Depleting Serotonin With BCAA

haidut

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Hi all,

I mentioned a similar idea in one of my other posts, but a new study just came out and I wanted to follow up on it. As many of you are aware the BCAA compete for transport into the brain (and other cells maybe??) with tryptophan, tyrosine, and phenylalanine. So, if you raise the ratio of BCAA to the other acids less tryptophan will get into the brain/cells and thus less serotonin will be produced. There have been many studies testing this idea and at this point it has been pretty well established that it works. The problem with this approach is that BCAAs will also deplete tyrosine, which is the amino acid from which dopamine is synthesized. So, the question scientists have been trying to answer is whether BCAA can be used to deplete serotonin only but leave dopamine unchanged. The reason for these tests is that in theory reducing serotonin and raising dopamine will have a positive effect on physical (and maybe) performance.
So, the attached study recently came out and it confirmed that one can reduce serotonin BUT keep dopamine intact (maybe even increase it a little) by ingesting a BCAA combo in the dosage 19mg/kg:12mg/kg:12mg/kg (leucine:isoleucine:valine) AND adding tyrosine at the dosage of 14mg/kg. To me this amounts to about taking 3500mg of BCAA and 1500mg tyrosine.
I am using the BCAA products from Ajinomoto since they are the only vendor claiming that the product is of pharmaceutical quality, and I have found that I don't get stomach irritation from their products.
My results so far are very positive. I get very calm and sleepy after taking the above combo. In fact it makes me feel almost exactly like taking cyproheptadine.
Speaking of the cyproheptadine, I thought that I can amplify the effects by doing cypro and BCAA combo together. So I took 2mg cypro and the BCAA+tyrosine combo together. Even more potent effect! My temperature rose to about 38 degrees Celsius, which is considered fever levels. I managed to get even more potent effects by doing cypro + (BCAA+tyrosine) + goat milk protein + gelatin. Both goat milk protein and gelatin have no tryptophan (actually goat milk protein has very very little) and contribute to the tryptophan depletion effect. I would not recommend the last option to anybody unless they have way too much serotonin that they want to get rid of. To me, this resulted in a heartbeat of over 100 BPM, temperature of 39 Celsius, and absolute inability to sleep. I felt like I had ingested some sort of supercharged gasoline and I kept turning and tossing all night while being madly thirsty no matter how much water I drink.
Given that drugs that increase dopamine in the body have very similar side effects on temperature, pulse, hunger, thirst, etc. I suspect that the last option depleted serotonin too much and/or raised dopamine too much. Keep in mind that since a lot of tyrosine will be getting into the brain/cells when you take it with BCAA, you WILL get an increase in dopamine TOGETHER with reduction in serotonin.
Moreover, BCAA seems to interfere with the absorption of both cysteine and methionine, and reduce their plasma levels by up to 50%.

http://www.ncbi.nlm.nih.gov/pubmed/7016402

So, BCAAs taken alone or combination with tyrosine and/or gelatin (and other tryptophan deficient protein) interfere with the absorption and metabolism of all 3 "bad" amino acids Ray Peat talks about - tryptophan, cysteine, methionine.

Finally, to make the super cocktail even more potent one can add taurine, which has a number of good effects on the liver, mitochondria and brain (through GABA modulation). Ray Peat talks about it in some of his articles.

http://suppversity.blogspot.com/2012/07 ... one-w.html

The human dosage is about 15g per day for the above effect to occur. So taking 5g with the BCAA+tyrosine combo seems like a very good way to give your health a super boost.

I would like to end with a question for the community. So far I have only been able to find studies on BCAAs depleting serotonin in the brain through the competitive inhibition of tryptophan transport. Ray Peat seems to think that the same happens in other cells/organs as well. Can somebody point me an article or interview of his where he says that? I just want to get more info on BCAA effects on cells other than brain cells.
Thanks in advance and I am looking forward to your comments/questions.
 

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gretchen

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I read goat milk has a lot of tryptophan. This is interesting though, thanks for posting.
 

haidut

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gretchen said:
I read goat milk has a lot of tryptophan. This is interesting though, thanks for posting.


