Updated: Nov 22
Educational summary by Dr. Srinivasa, Medical Advisor, and team. Based on Katsube M. et al. (2022), DOI 10.1016/j.jff.2022.105165. Educational only, no product endorsement.
Sleep problems are increasingly common in modern life. Stress, late-night screens, and irregular schedules can disturb the delicate balance of brain chemistry that controls rest and recovery.
L-Ergothioneine (EGT) is an amino acid that can be found in trace amounts in some foods. Researchers have suspected EGT might influence how the brain manages stress and sleep cycles. It is transported into the brain through a special "transporter" called OCTN1. This is extraordinarily uncommon and has excited many scientists to test their theories.
Here we review the first, placebo-controlled (dummy vs EGT) human trial of its kind to test whether daily EGT supplementation could improve sleep quality in adults who frequently felt anxious or had difficulty sleeping.
Short Summary of Findings
If you just want the TL;DR on L-Ergothioneine (EGT) from the study:
Better Sleep Quality: Participants taking EGT reported fewer sleeping difficulties than those taking a placebo (dummy) treatment.
Deeper, More Stable Sleep: Brainwave recordings showed increased N2 (stable sleep) and reduced N1 (light sleep) stages, with fewer nighttime awakenings.
Balanced Brain Chemistry: EGT intake reduced circulating "glutamate" (an excitatory neurotransmitter), lowered markers of stress metabolism, and boosted natural antioxidants.
Together these findings suggest that dietary EGT may support healthy sleep through antioxidant protection, neurotransmitter balance, and stress modulation.
Sleep Quality and the Clinical Study
Healthy adult men and women aged 40–75 with self-reported poor sleep joined a 4-week trial. Each took either a 20 mg capsule of EGT or a placebo dummy capsule daily. Researchers monitored sleep using home electroencephalography (EEG) over three nights before and after the intervention.
After 4 weeks, participants taking EGT showed statistically significant improvements in sleep structure compared to placebo, with no adverse effects reported. Specifically, study participants taking the EGT supplement experienced:
Less light sleep and more stable sleep, or a smoother transition into deeper rest.
Fewer nighttime awakenings.
Shorter delay before entering slow-wave sleep.
In plain language: People taking EGT spent less time tossing and turning and more time in restorative sleep without needing to change bedtime habits.
Metabolic Effects: How EGT Calmed the Brain
Researchers analyzed blood samples to explore possible biological reasons why EGT improved sleep. It is difficult to sleep when the brain is excited. The blood can indicate an excited brain if it has a high concentration of "glutamate".
The study found that glutamate decreased in the blood after EGT intake. By lowering glutamate, EGT may help the brain settle into calm, synchronized activity needed for deep sleep.
At the same time, EGT users had higher levels of natural antioxidants in their blood. Both EGT and natural antioxidants that the brain can produce itself protect cells from oxidative stress. This suggested that EGT reinforced the body’s own antioxidant network during sleep.
In plain language: EGT seemed to nudge brain chemistry toward relaxation. It reduced excitatory molecules that make sleep difficult and also helped antioxidant defenses do their nightly repair work.
Stress Hormones and Lipid Metabolism
The study found intriguing results of EGT on stress hormones. There was reduced activity in the production line of "corticosterone", a stress hormone that rises when the brain perceives threat or pressure. At the same time, researchers observed an increase in "pregnenolone-type" hormones, which are linked with calm mood. This shift points to improved regulation of the HPA axis, the hormonal system that can be steered toward rest and recovery when stress signals are reduced.
In a related finding, EGT also appeared to upregulate lipid metabolism in the brain. The resulting increase in these metabolites provides steady energy reserves that help the brain recover and repair from the day’s stresses during sleep cycles.
In plain language: EGT helped tune down stress chemistry while supporting healthy nighttime metabolism.
Final Thoughts
L-Ergothioneine (EGT) is emerging as a remarkable dietary molecule that appears to help the body and brain cope with everyday stress. In this carefully controlled human trial, daily EGT supplementation improved several measured markers of sleep quality without any side effects.
While further studies in larger populations are needed, these results strengthen the view that EGT contributes to healthy sleep and overall mental resilience by acting on antioxidant, neurotransmitter, and hormonal pathways.
As research continues, EGT may offer new insight into how nutrition supports the body’s natural rhythms of rest, recovery, and resilience.
