Simplified Methylation Protocol Revised as of Today

[richvank]

Hi Rich,

I have been on the SMP for three months now, and while I have retained the sleep gains, can't say I feel other significant improvement.
Having done the panel at the outset, it's a bit pricey to retest now. What kinds of adjustments would one consider to the protocol wwithout firther testing?
I would also like to know what the appropriate ratio is in your experience/opinion, between mB12 and the Methylfolate. I increased each by one drop a few weeks ago.
At the beginning of (overly lengthy) post #362 of this thread I included the modified version I am currently taking.

Thanks for your input, if you have a moment

~leela

Hi, leela.

Sorry I didn't respond to your earlier post.

You mentioned in it that your house is moldy and you can smell the mold. I'm concerned about this. I don't know whether the molds are toxic types or not, or whether you are among the 24% of the population who are susceptible to mold toxicity. Some of your symptoms sound as though they could be due to mold illness. Slayadragon (Lisa) and others have reported that they did not respond favorably to the methylation treatment until they were free of mold exposure. So I would encourage you to look into this. I realize that testing always costs money, but I think that this might be an important thing in your case. There is a test for homes that was developed by the U.S. EPA called the ERMI test. This is a DNA test that identifies molds from a filter that one connects to a vacuum cleaner and uses to vacuum a specified amount of floor area in the bedroom and living room. It is available from www.mycometrics.com This test can tell you what kinds of molds are present in your house. You can also run an inexpensive eye chart type test called a visual contrast sensitivity test that will tell you whether it is likely that you have neurotoxins, including biotoxins from mold, in your brain. You can do this on your computer. It's available from Dr. Ritchie Shoemaker's site, www.chronicneurotoxins.com. I realize that it is a major thing to move out of a house, but some PWMEs have found this to be necessary. I recommend doing some testing first, to see if this is an issue in your case.

With regard to your question about the best ratio of methyl B12 and methylfolate, I usually suggest a dose of methylfolate that is comparable to the RDA for folate, which is 400 micrograms per day, or perhaps no more than twice that amount. The methylB12 may need to be up as high as several milligrams per day, but I think it's best to increase it gradually to see how well it is tolerated.

You mentioned that you are a vegetarian. In view of that, I wonder if you might be low in one or more of the essential minerals or in amino acids. It can be difficult to get enough of all of these on a vegetarian diet. You are taking B12, of course, and that is also not found in a purely vegetarian diet. Without testing, it isn't possible to say for sure whether there are deficiencies in these nutrients, so it becomes sort of hit or miss. I hope this is helpful.

Best regards,

Rich

 

[leela]

Thanks so much, Rich. You reply is, as always, very useful and much appreciated.

My growing instinct to get out of the moldy house is confirmed by your concern.
When my lease runs out in a couple months I hope to be well enough to move to a drier climate.
I was listening to Deitrich Klinghardt today in an interview wherein he strongly stressed, several times, that
he asks patients to FIRST deal with mold and EMF exposure before attempting any other protocol, or it won't work.
<sigh>
I feel like I've been doing everything backwards, and blindfolded, trying to understand this illness!

Thanks again for your input; it is so great to have your expertise so close at hand

 

[Lou]

Thanks very much, Rich, I'll get that test ordered, see about trying methylation treatment once again.

 

[maddietod]

It's illegal to sell a house that has mold. I would imagine that it's also illegal to lease a moldy apartment. If you have the energy for a few phone calls, you might find that your landlord has to test and fix the problem. You'd need to be able to leave the apartment when they kill the mold, and possibly again when they clean the air.

Madie

 

[Valentijn]

It's illegal to sell a house that has mold. I would imagine that it's also illegal to lease a moldy apartment. If you have the energy for a few phone calls, you might find that your landlord has to test and fix the problem.

This probably varies quite a bit from one state to another.

 

[Waverunner]

Hi Rich,

do you think that the "23 and me" SNPs are relevant to your methylation protocol? I will get my results in a few weeks and I remember for example that you talked about MTHFS and that in cases where this gene is defect the conversion from folic acid to its active form is problematic. I know that you have lots of things to do but since testing for SNPs has become so cheap we maybe should make a thread/sticky for genes/SNPs and their relevance for the methylation protocol? I mean we have lots of time to do so but I guess it would be important since many people react differently to the protocol.

