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Just got my Methylation and Detox Profile Results: can the Experts Kindly Provide Commentary Please

Hip

Senior Member
Messages
17,824
Lotus97

That is a very interesting excerpt from Rich that you posted, thanks. Like most ME/CFS patients, I also very rarely get colds.

What Rich said makes a lot of sense: that the likely reason ME/CFS patients rarely get colds is because the interferon response is permanently switched on.

And the interferon response is permanently switched on because the two branches of our immune system — our natural killer cells and our CD8 killer T-cells — are dysfunctional, so the interferon response has to remain activated in order constantly make up for the failures of these two dysfunctional branches.

If only we could stop viruses like coxsackievirus B from thwarting the functioning of our CD8 killer T-cells, then these CD8 killer T-cells would likely rapidly eliminate these viruses from our bodies.

When viruses, bacteria and other microbes deliberately disrupt our immune systems (for the purpose of thwarting the immune attack upon them), this is known as immune evasion. If you could stop immune evasion from happening, I expect ME/CFS would very quickly resolve and clear up.
 

Lotus97

Senior Member
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United States
One of the most passive evasion strategies is to hide inside the host cell in a dormant form, as is the case with some bacteria
Hip
I'm not too familiar with all the different types of pathogens people here are dealing with, but I have been studying Lyme and that line I'm quoting above is from one the articles you linked to jumped out at me. I've been reading Buhner's book and it seems that the Lyme bacteria are very clever at avoiding detection. He says they actually share similarities with more complex pathogens such as protozoa. One of the things they do is go into cyst form to avoid detection. The first time my rash appeared was 15 years after I was bitten. My rashes appeared two and half years apart. The only commonality I could think of was that both times they appeared was a month or two after seeing a chiropractor. The Lyme bacteria encyst in the spinal fluid so I think the chiropractic adjustments "woke them up". Buhner says that Lyme is a Th1 illness where the Th1 system becomes overactive, but someone told me she had heard from people with Lyme that are Th2 dominant. Maybe they're both right. Maybe the illness does cause a shift towards Th2 as well as suppress certain aspects of Th1, but then also cause the Th1 response to be overactive. It's a delicate balancing act, but Buhner's protocol using herbs promises to be more effective than just antibiotics because the Lyme can just hide in cyst form to avoid the antibiotics. It's possible that a combination of both herbs and prescription antibiotics would be the best treatment.
 

OkRadLakPok

Senior Member
Messages
124
You do have a lot on the detox. I have about 12 but only one red. I will try to post it, too so you can compare. It is very hard because it is so hard to get metals out if they are part of it. Please post on what helps you. I found Ip6 to help me a lot.
 

Hip

Senior Member
Messages
17,824
Astragalus stimulates CD8 and NK killer cells.

The problem seems to be not so much a dysfunction with the CD8 T-cells themselves, but that in coxsackievirus B infected cells, the virus cunningly decreases the expression of the major histocompatibility complex class I molecules on the cell surface — molecules critical for the CD8 T-cell response.

Without these MHC class I molecules on the cell surface, the CD8 T-cells cannot "see" the virally infected cells. In this way, coxsackievirus B evades the immune response. Reference: 1.
 

Lotus97

Senior Member
Messages
2,041
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I was taking this nucleotide supplement
http://www.swansonvitamins.com/swanson-ultra-mixed-nucleotides-imunil-300-mg-60-caps

I found out that it stimulates CD4+ and CD8+
http://www.bioiberica.com/Health_solutions/Inmunactive/Studies/Sport_Nutrition.html

Which is actually why I stopped it since I seem to be dealing with a lot of inflammation possibly due to an overactive Th1 immune response since I have Lyme. Cat's claw also increase CD4 and CD8 as well as IL-1 and IL-6 so I've stopped that as well. Cat's Claw does have anti inflammatory properties though, such as suppressing TNF-alpha.

I'm mentioning these supplements because they, like astragalus, could be beneficial for some people here which is why I assume adreno mentioned astragalus. But I'm a different situation. At some point cat's claw will help me fight Lyme and if I do get Lyme in remission astragalus would most likely also be beneficial as it's recommended for early stage and post stage Lyme (just not chronic/late-stage Lyme). Even though many of the people here have similar symptoms, some of the treatments are going to vary from person-to-person.
 

