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Simplified Methylation Protocol Revised as of Today

maddietod

Senior Member
Messages
2,859
Yes, my naturopath wants to do chelation once the candida protocol is finished. Something taken by mouth. I also wonder if leaky gut (I've had candida for a very long time) creates problems for the SMP.

I'll look into the sauerkraut idea.

I know I don't have the folic acid problem Freddd has; I recently started juicing regularly, with an emphasis on dark leafy greens, and nothing has changed. Can I run a test by taking a dose of dibencozide one day and B12 Infusion the next, and see what happens? Or is it better to stop the SMP and jump fully into Freddd's? I thought I might switch over during the summer, so I've already bought all of the supplements.

And in terms of understand what is doing what, is it better to wait until I've done the chelation, before changing protocols?

EDIT: I started juicing on Thursday (4 cups). On Friday I noticed tight muscles. On Saturday I drank 6 cups of juice, and that night I couldn't sleep on my side because the pressure on my shoulder joints was too much. I also couldn't turn my head to one side. This has never happened before. Yesterday, Sunday, I drank 3 cups of juice and the muscle cramping is less, but now I have a runny nose and mild sore throat.

I'm juicing swiss chard, curly kale, zucchini, fennel, parsley, cooked beet, carrot, apple, and red grapes.
 

Mya Symons

Mya Symons
Messages
1,029
Location
Washington
Hi Mya,

I would suggest trying D-Ribose. However, it comes at the end of this chain in my opinion, and experience; adneosylb12, l-carnitine fumatare, Alpha Lipoic acid and then finally D-Ribose to see if it helps after all those other things useful in producing the ATP in the first place that D-ribose plays a part in recycling. Also, the effect that might be present before those things might disapperar if more ATP is being made in the first place.

Also, in regards to folinic acid, for some people it will cause worse paradoxical folate deficiency than folic acid. FOr those who experience that they will also find problems with vegetable food source folate. For most it appears to be just fine. It's only a disaster for some people. It is important to find out whether you are one of those. I'm working on a questionaire in cooperation with Rich, that hopes to be able to help elicit that information. It will be posted and we will collect some info and then come to whatever comnclusions we each come to. The more focused brainpower we can bring to bear on this the better.


Thank you. Does anyone have a link to the finalized version of the simplified methylation protocol?

What is the difference between adenosyl B-12 and Hydroxy B-12? Please and thank you.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thank you. Does anyone have a link to the finalized version of the simplified methylation protocol?

What is the difference between adenosyl B-12 and Hydroxy B-12? Please and thank you.

Hi Mya,

Hydroxycbl is an inactive form of cobalamin that can be converted just a little and not in everybody to mb12 and adb12, the only two active forms of b12 in the human body. Adenosylb12 is immediately active without conversion and occupies the mitochondria and generates energy (ATP) if it has the needed cofactors. The best Mb12 and adb12 are approximately 100 to 10,000 times more effective than cycbl and/or hycbl.

Hydroxycbl, in studies, works for about 2/3 of people in any given study for any specified symptoms chosen from the set in which hycbl might work. It doesn't work at all on about 2/3 of symptoms. Each of the different cobalamin forms have at least half a dozen variations in how they are spelled or specified around the world. I use several of those interchangeably.
 

richvank

Senior Member
Messages
2,732
Thank you. Does anyone have a link to the finalized version of the simplified methylation protocol?

What is the difference between adenosyl B-12 and Hydroxy B-12? Please and thank you.

Hi, Mya.

Here's the most recent version of the simplified methylation protocol:


March 30. 2011

SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE PARTIAL METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROMEMarch 30, 2011 Revision
Rich Van Konynenburg. Ph.D.
(Based on the full treatment program
developed by Amy Yasko, Ph.D., N.D.
which is used primarily in treating autism [1])

SUPPLEMENTS

1. General Vitamin Neurological Health Formula [2]: Start with tablet and increase dosage as tolerated to 2 tablets daily
2. Hydroxy B12 Mega Drops [3]: 2 drops under the tongue daily
3. MethylMate B [4]: 3 drops under the tongue daily
4. Folinic acid [5]: capsule daily
5. Phosphatidyl Serine Complex [6]: 1 softgel capsule daily (or lecithin, see below)