 

[richvank]

Hi Rich,

do you think that the "23 and me" SNPs are relevant to your methylation protocol? I will get my results in a few weeks and I remember for example that you talked about MTHFS and that in cases where this gene is defect the conversion from folic acid to its active form is problematic. I know that you have lots of things to do but since testing for SNPs has become so cheap we maybe should make a thread/sticky for genes/SNPs and their relevance for the methylation protocol? I mean we have lots of time to do so but I guess it would be important since many people react differently to the protocol.

Hi, waverunner.

I think this has a lot of potential. At present, I don't think there is enough information known about what all the various SNPs do, so it isn't possible to make very much use of most of the data yet. There has been a 23andme thread on these forums, and some people have translated their results into the format of the results from Amy Yasko's nutrigenomic panel (from holisticheal.com), which is a little tricky, because she uses the opposite DNA strand. Most, but not all, of her SNPs are on the 23andme panel, so it is possible to use some of her interpretive information (such as from her books "Autism, Pathways to Recovery" and "Genetic Bypass").

A lot of what Amy has written about these SNPs is inferred from her study of data from a large number of autistic children, who also have a partial block in their methylation cycle. She has correlated the presence of various SNPs with biochemical lab data, symptoms and treatment response to various supplements. She is probably correct about most of this, but there is no published supporting research literature for much of it. I would feel more comfortable if there were, but this kind of research is expensive because a large number of cases must be included to get statistically significant results. I hope that more of this will be done in the future, but it is not easy to find a source of funding for it. Where particular SNPs might be relevant to diseases that have a lot of political interest, or where drug companies might see some value in characterizing them, there are opportunities to get funding. Autism has more support than ME/CFS, so we can ride on its shirt tails to some degree. But I think it is likely to be a long time before there will be enough knowledge of the effects of many of the SNPs that are characterized on the 23andme panel to make effective use of the data.

I think that it would be possible to focus on SNPs in certain enzymes and other proteins based on what I think the core mechanism is in the pathogenesis and pathophysiology, but so far the larger ME/CFS community has not bought into my model to a very large degree. I would like to see more work done on the SNPs in enzymes that I think are involved in the initial onset of ME/CFS. For example, those in the glutathione system, the wider antioxidant system, the detox system, the immune system, and the B12 metabolism. I think this would help to explain why some people get ME/CFS, while the large majority of the population do not. If we knew that, I think we could better focus on supplements for prevention.

Anyway, I do think you are on the right track here. We might be able to make up for lack of funding by thinking a little harder so that we can better focus the work. A lot of the genetic stuff seems to be done as a "fishing expedition," without a very well thought out hypothesis. I think the process can be more efficient if it is hypothesis-driven, using a "systems approach" to develop hypotheses, i.e. pulling together all the types of information we can find into a coherent story.

Best regards,

Rich

 

[Waverunner]

Hi Rich,

I like this "systems approach" and I'm excited about the 23andme results. Hopefully we get it all working.

Best Wishes

Waverunner

 

[Sasha]

Last Sunday I came off Freddd's protocol altogether because I was getting symptoms of induced potassium and/or magnesium deficiency (profound exhaustion and sore muscles).

Yesterday evening, and for most of today, I've felt a bit short of breath and have had occasional nausea. Nausea and difficulty breathing are symptoms of too much magnesium and/or too much potassium (according to the symptom lists I've seen).

I haven't taken any potassium for a week. I've had an Epsom salts bath (500g) on Monday night and Thursday night and 180mg of magnesium as an oil spray each of yesterday and today.

I came down with a new viral infection on Sunday but the symptoms didn't include breathlessness or nausea until yesterday.

Are my problems likely to be due to any kind of rebound from stopping the protocol suddenly? Or is it likely that I've overloaded myself with magnesium?

I've discovered that the facial twitching that has been developing over the past few days on top of all this stuff is a sign of magnesium deficiency. I think a question I should have asked is, if one stops the relatively high-dose b12 protocol (i.e. Freddd's), does it immediately stop the ramping up the body's healing process that in turn drives the need for more potassium/magnesium? I'm wondering if I should have carried on with Mg and K for a while after stopping the b12.

