Some questions - please help

[Wickie]

Hi@Wickie
I am sorry to hear how bad it is for you at the moment. I have tried methylation and in my experience I found that it was better when I stopped the methylation and did other support supplements first.
As possible choices to start I would suggest a good multi-mineral formula along with a magnesium.
And a low dose multi-B formula.
And vitamin C. But you might want to further research (if you can) your specific symptoms and consider what might be useful.
That said, there are no guarantees of anything. But I would take a break from trying to figure out the methylation for a while and reassess.
I just went back and looked at your post. Most people are deficient in magnesium more than they need potassium. These two minerals give similar symptoms.

Perhaps you can talk about what symptoms are worst for you and that you are trying to treat.

Hi Snowdrop,
Thanks for your sympathy and that you share your ideas. Magnesium was one of the first supplements I was taking due to muscle cramps and I am taking it for years now. Blood testing always shows normal values, so it seems like my body needs it.

Perhaps it is helpful, if I list up the substances I am taking:
Magnesium
Potassium
Vitamin A, C, D, E
Benfotiamine (I decreased the amount to 20mg before I started taking Folate)
Biotin
Lecithin
Ab12, Mb12
Papain Enzymes


I tried several Multi formula and the b complex, but had always problems with that. So I tried to take seperate substances.

A symptom list is hard to tell, because they change very often and when I am having a migraine all the other symptoms take a back seat.

Main symptoms are:
fatigue (head and body)
bad sleep
pain (Joints, muscle, nerves, head, back)
digestive trouble

 

[Valentijn]

Great. Could you look at the following SNPs and tell us which Homozygous/Heterozygous mutations you have?

How are you determining which variation is supposedly risky? I took a look at the first one, rs643788, and the variations have been officially labeled as benign. Additionally, the C allele which you label as "risky" is extremely common, with a 43% prevalence rate. That means that 18.5% of the general population around the world is homozygous for CC and an additional 49% are heterozygous with CT. Does 67.5% of the world have a problem you think that they need to know about?

If i have C;C then i have homozygous SNP. If i have either :
C;T or T;C
then i have heterozygous SNP.

23andMe will always list alleles in alphabetical order. Hence someone would never have "TC" as a result.

If i have
T;T
Then this means that there are no SNPs occurring to this gene.

No, that means someone is simply homozygous for the presumed "non-riskly" allele, instead of the minor allele. Everyone has every SNP (single nucleotide polymorphism), except in the somewhat rare case of having a deletion. Every rs number represents a SNP, hence no one can really be said to "not have" that SNP.

Since you have SNPs on the genes listed, please consider looking at my original post and try the regimen.

Everyone has SNPs on those genes, typically thousands of them. And if those variations you're listing are extremely common, they don't seem like a good indication of either a dysfunction or a need for a treatment.

 

[brenda]

Brenda, if you don't have any improvements and increased inflammation, why are you taking it?

I am hoping that I will eventually show improvement. The inflammation has probably gone down some, its hard to say.

 

[mariovitali]

How are you determining which variation is supposedly risky? I took a look at the first one, rs643788, and the variations have been officially labeled as benign. Additionally, the C allele which you label as "risky" is extremely common, with a 43% prevalence rate. That means that 18.5% of the general population around the world is homozygous for CC and an additional 49% are heterozygous with CT. Does 67.5% of the world have a problem you think that they need to know about?

23andMe will always list alleles in alphabetical order. Hence someone would never have "TC" as a result.

No, that means someone is simply homozygous for the presumed "non-riskly" allele, instead of the minor allele. Everyone has every SNP (single nucleotide polymorphism), except in the somewhat rare case of having a deletion. Every rs number represents a SNP, hence no one can really be said to "not have" that SNP.


Everyone has SNPs on those genes, typically thousands of them. And if those variations you're listing are extremely common, they don't seem like a good indication of either a dysfunction or a need for a treatment.

