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Health Claims: Ergothioneine
How to market something you can never remember how to spell
^{Introduction
The final section of this three-part overview finally brings me to ergothioneine, chemical notation C9H15N3O2S. Ergothioneine is that weird chemical that pretty much only fungi synthesize. Now the compound is almost reaching buzz word status. Ergothioneine is the reason why people in the mushroom industry everywhere have started using the term bioactives as shorthand for all the beneficial chemical compounds in mushrooms. Thankfully, ergothioneine is less complicated to explain than Vitamin D (we also don’t know as much about it), and unlike beta-glucans it’s not a highly-varied class of compounds and doesn’t have several different potential biological actions. However, ergothioneine is still a poorly understood compound, and so I will attempt to go over its history, potential functions, what to be skeptical about, and thoughts on how to (or whether to) market it at all.
The name is not as weird or hard to remember if you know that the compound was discovered by Charles Tanret in 1909 as he studied ergot, the rye-destroying fungus ( potential source of mass hallucinations and 16th century witch hunts, as well as where LSD was first discovered). In Greek, theion means “sulfur” and thion is a prefix that in chemistry means “containing sulfur.” Compared to calling it a “trimethylbetaine of 2-thiol-L-histidine” I think ergothioneine works okay. As the name then implies, ergothioneine was first isolated from ergot and contains sulfur. Ergothioneine is actually a very rare type of chemical compound in nature, as very few alkaloids are synthesized out of histidines.}
While mushrooms are the most concentrated source of ergothioneine, the compound is taken up from mycorrhizal fungi in the soil and is widely distributed throughout nature. Legumes and oats are rich in ergothioneine as are animal livers. Humans utilize a cell membrane transport protein called OCTN1, which is very efficient at taking up ergothioneine from the digestive tract. Ergothioneine is found throughout the body, with a particularly high concentration in red blood cells, the liver, kidneys, bone marrow, the brain, and eyes.

Function of Ergothioneine
The most pressing reason for caution when dealing with ergothioneine is that there isn’t any clear evidence or clinical trials that support functional claims for it. There was a Swedish health study that showed plasma levels of ergothioneine had the strongest correlation with cardiovascular disease risk and mortality out of 112 metabolites measured in the study. There are also population studies, in Japan and Europe that have linked mushroom consumption to lower risk of dementia and degenerative diseases of the brain, as well as studies that show ergothioneine levels are lower in those with dementia and Parkinson’s disease than the baseline population. Research has also shown that mushroom consumption appears to protect against macular degeneration as well.

In vitro, which is to say, in a test tube or laboratory setting, ergothioneine has demonstrated powerful antioxidant capacities for both reactive oxygen species (like singlet oxygen) and reactive nitrogen species, as well as heavy metal cations. Ergothioneine has been found to be readily retained by the body, and compared to other antioxidant compounds is extremely stable and slow to undergo auto-oxidation. The fact that even after consumption of oral doses of ergothioneine, the human body excretes almost none of it, and the fact that it is present at millimolar concentrations (in biological terms, this is a very high concentration) in tissues prone to oxidative stress, all suggest an antioxidant role in the human body, with ergothioneine perhaps serving as a critical adaptive response to oxidative stress.

Let me contextualize this in the context in which recent research on ergothioneine has been done. The leading scientific theories of aging have typically explained aging and the wide variations and patterns in aging found within animals, as an evolutionary trade off. To be more specific, the most important thing to determine the survival of any species is reproduction and the spawning of viable descendants. Therefore, the selective pressures are to ensure an animal survives long enough to reproduce, and only in higher mammals with complex social structures and functional roles for elderly, like humans, elephants, and orcas for example, do you begin to find selective pressures for longer lifespans.

The famed biochemist-turned-nutritionist Dr. Bruce Ames introduced a potential mechanism for how this selective pressure works in practice, and Ames’ “Triage theory” is the one most referenced in literature about ergothioneine, which Ames also proposed as a what he calls a “longevity vitamin.” Triage theory goes pretty much as the name implies: for every mineral and chemical compound that humans must obtain from diet there are numerous proteins and biological processes that use said minerals and chemical compounds, usually as enzyme cofactors. Given a nutrient-deficient diet, the body then prioritizes short-term survival, "triaging" long-term survival.

The main example offered for Triage theory is generally Vitamin K, where researchers found that human tissues ration Vitamin K, with the production of certain enzymes related to blood coagulation getting prioritized over those related that remove calcium from the blood and thus prevent calcification of the arteries or help to maintain bone health. Ames and his collaborators also found similar support for Triage theory in studying the mineral selenium. This theory then suggests 2 very important ideas. First, the theory is an explanation for why poor nutrition (but not poor enough to cause diseases of deficiency like beri-beri) has an association with higher rates of diseases of aging and higher rates of chronic illness. The idea is that many of what are termed old-age diseases are caused by the buildup of cumulative damage from otherwise modestly insufficient nutrition over a long time period.
Second, given that all current essential vitamins and minerals are designated as such because their absence from diet will inevitably lead to severe if not fatal diseases (like scurvy), then this theory suggests there are other potential nutrients (bioactives) whose absence from diet is not marked by any immediate disease or disorder, but who nonetheless do have a positive biological function in reducing oxidative stress and otherwise preventing aging. Triage theory terms these compounds, which are not classified as essential nutrients, as “longevity vitamins,” i.e., they don’t have any immediate survival functions but their presence or deficiency in diet has an effect on aging and risk of certain diseases like cancer, diabetes mellitus, dementia and more.

