A single administration of ‘microbial’ D-alanine to healthy volunteers augments reaction to negative emotions: a comparison with D-serine

Abstract

Background Activation of the glutamate N-methyl-D-Aspartate receptor (NMDAR) with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers.

D-alanine is another potent NMDAR co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary.

This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion.

Aims The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers.

Methods In a double-blind, placebo-controlled randomised study, participants (N=63) received a single oral dose of either D-serine, D-alanine (60mg/kg) or placebo and then performed the Emotional Test Battery (ETB) and N-back task (2hrs post-administration) and provided saliva samples at fixed intervals.

Results/Outcomes Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words.

Participants on D-alanine also showed a trend to recall more words than placebo in a memory task.

D-serine did not have any meaningful effects in any of the tasks.

Neither amino acid had a significant effect on salivary cortisol or working memory.

Conclusions/Interpretations This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose.

The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies.

A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.

Citations

Liliana P. Capitão, Jessica Forsyth, Mia A Thomaidou, Mark D. Condon, Catherine J. Harmer, Philip W.J. Burnet. A single administration of ‘microbial’ D-alanine to healthy volunteers augments reaction to negative emotions: a comparison with D-serine. Journal of Psychopharmacology 13 March 2020

Page last reviewed: 12 June, 2025

Metadata

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Collection: 123456789/11

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Date issued: 2020-03

ISSN: 14617285

ID: 482