Simplified Methylation Protocol Revised as of Today

[richvank]

Hi,all.

As of today, I am suggesting a revised form of the Simplified Treatment Approach
for lifting the partial methylation cycle block in ME/CFS. The revised form is
shown below.

The changes involve using liquid supplements where possible, and a capsule
rather than a tablet, so that dosages can be divided more easily. Hopefully
this will be more convenient than having to split tablets.

I've eliminated folic acid from the protocol in favor of the active, reduced
forms of folate, exclusively, since folic acid is not readily utilized by some
patients, and it competes with the active forms for absorption.

I've also provided for use of lecithin in place of phosphatidylserine complex,
because the latter can decrease cortisol in patients whose
cortisol is already too low.

Because the revised protocol has substantially the same content as the protocol used in the clinical study conducted by Neil Nathan, M.D. and myself, the results of that study should apply to the revised protocol as well.

I would appreciate any feedback on how this works out for those of you who
decide to try it.

Best regards,

Rich


March 30. 2011


SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROME

 

[LaurieL]

I've eliminated folic acid from the protocol in favor of the active, reduced
forms of folate, exclusively, since folic acid is not readily utilized by some
patients, and it competes with the active forms for absorption.

Active forms being the folinic acid and the methylfolate (metafolin)? I have responded really well to the metafolin, and not at all well to the folic acid. I have been interested in yours and Freddd's debate and observations concerning folinic acid. Do these active forms also compete? Is there a possibility that one is deficient and the other form is not? If this could happen, could you explain this. I ask because I am trying to learn about the nucleotides, and I believe its the folinic acid that has a place in the RNA/DNA?

I've also provided for use of lecithin in place of phosphatidylserine complex,
because the latter can decrease cortisol in patients whose
cortisol is already too low.

There are many that have intolerance to soy in which most lecithin on the market is derived. Most soy in the US is now GMO as well. There is an egg yolk lecithin that I take now and again, but then again, many have an intolerance to eggs. But I am thinking the intolerance may stem from the protein in the egg whites for some.

Nature's Made Egg Yolk Lecithin.

Laurie

 

[richvank]

Active forms being the folinic acid and the methylfolate (metafolin)? I have responded really well to the metafolin, and not at all well to the folic acid. I have been interested in yours and Freddd's debate and observations concerning folinic acid. Do these active forms also compete? Is there a possibility that one is deficient and the other form is not? If this could happen, could you explain this. I ask because I am trying to learn about the nucleotides, and I believe its the folinic acid that has a place in the RNA/DNA?

There are many that have intolerance to soy in which most lecithin on the market is derived. Most soy in the US is now GMO as well. There is an egg yolk lecithin that I take now and again, but then again, many have an intolerance to eggs. But I am thinking the intolerance may stem from the protein in the egg whites for some.

Nature's Made Egg Yolk Lecithin.

Laurie

Hi, Laurie.

Yes, folinic acid and methylfolate are the active coenzyme forms that are available as supplements. Yes, these active forms do compete for absorption from the gut and for transport into cells. Yes, it is possible for either or both to be deficient. Normally, folinic acid can be converted in the body to methylfolate. A sequence of three reactions are necessary to do this. Some people have one or more SNPs in the enzymes that catalyze these reactions, and that can slow them down. In that case, the person may not be able to use folinic acid to make methylfolate readily. NADPH is also necessary for this conversion, and if it is in short supply, that could make the conversion slow, also.

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 of folate that are used in the production of DNA and RNA. I think this is important early in treatment, especially, when the methionine synthase reaction is still significantly blocked.

I understand that lecithin is available from several food sources now. Hopefully people will be able to find one to which they are not allergic.

Best regards,

Rich

 

[fds66]

Thanks Rich. Are you going to post up the new protocol? I can't see it posted on this thread. Is it somewhere else on the board? Of course I may be missing the obvious in which case I apologise.

fds

 

[Jimk]

Thanks Rich. Could you post the link to the revised protocol. I can't seem to find it anywhere.
Also, I've seen Solgar's "Folate, 800 mcg (as Metafolin)" in tablet form, much cheaper than the Folapro. I'm a bit confused as to equivalence. If this has already been posted, please direct me to the thread, thanks.

 

[ukme]

Thank you Rich you are a star! We have been assiduously following your protocol; please could you post a link to the new one, many thanks.

 

[richvank]

SIMPLIFIED TREATMENT APPROACH
FOR LIFTING THE METHYLATION CYCLE BLOCK
IN CHRONIC FATIGUE SYNDROM (March 30, 2011 Revision)
Rich Van Konynenburg. Ph.D.
(Based on the full treatment program
developed by Amy Yasko, Ph.D., N.D.
which is used primarily in treating autism [1])

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.
The fourth supplement comes in capsules that contain 800 mcg. It will be necessary to open the capsules, dump the powder onto a flat surface, and separate it into quarters using a knife to obtain the daily dose. The powder can be taken orally with water, with or without food.
These supplements can make some patients sleepy, so in those cases they take them at bedtime. In general, they can be taken at any time of day, with or without food.
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. Lecithin is also available from http://www.holisticheal.com.
GO SLOWLY. As the methylation cycle block is lifted, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.

