Connecting several treatments with methyl cycle

[ThisType]

There have been a range of methods people have found to reduce pois symptoms.  Many of them to relate and tie together directly by using the methyl cycle. I believe there's an interesting pattern here worth discussing and researching.

Part of the cycle: http://www.benbest.com/health/MethCyc6.jpg

(Version 0.1 - draft)
Treatment   Connection
-----------------   ------------------
Eggs.            Choline
Beets.           Betaine
Beer & wine betaine
Naicin.          Processed by methyl
Exercise.      B12/folate.
Fenugreek. Choline, leutine
Taurine.       Taurine
(More to come - please suggest additions)

It might also be worth discussing:
* Are the variations in types of pois due to various genetic or other failures in various parts of the methyl cycle

++++++ Hypothesis +++++++

Try #1: Version 0.1  (I will edit in details as I have the time to do more research).
Orgasm ->  Methyl Cycle -> Choline, Betain requirement -> Symptoms (first cut) 

Orgasm -> high dopamine (then dips), high prolactin levels (http://sites.tufts.edu/emotiononthebrain/2014/11/18/postcoital-neurochemistry-the-blues-and-the-highs/)
Prolactin ->  methionine  (and choline/betaine) (https://www.ncbi.nlm.nih.gov/pubmed/3131380)
Dopamine -> methionine (and choline/betaine) (http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2001.00471.x/full)
SNP genetic defects -> Choline & Betain deficiency (https://www.ncbi.nlm.nih.gov/pubmed/28134761)
Choline deficiency -> mood, memory, axiety  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518394/)

++++++ Testing +++++++
Methods of testing:
SNP's: genetic testing (23&me)
Choline:  Choline, Betaine, Folate, Homocystein related blood tests, prolactin


+++++ Results ++++++++
23&me results back and of the 8-9 snp's mentioned in the gentic mutations paper I'd mentioned above (https://www.ncbi.nlm.nih.gov/pubmed/28134761), 6 were tested. I have 4 of those 6 mutations relating to choline and betaine processing. Doing some rough calculations on probabilities of those snp's (using links like this http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs10791957 ), which in themselves are fairly common, I would guess that roughly 3% of the population (1/33) would be in the same boat. This seems at least a start, but given how common these variants are, they probably aren't the whole answer. If I also have the three untested mutations that would put me at 1/6600 people, which is still somewhat common (roughly 1 million people worldwide).

 I have since also noted that I have several other mutations in the methyl related snp's that are part of those screened on the genetic genie website.

recent addition relating to Congenital Myasthenic Syndrome - Ihave double mutations in the following SNP's (may not be sufficient either but appear relevant)
rs16969968 Nicotinic Acetylcholine Receptors
rs1051730 Nicotinic Acetylcholine Receptors
rs1824024 Muscarinic Acetylcholine Receptors


I have received a second test - I have had a slightly elevated level of prolactin outside of normal ranges. That came down much closer to normal ranges after 2-3 months on 2eggs/day (choline) and a week of increased betaine intake (beets).

Physical symptoms have improved with increased choline.  Mental fog with betaine and exercise.
The hypothesis is holding up so far.

here's what I appear to observe so far:
1) choline affects mouth muscles and speech in a positive way (if taken early, it relieves all symptoms in general)
2) betaine affects mental fog in a positive way but isn't sufficient alone
3) B vitamins (simple) have so far improved mental fog (using Thorne basic B complex vitamins)
4) too much choline appears to generate runny nose, which makes me wonder if that connects the two different reactions pois sufferers have to choline, eggs, etc (some people have mutations the result in too much choline, some people way too little, etc)
5) genetic mutations in handling of choline and Congenital Myasthenic syndrome (written on other threads) appear to relate
6) caffeine has direct improvement on brain fog.

---- prior solution ------
I've found the following gets rid of the majority (~90%) of my symptoms:
1) I take a phosphatadylcholine (using Thorne) pill every night or 30 minutes before O
2) exercise intensely for 15 minutes every day (swimming for me) helps with brain fog

3) some mornings (few times a week) i take 1/5 of a basic b complex (Thorne) pill with water. I find that much more of the b complex makes my heart race / etc.
4) some mornings (few times a week) I'll eat over easy eggs (2) for breakfast (another source of choline)

** Update solution July 21 2019 **
For the last few months I've changed things around a bit. My suspicion was that vitamin b was only useful in that it increased my blood pressure or pulse. My routine, which continues to evolve, is now:
1) take 1 choline every morning regularly before breakfast (as milk reduced effectiveness for me)
2) exercise 3 times weekly (HIIT/Bike 12 miles high speed)
3) caffeine (1/3 cup black coffee no sugar or cream) on days with any brain fog.