Lotus97

Senior Member
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2,041
Location
United States
In general, when I try high dose vitamin B12 injections or high dose B12 sublingually, I don't experience very much in terms of benefits. I have tried methylcobalamin, adenosylcobalamin and hydroxocobalamin, often all together.

Similarly, when I try the full methylation protocol, including vitamin B12, methylfolate, P5P, glutathione, phosphatidylserine, fish oil, vitamin B complex, I also don't seem to get much benefit.

I get neither much benefit, nor experience any negative symptoms, such as Herxheimer or detox symptoms.

When I first started taking high dose vitamin B12 fro my ME/CFS several years ago, the improvements I experienced then were a little better; but now, taking B12 or doing a methylation protocol hardly makes any difference.

So I wonder of one or more parts of my methylation cycle is blocked?
How much methylfolate were you taking? Were you taking R5P? Were you always taking glutathione? It's unlikely, but you could have what Freddd has where glutathione reduces his B12. Also, did you try DMG? Some people have said it's a weak methyl donor, but I've heard from two people who had good results with it. Also, how much B3 were you taking? B3 uses up SAMe thereby reducing methylation. Hydroxocobalamin works the same way. Which brings me to something else I was thinking about. What if your reaction to SAMe is because you're low in SAMe? Sometimes deficiency can cause strange reactions. Rich hypothesized something similar in regards to some people's reaction to raising acetylcholine. If you're low in SAMe that could possibly be why you can't get methylation going. I just noticed that you're BHMT so maybe DMG wouldn't be a good idea since it diverts the flow away from the BHMT pathway. I also noticed you're COMT +/- and VDR Taq which seems like you'd be prone to overmethylation. Even with a lot of B3 enough methylfolate and methylcobalamin seems like that would outweigh it. I don't know enough to know if my theory about SAMe is valid or not, but it does seem to make the most sense.
 

Hip

Senior Member
Messages
17,824
How much methylfolate were you taking? Were you taking R5P? Were you always taking glutathione?

My typical daily methylation protocol, when I take it, is something like this:

Methylation protocol:
B12 methylcobalamin sublingual 20 mg
B12 adenosylcobalamin sublingual 4 mg
Potassium 200 mg
Glutathione transdermal 100 mg
Phosphatidylserine 400 mg
L-5-MTHF 1000 mcg
Folinic acid 800 mcg
Vitamin B6 100 mg
Pyridoxal-5-phosphate (P5P) 50 mg
Vitamin B complex, giving 25 mg for each B vitamin
Cod liver oil, giving EPA & DHA 500 mg

All the above were taken once daily. I also tried variations on the theme (eg: no glutathione, no folinic acid).

What if your reaction to SAMe is because you're low in SAMe

I think what I mentioned above — that SAMe and TMG increase the interferon alpha response and interferon causes depression — may explain why I feel a little depressed when I take SAMe or TMG.

I also noticed you're COMT +/- and VDR Taq which seems like you'd be prone to overmethylation. Even with a lot of B3 enough methylfolate and methylcobalamin seems like that would outweigh it.

That's very interesting. Do you have any goods links that detail the SNPs that are linked to overmethylation? Are you saying that the methylation protocol may not benefit me, because my SNPs indicate a tendency to overmethylation?

Might a tendency to overmethylation also provide an explanation as to why taking SAMe and TMG make me depressed: because some researchers believe overmethylation can cause depression?
 

