Methylation and neurotransmitters

[Billx123]

I want to understand how are neurotransmitters like serotonin and dopamine really made and how much does methylation effect them. Im clearly very low on both dopamine and serotonin. I recently started methylation protocol and havent noticed anything major yet. So can someone enlighten me:

How much does properly working methylation improve neurotransmitters and how fast can i expect something? Most antidepressents start working slowly in 1-2 months so can i expect similiar neurotransmitter build up time with methylation supplements aswell?

Ive read that, i think it was Dr Walsh who wrote that l-methylfolate actually reduces serotonin and people who are undermethylators with high histamine shouldnt take it? Now isnt this a bit wierd? You're a undermethylator and cant take the vitamin that improves that? Instead he recommends l-methionine, calcium and magnesium? How does taking pure methionine work with that? Because it transfer to sam-e?

 

[Eastman]

Does this article help you understand better?

 

[ahmo]

@Billx123 I can't answer your question about neurotransmitters. But I was undermethylated, and have ongoing histamine problems. Getting methylation sorted changed my life. In itself, B12 resolved my terrible insomnia, which had been intermittent throughout my life, before it became chronic and debilitating. My other neurological symptoms resolved or greatly improved. As did my mood. I also began taking lithium, which is said to help B12 absorption. I now only need lithium about once a week. Lithium definitely stabilized my moods, stopped me bursting into tears at any sad story.

 

[J.G]

An important interaction between 5-MTHF (i.e. bioactive Vit B9) and neurotransmitters runs through a cofactor called BH4. BH4 is the cofactor to the two rate-limiting enzymes governing the synthesis of dopamine and serotonin. BH4 is very sensitive to oxidation by ROS, and oxidative stress is often seen in inflammatory pathology.

5-MTHF does two things in this context. First, it is capable of regenerating oxidised BH2/BH3 into BH4. Second, due to highly similar biochemical structures, 5-MTHF is capable of standing in for BH4 in the generation of eNOS, thus relieving pressure on its availability for neurotransmitter synthesis.

I hope that helps. For more detail see e.g. here, especially the bottom figure.

 

[Billx123]

Yep i understand it now. But why theres is this completely differenta approach that dr Walsh says, that uses methionine etc. And says to avoid folates? This b12 + methylfolate makes sense to me but why these both protocols use the same name undermethylator and how do they differ?

 

[Eastman]

In addition to BH4 and methylfolate, SAMe appears to be important as well. Here's how MentalHelp.net put it:

While the use of SAMe in your body is diverse (it participates in over 35 biochemical processes), the process of interest in depression is the creation of the neurotransmitters dopamine, serotonin and norepinephrine. SAMe affects these neurotransmitters in different ways. First, SAMe slows the breakdown of these brain chemicals, allowing them to work longer. In addition, SAMe speeds production of the receptors which receive these neurotransmitters. The presence of additional receptors allows the neurotransmitters that are present to work more effectively. Some research suggests that SAMe may also make the existing receptors more responsive (better able to receive messages from neurotransmitters). All of these functions combine to create increased levels of neurotransmitters, which decreases depressive symptoms.

Yep i understand it now. But why theres is this completely differenta approach that dr Walsh says, that uses methionine etc. And says to avoid folates? This b12 + methylfolate makes sense to me but why these both protocols use the same name undermethylator and how do they differ?

Bill Walsh thinks that folate may increase the reuptake of serotonin in some people. See Bill Walsh Finally Explains Over-Methylation In A Way I Can Understand

 

[Billx123]

In addition to BH4 and methylfolate, SAMe appears to be important as well. Here's how MentalHelp.net put it:





Bill Walsh thinks that folate may increase the reuptake of serotonin in some people. See Bill Walsh Finally Explains Over-Methylation In A Way I Can Understand

I cant get my hands on SAMe at this time because it needs prescription here but how about l-methionine? This study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC543840/ says that its more effective raising brain SAMe than SAMe itself? Should work the same right?

But ive also found studies that say that SAMe actually decreases dopamine. Found these from some website that discussed about increasing dopamine:


https://www.ncbi.nlm.nih.gov/pubmed/9247319?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/7888091?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/8503824?dopt=Abstract

What you guys think about?

 

[Eastman]

I cant get my hands on SAMe at this time because it needs prescription here but how about l-methionine? This study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC543840/ says that its more effective raising brain SAMe than SAMe itself? Should work the same right?

But ive also found studies that say that SAMe actually decreases dopamine. Found these from some website that discussed about increasing dopamine:


https://www.ncbi.nlm.nih.gov/pubmed/9247319?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/7888091?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/8503824?dopt=Abstract

What you guys think about?

I have misgivings about taking methionine since methionine restriction is associated with life extension.

As far as I am aware, the studies showing that SAMe decreases dopamine were done on rats. Nevertheless, Ben Lynch seemed concerned enough to warn that increased methylation may cause neurological symptoms.

I guess this is another reason to be careful with the methylation protocol.

 

[Billx123]

I quess trying each supplement for few weeks doesnt do much harm? Its hard with these methylation supps because first time i tried methylb12, methylfolate and adeb12 i got huge detox reactions and i still get them when i take those supps so i quess i have to just push through. Ive read that i means i have deficiencys if i react to them right?

 

[Eastman]

I experienced both detox and overstimulation from B12. In my case, I chose to cut back the dose.

Pushing through can be risky if you get potassium deficiency since that can be life-threatening, although I think Freddd did recommend doing so once you get the symptoms under control.

 

[pumpkin]

@Billx123 I also began taking lithium, which is said to help B12 absorption. I now only need lithium about once a week. Lithium definitely stabilized my moods, stopped me bursting into tears at any sad story.

Hi @ahmo may I ask what form of lithium you took? Was it Orotate? Any recommendations on brand and dosage?
For the past month I've been taking Trace Minerals Liquid drops which give about 1.5mg of Lithium a day along with other trace minerals. I was hoping it might stabilise my moods and reduce my aggression a bit (I'm not actually aggressive I just feel it sometimes) but I haven't noticed much change in that respect. Thank you and very glad to hear you feel better!

 

[pumpkin]

i tried methylb12, methylfolate and adeb12 i got huge detox reactions and i still get them when i take those supps so i quess i have to just push through. Ive read that i means i have deficiencys if i react to them right?

Hi @Billx123 I'm about 6 weeks into my 2nd attempt at methylation, the first time I ended up in hospital with heart palpitations etc. I had taken Mb12 5000mcg every day plus folate etc and went massively into overmethylation. I'm now starting off low and slow as everyone recommends lol, literally divided the doses by 8 and have been increasing it by an 1/8 every couple of weeks, accompanied by massive potassium amounts and so far I am doing fine so I hope with time you too will find it easier. Good original question by the way

 

[ahmo]

@pumpkin Initially I used a lithium orotate from iherb. I used about 5mg/day, as I recall. Then that was unavailable, and I switched to Australian brand Biovea. When I look at their website now, I don't see this listed. So I don't know what I'll use in the future. I'm now only using it about once/week. I dose according to self-testing.