At this point I do not notice pois for the most part and am sharp. I do find at times my patience in the evening is more limited (choline effect I believe).

--update November 23, 2020 --
So since last year, I've dropped caffeine (too many headaches, sometimes made me too wired) and I take choline immediately before bed at night every night. I still do hiit equivalent workouts three times a week.  I don't overdo sugars. I find that I also need to reset things with an (O) at about 5-7 days or speech issues come back ina different form.  This is a 90% solution for me but works consistently.


---- reference links-------
(Version 0.1)
Choline and eggs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782876/
https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

Beets and betain
https://www.ncbi.nlm.nih.gov/pubmed/24467616

Insufficient choline internally produced.
Genetic and other factors can worsen:
http://www.beyondmthfr.com/estrogen-methylation-and-choline-deficiency/

Beer and wine:
https://www.ars.usda.gov/ARSUserFiles/80400525/Articles/IFT2004_Betaine.pdf

Fenugreek​
http://www.ucdenver.edu/academics/colleges/pharmacy/currentstudents/OnCampusPharmDStudents/ExperientialProgram/Documents/nutr_monographs/Monograph-fenugreek.pdf

Exercise https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819126/

prolactin - choline connection
https://www.ncbi.nlm.nih.gov/pubmed/639755

Naicin
https://www.ncbi.nlm.nih.gov/books/NBK114304/

[Note 8/5/17 fused a few of the conversation pieces below into this summary]
[Note 8/17/17 added some observations]
[Note 12/20/17 added current solution]
[Note 1/2/18 clarifying ambiguous comments]
[Note 5/13/18 modified current solution]
[Note 7/21/19 modified to most recent solution]

[Quantum]

Hi TT,

Thanks for sharing your thoughts and hypothesis about POIS.   You have search and read a lot, that shows in your post.   By sharing ideas and looking at POIS thought different angles, we make progress toward understanding it.

I agree with you that what seems to be different types of POIS ( because they are relieved by different substances) may be linked to defect in different metabolic pathways.   Of course, methylation can be affected, but other detox pathways like sulfonation or glucuronidation could be impaired in some other POIS sufferers, contributing to the complexity of understanding POIS.

I think that those defects in detox and metabolic pathways may be responsible for the very long time needed for recovery after release.   I am not sure, however, that methylation defect or other detox pathways defects induce POIS - I think there is something going wrong after release in POIS sufferers, be it immunological, neurologic or hormonal, and our body has a hard time to bring back the balance because of some dysfunctional processes like inefficient methylation or other metabolic reactions, so we are ill for a couple of days, or more, depending of your usual POIS cycle duration.

Like I have already written here, and it is in line with this thread, supporting and promoting a healthy liver function, where many of those reactions occur, can only be beneficial for POIS sufferers, and for anybody, for that matter.

Fenugreek, beets, taurine,  exercise, are all good for the liver function.  You could add to your list: artichoke, milk thistle, black radish, vitamin C, and so on....  Methylation support suppements, of course, are part of this.

I can point out that regularly eating organic veggies and fruits is a very natural and efficient way to help all of the metabolic pathways.   I remember reading one of Kurtosis' posts, where he said that eating veggies and fruits regularly was more efficient for him than taking methylation support supplementation.   I think it's because healthy food bring much more than just on or two valuable substances - they bring hundreds of them, and they all work together in synergy. Kale, brocoli, beets, spinach, blueberries, blackberries, etc....   They are all good medicine

[ThisType]

Hi Quantum,
thank you - it's clear you've thought through this and have been giving well reasoned responses to many threads for years.  In regards to generally keeping the liver functioning smoothly, you're right that there are many different potential mechanisms and this may not be the fundamental cause. 

In this case, however, I'd like to take a dive into a specific area where a number of somewhat effective approaches seem to connect.  I find it's sometimes useful to dive into an area and understand as best as possible what is and could be happening before generalizing, especially in complex systems.

