Ergothioneine: A Mushroom-Derived Antioxidant That May Be A Potent Adjunct For Lyme Treatment
Boletus edulis mushrooms - a delicacy known throughout Central and Southern Europe - are rich in the amino acid Ergothioneine
Our ancestors have used mushrooms as medicine for thousands of years. Indigenous peoples of North America used puffball mushrooms as wound healers. The frozen mummy, Otzi, living nearly 5300 years ago, carried Amadou and a Birch polypore tethered in a pouch to help him survive the Alps of northern Italy. Otzi is also the oldest known case of Lyme disease, revealed through genetic analysis [1].
Today, there is a growing interest in the accumulated data indicating that certain mushrooms contain a unique and potent antioxidant called Ergothioneine. What is Ergothioneine, and what makes this antioxidant so special?
Ergothioneine: An Overview
Egrothioneine is named for the ergot fungus (Claviceps purpurea) from which it was first isolated in 1909. It is a naturally occurring amino acid, and is a thiol/thione derivative of histidine. It’s highest concentrations are found in mushrooms and bacteria, as well as in lower amounts in some foods, including beef, pork, lamb and chicken [2 , 3].
Despite the presence of this compound among these foods, it’s biosynthesis has only been observed in certain bacteria and fungi. For this reason, it is most highly concentrated in certain species of mushroom, as well as a select few foods that take it up from the conditions of the soil (such as asparagus, for example). However, the amounts of Ergothioneine present in the United States food supply chain are likely deficient due to reduced fungal populations in agricultural soils caused by modern cultivation practices [4, 5].
It’s potential significance to human health is based on the presence of specific transporters for Ergothioneine in the human body, which make it highly bioavailable and readily retained. The presence of a highly specific transport protein, called OCTN1, suggests that this compound serves a specific set of functions in the body. Specific transporters are rarely present for non-nutrient bioactive compounds, as such [5].
So what does Ergothioneine do in the body?
A Major Cell Protector
Ergothioneine is a highly stable water-soluble antioxidant, demonstrating the ability to resist autooxidation. It has been demonstrated to scavenge reactive oxygen and nitrogen species, and protect cells from a variety of apoptotic insults. It is as powerful as glutathione, the other major water-soluble antioxident, in protecting against cytotoxicity from superoxide generation. But unlike glutathione, Ergothioneine is avidly retained in the face of oxidative stress, whereas glutathione is rapidly depleted. It’s pharmacokinetics are notable - it has been shown that levels of Ergothioneine administered to humans continued to increase in the blood and plasma for up to four weeks [6, 7, 8].
Mitochondria Protectant
Water-soluble (hydrophilic) antioxidants such as Ergothioneine and glutathione preferentially protect water-soluble proteins, such as mitochondria, from oxidative damage. Some studies suggest that Ergothionine in particular might be uniquely involved in the protection of mitochondrial DNA [7].
Selective damage to mitochondrial DNA by oxidative stress has been implicated in chronic conditions, especially Lyme disease (Borrelia Burgdorferi). Increased mitochondrial superoxide has been directly linked to infection with Borrela Burgdorferi, the bacteria that causes Lyme disease.
B. Burgdorferi, for instance, has been shown to passively absorb cysteine within infected cells, which is one of the main amino acids to synthesize glutathione. As mentioned above, glutathione is a powerful water-soluble antioxidant that plays a critical role in ROS scavenging. The depletion of cysteine concomitantly lowers the levels of glutathione in the host, increasing mitochondrial ROS, and subsequent host weakening. Reducing mitochondrial ROS may be regarded as a key strategy in Lyme treatment, that in turn reduces NADPH oxidase, a superoxide radical involved in initiating ROS within the host [9, 10, 11].
Ergothioneine may specifically reduce the ROS in the mitochondria initiated by Borrelia Burgdorferi.
To quote Paul & Snyder (2019): “The high density of ETT (Ergothioneine) in mitochondria implies a unique role in protecting this organelle from the reactive oxygen species that accumulate even with normal oxidative metabolism” [7].
