Summary

• Ergothioneine is an amino acid thiol present in various foods, including mushrooms, various plants, and spirulina.
• Ergothioneine can extend the lifespans of roundworms and mice. Large-scale studies of humans have found that blood levels of ergothioneine decrease after young adulthood and are related to risks of various diseases, frailty, and dying from all causes combined.
• Ergothioneine can improve cognitive function in adults. There has been little research on human supplementation with ergothioneine, but studies of other animals point to positive effects on numerous bodily tissues, which hungrily take up and accumulate ergothioneine via a transporter specific to it.
• Ergothioneine is in the morning step of PRODUCT NAME at the same dose as used in the clinical trial finding improved cognition.
• Ergothioneine has an excellent safety profile. Several food safety authorities have deemed it safe.

What is Ergothioneine?

Ergothioneine is a sulfur-containing amino acid thiol that protects cells and functions as a potent antioxidant that can bind (“chelate”) and remove metals that could otherwise wreak havoc. You might have come across glutathione as the so-called “master” antioxidant made by your body. Ergothioneine is somewhat similar to glutathione, but ergothioneine is very stable and less prone to degradation by “autoxidation” than glutathione. 

The human body seems to really value ergothioneine, for it is rapidly taken up by cells via its own bespoke transporter, the organic cation transporter 1 (OCTN1, technically SLC22A4 and SLC22A15). Furthermore, less than 4% gets excreted in urine, so cells hold onto ergothioneine, and their ergothioneine stores seem to protect structures such as mitochondria against damage from excessive oxidative stress, among other roles. 

Ergothioneine is a normal part of the human diet, and mushrooms, spirulina (a type of algae), and some fermented foods, such as tempeh, are especially rich sources.

Effects of ergothioneine on lifespan and healthspan 

Studies of people have hinted at roles of ergothioneine in longevity. Perhaps the most striking of this type of research is a study that looked at how changes in blood metabolites associated with cardiovascular disease and mortality in middle-aged adults over an average follow-up of 21 years. It found that, of 112 metabolites analyzed, higher blood ergothioneine was the metabolite most strongly negatively associated with risk of developing coronary heart disease, stroke, passing away from cardiovascular disease, or passing away from all causes combined, and this was after statistically adjusting for various factors that could confound such associations. This is very intriguing, but it neither reveals whether low blood levels drive these problems, nor do we know what causes low levels in these states — for example, low blood levels could be due to lower intakes, absorption, or greater clearance. 

To test whether ergothioneine intake per se really could extend life, recent research tested the effects of ergothioneine intake from early life (the human equivalent age is about 5 years old) until the end of life in male mice. It found that ergothioneine extended the mice’s lives, and separate experiments showed ergothioneine also prolonged lifespan and warded off measures of frailty in roundworms. Returning to the mice, ergothioneine also reduced age-related changes in body composition, physical activity, and learning and memory, while positively affecting markers of cardiovascular health. 

To forecast where ergothioneine is acting in the body to exert these benefits, it’s helpful to look at how its receptor is distributed between tissues. OCTN1 is on most, if not all, tissues, and the gene that holds the blueprint for OCTN1 is widely expressed on human tissues. Notably, it’s expressed in the small intestine, so dietary ergothioneine is taken up in the gut. It’s also expressed in the kidney tubules, so ergothioneine is reabsorbed, not just peed out. And it’s expressed on immune cells such as monocytes and neutrophils. Based on OCTN1 distribution, it might be that ergothioneine helps protect cells that are prone to excessive oxidative stress, stepping in to support primary antioxidant defences when they’re taxed to near their limits. 

Some of ergothioneine’s antioxidant activity seems to be mediated by ergothioneine’s interaction with NRF2, a key coordinator of cellular antioxidant responses that defend against subsequent stressors. Within cells, OCTN1 isn’t distributed evenly, and mitochondria seem to really value ergothioneine. OCTN1 isn’t the only way cells and their constituents take up ergothioneine, and mitochondria probably use other transport mechanisms to take up ergothioneine. It’s thought that ergothioneine acts via these transporters to help protect mitochondrial DNA from damage. Ergothioneine thereby targets several hallmarks of aging, including genomic instability, mitochondrial dysfunction, and chronic inflammation. 

Positive effects of ergothioneine on human health

Blood levels of ergothioneine increase during growth and development, reach a peak in early adulthood, then dwindle until the end of life. Frailty, dysfunction, and several chronic, age-related diseases are associated with particularly low levels, including mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, Crohn’s disease, and several cardiovascular and metabolic diseases. One of the things that’s most compelling about some of these studies is that they use unbiased methods in which they look whether any of hundreds or thousands of markers in the blood associate with disease… and ergothioneine keeps popping up. 

We look forward to future clinical research on ergothioneine, for the research done on other animals is hugely encouraging and raises the possibility that ergothioneine might be a conditionally essential nutrient. This work has shown positive effects of ergothioneine intake on many bodily tissues. To give just a few examples, ergothioneine improves proxies of mood and sleep in a rat model of depression, defends the eye against excessive oxidative stress, mitigates age-related hearing loss (in males only), protects the liver and kidneys against diabetes-related damage, minimises lung damage in an experimental model of acute respiratory distress syndrome, helps to maintain sperm numbers and health during exposure to the chemotherapy drug cisplatin, boosts exercise performance by enhancing mitochondrial function, and protects the skin against damage from UV radiation. 

