Simplified Methylation Protocol Revised as of Today

[Freddd]

Hi Madie,

I too would be fascinated to see the results if you are able to get the tests done, one now and one after you have stabilized and customized for maximum improvement on the active protocol.

 

[maddietod]

Freddd and Rich -

Rich -I've ordered the DirectLabs test, and will find myself a doctor to order the Health Diagnostics test. I've got an appointment on Monday with a chiropractor willing to work with me re. the Methylation panel. Results should come 4 weeks from Monday.

Freddd, I took potassium back in early May, and it coincided with increased nausea and continued poor sleep. I can't say it caused anything, because who knows? But it didn't help either.

Are there other tests you'd like me to do before I start? I have 6 children, so I'm interested in gathering information that might also help them in their futures.

Should I go ahead and order all of the supplements, or wait for test results?

Thanks to you both,

Madie

 

[richvank]

Hi, biophile.

Sorry for the long delay in responding. My responses are at the asterisks below:

Hi richvank,

I have to ask, would a partial block in the methylation cycle help explain why I responded negatively to SAM-e, vitamin E, and vitamin C? (the last 2 often recommended due to being anti-oxidants).

SAM-e: horrible bilious and strong malaise feeling all over, especially in the liver area, tingling in right arm.

Vitamin E: unusual nausea and weird "scratchy" headache.

Vitamin C: dull headache.

The response to SAM-e was bad and prolonged enough that you couldn't pay me to try it again. I would be reluctant to try vitamin E again, but the effects only lasted 48 hours. The effect from vitamin C isn't bad enough to fear it but I wouldn't take it regularly. These reactions only occurred when illness reached a certain phase of severity, a few years after trying numerous medications and treatments using recommended dosages (not all at once or together).

Until then the above listed supplements had no noticeable effect at all. Something strange occurred during the worsening of illness and ever since then, tolerance to medications and supplements in general took a nose dive and post-exertional symptoms have become much worse.


***Yes, I think that a worsening methylation cycle block could explain these negative responses. With regard to SAMe, a person with a normally functioning methylation cycle and sulfur metabolism in general does not respond that way to SAMe supplementation. So the negative response itself points to a problem there. I'm not sure why you experienced those particular symptoms. Normally the liver is the largest producer of SAMe in the body. If you had a partial methylation cycle block, your SAMe availability would have been low. In this situation, there was probably an upregulation of the enzymes that normally make use of SAMe (the methyltransferase enzymes). They would therefore have become much more sensitive to the SAMe level. When you then supplemented SAMe directly, it seems probable that these reactions would have surged faster than normal, and this would have affected your biochemistry in many ways, all of a sudden.

***With respect to vitamins C and E, if you had a partial methylation cycle block which was coupled to glutathione depletion, your body was likely in a condition of fairly high oxidative stress. As you noted, vitamins C and E are antioxidants. However, in normal conditions, they are recycled by glutathione as they become oxidized, so that they can be used again. If glutathione is depleted, they tend to remain oxidized, and this will have a pro-oxidant, rather than an antioxidant effect.

It has been a long time since I have read anything which may help to explain what happened and why it still mostly seems stuck there without sign of further improvement. I think your hypothesis on the partial block in the methylation cycle is a good candidate, and I would appreciate your opinion.

Last year I tried 1/4 dose FolaPro and 1/4 dose hydroxy-B12 for roughly 2 months. I couldn't sustain or tolerate a higher dosage. I stopped altogether, perhaps because I got impatient or just forgot 3 months is the suggested minimum. That was about 12 months ago and I regret not staying on it because I have recently become interested in trying it again due to the 23andme results. I ordered more FolaPro as the last bottle was out of date. The hydroxy-B12 bottle I have is still within date. I also ordered folinic acid and methyl-B12 drops. I am reluctant to get other peripheral cofactors, due to cost and potential tolerance issues.

***I can understand that, but it may be that your body is deficient in some of the cofactors that are needed by this part of the metabolism. I think that some of the failures of methylation treatment to help PWCs are a result of these deficiencies.

Apparently I am "(+/+)" for several of the relevant SNP's according to 23andme testing, so I guess this may point towards an increased susceptibility to a functional issue within the methylation cycle?

***Yes, I think that the SNPs that Amy Yasko has identified as being important in autism are also important in ME/CFS. The partial methylation cycle block and glutathione depletion are common to both.