 

[richvank]

I've discovered that the facial twitching that has been developing over the past few days on top of all this stuff is a sign of magnesium deficiency. I think a question I should have asked is, if one stops the relatively high-dose b12 protocol (i.e. Freddd's), does it immediately stop the ramping up the body's healing process that in turn drives the need for more potassium/magnesium? I'm wondering if I should have carried on with Mg and K for a while after stopping the b12.

Hi, Sasha.

It's true that magnesium deficiency can cause muscle twitching.

I don't have experience with Freddd's protocol, so can't say whether continuing these minerals is a good idea or not.
I suspect that the higher dosages used in Freddd's protocol cause changes to occur more rapidly, and this can cause
things to become out of balance more readily.

For what it's worth, food sources rich in potassium include the fruits and above-ground vegetables.
Magnesium is high in seeds, nuts, whole grains and green leafy vegetables.

Best regards,

Rich

 

[Sasha]

Hi, Sasha.

It's true that magnesium deficiency can cause muscle twitching.

I don't have experience with Freddd's protocol, so can't say whether continuing these minerals is a good idea or not.
I suspect that the higher dosages used in Freddd's protocol cause changes to occur more rapidly, and this can cause
things to become out of balance more readily.

For what it's worth, food sources rich in potassium include the fruits and above-ground vegetables.
Magnesium is high in seeds, nuts, whole grains and green leafy vegetables.

Best regards,

Rich

Thanks, rich - I went to the shops earlier and loaded up on pumpkin seeds (150mg Mg/oz), Brazil nuts (107mg Mg/oz) and dark chocolate (a mere 60mg Mg/oz but I think I have earned it!). I think I need to get stuck into potassium-rich foods as well and build up my levels.

 

[SJB944]

Hi Rich,

Can you please tell me what the difference is between TMG and Betaine HCI? I take the latter at 648mg twice a day, with meals, for digestion support. If I already take Betain HCI, have I cover TMG?

Appreciate your thoughts.
SJB

 

[richvank]

Hi Rich,

Can you please tell me what the difference is between TMG and Betaine HCI? I take the latter at 648mg twice a day, with meals, for digestion support. If I already take Betain HCI, have I cover TMG?

Appreciate your thoughts.
SJB

Hi, SJB.

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

Best regards,

Rich

 

[SJB944]

Thanks Rich,

Cheers
SJB

 

[Zuriel]

When to commence the Methylation Protocol?

Rich,

Should one start the protocol right away or after some lab tests? If so, what are the tests and can they be ordered online as I'm not from the US?

Thanks.

 

[richvank]

Rich,

Should one start the protocol right away or after some lab tests? If so, what are the tests and can they be ordered online as I'm not from the US?

Thanks.

Hi, Zuriel.

I favor doing some testing first to see what the important issues are in a particular case. Some people just go ahead and try the protocol without testing because of the expense and other factors, which I understand, but it is better to find out what you are dealing with first.

The most important test, in my opinion, is the methylation pathways panel, which is offered by the European Laboratory for Nutrients in the Netherlands and by the Health Diagnostics and Research Institute in the U.S. This test requires an order from a physician or a chiropractor. You can find information on ordering it from the U.S. and interpreting it in my documents, which are in the Wiki section of this forum (under General Wiki). I know that some people in Australia have also ordered it from the lab in the Netherlands. Shipping of samples is done via FedEx, using a pack of ordinary ice. The lab likes to get the blood samples within 48 hours, but if it is a little longer, it still seems to be O.K., because they use special preservatives in the sample vials.

I have read your posts to this forum, and based on them I would say that you also need a comprehensive stool test to find out what all the issues are with your digestive system. I know that Metametrix serves Australia, and they offer a G.I. Function test. There are other good ones available, too. I especially like the Diagnos Techs Expanded G.I. Panel available in the U.S., and it requires a doctor's order, but is very comprehensive. Dr. Kenny de Meirleir in Belgium probably does the most complete workup on the digestive system in ME/CFS patients. Among other tests, he uses one developed by Dr. Butt in Australia, which is especially designed to measure the anaerobic bacteria. Dr. de Meirleir consults with Dr. Lewis in Melbourne, whom I understand you have seen, but from your posts, it sounds as though he is swamped with patients.