This all sounds very nice on paper, but it is impossible to test it given the practical restrains of the real world, something the proponents of the theory readily admit. I will acknowledge that this theory of aging and disease provides a compelling biological pathway and explanation for much of the complexity and variability seen in studies into human health and nutrition, but at the same time I also retain a large dose of wariness. Especially since this theory can be attached to any compound that seems like it might have a biological effect, and fits in well with a long line of snake-oil salesmanship of food and supplements.

To double back again, ergothioneine has a stronger case for being such a “longevity vitamin” than most of the candidates proposed by Triage theory. The fact that ergothioneine is preferentially concentrated in body tissues exposed to high oxidative stress offers at least some evidence for antioxidant function in vivo (in vitro studies have already established ergothioneine is a powerful antioxidant, but many compounds that are antioxidants in a test tube do not end playing much of a role at biological concentrations or are not absorbed through metabolic processes intact). Despite the fact that no animals or plants are capable of synthesizing it, ergothioneine is present and retained in the tissues of nearly all animals, which strongly indicates that the compound has to have to some kind of benefit for such a widespread adaptation, which includes a specialized cell membrane transport protein. Ergothioneine has been shown in laboratory tests to have powerful antioxidizing effects in conditions mimicking those found inside the human body, and a study involving rats with the OCTN1 gene (the specialize transport protein for ergothioneine) “knocked out” showed a greater tendency to oxidative stress and related health issues. This then correlates with the aforementioned connections between ergothioneine as a health marker and mushroom consumption as correlating to a lower risk of cognitive and macular diseases.

The issue is squaring the compelling evidence with the lack of controlled studies and the still unclear mechanisms for ergothioneine’s function in the human body. There is no evidence or study for what specific diseases ergothioneine can prevent or treat and how it does so, nor any dosing guidelines. In the case of supplements, I strongly feel we should know first what the safety profile is for consuming ergothioneine in vastly higher concentrations than those found in nature. Bad science can still be good business, but I would rather do good business with good science.

In that context, the jury is still very much out on ergothioneine. In my opinion, ergothioneine is extremely interesting; I feel like there is at least a plausible and compelling argument with a modicum of scientific grounding for the compound’s benefit in diet, paired with ample evidence that, at least in the case of regular consumption of mushrooms, there aren’t any notable risks associated with it. This ticks off the cardinal rule of “do no harm”, much like with beta-glucans.

Promoting Ergothioneine

Ergothioneine, just like beta-glucans, offers an excellent exotic mushroom-specific marketing tool if done right, in that compared to regular button mushrooms oyster mushrooms, shiitake, maitake and other exotic wood-decaying varieties of mushroom have much higher concentrations of ergothioneine (and beta-glucans) than button mushrooms. That makes it very tempting to try and plug these two points, (over other things like vitamin D, B-vitamins, selenium content or potassium content), as a way to create more demand for exotic mushrooms as a health-conscious food source.

This brings me back to the title, which was not entirely humorous. How do you market something that nobody can even remember how to pronounce correctly, much less a word that seems like it would be a late-stage question for the American national spelling bee. How do you deal with the huge information gap between say, a grower who is passionate about fungi and nutrition, and the average consumer who doesn’t even know how mushrooms grow? There are also other antioxidant compounds like glutathione present in high concentrations in mushrooms, but if you just slap the antioxidant label on your marketing, well, then congratulations, you’ve joined nearly every other food and drink producer in the Western world in the past 30 years in telling people your product is rich in antioxidants. And the average consumer also doesn’t really know what the heck an antioxidant is either, only that it’s supposed to be healthy for you, maybe.
There aren’t easy answers. I’ve started complex and designed this 3-part series in a way to emphasize that functional simplicity and effective content marketing for health claims is in fact very difficult. I’m not getting paid to research ergothioneine and anyone running a mushroom business has better things to worry about. The choice isn’t between making wild and over-reaching health claims or completely ignoring the powerful appeals to health and lifestyle that can be made with exotic mushrooms. The real reason for the series lies in informing growers so that they have a clear idea of the evidence behind any potential claims and the limits as well.

I did this because every market, and indeed even each individual operation within a market, faces different demands, has different clientele, and grows different varieties. There is no one magic formula for health marketing that works everywhere, but I envisioned writing this series as a way to give growers in our network the tools to make informed decisions about how to promote their mushrooms. I didn’t shy away from complexity, but I also wasn’t trying to write a graduate thesis. Simplicity usually comes at the end of embracing complexity in all of its ambiguities, and I have written some compact summaries and explanations of the key elements needed to understand beta-glucan, vitamin D and ergothioneine health claims as of 2023.

As for what kind of form promotions, content marketing, labeling, and other materials used by exotic mushroom growers takes, I look forward to seeing what comes out of the industry in the coming years. There may even be an opportunity to share some examples in this journal. Marketing is a job that never finishes, and often the direct connection to sales can feel a bit lacking, but this is nonetheless crucial work, especially for new and unfamiliar products. This journal aims to be a long-standing partner to help lay that groundwork for the exotic mushroom industry. In the future, where possible, I will continue to share translated Japanese research on the subject in order to keep Western growers up to date with Japanese industry and consumers.

I also welcome any contact on health marketing. I can be reached at jemj@salai.jp, so please feel free to send me content marketing examples, links to news articles and scientific research on mushroom-related subjects, and even make corrections or addendums for this series.

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Health Claims: Ergothioneine

How to market something you can never remember how to spell