Phenylalanine Better Than Tyrosine For Serotonin Depletion

[Travis]

I posted a study recently where 20g tyrosine increased prolactin in humans - @Travis was speculating that tyrosine could be displacing peripheral endorphins, freeing more of them to travel to the brain and increase serotonin/prolactin there.

Well, prolactin concentrations did rise in every group—those given every amino acid or every amino acid combination—which had been tested. The subjects had also been exercising (cycling), but I had forgotten exactly what food the subjects were given (if they'd been given any at all). I think it is likely that all subjects were given food beforehand, and those containing exorphins—i.e. wheat, milk, soy—are some of the more common ones. I think perhaps tyrosine could have been potentiating the opiates in some way: either by displacing them from binding sites, occupying the more peripheral receptors beforehand (i.e. intestines), or perhaps even inhibiting the enzyme which normally inactivates (acetylates) it. All endorphins and exorphins have a terminal tyrosine group and all of them increase prolactin. For these reasons I think there could have been some tyrosine–opiate peptide interactions—and especially if the subjects had been given soy, wheat, or casein beforehand.

The active end of most opiate peptides have this N-terminal tyrosine–proline dipeptide.

Beta-endorphin has been shown to be N-acetylated in the rat. This acetyl group abrogates its opiate activity near-completely :

Glembotski, C. C. "Acetylation of alpha-melanotropin and beta-endorphin in the rat intermediate pituitary. Subcellular localization." Journal of Biological Chemistry (1982)​

'α-N-Acetyl-β-endorphin possesses less than 0.2% of the opiate-like activity of β-endorphin.' ―Glembotski​

The enzyme responsible for the acetylation of opiate peptides appears to be choline acetyltransferse. This is especially interesting because this enzyme has actually been found colocalized with enkephalin,⁽¹⁾ perhaps leading to the speculation that opiate peptides work by blocking this enzyme directly—and then being acetylated in the process. This would harmonize with the known effects of opiates, a classic known function of which is to reduce acetylcholine concentrations. Choline acetyltransferse is found everywhere acetylcholine is found,⁽²⁾ and not just in the brain where it's most commonly looked for. So perhaps tyrosine itself could have some opiate-potentiating properties before it's turned into thee catecholines, and also dopamine, where then it would have the opposite effect.

[1] Kondo, H. "Evidence for the coexistence of acetylcholine and enkephalin in the sympathetic preganglionic neurons of rats." Brain research (1985)
[2] Furness, J. B. "Choline acetyltransferase-and peptide immunoreactivity of submucous neurons in the small intestine of the guinea-pig." Cell and tissue research (1984)​

 

[Broken man]

Well, prolactin concentrations did rise in every group—those given every amino acid or every amino acid combination—which had been tested. The subjects had also been exercising (cycling), but I had forgotten exactly what food the subjects were given (if they'd been given any at all). I think it is likely that all subjects were given food beforehand, and those containing exorphins—i.e. wheat, milk, soy—are some of the more common ones. I think perhaps tyrosine could have been potentiating the opiates in some way: either by displacing them from binding sites, occupying the more peripheral receptors beforehand (i.e. intestines), or perhaps even inhibiting the enzyme which normally inactivates (acetylates) it. All endorphins and exorphins have a terminal tyrosine group and all of them increase prolactin. For these reasons I think there could have been some tyrosine–opiate peptide interactions—and especially if the subjects had been given soy, wheat, or casein beforehand.

View attachment 8689The active end of most opiate peptides have this N-terminal tyrosine–proline dipeptide.

Beta-endorphin has been shown to be N-acetylated in the rat. This acetyl group abrogates its opiate activity near-completely :

Glembotski, C. C. "Acetylation of alpha-melanotropin and beta-endorphin in the rat intermediate pituitary. Subcellular localization." Journal of Biological Chemistry (1982)​

'α-N-Acetyl-β-endorphin possesses less than 0.2% of the opiate-like activity of β-endorphin.' ―Glembotski​

The enzyme responsible for the acetylation of opiate peptides appears to be choline acetyltransferse. This is especially interesting because this enzyme has actually been found colocalized with enkephalin,⁽¹⁾ perhaps leading to the speculation that opiate peptides work by blocking this enzyme directly—and then being acetylated in the process. This would harmonize with the known effects of opiates, a classic known function of which is to reduce acetylcholine concentrations. Choline acetyltransferse is found everywhere acetylcholine is found,⁽²⁾ and not just in the brain where it's most commonly looked for. So perhaps tyrosine itself could have some opiate-potentiating properties before it's turned into thee catecholines, and also dopamine, where then it would have the opposite effect.

[1] Kondo, H. "Evidence for the coexistence of acetylcholine and enkephalin in the sympathetic preganglionic neurons of rats." Brain research (1985)
[2] Furness, J. B. "Choline acetyltransferase-and peptide immunoreactivity of submucous neurons in the small intestine of the guinea-pig." Cell and tissue research (1984)​

Could I reduce the opiate potentiating effect of tyrosine with something? Thank you.

 

[Travis]

Could I reduce the opiate potentiating effect of tyrosine with something? Thank you.