“ET (Ergothioneine) may afford a more stable mode of cytoprotection. It is not metabolized to any notable extent in mammalian tissues, the half-life of dietary ET being approximately 1 month. Its cycling between oxidized and reduced sulfur takes place non-enzymatically and is facilitated by the intrinsically tautomeric structure of the molecule. These properties suggest a role for ET as a bulwark, a final defense for cells against oxidative damage. Its stability may help mitochondria cope with otherwise overwhelming stresses encountered even during relatively physiologic metabolism.” (Italics mine) [7].
Glutathione, on the other hand, is notoriously unstable in the face of oxidative stress. Supplementation with Ergothioneine, due to its resistance to auto-oxidation, may provide a much more stable alternative to glutathione for providing the support needed to resist oxidative bursts induced by B. Burgdorferi [13].
An “Adaptive” Antioxidant
Some studies present evidence that Ergothioneine accumulates specifically at the sites of injured tissue, suggesting that it plays a major role in responding selectively to tissue where reactive species due to ROS-generating toxins, and diseases causing oxidative damage, accumulate. Although Ergothioneine may have a limited role in healthy humans, scenarios where a chronic illness or damage to the tissue is involved, it may be of significant therapeutic benefit [14].
Additionally, Ergothioneine crosses the blood-brain-barrier, and accumulates in nearly all tissues, including the brain, heart, lung, kidney, spleen and eye [15].
This insight makes me think that the pharmacokinetics of Ergothioneine may provide additional support for those with Lyme disease. Lyme has been called ‘the great imitator”, due to the ability of the pathogen to mimic most known disease conditions. This is because the bacteria can mobilize and sequester into most tissue sites in the body, including the brain, heart, lungs, kidneys, spleen, eye, liver and bladder, where they can degrade the cells and proteins, causing a unique symptom constellation from host to host.
It may then be possible to supplement with Ergothioneine for selective support to the specific areas where the bacteria are doing damage.
Ergothioneine Is Neuroprotective
Ergothioneine is highly protective of the brain and the structures that support it. A range of studies have demonstrated the neuroprotective effects of Ergothioneine consumption in mice and humans, decreasing amyloid-induced cell death, protecting the hippocampus (which is frequently damaged during neuro-Lyme), and increased lifespan of Alzheimer's induced neurodegeneration [18, 19].
Furthermore, a direct correlation has been established that reduced levels of Ergothioneine in humans is linked to cognitive decline [17]
Human dietary consumption of mushrooms have been shown to have neuroprotective effects. Mushrooms contain many active biocompounds that act in synergy together, so this cannot be taken as evidence of ingestion of Ergothioneine alone in producing these effects, although it may be a significant constituent in certain mushrooms responsible for this effect.
The innovation of a specific pathway for Ergothioneine, OCTN1, however, indicates a possibly significant role for regular consumption of fungi (or other Ergothioneine-rich food sources) for the development and survival of human emergence. This speculation on my part is not necessarily unfounded [16].
Bear in mind, a medicinal plant or mushroom is like a symphony. It’s constituents, the individual notes. Natural foods and medicines act as a coherent whole, involving an enormous range of co-factors for which we know very little. With perhaps some exceptions, isolated compounds rarely do much good in the long term.
Rich Sources Of Ergothioneine
A number of studies have gathered data on Ergothioneine levels among various food sources. Interestingly, although the genome of plant-based foods do not contain the ability to synthesize Ergothioneine, certain foods grown in different regions shown higher levels. This is likely due to the conditions of the soil where these foods were grown.
Foods that have been fermented, such as tempeh, or share a symbiotic relationship with fungi, such as asparagus, demonstrated the highest levels of non-fungus derived Ergothioneine. Again, the levels depended on the soil region where it was grown [20].
As an aside, I would like to point out that a widely used herbal adaptogen and tonic, Shatavari (asparagus racemosus), is the root of Asparagus. I have so far observed that no studies have been done on the possible levels of Ergothioneine that are concentrated within the root as a result of mycorrhizal symbiosis, but a cross-section of its traditional use and current studies may reveal some interesting findings. One again, however, I would like to emphasize that a plant medicine deserves recognition as a whole dynamic and living organism, rather than a machine that can be reduced to its constituent makeup.
