The Connection Of Serotonin And Bowel Movements?

[Terma]

Well, some people get that from salicylates and it can affect the blood... If you're not getting clear benefits from aspirin I would stop it.

I had eye problems but I don't know what fixed them. Amino acids are a good bet, and also things that help shuttle fatty acids like carnitine (because they help control the levels of FFA, which cause eye damage) which happens to be mostly lysine and methyl.

If I had to go back I would probably focus on the ideas about circadian rhythm I laid out:
Rhythmic Diurnal Synthesis And Signaling Of Retinoic Acid In The Rat Pineal Gland And Its Action To
because this strategy would for example help give eyes better resources to heal during the nighttime. If your eyes never heal, that is actually not a bad indicator of disrupted circadian rhythm and nighttime repair.

 

[Astolfo]

@Terma I got the MK7(100mcg) and Magnesium(200mg elemental). Riboflavine was pretty expensive.
As I said, I no longer read pubmed articles. I don't even read forums anymore, just this topic.
I would be happy if there is anything I can try. And if needed, I can try to give every clue I find.
For example, Watermelon gives me brainfog. It's the only fruit affects me that much.
Hopefully, I will get some naltrexone in the next month.

My muscle control issue improved a bit. That was never happened before, except the ketogenic diet. I'm nowhere near to my oldself though, I just type on keyboard a bit easily.

Emotions are getting worse. Actually they've been negatively affected from aspirin imo. Maybe it's not related to aspirin at all, because they are already getting worse by time.

 

[Terma]

I can tell you from memory watermelon contains citrulline (NO precursor):
Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance. - PubMed - NCBI
Even aspirin can increase NO in circumstances (eNOS, I don't usually suspect this since it should also logically have ability to lower iNOS):
Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action
And of course lysine can lower NO:
Effect of L-lysine on nitric oxide overproduction in endotoxic shock. - PubMed - NCBI

In rats treated with saline, LPS produced a large increase in plasma nitrate and L-citrulline concentrations at 5 h, both markers of enhanced NO production. LPS also caused severe hypotension, low cardiac output and marked hyperlactataemia. All these changes were significantly reduced by L-lysine administration.

Some of these could be high doses however, I'm not sure these are all the right articles, but this isn't news.

I wish I knew exactly what 'cured' my bloodshot eyes - it looked very much like that - but it was anything among, or not: something in my environment that was removed (different soaps, note that some brands contain salicylic acid - check stuff in your environment), lysine, taurine, retinol (probably not) - it was impossible to keep track. Too much riboflavin aggravated it so don't take huge doses for extended time - though it's worth a shot, since it could improve some other aspects of gut health and those could be upstream of some of your symptoms, and of course will help kynurenine pathway function (along with B6/P5P, you can always try B3 to shortcut it too or self-diagnosis, though I'd expect benefits to be limited or temporary for B3 if kynurenine is broken). I figured it was most likely fatty-acid processing substances that helped because there was a patent on an eye health supplement that was a combination of 'lipotropic' (lipid-handling/burning) supplements that included choline and such (related to carnitine and lysine, maybe TMG? Can't find it), and it's logical for eyes to be especially sensitive to free fatty acids and things like tryptophan. Note that if ketones drove more Trp into your brain it might leave less available to do damage in the rest of the body including the eyes.

I thought for awhile I was developing Srojen's, and that could be perpetuated by kynurenine pathway dysfunction, but I'm not sure, and it went away.

Sorry if other people posted, exhausted my 20 mins on this.

 

[Terma]

I'm sorry I can't do more right now man, we all need to go way further than this. I know how much it sucks. Believe me I know how much it sucks to have your life ripped from you and not one damn doc takes responsibility for any of it. I literally wanted to murder the CEO of Bayer pharmaceuticals in front his family by drowning him with his own pills, it felt morally right at the time. I'm sorry if anything I suggested makes things worse. You gotta navigate the waters yourself. If I get any good ideas believe me I'll post them here, but you might have to try some stronger patches to get by in the meantime, even if it's just weed or beta-blockers (these may not necessarily be appropriate) or something like that. The notion of drugs vs supplements is arbitrary and fluid and those supplements are relatively weak. You'll figure it out eventually but it might take some time, so you gotta plan for the interim. It's just the way she goes. Til the world gets smarter and this doesn't have to happen anymore.

