starting this diet a few months ago as well.

I stopped all supplements 4 days before the test. Normally, however, I take milk thistle, fermented cod liver oil, vitamin C, vitamin D, betaine HCL with meals, selenium, and synthroid.

Hello again minniemom2011,

Thanks for the comprehensive reply - it's very helpful.

I think what we eat is bound to influence these types of results - perhaps quite dramatically. And the problem here is that the lab norms are probably based on people who follow the SAD (standard American diet) diet, or a version thereof i.e. lots of grains, not much fat, loads of sugar/carbs. You know, the opposite of what's working for you (and me).

So I'm with you on the kind of diet you're on. Fats are friends and I'm inclined to think that the demonisation and pathological avoidance of them is leading to many diseases now. It's certainly not making the population thinner...

I wonder though, perhaps your apparently high oxidative stress is just be a marker of the diet you're on (oxidising more fats as energy) and not necessarily a big deal per se. Whether or not you should add some extra antioxidants to bring that level down I don't know. It's worth considering. Perhaps if you had been taking the vitamin C at the time of the test the results would have been normal? I know that when bodybuilders take large amounts of carnitine to help burn fat they usually take something like lipoic acid to counter the free radicals.

The high methionine and taurine could be explained by your higher than average protein intake, the high methylhistidine and beta alanine too, especially if you consume significant amounts of poultry. Poultry is a rich source of anserine (beta-alanyl-N-methylhistidine). The low lysine may be a side effect of not consuming dairy. Your arginine level is OK - balancing this with extra lysine may be helpful. Be wary of taking extra arginine as it seems to be implicated in some viral problems. I would prefer to see higher lysine than arginine if anything.

The ketone BHBA is high but again that may just be the results of your higher-fat-than-average diet. Have you ever monitored your level of ketosis using Ketostix? Could you have been in "deep" ketosis when the sample was taken?

Your GABA (γ-Aminobutyric acid) levels are towards the lower end - do you have problems relaxing or sleeping?

P.

 

[minniemom2011]

Hi pken,

Thanks for your insight! As I was looking over my test results, I wondered too if the "normal" ranges that are shown are normal for those eating a SAD diet. I do think my diet is highly nutritious and I honestly don't know what I could do to improve it much. My nutritionist did suggesting eating walnut butter to increase my omega-6's and decreasing red meat by a bit to lower arachidonic acid levels - though I don't eat a LOT of read meat anyway.

So glad to hear someone else agrees with my diet. It's like an uphill battle trying to convince people that fats are not evil!!

I do think I could have been in ketosis when the samples were drawn. At that time I was primarily eating chicken, chicken liver, and broccoli. I'm not familiar with Ketostix, but will check into them.

My sleep is extremely variable. Although I never feel rested in the morning - I'm always stiff and sore and at 33, I'm just too young for that - I have times where I don't have trouble sleeping. At other times, though, I'll struggle to fall asleep and will usually wake in the middle of the night and take hours to get back to sleep. I think I'll check into GABA. Thanks for the suggestion.

 

[pken]

You're more than welcome.

Ketostix are interesting - especially for Atkins-type diets as they show you (roughly) the degree of ketosis you're in. They're pretty inexpensive too.

The GABA was only a guess based on your levels. You can buy it in pill or powder form if you want to try some before bed. The powder form is cheaper and gives you the advantage of infinite dosing options. Like pretty much anything you can get side effects so read up and start low. iHerb has reviews and are generally well priced.

If you were eating primarily eating chicken that could explain your high beta alanine and methylhistidine.

I found my sleep is much better on a ketogenic diet - but I need to stop eating perhaps 6 hours before bed. Have you tried that?

One last thing, walnuts are also a significant source of arginine which, as I mentioned, may cause increased viral problems - especially with low lysine (which your tests showed). Going further out of balance is probably not a good idea regardless of viral issues. Since omega 6 can be pro-inflammatory I might reconsider that aspect or at least get additional omega 6 from a non arginine source.

 

[richvank]

Hi Rich,
Thanks again for all this information. I thought the Genova NutrEval test I had done was supposed to show whether or not I had a methylation cycle block. Can you see if that is represented on my test results? http://forums.aboutmecfs.org/showthread.php?10459-Can-anyone-help-with-NutrEval-results

Is there any real harm in assuming one has a partial methylation cycle block and glutathione depletion and treating for it without having the panel done?

