Does increasing serotonin levels improve Crohn's symptoms?

Serotonin in Wikipedia

"How to increase serotonin in the human brain without drugs" by Simon N. Young in Journal of Psychiatry and Neuroscience (2007) [full article]
"Serotonin may be associated with physical health as well as mood. In otherwise healthy individuals, a low prolactin response to the serotonin-releasing drug fenfluramine was associated with the metabolic syndrome, a risk factor for heart disease,35 suggesting that low serotonin may predispose healthy individuals to suboptimal physical as well as mental functioning.

Nonpharmacologic methods of raising brain serotonin may not only improve mood and social functioning of healthy people — a worthwhile objective even without additional considerations — but would also make it possible to test the idea that increases in brain serotonin may help protect against the onset of various mental and physical disorders. Four strategies that are worth further investigation are discussed below.

...
The primary purpose of this editorial is to point out that pharmacologic strategies are not the only ones worthy of study when devising strategies to increase brain serotonin function. The effect of nonpharmacologic interventions on brain serotonin and the implications of increased serotonin for mood and behaviour need to be studied more. The amount of money and effort put into research on drugs that alter serotonin is very much greater than that put into non-pharmacologic methods. The magnitude of the discrepancy is probably neither in tune with the wishes of the public nor optimal for progress in the prevention and treatment of mental disorders."

The article proposes four strategies for increasing serotonin in the brain:

1. altered thoughts/mood influencing serotonin levels (self- or psychotherapy induced)
2. exposure to bright light
3. exercise
4. diet (tryptophan)

"10 Quick Tips to Boost Your Serotonin" from Mark's Daily Apple
"10. Avoid the fast track to happiness. ...
9. Don’t avoid carbs entirely. ...
8. Eat protein. ...
7. Eat fat. ...
6. Take a fish oil supplement! ...
5. Exercise to feel good. ...
4. Avoid the stimulant cycle. ...
3. Sleep right. ...
2. Investigate supplements wisely. ...
1. Boost other hormones! ..."

Does 5-HTP supplementation improve Crohn's symptoms?

Hydroxytryptophan from Wikipedia

5-HTP from The University of Maryland Medical Center


"The serotonin precursor 5-hydroxytryptophan reinforces intestinal barrier function" from Top Institute Food and Nutrition, Wageningen [no date]
"Tight junctions between intestinal epithelial cells form a selective barrier that contributes to gut homeostasis. Alterations in intestinal barrier function are considered to be early factors in the pathogenesis of irritable bowel syndrome (IBS). ... Oral administration of 5-HTP reinforces small intestinal barrier function by lowering intestinal sugar permeability, inducing the expression of the tight junction protein ZO-1 and rearranging tight junction proteins. These changes are associated with 5-HTP-induced alterations in mucosal serotonin metabolism. These data point to a role for serotonergic metabolism in reinforcing intestinal barrier function."

"Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin" in Int J Tryptophan Res (2009) [full text]
"Physiological roles of 5-HTP in the brain have not been reported. On the other hand, 5-HTP has a specific function in the gut. As a unique BH4 [ 6R-L-erythro-5,6,7,8-tetrahydrobiopterin] transport mechanism, BH4 that transiently enters cells can be rapidly oxidized to BH2 and is exported back to the extracellular space. Meanwhile, the intestinal epithelial cells take up BH4 as its reduced form. Therefore, the intestine shares a unique BH4 transporter mechanism and a specific function of 5-HTP. Further studies would clarify the intestine-specific machinery linking the specific mechanism of BH4-dependent 5-HTP production to the specific function of 5-HTP. A 5-HT precursor 5-HTP is sometimes administered to patients with metabolic disorder.27 The finding on the function of 5-HTP in the intestine might create an opportunity to explore the effects of exogenously-applied 5-HTP on the intestine in man."

