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Simplified Methylation Protocol Revised as of Today

Sasha

Fine, thank you
Messages
17,863
Location
UK
UK sources of protocol items

Where do people in the UK get the following protocol items from?:

Hydroxy B12 Mega Drops
MethylMate B
Folinic acid
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Where do people in the UK get the following protocol items from?:

Hydroxy B12 Mega Drops
MethylMate B
Folinic acid

Actually just got an answer to my own question by phoning the UK suppliers of the Neuro Health Formula - it's all available from healthreaction.com, who import the holisticheal.com stuff but don't list it all on their website. The prices are:

Neurological Health Formula 27.66
Hydroxy b12 Mega Drops 44.99
Methylmate B 18.99
Folinic Acid 12.99

They told me that what they don't have in stock they get FedEx'ed over so get it within a few days and this makes me feel more secure than trying to buy it direct from the US where it might get lost in the post and take ages.

They told me that AfME members get a 10% discount but I don't wish to support AfME and won't be joining. They said a lot of PWME are buying this stuff (I didn't tell them I had ME, they just volunteered that in response to what I was buying).
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Timescale for detox/yuk effects on protocol?

Hi Rich,

I'm about to switch entirely to your SMP but have been following a similar version of Fred's protocol (general vits A to E, lecithin, folate, 1mg ab12, 1mg mb12) for about six weeks. For the last two weeks, I've been feeling much worse, starting with a bitter taste in my mouth for five days, sore ears and feeling a fluey ache in my muscles, with extra fatigue and burning leg muscles if I walked outside. I generally just feel ill and am having to take a lot of extra bed rest. I have no runny nose, which an immunologist told me some years ago means no new viral infection (whether that's true or not for a PWME, I've no idea).

I'm wondering if this is likely to be a detox reaction. I read the account of the trial you did with Dr Nathan and it sounded as though if people were going to get ill effects they happened within the first few days, lasted a few days, and then it was a generally upward trajectory with people seeing benefits in the range of two to eight weeks.

Do I have the correct impression of when people people feel worse, and for how long?

I'm also wondering if I should restart taking True Whey nondenatured whey to raise my glutathione directly in order to feel better faster. I realise that might mask what's happening with the SMP but I think my body could maybe do with a bit of a support. I've taken it before for other reasons and had considerable improvement initially, which then disappeared, but at least I know I don't have any problems with it. Are there any reasons I shouldn't start supplementing now? I saw in your Sweden talk that Dr Nathan tided some people over in the initial stages of the SMP with glutathione.
 

richvank

Senior Member
Messages
2,732
Hi, Sasha.

I'm sorry that you are feeling so much worse. I'm not very familiar with the results of Freddd's protocol, but since the dosages are higher, I expect that they can be more severe than with the simplified protocol.

A variety of symptoms have been reported by people in the early part of treatment with the simplified protocol. Here's a quotation from the report on our clinical study:

"Various patients reported some early exacerbation of symptoms, which in most cases was followed by a greater improvement in symptoms. Three of the patients found it necessary to decrease their dosage frequency to every second or third day for several days, until they could tolerate the full daily dosage schedule.

"Sixteen of 30 patients (53%) reported an initial worsening of symptoms, beginning in most of these cases within 3 or 4 days, but in some cases beginning at up to 2 weeks. Most of the symptoms were mild, and none of the patients discontinued usage of the supplements during the first 3 months. The most common side effects were gastrointestinal (pain, cramps, constipation, or diarrhea), reported by 6 out of 30 patients or 20%; increase in pain, reported by 4 out of 30 or 13%; and increase in fatigue, reported by 3 out of 30 or 10%. Other symptoms, reported by one patient each, were a decrease in appetite, poor sleep, weak legs, flu-like symptoms, and an increase in anxiety and depression.

"For those who experienced improvement, the time to self-reported improvement on the protocol was an average of 5.6 weeks, with a range from immediate improvement (which was rare) to as long as 8 weeks before improvement was experienced."

True Whey may be helpful to you. Some people do well with it, while others do not. It sounds as though you have a good history with it, so it is probably worth a try.

