The Travis Corner

[InChristAlone]

You think I was right? Is this what serotonin feels like?

I still need to take some tryptophan one of these days, as an experiment. Fernstrom lets us know how serotonin is synthesized from tryptophan. What is amazing is how nearly perfect the line is for the Fernstrom Ratio: W/Σ(T+F+V+L+I) :

'These data indicate that small doses of tryptophan, which do not cause plasma or brain tryptophan concentrations to exceed their normal daily peaks and which do not influence plasma concentrations of other amino acids, produce significant elevations in brain serotonin.' ―Fernstrom​

View attachment 7719

{The amino acid letter 'P' has actually been designated to represent proline; Fernstom uses this letter to represent phenylalanine↑.}
​

'If, as seems likely, physiological changes in plasma tryptophan concentrations can cause parallel changes in brain serotonin synthesis, the factors that control plasma tryptophan levels must be considered, for they represent potentially important determinants of the activity of a population of central nervous system neurons.' ―Fernstrom​

Fernstrom had also shown that tyrosine lowers prolactin, highly suggesting that it converts to dopamine. The idea that tyrosine hydroxylase is normally saturated appears to be incorrect, although it does appear to be closer to its saturation point than tryptophan hydroxylase.

Fernstrom, John D. "Brain serotonin content: physiological regulation by plasma neutral amino acids." Science (1972)
Fernstrom, John D. "Tyrosine administration decreases serum prolactin levels in chronically reserpinized rats." Life sciences (1979)
​

I wouldn't risk taking tryptophan! Unless you want insomnia, depression, lethargy, stomach ache, fever, tachycardia, racing thoughts, nightmares, skin sensations. Just see all the negative reviews on Amazon for it and 5htp. While there are glowing reviews... Who knows if they are real as Amazon is flooded with fake reviews.

 

[peep]

@Janelle525
Not everybody is the same. Maybe thats why on every product will be some negative and some positive feedbacks.

Otherwise , would you say tryptophane in the body is useless?

 

[InChristAlone]

@Janelle525
Not everybody is the same. Maybe thats why on every product will be some negative and some positive feedbacks.

Otherwise , would you say tryptophane in the body is useless?

I'm fine with people consuming it from food, it is when you take it in a supplement that side effects usually pop up. It is suggested to take 500mg three times a day on those supps.

 

[peep]

@Janelle525 Ok your opinion. But who said you need to take 1.5g.

I just dont like it when people say this or that is bad.
Thats just false.

You will find a scenario for almost everything, to be good or bad. Especially if its a amino acid.

And if someone is missing tryptophane (not important what cause) then tryptophane will help. (And not talking about fixing the root problem).

 

[InChristAlone]

@Janelle525 Ok your opinion. But who said you need to take 1.5g.

I just dont like it when people say this or that is bad.
Thats just false.

You will find a scenario for almost everything, to be good or bad. Especially if its a amino acid.

And if someone is missing tryptophane (not important what cause) then tryptophane will help. (And not talking about fixing the root problem).

I don't generally say something is always bad, except in the case of toxic things. Just saying that trytophan will usually come with side effects eventually, side effects is not the same as saying it's toxic.

 

[Travis]

I wouldn't risk taking tryptophan! Unless you want insomnia, depression, lethargy, stomach ache, fever, tachycardia, racing thoughts, nightmares, skin sensations. Just see all the negative reviews on Amazon for it and 5htp. While there are glowing reviews... Who knows if they are real as Amazon is flooded with fake reviews.

I was thinking just as a one‐time experiment. I would like to match each neurotransmitter to the thought processes, feelings, and idiosyncracies which characterize them; dopamine, histamine, and serotonin are neurotransmitters that I'd like to get a feel for.

Yesterday, I think the serotonin from the massive amounts of chicken eggs had become melatonin—basicially methylated and acetylated serotonin—despite having been in a well‐lit environment. [Now, I do know exactly what melatonin feels like since I have it in the cabinet, and had taken it twice.] It's rather clownish; I had found myself watching music videos on YouTube from the '80s, but actually enjoying them! [⁉]

I usually hate '80s music, but for some reason David Bowie's Let's Dance, Queen's Under Pressure, and even the Talking Heads' Burning Down the House seemed like good things to watch. But thankfully, I'm feeling much better now.

[And also thankful that it wasn't bad enough to watch this.]

 

[Terma]

I was going to do this very similar thing in the next year (already have the aminos, missing the planning):
1) best-effort full tryptophan depletion using Amino Acid Supplementation For People With Poor Digestion
2) take 5-htp
3) see what happens

I tried the 500-5g tryptophan before and there was no way to tell what it was doing and also it sucked. There are so many ways it can go wrong. The 5-htp still has some immune modulating properties but it should just go to serotonin and melatonin if I got everything right.

