Rich Vank's Simplified Methylation Protocol Poll

[Joopiter76]

Hi to Rich,

can you please explain something about methionine-synthase, it is:
As I know methionine-synthase (MTR) transfers the methyl group from methyl-folate to B12 so that methyl-b12 is generated then methionine-synthase transfers the methyl-group from methyl-b12 to homocystein and remethylates to methionine. During this process the B12 as a cofactor of methionine-sysnthase becaomes oxidized and must be regenerated. This is the job of the methionine-synthase-reductase (MTRR).
Yasko wirites that for regenartion of B12 SAMe is needed but I dont understand this because the methyl group to methylate B12 comes form methyl-folate and not from SAMe or is it if there is not enough methyl-folate then the methyl-group comes form SAMe?? It wouldnt make sense to first use up SAMe and then generate SAMe again. And does methyl-B12 becomes OH-b12 after the transfer of the methyl group to homocystein? So what I need to kno is the exact mechanism of MTR/MTRR I couldnt find this in detail anywhere. CAn you explain it please?

And then Ive got another question, do the different B12s compete with each other for transport into the cell? Could this be a reason why methyl-b12 is tolaerated and oh-b12 and others not because they would suppress the use of methyl-b12 if anyway methyl-b12 is very low or on the other hynd if OH-B12 uses up SAMe this could also be a reason why OH-B12 might be tolerated bad and methyl-B12 is tolerated good.

Thanks to you Rich.

 

[aquariusgirl]

what was the best thing you did Joopiter?
Supplement nucleotides?

 

[richvank]

Hi to Rich,

can you please explain something about methionine-synthase, it is:
As I know methionine-synthase (MTR) transfers the methyl group from methyl-folate to B12 so that methyl-b12 is generated then methionine-synthase transfers the methyl-group from methyl-b12 to homocystein and remethylates to methionine. During this process the B12 as a cofactor of methionine-sysnthase becaomes oxidized and must be regenerated. This is the job of the methionine-synthase-reductase (MTRR).
Yasko wirites that for regenartion of B12 SAMe is needed but I dont understand this because the methyl group to methylate B12 comes form methyl-folate and not from SAMe or is it if there is not enough methyl-folate then the methyl-group comes form SAMe?? It wouldnt make sense to first use up SAMe and then generate SAMe again. And does methyl-B12 becomes OH-b12 after the transfer of the methyl group to homocystein? So what I need to kno is the exact mechanism of MTR/MTRR I couldnt find this in detail anywhere. CAn you explain it please?

And then Ive got another question, do the different B12s compete with each other for transport into the cell? Could this be a reason why methyl-b12 is tolaerated and oh-b12 and others not because they would suppress the use of methyl-b12 if anyway methyl-b12 is very low or on the other hynd if OH-B12 uses up SAMe this could also be a reason why OH-B12 might be tolerated bad and methyl-B12 is tolerated good.

Thanks to you Rich.

Hi, Joopiter.

Normally, methylfolate does supply the methyl group to form methylcobalamin. However, about every 2000 cycles of the methionine synthase enzyme, the cobalamin becomes oxidized during the time it does not have a methyl group attached. When this happens, it is the job of methionine synthase to chemically reduce the cobalamin and to add a methyl group to it, which does come from SAMe. When a person is under oxidative stress, as in ME/CFS, the cobalamin oxidizes more frequently. In fact this mechanism is supposed to direct more of the homocysteine toward synthesis of glutathione in order to compensate for the oxidative stress. However, in ME/CFS, this mechanism does not work properly, because severe depletion of glutathione has removed protection from B12, so that the amount of methylcobalamin is insufficient to keep the methionine synthase reaction going at a normal rate. Eventually, SAMe may also drop, so that the methionine synthase reductase reaction doesn't work well, either.

If the forms of B12 are taken orally, they are all absorbed similarly and transported similarly to the cells. In the cells, the beta ligands (such as methyl or hydroxo) are removed, and then the cells re-form appropriate amounts of methylcobalamin and adenosylcobalamin.

