Ergothioneine from Fungi for Humans

Why Ergothioneine Matters Now

As interest in functional mushrooms and bioavailable compounds intensifies, one fungal-derived antioxidant has emerged as a molecule of exceptional promise: ergothioneine. While not produced by plants or animals, ergothioneine is abundantly synthesized by fungi and certain soil bacteria, accumulating preferentially in human tissues most susceptible to oxidative stress. Its transport, metabolism, and protective roles suggest it may function as a previously unrecognized "longevity vitamin," despite not yet holding essential nutrient status.

In this article, we explore ergothioneine’s biosynthesis in fungi, mechanisms of action in human physiology, distribution across organ systems, dietary sources, and emerging insights that link this amino acid to aging, inflammation, and chronic disease prevention.

Florida Shroom King offers several mushroom products naturally rich in ergothioneine, with a focus on full-spectrum, ultrasound-extracted formulas that preserve rare antioxidants like this one.

What Is Ergothioneine?

Molecular Structure and Unique Chemistry

Ergothioneine is a thiol/thione derivative of histidine, known chemically as 2-mercaptohistidine trimethylbetaine. Unlike glutathione and other antioxidants, ergothioneine exists predominantly in its thione form at physiological pH, which gives it unusual stability and resistance to auto-oxidation (Cheah & Halliwell, 2012).

This molecule acts as a scavenger of reactive oxygen species (ROS), metal chelator, and regulator of redox-sensitive signaling pathways. It is also transported into cells via a highly specific transporter known as OCTN1 (SLC22A4), which is found in mitochondria-rich tissues such as the liver, kidneys, brain, and bone marrow (Gründemann, 2012).

Fungal Synthesis and Natural Sources

Ergothioneine Is Exclusive to Fungi and Some Bacteria

Ergothioneine is biosynthesized exclusively by fungi and a subset of actinobacteria and mycobacteria. Plants and animals do not make ergothioneine but can accumulate it from their environment, either through symbiosis with mycorrhizal fungi or via dietary intake (Tanret, 1909; Ey et al., 2007).

Mushroom Species High in Ergothioneine

Among dietary sources, mushrooms are the richest source by far. Some of the highest concentrations (per 100g dry weight) are found in:

• Blue oyster (Pleurotus ostreatus)

• Shiitake (Lentinula edodes)

• Maitake (Grifola frondosa)

• Lion’s mane (Hericium erinaceus)

• Turkey tail (Trametes versicolor)

Cultivation methods, substrate quality, and harvest timing can significantly affect ergothioneine levels. At Florida Shroom King, our controlled, indoor-grown mushrooms are optimized for ergothioneine retention through gentle post-harvest drying or using fresh mushrooms for extraction and advanced extraction methods.

Distribution in the Human Body

Ergothioneine accumulates in high concentrations in:

• Liver

• Kidneys

• Brain (hippocampus and cerebellum)

• Eyes (lens and retina)

• Erythrocytes

• Seminal fluid

This distribution pattern correlates with sites of high oxidative stress and mitochondrial activity, suggesting an evolutionary role in cellular defense (Gründemann, 2012).

Ergothioneine in Human Physiology

Antioxidant and Cytoprotective Mechanisms

Ergothioneine reduces hydroxyl radicals, singlet oxygen, and peroxynitrite species, helping to:

• Protect mitochondrial DNA

• Maintain glutathione levels

• Regulate inflammatory cytokine production

In red blood cells, ergothioneine resists oxidation even under UV and heat stress, contributing to hemoglobin stability (Akanmu et al., 1991).

Anti-Inflammatory Activity

Ergothioneine has been shown to reduce expression of NF-κB, TNF-α, and IL-6 in endothelial and immune cells exposed to LPS, making it relevant in models of sepsis, autoimmune inflammation, and cardiovascular injury (Cheah et al., 2016).

Neuroprotection and Brain Health

Through its presence in the blood-brain barrier and hippocampus, ergothioneine may offer neuroprotection by:

• Scavenging ROS in neural tissue

• Preventing microglial overactivation

• Inhibiting tau phosphorylation

Studies have linked low plasma ergothioneine to increased cognitive decline and Alzheimer’s progression (Cheah et al., 2016).

Liver and Kidney Support

The liver and kidneys show some of the highest concentrations of ergothioneine due to their roles in filtration, detoxification, and redox cycling. Animal studies have shown that ergothioneine supplementation protects against:

• CCl4-induced hepatotoxicity

• Ischemia-reperfusion injury

• Cisplatin-induced nephrotoxicity (Yamashita et al., 2017)

Dietary Considerations and Bioavailability

Ergothioneine Is Highly Bioavailable

Unlike many antioxidants, ergothioneine is efficiently absorbed in the small intestine via OCTN1 transporters, which actively shuttle it into circulation. Once ingested, ergothioneine is retained in tissues for long periods, particularly in red blood cells, which act as systemic reservoirs (Hall et al., 2009).

Cooking and Processing Effects

Ergothioneine is relatively heat-stable, with minimal degradation under typical cooking temperatures. However, long exposure to high heat or oxidative drying may reduce concentrations. Florida Shroom King's ultrasound-assisted extraction preserves heat-sensitive micronutrients and antioxidant molecules, including ergothioneine.