For example, since this relates to the type of POIS I seem to be experiencing (and therefore can test against), I'd like to fill out potential causal chains that connect through the methylation cycle to then understand what tests could prove or disprove the hypothesis. In this way, I would hope to make progress in understanding at least one fundamental causal chain that could be built off of with future research to understand other variants on POIS.  Given the complexity of the feedback loops in the body, I won't pretend that will be easy, but you have to start somewhere...

Try #1: Version 0.1  (I will edit in details as I have the time to do more research).
Orgasm ->  Methyl Cycle -> Choline, Betain requirement -> Symptoms (first cut) 

Orgasm -> high dopamine (then dips), high prolactin levels (http://sites.tufts.edu/emotiononthebrain/2014/11/18/postcoital-neurochemistry-the-blues-and-the-highs/)
Prolactin ->  methionine  (and choline/betaine) (https://www.ncbi.nlm.nih.gov/pubmed/3131380)
Dopamine -> methionine (and choline/betaine) (http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2001.00471.x/full)
SNP genetic defects -> Choline & Betain deficiency (https://www.ncbi.nlm.nih.gov/pubmed/28134761)
Choline deficiency -> mood, memory, axiety  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518394/)

Methods of testing:
SNP's: genetic testing (23&me)
Choline:  Choline, Betaine, Folate, Homocystein related blood tests

[Note 1: out of time today, will keep editing this and earlier post in coming weeks.  Quantum, enjoy your vacation!)
[Edit: simplified visual on chart for the moment, as the chain seems to stand and is confirmed at least partially by the 23&me results below]

[b_jim]

Very good job.

[Quantum]

Hi Quantum,
thank you - it's clear you've thought through this and have been giving well reasoned responses to many threads for years.  In regards to generally keeping the liver functioning smoothly, you're right that there are many different potential mechanisms and this may not be the fundamental cause. 

In this case, however, I'd like to take a dive into a specific area where a number of somewhat effective approaches seem to connect.  I find it's sometimes useful to dive into an area and understand as best as possible what is and could be happening before generalizing, especially in complex systems.

For example, since this relates to the type of POIS I seem to be experiencing (and therefore can test against), I'd like to fill out potential causal chains that connect through the methylation cycle to then understand what tests could prove or disprove the hypothesis. In this way, I would hope to make progress in understanding at least one fundamental causal chain that could be built off of with future research to understand other variants on POIS.  Given the complexity of the feedback loops in the body, I won't pretend that will be easy, but you have to start somewhere...

Try #1: Version 0.1  (I will edit in details as I have the time to do more research).
Orgasm ->  Methyl Cycle -> Choline, Betain requirement  (NOT YET RESEARCHED ENOUGH - some rough thoughts below) 
  * part 1:   Orgasm -> high dopamine (then dips), high prolactin levels (http://sites.tufts.edu/emotiononthebrain/2014/11/18/postcoital-neurochemistry-the-blues-and-the-highs/)
   *part 2A:  prolactin ->  methionine connectin (https://www.ncbi.nlm.nih.gov/pubmed/3131380)
   *part 2B: dopamine -> methionine need (http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2001.00471.x/full)
SNP genetic defects -> Choline & Betain deficiency (https://www.ncbi.nlm.nih.gov/pubmed/28134761)
Choline deficiency -> mood, memory, axiety  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518394/)

Methods of testing:
SNP's: genetic testing (23&me)
Choline:  Choline, Betaine, Folate, Homocystein related blood tests

[Note 1: out of time today, will keep editing this and earlier post in coming weeks.  Quantum, enjoy your vacation!)

Hi TT,

Thanks for your kind words about my contributions here 


Thanks also for your great post.   Its important to keep on searching and making hypothesis, one thing leads to another, and that's how we may arrive at something significant.


Your research plan above make me think a lot about such readings and nots I take - I have tons of pages with notes on POIS and everything related, gathered in the last 2 and a half years.

I will, for sure, stay tuned and read about what you come up with, when you will have time to  ( but, obviously, we have to take care first of our obligations, and have the rest we need, take some healthy time off, and then spend some time off on our POIS hypothesis, and then test them on ourselves, safely... that's a slow process, but that's how I came with my pre-pack).