If forms of B12 are taken sublingually or by injection in milligrams-level dosages, the transcobalamin carrier is overwhelmed, and free B12 forms exist in the blood plasma. Some of this is apparently able to diffuse into the cells though the cell membrane, without help from the transcobalamin carrier. If methylcobalamin or adenosylcobalamin are taken in this way, as recommended by Freddd on this forum, then I think it can be used directly by the cells, without further processing.

If hydroxocobalamin is taken, it must be methylated by SAMe before it can be used to support methionine synthase. Some people are low in SAMe, so that this does not work well. These people need to take methylcobalamin instead of hydroxocobalamin. Dr. Yasko determines this from genomic polymorphisms. In the simplified treatment, I have just chosen hydroxocobalamin. If this doesn't work, switching to methylcobalamin may work. I chose hydroxo because it allows the cells to determine how much methylcobalamin to make, so that the methylation cycle will not be overdriven. I also had some concern about methylation of mercury, but still don't know for sure if that is really a problem.

Rich

 

[fla]

Would renting a cabin in the woods away from most EMR be a good idea to do in parallel with starting the methylation protocol? There was another thread about EMR sensitivity and methylation so my gut feeling is that it might improve my odds of getting some progress. Need some scientific arguments otherwise insurance will accuse me of being so healthy I'm going on vacation and cut me.

 

[monobear]

I started the multivit this weekend and had a strong reaction- fluish aches, muscle twitching, and pains in the flanks of my abdomen. i also felt a little more energy. i had been expecting bad side effects with the b12 and folate, but not the multivit alone. i've lowered the doseage and will wait a day before trying again. but meanwhile, should i be concerned, especially about the dull pain in my abdomen flanks? i know that's kidney/liver/spleen area, so i really want to be careful. the pain started after taking guiffasnesen for a stuffy nose; i dont know if that could be a factor. i'll be laying off the guiffanessen for now. in the meantime, should i be worried, or is it a normal reaction? if it is toxin die off, any suggestions to make it safer? thanks!

 

[monobear]

ps- i accidentally started with 1/2 dose and not 1/4 dose- won't be making tha mistake again! don't know if that accounts for the side pain, whatever it is. i was still surprised the multivit alone can such a strong reaction- gonna be a rollercoaster when i actally get to the folate!

 

[camas]

Rich,

Thanks for your patience in explaining the protocol. Can you tell us the purpose of the Phosphatidyl Serine Complex, and can it be substituted with something that is not soy-based?

 

[anne_likes_red]

I'm interested in the answer to the P.Serine question too, re what it's exact purpose is in supporting methylation/start up healing.
I know Rich mentioned on another group that he is considering modifying the simplified protocol, and there is a possibility this could include dropping the P.Serine complex but that extra Omega EFAs would be needed to support some of the same processes (I think I've got that right).
I understand some people feel they do very well with the PS complex.

Monobear do you mean you had that reaction to the Neurological Health Formula? I guess that means you're absorbing it well
(I had what felt like start-up symptoms or detox attempt from starting just Mag Chloride last week. Have had to stop taking it the reaction was so severe!)

 

[monobear]

yes anne_likes_red, the reaction was to the neurological health formula alone. i'm ok with dealing with the flu like symptoms, as long as i know i'm not damaging my body. that's why i was concerned about the abdomen pains.

 

[Vegas]

I started the multivit this weekend and had a strong reaction- fluish aches, muscle twitching, and pains in the flanks of my abdomen. i also felt a little more energy. i had been expecting bad side effects with the b12 and folate, but not the multivit alone. i've lowered the doseage and will wait a day before trying again. but meanwhile, should i be concerned, especially about the dull pain in my abdomen flanks? i know that's kidney/liver/spleen area, so i really want to be careful. the pain started after taking guiffasnesen for a stuffy nose; i dont know if that could be a factor. i'll be laying off the guiffanessen for now. in the meantime, should i be worried, or is it a normal reaction? if it is toxin die off, any suggestions to make it safer? thanks!