I used the following website to find Risk Alleles :

https://www.pharmgkb.org/index.jsp


so for MTHFR (rs1801133) i get these results :

https://www.pharmgkb.org/variant/rs1801133?previousQuery=rs1801133

Under alleles it has the following entry :

G > A

I know that i have homozygous mutation to MTHFR therefore i am (A/A).

Of course you are *much* more knowledgeable than i am to genes/snps so perhaps could you tell me what is the right way to find risk alleles?

I would also really appreciate if you could go through my post and share your comments and feedback and in the case that erroneous information exists it can be swiftly corrected!


The post is located here : http://forums.phoenixrising.me/inde...ponse-and-a-possible-treatment-for-cfs.37244/


Thanks

 

[Valentijn]

Under alleles it has the following entry :
G > A

Okay, that's just showing the ancestral and rarer allele. The only data I see for rs643788 (for example) is about prevalence rates, and that part has nothing at all to do with risk.

Of course you are *much* more knowledgeable than i am to genes/snps so perhaps could you tell me what is the right way to find risk alleles?

SNPedia can be a quick way to get summaries, but isn't particularly comprehensive and suffers a bit from anyone being able to contribute to it. But it does typically link to papers along with brief summaries, so data can be verified by reading the actual research papers.

But the best ways are via dbSNP and Google Scholar. So to use dbSNP for rs643788 you can go to http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs643788 . There's a ton of data there, including pathological status for missense mutations. In the case of rs643788 they say it's "Benign" based on a review of the available data. Sometimes these can still have an impact though, in which case it's good to look at the OMIM entry for it. If there is an OMIM entry, it will be linked near the top of the dbSNP page, right next to where it says "With Benign Allele", except that it would usually say "pathogenic" instead of "benign" if there's an OMIM entry.

Further down on the dbSNP page is a map view. A fat green horizontal bar (the gene) and lots of red blocks (SNPs) can be seen. If you hover over the light blue box for the SNP (in the light green vertical line), it lists a few big numbers after "Pubmed:". Those numbers link to specific Pubmed articles which mention the SNP. Though sometimes they're in the supplementary data instead of the main body.

The other way to find the research articles is at https://scholar.google.com/ . Just search for the rs number, and usually that will find whatever is there. It can bring in more results, if there is research which is not on Pubmed. In the case of missense mutations it might be referred to by the gene name and protein position instead of the rs number, especially in older research. So it can also help to search for "DPAGT1 I393V" instead of just the rs number. These position numbers can change over time as the position is recalculated, though usually they're pretty consistent in using the same position for research.

I would also really appreciate if you could go through my post and share your comments and feedback and in the case that erroneous information exists it can be swiftly corrected!

I've been pretty busy and sick lately, but I might have a couple days coming up where I'll be stuck in a hotel room while it's pouring rain outside. I'll try to take a more in-depth look then if I can handle it.

 

[mariovitali]

@Valentijn

Thank you for all this, much appreciated. I hope you feel better ASAP. Whenever you can please have a look at my post and perhaps you could also give the regimen a try.

In the meantime i will look through all the Genes/snps i listed on my post and take all corrective actions.


Take care!

Mario

 

[Wickie]

@ahmo

As far as I have read you have been on a high dose of methylation supplements.
How long are you taking B12 and folate?
Did you make it to switch on the methylation cycles?
Do you have any improvements from that? If so, what are the main improvements?
Are you able to have a normal life now?

 

[Wickie]

@mariovitali

Here are the results. What do you infer out of it?

