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SAM-e methylation confusion

NotThisGuy

Senior Member
Messages
312
Hi,
I found something odd about SAM-e which I can't quite explain.
The reactions people have to SAM-e (wether CFS or not) seems to be all over the place.
Some people feel better on it and others seem to get a lot of depression and anxiety.

I tried SAM-e myself and at first I felt good on it.
I had less allergic symptoms probably due less histamines and my mind was clearer. It was easier to think and express myself.
Than on the third day something hit me. Severe muscle fatigue. It was almost like in a crash but not quite like a crash. There was something different.

It might have been a phosphorus deficiency. I'm not completely sure about this but takin phosphorus made me feel better.

Anyways I read on this forum and found a post of someone saying, he only uses the SAM-e Tosylate disulfate.
Appearently SAM-e is very labile and unstable and to have it as a supplement there are 2 different stable forms on the market.

The SAM-e Tosylate disulfate with 68-80% SAM-e and the SAM-e Butanedisulfonate with to me unkown amount of SAM-e.

SAM-e Tosylate disulfate has only the S,S form of SAM-e which is the bioactive form.
Im not sure about what form is in SAM-e Butanedisulfonate.

Now I found this interesting study:
https://www.ncbi.nlm.nih.gov/pubmed/685755

Summery:
-mice where injected with 96% purity SAM-e and methylation was blocked
-mice where injected "pure SAM-e" from another source and methylation was not blocked

now the abstract is really terrible and I assume that the study probably was terribly designed. Would like to read the full study but can not find it anywhere.

So now I'm wondering if we possibly are missing something about SAM-e and methylation.
I dont think it would be possible for us to source "pure SAM-e" and I dont know of SAM-e with 96% purity would match SAM-e Butanedisulfonate.
They also dont state if they are using S,S SAM-e or R,S SAM-e but I'm wondering if people who react poorly to SAM-e might be the ones blocking their methylation somehow through SAM-e and I wonder if this could be undone by taking the right SAM-e.

As usual tagging @Hip who will hopefully know more about this but I'd be glead to hear all of you guys thoughts on this topic.
 

Hip

Senior Member
Messages
17,824
Some people feel better on it and others seem to get a lot of depression and anxiety.

I've noticed increased depression from taking SAM-e, and also when taking TMG or betaine hydrochloride, which are all methyl donors.

This depression may arise because methyl donor supplements increase the interferon alpha response (ref: here), and interferon alpha is well known to cause depression. Depression is one of the main problematic side effects of interferon therapy.

ME/CFS patients have chronic viral infections, so their body's interferon response is likely ongoing much of the time (which may, incidentally, play a role in creating the ME/CFS fatigue, as interferon causes fatigue).

So when an ME/CFS patient takes a methyl donor like SAM-e, that's probably going to further ramp up the secretion of interferon alpha, and may thus explain why depression if felt.


I've never noticed any increase depression from B12 injections however.
 

NotThisGuy

Senior Member
Messages
312
I've noticed increased depression from taking SAM-e, and also when taking TMG or betaine hydrochloride, which are all methyl donors.

This depression may arise because methyl donor supplements increase the interferon alpha response (ref: here), and interferon alpha is well known to cause depression. Depression is one of the main problematic side effects of interferon therapy.

ME/CFS patients have chronic viral infections, so their body's interferon response is likely ongoing much of the time (which may, incidentally, play a role in creating the ME/CFS fatigue, as interferon causes fatigue).

So when an ME/CFS patient takes a methyl donor like SAM-e, that's probably going to further ramp up the secretion of interferon alpha, and may thus explain why depression if felt.


I've never noticed any increase depression from B12 injections however.

That sounds logic hip.
But I still think that some peoples experience go a bit beyond increased interferon alpha.
I know of one user here who didnt get rid of the depression one month after taking some SAM-e. As far as I understood his posts it was only when he added meB12 and methylfolate, that his severe depression was gone.
I read one post of someone who didnt get rid of his anxiety anymore after taking SAM-e even when taking GABA. Actually as far as I remember GABA made him/her even more anxious which wasnt the case before taking SAM-e.
So I think in some cases there is another cause than just increased interferon alpha especially if the SAM-e sideeffects dont go away shortly after dropping SAM-e.

thats why im wondering if there is a SAM-e version out there that might block methylation just like the study claims.

Of course the study I posted is a bit old now and SAM-e production might be a bit different now. We only know that back then there was an SAM-e product with 96% purity and one SAM-e product with higher purity. The 96% induced methylation block.

Nowadays you can buy SAM-e stabilized with a salt either Tosylate disulfate or Butanedisulfonate.
One question is, before binding SAM-e with a salt, do they use the 96% SAM-e or the one with the higher purity.
The other question is does butanedisulfonate contain R,S SAM-e or S,S SAM-e and which one is superior.

I found this website
https://www.frost.com/prod/servlet/market-insight-print.pag?docid=CEHR-4SNPKD

There is the rumor going around that Butanedisulfonate is superior to the other salt and they also list some brands that contain Butanedisulfonate.
However the source is 18 years old and I checked all the brands and they all use Tosylate disulfate now.

Wondering what happened that they changed their SAM-e formula and also wondering what kind of brands out there still use Butanedisulfonate.