Simplified Methylation Protocol Revised as of Today

[maddietod]

I would like it if whatever I do/learn can be useful to this group. I've long since given up on doctors, so I can't offer blood test results. So I'm trying to be clear about how to run a test on myself. To challenge myself re. folic acid, I just keep everything I've ordered and see what happens. That's part A. [This is the multivitamin, B12 megadrops, methylmate B, folinic acid, lecithin]. Then once I've used up the Bs (about 4 months) I switch out everything with folic acid for the substitutions already discussed above, and see what happens. That's part B. Yes?

My marker for healing is increased stamina, mental and physical, because that's the only area that doesn't also get messed up by food/environmental reactivity. So I'll be looking for improvement in distance driving, ability to tolerate any exercise at all, and comfort in social situations with more than 4 people.

 

[leela]

So are we talking synthetic folic/folinic acid as the bad guy here? Since these things are unavoidable in food anyway, I have pondered purchasing a food-based b-complex, since the place I order from doesn't have the Douglas Labs B without folic. Any thoughts from the log-time methylators?

 

[richvank]

I would like it if whatever I do/learn can be useful to this group. I've long since given up on doctors, so I can't offer blood test results. So I'm trying to be clear about how to run a test on myself. To challenge myself re. folic acid, I just keep everything I've ordered and see what happens. That's part A. [This is the multivitamin, B12 megadrops, methylmate B, folinic acid, lecithin]. Then once I've used up the Bs (about 4 months) I switch out everything with folic acid for the substitutions already discussed above, and see what happens. That's part B. Yes?

My marker for healing is increased stamina, mental and physical, because that's the only area that doesn't also get messed up by food/environmental reactivity. So I'll be looking for improvement in distance driving, ability to tolerate any exercise at all, and comfort in social situations with more than 4 people.

Hi, madietodd.

That sounds like an interesting test to me. If you haven't experienced benefit from the Simplified Treatment Approach in four months, I would say that it would be time to try something else.

What to try if the Simplified protocol doesn't help would be a question to consider. If you want to try to pin things down, then changing only one thing at a time is the best way to go, such as only eliminating folic acid. On the other hand, if you just want to get better as fast as possible, I'm guessing that Freddd would suggest switching entirely to the protocol he has suggested. Of course, I don't know what the results would be for you either way, but it would be your decision to make, and you might want to kick it around a little before deciding.
Of course, I'm hopeful that the Simplified protocol will work for you, and if it does, this will become a moot point!

Best regards,

Rich

 

[maddietod]

OK, and thanks, everybody, for the input. I'm going with the simplified protocol as written, and you won't hear from me about it again until I (a) nosedive, (b) feel better, or (c) need to order more of the multivitamin, in about 3 weeks. It sounds like if there IS a problem, it's likely to be the folic/folinic acid, so there's no reason for me to introduce these supplements one at a time. So I'm starting them all on Sunday (the day AFTER my mother's ginormous 90th birthday party, just in case...).

Thanks again, everybody!

Madeleine

 

[Freddd]

So are we talking synthetic folic/folinic acid as the bad guy here? Since these things are unavoidable in food anyway, I have pondered purchasing a food-based b-complex, since the place I order from doesn't have the Douglas Labs B without folic. Any thoughts from the log-time methylators?

Hi Leela,

I wonder what a log-time methylator is. Is there a specific type of log like pine or birch or oak? Getting serious for a moment folic/folinic acids are a definite problem for some unknown percentage of people. I was never able to recognize it as I was folate deficient since childhood and had no basis of comparison. It wasn't until after I tried Metafolin that I found out the difference then having a basis for comparison of not being folate deficient.

They are not unavoidable in food. I don't eat white flour except on rare occasion and I don't eat any fortified foods such as vitamin cereals or drinks. Folic acid is not the form in green leafy foliage. There are other brands of b-complex without folic acid or cyanocbl. I found one at a local pharmacy by asking the pharmacist.

 

[Freddd]

OK, and thanks, everybody, for the input. I'm going with the simplified protocol as written, and you won't hear from me about it again until I (a) nosedive, (b) feel better, or (c) need to order more of the multivitamin, in about 3 weeks. It sounds like if there IS a problem, it's likely to be the folic/folinic acid, so there's no reason for me to introduce these supplements one at a time. So I'm starting them all on Sunday (the day AFTER my mother's ginormous 90th birthday party, just in case...).

Thanks again, everybody!

