The Connection Of Serotonin And Bowel Movements?

[Terma]

Maybe one important addendum to your first article:

BH4 is also an important candidate for future cancer immunotherapies, as activated T cells sense and fight cancer cells. Analyzing mice, the researchers discovered that higher levels of BH4 activate proliferation of T cells, causing tumors to shrink. Intriguingly, the research team now found that kynurenine, a molecule that can turn off the immune system in tumors, blocks T cell growth – which can be overcome by BH4, allowing T cells to escape local immunosuppression in the tumor environment. "We studied BH4 in pain perception earlier. This is a great example how different fields of research, working together, can make novel discoveries at the interfaces of different kinds of biology”’ says Harvard’s Clifford Woolf. “In our case, a molecule recognized as essential for many functions in neurobiology, is now identified as key for completely novel therapies – when we dial it down we block T cell proliferation in autoimmune diseases or asthma. When we dial it up, we can trigger T cells to grow and attack tumor cells, even under adverse conditions – and hence have discovered a new pathway to induce anti-cancer immunity, one that should greatly expand the effectiveness of the check-point inhibitors currently used". Since the researchers developed a potent and orally available inhibitor, this new concept can soon be tested in human patients.

Indeed this can be true about kynurenine since it's an important precursor but they can only say this safely if KMO is functional (not NADPH-starved or otherwise) because kynurenine itself surprisingly appears to be an mTorC1 agonist except weaker than tryptophan and without the amino contribution (this gets impossible to follow, because in articles they don't always distinguish properly between kynurenine and its derivatives). Meaning it would be expected to trigger apoptosis only if it lead to a nutrient depletion through mTorC1 (or some other effect) - but that should require higher amounts [of kyn] while nutrient depletion is not quite synonymous with cancer. I think it only safely "disarms" proliferation after KMO consumes the NADPH and goes down the pathway, although the other metabolites also have various of their own effects on the immune system and other cells, and later you end up with more NAD. (I am still unsure how much the NADPH consumption itself alters growth quantitatively, but it is anabolic...)

It's also interesting to note that several years ago members of forums were trying to increase BH4 (oops?). It's synthesized de-novo from purines (GTP) and then recycled. Anyway BH4 does add an interesting angle and it might morph some of my ideas.

Note I reserve the right to adjust these ideas lol because kyn pathway could represent so many states - like a state machine - it's not funny.

 

[Terma]

I still need to read the full article, but this is interesting (!!!):
Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid

Tryptophan metabolites in the kynurenine pathway are up-regulated by pro-inflammatory cytokines or glucocorticoids, and are linked to anti-inflammatory and immunosuppressive activities. In addition, they are up-regulated in pathologies such as cancer, autoimmune diseases, and psychiatric disorders. The molecular mechanisms of how kynurenine pathway metabolites cause these effects are incompletely understood. On the other hand, pro-inflammatory cytokines also up-regulate the amounts of tetrahydrobiopterin (BH4), an enzyme cofactor essential for the synthesis of several neurotransmitter and nitric oxide species. Here we show that xanthurenic acid is a potent inhibitor of sepiapterin reductase (SPR), the final enzyme in de novo BH4 synthesis. The crystal structure of xanthurenic acid bound to the active site of SPR reveals why among all kynurenine pathway metabolites xanthurenic acid is the most potent SPR inhibitor. Our findings suggest that increased xanthurenic acid levels resulting from up-regulation of the kynurenine pathway could attenuate BH4 biosynthesis and BH4-dependent enzymatic reactions, linking two major metabolic pathways known to be highly up-regulated in inflammation.

