Glycine

Activates NMDA receptors in the suprachiasmatic nucleus (SCN) to promote peripheral vasodilation and core body temperature drop. Acts as an inhibitory neurotransmitter at glycine receptors in the brainstem and spinal cord.

• Clozapine therapy (glycine may interact with clozapine efficacy)
• Severe renal impairment (high-dose use requires monitoring)
• Generally considered safe for most populations

Multiple double-blind, placebo-controlled RCTs published in Sleep and Biological Research (Yamadera et al., 2007; Bannai et al., 2012; Inagawa et al., 2006) demonstrated that 3g of glycine before bedtime significantly improved subjective sleep quality, reduced sleep onset latency, and enhanced next-day performance on cognitive tasks. Polysomnography data showed faster transition to slow-wave sleep. The mechanism was elucidated by Kawai et al. (2015), who demonstrated that glycine acts on NMDA receptors in the SCN to trigger peripheral vasodilation and core temperature reduction — a physiological prerequisite for sleep onset. Glycine has GRAS (Generally Recognized as Safe) status with the FDA.