[ThisType]

Hi Quantum,
Thank you - I suspect you and many others have gone down similar paths (I don't claim this to be original work guven how many different people's work this based  on - just hope to collect thoughts and see if something useful comes out of it). You're definitely correct that doing the testing takes time.

So I got my 23&me results back and of the 8-9 snp's mentioned in the gentic mutations paper I'd mentioned above (https://www.ncbi.nlm.nih.gov/pubmed/28134761), 6 were tested. I have 4 of those 6 mutations relating to choline and betaine processing. Doing some rough calculations on probabilities of those snp's (using links like this http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs10791957 ), which in themselves are fairly common, I would guess that roughly 3% of the population (1/33) would be in the same boat. This seems at least a start, but given how common these variants are, they probably aren't the whole answer. If I also have the three untested mutations that would put me at 1/6600 people, which is still somewhat common (roughly 1 million people worldwide)

A side thought: the supplements used in the paper may be worth reviewing

More when time allows
TT

[ThisType]

added some more observations above:
here's what I appear to observe so far:
1) choline affects mouth muscles and speech in a positive way
2) betaine affects mental fog in a positive way
3) B vitamins (simple) have so far improved things (using Thorne basic B complex vitamins)
4) too much choline appears to generate runny nose, which makes me wonder if that connects the two different reactions pois sufferers have to choline, eggs, etc (some people have mutations the result in too much choline, some people way too little, etc)
5) mutations in absorption of choline and folate appear to be directly related
6) high prolactin levels appear to be inversely correlated to taking choline/eggs. limited testing done on this.

[romies]

Hi Quantum,
Thank you - I suspect you and many others have gone down similar paths (I don't claim this to be original work guven how many different people's work this based  on - just hope to collect thoughts and see if something useful comes out of it). You're definitely correct that doing the testing takes time.

So I got my 23&me results back and of the 8-9 snp's mentioned in the gentic mutations paper I'd mentioned above (https://www.ncbi.nlm.nih.gov/pubmed/28134761), 6 were tested. I have 4 of those 6 mutations relating to choline and betaine processing. Doing some rough calculations on probabilities of those snp's (using links like this http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs10791957 ), which in themselves are fairly common, I would guess that roughly 3% of the population (1/33) would be in the same boat. This seems at least a start, but given how common these variants are, they probably aren't the whole answer. If I also have the three untested mutations that would put me at 1/6600 people, which is still somewhat common (roughly 1 million people worldwide)

A side thought: the supplements used in the paper may be worth reviewing

More when time allows
TT

Hi TT,

The two papers you linked above are very interesting, with some new results. Have you developed a set of rules of thumb for interpreting these SNPs? If so, it would be great to read it, because many people here have 23andme testing results.

Thanks,
Romies

[ThisType]

Hi Romies,
I'm afraid I don't have a good rule of thumb for interpreting the SNPs in the papers.  From my perspective, they represent a few measures of possible blocks to smooth processing in the Methyl cycle and are shown to be able to be compensated for using Choline supplements. This seems to match my experience with some of the POIS symptoms.  From reading further, since these are just ones that have been identified so far, I'd expect that there are a number of additional SNPs that also have negative (and positive) effects that will eventually be identified.  What's great about 23&me and similar services is that as they are identified you can go back and check.
Best,
TT
ps. I've updated the first post with what's currently working for me ~90%+

[Quantum]

ps. I've updated the first post with what's currently working for me ~90%+

Hi TT,

Do you mean you get 90% relief from your POIS symptoms with : Eggs + Beets + Beer & wine + Niacin + Fenugreek + Taurine, and regular exercise ?

If so, you take all of the above on a daily basis, or before release ?

Thanks for clarifying, could be of interest for other members.

[ThisType]

Hi Quantum,
Thanks for the follow-up on the ambiguity - so I don't use most of those items - they're just the list of items that others have had success with and have a solid connection to the line of thinking above. I'm currently only doing the following (listed at the end of the first post)

I've found the following gets rid of the majority (~90%) of my symptoms:
1) I take a choline (using Thorne) pill once within a few hours of O. This treats the swollen mouth and tongue / speech.
2) eating 2 eggs for breakfast days 1-3 cooking the over easy (and every few days  otherwise). I find this also helps with speech.
3) i take 1/3 of a simple b complex (Thorne) pill with water each morning (skipping days I don't normally need it such as 4 and 5). This handles the mental acuity/brain fog. I find that much more of the b complex makes my heart race / etc.
4) exercise intensely for 10-15 minutes every other day (swimming for me) also helps with brain fog

Happy New Year,
TT

[Quantum]

Thanks TT for clarifying !