Beyond these, you might consider the ION panel, also offered by Metametrix. This is a combination of tests that will indicate what is going on in your metabolism and what nutritional deficiencies you have.

These tests cost money and take time, but they will give you basic information needed to guide your treatment most effectively. I read in your posts that you have found a naturopath. Usually naturopaths are compatible with the types of testing and treatment that I find most helpful, so perhaps this naturopath would help you with the testing I have described.

You could try the protocol without testing, and you may be lucky and have success with it, but I think your chances would be better if you tested first to see what your issues are. It's particularly important to get your digestive system working fairly well for this protocol, because it is necessary to absorb nutrients needed by the cells, and also to take out toxins, which will be mobilized by this protocol. The digestive system and the methylation-related issues are very interactive, and I think the best chance for success is to deal with them together.

I hope this is helpful.

Best regards,

Rich

 

[Zuriel]

Hi Rich,

Thank you very much for the insightful information you provided. They are extremely helpful and very concise. I often feel very lost and overwhelmed by so many theories and information on this often
maligned and misunderstood condition. Appreciate folks like you and many others who offer fellow sufferers a helping hand.

On the list of tests offered by European Laboratory for Nutrients in the Netherlands, I could not find the Methylation Pathways Panel test. Is this classified under Tests for (functional) nutrient status/
metabolism?

Have found the website for Metametrix Australia- www.diagnosticinsight.com.au. Shall be requesting my GP to order the tests you suggested.

Thanks again.

Warmest regards,
Zuriel

 

[richvank]

Hi, Zuriel.

You might have to write in "methylation pathways panel" on the ELN order form. I think their newer forms include it specifically, but the older ones don't.

Best regards,

Rich

 

[Valentijn]

On the list of tests offered by European Laboratory for Nutrients in the Netherlands, I could not find the Methylation Pathways Panel test. Is this classified under Tests for (functional) nutrient status/metabolism?

If you go to http://www.europeanlaboratory.nl/ and set the language (on the right side) to Nederlands, you can get to the page by selecting "Labtesten", then "Overige testen en specifieke testen" then "Foliumzuur metabolieten (Methylation)". That page then describes very briefly what methylation is, and the disorders where a methylation test is useful.

On the "meer informatie" pdf file it explains a bit more in depth and lists the relevant things tested, roughly translated:
"The ELN offers two packages:
- Folic acid/Folate metabolism: Folic acid (plasma + RBC), folinic acid (plasma),
Tetrahlateydrofolate (THF, plasma), 5-methyl-tetrahydrofolate (5-methyl-THF,
plasma), 5-formyl-Tetrahydrofolate (5-formyl-THF, plasma), 10-formyltetrahydrofolate
(10-formyl-THF, plasma).
- Methylation panel: Folic Acid Metabolism Panel + Methyl-cobalamine (methyl-vitamin B12,
plasma), S-adenesylmethionine (SAM) (RBC), S-Adenesylhomocysteine (SAH, RBC).
"

"Foliumzuur" seems to be used interchangeably between folic acid and folate, so I'm not sure which is getting tested in each item.

On http://www.europeanlaboratory.nl/documents/us_prijslijst_en.pdf it has the Folic Acid panel listed at $300.00, but doesn't list the other items or a general methylation panel.

But the dutch pricelist does: http://www.europeanlaboratory.nl/documents/nl/pricelist_nl.pdf . 400 euros for the methylation test, which includes the folic acid stuff too. That might be about $600 for the equivalent in the US.

 

[Valentijn]

You might have to write in "methylation pathways panel" on the ELN order form. I think their newer forms include it specifically, but the older ones don't.

They have a box on the english form to check in the "panels" on the top row, far right Folic-acid metabolites (Methylation; 2P; !). And the 2nd page of the order form lists everything included in that panel. Yay!

Wish their website was a little more user friendly! Which reminds me: the order form is at http://www.europeanlaboratory.nl/documents/en/orderform_en.pdf . There's a link on the main page to an order form that is badly broken.

I've been spending a lot of time on their site lately ... may be going for some of those tests soon. Will try to talk a Dutch doctor into ordering them so they get covered by insurance