Hi, minniemom2011.

I looked over your NutraEval results, and I pretty much concur with what pken has written. More comments on that below.

The NutraEval panel will give indirect results as to whether one has a partial methylation cycle block. If MMA and Figlu are both somewhat elevated, this suggests that there is such a partial block. I would say that you do have one, based on your results, and I think it is likely that the Simplified Treatment Approach for lifting the partial methylation cycle block would help you.

No, there's no harm in treating for the partial methylation cycle block without running the Health Diagnostics panel first. However, I have heard from people who have written after starting this that they wish they had run the panel first, because they then would have had numbers to compare with to see how the treatment is going. The treatment takes time, usually at least a few months, and during this time, there are usually detox symptoms, so it's difficult to tell how the treatment is going from symptoms alone. It gets worse before better in many cases, and it takes hope and faith to stick with it if that happens. Having some improved numbers to look at can be encouraging at times like that. When the methylation cycle comes back up, it brings both the immune system and the detox system back up, too, and that causes toxins to be mobilized into the blood. There is a time delay in getting them excreted, via the kidneys and liver, and meanwhile, the cells are being bathed in these mobilized toxins, which causes some unpleasant symptoms.

Here are my thoughts on your NutraEval results:

1. You have some gut problems, but they aren't too bad. Some yeast and some intestinal dysbiosis. Having the gut in reasonable condition is important for making sure that when the detox starts, the toxins really do get excreted in the stools, and not just recirculated via the enterohepatic circulation. This should stand you in good stead if you decide to boost your methylation cycle.

2. You weren't burning much in the way of carbs when this panel was run. You were in ketosis, burning mostly fats. You weren't burning amino acids (from protein) much, either. The low carb, high fat diet you reported is reflected in your results. So is the high chicken consumption, as pken noted. Generally speaking, PWMEs/PWCs do better on a high-protein, low-carb, low-fat diet. The reason is that there is usually a partial block in the Krebs cycle at aconitase, because of oxidative stress, resulting from glutathione depletion, and this limits the ability to process both carbs and fats, which have to enter the Krebs cycle just upstream of this partial block. In your case, I can't tell whether you have that partial block, because you were not challenging your Krebs cycle with carbs when the test was taken. It looks as though you were burning fats, but not at a very high rate, judging from the low levels of the first three Krebs metabolites. My guess is that your glutathione was holding up pretty well, so that you didn't have a lot of oxidative stress, and thus were able to burn fats, at least at a low rate.

3. Your methylation cycle was partially blocked, but your methionine was staying high, apparently because of your high protein consumption from chicken and meat. Sarcosine was being pushed up in order to control the SAMe level and the ratio of SAMe to SAH, because the methionine synthase enzyme was partially blocked, but you were pumping in methionine with your diet. There was a pretty good flow down the transsulfuration pathway to make cysteine, because of the partially blocked methylation cycle, and your glutathione production was apparently holding up pretty well, so you weren't suffering from too much oxidative stress. Note that Genova does a whole blood total glutathione measurement, which is not very indicative of tissue cell reduced glutathione levels, which are the important ones, but your pyroglutamic acid looked pretty good, and your oxidative stress markers weren't too high, so I'm guessing that your glutathione level is not too bad. The Health Diagnostics panel would give a better measure of glutathione status, as well as folate status and methylation cycle status.

4. You appeared to have some neurotransmitter issues. Tryptophan was high, but probably not being converted to serotonin at a normal rate. This may have been due to low tetrahydrobiopterin (suggested by the relatively high phenylalanine to tyrosine ratio), which would correspond to a block in the folate metabolism, which would be expected from the partial methylation cycle block and is also indicated by the elevated figlu. Low serotonin could explain your sleep issues.

5. Your urea cycle might have been partially blocked at the arginosuccinate synthase reaction, possibly because of low intracellular magnesium (Note that the RBC magnesium measurement does not reflect tissue cell intracellular magnesium levels very well). It doesn't look as though you were pushing your urea cycle very hard, though, because you weren't burning amino acids for fuel at a very high rate, presumably because of the high fat intake, and also because of the functional deficiency in B12 indicated by the high MMA. It looks as though you also had a significant B6 deficiency, and B6 is necessary for transamination reactions that convert one amino acid to another. That probably partially explains some of the abnormalities in amino acids levels.

