L-Histidine Makes Me Feel Like SUPERMAN

[Jigend]

Never have I seen histidine mentioned as possessing nootropic-like qualities, but (in my layman way of understanding it) it seems like histamine is a stress hormone, no? Because the effects described by OP definitely seem dopaminergic, and not stress induced at all.

Is there any consensus regarding the supplementation with L-histidine?

And if it is unsafe, would supplementing with tyrosine achieve similar effects? I'm looking for ways to banish brain fog, procrastination, and somewhat depressive-like symptoms. That would help me get my life on track, get more work done throughout the day, and succeed. I am already peating - somewhat, that is. I drink tons of coffee, try to keep my sugar intake high throughout the day, and limit PUFA. I definitely feel my temps have gone up, but the focus and motivation still isn't quite there yet. Aspirin sometimes does it for me, but I need to get 2 500mg pills to get that effect, and I don't want to overdo it. All I'm seeking is a safe dopaminergic like effect that is safe to take for a month or so. That would do it for me. If L-histidine is safe for that amount of time, I'll do it. OP's description is exactly what I'm looking for.

Edit: I was googling niacin when stacked with histidine, and came up with this reddit thread.
The OP in that thread seems to support the idea that niacin flushes histamine out of the body. Is this yet another mainstream misconception? I thought niacin - although beneficial from a Peat standpoint - was supposed to increase histamine?

Edit 2: Assuming there's an aggravated risk of having L-histidine increase histamine, even without niacin, would taking an anti-histamine eliminate all the downsides of this amino?

 

[Travis]

I was thinking tyrosine would be interesting, especially if a person consumes exorphins (which decrease dopaminergic transmission). This could both increase metabolism, nerve conduction, and lower prolactin—the release of which is controlled directly by dopamine on the pituitary.

 

[Koveras]

I did look into this, and it appears to follow Fernstom style mechanics—in the brain—and depends on its own competitors across the blood–brain barrier. I know that valine, leucine, isoleucine, tyrosine, and phenylalanine compete with serotonin, but I cannot remember the competitors for histamine.

Should be the same competitors - all the large neutral amino acids.

 

[DaveFoster]

Histamine is excitotoxic. End of.

"Cortisol makes me feel like Superman."

 

[Jigend]

"Cortisol makes me feel like Superman."

Is this all there is to histidine? The release of the stress hormone histamine, and thus a temporary stress rush?

Could L-tyrosine supplementation be a healthier alternative to L-histidine? Some people do report on it's dopaminergic effects with words very similar to those that OP used to characterize histidine.

 

[DaveFoster]

Is this all there is to histidine? The release of the stress hormone histamine, and thus a temporary stress rush?

Could L-tyrosine supplementation be a healthier alternative to L-histidine? Some people do report on it's dopaminergic effects with words very similar to those that OP used to characterize histidine.

L-tyrosine has some benefits, but it's likely impure and allergenic. Have you tried thyroid or thiamine?

 

[Regina]

"Cortisol makes me feel like Superman."

oh yes, and that crazy estrogen strength when my endorphins are screaming makes me omnipotent.

 

[Jigend]

1. At this very moment, I was just about to order some Tyrosine from NOW. It sits at 500mg per capsule, and according to the description on the box, there's gelatin, stearic acid and magnesium stearate in the mix. Unless there are other unlisted impurities, this doesn't seem that bad: We don't have any silica in here, and I can almost swear I saw a thread earlier on about the mitochondrial benefits of stearic acid.
2. Now, when it comes to thyroid (I'm recent to the writings of Ray Peat, so bear with me) I assume you're referring yourself to dissected thyroid supplements, no? They were one of the first things I researched, regarding the availability in my country (right alongside DHEA and pregnenolone). To my dismay I found out that in here (Portugal) not only is thyroid very seldomly prescribed, it is not available as an OTC. I assume most of the readers of this forum to be American, and during my time in here (I've been a lurker for 2.5 years), it seems that given the ease at which many people in here get their hands on thyroid, it is either available as an OTC, or doctors prescribe it rather frequently in the US of A.
   Before peating, I did have many hypothyroid symptoms (very cold extremities, nervousness, etc) and most of those symptoms are either disappearing or fully gone. But as the adage "listen to your body" goes, I'd like to try low dose thyroid for a while, to see how it goes. Just need to find if a 26yr old male would ever be prescribed that in this country, without serious Hashimoto's symptoms.
3. Thiamine is one of the supplements I was thinking about ordering just now (Tyrosine + Taurine + Thiamine). I have only supplemented with zinc (great androgenic effects + much better skin) and magnesium before (taken before bed; profound sleep, plus great energy during the following day). I have read at least 2 users in here say that thiamine makes their brain work like a super computer. I know that thiamine helps the body greatly improve the way in which glucose is oxidized, but is the nootropic effect that good?
   
