OPINION

There is constant discussion about the effects of serotonin-producing tumours and issues of depression, anxiety, and ‘rage’. However, it’s a really complex issue for laypeople and I have no intention of trying to resolve it in this article. However, it’s clear to me from listening and reading these discussions in patient forums for many years, that most of the discussion appears to be based on years of unsubstantiated and unmoderated debate inside patient forums without professional input.  This is not an attempt to bash patient leaders and forum administrators, because a full understanding of these issues needs a much wider moderation. I’ve spent a considerable time researching and analysing what science is known and I can tell you now that the behaviour of serotonin in the human body is not entirely tied down.  I can also tell you that trying to work this out as a layperson is like walking through treacle but it does need to be explained in layman’s terms if possible.  There’s a lot of science behind it and some of this science is not 100% confirmed, and some of it is theoretical based on scientific opinion.  This is therefore an opinion post and not the professional input I referred to above.

It’s about Serotonin, right? 

What do we know?  This is an extract from my original article Serotonin – the NET Effect, which is really focused on Serotonin in relation to Neuroendocrine Tumours (NETs).  Serotonin is separately manufactured in the brain (5-10%) and in the gastrointestinal tract (90-95%). The serotonin in the brain must be manufactured in the brain, it cannot be directly reinforced by gastrointestinal tract (gut) serotonin (sometimes known as peripheral serotonin). It follows that ‘brain serotonin’ and ‘gut serotonin’ are held in separate stores, they are manufactured in those stores and remain in those stores – there is no cross-pollination.  This is managed by something called the blood-brain-barrier (BBB). Therefore, excess serotonin from NETs does not infiltrate the brain. As low-level of ‘brain serotonin’ is often linked to depression, it also follows that it’s possible to have high levels of serotonin in the gut but low or normal levels in the brain. It’s also possible to have high serotonin levels manufactured in the brain – that is known as Serotonin Syndrome, which is unrelated to NETs; and will be covered below.  Worth noting that serotonin measurements via blood are only measuring gut serotonin.  Also, worth noting that serotonin levels fluctuate throughout the day and any blood draw for serotonin is a snapshot.  Thus, why measuring the serotonin metabolite 5HIAA is a better test and indication of elevated serotonin levels in the gut. 

How Serotonin is made

Serotonin is not something in food (as some sites wrongly claim (including some NET sites)), it is manufactured in the body, mainly from an amine called L-tryptophan which is found in food. In the body it is converted to 5-hydroxytryptophan (5-HTP) before being converted to serotonin (5-HT). My simple way of thinking about such things as outlined above is that low levels of 5-HT (a metabolite of L-Tryptophan) in the brain might be contributing to low levels of serotonin in the brain.  But unlike serotonin which cannot pass through the BBB, 5-HTP can, and this is how serotonin is manufactured by converting 5-HTP in the brain. It follows that if you cut off or reduce the flow of L-tryptophan and its metabolites, it can reduce serotonin levels and potentially make you very unhappy.  And for those who are now thinking of supplementing brain serotonin levels via 5-HTP supplements, I advise great care, particularly if you are taking anti-depressant medications such as SSRI/SNRI or other serotonergic drugs – see Serotonin Syndrome section below. 

Serotonin and Carcinoid Syndrome

Certain types of NETs can produce an excess of serotonin (but also other hormones such as bradykinin, histamine, and prostaglandins).  These tumours were once called ‘carcinoid tumours’ but this misnomer has been made obsolete via up-to-date and pragmatic descriptions of Neuroendocrine Neoplasms via the International Agency for Research on Cancer (IARC) publication of Classification of Tumours (WHO Blue Books).

Excess levels of these hormones can sometimes result in a diverse set of symptoms called carcinoid syndrome. When these tumours occur in the digestive tract, the substances they produce are released into a blood vessel that flows directly to the liver (portal vein), where enzymes destroy them. Therefore, tumors that originate in the digestive tract generally do not normally cause symptoms of carcinoid syndrome unless the tumors have spread to the liver.  If the tumours have spread to the liver, the liver is unable to process the substances before they begin circulating throughout the body. Depending on which substances are being released by the tumours, the person will have the various symptoms of carcinoid syndrome. Neuroendocrine tumours of the lungs, testes, and ovaries also cause symptoms because the substances they produce bypass the liver and circulate widely in the bloodstream. Given the description above, clearly the over-secretion of serotonin remains within the area of the gut (peripheral) and does not cross into the brain.  Although this blog post is essentially about serotonin, it’s worth mentioning that this is only one hormone among many related to several hormonal syndromes related to NETs.