adreno
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I believe that should be 7.5mg and 15mg, with only the 15mg dose being effective.
Simplified Methylation Protocol Revised as of Today
- Thread starter richvank
- Start date
I believe that should be 7.5mg and 15mg, with only the 15mg dose being effective.
Freddd
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You are right. 7.5 and 15 with the 30mg dose being 2x15. OOPS.
I'm new here and from the Netherlands. I'm trying to learn al that stuff and it is very interesting. And a little bid scary. I don't know where to start. I have a cabinet full of supplements I can't tolerate so I ordered a genetic test by 23andme. As far as I figured out this are the genes and snp involved in the methylation and it seems best to address first the CBS mutations with molybdenum and magnesium.
CBS A360A +/-
CBS C699T +/-
COMT H62H -/+
COMT V158M +/-
MAO A R297R +/+
MTHFR C677T -/+
MTHFR A1298C -/+
MTRR A66G -/+
MTRR-11 A664A +/+
VDR BSM/TAG +/-
BHMT-04 N/A +/+
Do I need more testing before I start?
Btw I’m also positive on HPU
CBS A360A +/-
CBS C699T +/-
COMT H62H -/+
COMT V158M +/-
MAO A R297R +/+
MTHFR C677T -/+
MTHFR A1298C -/+
MTRR A66G -/+
MTRR-11 A664A +/+
VDR BSM/TAG +/-
BHMT-04 N/A +/+
Do I need more testing before I start?
Btw I’m also positive on HPU
You should definitely invest in the Methylation Pathways Panel via ELN (which is a lab in the Netherlands!). This will show your methylation capacity via the SAM:SAH ratio, your glutathione status via the GSH:GSSG ratio. It will show your folate cycle, if you have methylfolate deficiency, if you have oxidative stress via the red cell folate levels.
You can only rely so much on genetic testing, because there are recommendations on how to address these particular genes but what about the other several hundreds of enzymes that are involved at each step within the methylation and associated cycles!!
This test is highly recommended for people with CFS or any neurological or psychiatric or even things like liver problems, autoimmune diseases etc etc.
I have been doing some research on the area of methylation and function and how the body performs it's various conversions of folate, B12 etc etc.
Below, I have posted some summary forms of research from three notable researchers/physicians: Dr. Neubrander, Prof. James and Prof. Deth.
I have raised a question for Rich and Freddd regarding their protocols but I look forward to everyone's response if they have any thoughts/technical data that can help the community in understanding the "why" and "how" of the protocols for recovery.
- Rich:
If a person doesn't have a pathology defined B12 deficiency, why not just supplement with methylfolate to get the conversion to mb12? What is the purpose of adding in hydroxyB12 if no B12 deficiency exists (no deficiency defined as the liver having sufficient stores of hydroxy/adenosyl forms, which are the two forms it can store well)?
- Freddd:
1) What is the purpose of adding in methylfolate when high doses of methylB12 are being recommended? Afterall, it's the methylfolate that is the end product of the combination of methylfolate and hydroxyB12. The only time I can see methylfolate being required is if it is deficient on the methylation panel, in which case, other enzymes [such as PAH, which converts phenylalanine to tyrosine] may require it too.
2) If the purpose of adenosylB12 is to saturate the mitochondria in the CNS and increase ATP production, wouldn't this be a bad thing in the presence of GSH depletion? If most of the oxidative damage stems from the electron transport chain, doesn't it seem like a bad idea to boost ATP production without first attending to the methylation cycle blockage and it's associated GSH depletion in order to provide the CNS with a REDOX positive state so that an increase in ATP generation doesn't cause further odixative damage?
Some research summaries:
- Dr. Neubrander, Autism specialist, has an amazing 94% responder rate with his autism patients. His protocol consists of no methylfolate, no hydroxy or adenosyl B12's...just methylB12 at a specific dosage, given at a specific injection site which then gives a "slow release" over 3 days from the one shot. He says the slow release allows the mB12 receptors to reach AND maintain saturation for this extended period.
- Prof. Jill James, Autism researcher, states that in her extensive testing, non-mB12 forms could balance CH3 cycle markers but it is ONLY methylB12 that consistently balances GSH:GSSG in addition to the CH3 markers . Her clinical research has shown that children who's CH3 chemistry balanced out but GSH wasn't optimal and only methylB12 was able to bring GSH:GSSG ratio to optimal levels, as compared to the control group.
If I remember correctly, it was also Jill James' research that showed the addition of cyano/hydroxyB12's was NOT able to prevent a disruption to CH3 cycle in the presence of thimerosal (the mercury containing preservative in vaccinations). When methylB12 was added in, there was NO disruption to CH3 biochemistry in the presence of thimerosal. This suggests that methylB12 can potentially be used as a preventative measure against autism!...kind of like a "vaccine against a vaccine"!