Madeleine

Hi Madeleine,

If you keep track of every symptom and how it changes day by day during the next 3 weeks there could be clues that could help you pick what you are ordering next. It's difficult to notice the folate deficiency symptoms if you are already deficient because nothing changes which otherwise might change rapidly. If for instance you have IBS and cheilitis, multiple chemical sensitivity, allergies, asthma and those don't change that MIGHT be a clue, depending upon what does change, if anything.

 

[maddietod]

Fredd - I will keep a comprehensive diary; I've been writing up my baseline. Also, I notice that the protocol says to take 2 of the multis daily, not the 6 recommended on the label. So I won't run out for 3 months. Will I bore everybody to tears if I check in anyway in a few weeks? Tracking changes in symptoms is an interesting challenge, because I don't have obvious things like IBS (any more, because I gave up cocoa), or asthma. I successfully avoid chemicals and food allergens, so no help there. I'll write down all the things I DO have, and see what changes. But really, the thing I can't ever fix through any of my intervention strategies is insufficient energy/lack of stamina.

I very much appreciate all the help I'm getting. I feel like I've finally found a home. Thanks, y'all.

 

[toddm1960]

I started the new simplified protocol two weeks ago, haven't felt any difference so far. I had been taking 25 mg three times a day of leucorvin, I stopped this while I'm trying the protocol. What kind of percentage show no changes?

How many others with known mitochondrial disease have tried the protocol? Did any of you have any luck?

 

[dannybex]

Agree with the move. Let me sneak one last post regarding clonazepam nutrient depletion.

Benzodiazepines. What to do before reducing a benzodiazepine. Valium, Klonopin withdrawal.
...prolonged use of a benzodiazepine will deplete biotin massively and lead to depression and the tingling or numbness.

Biotin
Extra biotin is also needed during long-term anticonvulsant treatment which depletes biotin.

Biotin (vitamin H, vitamin B7)
Long-term use of anti-seizure medications may also lead to biotin deficiency. Biotin deficiency results in fatigue, depression, nausea, muscle pains, hair loss, and anemia.

Linus Pauling Institute
Individuals on long-term anticonvulsant (anti-seizure) therapy reportedly have reduced blood levels of biotin as well as increased urinary excretion of organic acids that indicated decreased carboxylase activity.

Interactions with Clonazepam

Hi David,

Besides the first link, which specifically was connected to benzos, could you find any other references that back up their claim. I was taking biotin quite regularily...and maybe it speeded me up too much...but cut it out as it contains sulfur, and I may have that CBS upregulation gene (don't know yet), but seem to fit the profile, and if so, they recommend cutting back on as many sulfur containing supplements and foods (MEAT! and a lot of veggies) as possible until methylation / transsulfuration can be 'restored'.

Thanks!

d.

 

[dmholmes]

Hi David,

Besides the first link, which specifically was connected to benzos, could you find any other references that back up their claim.

Hi Danny, here is a quote from Dr. Cass' book on nutritional deficiencies caused by prescription medications.

Supplement Your Prescription: What Your Doctor Doesn't Know About Nutrition

"Barbiturates deplete biotin, folic acid, and vitamins D and K. Benzodiazepines deplete these nutrients, plus calcium and melatonin."

Peace

 

[Freddd]

Fredd - I will keep a comprehensive diary; I've been writing up my baseline. Also, I notice that the protocol says to take 2 of the multis daily, not the 6 recommended on the label. So I won't run out for 3 months. Will I bore everybody to tears if I check in anyway in a few weeks? Tracking changes in symptoms is an interesting challenge, because I don't have obvious things like IBS (any more, because I gave up cocoa), or asthma. I successfully avoid chemicals and food allergens, so no help there. I'll write down all the things I DO have, and see what changes. But really, the thing I can't ever fix through any of my intervention strategies is insufficient energy/lack of stamina.

I very much appreciate all the help I'm getting. I feel like I've finally found a home. Thanks, y'all.

Hi Madeleine,

Also, I notice that the protocol says to take 2 of the multis daily, not the 6 recommended on the label.

Is there a specific multivitamin listed that you do have or is the one expected a 2 per day and the ones you have are a 6 per day so that 2 per day are only 1/3 of the expected dose?

There is a list of symptoms at the beginning of the B-12 - The Hidden Story thread that is reasonably complete though I am working on an update. It can be used as a checklist to make sure you don't miss anything.

But really, the thing I can't ever fix through any of my intervention strategies is insufficient energy/lack of stamina.