[1] Yasko, Amy, Autism, Pathways to Recovery, Neurological Research Institute, 2009, available from http://www.holisticheal.com or Amazon.
[2] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
[3] Hydroxy B12 Mega Drops is a liquid form of hydroxocobalamin (B12), supplied by Holistic Health Consultants. 2 drops is a dosage of 2,000 mcg.
[4] MethylMate B is a liquid form of (6s)-methyltetrahydrofolate supplied by Holistic Health Consultants, based on Extrafolate S, a trademark of Gnosis S.P.A. 3 drops is a dosage of 210 mcg.
[5] Folinic acid is 5-formyltetrahydrofolate. one-quarter capsule is a dosage of 200 mcg.
[5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center. 1 softgel is a dosage of 500 mg.
[7] Lecithin is a combination of phospholipids without phosphatidylserine. One softgel is a dosage of 1,200 mg.

 

[fds66]

Thank you Rich

fds

 

[Jenny]

Thanks very much Rich.

Just one question - is there any alternative to getting these products from Holistic Health? When I bought things from them a few years ago the shipping costs to the UK were horrendous - around 25 pounds for two tubs of multivits. (And the supplements themselves are expensive compared to similar ones from other manufacturers.)Perhaps these costs are different now though.

Jenny

 

[drex13]

Hi Rich,

I have a couple of questions. Maybe this has been addressed or answered on one of the other b-12 related threads, but I'll ask anyway. Is there a specific reason you recommend the hydroxy b-12 in your simplified protocol vs. methyl b-12 or methyl/ad b-12 as used in Freddds protocol ? Also the Neurological Health formula contains 100 mcg of folic acid. Should we be looking for another multi that doesn't have folic acid in it (so far I think I have found one) or is the low amount of 100 mcg negligible ? I'm sure I'll have other questions but those are the only two I can think of at the moment. Thanks, Rich.

 

[anne_likes_red]

Jenny, I paid nothing like that to NZ (last month). Perhaps they've reduced their handling costs?
Some of the products are only available at HH.

Anne.

PS I'm using the hydroxy drops and I like them.

 

[leela]

Great Timing

Thank you, Rich, this is extremely useful as well as timely, as I have just
emptied my wallet doing the methylation panel.

Also, to those concerned, there is now lecithin available derived from sunflower seeds.

 

[Freddd]

Thanks Rich. Could you post the link to the revised protocol. I can't seem to find it anywhere.
Also, I've seen Solgar's "Folate, 800 mcg (as Metafolin)" in tablet form, much cheaper than the Folapro. I'm a bit confused as to equivalence. If this has already been posted, please direct me to the thread, thanks.

Hi Jimk,

Yes, the Solgar Metafolin is much less expensive, especially in the 800mcg dose size. Metafolin is Metafolin is Metafolin. It is all produced by Merck and they hold the licensees to very high standards. The Solgar product is high quality and highly effective. So be careful, generic methylfolate is not the same and I can't speak for it's effectiveness. Merck's patent was for a process that produces a stable form of methylfolate called Metafolin.

 

[Freddd]

Hi Rich,

I have a couple of questions. Maybe this has been addressed or answered on one of the other b-12 related threads, but I'll ask anyway. Is there a specific reason you recommend the hydroxy b-12 in your simplified protocol vs. methyl b-12 or methyl/ad b-12 as used in Freddds protocol ? Also the Neurological Health formula contains 100 mcg of folic acid. Should we be looking for another multi that doesn't have folic acid in it (so far I think I have found one) or is the low amount of 100 mcg negligible ? I'm sure I'll have other questions but those are the only two I can think of at the moment. Thanks, Rich.

Hi Drex,

I'll make a stab at an answer too. Mb12/adb12 can correct several hundred symptoms whereas hydroxcbl might correct about 1/3 of those for about 2/3 of people. Mb12/adb12 is somewhere between 100 to 10,000 times more effective, dependent upon person and brand of b12 and how taken. I am eliminating folic acid 100%. In one day I am noticing the difference but more time is needed to make sure of the differences and how extensive they might be. I'm not sure 100mcg has no effect. However, if taken with plenty of Metafolin with the right timing it might not matter. For me at least, folinic acid was worse than folic acid, it more successfully blocked more Metafolin for 24 hours per day per dose.

 

[drex13]

Thanks Freddd.

 

[richvank]

Thanks very much Rich.

Just one question - is there any alternative to getting these products from Holistic Health? When I bought things from them a few years ago the shipping costs to the UK were horrendous - around 25 pounds for two tubs of multivits. (And the supplements themselves are expensive compared to similar ones from other manufacturers.)Perhaps these costs are different now though.

Jenny

Hi, Jenny.

