Revised Simplified Methylation Protocol (August 25, 2012 Revision)

xjhuez

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I'm wondering why there is no mention of supplemental SAMe in this protocol? I'd read elsewhere that this was recommended for undermethylators.
 

Lotus97

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I'm wondering why there is no mention of supplemental SAMe in this protocol? I'd read elsewhere that this was recommended for undermethylators.
Rich based his protocol mainly on the study he conducted with Dr. Nathan. I assume undermethylators would need extra methyl donors such as SAMe and/or TMG, but I don't know much about SNPs. They might also need methylcobalamin and higher doses of methylfolate. Before Rich's most recent protocol, he would just tell people who didn't have success with his protocol to try Freddd's protocol which seems to be more geared towards undermethylators. In this protocol (his most recent one), Rich does say to switch to methylcobalamin and adenosylcobalamin if you aren't improving and also suggests increasing methylfolate. This is what Rich has said in the past about this subject
A little TMG is often helpful when methylfolate and B12 supplementation are started, because it can help to raise SAMe, needed for recycling methyl B12. After these supplements are well underway and methionine synthase is coming up in activity, the TMG can be stopped, or DMG can be added to counter the BHMT pathway, so as to route more of the homocysteine to the methionine synthase pathway and the transsulfuration pathway.

Some people have had good experience with methylcobalamin. It can be especially helpful if a person has a shortage of methyl groups, though that can also be helped by taking some additional trimethylglycine (some of which is in the multi that is part of the simplified treatment). or some SAMe. It's used a lot subcutaneously by the DAN! doctors in autism treatment, and as you probably know, freddd on this forum advocates its use as well. In his case, because of a mutation in the intracellular B12 processing enzymes, his body is not able to utilized hydroxocobalamin readily. But I believe that this is a rare situation, based on the published literature. freddd does not agree that it is rare, based on his experience.

TMG stimulates the BHMT (betaine homocysteine methyltransferase) reaction, as it is a reactant for it. This reaction takes place in the liver and kidneys. It is an alternative pathway for converting homocysteine into methionine, and it will help to produce SAMe in those organs.

There are a couple of ways that it might produce symptoms. One is that it will initially lower the flow of homocysteine into the transsulfuration pathway, so the rate of production of glutathione may drop lower initially. So symptoms could be caused by initially making the glutathione depletion somewhat more severe.

Another possible mechanism is that it can also take homocysteine away from the main methionine synthase pathway initially, and that will impact the folate metabolism, since the conversion of methylfolate to tetrahydrofolate will decrease in the liver and kidneys.

Betaine and TMG are the same substance. Betaine HCl has a hydrochloric acid molecule bound to it. Yes, if you take betaine HCl, you will also have the benefit of TMG. However, note that TMG stimulates the alternative BHMT pathway from homocysteine to methionine in the liver and kidneys. TMG will promote production of SAMe, but it can shunt flow away from the methionine synthase enzyme, which is partially blocked in ME/CFS. It's important to get this enzyme going, because it is linked to the folate metabolism, which is needed to make new DNA and RNA, and also because it regulates the entire sulfur metabolism. In Amy Yasko's protocol, she recommends starting with some TMG, and then after the B12 and folate have been built up some, to add DMG, which will inhibit the BHMT reaction by product inhibition, and that will push more of the homocysteine through the methionine synthase reaction. The benefit of doing TMG first is that it can increase the level of SAMe, and that is needed by the methionine synthase reductase reaction, which rescues the cobalamin coenzyme of methionine synthase when it becomes oxidized, thus restoring it to the +1 oxidation state and giving it a methyl group, so that it is a functional methylcobalamin molecule again. I don't know what dosage of betaine HCl will interfere with the methionine synthase reaction. Some people use the Allergy Research Group's dilute HCl solution to augment their stomach acid, and then there is no TMG (betaine) involved. Others use lemon juice (note that it is important to use a drinking straw and to flush the teeth with water afterward, because the citric acid in lemon juice chelates calcium and can damage the enamel on the teeth over time).
 

