16 replies to this topic

[iseethelight]

Choline is converted into TMG (betaine) and then DMG. The latter two AAs (tmg & dmg) are the main causes of depression from choline. If your methylation is messed up, usually due to issues in the methionine synthase / reductase cycle , your body will try to use the shortcut pathway for methylation, BHMT. . . How do they cause depression? They fuck up your methylation cycle, either by overmethylating you or by depleting homocysteine that's also needed for glutathione synthesis and other sulfur based AAs. 

 

Another effect of this is for those of us who are sensitive to methyl donors due to certain genetic mutations (Eg: COMT/CBS). Choline has 4 methyl groups, if it's used for acetylcholine synthesis by the body, then it doesn't increase methylation, but if it is, then it becomes a strong methyl donor in converting to tmg and dmg, sarcosine, and eventual serine and glycine.

 

 

I've personally tested both TMG and DMG and I have gotten the same depression I get with choline. Now I think if we combine choline with high dose folic acid, or maybe b12, we might be able to prevent the choline  from converting to TMG(betaine)

Edited by iseethelight, 04 April 2017 - 12:46 AM.

[gamesguru]

Just take an AChE inhibitor (tea [also inhibits DNA methylation], ginkgo, bacopa) instead of choline, you skip 10 steps in the ladder that way.  Although tea can cause too much serotonin in some regions that mediate depression.. so there's always something to watch out for.  I thought ginkgo was relatively clean, but it makes any new bad memories much, much worse.  Just a consequence of being more aware I suppose

[Hyperflux]

Are curcumin, caffeine and melatonin also methyl donors? Some sources say so but there is no substantiation to these claims so I'm torn. I'm also sensitive to methyl donors but I don't think it's due to COMT even though I'm +/- for it. Yasko has seriously misinterpreted the literature by saying COMT polymorphisms = intolerance to methyl donors because there are plenty of people who can handle them fine. 

[gamesguru]

COMT has nothing to do with methyl donation.  It's just most happen to be.  chlorogenic acid is a counter-example, it inhibits methylation and COMT.  No, caffeine and curcumin, like exercise, inhibit methylation.  Melatonin, however, is a donor.

[Hyperflux]

COMT has nothing to do with methyl donation.  It's just most happen to be.  chlorogenic acid is a counter-example, it inhibits methylation and COMT.  No, caffeine and curcumin, like exercise, inhibit methylation.  Melatonin, however, is a donor.

 

Why do you think one may respond poorly to methyl donors? I don't respond favorably to any doses of methylfolate or methylB12, and TMG made me irritable. What's confusing is SAM-e is ok for me (400mg). I'm COMT +/- for both, MTHFR A1298C, MTRR MTR +/-, and have some VDR +/-. 

[iseethelight]

COMT has nothing to do with methyl donation.  It's just most happen to be.  chlorogenic acid is a counter-example, it inhibits methylation and COMT.  No, caffeine and curcumin, like exercise, inhibit methylation.  Melatonin, however, is a donor.

 COMT mutations usually cause one to release neurotransmitters slowly, so you build excess neurotransmitters. So taking methyl donors will causes already excess level of the NTs to get even higher causing ADHD, depression, irritability. Both Caffeine and curcumin are methyl donors, albeit not very strong ones, and COMT and CBS mutated individuals should avoid them.

[gamesguru]

I wasn't aware of the breakdown of the percentages of COMT mutations, being slowed down vs sped up.  Now i know they're usually slowed down.

 

You're right about the methyl donor boosting NTs[1], but where are you getting the idea that caffeine and curcumin are methyl donors?  Thanks

 

The DNA changes in question are known as epigenetic modifications and involve the gain or loss of chemical marks on DNA over and above the familiar sequence of As, Gs, Ts, and Cs. The new study shows that the DNA within skeletal muscle taken from people after a burst of exercise bears fewer chemical marks (specifically methyl groups) than it did before exercise. Those changes take place in stretches of DNA that are involved in turning "on" genes important for muscles' adaptation to exercise.

When the researchers made muscles contract in lab dishes, they saw a similar loss of DNA methyl groups. Exposure of isolated muscle to caffeine had the same effect.

https://www.scienced...20306131254.htm

 

Only a few reports have so far investigated the effect of curcumin on DNA methylation. Molecular docking of the interaction between curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of DNMT1 to exert its inhibitory effect on DNA methylation (Liu et al. 2009).

https://www.ncbi.nlm...les/PMC3092901/

[Hyperflux]

 

COMT has nothing to do with methyl donation.  It's just most happen to be.  chlorogenic acid is a counter-example, it inhibits methylation and COMT.  No, caffeine and curcumin, like exercise, inhibit methylation.  Melatonin, however, is a donor.

 COMT mutations usually cause one to release neurotransmitters slowly, so you build excess neurotransmitters. So taking methyl donors will causes already excess level of the NTs to get even higher causing ADHD, depression, irritability. Both Caffeine and curcumin are methyl donors, albeit not very strong ones, and COMT and CBS mutated individuals should avoid them.