Of the species of edible fungi that have been tested for Ergothioneine, among the highest found were Willow, Enoki, Shiitake, Buna shimeji, King oyster and Boletus edulis. Among the mushrooms studied for Ergothioneine, Boletus scored the highest, at 181 mg of Ergothioneine per 100 grams of dry weight, compared to only 54.17 mg from the second highest, king oyster [20].
Mushy Love: Boletus Edulis (And The Original Inter-Net)
Boletus is a popular culinary mushroom, considered a delicacy nearly everywhere it grows. In England, it is known as penny bun. In Italy, Porcini, and in France, Cepe.
Since the ancient world, Boletus has been, and continues to be, prized as a choice edible in central and southern Europe, as well as parts of Asia. Due caution for harvesting Boletus as a food or medicine should be taken, as it is prone to accumulate toxic metals (such as mercury). However, the ability for Boletus species to thrive in polluted soils and neutralize heavy metals through chelation (without damaging the mushroom) does make it an excellent remediator for contaminated landscapes. [24].
Boletus is eaten raw, ground up in soups and pastas, canned (they are one of the few mushrooms that are picked), sauteed in butter or even frozen. After drying, they are exported the world over, including regions where they do not grow naturally.
Boletus is notoriously difficult to cultivate. Thankfully, populations of Boletus species are not facing imminent threats from overpicking. However, some species, notably in the Mediterranean region, have seen a decline in recent years. It has been speculated that this decline is due to rising temperatures in that region.
One important thing to consider is the following historical example of one instance when the overharvesting of Boletus may have came close. Since the fall of the Iron Curtain in 1989, many eastern European countries with local mushroom harvesting traditions developed into exporters of Boletus, primarily for Italian markets. Many of the unemployed within these communities relied on their pickings of Boletus for their annual income. The lack for financial and ecological controls eventually led to heavy exploitation of this mushroom as a commodity [25, 26].
In resisting domestication, it’s as if this special mushroom teaches us that in order to heal, we must encounter the living Earth on its own terms. For many of us struggling with chronic Lyme, an atmosphere of fear surrounds wild nature. After all, it is often where we first met our illness. But perhaps it is there also where we must go in order to become whole. Boelus teaches this.
Nutrition And Constituents Of Boletus
Boletus is rich in protein, especially dried. Some of the active compounds in Boletus species include Ergothioneine, alkaloids, Magnesium, Iron, B-vitamins, Quercetin and Lycopene. It is also rich in tocopherols, polyphenols, and especially high in Rosmarinic acid (also found in Rosemary - hence its name) and Ergothioneine [27].
Extracts of the Boletus mushroom have been shown to kill colon cancer cells, as well as strongly protect the lungs in asthma-induced mice [28, 29]
It’s traditional medicinal use extends to treating lumbago, numbness in the limbs, and tendinitis.
Concluding Remarks
Ergothioneine is a unique and potent antioxidant found throughout the mushroom kingdom, and especially in the Boletus species of fungi. I'm somewhat astounded that there hasn't been much, if any, discussion on the use of Ergothioneine for treating Lyme (or chronic illness in general). It turns out it is very specific for a number of things that Lyme does in the body. One of these is that it acts as an extremely potent mitochondria protectant.
To recap from above - protecting the mitochondria is very critical - one the priorities in fact - during Lyme treatment. During infection, the bacteria will degrade cysteine, which synthesizes glutathione in the human body. Glutathione (which protects mitochondria) is the only other major water-soluble antioxidant on par with Ergothioneine. But active Lyme infection depletes glutathione rapidly, especially in the face of ROS.
Ergothioneine, on the other hand, is avidly stable in the face of this stress - and concentrates in the mitochondria. In fact, the human body has a specific transport pathway for Ergothioneine, which is extremely uncommon for a nutrient that cannot be biosynthesized by the human body, and which suggested that Ergothioneine plays a very important role for humans.
I suspect we will start hearing more about this in the coming years. Let's start paying attention to this now.
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