Sushi

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I'm wondering why there is no mention of supplemental SAMe in this protocol? I'd read elsewhere that this was recommended for undermethylators.
Hi,

Rich did suggest SAMe in the first version of his protocol (2007), but found that many did not tolerate it so later he suggested SAMe if you were low in it and if you tolerated it.

Best,
Sushi
 

Lotus97

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For anyone who is taking the Neurological Health Formula, I noticed that it includes Intrinsic Factor. Intrinsic factor will improve absorption of B12 in the gut. While you absorb most of your B12 sublingually (holding the tablet under the tongue or between the lower or upper lip), the sublingual will eventually be digested after it dissolves so it would be a good idea to take at least some of the NHF tablets at the same time as you take your sublingual. I can't really say for sure how much this will help though.
 

Lotus97

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I found a store that ships international and carries the Perque Hydroxocobalamin.
http://pureformulas.com/activated-b12-2000mcg-100-lozenges-by-perque.html#sthash.mIWXmygN.dpbs
They also ship free on any size order (at least for US orders I'm not sure about international). And if you use next10 as a code in your shopping cart (different from the referral code they ask for when signing up) you'll get 10% off your entire order. If that coupon code is expired there might be a new one on retailmenot, but I just checked and next10 is still valid as of this post.
 

shannah

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Can someone clarify the brand or name of folinic acid that Rich is recommending here other than the one available from Yasko's site.

At one time Metagenics 'Intrinsi B12/Folate' was being used but I see it's been discontinued at iherb which is where I normally shop.

Are there others or can you tell me the specific term of the ingredient I look for on the label?
 

Lotus97

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Can someone clarify the brand or name of folinic acid that Rich is recommending here other than the one available from Yasko's site.

At one time Metagenics 'Intrinsi B12/Folate' was being used but I see it's been discontinued at iherb which is where I normally shop.

Are there others or can you tell me the specific term of the ingredient I look for on the label?
Rich doesn't recommend a specific brand for folinic acid. The reason Rich doesn't recommend intriniB12 is because the formula changed so it no longer has folinic acid. Source Naturals sells Megafolinic which seems to be reasonably priced.

Also, calcium folinate is the same as folinic acid. Thorne has a few b complexes with both calcium folinate/folinic acid and methylfolate. I'm not sure if Thorne's methylfolate is as potent as Metafolin which is in the Metagenics and Solgar brand of methylfolate.

There's also a b complex with only folinic acid. Supplement facts listed are for 2 capsules.
http://www.wellnessresources.com/products/super_b_complex.php
And a multi vitamin with only folinic acid. Supplement facts are for 4 capsules or 2 tablets.
http://www.integratedhealth.com/hpdspec/two.html
That same shop also has multi with both folinic acid and methylfolate. Supplement facts are for 4 capsuels.
http://www.integratedhealth.com/vitamin-formulas/mighty-multi-vite.html
 

shannah

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Hi Lotus,

Thanks so much for clarifying this and also for the providing the links. Much appreciated. I'm getting ready to retry the protocol and of course, have to relearn all of the pertinent information again.

Best Wishes,
shannah
 

Lotus97

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Hi Lotus,

Thanks so much for clarifying this and also for the providing the links. Much appreciated. I'm getting ready to retry the protocol and of course, have to relearn all of the pertinent information again.

Best Wishes,
shannah
No problem. What happened with your earlier attempt(s)?
 

shannah

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When trying it years ago, I can't remember all the reasons for setting it aside. Probably have notes on it somewhere. But I do remember there were major problems with passing out. Was always running for the closest couch or bed.
 

Lotus97

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When trying it years ago, I can't remember all the reasons for setting it aside. Probably have notes on it somewhere. But I do remember there were major problems with passing out. Was always running for the closest couch or bed.
It's always good to start with low doses and also make sure you don't have low potassium. I'm not sure if the passing out is from low potassium or not, but you might want to look into that.
 

Whit

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I'm sorry I can't read very much right now, but can someone help me by letting me know how a B complex like Jarrow B Right fits into this? If it has Methyl B12 can I also take Hydroxy B12?
 

