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

Michihiro Ohashi; Sang-Il Lee; Taisuke Eto; Nobuo Uotsu; Chie Tarumizu; Sayuri Matsuoka; Shinobu Yasuo; Shigekazu Higuchi

doi:10.1186/s40101-022-00306-z

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

J Physiol Anthropol. 2022 Aug 26;41(1):31. doi: 10.1186/s40101-022-00306-z.

Authors

Michihiro Ohashi^{1

2}, Sang-Il Lee³, Taisuke Eto^{2

4}, Nobuo Uotsu⁵, Chie Tarumizu⁵, Sayuri Matsuoka⁵, Shinobu Yasuo⁶, Shigekazu Higuchi⁷

Affiliations

¹ Department of Kansei Science, Graduate School of Integrated Frontier Sciences, Kyushu University, 4-9-1 Shiobaru, Minami-ku, Fukuoka, 815-8540, Japan.
² Research Fellow of the Japan Society for the Promotion of Science, 4-9-1 Shiobaru, Minami-ku, Fukuoka, 815-8540, Japan.
³ Laboratory of Environmental Ergonomics, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.
⁴ Department of Human Science, Faculty of Design, Kyushu University, 4-9-1 Shiobaru, Minami-ku, Fukuoka, 815-8540, Japan.
⁵ Research Institute, FANCL Co., 12-13, Kamishinano, Totsuka-ku, Yokohama, Kanagawa, 244-0806, Japan.
⁶ Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
⁷ Department of Human Science, Faculty of Design, Kyushu University, 4-9-1 Shiobaru, Minami-ku, Fukuoka, 815-8540, Japan. higu-s@design.kyushu-u.ac.jp.

Abstract

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).

Keywords: Amino acids; Circadian rhythm; Field study; L-Serine; Sleep; University students.

MeSH terms

Circadian Rhythm
Double-Blind Method
Female
Humans
Male
Melatonin*
Saliva
Serine*
Sleep

Substances

Serine
Melatonin

Grants and funding

16K21225/JSPS KAKENHI