6 replies to this topic

[Advanc3d]

since Methionine and TMG (betaine) are precursors to sam-e. is taking the aminoacid combination as good as taking the sam-e as a product?
if so, are the effects the same and how should dosing be changed with comparison between the two

sam-e is pretty damn expensive it self

Edited by Advanc3d, 06 August 2008 - 12:28 PM.

[jake]

since Methionine and TMG (betaine) are precursors to sam-e. is taking the aminoacid combination as good as taking the sam-e as a product?
if so, are the effects the same and how should dosing be changed with comparison between the two

sam-e is pretty damn expensive it self

I tried both. No effect for me from TMG. Sam-e made feel feel speedy and euphoric sometimes. Didn't like it.

Edited by jake, 12 August 2008 - 08:52 PM.

[Wulf]

I've been wondering about this myself and learned the following: (standard disclaimer applies: check my statements on your own, please correct me if I'm wrong)

- Trimethylglycine (TMG) isn't really a precursor to S-adenosyl-L-methionine (SAMe). TMG is a methyl donor in the conversion of homocysteine to methionine by betaine-homocysteine methyltransferase (BHMT). BHMT is not active in the brain.

Other important cofactors in the conversion of homocysteine to methionine are: methylcobalamin(B12) and folate.

Methylcobalamin is the other methyl donor in the conversion of homocysteine to methionine through methionine synthase. Methionine synthase uses 5-methyltetrahydrofolate(5MTHF) to donate a methyl group to cobalamin, creating methylcobalamin.

We get 5MTHF from:
folate -> dihydrofolate -> tetrahydrofolate -> Methylene-THF -> 5-methyltetrahydrofolate

- Methionine is converted to SAMe by methionine-adenosyl-transferase with magnesium (required), potassium (required), atp and water as cofactors.

This article provides a great more detail of all the above. It also summarizes everything in a visual manner, which I think is worth showing in the post:

I tried and failed to locate the oral bioavailability of l-methionine. I did find two studies that examined the relationship of oral methionine and the observed increase of homocysteine, which indicates that the oral methionine is being converted to SAMe, as:

methionine->SAMe->S-adenosylhomocysteine->homocysteine

The two studies are:
Hanratty CG, McGrath LT, McAuley DF, Young IS, Johnston GD. The effects of oral methionine and homocysteine on endothelial function. Heart. 2001 Mar;85(3):326-30.

Fukagawa NK, Martin JM, Wurthmann A, Prue AH, Ebenstein D, O'Rourke B. Sex-related differences in methionine metabolism and plasma homocysteine concentrations. Am J Clin Nutr. 2000 Jul;72(1):22-9

Both of these studies use a 100mg/kg human dose, which in a 60kg adult is 6 grams of l-methionine.


Based on all of this, my thoughts are:

- Assuming I don't have a methionine-adenosyl-transferase(MAT) deficiency of some sort, then I should be able to produce SAMe from normal dietary intake of methionine.
- By supplementing with TMG, methylcobalamin, folate and B6, I should be able to reduce my homocysteine and in turn increase methionine to ensure optimal levels of SAMe. I would prefer this approach rather than supplementing with l-methionine and risk increasing my homocysteine levels.
- If I do not observe any sort of mood enhancement from the previous supplementation, I may have to supplement with SAMe directly.

Topics for another post/ more research

- Something I found while researching SAMe was how non-academic texts, i.e. websites, categorically state that SAMe alleviates depression by contributing to the synthesis of serotonin and other monoamines (poor evidence for this). The academic texts (at least the several dozen I've read) are still quite uncertain about the exact mechanisms through which SAMe helps depression. If I have an opportunity, I'll put together everything I've found in a post or post in an appropriate existing topic.

- hypermethylation vs hypomethylation, in the epigenetic sense.

- While looking into all of this, I ran into the concept of dietary methionine restriction and its relation to an observed increase in life span, which I still don't understand completely. I really need to dig into that, considering it results in a reduction of SAMe levels in the body.