Lotus97

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I'm sorry I can't read very much right now, but can someone help me by letting me know how a B complex like Jarrow B Right fits into this? If it has Methyl B12 can I also take Hydroxy B12?
B12 taken orally (such as that in the B Right) isn't very effective for the people here because the absorption rate in the gut is very low compared to B12 taken sublingually. The B Right b complex isn't recommended though because it has folic acid and folic acid can cause problems for some people. I don't know if it's absolutely necessary for you to stop folic acid immediately, but it would be good to transition towards using supplements without folic acid. In post #67 of this thread, I recommended a b complex and multi dose multivitamins that can be used as b complexes. If you do try one of these b complexes, make sure you adjust your methylation dose accordingly since they either have folinic acid (as calcium folinate) or folinic acid and methylfolate. It would be good to stick to the recommended doses when starting the protocol. If you're taking the Neurological Health Formula you might not want to also take the one with a lot of P5P since the NHF also has P5P. There's also a supplement on sale (buy one get one free) at Swanson's that has B1, B2, B3, B5, and choline (no B6/P5P or biotin) which could be used as a b complex.
http://www.swansonvitamins.com/swanson-condition-specific-formulas-fibro-essentials-90-caps
They're also having a 10% off sale along with free shipping over $50 until the 30th. This is the code SAVEATSHP.

As for the difference between hydroxocobalamin and methylcobalamin, methylcobalamin is what's needed for methylation. Rich recommends starting with hydroxocobalamin because most people can convert it into an adequate amount of methylcobalamin (and adenosylcobalamin). In the first post of the thread, Rich explains in more detail why he recommends starting with hydroxocobalamin and also gives instructions on switching to methylcobalamin if necessary.
 

Lotus97

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Some people have said that holding B12 is better absorbed when held between your upper lip and gum (rather than under your tongue) because it lasts longer. I have found that the Perque hydroxocobalamin dissolves rather quickly under the tongue, but sometimes doesn't seem to dissolve at all when put between the upper lip and gum. It does dissolve slower between the lower lip and gum. I don't know for sure if it's better absorbed than under the tongue. There was a study using an older version of Rich's protocol that used Perque's hb12 and my guess is they just held it under their tongue and the study still produced good results. Maybe between the lower lip and gum (rather than under the tongue) would have produced better results.
 

Lotus97

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So I found out the 10% off NEXT10 code for Pureformulas no longer works on certain brands including Perque. Holistic Health does sell Perque hydroxocobalamin now so you can order it from them when you order the Neurological Health Formula. The methylfolate, folinic acid, and lecithin would be cheaper at either iHerb or Swanson. There's coupon codes at retailmenot for these stores. The lecithin can also be bought in powder form which is cheaper. One teaspoon would be the equivalent of Rich recommends. Even though the buy one get one free offer expired on that Fibro Essentials supplement from Swanson I think it's still a pretty good deal and would be good to order if you're not taking any b complexes since the NHF is low in other b vitamins besides B6/P5P.
 
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I hoped I could ask a further few questions about treatment (apologies for cross posting):

1. Is it acceptable to post up the Methylation Pathway Panel analysis here? I don't have a doctor to do this for me.

2. What does "rebalancing" mean in terms of doses of mythylfolate and Metafolin? I only see, for example, 200mcg of methylfolate as the dose to use.

3. I'm having real difficulty establishing the vitamins/mineral base - 100mg of Vit C (powder) seemed to give me a sore throat; 100mg of magnesium oxide seems to make my heart beat hard for about 10-15 mins (and epsom salt baths wipe me out for days) . I'm now getting a bit gun shy. Are these normal? I've a very leaky gut due to candida and seem to be reacting to many foods. I'm also willing to accept that some symptoms could be psychosomatic!

