SAM-E & TMG Question

Amber

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what about vit e ,vitamin b6, niacin, folate and b12 those not important??

P5p=activated form of b6. Some people have problem converting b6 into p5p which is why i said to take p5p and not normal b6. Regular B6 can also have negative side effects.

Vitamin E can be good too especially for its anti oxidant function.

Niacin quickly downregulates methylation so it would definitely help.

Folate and b12 increase methylation so taking those when you are overmethylating will make it worse
 
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P5p=activated form of b6. Some people have problem converting b6 into p5p which is why i said to take p5p and not normal b6. Regular B6 can also have negative side effects.

Vitamin E can be good too especially for its anti oxidant function.

Niacin quickly downregulates methylation so it would definitely help.

Folate and b12 increase methylation so taking those when you are overmethylating will make it worse
weird because the link suggest those for overmethylation
 
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So ZMA supplement are on to something...
 

success23

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Sam-e is needed for the creation of dopamine also. Sam-e does not create serotonin it just slows its breakdown.

Tmg is great. Lowers hemocysteine and helps recycle methionine and keeps the need for it very low.. Also good for the heart and dopamine production:)
 

Zpol

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Sam-e is needed for the creation of dopamine also. Sam-e does not create serotonin it just slows its breakdown.

Tmg is great. Lowers hemocysteine and helps recycle methionine and keeps the need for it very low.. Also good for the heart and dopamine production:)

@tisho23
Keeps need for methionine low... I didn't know this, that's a plus. I'm going to research this function more in depth, and in regards to dopamine too. If you have any sources to share, that'd be cool.
I'm debating taking TMG for reducing Homocysteine and for gut/digestion help. Taking methyl donors in supplement form can be tricky... don't want to have too many methyl donors floating around, it's my understanding they could end up attaching to DNA and altering gene expression.
 

BingDing

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SAM-e is the general purpose methyl donor of the body, it is used in dozens of reactions that are essential and healthy. When it is made, methionine is converted into homocysteine. Lots of information on the forum and WIKI, though it takes a lot of study to figure it out (to the extent that is even possible). Supplementing SAM-e does not make any sense to me. Supplementing TMG does, even for people without the MTHFR problem.

 

x-ray peat

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Doesnt it just convert homocysteine in the body to methionine? Homocysteine isn't a good thing
I had to refresh my memory on this but I think that most of the reduction of homocysteine by TMG is only seen in unhealthy people, people with B6 deficiency or people with high homocysteine levels. I also remember @haidut warning against TMG because of the increase in methionine and that there are better ways to reduce homocysteine, like glycine. Maybe he can clarify again why its bad.

METHIONINE, SAMe, HOMOCYSTEINE, AND THE METHIONINE CYCLE
V. Betaine (TMG)

TMG converts homocysteine to methionine in the liver, whereas folate-dependent remethylation of homocysteine takes place in all cells. TMG strongly reduces plasma homocysteine in subjects with low serum folate, and has a weaker effect when folate is high, whereas Vitamin B6 has little or no effect on plasma homocysteine levels [ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY; Holm,PI; 25(2):379-385 (2005)]. TMG has little effect on plasma homocysteine in healthy subjects [EUROPEAN JOURNAL OF CLINICAL NUTRITION; Schwab,U; 65(1):70-76 (2011)], but can protect against the elevated homocysteine resulting from feeding methionine [NUTRITION, METABOLISM, AND CARDIOVASCULAR DISEASES; Atkinson,W; 19(11):767-773 (2009)].

Much of the SAMe in the liver is converted to the water-phase antioxidant glutathione. Six grams of TMG daily for three months reduced plasma homocysteine levels by 9% in 22 obese subjects [AMERICAN JOURNAL OF CLINICAL NUTRITION; Schwab,U; 76(5):961-967 (2002)]. TMG decreases plasma homocysteine more in patients with high plasma homocysteine than in healthy volunteers [ARCHIVES OF INTERNAL MEDICINE; Brouwer,IA; 160(16):2546-2547 (2000)]. Because TMG helps reduce homocysteine, it could protect against heart disease — but see the sections above on folic acid and Vitamin B12.
 
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Mito

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I had to refresh my memory on this but I think that most of the reduction of homocysteine by TMG is only seen in unhealthy people, people with B6 deficiency or people with high homocysteine levels. I also remember @haidut warning against TMG because of the increase in methionine and that there are better ways to reduce homocysteine, like glycine. Maybe he can clarify again why its bad.

Homocysteine converts to methionine via the folate path (MTHFR) or the “short cut” path (BHMT). Supplementing TMG will push homocysteine down the BHMT path. Either of these paths increase methionine. Haidut warns about the too much methionine and potential excess methylation. Travis warns about methionine potentially becoming polyamines. Homocysteine can also convert to cysteine via the CBS (B6 dependent) path.