Are there any observations in the literature suggesting that increased concentrations of xanthurenic acid, resulting from up-regulation of the kynurenine pathway, cause an inhibition of BH4 biosynthesis? Characteristic biochemical markers for the diagnosis of human genetic SPR deficiency include decreased dopamine and homovanillic acid and increased BH2 and sepiapterin levels in the cerebrospinal fluid (CSF) (29). Symptoms of the patients are characteristic of catecholamine and serotonin deficiency with cognitive and motor dysfunction (29), and resemble those observed upon administration of high doses of synthetic SPR inhibitors penetrating into the CNS (8). Patients also have impaired phenylalanine hydroxylation, as demonstrated by phenylalanine loading tests. Mild hyperphenylalaninemia was induced in healthy subjects treated with sulfamethoxazole (30, 31), which we have shown to be a potent SPR inhibitor (8). The kynurenine pathway is up-regulated upon IFN-α treatment, as evidenced by increased peripheral levels of kynurenine and increased levels of kynurenic acid and quinolinic acid in the CSF (xanthurenic acid levels in the CSF upon IFN-α treatment have not been reported) (32). Long-term IFN-α treatment is used for certain cancers and viral infections, but has adverse psychiatric effects including mental depression, anxiety, and psychomotor retardation in a significant number of patients (33). It has been demonstrated that chronic IFN-α treatment causes decreased dopamine and homovanillic acid and increased BH2 levels in the CSF, hallmarks of human SPR deficiency (34, 35). Furthermore, diminished conversion of phenylalanine to tyrosine in IFN-α treatment has been reported, indicating hepatic BH4 deficiency (34, 36). This higher phenylalanine/tyrosine ratio and this higher serum phenylalanine level are described in other diseases with immune activation and inflammation such as infectious diseases of HIV-1, dengue, and severe malaria, as well as trauma, sepsis, and cancer, indicating a common mechanism of action (37–39). Our findings raise the possibility that the biochemical and psychiatric/behavioral symptoms observed during IFN-α treatment are at least partially due to an up-regulation of the kynurenine pathway and inhibition of BH4 synthesis by xanthurenic acid. Measuring xanthurenic acid and sepiapterin levels in CSF of patients undergoing chronic IFN-α treatment would allow testing this hypothesis.

 

[Astolfo]

@Terma I can't understand well anymore, sorry. But I guess you mean BH4 is possibly responsible from most of? Is there any specific thing I can tell you to give you a clue?


Extreme sleepiness. It was the first symptom I can recall. It's like my body produces sleep hormones 5x faster. Sometimes my vision even go blurry because how bad I'm sleepy. It doesn't matter If I sleep for longer, although I can't sleep as comfortable as before, it's not refreshing anymore.


Cognitive impairment - I don't think I can properly explain how complex is this. It's far from being something like a brainfog. I feel my IQ decreased because it affects every aspect of my life. Reasoning, visual perception, imagination, long-term/short-term/working memory, memory recalling, talking ability(I have a much dumber personality if you compare me with my oldself), coordination, etc. That lobothomized feeling is so bad. It got progressively worse day by day as like as all other symptoms did.

Motor dysfunction -- The third symptom I noticed. It started with a bit worse ability to play FPS games. Today it has gotten so bad thst it also affects my walking, word pronouncing etc. Typing on keyboard or moving the mouse is so hard.

Emotional numbness - I think it's purely connected to the cognitive impairment. I can't even cry these days because I feel so empty, like I'm in a vegetable state.

My anxiety was so extreme before the antidepressant. I don't have any anxiety problem at all now. The disease slowly solved my anxiety problem.


Hyperactive bowel - It's a sudden effect, happens when I'm under a bit of stress or when I'm trying to do a mental task. I think it's like something in my body made the vagus nerve 500x more sensitive. School starts again in 30-40 days, and I don't think I can stand it again. It's the worst symptom when I'm at the school.

Myoclonic jerks - Random parts of my body trembles at random times. it sometimes happens at the same time with the above.

Turkish/arabic coffee makes all the symptoms much worse. Bloathing, noise and discomfort, lightheadness, muscle trembling etc. But I can drink several cups of nescafe or tea in a day. There is something special in the turkish coffe.

 

[Terma]

BH4 supports monoamine synthesis like dopamine but the same molecule triggers the immune system so it's a double-edged sword. It was already thought to be a rate-limiting factor in monoamine synthesis at least under circumstances. Xanthurenic acid (XA) appears to be - among other things - a switch to turn off BH4.

To me it seems like KYNA is a soft pedal brake that you press on and off as your metabolism (NAD) drives to help control its effects on NMDA, acetylcholine, dopamine - but it can go too far and kill off cognition and your drive. XA would be the parking brake because it affects at least BH4 and mGlu2R which are major targets. So, you could definitely have problems with these. In what direction for you? I'm not sure. They could both help or worsen symptoms. XA struck me as something powerful, but it's hard to relate it because it could rather temporarily make someone feel better. It's possible fasoracetam could give someone a clue, as being a mGlu2R agonist it might share some effect overlap with XA (only without affecting BH4), but I don't get the impression anyone's looked at that...