I also wonder if it would be possible for me to fine-tune the protocol by looking at personal differences in my 23andme profile and do research on the mechanisms behind these processes?

http://www.knowyourgenetics.com/The Methylation Pathway_files/diagram-1.jpg

http://www.knowyourgenetics.com/The...ting a personalised 23andme analysis as well.

***Yes. I think the 23andme panel offers a lot of promise for the future. At this point, I don't think we know enough to effectively make use of all the data it provides, but it does include about two-thirds of the SNPs that Amy has identified, and that's a start. Once you have your genotype analysis, assuming they did it right, it will be the same for the rest of your life, and research should continue to give us more insight on how to use these data, so I think it's a good investment, even though we are still having to grope about, trying to make use of it as well as we can.

***Best regards,

***Rich

 

[richvank]

Hi Rich,

Do you think that taking a diamine oxidase supplement could impact negatively on the methylation cycle in any way?

Best wishes,

Sandra

Hi, Sandra.

As far as I know, it would not.

Best regards,

Rich

 

[richvank]

Hi Rich

I thought your response to dreambiride & her reaction to glutathione were very interesting.

Based on what you said, I am thinking that a person deficieint in B2 &3 and with poor blood sugar control might not respond all that well to gluthatione supplementation.

I just took a tspn of the liposomal stuff & now I have to go to bed...but like dreambirdie I have found it helpful to ease liver congestion in the past.

Hi, aquarius.

That makes sense to me. Dr. Cheney recently wrote me that he has tested for NADPH in PWCs for many years, and they always come out low.

Rich
A

 

[richvank]

Hi Rich
I finally got the supplements for the protocol and did the blood draw for the Methylation Pathways test. I am slowly starting to add the supplements. I noticed that I bought the HYdroxy B12 sublingual tablets rather than drops. They are 1000mcg. Will that be OK? I opened the bottle before realizing the mistake.
I also notice that people are playing around with many forms of B12. is that fine to do w this protocol. Could you explain the parameters with that. I know Fredd was offering a B12 protocol. Are people drawing from both?

Lucy

Hi, Lucy.

I'm happy to hear that you are running the methylation pathways panel. The sublingual tablets of hydroxocobalamin should be fine.

Yes, people are trying different versions of treatment. Some seem to do better on one, and some on another. At this point, I don't know how to predict which would be best for a given person. There haven't been controlled clinical studies comparing the various versions.

Dr. Amy Yasko does genomic testing (mostly on children who have autism) and bases her advice about which form or forms of B12 to use on the person's set of SNPs (genomic polymorphisms). I proposed the so-called Simplified Treatment Approach to decrease the cost and complexity of the Yasko program so that it would be more affordable and understandable to many people who have ME/CFS and who have financial and cognitive challenges, and it has helped quite a few people and has done well in a clinical study. I chose to use hydroxo-B12 in this protocol for various reasons, and have used both folinic acid and 5L-methyltetrahydrofolate as the folate forms. (The original version included more folic acid, but I have recently revised it to lower this, because some people are not able to utilize folic acid very well.) About two-thirds of the patients in the clinical study experienced significant improvement on this protocol and two or three achieved what appeared to be full recovery. However, some did not respond to this treatment. It has not been optimized, and is likely not the best for all people with ME/CFS.

Freddd is recommending a protocol that incorporates methyl B12 and adenosyl B12 as the B12 forms, and 5L-methyltetrahydrofolate alone as the folate form. He also includes some additional nutrients as cofactors, notably carnitine fumarase. The dosages he recommends are somewhat higher than those I have suggested.

Freddd's protocol is applicable to people with the whole range of B12-related problems, not only those who have ME/CFS. Some people are reporting that they are doing well on it. Others have not been able to tolerate the symptoms that have arisen for them on this treatment.

Perhaps if we had genomic information and a more complete understanding, we would be able to select the appropriate treatment for each person ahead of time. Freddd's view seems to be that his recommended treatment will work for everyone who has a B12-related problem, including all those with ME/CFS. So far, I have not been able to agree with him on this point, in view of the reports I have seen from various people who have tried it, but I am keeping an open mind, and am interested in hearing from more people about their experiences with the various methylation-related protocols.