I am getting confused. The several sources I checked say that goat milk protein has very little tryptophan. Much less than cow milk in fact:

http://www.swansonvitamins.com/swanson- ... grams-pwdr

http://www.mtcapra.com/data-sheets/caprotein.pdf

Above sources say that 20g of goat milk protein has about 40mg of tryptophan. This is much less than the 350mg-500mg of tryptophan in 20g of cow milk protein.
Can you please provide some sources which state that goat milk has lots of tryptophan? If it turns out it does, I'll definitely cut down on it.
Thanks.
 

jaguar43

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haidut said:
Hi all,

I mentioned a similar idea in one of my other posts, but a new study just came out and I wanted to follow up on it. As many of you are aware the BCAA compete for transport into the brain (and other cells maybe??) with tryptophan, tyrosine, and phenylalanine. So, if you raise the ratio of BCAA to the other acids less tryptophan will get into the brain/cells and thus less serotonin will be produced. There have been many studies testing this idea and at this point it has been pretty well established that it works. The problem with this approach is that BCAAs will also deplete tyrosine, which is the amino acid from which dopamine is synthesized. So, the question scientists have been trying to answer is whether BCAA can be used to deplete serotonin only but leave dopamine unchanged. The reason for these tests is that in theory reducing serotonin and raising dopamine will have a positive effect on physical (and maybe) performance.
So, the attached study recently came out and it confirmed that one can reduce serotonin BUT keep dopamine intact (maybe even increase it a little) by ingesting a BCAA combo in the dosage 19mg/kg:12mg/kg:12mg/kg (leucine:isoleucine:valine) AND adding tyrosine at the dosage of 14mg/kg. To me this amounts to about taking 3500mg of BCAA and 1500mg tyrosine.
I am using the BCAA products from Ajinomoto since they are the only vendor claiming that the product is of pharmaceutical quality, and I have found that I don't get stomach irritation from their products.
My results so far are very positive. I get very calm and sleepy after taking the above combo. In fact it makes me feel almost exactly like taking cyproheptadine.
Speaking of the cyproheptadine, I thought that I can amplify the effects by doing cypro and BCAA combo together. So I took 2mg cypro and the BCAA+tyrosine combo together. Even more potent effect! My temperature rose to about 38 degrees Celsius, which is considered fever levels. I managed to get even more potent effects by doing cypro + (BCAA+tyrosine) + goat milk protein + gelatin. Both goat milk protein and gelatin have no tryptophan (actually goat milk protein has very very little) and contribute to the tryptophan depletion effect. I would not recommend the last option to anybody unless they have way too much serotonin that they want to get rid of. To me, this resulted in a heartbeat of over 100 BPM, temperature of 39 Celsius, and absolute inability to sleep. I felt like I had ingested some sort of supercharged gasoline and I kept turning and tossing all night while being madly thirsty no matter how much water I drink.
Given that drugs that increase dopamine in the body have very similar side effects on temperature, pulse, hunger, thirst, etc. I suspect that the last option depleted serotonin too much and/or raised dopamine too much. Keep in mind that since a lot of tyrosine will be getting into the brain/cells when you take it with BCAA, you WILL get an increase in dopamine TOGETHER with reduction in serotonin.
Moreover, BCAA seems to interfere with the absorption of both cysteine and methionine, and reduce their plasma levels by up to 50%.

http://www.ncbi.nlm.nih.gov/pubmed/7016402

So, BCAAs taken alone or combination with tyrosine and/or gelatin (and other tryptophan deficient protein) interfere with the absorption and metabolism of all 3 "bad" amino acids Ray Peat talks about - tryptophan, cysteine, methionine.

Finally, to make the super cocktail even more potent one can add taurine, which has a number of good effects on the liver, mitochondria and brain (through GABA modulation). Ray Peat talks about it in some of his articles.

http://suppversity.blogspot.com/2012/07 ... one-w.html

The human dosage is about 15g per day for the above effect to occur. So taking 5g with the BCAA+tyrosine combo seems like a very good way to give your health a super boost.