I'm sorry that this type of treatment makes you feel miserable. Perhaps the whey will speed up the process. It does seem that most people have to go through this to get better.

Best regards,

Rich
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Thanks, Rich - I had read the account of your study but hadn't remembered that it went into such detail about the timeframe of adverse effects - sorry to have made you repeat it!

I'm on the second day of the Neurological Health Formula (the first thing to arrive in the mail) and I'm already up to half a tablet with no ill effects so that's a good start.

I will get some True Whey in - it will be good to have the chance of a bit of a boost!

On another thread I raised the question of whether it was possible to raise glutathione by eating raw foods (some of which are higher in glutathione than their cooked versions) and by extra resting (which wouldn't so much raise glutathione as stop it being depleted as fast, maybe). Any thoughts?
 

Dreambirdie

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

Here's my update and a question.

In June I began to take regular doses of methyl B12 along with approx 200 mcg of Folapro. I also began taking a strong curcumin product for inflammation, called Enhansa, which is made for kids with autism. By the end of July I was feeling considerably better, with more energy and less flu symptoms... BUT THEN in mid August I had to go to the dentist for a filling... which led eventually to a slight abscess and then an extraction 2 weeks ago. That has set back a bit of my progress.

I recently (October 1) started the hydroxo B12 Mega drops @ 1000 mcg with the Methylmate @ 200 mcg. The HB12 is definitely easier to tolerate than the MB12, but I have decided to add the MB12 back in, to help the process along.

DO you foresee any problems with this? Thanks in advance for your response.
 

rydra_wong

Guest
Messages
514
Rich said: Methylfolate cannot be converted to folinic acid or to other folate forms readily if the methionine synthase reaction is partially blocked. That's why I am including folinic acid in this protocol. It can be used by most people to make other forms So therof folate that are used in the production of DNA and RNA.
Rich said: Phosphatidyl serine can lower cortisol levels. Patients who already have lower than normal cortisol may wish to substitute lecithin [7] (at one softgel daily) for supplement number 5 above.

So there are other active forms of folate? I genetically have to take folinic acid and was concerned when Fredd thought it similar to folic acid in preventing use of / absorption of methylfolate. I take both at once in Thorne Basic B. Then I also take extra methylfolate. I have tried AOR B complex (which has only methylfolate) and noted no difference so I have returned to that prescribed by my doctor (methylfolate plus folinic acid).

I have also been prescribed to take PS by Dr. Roberts regarding my genetics. I rarely take it. I take so many pills and never noticed any difference with that so frequently forget it. However I eat an egg each and every day and have forever (or I get low blood sugar -- it's the protein at breakfast I need). Do you think that has enough lecithin? I also have occasionally taken choline capsules and have a "note to self" to order more next time because in the past I noticed they improved my memory (I had excellent memory though so never bothered with them but now I am interested in revisitting this). I take 1-2 g. TMG every day so not sure the choline would provide anything more as I'm not sure if it's anything more than a methyl source with an extra methyl than TMG. So, I guess I am also asking if TMG will function the same in your protocol. Does lecithin contain serine or just methyls?

Thank you for adding to my knowledge of the methyl cycle! It is wonderful to begin to get even a bit of a handle on these health problems over time. Science is making advances with lightning speed these days. I have to stay connected to keep up!
 

rydra_wong

Guest
Messages
514
SIMPLIFIED TREATMENT APPROACH
...
SUPPLEMENTS

1. General Vitamin Neurological Health Formula [2]: Start with one-quarter 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]: one-quarter 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.
Rich, I looked at that neurological formula and it contains both folic acid (which Fredd has found interferes with methylfolate) and cyanocobalamin (ditto interferes with methylcobalamin). I know I cannot process either of these as my enzymes are genetically broken, but don't you think others might be in the same boat? This is just another reason I have chosen and been following Fredd's protocol. That neurological formula also contains NAC which not only Fredd, but many doctors (I thought even Yasko) know can cause reactions especially in autistic people. I would never take it - never, never! It took Fredd a long time to get over it when he took it - I think like 6 months. I take Milk Thistle in a small dose and it seems to cause no problem. I wonder how these relate because milk thistle raises glutathione? I suppose it might contain a small dose of NAC? Not sure. But I take a very tiny dose (2 of a 6 a day).

