Simplified Methylation Protocol Revised as of Today

[roxie60]

Rich,

I am trying to get some additional tests including 23andme, methylation pathways panel, nutirents panel, mitochondrial dysfunction (not sure what test gives this, MyHills?). I was feeling my worst 6 weeks ago. I am starting to feel better but I have been on shortterm diability for 4 weeks (I dont think the less stress can account for my improvement but I'm sure it helps). I wanted to know if you think it wise to waitfor next flare up/storm to take some of these tests (obviously the gene test should not matter) or should I go ahead and take them now even though I am feeling loads better (increased hrs feeling functional)? I would expect if I'm sarting to feel better again then my results would not reflect worse case when I am bedridden, too fatigues do anything, is this a correc assumpion?

 

[golfbuddy]

Rich, please please review my Methylation panel

Rich,

I finally got this methylation panel result back. Somehow the amino acids profile was never sent, so I may have to do that again. I am posting my results as well as the ref ranges for your convenience. Below that I have pasted your previous replies to me regarding my SNP's and that I have been following your protocol for about 6 months. Thank you so much!

AA in Plasma
Glutathione(oxidized) 0.51 (0.16-0.50)
Glutathione(reduced) 3.2 (3.8-5.5)

Derivates
S-Adenosylmethionine (RBC) 225 (221-256)
S-Adenosylhomocysteine (RBC) 49.7 (38.0-49.0)
FOLIC ACID DERIVATES
5-CH3-THF 8.8 (8.4-72.6)
10-Formyl-THF 3.6 (1.5-8.2)
5-Formyl-THF 3.90 (1.20-11.70)
THF 0.61 (0.60-6.80)
Folic Acid 10.9 (8.9-24.6)
Folinic Acid (WB) 8.3 (9.0-35.5)
Folic Acid, active (RBC) 341 (400-1500)
NUCLEOSIDE
Adenosine 23.9 (16.8-21.4)

Thanks so much for any recommendations.

I have read as much of the basic info that my numb brain can take in. At the moment I am mostly confused about my snp's and how they should change the treatment. I am not even sure which are most important, but I will list those for which I am have a double mutation or a +/-.

COMT V158M +/+
COMT H62H +/+
VDR Taq +/-
VDR Fok +/-
MAO A +/+
ACE +/-
MTRR +/+
BHMT 1,2,4,8 +/-
CBS C699T +/+
NOS D298E +/-

***Your COMT and VDR SNPs suggest that hydroxocobalamin will be an O.K. form of B12 for you.

I am wondering about the CBS mutation and concern for supplementing B6 with the B complexes, as well as avoiding sulfur. Is SamE safe to as a cofactor? I definitely have an ammonia problem that is documented on blood tests as well as anytime I sweat!

***Given that you have evidence for an ammonia issue and the CBS SNP, it would probably be best not to go too high on B6 until you get your methylation cycle working better, assuming that you do have a partial methylation cycle block. I would suggest not going over 50 mg per day of B6. Avoiding high-sulfur foods and supplements would be a good idea, again until you get your methylation cycle working better. You might consider taking the Yasko ammonia support RNA formulation.

I also have elevated mercury and was considering chelation but is DMSA a bad idea due to the sulfur?

***It would probably be best to work on the methylation cycle block first, and see if you can bring glutathione up that way, before trying to chelate the mercury. If that won't work, you will have to chelate first. You might consider the Cutler protocol for removing the mercury.

I have been getting weekly IV push of glutathione for some time, and understand that it may worsen the B12 problem.

***Not necessarily. That is true for Freddd and others who apparently have certain mutations in their intracellular B12 processing enzymes, but this does not appear to me to be very common. If you are tolerating the IV glutathione, I think it would be O.K. to continue it. This primarily benefits the kidneys and the lungs.

I am very confused and want to start a protocol but don't want to do things wrong. Thanks for any input! If I have posted in the wrong place please tell me where to re-direct.