- Prof. Richard Deth, methylation biochemistry researcher, demonstrates that non-CNS methionine synthase (MTR) is very different to CNS MTR, whereby the CNS is lacking the SAM domain. This observation is of importance to CFS because there are issues with low GSH (which is used in order to prevent the cobalt ion from oxidizing during its "transit" from cyano/hydroxy to methyl) and low SAM.
When methylB12 is oxidized (as often the case in CFS), the body can "save" the B12 by donating a methyl group from SAM. The CNS doesn't have this SAM domain and thereby can't save the oxidized B12. This is where the research demonstrates that supplementing straight with methylB12 removes the pressure off this enzyme as there is no "wait time" for the transfer of methyl from methylfolate to B12 (which is usually the period where the cobalt ion oxidizes).
Below, I have posted some summary forms of research from three notable researchers/physicians: Dr. Neubrander, Prof. James and Prof. Deth.
I have raised a question for Rich and Freddd regarding their protocols but I look forward to everyone's response if they have any thoughts/technical data that can help the community in understanding the "why" and "how" of the protocols for recovery.
- Rich:
If a person doesn't have a pathology defined B12 deficiency, why not just supplement with methylfolate to get the conversion to mb12? What is the purpose of adding in hydroxyB12 if no B12 deficiency exists (no deficiency defined as the liver having sufficient stores of hydroxy/adenosyl forms, which are the two forms it can store well)?
- Freddd:
1) What is the purpose of adding in methylfolate when high doses of methylB12 are being recommended? Afterall, it's the methylfolate that is the end product of the combination of methylfolate and hydroxyB12. The only time I can see methylfolate being required is if it is deficient on the methylation panel, in which case, other enzymes [such as PAH, which converts phenylalanine to tyrosine] may require it too.
2) If the purpose of adenosylB12 is to saturate the mitochondria in the CNS and increase ATP production, wouldn't this be a bad thing in the presence of GSH depletion? If most of the oxidative damage stems from the electron transport chain, doesn't it seem like a bad idea to boost ATP production without first attending to the methylation cycle blockage and it's associated GSH depletion in order to provide the CNS with a REDOX positive state so that an increase in ATP generation doesn't cause further odixative damage?
Some research summaries:
- Dr. Neubrander, Autism specialist, has an amazing 94% responder rate with his autism patients. His protocol consists of no methylfolate, no hydroxy or adenosyl B12's...just methylB12 at a specific dosage, given at a specific injection site which then gives a "slow release" over 3 days from the one shot. He says the slow release allows the mB12 receptors to reach AND maintain saturation for this extended period.
- Prof. Jill James, Autism researcher, states that in her extensive testing, non-mB12 forms could balance CH3 cycle markers but it is ONLY methylB12 that consistently balances GSH:GSSG in addition to the CH3 markers . Her clinical research has shown that children who's CH3 chemistry balanced out but GSH wasn't optimal and only methylB12 was able to bring GSH:GSSG ratio to optimal levels, as compared to the control group.
If I remember correctly, it was also Jill James' research that showed the addition of cyano/hydroxyB12's was NOT able to prevent a disruption to CH3 cycle in the presence of thimerosal (the mercury containing preservative in vaccinations). When methylB12 was added in, there was NO disruption to CH3 biochemistry in the presence of thimerosal. This suggests that methylB12 can potentially be used as a preventative measure against autism!...kind of like a "vaccine against a vaccine"!
- Prof. Richard Deth, methylation biochemistry researcher, demonstrates that non-CNS methionine synthase (MTR) is very different to CNS MTR, whereby the CNS is lacking the SAM domain. This observation is of importance to CFS because there are issues with low GSH (which is used in order to prevent the cobalt ion from oxidizing during its "transit" from cyano/hydroxy to methyl) and low SAM.
When methylB12 is oxidized (as often the case in CFS), the body can "save" the B12 by donating a methyl group from SAM. The CNS doesn't have this SAM domain and thereby can't save the oxidized B12. This is where the research demonstrates that supplementing straight with methylB12 removes the pressure off this enzyme as there is no "wait time" for the transfer of methyl from methylfolate to B12 (which is usually the period where the cobalt ion oxidizes).
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Thanks, Rich!
