Posted by Larry Hoover on August 1, 2003, at 6:53:38
In reply to stimulants: tyrosine, phenylalanine, dexedrine, posted by andys on July 29, 2003, at 13:33:16
> There's a lot of confusion about tyrosine and phenylalanine (and its benefit, used with dexedrine). I have whittled it down to what makes sense to me, and would like this critiqued by those in the know:
You've gotten many of the ideas mixed up, Andy. For example, the hydroxylases you refer to are enzymes, not amino acids.
> A---It’s the HYDROXYLAZE version of the aminos that cross the blood/brain barrier.
The amino acids are literally pumped across the blood-brain barrier, but they do so in their simple amino acid form. That said, some supplements (e.g. L-dopa, 5-HTP) will also cross the blood-brain barrier, but those are not normally found in blood to begin with. The only reason they would be in the blood would be supplementation.
> B---Tyrosine hydroxylaze is desirable, because it supports brain dopamine and norepinepherine.
Tyrosine hydroxylase is an enzyme. It hydroxylates tyrosine to L-dopa. L-dopa is then converted to dopamine.
> Phenylalanine hydroxylaze is NOT desirable, because it gives a stimulant effect in the brain, and in the rebound, may actually DEPLETE brain dopamine and norepinepherine.
I don't know where you got this idea. Phenylalanine is converted to tyrosine, which then goes to L-dopa and dopamine. Phenylalanine also does other things, but there most certainly is no rebound effect to consider.
> C---Tyrosine hydroxylaze is converted to L-dopa in the brain, and then converted to dopamine, and to a lesser extent, norepinepherine.
Tyrosine hydroxylase is the rate-limiting step in the conversion of tyrosine leading to dopamine. What that means is that the body uses this enzyme to control total dopamine availability. The second step in the conversion, from L-dopa to dopamine, occurs virtually instantaneously, because that step is not rate-controlled. There is less norepinephrine produced than dopamine from a given amount of tyrosine simply because norepinephrine is further down the process.
> D---The tyrosine hydroxylaze BOTTLENECK:
> Although tyrosine hydroxylaze is very desirable in the brain, there is a bottleneck at the blood/brain barrier, where only a minimal amount of tyrosine hydroxylaze can cross into the brain.
The pumps I mentioned earlier control the availability of tyrosine in the brain (also diet is a factor, as you have to have the tyrosine in your blood for it to be pumped). There is competition at the pumps, so the relative availability of the aminos is also a factor, i.e. eating poor quality protein can cause amino acid imbalances.
> Because of this bottleneck, there are only two reasons to take tyrosine:
> 1---You’re not getting sufficient tyrosine in your diet (which is rarely the case, unless vegetarian).
I agree with that, but.... you can enhance the availability of tyrosine (by supplementation, taken on an empty stomach), which will, at least temporarily, over-ride the rate-limiting effect of the enzymes, and increase brain dopamine supply.
> 2---You’re on a stimulant, such as Dexedrine, and tyrosine can restore the dopamine/norepinepherine lost through
> Dexedrine use.
Again, diet should supply your needs. Your body should also adapt to the routine use of stimulants. That said, you can boost your body's "efficiency" at producing dopamine with appropriate supplementation. Either tyrosine or phenylalanine will do the trick.
> Where does PEA fit in this equation?
PEA is phenylethylamine. It is one of the other products of phenylalanine (i.e. not produced from tyrosine). Taking the racemic form of phenylalanine (d-,l-phenylalanine, or DLPA) will enhance PEA formation.
> Tyrosine is very beneficial, if taking Dexedrine
> Although several articles and actual studies support this, it doesn’t quite make sense: Since the tyrosine hydroxylaze is limited in its amount that can cross the blood/brain barrier, I doubt if MORE is allowed past the barrier, just because dopamine is depleted by Dexedrine.
The pumps will work more efficiently if there's more tyrosine or phenylalanine in the blood. The level of hydroxylase enzymes is probably more under genetic control than environmental (i.e. diet and stress), but all enzymes work better when you supply more raw materials. They don't think. They are processing machines, and more input equals more output. Period.
> Take tyrosine with juice, on an empty stomach, and not with other protein, aminos, or phenylalanine.
Juice not required, but wouldn't hurt. The idea is to get the pure amino in relative high concentration at the pump. The more tyrosine "lining up" at the pump, the more gets into the brain. Empty stomach (no protein) is essential for the high concentration effect to occur.
> My understanding of this theory is that you can maximize the amount of tyrosine hydroxylaze that crosses the blood/brain barrier, if it isn’t competing with other aminos crossing the barrier at the same time. This is true for other aminos, but especially for phenylalanine, which is why you shouldn’t take phenylalanine within HOURS of taking tyrosine.
They both compete for the same pump. I see no reason to choose between the two (tyrosine or phenylalanine), but you may have reasons that appeal to you. The pump in question, the LNAAT (Large Neutral Amino Acid Transporter), also is responsible for tryptophan uptake (precursor to serotonin). You have to balance your manipulations out, so you don't block tryptophan uptake entirely.
> The reasons to not take phenylalanine
> A---The reason for not taking phenylalanine with tyrosine:
> Since phenylalanine DIRECTLY converts to phenylalanine hydroxylase, it FLOODS the access to the blood/brain barrier, competing with the tyrosine hydroxylaze. But since phenylalanine DIRECTLY converts into phenylalanine hydroxylaze, it is going to reach the blood/brain barrier faster than tyrosine, which hs several metabolic steps for tyrosine hydroxylaze.
That's just not how it works.
> B---The reason for not taking phenylalanine AT ALL
> 1---Phenylalanine gives a short stimulant effect in the brain, but then has a rebound effect of DEPLETING dopamine and norepinepherine.
Again, not correct.
> 2---Poop-out of phenylalanine is very common, and, like other stimulants, you have to take some days off, to get the benefit back. However, this yo-yo effect is probably destabilizing for bipolars (or unipolars as well).
Again, that's not how I understand things.
Tyrosine is considered to be a stimulating amino. Phenylalanine also, but less so (for most people). They have equal access to the LNAAT pump (similar affinity), so which one gets into the brain in higher concentration is determined by blood concentration, more than anything else. Tryptophan does not compete well with either one, at the pump (lower binding affinity). After a high-protein meal, eat something with a high glycemic index (something that will cause insulin levels to spike), like something sweet. That will cause the muscles to turn on their amino uptake pumps, but muscles don't take up tryptophan to any appreciable extent. That will clear the blood of all the competitors to tryptophan at the blood-brain uptake pump, and promote tryptophan uptake.