I would like to end with a question for the community. So far I have only been able to find studies on BCAAs depleting serotonin in the brain through the competitive inhibition of tryptophan transport. Ray Peat seems to think that the same happens in other cells/organs as well. Can somebody point me an article or interview of his where he says that? I just want to get more info on BCAA effects on cells other than brain cells.
Thanks in advance and I am looking forward to your comments/questions.
 

jyb

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Interesting, I remember your previous posts on this. I'm personally reluctant to do experiment with this as I haven't found a source of BCAA that seems pure. All I get is these BCAA from bodybuilding shops.
 

baggiostyle

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I find this very interesting as I have experienced exactly the results you're describing with BCAA's, leucine and glutamine (which I know is anti-peat more or less).

I've been scouring this forum, peat's articles, josh rubins', and danny roddys' interpretations in hope of gaining an understanding of what was happening and this has really cleared things up for me.

I haven't tried tyrosine yet but I've been considering it and I think your testimony has convinced me :)
 

jyb

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Haidut, you mentioned that depleting some AA like trypt. could increase your metabolism, at least for some time. Does that mean that trypt. is being depleting everywhere, not just in the brain? Can reduced serotonin in the brain only be enough to increase say heart rate? I don't know how what determines the heart rate.
 

dukez07

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Above sources say that 20g of goat milk protein has about 40mg of tryptophan. This is much less than the 350mg-500mg of tryptophan in 20g of cow milk protein.
Thanks.

Hmm. Am I misreading something here? That's a whopping figure of tryptophan for cows milk. So you're saying that in as little as 40g of cows milk there is 700mg-1,000mg? I mean, 2quarts of milk is just under 2000g. Unless the chronometer is very wrong, or my calculations are wrong, I'm not sure what to make of this?
 

haidut

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dukez07 said:
Above sources say that 20g of goat milk protein has about 40mg of tryptophan. This is much less than the 350mg-500mg of tryptophan in 20g of cow milk protein.
Thanks.

Hmm. Am I misreading something here? That's a whopping figure of tryptophan for cows milk. So you're saying that in as little as 40g of cows milk there is 700mg-1,000mg? I mean, 2quarts of milk is just under 2000g. Unless the chronometer is very wrong, or my calculations are wrong, I'm not sure what to make of this?[/quote]


My post said "20g goat milk protein", which means in 20g of protein there is only 40mg of tryptophan. The 20g of protein is not anywhere equal to 20g of milk. In cow milk protein, in 20g of protein there is a lot more tryptophan.
 

mt_dreams

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cow's milk contains roughly 125mg of tryptophan per cup. Meaning you would get around 500mg per liter. Goat's milk has less, but not by much. A rough estimate would have it around 100mg per cup, so 80% that of cow's milk.

Whey Protein concentrate usually contains roughly 1.75 grams of tryptophan per 100 grams of protein. Assuming one scoop is 20 grams which is the norm, that amount would contain 350 mg of tryptophan. The number is equal to 2.5 glass of milk which yields 20 grams of protein within it. So you can't avoid tryptophan if you take in milk protein be it in it's raw state, or concentrated.

The problem with protein powders is that the protein is heated which denatures/oxidizes the tryptophan which leads to issues in the body. In one of Josh Rubin's interviews (probably the one on milk), I remember Peat saying that the tyrptophan in milk (especially if it's raw un-homogenized), has a different effect on the body than that from cooked meat or concentrated protein powders.

BCAA is not a natural protein, so although it may at first lead to lowering serotonin, it may have other consequences if taken long term.
 

haidut

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mt_dreams said:
cow's milk contains roughly 125mg of tryptophan per cup. Meaning you would get around 500mg per liter. Goat's milk has less, but not by much. A rough estimate would have it around 100mg per cup, so 80% that of cow's milk.

Whey Protein concentrate usually contains roughly 1.75 grams of tryptophan per 100 grams of protein. Assuming one scoop is 20 grams which is the norm, that amount would contain 350 mg of tryptophan. The number is equal to 2.5 glass of milk which yields 20 grams of protein within it. So you can't avoid tryptophan if you take in milk protein be it in it's raw state, or concentrated.

The problem with protein powders is that the protein is heated which denatures/oxidizes the tryptophan which leads to issues in the body. In one of Josh Rubin's interviews (probably the one on milk), I remember Peat saying that the tyrptophan in milk (especially if it's raw un-homogenized), has a different effect on the body than that from cooked meat or concentrated protein powders.