   Note: I use the term "nootropic" as in "compound which clears and improves one's cognition". I do realize there are no smart pills, and I have a natural distrust of racetams. But I do not see anything wrong in stating that, for example, supplemental magnesium, has a nootropic effect.

 

[Travis]

Should be the same competitors - all the large neutral amino acids.

But if it competed with serotonin, it would be included in the Fernstrom ratio—yet it's not; only valine, leucine, isoleucine, phenylalanine, and tyrosine are.

 

[Koveras]

But if it competed with serotonin, it would be included in the Fernstrom ratio—yet it's not; only valine, leucine, isoleucine, phenylalanine, and tyrosine are.

Oh well pardonnez-moi for challenging Fernstrom

Nobody's perfect

Maybe he overlooked it because he thought it was a basic B... AA

"ATD is accomplished through the administration of a mixture of large neutral amino acids (LNAAs) lacking tryptophan (TRP)."

"The majority of free TRP uses the active transport system L-1, a carrier in the capillary cell plasma membrane specialized for the transportation of all LNAAs, to cross the BBB (14)."

"An affinity to the aforementioned AA, increased by 100 1,000 times, characterizes the BBB-specific type of the L-1 system (15)"​

Linden, M., Helmbold, K., Kempf, J., Sippas, S., Filss, C., Langen, K. J., . . . Zepf, F. D. (2016). Dietary tryptophan depletion in humans using a simplified two amino acid formula - a pilot study. Food Nutr Res, 60, 29272. doi:10.3402/fnr.v60.29272

[15]

"Although most of the amino acids studied here were those having unmeasurably low uptakes by the previous technique, L-histidine was included in this study, despite its high uptake, because of its unusual charge characteristics. It is commonly considered as a basic amino acid, being isoelectric at pH 7.59. Previous investigation of its brain uptake using carotid injection and a diffusible internal standard (4) indicated it was transported by the neutral carrier, but some lesser affinity for the basic carrier was also evident. This apparent affinity for the basic carrier was based on a single animal. In the present, more extensive studies, L-phenylalanine cross-inhibited L-histidine while L-arginine did not. A further delineation of L-histidine properties in this system was elucidated by studying its ability to inhibit the uptake of L-aspartic acid, an acidic amino acid. In the presence of 10 mM L-histidine, the BUI of L-aspartic was unchanged (BUI 2.39 ±0.82, n=3, P < 0.9), indicating no affinity for the acidic carrier system. The biological behaviour of L-histidine as a neutral amino acid at the BBB is thus established. The charge effect of the imidazolium group (pK 6.00) at the carrier site appears to be negligible, thus creating a neutral molecule at physiological pH)."

Oldendorf, W. H., & Szabo, J. (1976). Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol, 230(1), 94-98. doi:10.1152/ajplegacy.1976.230.1.94​

[16]



Smith, Q. R., Momma, S., Aoyagi, M., & Rapoport, S. I. (1987). Kinetics of neutral amino acid transport across the blood-brain barrier. J Neurochem, 49(5), 1651-1658.​

 

[Travis]

Perhaps we should calculate a modified Fernstrom ratio? I am looking for that Fernstrom article which has graphs of each amino acid vs tryptophan uptake.. . He has just so so many articles on serotonin and amino acids—like literally hundreds of them over the span of 50 years.

But I did find something interesting: This graph below shows what an injection of tyrosine does to blood pressure, and also how valine can inhibit this change:

Since it takes two hours to bring about the greatest change in blood pressure, you might think some product of tyrosine was responsible for this effect. I found this counter-intuitive because I had thought dopamine and the catecholamines would act to increase blood pressure.. .

Fernstrom, John D. "Branched-chain amino acids and brain function." The Journal of nutrition (2005)​

The plot of octanol-solubility vs amino acid brain uptake is very similar to the octanol-solubility vs brain uptake curve for general anesthetics—later found a better fit with olive oil ⟶ then better yet with phosphotidylcholine (r≈.95). Also, the data of skin permeability vs polarity for steroids has the same linear relationship—polarity is merely the opposite of nonpolarity, or neutrality. It appears as though the uptake through any physiological barrier is proportional—and with very good fit—to the molecule's solubility in oil, so I don't think we have to hypothesize very many 'transporters,' 'carriers,' 'specialized pores,'—either 'toll-like,' 'gate-like,' 'turnstyle-fashioned,' what have you—to account for this data; it all appears to suggest that lipid membrane solubility alone is the primary determinant for the diffusion for nonpolar molecules, large or small. This could also have implications for the metabolism of short-chain fatty acids.

