Cholinergics are the only thing that makes my digestion move

[LucH]

Is there anything that improves transit which I can take with cypro other than cascara (which causes me to develop infections each time I try it) and magnesium (which doesn’t help my transit time?

Hi,
What about your MMC.?
Prokinetics and Intestinal Motility
Dr D’ORO (Swiss Dr)

Mechanism of prokinetics Prokinetics are products, either natural or medicinal, that stimulate and coordinate intestinal motility, making it more effective. They act on various receptors in the intestine, thus allowing varied mechanisms of action. Some prokinetics inhibit dopamine which acts as an inhibitor on the digestive system. (…) Other substances also act on acetylcholine receptors which is a stimulating neurotransmitter of the intestine, other substances act on antagonistic (5-HT3) or agonist (5HT4) serotonin receptors. Etc. Thanks to these combinations of action, prokinetics have the capacity to amplify and coordinate muscular contractions of the intestine. They can act on different sites of action, both on the upper part of the digestive system such as the stomach or the small intestine and on the colon. Prokinetics can improve gastric emptying by coordinating the closing of the lower esophageal sphincter and the opening of the pyloric sphincter while the stomach contracts. They are known for their ability to stimulate the migrating motor complex (MMC) to clean the small intestine of this waste. Certain prokinetics have the ability to improve intestinal transit and can be used for example during constipation. However, prokinetics should not be confused with laxatives. (…) We will see that there are natural or medicinal prokinetics.

Note: I’ve used Resolror 0.5 gr as prokinetic.

Info on MMC
“The complexity of the relationships between motility, transit and absorption is mainly due to the numerous parameters which characterize an intestinal contraction and to the nature of the intestinal contents.” (1)
1. Role of motility in intestinal transit and absorption
J Fioramonti 1, L Buéno. Presse Med. 1989 Feb 15;18(6):249-54.

 

[frannybananny]

A decent dose of B2 definitely improved mine. (I was taking B1 (I forget which form, probably TTFD) sporadically at the time.)

I recently bought the B-2 and was very optimistic because of everything I have read here. I took it early one evening to help with sleep and indeed it did relax me... I only took maybe a third of a capsule. But I had a restless night with some sleep but not a deep sleep. So I let a day go by and I took it the next day around noon. I got very tired but not sleepy and had trouble falling asleep the next night. I know I am probably deficient but really don't know what time of day to take it. I guess I will keep experimenting. I don't take cypro or anything except herbs and olive leaf extract at night to sleep... also Vit K-2 seems to make me pretty sleepy and relaxed so I guess I will keep taking that.

 

[feedandseed]

I recently bought the B-2 and was very optimistic because of everything I have read here. I took it early one evening to help with sleep and indeed it did relax me... I only took maybe a third of a capsule. But I had a restless night with some sleep but not a deep sleep. So I let a day go by and I took it the next day around noon. I got very tired but not sleepy and had trouble falling asleep the next night. I know I am probably deficient but really don't know what time of day to take it. I guess I will keep experimenting. I don't take cypro or anything except herbs and olive leaf extract at night to sleep... also Vit K-2 seems to make me pretty sleepy and relaxed so I guess I will keep taking that.

I might be K deficient now that I think about it.

 

[Peater]

I recently bought the B-2 and was very optimistic because of everything I have read here. I took it early one evening to help with sleep and indeed it did relax me... I only took maybe a third of a capsule. But I had a restless night with some sleep but not a deep sleep. So I let a day go by and I took it the next day around noon. I got very tired but not sleepy and had trouble falling asleep the next night. I know I am probably deficient but really don't know what time of day to take it. I guess I will keep experimenting. I don't take cypro or anything except herbs and olive leaf extract at night to sleep... also Vit K-2 seems to make me pretty sleepy and relaxed so I guess I will keep taking that.

I don't think I would take any B vits before bed but that's just me!

 

[frannybananny]

I don't think I would take any B vits before bed but that's just me!

Gotcha.... thanks.

