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

[Lotus97]

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

I don't know if there's an additional mechanism with methylcobalamin specifically, but in general I think it's methylation itself that causes the hypokalemia. I know someone that was taking high doses of methylcobalamin, but didn't have problems until they added methylfolate. Also, as I mentioned earlier, when Freddd and dbkita added B2 and R5P that increased their need for potassium.

 

[LaurieL]

I don't know if there's an additional mechanism with methylcobalamin specifically, but in general I think it's methylation itself that causes the hypokalemia. I know someone that was taking high doses of methylcobalamin, but didn't have problems until they added methylfolate. Also, as I mentioned earlier, when Freddd and dbkita added B2 and R5P that increased their need for potassium.

I have taken vitamin B2 for as long as I have been taking methylation supplements. At the doses I am at, I do not have potassium issues, and my healing progresses.

The reason I have spoken up is my concern that the two very different active B's used in the methylation protocol target two very different processes, and that one is being completely ignored by most of us, while doing the other. Add methylfolate into the mix, and one could have some very serious problems. And we have seen that in some here.

You mentioned the additional mechanism. Let me throw this out there if you are interested. Adenosylcobalamin is the neuro B vitamin. Lack of AdoB12 leads to all sorts of neurological damage. Methylcobalamin is the DNA vitamin. Folate not folic acid is the myelin vitamin. Methylfolate does not affect adenosylcobalamin supplementation, but it does have an adverse consequence when supplemented with methylb. That adverse consequence can result in hypokalemia and gout. And that is megablastic anemia. Supplement this anemia with methylb and you mask the folate deficiency. Supplement large doses of methylb with folate, and you have some serious methyl trapping going on.

MethylB is through the MTR enzyme and adenosylcobalamin is through the MUT enzyme. Why ignore the second half, the concurrent half that belongs alongside methylation and active B supplementation? It is adenosylcobalamin that is stored in the body, in the liver, not methylcobalamin. I suspect what we will be discovering in the near future is that adenosylcobalamin in high doses with very conservative doses of methylfolate and methylcobalamin, lead to bigger, and maintained improvements, and less complications and roadblocks.

I have no extra need for potassium but I do however need L-Carnitine.

LaurieL

I would also like to add, that it is adenosylcobalamin that is used by the mitochondria, not methylb. I can't speak for everyone here, but I have mitochondrial problems, TCA problems, methylation problems, and detox problems. These all go together for wellness.

 

[Lotus97]

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.

I'm not sure if this is significant or not, but Nandixon said that vitamin A (in forms other than beta carotene) can inhibit SHMT (just as folinic acid inhibits SHMT for Freddd causing folate deficiency).

BTW, in theory, P-5-P and zinc should increase the activity and quantity of SHMT. Too much vitamin A (not beta-carotene) may decrease it.

This is from Rich about what happens if the SHMT reaction is inhibited. He's talking about folinic acid, but I think Nandixon was saying that vitamin A could also have the same effect.

Folinic acid is a buffer or storage form of folate that can be converted to other forms readily in most people.

The reason for including it in the simplified methylation protocol is that it can supply forms of folate needed to make new RNA and DNA while the methionine synthase enzyme is still running its reaction slowly. This reaction is fed directly by methylfolate, but until it goes through the reaction to produce tetrahydrofolate, it can't be used for forming other folates.

In order to use folinic acid a person must have a normally functioning MTHFS enzyme (not the same as MTHFR). If this enzyme is slow for genetic reasons, folinic acid can build up. and that will inhibit the SHMT reaction, which in turn will inhibit the normal production of MTHF, which in turn will hinder formation of DNA and formation of methylfolate.

According to Freddd, he cannot tolerate folinic acid, and there seem to be some others who can't, also. It would be helpful to pin down what SNP or SNPs are responsible for this.