So you might think that the brain uptake competitors of a particular amino acid would all be similar in solubility, and perhaps with emphasis on the ones being slightly less so (maybe causing a bottleneck! with the ones moving slightly faster through the membrane being less 'inhibitory').

[The Fernstrom Ratio provides a good fit for brain tryptophan uptake, which in turn determines serotonin synthesis in real time.]​

So why hadn't Fernstrom examined histamine? I had started-off giving him credit for being the greatest authority in this area; I had assumed that he'd actually tested for histamine and had found it noncompetetive, but now I'm starting to wonder.. .

The octanol–water partition graph puts histamine right near valine, an amino acid which Fernstrom had classified as a 'large neutral amino acid.' However, this graph of octanol–water partition had been drawn from data compiled at pH 7.0.

Yunger, L. "Measurement and correlation of partition coefficients of polar amino acids." Molecular pharmacology (1981)

'Values obtained for the logarithm of the ratio of distribution between octanol and 10 mM phosphate buffer, pH 7.0, are as follows: tryptophan, −1.11; histidine, −1.95; valine, −2.26; proline.. .' ―Yunger​

At pH of seven, histidine statistically has a greater postitive charge than at pH 7.4, the physiological pH. At these higher pH values, histidine tends more to lose the hydrogen on its imidazole ring, tending towards neutrality and lipid solubility:

'The conjugate acid (protonated form) of the imidazole side chain in histidine has a pKa of approximately 6.0. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge. ' ―Wikipedia​

As it turns out: The pH in which histidine is neutral, or uncharged—the isoelectric point—occurs at pH 7.5; this is very close to the body pH of 7.4. This would suggest that when found in the body, histidine would have less charge, greater lipid solubility, and hence a higher brain uptake than at pH 7.0.

Vinu, A. "Adsorption of L-histidine over mesoporous carbon molecular sieves." Carbon (2006)​

'Histidine adsorption was observed to be pH dependent with maximum adsorption near the isoelectric point of the amino acid.' ―Vinu

'At near the isoelectric point of histidine, pH 7.5, CMK-3 registers the histidine adsorption capacity of.. .' ―Vinu
​

Had Fernstrom simply classified histidine as 'polar' in his mind based merely on its published charge values at pH seven?—the value at which the majority of chemical data is compiled—while ignoring the fact that it tends towards neutrality in the body? This could very well be considered a 'large neutral competing amino acid;' the fact that histidine has a higher molecular mass than valine, leucine, and isoleucine means that it fulfills the other criteria—exceeded in mass only by tyrosine and tryptophan.

 

[Vinero]

1. At this very moment, I was just about to order some Tyrosine from NOW. It sits at 500mg per capsule, and according to the description on the box, there's gelatin, stearic acid and magnesium stearate in the mix. Unless there are other unlisted impurities, this doesn't seem that bad: We don't have any silica in here, and I can almost swear I saw a thread earlier on about the mitochondrial benefits of stearic acid.
2. Now, when it comes to thyroid (I'm recent to the writings of Ray Peat, so bear with me) I assume you're referring yourself to dissected thyroid supplements, no? They were one of the first things I researched, regarding the availability in my country (right alongside DHEA and pregnenolone). To my dismay I found out that in here (Portugal) not only is thyroid very seldomly prescribed, it is not available as an OTC. I assume most of the readers of this forum to be American, and during my time in here (I've been a lurker for 2.5 years), it seems that given the ease at which many people in here get their hands on thyroid, it is either available as an OTC, or doctors prescribe it rather frequently in the US of A.
   Before peating, I did have many hypothyroid symptoms (very cold extremities, nervousness, etc) and most of those symptoms are either disappearing or fully gone. But as the adage "listen to your body" goes, I'd like to try low dose thyroid for a while, to see how it goes. Just need to find if a 26yr old male would ever be prescribed that in this country, without serious Hashimoto's symptoms.
3. Thiamine is one of the supplements I was thinking about ordering just now (Tyrosine + Taurine + Thiamine). I have only supplemented with zinc (great androgenic effects + much better skin) and magnesium before (taken before bed; profound sleep, plus great energy during the following day). I have read at least 2 users in here say that thiamine makes their brain work like a super computer. I know that thiamine helps the body greatly improve the way in which glucose is oxidized, but is the nootropic effect that good?
   