Other differences that jump out at me, but don't you tell people to take a source of methyls like TMG, choline, or SAME? I m not sure because I haven't measured my homocysteine in enough permutations yet, but I suspect it is the TMG doing the most for me actually. If I do not take the B12 sublinguals (but still take the Thorne Basic B 2x/day and the extra mfolate and P5P and 2g. TMG) my homocysteine goes 6.1->6.5 (which hardly seems significant). If I take only Thorne Basic B 2x/day and nothing else, it goes up to 9 (which means 35% greater chance of stroke). So that leaves the mfolate, P5P, or TMG being what helps me the most. With only B100 (nonactive B's) it goes up to 12 (maybe higher now I'm older actually). If one doesn't get one's homocysteine to around 6.3 one is not methylating correctly. A homocysteine of 6.3 does not mean you ARE methylating correctly, but I regard it as a very first-step type measure. How can you fine tune what is obviously way out of control? I do not know what study yu are referring to (I don't know what link it is at) but in future studies could you look at what these protocols do to homocysteine as a crude objective measure of success?

Next thing that jumps out is Fredd's basic protocol includes omega-3. His is concerned with rebuilding nerves so that may be why it is not on yours. But if the myelin sheath of the nerves needs to be rebuilt, my understanding is that omega-3 is needed for that.

Last thing I wanted to ask about is whether you have ever looked at the impact of hormone replacement on these protocols? It made the hugest difference to me and I wish I had known to start replacing DHEA the MINUTE it started to wane at age 30. I asked Fredd about it and although he does not (I don't think) list it as part of his protocol, he uses full hormone replacement with DHEA and pregnenolone as I do. I see many people here who develop these ME symptoms as they get older (translate hormones wane) so it seems to me that it makes sense to replace those hormones first and foremost. I know they interact with the methyl cycle. Science is really not there yet although some studies have shown interaction. But it is obvious to me on an individual level.
 

rydra_wong

Guest
Messages
514
Oh Holy Bat Guano, Fredd! I thought you were just guessing that folinic acid is as bad as folic acid. What about those of us whose genetic mutations require folinic acid? Well I am one such and I did not notice any difference when I switched from Thorne Basic B (methylfolate plus folinic acid) to AOR B Complex which has only methylfolate.
Thorne Basic B keeps my homocysteine normal so I guess I am not going to worry about it. Not sure what else I could do anyway...
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
I'm building up to the SMP and am now at 2 tablets (1 morning, 1 evening) of the Neuro Health Formula a day, and yesterday added first one drop of b12, then another later, since I was OK, and then a drop of MethyMate B since I was still OK. Then I felt like I had the flu. I feel OK today. I'll just build up slowly.

My questions:

Is it best, once you've got going, to take the whole daily dose of b12 & folates together in one go? Presumably the b12 needs the folates to work. Or is there any reason to space them out, either biologically (to maintain an effect) or symptomwise (e.g. to minimise symptoms)? E.g. take a drop of b12 and a drop of MethB and then repeat later in the day?

I think Rich has said that some people take their stuff at night because it makes them sleepy. Any other timing issues?

Edit: I took two drops of MethB yesterday and had fluey aching symptoms again. Quite pleased to be getting a nasty effect early on, it must mean something is happening!
 

cigana

Senior Member
Messages
1,095
Location
UK
Hi,

It is difficult for people outside of the US to get hold of the multi that is part of the protocol. Is it possible to say which ingredients in the multi are important for supporting the methylation cycle (and in what quantities) so that we can find these in supplements in Europe?

Thanks!

Mark
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Hi,

It is difficult for people outside of the US to get hold of the multi that is part of the protocol. Is it possible to say which ingredients in the multi are important for supporting the methylation cycle (and in what quantities) so that we can find these in supplements in Europe?

Thanks!

