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Ergothioneine (ERGO) is a unique naturally occurring amino acid produced by mushrooms, yeast, and some types of bacteria.
It is unique because it behaves much like a vitamin in humans. Vitamins are essential for humans to ingest because we cannot make them in the body, and they are required in critical chemical reactions. While not considered a vitamin (yet), the importance of ERGO to human cellular metabolism is evident because our bodies have a cell membrane protein that is specific to transporting ERGO into cells. The presence of this transport protein signifies that ERGO is a critical component of cellular function.
Once incorporated into cells, ERGO exerts several biological actions that protect and enhance cellular function, including acting as an antioxidant, inflammation regulator, and detoxification aid.
Emerging evidence shows that diets rich in ERGO exert these protective effects and promote longevity. For these reasons, ERGO has been referred to as the "longevity vitamin."
ERGO is a thiol, meaning it is a sulfur-containing compound. Some of its antioxidant and potential antiaging effects are similar to other thiol-containing compounds, such as glutathione and coenzyme Q10.
ERGO is different because it is a much smaller molecule distributed throughout the body and all the compartments of the cells, including the internal cellular environment (cytoplasm) and within mitochondria (the energy-producing compartment of cells).
A clinical study in humans has shown that taking ERGO as a dietary supplement raises blood levels of ERGO, improves thiol status, and may increase antioxidant status to produce various health benefits.
Dr. Bruce Ames, a scientist at the University of California, is among those who have suggested that ERGO be considered a "longevity vitamin" based on his Triage Theory. In this theory, the human body uses micronutrients on a priority basis for functions of survival and reproduction. ERGO exerts considerable functions in this regard. But is it truly a vitamin?
Vitamins are compounds in food without which we cannot live or be healthy. We cannot make them in our bodies, so they must be ingested.
With classic vitamins like vitamin A, B vitamins, and vitamin C, the identification of their importance to human health was discovered by the link between a dietary deficiency of the vitamin and a particular set of signs and symptoms of deficiency disease.
ERGO is different in that a deficiency state has not yet been identified because it is found in small quantities in all food. That low level probably keeps a severe deficiency from appearing, but it is far from optimal.
Another factor that suggests how important ERGO is to human health is how efficient the human body is in concentrating and holding on to this compound. If ERGO were unimportant, it would not be concentrated and retained so efficiently.
In particular, body tissues highly active in energy metabolism and susceptible to oxidative stress and inflammation contain the richest concentration of ERGO. Specifically, the brain, liver, intestinal cells, testes, bone marrow, kidney, spleen, lung, and eyes. Tissues that ERGO is also found in higher concentrations in seminal fluid and breast milk. Again, all of this data indicates ERGO may be an essential vitamin.
The brain may be the most sensitive to low ERGO levels in the tissues where ERGO is concentrated. After all, the brain is the most metabolically active tissue in the body. The decline in brain function with aging might eventually be linked to lowered ERGO status and be one of the signs of an ERGO deficiency if it is established as a vitamin.
Levels of ERGO decrease with age due to both a drop in dietary intake and a decrease in the genetic expression for the ERGO transport proteins. This scenario indicates that ERGO deficiency may significantly affect aging-related impaired brain function. There is data to support this connection, as two human studies show ERGO is lower in elderly patients with mild cognitive impairment than those without. And there is evidence that ERGO accumulates in the brain, where it may protect against oxidative damage, inflammation, and decreased mitochondrial function linked to cognitive decline in older adults.
Frailty is another condition associated with aging, and when researchers sought to determine the metabolic basis of frailty, ERGO levels were significantly lower in frail elderly subjects compared to the non-frail elderly subjects.
And another study showed that ERGO levels were associated with the preservation of gait (manner of walking). Disturbance in gait is a common sign of aging. The basis of gait disturbance in older adults is oxidative damage of skeletal muscle. ERGO appears to help protect against this underlying damage.
ERGO has been shown to decrease oxidative stress in virtually every tissue and cell type studied, including the lining of blood vessels, liver, kidney, heart, and other organs. It also helps reduce the toxic effects of many harmful chemicals. ERGO antioxidant and detoxification effects are at its core in all applications. It is particularly well-suited for protecting the heart and vascular system and against the increased oxidative stress associated with diabetes and obesity.
Lower intakes of ERGO from the diet may explain why Americans have more age-related health issues and a lower life expectancy than other countries. For example, the estimated intake level of ERGO in the United States is 1.1 mg/day compared to up to 4.6 mg/day in Italy.
When researchers analyzed a twenty-year study of the dietary habits of over 15,000 American participants, they found that individuals that consumed even small amounts of mushrooms had a 16% reduction in their mortality rate and a 35% reduced rate if mushroom intake was coupled with a lower red meat intake.
ERGO may be the key mushroom component for this benefit.
All foods have at least trace levels of ERGO. But the common conventional agricultural practice of excessive soil tillage may be why dietary levels may be much lower now. Excessive tillage disrupts the fungal mycelia in the soil that feeds crops nutrients, including ERGO.
Mushrooms are the key dietary source of ERGO, representing about 95% of the total dietary intake. Other foods with modest levels of ERGO include oat bran, black or red beans, and organ meats (e.g., liver and kidney). The ERGO content of mushrooms varies considerably based on variety. A 3-ounce serving of crimini, portabella, or button mushrooms has an ERGO content of roughly 5 mg.
Shiitake, oyster, lion's mane, or maitake mushrooms have a higher ERGO content of up to 13 mg per 3-ounce serving. Cooking does not diminish the ERGO content, and studies show that ingesting mushrooms raises blood levels of ERGO.
Since mushrooms are by far the primary dietary source, if a person is not regularly eating mushrooms, they are likely deficient in ERGO. And evidence indicates that it could accelerate aging and the development of age-related disorders.
Taking supplemental ergothioneine may be a good option, given its safety and the possible health benefits of raising the intake of ERGO.
Regarding the safety of ERGO, it has undergone extensive studies to determine safety. Even at extremely large doses, no adverse effects were seen in animal studies. And the recommended supplemental dosage level of 30 mg per day is well below the no observed adverse effect level (NOAEL) of 800 mg per kg body weight per day established by the European Food Safety Authority (EFSA). ERGO has also been established as Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration (FDA).
A human clinical trial verified the effectiveness of ERGO as a dietary supplement showing that it is absorbed and retained in the body based upon increased levels of ERGO in the red blood cells (preferentially) and plasma combined with minimal excretion in the urine (less than 4% of oral dosage). The increase in ERGO was associated with a downward trend in inflammation and oxidative damage biomarkers.
While ergothioneine naturally occurs in all foods, more than general dietary intake may be required to provide optimal intake, especially in those who do not or cannot eat mushrooms regularly.
There are also some genetic variations among individuals where higher levels of dietary intake or supplementation may be indicated. In studies measuring blood levels of ERGO after consuming standardized intake levels of high ERGO mushrooms, the blood values varied more than ten-fold. Eventually, blood measurements, especially red blood cell levels of ERGO, may be used to ensure optimal ERGO intake.
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By Dr. Michael Murray, N.D. 
