Ergothioneine: The Mushroom Longevity Amino Acid?

Ergothioneine is a sulfur-containing amino acid discovered in 1909 but which until recently was little paid attention by scientists. But this has changed with the discovery this amino acid has antioxidant effects and some evidence it may slow the aging process. In this review, you'll discover the research on this interesting amino acid, the foods that contain ergothioneine, side effects, as well as the research on the ErgoActive brand and its effects on telomeres which is at the heart of its potential longevity effects.

What is Ergothioneine?

Ergothioneine (Ergo) is a sulfur-containing amino acid. It's derived from the amino acid, histidine and is found in various fungi and bacteria (cyanobacteria and mycobacteria). Since humans cannot manufacture ergothioneine we must obtain it from the diet (foods or supplements). Does that mean ergothioneine is an essential amino acid? This requires more study.

“L ergothioneine” means the amino acid is “left-handed.” Other amino acids start with the letter D (eg. D-aspartate) which means it's right-handed. Don't be confused by L or D. This is not important to understanding ergothioneine.

It Was Discovered In Ergot

Ergot is a fungus that grows on wheat and rye bread. When consumed by humans, the ergot fungus can cause hallucinations. Some have speculated ergot poisoning was behind the infamous Salem witch trials in colonial America. While not all experts agree on this, it's an interesting bit of ergot trivia.

Unlike the fungus, ergothioneine does not cause hallucinations.

Ergothioneine Is An Antioxidant

Several studies document the antioxidant properties of Ergo. For example, when mice are prevented from absorbing ergothioneine, their free radical damage (oxidative stress) increases. When cells are bathed in Ergo, it activates Nrf2 (nuclear factor erythroid 2–related factor 2), a regulator of how well we can defend against oxidative stress. It is noteworthy that some dietary supplements – like Protandim and PB-125 – are also touted for their ability to activate Nrf2.

In bacteria, Ergo has been shown to protect against UV and gamma radiation. While this opens the possibility the amino acid protects skin against sun damage, we won't know if it does until better studies are conducted.

Ergo is one of the few antioxidants that's concentrated in the mitochondria, an important player in cellular energy production. This makes sense since the mitochondria generate large amounts of free radicals as they make cellular energy. Some speculate defects in the mitochondria contribute to the aging process.

 

How Do We Absorb It?

Humans can absorb this amino acid because we possess an ergothioneine transporter. Ergo is absorbed in the intestines via the OCTN1 transporter protein which shuttles the amino acid throughout the body. The Ergo transporter is especially abundant in the mitochondria.

When researchers gave pure ergothioneine to 45 healthy people for a week, it was rapidly absorbed and retained in the blood. Not much was excreted in the urine. This tells us the body was holding on to the amino acid. Even 4 weeks later, the levels of Ergo in the plasma were still higher than before supplements were given. What's interesting about this study is they used between 5 mg (about the amount in a serving of mushrooms) and 25 mg, which is not much.

When absorbed by animals, Ergo is transported to a variety of cells and organs such as:

• red blood cells
• liver
• spleen
• brain
• heart
• eyes
• lungs
• kidneys

The fact that we have a transport system for this amino acid and that it is stored in the body lends evidence that we need it to stay healthy.

 

What Foods Have Ergothioneine?

Most Americans get about 1-2 mg of Ergo per day from food. If trying to naturally raise your ergothioneine levels here are the amounts found in 3 oz. of various foods:

• Tempeh: 200 mg
• Asparagus (grown in Mexico): 163 mg
• King oysters: 54 mg
• Shitake mushrooms: 35 mg
• Garlic: 35 mg
• Portobello mushrooms 19 mg
• White asparagus: 18 mg
• White button mushrooms: 15 mg
• Reishi mushrooms: 8 mg
• Basil leaves 5 mg
• Kidney beans: 2 mg
• Brazil nuts: 4 mg
• Oatmeal: 2 mg

Other foods include chicken liver and milk from both cows and goats as well as human breast milk.  Ergothioneine in breast milk suggests growing babies need this amino acid. Foods with lower levels of Ergo include chicken, pork, crab, and lamb.

Most Studies Are Observational

The gold standard of research is double-blinded studies that compare something to a placebo. Even though the amino acid has been known to exist for over 100 years, most of the research involves mice, isolated cells, or observing what happens to people who eat foods that contain ergothioneine. Thus, more human studies are required.  That said, the research however is intriguing.