Ergothioneine sharpens brain function 

While there’s been little controlled research on how changing ergothioneine intake affects human health, so far the results have been encouraging. A randomized controlled trial found that 5 mg ergothioneine each day for 12 weeks improved memory, and memory performance was correlated with blood ergothioneine. This is consistent with previous findings that older adults with lower blood ergothioneine levels experience faster cognitive decline in the subsequent 5 years, which appears to be related to the brain shrinking at a faster rate. Similarly, lower blood ergothioneine levels correlate with dementia and a smaller hippocampus, a key brain structure in short-term memory.

To understand ergothioneine’s actions in the brain, we have to refer to studies of other mammals and cells. Based on these, it seems that ergothioneine crosses the famously selective blood-brain barrier and then accumulates in brain. The scientists who did the clinical trial on humans mentioned above did a series of experiments on mice too. Their tests support the idea that ergothioneine supports the brain’s ability to rewire itself in response to ongoing demands. Specifically, ergothioneine might boost this so-called neuroplasticity by acting on a receptor named tropomyosin receptor kinase B (TrkB). Consistent with this, people who supplemented ergothioneine had greater levels of activated (“phosphorylated”) TrkB in little particles (“extracellular vesicles”) that traffic things between cells.

Prior research has pointed to other related actions of ergothioneine in the brain. For example, ergothioneine might promote neurogenesis, the formation of new nerve cells in brain tissue. Ergothioneine also protects against mitochondrial dysfunction, which is key to brain health, and ergothioneine’s antioxidant actions protect against oxidative stress, reactive nitrogen species, and inflammation. Damage incited by such stress is involved in the accumulation of amyloid, dysfunctional protein aggregates that build up in the brains of people with Alzheimer’s, and ergothioneine intake can reduce amyloid accumulation in mice. Regarding other proteins, research on the types of cells that line the brain’s small blood vessels indicates ergothioneine may reduce the formation of the advanced glycation end products that accrue as high levels of blood sugar stick to proteins, impairing protein function. In these ways, ergothioneine appears to also counter the loss of proteostasis hallmark of aging. Ergothioneine might matter for the young, developing brain too. OCTN1 is expressed on the placenta, OCTN1 density in breast cells increases during lactation, and ergothioneine makes its way into breast milk, so it’s thought that ergothioneine might be important for healthy development of the infant brain.

Ergothioneine might reduce skin wrinkling and improve skin hydration

Clinical trials showing positive effects of people consuming ergothioneine-rich mushroom products also strengthen the hypothesis that ergothioneine boosts human health. For example, a recent study found that women who consumed an oyster mushroom extract containing 25 mg ergothioneine for 12 weeks had improved skin hydration and skin wrinkling relative to controls. Since mushroom extracts used in such studies don’t exclusively contain ergothioneine, we can’t determine it’s the ergothioneine per se that’s at work, but when changes in bodily ergothioneine levels correlate with improvements in outcomes, as in this study, it’s very likely the ergothioneine is contributing to the results. 

Our use of Ergothioneine

Regarding dose, the 5-mg dose in Coastline matches that used in the recent clinical trial finding positive effects of ergothioneine on cognition. This is also one of two doses being studied in an ongoing clinical trial testing the effects of ergothioneine in the metabolic syndrome. 

Regarding timing, ergothioneine is in the morning step of Coastline. It isn’t clear if the timing of ergothioneine intake matters, especially as regular intake makes it accumulate over time in tissues. Nevertheless, part of the reason for our choice is that a study of other animals documented higher levels of ergothioneine in the blood and in part of the brain during wakefulness than during sleep, implying possible roles in the regulation of wakefulness and sleep, respectively.

Regarding form, Coastline contains L-ergothioneine, the same form used in clinical trials.

Ergothioneine typical dietary intakes and safety

Most of us consume a small amount of ergothioneine each day. Mushrooms are the richest sources of ergothioneine and contain roughly 0 to 1.8 mg per g dry weight, so an 80-g portion of fresh mushrooms is likely to contain about 8 mg ergothioneine. Their ergothioneine concentrations vary hugely though, depending on factors such as soil. Similarly, the ergothioneine concentrations of fermented foods such as tempeh vary depending on the bacteria used in fermentation. Ergothioneine is also present in plant foods (they take it up from soil) and animal foods (it accumulates in tissues following food intake), but only in small quantities.

While clinical trials on ergothioneine are in their infancy, major bodies agree on its safety. Indeed, the European Food Safety Authority has deemed synthetic ergothioneine to be safe up to 20 mg per day in kids and 30 mg per day in adults, even for pregnant and nursing women and their offspring. Similarly, the US Food and Drug Administration lists ergothioneine as Generally Regarded as Safe, meaning it can be used as a food additive and in supplements.