I might mention that the protocols that Freddd and I have suggested are only two of the various methylation-related protocols that are currently in use. Others include those tested by S. Jill James and colleagues for autism, those used by the DAN! project doctors for autism which include subcutaneous methyl B12 and oral folinic acid, the protocol of Dr. Alan Vinitsky, which uses sublingual folic acid together with sublingual hydroxo B12, the updated protocol of Prof. Martin Pall, which includes liposomal hydroxo B12 and oral 5-methyltetrahydrofolate, and the prescription medical foods supplied by PamLab, including Metanx and CerefolinNAC, which use oral methyl B12 and 5L-methyltetrahydrofolate.

I would like to see some controlled clinical studies to determine the best approach for various people, but so far we are just having to try things on an individual basis.

Best regards,

Rich

 

[richvank]

Freddd and Rich -

I've ordered the DirectLabs test, and will find myself a doctor to order the Health Diagnostics test.

Freddd, I took potassium back in early May, and it coincided with increased nausea and continued poor sleep. I can't say it caused anything, because who knows? But it didn't help either.

Are there other tests you'd like me to do before I start? I have 6 children, so I'm interested in gathering information that might also help them in their futures.

Should I go ahead and order all of the supplements, or wait for test results?

Thanks to you both,

Madie

Hi, Madie.

Wow! It sounds as though you're not messing around!:victory:

I hesitate to recommend more testing, because I know the cost can add up very rapidly, but since you asked, yes, there are some more tests I would suggest. I'll give you the rationale for each of them:

First, I've already suggested the Health Diagnostics methylation pathways panel. It will give you direct measures of methylation cycle metabolites, folate metabolites, and both reduced and oxidized glutathione. This panel will show the current status of your biochemistry in these areas, all of which are tied together in the vicious circle mechanism that I believe is at the core of the pathophysiology of ME/CFS.

Second, I've suggested the plasma amino acids profile. This will give direct measures of amino acids that are important to this part of the metabolism. This includes methionine, which is the feed material for the methylation cycle, glycine and sarcosine, which are involved in limiting the ratio of SAMe to SAH, important when the methylation cycle is being overdriven, serine, which is needed in the folate metabolism as well as in feeding the transsulfuration pathway, cystathionine, which indicates flow in the transsulfuration pathway, cystine, which gives an indication of cysteine synthesis, glycine and glutamate, which are needed with cysteine to make glutathione, and taurine, which indicates flow through the sulfur metabolism. In addition this panel will give information to evaluate protein digestion and amino acid absorption, and the rate of burning of amino acid for energy production.

Beyond these two, I would suggest the following:

Genova Diagnostics Metabolic Analysis Profile (available without a doctor's order from www.directlabs.com at

https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx

This is a urine organic acids panel. It will give information on several aspects of the overall metabolism. With respect to B12, it will evaluate methylmalonic acid, which is an indicator of the availability of adenosyl B12. With respect to folate, it will evaluate figlu, which is marker for low tetrahydrofolate. With respect to glutathione, it will measure pyroglutamic acid, which will indicate the glutathione status in the kidneys. It also gives values for citric acid and the following Krebs cycle metabolites, and this gives information on the glutathione status in the muscles, primarily. This panel also gives a variety of other information, and is very powerful when interpreted together with the amino acids panel.

Urine Toxic and Essential Elements panel

https://www.directlabs.com/OrderTests/tabid/55/language/en-US/Default.aspx

This one is a Doctor's Data Lab panel. It gives measurements of both toxic elements and essential elements in the urine. I favor doing a 24-hour urine collection for this test, because that gives the additional information about daily urine volume and daily creatinine excretion. Both toxic and essential elements can impact the methylation cycle and related pathways, and toxic metal excretion increases as the methylation cycle recovers. It is helpful to have this panel to analyze together with the amino acids and organic acids panels, because one will help to interpret the other.

Genomics panel. I understand that getting the Yasko nutrigenomics panel is problematic in Maryland. If you could get this panel

http://www.holisticheal.com/health-tests/nutrigenomic-testing

it would be helpful, because it would shed light on which B12 forms and how much B12 you might need. If it is not possible to get this one, you might consider the www.23andme genotyping panel, which is a saliva test and is less expensive. It includes most of the SNPs that are on the Yasko panel, plus many, many more (about a million total).

