Author Topic: POIS treatment: theory & supplement stack  (Read 204522 times)

demografx

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Re: POIS cure: theory & supplement stack
« Reply #520 on: February 21, 2020, 11:58:28 AM »
nanna1, thank you for that...from this caffeine addict :)
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

BoneBroth

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Re: POIS cure: theory & supplement stack
« Reply #521 on: February 22, 2020, 03:42:40 AM »
these results seem to confirm that epinephrine and norepinephrine are the chemical triggers for Post Orgasmic Illness Syndrome.

I concur that epinephrine and norepinephrine seem to be tied to POIS. I realize I can get POIS symptoms without orgasm in periods of acute stress. I also realize I have a major problem dealing with stress and anxiety. I'm starting a course of Alfuzosin prescribed by my doctor. I don't believe it is the solution for me but it will be an interesting test. I also have some urinary symptoms it may help like having to urinate often and leakage after I go.

Last week, and for the first time in my life, I also experienced a horrible one-week POIS period without orgasm/NE but after some stressful days. But in addition to the stress it started within a day after a restaurant visit where I ate unusual amounts of carbohydrate (French fries and some spicy sweet sauce) and particularly a dessert with lots of ice cream and a belgian wheat-waffle together with coffee. I dont use to eat that much sugar/wheat in one day since I 've been cutting down on all that. I believe that it was the stress in combination with a sugar-coffein-carbohydrate spike that released this POIS!!!

Both stress, sugars and coffein do release hight amounts of cortisol and the symptoms of extraordinary hight cortisol is inflammation, hight sebum production, muscle weaknes/pain (for me: mostly on the achilles tendon and the thigh muscle), headache, acne, hight sebum, red eyes, enlarged blood vessels, rosacea-like skin issues. I use to get it all on POIS and I got it now too, it was one of the worst POIS weeks I ever had! Totally mental paralyzed.

Now, this makes me start wondering if spikes of cortisol (or perhaps adrenaline in the absent of cortisol?) are the bad guy after all, at least one of the bad guys. Another POIS starter for me is nocturnal emissions, and very much "close-to-nocturnal-emissions" but why would hight amount of cortisol be secreted at NE's? I dont experience stress when I dream such dreams. Inflammation is certainly the main activity in POIS but are there diffrent inflammatory substances/hormones that have the same effect but are release from different triggers? I'm ever batteling with these hypothesis:

1. Hight cortisol spikes (because of mental or chemical stress) causes POIS.
2. Long time hight cortisol causes depletion of cortisol which is substituted with hight adrenaline which at spikes causes POIS.
3. Long time hight cortisol/dopamin etc causes overactive adrenals/pitutary gland that causes excess cortisol/adrenaline spikes that causes POIS.
4. Chronical low levels of oxitocin, enorphones or other feel-good hormones

Of cource everyone can have adrenaline/cortisol spikes without having POIS so there must be another factor involved and a believe that POISers have either abnormally: hight cortisol/adrenaline secretion, hight receptor response, low anabolic hormone response (testosterone, oxytocin etc) or combinations of those.

Please give your thougts about that!
« Last Edit: February 22, 2020, 06:24:15 AM by BoneBroth »

BoneBroth

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Re: POIS cure: theory & supplement stack
« Reply #522 on: February 22, 2020, 04:45:09 AM »
Thank you in advance and it is very good to have you in the group.
Nanna 1 could you explain to me why I am having pois with pre-seminal liquid. Which battery would bless me well in this case?
infinite thanks

Hi Eliasjoelrivera!

If the pre-seminal liquid comes in addition to an initial cause like sexual arousal, nocturnal dreams etcetera maybe it is the hormons involved with the arousal that causes the POIS rather than the liquid in itself.
« Last Edit: February 22, 2020, 06:31:00 AM by BoneBroth »

BoneBroth

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Re: POIS cure: theory & supplement stack
« Reply #523 on: February 22, 2020, 05:29:32 AM »
I happen to have a different version of POIS.