Homocysteine is bad so we want it to convert to either methionine or cysteine, but maybe the cysteine path is safer? Or an even better idea might be to limit homocysteine from being created in the first place. Masterjohn has discussed strategies for that which include supplementing creatine.
 

ddjd

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Homocysteine converts to methionine via the folate path (MTHFR) or the “short cut” path (BHMT). Supplementing TMG will push homocysteine down the BHMT path. Either of these paths increase methionine. Haidut warns about the too much methionine and potential excess methylation. Travis warns about methionine potentially becoming polyamines. Homocysteine can also convert to cysteine via the CBS (B6 dependent) path.

Homocysteine is bad so we want it to convert to either methionine or cysteine, but maybe the cysteine path is safer? Or an even better idea might be to limit homocysteine from being created in the first place. Masterjohn has discussed strategies for that which include supplementing creatine.
Isn't creatine made up of Methionine and Lysine?

Surely it would make far more sense to reduce your overall intake of Methionine rich foods.

Using tmg to convert homocysteine stores would affect methionine levels minimally compared to the amount of Methionine you're getting directly in the diet
 

ddjd

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I had to refresh my memory on this but I think that most of the reduction of homocysteine by TMG is only seen in unhealthy people, people with B6 deficiency or people with high homocysteine levels. I also remember @haidut warning against TMG because of the increase in methionine and that there are better ways to reduce homocysteine, like glycine. Maybe he can clarify again why its bad.
Can you find this quote where haidut says glycine reduces homocysteine
 

Mito

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Isn't creatine made up of Methionine and Lysine?
No.
07A86FB9-A5DF-4751-B30C-6342B15732E3.jpeg

About 40-45% of all methylation is used to synthesize creatine. Homosysteine is a byproduct of the methylation reaction that must occur to make homocysteine. So the idea is if you make less creatine (because your supplementing it exogenously) then less homocysteine will be generated.

Using tmg to convert homocysteine stores would affect methionine levels minimally compared to the amount of Methionine you're getting directly in the diet
Do you have any data that shows that to be true? Please share if you do.
 

x-ray peat

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Can you find this quote where haidut says glycine reduces homocysteine[/QU
A few recent human studies showed high homocystein is simply a symptom of vitamin B6 deficiency. So, you can try a bit of that if the goal is to reduce homocysteine. Glycine can lower both methionine and homocysteine, so that would be another thing to try. Glycine also improves gastric acid production, which is why most people take betaine Hcl. So, glycine could (maybe) safely replace betaine Hcl supplementation altogether.
TE]
 

ddjd

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great thanks a lot! i think its because glycine must help with CBS gene and that transulfation pathway which uses homocysteine
 

Mito

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don't want to have too many methyl donors floating around, it's my understanding they could end up attaching to DNA and altering gene expression.
When we have an excess of methyl groups coming in, we have a buffer system to get rid of the extra. That buffer is the amino acid glycine. Glycine soaks up methyl groups from SAMe and, itself, becomes sarcosine. In doing so, it acts just as any other methyl acceptor would. And because it took a methyl group from SAMe, it generates homocysteine. More specifically, it generates S-Adenosylhomocysteine, or SAH, and then the adenosyl group that came from ATP with the help of magnesium is then hydrolyzed off to generate homocysteine.

So the glycine buffer system is not doing anything to buffer the accumulation of homocysteine. What it’s doing is it’s buffering the excess of methyl groups so that you don’t methylate things that you’re not supposed to. That sarcosine can go into the mitochondrion—all this stuff is happening in the cytosol, the main fluid of the cell. That sarcosine can go into the mitochondrion, and it can regenerate glycine. However, it can also spill out of the cell, and it can spill into the urine. So although you’re not getting a one-to-one loss of glycine every time you use this buffer system, you’re losing some of the glycine. I don’t know how much, but you’re losing some of the glycine as sarcosine that is essentially peed out into your urine.

That buffer system is catalyzed by the enzyme glycine N-methyltransferase, or GNMT. When you have this excess of methyl groups and you’ve used GNMT and now you have homocysteine, you now wind up with an excess of homocysteine. So what you do with it is you use the enzyme cystathionine beta-synthase to make cystathionine. And you do that with the help of serine, which you can consume in the diet or you can interconvert from glycine.”


https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/
 
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Most site and video suggest use B12 and Folic acid for Overmethylation. Is safe this or not ? Thanks
 

ddjd

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Homocysteine can also convert to cysteine via the CBS (B6 dependent) path.
im pretty sure the cbs pathway, like mthfr and bhmt, also converts homocysteine to methionine first.
 

ddjd

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Travis warns about methionine potentially becoming polyamines.
can you link to this thread if possible. ive never heard about this. from a search of the forum the only mention of "polyamine" is from you
 

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