As long as I'm at it, I will mention that if you have problems with your digestive system, then a comprehensive stool analysis would also be helpful. There are several available. At directlabs.com, there are stool tests offered by Genova Diagnostics, Metametrix, and Doctor's Data labs. These do not require a doctor's order, and they can all be helpful. However, I actually prefer the Diagnos Techs Expanded G.I. Panel

http://www.diagnostechs.com/TestPanels/GIHealthPanels.aspx

because it is more comprehensive.

If you plan to proceed with the protocol recommended by Freddd, I would say that as soon as you have submitted the samples for the tests you decide to run, you could proceed to begin the protocol. I have given you a long list of lab tests. Please feel free to do as many or as few as you determine to be appropriate.

Best regards,

Rich

 

[maddietod]

Mostly Rich and also Freddd -

Thanks for all that information! I've ordered the tests that I can purchase on my own**. My chiropractor has pretty much agreed that he will order the Methylation pathways panel for me on Monday (from Health Diagnostics); I've already had them fax a requisition to the chiro. The HolisticHeal genomes panel (you meant the Comprehensive Methylation Panel, right?) is on it's way to Virginia!

The uncertainty lies with the GI panel. The website doesn't give information about cost, and it clearly has to be ordered by a doctor (only MDs? Can't tell.) I don't have obvious or terrible GI symptoms, but on the other hand I have a goodly number of food sensitivities. I had a stool test done probably 10 years ago - I think it was from Great Smokeys - that turned up nothing. But that was long ago, and a different test.

I'm attracted to getting the big picture all at once. I'm thrilled by your willingness to help me understand the results. But I don't want to overwhelm my chiropractor, who I haven't seen in 4 years. Can I get the Diagnos panel results through a combination of DirectLabs tests? I'm REALLY liking their prices.

If you want copies of my test results, I'll email or send them to you (depending on how I receive them). You too, Freddd, if you want them.

I feel like I'm moving forward again - very exciting.

** DirectLabs: Amino acids, metabolic analysis profile, urine toxic.

 

[Dreambirdie]

Hi Rich--

I can't find the Health Diagnostics Methylation PAnel on this site which you recommended: https://www.directlabs.com/default.aspx?tabid=71

Where is it? Am I totally missing it?

 

[maddietod]

Hi Rich--

I can't find the Health Diagnostics Methylation PAnel on this site which you recommended: https://www.directlabs.com/default.aspx?tabid=71

Where is it? Am I totally missing it?

This one isn't available from directlabs. I called them (phone # given, extension 0), and gave them my chiropractor's fax number, to send the paperwork to. You can't order this test yourself.

Good luck!

Madie

Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinicians letterhead.


Available from:

Health Diagnostics and Research Institute
540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879
USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Lab Director: Elizabeth Valentine, M.D.

 

[maddietod]

Freddd -

I'm about to place an order with iherb. Could you direct me to posts about dosage? I'm wondering how much of each supplement to buy, and I don't see any information about starting doses (or most common maintenance doses). I'm also wondering if my test results might change my protocol. Does everybody start out with the same supplements?

Also, since I'm switching from Rich's protocol to yours, I'll need to move to one of your threads. Does it matter where I go?

Oh - I also saw something about starting the methylb12s first, and adding adb12 later. Do I need to do that?

Madie

 

[biophile]

Folinic acid, good or bad?

Freddd and richvank have conflicting viewpoints on taking folinic acid. I recently acquired folinic acid and methyl-B12 to add to the FolaPro and hydroxy-B12 I'm already taking but haven't experimented enough yet with them to comment. IIRC on another thread anna_likes_red reported a possible benefit from adding folinic acid which she noticed after ceasing it and then resuming it? Anyway, I don't know how reliable or relevant this following small study is, but it is all I could find on PubMed regading folinic acid and CFS:

A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

http://www.ncbi.nlm.nih.gov/pubmed/16889122

 

[maddietod]

Rich, I updated my post # 308 to reflect all of the tests I've ordered. I was able to order the Holistic Heal 'Comprehensive Genomes Panel.' The only remaining testing question is how to get GI information.

