Intake of l-serine before bedtime prevents the delay of the circadian phase in real life

BACKGROUND: It has been shown in laboratory experiments using human subjects that ingestion of the non-essential amino acid l-serine before bedtime enhances the advance of circadian phase induced by light exposure the next morning. In the present study, we tested the effect of ingestion of l-serine before bedtime on circadian phase in real life and whether its effect depends on the initial circadian phase. METHODS: The subjects were 33 healthy male and female university students and they were divided into an l-serine group (n = 16) and a placebo group (n = 17). This study was conducted in a double-blind manner in autumn and winter. After a baseline period for 1 week, the subjects took 3.0 g of l-serine or a placebo 30 min before bedtime for 2 weeks. Saliva was collected twice a week at home every hour under a dim light condition from 20:00 to 1 h after habitual bedtime. Dim light melatonin onset (DLMO) was used as an index of phase of the circadian rhythm. RESULTS: DLMO after intervention was significantly delayed compared to the baseline DLMO in the placebo group (p = 0.02) but not in the l-serine group. There was a significant difference in the amount of changes in DLMO between the two groups (p = 0.04). There were no significant changes in sleeping habits after intervention in the two groups. There were significant positive correlations between advance of DLMO and DLMO before intervention in the l-serine group (r = 0.53, p < 0.05) and the placebo group (r = 0.69, p < 0.01). There was no significant difference in the slopes of regression lines between the two groups (p = 0.71), but the intercept in the l-serine group was significantly higher than that in the placebo group (p < 0.01). The levels of light exposure were not significantly different between the two groups. CONCLUSIONS: Our findings suggest that intake of l-serine before bedtime for multiple days might attenuate the circadian phase delay in the real world and that this effect does not depend on the initial circadian phase. TRIAL REGISTRATION: This study is registered with University Hospital Medical Information Network in Japan (UMIN000024435. Registered on October 17, 2016).