Food-derived antioxidant ergothioneine improves sleep difficulties in humans

Sleep disorders interfere with daily life and are associated with the development of various diseases. Here, we evaluated the effect of orally ingested ergothioneine (EGT) on improving sleep quality. We conducted a randomized, placebo-controlled, double-blind, parallel-group comparison study. A 20 mg EGT or placebo capsule was ingested daily for 4 weeks by volunteers with reported high anxiety and sleep complaints. A survey showed that EGT significantly ameliorates sleeping difficulties. Electroencephalograph measurements showed that EGT intake increases the N2 stage, while decreasing the N1 stage in non-REM sleep and the frequency of waking after sleep onset. Serum metabolome analysis suggested that EGT reduces serum glutamate as well as the consumption of antioxidant and anti-inflammatory substances while enhancing lipid metabolism. Molecular targeting assays revealed that EGT inhibits histamine N-methyltransferase and aldehyde dehydrogenase activity and binding to α3β4 nicotinic acetylcholine receptor. Hence, EGT may improve sleep difficulties via multiple mechanisms of action.