The ingredients of the magnesium tablets are as followed:

Magnesium Oxide, Bulking Agent (Microcrystalline Cellulose), Sodium Carboxymethylcellulose, Anti- Caking Agents (Magnesium Stearate, Magnesium Silicate), Glazing Agents (Hydroxypropyl Methylcellulose, Glycerine, Carnauba Wax), Colour (Titanium Dioxide).

Has anyone tried magnesium oil?

4. I know magnesium and potassium are both electrolytes, so I wondered if titrating the dose of one could intensify the deficiency in the other?

Thanks very much.
 
I hoped I could ask a further few questions about treatment (apologies for cross posting):

1. Is it acceptable to post up the Methylation Pathway Panel analysis here? I don't have a doctor to do this for me.

2. What does "rebalancing" mean in terms of doses of mythylfolate and Metafolin? I only see, for example, 200mcg of methylfolate as the dose to use.

3. I'm having real difficulty establishing the vitamins/mineral base - 100mg of Vit C (powder) seemed to give me a sore throat; 100mg of magnesium oxide seems to make my heart beat hard for about 10-15 mins (and epsom salt baths wipe me out for days) . I'm now getting a bit gun shy. Are these normal? I've a very leaky gut due to candida and seem to be reacting to many foods. I'm also willing to accept that some symptoms could be psychosomatic!

The ingredients of the magnesium tablets are as followed:

Magnesium Oxide, Bulking Agent (Microcrystalline Cellulose), Sodium Carboxymethylcellulose, Anti- Caking Agents (Magnesium Stearate, Magnesium Silicate), Glazing Agents (Hydroxypropyl Methylcellulose, Glycerine, Carnauba Wax), Colour (Titanium Dioxide).

Has anyone tried magnesium oil?

4. I know magnesium and potassium are both electrolytes, so I wondered if titrating the dose of one could intensify the deficiency in the other?

Thanks very much.
Rich Vank made an excellent interpretation of the Methylation Pathways Panel. The link is in my signature.
Magnesium oxide, while cheap, doesn't absorb very well. Plus yours has all kinds of fillers which you may or may not tolerate. Magnesium should be calming, not causing heartbeats, so maybe it is the fillers.

I'm having good luck with Vinco's magnesium glycinate powder. You mix it in water and drink it. I haven't personally tried magnesium oil, but I know someone who uses it on occasion. I require a lot more magnesium than I could get out of magnesium oil (I think it's something like 200mg per application?)

I don't think increasing the mag would decrease the potassium, at least that has not been my experience. I take lots of magnesium and no potassium. My potassium levels are high normal on my Nutreval test.

I'm not sure about the Vit. C. It sounds like maybe it's causing some throat irritation? Are you mixing it with water and drinking it? 100mg isn't very much in the scheme of things.

I'm having good luck with BioEnergyC which is vitamin C buffered with ribose. Kind of expensive, but it lasts a long time at the rate I take it (1/8 to 1/4 tsp 4X a day). You may or may not tolerate the ribose. It gives me a bit of energy, so I like it.

I mix all of my electrolytes and the vit. C together in water and drink it four times a day. My particular formula is magnesium, salt and vit C/ribose. You may or may not need potassium in addition.
 

jimmy86

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I think this is only the second report I've seen, the other one being from a person in Germany, who also had good results. I think the cost has prevented some people from trying it. I started suggesting it, as well as liposomal glutathione, some time back, as two possibilities for actually getting glutathione into the cells to help raise it faster on the methylation protocol. Most IV glutathione is taken out of the blood by the kidneys, which probably do benefit, but it isn't a very effective way to raise glutathione in other organs, tissues and cells, and especially not for the longer term. I'm glad to hear that Dr. Klinghardt is encouraging the use of S-acetyl glutathione, too.
Indeed, there are more and more reports in Germany from people that got better with s-acetyl glutathione. It is called eumetabol (you can google it but the page will be in German). I tried Rich's protocol for about a year and got mildly better. I am getting my glutathione levels checked this week and will start to supplement glutathione directly.
 
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Could you point me to any of these reports? I am following symptome.ch - as I saw you do as well ;-), but I can only find one success story there regarding Eumetabol. If there were more, that would be great! :)