 

[Travis]

I was going to do this very similar thing in the next year (already have the aminos, missing the planning):
1) best-effort full tryptophan depletion using Amino Acid Supplementation For People With Poor Digestion
2) take 5-htp
3) see what happens

I tried the 500-5g tryptophan before and there was no way to tell what it was doing and also it sucked. There are so many ways it can go wrong. The 5-htp still has some immune modulating properties but it should just go to serotonin and melatonin if I got everything right.

As far as I know, the only real psychoactive products are serotonin and melatonin. Sure there is N‐acetylserotonin, but this is probably not too much different than serotonin itself.

I think a few kyneurenine metabolites could be psychoactive, but I don't think they are nearly as potent on a gram‐per‐gram basis. What is interesting though about N‐acetylindolamines is that they can cyclicize to β-carbolines—even within the body—and can be even more psychoactive than indoles (i.e. harmaline; harmine)

'It was particularly interesting that some of the β-carbolines that were shown to have high affinity also occur endogenously in mammalian tissue, raising the possibility that harmane, norharmane, and tetrahydro-norharmane (THN) may represent endogenous ligands for IBS [imidazalone binding site].' ―Robinson​

So melatonin and N‐acetylserotonin could all perhaps form their respective β-carbolines. This would add a slight twist to tryptophan experiments.

I think one could find out if they were to read about the concentrations found in the brain:

Robinson, E. S. J. "Endogenous β‐Carbolines as Clonidine‐Displacing Substances." Annals of the New York Academy of Sciences (2003)​

 

[Terma]

As far as I know, the only real psychoactive products are serotonin and melatonin. Sure there is N‐acetylserotonin, but this is probably not too much different than serotonin itself.

Thanks, did kind of need confirmation on that. This could've been a hilarious waste of time. I brought this up with another guy who was a gut expert (who suggested avoiding tryptophan while I brought up the 5-htp thing) and just got a blank stare's worth of a post.

I think a few kyneurenine metabolites could be psychoactive, but I don't think they are nearly as potent on a gram‐per‐gram basis. What is interesting though about indoles is that they can cyclicize to β-carbolines—even within the body—and can be even more psychoactive than indoles (i.e. harmaline; harmine)

I agree this could be the case for healthy person, but I'm not and between high cortisol (TDO) and immune activation I think most of mine likely goes down kynurenine pathway and may be affecting me more than serotonin. (I've gotten very little from trying to antagonize serotonin, this is my last attempt to verify its relevance to me)

Never heard about those carbolines, interesting.

 

[Travis]

Terrence McKenna can be heard on YouTube talking about the β-carbolines, which are found in certain seeds consumed for psychedelic effect.

Here are a few quotes from the article:

'In the presence of a monoamine oxidase inhibitor, [³H]tryptamine and pyruvic acid were shown to form β-carbolines in vivo. This process seemed to be enzymatic, because it did not occur in vitro under pseudophysiologic conditions.' ―Robinson

'The first endogenous β-carboline, pinoline, (6-methoxy-tetrahydro-β-carboline), was identified from pineal gland tissue by McIsaac in 1961.'―Robinson​

The indolamines do need that extra carbon to close the ring, so they have to be N‐acetlylated or react with endogenous carbonyls such as pyruvate or methylglyoxal. And as Robinson has pointed out, we could even have enzymes that make β-carbolines specifically.

I think I know what that immune activation feels like after eating imunogenic oats and reading about this. Interferon-γ has been shown to be released after the ingestion of immunogenic peptides, and also has been experimentally determined to decrease serum tryptophan by 50% [sic] with no significant effect on other amino acids.

And mast cells have been shown capable of migrating to the brain (rat). Mast cells have also been estimated to acount for up to 90% of brain histamine (in same species). The range in brain mast cells is significant, ranging from zero to thousands (in humans, monkeys, rats, and cats).

Gamma-interferon activates the kyneurenine pathway by inducing the transcription of tryptophan dioxygenase.

So the immunogenic neurotransmitter profile of high interferon-γ would likely be characterized by higher kyneurenine metabolites, higher histamine, lower serotonin, and lower melatonin. I am convinced this is schizophrenia, as histamine is a stimulant which also impairs memory consolidation. This gives a person drive, and the extremely low serotonin could contribute to a more introspective and serious outlook. Indeed, schizophrenics have been found to have 5× higher brain histamine; and schizophrenia vs celiac disease has resulted in odds ratios of over four—multiple times.

I'm getting the impression that the ideal neurotransmitter profile is essentially zero mast cell histamine (the tubermammillary nucleus provides enough) with moderate level of serotonin, but still lower than the average Westerner. Cultures such the Chinese, Japanese, and Central Europeans could fairly be expected to have lower serotonin levels. Fernstrom himself had shown corn to lower serotonin, notorious for its low tryptophan content.

The above chart demonstrates this, and casein isn't even particularly high in tryptophan. I would like to see a similar study done on corn vs whey, almonds vs eggs, or any other juxtaposition of two foods having a greater difference in tryptophan content than corn vs casein.

Fernstrom, J. D. "Effect of chronic corn consumption on serotonin content of rat brain." Nature (1971)​

 

[Terma]

That's a little tougher for me, because as far as I can figure I must be in a constant state of immune derangement (Interferon-γ most likely involved) and eating oats or wheat usually changes nothing, and without supplements I live in a constant state of brain imbalance possibly not unlike schizophrenia though not quite the same. This is a little personal and not so scientific.

Histamine is probably relevant, and especially to this protocol Amino Acid Supplementation For People With Poor Digestion since it restricts it and you could easily misinterpret the results. Luckily I got a bag of histidine from two years ago (does this stuff expire?) so maybe I can figure out, as long as stick to the right foods. Problem is the diet adjustment required to do this will probably affect histidine metabolism and mast cells in ways impossible to predict.

It is a good point to keep histamine in mind. I think it's probably more important than serotonin too. For me personally, I think it's somewhere between endogenous opioids (in particular kappa-opioids - some overlap with histamine in effects, and closely tied to the CRH response and glucocorticoids), kynurenine metabolites, and in fact histamine, with inevitable problems to- and from- compromised 5-ar expression. I have a ways to go. This is supposed to be your corner, I'm just trying to relate to your writing without doing a blogpost.

 

[opiath]

@Travis

In people infected with Lyme's disease and other CNS infections studies show a buildup of quinolinic acid in the CNS from tryptophan breakdown.
Interferon-γ together with LPS from bacteria induce the IDO pathway.
Many practitioners use herbs that block IDO pathway such as Japanese knotweed (resveratrol), Curcumin, Andrographis etc in order to reduce quinolic acid levels.
It is believed it acts as a neurotoxin and it's buildup is a negative consequence from the infection.

Do you think in a case like this it is really beneficial to block IDO or is it more likely that its activation is important for the function of the immune system?

If IDO induction continues for a long time and protein digestion is handicapped at the same time, tryptophan levels can go dangerously low.

 

[Travis]

@Travis
Do you think in a case like this it is really beneficial to block IDO or is it more likely that its activation is important for the function of the immune system?

I think it is beneficial for the immune system since it ostensibly depletes tryptophan as a device to restrict it from invading pathogens. However, this is obviously not the case during immunogenic food peptide reactions. In this situation, I view interferon-γ release as a biological accident—or biochemical noise resulting from the similarity between gliadin peptide epitopes and those of invading pathogens, such as spirochetes. But in the case of immunogenic food peptides, it would be more effective to simply stop eating them than to inhibit tryptophan dioxygenase.

But it would be interesting to know what the most specific inhibitor of this enzyme is, perhaps for people in the process of weaning themselves off of immunogenic peptides which are also somewhat addictive. Wheat gliadin also releases peptides which act as δ-exophins; and casein, though far less immunogenic, is also a protein having both immunogenic and opiate-like effects—but acting on the more powerful μ-opiate receptor.

But I think inhibiting tryptophan dioxygenase in the presence of infection is tantamount to inhibiting the immune system. This is a logical result of viewing tryptophan dioxygenase induction by interferon-γ teleologically as a way of restricting the proliferation of such things as spirochetes and filaria through tryptophan restriction.

 

[Such_Saturation]

You eat an egg, that’s a few hundred milligrams linoleic acid. But you will hardly limit yourself to a handful of nuts. Nuts are no good.

 

[ilikecats]

@Travis if you don't mind me asking, what do you do for a living? Are you some type of research scientist or a professor?

 

[Travis]

But you will hardly limit yourself to a handful of nuts.

Shhh‼ . . . (What happens in San Fransisco stays in San Fransisco.)

Luckily I got a bag of histidine from two years ago (does this stuff expire?) so maybe I can figure out, as long as stick to the right foods.

I think the histidine should be fine; but as a fluorescent amino acid, it could be light‐sensitive.

'Based on the experimental results of this study, it appears that gamma radiation results in the scission of the alkyl side chain C–C backbone (reaction D), whereas with UV irradiation, scission of the phenyl ring C–C (reaction C) appears to dominate.' ―Onyiriuka​

Urocanic acid is essentially the amino acid histidine sans amino group (and with the addition of a double bond). This is produced in the body, has high UV‐absorbing potential, and is thought to represent—along with melanin—and endogenous 'sunblocking' molecule:

'Urocanic acid (UCA), present in the stratum corneum, is a major absorber of ultraviolet (UV) radiation and, on UV exposure, is induced to isomerize from the naturally occurring trans-isomer to the cis-isomer. CisUCA has been shown to have immunosuppressive properties, while transUCA may act as a natural sunscreen due to its UV-absorbing properties. The photoprotective capacity of UCA was investigated in this study. Minimal erythema dose (MED) was determined . . .' ―Olivarius​

Normally, I'd leave off there. But I think it's the high melatonin giving me the giggles . . .