***I understand the reason for the confusion. We don't have a consensus on the protocol that should be used. The protocol I have suggested can be found at the end of this file:

http://forums.phoenixrising.me/showt...nenburg-Part-7

This protocol was subjected to a clinical study and was found to produce significant improvement in about two-thirds of the people in the study.

Freddd advocates a somewhat different protocol, based on his experience and that of some other people. His protocol has also helped quite a few people.

Best regards,

Rich

was in the right place. I have actually been following your protocol for about 6 months. I do think that it has helped me but I am kind of in a plateau and was hoping to get better. That is why I was asking about other things, wondering if the glutathione, or the type of B12 and folate, or adding Same, or avoiding sulfur could be holdiing me back. With the continual up and down of symptoms it can be so hard to ID what is making you fell better or worse. I have never tried avoiding B6 nor sulfur. I did a lot of EDTA chelating in the past which helped everything except the mercury which I was told needed DMSA. What would be the risk of doing it? I don't really understand how the CBS+/+ plays into everything and am willing to try things but don't want to do more harm than good. It seems that knowing the snps should at least allow you to avoid some pitfalls. I appreciate your advice more than you know.

 

[richvank]

Hi, golfbuddy.

Here are some comments on your methylation pathways panel results:

You do have glutathione depletion, a functional B12 deficiency (inferred from the other results), a partial block of methionine synthase (which links the methylation cycle with the folate metabolism), and loss of folates from the cells. You are suffering from oxidative stress.

I realize that you have been on the methylation protocol for several months. Something appears to be holding back your progress. Here is part of a post I wrote a short time ago:

"What are some possible reasons why a PWME would experience no response from the methylation treatment? One obvious possibility might be that the person does not have the vicious circle mechanism described above. Though this mechanism appears to be fundamental to the pathophysiology of ME/CFS, there may be some people who have similar symptoms but do not have this vicious circle. This is one of the main reasons it is helpful to run the methylation pathways panel (I refer here to the biochemical panel, not the genomic panel with a similar name.) [golfbuddy: This one clearly does not apply to you!]

"I suspect that another possibility is deficiency in one or more of the essential nutrients for the methylation cycle and related pathways. There are several vitamins, minerals and essential amino acids needed to support this part of the metabolism, and many PWMEs have been found to be deficient in some of them. Those who have hemopyrrollactamuria (HPU) are a subset of this group. Again, testing is available to determine whether there are deficiencies. This includes direct determination of the levels of the nutrients in the blood, measurements of certain enzyme activities that are specific to particular nutrients, and inferring deficiencies from metabolic tests (such as urine organic acids and amino acids in the urine), hair mineral tests, and essential element tests in the urine. The interpretation of hair testing is not simple or straightforward and requires considerable understanding and experience. Testing for HPU is also available.

"Another possibility is high body burdens of one or more toxic metals, such as mercury, that are capable of blocking enzymes in this part of the metabolism. Testing is available to look for these in urine, blood, feces and hair, and chelation may be needed if the levels of the toxic metals are high."


Perhaps running the amino acids panel will help to clarify what is going on in your case. If feasible, you might consider running the Metametrix ION profile (w/ 40 plasma amino acids). That will cover all the cofactors and allow us to see what might be deficient. This profile is available without a doctor's order here:

https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx

Best regards,

Rich

 

[richvank]

Rich,

I am trying to get some additional tests including 23andme, methylation pathways panel, nutirents panel, mitochondrial dysfunction (not sure what test gives this, MyHills?). I was feeling my worst 6 weeks ago. I am starting to feel better but I have been on shortterm diability for 4 weeks (I dont think the less stress can account for my improvement but I'm sure it helps). I wanted to know if you think it wise to waitfor next flare up/storm to take some of these tests (obviously the gene test should not matter) or should I go ahead and take them now even though I am feeling loads better (increased hrs feeling functional)? I would expect if I'm sarting to feel better again then my results would not reflect worse case when I am bedridden, too fatigues do anything, is this a correc assumpion?