Lotus97

Senior Member
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That's very interesting. Do you have any goods links that detail the SNPs that are linked to overmethylation? Are you saying that the methylation protocol may not benefit me, because my SNPs indicate a tendency to overmethylation?
No, what I was saying was that the doses of methylcobalamin and methylfolate would generally be too high and would cause unpleasant symptoms for most people with your SNPs. Mainly hypokalemia (low potassium) and excitotoxicity (anxiety). Some people can't even tolerate 200 mcg of methylfolate and 250 mcg of methylcobalamin when starting methylation (and might not even need much more than that) This is from a recent article by Yasko about which SNPs tolerate which types of B12.
http://www.scribd.com/doc/132017201/Dr-Amy-s-Simplified-Road-Map-to-Health
index.php


I think part of the reason hydroxocobalamin is tolerated better is because it uses up SAMe to make the conversion to the active forms of b12 (methylcobalamin and adenosylcobalamin). There might be more to it than that. Maybe also the conversion process is slower so you're not hit with the methylcobalamin all at once. If someone following this thread knows of any other reason than what I mentioned about how hydroxocobalamin works I'd like to know.
I think what I mentioned above — that SAMe and TMG increase the interferon alpha response and interferon causes depression — may explain why I feel a little depressed when I take SAMe or TMG.
If there is another reason, I don't know of any. What you said explains why it could happen, but it still doesn't explain what's going on specifically with you. I just reread some of the early posts in this thread. It seems you did try TMG with methylation and you say it didn't do anything. I assume you meant as far as positive benefits or increasing methylation, but did TMG trigger a depression back then or is this something more recent?

My theory about you being low in SAMe was just a shot in the dark. There might be something else missing. For example, Freddd has been taking high doses of methylcobalamin and methylfolate for years. I assume he has also been taking TMG and SAMe. But when he added B2, he ran into serious problems
http://forums.phoenixrising.me/inde...kalemia-and-methylfolate-insufficiency.22968/

You said you were taking 25 mg of B2. It's possible you can't make the conversion into coenzymated forms. You could try R5P, or Source Naturals sells a coenzymated sublingual B2. The sublingual might be better because there's something about taking the coenzymated form orally where it is converted back into the non-enzymated form in the gut. I don't really understand this, but I can give you some links where I think it's explained in more detail.

I don't know if low B2 is what's going on with you, but it's another thing to rule out. This is what dbkita said to Freddd about B2.
P5p is the cofactor most people focus on since it controls methionine synthase, shmt, and cystathione beta, and dopamine and serotonin production.

But r5p is the cofactor for mthfr. And r5p will also increase b6 to p5p conversion. This is relevant since anyone taking oral p5p has it all turn to b6 in their stomach due to the low ph (unless enteric coated which is rare). So their b2 levels will regulate their b6 to p5p levels.

My guess is that increasing b2 is ramping your conversion of 5, 10 methylene thf to methylfolate while you are ingesting methylfolate throughout the day. You have lots of thf from driving the methylation cycle, you have no rate limitation on making 5, 10 methylene thf due to adequate p5p and adequate shmt activity, add the b2 at sufficient concentration and even with a defective mthfr you still get a big shift in your equilibrium. Hypokakemia accelerates, and the reaction rates of the folate cycle and the methylation cycle "uncouple" in the new state. You probably are not in methyl trap since you have adequate b12s but for some people that may also come into play if they shift b2 in to high gear.

In my own case I seem ok on 100 mg b2 single dose provided I am not going above 800 mcg of methylfolate. Last year the additional 400-800 mcg of methylfolate, on and off 800 mcg folinic acid, SAM-e, tmg, etc along with 100 mg b2 was a mess with hypokalemia. When I switched to 50 mg b2 and 50 mg r5p it was hypokalemia wasteland.

I also mentioned DMG earlier. I'm not sure if it would help either. As I said earlier, I don't know much about SNPs, but I assume you need to take supplements such as TMG, betaine hcl, phosphatidylserine, Seriphos, and/or choline to stimulate the BHMT pathway so if you're taking DMG which diverts the flow away from the BHMT pathway then you might need more of the other supplements to balance it out. These, are the accounts I was referring to about DMG benefiting some people.
http://forums.phoenixrising.me/inde...nd-the-simplified-methylation-protocol.15385/
One person said they tried TMG with no effect, but DMG helped a lot
http://forums.phoenixrising.me/inde...mg-bhmt-vs-methionine-synthase-pathway.21403/

There's been other nutrients listed as possible cofactors. I'm not too sure about these, but I think zinc and vitamin d were mentioned. One point I do want to emphasize is that when you do figure out what's missing and you get things going, it's a distinct possibility that you'll be hit with massive hypokalemia so you should be prepared for that.
 