I wouldn't worry about the symptoms; they are similar to what I and others have experienced. Pains all over the body are common. For me it has been mostly dull, achy pain and re-emergence of old tender points...not true trigger points. These pains come and go, and sometimes appear in strange locations. You should be able to separate kidney pain from flank pain, but I had some of both. Take it slow. Some magnesium for the twitching, this might help the achiness too. If your getting this reaction from the multi only, then I suspect you have a long road ahead of you, and unfortunately it may get worse before it gets better. Expect, initial improvement, worsening, a highly variable period, followed by very slow but noticeable improvement.

 

[monobear]

thank you vegas for the info. i will keep taking it slow and steady.

 

[Joopiter76]

rich: Thank you very much. B12 is always named "cofactor" but as I understand it directly becomes part of the methionine-synthase so an oxidation of B12 means an oxidation of methionine-synthase?? So the way is that OH-B12 first becomes methylated by SAMe to methyl-B12 this methyl-b12 becomes part of the methionine-synthase and transfers its methyl-group to homocysteine. Then it becomes ??? What? OH-B12 again?? Then the b12 of the methionine-synthase gets its methyl group from methyl-folate and this way is what it always works. So as I understand what you described is that B12 can only be used in the first step e.g. after injection when it became methylated by SAMe it cant get the methyl group in the first step from methyl-folate because its not part of the methionine-synthase and can only become part of the methionine-synthase after methylation through SAMe. Right??

Thanks again, very interesting.

 

[PokerPlayer]

How would one transition from the freddd protocol to the simplified methylation protocol?

I have been looking for the answer to this everywhere but could not find one. So I have been doing the "freddd" protocol for 3 weeks and noticed a huge improvement! However, the last 4 days I have felt as fatigued as ever. When I first started the protocol my mental clarity and brain fog reduction was absolutely miraculous. I have kind of decided the "freddd" protocol is a bit too aggressive, at least if there is a more gentler and scientifically backed approach out there.

I was wondering, if one has been on high dosages of methylb12 10,000mcg, adb12 3,000mcg , methylfolate 2400mcg, how should one transition to the simplified methylation protocol? I was only on these dosages for 3 weeks. I am aware that high dosages of mb12 and methyfolate can cause problems by "overdriving" the methylation cycle, which I think I have done, as it seems by body was stimulated but now is exhausted, and a slower and gentler approach would be great.

I am thinking take a break off all supplements, and then start on the protocol. But how long of a break? 1 week? A month? No break?

Is an ssri antidepressant something that may interfere with methylation? I find them to be helpful and do think that they possess some anti inflammatory properties that are underrated by most people in regards to me/cfs.

Would like to add, that compared to most people here I am not as bad. Just severe brain fog and fatigue, but I can walk an hour a day without a problem.

 

[richvank]

Rich and everyone, I have a question regarding Glutathione nasal spray supplementation. I have read snippets of info suggesting that it's a bad idea because it may encourage the innate methylation cycle to continue malfunctioning, and may even add to the partial block. I am wondering if there is much validity to this idea, especially for me already having made significant improvement on the Simplified Protocol for the last 8 months?

I want to give the Glutathione nasal spray a try....any concerns?

Hi, Cloud.I haven't heard from anyone who has tried glutathione nasal spray with the simplified treatment approach. I think it would be worth a try. I did hear a talk a few years back by Jim Seymour of Key Pharmacy in Kent, WA, which produces a glutathione nasal spray. He reported that it has been helpful to produce quick recovery for people who have MCS and who receive an acute exposure to something to which they are sensitive.

Best regards,

Rich

 

[richvank]

Dear Rich,

in case you are reading this, I'd love your take.
I'm thiking of trying the simplified methylation protocol.
What are the essential components? What is the monthly budget? And what is the best source for supplements.
(I'm a huge fan of simple -- the fewer pills, powders and potions, the better.)

My google search turned up this, from 2007:
www.ei-resource.org/articles/chroni...atment-protocol-for-chronic-fatigue-syndrome/

Is this still the most efficient approach?