Hi, Roxie.

I think you can go ahead and run the tests. They should show the underlying problems, even though you are doing better at the moment. The mitochondrial panel might look better when you are doing better, but I think that even it will show some abnormality.

Best regards,

Rich

 

[roxie60]

Thx Rich. Can anyone reco a mitochondrial function panel? I also looked at the Genovo nitrients website but hey have a gazzillion tests, not sure which one is the most appropriate, NutrEval FM??

 

[golfbuddy]

Rich,

Thank you so much for this feedback. I do have a high mercury burden, so I guess that chelation would be the next step. You had mentioned the "Cutler protocol". Is that available somewhere?

Should I even continue with the methylation protocol? I can and will do the amino acids panel as well. I had planned to do them together but they screwed it up.

Regards,
Steve

Hi, golfbuddy.

Here are some comments on your methylation pathways panel results:

You do have glutathione depletion, a functional B12 deficiency (inferred from the other results), a partial block of methionine synthase (which links the methylation cycle with the folate metabolism), and loss of folates from the cells. You are suffering from oxidative stress.

I realize that you have been on the methylation protocol for several months. Something appears to be holding back your progress. Here is part of a post I wrote a short time ago:

"What are some possible reasons why a PWME would experience no response from the methylation treatment? One obvious possibility might be that the person does not have the vicious circle mechanism described above. Though this mechanism appears to be fundamental to the pathophysiology of ME/CFS, there may be some people who have similar symptoms but do not have this vicious circle. This is one of the main reasons it is helpful to run the methylation pathways panel (I refer here to the biochemical panel, not the genomic panel with a similar name.) [golfbuddy: This one clearly does not apply to you!]

"I suspect that another possibility is deficiency in one or more of the essential nutrients for the methylation cycle and related pathways. There are several vitamins, minerals and essential amino acids needed to support this part of the metabolism, and many PWMEs have been found to be deficient in some of them. Those who have hemopyrrollactamuria (HPU) are a subset of this group. Again, testing is available to determine whether there are deficiencies. This includes direct determination of the levels of the nutrients in the blood, measurements of certain enzyme activities that are specific to particular nutrients, and inferring deficiencies from metabolic tests (such as urine organic acids and amino acids in the urine), hair mineral tests, and essential element tests in the urine. The interpretation of hair testing is not simple or straightforward and requires considerable understanding and experience. Testing for HPU is also available.

"Another possibility is high body burdens of one or more toxic metals, such as mercury, that are capable of blocking enzymes in this part of the metabolism. Testing is available to look for these in urine, blood, feces and hair, and chelation may be needed if the levels of the toxic metals are high."


Perhaps running the amino acids panel will help to clarify what is going on in your case. If feasible, you might consider running the Metametrix ION profile (w/ 40 plasma amino acids). That will cover all the cofactors and allow us to see what might be deficient. This profile is available without a doctor's order here:

https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx

Best regards,

Rich

 

[richvank]

Hi, Steve.

Information on the Cutler protocol can be found here:
http://www.noamalgam.com/

Since you have plateaued on the treatment, it might be a good idea to work on removing the mercury first, and then to go back on methylation treatment after the mercury levels are down.

Best regards,

Rich

 

[daniariete2000]

Hi ,

are all the forms of folate in the protocol (folinic,folic etc..) to take at the theme moment ?

Thanks

Daniele

 

[richvank]

Hi ,

are all the forms of folate in the protocol (folinic,folic etc..) to take at the theme moment ?

Thanks

Daniele

Hi, Daniele.

A lot of people do take them at the same time, and it seems to work O.K. for most PWMEs, based on our clinical study and experiences reported by others. Freddd has found that he and some others do not do well with folic acid, and also he and some others do not do well with folinic acid. The most important one is the methylfolate. If you want to take that separated about 2 hours from the others, it may be better absorbed by the gut, because the folates compete with each other for transporters.

Best regards,

Rich

 

[Lynn_M]

What is best timing for Methylation Pathway and NutraEval tests?