I can say I had the same experience regarding anxiety: anxious in the past but after much disease it kind of went away and with supplements it's completely obliterated. Lots of magnesium and steroids and phenibut.

Bowel issues and other pain sensitivity can tie into TRP (pain/heat/cold) channels that are tied together by the serotonin system via 5-HT3, which is also in the gut - I have such issues myself - pain in one area can sensitize another area through this system. Alternatively, acetylcholine/receptors could be messed up for you. Histamine receptors could be an issue, but I can't really tell.

If I were you I would first look into your more unique symptoms like myoclonic jerks - sounds like acetylcholine (not sure if nicotinic or muscarinic receptors). Coffee wouldn't help that. The jerks you could possibly even get a specialist to at least diagnose, like a neurologist. Along with motor dysfunction. Histamine could be involved in that one too. That's about all I can think of today. I probably can't tie all your issues this way, I can only give you some hints.

 

[Terma]

You could always try 1200-2400mg NAC (n-acetylcysteine), with some magnesium (and maybe glycine), it's a go-to in these situations for symptom relief and if you think kyn pathway is involved it helps spare NADPH and quell several excitatory neurotransmitters - but it's not a great thing to take for extended periods. Well there's tons of things like that (I use phenibut and THC but you have to use very judiciously - I'm not sure these are appropriate for you).

About acetylcholine I meant as in it could be a specific type of receptor you have an issue with now (e.g. antibodies to muscarinic receptors).

 

[Terma]

You can see hints of what I wrote in this (note the last sentence), and iirc there are even more putative explanations than this for the effects of fluoxetine deeper in the literature:

Fluoxetine - Wikipedia

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and does not appreciably inhibit norepinephrine and dopamine reuptake at therapeutic doses. It does, however, delay the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Large doses in rats have been shown to induce a significant increase in synaptic norepinephrine and dopamine.[72][73][74][75] Thus, dopamine and norepinephrine may contribute to the antidepressant action of fluoxetine in humans at supratherapeutic doses (60–80 mg).[74][76] This effect may be mediated by 5HT2C receptors, which are inhibited by higher concentrations of fluoxetine.[77]

Fluoxetine increases the concentration of circulating allopregnanolone, a potent GABAA receptor positive allosteric modulator, in the brain.[75][78] Norfluoxetine, a primary active metabolite of fluoxetine, produces a similar effect on allopregnanolone levels in the brains of mice.[75] Additionally, both fluoxetine and norfluoxetine are such modulators themselves, actions which may be clinically-relevant.[79]

In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.[80][81] Fluoxetine also functions as a channel blocker of anoctamin 1, a calcium-activated chloride channel.[82][83] A number of other ion channels, including nicotinic acetylcholine receptors and 5-HT3 receptors, are also known to be inhibited at similar concentrations.[79]

To me it's clear kyn will be affected, but in what direction and how it relates back to these isn't totally clear yet (besides the auto-immunity thing, which NAC appears to help).

 

[Astolfo]

@Terma I tried NAC before (600 mg / daily), but it didn't seem like helping. It was making my emotions even more number also.

Magnesium oxide or citrate would be nice?

I have been taking 100 mg aspirin daily since a week. At first it seemed like it improved my muscle control but somehow my gut problems and my cognition is worse now. Also my emotions are number. I don't know if it's because aspirin but I don't plan to stop taking it for now.

 

[Terma]

NAC may be dose-dependent and you may get different effects depending whether lower-dose or higher-dose. Lower-dose did little for me. It has complexities in the way it increases GSH and I don't remember all the details, but I didn't get much from only 600mg. (I only take it for a couple days, if I get sick)

However, NAC counteracts glutamate and/or NMDA activation so it could exacerbate low activity there (could be different things: KYNA, XA, endocannabinoids...), and so it might just not help you.

I don't really do well on aspirin, and it has enough potential issues for some people that I would not take it on faith alone.