BCAA is not a natural protein, so although it may at first lead to lowering serotonin, it may have other consequences if taken long term.
In terms of whether goat or cow milk contain more tryptophan - I agree they are pretty similar. My post was about a goat milk protein isolate, which on its label claimed to contain only 40mg of tryptophan per 20g of protein serving. That's certainly low and the lowest I have ever seen in a commercial protein isolate supplement.
Finally, BCAA may not be complete protein but have well documented effects on mitochondrial biogenesis and also extend maximum lifespan. Most likely there tryptophan, methionine, and cysteine antagonism have something to do with it. Here is one study:
http://www.ncbi.nlm.nih.gov/pubmed/20889128

The dosage was a human equivalent of 9g-11g per day.
 

mt_dreams

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It's been a while since I've looked at protein isolate, as once I discovered the process of isolation in protein powders, I was turned off of them immediately. I guess the question now would be if taking isolates to keep tryptophan down is beneficial given the other issues that may arise with ingesting the isolates ... I'm not so sure, but then again I'm no expert.

The protein supplementation industry is a billion dollar enterprise, so I'm not surprised there's studies touting specific protein powder benefits. The only problem with pubmed (who has been known to screen what get's onto the site) or any journal for that matter, is that at times they contain studies done by individuals who are being funded by companies that end up benefiting with the positive exposure. As per some info on wiki regarding Elsevier who published this article, "In 2010, Elsevier reported a profit margin of 36% on revenues of US$3.2 billion" and "Elsevier's high profit margins and copyright practices have subjected it to much criticism.", so you be the judge.
 

dukez07

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haidut said:
In terms of whether goat or cow milk contain more tryptophan - I agree they are pretty similar. My post was about a goat milk protein isolate, which on its label claimed to contain only 40mg of tryptophan per 20g of protein serving. That's certainly low and the lowest I have ever seen in a commercial protein isolate supplement.
Finally, BCAA may not be complete protein but have well documented effects on mitochondrial biogenesis and also extend maximum lifespan. Most likely there tryptophan, methionine, and cysteine antagonism have something to do with it. Here is one study:
http://www.ncbi.nlm.nih.gov/pubmed/20889128

The dosage was a human equivalent of 9g-11g per day.

Where does one find the quality of BCAA that you're taking?
 

dukez07

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mt_dreams said:
The problem with protein powders is that the protein is heated which denatures/oxidizes the tryptophan which leads to issues in the body. In one of Josh Rubin's interviews (probably the one on milk), I remember Peat saying that the tyrptophan in milk (especially if it's raw un-homogenized), has a different effect on the body than that from cooked meat or concentrated protein powders.

BCAA is not a natural protein, so although it may at first lead to lowering serotonin, it may have other consequences if taken long term.

Did he specify what that 'different' effect was? Tryptophan is handled differently then, if it comes from a raw source?
 

haidut

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mt_dreams said:
It's been a while since I've looked at protein isolate, as once I discovered the process of isolation in protein powders, I was turned off of them immediately. I guess the question now would be if taking isolates to keep tryptophan down is beneficial given the other issues that may arise with ingesting the isolates ... I'm not so sure, but then again I'm no expert.

The protein supplementation industry is a billion dollar enterprise, so I'm not surprised there's studies touting specific protein powder benefits. The only problem with pubmed (who has been known to screen what get's onto the site) or any journal for that matter, is that at times they contain studies done by individuals who are being funded by companies that end up benefiting with the positive exposure. As per some info on wiki regarding Elsevier who published this article, "In 2010, Elsevier reported a profit margin of 36% on revenues of US$3.2 billion" and "Elsevier's high profit margins and copyright practices have subjected it to much criticism.", so you be the judge.