I'm trying to figure out when to do a HRNI methylation pathway panel (MPP) and possibly a NutraEval. In March I found out I am homo for MTHFR A1298C. I don't have CFS, but my symptoms are low energy and low neurotransmitter levels, and various functional tests have showed I was low in cobalamin and methylation ability. I am also working with a friend who is hetero A1298C and has many symptoms of CFS, and I will be passing the advice on to her as well. I'm trying to minimize my testing costs.

I started on the Active B Protocol in early April 2012. I have a doctor's appointment in mid-July and will be asking him to order a HRNI methylation pathway panel then. I'm thinking that I could wait on the results of the MPP to see if I need to then order the Genova NutraEval test. If the MPP results aren't too bad, maybe I don't even need to do a NutraEval test? Or do I need to do the NutraEval test at the same time as the MPP to facilitate interpretation of the MPP results?

Anybody know what ICD codes need to be used to get Medicare coverage of the NutraEval test? Or of the MPP test, if Medicare covers it? If I could get Medicare coverage of either test, I could do them at the same time.

 

[antfab]

Hi Rich,
I started the protocole ca 2 weeks ago. The first week I felt not so much different but for the last week I feel more tired and have a slightly tight chest as I try to keep up the same activities ie work. I have been taking the Phosphatidyl Serine. I don't know what my colesterol levels are. I am very thin. Should I switch to Lecitin?

Thanks,

Tony

 

[richvank]

Hi, Tony.

I'm guessing that you meant cortisol rather than cholesterol.
I would suggest taking the phos. serine complex at bedtime, because cortisol is supposed to be low at night. It's difficult to say whether lecithin would be better for you without running a 24-hour saliva cortisol test. The Sabre Science version of that is available from www.directlabs.com without a doctor's order, and you can run it at home and send the samples to the lab directly. They will send you the results.

I do recommend working with a physician while on this protocol.

Best regards,

Rich

 

[richvank]

What is best timing for Methylation Pathway and NutraEval tests?


I'm trying to figure out when to do a HRNI methylation pathway panel (MPP) and possibly a NutraEval. In March I found out I am homo for MTHFR A1298C. I don't have CFS, but my symptoms are low energy and low neurotransmitter levels, and various functional tests have showed I was low in cobalamin and methylation ability. I am also working with a friend who is hetero A1298C and has many symptoms of CFS, and I will be passing the advice on to her as well. I'm trying to minimize my testing costs.

I started on the Active B Protocol in early April 2012. I have a doctor's appointment in mid-July and will be asking him to order a HRNI methylation pathway panel then. I'm thinking that I could wait on the results of the MPP to see if I need to then order the Genova NutraEval test. If the MPP results aren't too bad, maybe I don't even need to do a NutraEval test? Or do I need to do the NutraEval test at the same time as the MPP to facilitate interpretation of the MPP results?

Anybody know what ICD codes need to be used to get Medicare coverage of the NutraEval test? Or of the MPP test, if Medicare covers it? If I could get Medicare coverage of either test, I could do them at the same time.

Hi, Lynn.

If you can swing it, doing both initially is best. The NutrEval will tell you if you have particular deficiencies that need to be corrected for the methylation treatment to work. The methylation pathways panel will give you baseline data for comparison later to see how the treatment is going. Symptoms are not always a good indicator.

I don't think the methylation pathways panel is covered by Medicare. Perhaps the NutrEval panel could be, but I don't know the diagnostic code to use. Maybe you could find out from Genova Diagnostics.

Best regards,

Rich

 

[Lynn_M]

Thanks Rich.

I had called Genova Diagnostics earlier. They said Medicare would cover the NutraEval test if qualifying diagnostic codes were used. However, they wouldn't tell me what codes qualified and said they were something my doctor should know.

HDRI said they don't process Medicare claims, but they would send me an invoice and I could submit to Medicare myself. I have no expectation that Medicare will reimburse for the methylation pathways panel.