Best regards,

Rich

There's more information about SHMT, MTHFS, and folinic acid in this thread
http://forums.phoenixrising.me/inde...d-intolerance-request-for-genetic-data.19168/

I still think your experience with SAMe might be significant. I don't know what it means or if there's anything that could be done (I wouldn't want to try to "push through" depression). But it is important to note that it's one of the only methylation supplements that causes a reaction of some kind for you.

 

[Hip]

Nandixon said that vitamin A (in forms other than beta carotene) can inhibit SHMT

Thanks, that's interesting. I couldn't find any references to vitamin A inhibiting SHMT when I Googled it; but in any case I think I will stop taking vitamin A for a while, and see if that helps.

 

[Lotus97]

Thanks, that's interesting. I couldn't find any references to vitamin A inhibiting SHMT when I Googled it; but in any case I think I will stop taking vitamin A for a while, and see if that helps.

This could just be wild goose chase (just as the B2/R5P angle I mentioned might also), but I figured you would at least want to have all the information available so you could consider all the variables. You seem to have a better grasp of health issues on a technical level so maybe you can piece it all together and come up with something. However, I talked to dbkita about vitamin A inhibiting SHMT and this is what he said:

I think you would have to have pretty high intake levels of vitamin A to make any real impact. In general for multiple reasons retinol vitamin A is the best form.

25,000 iu does seem like a high dose though. I am concerned about retinol blocking vitamin D though. That's why I'm only taking beta carotene. My vitamin d hydroxy 25 and dihydroxy 1,25 were both low even though I was taking 6000 iu of vitamin D. Have you had your vitamin d levels tested? I have considered taking some of my vitamin a in the form of retinol. I'm not sure if I have brain inflammation, but it seems like it might be a common issue. And I'm also not sure if I'm converting enough of the beta carotene into retinol. With many of these supplements you treat on condition, but then it potentially has a detrimental impact on something else. Just as another example, alpha lipoic acid can cause a biotin deficiency. Biotin is a good supplement to take regardless of whether you're taking ALA, but a lot of people don't have comprehensive supplement regimen and even then you might be missing out on something.

 

[Lotus97]

As for the vitamin D dihydroxycholecalciferol, this is what dbkita told me

1,25 calcitriol is a secondary inflammatory marker that looks at Th1 level macrophage inflammation (provided you do no have sarcoidosis).

and this is what Ema told me

I accidentally got the *wrong* Vitamin D test during some routine labs, the active form 1,25 D, instead of the storage form 25-OH. It came back elevated despite "optimal" 25-OH levels of 70-90 and so I started trying to figure out what might have gone wrong. I was especially concerned because having high 1,25 D levels looks to be immune suppressive.

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Here are some links to things I found useful:​

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http://arizonaadvancedmedicine.com/articles/immune_system_dysfunction.html​

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http://perfecthealthdiet.com/2010/08/vitamin-d-dysregulation-in-chronic-infectious-diseases/​

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So I stopped my Vit D supplementation and my 25-OH level fell down to 30 or so and my 1,25 D level also fell to about 35. Since then, I've gone back on Vit D supplementation (approx 2000 to 4000 IU/day) which keeps my levels around 50. That also seems to keep the active 1,25 D in the appropriate range as well for me without letting the storage 25-OH get too low either.​

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I think it is fine for people who have a "normal" VDR to take as much Vitamin D as they like because their body will keep the active form tightly regulated in the proper range. But I think it is a real problem (that will likely come back to bite some of these high D recommenders in the bottom) not to test 1,25D at least once when supplementing with D over 5000 IU/day to make sure that the VDR is working correctly.​

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[Lotus97]

Hip
Have you tried lithium? That's supposed to help with brain inflammation, but also B12 transport. This is what greenshots said:

I think transport issues have alott of impact. My B12 levels used to be very high but I apparently wasn't using it. When I got my methylation going along with lithium orotate, my B12 levels normalized.