Lotus97

Senior Member
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Hip
A few things I forgot to mention in my previous post. It's unlikely, but potassium, vitamin C, and iron can block absorption of methylfolate in the gut. I'm not sure if they block it completely, but they do block it to a certain extent.

Which brand of methylcobalamin were you taking? Some brands are better than others. Even if you were taking a bad brand, it seems like the methylfolate still would have had an effect. This, like the other things I'm mentioned are seem like unlikely possibilities, but I guess it's good to rule everything out. It's also good for people to know that certain brands of methylcobalamin are better than others.

And did the b complex you were taking have folic acid? I'm assuming it didn't or you would have mentioned it, but I thought I'd ask anyway

Also, the vitamin A in cod liver oil can block vitamin D. I'm not too clear about other possible cofactors such as vitamin D and zinc and possibly other ones as far as whether or not they're involved in methylation. There's been some mention of them and others, but I'm hoping someone following this thread can confirm this information for me.
 

adreno

PR activist
Messages
4,841
Dbkita showed earlier in another thread that the VDR taq is bogus. In others words, it won't affect methyl group tolerance.
 

Hip

Senior Member
Messages
17,824
One point I do want to emphasize is that when you do figure out what's missing and you get things going, it's a distinct possibility that you'll be hit with massive hypokalemia so you should be prepared for that.

I often don't take potassium with my high dose B12, as I actually would like to experience some hypokalemia (just temporarily!), in order to prove that the B12 is having some effect! But B12 never seems to do much for me.

Incidentally, I also don't seem to get any good or bad effects from low-dose naltrexone either. So it seems my body is sluggish or resistant to both therapies.

Which brand of methylcobalamin were you taking? Some brands are better than others. Even if you were taking a bad brand, it seems like the methylfolate still would have had an effect. This, like the other things I'm mentioned are seem like unlikely possibilities, but I guess it's good to rule everything out. It's also good for people to know that certain brands of methylcobalamin are better than others.

I take Jarrow Formulas B12 methylcobalamin 5000 mcg, but I have also tried others. I have also tried B12 hydroxocobalamin 500 mcg subcutaneous injections.

I just reread some of the early posts in this thread. It seems you did try TMG with methylation and you say it didn't do anything. I assume you meant as far as positive benefits or increasing methylation, but did TMG trigger a depression back then or is this something more recent?

TMG has always triggered some depression in me, as has SAMe. In fact, I remember taking SAMe over a decade ago, before I had ME/CFS, and even then, SAMe still caused some depression symptoms.

Though I guess it is conceivable this depression symptom might be an adverse reaction or herx reactionas my methylation cycle begins to kick in, and if this were the case, rather than quitting the TMG / SAMe to avoid depression, perhaps I should persevere for a while, to see if taking these supplements ultimately leads to some benefits of methylation.

On Dr MyHill's webpage on methylation, she lists depression as a possible herx reaction to starting methylation.
And did the b complex you were taking have folic acid? I'm assuming it didn't or you would have mentioned it, but I thought I'd ask anyway

Unfortunately the B complex brand I have at the moment does contain 200 mcg of folic acid. (I have Swanson Premium Super Stress Vitamin B-Complex with Vitamin C).

Also, the vitamin A in cod liver oil can block vitamin D. I'm not too clear about other possible cofactors such as vitamin D and zinc and possibly other ones as far as whether or not they're involved in methylation.

I do take 25,000 IU of vitamin A daily, which is a very high dose. I take this because I find it helps lower my brain inflammation (along with the other anti-inflammatory supplements I take), which in turn reduces my anxiety and "wired but tired" symptoms.
 

