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==Tryptophan==
 
==Tryptophan==
Tryptophan is an amino acid which is used to form serotonin. Low levels of tryptophan in the diet are thought to be linked to a fall in serotonin levels. This may have an affect on mood and can be used in alongside conventional pharmacological treatments, however care should be taken to look for any signs of serotonin syndrome. Studies have shown a reduction in behaviours related to stress and a decrease in signs of anxiety in cats supplemented with L-tryptophan<ref>Da Graca Pereira, G., Fragoso, S., L-tryptophan supplementation and its effect of multi-housed cats and working dogs. Proceedings of the 2010 European Veterinary Behaviour Meeting. Hamburg, 2010, 30-35.</ref><ref>Kato, M., Miyaji, K., Ohtani, N., et al. Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. 2012; 7:21-6</ref>Tryptophan can be added to the diet or is available at higher levels in some commercial diets.
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l-Tryptophan is large neutral amino acid (LNAA) which acts as a precursor for serotonin. l-Tryptophan is actively transported across the blood brain barrier by the L1 carrier<ref>Hawkins, R.A., O’Kane, R.L., Simpson, I.A., Vin ̃az, J.R. (2006) Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids. J. Nutr. 136: 218S–226S.</ref>. l-Tryptophan is therefore in competition for this carrier with other LNAAs (such as leucine, valine, methionine, histidine, isoleucine, tyrosine, phenylalanine, and threonine) leading to theories that l-tryptophan supplementation might increase serotoinin availability and therefore alter mood and behaviour. However, l-tryptophan is converted to kynurenine by the enzyme indoleamine 2,3,-dioygenase (IDO), which is activated by cortisol or pro-inflammatory cytokines<ref>Oxenkrug, G.F. (2010) Tryptophan–Kynurenine Metabolism as a Common Mediator of Genetic and Environmental Impacts in Major Depressive Disorder: The Serotonin Hypothesis Revisited 40 Years Later. Isr J Psychiatry Relat Sci. 47(1): 56–63.</ref>. Activation of IDO leads to depletion of l-tryptophan, and therefore of serotonin, which indicates a significant role in anxiety and depression<ref> Wichers, M.C., Maes, M. (2004) The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression. J Psychiatry Neurosci. 29(1):11-7.</ref> <ref>Elovainio, M., Hurme, M., Jokela, M., Pulkki-Råback, L., Kivimäki, M., Hintsanen, M., Hintsa, T., Lehtimäki, T., Viikari, J., Raitakari, O.T., Keltikangas-Järvinen, L. (2012) Indoleamine 2,3-dioxygenase activation and depressive symptoms: results from the Young Finns Study.Psychosom Med. 74(7):675-81.</ref>. Through IDO there is therefore an interaction between stress hormones (e.g. cortisol), inflammation and serotonin production. Supplementation of l-tryptophan in stressed individuals might therefore be expected to have variable effects. Supplementation with 5-hydroxytrptophan, which is converted directly to serotonin and bypasses IDO, might be expected to circumvent this problem. However, despite a large number of trials, evidence of the clinical effect of l-tryptophan supplementation in humans is weak, with a Cochrane Report concluding that evidence for effect above placebo was positive but of insufficient quality to be conclusive both for l-tryptophan and 5-hydroxytryptophan <ref>Shaw, K.A., Turner, J., Del Mar, C. (2008) Tryptophan and 5-Hydroxytryptophan for depressions.The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</ref>.  
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Dysfunction of the serotonergic neurotransmitter system in dogs has been linked to a number of problems, including aggression<ref>Rosado, B., Garcia-Belenguer, S., Leon, M., et al. Blood concentrations of serotonin, cortisol, and dehydroepiandrosterone in aggressive dogs. Appl Anim Behav Sci 2010; 123:124-30</ref>. However, evidence for the efficacy of l-tryptophan supplemented diets is as equivocal and unreliable as in humans.
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In both dogs and cats fed a L-tryptophan supplement, lower levels of behaviours related to stress and fewer signs of anxiety were seen in one study, but this was not in a peer-reviewed journal<ref>Da Graca Pereira, G., Fragoso, S., L-tryptophan supplementation and its effect of multi-housed cats and working dogs. Proceedings of the 2010 European Veterinary Behaviour Meeting. Hamburg, 2010, 30-35</ref>. In another study, an axiolytic effect was fond, but the diet contained alpha-casozepine as well as l-tryptophan, so any effect cannot be ascribed to amino acid acid supplementation alone<ref name="Kato">Kato, M., Miyaji, K., Ohtani, N., et al. (2012) Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. Journal of Veterinary Behavior: Clinical Applications and Research. 7(1). 21–26.</ref>. A randomised double-blinded, placebo-controlled study showed no effect of an l-tryptophan enriched diet on behaviour or salivary cortisol in dogs, despite measurable increases in plasma levels of the amino acid<ref name="Kato">Kato, M., Miyaji, K., Ohtani, N., et al. (2012) Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. Journal of Veterinary Behavior: Clinical Applications and Research. 7(1). 21–26.</ref>Bosch, G., Beerda, B., Beynen, A.C., van der Borg, J.A.M.,  b, van der Poel, A.F.B., Hendriks, W.H.,  (2009) Dietary tryptophan supplementation in privately owned mildly anxious dogs. Applied Animal Behaviour Science. 121. 197–205</ref>.
    
==References==
 
==References==
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