All these supplements can be obtained from http://www.holisticheal.com.
The fourth supplement comes in capsules that contain 800 mcg. It will be necessary to open the capsules, dump the powder onto a flat surface, and separate it into quarters using a knife to obtain the daily dose. The powder 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. In general, they can be taken at any time of day, with or without food.
Phosphatidyl serine can lower cortisol levels. Patients who already have low evening cortisol levels may wish to substitute lecithin [7] (at one softgel daily) for supplement number 5 above. Lecithin is also available from http://www.holisticheal.com.
For those allergic to soy, lecithin from other sources is available.
GO SLOWLY. As the methylation cycle block is lifted, toxins are mobilized 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, Autism, Pathways to Recovery, Neurological Research Institute, 2009, available from http://www.holisticheal.com or Amazon.
[2] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
[3] Hydroxy B12 Mega Drops is a liquid form of hydroxocobalamin (B12), supplied by Holistic Health Consultants. 2 drops is a dosage of 2,000 mcg.
[4] MethylMate B is a liquid form of (6s)-methyltetrahydrofolate supplied by Holistic Health Consultants, based on Extrafolate S, a trademark of Gnosis S.P.A. 3 drops is a dosage of 210 mcg.
[5] Folinic acid is 5-formyltetrahydrofolate. capsule is a dosage of 200 mcg.
[5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center. 1 softgel is a dosage of 500 mg.
[7] Lecithin is a combination of phospholipids without phosphatidylserine. One softgel is a dosage of 1,200 mg.

Best regards,

Rich
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Hey Rich--

What is OVER-METHYLATION? Does that necessarily mean detox? Or are other things at work when one over-methylates?

I am finding that I reach point with the SMP, or with just the MB12, where I am so symptomatic (wired, sleepless, anxious, with intense pressure in my frontal brain), that I have to stop completely for several days or weeks to clear the toxins that come up with that. My detox system cannot handle the overload. Even when I use the TD-glutathione, it can be too much.

I am curious if there are lab tests that can help me figure what is happening... Does the methylation pathways panel test include info on polymorphisms, or do you have to get the Yasko test to get that kind of info? And how much does the Yasko test cost these days?
 

richvank

Senior Member
Messages
2,732
Hey Rich--

What is OVER-METHYLATION? Does that necessarily mean detox? Or are other things at work when one over-methylates?

I am finding that I reach point with the SMP, or with just the MB12, where I am so symptomatic (wired, sleepless, anxious, with intense pressure in my frontal brain), that I have to stop completely for several days or weeks to clear the toxins that come up with that. My detox system cannot handle the overload. Even when I use the TD-glutathione, it can be too much.

I am curious if there are lab tests that can help me figure what is happening... Does the methylation pathways panel test include info on polymorphisms, or do you have to get the Yasko test to get that kind of info? And how much does the Yasko test cost these days?

Hi, DB.

I don't use the term "over-methylation," because it suggests a connection to Carl Pfieffer's use of that term, and I have not found his description of over or under methylators to apply very well to people who have ME/CFS.

I prefer to advise people to run the methylation pathways panel, which will give direct information about the status of the methylation cycle, the folate metabolism and glutathione. I prefer this also above doing the polymorphisms panel. The latter only gives tendencies, while the former tells you what the status of the biochemistry actually is. I have used the methylation pathways panel a lot, and have probably seen several hundred of the results of it by now, and I have confidence in it, because it jibes with other testing and with the health status of the person tested. It also shows the improvement as the person is treated and has symptomatic improvement.

I do believe that it is possible to overdrive the methylation cycle, and I have seen at least three cases of this, based on lab testing. This occurs when high dosages of methylcobalamin and methylfolate are taken together. When this is done, the cells are not able to control the activity of the methionine synthase enzyme, as they normally are. This enzyme, which is partially blocked in ME/CFS and is driving its reaction too slowly, then starts driving its reaction too fast. That does improve the methylation status, but the problem is that too much of the homocysteine gets rapidly converted back to methionine, leaving little of it to enter the transsulfuration pathway to support the synthesis of glutathione. Thus, glutathione does not rise as it should. What is needed is to run this reaction not too slow, and not too fast, but just right, as Goldilocks preferred.

The symptoms you described are those of excitotoxicity. Low glutathione is a possible cause of excitotoxicity.

If you do want to run the polymorphisms panel, you can find it at www.holisticheal.com

It is less expensive to run the www.23andme.com genotypes panel, which covers about 1 million polymorphisms, including about two-thirds of those on the Yasko panel. There are estimated to be about 10 million possible total polymorphisms in the human genome.

Best regards,

Rich
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Thank you Rich, for all the info.

I was confusing the term "over-methylation" with the term "overdriving the methylation cycle." I guess I thought they were the same thing.

Good to hear your thoughts about the polymorphisms panel, as well.

Much appreciated, as always.

PS And yes, Goldilocks was a very smart chick. :rolleyes::D:D
 
Messages
39
Location
Bay Area, CA
I do believe that it is possible to overdrive the methylation cycle, and I have seen at least three cases of this, based on lab testing. This occurs when high dosages of methylcobalamin and methylfolate are taken together. When this is done, the cells are not able to control the activity of the methionine synthase enzyme, as they normally are. This enzyme, which is partially blocked in ME/CFS and is driving its reaction too slowly, then starts driving its reaction too fast. That does improve the methylation status, but the problem is that too much of the homocysteine gets rapidly converted back to methionine, leaving little of it to enter the transsulfuration pathway to support the synthesis of glutathione. Thus, glutathione does not rise as it should. What is needed is to run this reaction not too slow, and not too fast, but just right, as Goldilocks preferred.

