Phenylalanine Stimulates Dopamine Release

[Frankdee20]

The problem with taking these isolated Amino's for Dopamine is that eventually, the efficacy will stop. Must be a rate limiting step or something gets saturated, and the brain knows to tone it down. Trust me, the ***t will only work for a short time.

 

[milkboi]

The problem with taking these isolated Amino's for Dopamine is that eventually, the efficacy will stop. Must be a rate limiting step or something gets saturated, and the brain knows to tone it down. Trust me, the ***t will only work for a short time.

Bad news

 

[Waynish]

There is a U-curve phenomenon for phenylalanine and dopamine. The effective dose was 200mg/kg in rats, which translates to about 2.5g for a human in a single dose. More than that inhibits dopamine release. So, for the people doing the serotonin depletion protocol with BCAA a good starting dosage would be 5g BCAA and 2.5g of Phe. You can probably repeat that dose safely every 6 hours.

Phenylalanine administration influences dopamine release in the rat's corpus striatum. - PubMed - NCBI

Seems pretty stimulating... I've seen people behave like its cocaine around it.

 

[haidut]

Which kinds of restriction?

I don't think it inhibits tyrosine hydroxylase like phenylalanine does in higher doses.

 

[milkboi]

I don't think it inhibits tyrosine hydroxylase like phenylalanine does in higher doses.

Is that enzyme downregulated by chronically high levels of dopamine, therefore responsible for lower overall dopamine levels after abuse of dopaminergic substances (like phenylalanine)?

If so, would aspirin be enough to prevent that downregulation?

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase And Increases Dopamine Production

 

[Lokzo]

Bumping this thread.

I been using 1000mg Phenylalanine in the mornings, and boy I forgot how powerful this amino is.

Effects noticed:
1. Stimulating/alertness enhancing effects.
2. Better mood/more outgoing and confident.
3. Better digestion.
4. Warmer temps?
5. Sweating more pre-workout.
6. Difficulty falling asleep.

 

[cs3000]

The problem with taking these isolated Amino's for Dopamine is that eventually, the efficacy will stop. Must be a rate limiting step or something gets saturated, and the brain knows to tone it down. Trust me, the ***t will only work for a short time.

Thats what I was wondering - wouldn't sensitivity of dopamine receptors just decrease / sensitivity of serotonin receptors increase in response to the neurotransmitter availability changing?

which would make this only effective for acute use right, instead of how people use it for ongoing serotonin lowering effect


"studies have shown that TRP depletion produces postsynaptic receptor supersensitivity, presumably secondary to reduced synaptic availability of 5-HT" - Tryptophan depletion and its implications for psychiatry | The British Journal of Psychiatry | Cambridge Core - acutely 1 day lowering tryptophan lowered anxiety in anorexic people http://eatingdisorders.ucsd.edu/research/pub/imaging/doc/2003/kaye2003anxiolytic.pdf

but there's a lot of studies showing mood worsening affect with tryptophan depletion - "supersensitive" serotonin receptor rebound effect causing worse mood?

Effects on Mood of Acute Phenylalanine/Tyrosine Depletion in Healthy Women - Neuropsychopharmacology this one even shows worsening of mood from tryptophan depletion acutely which is surprising, was done with broad AAs which also lowered tyrosine a little but authors say it shouldn't have affected dopamine synthesis much, ,also shows worsened mood from phenylalanine depletion separately
another one Influence of acute tryptophan depletion on mood and immune measures in healthy males - PubMed
another one Relapse of depression after rapid depletion of tryptophan - PubMed


so how can this be done to ensure no major serotonin sensitivity rebound? or dopamine receptor sensitivity decrease

would be useful to find out how this sensitising mechanism works in the brain. how we can set it to a lower baseline sensitivity without having increased levels
(is it possible to sneak in some lowering slowly over time to prevent serotonin receptors freaking out & sensitizing as a response?)

 

[cs3000]

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine - Respiratory Research

Background There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to...

respiratory-research.biomedcentral.com

Results
The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool.
Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS.
Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS.

Inhibition of the Immune Response by Phenylalanine

In a previous study,1 phenylalanine (L-phenylalanine) was found to cause an inhibition of the immune response to diphtheria toxoid in rabbits and rats. Because phenylalanine interferes with the in vitro uptake of histidine, ornithine and tyrosine by the brain,2 it appeared that phenylalanine may...

jamanetwork.com

Phenylalanine and COVID-19: Tracking disease severity markers

Although there are several severity predictors for COVID-19, none are specific. Serum levels of phenylalanine were recently associated with increased inflammation, higher SOFA scores, ICU admission, and mortality rates among non-COVID-19 patients. Here, ...

www.ncbi.nlm.nih.gov

Phenylalanine and tyrosine were significantly lower in mild disease as compared to moderate and severe groups. Linear regression models showed that phenylalanine is independently and positively associated with disease severity regardless of the cytokine analyzed and after adjustment for potential confounders. In addition, mild cases showed consistently lower serum phenylalanine levels within the first ten days from disease onset to hospital admission.


Plasma amino acid levels in individuals with bacterial pneumonia and healthy controls Plasma amino acid levels in individuals with bacterial pneumonia and healthy controls

Patients with CAP had markedly decreased PAA of 12 amino acids on Day 0. Citrulline, histidine, and tryptophan remained low in male, while aspartic acid, asparagine, ornithine, proline, and threonine were higher on Day 7 in both males and females. Phenylalanine increased at Day 0 and Day7.


Elevated Plasma Phenylalanine in Severe Malaria and Implications for Pathophysiology of Neurological Complications Elevated Plasma Phenylalanine in Severe Malaria and Implications for Pathophysiology of Neurological Complications

Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 μM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] μM; P < 0.0001) and adults with all forms of severe malaria. In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement
Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.


So looks best to drop the phenylalanine during respiratory infection. i don't think it's a positive rise in response to infection i think its more of a negative association - the rabbit study found impairment of immunity, and considering arginine is beneficial in respiratory infection and phenylalanine could lower this that also might play a role.
also there's some papers mentioning possible neurotoxicity of phenylalanine metabolites Phenylacetic acid and its sodium salt toxicity reports, review - hazard potential, risk but not sure on dosing / significance. This study showed no adverse neurological effects over 12 months in people with high levels of phenylacetic acid ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO

 

[PeatReader]

I been using 1000mg Phenylalanine in the mornings, and boy I forgot how powerful this amino is.

Were/are you taking it without BCAA?