Let's look at some of the research on this obscure amino acid.

Help For Heart Disease?

Heart disease is the leading cause of death in America. Is it possible ergothioneine may help? When researchers followed 3200 people for over 20 years they noticed out of 112 different metabolites tested, ergothioneine had the strongest association with low levels of heart disease or dying from it. The study does not prove this amino acid reduces heart disease. Better studies need to be conducted to understand how Ergo helps cardiovascular disease.

It Reduces Inflammation

In cells, Ergo has been shown to reduce inflammation. Too much cellular inflammation is linked to aging and disease. The amino acid can also act as a chelating agent, binding up iron and copper which can promote free radical damage. By reducing inflammation and binding with copper and iron, Ergo has been shown to modulate apoptosis, better known as programmed cell death. Interestingly, Ergo has not been shown to reduce CRP, a marker of inflammation, suggesting it may work through other pathways.

Ergothioneine As a Cellular Protectant

Since the nutrient seems to concentrate at the site of tissue injury, some researchers have speculated it helps the body heal itself. For example, in rats, ergothioneine decreases inflammation in the lungs. In guinea pigs with fatty liver disease, ergothioneine accumulates in the liver. While human studies need to validate this, is it possible this nutrient is being used by the body as a defense against disease and cellular injuries?

Benefits For Older Adults?

When researchers in Japan analyzed blood markers in 19 frail people who were not able to move well, they found low levels of ergothioneine were associated with being frail and weak. They further pointed out that Ergo was “neuroprotective.” In other words, the amino acid protected brain cells. Future studies will investigate if the amino acid helps memory, dementia, and other forms of cognitive decline like Alzheimer's.

Video Review

In this interview, I sat down with Dr. Pricilla Samual, Chief Science Officer at Blue California, the maker of ErgoActive ergothioneine,  which I discuss below.

Watch on my Youtube channel if you prefer.

Ergothioneine: Longevity Vitamin?

The phrase longevity vitamin was coined by Dr. Bruce Aims in 2018. Among the list of life extension nutrients proposed by Dr. Aims is ergothioneine. But, since Ergo is an amino acid, it's not a vitamin.  So it might be more appropriate to call it a longevity amino acid. The larger question is can Ergo help with healthy aging?

One way to investigate this is to look at telomeres. Telomeres are little pieces of DNA at the end of chromosomes. They act like the caps at the ends of shoelaces and help DNA stay intact. As we age, telomeres shorten. So it's a sign of cellular aging. Some consider telomere shortening to be a marker of both aging and diseases like cancer, high blood pressure and heart disease. In one study, people with shorter telomeres had tripled the risk of heart attacks. Shorter telomeres are also seen in:

• smokers
• long term stress
• exposure to pollution
• diets low in fruits and vegetables
• being overweight
• lack of exercise

Free radical oxidative stress can also cause telomere shortening. Since ergothioneine is an antioxidant, is it possible this amino acid may slow aging by helping reduce telomere shortening?

Maybe. Let's look at the evidence…

Ergothioneine And Telomeres

In a first-of-its-kind investigation, researchers bathed human cells called fibroblasts (cells that produce collagen) in ergothioneine for up to 8 weeks. They noted  Ergo slowed down telomere shortening. Specifically, after 8 weeks, the ErgoActive supplement slowed telomere shortening by between 27% and 52%. While the telomeres did not grow longer, their rate of shortening was slower than cells not bathed in Ergo.

In addition, researchers also saw an increase in telomerase, the enzyme responsible for lengthening telomeres.

This study used ErgoActive ergothioneine made by Blue California. The Blue California company makes ErgoActive and licenses it out to other supplement companies to use in their supplements. See the video above for more insights.

So does it work humans? The results are interesting and need to be followed up by human clinical trials.

Can It Improve Memory?

While human studies need to know for sure, preliminary research is intriguing. For example, mice, given ergothioneine showed improved ability to recognize objects. Other researchers have demonstrated that ergothioneine production declines after age 60 and that some people with mild memory problems had lower Ergo levels too. This suggests that Ergo may play a role in memory.

So, is it possible Ergo improves memory in people with cognitive impairment? Stay tuned.