I don't think it's really an issue. These subjects had consumed quite a bit and were also cycling, with prolactin being increased in all of them. I think with smaller doses and more moderate activity it wouldn't have much effect. But of course coffee does have a powerful anti-opiate molecule called caffeoyl quinide that is formed upon roasting; since (most) coffee is cheap, available, and delicious, this could be thing to use. But perhaps L-dopa would be a better dopamine precursor anyway, and perhaps not even capable of stirring-up opiate peptides the slightest—this being more different molecularly, having two hydroxyl groups on the phenylalanine ring as opposed to only one on the N-terminus of opiate peptides. I would think taking L-dopa with coffee in the morning would be a good way to upregulate the dopamine circuitry.

 

[Koveras]

I don't think it's really an issue. These subjects had consumed quite a bit and were also cycling, with prolactin being increased in all of them. I think with smaller doses and more moderate activity it wouldn't have much effect. But of course coffee does have a powerful anti-opiate molecule called caffeoyl quinide that is formed upon roasting; since (most) coffee is cheap, available, and delicious, this could be thing to use. But perhaps L-dopa would be a better dopamine precursor anyway, and perhaps not even capable of stirring-up opiate peptides the slightest—this being more different molecularly, having two hydroxyl groups on the phenylalanine ring as opposed to only one on the N-terminus of opiate peptides. I would think taking L-dopa with coffee in the morning would be a good way to upregulate the dopamine circuitry.

L-dopa is usually given with a dopa decarboxylase inhibitor to increase availability in the brain - in this really necessary or are there valuable peripheral effects to elevating circulating dopamine?

 

[Travis]

L-dopa is usually given with a dopa decarboxylase inhibitor to increase availability in the brain - in this really necessary or are there valuable peripheral effects to elevating circulating dopamine?

I think that's only really given to people who need megadoses to even function—those with their substantia nigra destroyed by the residual aluminum found in cocaine, from working in an aluminum foundry, or from welding nonferrous metals. For the rest of us—those staying under one gram per day— don't know if I'd mess with a new drug just for that. However: an O-methylated congener of L-dopa can be somewhat debilitating, this being what best explains Parkinson's dyskinesia. So taking a COMT inhibitor could also be a good idea with L-dopa, and of this class there are none better than epicatechin gallate. While it's true that there are hundreds of Asian scientists frantically trying to promote natural molecules of all sorts, and especially those from soy and green tea, it can't be argued that this is essentially the highest-affinity COMT inhibitor ever tested. But with drinking green tea, you drink flouride ions; you'd be trading the neurological effects derived from O-methyldopa for those coming from the F⁻ ion. But boron is a partial antidote for fluoride ions, having a natural affinity, of which it turns into boron fluorides for excretion.

 

[lampofred]

...

 

[Broken man]

I don't think it's really an issue. These subjects had consumed quite a bit and were also cycling, with prolactin being increased in all of them. I think with smaller doses and more moderate activity it wouldn't have much effect. But of course coffee does have a powerful anti-opiate molecule called caffeoyl quinide that is formed upon roasting; since (most) coffee is cheap, available, and delicious, this could be thing to use. But perhaps L-dopa would be a better dopamine precursor anyway, and perhaps not even capable of stirring-up opiate peptides the slightest—this being more different molecularly, having two hydroxyl groups on the phenylalanine ring as opposed to only one on the N-terminus of opiate peptides. I would think taking L-dopa with coffee in the morning would be a good way to upregulate the dopamine circuitry.

What is better? L-tyrosine or N-Acetyl L-tyrosine? Thank you.

 

[haidut]

I posted a study recently where 20g tyrosine increased prolactin in humans - @Travis was speculating that tyrosine could be displacing peripheral endorphins, freeing more of them to travel to the brain and increase serotonin/prolactin there.

The 20g tyrosine dose is known to elevate GH and adrenaline and that will lead to increased prolactin even without displacement of endorphins.

 

[Captain_Coconut]

I have had good success with Mucuna Pruriens in just a week of use, much greater than the multiple months of attempting to raise dopamine with similar aminos: dlpa, l-phena, l-tyro, nalt, for whatever reason all of those would always give me an uncomfortable adrenaline surge followed by 'wired but tired' for hours - hardly felt any of the happy / warm / stability of dopamine from those. With Mucuna I feel the lowered seratonin, calm cool happy energy, if I take a huge amount then I start to feel the norepinephrine overload. I think it pairs very well with L-Lysine, and a meal of mainly carbs and fat. I don't feel as much from it if I take it around other proteins. Pairing with DLPA also only brought out more of the adrenaline effects, seemed to be counterproductive. I think Mucuna gets a bit of a bad wrap because people confuse it with pure L-Dopa. I put it off for a very long time because it seemed like it was a sketchier version of tyrosine, I regret having done that now, it agrees with me a lot better - the only effects I ever felt from tyrosine were rage and wired/tired.

 

[Fractality]

I think that's only really given to people who need megadoses to even function—those with their substantia nigra destroyed by the residual aluminum found in cocaine, from working in an aluminum foundry, or from welding nonferrous metals.

