Tryptophan supplementation and serotonin function: genetic variations in behavioural effects

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The neurotransmitter serotonin has a role in affective disorders such as depression and anxiety, as well as sleep, cognitive function and appetite. This review examines the evidence that serotonin-related genotypes may moderate the behavioural effects of supplementation with the serotonin precursor amino acid tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT) depends. However, 95% of serotonin is synthesised and used in the periphery, and TRP is also metabolised via non-5-HT routes such as the kynurenine pathway. Moreover, understanding of genotypes involved in regulation of serotonin raises questions over the generalisability of TRP effects on behaviour across individuals with varied serotonergic genotypes. To date, only differences between variants of the 5-HT transporter-linked promoter region (5-HTTLPR) have been investigated in relation to behavioural effects of TRP supplementation. Effects of 5-HTTLPR genotypes are usually compared between the alleles that are either high (L/L’) or low (S/S’) expressing of mRNA for the 5-HT transporter receptor. Yet, another key genetic variable is sex: in women, the S/S’ genotype predicts sensitivity to improved mood and reduced cortisol by TRP supplementation, during stressful challenges, whereas the L/L’ genotype protects against stress-induced mood deterioration. In men, the L/L’ genotype may confer risk of stress-induced increases in negative affect; there are insufficient data to assess effects in male S/S’ genotypes. However, better powered studies to detect sex by genotype by stress by TRP interactions, as well as consideration of more genotypes, are needed before strong conclusions and recommendations for 49 behavioural effects of TRP treatment can be reached.

© The Author 2018, published by Cambridge University Press. The attached document is an author produced version of a paper, uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.
Original languageEnglish
Pages (from-to)1-15
Number of pages16
Early online date25 Jan 2018
Publication statusE-pub ahead of print - 25 Jan 2018


  • ryptophan supplementation
  • serotonin and behaviour
  • 5-HTTLPR
  • genetic polymorphism
  • stress

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