A natural compound attracting public attention as a longevity vitamin
Ergothioneine (EGT), a rare amino acid, is a natural compound produced by small populations of microbes, namely certain types of mushrooms (in the class basidiomycetes) and fungi, such as Aspergillus oryzae; Streptomyces species; and cyanobacteria [1]. The compound has been newly proposed as a putative longevity vitamin, the appropriate supplementation of which must reduce the consequent risk of chronic disease and premature aging [2]. EGT has gained attention due to its functional potential.

Excellent antioxidant properties and high safety
The greatest feature of EGT is its powerful antioxidant activity to detoxicate dangerous reactive oxygen species (ROS), leading to various diseases and skin aging (Table 1). Vitamin A was thought to be an exclusively potent reductant for singlet oxygen. However, under physiological conditions in the body, EGT deactivates singlet oxygen at a higher rate than vitamin A [3]. Furthermore, it inhibits hydroxyl radical (OH) production, the most toxic oxidant among ROS, and scavenges OH, which can compensate for the antioxidant defense system possessed in the body. Additionally, supplemented EGT is safe, showing no toxicity to the human body [4,5].

EGT accumulation system against oxidative stress
The high concentration of EGT is known to be accumulated in the organs and cells where oxidative stress is apt to be produced [6]. In the body, the ergothioneine transporter (ETT) efficiently uptakes EGT into the cells [7]. Accordingly, the organs where high concentrations of EGT are accumulated show a high ETT expression level [8]. For instance, the skin exposed to UV-associated oxidative stress stores a high concentration of EGT, resulting from the increased ETT expression in epidermal keratinocytes [9].
Effects of EGT on various diseases
Various beneficial effects of EGT are expected against neurodegenerative disorders (Alzheimer’s and Parkinson’s diseases), depression, UV-induced skin aging (wrinkles and spots), cataract, cardiovascular diseases, and oxidative stress.
As mentioned above, our bodies possess an EGT accumulation system, the efficiency of which is reduced by aging. Older adults with mild cognitive impairment show a low plasma EGT level. Therefore, supplementation with EGT is likely to ameliorate cognitive impairment [10]. This is the reason why EGT is termed a longevity vitamin.
References
- Borodina, I., et al. The biology of ergothioneine, an antioxidant nutraceutical. Nutr. Res. Rev. 2020, 33: 190–217.
- Ames, B.N. Prolonging healthy aging: Longevity vitamins and proteins. Proc. Natl. Acad. Sci. USA 2018, 115: 10836–10844.
- Rougee, M., et al. Deactivation of singlet molecular oxygen by thiols and related compounds, possible protectors against skin photosensitivity. Photochem. Photobiol. 1988, 47: 485-489.
- Chu, W. EFSA classes antioxidant l-ergothioneine safe for kids and pregnant women. NUTRA ingredients com. 15-Nov-2017.
- Turck, D., et al. Safety of synthetic L-ergothioneine (Ergoneine ®️) as a novel food pursuant to Regulation (EC) No 258/97. EFSA J. 2016, 14:4629.
- Cheah, I.K., et al. Ergothioneine; antioxidant potential, physiological function and role in disease. Biochim. Biophys. Acta 2012, 1822:784–793.
- Gründemann, D., et al. Discovery of the ergothioneine transporter. Proc. Natl. Acad. Sci. USA 2005, 102:5256-5261.
- Kato, Y., et al. Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1. Pharm. Res. 2010, 27:832-840.
- Markove, N.G., et al., Skin cells and tissue are capable of using L-ergothioneine as an integral component of their antioxidant defense system. Free Radic. Biol. Med. 2009, 46:1168–1176.
- Cheah, IK., et al. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem. Biophys. Res. Commun. 2016, 478:162-167.
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