6. Looks like you might have had some lead toxicity. Can't tell about chronic mercury toxicity from a blood test. Manganese and selenium look a little low.

I guess those are my main impressions. Your NutraEval results are kind of unusual, probably because of your diet. Usually I see results from people who are still taking in quite a lot of carbs, which they can't burn very well, so they are storing them as fat, and usually their guts are not in as good a condition as yours appears to be, in terms of dysbiosis, and that leads to a lot of other problems. I'm glad you decided to give up vegetarianism. It's hard to get enough B12 on a vegetarian diet, and I think that can help to push a person who is genetically predisposed to developing a partial methylation cycle block over the edge.

Best regards,

Rich

 

[minniemom2011]

Thanks so much for all this info Rich! I so appreciate it! I hope you don't mind if I ask a few more questions. I'm trying to research as much as I can, but to be honest I feel nothing short of dumb these days with all the brain fog I've got going on!

The treatment takes time, usually at least a few months, and during this time, there are usually detox symptoms, so it's difficult to tell how the treatment is going from symptoms alone. It gets worse before better in many cases, and it takes hope and faith to stick with it if that happens. Having some improved numbers to look at can be encouraging at times like that. When the methylation cycle comes back up, it brings both the immune system and the detox system back up, too, and that causes toxins to be mobilized into the blood. There is a time delay in getting them excreted, via the kidneys and liver, and meanwhile, the cells are being bathed in these mobilized toxins, which causes some unpleasant symptoms.

I've been doing an anti-candida diet for close to a year now and started out with extreme die-off, so I understand those issues. I wish I could do all the testing you suggested, but I've spent so much in the last few months that I just can't afford it right now. I'm willing to go "blindly" into the recommended treatment and see what happens.

I'm so thrilled to hear you say the gut problems don't seem too bad. I do feel like things are improving on the GAPS diet for me. Reactions that I have to food now are not nearly as severe as they once were, so I'm hopeful that my leaky gut is beginning to heal.

It has been suggested to me that I try to use molybdenum as a detox agent. Do you have any thoughts on that? Can that be taken in addition to the course of treatment you linked to? I was told that I probably have a high level of acetalhydes in my body from candida and/or other toxins dying off and the molybdenum would help excrete these.

Can I ask what led you to believe I have some lead toxicity? I've been thinking about getting a hair test when I can afford it. Do you think that would be worthwhile for both the lead and mercury?

If I do have low serotonin, I assume this treatment that you linked to will help with that?

I am trying to supplement both B12 and Magnesium. I seem to just waste Mag as low doses just cause diarrhea, so I ordered a cream and will try it topically. The B12 seems to work some days and give me a bit of extra energy and other days causes extreme fatigue. Any idea what's going on there? I just started supplementing with P5P, so I'm hoping that will help the B6 levels.

Lastly, you mentioned that some have a genetic predisposition to a partial methylation cycle block. Is there a test for this? I don't know if it would be worthwhile or if there's anything that can even be done to prevent it, but it has me concerned for my children.

One other thing I just thought of is that I was also told to start taking TMG. I haven't even a clue what that is. Is this something you're familiar with and that you think may be helpful?

Thank you again. I appreciate your time!

 

[Joopiter76]

the next time you do the test stay on your supps otherwise you dont know if it is enough what you take or whre you have to increase.

 

[minniemom2011]

the next time you do the test stay on your supps otherwise you dont know if it is enough what you take or whre you have to increase.

Yes, I kind of wish I would have done that, but I was specifically told to stop all supplements for 4 days prior to the test. I can understand the reasoning behind that though as they wanted to see which supplements I actually NEED to be taking.

 

[Joopiter76]

if you order the tests the next time through Dr. Yasko you will get special advice from her how to proceed. You can sign up to the CFS_Yasko group at Yahoo and there you can see some test results an how she has commented the results of others.

 

[minniemom2011]

if you order the tests the next time through Dr. Yasko you will get special advice from her how to proceed. You can sign up to the CFS_Yasko group at Yahoo and there you can see some test results an how she has commented the results of others.

Just joined the Yahoo group. Thanks!