Best,

Madie

 

[Freddd]

Freddd and richvank have conflicting viewpoints on taking folinic acid. I recently acquired folinic acid and methyl-B12 to add to the FolaPro and hydroxy-B12 I'm already taking but haven't experimented enough yet with them to comment. IIRC on another thread anna_likes_red reported a possible benefit from adding folinic acid which she noticed after ceasing it and then resuming it? Anyway, I don't know how reliable or relevant this following small study is, but it is all I could find on PubMed regading folinic acid and CFS:

Hi Biophile,

I can't answer that. I KNOW that folinic acid was even longer lasting than folic acid in it's ability to cause paradoxical folate deficiency for me and some others. The point is nobody knows without a trial themselves whether that is the case. At this point I can't even guess what percentage that might be. 20% or so might be the most severely affected by folic acid based on genetic research. So the folinic acid group might be some unknown part of that set.

 

[Freddd]

Freddd -

I'm about to place an order with iherb. Could you direct me to posts about dosage? I'm wondering how much of each supplement to buy, and I don't see any information about starting doses (or most common maintenance doses). I'm also wondering if my test results might change my protocol. Does everybody start out with the same supplements?

Also, since I'm switching from Rich's protocol to yours, I'll need to move to one of your threads. Does it matter where I go?

Oh - I also saw something about starting the methylb12s first, and adding adb12 later. Do I need to do that?

Madie

Hi Madie,

You can discuss it anywhere you like, especially as you are doing a comparison. I would prefer that it not be discussed on the BASICS thread to keep that short and easy to read. For the most part when specific information on doses is not available I and others are using the label instructions at first and customizing as we see effects. Before I took mb12 no amount of anything else except Vit C made a NOTICEABLE difference. After starting the mb12 almost EVERYTHING made a noticeable difference when going from "not enough" to "enough". This is one of the things gained with the "hyper" responsiveness characteristic to the mb12, a person can see the differences for themselves.

As regards adding the adb12 after the mb12, or the reverse, the only advantage to that is that you then know if you have separate responses to the two items or not, and of what magnitude.

 

[richvank]

Rich, I updated my post # 308 to reflect all of the tests I've ordered. I was able to order the Holistic Heal 'Comprehensive Genomes Panel.' The only remaining testing question is how to get GI information.

Best,

Madie

Hi, Madie.

If it is not feasible to get the Diagnos-Techs Expanded G.I. Panel, then I would suggest that you order the Metametrix G.I. Function Profile from www.directlabs.com It does not include everything that is on the Diagnos-Techs panel, but it is a DNA test and is able to identify pathogens pretty well, even those that don't grow well in culture.

Best regards,

Rich

 

[richvank]

Freddd and richvank have conflicting viewpoints on taking folinic acid. I recently acquired folinic acid and methyl-B12 to add to the FolaPro and hydroxy-B12 I'm already taking but haven't experimented enough yet with them to comment. IIRC on another thread anna_likes_red reported a possible benefit from adding folinic acid which she noticed after ceasing it and then resuming it? Anyway, I don't know how reliable or relevant this following small study is, but it is all I could find on PubMed regading folinic acid and CFS:

Hi, biophile.

I remember when this paper was published. I cited it as reference #46 in my 2007 IACFS pathogenesis paper As I recall, they used a very high dosage of folinic acid compared to the RDA level, also, though I can't locate my copy of the full paper right now. This is part of the reason I have kept folinic acid in the simplified protocol. I think it is beneficial for most PWCs. On the other hand, I believe Freddd when he describes his deleterious experience with it. I think this could be due to a particular genomic makeup that he and some others have.
Another possibility might be a particularly low level of NADPH, because NADPH is needed to convert folinic acid into 5L-methyltetrahydrofolate. My hope is that by giving both folinic acid and 5L-methyl THF, the folinic acid can be used for other purposes, such as supporting synthesis of DNA for the formation of new cells.

Best regards,

Rich

 

[biophile]

richvank wrote: Sorry for the long delay in responding. My responses are at the asterisks below:

No worries, thanks for the reply!

***Yes, I think that a worsening methylation cycle block could explain these negative responses. With regard to SAMe, a person with a normally functioning methylation cycle and sulfur metabolism in general does not respond that way to SAMe supplementation. So the negative response itself points to a problem there. I'm not sure why you experienced those particular symptoms. Normally the liver is the largest producer of SAMe in the body. If you had a partial methylation cycle block, your SAMe availability would have been low. In this situation, there was probably an upregulation of the enzymes that normally make use of SAMe (the methyltransferase enzymes). They would therefore have become much more sensitive to the SAMe level. When you then supplemented SAMe directly, it seems probable that these reactions would have surged faster than normal, and this would have affected your biochemistry in many ways, all of a sudden.

