Changes

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>. It 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,-dioxygenase (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 may 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>.  

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>. It 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,-dioxygenase (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 may 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>.  

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.

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 [[Effect of Diet on Behaviour#Protein, Tryptophan and Carbohydrate|l-tryptophan supplemented diets]] is as equivocal and unreliable as in humans.

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 anxiolytic effect was found, 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"/><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>.

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 anxiolytic effect was found, 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"/><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>.