Rediscovering a Forgotten Molecule: Royal Lee, Mushrooms, and the Early Clues to Ergothioneine’s Power
By Lee Carroll, Medical Herbalist
Did Royal Lee know about ergothioneine (ERGO) in 1929? It’s a provocative question. One that connects nutrition history, biochemical curiosity, and the legacy of one of the most visionary—yet often under-recognized—figures in natural medicine.
As a long-time educator within the Standard Process/MediHerb network (2001 to 2020), I’ve often found myself pondering the foundational products and ideas of Dr. Royal Lee. His formulations, including Catalyn, reflected a genius not just for whole food synergy—but for spotting clinical value long before mainstream science caught up. His theories on protomorphogens, for example, might be viewed as an early conceptual parallel to the recent discovery of microRNA.
And recently, I had this epiphany about Catalyn!
Catalyn was launched in 1929—and it contained mushrooms. That’s extraordinary. It made Catalyn the first mushroom supplement nearly 100 years before today’s mushroom and fungal renaissance.
Put yourself in that era. In 1929, mushrooms weren’t seen as health food. They weren’t even considered nutritious. The only mushroom most Americans had ever heard of was the humble white button—and even that was a rare garnish for the wealthy. It wasn’t until the 1950s and 60s—two to three decades after Catalyn hit the market—that white button mushrooms became a regular feature in grocery stores.
The idea of mushrooms as a delivery system for unique health compounds like ERGO or beta-glucans? Completely unheard of. In fact, the immune relevance of mushroom beta-glucans wasn’t discovered until the 1960s—more than 30 years after Catalyn launched.
But I think Royal Lee saw the clues. He was a voracious reader of global research, a creative thinker, inventor, and visionary with multiple patents to his name. He understood mushrooms offered something the science hadn’t yet explained.
Today, we understand that mushrooms—especially porcini, oyster mushroom of all types but especially golden oyster, Lion’s mane, maitake, shiitake—are the richest known sources of ergothioneine, a unique sulfur-containing compound that’s showing up in cutting-edge research on healthy aging, cognitive resilience, and mitochondrial health.
But back in 1929?
Let’s rewind a bit.
A Forgotten Molecule Comes Into View
Ergothioneine was first isolated in 1909 by French chemist Charles Tanret, who discovered it in ergot fungus (Claviceps purpurea). At that time, it was simply categorized as an unusual sulfur-based amino acid. The tools didn’t yet exist to understand its function.
The turning point came in 1927, when Moureu and Gallois, also in France, published a brief but groundbreaking note in Comptes Rendus de l’Académie des Sciences stating that ERGO was present in human blood. Suddenly, this fungal compound had a physiological footprint.
What they didn’t yet realize was that ergothioneine existed beyond ergot fungus—it was also present in edible mushrooms. That connection wouldn’t be confirmed for decades. But think about it: ergot is toxic. Humans weren’t consuming it as food. Yet ergothioneine was turning up in our blood.
Where did it come from, and why was it being retained?
It would take a genius to speculate on the dietary source. And Royal Lee, with his voracious reading habits, creative mind, and deep respect for overlooked natural compounds, could well have joined those dots long before the science and the textbooks caught up. Even though Lee developed a significant number of animal-based products, his vegetarian lifestyle likely made him equally motivated to explore underappreciated health-building molecules from plants and fungi—including mushrooms.
1929–1935: The Forgotten Clues
Between 1929 and the mid-1930s, a handful of European and British researchers quietly explored this molecule. Most notably:
Hunter & Eagles (1934), in the Biochemical Journal, demonstrated that ERGO was found in animal tissues and concentrated in red blood cells. They speculated on its biochemical role, especially its behavior under hypoxia and its sulfur content.
Others, like Roche and Perreault, noted its unusual metal-binding properties, laying the early foundation for understanding ERGO’s chelating and protective antioxidant behavior.
Keep in mind, the word “antioxidant” wasn’t even in common scientific use yet. But the patterns were emerging.
So was Royal Lee aware of these early findings? I think so.
He may not have named the molecule. But he absolutely had access to European chemical journals, and his work shows a pattern of responding to early biological signals long before others did. He clearly understood that mushrooms held some underappreciated biological value.
Ergothioneine Today: Science Catches Up
Fast forward almost a century. We now know that ergothioneine is:
Transported into cells by the ERGO transporter, ETT (SLC22A4), a highly specific transporter our bodies make just for this compound.
Concentrated in tissues vulnerable to oxidative damage: brain, liver, eyes, kidneys, immune cells, reproductive tissues.
Involved in modulating redox balance, protein persulfidation, and potentially NAD+ metabolism.
Ergo is effective in low doses and the body retains it avidly, hence the low amounts in Catalyn are highly likely to be clinically effective across a lifetime of use—as Catalyn was intended.
Recent research has associated low ERGO levels with increased risk of cognitive decline, vascular dementia, AD, Parkinson’s, cardiovascular disease, age-related macular degeneration, and even frailty in aging populations.
In my own work (reading the research), I’ve been developing theories to explain the clinical and epidemiological findings exploring ERGO’s connection to:
- Mitochondrial integrity
- Hydrogen sulfide (H2S) signaling through enzymes like MPST and CSE
- Proteome protection (via persulhidation) and its connection with increased healthspan and lifespan.