Well , the things that will usually directly go after these items in the muscles are the combination of adb12, l-carnitine fumarate and Alpha Lipoic Acid with Metafolin after the base is built. However, there is also a separate central mediated "fatigue" which may be involved that takes a separate strategy. After the energy is being generated and exercise tolerance has returned, then exercise itself is needed to build stamina and capacity. So for the exercise to work at rebuilding stamina the base factors for cell reproduction have to be established and healing under way already. Just turning on the mitochondria without the basic healing under way isn't effective. There is only the temporary feeling of more energy without the stamina and capacity.

You have to get started somewhere. You are not getting married to any specific supplements so adjustments will get made over and over. Good luck. And if something isn't working, you don't have to wait until you run out to change it or do some back and forth trials. Every reason on the list of why b12 therapies might not work are things I and others have discovered the hard way, things didn't work. So there is lots of trial and error. I and Rich and others can suggest what we each think might be more likely to work. For any given person it comes down to what works best for them.

 

[Freddd]

I started the new simplified protocol two weeks ago, haven't felt any difference so far. I had been taking 25 mg three times a day of leucorvin, I stopped this while I'm trying the protocol. What kind of percentage show no changes?

How many others with known mitochondrial disease have tried the protocol? Did any of you have any luck?

Hi Todd,

On the subject of "diagnoses" I'm a real pessimist. I have had a lot of diagnoses through the years and while a lot of them were correct in a certain way, ie I did have neuropathies, virtually any kind a doc might be inclined to name and then some. However, naming them never once led to any effective treatment. So I collected an alphabet soup of diagnoses of which not a single one ever suggested an effective treatment. I had to find the mb12-body deficiency, the adb12-deficiency, the adb12-CNS deficiency, the mb12-CNS deficiency, the folate deficiency and the paradoxical folate deficiency. The docs were not able to come up with any b12 or folate deficiencies so they prescribed more than 100 different drugs most of which had intolerable side effects with zero benefit.

What does "mitochondrial disease" actually mean? There are a multitude of forms, some of them being a description of adb12 deficiency, some of them not. Some mitochondrial malfunctions can be corrected with adb12, l-carnitine fumarate, Metafolin and other factors, some can't.

However, if folinic acid causes paradoxical folate deficiency for you it will block any chance of having an effective treatment. In debugging a program we work through all the blocks one thing at a time. A very obvious starting point is the folinic acid. It might not be the problem or it might be one of a dozen. It looks like the best place to start.

I stopped this while I'm trying the protocol.

So have you started the Metafolin to actually start correcting the problem? If the folinic acid starts a deficiency it doesn't go away just because you have stopped taking it.

 

[soulfeast]

OK.. so we are talking two different methylation protocols in one thread here, right?

The multi is the yasko multi and part of the simplified (yasko) protocol that Rich has authored. Then we have Freddd's methylation protocol that is similar but different in that it is a methyl and adenyl b12 and metafolin protocol all high dose. Rich's protocol calls for hydroxo b12, a little folinic and metafolin. The yasko multi has small doses of tmg that she uses to supplement or bypass the short pathway in the methylation cycle along with phospho serine and what.. I forget. BHMT pathway. The yasko multi she feels is sufficient for our needs and suggests no more than 2 though the bottle says 6 is one dose. She goes by test results to determine additional needs.

QUESTION FOR FREDDDD and RICH: Freddd, you are saying that folinic in addition to FA competes with the methylated form of FA and therefore folinic (tetrahydrofolate) is counterintuitive to methylation.. and if so, then do you think THF folate (folinic) is needed by the body at all and how to compensate for that?

Rich, your thoughts?

What I am finding as interesting is that though I am COMT++ and not supposed to need or be able to tolerate too many methyl donors, my body seems to crave methyl b12 and it also seems to crave gluathione which seems to contradict both protocols unless the hydroxo is creating more of a need for glut? Or methylation is pushing out toxins faster than it can create enough glut or can you create enough glut to "cover" a backlog of toxic soup?

Thnk you!

 

[Freddd]

OK.. so we are talking two different methylation protocols in one thread here, right?

The multi is the yasko multi and part of the simplified (yasko) protocol that Rich has authored. Then we have Freddd's methylation protocol that is similar but different in that it is a methyl and adenyl b12 and metafolin protocol all high dose. Rich's protocol calls for hydroxo b12, a little folinic and metafolin. The yasko multi has small doses of tmg that she uses to supplement or bypass the short pathway in the methylation cycle along with phospho serine and what.. I forget. BHMT pathway. The yasko multi she feels is sufficient for our needs and suggests no more than 2 though the bottle says 6 is one dose. She goes by test results to determine additional needs.