That's all I have.

Edited by Wulf, 20 August 2008 - 12:01 PM.

[stephen_b]

Here's a link to a thread which discusses a study that shows that a methionine restriction "resulted in a 42% increase in mean survival and a 44% increase in maximal longevity". Also, "methionine restriction brought about a 2-fold increase over controls" in GSH production.

It would seem that methionine supplementation is not needed.

Have you looked at supplementing tryptophan at night and tyrosine in the morning (both on an empty stomach) for mood enhancement?

Stephen

Edited by stephen_b, 20 August 2008 - 01:11 PM.

[abelard lindsay]

I tried SAM-E for a while. It was very expensive, had to be stored in the fridge and didn't do much for me. I recently tried TMG because another Imminst member recommended it for mood improvement. TMG was incredible! I got a huge mental boost from it and I would definitely recommend it for people needing a good clean dopamine boost that also happens to lower dangerous homocysteine levels.

[Advanc3d]

I tried SAM-E for a while. It was very expensive, had to be stored in the fridge and didn't do much for me. I recently tried TMG because another Imminst member recommended it for mood improvement. TMG was incredible! I got a huge mental boost from it and I would definitely recommend it for people needing a good clean dopamine boost that also happens to lower dangerous homocysteine levels.

what was ur dosage of TMG? was it oral? because i have heard of good reports with sublingual administration

[Wulf]

Here's a link to a thread which discusses a study that shows that a methionine restriction "resulted in a 42% increase in mean survival and a 44% increase in maximal longevity". Also, "methionine restriction brought about a 2-fold increase over controls" in GSH production.

It would seem that methionine supplementation is not needed.

That is the thread that piqued my interest in methionine restriction. While I haven't read the papers ( I'm the process of reading them), my main concern is that SAMe is the substrate for most of the 38 methyltransferase enzymes in the human body. The only way to get SAMe is through methionine (neglecting the supplement). My other concern is inhibiting DNA methylation. In the article from the AMR I link above, the author provides a good example of this: The gene for amyloid precursor protein, the protein that builds up in the brain in Alzheimer's, is usually highly methylated (suppressed). Hypomethylation is though to be responsible for the increased expression of amyloid precursor protein. When I'm through with all the literature, I'll probably post my thoughts on that thread.

I tried SAM-E for a while. It was very expensive, had to be stored in the fridge and didn't do much for me. I recently tried TMG because another Imminst member recommended it for mood improvement. TMG was incredible! I got a huge mental boost from it and I would definitely recommend it for people needing a good clean dopamine boost that also happens to lower dangerous homocysteine levels.

The only thing TMG does is donate a methyl group to betaine-homocysteine methyltransferase, to convert homocysteine to methionine. Betaine-homocysteine methyltransferase isn't expressed in the brain. I'm also relatively sure that TMG does nothing for dopamine synthesis. Here is how you get dopamine, with enzymes in parenthesis:

dietary phenylalaline -> (phenylalanine hydroxylase) -> Tyrosine -> (Tyrosine hydroxylase) -> dihidroxyphenylalanine -> (Aromatic-L-amino-acid decarboxylase) -> dopamine

TMG is not a substrate for any of these enzymes.

Here is how TMG is metabolized:

N,N,N-trimethylglycine -> (betaine-homocysteine methyltransferase) -> N,N-dimethylglycine -> (dimethylglycine dehydrogenase) -> N-methylglycine -> (sarcosine oxidase) -> glycine

Dimethylglycine and methylglycine seem to help with schizophrenia, autism and epilepsy. The thought behind this is the increase of glycine, resulting in increased NMDA receptor activation.

One of the possible reasons TMG might result in an observed effect is how homocysteine can be reversed to S-adenosylhomocysteine (SAH). SAH can inhibit methyltransferases in the CNS. By reducing homocysteine and thus SAH, you could get a positive effect on mood and cognition.