 

[feedandseed]

Hi,
What about your MMC.?
Prokinetics and Intestinal Motility
Dr D’ORO (Swiss Dr)

Mechanism of prokinetics Prokinetics are products, either natural or medicinal, that stimulate and coordinate intestinal motility, making it more effective. They act on various receptors in the intestine, thus allowing varied mechanisms of action. Some prokinetics inhibit dopamine which acts as an inhibitor on the digestive system. (…) Other substances also act on acetylcholine receptors which is a stimulating neurotransmitter of the intestine, other substances act on antagonistic (5-HT3) or agonist (5HT4) serotonin receptors. Etc. Thanks to these combinations of action, prokinetics have the capacity to amplify and coordinate muscular contractions of the intestine. They can act on different sites of action, both on the upper part of the digestive system such as the stomach or the small intestine and on the colon. Prokinetics can improve gastric emptying by coordinating the closing of the lower esophageal sphincter and the opening of the pyloric sphincter while the stomach contracts. They are known for their ability to stimulate the migrating motor complex (MMC) to clean the small intestine of this waste. Certain prokinetics have the ability to improve intestinal transit and can be used for example during constipation. However, prokinetics should not be confused with laxatives. (…) We will see that there are natural or medicinal prokinetics.

Note: I’ve used Resolror 0.5 gr as prokinetic.

Info on MMC
“The complexity of the relationships between motility, transit and absorption is mainly due to the numerous parameters which characterize an intestinal contraction and to the nature of the intestinal contents.” (1)
1. Role of motility in intestinal transit and absorption
J Fioramonti 1, L Buéno. Presse Med. 1989 Feb 15;18(6):249-54.

This is what I’m talking about. Thank you so much. I’d be concerned that cypro’s serotonin antagonism would interfere with the 5ht4 agonism though. Now to see if we have a cypro alternative…

 

[youngsinatra]

I don't think I would take any B vits before bed but that's just me!

Also B2 is best absorbed with a meal as bile acids improve its absorption by 4 fold or so.

Fasted absorption is only 15% vs 60% with food.

 

[aliml]

The influence of inositol and other B complex factors upon the motility of the gastro-intestinal tract​

Inositol markedly increases the peristalsis of the stomach and the small intestine. Nicotinic acid decreases the peristaltic action of the stomach and small intestine. The other members of the B complex available in pure form, thiamine, riboflavin, choline, pyri-doxine and pantothenic acid, have no apparent action of this type. Inositol and nicotinic acid are the members of the Vitamin B complex directly concerned with gastrointestinal motility, and it is suggested that the balance or ratio of nicotinic acid or similar compounds to inositol is the nutritional factor which determines hypo- or hypermotility.

https://doi.org/10.1007/BF02998327

The influence of single and multiple B complex deficiencies upon the motility of the gastro-intestinal tract​

Young dogs 6 to 8 weeks old were given a basal diet devoid of the B vitamins, supplemented with cod liver oil and various combinations of members of the vitamin B complex, and, after 2 months, gastric motility was observed by X-ray after a barium meal. When vitamin B1 and riboflavin were the only vitamin B supplements the motility of the small intestine was increased and that of the colon decreased. When all vitamin B factors were given except nicotinic acid, inositol and p-amino-benzoic acid there was poor peristalsis in stomach and intestine with ileal stasis and much formation of gas. Lack of inositol, with or without deficiency of other vitamin B factors, delayed gastric emptying time and intestinal movement. Deficiency of pantothenic acid also slowed peristalsis even when inositol was given; in dogs deprived only of pantothenic acid the passage of the test meal into the colon was irregular and considerable amounts of gas were formed. When the basal diet was supplemented with all known B vitamins, except biotin, gastro-intestinal function appeared to be normal. Since inositol and pantothenic acid both produced a general condition of. hypertonicity with hypomotility it is suggested that the two factors should be given together in clinical practice.

https://doi.org/10.1007/BF02996960

 

[Kyle970]

I do okay with quail eggs from the Asian market. Sprouts has soy free eggs. I can only do these, the rest seem to cause slow digestion for me. Tested at home.
I agree and suspect the same reasons for this as you.

 

[peter88]

Any updates? I’ve struggled with digestive issues ever since I quit using nicotine everyday. Coffee also. I’ve tried thyroid on and off and it has never helped my bowels.

 

[feedandseed]

Any updates? I’ve struggled with digestive issues ever since I quit using nicotine everyday. Coffee also. I’ve tried thyroid on and off and it has never helped my bowels.

Well, Mirtazapine doesn't seem to have any negative effect on my regularity whatsoever so it's seeming like it's not 5ht3 related (That or mirtazapine's affinity for 5ht3 is negligible - possible) I've continued to use nicotine though combined with taurine, b3 to fight the fatty acid release. Regularity continues to be fine as long as I have my coffee and tobacco. I'll probably try to quit tobacco by substituting it out when I start a steroid cycle. I think caffeine alone is doing most of the heavy lifting here.

One other thing to mention is I started using EstroBan and it roughly coincided with a return to regularity so I wonder if it corrected some deficicency. Possibly D3 related.

 

[Wolf]

Allergic. Probably from vaccines. I supplement choline and it doesn’t seem to do much.

B1 doesn’t seem to do anything for transit time. Open to the idea of the others being deficient. I’ll have to try.

TTFD has done wonders for me and I take it every now and then.

TTFD IBS Archives - Hormones Matter

www.hormonesmatter.com

 

[EvanHinkle]

Vitamin E seems to reliably move my bowels. 200-400 ius once or twice a day.

 

[youngsinatra]

Vitamin E seems to reliably move my bowels. 200-400 ius once or twice a day.

It‘s also a strong pro-cholinergic, in a dose-dependent manner. :)

 

[supercoolguy]

Psyllium husk tends to normalize GI function.

That, would be too simple!
I use generous amount of water and combine a shot or two of vinegar to fight lower gut bacteria. 2-3 consecutive days of this and That's-That.
After that, just adding a smaller amount of my psyllium drink to my meals helps.
This give me a solution while I identify/adjust my food or pharma consumption.

 

[moa]

Trying to figure out a good solution for a dilemma I have.

On one hand, I don’t like taking nicotine because of the dependence factor and potential for negative hormonal impact On the other, the cholinergic stimulation (I assume) is seemingly the only thing that makes my digestion move.

On top of this, I benefit massively from cypro for sleep, among other benefits (stops hair shedding, calms eczema, helps allergies) but it seems to slow down my transit time substantially.

Coffee helps a little; but like nicotine, seems to dramatically worsen my sleep (I don’t dream above 40 mg of caffeine a day) and the only way around this is taking cypro for sleep (the anti ACTH/CRH effect I assume) which defeats the transit benefits for the 8-10 hours I’m asleep. Big endotoxin buildup during this time based on morning symptoms.

Is there anything that improves transit which I can take with cypro other than cascara (which causes me to develop infections each time I try it) and magnesium (which doesn’t help my transit time?

OR

is there a powerful anti-CRH (5ht2c?) substance I can use instead of cypro in combination with caffeine so I can get both the good sleep of cypro and transit of caffeine/nicotine?

(I benefit from t3/t4 but it doesn’t seem to improve transit)

seems like very similar with my own.

the solution for me, for transit time, was increase acetylcholine, with zinc, eggs and some b vitamins like B1, B5.

but it's not serotonin or endotoxin symptoms i have, those have not gone after improving transit time, only less painful because transit is improved.

those are, it think, mast cell activation and histamine release, causing a wide area of symptoms in the body from pain in the shoulder, difficulty breathing, difficulty sleeping, etc.

the reason is : low bh4, caused by high oxydative stress. this is complex, linked to upregulation of CBS gene, and other factors i think.

the key is increasing CuZnSOD enzymes, copper++ and increase antioxidants like vitamin c, or other

also copper inhibits CBS by up to 70% in vitro.

CBS gene upregulation cause bh4 depletion and high ammonia and sulfur and low glutathione.

https://www.researchgate.net/figure/The-inhibitory-effect-of-copper-on-CBS-activity-All-data-points-N-3-represent-the_fig1_7958328

finally my view is that is not a gut digestion problem as much as a problem with sulfur metabolism and oxydative balance.

it's not as much linked to endotoxin, or to serotonin as it is linked to low bh4. i checked all the 6 related enzymes that i have with mutations involved in lowering bh4 indirectly, and everything is copper dependent and magnesium.

histamine clearing is also copper depending, and sod is copper dependent too, the main antioxidant that protects bh4, because bh4 is destroyed by nitric oxide when it's not protected by sod.

higher nitric oxide is a major factor in lowering bh4 levels in case of oxidative stress (even tho bh4 is required to produce nitric oxide). because of it peroxynitrite.

low bh4 is a major trigger of histamine release from mast cells, and is also causing low dopamine and problems with glutamate.

High glutamate is problematic, when not enaught GABA. When glutamate signaling is high, it trigger nitric oxide. But because of low bh4, i think it triggers production of SO superoxide causing serious damage.

nitric oxide is actually better than so i think.

now, bh4 supplements are very expensive, out of price, and the dose is very high since you need to take them all the time, as they don't stay long in the system.

b12 with high dose methyl folate (like 1mg per day) is a bit too dangerous i think, in order to restore bh4 levels.

so, increasing antioxidant is the only way to protect against bh4 degradation into bh2.

i will try this mix : vitamin C, copper, fisetin, quercetin low dose, alpha lipoic acid, glycine, probably niacinamide 100mg.

maybe i should add some NAC or glutathione or MSM, not sure yet, i don't want to increase sulfur amino acids.

 

[moa]

taurine also seems to help with CuZnSOD, needed to protect bh4.

bioaviability of arginine also helps bh4 by using bh4 to produce NO with coupled eNOS enzyme instead of using these other enzyme, iNOS that can produce NO without the bed for bh4.

it seems citrulline supplementation could help with arginine availability, and it also can help with lowering ammonia (when CBS upregulation is the cause of low bh4).

I'm not sure how citrulline could be considered, as NO is not very peaty, considering it's role in blocking complex IV. on the other hand, only a small amount of arginine gets converted to NO, it's not there limiting factor, and citrulline is only a precursor anyway.

Taurine plays an important role in the protection of spermatogonia from oxidative stress - PubMed

It has been demonstrated that taurine has various physiological functions in the body. We demonstrated that taurine is abundant in the serum, liver, muscle and testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is found mainly in spermatogonia and is weakly expressed also...

pubmed.ncbi.nlm.nih.gov

 

[moa]

downregulation of iNOS improves IBS symptoms in rats (visceral hyperalgesia).

Downregulation of iNOS, IL-1β, and P2X7 Expression in Mast Cells via Activation of PAR4 Contributes to the Inhibition of Visceral Hyperalgesia in Rats

Protease-activated receptor 4 (PAR4) is implicated in the inhibition of visceral hyperalgesia. In the present study, the effects of PAR4 activation on visceral hypersensitivity and expression of inflammatory mediators, including interleukin-1β ...

www.ncbi.nlm.nih.gov

The availability of Cys-249 significantly affects the activity of dimethylarginine dimethylaminohydrolase (DDAH). The presence of Cys-249 in the active site of DDAH suggests that its activity might be directly regulated by S-nitrosylation of this residue by nitric oxide (NO). nitrosylation of DDAH has been shown to reversibly inhibit its activity, potentially modulating NO production in vivo

Reduced arginine availability to the nitric oxide synthase (NOS) site can lead to increased oxidation of tetrahydrobiopterin (BH4)

Cys-249, produced from cystein, is high when CBS is upregulated. upregulated CBS is linked to low bh4 levels.

low Cooper will not slow down CBS, thus more Cys-249, meaning less available arginine, meaning nos slow down and loss of bh4, ans finally mast cell activation and histamine release, that is not cleared because low copper.

high zinc is also supposed to play the same role as Cys-249, further reducing bh4.

so,
high zinc, and low copper cause arginine to be unavailable and bh4 loss???

increased arginine oxidation observed during conditions such as sepsis can reduce arginine availability for NO production. At normal concentrations of arginine, endothelial NOS (NOS3) should be saturated. However, increased NOS3 activity occurs with arginine supplementation, known as the arginine paradox, due to enhanced L-arginine-induced BH4 production, promoting NO production by NOS3.

The "arginine paradox" refers to the phenomenon where exogenous L-arginine causes nitric oxide (NO)-mediated biological effects despite the fact that nitric oxide synthases (NOS) are theoretically saturated with the substrate L-arginine


citrulline should also have the benefit of reducing ammonia more than just arginine.

I'm not sure how good it is, does citrulline supplementation have any side effects at normal dose ?

 

[LucH]

i will try this mix : vitamin C, copper, fisetin, quercetin low dose, alpha lipoic acid, glycine, probably niacinamide 100mg.

OK but mind the kind of B3: No nicotinic acid. OK for niacinamide.
=> Inositol, niacinamide and pantothenic acid (B5) are useful for peristalsis. As already posted by aliml.
Source:
1. “Inositol markedly increases the peristalsis of the stomach and the small intestine. Nicotinic acid decreases the peristaltic action of the stomach and small intestine.”
https://doi.org/10.1007/BF02998327

2. “Since inositol and pantothenic acid both produced a general condition of hypertonicity with hypomotility it is suggested that the two factors should be given together in clinical practice.”
https://doi.org/10.1007/BF02996960

Note: I’d take 3 times a week a vitamin B complex co-enzymed (B-50). B1 B2 B3 are usually required to assimilate sugars. I won’t supplement B3 without B2.

B) Moa says:

“High glutamate is problematic, when not enough GABA”

Right. When taking L-glutamine, taurine is needed.
Taurine should be used with magnesium bisglycinate.
Note: Glutamine and vitamin B6 (pyridoxal phosphate) = GABA (central nervous system calming switch).

=> Taurine protects against excitotoxicity by blocking and reducing overstimulation caused by excess glutamate. Normally, cells die shortly after being exposed to high concentrations of glutamate. But when they are pretreated with taurine, the cells survive in these conditions.

=> Taurine is an inhibitor: taurine stabilizes and allows recovery in the event of ischemia. It has an effect which can be associated with an anti-oxidant effect (indirect effect).

For histamine, I’d take DAOzym 1 000 000 Unit (5-10’ before meal) and one caps of quercetine anhydre at midday (with meal).

Note: No dairy with Cu Zn supplement (same way).

 

[moa]

OK but mind the kind of B3: No nicotinic acid. OK for niacinamide.
=> Inositol, niacinamide and pantothenic acid (B5) are useful for peristalsis. As already posted by aliml.

thanks for the advice.
i have a nicotinamide of 100mg dose.

Note: I’d take 3 times a week a vitamin B complex co-enzymed (B-50). B1 B2 B3 are usually required to assimilate sugars. I won’t supplement B3 without B2.

i wouldn't take 50mg of B6 long term

Right. When taking L-glutamine, taurine is needed.
Taurine should be used with magnesium bisglycinate.

I think it's time to take taurine seriously and take it :) sometimes when is too cheap we think it's not "as good" but that's false.

For histamine, I’d take DAOzym 1 000 000 Unit (5-10’ before meal) and one caps of quercetine anhydre at midday (with meal).

DAO is nice, is does help, but it seems my problem is more systemic, related to the other one nhmt and mast cell activation.

actually what i experienced now, with both gut and systemic histamine rush, has started when i took very high dose thiamine HCl.

then it's been up and down even after stopping b1. it seems that thiamin without magnesium can trigger mast cell activation, but the degree to which it triggered in my case, quite strong, and the fact that some of the symptoms in the gut (not the other like joint pain, skin scratching) are very similar to older symptoms i had before that i never thought were caused by mast cell activation.

in the past, before i increased my acethylcholine levels (with zinc, choline and b5), i had transit problems and IBS-c, but now my transit is very good still the same pain is there without any problem in stool consistency or regularity.

so i concluded that the real problem with my old IBS -c was low acethylcholine and high histamine with mast cell activation.

that's why I'm taking all that antioxidants, to help mast cell activation and raise bh4. i have upregulated CBS gene, mthfr and mtrr, and mao-a inhibited and the other one that helps with transport of catecholamines impaired.... in total i have 6 mutations that lower bh4, that's why i have mast cell activation.

magnesium is needed to stabilize mast cells i think, with high dose thiamine, but oral magnesium gives me GERD and apparently even some colon irritation.

do in the meantime, before i can take more magnesium orally, i need to stop this past cell activation and it will probably allow me to take again high dose B1 with magnesium (right now i can't).

Note: No dairy with Cu Zn supplement (same way).

inositol is interesting, because of reducing bipolar and ocd, and I'm genetically at risk in my family.

i don't understand, copper only with food, i can't take it without food it makes me nauseous. dairy is problematic ?