 

[Hip]

Hip
Have you tried lithium? That's supposed to help with brain inflammation, but also B12 transport. This is what greenshots said:

Coincidentally enough, I read the same thing last week, and have just begun to include lithium in my methylation regimen (125 mg of lithium orotate daily, providing 5 mg of lithium). We'll see if any improvements appear.

I have also stopped taking vitamin A, in case this is inhibiting SHMT.

 

[Lotus97]

Coincidentally enough, I read the same thing last week, and have just begun to include lithium in my methylation regimen (125 mg of lithium orotate daily, providing 5 mg of lithium). We'll see if any improvements appear.

I have also stopped taking vitamin A, in case this is inhibiting SHMT.

I've been taking lithium for a couple of months. I'm not sure it's helped my anxiety or depression, but most of my supplements I can't tell whether they're working or not. I was thinking about dropping it until I read about the B12 transport and brain inflammation thing.

Are you also taking zinc and P5P for SHMT? dbkita seemed to think some retinol was good, but I don't know how much is too much.

And have you tried R5P also? It's hard to know what step is blocked without getting tested (which is expensive), but you saw how big an impact B2 and R5P had on dbkita and Freddd so for some people it does seem to be important.

 

[Hip]

Lotus97

I have tried zinc and P5P, without seeing any major benefits. Though I have not yet tried riboflavin 5 phosphate (R5P), and I think I ought to really.

 

[Lotus97]

If you do switch to beta carotene, zinc is a cofactor in converting it into retinol. I'm actually thinking of taking some retinol and just upping my vitamin D dossage. P5P is still important for folate metabolism and all of the b vitamins are important for various functions. B2 and B3 recycle glutathione for example. And most of them are involved in Krebs which would also help increase glutathione.

 

[greenshots]

This isn't an easy answer but my doc used methylation, nervous system, and immune supports for us and that seemed to make all the difference in the world! Knowing your nervous system type seems to help by supporting with the right stuff whereas knowing your biggest immune or infection issues helps with using the right immune factors. As for the methylation stuff, that is all about layering and when I see the mention about TMG for a couple weeks without anything major happenng.......well.......I wouldn't expect anything major, other then maybe some detox. If you get on the right mix,,its gonna be more about overlapping the right things, with the other variables mentioned, and then some time. It took us decades to get in this fix so it usually takes at least a couple years to get out and thats hard to stomach let alone wait for! But it seems to be consistent in my biomed group's recovery, too. So if you try something but stop some of them when there's no big change, its probably going to be premature. It took 9-12 months for me to see some heavy improvements and I really can't say that any one thing completely knocked my socks off.

In your case, I don't see snps that are that big of a deal considering the low number of defects but the detox profile seems pretty important. i don't know allot about that panel but my doc has worked with people she says don't always have terrible methylation panels but when she combines the detox panel with the toxic triggers they've had its really telling. It seems to me you might be one of the one of the ones she was talking about. Like Caledonia said, the SHMT and CBS are important but overall, your panel is not that bad. On average, the people in my biomed group had an average of 14-18 defects and Several of us have 22 or 24 of them. Seems like your toxic load and infections may be one heckuva big deal.

Just received my 23andme genotyping results, and having downloaded the raw data file of my gene results (available here on the 23andme website), and having run this file through the Genetic Genie website (here), I obtained my methylation and detox profile results, were are both given below.

I'd be most grateful if the interpretation experts here on Phoenix Rising could make some comments regarding my results.

Methylation Analysis Results
View attachment 4601



Detox Profile Results
View attachment 4602


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?

 

[Hip]

In your case, I don't see snps that are that big of a deal considering the low number of defects but the detox profile seems pretty important. i don't know allot about that panel but my doc has worked with people she says don't always have terrible methylation panels but when she combines the detox panel with the toxic triggers they've had its really telling. It seems to me you might be one of the one of the ones she was talking about.

Thanks for your comments, greenshots.

So you are saying that I ought to look into my detox panel a bit more, to see if can support the weak detox pathways.