Also, I'm wondering if and how I would need to change my current protocol, which I believe has been helpful:

-Vit. C: 3000 mg/day
-Fish Oil
-CoQ10: 200 mg /day
-Vit. D: 3000 IU/day
-Half scoop of Teitelbaum's daily powder
-Weekly IM injctions (Dr. Enlander's formula) with Kutapressin, Magnesium Sulphate, Folic Acid, B12, Calphosan, Glutathione, Trace elements


Many thanks for any and all advice.

Hi, firefly.

Sorry to be so slow in responding. I've gotten a little behind!

The current version of the protocol for the simplified treatment approach is pasted below.

There are five components to it, as shown below. The most important are the high-dose sublingual B12 and the folate-containing supplements. The others provide cofactors and other nutrients, and are important to cover deficiencies that might be present.

I think the cost is still less than $3.00 per day.

The supplements can all be obtained from www.holisticheal.com but you might find lower prices for some of them elsewhere.

I don't know how compatible your other supplements would be with the simplified treatment approach. The Teitelbaum supplement contains too much TMG as I recall, which can prevent the methionine synthase reaction from coming up. It also contains folic acid, as does the injection you mentioned. Folic acid is an oxidized form of folate and is not as available as the active forms that are in the simplified treatment approach, and when taken orally, it may compete for absorption in the gut with the active forms. I have communicated with both Drs. Teitelbaum and Enlander about these issues in the past. I am on good terms with both of them, but we have some differences in approach.

Best regards,

Rich

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.

 

[richvank]

Would renting a cabin in the woods away from most EMR be a good idea to do in parallel with starting the methylation protocol? There was another thread about EMR sensitivity and methylation so my gut feeling is that it might improve my odds of getting some progress. Need some scientific arguments otherwise insurance will accuse me of being so healthy I'm going on vacation and cut me.

Hi, fla.

I've read reports from some PWMEs/PWCs who found that they did have to get away from sources of EMR in order to avoid neurological symptoms produced by them. I've suggested that a methylation deficit will result in myelin not being kept in good repair, and that this may be the cause of sensitivity to EMR, but this is just a hypothesis. The basis of it is that at least three components of myelin require methylation for their synthesis, and myelin acts as electrical insulation on nerves.

Best regards,

Rich

 

[richvank]

How would one transition from the freddd protocol to the simplified methylation protocol?

I have been looking for the answer to this everywhere but could not find one. So I have been doing the "freddd" protocol for 3 weeks and noticed a huge improvement! However, the last 4 days I have felt as fatigued as ever. When I first started the protocol my mental clarity and brain fog reduction was absolutely miraculous. I have kind of decided the "freddd" protocol is a bit too aggressive, at least if there is a more gentler and scientifically backed approach out there.

I was wondering, if one has been on high dosages of methylb12 10,000mcg, adb12 3,000mcg , methylfolate 2400mcg, how should one transition to the simplified methylation protocol? I was only on these dosages for 3 weeks. I am aware that high dosages of mb12 and methyfolate can cause problems by "overdriving" the methylation cycle, which I think I have done, as it seems by body was stimulated but now is exhausted, and a slower and gentler approach would be great.

I am thinking take a break off all supplements, and then start on the protocol. But how long of a break? 1 week? A month? No break?

Is an ssri antidepressant something that may interfere with methylation? I find them to be helpful and do think that they possess some anti inflammatory properties that are underrated by most people in regards to me/cfs.

Would like to add, that compared to most people here I am not as bad. Just severe brain fog and fatigue, but I can walk an hour a day without a problem.

Hi, PokerPlayer.

It sounds as though you definitely do need support for your methylation cycle.

I don't know how long a break would be best for transitioning to the simplified treatment approach. Perhaps a couple of weeks.

SSRI drugs act by blocking the reuptake of serotonin, so that it can stay in the nerve synapses longer. Restoring proper function of the methylation cycle should normalize the synthesis of new serotonin, as well as the conversion of serotonin to melatonin. Hopefully, when your methylation cycle is functioning normally, you will no longer need the SSRIs.