   Note: I use the term "nootropic" as in "compound which clears and improves one's cognition". I do realize there are no smart pills, and I have a natural distrust of racetams. But I do not see anything wrong in stating that, for example, supplemental magnesium, has a nootropic effect.

If you are a young male I doubt you need thyroid hormone. I would try to use food to heal first.
Try eating at least 3 meals a day, each combining a protein with some saturated fat, starch and sugar.
Example of a meal would be Ground Beef with Cheese and Potatoes, with Milk and Coke
I wouldn't supplement with isolated amino acids, a lot of people seem to get side effects from tyrosine in particular.

 

[Koveras]

I was thinking tyrosine would be interesting, especially if a person consumes exorphins (which decrease dopaminergic transmission). This could both increase metabolism, nerve conduction, and lower prolactin—the release of which is controlled directly by dopamine on the pituitary.

Interestingly, in this study (below), a condition where subjects were given 20g tyrosine actually resulted in higher prolactin levels. They reference a few studies that mention tyrosine administration doesn't increase baseline dopamine levels, doesn't necessarily increase the amount released in response to a stimulus, although it maintains dopamine release that would otherwise be lowered under conditions of stress.

Struder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K. Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res (1998) 30(4):188-94. Epub 1998/06/12. doi: 10.1055/s-2007-978864. PubMed PMID: 9623632.

(Triangles represent condition with tyrosine administration)

​

 

[Travis]

Interestingly, in this study (below), a condition where subjects were given 20g tyrosine actually resulted in higher prolactin levels. They reference a few studies that mention tyrosine administration doesn't increase baseline dopamine levels, doesn't necessarily increase the amount released in response to a stimulus, although it maintains dopamine release that would otherwise be lowered under conditions of stress.

Struder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K. Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res (1998) 30(4):188-94. Epub 1998/06/12. doi: 10.1055/s-2007-978864. PubMed PMID: 9623632.


View attachment 8605
(Triangles represent condition with tyrosine administration)

View attachment 8606​

I have to admit that this is bizarre. Adrenaline levels weren't any different so you cannot explain this through any catecholamines produced (tyrosine is also the precursor for norepinephrine). Perhaps knowledge of the pituitary is crude and in need of further refinement; prolactin release perhaps being biphasic in response to low–high doses of dopamine? Or perhaps, and even better in my opinion: Tyrosine could be physically blocking the opiate receptors peripherally, increasing the activity of small opiate peptides and displacing them into the circulation and then into the brain; these endorphins then releasing prolactin, as they're certainly known to do. It should be noted that all exorphins and endophins—including enkephalins, β-endorphins, soymorphin, gluten exorphin B5, gluten exorphin C, neuropeptide Y, and β-casomorphin—have an N-terminal tyrosine molecule at their respective active ends (the other end being allowed to vary in length with retention of activity). Naloxone has been shown to displace morphine and opiate peptides from binding sites, and tyrosine would certainly be the sole amino acid to do this if you'd expect that any could. And henceforth, I'll match your graph and raise you one of my own; taken from the very same study:

Exhibit B: Graph depicting the greatest increase of β-endorphin is seen among cyclists in the tyrosine group.

Strüder, H. K. "Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans." Hormone and Metabolic Research (1998)​

 

[Lokzo]

I was right all along... L-Histidine is ultra-underrated.

Role of dietary histidine in the prevention of obesity and metabolic syndrome

 

[managing]

Reviving this slightly aging thread. Going to give histidine a try and report back.

@Lokzo et al. did you ever have any experience with it?

 

[Lokzo]

Reviving this slightly aging thread. Going to give histidine a try and report back.

@Lokzo et al. did you ever have any experience with it?

It is still super useful. I enjoy using it for a boost and especially pre-workout. I've since been able to up my dosage to around 2000mg-3000mg. Zero side effects, apart from warm body flushes.

 

[lvysaur]

I know that histidine levels are higher in men, and that they increase secretory fluids.

This is why men have better teeth (more saliva) and crave meat more (more stomach acid)

 

[managing]

I have been taking 2-3 g two times per day. It has a distinct calming, anti-inflammatory effect and seems to significantly extend tolerable time between meals. No signs of histamine issues at all.

But it has significantly reduced my auditory discrimination. And hearing is already a problem for me. What could be going on with this?

 

[GAF]

Histidine adds sensitivity to the male ICBM in a good way, if you are 62.

If she takes it, Histidine makes your girl friend scream louder and longer and more often, if you know what I mean and I hope you do.

Histidine has not made my morning mucus issue any worse or any better.

I like the stuff.