I just received my supplements from Holistic Health and I'm kinda surprised it passed through the german customs without any problems; so I'm starting today (with testing if I tolerate each of these in general). But I have one concern:
Two years before I got 2x cisplatin chemotherapy for cancer (successful), but I'm ME/CFS-ill for 8 years now, so it hasn't really to do anything with it. So... I really don't know if this heavy metal complex or whatever of it remained in the body will/can cause problems, (although I studied biochemistry until recently). I'm thankful for every answer and regardless if they are reasonable or not, I'll just be very cautious and start slowly with the supplements.
Greetings~
I just received my supplements from Holistic Health and I'm kinda surprised it passed through the german customs without any problems; so I'm starting today (with testing if I tolerate each of these in general). But I have one concern:
Two years before I got 2x cisplatin chemotherapy for cancer (successful), but I'm ME/CFS-ill for 8 years now, so it hasn't really to do anything with it. So... I really don't know if this heavy metal complex or whatever of it remained in the body will/can cause problems, (although I studied biochemistry until recently). I'm thankful for every answer and regardless if they are reasonable or not, I'll just be very cautious and start slowly with the supplements.
Greetings~
Hi, I.R.
You're very welcome!
I'm glad you were successfully treated for cancer, and also that you were able to get your supplements through customs. I hope the treatment will work well for you. I don't know whether there will be any reaction with the prior cisplatin treatment, but if there are still heavy metals in your body, the treatment should help to improve the function of your detox system, which may cause them to be mobilized and excreted. I do recommend working with a physician while on this treatment.
Best regards,
Rich
Hi, nkm.
The problem with B12 in ME/CFS is that there is a functional deficiency of it due to the depletion of glutathione. While there may be enough B12 in the body by normal standards, in ME/CFS the cells are not able to use it at normal rates, because the depletion of glutathione drastically decreases the affinity of the CblC complementation group in the cells for cobalamin. A high-dose regimen of B12 supplementation is necessary to overcome this until glutathione comes back up. In the past, we just tried to boost glutathione directly, but this was not successful as a permanent means of raising it. On the other hand, if a combination of a reduced form of folate is taken orally, together with high-dose B12 taken sublingually or by injection, the vicious circle can be broken, and methylation, folates, and glutathione can be restored. We have verified this by lab testing, and it works.
The reason that folate must also be taken is that peroxynitrite reacts with methylfolate and breaks it down. So the oxidative stress in ME/CFS has depleted the folates, and they must be supplemented also.
Best regards,
Rich
The problem with B12 in ME/CFS is that there is a functional deficiency of it due to the depletion of glutathione. While there may be enough B12 in the body by normal standards, in ME/CFS the cells are not able to use it at normal rates, because the depletion of glutathione drastically decreases the affinity of the CblC complementation group in the cells for cobalamin. A high-dose regimen of B12 supplementation is necessary to overcome this until glutathione comes back up. In the past, we just tried to boost glutathione directly, but this was not successful as a permanent means of raising it. On the other hand, if a combination of a reduced form of folate is taken orally, together with high-dose B12 taken sublingually or by injection, the vicious circle can be broken, and methylation, folates, and glutathione can be restored. We have verified this by lab testing, and it works.
The reason that folate must also be taken is that peroxynitrite reacts with methylfolate and breaks it down. So the oxidative stress in ME/CFS has depleted the folates, and they must be supplemented also.
Best regards,
Rich
alice
Senior Member
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- No. CA, USA
If a B-Complex vitamin ingredient is listed like this: 'Folate (Folic Acid), then what is it --- Folate or Folic Acid? This is in Carlson B-50 Gel. I'm trying to get away from taking any folic acid and I don't know how to interpret this. Thanks.
Alice
Alice
Hi. Alice.
It means that it contains folate in the form of folic acid. Folic acid is one form of the general category of folates.
Best regards,
Rich
alice
Senior Member
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- Location
- No. CA, USA
Thanks Rich.
To me this seems a bit 'tricky' on their part. Seems like they should just say folic acid - which is the synthetic form, right? - - if that's what is really in there. After reading and rereading prior posts I understand a little more about the categories of folate and the different cobalamins now. One year of chemistry and one year of biology a long time ago just does not help much.
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Hello. I'm in the UK and wanted to buy ingredients for SMP from holistichealth but they never replied my two attempts to contact them. Do they still work? Do they ship to the UK?
Thank you.
Thank you.
After one or two doses of Metafolin I developed a painful lump deep in the back/right side of my neck.
It was deep in, about 2cm in diameter, no redness or heat. The skin slid back & forth over it so I am certain it wasn't a skin eruption.
Has anyone else had this happen? It's almost gone after about 8 days.
It was deep in, about 2cm in diameter, no redness or heat. The skin slid back & forth over it so I am certain it wasn't a skin eruption.
Has anyone else had this happen? It's almost gone after about 8 days.
