Why should 5-htp cause cardiac fibrosis if MAOIs seem to be safe?

[Morpheus19]

It is a well-known fact that there is a good theoretical reason to assume that 5-htp may cause cardiac fibrosis by raising blood serotonin levels considerably. I understand that SSRIs have a different enough mechanism of action to justify the risk of using them. But taking MAOis should lead to the exact same thing as 5htp - increased free-floating peripheral serotonin. Yet, MAOIs have been in use since ages and are still in use today without any evidence of causing cardiac fibrosis. So what should I make of this?

 

[sekio]

It wrong to assume that more peripheral serotonin = cardiac fibrosis. That's the 5ht2b receptor only and as far as I know there are other regulatory systems that keep heart valves in check. Otherwise like you said every serotonin releaser/SSRI/MAOI would increase the risk for fibrosis which is obviously not the case.

 

[Morpheus19]

Serotonin-producing neuroendocrine tumours are known to cause cardiac fibrosis (but there may be more to it than just elevated SE) and there is at least one controlled study that showed early signs of cardiac fibrosis in MDMA users (https://www.ncbi.nlm.nih.gov/pubmed/17950805). One metabolite of MDMA is a strong 5ht2b agonist, so that's no surprise (as far as I know, activiation of the 5ht2b receptor is needed for ALL SE-releasers). You clearly don't need elevated SE-levels to cause heart damage, 5ht2b agonism is enough. This study suggests that fenfluramine caused valvular heart disease in many people not because it releases some SE, but one metabolite is a 5ht2b agonist. Serotonin itself is a 5ht2b agonist, so one could argue that high levels of peripheral serotonin over prolonged periods of time could lead to heart damage. Also this study suggests another mechanism which could be a cause.

There is some evidence for the claim that serotonin alone can cause problems: This study and this study. The second showed a correlation between higher SE-levels and the occurence of heart disease.

Medications which produce "some" plasma elevation of SE tend not to cause heart damage. So the question is, how much is to much? I can't imagine that taking 5-htp even long-term can possibly be of any concern. I quite liked the combination of Moclobemid and a small dose of 5htp (yeah I'm aware of the SE-syndrome risk here), but I guess that combo seems to risky to do it more often than once in a while.