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====Protein, Tryptophan and Carbohydrate====
 
====Protein, Tryptophan and Carbohydrate====
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, methio- nine, histidine, isoleucine, tyrosine, phenylalanine, and threonine. l-Tryptophan is converted to kynurenine by the enzyme indoleamine 2,3,-dioygenase (IDO), which is activated by pro-inflammatory cytokines. Activation of Ido leads to depletion go -l-tryptophan, and therefore of serotonin, leading to signs of 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>.
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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. 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.
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The serotonin theory of depression and anxiety led to consideration of dietary manipulation to enhance CNS availability of  l-tryptophan in order to improve psychiatric symptoms. However, evident of clinical effect of l-tryptophan supplementation in humans is weak, with a Cochrane Report concluding that evidence for effect above placebo was 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>.
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The serotonin theory of depression and anxiety led to consideration of dietary manipulation to enhance CNS availability of  l-tryptophan in order to improve psychiatric symptoms. However, evident of clinical effect of l-tryptophan supplementation in humans is weak, with a Cochrane Report concluding that evidence for effect above placebo was 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:
 
  There are several theories about how protein, tryptophan and carbohydrates may affect behaviour. These include the following:
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