Advances on the edible safety and biological activities of L-Ergothioneine

L-Ergothioneine （L-EGT） is a histidine-derived compound widely present in edible mushrooms， certain legumes， animal organ meats， which must be obtained through dietary intake as it can’t be synthesized by humans. This review aims to evaluate the safety and health benefits of L-EGT based on a systematic literature assessment. Safety evaluations indicated an acute oral LD₅₀ >2 000 mg/（kg·BW）. In subchronic toxicity studies， the no-observed-adverse-effect level （NOAEL） was established at 800 mg/（kg·BW）， while subacute testing revealed no adverse effects even at the highest administered dose ［615-725 mg/（kg·BW）］. Additionally， all assessed genetic and reproductive/developmental toxicity endpoints were negative. Human studies have shown no adverse health effects associated with a daily L-EGT intake of up to 25 mg. In terms of health benefits， L-EGT exerts physiological effects primarily through antioxidant， anti-inflammatory， anti-apoptotic， autophagy-promoting， cognitive function improvement， metabolic disorders amelioration， and various organ injuries alleviation. Currently， L-EGT has been approved as a novel food ingredient in the EU and is regulated as a Generally Recognized as Safe （GRAS） substance in the US， while Japan and Canada also permit its use in foods or health products. In China， its application as a novel food ingredient was accepted for review in May 2024. In conclusion， based on available literature， L-EGT exhibits multiple health benefits at appropriate doses， indicating considerable potential for food applications. Future research should focus on long-term dietary safety and standardization of analytical methods to ensure its scientific-based application and regulation.