DPAGT1

rs643788(Risk C) CC
rs28934876 (Risk C) TT


ER Stress response

rs13045 (EIF2AK3-PERK) : Risk C not found
rs2239815(XBP1) : Risk C TT
rs10918270(ATF6) : Risk A AG
rs391957 (HSPA5) : Risk C not found

GCH1, associated with lower levels of BH4

rs10483639( Risk C) CG
rs3783641(Risk A) TT
rs8007267(Risk T) CC
rs12147422 -(Risk C) TT
rs3783637 - (Risk T) CC
rs3783641 - (Risk A) TT
rs41298442 - ( Risk T) TT
rs4411417 - (Risk = C) CT
rs752688 - (Risk = T) CT
rs841 - (Risk A) not found
rs998259 - (Risk=T) CT
rs7147286 - (Risk=A) GG


NDUFS7

rs2332496( Risk A) GG
rs11666067 (Risk A) not found
rs1142530 (Risk T) --
rs11666067(Risk A) not found
rs2074895(Risk A) not found


PAH Gene - Phenylalanine levels handling

rs10860936 (Risk C) not found
rs1722387 (Risk C) not found
rs1522305 (Risk C) GG
rs1522296 (Risk A) GG
rs772897 (Risk C) CG
rs1522307 (Risk G) AA
rs11111419 (Risk T) AA

Choline

rs3733890 (Risk A) AG
rs2461823 (Risk C) NAFLD Disease CC
rs7643645 (Risk G) NAFLD Disease AA
rs7946 (Risk T) (PEMT) not found
rs4244593 (Risk G) (associated with PEMT) GT
rs2236224 MTHFD1 (Risk A) GG
rs2236225 (Risk A) (MTHFD1) GG


CHDH (Susceptibility to Choline deficiency)
rs9001 (Risk G) --

 

[mariovitali]

@Wickie

We had a discussion earlier with @Valentijn regarding the Genes/SNPs listed. It appears that some genes which i listed are not of Clinical Significance but i would like to clarify this more (which means that i have a lot of reading to do).

In the meantime Some questions :

-How often do you eat meat?
-Do you often eat Phenylalanine sources (e.g Chewing Gum containing Aspartame )?
-How often do you eat Eggs?
-Have you ever had your liver tested recently? (AST, ALT) Where these values elevated?
-Do you have mutations in genes related with Tetrahydrobiopterin (BH4) Production?
-Have you tested your Homocysteine levels?
-How is your LDL/HDL Cholesterol?

Sorry for the many questions there ;-)

 

[ppodhajski]

@Wickie

We had a discussion earlier with @Valentijn regarding the Genes/SNPs listed. It appears that some genes which i listed are not of Clinical Significance but i would like to clarify this more (which means that i have a lot of reading to do).

I want to point out that just because there is no CLINICAL significance does not mean it is not significant. Since it might not have been studied in any depth yet or researched in relation to a system it might effect. In many of these cases we can might uses slight evidence to form a hypothesis which we can test. I think people like you are doing the hypothesizing that science needs to do to find cures for our conditions.Studying single genes is important but seeing how they all play together, that is the art of the cure.

I am more experimental and artistic in my interpretations as well and I think that is why both of us are recovered.

A little video on the "absence of evidence"

 

[Snowdrop]

I found that my migraines are alleviated with electrolytes and more water intake. So given the supplements you take maybe more salt.
Do you have the symptoms of POTS?
Many here do.

And there is no consensus I think on whether potassium is really needed in the quantities ingested. Potassium is a main fertiliser ingredient and therefore easily available in food. Just my opinion. I read somewhere here in a thread that Jonathan Edwards thought it was a waste of supplement but I forget in what context. But selenium, manganese, zinc, sometimes chromium are often mentioned here as needed for metabolic pathways. And they are more difficult to acquire from food in today's overused soil.

Also, if you start up on methylation again there is no reason not to try using the HydroxyB12. It soaks up any excess arsenic in the system.
And the Methyl donor can still come from the MTHF (B9).

Just some more thoughts. These issues are not easily resolved.

 

[ahmo]

@ahmo

As far as I have read you have been on a high dose of methylation supplements.
How long are you taking B12 and folate?
Did you make it to switch on the methylation cycles?
Do you have any improvements from that? If so, what are the main improvements?
Are you able to have a normal life now?