I think MandiMart sells some of them, or supplements that are more or less equivalent, in the UK. I've tried to spell out the content of all but the multi, which has a large number of constituents, so people can make substitutions if necessary. I realize that cost is a factor. I chose to specify holistichealth for "one-stop shopping," and also because the multi is available only there, and the liquid form of methylfolate, likewise, as far as I know.

Best regards,

Rich

 

[leela]

Rich and Fredd,

I am still quite confused by the methyl/hydroxy/adenosyl conundrum.
How does one determine which to take?
I injected methylcobalamin subQ with no effect (good or bad) for some time, but I think I am still dumping mercury right now--
in which case does it seem prudent to stay away from it?
I also wonder if one choses folic vs folinic etc based on the results of the methylation panel? I am especially brain dead lately
and having trouble making heads and tails of it all.
Thanks for any pointers from anyone who wants to pipe in. Disclaimers already understood and implicit

 

[richvank]

Hi Rich,

I have a couple of questions. Maybe this has been addressed or answered on one of the other b-12 related threads, but I'll ask anyway. Is there a specific reason you recommend the hydroxy b-12 in your simplified protocol vs. methyl b-12 or methyl/ad b-12 as used in Freddds protocol ? Also the Neurological Health formula contains 100 mcg of folic acid. Should we be looking for another multi that doesn't have folic acid in it (so far I think I have found one) or is the low amount of 100 mcg negligible ? I'm sure I'll have other questions but those are the only two I can think of at the moment. Thanks, Rich.

Hi, drex13.

I think that it depends on a person's genetic makeup whether hydroxocobalamin or methylcobalamin will be more helpful. In the full Yasko treatment, on which this simplified treatment is based, certain genetic polymorphisms (SNPs) are characterized, and the form of B12 used is based on the results. In this simplified approach, no knowledge of SNPs is assumed. Using hydroxocobalamin allows the cells to convert as much to methylcobalamin and adenosylcobalamin as they need, assuming that the intracellular B12 processing metabolism is operating normally. This avoids overdriving the methylation cycle, and it also decreases the possibility of methylating inorganic mercury that may be in the body, and making it therefore easier to move into the brain. Neither of these has been proven to be a problem, but neither has been well-studied. There is a theoretical basis for these concerns in the biochemistry, and I prefer to be cautious in the absence of more complete information. It's possible that I am being overcautious, but I really do not want to cause people more problems than they already have.

Another reason for continuing to recommend hydroxocobalamin is that the clinical study that Dr. Nathan and I conducted used this form. I wish there was funding available to do comparative clinical testing of various versions of the methylation treatment, but so far that hasn't happened, and I think there is value in staying with a treatment that has some support from clinical testing that is supported by laboratory measurements, as our study was.

Yes, the Neurological Health formula does contain some folic acid. My preference would be to eliminate folic acid, but this multi contains several other constituents that are directed toward supporting the methylation cycle and related pathways, which other multis do not have. Based on our clinical study, the active forms of folate were apparently absorbed well enough when the total folic acid was higher than in this revised protocol, so I think this version should supply active folate at least as well, and probably better.

This revised protocol is again a compromise, as was its predecessor. I can't say that it's optimum. I know that Freddd has different views, and his ideas do seem to have merit for his case and the cases of some others. Note that his approach is likely to be effective in a wider range of cases, including those with absolute, as opposed to functional, B12 deficiency, than only the case of a person with ME/CFS who has normal intracellular B12 processing metabolism, and a functional B12 deficiency, which is the focus of my treatment selection effort. Freddd's treatment approach bypasses essentially all of the body's B12 absorption, transport and processing pathways. In this way, he is able to get the active, coenzyme forms of B12 directly into the cells, and that is clearly what is needed in Freddd's case and in some other cases in which parts of these pathways are dysfunctional for genetic reasons. My philosophy is to bypass only the parts that must be bypassed in a functional B12 deficiency, in order to preserve as much of the cell's normal control mechanisms as possible.

Best regards,

Rich

 

[richvank]

Jenny, I paid nothing like that to NZ (last month). Perhaps they've reduced their handling costs?
Some of the products are only available at HH.

Anne.

PS I'm using the hydroxy drops and I like them.

Hi, Anne.

Thanks for this information.

Rich

 

[richvank]

Thanks Rich. Could you post the link to the revised protocol. I can't seem to find it anywhere.
Also, I've seen Solgar's "Folate, 800 mcg (as Metafolin)" in tablet form, much cheaper than the Folapro. I'm a bit confused as to equivalence. If this has already been posted, please direct me to the thread, thanks.

Hi, JimK.

I've now gotten the protocol posted on this thread. Metafolin, FolaPro, and Deplin are all the same substance. Dr. Amy Yasko's new MethylMate B, which is in the revised protocol, is a liquid form of the same substance, which is the biologically active form of methylfolate. I have switched to the liquid form in the revised protocol because many people with ME/CFS find that they are not able to tolerate very much of it at first, and using the liquid form is more convenient than having to split or crush tablets, which can be difficult especially for people who are very ill.

Best regards,

Rich