- Messages
- 18
Rich,
I also wanted to ask if this protocol should be tired, if one has a problem with dumping toxins. As far as I understand, it only mobilizes toxins but doesn't help their excretion, which will end with mobilized toxins circulating in your system, if you have problem dumping them. Could you tell me if I'm right?
I also wanted to ask if this protocol should be tired, if one has a problem with dumping toxins. As far as I understand, it only mobilizes toxins but doesn't help their excretion, which will end with mobilized toxins circulating in your system, if you have problem dumping them. Could you tell me if I'm right?
Hi, randal.
I don't know if holisticheal ships to the UK. Perhaps someone else who lives there can comment on this. There are a couple of sites I've heard of that supply the supplements or similar ones in the UK. They are vitaminsuk.com and mandimart. Maybe you can get what you need from them.
Best regards,
Rich
Hi, randal.
The methylation protocol restores the sulfur metabolism, including the parts that support the detoxication system. This will cause stored toxins to be mobilized and excreted. However, there is a time lag between the mobilization and the excretion, and in between the levels of toxins are higher in the blood, which serves all the cells of the body. So there can be some exacerbation of symptoms as a result of this temporary exposure of all the cells to higher levels of toxins.
Some people have added other supplements to speed the excretion. These have included activated charcoal and modified citrus pectin as binders in the gut, and lemon juice to alkalinize the urine and increase the extcretion there.
I've heard of dosages of 3 or 4 grams per day of charcoal. If it causes constipation, it can be slurried with milk of magnesia.
If lemon juice is used, it should be drunk with drinking straw, and the teeth flushed with water afterward, to avoid removing calcium from the tooth enamel.
Best regards,
Rich
anne_likes_red
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They ship to New Zealand so more than likely they'll ship to you. I think Jenny ordered from them in the past too.
If you go through the order process and UK is available as a shipping option that will be your answer, but I am surprised you didn't hear back from them. I've found their customer service really good.
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- 18
Thank you to those, who replied.
It looks like the protocol won't help me with my problem of excreting toxins, and I would have to stop it because symptoms become too much.
They indeed ship to the UK, they eventually replied.
It looks like the protocol won't help me with my problem of excreting toxins, and I would have to stop it because symptoms become too much.
They indeed ship to the UK, they eventually replied.
alice
Senior Member
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- 109
- Location
- No. CA, USA
Rich,in an earlier post on this thread you wrote:
"The problem with B12 in ME/CFS is that there is a functional deficiency of it due to the depletion of glutathione. While there may be enough B12 in the body by normal standards, in ME/CFS the cells are not able to use it at normal rates, because the depletion of glutathione drastically decreases the affinity of the CblC complementation group in the cells for cobalamin. A high-dose regimen of B12 supplementation is necessary to overcome this until glutathione comes back up. In the past, we just tried to boost glutathione directly, but this was not successful as a permanent means of raising it. On the other hand, if a combination of a reduced form of folate is taken orally, together with high-dose B12 taken sublingually or by injection, the vicious circle can be broken, and methylation, folates, and glutathione can be restored. We have verified this by lab testing, and it works."
Are you suggesting that supplementation with glutathione (lyposomal) is really not necessary ?
.What do you consider an appropriate "high dose regimen" of sublingual B12?
I recently bought MegaFood Balanced B Complex (whole food B complex) since it did not have folic acid in it as most B Complex vitamins do. However it says it has 25 MG B-12, and 40 MG Folate. These seems to be huge amounts - or is most of it ineffective because it is taken orally.
Thanks,
alice
"The problem with B12 in ME/CFS is that there is a functional deficiency of it due to the depletion of glutathione. While there may be enough B12 in the body by normal standards, in ME/CFS the cells are not able to use it at normal rates, because the depletion of glutathione drastically decreases the affinity of the CblC complementation group in the cells for cobalamin. A high-dose regimen of B12 supplementation is necessary to overcome this until glutathione comes back up. In the past, we just tried to boost glutathione directly, but this was not successful as a permanent means of raising it. On the other hand, if a combination of a reduced form of folate is taken orally, together with high-dose B12 taken sublingually or by injection, the vicious circle can be broken, and methylation, folates, and glutathione can be restored. We have verified this by lab testing, and it works."
Are you suggesting that supplementation with glutathione (lyposomal) is really not necessary ?
.What do you consider an appropriate "high dose regimen" of sublingual B12?
I recently bought MegaFood Balanced B Complex (whole food B complex) since it did not have folic acid in it as most B Complex vitamins do. However it says it has 25 MG B-12, and 40 MG Folate. These seems to be huge amounts - or is most of it ineffective because it is taken orally.
Thanks,
alice