Rich

Can the adenosyl b12 also contribute to overdriving the methylation cycle, or is this only done through large dosages of methylb12 and methylfolate? I'm curious if there might be an advantage or disadvantage in adding adenosyl b12 to the SMP. I felt that the adb12 seemed to quickly help increase my energy levels a bit.

I am quite concerned about overdriving the cycle. Taking the high dosages of mb12, adb12 and methylfolate together definitely gave me some excitotoxicity symptoms. At first I confused them for low potassium, but taking potassium did not completely alleviate them.

I have since switched to the hydroxocobalamin and have reduced my methylfolate, but I'm wondering if it would be okay to try adding a little of the adb12 back in. Have there been cases where people have experienced problems from the adb12?

Thanks!
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Hi lolasana--

In my case, the adB12 caused a lot of excitotoxicity symptoms and big heavy metal detox. I was not taking any mB12 or hB12 at that time, so I am fairly certain it was caused by taking the abB12. I was able to verify the heavy metal detox with lab work during the time of the symptoms.

Everybody is different of course, so I have no idea how the adB12 would pan out for you.
 

richvank

Senior Member
Messages
2,732
Can the adenosyl b12 also contribute to overdriving the methylation cycle, or is this only done through large dosages of methylb12 and methylfolate? I'm curious if there might be an advantage or disadvantage in adding adenosyl b12 to the SMP. I felt that the adb12 seemed to quickly help increase my energy levels a bit.

I am quite concerned about overdriving the cycle. Taking the high dosages of mb12, adb12 and methylfolate together definitely gave me some excitotoxicity symptoms. At first I confused them for low potassium, but taking potassium did not completely alleviate them.

I have since switched to the hydroxocobalamin and have reduced my methylfolate, but I'm wondering if it would be okay to try adding a little of the adb12 back in. Have there been cases where people have experienced problems from the adb12?

Thanks!

Hi, lolasana.

I think that adding adenosyl B12 would be O.K. That won't overdrive the methylation cycle, because the cells would have control over how much of the adenosyl B12 would be converted to methyl B12, and methyl B12 is the only form that can drive the methylation cycle.

Best regards,

Rich
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi, lolasana.

I think that adding adenosyl B12 would be O.K. That won't overdrive the methylation cycle, because the cells would have control over how much of the adenosyl B12 would be converted to methyl B12, and methyl B12 is the only form that can drive the methylation cycle.

Best regards,

Rich

HI Rich,

A question about how widespread ATP use is within the body is in order. Any idea how many different reactions and enzymes and so on are dependent on having ATP availalble?
 

richvank

Senior Member
Messages
2,732
HI Rich,

A question about how widespread ATP use is within the body is in order. Any idea how many different reactions and enzymes and so on are dependent on having ATP availalble?

Hi, Freddd.

I don't know, but ATP drives essentially all the reactions that need energy to drive them. I've read that a human being turns over his or her own body weight in ATP each day. A human doesn't make that much from scratch each day, but recycles it back from ADP and AMP when it is used to drive reactions. Very important stuff.

Best regards,

Rich
 
Messages
6
Please help with protocol

I hope that this is the place to post for advice on methylation protocols. 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 +/-

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! I also have elevated mercury and was considering chelation but is DMSA a bad idea due to the sulfur? I have been getting weekly IV push of glutathione for some time, and understand that it may worsen the B12 problem. 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.
 

richvank

Senior Member
Messages
2,732
***Hi, golfbuddy.

I hope that this is the place to post for advice on methylation protocols.

***Yes, it's fine.

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/showthread.php?12934-Documents-by-Rich-Van-Konynenburg-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
 
Messages
6
Thank you Rich. I should have been more thorough in my post but I wasn't sure if I

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.



***Hi, golfbuddy.

I hope that this is the place to post for advice on methylation protocols.

***Yes, it's fine.

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/showthread.php?12934-Documents-by-Rich-Van-Konynenburg-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
 

richvank

Senior Member
Messages
2,732
Hi, golfbuddy.

O.K., I didn't realize that you were that far along. I don't know if it would be feasible for you to run the mehtylation pathways panel from the Health Diagnostics and Research Institute, but if you could do that, it would give you a good picture of where things are now. If your methylation cycle and glutathione are in fairly good shape now, I think that going after the mercury would be a good thing to try. At this point, you may be beyond having to be concerned about the CBS SNPs. In our clinical study, we found that even if we ignored them, people responded to the methylation protocol and their SAMe and SAH levels improved pretty well in a few months.

Best regards,

Rich
 
Messages
6
OK I will do that. Is there any prep, i.e., do I just continue what I am currently

OK I will do that. Is there any prep, i.e., do I just continue what I am currently doing during the blood testing? Thank you so much. When I get a result I will come back and post it.

Steve