Magnesium I use aspartate but you might want to find a topical product that works and for which you can feel its effects (this guarantees at least something is absorbing and hitting your brain and not just getting lost in diarrhea/urine). Gut issues emphasize that. But I have no way of knowing if you really need/want the pharmacological effects of Mg; if it turns out it does more harm than good (e.g. very low blood pressure), then you only want it for sufficiency and not pharmacological effect. You'll have to see, but note that if you don't do the pharmacologic doses first you might not be able to tell if it's absorbed.

 

[Astolfo]

@Terma I'm going to try 1200 mg daily for a week if so.

I may find some magnesium oil from pharmacies here. Should I worry about heavy metals? Are they absorbed topically too?

Low dose aspirin is seen to be able to reverse MS. I have pratically nothing to lose just now. Will keep taking it for a while.

 

[Terma]

I didn't worry about heavy metals when using topical magnesium gel but I don't know if they were in it. Can't answer that. I would have taken it anyway because I depended on it to function.

Food for thought: Aspirin is related to the kynurenine pathway in a curious way: it's a close cousin of anthranilic acid, which is anti-bacterial and part of one of the kyn pathway metabolites:
Anthranilic Acid: A Potential Biomarker and Treatment Target for Schizophrenia
It almost seems like anthranilic is the the mammal equivalent of salicylic acid, but I didn't get a chance to get that deep into it. ...

[It's conceivable AA might be responsible for some autoimmune effects in the other studies like the lupus one]

 

[Astolfo]

I didn't worry about heavy metals when using topical magnesium gel but I don't know if they were in it. Can't answer that. I would have taken it anyway because I depended on it to function.

I understand

Seems like, excess AA opposes NAD+ just like 3-HK. I'm keeping the dosage as low as 80 mg.
Despite this, It seemed strange that you don't do well on aspirin. It's being called helpfull in several AI diseases.

I remember I have seen this name when I was reading about kynurenine and dementia:
"Experimental Autoimmune Encepalomyelitis"

Mode of Action of Aspirin in Experimental Autoimmune Encephalomyelitis. - PubMed - NCBI


Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus. - PubMed - NCBI

I don't have diabetes, but I have these problems.

• Increased thirst
• Frequent urination
• Extreme hunger
• Irritability and other mood changes
• Fatigue and weakness
• Blurred vision

I'm starting to take B complex NAC again. It has titanium dioxide as an additive, would it be a problem?
Also do you recommend me to take riboflavine?

Is there anything I can try? Because I have nothing different than what I tried before, Also I may not be able to get naltrexone.

 

[Terma]

Thanks for the information, if there's something in there I'll comment on it later. (The second one looks great) [As for aspirin's effects on the immune system I'm not sure, but it's plausible cAMP has something to do with it I guess]

I did avoid titanium dioxide personally. Yeah some B2/R5P is essential, but don't overdo. I did better on R5P even though it's not supposed to be better than B2. For B vitamins in general I only supplement any one every 2 or 3 days.

Again I used: phenibut, THC (+ Mg + DHEA + ...), tianeptine (better off not) + progesterone, 5a-DHP, and these all helped substantially as temporary patches - but some stop stress signals while improving memory and other effects and helped me get out of ruts. For prescriptions, lyrica...

... But you have extra symptoms such as motor dysfunction that I did not have. You could have different blood pressure issues, for example, so what might help you might be different and at an extreme some of these things could harm you.

There were things that increase NADPH (like high-dose folate) but I didn't particularly think they were great. You could opt to take things that generate NAD+ (niacin/niacinamide + ribose, nicotinamide riboside). Of course ketones effectively increase NAD+ so you can take that as a loose hint. However (!) note that taking niacin (or even niacinamide) will not help tryptophan usage, so if issues come from tryprophan or those metabolites, you might want to do the opposite and explicitly avoid niacin/niacinamide and instead take all the cofactors of the kyn pathway (NADPH/[methyl]folate/etc, B6/P5P, B2/R5P, Magnesium, D-ribose; and yes ketones/caprylic acid, to drive Trp into neurons/astrocytes and its other effects) with your proteins. [Personally I would do the latter at this point.]