 

 

Source on caffeine/curcumin being methyl donor and is melatonin not a methyl donor?

[gamesguru]

i'm fairly certain he's going with the first result in google.. what some guy posted on facebook.  nothing in the literature to back it up.  stay in school kids, you could wind up on a silly forum with a real serious avatar

 

as for why SAM-e isn't irritating you like the other supps, one possible explanation is that methyl donors apparently decrease serotonin and dopamine.  depending on your chemistry that might be a bad, neutral or good thing.  but the SAM-e raises serotonin, as I'm sure you're aware, so its plus and minus effects sort of balance each other out.

 

regardless of stress-conditions, methyl donor deficient diet decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus and selectively 5HIAA/serotonin ratio in the sensorimotor cortex

[iseethelight]

 

i'm fairly certain he's going with the first result in google.. what some guy posted on facebook.  nothing in the literature to back it up.  stay in school kids, you could wind up on a silly forum with a real serious avatar

 

as for why SAM-e isn't irritating you like the other supps, one possible explanation is that methyl donors apparently decrease serotonin and dopamine.  depending on your chemistry that might be a bad, neutral or good thing.  but the SAM-e raises serotonin, as I'm sure you're aware, so its plus and minus effects sort of balance each other out.

 

 

Serioulsy kid? I mean you are the most clueless high post count poster on this board. All you do is search pubmed abstracts using keywords people use to ask questions and post them in threads, even when they have little relevance to the topic at hand. I never get any value from your posts in any of my threads. 

Anyways I read about about caffeine being a methyl donor in some book I can't recall.. I see you spent some time searching google to try to prove me wrong, thin-skinned much? http://blogs.discove...p/#.WO66F1Pyvq0

 

Anyways back to topic:

 

I've experimented with choline metabolites >tmg-->dmg-->sarcosine aka trimethylglycine-->dimethylglycine--methylglycine and I pretty much get the same negative effects with all of them, except the jitteriness is only present with tmg and choline.  DMG destroys my verbal fluency while tmg improves it. But they all make me depressed and lethargic and tired... 

 

Pure glycine on the other hand doesn't make me depressed at all but it has no real effect on my brain. So it's the methyl groups in choline causing this issue. Too bad because both choline improves my verbal fluency and creativity 2 fold but the side effects are too much.

[gamesguru]

i mean a compound could be both a phosphate donor and a (more potent) inhibitor of phosphorylation.  net effect is negative, so yeah im clueless for not having tried TMG forgive me 

[Gravy]

I've been experimenting with TMG for it's purported energy/performance effects. So far I've noticed if I take too much I'll get an overstimulated/tunnel type feeling/focus. It'll eventually die down by a decent amount after 2hrs. I haven't noticed any depressive effects. However I'm still dealing with a lot of fatigue/energy issues. TMG haven't put a dent on that. But I would say it provides more of stimulant than depressive type effect for me.

[Zed]

 

Anyways back to topic:

 

I've experimented with choline metabolites >tmg-->dmg-->sarcosine aka trimethylglycine-->dimethylglycine--methylglycine and I pretty much get the same negative effects with all of them, except the jitteriness is only present with tmg and choline.  DMG destroys my verbal fluency while tmg improves it. But they all make me depressed and lethargic and tired... 

 

Pure glycine on the other hand doesn't make me depressed at all but it has no real effect on my brain. So it's the methyl groups in choline causing this issue. Too bad because both choline improves my verbal fluency and creativity 2 fold but the side effects are too much.

 

 

Similar reactions to Choline/TMG.  I generally take choline at night and cycle it every other day and notice an overall positive effect with this.

 

[Lufega]

I always feel depressed for cholinergics. Even green tea makes me depressed as it inhibits ACHi. It's terrible.

Figured out to take it with inositol amd no depression. Now i'm taking straight up choline bitartrate and i'm perfectly fine.

Ofcourse, this is my n=1 anecdote. Curious to see if any of you can duplicate this effect.

Inositol is the bomb btw. Losing weight on it like my body's allergic to fat.

[jack black]

Inositol is the bomb btw. Losing weight on it like my body's allergic to fat.

 

I wish I had a response like that. I only felt a reaction once, 1st time, sudden serotonin like release and feeling mellow for an hr or two. Nothing since in various doses. Maybe bad batch?

[Lufega]

I wish I had a response like that. I only felt a reaction once, 1st time, sudden serotonin like release and feeling mellow for an hr or two. Nothing since in various doses. Maybe bad batch?

To inositol? Maybe it's not what your body needs. Been trying supplememts for over 10 years. It's rare to find something that agress with my chemistry.

I hope this can help other people with this cholinergic dilemma

Edited by Lufega, 29 October 2018 - 02:46 AM.

[j87]

I've found this to be my experience as well... Is there anything that counteracts this effect? I have to take benedryl to reduce acetylcholine levels.