Makrosky said:haidut said:Makrosky said:haidut said:Makrosky said:HDD said:Makrosky said:BobbyDukes said:Your comment doesn't really make sense. Do you think that SSRIs work for depression by increasing serotonin? And I'm not talking about the acute phase, where they flood the synapses with serotonin. I'm talking about the efficacious effects that occur when the drug plateaus. Even Peat himself has said that they may actually work by lowering setotonin, not increasing it. Added to that, SSRIs are highly complex drugs, and there is a lot more going on than 'serotonin'. Sorry to hear about your experience, though. Seems there are a few of us about. Mine is probably part genetic.
And you're probably right. It's not all going to be about serotonin. Let me know if you've got any other ideas.
Well, my comment makes sense because that's what happened. I don't know why SSRIs work. I don't think Peat knows either. Not at all. He doesn't provide much info for it. I don't have any other ideas, just wanted to share my experience to see if someone would have an hypothesis for it.
One thing I'm wondering since starting to dig into RP's world is this : When he talks about serotonin being bad, where and when is that serotonin ? Blood, presynaptic vesicles, intersynaptical space, which part of the brain, at which time of the day, which organs, and so many other questions. "serotonin is bad". Well...
This thread has a study shedding light on the mechanism of Prozac and other ssri's:
viewtopic.php?f=68&t=1964
Thanks! Though I find the linked evidence to be clearly insufficient to explain the SSRI issue.
Most SSRI's raise levels of allopregnanolone, which has undisputed antidepressant and neurogenesis effects. You can search Google for "Prozac allopregnanolone". However, it only happens after 2-4 weeks, which may explain why people are much more likely to commit suicide in the first 2 weeks of SSRI use when the only thing they do is raise serotonin. I posted a study recently where even big pharma said the theory is wrong and backwards - i.e. serotonin causes depression. In addition, fluoxetine (Prozac) is a 5-HT2 receptor antagonist, similar to mianserin and cyproheptadine btoh if which are known to be antidepressants. So, at least some of the SSRIs seem to be a mixed bag in terms of serotonin and also have desirable side effects on neurosteroids.
Thanks haidut!!! Very interesting info as always. I didn't know about the existence of allopreg. Apparently it's synthesized after progesterone, not pregnanolone itself.
I am interested in your views on why there's a mass of evidence in pubmed studies, clinical practice and anecdotal stories of direct serotonin precusors to alleviate or heal (while under treatment) depression and anxiety. I mean 5-HTP and L-Tryptophan.
I never found an explanation for that on RP's articles.
I just responded to you question as part of another post in the same thread. Tryptophan per se is not very bad but most of its metabolites are very very dangerous and serotonin is just one example. So, Peat may be just being practical and avoiding the whole cascade by simply avoiding tryptophan.
The studies on using free amino acids for cancer show that as little as 500mg tryptophan daily combined with the proper ratio of other essential amino acids is enough to put you in an anabolic state without being pro-carcinogenic as a result of its metabolites. However, we get a lot more than 500mg of tryptophan from our protein and the more we age the more likely we are to metabolize it into one of the toxic byproducts. So, the positive effects of glycine and BCAA are probably due to the inhibition of toxic tryptophan metabolism as well as boosting the thyroid, which tryptophan itself may inhibit.
haidut, sorry for the delay answering. Thanks a lot for the sound info man! i didn't know all that and the cancer stuff. That is a beginning of a possible explanation. It makes more sense that just what Ray says. Anyway, why are only the tryptophan metabolites the only dangerous ? Strange than nature put such dangerous metabolites in just one essential aminoacid and left the others "clean". Strange.
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For the Prozac issue: Then drugs like SSRI should be considered not only safe but beneficial after the first 2-3 weeks of serotonin raising ?
Cheers
Well, to be fair it should be said that cysteine, methionine, arginine and asparigine all have dangerous metabolites that can impact conditions such as cancer. Of these, arginine is probably the most nefarious due to its conversion of NO, which is a universal metabolic poison for every cell.
Why most of the tryptophan metabolites tend to be toxic I don't know. Since it exists in virtually all protein except gelatin it could be a mechanism for controlling how much protein we eat. It could also be a situation similar to iron - we need a lot while young but at older age it's better to be copper dominant. Ray said that our tryptophan requirements decrease greatly with age but he did not elaborate why. The same seems to be true with cysteine, methionine and arginine. There are studies with all of these aminos showing reduced intake improved health and/or increased lifespan.