 

[Astolfo]

@Terma

Really thanks for your thoughtful comments. I know how bad the situation where I'm at now. You helped me enough.

I'm going to try some naltrexone, hopefully next month. Do you have thought on it? Can that solve anything like an autoimmune or kynurenic dysfunction?

If that doesn't work, maybe I would try hardcore raypeat style. And I would finally give everything up when I no longer stand any more disassociation, cognitive deterioriation and physical symptoms.

 

[Terma]

I never tried LDN. It seems very hit or miss. It's worth a shot as a "patch" (assuming it doesn't do more I haven't seen). I had a stint with opiates, which of course really help temporarily (before tolerance ofc), but I believed they reflected some kind of competition with the dynorphin/KOR system, or on the other hand because they interact with adrenergic receptors (linked above). Or even histamine. Or even the gut, since they significantly slow down gut transit (you could try 2-6-mg loperamide to slow down your gut, but THC and DHEA are probably less damaging in the long run). They can also increase the conversions of steroids toward downstream ones. Connection between kynurenine and opiates is probably indirect but I couldn't see one last time I looked, though could be something I overlooked. It should have some effect on the immune system, so it's not impossible it links back somehow, not sure.

I am sure you can find something for cognitive degeneration, because I did. 5 years ago I could not read past the abstracts of scientific articles and was stuck in permanent brain fog. It might just not be a permanent solution. Anyway you get to a point where you'll try anything. The silver lining is it kind of opens your mind, though I know you probably don't care much about that right now.

(Not in a state to answer other posts right now, but this ***t bothers me because it hits so close to home)

 

[Terma]

The only thing I have left to suggest for you is the mega protocol I started using myself:
Consciousness Is Quantum, Can Be Modulated With Specific Chemicals

Everything from magnesium, cannabinoids to methylfolate are well known as adjuncts in antidepressant therapy (it is basically all the adjuncts in antidepressant therapy!). But you would have to adjust this depending on your state: blood pressure & heart rate (it lowers blood pressure and increases heart rate), motor control (some of these could in fact worsen this), etc.

I'm aware the problem is access to medication and funds. I'm really sorry, I don't know what you can do about that. I didn't catch where you live but that's not fair to say the least.

 

[Astolfo]

@Terma Thanks. Unfortunately, there is few things I can buy at where I am now. I want to mention a page to you.

Chronic Fatigue Syndrome (ME/CFS) May Be Caused By Increased Serotonin Sensitivity

I think it was cypro, in higher doses like 8mg daily in divided doses, and one took thyroid. The girl said it took about a week of cypro at high doses and then suddenly the depression and fatigue were gone. I am guessing it was either the re-sensitization of glucocorticoid receptors or the antiviral effect.

What do you think? I got the first symptom after just a few days of fluxoetin usage, that was excessive sleepiness. And, my brain slowly retarted since that day. Nowadays, I don't do anything and lie down to couch all day. I really lost my intelligence, this is more than a brain fog. My brain feels alive, there is no any fog at all, but I have much more tiny intellectual ability

I guess, really low level of glucocorticoid signalling causes autoimmunity, loss of anxiety and encephalopathy.

What do you think? If there is a problem with kynurenine, there must be a underlying problem and I think that can be this. I once tried 4 mg cypro, then got really serious hypoglycemia symptoms, so 8 mg is a really huge dosage. Should I give it a try? How much dangerous is it?

 

[Astolfo]

@haidut I guess I need more help at now. Please.

 

[Terma]

Unfortunately cyproheptadine is such a blunt weapon it's impossible to tell what it does. It could readjust the relative sensitivities of the different 5-HT receptors, conceivably yes help resensitize the GR receptor with chronic use, and about 50 other things. I'd say it's worth a shot but you should monitor your vitals (heart rate, blood pressure, unfortunately you probably can't test your liver...) - but I couldn't make use of it at all. Yeah GR insensitivity will affect autoimmunity but I tend to think the kynurenine metabolites are more important there.

 

[Astolfo]

Unfortunately cyproheptadine is such a blunt weapon it's impossible to tell what it does. It could readjust the relative sensitivities of the different 5-HT receptors, conceivably yes help resensitize the GR receptor with chronic use, and about 50 other things. I'd say it's worth a shot but you should monitor your vitals (heart rate, blood pressure, unfortunately you probably can't test your liver...) - but I couldn't make use of it at all. Yeah GR insensitivity will affect autoimmunity but I tend to think the kynurenine metabolites are more important there.

So, why there is a problem with kynurenine metabolites, what causes that? I don't think taking magnesium and B vits will help. All other things you have tried is not available at here

I guess cypro will be second thing I will try as last chance.

 

[Terma]

Sorry bud I don't know what else to suggest right now. Again you might need something for temporary relief even if it doesn't cure you. You know what I use. Whatever you can get your hands on. You'll find something.

 

[Terma]

What part of the world are you in anyway, if you don't mind me asking?

 

[Astolfo]

Turkey.

 

[Terma]

If funds are part of the issue I'd be willing to paypal you what I can spare if you PM me [If PM doesn't work - someone told me they weren't working once, no idea - let me know and I'll post an email here]. But short of emigrating or illegal markets I just don't know what your options are there.

 

[Astolfo]

Really thanks, but I can't accept that.

I have read the page once again which I posted here yesterday. It seems, 5ht2a receptors affect blood clotting, anxiety, cognition, vagus nerve, sleep cycle and so on. Is there anything I can try to see if 5ht2a has a role in my condition?

Also there is a few thing I want to add.

At last days, my gut problems worsened A LOT. I ate meat for a week at this week. I suspect, this and masturbation both have a role.

I guess, normally people at morning feels generally bad until drink a cup of coffee. I feel better and have a deeper thinking ability. I'm drinking 5-6 packets of instant coffee a day, yet I haven't experienced any negative symptom from withdrawal at all.

 

[Terma]

Most likely you're not going to absorb amino acids from meat well. That's what I assume for myself and undoubtedly why whey and amino acid supplements have helped me.

I mean cyproheptadine is not the worst idea in the world (and sure it'll blunt 5-HT2a), it's just I don't know if it's appropriate for people under 20 or not and you have to plan to be incapacitated and useless for a week at least, cause it's strong and kills off dopamine, histamine and acetylcholine for awhile. But in my opinion it might be for nothing if you don't load up on successfully-absorbed amino acids and nutrients at the same time. Neurons and receptors (e.g. GR assembly) need aminos for protein synthesis, and of course carbs. You should probably capitalize on ketones (caprylic acid?) at the same time if they worked for you (iirc). I suppose I never tried a cypro+ketone combo, might be interesting (might be similar to what happens on my protocol). Try to capitalize on the things you know already worked. Also higher dose magnesium - you can go up to 800mg temporarily if it doesn't bother your gut too much (it's an effective pharmacological antidepressant on its own for some people - at high doses), although you'll lose a lot through the gut. Same for riboflavin though I know you said it was expensive. In some ways cypro + nutrients is not that far from the protocol I use (since tetrahydrocannabinol is a blunt weapon retrograde neurotransmitter) except I do the opposite of that person and avoid chronic use for my purposes, so I can barely comment. But in theory it'll kill off a ton of neurotransmission and this might allow your neurons to recover in the meantime with nutrients - but you have to absorb them.

But again I've never tested this at all and I defer to others for experience with cyproheptadine. I'd also tell you you might have to stop or lower caffeine before doing that. I got no idea how high dose caffeine interacts with cypro (you can probably see if a little helps afterward) but caffeine > 50-100mg always distorted my system and now I do better without it entirely. Watch out for your cardiac system although it might have some resilience at your age.

Aminos will also help protect your liver from negative effects of drugs like cyproheptadine. Don't forget taurine which is cheap in bulk globally and can be used in high doses safely [except don't high dose if low blood pressure] and may have desirable effects of its own, if you find it.

 

[Astolfo]

I won't take cypro. I have finally found something valuable!!!

I'm very lucky because that's study is what I have read with my last brain cells left.

Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance

I have read the whole page. And that's the simple explanation of the situation:

I had been an extremely anxious person ---> desenstization of glucocrticoid receptors and loss of negative feedback ---> chronic stress shifted my immune system to the th2 also all my body homeostasized properly to compensate chronic stress ---> I took a few dose of fluoxetine ---> that bombarded everything in my body including glucocorticoid receptors ---> I left with hypocortisol/hypostress state and the immune system shifted to th1 ---> progressive brain damage, diabete(I have pretty much diabete symptoms, you know?), CFS, etc.

Also regarding to kynurenine metabolism, glucocorticoids are responsible of inducing the TDO enzyme. It's the enzyme responsible of degrading %95 of tryptophan.

Less TDO ---> more free tryptophan --> more serotonin --> more melatonin etc..

You understand? If you don't have the time to read the page, I have some quotes here.

"Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift."​

"Interestingly, some studies show that a hypoactive stress system may facilitate or sustain the Th1 shift in Th1-mediated diseases, such as rheumatoid arthritis "

"In summary, several immune-mediated diseases seem to be characterized by a multistep process resulting from complex interaction between predisposing genetic traits, infections, episodic and chronic activation of the neuroendocrine stress system and fluctuations in the Th1-Th2 system."​

"Episodic or chronic activation of the neuroendocrine stress system due to several causes, including stressful events and intercurrent infections together with genetic polymorphisms and epigenetic factors, affects the Th2 response, while the Th2-to-Th1 switch has been in some cases linked to a hypoactive stress system."​

"Chronic activation of the Th2-related stress system seems to lead to a Th1 switch with elevation of both Th1 and Th2 inflammatory cytokines that result in chronic systemic inflammation associated with a cluster of metabolic disturbances named metabolic syndrome, including arterial hypertension, dyslipidemia and obesity (specifically the visceral type), insulin resistance and/or diabetes type 2, in addition to endothelial inflammation and hypercoagulability of the blood [101]."

Dyslipidemia ---> I don't remember if I said before, but I have been reacting to "turkish coffee" pretty bad. I makes all my sympoms worse, plus gives me jitters. I don't get the same effects from even 6 cups of filter coffee a day. That's clearly a problem about cholesterol.

"So, depressive and anxiety syndromes seem to be mainly characterized by chronic hyposerotonergic state, HPA axis hyperactivation and Th2 shift. Nevertheless, other studies suggest an imbalance Th1/Th2 shifted towards Th1 in depression [267, 268]. In this regard, a dimensional approach could lead to further insight of the issue. In melancholic depression, condition in which patients have anxiety, insomnia, anorexia and circadian variation with worsening in the morning, appears to be associated with significantly higher CSF NE and plasma cortisol levels that are increased around the clock, with inappropriately high plasma ACTH and CSF CRH levels considering the degree of their hypercortisolism. These data suggest a central hyper-noradrenergic state in association to hyperfunction of central CRH pathway [269]; furthermore, the chronic hyper-noradrenergic state may drive the increase in systemic IL-6 levels, since NE up-regulates IL-6 production, and, theoretically, to a Th2 shift [1]. On the other hand, atypical depression, condition in which patients have hypersomnia, hyperphagia and fatigue, appears to be associated with a central hypo-noradrenergic state in association to hypofunction of central CRH pathway [270, 271] and so, hypothetically, to a Th1 shift. It is noteworthy that atypical depression, ideally characterized by Th1 shift,"​

Before fluoxetine --> Insomnia, melancholic depression, anxiety etc.
After fluoxetine --> Hypersomnia, emotional numbness, zero anxiety.