What you said makes sense. I had tried SAMe several times over the years, but I think the bad experience was the final straw after being on a slow downwards spiral for a number of years.

A few years earlier, as my health declined I started noticing my body wouldn't process drugs as it was supposed to or how it used to, beyond what would seem "normal" at low doses and even after stopping them, and despite still being in my early 20's back then (in other words I'm not saying I was a party animal who then hit 40 and started complaining about not being able to stay up all night drinking anymore). I also lost weight.

Then something which really knocked me further down was weekly IV EDTA chelation therapy for an alleged copper excess. In the beginning it didn't do much, then it started helping for a few weeks and I thought I was on the road to recovery, then later it made me significantly worse along with a bunch of strange symptoms and my digestion became sluggish and I lost more weight. The most obviously unusual blood test at the time was an abnormally low level of haptoglobin but without other blood test evidence for hemolytic anemia. Digestive supplements seemed to help a little. I also tried zinc after reading on some "quackwatch"-like website that IV EDTA can induce zinc deficiency, that seemed to improve fitness levels somewhat.

Afterwards I was still occasionally trying different supplements including SAMe without major adverse effects. Then I was on some supplement protocol after seeing a orthomolecular doctor, which reminds me, you mentioned the methylation cycle and sulfur metabolism, I don't know if this is related but I was on 250mcg molybdenum per day for several weeks before this "SAMe incident" (aftewards that I found it difficult to tolerate the molybdenum and eventually gave it up).

A few weeks earlier though, since some of my symptoms supposedly reflected a "sluggish liver" I also tried some "liver stimulant" herbs which was a mistake as well. After the SAMe incident my digestion worsened and it was difficult to tolerate food, especially fat, so I lost even more weight and became clinically and medically cachexic but since then I did eventually regain most of all the above mentioned weight back. One of the keys was focusing on consuming carbohydrates for energy, because fat was very poorly tolerated at that time, although that has improved.

However I have never really recovered from the above in terms of post-exertional sysmptoms becoming worse and not being able to tolerate medications and supplements very well. So as you can see something went wrong somewhere along the line.

It's embarrassing really. When I was first diagnosed with "CFS", supplements had no noticeable effects at all, and although I wouldn't say my ability to process toxins was entirely healthy, I could still sometimes have a few alcoholic drinks or painkillers etc without too much trouble as long as I took it easy. I remember reading stories about patients who became unbelievably sensitive to certain things where they couldn't drink any alcohol at all and even respond badly to vitamins etc, I thought "that's weird, I'm glad I'm not like that". And several years later it happened to me.

Many of these stories are dismissed as mental illness, having a "nocebo" or psychosomatic response to cognitive cues, etc. Such "unexplained" sensitives are often lumped together as "MCS", which is especially prone to these accusations. I don't know if I qualify for MCS but my above experience with ingested substances makes me more open to the reality of it. I became more sensitive to cigarette smoke and perfumes but they don't really cause me significant symptoms from casual exposure, whereas some patients seem to become incapacitated at one smell of these or even the smallest trace of detergent in their washed clothes on their skin.

However I hate and try to avoid certain fumes like those from bleach and methylated spirits and gasoline, an occasional wiff is probably OK but constant exposure like cleaning tiles in a poorly ventilated area etc seems to cause problems that go beyond post-exertional symptoms from that same level of activity. Some of these substances are very toxic, but I have no idea how much exposure a "healthy" person can endure before symptoms such as brainfog and headpain can arise without being ridiculed by skeptics.

***With respect to vitamins C and E, if you had a partial methylation cycle block which was coupled to glutathione depletion, your body was likely in a condition of fairly high oxidative stress. As you noted, vitamins C and E are antioxidants. However, in normal conditions, they are recycled by glutathione as they become oxidized, so that they can be used again. If glutathione is depleted, they tend to remain oxidized, and this will have a pro-oxidant, rather than an antioxidant effect.

I forgot to say about the vitamin E, I had a somewhat similar experience with 2 different supplements from the same brand which all used sodium sulphite as a preservative, so perhaps it could have been that instead or as well, or maybe those were coincidences and it was the vitamin E afterall, who knows. I also had issues with items such as milk thistle and MSM (headachy so-called "detox" symptoms).

