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.