Comment · Sun, April 7, 2013 · Ceretropic
Skepticism on 5-HTP's Possible Cardiological Risk - Thoughts?
Original post in this thread
[deleted] · 30 points
5-HTP is recommended to be taken with a decarboxylase inhibitor (such as EGCG) so that 1. the 5-HTP isn't converted into serotonin until it reaches the brain and 2. Because serotonin agonism on the heart (which would happen with peripherally-converted serotonin) causes the muscles to stiffen, potentially leading to cardiac fibrosis in the long term.
Something hit me today - SSRIs block the reuptake of serotonin all around the body (that's part of why they tend to increase appetite/lead to weight gain). Blocking reuptake = more serotonin able to bind to receptors = increased serotonin agonism, including on the heart. With the potency and daily use needed for SSRIs, shouldn't we be seeing people who have used such medications for years developing cardiac fibrosis?
It's paradoxical to me. Chances are, I'm missing a key piece of information here. What do you guys think about this?
What they were answering
probablytoomuch · 5 points
Okay, I spend a fair amount of time dispelling these rumors, so let me see if I can cover all your bases.
First off-- when serotonin is synthesized in the body from tryptophan, it's stored in the gut-- mostly. I'm sure you're at least partially familiar with the concept, but about 90 percent of all serotonin in the body just chills there until it's needed / excreted by enterochromaffin cells in there- directly into your bloodstream. By and large a massive percentage of serotonin is floating around your bloodstream right now, already converted. The rest, either tryptophan or 5-HTP, passes the blood-brain barrier and gets synthesized up there to create 5-HTP-> serotonin, regulated by rate-limiting enzymes (for trypophan and for dopamine/serotonin) that ensure you're not easily overdosing on serotonin (ensuring the relative difficulty of serotonin syndrome occurring) and further enforced by mechanisms that flush excess processed serotonin back into the bloodstream to get cleaned out of your body (especially quickly when taken with B6- but quick either way).
The danger presented by carcinoid tumors to heart valves is because the tumors continuously excrete massive amounts of serotonin directly into the bloodstream- the amount is so high you can't efficiently expel it, and it causes said problems. It's exceedingly unlikely to occur in healthy humans because 1) direct injections o…
u/MisterYouAreSoDumb · Ceretropic
First off, Saint John's Wort, or it's active ingredient hyperforin, does not rely on it's MAOI activity to alleviate depression. It increases extracellular sodium levels, which signals the 5-HT receptors to up-regulate. It also is a non-competitive re-uptake inhibitor of L-glutamate and GABA, as well as being a mild re-uptake inhibitor of 5-HT, DA, and NE. It also modulates certain gene expressions. It's much more than just an MAOI.
http://jpet.aspetjournals.org/content/290/3/1363.short
https://www.thieme-connect.com/ejournals/abstract/10.1055/s-2007-979530
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Now on to the 5-HTP. Your postulation that 5-HT being non-selective to the 5-HT2B sites does make sense. However, elevated peripheral 5-HT levels can cause a lot more than just heart valve damage. The most common side effect is stomach pain. Many people have serious stomach issues when taking 5-HTP without an aromatic L-amino acid decarboxylase inhibitor. Since that enzyme is found in the GI tract and in the blood, dumping a ton of 5-HTP in there, especially with B6, is definitely going to start the conversion early. This will lead to elevated peripheral serotonin levels. Even if it did not cause serious issues, you are still wasting the 5-HTP. Using EGCG is a safe and effective way to combat this, since it is an irreversible inhibitor of aromatic L-amino acid decarboxylase inhibitor. Also, only 5%-10% of your EGCG dose crosses the blood brain barrier. This means that most of that inhibition is in your periphery. It is a perfect candidate to prevent the peripheral conversion of 5-HTP to 5-HT.
Regardless if the cardiac dangers are overstated, the other issues are very much a factor. Why elevate your peripheral 5-HT levels if we know there are risks and it wastes the 5-HTP? I do not think 5-HTP should be a long term supplement. If a person is having issues with serotonin production, then the cause of that should be treated. However, sometimes 5-HTP can be used for a short period of time to replenish 5-HT stores when your tryptophan hydroxylase levels are low. When doing this EGCG should be taken with the 5-HTP. If nothing else, it just makes your supplement more efficient, and prevents stomach upset. I do not think you should be spreading the idea that since the studies of heart trouble are not 100% conclusive, that the entire concept is bunk. The mechanisms are proven, and there are many anecdotes to corroborate the effectiveness of the 5-HTP/EGCG combo.