| 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. 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<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>. 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. 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<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>. |
− | There are several theories about how protein, tryptophan and carbohydrates may affect behaviour. These include the following:
| + | Dysfunction of 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>. In one study feeding dogs a diet with a lower protein content decreased territorial aggression<ref>Dodman, N.H., Reisner, I., Shuster, L., et al. Effect of dietary protein content on behaviour of dogs. J Am Vet Med Assoc 1996; 208:376-9</ref>, although other types of aggression seemed to be uninfluenced. |
− | *It is thought that very high protein diets could possibly result in a reduction in in the brain of levels of serotonin. Serotonin is formed from tryptophan and if amino acid levels are high competition for the carrier with tryptophan is increased. This means that lower quantities of tryptophan are able to cross the blood-brain barrier. Aggression has been linked to low serotonin levels in some cases<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> and in a small percentage of dogs, diets with lower protein levels decreased territorial aggression<ref>Dodman, N.H., Reisner, I., Shuster, L., et al. Effect of dietary protein content on behaviour of dogs. J Am Vet Med Assoc 1996; 208:376-9</ref>, although other types of aggression seemed to be uninfluenced. In both dogs and cats fed a L-tryptophan supplement, lower levels of behaviours related to stress and fewer signs of anxiety were seen<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 name="Kato">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>
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