"Selective Serotonin Reuptake Inhibitors (SSRIs)

In rigorous and long term clinical study, SSRIs seem to increase Th1 cytokines, such as IL-1β, IL-2 and IFN-γ, and decrease Th2 cytokines, such as IL-4, IL-10 and IL-13, and cortisol levels after 52 weeks treatment in depressed patients [252], although other in vitro and short term ex-vivo studies reported conflicting results, showing decrease in IL-1β, IL-6, IL-10, IFN-γ and TNF-α after SSRI treatment in a dose dependent manner [284-288]. In that study, administration of SSRI in MDD patients, confirming baseline high levels of cortisol, IL-4, IL-13 and IL-10 (Th2) compared with healthy volunteers, induced clinical remission at week 20 of treatment, concomitantly with an increase in IL-2 and IL-1β levels (Th1) without changes in cortisol level. At week 52 of treatment, SSRI administration induced an increase in IL-1β and IFN-γ levels (Th1), together with a reduction in IL-4, IL-13 and IL-10 levels (Th2) and in cortisol levels (a 30% diminution compared to baseline) [252]. Variations in these parameters could be caused by SSRI effects both on 5-HT and glucocorticoid receptors, as a result of chronic intake of these drugs. SSRIs exert a relatively selective blockade of 5-HT transporter [289], progressively increasing 5-HT levels, also in the circulation [290, 291], and influencing the immune response in a dose-dependent manner [252]. As a consequence, long-term SSRI treatment desensitizes the inhibitory somatodendritic 5-HT1A autoreceptors in the dorsal and medial raphe, and 5-HT neurotransmission is enhanced [292-294]. Furthermore, a desensitization of 5-HT2A and 5-HT2C receptors occurs as a consequence of prolonged exposure to elevate levels of 5-HT [295, 296]. Finally, since 5-HT neurons exert a tonic inhibitory effect on locus coeruleus neurons, it appears that enhancing 5-HT neurotransmission by sustained SSRI administration leads to a reduction in the firing rate of noradrenergic neurons [35]. Thus, drug-mediated enhancement of 5-HT activity exerts immunostimulatory effects on Th1 cytokines [32], possibly acting on 5-HT1A receptors, and concomitant immunoinhibitory effects on Th2 cytokines. Furthermore, it has been proposed that long term SSRI treatment in depressed patients causes a decrease in circulating cortisol levels by reestablishing the down-regulated glucocorticoid receptor sensitivity [27], thus restoring negative feedback by cortisol on the HPA axis [297-299]. "

 

[Astolfo]

@Terma Forgot to mention you...

 

[Terma]

What you're saying makes some sense. You do have to make a distinction between cortisol levels and GR insensitivity, even though the effect may appear the same (it is not guaranteed the same since it has some non-GR effects). But iirc the TDO effects are through the GR so yeah that is certainly possible, though I only read about that dynamic in the liver (can't remember about neurons).

I'm not sure about turkish coffee, because that could contain a lot of different compounds.

In general yes I would expect changes in immunity along those lines - the major kynurenine metabolites have immunosuppressive properties usually - but yes from serotonin too - and absence of GR activity.

Anyway I think you're pretty clever. It's just practically-speaking I'm not sure how approach that. Cypro wasn't the worst idea ever but it's certainly up to you since I wouldn't use it on myself anymore lol. I really do think amino acids will be important to you - especially from an immune angle, because the immune system sucks them up. The fact you have digestive troubles speaks to this. [But you may need something not unlike cypro to help your body absorb and fully utilize them - and other nutrients - including cholesterol for sure]