I started Freddd's Protocol 2 years ago. I started for methylation issues, especially after uncovering MTHFR snp. Once I was on theraputic levels of B12, my neurological complaints resolved, including insomnia. After life-long tendency, chronic since ME, I now sleep just fine. Other neurological clearings: heat intolerance and overheating, decreased sensitivity to noise, light, smells; decreased orthostatic intolerance; balance...

I'd gotten up to 30mg Mfolate a year ago, until I discovered that green vegetables was blocking folate, forcing me to take more, which was stressing adrenals. Stopped green veggies, and my needs for folate reduced by half. Later started taking it sublingually, and reduced further, by 2/3. I've also been doing detox programs, and have reduced my needs now to 2mg Mfolate and about 2.5mg MB12/day.

I still have constraints on my ability to think and act, but I no longer have all the terrible symptoms I had for years. I don't have a *normal life*, but I am comfortable.

 

[Wickie]

Once I was on theraputic levels of B12, my neurological complaints resolved, including insomnia. After life-long tendency, chronic since ME, I now sleep just fine. Other neurological clearings: heat intolerance and overheating, decreased sensitivity to noise, light, smells; decreased orthostatic intolerance; balance...

I'd gotten up to 30mg Mfolate a year ago, until I discovered that green vegetables was blocking folate, forcing me to take more, which was stressing adrenals. Stopped green veggies, and my needs for folate reduced by half. Later started taking it sublingually, and reduced further, by 2/3. I've also been doing detox programs, and have reduced my needs now to 2mg Mfolate and about 2.5mg MB12/day.

I still have constraints on my ability to think and act, but I no longer have all the terrible symptoms I had for years. I don't have a *normal life*, but I am comfortable.

Hi ahmo,

wow - it sounds like Methylation therapy is worthwhile for you and I am glad to hear that.
To sleep fine is so wonderful, when you were suffering from insomnia for a longer time.
It is the symptom I would choose, if I could wish only one of them away!

What would you call a therapeutic level of B12?

I am asking myself, what "reactions" to the protocol should be acceptable to bear and when is the point to reduce doses? What is a normal reaction?

Thanks a lot for sharing your experience!

Wickie

 

[Wickie]

I found that my migraines are alleviated with electrolytes and more water intake. So given the supplements you take maybe more salt.
Do you have the symptoms of POTS?
Many here do.

And there is no consensus I think on whether potassium is really needed in the quantities ingested. Potassium is a main fertiliser ingredient and therefore easily available in food. Just my opinion. I read somewhere here in a thread that Jonathan Edwards thought it was a waste of supplement but I forget in what context. But selenium, manganese, zinc, sometimes chromium are often mentioned here as needed for metabolic pathways. And they are more difficult to acquire from food in today's overused soil.

Also, if you start up on methylation again there is no reason not to try using the HydroxyB12. It soaks up any excess arsenic in the system.
And the Methyl donor can still come from the MTHF (B9).

Just some more thoughts. These issues are not easily resolved.

Hi Snowdrop,

I found out that my migraines occur every four weeks, so I guess the have a hormonal reason. I always drink a lot of water then, but I never tried electrolytes. Thanks for the hint, I will try it next time.

I guess, I have no POTS.

I started the potassium in preparation to the Methylation therapy. I think I will leave them now. Manganese did nothing to me. I have problems with zinc and chromium.

Regarding the HydroxyB12 I thought that it would block the methylation, that's why I didn't take it.

 

[ahmo]

What would you call a therapeutic level of B12?

I am asking myself, what "reactions" to the protocol should be acceptable to bear and when is the point to reduce doses? What is a normal reaction?

Thanks a lot for sharing your experience!

I was up to 25mg B12 Others report also, it seems that we need to saturate the cells after a long time of depletion. I'm only using about 2.5mg now, 1/10 of what was my highest dose. I'm also using transdermal, which may increase absorption.