Mark

Hi Mark - I'm in the UK and just bought all the stuff on the protocol including the multi, online in the UK from a company that imports the Holistic Health products. Here's my post on it (with prices). You have to contact them to order all the stuff - apart from the multi, the other stuff isn't listed on their website.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
I've been building up to the full protocol over the last few days and have now arrived (yippee!). Curiously, I've had some identical and some different symptoms to when I started Fred's protocol. With both, I had a weird sensation in my face, particularly in my upper lip, plus in my tailbone, some facial twitching, and sore muscles. On Fred's protocol I had severe headaches early on and developed severe and unrelenting fatigue which no amount of potassium or magnesium would shift. I don't have either of those with the SMP but I do have a severe flu-like feeling of being ill with muscle (inflammatory?) pain which appear 60-90 minutes after each folate dose, put me in bed for 2-3 hours and then disappear.

Interesting how different the experience is - I wonder whether it's just the difference between hb12 and a/mb12 or some of the other stuff.

Still wondering about the timing of doses, once this all settles down, as per my post above - all down the neck at once or space out?
 

richvank

Senior Member
Messages
2,732
I'm building up to the SMP and am now at 2 tablets (1 morning, 1 evening) of the Neuro Health Formula a day, and yesterday added first one drop of b12, then another later, since I was OK, and then a drop of MethyMate B since I was still OK. Then I felt like I had the flu. I feel OK today. I'll just build up slowly.

My questions:

Is it best, once you've got going, to take the whole daily dose of b12 & folates together in one go? Presumably the b12 needs the folates to work. Or is there any reason to space them out, either biologically (to maintain an effect) or symptomwise (e.g. to minimise symptoms)? E.g. take a drop of b12 and a drop of MethB and then repeat later in the day?

I think Rich has said that some people take their stuff at night because it makes them sleepy. Any other timing issues?

Edit: I took two drops of MethB yesterday and had fluey aching symptoms again. Quite pleased to be getting a nasty effect early on, it must mean something is happening!

Hi, Sasha.

I'm glad to hear that you have been able to tolerate the protocol, and that it seems to be doing something in your case.

I don't have answers about the best timing for taking the various supplements. There just haven't been detailed clinical studies of this, and I don't know how to approach it from a theoretical biochemical point of view. I think the residence times for the B12 and folate in the body should be long enough that the relative timing shouldn't matter much, but that is just a guess.

Best regards,

Rich
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Hi, Sasha.

I'm glad to hear that you have been able to tolerate the protocol, and that it seems to be doing something in your case.

I don't have answers about the best timing for taking the various supplements. There just haven't been detailed clinical studies of this, and I don't know how to approach it from a theoretical biochemical point of view. I think the residence times for the B12 and folate in the body should be long enough that the relative timing shouldn't matter much, but that is just a guess.

Best regards,

Rich

Thanks, Rich - I think I'll take the whole day's worth at one go in that case, to get rid of the risk of forgetting doses.

I've been on the full protocol for two weeks now and the flueyness has worn off, which is good. I'm still having to rest a lot more than normal but I think that's to do with having caught a bug. I'm looking forward to seeing how I do a few months down the line!
 

richvank

Senior Member
Messages
2,732
Rich, I looked at that neurological formula and it contains both folic acid (which Fredd has found interferes with methylfolate) and cyanocobalamin (ditto interferes with methylcobalamin). I know I cannot process either of these as my enzymes are genetically broken, but don't you think others might be in the same boat? This is just another reason I have chosen and been following Fredd's protocol. That neurological formula also contains NAC which not only Fredd, but many doctors (I thought even Yasko) know can cause reactions especially in autistic people. I would never take it - never, never! It took Fredd a long time to get over it when he took it - I think like 6 months. I take Milk Thistle in a small dose and it seems to cause no problem. I wonder how these relate because milk thistle raises glutathione? I suppose it might contain a small dose of NAC? Not sure. But I take a very tiny dose (2 of a 6 a day).