 

[Terma]

I think another good bet - assuming the gut doesn't consume it first or something - is serine (this is from the folate NADPH article posted in other threads):
Quantitative flux analysis reveals folate-dependent NADPH production

The main folate-dependent NADPH-producing pathway was predicted to involve transfer of a one carbon unit from serine to THF, followed by oxidation of the resulting product (methylene-THF) by the enzyme MTHFD to form the purine precursor formyl-THF with concomitant NADPH production. To assess whether this pathway indeed contributes to NADPH production, we fed cells 2,3,3-2H-serine and observed labeling of both NADP+ and NADPH. The NADP+ labeling results from incorporation of the serine-derived formyl-THF one-carbon unit into NADP+'s adenine ring. Relative to NADP+, the labeling pattern of NADPH was shifted towards more heavily labeled forms, indicating specific labeling of NADPH's redox active hydrogen (Figure 2e, Extended Figure 5c,d). Thus, we were able to directly confirm that serine-driven folate metabolism contributes to NADP+ reduction.

In a circumstance where NADPH is low (the opposite of cancer, more or less), it's probably a better bet to get serine than glycine (and the reverse is true in cancer). [I wonder about sarcosine? More likely to behave like serine if it can donate methyl to it than to behave like glycine... I still wonder if some of the benefits of methylation supplements in general might not have been in supporting NADPH synthesis, to allow the processing of kynurenine, retinoic acid, etc. and for production of GSH/cholesterol/steroids/etc.] [Note that NADPH is also one way in which the methylation cycle can sustain cancer, and there are multiple NADPH-producing pathways in the cell]

Another note from that article I didn't emphasize anywhere:

We also investigated the consequences of elimination of serine from the medium (Extended Figure 8). As has been observed previously both in vitro17,18 and in tumor models19, serine depletion impaired cell growth (Extended Figure 8b). Consistent with one important downstream product of serine being NADPH, its removal decreased NADPH/NADP+ (Extended Figure 8c). Glycine is both a product of serine metabolism, and itself a potential source of one-carbon units via the mitochondrial glycine cleavage system, whose expression has been linked to oncogenic transformation20. We accordingly tested the impact of both removing serine and increasing glycine in the culture media. We found that increased glycine further impaired cell growth and decreased the NADPH/NADP+ ratio (Extended Figure 8 b,c). These results are consistent with increased glycine impairing methylene-THF production, perhaps due to reverse flux through serine hydroxymethyltransferase (Extended Figure 8d,e).

It suggests a way that glycine could even make someone worse (depending on its usage by different cell types and conditions): by negatively affecting NADPH production [and purine synthesis]. This could conceivably be dose-dependent or time-dependent because kidneys can use glycine to regenerate serine.

Oh and also malic acid was something people tried on other forums (it's sold as a supplement, not sure about food additive):

The model, assessed via flux balance analysis with an objective of minimizing total enzyme expression requirements and hence flux14 (see Methods), predicted that both the oxPPP and malic enzyme contribute ∼ 30% of NADPH (Figure 2d). Surprisingly, however, ∼ 40% of NADPH production was predicted to come from one carbon metabolism mediated by tetrahydrofolate (THF).

Malic acid was really not a bad idea because the enzyme even produces pyruvate. There are also ways to support it endogenously but I cannot recall at the moment.

 

[Astolfo]

@Terma

100 mg riboflavine(solgar) and 400 mcg metafoline per day. I got some money, so I plan to buy the supplements in a day or two.
About magnesium, I couldn't find the oil form but I may be able to get some epsom salt.

What do you think about extreme hungriness/thirsteness? I'm afraid of becoming obese because most of the day I'm hungry. A google search about kynurenine and diabete gives many results, but I wish I have had read them a few months ago, when I was still able to.

https://www.google.com/search?client=firefox-b-d&q=diabete+kynurenin


For now, I only want to focus on gut problems. It's really bad problem for me, because there is no way I can go to school or anywhere. Even at home, I feel there are hundreds of muscles contracting inside, and it makes terrible noises. I don't even mention the hungriness problem, it gets worse day by day.