I can't answer that about reactions, what's too much. Fred makes some comments in the Guide about especially things that create mental distress. I constantly balanced supps, diet, to eliminate my symptoms. Including detox/herx reactions, which can happen when working on methylation. Because I kept on top of the minerals and aminos, plus antihistamines, I didn't suffer much. I used self-testing for my doses.

 

[Wickie]

I was up to 25mg B12 Others report also, it seems that we need to saturate the cells after a long time of depletion. I'm only using about 2.5mg now, 1/10 of what was my highest dose. I'm also using transdermal, which may increase absorption.

I can't answer that about reactions, what's too much. Fred makes some comments in the Guide about especially things that create mental distress. I constantly balanced supps, diet, to eliminate my symptoms. Including detox/herx reactions, which can happen when working on methylation. Because I kept on top of the minerals and aminos, plus antihistamines, I didn't suffer much. I used self-testing for my doses.

25mg B12, do you mean only MB12 or a mixture of MB12 and AB12?

Did you write your story somewhere in this forum? I would like to read that and maybe I don't have to ask all these questions.

Self testing sounds great. Perhaps I can learn that.

 

[Wickie]

I am hoping that I will eventually show improvement. The inflammation has probably gone down some, its hard to say.

I can understand that. But perhaps you have a problem to tolerate one of the substances of the b complex that are not necessarily needed for the methylation protocol. What if you could take more of the methylation substances.

That is just a thought.

 

[brenda]

I can understand that. But perhaps you have a problem to tolerate one of the substances of the b complex that are not necessarily needed for the methylation protocol. What if you could take more of the methylation substances.

That is just a thought.

Thanks l did take b12 in both forms and methyl folate and reacted to them. I have bought some liver to try.

 

[ahmo]

25mg B12, do you mean only MB12 or a mixture of MB12 and AB12?

MB12 only. The AdB12 is separate. I'm taking 40 mg AdB12. Fred suggested on a day away from MB12, dose between 30-50mg.

I've been meaning to summarize my progression, but have not done so yet. What exactly would help you to know? Initially I'd experienced skin symptoms when I began folate without B12. I thought this rash was 'detox', as Fred notes. It made me tooto increase folate, for too long. Once I began increasing Mfolate by 100-200mcg/day, and increasing MB12 along with it, my improvements began. The most obvious were neurological. When I had negative symptoms from increasing folate, I immediately took a 1mg Enzymatic Therapies MB12, and it cleared the symptoms almost immediately. These symptoms included restlessness, itchiness, histamine flood, slight breathlessness, euphoria.

I kept increasing folate as I continued to get deficiency symptoms, though it might take a week for them to appear. This is when I recognized that vegetable folate, folinic, was blocking the Mfolate, quit vegetables, and dropped folate doses. So there was an endpoint. If not for this incident, I would have stopped increasing when there were no recurrent symptoms. It took me about 1 year to reach my end dose.

Self-testing http://www.youtube.com/watch?feature=player_detailpage&v=Ex59wHLk3Q0

Good written description of simple self-testing: http://www.goodhealthinfo.net/herbalists/muscle_testing.htm

 

[Wickie]

MB12 only. The AdB12 is separate. I'm taking 40 mg AdB12. Fred suggested on a day away from MB12, dose between 30-50mg.

I am far away from that!

And unfortunately the unbearable fatigue and weakness are still there. With the fatigue I have increased intolerance to light, sounds, smell. I have to be in bed most of the time. I haven't had such a bad level for years now. So I fear that it will not go away again.

Do you have any idea how to come over that?

I read through your guide again and it became clear to me, that I am not able to do it that way.

Do you know of others, who are +/+ for COMT + MAO-A and tried a methylation protocol? Perhaps I should open another thread to ask for that?

I will look through the self-testing links the next days.

ahmo, thanks again for all your help. I highly appreciate it.

Wickie