Best regards,

Rich

 

[richvank]

@Rich: Thank you very much. B12 is always named "cofactor" but as I understand it directly becomes part of the methionine-synthase so an oxidation of B12 means an oxidation of methionine-synthase?? So the way is that OH-B12 first becomes methylated by SAMe to methyl-B12 this methyl-b12 becomes part of the methionine-synthase and transfers its methyl-group to homocysteine. Then it becomes ??? What? OH-B12 again?? Then the b12 of the methionine-synthase gets its methyl group from methyl-folate and this way is what it always works. So as I understand what you described is that B12 can only be used in the first step e.g. after injection when it became methylated by SAMe it cant get the methyl group in the first step from methyl-folate because its not part of the methionine-synthase and can only become part of the methionine-synthase after methylation through SAMe. Right??

Thanks again, very interesting.

Hi, Joopiter.

I don't know the answer to whether it becomes OH2-B12 again, nor do I know whether B12 receives its methyl group from SAMe before it binds to methionine synthase, but I would encourage you to look at Prof. Richard Deth's slides on methionine synthase:

https://www.autismeval.com/danwebcast/webcast_washdc/powerpoint/DC_06_Deth.pdf

Also the researcher who is probably the leading authority on this is Dr. Ruma Banerjee at the University of Michigan, USA. If you look up her papers on PubMed, you can get the latest understanding of B12 metabolism, I think. As I understand it, there are still some aspects of the intracellular metabolism of B12 that are not completely understood, but I think her group is the most likely to figure them out.

Best regards,

Rich

 

[richvank]

Rich,

Thanks for your patience in explaining the protocol. Can you tell us the purpose of the Phosphatidyl Serine Complex, and can it be substituted with something that is not soy-based?

Hi, camas and anne-likes-red.

The phosphatidyl serine complex has several purposes in the simplified protocol. It is a collection of phospholipids, and as such will support the cellular membranes. In ME/CFS, the membranes suffer a lot of damage from the oxidative stress. This is particularly true of the mitochondrial membranes. Repairing them is important to restoring the function of the mitochondria.

In addition, the phosphatidyl choline in this complex can be used to supply choline for the synthesis of acetylcholine, an important neurotransmitter. Choline requires methylation for its synthesis in the body, and there is a deficit in that.

Also, choline can be converted to betaine (trimethylglycine or TMG) in the body, and betaine can be used to drive the alternate BHMT pathway from homocysteine to methionine that is in the liver and kidneys, which will help to build up SAMe, which in turn can be used to support synthesis of methylcobalamin for the methionine synthase pathway.

I do have one unsettled issue in connection with this supplement, however, and that is that phosphatidylserine tends to lower cortisol, at least at first. As you probably know, most PWMEs/PWCs have low cortisol except at the very beginning of their illlness, when it is raised. In autism, by contrast, it appears from the published studies that cortisol is either at normal levels or is elevated. I extracted the simplified protocol from the full Yasko treatment program that is used primarily in autism. The question arises as to whether it is appropriate to be using phosphatidylserine in the treatment of ME/CFS. Some people have avoided this complex out of concern that it would further lower their cortisol. Others take it before bedtime, because cortisol is supposed to be low at night, which helps with sleeping. I don't have a good answer to the question of whether this supplement should be included for all PWMEs/PWCs. I can tell you that in our clinical study we gave it to all thirty patients, and the overall results were that over two-thirds of the patient experienced significant benefit from the protocol as a whole.

With regard to a non-soy-based substitute, Dr. Amy Yasko has suggested using Seriphos, which is phosphorylated serine. It does not have the other phospholipid ligands beside serine, so I don't know how appropriate it would be for ME/CFS. As Anne mentioned, I have suggested that if a phospholipid supplement is not included, it would probably be a good idea to include something like an omega 3-6-9 fatty acids supplement to support the rebuilding of cellular membranes, at least. The omega-3 and omega-6 fatty acids are essential nutrients, which the body cannot make itself.

I hope this is helpful.

Best regards,

Rich

 

[camas]

Thanks for the detailed info, Rich. It was quite helpful.

Even though I've been ill for decades, I recently had a test that showed elevated levels of cortisol. (How my adrenals have hung in there this long, I don't know.) So I'll probably continue with the phosphatidyl serine complex despite my moderate allergy to soy.