• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

28 y/o, not well, looking for help

Messages
16
I have many CFS symptoms, plus many more. I'm not sure if this could be causing my issues, or just part of it. Could anyone please help and advise?
 

Attachments

  • MTHFR.png
    MTHFR.png
    34.6 KB · Views: 30
Messages
61
Location
Germany
With all that COMT maybe HB12 would be better.
I know that methylfolate directly interacts with COMT, thus I wouldnt recommend methylfolate.
Could you tell me how MB12 biochemically interacts with COMT?
thank you

EDIT: I did a little research and found that mb12 would increase SAMe which would increase COMT activity. His COMT mutation would let him have increased dopamine. So increased SAMe would be good to help his COMT get rid of too much histamine. So in this sence I would think mb12 would be a good idea.

But Im sure there are other pathways Im missing out. Pls help me out.
Btw: Finally I know why I had restless legs type symptoms from b12.
 
Last edited:
Messages
6
Gandalf,

In COMT "--" the mechanism is that the breaking down of dopamine requires methyl groups, so they get used up, and having extra methyl groups around is a good thing. But in COMT++ the breakdown is not happening, and those methyl groups are not being used up, and potentially causing hyperactivity, and sensitivity to pain.

So it's methyl groups whether it comes from methyl folate or methyl b12.
 
Messages
61
Location
Germany
@MTHFREase
After furter evaluation, I came to the conclusion, that you are correct with the fact, that hb12 should work better than mb12 for decreasing dopamine. But I dont fully agree with the mechanism you have presented.
I would say hb12 is better because it pulls away more methyl groups from methylfolate,leaving less there for BH4 and thus Dopamine production. The 2nd good effect is the increase in SAMe, which breaks down the dopamine even quicker. These 2 effects combined make it very effective in lowering dopamine levels.
 
Last edited:

Helen

Senior Member
Messages
2,243
I have many CFS s ymptoms, plus many more. I'm not sure if this could be causing my issues, or just part of it. Could anyone please help and advise?

Please post your detox panel too. You will probably feel much better when you have found the right combinations and doses of B12 and methylfolate. Check the links under @caledonia ´s posts e.g. and @Freddd ´s suggestions.

@Gandalf , @MTHFREase I have 5 out of 6 possible polymorphisms in the COMT SNP´s and I have never had any problems with methylcobalamin in high doses. I have taken injections for 20 years, 3-4 every week, 10 mg MeCbl.

I think we should be careful with advice that is based on unconfirmed theories. I know that there are people with COMT polymorphisms that have reacted strongly on methylcobalamin, but I am sure from myself and some others that all don´t.
 
Messages
61
Location
Germany
The reason why I would start with mb12 is because:
-he has MTHFR -> low methylfolate -> very few methyl-groups
-Also he has COMT so methylfolate would increase Dopamine
-But due to MTHFR, methyl groups are missing and needed.
-ppl with COMT may have problems with methyl-b12

If I take all this together, I logically come to the conclusion, that I would try a low methyl-b12 dose.

Wouldnt you agree?
 

caledonia

Senior Member
The cause is always a combination of genetics plus environmental factors. A Nutreval test can help pick up what is going on functionally with your body - it tests the gut, metals, amino acids, vitamins, minerals, Kreb's cycle, etc. It's also important to look back at your history of toxic exposures, viruses, extreme stress, etc. It all adds up.

According to Yasko - you have three First Priority mutations which need to be addressed before diving into B12 and folate.

For SHMT, take folinic acid. For ACAT, bile salts. Those two SNPs are also the "leaky gut" genes, so if you have gut issues you should also address that first while taking SHMT and ACAT supps. Use the 4R Gut Rebuilding program to fix the gut.

You also have CBS which may or may not be expressed. If you have trouble tolerating methyl supps, such as a stress/anxiety reaction or a head pressure, then CBS is expressed and you'll have to treat that. Heartfixer has a good CBS protocol, which I've used successfully, except for I used the Free Thiol diet and no Yasko RNAs.

For MTHFR C677T, take methylfolate. For MTRR, B12.

