MTHFR Gene Mutation and which protocol to use

[Vanguard]

Hey everyone,

So in my supplement stash I now have hydroxy b12, Methyl b12 and adeno b12. I have most of the parts of Freddd and Rich's protocols. I have been tested to have the A1298c and C9776 (or something) gene mutations of the MTHFR genes and many others have.

Does this mean I should absolutely be on Freddd's protocol (using Methyl and adeno b12) instead of Rich's?

Thanks
Vanguard

 

[richvank]

Hey everyone,

So in my supplement stash I now have hydroxy b12, Methyl b12 and adeno b12. I have most of the parts of Freddd and Rich's protocols. I have been tested to have the A1298c and C9776 (or something) gene mutations of the MTHFR genes and many others have.

Does this mean I should absolutely be on Freddd's protocol (using Methyl and adeno b12) instead of Rich's?

Thanks
Vanguard

Hi, Vanguard.

Having the MTHFR C677T SNP will mean that your cells will not be able to make methylfolate at the rate they would be able to if you did not have this SNP. Both protocols include methylfolate, so having this SNP would not be a deciding factor. I think that taking adenosylcobalamin is fine, though it isn't part of the simplified protocol I've suggested. It might help to give you more energy sooner. Whether methyl- or hydroxocobalamin is preferable depends, in my opinion, on what the levels of glutathione and SAMe are. If either is very low, methyl B12 may be needed. If not, hydroxo is preferable, in my opinion, because it leaves control of the appropriate methyl B12 production to the cells themselves, and avoids overdriving the methylation cycle. I also favor the lower dosages of the folates and B12 that I've suggested, for the same reason. All of this applies to most PWCs. I acknowledge that there are some people who have the types of genetic issues that Freddd apparently has, and the higher dosages that Freddd recommends are vital for them. I still think they represent a small part of the ME/CFS population, but this has not been quantified.

Best regards,

Rich

 

[Vanguard]

Ok, thanks Rich,

So I thought Freddd's genetic issues were just the same as me (the SNP) but maybe he has other issues that require different b12s.

 

[richvank]

Ok, thanks Rich,

So I thought Freddd's genetic issues were just the same as me (the SNP) but maybe he has other issues that require different b12s.

Hi, Vanguard.

As far as I know, Freddd's polymorphisms and mutations have not been characterized by a lab, but based on what he has reported, I'm suggesting that he has an inborn error of metabolism in his intracellular B12 processing enzymes, probably one of the CblC mutations, and also he appears to have a deficiency in only enzyme that can react with folinic acid to begin its conversion to other, useful forms of folate, which is the MTHFS enzyme, not to be confused with the MTHFR enzyme.

Best regards,

Rich

 

[u&iraok]

I have the ineffective SNP for MTHFR. Also:

EPHX - Microsomal Epoxide Hydrolase - Detoxifies epoxides

GPX1- Glutathione Peroxidase - Eliminates hydrogen peroxide

TNF-a - Tumor Necrosis Factor-alpha - Multifunctional, proinflammatory cytokine

PON-1 - Parioxonase-1 - Hydrolizes oxidized phospholipids

CYP11B2 - Aldosterone Synthase - Regulates blood pressure via kidney and fluid balance

APOB - Apolipoprotein B - Main lipoprotein of chylomicrons and LDL

VDR - Vitamin D receptor - Bone mineral density


Any insights for me? Any other PWCs with similar?

 

[determined]

Hi u&iraok,

Are these results from 23andme or somewhere else? Do you have the rs numbers for them?

 

[u&iraok]

The test was done by Integrative Genomics. I don't have the rs numbers. Unfortunately all I have is the above.

 

[Vanguard]

Rich what about taking a small amount, say 1 or 2 mgs of Methyl B12 along with the hydroxy and adeno b12? Would that small amount still possibly overdrive the cycle? I've read someone saying they tried a combo of the three B12s and it seemed to help.

Thanks

 

[Vanguard]

It also confuses me how my doctor wants me to take a giant 15 mg Deplin pill every day but the protocol's here call for less than 1/15th of that daily. I believe your research over my doctor's guess of how much to give me, of course it's still frustrating when a doctor tells you different than what your research shows.

 

[richvank]

Hi, Vanguard.

I think that would be an interesting thing to try. I don't know exactly where the point is above which the methylation cycle will be overdriven, and it will probably vary from one person to another. Unfortunately, there just hasn't been enough controlled clinical testing of various protocols to answer excellent questions like this one.
If you decide to try this, I will be interested to hear what you experience from it.

Also, if you should be interested in running some lab tests to see what the effect is biochemically, I would be interested in that, as well. A combination of the Health Diagnostics methylation pathways panel and the Doctors Data 40 plasma amino acids panel would tell the story.

Best regards,

Rich

 

[richvank]

It also confuses me how my doctor wants me to take a giant 15 mg Deplin pill every day but the protocol's here call for less than 1/15th of that daily. I believe your research over my doctor's guess of how much to give me, of course it's still frustrating when a doctor tells you different than what your research shows.

Hi, Vanguard.

Your doctor is probably following the guidance given by PamLab, the supplier of Deplin. Deplin is normally prescribed alone as a treatment for depression. In ME/CFS, 5L-methyltetrahydrofolate (the active ingredient in Deplin) is given together with vitamin B12. This combination has a synergistic effect, because it overcomes both the draining of folate from the cells as well as the functional deficiency of vitaming B12 in this disorder. These two come together at the enzyme methionine synthase, which is partially blocked in ME/CFS, and the two together thus produce a much more powerful effect than Deplin taken alone, for a person who has this partial block.

Best regards,

Rich

 

[rydra_wong]

Hi, Vanguard.

Having the MTHFR C677T SNP will mean that your cells will not be able to make methylfolate at the rate they would be able to if you did not have this SNP. Both protocols include methylfolate, so having this SNP would not be a deciding factor. I think that taking adenosylcobalamin is fine, though it isn't part of the simplified protocol I've suggested. It might help to give you more energy sooner. Whether methyl- or hydroxocobalamin is preferable depends, in my opinion, on what the levels of glutathione and SAMe are. If either is very low, methyl B12 may be needed. If not, hydroxo is preferable, in my opinion, because it leaves control of the appropriate methyl B12 production to the cells themselves, and avoids overdriving the methylation cycle. I also favor the lower dosages of the folates and B12 that I've suggested, for the same reason. All of this applies to most PWCs. I acknowledge that there are some people who have the types of genetic issues that Freddd apparently has, and the higher dosages that Freddd recommends are vital for them. I still think they represent a small part of the ME/CFS population, but this has not been quantified.

Best regards,

Rich

Rich, I am curious whether the possibility of overdriving the methyl cycle has ever been proven? I have never seen any proof of this myself. I know people get reactions but that does not necessarily mean the cycle is being overdriven in and of itself, right? So there must be more evidence? Because Fredd says that when you start up the methylation biochemical pathways now you are exposing other biochemical pathways which were previously blocked and that it is THAT which causes reactions as secondary deficiencies are exposed.

So, for instance, if you are hyperthyroid lbut you did not have enough methylcobalamin to make excess thyroid hormone then you would not have excess thyroid hormone. But as soon as you got sufficient methylcobalamin you would make excess thyroid hormone which would make you "keyed up" for sure! In Fredd's case, if your Kreb cycle is not working and you supply it the aB12 and etc from the methyl cycle to make it work, now you are exposed to any potassium shortage you may have because the Kreb cycle needs potassium to work. There are studies which show a magnesium shortage causes a potassium shortage and magnesium is also needed to produce ATP. These deficiencies become exposed when the methyl cycle is no longer the roadblock.

I would like to know if there is any evidence the cycle can be overdriven, because I am just a doubting Thomas. Thanks

Rydra Wong