Can L-(+)-Ergothioneine be used to treat depression? How safe is it?

L-(+)-Ergothioneine is a naturally occurring histidine-derived betaine synthesized by bacteria and fungi and is ubiquitous in plants and animals. It is present in many human foods, such as edible golden mushrooms. L-(+)-Ergothioneine is hydrophilic and membrane-impermeable, but is easily absorbed from the gastrointestinal tract due to the presence of a specific carrier-mediated transport system, the carnitine/organic cation transporter OCTN1/SLC22A4. Clinically used antidepressants have various side effects, and the development of drugs with minimal side effects is desirable.

Antidepressant efficacy

L-(+)-Ergothioneine is an antioxidant that scavenges hydrogen peroxide and peroxynitrite. It prevents oxidative damage to DNA and proteins and protects neurons from b-amyloid-induced cytotoxicity. On the other hand, in patients with depression, oxidative stress is increased and antioxidant levels are reduced, and interestingly, preclinical studies have shown that antioxidants may have antidepressant-like effects in rodents. In addition, L-(+)-Ergothioneine has been reported to exhibit antidepressant activity after oral administration and promote neuronal differentiation in cultured neural stem cells (NSCs) in mice. Its mechanism of action may be to promote neuronal differentiation by activating mTORC1 and NT5/TrkB signaling in NSCs. This suggests that L-(+)-Ergothioneine or its derivatives may be candidates for the treatment and/or prevention of certain neuropsychiatric disorders, including depression, as defects in mTORC1 and NT5/TrkB signaling have been associated with the exacerbation and/or onset of these diseases.

Safety

In the evaluation of the potential reproductive toxicity of L-(+)-Ergothioneine, no clinical signs of toxicity were observed. Its treatment had no effect on mating and reproductive performance or fertility parameters. Furthermore, L-(+)-Ergothioneine treatment had no effect on pregnancy duration, pre- and post-implantation losses, number of pups born and survival indices, or on litter parameters (litter size, clinical signs, weight or sex ratio) and redistribution of dead/cannibalistic pups found.

Another study found that daily supplementation of diabetic pregnant rats with L-(+)-Ergothioneine (1.147 mg/kg body weight) for 11.5 days before gestation also reduced the rate of embryonic malformations to that of non-diabetic animals. It had no effect on plasma glucose levels in either diabetic or control animals. Ergothioneine's inhibition of glucose-mediated free radical-dependent embryonic malformations is an important antioxidant preventive mechanism and may be beneficial in combination with vitamin E in the treatment of diabetic embryopathy. Overall, oral administration of L-(+)-Ergothioneine was well tolerated with no serious adverse effects reported.

References:

[1] TAKAHIRO ISHIMOTO. PS204. Food-derived antidepressant-like compound ergothioneine promotes neuronal differentiation via activating mTORC1 and neurotrophic factor signaling in neural stem cells.[J]. International Journal of Neuropsychopharmacology, 2016, 19 1: 75-75. DOI:10.1093/ijnp/pyw043.204.

[2] ROY FORSTER . Reproductive safety evaluation of L-Ergothioneine[J]. Food and Chemical Toxicology, 2015, 80: Pages 85-91. DOI:10.1016/j.fct.2015.02.019.

[3] M.V. GUIJARRO . Effects of ergothioneine on diabetic embryopathy in pregnant rats[J]. Food and Chemical Toxicology, 2002, 40 12: Pages 1751-1755. DOI:10.1016/S0278-6915(02)00177-1.

You may like