"Gut hormones: emerging role in immune activation and inflammation" in Clinical and Experimental Immunology (2010) [full article]
"The studies discussed in this review provide evidence in favour of a key role of gut hormones in intestinal inflammation. In addition to the contribution in GI physiology, such as motility and secretion, gut hormones can also play an important role in immune activation and in the generation of inflammation in gut. The precise mechanisms by which gut hormones regulate the inflammation remain to be determined. The data generated from the studies on 5-HT in gut inflammation suggest strongly that increased 5-HT released by luminal inflammatory stimuli can activate immune cells such as macrophages, dendritic cells, lymphocytes and enteric nerves via specific 5-HT receptors, which can enhance the production of proinflammatory mediators via triggering activation of the NF-κB pathway and/or other possible proinflammatory signalling systems, and which subsequently can up-regulate the inflammatory response (Fig. 1). It will be interesting to see roles of specific 5-HT receptor subtype(s) in immune activation and generation of intestinal inflammation.
...
These studies provide novel information on the role of gut hormones in immune signalling and regulation of gut inflammation. Despite being a challenging and complicated area to explore, recent studies on immunoendocrine interaction has generated new interest to elucidate the role of gut hormones in the inflammatory process and immune function. In addition to enhancing our understanding on the pathogenesis of inflammatory changes, these studies give new information on 5-HT and Cgs [chromogranins] in the context of immunoendocrine interactions in gut and intestinal homeostasis. This is very important, due not only to the alteration in enteric endocrine cells functions observed in various GI inflammatory conditions but also in non-GI inflammatory disorders and functional GI disorders such as IBS. These data may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammation, which may lead ultimately to improved therapeutic strategies in inflammatory disorders."

If 5-HTP improves intestinal barrier function, but serotonin stimulates Crohn' symptomology, how can this be reconciled? Is 5-HTP supplementation helpful or ultimately harmful?

See my post entitled Does serotonin production worsen Crohn's symptoms?"

Does serotonin production worsen Crohn's symptoms?

Wishing Away Inflammation? New Links between Serotonin and TNF Signaling

"Pharmacology of serotonin: what a clinician should know" in Gut (2004) [full text]

"The pharmacology of serotonin (5-hydroxytryptamine or 5-HT) in the gut has been the centre of intense interest and research for several decades. Although it is now recognised that 5-HT is contained in intrinsic enteric neurones (where it works as a neurotransmitter), enterochromaffin cells of the mucosa are the main source (more than 90%) of the body’s 5-HT. In the gut, 5-HT is an important mucosal signalling molecule targeting enterocytes, smooth muscle cells, and enteric neurones. Application of exogenous 5-HT evokes so many responses that it is difficult to determine which are physiologically relevant. This bewildering range of effects is largely due to the presence of multiple receptor subtypes, which appear to be present on several classes of myenteric neurones, on smooth muscle cells, and on epithelial cells. 5-HT is thought to be involved in the pathophysiology of several clinical entities such as functional gut disorders (namely, irritable bowel syndrome), carcinoid diarrhoea, and chemotherapy induced emesis. In this review, the possible targets for pharmacological intervention are analysed in the light of the most recent advances of our understanding of the role of 5-HT in gut pathophysiology. Indeed, the recent regulatory interventions on cisapride (a 5-HT4 receptor partial agonist) and alosetron (a 5-HT3 receptor antagonist) have prompted a rethinking of our approaches to the pharmacological modulation of serotonergic pathways. In gut disorders, the most interesting targets for pharmacological intervention are:(1) the 5-HT receptor subtypes known to affect gut function such as those belonging to the 5-HT1, 5-HT3, 5-HT4, and 5-HT7 subtypes; and (2) the 5-HT reuptake mechanism which, apart from the central nervous system, is expressed in enteric neurones and enterocytes and is blocked by antidepressants.