For your combination of COMT and VDR taq, Yasko suggests hydroxycobalamin and adenosylcobalamin, otherwise you could be prone to mood swings.

Like the others are saying, even if your genetics suggest something, something different could be going on functionally to change that. So the best thing is to take it easy when starting methylation supplements in case of adverse reactions.

Watch the Methylation Made Easy videos (in my signature), and then read the Start Low and Go Slow document.

The other things I've mentioned are also linked in my signature.

Looking at the detox SNPs can also be helpful. Biggies there for ME/CFS are GST and SOD. Plus you can get insight into why you don't tolerate certain medicines.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
The reason why I would start with mb12 is because:
-he has MTHFR -> low methylfolate -> very few methyl-groups
-Also he has COMT so methylfolate would increase Dopamine
-But due to MTHFR, methyl groups are missing and needed.
-ppl with COMT may have problems with methyl-b12

If I take all this together, I logically come to the conclusion, that I would try a low methyl-b12 dose.

Wouldnt you agree?

Hi Gandalf,

The whole problem with MeCbl as a methyl donor is that it is 18 methyl on a 1335 molecular weight. Of an injected dose 99% is excreted via urine within 2 days unchanged, methyl groups all in place. MeCbl is NOT a net methyl donor. It plays pass the hot potato with methyl groups in its operations but it doesn't supply the methyl group. HyCbl makes use of this reclamation system that allows this but exhaust methyl groups and required ATP as well. MeCbl is a NET ZERO on methyl donation under normal circumstances, except when toxins strip the methyl. SAM-e is part of the methionine - homocysteine - methionine cycle too. So is methylfolate. So MeCbl causing production of SAM-e by passing on a methyl group it no longer had makes the SAM-e with no net difference which passes it along but ultimately the methyl groups come from bulk sources. According to the theories the HyCbl should work as well as MeCbl once it has donated once, or if other theories are right it is stripped immediately and so functionally it "should not" perform differently from HyCbl, but everybody knows how bogus that idea is. The main upset is that 60 years of research mainly on CyCbl and HyCbl has not prepared people for the idea that MeCbl/AdoCbl are 100x more effective for everybody deficient and it is NOT because it is a net methyl donor because it isn't. However, the main circulating form of cobalamin is MeCbl according to research. It acts far more as a catalyst. Neither MeCbl or AdoCbl are "used up" in their normal functioning. They act like a catalyst. Some things poison them.. In the mitochondria AdoCbl only turns over with mito replacement. In serum it is as vulnerable as MeCbl. MeCbl keeps recycling until a toxin like Nitrous Oxide or cyanide or glutathione (in excess amounts) oxidizes it and then quickly excreted.

I believe that the ideas behind interpretation of the genetic material is based on the 60 years of research on folic acid and CyCbl/HyCbl and just plain not predictive of MeCbl, AdoCbl and l-methylfolate and how they work.


However, I also have no objection to somebody who wants to titrate from a crumb on up or put a sublingual in their mouth and chew it and swallow as soon as they feel an effect. The effect stops increasing within minutes of chewing and swallowing. Depending upon the exact nature of the hypersensitivity it might control things. Part of the problem is that with MeCbl and/or AdoCbl and/or l-methyfolate, things turn on in layers. When layer "X" gets turned on, layers "Y" and "Z" get shorted much worse in order to supply layer "X". That causes these paradoxical folate and b12 deficiency symptoms when healing is going on in some ways and getting worse in other ways.

My experience was of 5 years of CNS deterioration at the same time as 5 years of profound physical healing. By the time my peripheral neuropathies were undetectable my Subacute Combined Degeneration was getting worse almost daily. I was in paradoxical folate insufficiency the whole time on who knows how many levels, several at least. I wasn't having mitochondria proliferation. I wasn't having muscles growing. My CNS was deteriorating. I had miserable IBS. That was just before LCF and increased Metafolin.

Personally I wouldn't want to maintain partial B12 and/or folate starvation as a means of slowing healing. It doesn't "slow healing" a little all over or anything. It heals some things and cuts others off and leaves them to increasing damage.
 
Last edited: