| By Professor Barry Halliwell and Dr Irwin Cheah |
Ergothioneine is a unique compound that was first identified in the early 1900’s in the ergot fungus. Despite being known for over 100 years, and being present throughout the plant and animal kingdom, it is surprising that little is known about its role within the human body. However, in 2005, the identification of a specific transporter in animals and humans that facilitates the uptake and accumulation of ergothioneine in cells and tissues of the body, sparked a resurgence of interest in this compound.
Our laboratory at NUS and many others have shown that ergothioneine can act as an antioxidant and cytoprotectant in cell-free, cell culture and animal models. But unlike many other dietary antioxidants, our studies in humans show that ergothioneine is avidly retained by the body following oral consumption, with very low excretion in urine, and is not rapidly metabolised, suggesting it may play an important function — otherwise why accumulate it?
There is currently no evidence that it can be synthesised by animals and humans (only by certain fungi and bacteria), so it is actively taken up from the diet, predominantly from mushrooms. Mushrooms contain the highest levels of ergothioneine since they are able to synthesise this compound, but it is also present in a wide range of other foods albeit at much lower levels.
Ergothioneine appears to be universally present in human and animal tissues but has been shown to concentrate at high levels in certain cells and tissues such as bone marrow, blood cells, liver, kidney, brain, heart and eye. It can also be found at high levels in a range of animal and human extracellular fluids and secretions including cerebrospinal fluid, aqueous humour of the eye, tears, and seminal fluids.
In the human body, inevitable by-products of energy production and other biological processes, are highly-reactive and short-lived molecules known as free radicals. It is possible that these free radicals may play important roles that we are not aware of yet. However, in excess they may cause damage to biological molecules, and this damage contributes to the progression of many diseases, including neurodegeneration, cardiovascular disorders, cancer, and more.
Logically then, since free radical damage plays an important pathological role in a wide range of diseases, and ergothioneine can accumulate in a range of tissues of the body, ergothioneine may therefore have potential therapeutic applications in a wide array of disorders.
The first piece of evidence we found to support this came from witnessing decreased levels of ergothioneine in blood and tissues in certain disorders relative to healthy controls. The disorders include mild cognitive impairment, Parkinson’s disease, and possibly certain cancers. This suggests that a deficiency of ergothioneine could be important to the onset or progression of a disease, and possibly, ergothioneine supplements may help alleviate or prevent the disorder.
Secondly, supplementation of ergothioneine in a wide range of in vitro and in vivo models for neurodegeneration, cardiovascular diseases, ocular (eye) disorders, chronic kidney disease, skin conditions, and many others, have demonstrated the cytoprotective abilities of this unique compound.
Lastly, we have also found evidence to suggest that the body may actively increase the expression of the transporter at sites of tissue injury or tissues predisposed to stress. This may be to concentrate ergothioneine as a possible protective mechanism to minimise free radical damage, for example in fatty liver disease.
Beyond protecting against disease, there may be other functions for ergothioneine we have yet to identify in human health and development. Some studies have suggested that ergothioneine may be involved in erythropoiesis — the generation of new blood cells — or neuronal differentiation — brain development or repair, however these have yet to be fully verified.
Interestingly however, we have identified that ergothioneine is present in human breast milk, as well as also in cow and goat milk on which infant formulas are based, and expression of the ergothioneine transporter is significantly elevated in lactating versus non-lactating cultured mammary epithelial cells. Studies have shown ergothioneine is present in new-born babies, so it is likely crossing the placenta and/or taken up by the infant from breast milk. This suggests that the ergothioneine is of importance to the developing infant; however, more work is needed to establish this link.
Finally — an important point to note for therapeutic applications or use as a supplement — studies in animals and humans have found no toxicity or adverse effects associated with the administration of ergothioneine, even at very high doses. As such it has been granted the European Food Safety Authority approval (even for pregnant women and infants) by the European Union and is generally recognised as safe by the US Food and Drug Administration.
Overall, ergothioneine appears to be a safe, natural, diet-derived antioxidant. While much remains to be uncovered through in-depth research, if its benefits are validated through properly controlled, blinded human clinical trials, the therapeutic potential of ergothioneine could be huge.
About the authors
Dr Irwin Cheah is a Senior Research Fellow at NUS Biochemistry. He received his Bachelor of Science and later his PhD from Monash University in Australia, and his research interests include how ergothioneine affects ageing and disease, as well as oxidative damage biomarkers in ageing and disease, and quantification of biomarkers and metabolites.
Professor Barry Halliwell is a Tan Chin Tuan Centennial Professor and Senior Advisor in the Office of the Senior Deputy President and Provost at NUS. He is one of the world’s most highly cited researchers in Biology and a world authority on the role of free radical damage and antioxidant biology in human health and disease. He has a longstanding interest in the role of ergothioneine in human health and his earlier work helped establish the powerful antioxidant properties of ergothioneine.