 

[richvank]

***Hi, minniemom2011.

***My responses are at the asterisks below:

Thanks so much for all this info Rich! I so appreciate it!

***You're welcome.

I hope you don't mind if I ask a few more questions. I'm trying to research as much as I can, but to be honest I feel nothing short of dumb these days with all the brain fog I've got going on!

***i'll answer them if I can.

The treatment takes time, usually at least a few months, and during this time, there are usually detox symptoms, so it's difficult to tell how the treatment is going from symptoms alone. It gets worse before better in many cases, and it takes hope and faith to stick with it if that happens. Having some improved numbers to look at can be encouraging at times like that. When the methylation cycle comes back up, it brings both the immune system and the detox system back up, too, and that causes toxins to be mobilized into the blood. There is a time delay in getting them excreted, via the kidneys and liver, and meanwhile, the cells are being bathed in these mobilized toxins, which causes some unpleasant symptoms.
I've been doing an anti-candida diet for close to a year now and started out with extreme die-off, so I understand those issues. I wish I could do all the testing you suggested, but I've spent so much in the last few months that I just can't afford it right now. I'm willing to go "blindly" into the recommended treatment and see what happens.

I'm so thrilled to hear you say the gut problems don't seem too bad. I do feel like things are improving on the GAPS diet for me. Reactions that I have to food now are not nearly as severe as they once were, so I'm hopeful that my leaky gut is beginning to heal.

***It sounds as though your impression of your gut function agrees with what I think the urine organic acids part of the panel said. I'm happy for you, too. Getting the gut working well is a big part of recovering from ME/CFS, and it will make other parts of the treatment go better.

It has been suggested to me that I try to use molybdenum as a detox agent. Do you have any thoughts on that? Can that be taken in addition to the course of treatment you linked to? I was told that I probably have a high level of acetalhydes in my body from candida and/or other toxins dying off and the molybdenum would help excrete these.

***Moly is compatible with the methylation treatment, and some people actually need to add it because they have difficulty processing sulfur-containing foods and supplements. Bringing up the methylation cycle can increase the flow through sulfite oxidase, and it uses moly as a cofactor. If it is deficient, sulfite can build up, and that causes headaches and other problems. Moly is used by three enzymes in the body. The other two are aldehyde oxidase, to which you referred, and xanthine oxidase, which is part of the pathway that converts purines to uric acid. Yeasts produce alcohol, and the breakdown product is acetaldehyde.

Can I ask what led you to believe I have some lead toxicity?

***It showed up in your red blood cells. The lab reference range indicates that it's in the normal range, but the reference ranges are not always so dependable.

I've been thinking about getting a hair test when I can afford it. Do you think that would be worthwhile for both the lead and mercury?

***Hair testing is not always very reliable. I prefer a DMSA-challenged urine toxic and essential elements test, from Doctor's Data Lab. It's available through some doctors, or through www.directlabs.com without a doctor's order.

If I do have low serotonin, I assume this treatment that you linked to will help with that?

***Yes, it should. When the partial methylation cycle block is lifted, the folate metabolism recovers, also, since they are linked. The folate metabolism is also associated with the biopterin cycle, so that when it recovers, the level of tetrahydrobiopterin (BH4) should come up, too. BH4 is essential for converting tryptophan to serotonin, and converting tyrosine to dopamine and the other catecholamines.

I am trying to supplement both B12 and Magnesium. I seem to just waste Mag as low doses just cause diarrhea, so I ordered a cream and will try it topically.

***It's difficult to get the intracellular magnesium up until glutathione is brought up to normal. Some people inject magnesium sulfate, together with taurine, and that seems to work, without hurting so much. Other people bathe in Epsom salts, which is magnesium sulfate. Some people find that soothing, and others can't tolerate it, I think because they have sulfate-reducing bacteria in their gut, which convert sulfate to hydrogen sulfide, which is toxic at high levels.

The B12 seems to work some days and give me a bit of extra energy and other days causes extreme fatigue. Any idea what's going on there?

***It might be that you are "tickling" the methylation cycle and increasing the mobilization of toxins. Unfortunately, I don't know of a way to get the methylation cycle working properly without going through some detox. The longer a person has been ill, the more toxins they have accumulated, and they have to come out in order for recovery to occur.

I just started supplementing with P5P, so I'm hoping that will help the B6 levels.