Lotus97

Senior Member
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I take Jarrow Formulas B12 methylcobalamin 5000 mcg, but I have also tried others. I have also tried B12 hydroxocobalamin 500 mcg subcutaneous injections.
I assume this is before summer 2012?
http://forums.phoenixrising.me/index.php?threads/jarrow-did-it-change.18154/
I do take 25,000 IU of vitamin A daily, which is a very high dose. I take this because I find it helps lower my brain inflammation (along with the other anti-inflammatory supplements I take), which in turn reduces my anxiety and "wired but tired" symptoms.
Have you had your vitamin D tested? If so, both vit D 25 hydroxy and vit D 1, 25 dihydroxy? Did you notice any correlation between anxiety and methylation supplements? As I said before, anxiety/excitotoxicity is one of the most common symptoms other than hypokalemia as far as taking too high of a dose.
Unfortunately the B complex brand I have at the moment does contain 200 mcg of folic acid.
I suppose that's a possibility. I know for myself, folic acid doesn't block methylfolate. At least not in the convential sense as far as not experiencing symptoms. I was taking 1500 mcg of folic acid and only 100 mcg of Quatrefolic methylfolate and I still felt the effects. I'm not sure what happened. Maybe the folic acid I had been taking before I added the methylfolate made me deficient and because I was deficient I was extra sensitive. I've only been taking folinic for the past month or so. I'm hoping I'll be able to tolerate methylfolate better now unless I have a polymorphism that also causes folinic acid to block folic acid.
TMG has always triggered some depression in me, as has SAMe. In fact, I remember taking SAMe over a decade ago, before I had ME/CFS, and even then, SAMe still caused some depression symptoms.

Though I guess it is conceivable this depression symptom might be an adverse reaction or herx reactionas my methylation cycle begins to kick in, and if this were the case, rather than quitting the TMG / SAMe to avoid depression, perhaps I should persevere for a while, to see if taking these supplements ultimately leads to some benefits of methylation.

On Dr MyHill's webpage on methylation, she lists depression as a possible herx reaction to starting methylation.
It seems some people here have atypical responses and we're not exactly sure why. I spoke to someone who said any form of folate (folic acid, folinic acid, or methylfolate) makes him depressed. There doesn't seem to be any explanation why.

When I said earlier that I couldn't think of any other reason, that wasn't entirely correct. For you seems almost a certainty that TMG, betaine HCL, and SAMe are what's triggering the depression based on your trials, but I suppose it's not a bad idea to keep an open mind. I don't know all the ways that methylation can cause inflammation (which could then cause depression), but one of the ways is releasing toxins. I've heard from two people with metal toxicity that experienced depression when starting methylation. A week or two after starting methylation one of them had their urine tested and the other had a fecal test so we know they were excreting the metals and there was a study that toxic metals cause inflammatory cytokines. Methylation can also trigger inflammation for people with viral or bacterial infections. Rich thought it was due to the immune system being reactivated and fighting infections. It looks like Myhill has similar thoughts about methylation reactivating the immune system. Methylation can also increase norepinephrine levels which in some instances can be pro-inflammatory (other times norepinephrine can be anti-inflammatory).
I often don't take potassium with my high dose B12, as I actually would like to experience some hypokalemia (just temporarily!), in order to prove that the B12 is having some effect! But B12 never seems to do much for me.
Were you taking high doses of B3 at that time? I remember you saying that in the past you did that, but I'm not sure what the timeline is. And is there a reason why you didn't go above 1000 mcg of methylfolate when you were taking the high doses of B12. I'm not necessarily recommending you do that, but some people do seem to need much higher methylfolate. Metabolic Maintenance makes a 10 mg methylfolate capsule. Again, I'm not recommending this. I'm only pointing out that a few people do need higher doses, but most people don't. I usually recommend people be cautious. Based on what happened to Freddd and what dbkita said about B2 being a cofactor for MTHFR, maybe R5P would do something. Like I said before, I'm kind of stumped. Maybe Freddd or dbkita would know since they know a lot more than me. But it might be something completely unsuspected. Freddd was completely blindsided with B2 and dbkita had a similar experience a year or two when he switched from B2 to R5P:
Last year switching from 100 mg b2 to 100 mg r5p sodium was one of the main changes that forced me into hypokalemia and not even 11 grams per day could contain it. More recently I went to two split two doses of 50 mg of riboflavin and while I had more verve and energy at first, within a few days I had charlie horses and terrible foot cramps.