' . . . on normal buttock skin in 36 healthy subjects and the concentration of UCA isomers was measured on the skin adjacent to the test site. On the contralateral buttock, MED was determined 20 min after application of trans-UCA 5% in a cream base. The UCA cream gave a sun protection factor of 1.58. The amount of UCA applied was, however, 20-200 times higher than the amount of UCA found in normal skin, making a sunscreening effect of naturally occurring UCA very low. This was further supported by a lack of correlation between naturally occurring UCA and the UV sensitivity of each I subject determined by the MED.' ―Olivarius​

So you have a group of men doing an experiment on UV‐induced erythema vs urocanic acid concentration on other men, who decide—of all locations possible—to do this on the ****. I mean, you'd think they'd have a hard time getting volunteers for this . . .

'The study demonstrates that trans‐UCA has an effect in reducing UV‐induced erythema. The protective effect can be attributed to UCA itself, as the cream base without UCA gave no protection.' ―Olivarius​

But I think it should be fine. I know the higher energy X‐rays can break the tryptophan ring during X‐ray crystallography investigations of protein structure, but I would imagine your histidine was kept away from strong UV light and X‐rays—the two things which could break it's bonds.

If you do a histidine challenge, it would be great to hear a report. I need to get my hands on these amino acid precursors someday so I can better understand how food affects the brain.

Onyiriuka, E. C. "The effects of high‐energy radiation on the surface chemistry of polystyrene: A mechanistic study." Journal of applied polymer science (1993)
Olivarius, F. "The sunscreening effect of urocanic acid." Photodermatology, photoimmunology & photomedicine (1996)​

 

[raypeatclips]

@Travis When you talk about corn lowering serotonin are you talking about regular old sweet corn?

 

[Mito]

As far as I know, the only real psychoactive products are serotonin and melatonin. I think one could find out if they were to read about the concentrations found in the brain.

Which tests (if any) do you think best correlate to concentrations of serotonin in the brain? Whole blood serotonin, urinary serotonin, or the tryptophan metabolite 5-hydroxyindoleacetic (5-HIAA) urinary organic acid?

 

[Travis]

@Travis When you talk about corn lowering serotonin are you talking about regular old sweet corn?

I think rats are generally fed that field corn given to cows. If the Central Americans has sweet corn, I don't think they'd bother with making tortillas. I think sweet corn is a relatively new hybrid, but the proteins—I would imagine—would be similar.

Still waiting on Monsanto's new Pellagra‐Free™ variety with genetically‐enhanced tryptophan and niacin (and perhaps just as important: a reduced leucine concentration).

Which tests (if any) do you think best correlate to concentrations of serotonin in the brain? Whole blood serotonin, urinary serotonin, or the tryptophan metabolite 5-hydroxyindoleacetic (5-HIAA) urinary organic acid?

You know, I've though a bit about that. The cerebospinal fluid N‐acetylserotonin has been measured, and provides a direct measurement, but this says nothing about how saturated the raphe nucleus is. The rat experiments measure‐whole brain serotonin after they're Lennied, so there is no ambiguity there.

Would the cerebospinal fluid N‐acetylserotonin represent previous serotinin? How long does it last? Does it build‐up?

Not sure, but one could find out. Since the spinal tap is an uncomfortable procedure, it could be helpful in knowing about the others. But urinary 5-hydroxyindoleacetic acid would represent peripherally‐synthesized serotonin, which is significant, and I wouldn't think it would say much about the brain.

I think we just have to extrapolate the rat studies, and have confidence in Fernstrom's graphs showing brain serotonin synthesis to be a direct function of serum tryptophan over the sum of competing amino acids. The strength of his correlation (r≈.92) was good enough that the best measure of brain serotonin could very well be serum tryptophan, although this says nothing about the speed in which it's cleared from the brain. Perhaps even those with average tryptophan can have high brain serotonin if their enzymes are slow enough (or monoamine oxidase is inhibited?)

 

[Mito]

But urinary 5-hydroxyindoleacetic acid would represent peripherally‐synthesized serotonin, which is significant, and I wouldn't think it would say much about the brain.

I have measured all three (not the same day but within 6 months) but the results seem somewhat contradictory. 5-HIAA was very low and serotonin in urine was low (slightly below low end of reference range) so they match pretty well. But whole blood serotonin was close to the top of the reference range.