...
Concerning possible pathophysiological roles of SERT [serotonin transport], apart from changes in the expression or pharmacological profile of SERT associated with dysfunctions of central serotonergic transmission (for example, depression and migraine), it is noteworthy that in guinea pigs with experimental colitis, a concomitant increment in 5-HT availability and a decrease in mRNA SERT expression were detected in the inflamed colonic mucosa.175 Clinical evidence suggests that similar alterations may also occur in patients with either IBS or inflammatory bowel disease.176 Moreover, SERT polymorphisms may be responsible for pharmacogenetic differences, as suggested by the colonic transit response to alosetron in patients with diarrhoea predominant IBS.177" [Emphasis mine.]

From this article "Pharmacology of serotonin," don't miss Table 1 entitled "Main serotonin (5-hydroxytryptamine or 5-HT) receptor subtypes in the gut".

"Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission" in Clinical Gastroenterol Hepatol (2007)
Symptoms resembling irritable bowel syndrome (IBS) are reported frequently in Crohn's disease (CD) patients in remission. Studies of the mucosal content of serotonin, which is a pivotal neurotransmitter in the gut, suggest that serotonin availability is altered in IBS patients. We aimed to study the role of serotonin in the generation of IBS-like symptoms in CD patients in remission. ...
CD patients in remission who experience IBS-like symptoms have increased mucosal TpH-1 levels in the colon, suggesting that increased serotonin biosynthesis in the colon plays a role in the generation of the symptoms."

"Amino Acid Responsive Crohn’s Disease: a case study" in Clin Exp Gasteroenterol (2010)
"In the intestinal tract of Crohn’s patients there is excessive synthesis with associated increased tissue levels of serotonin.8,9. In Crohn’s disease high levels of serotonin dominate synthesis, metabolism and transport leading to dopamine and catecholamine levels that are low relative to the balance needed to function properly with the serotonin levels present. ...
There is a known genetic defect of the organic cation transporters, OCTN1 and OCTN2, in the colon of patients suffering from Crohn’s diease. All OCT and OCTN transporters are capable of transporting organic cations including serotonin, dopamine, and their precursors.8 In Crohn’s disease the serotonin content of the mucosa and submucosa of the proximal and distal colon is increased. Increased synthesis of serotonin is known to be associated with Crohn’s disease.  No reasonable explanation of the etiology of serotonin elevation in the colon tissue of Crohn’s disease patients has been put forth previously.
It is postulated that the known OCTN1 and OCTN2 genetic deficit may be tied to the increased synthesis and tissue levels of serotonin seen with Crohn’s disease. Based on OCT assay interpretation, it appears that a severe imbalance between serotonin and dopamine transport, synthesis, and metabolism is at the heart of Crohn’s disease.
Imbalance of the serotonin-dopamine transport system has been linked to numerous diseases. It is purposed that much of the clinical constellation found with Crohn’s disease may be induced by a serotonin toxicity of the colon exacerbated by relatively low levels of dopamine resulting from defective OCTN transport....
There appears to be a defect in transport of serotonin precursors of the colon. Serotonin precursors are transported preferentially at the exclusion of dopamine precursors leading to high levels of synthesis, high levels of serotonin in portions of the colon, and compromise of catecholamine synthesis. Properly balancing the serotonin and dopamine precursor transport leads to less serotonin synthesis, less serotonin in the tissue of the proximal and distal colon, along with increase synthesis of dopamine, norepinephrine, and epinephrine. Increased serotonin levels of Crohn’s disease lead to increased monoamine oxidase activity (MAO) which without reciprocal increases of the catecholamines leads to increased metabolism of the catecholamines further exacerbating the imbalance.
... [T]he patient was then taking the following in divided daily doses: 300 mg 5-HTP, 6000 mg L-tyrosine, 240 mg L-dopa, and 4500 mg L-cysteine with cofactors. Following this change in amino acid dosing values, the patient continued to be asymptomatic, a state that exists to this day as long as he is compliant with the prescribed amino acid dosing values." [Emphasis mine.]