A- If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS and they last for 3-4 days. During this time i suffer from brain fog, excessive sleepiness, light headed, excessive sweating, irritated, cognitive impairment, fatigue, muscle weakness and headache/migraine. The more i sleep the sooner i can recover from these symptoms but they still take about 3 days at least although the symptoms become milder as i sleep more.
POIS is not triggered if i sleep at night right after sex. And due to this awkward strange reaction to sex i can not go for sex during day time. I can only have sex at night and sleep right after (in order to avoid POIS)

B- If i orgasm after masturbate, then POIS kicks in within an hour and gets worse the next day and lasts for 3-4 days. Even if i go to sleep right after masturbation/orgasm at night, it still does not help ! I get plenty of sleep yet the next day the symptoms of POIS starts to appear and gets worse the following day and then begin to subside the 3rd day and almost fully disappear by the end of 4th day from masturbation/orgasm. I did experiment few supplements but they either did not work or their effects were very short lived. I was also deficient in vitamin D3 and after taking supplements for it, the POIS symptoms got a little bit better.

In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation? And why do i have to sleep within 20min or so after sex to avoid POIS? And i don't understand why i get so heavily sleepy headed with POIS as if i am drugged and i am literally dragging myself to do daily chores not to mention the anxiety and discomfort that comes with it/pois.

Hi Luminous!

I believe that your experience has a very important piece of te POIS puzzle. The severeness of my POIS (and others here) is also dependent on such things you mention. If I would list the POIS-triggers from the worst (top) to the least it would be like this:

1. Nocturnal emission (NE) or masturbation (MB)/orgasm (O) (what time doesnt matter)
2. Hight stress + loads of sugar/coffein (new cause that I just experienced last week)
3. Near nocturnal emision (sexual arousal)
4. Orgasm from sex in morning
5. Orgasm from sex in night

So what is the difference between the top and bottom? I believe its oxytocin (and perhaps other endorphins and feel-good-hormones that are known for primarily helping one deal with stress and reduce feelings of pain)! Spikes of adrenaline/cortisol causes inflammation but oxitocin is anti-inflammatory and balances the cortisol/adrenalin immediately, on seconds! Ocytocin is released when you feel relaxed, during hugging, meditation, deep breathing, hot shower, petting a cat/dag and at normal sex with lot of skin contact. It is associated with love, but not nessecary orgasm in itself. So thats why you dont get enought of it on masturbation, or viewing porn where you produce cortisol/adrenalin, and specially too much dopamin, but not enought levels of oxitocin and/or other feel-good hormones.

It further seems that those hormones need to be secreted at the same time (probably within seconds) as orgasm (or already be in adequate amounts in the blood) to be able to stop inflammation from occuring. So they dont stop inflammaton, they stop inflammation from occuring. If you wait an hour, its too late, the damage is already done.

This also explaines why users on POIS forum has described why the POIS gett less worse if they use the following practise/products of which some are notoriously known for increasing oxytocin/endorphin levels:

Vitamin D
Vitamin C
Magnesium
Taurin
Coffee (if taken right after O, not in the long term, where it messes with hormonal balances by increases cortisol and lowering testosterone)
Lactobacillus (better gut)
Chamomile
Melatonin (higher amounts at evening/night, so sex at night causes less POIS)
Fenugreek
5HTP
GABA
L-Theanine
Green Tea
Eggs
Massage
Deep breathing immitiately after NE
Yoga
Warm and Cold showers
Normal sex (skin touching)
Sauna
Summer vacation
Exercise

Other anti-inflammatory foods and drugs could also work in the right amounts, but probably not as good as oxytocin, the bodys own super anti-inflammatory, that could be secreted in the right amounts at exactly the right time.