Do you have any data to illustrate a comparison between the amount of aluminum in cocaine and the amount of aluminum in foods listed here?

 

[Travis]

Do you have any data to illustrate a comparison between the amount of aluminum in cocaine and the amount of aluminum in foods listed here?

Yeah, I've read two analytical studies on this. I had concluded that the aluminum must be derived from the limestone used to raise pH during the extraction procedure. Would you like to see those two analytical studies?

There is also considerable evidence that migration can occur from the nasal cavity into the brain, the substantia nigra being very close to this area. There is even a theoretical scientific article on inhaled aluminum nanoparticles being a cause for dementia, and I do think there'd been studies proving such transport using rats.

 

[Fractality]

Yeah, I've read two analytical studies on this. I had concluded that the aluminum must be derived from the limestone used to raise pH during the extraction procedure. Would you like to see those two analytical studies?

There is also considerable evidence that migration can occur from the nasal cavity into the brain, the substantia nigra being very close to this area. There is even a theoretical scientific article on inhaled aluminum nanoparticles being a cause for dementia, and I do think there'd been studies proving such transport using rats.

Yes I would like to see those studies. I'm most curious about how much aluminum in cocaine compares to how much is found in foodstuffs; some sort of equivalency dose. Is 1 gram of cocaine equivalent to eating one frozen pizza? etc etc

 

[Travis]

Yes I would like to see those studies. I'm most curious about how much aluminum in cocaine compares to how much is found in foodstuffs; some sort of equivalency dose. Is 1 gram of cocaine equivalent to eating one frozen pizza? etc etc

Your'e going to have to mentally thank the author for this one because he kindly donated this .pdf. Whenever I can't get an article using sci-hub, which is not often, I click on the 'request article' link on researchgate.com:

Bermejo-Barrera, Pilar. "A study of illicit cocaine seizure classification by pattern recognition techniques applied to metal data." Journal of Forensic Science (1999)​

 

[Travis]

Violante, N. "Characterization of cocaine and heroin samples as a function of their trace element content: An analytical pilot study." Microchemical journal (1992)

Bermejo-Barrera, P. "Determination of aluminium and strontium in illicit drugs by electrothermal atomic absorption spectrometry." Analusis (1996)​

 

[Waynish]

Why isn't it's short half-life an issue with supplementing it?

 

[ecstatichamster]

Tyrosine or phenylalanine?

 

[papaya]

I have had good success with Mucuna Pruriens in just a week of use, much greater than the multiple months of attempting to raise dopamine with similar aminos: dlpa, l-phena, l-tyro, nalt, for whatever reason all of those would always give me an uncomfortable adrenaline surge followed by 'wired but tired' for hours - hardly felt any of the happy / warm / stability of dopamine from those. With Mucuna I feel the lowered seratonin, calm cool happy energy, if I take a huge amount then I start to feel the norepinephrine overload. I think it pairs very well with L-Lysine, and a meal of mainly carbs and fat. I don't feel as much from it if I take it around other proteins. Pairing with DLPA also only brought out more of the adrenaline effects, seemed to be counterproductive. I think Mucuna gets a bit of a bad wrap because people confuse it with pure L-Dopa. I put it off for a very long time because it seemed like it was a sketchier version of tyrosine, I regret having done that now, it agrees with me a lot better - the only effects I ever felt from tyrosine were rage and wired/tired.

hi captain coconut, are you still using/ happy with mucuna?

 

[Captain_Coconut]

hi captain coconut, are you still using/ happy with mucuna?

I only take it now a few times a month. It is great stuff but I think it did some healing and now I don’t really need it that often. After a few weeks taking daily I noticed little effect from taking it, but a general better feeling over all. I feel more awake and energetic now even with no supplements than I did last year. I think it has an adaptogenic quality, my experience with other adaptogens has always been a good couple months followed by feeling good with or without it.

 

[Lokzo]

I have had good success with Mucuna Pruriens in just a week of use, much greater than the multiple months of attempting to raise dopamine with similar aminos: dlpa, l-phena, l-tyro, nalt, for whatever reason all of those would always give me an uncomfortable adrenaline surge followed by 'wired but tired' for hours - hardly felt any of the happy / warm / stability of dopamine from those. With Mucuna I feel the lowered seratonin, calm cool happy energy, if I take a huge amount then I start to feel the norepinephrine overload. I think it pairs very well with L-Lysine, and a meal of mainly carbs and fat. I don't feel as much from it if I take it around other proteins. Pairing with DLPA also only brought out more of the adrenaline effects, seemed to be counterproductive. I think Mucuna gets a bit of a bad wrap because people confuse it with pure L-Dopa. I put it off for a very long time because it seemed like it was a sketchier version of tyrosine, I regret having done that now, it agrees with me a lot better - the only effects I ever felt from tyrosine were rage and wired/tired.

Which Mucuna did you use?

 

[Lokzo]

I had 300mg of L-Phenylalanine this morning, after 1mg of cypro last night.

Felt literally euphoric and was enjoying and FEELING music so much!!

L-Phenylalanine definitely suppresses appetite though.