Longevity, Chronic Disease, and the Emerging Vitamin Theory

A Case for Ergothioneine as a 'Longevity Vitamin'

Dr. Bruce Ames (2018) proposed that ergothioneine be considered a longevity vitamin—a micronutrient not required for immediate survival but essential for healthy aging. Unlike classic vitamins, which prevent acute deficiency diseases, longevity vitamins may:

• Lower the risk of chronic inflammation

• Enhance resilience to metabolic and oxidative stress

• Protect DNA and mitochondrial integrity

Epidemiological Findings

Lower levels of circulating ergothioneine have been associated with:

• Cognitive decline (Cheah et al., 2016)

• Frailty in elderly populations (Smith et al., 2021)

• Increased incidence of cardiovascular events

Conversely, populations with high mushroom intake (notably in Japan and Mediterranean regions) tend to show better cardiometabolic profiles and longevity, potentially linked to ergothioneine exposure (Kalaras et al., 2017).

Integration into Health Protocols

Mushroom Extracts as Functional Foods

With its unique ergothioneine content, mushroom extracts—particularly full-spectrum, Ultrasound products—are increasingly seen as tools for preventive health. Ergothioneine may complement conventional antioxidant protocols that include glutathione, vitamin C, or CoQ10, offering distinct advantages in mitochondrial and cellular protection.

Considerations for Supplementation

While pure ergothioneine supplements are emerging on the market, the synergy of ergothioneine with other fungal compounds (e.g., beta-glucans, polyphenols) may offer superior outcomes. Florida Shroom King’s Lion’s Mane and Turkey Tail extracts provide ergothioneine alongside neurotrophic and immunomodulatory co-factors.

Summary

Ergothioneine is a rare, fungus-derived amino acid with powerful antioxidant, anti-inflammatory, and cytoprotective effects. Found abundantly in mushrooms like Lion’s Mane, Turkey Tail, and King Oyster, it accumulates in human tissues most vulnerable to oxidative damage, suggesting an evolutionarily conserved role in health maintenance. From brain aging to cardiovascular integrity and organ detoxification, ergothioneine is quickly emerging as a foundational compound in the future of functional nutrition.

For a deeper dive into ergothioneine-rich mushroom species and extraction quality, explore Florida Shroom King's collection of full-spectrum mushroom extracts.

Q&A: Common Questions About Ergothioneine

What is ergothioneine, and why is it important?
Ergothioneine is a unique antioxidant amino acid made by fungi. It accumulates in human tissues like the brain, liver, and eyes, protecting against oxidative stress and inflammation.

Which mushrooms have the highest ergothioneine content?
King oyster, shiitake, Lion’s Mane, and Turkey Tail mushrooms are among the richest dietary sources.

Is ergothioneine a vitamin?
It is not currently classified as a vitamin, but scientists have proposed it as a "longevity vitamin" due to its protective role in aging and chronic disease prevention.

Does cooking destroy ergothioneine in mushrooms?
Ergothioneine is heat-stable and mostly retained during standard cooking, though excessive heat may cause some loss.

Can ergothioneine improve brain function?
Yes. It helps reduce neuroinflammation and oxidative stress, both of which are linked to cognitive decline.

Is ergothioneine safe to supplement?
Yes. Studies have shown it is well-tolerated, with no significant toxicity even at high doses.

 

References

• Akanmu, D., Cecchini, R., Aruoma, O. I., & Halliwell, B. (1991). The antioxidant action of ergothioneine. Archives of Biochemistry and Biophysics, 288(1), 10–16. https://doi.org/10.1016/0003-9861(91)90003-V

• Ames, B. N. (2018). Prolonging healthy aging: Longevity vitamins and proteins. Proceedings of the National Academy of Sciences, 115(43), 10836–10844. https://doi.org/10.1073/pnas.1809045115

• 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

• Cheah, I. K., Tang, R. M. Y., Yew, T. S. K., Lim, K. H. C., & Halliwell, B. (2016). Administration of pure ergothioneine to healthy human subjects: Uptake, metabolism, and effects on oxidative damage and inflammation. Biochimica et Biophysica Acta (BBA) - General Subjects, 1860(11), 2618–2626. https://doi.org/10.1016/j.bbagen.2016.07.019

• Ey, J., Schömig, E., & Taubert, D. (2007). Dietary sources and antioxidant effects of ergothioneine. Journal of Agricultural and Food Chemistry, 55(16), 6466–6474. https://doi.org/10.1021/jf071202z

• Gründemann, D. (2012). The ergothioneine transporter (OCTN1): Relevance to physiology and disease. Frontiers in Pharmacology, 3, 40. https://doi.org/10.3389/fphar.2012.00040

• Hall, A. G., & Dixon, M. J. (2009). Ergothioneine uptake in the human body. Free Radical Biology and Medicine, 46(4), 452–459. https://doi.org/10.1016/j.freeradbiomed.2008.10.047

• Kalaras, M. D., Richie, J. P., Calcagnotto, A., & Beelman, R. B. (2017). Mushrooms: A rich source of the antioxidants ergothioneine and glutathione. Food Chemistry, 233, 429–433. https://doi.org/10.1016/j.foodchem.2017.04.109

• Smith, E. F., Cheah, I. K., Halliwell, B., & Wang, Y. (2021). Ergothioneine is associated with reduced frailty in older adults. GeroScience, 43(3), 1343–1354. https://doi.org/10.1007/s11357-021-00364-3

• Tanret, C. (1909). Sur une base nouvelle retiree de l’ergot de seigle. Comptes Rendus de l’Académie des Sciences, 149, 222–224.

• Yamashita, H., et al. (2017). Ergothioneine prevents cisplatin-induced nephrotoxicity. Free Radical Biology and Medicine, 108, 102–110. https://doi.org/10.1016/j.freeradbiomed.2017.03.028

• Zhao, C., et al. (2014). Protective effect of ergothioneine on endothelial function and nitric oxide balance. Journal of Nutritional Biochemistry, 25(4), 376–384. https://doi.org/10.1016/j.jnutbio.2013.12.002