Given that you get consistent relief for some months now, at 90%, I have added your name to the "Cholinergic deficit type", because of the choline and eggs supplementation.  Tell me if you are ok with this.

[b_jim]

Good job TT. I wwould like to know if you are normal or underweight and if you have malarbsobtion or gallbader trouble when eating fats or white sugar.

I have often these troubles especially NOW (new year and christmas food, too much fats and chocolate! ). I usually take a med for this. The ingredients of this med are : choline, betaine, inositol + some other one.
In french we called it "crise de foie" (liver crisis) with is incorrect medical word for indigestion and bile bad streaming.

This night I can't sleep cause of this and i wonder if there is a link with Pois.
-I have increased lipase enzyme (339U/L normal<286)
- Low cholesterol (1.46 normal 1.50)
- Taurine really helps my Pois. Taurine is close to bile and it helps with fats like choline.
- Underweight

I really wonder if bile salts/bile acid supplements couldn't help my Pois and help me to gain weight.
Bile salts + (choline?) + (taurine?) + Fats => good fats absobtion => good testosterone homeostasis 

The scientific formula is :

Cholesterol => cholic acid + Chenodeoxycholic acid ( = primary bile acids)

Primary bile acids + taurine + glycin(glycocolle) => 4 Primary bile salts
1: glycocholate  2: glycochénodésoxycholate 3:  taurocholate   4: taurochénodésoxycholate

These primary bile salts work with lipase to digestion/absobtion of fats.
These primary bile salts and lipase go in the intestine from liver/gallbader/pancreas

[b_jim]

Since the start of the year, I have digestive problem and I take a med with choline, betaine and inositol to help the gallbader.

I really wonder if inositol might help my Pois. It seems inositol is present in sperm.
i'm searching info on this.

[ThisType]

Thanks TT for clarifying !

Given that you get consistent relief for some months now, at 90%, I have added your name to the "Cholinergic deficit type", because of the choline and eggs supplementation.  Tell me if you are ok with this.

Hi Quantum,
That is fine with the caveat that from choline/eggs I only get relief from my speech and related swelling of the lips and the tongue that make me inarticulate. I find I need the exercise and b complex to improve my brain fog. I still see some level of failure to find the right word, but in general vastly improved.
Best,
TT

[ThisType]

Good job TT. I wwould like to know if you are normal or underweight and if you have malarbsobtion or gallbader trouble when eating fats or white sugar.

Hi b_Jim,
Thank you - I don't believe I have those symptoms - i am not underweight.
Best
TT

[ThisType]

updated current solution in top post

[Jacob]

Hi TT,

thank you for the great summary.

Has anyone noticed differences between different choline types? Choline-Bitartrat seems to be the cheapest type. In TT's Thorne supplement Phosphatidyl Choline is used. But there is also the option of Alpha GPC as a predecessor to choline.
I heard all types mentioned above result in 40% of actual choline. Lecithine is supposed to only have 13% actual choline.

Is there a reason why you didn't include Mytelase in this summary post? Has anyone tried Huperzine A as cholinesterase inhibitor?

Best wishes,
Jacob

[ThisType]

Hi Jacob,
I'm not aware of a study/compatible between the different types, though I'm sure there is a difference. My suspicion is that of I get too early in the chain, it would be less effective (.e.g. if I have a limited rate of processing due to genetic mutations, further down the chain may be preferable depending on where that mutation is). It is likely worth looking into. You may find a subset of those on different threads here.
Best
TT

[ThisType]

** Update solution July 21 2019 **
For the last few months I've changed things around a bit. My suspicion was that vitamin b was only useful in that it increased my blood pressure or pulse. My routine, which continues to evolve, is now:
1) take 1 choline every morning regularly before breakfast (as milk reduced effectiveness for me)
2) exercise 3 times weekly (HIIT/Bike 12 miles high speed)
3) caffeine (1/3 cup black coffee no sugar or cream) on days with any brain fog.

At this point I do not notice pois for the most part and am sharp. I do find at times my patience in the evening is more limited (choline effect I believe).