***I think it will. I suspect that if you supplemented with P5P together with sublingual adenosylcobalamin (Dibencozide), you would experience quite a boost of energy, because your branched-chain amino acid levels are pretty high, and they are "just waiting" to be processed into the Krebs cycle to be burned for energy production.

Lastly, you mentioned that some have a genetic predisposition to a partial methylation cycle block. Is there a test for this? I don't know if it would be worthwhile or if there's anything that can even be done to prevent it, but it has me concerned for my children.

***Dr. Amy Yasko offers a genomics panel at www.holisticheal.com that looks at several of the genetic polymorphisms that influence methylation. I don't think anyone yet knows all of the ones that are important. Dr. Yasko's panel is worthwhile for people who want to do her full treatment program. It can be more helpful than the "stripped-down" version of it that I have suggested, but it is also quite a bit more complex and expensive, and depends on the person studying a lot to understand how to tailor it to their particular case.

One other thing I just thought of is that I was also told to start taking TMG. I haven't even a clue what that is. Is this something you're familiar with and that you think may be helpful?

***That's trimethylglycine, also called betaine. It feeds an alternative methylation pathway (the BHMT pathway) that is in the liver and kidneys. The simplified treatment I have suggested includes Dr. Yasko's multi, which has some TMG in it. The benefit of TMG, especially at the beginning of treatment, is that it will help to build up SAMe in the liver and kidneys. This is useful for supporting the remethylation of cobalamin (B12) in its support of methionine synthase, which is in the main methylation pathway. So for start-up, TMG can be helpful. It's important not to go too high with TMG, though, because it can shunt the flow of homocysteine away from the main methylation pathway, which we are trying to restart. The latter is important, because it supports the folate metabolism and also regulates the sulfur metabolism as a whole. Until it is brought up, these other parts of the overall metabolism will not work well, and they affect many other aspects.

***One of the "interesting" features of ME/CFS is that usually the stomach acid production is low (I think because of glutathione depletion in the parietal cells), and that impacts the digestive system in several unfortunate ways. Stomach acid can be supported by taking betaine-HCl, which brings in TMG or betaine as a carrier, as well as the hydrochloric acid. Sometimes people get caught between trying to build up their stomach acid, which is very beneficial for the digestive system, and trying to restart their methionine synthase, which requires not going too high on TMG. One way to deal with this is to also take DMG, which exerts backpressure on the BHMT pathway, because it is a product of this reaction.

Thank you again. I appreciate your time!

***You're welcome. I hope you have success.

***Best regards,

***Rich

 

[Joopiter76]

Hi Rich and all,

how much TMG do you think would be good for someone with very low SAMe (its not me)

And do you have any reports about eye Problems expecially in the morning, Problems with the contrast of letters on the ground, bands in teh letters although they are not there, I just see them and strewing letters what means that I cant read them clear so I have to get closer to the monitor to read. But this gets better and better through the day and much has gone in the evening. Is this a kind of detox? A kind of toxins Dr. Shoemaker is talking about? It seems to have increased since I take more Methyl-B12 (I have so many mutations in the MTRR hydroxy is not enough.

regards, Joopiter

 

[Freddd]

Hi Rich and all,

how much TMG do you think would be good for someone with very low SAMe (its not me)

And do you have any reports about eye Problems expecially in the morning, Problems with the contrast of letters on the ground, bands in teh letters although they are not there, I just see them and strewing letters what means that I cant read them clear so I have to get closer to the monitor to read. But this gets better and better through the day and much has gone in the evening. Is this a kind of detox? A kind of toxins Dr. Shoemaker is talking about? It seems to have increased since I take more Methyl-B12 (I have so many mutations in the MTRR hydroxy is not enough.

regards, Joopiter

Hi Joopiter,

Methylb12 and Metafolin will often get methylation going essentially right away resulting in hypokalemia in 3 days or so as cell production steps up suddenly. All the basics are needed such as b-complex, magnesium, a,d,e,c,zinc etc. Since so many things start at once there are usually startup reponses that can be quite intense or not. The things that respond right away are the things that usually heal most rapidly. Everything starts changing but there may be hundreds of steps with intermediate effects on the way. Mb12 also affe3cts the nervous system and intensifies much sensory info including pain and discomforts.