- Its adaptive behavior as a thione/thiol switch, responding to local pH and oxidative status
These findings suggest that ERGO is not just another antioxidant, it’s cytoprotective and may be a core regulator of cellular resilience, helping the body adapt at the protein, mitochondrial, and even epigenetic level.
Low-Dose Mushrooms: The Epidemiological Evidence
Here’s where it gets even more interesting.
Recent population studies reveal that small amounts of mushrooms—taken regularly—are associated with tangible health benefits. Exactly the kind of low-dose, food-based strategy that Royal Lee championed.
For example, Cha et al. (2024) analyzed nearly 5400 participants from the EPIC-Norfolk cohort in the UK, tracking dietary patterns over time and assessing cognition with validated neurocognitive tests. Their findings? In cognitively healthy people, consuming approximately 45 grams (1 ½ oz) of fresh mushrooms per week—the equivalent of just one modest serving. This was associated with better memory, executive function, and processing speed—even after adjusting for fruit, vegetable, and other dietary intake. Importantly, those eating more than one portion per week performed best across cognitive domains. The authors concluded that mushroom intake, independent of broader plant-food patterns, supports cognitive resilience during aging.
Ba et al. (2021) came to a similar conclusion analyzing global data on nearly 600,000 people—modest mushroom consumption correlated with lower risk of all-cause mortality.
What’s noteworthy is that both research groups highlight ERGO as the most likely driver of these effects. Beta-glucans certainly have documented health benefits, particularly for immune modulation, but these effects typically require significantly higher daily intake levels—far beyond the 45 grams or so of fresh mushrooms consumed once per week in the Cha et al. study. Ergothioneine, on the other hand, is highly bioavailable, retained in the body, and uniquely capable of exerting antioxidant, anti-inflammatory, and cytoprotective effects at these low, food-based doses. At present, it remains the only compound in mushrooms—especially common dietary species—known to plausibly explain these population-level cognitive and mortality benefits.
Sound familiar? Catalyn contains mushrooms. Not in heroic doses. But enough, as we now see from modern science, to nudge biological systems toward resilience.
It raises the question: Did Royal Lee intuitively grasp what the epidemiology now confirms? That low-dose mushroom intake—sustained over time—supports health.
Was Royal Lee 100 Years Ahead of Science?
In the Standard Process community, we often talked about how Royal Lee was ahead of his time.
Ergothioneine may be one of the most striking examples. He included mushrooms in his first product—at a time when their nutritional value was unknown, and when the term “ergothioneine” would’ve meant nothing to most researchers. Yet nearly a century later, modern science is spotlighting this molecule as a potential longevity nutrient—definitely a conditionally essential nutrient and maybe even deserving recognition as a new vitamin—what some researchers are already calling ‘Vitamin L’.
A Humble Suggestion and Reflection
As someone deeply grateful for my years within the SP family—and for the enduring impact of educators like Dr. Michael Dobbins, DC, whose tireless advocacy for Catalyn inspired so many—I offer this thought:
Imagine enhancing Catalyn for the next century. The original formula didn’t specify the mushroom species, though it was likely white button, given what was available at the time. Today, Catalyn uses shiitake—a valuable choice. But upgrading to a whole Golden Oyster variety, naturally rich in ergothioneine, and upto 7 or 8 times more than shiitake, could honour both tradition and innovation. A simple evolution that keeps Dr. Lee’s spirit alive—blending history with new science.
And here’s a challenge: Royal Lee left behind a vast library. Imagine going back through those archives to see if any of those original European papers on ergothioneine are sitting there, quietly waiting to be rediscovered. How cool would that be?
To my practitioner colleagues, friends, and fellow educators in the SP network: I share these reflections with respect, curiosity, and a deep hope that our shared commitment to human health continues evolving—just as Dr. Lee intended.
If you’re working with mushrooms in clinical practice, or you’re part of the SP community, this is the time to revisit what Royal Lee set in motion.
Let’s keep asking the big questions.
Let’s keep rediscovering what was hidden in plain sight.
—Lee
References
Ba, D.M., Gao, X., Al-Shaar, L., Muscat, J., Chinchilli, V.M., Ssentongo, P., Richie, J. (2021). Prospective study of dietary mushroom intake and risk of mortality: results from continuous NHANES 2003–2014 and a meta-analysis. Nutr J, 20(80). https://doi.org/10.1186/s12937-021-00738-w
Cha, S., Bell, L., Williams, C.M. (2024). The Relationship between Mushroom Intake and Cognitive Performance: An Epidemiological Study in the EPIC-Norfolk Cohort. Nutrients, 16(3), 353. https://doi.org/10.3390/nu16030353
Cheah, I. K., & Halliwell, B. (2012). Ergothioneine; antioxidant potential, physiological function and role in disease. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1822(5), 784–793. https://doi.org/10.1016/j.bbadis.2011.09.017
Hunter, A., & Eagles, B. A. (1934). Studies on Ergothioneine. Biochemical Journal, 28, 1644–1654.
Moureu, C., & Gallois, A. (1927). Presence of Ergothioneine in Human Blood. Comptes Rendus Acad. Sci. Paris, 184, 1036–1038.