 

[Terma]

I'm not in the headspace to give a good answer, but for hunger amino acids helped a bit (lysine, taurine maybe) and they help rebuild the gut. It gets mediated by hormones like ghrelin but my guess is you remain hungry until you actually absorb things (and utilize), and the aminos themselves have to make it to the brain to signal, and if you don't break them down/absorb from food you might as well be starving. Things like taurine help digestion and also my gut pain but tends to make diarrhea worse (I take it anyway sometimes). Of course there are carbs too. I can't remember what thirst was for me but at least a part of it was minerals. Definitely take MCT (ketones) with food and other supplements, or it'll get you gut problems. I'll keep those problems in mind when I get back into this but the gut is a black box, I mostly understood the stuff around it. I still have a ways to go before getting a good handle on my own problems, which are a variant of yours, but it's gonna take me ages (I don't get out much either). [Some things I haven't mentioned like adamantane, opioids, I think agmatine, B2/R5P, DHEA and others could have some benefit as they did for me - but they could just as easily mess you up]

 

[Terma]

I can see why you were interested in this:
Sci-Hub | The role of kynurenines in diabetes mellitus. Medical Hypotheses, 18(4), 371–376 | 10.1016/0306-9877(85)90104-5

The kynurenine metabolites can potentially interfere with pancreatic function in several ways. For example, Kotake et al. (1) showed that xanthurenic acid combines easily with insulin to form a complex with reduced insulin activity. It is important to note that this complex formation would not lead to a reduced apparent concentration of insulin in placma as the complex was antigenically indistinguishable from normal insulin (1). The same group indeed demonstrated that the administration of xanthurenic acid to rats produced a diabetic state (1).

Stands to reason if xanthurenic acid were too high (could be induced by B6/P5P deficiency) and it messed with the pancreas or it was prevented from converting you'd get some digestive issues, but they're talking straight-up diabetes (the insulin antagonism seems logical). Is this you? No way to say.

 

[Terma]

Besides the theoretical stuff about 5-HT2c in the other thread, you could go over these to see if they match any patterns of symptoms you have:
Adrenergic receptor - Wikipedia
Adrenergic receptor - Wikipedia

Adrenergic problems are likely downstream of HPA axis (GR) dysfunction. Modulating this likely doesn't fix the root in most cases but it could be part of a cycle and even if not could be useful in devising patches for yourself.

Some of these may overlap with nicotinic/muscarinic receptor effects and other things.

You might have had a relative drop of KYNA levels in brain after you stopped fluoxetine, which would exacerbate the GR insensitivity and 5-HT2c signaling, hence why ketones helped, though NAD is also likely to help something. [If you haven't, you could try high doses of B3 + ribose to see how much they influence you compared to ketones, as an unreliable diagnostic tool.] Again it's also not unlikely 5-HT3 is involved in this.

On the other hand: I'm not 100% sure about some of the effects of KYNA on things like motor control, however this doesn't seem to contradict what you said, I think, in the circumstances of fluoxetine withdrawal:
Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury

And also: Alternative modes of KYNA formation might have to be considered:
Alternative kynurenic acid synthesis routes studied in the rat cerebellum

It is always possible for KYNA itself to cause problems... I have trouble saying with certainty which direction it's going among all the symptoms and the other problematic neurotransmitters. Here is an example:
Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord

Result
In all rats continuous long-lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub-pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia.

Conclusions
We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role of KYNA in control of physiological myelination process.

 

[Astolfo]

@Terma I have searched all day long, but there is not any single niacinamide supplement being sold at my country. I could only find Inositol Hexanicotinate but I heard that plain Niacin causes Liver damage. The B-complex I have at my home has niacinamide(50 mg) but it also contains titanium dioxide, so I don't know if it's overall bad or good to take it.

About the magnesium, I found a supplement that contains 100 mg magnesium citrate(elemental), 50 mg magnesium maleate(elemental) and 50 mg mangesum biglycinate(elemental). I guess it's better to take 3 different forms of it.

I'm unsure to pay 85 bucks to riboflavine, I rather pay it to eat some liver. You mostly pointed out at niacinamide and other things I couldn't find here, I'm out of all luck. It's a poor country.

 

[Terma]

Sorry, that sucks. You can't order from purebulk.com, bulksupplements.com, idealabsdc.com? Yes liver can be good if the copper and retinol is not too much.

 

[Astolfo]

Sorry, that sucks. You can't order from purebulk.com, bulksupplements.com, idealabsdc.com? Yes liver can be good if the copper and retinol is not too much.

Unfortunately, I need a prescription from doctor(doctors usually don't do that) and also have to pay lots of tax to get a supplement from abroad. Economical issues...

It's 15th day on daily aspirin(100 mg). I think I can control my muscles better. But since a few days I have bloody veins in my eyes. I don't know if it has nothing to do with aspirin.