***I can understand that, but it may be that your body is deficient in some of the cofactors that are needed by this part of the metabolism. I think that some of the failures of methylation treatment to help PWCs are a result of these deficiencies.

Since I posted that I have been reading more about the cofactors. Freddd also suggests that adverse effects from the protocol could be explained by co-factor deficiencies. I think what I'm going to do is just gradually add them.

***Yes, I think that the SNPs that Amy Yasko has identified as being important in autism are also important in ME/CFS. The partial methylation cycle block and glutathione depletion are common to both.

***I think the answer is yes, but it takes a lot of work, and it takes additional supplements to do this. Amy Yasko has been helping literally thousands of autism patients to do this for several years. The reason I suggested the simplified treatment approach was that many PWCs could not follow her program, for financial or cognitive reasons, or both. But for those who are able to do so, I think there can be additional benefit.

***These can help, also. My hypothesis says that the mito dysfunction in ME/CFS results initially from glutathione depletion and the partial methylation cycle block, and that over time the lack of enough glutathione allows buildup of toxins in the mitochondria, which cause additional problems. Some of the mito supplements, such as carnitine and Co Q10, require methylation for their synthesis, and I think that the partial methylation cycle block explains why they are low in ME/CFS. As Freddd has found, though, there can be benefit in mito supplements to speed the process of recovery. Adenosyl B12 is a mito supplement, as is carnitine fumarate.

***Yes. I think the 23andme panel offers a lot of promise for the future. At this point, I don't think we know enough to effectively make use of all the data it provides, but it does include about two-thirds of the SNPs that Amy has identified, and that's a start. Once you have your genotype analysis, assuming they did it right, it will be the same for the rest of your life, and research should continue to give us more insight on how to use these data, so I think it's a good investment, even though we are still having to grope about, trying to make use of it as well as we can.

Thanks. I guess at this stage it would be wise to get further testing, like the methylation panel you have mentioned elsewhere. Like others here I have to keep a check on all the spending involved, but it is not outside the realm of possibility. A full spectrum of mitochondria related supplements isn't something I've tried properly before yet.

 

[biophile]

I can't answer that. I KNOW that folinic acid was even longer lasting than folic acid in it's ability to cause paradoxical folate deficiency for me and some others. The point is nobody knows without a trial themselves whether that is the case. At this point I can't even guess what percentage that might be. 20% or so might be the most severely affected by folic acid based on genetic research. So the folinic acid group might be some unknown part of that set.

Oops I forgot to mention your experiences/observations in my post, the reason you caution against it. Your warnings do make me concerned, but after skimming a few threads I'm still uncertain how to tell the difference between "detox" and "paradoxical folate deficiency". richvank suggests doing the methylation panel but I'm not going to do that right now and I think I have enough experience with FolaPro + hydroxy-B12 to notice any differences when adding folinic acid. Also I still have the methyl-B12 drops from holisticheal.com to try and I'm planning on getting the mB12 and aB12 lozenges you recommend.

I'm also amazed that you can tolerate such a high dosage of Metafolin. On the two occasions I tried 1/2 dose of FolaPro (400mcg) I had to stop the next day and then go back to 1/4.

I remember when this paper was published. I cited it as reference #46 in my 2007 IACFS pathogenesis paper As I recall, they used a very high dosage of folinic acid compared to the RDA level, also, though I can't locate my copy of the full paper right now. This is part of the reason I have kept folinic acid in the simplified protocol. I think it is beneficial for most PWCs. On the other hand, I believe Freddd when he describes his deleterious experience with it. I think this could be due to a particular genomic makeup that he and some others have.
Another possibility might be a particularly low level of NADPH, because NADPH is needed to convert folinic acid into 5L-methyltetrahydrofolate. My hope is that by giving both folinic acid and 5L-methyl THF, the folinic acid can be used for other purposes, such as supporting synthesis of DNA for the formation of new cells.

I think you mention somewhere else that folinic acid and methyltetrahydrofolate compete in the intestine? I will try taking them at different times.

 

[Valentijn]

freddd and richvank:

Would it be feasible for each of you to add your treatment protocols to the wiki section, with simple and full explanations, and relevant related info? Then the protocols could have their own semi-static pages instead of (or in addition to) getting buried in questions and comments here.