Be warned that b2 absorption is not linear after 30 mg. It saturates pretty quickly. 100 mg at once might net you 40-50 mg total. That is why I thought to split doses and bam. R5p sodium has no such saturation and high oral bioavailability which is probably why it was so devastating to switch to 100 mg of that almost a year ago.
One last thing, I'm not sure if this theory applies to methylation specifically or is even 100% accurate, but this is what Freddd said about certain cofactors:
Zinc, Vit D, Magnesium, p5p, Pantethine D-ribose, TMG, Vit C , SAM-e, B2, B1 <2% have major startup effect for each of these alone as first factor and delaying startup until added (increased). Generally some or all of these step up healing activity indicating that each of these has the potential to be the most limiting factor in some people. Kicking off overall startup is rare. Sam-e first isn’t a good test of need because it’s formation is dependent upon the Deadlock Quartet. As a later add-on it can break the logjam or rebalance the combinations..
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Lotus, very interesting...

Just curious about a few new things I did not know. How do you know methylation increases noradrenaline? Also I am not much on startup symptoms as I have been taking supplements my whole life, but I didn't know that anxiety is a major startup symptom. I experienced anxiety at age 50 and fixed mine with DHEA.

I am most interested in your comments about Fredd being blindsided about B2? I have pointed out for years that B2 is a cofactor for MTHFR but Freddd always said it was covered in the active B complex he recommends and, indeed, everything I read said only a small dose is needed. I just always hated when people failed to list it as a methylation supplement - including manufacturers who make (perscription even!) methylation supplements containing only some form of B6, some form of folate and some form of B12. So anyway, what blindsided Freddd? Is there some new info on the DOSE of B2 required?

ALso I am surprised about this:

Freddd said: Zinc, Vit D, Magnesium, p5p, Pantethine D-ribose, TMG, Vit C , SAM-e, B2, B1 <2% have major startup effect...

I have had electrolyte problems all my life (suddenly needing calcium, magnesium, or sugar at any time unpredictably) and I thought it was just me and my poor health. Potassium was not on my radar because the low dose pills had no effect. Still, it's hard to imagine some of the above supplements causing startup symptoms.
Zinc?? Magnesium?? C??

What also surprises me is that his list does NOT include folate. High dose folate is the only one that I KNOW causes effects on me -- I take that 800 mcg Solgar metafolin with no problem, but if I try higher doses I get immediate electrolyte problems and also symptoms of SAMe deficiency (the weak and painful wrist symptoms for example). So I would think FOLATE would be a big hitter on the 'startup' supplements list.

(Also, speaking of that, there was someone on that high dose folate thread - Phoenix or something like that - who dropped right out of this conference. I wonder if that person is even ok.

Triff
Triff
 

Lotus97

Senior Member
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triffid113
I posted about methylation and norepinephrine/noradrenaline in this thread
http://forums.phoenixrising.me/index.php?threads/mthfr-with-high-epinephrine.23005/#post-352099
There's also a thread about norepinephrine if you or anyone else is interested
http://forums.phoenixrising.me/index.php?threads/how-to-lower-norepinephrine.22518/

This is the thread about Freddd and B2.
http://forums.phoenixrising.me/inde...kalemia-and-methylfolate-insufficiency.22968/