Of cource this doesnt try to explain why POIS happens in the first place, only the diffrent severity on diffrent triggers. Everyone doesnt experience POIS on MB, porn etc. Maybe their hormon levels are always balanced, in all weather. Their adrenals have enought of hormonal storage to manage all these diffrent form of O, 24 hours a day, 7 days a week. So by working on your hormonal systems you might be able to restore normal hormonal capacity, but that could take time and requires sexual, dietary and supplemental discipline not to mention avoidance of stress, which for many people could be very hard.

https://www.optimallivingdynamics.com/blog/25-effective-ways-to-increase-oxytocin-levels-in-the-brain
https://medium.com/@jordanfallis/25-effective-ways-to-increase-oxytocin-levels-in-the-brain-fe5ac39bc57
« Last Edit: February 22, 2020, 07:46:25 AM by BoneBroth »

yesyesyes

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Re: POIS cure: theory & supplement stack
« Reply #524 on: February 23, 2020, 07:22:32 AM »
Anyone who tried binaural beats, recordings of white noise and nature sounds, and Solfeggio tones? I think they really do lower cortisol and stress in general.

Muon

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Re: POIS cure: theory & supplement stack
« Reply #525 on: February 23, 2020, 06:23:08 PM »
Last week, and for the first time in my life, I also experienced a horrible one-week POIS period without orgasm/NE but after some stressful days. But in addition to the stress it started within a day after a restaurant visit where I ate unusual amounts of carbohydrate (French fries and some spicy sweet sauce) and particularly a dessert with lots of ice cream and a belgian wheat-waffle together with coffee. I dont use to eat that much sugar/wheat in one day since I 've been cutting down on all that. I believe that it was the stress in combination with a sugar-coffein-carbohydrate spike that released this POIS!

Mast cells being triggered by multiple triggers all at once.

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #526 on: February 23, 2020, 11:31:48 PM »
Hi Luminous,
  Sorry I didn't see your questions. But they are good questions. Also thanks BoneBroth for bringing up Luminous' previous post!
...I happen to have (two) different version(s) of POIS.

A- If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS...The more i sleep the sooner i can recover from these symptoms...
POIS is not triggered if i sleep at night right after sex....

B- If i orgasm after masturbate, then POIS kicks in within an hour ...Even if i go to sleep right after masturbation/orgasm at night, it still does not help !... I was also deficient in vitamin D3 and after taking supplements for it, the POIS symptoms got a little bit better...

In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation?...
  There are two reason given in the POIS literature for a difference between POIS from sex versus masturbation. The first reason comes from the paper:
  Progesterone deficiency, "Benign coital headache relieved by partner's pregnancies with implications for future treatment" (Selwyn Dexter, 2009)
  In this paper, they conclude that the male POIS patient benefited from his wife's progesterone (exchange of sexual bodily fluids). They tested this by giving the man a progesterone mimicking drug which relieved his POIS 95 percent.
  The second reason is given by the paper:
Mu-opioid receptor dysfunction, "Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen" (Jia Yin, et al, 2015)
  In this paper, they suggest that low beta-endorphin stimulation is the reason that POIS occurs. Beta-endorphin blocks some of the negative (immune suppressing) properties of norepinephrine, epinephrine and prostaglandin PGE2 (see post). Social interaction (especially with the opposite sex) can increase endorphin release. Laughter (comedy) is also a major endorphin releaser!


...And why do i have to sleep within 20min or so after sex to avoid POIS?...
  The short answer may be that sleep boost your immune system. The sleep response is the immune system telling your body that it is not strong enough to handle POIS. The first thing that happens during sleep is that epinephrine and norepinephrine levels drop, and melatonin levels increase:

White circles: 24 hour sleep deprivation, Black circles: 24 hour normal sleep. Gray region (23:00 - 7:30): sleeping period
-Number and Function of Circulating Human Antigen Presenting Cells Regulated by Sleep


Effects of sleep and circadian rhythm on the human immune system

  Since the immune suppressors (epinephrine and norepinephrine) decrease and the immune enhancer (melatonin) increases, this leads to the release of immune stimulating cytokines (IL-2, IL-12, IFN-y, TNF-a, etc...). It also causes the immune suppressing cytokine IL-10 to decrease.