QUESTION FOR FREDDDD and RICH: Freddd, you are saying that folinic in addition to FA competes with the methylated form of FA and therefore folinic (tetrahydrofolate) is counterintuitive to methylation.. and if so, then do you think THF folate (folinic) is needed by the body at all and how to compensate for that?

Rich, your thoughts?

What I am finding as interesting is that though I am COMT++ and not supposed to need or be able to tolerate too many methyl donors, my body seems to crave methyl b12 and it also seems to crave gluathione which seems to contradict both protocols unless the hydroxo is creating more of a need for glut? Or methylation is pushing out toxins faster than it can create enough glut or can you create enough glut to "cover" a backlog of toxic soup?

Thnk you!

Hi Soulfeast,

I decided to give folinic acid a try as Rich built a very convincing case for it. I found that a single dose of 800mcg once a day caused a slower onset of paradoxical folate deficiency than multiple doses of folic acid, but there was the onset none the less. It appeared to have a longer duration of activity which appears to correspond with it's longer serum half life. Getting off of all folic and folinic acid with just the Metafolin has made a very significant difference though, through timing I could eliminate most of the effects of the folic acid, but not the folinic acid.

I don't know what percentage of people have such responses to folic and/or folinic acid. That is still somewhat of a mystery. However, there can be a number of indicators while taking it; cell formation breakdown leading to angular cheilitis, IBS, acne type lesions, skin breakdown around nails and fingertips, increased inflammation, allergy, asthma, multiple chemical sensitivity, nausea, "detox", fatigue, muscle pain and no doubt some others, some quicker and some requiring a longer onset time as folate deficiency leads to b12 deficiencies.

If the body needs a type of folate not available one would expect a characteristic set of symptoms pointing at it despite taking the mb12, adb12 and Metafolin. My dose of Metafolin was determined, and redetermined by titration to level that prevents return of folate deficiency symptoms. I am currently healing pretty quickly from the folate deficiency symptoms. After a while I will see what remains.

 

[richvank]

OK.. so we are talking two different methylation protocols in one thread here, right?

The multi is the yasko multi and part of the simplified (yasko) protocol that Rich has authored. Then we have Freddd's methylation protocol that is similar but different in that it is a methyl and adenyl b12 and metafolin protocol all high dose. Rich's protocol calls for hydroxo b12, a little folinic and metafolin. The yasko multi has small doses of tmg that she uses to supplement or bypass the short pathway in the methylation cycle along with phospho serine and what.. I forget. BHMT pathway. The yasko multi she feels is sufficient for our needs and suggests no more than 2 though the bottle says 6 is one dose. She goes by test results to determine additional needs.

QUESTION FOR FREDDDD and RICH: Freddd, you are saying that folinic in addition to FA competes with the methylated form of FA and therefore folinic (tetrahydrofolate) is counterintuitive to methylation.. and if so, then do you think THF folate (folinic) is needed by the body at all and how to compensate for that?

Rich, your thoughts?

What I am finding as interesting is that though I am COMT++ and not supposed to need or be able to tolerate too many methyl donors, my body seems to crave methyl b12 and it also seems to crave gluathione which seems to contradict both protocols unless the hydroxo is creating more of a need for glut? Or methylation is pushing out toxins faster than it can create enough glut or can you create enough glut to "cover" a backlog of toxic soup?

Thnk you!

Hi, soulfeast.

Folinic acid occurs naturally in the body and in natural foods. In the body, it does not have a direct role as a coenzyme form of folate. Its role may be to serve as a reservoir of chemically reduced folate, as it is convertible to other coenzyme reduced folate forms by reactions catalyzed by specific enzymes in the body. It does require NADPH for conversion to methylfolate, and that may be the reason it causes problems for freddd and some others.

I have included it in the Simplified Treatment Approach following Amy Yasko. The argument for including it is that when the methylation cycle is partially blocked, if only methylfolate is taken, initially there will not be enough of the folate forms needed to make new RNA and DNA, which is important especially for making cells that are replaced rapidly, such as blood cells and the cells lining the gut. The reason is that methylfolate must react with homocysteine in the methionine synthase reaction in order to form tetrahydrofolate, and then the latter can be used to make the other coenzyme forms of folate. But if this reaction is slow initially, there will not be much THF available. The methylation pathways panel typically shows that PWCs are low in THF.