Freddd said: Zinc, Vit D, Magnesium, p5p, Pantethine D-ribose, TMG, Vit C , SAM-e, B2, B1 <2% have major startup effect...
I don't know if Freddd was referring to methylation or not. I don't want to misstate his theory. If you get a chance to ask him, I'd like to know. Also, keep in mind he says that this is <2% (according to him).
What also surprises me is that his list does NOT include folate. High dose folate is the only one that I KNOW causes effects on me -- I take that 800 mcg Solgar metafolin with no problem, but if I try higher doses I get immediate electrolyte problems and also symptoms of SAMe deficiency (the weak and painful wrist symptoms for example). So I would think FOLATE would be a big hitter on the 'startup' supplements list.
He was just talking about things other than methylfolate and methylcobalamin. You can read his entire post in his HEALING thread. I don't remember exactly where it was, but I think it's on one of the first few pages. dbkita says he also takes 800 mcg of methylfolate, but if he tries to up the dose he's hit with hypokalemia.
I have had electrolyte problems all my life (suddenly needing calcium, magnesium, or sugar at any time unpredictably) and I thought it was just me and my poor health.
I don't know much about this, but have you tried taurine? That's supposed to help with electrolyte balance, but I assume the best thing would be to determine the underlying illness that's causing electrolyte imbalance.
(Also, speaking of that, there was someone on that high dose folate thread - Phoenix or something like that - who dropped right out of this conference. I wonder if that person is even ok.
I wonder about that stuff too. We only hear about the success stories of methylation. For anyone who has a bad experience they usually give up on methylation and don't post in the forums. Hopefully nothing serious has happened to anyone doing methylation, but if something did we'd probably never hear about it unless they had a friend or family member who was a member of Phoenix Rising.
 

Lotus97

Senior Member
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triffid113
I just realized that first thread I linked to just talks about how stimulating the BHMT pathyway can increase norepinephrine and also how methylation can increase epinephrine. Methylation does increase neurotransmitters in general though (not just norepinephrine). I don't know the specifics. Adreno and Caledonia were the ones who told me so they can explain in more detail if you're interested. Also, folinic acid, methylfolate, and B12 can all affect CNS and neurotransmitters. I don't know the details of those either, but I think folinic acid and methylfolate (and maybe B12) need to be taken in high doses for "CNS penetration and saturation". dbkita is the one who told me about that and those are the words he used that I put in quotes. Also, I'm not sure if the effect on neurotransmitters needs to be taken in high doses. For example, I seem to get wired just from hydroxocobalamin and I know someone who says she gets wired from low doses of methylcobalamin.
 

Lotus97

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Rich said something similar about cofactors
I've worked up to the full protocol and have been on it every day for two and a half weeks now. I'm not feeling anything, good or bad. Was wondering if it would be ok to try increasing the b-12, or is this a no-no? Suggestions?
Hi, monobear.

It would be O.K. to raise the dosage of B12, and it might help. There are also other possibilities:

You may be lacking enough of the vitamin and mineral cofactors that are needed by the enzymes in the methylation cycle and related pathways. These include the other B vitamins, zinc, magnesium, manganese, copper, and selenium. Some people have HPU, which depletes several of these cofactors, especially zinc and vitamin B6.

Another possibility is high levels of toxic heavy metals, such as mercury, which can block enzymes in this part of the metabolism. If this is the problem, it may be necessary to do some chelation before the methylation cycle will get going.

If it's feasible for you to do some testing, that could help to pin down what's going on. The Health Diagnostics and Research Institute methylation pathways panel will give direct measures of the status of the methylation cycle, the folate metabolism and glutathione. A Genova Diagnostics Metabolic Analysis Profile, together with amino acid testing preferably both plasma and urine, and urine essential elements panel, such as those offered by Doctor's Data) will indicate whether there are deficiencies in cofactors. A Doctor's Data urine toxic elements test, taken with and without chelator challenge with DMSA, will give an indication of the presence of toxic heavy metals. All of these except the first one are available without a doctor's order from www.directlabs.com.

Best regards,

Rich
 

LaurieL

Senior Member
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Location
Midwest
I ran across this conundrum a few months ago.....I have been away. Concerning potassium (hypokalemia) and methylcobalamin. They are antagonists. More methylcobalamin equals less potassium, and vice versa. If this is indeed the case, then there is an upper limit dose to methylcobalamin, but nobody knows what it is. This directly opposes Freddd's passive diffusion high dose induced healing on a theoretical level and may explain why with high dose diffusion therapy of methylcobalamin, one may develop potassium issues (electrolyte). I have held steady on my doses of methylcobalamin, methylfolate, and adenosylcobalamin for a very long time. My electrolyte issues have also seemed to have remained steady for a few months now. I take more adenosylcobalamin than I do methylcobalaimin. And in the literature, I have found a sway to the most active and the most dependant Vitamin B in the body is adenosylcobalamin, not methylcobalamin.

Nice to be back finally.

LaurieL