...And i don't understand why i get so heavily sleepy headed with POIS as if i am drugged and i am literally dragging myself to do daily chores not to mention the anxiety and discomfort that comes with it/pois(?)
  The immune system then produces sleep signals (adenosine, etc...) to force you to go to sleep. Once you are sleep, your immune system can increase its capabilities by using sleep to suppress norepinephrine/epinephrine levels and by releasing immune stimulating cytokines (IL-2, IL-12, IFN-y, TNF-a, etc...).

  I really appreciate, the questions because they highlight the connection between POIS, sleep and immunity. On this thread, I try to focus on practical solutions for relieving POIS symptoms. And I try to avoid talking about theory in this thread. So I won't go much further other than to say that sleep (as an immune booster) is required for recovery from POIS. For a deeper discussion on theory, I recommend the threads: Transiently Induced Immune Deficiency and Therapy and Ideas on Herpes Induced POIS. I hope this helps! :)
« Last Edit: February 24, 2020, 11:04:49 AM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Muon

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Re: POIS cure: theory & supplement stack
« Reply #527 on: March 07, 2020, 07:40:41 AM »
Mediator(s): Phospholipases (including PLA2) ---> Major pathophysiologic effects: Arachidonic acid generation, inflammation

Table 1:

Differential release of mast cell mediators and the pathogenesis of inflammation

"Eicosanoids (prostaglandins, leukotrienes, and thromboxanes) are produced by catalytic conversion of arachidonic acid by the action of phospholipase A2 on membrane phospholipids. Mast cells express COX1 and COX2, which converts arachidonic acid into prostaglandins and thromboxanes with the action of specific isomerases (38). Prostaglandins increase vascular permeability and attract neutrophils. Leukotrienes are involved with smooth muscle contraction, airway constriction, and mucous secretion (39). Eicosanoids act at the local area of mast cell degranulation. "

Mast Cell: A Multi-Functional Master Cell

Also MCs can release mediators which upregulate COX enzymes.

This is why NSAIDs are being used in MCAD patients. A subset of POIS patients may experience release of phospholipids from MCs or mediator release which upregulates COX. These people might benefit from NSAIDs.


You could replace the boxes above phospholipase A2 by a box with Mast Cell Activation or MCAD. And since ROS can be released from MCs along with other COX upregulators, you could draw a line from the MCAD box directly to ROS. An additional parallel line can be drawn from the upper MCAD box directly to PGE2 as well.
« Last Edit: March 07, 2020, 08:13:24 AM by Muon »

dklimbani1

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Re: POIS cure: theory & supplement stack
« Reply #528 on: April 07, 2020, 05:03:19 AM »
I think patients should keep wrist BP monitor or standard BP monitor at home, this will track blood pressure continuously, here is the trusted source of BP monitor recommendation - BP Machine Price

Hope it will help

Thanks

millstone

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Re: POIS cure: theory & supplement stack
« Reply #529 on: April 10, 2020, 10:27:29 PM »
Since we are on Page 36 of this thread...

Has anyone else actually tried the daily POIS Cascade Stack from Page 1 for at least a few months and seen any improvement?

I'm not referring to the pre-pack. I'm referring to the daily regimen intended to down-regulate a1A / h1H / COX-2.

I have a call with my functional doc on Tuesday to discuss options, and at this point I'm pretty sure I'm going to just dive into the supplement plan since I'm now already taking half of the stack daily anyway.