Other differences that jump out at me, but don't you tell people to take a source of methyls like TMG, choline, or SAME? I m not sure because I haven't measured my homocysteine in enough permutations yet, but I suspect it is the TMG doing the most for me actually. If I do not take the B12 sublinguals (but still take the Thorne Basic B 2x/day and the extra mfolate and P5P and 2g. TMG) my homocysteine goes 6.1->6.5 (which hardly seems significant). If I take only Thorne Basic B 2x/day and nothing else, it goes up to 9 (which means 35% greater chance of stroke). So that leaves the mfolate, P5P, or TMG being what helps me the most. With only B100 (nonactive B's) it goes up to 12 (maybe higher now I'm older actually). If one doesn't get one's homocysteine to around 6.3 one is not methylating correctly. A homocysteine of 6.3 does not mean you ARE methylating correctly, but I regard it as a very first-step type measure. How can you fine tune what is obviously way out of control? I do not know what study yu are referring to (I don't know what link it is at) but in future studies could you look at what these protocols do to homocysteine as a crude objective measure of success?

Next thing that jumps out is Fredd's basic protocol includes omega-3. His is concerned with rebuilding nerves so that may be why it is not on yours. But if the myelin sheath of the nerves needs to be rebuilt, my understanding is that omega-3 is needed for that.

Last thing I wanted to ask about is whether you have ever looked at the impact of hormone replacement on these protocols? It made the hugest difference to me and I wish I had known to start replacing DHEA the MINUTE it started to wane at age 30. I asked Fredd about it and although he does not (I don't think) list it as part of his protocol, he uses full hormone replacement with DHEA and pregnenolone as I do. I see many people here who develop these ME symptoms as they get older (translate hormones wane) so it seems to me that it makes sense to replace those hormones first and foremost. I know they interact with the methyl cycle. Science is really not there yet although some studies have shown interaction. But it is obvious to me on an individual level.

Hi, Rydra.

Thanks for your comments. I've been occupied with too many things lately, and have not been able to keep up with posts here, so sorry about the slow response.

I haven't read all of your posts, but I think I saw one in which you wrote that you don't have ME/CFS. Is that right?

I guess we haven't heard from Freddd for a while here, and I hope he's doing O.K. If you've read some of the past posts in this part of the forums, you know that he and I have kicked around several issues related to the differences between his protocol and the one I have suggested for ME/CFS. As you probably know, Freddd bases his recommendations on his personal experience and that of others, who I think he encountered largely on the WrongDiagnosis forum. As I understand it, Freddd has some inborn errors of metabolism involving the intracellular B12 processing enzymes himself, perhaps a variant of the CblC inborn error, based on what he has reported. Since he is also unable to tolerate folinic acid, I have suggested that he has a deficiency of the methenyl tetrahydrofolate synthetase enzyme (MTHFS) as well.

The protocol I have suggested is intended to lift the partial methylation cycle block in ME/CFS, based on the glutathione depletion--methylation cycle block hypothesis for the pathogenesis and pathophysiology of ME/CFS. This is described in detail in the video and slides of the invited seminar I presented in Sweden at the beginning of October:

http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/$%7Bweburl%7D

Much of the difference between the two protocols results from the differences between their origins. Freddd's genetic inheritance on the one hand, and a biochemical hypothesis for ME/CFS on the other. It happens that Freddd's protocol overlaps what is needed to lift the partial methylation cycle block enough that his protocol has been helpful to quite a few people with ME/CFS. However, his protocol is also effective for a whole range of B12-related disorders, because it basically leapfrogs over the whole normal pathway for intestinal absorption, transport in the bloodstream, cellular importation and intracellular processing of B12. Since it is not clear whether many of the people who have been helped by his protocol have ME/CFS or one of the other B12-related disorders, it is not possible to accurately infer from Freddd's personal experience or from their experiences how this protocol will work for most people who have ME/CFS, but do not have these other conditions. Please understand that this is not intended to be a criticism of what Freddd has done. He has apparently been able to help a lot of people as well as himself, and I'm glad for that. I've learned a lot from Freddd, and I continue to wish him well. I cited his work in the seminar I presented in Sweden. I'm only trying to explain why it is difficult to mesh what Freddd has done with ongoing efforts to improve treatment of ME/CFS per se.