Ergothioneine vs. Glutathione

Some consider glutathione to be the master antioxidant – and for good reason. It's a potent scavenger of oxygen-free radicals and there are many ways to naturally raise your levels. In a test tube, Ergo has been shown to be even more powerful than glutathione at mopping up free radicals. That said, mushrooms are a good source of both glutathione and ergothioneine. Even better is that cooking mushrooms do not seem to diminish Ergo levels.

Does Ergothioneine Raise NAD+ Levels?

Some research suggests aging may be related to a decline in cellular NAD+ levels. Because of this, raising NAD+ levels by the use of dietary supplements is a popular way to attempt slower aging. Given the potential of ergothioneine, how does it compare to NAD+ booster supplements like NMN and nicotinamide riboside? While Ergo is abundant in the mitochondria, it's not known if it raises NAD+ levels in humans, and if it does, what does this mean?

What's The Best Dosage To Use?

The optimal dosage is not known. The optimal amount to use for one health condition may differ from another condition. In the European Union, up to 30 mg per day is considered safe for adults while in the US, the FDA says 5 mg per capsule.

Where Do You Buy Ergothioneine?

It's possible you can find mushroom supplements at local stores like Walmart, CVS, and Walgreens. Mushroom supplements and powders may list Ergo in the Supplement Facts label. Several brands are also available on Amazon. ErgoActive, the brand shown to slow telomere shortening, is licensed by Blue California to other companies. Those companies should list ErgoActive on their labels.

Ergothioneine Side Effects

Animal research has not detected ergothioneine toxicity even at doses up to 800 mg per kilogram of body weight per day. In 2018, the Food and Drug Administration (FDA) granted ErgoActive generally recognized as safe (GRAS) status, which means it's safe to use. The FDA stated 5 mg per serving was safe. This may be why supplements often contain 5 mg per capsule. The European  Food Safety Authority (ESFA) is more liberal and has deemed Ergo safe at a dosage of up to 30 mg per day for adults and 20 mg a day for children above 3 years of age.

While human studies so far have not detected any downsides or adverse effects, here are some considerations if using supplements. This list is not complete so speak to your doctor/pharmacist for specific information.

• Start with less than suggested for the first week

Speak with your doctor first if you:

• have an allergy to mushrooms
• are pregnant or breastfeeding
• take any medications
• are having surgery

If you have tuberculosis, avoid ergothioneine supplements until we know more. Tuberculosis bacteria make ergothioneine as a defense mechanism. In theory, taking supplements may make tuberculosis worse. Some types of cancer (eg. liver and throat cancer) are associated with higher ergothioneine levels. Is it possible that cancer uses ergothioneine to protect itself? These are important questions there are best answered by your physician.

Can Ergothioneine Reduce Wrinkles?

Research shows Ergo can protect bacteria from the harmful effects of UV and gamma radiation. Ultraviolet radiation contributes to wrinkles. Before you run out and buy skincare and makeup containing mushrooms or Ergo, keep in mind researchers need to give it to humans to see if it reduces fine lines and wrinkles.

What About Hair Growth?

While seemingly outlandish at first glance, the idea of mushroom ingredients growing hair is linked to its antioxidant and anti-inflammation effects. Both free radicals and inflammation can lead to hair loss. So while on the surface it may make sense, so far, there is no good proof ergothioneine helps balding men or women. For more insights, see the reviews on Viviscal and Nutrafol. Also, see the low-level laser therapy review for before and after pictures.

Exercise Effects?

Exercise increases oxidative stress in the cells of the body. As such, some speculate that antioxidant nutrients may not only reduce this damage but improve exercise performance and recovery. Ergothioneine has not yet been tested under exercise conditions. So it's not known if it would help or not. As an aside, some research finds vitamin C and E (well-known antioxidants) do not help – and may actually hinder – exercise adaptations. Can the same be said for ET? More research is needed.

Does Ergothioneine Work?

The writing on the wall tells us humans use ergothioneine as an antioxidant and anti-inflammatory amino acid.  Early research also hints it may possess antiaging benefits too. While known to exist for over a century, serious research is only beginning. If you regularly eat mushrooms, you are already getting a steady supply of this amino acid. For those who don't, then a mushroom or ergothioneine supplement may be something to consider. For the best benefits, you can't go wrong by combining it with exercise and a healthy diet.

Here it is on Amazon if you want to check it out

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