Iwillbeatthis

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Re: POIS cure: theory & supplement stack
« Reply #530 on: April 18, 2020, 04:48:25 PM »
The methylation stack finally works for me in the past when I tried the full amounts from the stack it would cause bad brain fog and throw me off balance - bad anxiety speech problems. What did I do?  I was taking lipsoomal glutathione and a binder bentonite for a month and my head felt much clearer and normal but speech problems, brain fog and autistic symptoms persisted
Then I thought I would try supporting methylation again using 200mcg - folinic acid, 75mg - sam e, 500mg-methyl b12 liposomal vitamin c 1g - and just like that I feel incredible and euphoric all brain fog and anxiety speech issues have gone I have never been able to speak this well in my life. My bad reactions to showers have stopped also.

The key is to lower sam e and folate amounts - if its not working for you empty most of the capsules and just use tiny amounts so you can see what works for you. If you react badly to methyl folate use folinic acid. I'm assume I must have had high homocysteine levels as the difference has been life changing.

I had been using liposomal vitamin c and folinic acid on their own and I was reacting terribly to the folinic acid with vitamin c,  Sam e and methyl b12 were definitely needed
« Last Edit: April 18, 2020, 04:50:00 PM by Iwillbeatthis »

drop247

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Re: POIS cure: theory & supplement stack
« Reply #531 on: April 18, 2020, 09:28:50 PM »
Have you tried taking only SAM-E? It's the only thing in this stack that doesn't seem to make me feel sick. Other than Vitamin C.

I'm curious about Folinic Acid though.

Iwillbeatthis

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Re: POIS cure: theory & supplement stack
« Reply #532 on: April 19, 2020, 05:02:05 AM »
Drop I used to react badly to methyl folate and methyl b12 folinic acid if i took on them separately and even together the key was to lower the amounts. Sam e I haven't tried taking on its own but a full capsule I don't react well when taken with others.

drop247

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Re: POIS cure: theory & supplement stack
« Reply #533 on: April 19, 2020, 09:21:05 AM »
Where do get your folinic acid from?

Iwillbeatthis

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Re: POIS cure: theory & supplement stack
« Reply #534 on: April 19, 2020, 03:44:52 PM »
From Seeking health they have the best supplements as they know which forms/amounts of vitamins and minerals need to have an effect on you.

Muon

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Re: POIS cure: theory & supplement stack
« Reply #535 on: April 23, 2020, 06:47:46 PM »
In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation?...
  There are two reason given in the POIS literature for a difference between POIS from sex versus masturbation. The first reason comes from the paper:
  Progesterone deficiency, "Benign coital headache relieved by partner's pregnancies with implications for future treatment" (Selwyn Dexter, 2009)
  In this paper, they conclude that the male POIS patient benefited from his wife's progesterone (exchange of sexual bodily fluids). They tested this by giving the man a progesterone mimicking drug which relieved his POIS 95 percent.
  The second reason is given by the paper:
Mu-opioid receptor dysfunction, "Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen" (Jia Yin, et al, 2015)
  In this paper, they suggest that low beta-endorphin stimulation is the reason that POIS occurs. Beta-endorphin blocks some of the negative (immune suppressing) properties of norepinephrine, epinephrine and prostaglandin PGE2 (see post). Social interaction (especially with the opposite sex) can increase endorphin release. Laughter (comedy) is also a major endorphin releaser!

...And why do i have to sleep within 20min or so after sex to avoid POIS?...
  The short answer may be that sleep boost your immune system. The sleep response is the immune system telling your body that it is not strong enough to handle POIS. The first thing that happens during sleep is that epinephrine and norepinephrine levels drop, and melatonin levels increase:

Check this out. If you combine above theory with mast cell activation theory, all three parameters point in the same direction, coincidence?:

Melatonin: Inhibits mast cells (Increased melatonin = improved POIS symptoms)
Progesteron: Inhibits mast cells (Increased progesteron = improved POIS symptoms)
β‐Endorphin: Stimulates mast cells (Increased β‐Endorphin = worsening of POIS symptoms)