In the DAN! program for treating autism (which in my view is biochemically very similar to ME/CFS) folinic acid is the main folate form used, and it does seem to help quite a few.

It would be very nice if we could come up with a one-size-fits-all, cook-book, cookie-cutter type of treatment, but that may not be possible, because of genetic and biochemical individuality. Amy Yasko handles this by characterizing SNPs, but this is somewhat expensive and also somewhat complicated. Perhaps the cost of SNP profiling will keep coming down.
23andme has become a better deal lately. If we get smart enough, we may be able to run a panel like that and pinpoint what is best for an individual in terms of treatment. It will likely always be kind of complicated, though. This is a topic that really needs some careful study, but so far the funding to do a good study is not there, so we are just having to "wing it" with anecdotal experience and projecting as far as we can with known genetics and biochemistry.

Best regards,

Rich

 

[maddietod]

Freddd -

I bought the exact vitamin in the protocol, from holistic health. The protocol says 2/day, and the bottle says 6.

The whole exercise thing is strange. During the winter I was able to do a 5-minute warmup on a rowing machine (medium weight) + 1 circuit of the weight machines, low weight, low reps. Then suddenly, after maybe 2 months, I was unable to do it any more. The same thing has happened in the past with walking, at a different time of year. I keep detailed health journals (what I eat, how I sleep, supplements or not, etc) in case I later want to look for a pattern. And I looked, and couldn't see anything that had changed.

Madeleine


By the way, I jumped back onto this forum after a long absence because a local CFS friend went to her doctor, and he handed her a printout of Rich's January 10-14 2007 presentation of an earlier version of the protocol I'm starting. Everything beyond the information in that 4 page paper is new to me.

 

[maddietod]

Rich -

I'm starting your protocol on Sunday, and the only other thing I'm doing is transdermal magnesium (no gastric distress!). Is it best to just do this, or should I be taking supporting vitamins/minerals? I ask because your recommended dosing of the multivitamin is 1/3 of a "normal" dose. So I'm wondering if I should supplement that.

If nothing happens at all, how long should I stay on this exact protocol before checking in about tweaking it?

Thanks! Madeleine

 

[richvank]

Rich -

I'm starting your protocol on Sunday, and the only other thing I'm doing is transdermal magnesium (no gastric distress!). Is it best to just do this, or should I be taking supporting vitamins/minerals? I ask because your recommended dosing of the multivitamin is 1/3 of a "normal" dose. So I'm wondering if I should supplement that.

If nothing happens at all, how long should I stay on this exact protocol before checking in about tweaking it?

Thanks! Madeleine

Hi, Madeleine.

The dosages are set low because many people do not tolerate higher dosages. If you can handle more of the multi, it's fine to raise the dosage eventually up to 6 per day.

If you would like to read things I've written since Jan. 2007, you can find them at http://aboutmecfs.org.violet.arvixe.com/Trt/TrtGSHIntro.aspx

Here's a quotation from the report on our clinical study, which may give you some guidance about how long it takes for a response:

"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."

I hope the treatment will help you. Please keep us posted.

Best regards,

Rich

 

[bertiedog]

Hi Rich and Fredd

With regard to side effects of the protocols I think it might have been the extra niacin that was in the B Right that was causing the horrendous migraines and in fact nothing to do with the MB12. I am tolerating 3000 mcg MB12 but it isn't the Jarrow one, this one doesn't have any sweetner in it.

I have read that niacin is a vasodilator and I know I cannot tolerate much of any vasodilator. It meant I was getting a total of 27.5 mg niacin in all. After stopping the B Right the migraines stopped and I restarted the new MB12 and no migraines. Now I have added 1/2 Thorne Basic B Complex which gives an extra 5mg niacin and for 2 days on this I am ok.

I wonder if there is anything else in the B Right that could have caused migraines apart from niacin, I was only ever taking 1/2 tab? The Thorne Basic B only has active forms of both folate, and B12 and B6. I noticed a big difference in my energy when not taking any extra Bs, it was like I was running on empty. I even added 200 mg niacinamide but it didn't make any difference to my energy at all. I am glad to say the new B Complex is working well energy-wise.

This is certainly a very complicated journey for some of us. Once I know I am ok with the new B complex I will try the AdnB12 again and also the Jarrow MB12 but I will only do this once I have established the new B is definitely ok migraine-wise.

Thanks as always for all your help.

Pam

 

[maddietod]

Rich - Do the drops need to be held under the tongue for a long time, like sublinguals?

Madeleine