Getting to some of the specific questions you have raised, I am not fond of either folic acid or cyanocobalamin, but I have kept Amy Yasko's multi in the suggested protocol because it contains several nutritional supplements that she has chosen particularly to support the methylation cycle and related pathways. Please note that most of the folate and B12 in the suggested protocol is in the more usable forms for the body. I realize that Freddd personally is not able to tolerate several of the supplements in this protocol, but this does not seem to be the case for most people who have ME/CFS, which is what this protocol was designed to treat.

NAC is present in the Yasko multi at a small dosage, and this does not seem to be a problem for most people who have ME/CFS. I do not recommend taking large dosages of it, because it has been found to be capable of moving methylmercury into the brain, and some people who have ME/CFS are high in methylmercury (such as from eating tuna).

TMG is also present. Too much of it will shunt homocysteine flow into the BHMT pathway too much, so that methionine synthase will not get enough, and it's important to get it running properly to regulate the sulfur metabolism and to get the folate metabolism up to speed.

Choline is present in the phos. serine complex or the lecithin. Omega-3 fatty acids are also present there.

SAMe was in the early version of the protocol, but I took it out because so many people with ME/CFS reported that they could not tolerate it, though some found it helpful.

Milk thistle helps the liver in several ways, though some people are not able to tolerate it. That is one reason a few people have had to substitute another multi.

With regard to homocysteine, I have not found it to be a reliable marker in ME/CFS (and the same is true in autism, according to Amy Yasko). Some people are low, some are high, and some are normal. It seems to depend on several variables, including methionine status, availability of ATP, whether there is a partial block in the methylation cycle, the status of B vitamins and TMG, and polymorphisms in genes associated with the methylation cycle and related pathways, including the gene coding for the CBS enzyme. Because of all these variables, I have not found it to be straightforward to interpret what the homocysteine level means. I agree that it is desirable to have a normal homocysteine level for good reasons.

With regard to hormone replacement, I agree that it can be very important. In Dr. Neil Nathan's book On Hope and Healing for Those Who Have Fallen Through the Medical Cracks, DHEA is on of the important things he considers in addition to methylation treatment. I also like the book "Female Brain Gone Insane" by Mia Lundin. I think she has a good approach toward hormone issues. I have not included hormone replacement in the basic protocol. The philosophy behind it is to offer something relatively simple and relatively inexpensive so that people have a place to start. Once they find that it is helpful, many people have gone on to add other things. But if it is too complex at the outset, many people will not try it at all. That has been a problem with the full Yasko protocol from which it was extracted.

I hope this is helpful. From your posts, it looks as though you have a very interesting case yourself, and that you have put a lot of good effort into understanding it and determining the most effective treatment. We are all unique. It would be nice if a cookie cutter treatment would work for everyone, but it seems that that is not to be.

Thanks again,

Rich
 

richvank

Senior Member
Messages
2,732
Thanks, Rich - I think I'll take the whole day's worth at one go in that case, to get rid of the risk of forgetting doses.

I've been on the full protocol for two weeks now and the flueyness has worn off, which is good. I'm still having to rest a lot more than normal but I think that's to do with having caught a bug. I'm looking forward to seeing how I do a few months down the line!

O.K., Sasha. I hope it works out well for you.

Rich
 
Messages
94
Location
California
Timing

My questions: Is it best said:
Hi Sasha,
I'm sure that it is different for everyone, but I had a huge breakthrough recently by moving three of my supplements to two doses per day (methyl B12, methylfolate, and TMG.) I should note that the second dose doubled my initial intake. The difference for me has been amazing. No more brain fog, body pain gone, energy level up, reactions to stress much better, sleep hugely improved, ability to multi-task has skyrocketed. I have been on the new protocol for about ten days............................I usually have big reactions to everything! PS It has taken 6 months of low-and-slow to work up to this point. TMG and Methylfolate seem to be what my body responds to the most. I had to go back down to my original amount of mB12, but keep the others doubled.