Table 1:
Neuroendocrinology of mast cells: Challenges and controversies

Cursed

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Re: POIS cure: theory & supplement stack
« Reply #536 on: April 24, 2020, 05:17:33 AM »
The methylation stack finally works for me in the past when I tried the full amounts from the stack it would cause bad brain fog and throw me off balance - bad anxiety speech problems. What did I do?  I was taking lipsoomal glutathione and a binder bentonite for a month and my head felt much clearer and normal but speech problems, brain fog and autistic symptoms persisted
Then I thought I would try supporting methylation again using 200mcg - folinic acid, 75mg - sam e, 500mg-methyl b12 liposomal vitamin c 1g - and just like that I feel incredible and euphoric all brain fog and anxiety speech issues have gone I have never been able to speak this well in my life. My bad reactions to showers have stopped also.

The key is to lower sam e and folate amounts - if its not working for you empty most of the capsules and just use tiny amounts so you can see what works for you. If you react badly to methyl folate use folinic acid. I'm assume I must have had high homocysteine levels as the difference has been life changing.

I had been using liposomal vitamin c and folinic acid on their own and I was reacting terribly to the folinic acid with vitamin c,  Sam e and methyl b12 were definitely needed

Do you still need to continue taking liposomal glutathione or are the B vitamins and SAMe enough on their own right now?

ETA: actually Nancy Klimas, a ME/CFS researcher, recommends starting with antioxidants(just like you did) before introducing things like folate and b12. She recommends to begin with L-carnitine, glutathione, ubiquinol, vitamin C, NAC and only then proceed to folate, etc.
« Last Edit: April 24, 2020, 04:13:57 PM by Cursed »

Cursed

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Re: POIS cure: theory & supplement stack
« Reply #537 on: April 24, 2020, 08:46:36 AM »
Have you tried taking only SAM-E? It's the only thing in this stack that doesn't seem to make me feel sick. Other than Vitamin C.

I'm curious about Folinic Acid though.

Don't know if this applies to you, but I find that glycine(collagen) is often left out of methylation support protocols. I find that Chris Masterjohn's approach is the most sensible and I would recommend everyone to at least have a look. His other videos (unrelated to methylation) can also be very helpful sometimes.

https://chrismasterjohnphd.com/blog/2019/03/01/start-here-for-mthfr-and-methylation/

Also, another interesting article from Chris on SAMe and why it may be helpful for someone:
https://www.westonaprice.org/helps-consider-magnesium-metabolic-rate/

Basically, the reason why SAMe helps may be Mg deficiency or low metabolic rate/ATP deficiency.
« Last Edit: April 24, 2020, 11:04:55 AM by Cursed »

Cursed

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Re: POIS cure: theory & supplement stack
« Reply #538 on: April 24, 2020, 11:18:55 AM »
Sorry for multiple posts, but I also wanted to ask if anyone has any ideas about creatine vs SAMe? I see nanna has linked to a study that shows down regulation of a1A with SAMe, but it seems to be temporary and in rats so not sure about the significance.

For those who don't know, creatine should theoretically spare almost half of endogenous SAMe(or methyl groups in general), but creatine has been shown to have its antidepressant activity via UPregulation of a1A, so if nanna's theory is correct it should make POIS worse, but who knows.

The problem with creatine is that it affects the GI tract negatively, when its used as a monohydrate (most popular form). I wouldn't recommend this to anyone with POIS since so many people, including me, suspect that GI health is very important and we shouldn't mess with it. My experience with monohydrate was a double edge sword. It helped TREMENDOUSLY with energy, but completely messed my gut so the net effect was definitely negative.

There is creatine HCL, which seems to have no GI side effects. I have bought some, but haven't yet tested it enough to know one way or the other.