I am very suspicious of the PubMed studies as well, but the database has its uses given that it currently the largest public repository of biomedical research. One just has to be very careful when sifting through the junk that's out there. I always check the authors' affiliation and who funded them. In the case of the study above, the study was done at Pavia University (Italy) and not sponsored by private company.
Lately, I have just been eating a lot of stained yogurt and taking 6g of BCAA with each serving. It definitely gives me an energy boost; one that I do not get with yogurt alone.
 

haidut

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dukez07 said:
haidut said:
In terms of whether goat or cow milk contain more tryptophan - I agree they are pretty similar. My post was about a goat milk protein isolate, which on its label claimed to contain only 40mg of tryptophan per 20g of protein serving. That's certainly low and the lowest I have ever seen in a commercial protein isolate supplement.
Finally, BCAA may not be complete protein but have well documented effects on mitochondrial biogenesis and also extend maximum lifespan. Most likely there tryptophan, methionine, and cysteine antagonism have something to do with it. Here is one study:
http://www.ncbi.nlm.nih.gov/pubmed/20889128

The dosage was a human equivalent of 9g-11g per day.

Where does one find the quality of BCAA that you're taking?

Rumor is that Ajinomoto has the purest BCAA product and it is also not sourced from things like human hair and feathers. But it tends to be more expensive. Just search Google for "Ajinomoto BCAA".
As an alternative, Vitamin Shoppe in US is selling their own brand BCAA and the only ingredient listed other than BCAA is gelatin (for the capsule). That's what I am currently using, but I have to say the Ajinomoto brand was easier on my stomach for some reason. Experiment and find out what works for you:):
 

mt_dreams

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dukez07 said:
Did he specify what that 'different' effect was? Tryptophan is handled differently then, if it comes from a raw source?

In Ray's article "Tryptophan, serotonin, and aging", or possibly a Rubin interview with Ray, Ray somewhat alludes to the ratio of calcium to phosphate playing a major contributor in whether or not tryptophan is converted into excess serotonin or into the preferable b-vitamin, niacin. Milk's high calcium content does a good job of this assuming the rest of your diet is somewhat properly balanced with regards to calcium & phosphorus.

I believe in one of Rubin's interviews with Ray, Ray mentions that the process of turning milk liquid into a powder, like protein powder, or milk powder for that matter makes the tryptophan (among other things) possibly harmful. It's possible that he was talking about the body's ability to turn the tryptophan into niacin rather than serotonin, but I can't find my notes on that right now so I'm shooting in the dark at this one. I do recall him saying (probably in the same interview) if you plan on ingesting milk concentrate, to opt for condensed milk over milk powder. Then again I'm pretty sure in the recipes section there's an ice cream recipe charlie posted from Ray that includes powdered milk, so he's obviously messing around with these view points.
 

aguilaroja

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haidut said:
mt_dreams said:
.... The only problem with pubmed (who has been known to screen what get's onto the site) or any journal for that matter, is that at times they contain studies done by individuals who are being funded by companies that end up benefiting with the positive exposure. ... "Elsevier's high profit margins and copyright practices have subjected it to much criticism."...

I am very suspicious of the PubMed studies as well, but the database has its uses given that it currently the largest public repository of biomedical research. One just has to be very careful when sifting through the junk that's out there. I always check the authors' affiliation and who funded them....

The whole of academic publishing, not only biomedical, is problematic due to commercial interests. Access to full articles can be expensive, even when the research itself is publicly funded. This refers to the mark up in the publishing itself, separate from any benefit of products sales due to research suggestions. Elsevier, Springer and Wiley dominate the market. PubMed, as an index, "reports" a list of these dominants.

There is a good summary of the situation here:

http://www.monbiot.com/2011/08/29/the-l ... -learning/

Even conscientious researchers are largely stuck with this academic publishing system, not to mention inquiring readers.

The same group from Haidut's citation has a review article on BCAA whose FREE FULL text is available here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156598/

It would be difficult for anyone to review recent research while entirely omitting the results controlled by the monolith publishers.
 

jyb

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Anyone knows a way to makes those BCAA easier to swallow? The taste is pretty extremely bad, and that's coming from someone who can handle things like cascara just fine.
 

haidut

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jyb said:
Anyone knows a way to makes those BCAA easier to swallow? The taste is pretty extremely bad, and that's coming from someone who can handle things like cascara just fine.


If you are taking powder you can get flavored BCAA from Amazon (I think). For me, the solution was to use jasmine tea which has such a strong aroma that masks the unpleasant taste of BCAA. Also, I don't find the BCAA that repulsive. Certainly less unpleasant than thiamine (B1):):
 
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