 

[redo]

Because the revised protocol has substantially the same content as the protocol used in the clinical study conducted by Neil Nathan, M.D. and myself, the results of that study should apply to the revised protocol as well.

I would appreciate any feedback on how this works out for those of you who
decide to try it.

Best regards,

Rich

Hi Rich,

I wonder, do you have some sort of abstract for the study? I'd really like to have a document which I can present to my GP.

Thank you for your efforts for all of us.

 

[richvank]

Hi, redo.

You can print out the poster paper about our treatment study from this site in Australia:

http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf

Best regards,

Rich

 

[antfab]

Thanks Rich,
I have been doing a bit more homework reading posts and people's experiences and am treading a bit more carefully now. It's week 5 and there are some hopeful signs. Will add my experience to the poll for your protocol in a month or two.

Tony

 

[redo]

Hi, redo.

You can print out the poster paper about our treatment study from this site in Australia:

http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf

Best regards,

Rich

Thanks.
Do you have anything which is in a more compressed format? Kind of like a «pubmed length». Reason I ask is that it's easier to get my doc to take a look at it that way.

 

[iacyi]

This should probably be obvious but... How do you folk deal with salivation and the urge to swallow when you take a drop? Sometimes I feel like I accidentally swallow it, or I allow saliva to build up too fast and have to hold on to a mouthful of it.

And also, in those who respond badly to folinic acid, what is a safe dose of methylfolate to compensate? I figure 400 all together. I got carried away taking a higher dose after the folinic made me ill.

 

[Freddd]

This should probably be obvious but... How do you folk deal with salivation and the urge to swallow when you take a drop? Sometimes I feel like I accidentally swallow it, or I allow saliva to build up too fast and have to hold on to a mouthful of it.

And also, in those who respond badly to folinic acid, what is a safe dose of methylfolate to compensate? I figure 400 all together. I got carried away taking a higher dose after the folinic made me ill.

Hi Iacyi,

I have found generally that it takes 10-20 times as much methylfolate with the correct timing to get by the blockade set up with folinic acid found in veggies. When I was talking 800mcg of folinic I could not find a dose under 15mg that worked.

Right now to get past folinic acid in veggies with no folic or folinic acid, I take 2400mcg of Metafolin at wakeup, mid afternoon and bedtime. In addition 4000mcg at each of 2 meals competing with folinic acid from veggies for absorbtion. Deplin comes in two doses, 15mg and 30mg. Their study that did not account for folic acid, folinic acid or veggie folinic acid found 30mg far more effective. They were testing people for relief of depression, a common methylfolate and mb12 deficiency caused symptom. I have been healing the folate insufficiency symptoms and the deep tissue defects of the angular chelitis have finally fully grown out in 4 months and I'm symptom free of this for the first time in my life. Yet they can return in days if I eat too many veggies withtoo much folinic acid weven with my vary vareful pattern and 15.2mg daily. I also started building muscle again in response to exercise and have lost 12 pounds in the past 4 months without changing anything else. I have 25-35 pounds to go to get down to where I would like to be.


DISCLAIMER

I am a self taught systems analyst and consultant working in group healthcare since 1979, full time in group healthcare since 1985. I am not credentialed, certified or licensed to do anything besides drive a car. I have been disabled by the disease processes being discussed and affecting neurology in a multitude of ways for 10 years and impaired in a variety of ways and levels for 54 years before that. Everything I say is my opinion, synthesis, understanding or otherwise of my own creation except direct attributed quotes. Approximate paraphrases are also my interpretation of what I have read. All of this is at best my data analysis, understanding, synthesis and hypotheses and not to be construed as medical advice. I am not responsible for anything you do with any information provided in any way. Anything you do is your own responsibility and at your own risk. There are no published peer reviewed studies backing up my opinions or statements, except the incidental ones quoted or implicit in my synthesis or understanding, and then only in so far any reading of such papers may confer. Your interpretations, actions and variations of what I say are strictly at your own risk.