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #539 on: April 25, 2020, 01:55:42 AM »
Hi Cursed,
...I also wanted to ask if anyone has any ideas about creatine vs SAMe? I see nanna has linked to a study that shows down regulation of a1A with SAMe, but it seems to be temporary and in rats so not sure about the significance.
  Neuron receptor studies involving counting numbers or percentages of receptors are not done in humans when diet is being studied. These experiments are only done in animals because, in order to count the receptors you have to kill the animal and remove the brain. The brain is then sliced into pieces and treated with chemicals to stain/tag the receptor or a related marker. This is what I do in my research. I study the brain tissue after we sacrifice and remove the brain from mice.

  The regulation of receptors by SAMe is not specific to only the alpha1 adrenergic (a1A) receptor. It is a general regulator of neurotransmitter and hormone receptors through its production of phosphatidylcholine (PC) and neurotransmitter feedback loops.

"Normal membrane fluidity enhances receptor function and enhances the role of receptor coupling. To promote this function by methylating plasma phospholipids, SAMe may alter the fluidity of the neuronal membrane, affecting the function of proteins that traverse the membrane. This beneficial induction includes that of defined monoamine receptors, monoamine transporters, and other elements of the second messenger system."
-S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life (2018)

For example, SAMe increases:

For those who don't know, creatine should theoretically spare almost half of endogenous SAMe(or methyl groups in general),...

 I would distinguish between methyl-group cyclers ((SAMe, folate/vitamin B9, vitamin B12) and methyl-donors (TMG, choline) in the homocysteine cycle. Creatine has a very small and inefficient ability to spare methyl-donors (TMG, choline), but creatine cannot spare methyl-group cyclers (SAMe, folate/vitamin B9, vitamin B12).
  SAM-e is the sole methyl donor for more than 40 methyl-group transfer enzymes (methyltransferases) and cannot be replaced by any substance (natural or synthetic). In other words, there are many SAM-e dependent enzymes that no other methyl-donor can interact with (not even choline). It is important to note that SAM-e is not the source of methyl groups. SAM-e is cycled like folate and B12. When supplementing with SAM-e, you are not increasing the number of methyl-groups by any significant amount, you are increasing the number of parallel homocysteine cycles.


  As an analogy, consider the cylinders/pistons in a car engine. SAM-e is the cylinders and TMG is the gasoline. The car cylinders (SAM-e) are cycled and output energy (methyl-groups) each cycle. The more cylinders (SAM-e) you have, the more energy (methyl-groups) you can output per second. (By analogy, SAMe increases the horsepower). But you still need gasoline (TMG) to make the car run. ...SAM-e plays a much different role than choline or betaine. So the comparison in terms of methyl-group supplying/sparing should not be between SAM-e and creatine, it should be between TMG and creatine. And TMG (supplying three methyl-groups) is less expensive, being ~40% the cost per methyl-group of creatine (sparing one methyl-group).

  In terms of choline (methyl-group) sparing, there is no advantage to taking creatine instead TMG (or choline). However, creatine can have a very big benefit on reducing POIS symptoms as a phosphate cycler managing ATP levels.
In our car analogy, ATP would be the spark plug and creatine would be the battery. It is an imperfect analogy, but the point is that CREA and ATP supply the energy needed to recycle SAM-e and keep the homocysteine cycles going. This effect of CREA is not limited to the liver and occurs throughout the body. But it only occurs after Creatine loading.
  Creatine loading is required to see an effect (beyond placebo) because of creatine's poor bioavailability and the fact that muscles absorb most of it. The best methyl donors are CDP-choline, alphaGPC, and phosphatidylcholine (PC).
methyl group math...
...DMEA, which only has two methyl groups, cannot increase choline (3 methyl groups) without receiving a methyl group from TMG (Tri-Methyl Glycine, 3 methyl groups).

(supplement name, #methyl groups, #phosphate groups)

  Both choline and tri-methyl gylcine (TMG, betaine) are converted to L-glycine when they donate their three methyl groups. Which means that choline and TMG are sources of glycine for the body. Can you share your article about creatine and a1A receptor? I am interested to read about this.
« Last Edit: April 25, 2020, 02:44:22 PM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/